bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural evidence for a proline-specific glycopeptide recognition domain in an O-glycopeptidase
Authors: Noach Ilit , Boraston Alisdair B
Published: October 2020

The glycosylation of proteins is typically considered as a stabilizing modification, including resistance to proteolysis. A class of peptidases, referred to as glycopeptidases or O-glycopeptidases, circumvent the protective effect of glycans against proteolysis by accommodating the glycans in their active sites as specific features of substrate recognition. IMPa from Pseudomonas aeruginosa is such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction. IMPa, however, is a relatively large multidomain protein and how its additional domains may contribute to its function remains unknown. Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline. The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions. This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
Black Lives Matter in health promotion: moving from unspoken to outspoken
Authors: Leitch Stephanie , Corbin J Hope , Boston-Fisher Nikita , Ayele Christa , Delobelle Peter , Gwanzura Ottemöller Fungisai , Matenga Tulani Francis L , Mweemba Oliver , Pederson Ann , Wicker Josette
Published: October 2020

Racism is a public health crisis. Black communities (including Africans, the African diaspora and people of African descent) experience worse health outcomes as demonstrated by almost any measure of health and wellbeing—e.g. life expectancy; disease prevalence; maternal mortality rates. While health promotion has its foundation in promoting equity and social justice, it is clear that however well-intended, we are not affecting meaningful change for Black communities quickly enough. Through this article, we outline the intersection of social determinants of health and anti-Black racism. We describe how in the first 8 months of 2020 Black communities around the globe have been disproportionately affected by COVID-19, while also having to respond to new instances of police brutality. We assert that the time has come for health promotion to stop neutralizing the specific needs of Black communities into unspoken ‘good intentions’. Instead, we offer some concrete ways for the field to become outspoken, intentional and honest in acknowledging what it will take to radically shift how we promote health and wellbeing for Black people.
Genomics-based immuno-oncology: bridging the gap between immunology and tumor biology
Authors: DiNatale Renzo G , Hakimi A Ari , Chan Timothy A
Published: October 2020

The first hypotheses about how the immune system affects cancers were proposed in the early 20th century. These early concepts about cancer immunosurveillance were further developed in the decades that followed, but a detailed understanding of cancer immunity remained elusive. It was only recently, through the advent of high-throughput technologies, that scientists gained the ability to profile tumors with a resolution that allowed for granular assessment of both tumor cells and the tumor microenvironment. The advent of immune checkpoint inhibitors (ICIs), which have proven to be effective cancer therapies in many malignancies, has spawned great interest in developing biomarkers for efficacy, an endeavor that highlighted the value of dissecting tumor immunity using large-scale methods. Response to ICI therapy has been shown to be a highly complex process, where the dynamics of tumor and immune cells is key to success. The need to understand the biologic mechanisms at the tumor–immune interface has given rise to the field of cancer immunogenomics, a discipline that aims to bridge the gap between cancer genomics and classical immunology. We provide a broad overview of this emerging branch of translational science, summarizing common platforms used and recent discoveries in the field, which are having direct clinical implications. Our discussion will be centered around the genetic foundations governing tumor immunity and molecular determinants associated with clinical benefit from ICI therapy. We emphasize the importance of molecular diversity as a driver of anti-tumor immunity and discuss how these factors can be probed using genomic approaches.
RNA-Seq profiling of leukocytes reveals a sex-dependent global circular RNA upregulation in multiple sclerosis and 6 candidate biomarkers
Authors: Iparraguirre Leire , Alberro Ainhoa , Sepúlveda Lucía , Osorio-Querejeta Iñaki , Moles Laura , Castillo-Triviño Tamara , Hansen Thomas B , Muñoz-Culla Maider , Otaegui David
Published: October 2020

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, with higher prevalence in women, that leads to neurological disability. The disease course and clinical phenotype are highly variable, and therefore, biomarkers for the diagnosis, classification, monitoring of the disease and treatment assessment are needed. Studies have shown a dysregulation in the coding and non-coding RNAs and proposed some as biomarkers. However, still none of them have reached the clinical practice. Recently, circular RNAs (circRNAs) have emerged as new players in the transcriptome that hold a great potential as biomarkers in several diseases. Leukocytes from 30 MS patients and 20 healthy controls (HCs) were RNA-sequenced to study the linear and circular transcriptome. Differential expression analysis was performed by DESeq, and circRNA candidates were studied in a second cohort (70 MS and 46 HC) by RT-qPCR and in paired samples drawn during the relapse and remission phases (20 patients). Among the differentially expressed circRNAs, 96.1% are upregulated in patients compared with controls, but similar circRNA profiles are found between MS types. The same upregulation trend was observed in females but not in males or in the linear transcriptome. The upregulation of 6 circRNAs was validated, and a change in their expression was found between relapse and remission. The 6 circRNAs showed a good performance to discriminate patients from HC with a combined area under the curve of 0.852. There is global, specific and sex-dependent increase of circRNA expression in MS, and 6 circRNAs are proposed as potential biomarkers.
Declining female size at onset of maturity in Nephrops norvegicus in long-term surveys (1997–2016)
Authors: Sigwart Julia D , Lundy Mathieu , Dick Jamie T A , Becker Carola
Published: October 2020

Data on the demography and reproduction of marine species provide important information for a sustainable fisheries management. We show that the size at onset of maturity in female Nephrops norvegicus has been in decline for over 20 years and has always been above the established minimum landing size (MLS) in the Western Irish Sea. Determining the size at onset of maturity is one important factor to inform an effective MLS, such that individuals can reproduce at least once. The length at which half of females are sexually mature (L50) in the overall population declined by over 12% in two decades, from 23.6 mm in 1997 to 20.6 mm in 2016, while the MLS has remained at 20 mm. While L50 values differ among permanent sampling stations, the decline was observed at all stations. Current practice thus allows immature females to be landed before they reproduce and contribute to recruitment. While it is not always possible to identify the determining factors that drive the decline in SOM, we argue that it is appropriate to recognize this as an indicator of declining system productivity.
Prevalence of antimicrobial resistance genes and its association with restricted antimicrobial use in food-producing animals: a systematic review and meta-analysis
Authors: Nobrega Diego B , Tang Karen L , Caffrey Niamh P , De Buck Jeroen , Cork Susan C , Ronksley Paul E , Polachek Alicia J , Ganshorn Heather , Sharma Nishan , Kastelic John P , Kellner James D , Ghali William A , Barkema Herman W
Published: October 2020

Background

There is ongoing debate regarding potential associations between restrictions of antimicrobial use and prevalence of antimicrobial resistance (AMR) in bacteria.

Objectives

To summarize the effects of interventions reducing antimicrobial use in food-producing animals on the prevalence of AMR genes (ARGs) in bacteria from animals and humans.

Methods

We published a full systematic review of restrictions of antimicrobials in food-producing animals and their associations with AMR in bacteria. Herein, we focus on studies reporting on the association between restricted antimicrobial use and prevalence of ARGs. We used multilevel mixed-effects models and a semi-quantitative approach based on forest plots to summarize findings from studies.

Results

A positive effect of intervention [reduction in prevalence or number of ARGs in group(s) with restricted antimicrobial use] was reported from 29 studies for at least one ARG. We detected significant associations between a ban on avoparcin and diminished presence of the vanA gene in samples from animals and humans, whereas for the mecA gene, studies agreed on a positive effect of intervention in samples only from animals. Comparisons involving mcr-1, blaCTX-M, aadA2, vat(E), sul2, dfrA5, dfrA13, tet(E) and tet(P) indicated a reduced prevalence of genes in intervention groups. Conversely, no effects were detected for β-lactamases other than blaCTX-M and the remaining tet genes.

Conclusions

The available body of scientific evidence supported that restricted use of antimicrobials in food animals was associated with an either lower or equal presence of ARGs in bacteria, with effects dependent on ARG, host species and restricted drug.
PTCA (1-H-Pyrrole-2,3,5-Tricarboxylic Acid) as a Marker for Oxidative Hair Treatment: Distribution, Gender Aspects, Correlation with EtG and Self-Reports
Authors: Casati Sara , Ravelli Alessandro , Angeli Ilaria , Bergamaschi Roberta F , Binelli Giorgio , Minoli Mauro , Orioli Marica
Published: October 2020

Hair analysis is an important and reliable resource for the assessment of alcohol or drug abstinence in both clinical and forensic toxicology. Recently, it has been demonstrated that hair oxidative cosmetic treatments lead to the reduction in incorporated xenobiotics in hair, such as ethyl glucuronide (EtG), a marker of alcohol abuse, and the formation of 1-H-pyrrole-2,3,5-tricarboxylic acid (PTCA), a degradation product of melanin. The aim of the present study was to investigate PTCA trends in a large number of samples in order to evaluate the reliability of this biomarker in recognizing previous cosmetic treatment in forensic analyses. Therefore, a single-step extraction followed by an high-performance liquid chromatography--tandem mass spectrometry (HPLC--MS-MS) method was established and validated for the simultaneous determination of EtG and PTCA. This method was applied to 1,219 scalp hair samples from two groups, namely self-reported untreated and in vivo treated hair, exhibiting a concentration range of 6.7 to 440.0 pg/mg for EtG (mean 26.8 pg/mg, median 14.6 pg/mg) and 0.009 to 49.8 ng/mg for PTCA (mean 0.66 ng/mg, median 0.02 ng/mg). The PTCA content was significantly different among the two experimental groups, with the in vivo treated group showing significantly higher levels of PTCA than the untreated group. Finally, an in vitro bleaching was performed and the results confirmed that a strong hair oxidative treatment may negatively affect EtG test results (false negative), whereas the mean PTCA content increased showing statistically significant differences between untreated and in vitro oxidative treated samples. The present study suggests that the determination of PTCA in routine hair analysis procedure could be useful in order to discover previous cosmetic treatment including oxidation.
Estimating bat fatality at a Texas wind energy facility: implications transcending the United States–Mexico border
Authors: Weaver Sara P , Jones Amanda K , Hein Cris D , Castro-Arellano Ivan
Published: October 2020

Wind energy development causes bat fatalities. Despite emphasis on understanding and reducing these impacts, few data are available for the southwest region of the United States and northern Mexico. We monitored bat fatalities for a full year (March 2017–March 2018) at a wind energy facility in south Texas near the United States–Mexico border. We established search plots of 100-m radius at eight randomly selected turbines (of 255) and searched the roads and pads at an additional 92 turbines. We conducted weekly searches from spring through fall and bimonthly during winter. We used GenEst (Generalized Mortality Estimator) to estimate bat fatalities corrected for searcher efficiency, carcass removal, and density-weighted proportion of area searched. We found 205 bats during standardized searches, the majority of which were Brazilian free-tailed bats (Tadarida brasiliensis, 76%). The corrected fatality estimates were 16 bats/megawatt/year (95% confidence interval [CI]: 12 – 30 bats/megawatt/year) across all species. Species composition at our site is similar to that of northern Mexico, an area of expanding wind energy development with no published studies.
Lessons learned in a large-scale project to digitize and computationally analyze musical scores
Authors: McKay Cory , Cumming Julie , Fujinaga Ichiro
Published: October 2020

Many areas of the digital humanities (DH) have the potential to benefit greatly from recent advances in machine learning, big data, and statistical analysis. These sophisticated techniques come with pitfalls, however, and their accidental misuse can lead to erroneous results. This article outlines in broad terms our experiences with a large-scale, long-term international project to digitize musical scores, automatically analyze them, and share the results with other researchers. It then describes our experiences in order to help other researchers in the DH avoid some of the missteps we and other DH researchers have made. In addition to issues associated with data mining, this article also discusses approaches to sharing data, software, and intermediate analyses such that they are accessible to other researchers in ways that encourage repeatability, verifiability, iterative refinement, creative exploration, and multidisciplinary collaboration.
The dependence of the galaxy stellar-to-halo mass relation on galaxy morphology
Authors: Correa Camila A , Schaye Joop
Published: October 2020

We investigate the dependence of the local galaxy stellar-to-halo mass relation (SHMR) on galaxy morphology. We use data from the Sloan Digital Sky Survey (SDSS) data release 7 with morphological classifications from Galaxy Zoo, and compare with the EAGLE cosmological simulation. At fixed halo mass in the mass range $10^{11.7}\!-\!10^{12.9}\, {\rm M_{\odot }}$, the median stellar masses of SDSS disc galaxies are up to a factor of 1.4 higher than the median masses of their elliptical counterparts. However, when we switch from the stellar masses from Kauffmann et al. to those calculated by Chang et al. or Brinchmann et al., the median SHMR from discs and ellipticals coincides in this mass range. For halo masses larger than $10^{13}\, {\rm M_{\odot }}$, discs are less massive than ellipticals in same-mass haloes, regardless of whose stellar mass estimates we use. However, we find that for these high halo masses the results for discs may be affected by central/satellite misclassifications. The EAGLE simulation predicts that discs are up to a factor of 1.5 more massive than elliptical galaxies residing in same-mass haloes less massive than $10^{13}\, {\rm M_{\odot }}$, in agreement with the Kauffmann et al. data. Haloes with masses between 1011.5 and $10^{12}\, {\rm M_{\odot }}$, which host disc galaxies, were assembled earlier than those hosting ellipticals. This suggests that the discs are more massive because they had more time for gas accretion and star formation. In $10^{12}\!-\!10^{12.5}\, {\rm M_{\odot }}$ haloes, the central black holes in elliptical galaxies grew faster and became more massive than their counterparts in disc galaxies. This suggests that in this halo mass range the ellipticals are less massive because active galactic nucleus feedback ejected more of the halo’s gas reservoir, reducing star formation, and suppressing the (re)growth of stellar discs.
SPRAI-II: multifrequency radiative transfer for variable gas densities
Authors: Jaura Ondrej , Magg Mattis , Glover Simon C O , Klessen Ralf S
Published: October 2020

We present version 2 of the radiation transfer module sprai (Simplex Photon Radiation in the arepo Implementation). sprai is a novel method for solving the equations of transfer on an unstructured mesh using a variant of the short characteristics approach. It has several advantages compared to other approaches: its computational cost is independent of the number of radiation sources (unlike typical ray-tracing methods) and it is less diffusive than moment-based methods. Version 1 of sprai has already been shown to do an excellent job of modelling the growth of R-type ionization fronts in low-density gas. However, it does not perform so well with D-type fronts in denser gas unless run with a small time-step. Version 2 of the code addresses this weakness in the algorithm, allowing us to dramatically improve its performance in dense gas. Version 2 of sprai also includes two important updates to the microphysics treated in the code: a revised multifrequency framework that allows us to model helium photoionization, and a treatment of the effects of radiation pressure. In this paper, we describe these enhancements to sprai and also present several tests of the code.
LESSER: a catalogue of spectroscopically selected sample of Lyman-α emitters lensed by galaxies
Authors: Cao Xiaoyue , Li Ran , Shu Yiping , Mao Shude , Kneib Jean-Paul , Gao Liang
Published: October 2020

We introduce the LEnSed laeS in the Eboss suRvey (LESSER) project, which aims to search for lensed Lyman-α emitters (LAEs) in the Extended Baryon Oscillation Spectroscopic Survey (eBOSS). The final catalogue contains 361 candidate lensing systems. The lens galaxies are luminous red galaxies (LRGs) at redshift 0.4 < z < 0.8, and the source galaxies are LAEs at redshift 2 < z < 3. The spectral resolution of eBOSS (∼2000) allows us to further identify the fine structures of Lyman-α ($\rm Ly\alpha$) emissions. Among our lensed LAE candidates, 281 systems present single-peaked line profiles while 80 systems show double-peaked features. Future spectroscopic/imaging follow-up observations of the catalogue may shed light on the origin of diverse $\rm Ly\alpha$ line morphology, and provide promising labs for studying low-mass dark matter haloes/subhaloes.
Models of distorted and evolving dark matter haloes
Authors: Sanders Jason L , Lilley Edward J , Vasiliev Eugene , Evans N Wyn , Erkal Denis
Published: October 2020

We investigate the ability of basis function expansions to reproduce the evolution of a Milky Way-like dark matter halo, extracted from a cosmological zoom-in simulation. For each snapshot, the density of the halo is reduced to a basis function expansion, with interpolation used to recreate the evolution between snapshots. The angular variation of the halo density is described by spherical harmonics, and the radial variation either by biorthonormal basis functions adapted to handle truncated haloes or by splines. High fidelity orbit reconstructions are attainable using either method with similar computational expense. We quantify how the error in the reconstructed orbits varies with expansion order and snapshot spacing. Despite the many possible biorthonormal expansions, it is hard to beat a conventional Hernquist–Ostriker expansion with a moderate number of terms (≳15 radial and ≳6 angular). As two applications of the developed machinery, we assess the impact of the time-dependence of the potential on (i) the orbits of Milky Way satellites and (ii) planes of satellites as observed in the Milky Way and other nearby galaxies. Time evolution over the last 5 Gyr introduces an uncertainty in the Milky Way satellites’ orbital parameters of $\sim 15 \, \mathrm{per\, cent}$, comparable to that induced by the observational errors or the uncertainty in the present-day Milky Way potential. On average, planes of satellites grow at similar rates in evolving and time-independent potentials. There can be more, or less, growth in the plane’s thickness, if the plane becomes less, or more, aligned with the major or minor axis of the evolving halo.
The 2019 eruption of recurrent nova V3890 Sgr: observations by Swift, NICER, and SMARTS
Authors: Page K L , Kuin N P M , Beardmore A P , Walter F M , Osborne J P , Markwardt C B , Ness J-U , Orio M , Sokolovsky K V
Published: October 2020

V3890 Sgr is a recurrent nova that has been seen in outburst three times so far, with the most recent eruption occurring on 2019 August 27 ut. This latest outburst was followed in detail by the Neil Gehrels Swift Observatory, from less than a day after the eruption until the nova entered the Sun observing constraint, with a small number of additional observations after the constraint ended. The X-ray light curve shows initial hard shock emission, followed by an early start of the supersoft source phase around day 8.5, with the soft emission ceasing by day 26. Together with the peak blackbody temperature of the supersoft spectrum being ∼100 eV, these timings suggest the white dwarf mass to be high, $\sim 1.3\, {\rm M_{\odot }}$. The UV photometric light curve decays monotonically, with the decay rate changing a number of times, approximately simultaneously with variations in the X-ray emission. The UV grism spectra show both line and continuum emission, with emission lines of N, C, Mg, and O being notable. These UV spectra are best dereddened using a Small Magellanic Cloud extinction law. Optical spectra from SMARTS show evidence of interaction between the nova ejecta and wind from the donor star, as well as the extended atmosphere of the red giant being flash-ionized by the supersoft X-ray photons. Data from NICER reveal a transient 83 s quasi-periodic oscillation, with a modulation amplitude of 5 per cent, adding to the sample of novae that show such short variabilities during their supersoft phase.
Observation of an inertial-range energy cascade within a reconnection jet in the Earth’s magnetotail
Authors: Bandyopadhyay Riddhi , Chasapis Alexandros , Gershman D J , Giles B L , Russell C T , Strangeway R J , Le Contel O , Argall M R , Burch J L
Published: October 2020

The Earth’s magnetotail region provides a unique environment for the study of plasma turbulence. We investigate the turbulence developed in an exhaust produced by magnetic reconnection in the terrestrial magnetotail region. Magnetic and velocity spectra show broad-band fluctuations corresponding to the inertial range, with Kolmorogov scaling of −5/3, indicative of a well-developed turbulent cascade. We examine the mixed, third-order structure functions, and obtain a linear scaling in the inertial range. This linear scaling of the third-order structure functions implies a scale-invariant cascade of energy through the inertial range. A Politano–Pouquet third-order analysis gives an estimate of the incompressive energy transfer rate of ${\sim}10^{7}~\mathrm{J\, kg^{-1}\, s^{-1}}$. This is four orders of magnitude higher than the values typically measured in the 1-au solar wind, suggesting that the turbulence cascade plays an important role as a pathway of energy dissipation during reconnection events in the tail region.
Characterization of distinct molecular interactions responsible for IRF3 and IRF7 phosphorylation and subsequent dimerization
Authors: Dalskov Louise , Narita Ryo , Andersen Line L , Jensen Nanna , Assil Sonia , Kristensen Kennith H , Mikkelsen Jacob G , Fujita Takashi , Mogensen Trine H , Paludan Søren R , Hartmann Rune
Published: October 2020

IRF3 and IRF7 are critical transcription factors in the innate immune response. Their activation is controlled by phosphorylation events, leading to the formation of homodimers that are transcriptionally active. Phosphorylation occurs when IRF3 is recruited to adaptor proteins via a positively charged surface within the regulatory domain of IRF3. This positively charged surface also plays a crucial role in forming the active homodimer by interacting with the phosphorylated sites stabilizing the homodimer. Here, we describe a distinct molecular interaction that is responsible for adaptor docking and hence phosphorylation as well as a separate interaction responsible for the formation of active homodimer. We then demonstrate that IRF7 can be activated by both MAVS and STING in a manner highly similar to that of IRF3 but with one key difference. Regulation of IRF7 appears more tightly controlled; while a single phosphorylation event is sufficient to activate IRF3, at least two phosphorylation events are required for IRF7 activation.
The role of FACT in managing chromatin: disruption, assembly, or repair?
Authors: Formosa Tim , Winston Fred
Published: October 2020

FACT (FAcilitates Chromatin Transcription) has long been considered to be a transcription elongation factor whose ability to destabilize nucleosomes promotes RNAPII progression on chromatin templates. However, this is just one function of this histone chaperone, as FACT also functions in DNA replication. While broadly conserved among eukaryotes and essential for viability in many organisms, dependence on FACT varies widely, with some differentiated cells proliferating normally in its absence. It is therefore unclear what the core functions of FACT are, whether they differ in different circumstances, and what makes FACT essential in some situations but not others. Here, we review recent advances and propose a unifying model for FACT activity. By analogy to DNA repair, we propose that the ability of FACT to both destabilize and assemble nucleosomes allows it to monitor and restore nucleosome integrity as part of a system of chromatin repair, in which disruptions in the packaging of DNA are sensed and returned to their normal state. The requirement for FACT then depends on the level of chromatin disruption occurring in the cell, and the cell's ability to tolerate packaging defects. The role of FACT in transcription would then be just one facet of a broader system for maintaining chromatin integrity.
Hyponatremia and other electrolyte abnormalities in patients receiving immune checkpoint inhibitors
Authors: Seethapathy Harish , Rusibamayila Nifasha , Chute Donald F , Lee Meghan , Strohbehn Ian , Zubiri Leyre , Faje Alexander T , Reynolds Kerry L , Jhaveri Kenar D , Sise Meghan E
Published: October 2020

Background

Hyponatremia due to endocrinopathies such as adrenal insufficiency and hypothyroidism has been reported in patients receiving immune checkpoint inhibitors (ICIs). We determined the risk and predictors of hyponatremia and other electrolyte abnormalities in a ‘real-world’ sample of patients receiving ICIs to treat advanced malignancies.

Methods

This was a retrospective observational study of all patients who received ICIs from a single cancer center between 2011 and 2018. Patients were followed for 12 months after initiation of ICIs or until death. Common Terminology for Cancer Adverse Events version 5.0 criteria were used to grade the severity of hyponatremia and other electrolyte abnormalities. The predictors of severe (Grade 3 or 4) hyponatremia were determined using a multivariable logistic regression model. The etiology of Grade 3 or 4 hyponatremia was determined by chart review.

Results

A total of 2458 patients were included. Their average age was 64 years [standard deviation (SD) 13], 58% were male and 90% were white. In the first year after starting ICIs, 62% experienced hyponatremia (sodium <134 mEq/L) and 136 (6%) experienced severe hyponatremia (<124 mEq/L). Severe hyponatremia occurred on average 164 days (SD 100) after drug initiation. Only nine cases of severe hyponatremia were due to endocrinopathies (0.3% overall incidence). Risk factors for severe hyponatremia included ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor) use, diuretic use and non-White race. Other severe electrolyte abnormalities were also commonly observed: severe hypokalemia (potassium <3.0 mEq/L) occurred in 6%, severe hyperkalemia (potassium ≥6.1 mEq/L) occurred in 0.6%, severe hypophosphatemia (phosphorus <2 mg/dL) occurred in 17% and severe hypocalcemia (corrected calcium <7.0 mg/dL) occurred in 0.2%.

Conclusions

Hyponatremia is common in cancer patients receiving ICIs. However, endocrinopathies are an uncommon cause of severe hyponatremia.
Cutaneous Vasculitis in a Patient With COVID-19
Authors: Kösters Katrin , Schwarzer Sitha , Labuhn Achim , Rübben Albert , Yang Sara , Hessler Frank , Assaf Chalid
Published: October 2020

We describe a 43-year-old patient with coronavirus disease 2019 who developed a bullous hemorrhagic rash that progressed to necrotic lesions. Histopathology confirmed a vasculitis of small- and medium-sized cutaneous vessels.
Political Constitutionalism and Legal Constitutionalism—an Imaginary Opposition?
Authors: Latham-Gambi Alexander
Published: October 2020

This article argues that the opposition between political and legal constitutionalism can be traced to a cleavage in what philosophers have called the ‘social imaginary’: the shared understandings that underpin social life. Since social imaginary understandings are by their nature nebulous and ill-defined, political and legal constitutionalism should not be thought of as competing theories or heuristic models, but—more abstractly—contrasting ways of imagining the political world. Drawing on historical and contemporary examples, I argue that my claim is supported by the way in which legal constitutionalism embedded itself as the governing idea in the United States and in France, and also by the failure of the ‘new Commonwealth model of constitutionalism’ to yield a genuinely distinctive alternative to political and legal constitutionalism.
Rational Points on Elliptic K3 Surfaces of Quadratic Twist Type
Authors: Huang Zhizhong
Published: October 2020

In studying rational points on elliptic K3 surfaces of the form $$\begin{equation*} f(t)y^2=g(x), \end{equation*}$$ where f, g are cubic or quartic polynomials (without repeated roots), we introduce a condition on the quadratic twists of two elliptic curves having simultaneously positive Mordell–Weil rank. We prove a necessary and sufficient condition for the Zariski density of rational points by using this condition, and we relate it to the Hilbert property. Applying to surfaces of Cassels–Schinzel type, we prove unconditionally that rational points are dense both in Zariski topology and in real topology.
Familial risk of Behçet’s disease among first-degree relatives: a population-based aggregation study in Korea
Authors: Ahn Hyeong Sik , Kim Hyun Jung , Kazmi Sayada Zartasha , Kang Taeuk , Jun Jae-Bum , Kang Min Ji , Kim Kyoung-Beom , Kee Sun-Ho , Kim Dong-Sook , Hann Hoo Jae
Published: October 2020

Objective

Previous studies have indicated that Behçet’s disease (BD) has a genetic component, however population-level familial risk estimates are unavailable. We quantified the familial incidence and risk of BD in first-degree relatives (FDR) according to age, sex and type of family relationship.

Methods

Using the Korean National Health Insurance database, which has full population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 individuals comprising 12 million families, which were followed for a familial occurrence of BD from 2002 to 2017. Age- and sex-adjusted incidence risk ratios for BD were calculated in individuals with affected FDR compared with those without affected FDR.

Results

Among the total study population, 53 687 individuals had affected FDR, of whom 284 familial cases developed BD with an incidence of 3.57/104 person-years. The familial risk (incidence) for BD was increased to 13.1-fold (2.71/104 person-years) in individuals with an affected father, 13.9-fold (3.11/104 person-years) with affected mother, 15.2-fold (4.9/104 person-years) with an affected sibling and the highest risk was 165-fold (46/104 person-years) with an affected twin. Familial risks showed age dependence, being higher in younger age groups. The sex-specific familial risk was similar in males and females.

Conclusion

This study provides quantified estimates of familial incidence and risk in FDR of BD patients in an entire population. Familial risks were higher within generation (sibling–sibling) vs between generations (parent–offspring). This implicates complex interactions between genetic factors and shared childhood environmental exposures in the pathogenesis of BD.
Economic threat heightens conflict detection: sLORETA evidence
Authors: Nash Kyle , Tran Alex , Leota Josh , Scott Andy
Published: October 2020

Economic threat has far-reaching emotional and social consequences, yet the impact of economic threat on neurocognitive processes has received little empirical scrutiny. Here, we examined the causal relationship between economic threat and conflict detection, a critical process in cognitive control associated with the anterior cingulate cortex (ACC). Participants (N = 103) were first randomly assigned to read about a gloomy economic forecast (Economic Threat condition) or a stable economic forecast (No-Threat Control condition). Notably, these forecasts were based on real, publicly available economic predictions. Participants then completed a passive auditory oddball task composed of frequent standard tones and infrequent, aversive white-noise bursts, a task that elicits the N2, an event-related potential component linked to conflict detection. Results revealed that participants in the Economic Threat condition evidenced increased activation source localized to the ACC during the N2 to white-noise stimuli. Further, ACC activation to conflict mediated an effect of Economic Threat on increased justification for personal wealth. Economic threat thus has implications for basic neurocognitive function. Discussion centers on how effects on conflict detection could shed light on the broader emotional and social consequences of economic threat.
Evaluation of a novel threonine source for nursery pig diets
Authors: Humphrey Dalton , Becker Spenser , Lee Jason , Haydon Keith , Greiner Laura
Published: October 2020

Four hundred and eighty (PIC 337 X 1050, PIC Genus, Hendersonville, TN) pigs were used to evaluate a novel threonine source (ThrPro, CJ America Bio, Fort Dodge, IA) for nursery pigs from approximately 7 to 20 kg body weight (BW). After weaning, pigs were sorted by sex and fed a common diet for 1 wk. Upon completion of the first week, pigs were sorted into randomized complete blocks, equalized by weight, within 16 replications. Pigs were allocated to one of three dietary treatments: positive control (POS)—standard ileal digestible threonine-to-lysine ratio (SID; Thr:Lys) 0.60, negative control (NEG)—SID Thr:Lys ≤0.46, and alternative Thr source (TEST)—SID Thr:Lys 0.60. The alternative Thr source included fermentative biomass and was assumed to contain 75% Thr and a digestibility coefficient of 100% based on the manufacturer’s specifications. All other nutrients met or exceeded the NRC recommendations. Growth and intake data were analyzed as repeated measures with a compound symmetry covariance structure using the MIXED procedure in SAS 9.4 (SAS Institute Inc., Cary, NC) with pen as the experimental unit. Treatment, phase, the interaction between treatment and phase, and block were included as fixed effects in the model. Differences in total removals were tested using Fisher’s Exact Test of PROC FREQ. Results were considered significant at P ≤ 0.05 and considered a trend at P > 0.05 and P ≤ 0.10. During the first 14 d, pigs fed TEST had decreased gain-to-feed ratio (G:F; 0.77 vs. 0.80, P = 0.022) compared to POS and increased G:F (0.77 vs. 0.73, P < 0.001) compared to NEG. Over days 14–28, pigs fed TEST had similar G:F (0.71 vs. 0.70, P = 0.112) compared to POS and increased G:F (0.71 vs. 0.63, P < 0.001) compared to NEG. Overall (days 0–28), pigs fed TEST had similar average daily gain (ADG; 0.47 vs. 0.47 kg/d, P = 0.982) and G:F (0.76 vs. 0.74, P = 0.395) compared to POS and increased ADG (0.47 vs. 0.43 kg/d, P < 0.001) and G:F (0.76 vs. 0.67, P < 0.001) compared to NEG. The average daily feed intake was not significantly different across treatments for the entirety of the study. In conclusion, the replacement of crystalline L-Thr with a novel Thr source resulted in similar growth performance in nursery pigs from approximately 7 to 20 kg.
Going underwater: multiple origins and functional morphology of piercing-sucking feeding and tracheal system adaptations in water scavenger beetle larvae (Coleoptera: Hydrophiloidea)
Authors: Rodriguez Georgina , Fikáček Martin , Minoshima Yȗsuke N , Archangelsky Miguel , Torres Patricia L M
Published: October 2020

Larvae of water scavenger beetles (Coleoptera: Hydrophiloidea) are adapted to a wide variety of aquatic habitats, but little is known about functional and evolutionary aspects of these adaptations. We review the functional morphology and evolution of feeding strategies of larvae of the families Hydrophilidae and Epimetopidae based on a detailed scanning electron microscope (SEM) analysis, analysis of video records of feeding behaviour and observations of living larvae. There are two main types of feeding mechanisms: chewing and piercing-sucking. The character mapping using the latest phylogenetic hypothesis for Hydrophiloidea infers the chewing system as the ancestral condition. The piercing-sucking mechanism evolved at least four times independently: once in Epimetopidae (Epimetopus) and three times in Hydrophilidae (Berosini: Berosus + Hemiosus; Laccobiini: Laccobius group; Hydrobiusini: Hybogralius). The piercing-sucking apparatus allows underwater extra-oral digestion and decreases the dependence of larvae on an aerial environment. A detailed study of the tracheal morphology of the piercing-sucking lineages reveals four independent origins of the apneustic respiratory system, all of them nested within lineages with piercing-sucking mouthparts. We conclude that piercing-sucking mouthparts represent a key innovation, which allows for the subsequent adaptation of the tracheal system, influences the diversification dynamics of the lineages and allows the shift to new adaptive zones.
Art and Pediatric Orthopaedics: The Master of Alkmaar and an Act of Mercy
Authors: Joseph Benjamin
Published: October 2020

The painting, “The First Act of Mercy” shows a subject with complex lower limb anomalies. The probable diagnosis is discussed.
Outcomes After Surgical Fixation of Posterior Sternoclavicular Physeal Fractures and Dislocations in Children
Authors: Swarup Ishaan , Cazzulino Alejandro , Williams Brendan A. , Defrancesco Christopher , Spiegel David , Shah Apurva S.
Published: October 2020

Background:

Acute sternoclavicular fractures and dislocations (SCFDs) are a rare but important injury in pediatric patients. SCFDs are either true dislocations, or more commonly, physeal fractures in children. The reduction is advised given the proximity to surrounding vascular structures, and some authors advocate for routine fixation given rates of redisplacement after closed reduction. The purpose of the current study was to provide validated long-term functional outcome data following open reduction and surgical fixation of pediatric SCFDs, as well as provide injury and demographic information.

Methods:

This is a retrospective observational study with a subset of patients reporting functional outcomes. Patients under the age of 18 that had surgically managed acute posterior SCFD from 1990 to 2018 were included. A retrospective chart review was performed to obtain demographic, clinical, and surgical details. Patients with a minimum of 6-month follow-up were contacted to assess outcomes. Functional outcomes of interest included QuickDash, Visual Analog Scale pain rating, Single Assessment Numeric Evaluation of shoulder function, and PROMIS Upper Extremity questionnaire. Statistical analysis included descriptive statistics.

Results:

A total of 37 patients that sustained an acute posterior SCFD during the study period were included. The average age at the time of injury was 15.2±2.1 years and 89% were male. Patient-reported outcomes were obtained for 14 patients with a mean follow-up of 4.5 years. The mean QuickDash score was 5.1/100 with 0 being normal, and the mean Visual Analog Scale pain rating was 0.7/10. The mean Single Assessment Numeric Evaluation score was 96% with 100% being completely normal. The mean PROMIS score was 55 with 50 being the mean of the relevant reference population. Approximately 29% (4/14 patients) stated that their injury negatively affected their ability to participate in sports.

Conclusions:

There is a paucity of literature on functional outcomes after surgical management of pediatric acute posterior SCFD. Functional outcomes after surgery were satisfactory in this cohort with most patients being able to perform major activities of daily living. Additional future studies with larger cohorts and comparative groups are needed to better understand outcomes in this population.

Level of Evidence:

Level IV.
Assessing the Early Impact of the COVID-19 Pandemic on Spine Surgery Fellowship Education
Authors: Swiatek Peter R. , Weiner Joseph A. , Butler Bennet A. , McCarthy Michael H. , Louie Philip K. , Wolinsky Jean-Paul , Hsu Wellington K. , Patel Alpesh A.
Published: October 2020

Study Design:

This was a cross-sectional study.

Objective:

The objective of this study is to report the impact of COVID-19 on spine surgery fellow education and readiness for practice.

Summary of Background Data:

COVID-19 has emerged as one of the most devastating global health crises of our time. To minimize transmission risk and to ensure availability of health resources, many hospitals have cancelled elective surgeries. There may be unintended consequences of this decision on the education and preparedness of current surgical trainees.

Materials and Methods:

A multidimensional survey was created and distributed to all current AO Spine fellows and fellowship directors across the United States and Canada.

Results:

Forty-five spine surgery fellows and 25 fellowship directors completed the survey. 62.2% of fellows reported >50% decrease in overall case volume since cancellation of elective surgeries. Mean hours worked per week decreased by 56.2%. Fellows reported completing a mean of 188.4±64.8 cases before the COVID-19 crisis and 84.1% expect at least an 11%–25% reduction in case volume compared with previous spine fellows. In all, 95.5% of fellows did not expect COVID-19 to impact their ability to complete fellowship. Only 2 directors were concerned about their fellows successfully completing fellowship; however, 32% of directors reported hearing concerns regarding preparedness from their fellows and 25% of fellows were concerned about job opportunities.

Conclusions:

COVID-19 has universally impacted work hours and case volume for spine surgery fellows set to complete fellowship in the middle of 2020. Nevertheless, spine surgery fellows generally feel ready to enter practice and are supported by the confidence of their fellowship directors. The survey highlights a number of opportunities for improvement and innovation in the future training of spine surgeons.

Level of Evidence:

Level III.
Shortening Dome Osteotomy for Correction of Complex Multiplanar Elbow Deformities: A New Surgical Technique
Authors: Krishna Anant , Kumar Manoj , Singh Pritish , Gupta Vikas , Arora Sumit
Published: October 2020

Despite surgical advances in fracture management, it is not uncommon to find pediatric or adolescent patients with elbow deformities. Correction of severe deformities, often leaves the ingenuity of the treating surgeon asking for more. Various osteotomy techniques have been described in the literature for the correction of elbow deformities. Although, the concept of dome osteotomy did address certain inadequacies of the existing osteotomy techniques for distal humerus, but correction of complex deformities associated with deformation of trochlea and olecranon fossa still remain a surgical challenge which has not been adequately addressed in the literature so far. Our experience with the existing osteotomies for distal humerus led to the development of a new surgical technique of shortening dome osteotomy for correction of such complex multiplanar elbow deformities. Surgical steps, indications, and expected outcome is described.
Is it depression or is it bipolar depression?
Authors: Rolin Donna , Whelan Jessica , Montano Charles B.
Published: October 2020

This review is intended to guide primary care providers in differentiating patients with bipolar depression from those with unipolar depression and inform patient management. Up to 64% of clinical encounters for depression occur in primary care, with misdiagnosis of bipolar depression common in both primary care and psychiatry. Although bipolar disorder is characterized by manic, hypomanic, and depressive episodes, the most common and debilitating symptomatic presentation is depression. Misdiagnosis as unipolar depression is common, often resulting in mistreatment with an unopposed monoamine antidepressant. Antidepressants are often ineffective for treating bipolar depression and may cause detrimental consequences such as treatment-emergent hypomania/mania, rapid cycling, or increased suicidality. Factors that are suggestive of bipolar disorder versus unipolar depression include early-onset depression, frequent depressive episodes, family history of serious mental illness, hypomania/mania symptoms within the depressive episode, and nonresponse to antidepressants. Comorbid medical (e.g., cardiovascular disease, hypertension, obesity) and psychiatric (e.g., attention-deficit/hyperactivity disorder, anxiety disorder, personality disorders, and substance use disorder) conditions are common and contribute to premature mortality for patients with bipolar disorder compared with the general public. Cariprazine, fluoxetine/olanzapine, lurasidone, and quetiapine are approved to treat bipolar depression; only cariprazine and quetiapine are approved to treat both bipolar mania and depression. Primary care providers who can differentiate presenting symptoms of bipolar depression from unipolar depression and offer appropriate treatment options will optimize patient care in clinical practice. Relevant information for this review was identified through a multistep literature search of PubMed using the terms bipolar depression/bipolar disorder plus other relevant terms.
Staying alert to ethical challenges
Authors: Winland-Brown Jill E.
Published: October 2020

Nurse practitioners (NPs) are faced with many ethical challenges. It requires moral courage to stand up for ones' beliefs and resolve ethical issues. Ethical challenges of NPs are discussed including some specific disciplinary situations involving a state board of nursing. Solutions that may help NPs stay alert to ethical challenges include ethics courses and lifelong mentoring. In this “Year of the Nurse and Midwife,” NPs and other nurses should ensure that we maintain the designation of most trusted profession.