bluuebunny/crossref_metadata_2025 huggingface dataset:
Daratumumab Interference in Flow Cytometry Producing a False Kappa Light Chain Restriction in Plasma Cells
Authors: Kleinot William , Aguilera Nadine , Courville Elizabeth L
Published: November 2020

False kappa light chain restriction on hematogones (normal B-lineage precursors) has been described in patients on the therapeutic anti-CD38 monoclonal antibody daratumumab. In this article, we present a novel case report of pseudo-kappa light chain restriction on lambda-restricted neoplastic plasma cells in a patient with progressive plasma cell myeloma while on daratumumab. Flow cytometric technologists and pathologists need to be aware of this potential diagnostic pitfall.
Tidal disruption events in the first billion years of a galaxy
Authors: Pfister Hugo , Dai Jane Lixin , Volonteri Marta , Auchettl Katie , Trebitsch Maxime , Ramirez-Ruiz Enrico
Published: November 2020

Accretion of stars on massive black holes (MBHs) can feed MBHs and generate tidal disruption events (TDEs). We introduce a new physically motivated model to self-consistently treat TDEs in cosmological simulations, and apply it to the assembly of a galaxy with final mass $3\times 10^{10}\, \mathrm{M}_{\odot }$ at z = 6. This galaxy exhibits a TDE rate of $\sim 10^{-5}\, \mathrm{yr}^{-1}$, consistent with local observations but already in place when the Universe was one billion year old. A fraction of the disrupted stars participate in the growth of MBHs, dominating it until the MBH reaches mass $\sim 5 \times 10^5 \, \mathrm{M}_{\odot }$, but their contribution then becomes negligible compared to gas. TDEs could be a viable mechanism to grow light MBH seeds, but fewer TDEs are expected when the MBH becomes sufficiently massive to reach the luminosity of, and be detected as, an active galactic nucleus. Galaxy mergers bring multiple MBHs in the galaxy, resulting in an enhancement of the global TDE rate in the galaxy by ∼1 order of magnitude during $100\, \mathrm{Myr}$ around mergers. This enhancement is not on the central MBH, but caused by the presence of MBHs in the infalling galaxies. This is the first self-consistent study of TDEs in a cosmological environment and highlights that accretion of stars and TDEs are a natural process occurring in a Milky Way-mass galaxy at early cosmic times.
Explosion energies for core-collapse supernovae I: analytic, spherically symmetric solutions
Authors: Gogilashvili Mariam , Murphy Jeremiah W , Mabanta Quintin
Published: November 2020

Recent multidimensional simulations of core-collapse supernovae are producing successful explosions and explosion-energy predictions. In general, the explosion-energy evolution is monotonic and relatively smooth, suggesting a possible analytic solution. We derive analytic solutions for the expansion of the gain region under the following assumptions: spherical symmetry, one-zone shell, and powered by neutrinos and α particle recombination. We consider two hypotheses: (I) explosion energy is powered by neutrinos and α recombination and (II) explosion energy is powered by neutrinos alone. Under these assumptions, we derive the fundamental dimensionless parameters and analytic scalings. For the neutrino-only hypothesis (II), the asymptotic explosion energy scales as $E_{\infty } \approx 1.5 M_\mathrm{ g}\nu _0^2 \eta ^{2/3}$, where Mg is the gain mass, $\nu _0$ is the free-fall velocity at the shock, and η is a ratio of the heating and dynamical time-scales. Including both neutrinos and recombination (hypothesis I), the asymptotic explosion energy is $E_{\infty } \approx M_g \nu _0^2 (1.5\eta ^{2/3} + \beta f(\rho _0))$, where β is the dimensionless recombination parameter. We use Bayesian inference to fit these analytic models to simulations. Both hypotheses fit the simulations of the lowest progenitor masses that tend to explode spherically. The fits do not prefer hypothesis I or II; however, prior investigations suggest that α recombination is important. As expected, neither hypothesis fits the higher mass simulations that exhibit aspherical explosions. In summary, this explosion energy theory is consistent with the spherical explosions of low progenitor masses; the inconsistency with higher progenitor-mass simulations suggests that a theory for them must include aspherical dynamics.
Getting the model right: an information criterion for spectroscopy
Authors: Webb John K , Lee Chung-Chi , Carswell Robert F , Milaković Dinko
Published: November 2020

Robust model-fitting to spectroscopic transitions is a requirement across many fields of science. The corrected Akaike and Bayesian information criteria (AICc and BIC) are most frequently used to select the optimal number of fitting parameters. In general, AICc modelling is thought to overfit (too many model parameters) and BIC underfits. For spectroscopic modelling, both AICc and BIC lack in two important respects: (a) no penalty distinction is made according to line strength such that parameters of weak lines close to the detection threshold are treated with equal importance as strong lines and (b) no account is taken of the way in which a narrow spectral line impacts only on a very small section of the overall data. In this paper, we introduce a new information criterion that addresses these shortcomings, the Spectral Information Criterion (SpIC). Spectral simulations are used to compare performances. The main findings are (i) SpIC clearly outperforms AICc for high signal-to-noise data, (ii) SpIC and AICc work equally well for lower signal-to-noise data, although SpIC achieves this with fewer parameters, and (iii) BIC does not perform well (for this application) and should be avoided. The new method should be of broader applicability (beyond spectroscopy), wherever different model parameters influence separated small ranges within a larger data set and/or have widely varying sensitivities.
In search of radio emission from exoplanets: GMRT observations of the binary system HD 41004
Authors: Narang Mayank , Manoj P , Ishwara Chandra C H , Lazio Joseph , Henning Thomas , Tamura Motohide , Mathew Blesson , Ujwal Nitish , Mandal Pritha
Published: November 2020

This paper reports Giant Metrewave Radio Telescope (GMRT) observations of the binary system HD 41004 that are among the deepest images ever obtained at 150 and 400 MHz in the search for radio emission from exoplanets. The HD 41004 binary system consists of a K1 V primary star and an M2 V secondary; both stars are host to a massive planet or brown dwarf. Analogous to planets in our Solar system that emit at radio wavelengths due to their strong magnetic fields, one or both of the planet or brown dwarf in the HD 41004 binary system are also thought to be sources of radio emission. Various models predict HD 41004Bb to have one of the largest expected flux densities at 150 MHz. The observations at 150 MHz cover almost the entire orbital period of HD 41004Bb, and about $20{{\ \rm per\ cent}}$ of the orbit is covered at 400 MHz. We do not detect radio emission, setting 3σ limits of 1.8 mJy at 150 MHz and 0.12 mJy at 400 MHz. We also discuss some of the possible reasons why no radio emission was detected from the HD 41004 binary system.
Measuring individual masses of binary white dwarfs with space-based gravitational-wave interferometers
Authors: Wolz Anna , Yagi Kent , Anderson Nick , Taylor Andrew J
Published: November 2020

Unlike gravitational waves from merging black holes and neutron stars that chirp significantly over the observational period of ground-based detectors, gravitational waves from binary white dwarfs are almost monochromatic. This makes it extremely challenging to measure their individual masses. Here, we take a novel approach of using finite-size effects and applying certain universal relations to measure individual masses of binary white dwarfs using Laser Interferometer Space Antenna. We found quasi-universal relations among the mass, moment of inertia, and tidal deformability of a white dwarf that do not depend sensitively on the white dwarf composition. These relations allow us to rewrite the moments of inertia and tidal deformabilities in the waveform in terms of the masses. We then carried out a Fisher analysis to estimate how accurately one can measure the individual masses from the chirp mass and finite-size measurements. We found that the individual white dwarf masses can be measured with LISA for a 4-yr observation if the initial frequency is high enough (∼0.02 Hz) and either the binary separation is small (∼1 kpc) or the masses are relatively large (m ≳ 0.8 M⊙). This opens a new possibility of measuring individual masses of binary white dwarfs with space-based interferometers.
Further evidence to support a tidal disruption event in the changing-look AGN SDSS J0159
Authors: Zhang Xue-Guang
Published: November 2020

In this Letter, we report further evidence to support a tidal disruption event (TDE) in the known changing-look AGN SDSS J0159, through the unique variabilities of asymmetric broad Hα: broader but redder in 2010 than in 2000. If we accept that broad Hα emission regions are tightly related to accreting debris in a central TDE, the well-known relativistic accretion disc origination can be applied to explain the asymmetric broad Hα variabilities in SDSS J0159 well. Moreover, the model-determined broad Hα emission regions have sizes that do not follow the empirical R−L relation valid in normal broad-line active galactic nuclei (AGNs), but have locations basically similar to the regions of accreting debris from a central TDE in SDSS J0159, indicating tight connections between the broad Hα emission material and central TDE debris. Therefore, the explanation of asymmetric broad Hα variabilities through a relativistic accretion disc origination provides further clues to support a central TDE in SDSS J0159.
Alignment free identification of clones in B cell receptor repertoires
Authors: Lindenbaum Ofir , Nouri Nima , Kluger Yuval , Kleinstein Steven H
Published: November 2020

Following antigenic challenge, activated B cells rapidly expand and undergo somatic hypermutation, yielding groups of clonally related B cells with diversified immunoglobulin receptors. Inference of clonal relationships based on the receptor sequence is an essential step in many adaptive immune receptor repertoire sequencing studies. These relationships are typically identified by a multi-step process that involves: (i) grouping sequences based on shared V and J gene assignments, and junction lengths and (ii) clustering these sequences using a junction-based distance. However, this approach is sensitive to the initial gene assignments, which are error-prone, and fails to identify clonal relatives whose junction length has changed through accumulation of indels. Through defining a translation-invariant feature space in which we cluster the sequences, we develop an alignment free clonal identification method that does not require gene assignments and is not restricted to a fixed junction length. This alignment free approach has higher sensitivity compared to a typical junction-based distance method without loss of specificity and PPV. While the alignment free procedure identifies clones that are broadly consistent with the junction-based distance method, it also identifies clones with characteristics (multiple V or J gene assignments or junction lengths) that are not detectable with the junction-based distance method.
Efficacy and Safety of Eravacycline in Obese Patients: A Post Hoc Analysis of Pooled Data From the IGNITE1 and IGNITE4 Clinical Trials
Authors: Asempa Tomefa E , Izmailyan Sergey , Lawrence Kenneth , Nicolau David P
Published: November 2020

Background

The increasing prevalence of obesity worldwide merits an examination of the efficacy and safety profiles of agents dosed by weight.

Methods

Data for patients (n = 1037) were obtained from the pooled IGNITE1 and IGNITE4 randomized double-blind trials in which patients with complicated intra-abdominal infections received eravacycline 1 mg/kg (actual body weight [ABW]) every 12 hours or comparator (ertapenem 1 g every 24 hours or meropenem 1 g every 8 hours) intravenously. This post hoc analysis evaluated clinical cure rates, adverse events, and drug discontinuation rates stratified by body mass index (BMI) categories of BMI >40 kg/m2 (Obese, Class III), BMI 35–39.9 kg/m2 (Obese, Class II), BMI 30–34.9 kg/m2 (Obese, Class I), BMI 25–29.9 kg/m2 (Overweight), BMI 18.5–24.9 kg/m2 (Healthy weight), and BMI <18.5 kg/m2 (Underweight).

Results

Clinical cure rates were high across BMI categories and ranged from 82% to 94% in the eravacycline group and 88.5%–100% in the comparator group. Similar cure rates were observed among eravacycline-treated healthy weight (126/134; 94%), overweight (127/146; 87%), and obese (BMI ≥30 kg/m2; 110/129; 85.3%) patients. In the comparator group, a similar proportion of patients demonstrated clinical response (healthy weight [132/145; 91%], overweight [130/144; 90.3%], and obese [115/129; 89.1%]). Of the treatment-emergent adverse events that occurred in eravacycline-treated obese patients, a larger proportion were gastrointestinal-related (ie, nausea and vomiting); however, discontinuation rates were low and similar between eravacycline and carbapenems.

Conclusions

This post hoc analysis demonstrates the therapeutic utility and acceptable safety profile of eravacycline dosed by ABW in obese patients (BMI ≥30 kg/m2).
Isolated Cerebral Mucormycosis in Immunocompetent Adults who Inject Drugs: Case Reports and Systematic Review of the Literature
Authors: Meyerowitz Eric A , Sanchez Sarimer , Mansour Michael K , Triant Virginia A , Goldberg Marcia B
Published: November 2020

Background

Mucormycosis involves life-threatening rapidly progressive angioinvasion with infiltration across tissue planes, resulting in necrosis and thrombosis, most commonly seen in the setting of immunocompromised states. We describe 2 cases of isolated cerebral mucormycosis in immunocompetent adults and describe this syndrome in detail in the context of a systemic literature review.

Methods

Using the criteria (1) isolated cerebral disease, (2) mucormycosis (by polymerase chain reaction, culture, or pathology), and (3) affected an immunocompetent individual, we identified 53 additional cases from 1969 to 2020.

Results

Of these 55 cases, ~60% occurred in men, >70% were in patients under age 35, 92% were associated with intravenous drug use, and >85% had infection centered in the basal ganglia. Many presented with cranial nerve deficits, headache, focal weakness, or altered mental status.

Conclusions

No patient survived without amphotericin, and steroid administration was associated with worse outcomes. Given the current opioid crisis, this syndrome may be seen more frequently.
Poverty and survival from COVID-19 in Mexico
Authors: Millán-Guerrero Rebeca Olivia , Caballero-Hoyos Ramiro , Monárrez-Espino Joel
Published: November 2020

Background

Recent evidence points to the relevance of poverty and inequality as factors affecting the spread and mortality of the COVID-19 pandemic in Latin America. This study aimed to determine whether COVID-19 patients living in Mexican municipalities with high levels of poverty have a lower survival compared with those living in municipalities with low levels.

Methods

Retrospective cohort study. Secondary data was used to define the exposure (multidimensional poverty level) and outcome (survival time) among patients diagnosed with COVID-19 between 27 February and 1 July 2020. Crude and adjusted hazard ratios (HR) from Cox regression were computed.

Results

Nearly 250 000 COVID-19 patients were included. Mortality was 12.3% reaching 59.3% in patients with ≥1 comorbidities. Multivariate survival analyses revealed that individuals living in municipalities with extreme poverty had 9% higher risk of dying at any given time proportionally to those living in municipalities classified as not poor (HR 1.09; 95% CI 1.06–1.12). The survival gap widened with the follow-up time up to the third to fourth weeks after diagnosis.

Conclusion

Evidence suggests that the poorest population groups have a lower survival from COVID-19. Thus, combating extreme poverty should be a central preventive strategy.
Equilibrium of Two Rods in Contact Under Pressure
Authors: Turzi S , Zoppello M , Ambrosi D
Published: November 2020

We study the equilibrium of a mechanical system composed by two rods that bend under the action of a pressure difference; they have one fixed endpoint and are partially in contact. This system can be viewed as a bi-valve made by two smooth leaflets that lean on each other. We obtain the balance equations of the mechanical system exploiting the principle of virtual work and the contact point is identified by a jump condition. The problem can be simplified exploiting a first integral. In the case of quadratic energy, another first integral exists: its peculiarity is discussed and a further reduction of the equations is carried out. Numerical integration of the differential system shows how the shape of the beams and the position of the contact point depend on the applied pressure. For small pressure, an asymptotic expansion in a small parameter allows us to find an approximate solutions of polynomial form which is in surprisingly good agreement with the solution of the original system of equations, even beyond the expected range of validity. Finally, the asymptotics predicts a value of the pressure that separates the contact from the no-contact regime of the beams that compares very well with the one numerically evaluated.
EVALUATION OF ORGAN DOSE BASED ON PATIENT DATA IN EAST ASIAN DESCENT PEDIATRIC HEAD CT EXAMINATIONS
Authors: Kawamoto Keishin , Fukushima Yasuhiro , Matsuda Akira , Nakata Manabu
Published: November 2020

The purpose of this study was to investigate other indices estimating absorbed dose for eye lens and brain, using clinical images of East Asian pediatric patients. We simulated head computed tomography (CT ) examinations in 104 pediatric patients. Effective diameter (deff) and water equivalent diameter (dw) were measured on clinical images. Various size metrics and age were compared with absorbed dose normalised by CTDIvol (nD). The nD was estimated for eye and brain. The nD tended to decrease with advancing age. R2 between age and nD were 0.38 and 0.31 for eye and brain, respectively. Increasing head diameters decreased each nD. R2 between deff and dw, and nD were 0.20–0.24 and 0.51–0.53 for eye and brain, respectively. Head sizes allowed us to estimate absorbed dose in brain CT on East Asian pediatric patients. Scanning parameters for pediatric head CT may need to be based on individual patient information.
Inhibition of Acetyl-CoA Carboxylase Causes Malformations in Rats and Rabbits: Comparison of Mammalian Findings and Alternative Assays
Authors: Catlin Natasha R , Bowman Christopher J , Campion Sarah N , Davenport Scott D , Esler William P , Kumpf Steven W , Lewis Elise M , Nowland William S , Ross Trenton T , Stedman Donald S , Stethem Christine , Cappon Gregg D
Published: November 2020

Acetyl-CoA carboxylase (ACC) is an enzyme within the de novo lipogenesis (DNL) pathway and plays a role in regulating lipid metabolism. Pharmacologic ACC inhibition has been an area of interest for multiple potential indications including oncology, acne vulgaris, metabolic diseases such as type 2 diabetes mellitus, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. A critical role for ACC in de novo synthesis of long-chain fatty acids during fetal development has been demonstrated in studies in mice lacking Acc1, where the absence of Acc1 results in early embryonic lethality. Following positive predictions of developmental toxicity in the alternative in vitro assays (positive in murine embryonic stem cell [mESC] assay and rat whole embryo culture, but negative in zebrafish), developmental toxicity (growth retardation and dysmorphogenesis associated with disrupted midline fusion) was observed with the oral administration of the dual ACC1 and 2 inhibitors, PF-05175157, in Sprague Dawley rats and New Zealand White rabbits. The results of these studies are presented here to make comparisons across the assays, as well as mechanistic insights from the mESC assay demonstrating high ACC expression in the mESC and that ACC-induced developmental toxicity can be rescued with palmitic acid providing supportive evidence for DNL pathway inhibition as the underlying mechanism. Ultimately, while the battery of alternative approaches and weight-of-evidence case were useful for hazard identification, the embryo-fetal development studies were necessary to inform the risk assessment on the adverse fetal response, as malformations and/or embryo-fetal lethality were limited to doses that caused near-complete inhibition of DNL.
Specific leaf metabolic changes that underlie adjustment of osmotic potential in response to drought by four Quercus species
Authors: Aranda Ismael , Cadahía Estrella , Fernández de Simón Brígida
Published: November 2020

Osmotic adjustment is almost ubiquitous as a mechanism of response to drought in many forest species. Recognized as an important mechanism of increasing turgor under water stress, the metabolic basis for osmotic adjustment has been described in only a few species. We set an experiment with four species of the genus Quercus ranked according to drought tolerance and leaf habit from evergreen to broad-leaved deciduous. A cycle of watering deprivation was imposed on seedlings, resulting in well-watered (WW) and water-stressed (WS) treatments, and their water relations were assessed from pressure–volume curves. Leaf predawn water potential (Ψpd) significantly decreased in WS seedlings, which was followed by a drop in leaf osmotic potential at full turgor (Ψπ100). The lowest values of Ψπ100 followed the ranking of decreasing drought tolerance: Quercus ilex L. < Quercus faginea Lam. < Quercus pyrenaica Willd. < Quercus petraea Matt. Liebl. The leaf osmotic potential at the turgor loss point (ΨTLP) followed the same pattern as Ψπ100 across species and treatments. The pool of carbohydrates, some organic acids and cyclitols were the main osmolytes explaining osmotic potential across species, likewise to the osmotic adjustment assessed from the decrease in leaf Ψπ100 between WW and WS seedlings. Amino acids were very responsive to WS, particularly γ-aminobutyric acid in Q. pyrenaica, but made a relatively minor contribution to osmotic potential compared with other groups of compounds. In contrast, the cyclitol proto-quercitol made a prominent contribution to the changes in osmotic potential regardless of watering treatment or species. However, different metabolites, such as quinic acid, played a more important role in osmotic adjustment in Q. ilex, distinguishing it from the other species studied. In conclusion, while osmotic adjustment was present in all four Quercus species, the molecular processes underpinning this response differed according to their phylogenetic history and specific ecology.
Canola Growth Stage at Time of Infection Determines Magnitude of White Leaf Spot (Neopseudocercosporella capsellae) Impact
Authors: Murtza Tamsal , You Ming Pei , Barbetti Martin J.
Published: November 2020

White leaf spot (Neopseudocercosporella capsellae) is a persistent and increasingly important foliar disease for canola (Brassica napus) across southern Australia. To define the role of plant growth stage in the development of disease epidemics, we first investigated the response of different canola cultivars (Scoop and Charlton) at five Sylvester-Bradley growth stages against N. capsellae. White leaf spot disease incidence and severity was dependent on plant growth stage and cultivar (both P < 0.001), with plants being most susceptible at plant growth stage 1.00 (cotyledon stage) followed by plant growth stage 1.04 (fourth leaf stage). Then, to quantify the impact of this disease on canola yield, we investigated the in-field relationship of white leaf spot disease incidence and severity with seed yield loss following artificial inoculation commencing at growth stage 1.04 (fourth leaf stage). White leaf spot significantly (P < 0.001) reduced seed yield by 24% in N. capsellae inoculated field plots compared with noninoculated field plots. To our knowledge, this is the first time that serious seed yield losses from this disease have been quantified in the field. The current study demonstrates that N. capsellae disease incidence and severity on canola is determined by host growth stage at which pathogen infestation occurs. Emerging seedling cotyledons were highly susceptible, followed by less susceptibility in first true leaves to emerge, but then increasing susceptibility as plants subsequently aged toward the fourth leaf stage. This explains field observances where white leaf spot readily establishes on emerging seedlings and subsequently becomes more prevalent and severe as plants age.
Adaptation of advanced clinical virology assays from HIV-1 to SARS-CoV-2
Authors: McCormick Kevin D. , Mellors John W. , Jacobs Jana L.
Published: November 2020

Purpose of review

In response to the HIV–AIDS pandemic, great strides have been made in developing molecular methods that accurately quantify nucleic acid products of HIV-1 at different stages of viral replication and to assess HIV-1 sequence diversity and its effect on susceptibility to small molecule inhibitors and neutralizing antibodies. Here, we review how knowledge gained from these approaches, including viral RNA quantification and sequence analyses, have been rapidly applied to study SARS-CoV-2 and the COVID-19 pandemic.

Recent findings

Recent studies have shown detection of SARS-CoV-2 RNA in blood of infected individuals by reverse transcriptase PCR (RT-PCR); and, as in HIV-1 infection, there is growing evidence that the level of viral RNA in plasma may be related to COVID disease severity. Unlike HIV-1, SARS-CoV-2 sequences are highly conserved limiting SARS-CoV-2 sequencing applications to investigating interpatient genetic diversity for phylogenetic analysis. Sensitive sequencing technologies, originally developed for HIV-1, will be needed to investigate intrapatient SARS-CoV-2 genetic variation in response to antiviral therapeutics and vaccines.

Methods used for HIV-1 have been rapidly applied to SARS-CoV-2/COVID-19 to understand pathogenesis and prognosis. Further application of such methods should improve precision of therapy and outcome.
Structural basis of severe acute respiratory syndrome coronavirus 2 infection
Authors: Ge Jiwan , Zhang Senyan , Zhang Linqi , Wang Xinquan
Published: November 2020

Purpose of review

The spike glycoprotein plays a critical role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by recognizing the angiotensin converting enzyme 2 (ACE2) receptor and mediating fusion of the viral envelope with the cell membrane. It is also the major target for neutralizing antibodies and vaccines. This review summarizes recent studies on the structure and function of spike glycoprotein, which revealed the structural basis of SARS-CoV-2 infection.

Recent findings

SARS-CoV-2 spike glycoprotein, similar to those of SARS-CoV and Middle East respiratory syndrome coronavirus, spontaneously samples different prefusion states with the receptor-binding domain (RBD) adopting ‘up’ or ‘down’ conformations, and the RBD ‘down’ to ‘up’ conformational change is required for ACE2 binding. Receptor binding and spike glycoprotein priming by host proteases such as furin and transmembrane protease serine 2 induce pre to postfusion conformational changes of the spike trimer that enable membrane fusion. Interactions between SARS-CoV-2 RBD and ACE2 were elucidated at atomic resolution using high-resolution crystal structures. These structures, together with adapted and remodeled SARS-CoV-2 strains, further revealed critical residues of the spike glycoprotein for SARS-CoV-2 infection and cross-species transmission.

Recent studies on SARS-CoV-2 spike glycoprotein provide important structural knowledge for a better understanding of the molecular mechanisms of SARS-CoV-2 infection and cross-species transmission.
Development of a New Chelation Model: Bioassay Data Interpretation and Dose Assessment after Plutonium Intake via Wound and Treatment with DTPA
Authors: Dumit Sara , Miller Guthrie , Klumpp John A. , Poudel Deepesh , Bertelli Luiz , Waters Tom L.
Published: November 2020

The administration of chelation therapy to treat significant intakes of actinides, such as plutonium, affects the actinide’s normal biokinetics. In particular, it enhances the actinide’s rate of excretion, such that the standard biokinetic models cannot be applied directly to the chelation-affected bioassay data in order to estimate the intake and assess the radiation dose. The present study proposes a new chelation model that can be applied to the chelation-affected bioassay data after plutonium intake via wound and treatment with DTPA. In the proposed model, chelation is assumed to occur in the blood, liver, and parts of the skeleton. Ten datasets, consisting of measurements of 14C-DTPA, 238Pu, and 239Pu involving humans given radiolabeled DTPA and humans occupationally exposed to plutonium via wound and treated with chelation therapy, were used for model development. The combined dataset consisted of daily and cumulative excretion (urine and feces), wound counts, measurements of excised tissue, blood, and post-mortem tissue analyses of liver and skeleton. The combined data were simultaneously fit using the chelation model linked with a plutonium systemic model, which was linked to an ad hoc wound model. The proposed chelation model was used for dose assessment of the wound cases used in this study.
Role of Religion in Psychotic Illness in the Israeli Ultra-Orthodox Jewish Population
Authors: Serfaty David R. , Strous Rael D.
Published: November 2020

This study aims to describe the role that religion and belief may play in members of the Israeli ultra-Orthodox Jewish population hospitalized in the Mayanei Hayeshua Medical Center and diagnosed with a psychotic disorder. Religion was judged essential by the patients in the management of their illness. Forty percent of the patients perceive their illness as their destiny, 26.7% as an “affliction of love,” and 33.3% as resulting from their sins. Sixty percent of patients explained that faith is a source of hope in their life, with 76.7% indicating that collective religious practices help them face their illness. Ninety percent expressed no conflict between consulting a psychiatrist and their religious beliefs. Collective religious practices were correlated with higher treatment credibility. The use of religious coping methods was correlated with lower anxiety and tension among women. Higher conflict between religion and consulting a psychiatrist was correlated with lower treatment credibility among men.
Validation of CARE Scale-7 in treatment-seeking patients with chronic pain: measurement of sex invariance
Authors: Ziadni Maisa , You Dokyoung Sophia , Chen Abby , Wilson Anna C. , Darnall Beth D.
Published: November 2020

Objectives:

Social and interpersonal factors impact the trajectory of chronic pain. We previously developed and validated a 2-factor, 7-item measure to assess interpersonal factors, including relationship guilt and worry and difficulty prioritizing self-care in chronic pain. Here, we confirm the factor structure and examine the sex invariance of the two-factor structure of the CARE Scale-7.

Methods:

Data were collected as part of routine clinical care at a tertiary pain clinic using the Collaborative Health Outcomes Information Registry. Patient participants (67% women) were predominantly middle-aged (M = 50.9 years, SD = 17.8), married (55.2%), and White/non-Hispanic (55.7%). Data included demographics, pain characteristics, CARE Scale-7, pain catastrophizing, and Patient-Reported Outcomes Measurement Information System psychological and physical function measures. Confirmatory factor analysis was conducted to validate the factor structure of the CARE Scale, and a stepwise approach to measurement invariances by sex examined configural, metric, and scalar invariance.

Results:

Internal consistency of the scale items ensured suitability for factor analyses. Confirmatory factor analysis findings revealed an overall good fit of the 2-factor model among males and females and that CARE Scale-7 is in fact sex invariant. Finally, CARE Scale-7 showed convergent validity with pain-related outcomes.

Discussion:

The CARE Scale is the first validated instrument to assess self-care in both sexes among patients with chronic pain. The subscale of difficulty prioritizing self-care emerged as a potentially unique factor that should be integrated in clinical assessment. CARE Scale may facilitate standardized measurement in research and clinical contexts, which may inform a comprehensive treatment focus that integrates individualized self-care planning.
Collateral Status in Ischemic Stroke: A Comparison of Computed Tomography Angiography, Computed Tomography Perfusion, and Digital Subtraction Angiography
Authors: Kauw Frans , Dankbaar Jan W. , Martin Blake W. , Ding Victoria Y. , Boothroyd Derek B. , van Ommen Fasco , de Jong Hugo W.A.M. , Kappelle L. Jaap , Velthuis Birgitta K. , Heit Jeremy J. , Wintermark Max
Published: November 2020

Objective

To compare assessment of collaterals by single-phase computed tomography (CT) angiography (CTA) and CT perfusion-derived 3-phase CTA, multiphase CTA and temporal maximum-intensity projection (tMIP) images to digital subtraction angiography (DSA), and relate collateral assessments to clinical outcome in patients with acute ischemic stroke.

Methods

Consecutive acute ischemic stroke patients who underwent CT perfusion, CTA, and DSA before thrombectomy with occlusion of the internal carotid artery, the M1 or the M2 segments were included. Two observers assessed all CT images and one separate observer assessed DSA (reference standard) with static and dynamic (modified American Society of Interventional and Therapeutic Neuroradiology) collateral grading methods. Interobserver agreement and concordance were quantified with Cohen-weighted κ and concordance correlation coefficient, respectively. Imaging assessments were related to clinical outcome (modified Rankin Scale, ≤ 2).

Results

Interobserver agreement (n = 101) was 0.46 (tMIP), 0.58 (3-phase CTA), 0.67 (multiphase CTA), and 0.69 (single-phase CTA) for static assessments and 0.52 (3-phase CTA) and 0.54 (multiphase CTA) for dynamic assessments. Concordance correlation coefficient (n = 80) was 0.08 (3-phase CTA), 0.09 (single-phase CTA), and 0.23 (multiphase CTA) for static assessments and 0.10 (3-phase CTA) and 0.27 (multiphase CTA) for dynamic assessments. Higher static collateral scores on multiphase CTA (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1–2.7) and tMIP images (OR, 2.0; 95% CI, 1.1–3.4) were associated with modified Rankin Scale of 2 or less as were higher modified American Society of Interventional and Therapeutic Neuroradiology scores on 3-phase CTA (OR, 1.5; 95% CI, 1.1–2.2) and multiphase CTA (OR, 1.7; 95% CI, 1.1–2.6).

Conclusions

Concordance between assessments on CT and DSA was poor. Collateral status evaluated on 3-phase CTA and multiphase CTA, but not on DSA, was associated with clinical outcome.
Modeling Patient-Informed Liver Contrast Perfusion in Contrast-enhanced Computed Tomography
Authors: Setiawan Hananiel , Ria Francesco , Abadi Ehsan , Fu Wanyi , Smith Taylor B. , Samei Ehsan
Published: November 2020

Objective

To determine the correlation between patient attributes and contrast enhancement in liver parenchyma and demonstrate the potential for patient-informed prediction and optimization of contrast enhancement in liver imaging.

Methods

The study included 418 chest/abdomen/pelvis computed tomography scans, with 75% to 25% training-testing split. Two regression models were built to predict liver parenchyma contrast enhancement over time: first model (model A) utilized patient attributes (height, weight, sex, age, bolus volume, injection rate, scan times, body mass index, lean body mass) and bolus-tracking data. A second model (model B) only used the patient attributes. Pearson coefficient was used to assess predictive accuracy.

Results

Weight- and height-related features were found to be statistically significant predictors (P < 0.05), weight being the strongest. Of the 2 models, model A (r
2 = 0.75) showed greater accuracy than model B (r
2 = 0.42).

Conclusions

Patient attributes can be used to build prediction model for liver parenchyma contrast enhancement. The model can have utility in optimization and improved consistency in contrast-enhanced liver imaging.
Relationships of Language Lateralization with Diffusion Tensor Imaging Metrics of Corpus Callosum, Tumor Grade, and Tumors Distance to Language-Eloquent Areas in Glial Neoplasms
Authors: Timocin Gizem , Toprak Ali , Aralasmak Ayse
Published: November 2020

Purpose

The aim of the study was to search relationships between language lateralization and corpus callosum (CC) connectivity, tumor grade, and tumors distance to language-eloquent areas in glial neoplasms.

Materials and Methods

The functional magnetic resonance imaging and CC diffusion tensor imaging (DTI) metrics of 42 patients with glial neoplasm were evaluated for relationships of language lateralization (left, right, and bilateral) with CC DTI metrics (tracts number, voxel, volume, length, fractional anisotropy [FA], and apparent diffusion coefficient), tumor grade, and tumors distance to language-eloquent areas and relationships of CC DTI metrics with tumor grade. Kruskal-Wallis, Mann-Whitney U, and χ2 tests were used. All were repeated in 26 patients with left hemispheric masses.

Results

In glial masses, language bilateralism was more common than normal population and more pronounced in low grade than high grade. In right lateralism and bilateralism, tumor settlement nearby language-eloquent areas was more common. In the left lateralism, highest CC tract number, higher tumor grade, and more remote tumor settlements were noted. There was no relationship between CC DTI metrics and tumor grade but increase in CC tracts number and FA with increasing tumor grade.

Conclusions

Increased bilateralism in glial masses than normal population and in low grade tumors than high grade and increased nearby tumor settlement in right lateralism and bilateralism support interhemispheric reorganization and plasticity. This is more pronounced in low grade because of higher life span. Highest CC tract number, higher tumor grade, and more remote tumor settlement in left lateralized group suggest intact CC integrity with limited hemispheric destruction. Increasing CC tracts number and FA with increasing tumor grade support preserved CC integrity in the shorter life span of high-grade tumors.
Diagnostic Yield of Computed Tomography for the Identification of Coronavirus Disease 2019 Using Repeated Reverse Transcriptase Polymerase Chain Reaction Testing or Confirmed True-Negative State as Reference Standard: Systematic Review and Meta-Analysis
Authors: Bellini Davide , Panvini Nicola , Carbone Iacopo , Rengo Marco , Wang Carolyn L. , Mileto Achille
Published: November 2020

Objective

The aim of this study was to perform a meta-analysis assessing the diagnostic yield of computed tomography (CT) for the identification of coronavirus disease 2019 (COVID-19) using repeated reverse transcriptase polymerase chain reaction testing or confirmed true-negative state as reference standard.

Methods

In May 2020, we interrogated the MEDLINE, Embase, and CENTRAL databases. Pooled sensitivity, specificity, and diagnostic odds ratios of CT for COVID-19 identification were computed. Cumulative positive predictive value (PPV) and negative predictive value, stratified by disease prevalence, were calculated.

Results

Ten articles were included (1332 patients). Pooled sensitivity, specificity, and summary diagnostic odds ratio of CT were 82% [95% confidence interval (CI), 79%–84%], 68% (95% CI, 65%–71%), and 18 (95% CI, 9.8–32.8). The PPV and negative predictive value were 54% (95% CI, 30%–77%) and 94% (95% CI, 88%–99%) at a COVID-19 prevalence lower than 40%, and 80% (95% CI, 62%–91%) and 77% (95% CI, 68%–85%) at a prevalence higher than 40%.

Conclusion

CT yields higher specificity and PPV, albeit lower sensitivity, than previously reported for the identification of COVID-19.
Peripheral Nerve Sheath Tumors of Head and Neck: Imaging-Based Review of World Health Organization Classification
Authors: Abdel Razek Ahmed Abdel Khalek , Gamaleldin Omneya A. , Elsebaie Nermeen A.
Published: November 2020

We aim to review the imaging appearance of peripheral nerve sheath tumors (PNSTs) of head and neck according to updated fourth edition of World Health Organization classification. Peripheral nerve sheath tumor can be sporadic or associated with neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis. Schwannoma is the most common benign PNST that can be intracranial or extracranial and appears heterogeneous reflecting its histologic composition. Melanotic schwannoma is a different entity with high prediction of malignancy; it shows hypointense signal on T2-weighted image. Neurofibroma can present by localized, plexiform, or diffuse lesion. It usually appears homogeneous or shows a characteristic target sign. Perineurioma can be intraneural seen with the nerve fiber or extraneural appearing as a mass. Solitary circumscribed neuroma and neurothekeoma commonly present as dermal lesions. Nerve sheath myxoma may exhibit high signal on T1 weighted image. Benign triton tumors can be central, aggressive lesion, or peripheral nonaggressive lesion. Granular cell tumor shows hypointense signal on T2 weighted image. Neuroglial heterotopia most commonly occurs in the nasal cavity. Ectopic meningioma arises from ectopic arachnoid cells in the neck. In hybrid PNST, combined histological features of benign PNST occur in the same lesion. Malignant PNSTs are rare with an aggressive pattern. Computed tomography and magnetic resonance imaging are complementary studies to determine the location and extent of the tumor. Advanced magnetic resonance sequences, namely, diffusion-weighted imaging and dynamic contrast enhancement, can help in differentiation of benign from malignant PNST.
An ex vivo cystic fibrosis model recapitulates key clinical aspects of chronic Staphylococcus aureus infection
Authors: Sweeney Esther , Harrington Niamh E. , Harley Henriques Alicia G. , Hassan Marwa M. , Crealock-Ashurst Branagh , Smyth Alan R. , Hurley Matthew N. , Tormo-Mas María Ángeles , Harrison Freya
Published: November 2020

Staphylococcus aureusis the most prevalent organism isolated from the airways of people with cystic fibrosis (CF), predominantly early in life. Yet its role in the pathology of lung disease is poorly understood. In mice, and many experiments using cell lines, the bacterium invades cells or interstitium, and forms abscesses. This is at odds with the limited available clinical data: interstitial bacteria are rare in CF biopsies and abscesses are highly unusual. Bacteria instead appear to localize in mucus plugs in the lumens of bronchioles. We show that, in an establishedex vivomodel of CF infection comprising porcine bronchiolar tissue and synthetic mucus,S. aureusdemonstrates clinically significant characteristics including colonization of the airway lumen, with preferential localization as multicellular aggregates in mucus, initiation of a small colony variant phenotype and increased antibiotic tolerance of tissue-associated aggregates. Tissue invasion and abscesses were not observed. Our results may inform ongoing debates relating to clinical responses toS. aureusin people with CF.
rpoB mutations conferring rifampicin-resistance affect growth, stress response and motility in Vibrio vulnificus
Authors: Cutugno Laura , Mc Cafferty Jennifer , Pané-Farré Jan , O’Byrne Conor , Boyd Aoife
Published: November 2020

Rifampicin is a broad-spectrum antibiotic that binds to the bacterial RNA polymerase (RNAP), compromising DNA transcription. Rifampicin resistance is common in several microorganisms and it is typically caused by point mutations in the gene encoding the β subunit of RNA polymerase, rpoB. Different rpoB mutations are responsible for various levels of rifampicin resistance and for a range of secondary effects. rpoB mutations conferring rifampicin resistance have been shown to be responsible for severe effects on transcription, cell fitness, bacterial stress response and virulence. Such effects have never been investigated in the marine pathogen

Vibrio vulnificus

, even though rifampicin-resistant strains of

V. vulnificus

have been isolated previously. Moreover, spontaneous rifampicin-resistant strains of

V. vulnificus

have an important role in conjugation and mutagenesis protocols, with poor consideration of the effects of rpoB mutations. In this work, effects on growth, stress response and virulence of

V. vulnificus

were investigated using a set of nine spontaneous rifampicin-resistant derivatives of

V. vulnificus

CMCP6. Three different mutations (Q513K, S522L and H526Y) were identified with varying incidence rates. These three mutant types each showed high resistance to rifampicin [minimal inhibitory concentration (MIC) >800 µg ml−1], but different secondary effects. The strains carrying the mutation H526Y had a growth advantage in rich medium but had severely reduced salt stress tolerance in the presence of high NaCl concentrations as well as a significant reduction in ethanol stress resistance. Strains possessing the S522L mutation had reduced growth rate and overall biomass accumulation in rich medium. Furthermore, investigation of virulence characteristics demonstrated that all the rifampicin-resistant strains showed compromised motility when compared with the wild-type, but no major effects on exoenzyme production were observed. These findings reveal a wide range of secondary effects of rpoB mutations and indicate that rifampicin resistance is not an appropriate selectable marker for studies that aim to investigate phenotypic behaviour in this organism.
Innovation of Audio-Visual Triage system in Combating the Spread of COVID-19 Infection and its efficacy: A Novel Strategy
Authors: Hafeez Muhammad Mansoor , Azhar Mohammad , Zafar Chudhary Hafiz Rizwan , Rana Muhammad Asim , Malik Arif
Published: November 2020

During the novel coronavirus pandemic, also known as SARS-CoV-2 or COVID-19 pandemic, frontline healthcare professionals suffered psychological as well as pathological trauma due to the lack of preparation to cope with this unforeseen situation. The protocols to prevent the spread of this disease proved to be less effective than anticipated. In these circumstances, improvement of the existing triage system was felt and an AUDIO-VISUAL TRIAGE (AVT) system was introduced to enhance confidence as well as increase the safety of frontline healthcare professionals. The current analysis was performed from March 21, 2020, to April 28, 2020, until the completion of sixty response forms, at Bahria Town International Hospital, Lahore. Thirty participants (Group A) deployed on visual triage and other thirty (Group B) on AVT for screening suspected cases of COVID-19 infection. Anxiety levels were measured by using the GAD-7 scoring system and the participants of both groups were periodically tested for COVID-19 infection by PCR. Independent t-test was used to evaluate the significance of different variables at a confidence level of 95%. The result of the current study revealed the effectiveness of AVT for the screening of COVID-19 patients. There was a statistically significant increase in anxiety levels and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rate in group A as compared to group B. Almost all participants in group A wanted to shift their place of work or ready to quit the job if they were forced to perform their duties at the same visual triage. AVT system for COVID-19 screening found to be more safe and less stressful than visual triage. It is not only a simple and effective way to prevent the spread of diseases but also boosted the confidence of frontline healthcare professionals to fight against coronavirus spread.