bluuebunny/crossref_metadata_2025 huggingface dataset:
Subgroup analysis of Japanese patients in a phase III randomized, controlled study of neoadjuvant atezolizumab or placebo, combined with nab-paclitaxel and anthracycline-based chemotherapy in early triple-negative breast cancer (IMpassion031)
Authors: Saji Shigehira , Ohsumi Shozo , Ito Mitsuya , Hayashi Naoki , Kobayashi Kokoro , Masuda Norikazu , Niikura Naoki , Yamashita Toshinari , Kiyama Keiichiro , Hasegawa Ayumi , Nakagawa Shizuka , Hattori Masaya
Published: June 2022

Background

In the global phase III IMpassion031 study, neoadjuvant atezolizumab plus nab-paclitaxel/anthracycline-based chemotherapy improved pathological complete response in patients with early stage triple-negative breast cancer. Here, we report primary analysis results from a subgroup of Japanese patients.

Methods

Patients with histologically documented, previously untreated, stage cT2–cT4, cN0–cN3, cM0 triple-negative breast cancer were randomized 1:1 to receive intravenous atezolizumab 840 mg or placebo every 2 weeks in combination with chemotherapy consisting of nab-paclitaxel intravenous 125 mg/m2 once a week, followed by doxorubicin intravenous 60 mg/m2 and cyclophosphamide intravenous 600 mg/m2 every 2 weeks. Patients then underwent surgery. Pathological complete response (ypT0/is ypN0) in the intention-to-treat and PD-L1-positive (≥1% PD-L1-expressing tumor-infiltrating immune cells) populations were co-primary endpoints.

Results

This subanalysis (data cutoff: 3 April 2020) included 36 patients from Japan (intention-to-treat; atezolizumab arm, n = 17; placebo arm, n = 19). Pathological complete response occurred in 41% (n = 7; 95% confidence interval, 18–67) of patients in the atezolizumab arm and 37% (n = 7; 95% confidence interval, 16–62) in the placebo arm. In the PD-L1-positive population, pathological complete response occurred in 50% (n = 5; 95% confidence interval, 19–81) of patients in the atezolizumab arm and 45% (n = 5; 95% confidence interval, 17–77) in the placebo arm. Treatment-related grade 3–4 adverse events occurred in 71% and 68% of patients in the respective arms.

Conclusion

Atezolizumab added to neoadjuvant chemotherapy numerically improved pathological complete response versus placebo in this small exploratory analysis of Japanese patients with early stage triple-negative breast cancer, a trend directionally consistent with the global study results. No new safety signals were identified.
MAX2-dependent competence for callus formation and shoot regeneration from Arabidopsis thaliana root explants
Authors: Temmerman Arne , Marquez-Garcia Belen , Depuydt Stephen , Bruznican Silvia , De Cuyper Carolien , De Keyser Annick , Boyer François-Didier , Vereecke Danny , Struk Sylwia , Goormachtig Sofie
Published: June 2022

Although the division of the pericycle cells initiates both lateral root development and root-derived callus formation, these developmental processes are affected differently in the strigolactone and karrikin/KARRIKIN INSENSITIVE 2 (KAI2) ligand signalling mutant more axillary growth 2 (max2). Whereas max2 produces more lateral roots than the wild type, it is defective in the regeneration of shoots from root explants. We suggest that the decreased shoot regeneration of max2 originates from delayed formation of callus primordium, yielding less callus material to regenerate shoots. Indeed, when incubated on callus-inducing medium, the pericycle cell division was reduced in max2 and the early gene expression varied when compared with the wild type, as determined by a transcriptomics analysis. Furthermore, the expression of the LATERAL ORGAN BOUNDARIES DOMAIN genes and of callus-induction genes was modified in correlation with the max2 phenotype, suggesting a role for MAX2 in the regulation of the interplay between cytokinin, auxin, and light signalling in callus initiation. Additionally, we found that the in vitro shoot regeneration phenotype of max2 might be caused by a defect in KAI2, rather than in DWARF14, signalling. Nevertheless, the shoot regeneration assays revealed that the strigolactone biosynthesis mutants max3 and max4 also play a minor role.
Olfactory sensation
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

This chapter discusses the anatomic basis of the olfactory sensation (smell) and symptoms and signs caused by its impairment. The primary neurons of the olfactory system are the bipolar cells located in the olfactory epithelium of the nasal mucous membrane (Figure 6-1). Their peripheral axonal endings serve as the olfactory receptors, and an electric impulse generated there is conducted to the cell body, from which the central axon originates as the olfactory nerve. The sense of smell is tested by using a non-pungent stimulus such as a mild perfume. It is important to test the left and right nose separately. Bilateral disturbance of olfactory sensation is commonly seen in inflammation of the nasal mucosa such as rhinitis or common cold. Bilateral anosmia may be a manifestation of some hereditary neurodegenerative diseases.
Sense of equilibrium
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

This chapter discusses the anatomic basis of the sense of equilibrium, and symptoms and signs caused by its impairment, and representative diseases or syndromes presenting with balance disturbance.
Swallowing, phonation, and articulation
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

The final common pathway related to swallowing (deglutition), phonation (vocalization), and articulation involves the ninth cranial nerve (glossopharyngeal nerve), the 10th cranial nerve (vagus nerve), and the 12th cranial nerve (hypoglossal nerve). This chapter explains the symptoms and signs caused by impairment of this system.
Mental and cognitive functions
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

Along with an increasing aged population, cognitive disorder or dementia is the most serious problem in the world. Cognitive functions are composed of several higher brain functions, including memory; This chapter discusses anatomical basis of each of these functions, and symptoms and syndrome causes by impairment of each function or combination of multiple functions. Pathology and clinical manifestations are discussed for Alzheimer disease, diffuse Lewy body disease, frontotemporal lobar degeneration (FTLD), and various leukodystrophies.
Epilepsy and convulsion
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

Epileptic seizure is defined as “transient occurrence of symptoms and/or signs due to abnormal excessive or synchronous neuronal activity in the brain.” It is currently thought that most cases of epileptic seizures are based on organic cerebral lesions. The prevalence of epilepsy is believed to be as high as 0.5% of the population. Epileptic seizures are largely classified into three groups; generalized seizures, focal seizures and unknown, and the first two groups are further classified into subgroups mainly based on the clinical manifestations In this book, classification of epileptic seizures is explained by using the 2010 classification of the ILAE (Berg et al, 2010) by taking into account the revised versions of their classification.
Functional (psychogenic) neurological diseases
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

Many neurological symptoms may appear without organic lesions of the nervous system. Functional (psychogenic) neurological diseases, also called conversion disorders, are involuntary. There are two voluntary mimics of functional disorders: factitious disease, where patients have a psychiatric illness, and malingering, where persons have no illness and are just lying. The term “functional” is beginning to replace “psychogenic” in many circumstances. This chapter discusses clinical features of functional neurological disorders in detail. Negative neurological symptoms like loss of consciousness, blindness, constriction of visual field, motor paralysis, and loss of pain sense are commonly seen in functional diseases, but positive symptoms like convulsion and involuntary movements are more common. Among others, functional movement disorders are not infrequent and have drawn particular attention in the recent years. Within the movement disorders, functional tic-like movements might be difficult to distinguish from real tics, and in fact these two may overlap within the patient.
Relay center of all sensory and motor functions (thalamus)
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

Although this book is organized according to the functional anatomy of the nervous system, this chapter is especially arranged because the thalamus is the relay center for all kinds of ascending pathways to the cerebral cortex, and also because it is commonly involved by the cerebrovascular diseases.
Disability, functional recovery, and prognosis
Authors: Shibasaki Hiroshi , Hallett Mark
Published: June 2022

Degree of disability and prospect of functional recovery are the most important matters of concern for patients with neurological disorders. After completing the neurologic examination, it is important to consider the severity of disability, although detailed scoring of each activity of daily living can be assessed later. Disability can be evaluated in terms of neurological impairment found by the physical examination, disability expressed as activities of daily living (ADLs), and the resulting social handicap. Scales of disability have been established for some diseases like Parkinson disease and multiple sclerosis, but for other diseases, it is useful to evaluate each of the specific ADLs, such as brushing teeth, washing face, combing hair, dressing, use of toilet facilities, taking bath or shower, eating, walking indoors as well as outdoors, and so on.
How to Think Like a Neurologist
Authors: Meltzer Ethan
Published: June 2022

How to Think Like a Neurologist is a unique case-based approach to medical education. It begins by introducing a simple framework to the bedside approach of diagnosing neurologic disorders. This foundational framework, using pace and localization as the building blocks of identifying a clinical syndrome prior to generating a differential diagnosis, gives the reader a powerful tool to solve the cases contained in the book. Whereas other case-based approaches tend to focus on either basic neuroanatomy or the end diagnosis, How to Think Like a Neurologist focuses on the process of how to connect data gathered at the bedside to the ultimate diagnosis. It expands and explicitly teaches the next step of medical education that is often missing after neuroanatomy and introduction to neurologic disorders. The book contains 29 cases of rare and interesting neurologic disorders that the reader works through step by step to arrive at the diagnosis. The cases progress in difficulty throughout the book, and each case highlights different principles of the clinical method. Included in the book are accompanying imaging findings of the cases as well as neuroanatomic figures and tables to guide the reader. The style of the book is informal and conversational, and it is meant to encourage active participation by the reader in easy-to-digest short case vignettes.
Clinical and microbiological analysis of fungal keratitis in Toronto, Canada: A 20-year study
Authors: Trinh Tanya , Emami Seema , Gould Jonah , Mimouni Michael , Cohen Eyal , Rootman David S , Slomovic Allan R , Chan Clara C
Published: June 2022

Fungal keratitis is a devastating and difficult-to-treat ocular infection with high morbidity. Understanding geographic microbiological and clinical trends helps to guide rapid and effective treatment. We therefore report the characteristics and outcomes of fungal keratitis in Toronto,ON Canada, over a 20-year period. An electronic search of microbiology records at University Health Network, Toronto, ON, Canada identified all patients with positive corneal fungal culture over a 20-year period seen at our tertiary referral cornea practice. Review of corresponding patient charts identified demographic and microbiological details, clinical course, treatment regimen, and final outcomes associated with each episode of culture-positive fungal keratitis. A total of 46 patients with 51 discrete fungal keratitis episodes were included. Five patients experienced recurrent fungal keratitis. Candida species accounted for 60.8% of positive fungal cultures, followed by Filamentous species at 35.3%. Preferred initial anti-fungal treatment was topical amphotericin at 36.7% followed by topical voriconazole at 32.6%. Surgical intervention was required in 48.9% with therapeutic penetrating keratoplasty being the most common procedure (22.4%). Final visual acuity (VA) of <20/200 was attributed to 58% of patients in this study. Risk factors for poor outcomes included poor VA, topical steroid use at presentation, Candida involvement, history of ocular surface disease, organic ocular trauma, or prior corneal transplantation. Candida is the most frequent keratomycotic pathogen in Toronto. Risk factors for poor visual outcome include prior corneal transplantation, ocular surface disease/trauma, or pre-existing topical steroid use. Early suspicion, diagnosis and treatment are paramount for best clinical outcomes.

Lay Summary

Fungal keratitis can cause severe vision loss without effective treatment. In Toronto, Candida had been the most common species over a 20-year period. Poor clinical outcome was associated with low presenting visual acuity, previous corneal transplant, topical steroid use, trauma, and Candida involvement.
Magnetic fields and outflows in the large Bok globule CB 54
Authors: Pattle Kate , Lai Shih-Ping , Sadavoy Sarah , Coudé Simon , Wolf Sebastian , Furuya Ray , Kwon Woojin , Lee Chang Won , Zielinski Niko
Published: June 2022

We have observed the large Bok globule CB 54 in 850-$\mu$m polarized light using the POL-2 polarimeter on the James Clerk Maxwell Telescope (JCMT). We find that the magnetic field in the periphery of the globule shows a significant, ordered deviation from the mean-field direction in the globule centre. This deviation appears to correspond with the extended but relatively weak 12CO outflow emanating from the Class 0 sources at the centre of the globule. Energetics analysis suggests that if the outflow is reshaping the magnetic field in the globule’s periphery, then we can place an upper limit of $\lt 27\, \mu$G on the magnetic field strength in the globule’s periphery. Comparison with archival Planck and CARMA measurements shows that the field in the centre of the globule is consistent over several orders of magnitude in size scale, and oriented parallel to the density structure in the region in projection. We thus hypothesize that while non-thermal motions in the region may be sub-Alfvénic, the magnetic field is subdominant to gravity over a wide range of size scales. Our results suggest that even a relatively weak outflow may be able to significantly reshape magnetic fields in star-forming regions on scales >0.1 pc.
Asteroid (3200) Phaethon: results of polarimetric, photometric, and spectral observations
Authors: Kiselev N N , Rosenbush V K , Petrov D , Luk'yanyk I V , Ivanova O V , Pit N V , Antoniuk K A , Afanasiev V L
Published: June 2022

We present results of polarimetric, photometric, and spectral observations of the near-Earth asteroid (3200) Phaethon carried out at the 6-m BTA telescope of the Special Astrophysical Observatory and the 2.6-m and 1.25-m telescopes of the Crimean Astrophysical Observatory over a wide range of phase angles during its close approach to the Earth at the end of 2017 (α = 19°–135°) and in 2020 at α = 52.2°. Using our and other available in literature data, we found that the maximum degree of linear polarization of Phaethon in the V band is Pmax = (45 ± 1) per cent at the phase angle αmax = 124.0° ± 0.4°, whereas the inversion angle αinv = 21.4° ± 1.2° and polarimetric slope is h = (0.326 ± 0.027) per cent per degree. Using the dependence ‘polarimetric slope – albedo,’ we have found the geometric albedo of asteroid Phaethon to be pv = 0.060 ± 0.005. This value falls into the lower range of albedo values for asteroids determined by different methods. The mean colour indices U–B = 0.207 m ± 0.053 m and B–V = 0.639 m ± 0.054 m of the asteroid are derived at heliocentric and geocentric distances 1.077 au and 0.102 au, respectively, and phase angle α = 23.78°. The absolute magnitude of Phaethon is V(1,1,0) = 14.505 m ± 0.059 m. The effective diameter of Phaethon is estimated from obtained absolute magnitude and geometrical albedo, it is equal to 6.8 ± 0.3 km. The best fit to the observed polarimetric data was obtained with the Sh-matrix model of conjugated random Gaussian particles composed of Mg-rich silicate (90 per cent) and amorphous carbon (10 per cent).
Luminosity distribution of dwarf elliptical-like galaxies
Authors: Seo Mira , Ann Hong Bae
Published: June 2022

We present the structural parameters of ∼910 dwarf elliptical-like galaxies in the local universe (z ≲ 0.01) derived from the r-band images of the Sloan Digital Sky Survey (SDSS). We examine the dependence of structural parameters on the morphological types (dS0, dE, dEbc, dSph, and dEblue). There is a significant difference in the structural parameters among the five sub-types if we properly treat the light excess due to nucleation in dSph and dE galaxies. The mean surface brightness within the effective radius (〈μe〉) of dSph galaxies is also clearly different from that of other sub-types. The frequency of disc features such as spiral arms depends on the morphology of dwarf galaxies. The most pronounced difference between dSph galaxies and other sub-types of early-type dwarf galaxies is the absence of disc feature which is thought to be closely related to their origin.
BUDDI-MaNGA I: A statistical sample of cleanly decomposed bulge and disc spectra
Authors: Johnston Evelyn J , Häußler Boris , Jegatheesan Keerthana
Published: June 2022

Many galaxies display clear bulges and discs, and understanding how these components form is a vital step towards understanding how the galaxy has evolved into what we see today. The BUDDI-MaNGA project aims to study galaxy evolution and morphological transformations through the star-formation histories of the bulges and discs. We have applied our buddi software to galaxies from the MaNGA Survey in the SDSS DR15 in order to isolate their bulge and disc spectra, from which we derived their stellar populations. To date, this work provides the largest sample of clean bulge and disc spectra extracted from IFU datacubes using the galaxies light profile information, and will form the basis for a series of papers aiming to answer open questions on how galaxies have formed and evolved, and the role of their individual structures. This paper presents an introduction to the project, including an overview of these fits, a characterization of the sample, and a series of tests on the fits to ensure reliability.
MOCCA-SURVEY data base II – Properties of intermediate mass black holes escaping from star clusters
Authors: Maliszewski Konrad , Giersz Mirek , Gondek-Rosinska Dorota , Askar Abbas , Hypki Arkadiusz
Published: June 2022

In this work, we investigate properties of intermediate-mass black holes (IMBHs) that escape from star clusters due to dynamical interactions. The studied models were simulated as part of the preliminary second survey carried out using the MOCCA code (MOCCA-SURVEY Database II), which is based on the Monte Carlo N-body method and does not include gravitational wave recoil kick prescriptions of the binary black hole merger product. We have found that IMBHs are more likely to be formed and ejected in models where both initial central density and central escape velocities have high values. Most of our studied objects escape in a binary with another black hole (BH) as their companion and have masses between 100 and $\rm 140 {\rm ~M}_{\odot }$. Escaping IMBHs tend to build-up mass most effectively through repeated mergers in a binary with BHs due to gravitational wave emission. Binaries play a key role in their ejection from the system as they allow these massive objects to gather energy needed for escape. The binaries in which IMBHs escape tend to have very high binding energy at the time of escape and the last interaction is strong but does not involve a massive intruder. These IMBHs gain energy needed to escape the cluster gradually in successive dynamical interactions. We present specific examples of the history of IMBH formation and escape from star cluster models. We also discuss the observational implications of our findings as well as the potential influence of the gravitational wave recoil kicks on the process.
SDSS-IV MaNGA: a catalogue of spectroscopically detected strong galaxy–galaxy lens candidates
Authors: Talbot Michael S , Brownstein Joel R , Neumann Justus , Thomas Daniel , Maraston Claudia , Drory Niv
Published: June 2022

We spectroscopically detected candidate emission-lines of 8 likely, 17 probable, and 69 possible strong galaxy–galaxy gravitational lens candidates found within the spectra of $\approx 10\, 000$ galaxy targets contained within the completed Mapping of Nearby Galaxies at Apache Point Observatory survey. This search is based upon the methodology of the Spectroscopic Identification of Lensing Objects project, which extends the spectroscopic detection methods of the BOSS Emission-Line Lensing Survey and the Sloan Lens ACS Survey. We scanned the co-added residuals that we constructed from stacks of foreground subtracted row-stacked-spectra so a sigma-clipping method can be used to reject cosmic rays and other forms of transients that impact only a small fraction of the combined exposures. We also constructed narrow-band images from the signal to noise of the co-added residuals to observe signs of lensed source images. We also use several methods to compute the probable strong lensing regime for each candidate lens to determine which candidate background galaxies may reside sufficiently near the galaxy centre for strong lensing to occur. We present the spectroscopic redshifts within a value-added catalogue (VAC) for data release 17 (DR17) of SDSS-IV. We also present the lens candidates, spectroscopic data, and narrow-band images within a VAC for DR17. High resolution follow-up imaging of these lens candidates are expected to yield a sample of confirmed grade-A lenses with sufficient angular size to probe possible discrepancies between the mass derived from a best-fitting lens model, and the dynamical mass derived from the observed stellar velocities.
Electromagnetic follow-up observations of binary neutron star mergers with early warnings from decihertz gravitational-wave observatories
Authors: Kang Yacheng , Liu Chang , Shao Lijing
Published: June 2022

We investigate the prospects of electromagnetic follow-up observations for binary neutron star (BNS) mergers, with the help of early warnings from decihertz gravitational-wave (GW) observatories, B-DECIGO and DO-Optimal. Extending the previous work, we not only give quick assessments of joint short γ-ray burst (sGRB) detection rates for different γ-ray satellites and BNS population models, but also elaborate on the analyses and results on multiband kilonova detections for survey telescopes with different limiting magnitudes. During an assumed 4-yr mission time for decihertz GW observatories, we find that for the goals of electromagnetic follow-ups, DO-Optimal performs better than B-DECIGO as a whole on the detection rate, and has a larger detectable distance for joint sGRB/kilonova searches. Taking the lognormal population model for BNS mergers and a 1-d early-warning time as an example, we discuss the accuracy in localization and timing, as well as the redshift distributions for various synergy observations with electromagnetic facilities and decihertz GW detectors. Based on our analyses, we propose a feasible ‘wait-for’ pattern as a novel detecting mode for future multimessenger astrophysics.
What to expect from dynamical modelling of cluster haloes – II. Investigating dynamical state indicators with Random Forest
Authors: Li Qingyang , Han Jiaxin , Wang Wenting , Cui Weiguang , De Luca Federico , Yang Xiaohu , Zhou Yanrui , Shi Rui
Published: June 2022

We investigate the importance of various dynamical features in predicting the dynamical state (ds) of galaxy clusters, based on the Random Forest (RF) machine-learning approach. We use a large sample of galaxy clusters from the Three Hundred Project of hydrodynamical zoomed-in simulations, and construct dynamical features from the raw data as well as from the corresponding mock maps in the optical, X-ray, and Sunyaev–Zel’dovich (SZ) channels. Instead of relying on the impurity based feature importance of the RF algorithm, we directly use the out-of-bag (oob) scores to evaluate the importance of individual features and different feature combinations. Among all the features studied, we find the virial ratio, η, to be the most important single feature. The features calculated directly from the simulations and in three dimensions carry more information on the ds than those constructed from the mock maps. Compared with the features based on X-ray or SZ maps, features related to the centroid positions are more important. Despite the large number of investigated features, a combination of up to three features of different types can already saturate the score of the prediction. Lastly, we show that the most sensitive feature η is strongly correlated with the well-known half-mass bias in dynamical modelling. Without a selection in ds, cluster haloes have an asymmetric distribution in η, corresponding to an overall positive half-mass bias. Our work provides a quantitative reference for selecting the best features to discriminate the ds of galaxy clusters in both simulations and observations.
Spin transfer from dark matter to gas during halo formation
Authors: Li Jie , Obreschkow Danail , Power Chris , Lagos Claudia del P
Published: June 2022

In the protogalactic density field, diffuse gas and collision-less cold dark matter (DM) are often assumed sufficiently mixed that both components experience identical tidal torques. However, haloes in cosmological simulations consistently end up with a higher specific angular momentum (sAM) in gas, even in simulations without radiative cooling and galaxy formation physics. We refine this result by analysing the spin distributions of gas and DM in ∼50 000 well-resolved haloes in a non-radiative cosmological simulation from the SURFS suite. The sAM of the halo gas on average ends up ∼40 per cent above that of the DM. This can be pinned down to an excess AM in the inner halo (<50 per cent virial radius), paralleled by a more coherent rotation pattern in the gas. We uncover the leading driver for this AM difference through a series of control simulations of a collapsing ellipsoidal top-hat, where gas and DM are initially well mixed. These runs reveal that the pressurized inner gas shells collapse more slowly, causing the DM ellipsoid to spin ahead of the gas ellipsoid. The arising torque generally transfers AM from the DM to the gas. The amount of AM transferred via this mode depends on the initial spin, the initial axes ratios, and the collapse factor. These quantities can be combined in a single dimensionless parameter, which robustly predicts the AM transfer of the ellipsoidal collapse. This simplistic model can quantitatively explain the average AM excess of the gas found in the more complex non-radiative cosmological simulation.
Galaxy mergers can initiate quenching by unlocking an AGN-driven transformation of the baryon cycle
Authors: Davies Jonathan J , Pontzen Andrew , Crain Robert A
Published: June 2022

We use zoom simulations to show how merger-driven disruption of the gas disc in a galaxy provides its central active galactic nucleus (AGN) with fuel to drive outflows that entrain and expel a significant fraction of the circumgalactic medium (CGM). This in turn suppresses replenishment of the interstellar medium, causing the galaxy to quench up to several Gyr after the merger. We start by performing a zoom simulation of a present-day star-forming disc galaxy with the EAGLE galaxy formation model. Then, we re-simulate the galaxy with controlled changes to its initial conditions, using the genetic modification technique. These modifications either increase or decrease the stellar mass ratio of the galaxy’s last significant merger, which occurs at $z$ ≈ 0.74. The halo reaches the same present-day mass in all cases, but changing the mass ratio of the merger yields markedly different galaxy and CGM properties. We find that a merger can unlock rapid growth of the central supermassive black hole if it disrupts the co-rotational motion of gas in the black hole’s vicinity. Conversely, if a less disruptive merger occurs and gas close to the black hole is not disturbed, the AGN does not strongly affect the CGM, and consequently the galaxy continues to form stars. Our result illustrates how a unified view of AGN feedback, the baryon cycle and the interstellar medium is required to understand how mergers and quenching are connected over long time-scales.
Weak-lensing magnification of Type Ia supernovae from the Pantheon sample
Authors: Shah Paul , Lemos Pablo , Lahav Ofer
Published: June 2022

Using data from the Pantheon Type Ia supernovae (SN Ia) compilation and the Sloan Digital Sky Survey, we propose an estimator for weak-lensing convergence incorporating positional and photometric data of foreground galaxies. The correlation between this and the Hubble diagram residuals of the supernovae has 3.6σ significance, and is consistent with weak-lensing magnification due to dark matter haloes centred on galaxies. We additionally constrain the properties of the galactic haloes, such as the mass-to-light ratio Γ and radial profile of the halo matter density ρ(r). We derive a new relationship for the additional rms scatter in magnitudes caused by lensing, finding σlens = (0.06 ± 0.017)(dC(z)/dC(z = 1))3/2, where dC(z) is the comoving distance to redshift z. Hence, the scatter in apparent magnitudes due lensing will be of the same size as the intrinsic scatter of SN Ia by z ∼ 1.2. We propose a modification of the distance modulus estimator for SN Ia to incorporate lensing, which can be easily calculated from observational data. We anticipate this will improve the accuracy of cosmological parameter estimation for high-redshift SN Ia data.
Is there a sub-parsec-scale jet base in the nearby dwarf galaxy NGC 4395?
Authors: Yang Jun , Yang Xiaolong , Wrobel Joan M , Paragi Zsolt , Gurvits Leonid I , Ho Luis C , Nyland Kristina , Fan Lulu , Tafoya Daniel
Published: June 2022

NGC 4395 is a dwarf galaxy at a distance of about 4.3 Mpc (scale: ∼0.021 pc mas−1). It hosts an intermediate-mass black hole (IMBH) with a mass between ∼104 and ∼105 solar masses. The early radio observations of NGC 4395 with the very long baseline interferometry (VLBI) network, High Sensitivity Array (HSA), at 1.4 GHz in 2005 showed that its nucleus has a sub-mJy outflow-like feature (E) extending over 15 mas. To probe the possibility of the feature E as a continuous jet with a base physically coupled with the accretion disc, we performed deep VLBI observations with the European VLBI Network (EVN) at 5 GHz, and analysed the archival data obtained with the HSA at 1.4 GHz in 2008, NSF’s Karl G. Jansky Very Large Array (VLA) at 12–18 GHz and the Atacama Large Millimetre/submillimetre Array (ALMA) at 237 GHz. The feature E displays more diffuse structure in the HSA image of 2008 and has no compact substructure detected in the EVN image. Together with the optically thin steep spectrum and the extremely large angular offset (about 220 mas) from the accurate optical Gaia position, we explain the feature E as nuclear shocks likely formed by the IMBH’s episodic ejection or wide-angle outflow. The VLA and ALMA observations find a sub-mJy pc-scale diffuse feature, possibly tracing a thermal free–free emission region near the IMBH. There is no detection of a jet base at the IMBH position in the VLBI maps. The non-detections give an extremely low luminosity of ≤4.7 × 1033 erg s−1 at 5 GHz and indicate no evidence of a disc-jet coupling on sub-pc scales.
A dual-activity topoisomerase complex regulates mRNA translation and turnover
Authors: Su Shuaikun , Xue Yutong , Sharov Alexei , Zhang Yongqing , Lee Seung Kyu , Martindale Jennifer L , Li Wen , Ku Wai Lim , Zhao Keji , De Supriyo , Shen Weiping , Sen Payel , Gorospe Myriam , Xu Dongyi , Wang Weidong
Published: June 2022

Topoisomerase 3β (TOP3B) and TDRD3 form a dual-activity topoisomerase complex that interacts with FMRP and can change the topology of both DNA and RNA. Here, we investigated the post-transcriptional influence of TOP3B and associated proteins on mRNA translation and turnover. First, we discovered that in human HCT116 colon cancer cells, knock-out (KO) of TOP3B had similar effects on mRNA turnover and translation as did TDRD3-KO, while FMRP-KO resulted in rather distinct effects, indicating that TOP3B had stronger coordination with TDRD3 than FMRP in mRNA regulation. Second, we identified TOP3B-bound mRNAs in HCT116 cells; we found that while TOP3B did not directly influence the stability or translation of most TOP3B target mRNAs, it stabilized a subset of target mRNAs but had a more complex effect on translation–enhancing for some mRNAs whereas reducing for others. Interestingly, a point mutation that specifically disrupted TOP3B catalytic activity only partially recapitulated the effects of TOP3B-KO on mRNA stability and translation, suggesting that the impact of TOP3B on target mRNAs is partly linked to its ability to change topology of mRNAs. Collectively, our data suggest that TOP3B–TDRD3 can regulate mRNA translation and turnover by mechanisms that are dependent and independent of topoisomerase activity.
LncRNA EPR-induced METTL7A1 modulates target gene translation
Authors: Briata Paola , Caputo Luca , Zapparoli Ettore , Marcaccini Elisa , Passalacqua Mario , Brondolo Lorenzo , Bordo Domenico , Rossi Annalisa , Nicoletti Chiara , Bucci Gabriele , Puri Pier Lorenzo , Inga Alberto , Gherzi Roberto
Published: June 2022

EPR is a long non-coding RNA (lncRNA) that controls cell proliferation in mammary gland cells by regulating gene transcription. Here, we report on Mettl7a1 as a direct target of EPR. We show that EPR induces Mettl7a1 transcription by rewiring three-dimensional chromatin interactions at the Mettl7a1 locus. Our data indicate that METTL7A1 contributes to EPR-dependent inhibition of TGF-β signaling. METTL7A1 is absent in tumorigenic murine mammary gland cells and its human ortholog (METTL7A) is downregulated in breast cancers. Importantly, re-expression of METTL7A1 in 4T1 tumorigenic cells attenuates their transformation potential, with the putative methyltransferase activity of METTL7A1 being dispensable for its biological functions. We found that METTL7A1 localizes in the cytoplasm whereby it interacts with factors implicated in the early steps of mRNA translation, associates with ribosomes, and affects the levels of target proteins without altering mRNA abundance. Overall, our data indicates that METTL7A1—a transcriptional target of EPR—modulates translation of select transcripts.
Prospective associations of health literacy with clinical outcomes in adults with CKD: findings from the CRIC study
Authors: Estrella Mayra L , Allen-Meares Paula , Ricardo Ana C , Fischer Michael J , Gordon Elisa J , Carmona-Powell Eunice , Sondheimer James , Chen Jing , Horwitz Edward , Wang Xue , Hsu Jesse Y , Lash James P , Lora Claudia ,   the CRIC Study Investigators, Appel Lawrence J , Chen Jing , Feldman Harold I , Go Alan S , Nelson Robert G , Rahman Mahboob , Rao Panduranga S , Shah Vallabh O , Townsend Raymond R , Unruh Mark L
Published: June 2022

Background

Limited health literacy is associated with significant morbidity and mortality in the general population but the relation of health literacy with long-term clinical outcomes among adults with chronic kidney disease (CKD) is less clear.

Methods

Prospective data from the Chronic Renal Insufficiency Cohort (CRIC) Study (n = 3715) were used. Health literacy was assessed with the Short Test of Functional Health Literacy in Adults (dichotomized as limited/adequate). Cox proportional hazards models were used to separately examine the relations of health literacy with CKD progression, cardiovascular event (any of the following: myocardial infarction, congestive heart failure, stroke or peripheral artery disease), and all-cause, cardiovascular and non-cardiovascular mortality. Poisson regression was used to assess the health literacy–hospitalization association. Models were sequentially adjusted: Model 1 adjusted for potential confounders (sociodemographic factors), while Model 2 additionally adjusted for potential mediators (clinical and lifestyle factors) of the associations of interest.

Results

In confounder-adjusted models, participants with limited (vs adequate) health literacy [555 (15%)] had an increased risk of CKD progression [hazard ratio (HR) 1.34; 95% confidence interval (CI) 1.06–1.71], cardiovascular event (HR 1.67; 95% CI 1.39–2.00), hospitalization (rate ratio 1.33; 95% CI 1.26–1.40), and all-cause (HR 1.54; 95% CI 1.27–1.86), cardiovascular (HR 2.39; 95% CI 1.69–3.38) and non-cardiovascular (HR 1.27; 95% CI 1.01–1.60) mortality. Additional adjustments for potential mediators (Model 2) showed similar results except that the relations of health literacy with CKD progression and non-cardiovascular mortality were no longer statistically significant.

Conclusions

In the CRIC Study, adults with limited (vs adequate) health literacy had a higher risk for CKD progression, cardiovascular event, hospitalization and mortality—regardless of adjustment for potential confounders.
Glomerular deposition of galactose-deficient IgA1-containing immune complexes via glomerular endothelial cell injuries
Authors: Makita Yuko , Suzuki Hitoshi , Nakano Daisuke , Yanagawa Hiroyuki , Kano Toshiki , Novak Jan , Nishiyama Akira , Suzuki Yusuke
Published: June 2022

Background

Galactose-deficient immunoglobulin A1 (Gd-IgA1) plays a crucial role in the development of IgA nephropathy (IgAN). However, the pathological role of Gd-IgA1-containing immune complexes (ICs) and the mechanism of deposition in the mesangial region remain unclear.

Methods

To examine the deposition of Gd-IgA1-containing ICs in the mesangial region through glomerular endothelial cell injury, we evaluated the alteration of renal microvascular endothelial glycocalyx in nude mice injected with Gd-IgA1-IgG ICs. Human renal glomerular endothelial cells (HRGECs) were used to assess the potential capacity of Gd-IgA1-IgG ICs to activate endothelial cells.

Results

Nude mice injected with Gd-IgA1-containing ICs showed podocyte and endothelial cell injuries, with IgA, IgG and C3 depositions in glomerular capillaries and the mesangium. Moreover, albuminuria and hematuria were induced. Real-time glycocalyx imaging showed that renal microvascular glycocalyx was decreased immediately after injection of Gd-IgA1-containing ICs and then mesangial IgA deposition was increased. After coculture of Gd-IgA1-containing ICs with HRGECs, messenger RNA expression levels of endothelial adhesion molecules and proinflammatory mediators were upregulated significantly.

Conclusion

Gd-IgA1-IgG ICs had a high affinity for glomerular endothelial cells, which resulted in glomerular filtration barrier dysfunction mediated by glycocalyx loss. Furthermore, Gd-IgA1-IgG ICs accelerated the production of adhesion factors and proinflammatory cytokines in glomerular endothelial cells. The glomerular endothelial cell injury induced by Gd-IgA1-containing ICs may enhance the permeability of Igs in the mesangial region and subsequent inflammatory responses in the pathogenesis of IgAN.
Epidemiology of Complicated Urinary Tract Infections due to Enterobacterales Among Adult Patients Presenting in Emergency Departments Across the United States
Authors: Lodise Thomas P , Chopra Teena , Nathanson Brian H , Sulham Katherine , Rodriguez Mauricio
Published: June 2022

In this multicenter study of adult patients who presented to the emergency department with an Enterobacterales complicated urinary tract infection (cUTI), high rates of resistance and co-resistance to commonly used oral antibiotics (fluoroquinolones, trimethoprim-sulfamethoxazole, nitrofurantoin, and third-generation cephalosporins) were observed.
High Yield of Blood Cultures in the Etiologic Diagnosis of Cellulitis, Erysipelas, and Cutaneous Abscess in Elderly Patients
Authors: Taniguchi Tomohiro , Tsuha Sanefumi , Shiiki Soichi , Narita Masashi , Teruya Mariko , Hachiman Teruyuki , Kogachi Noriyasu
Published: June 2022

Background

Cellulitis is a common disease in the elderly, and detecting etiologic organisms with blood cultures is difficult because of the low positive rate and occasional skin contamination. Therefore, routine blood cultures are not recommended for uncomplicated cellulitis. However, it is unclear whether blood culture collection for the diagnosis of cellulitis in elderly patients is useful.

Methods

This single hospital–based observational study was performed between April 2012 and March 2015 in Okinawa, Japan. All enrolled patients were aged 15 years or older and admitted to the Division of Infectious Diseases with suspected cellulitis, erysipelas, and cutaneous abscess. Two routine sets of blood cultures were obtained.

Results

Two hundred and twenty-one patients were enrolled. The median age was 77 years. The proportion of bacteremia was 21.7% for all patients (48/221), 8.5% (4/47) for those <65 years, and 25.3% (44/174) for those ≥65 years old (P = .013). The skin contamination rate was 0.9% (2/221). The most common pathogen was Streptococcus dysgalactiae (62.5%). Gram-negative bacteremia not susceptible to cefazolin was detected in 8.3%. Cefazolin and ampicillin were the first- and second-most commonly used therapies. Anti–methicillin-resistant Staphylococcus aureus therapy was required in 3.6% of patients. In addition to age and severe infection, shaking chills and white blood count ≥13 000 cells/µL were independent risk factors of bacteremia.

Conclusions

Two routine sets of blood cultures are recommended for the precise diagnosis and appropriate treatment of cellulitis in elderly patients, especially in patients with shaking chills or leukocytosis.
Effects of depolarizing intervening galaxies on background radio emission. I. Global disk magnetic field
Authors: Omae Rikuto , Akahori Takuya , Machida Mami
Published: June 2022

External galaxies often intervene in front of background radio sources such as quasars and radio galaxies. Linear polarization of the background emission is depolarized by Faraday rotation of inhomogeneous magnetized plasma of the intervening galaxies. Exploring the depolarizing intervening galaxies (DINGs) can be a powerful tool to investigate the cosmological evolution of the galactic magnetic field. In this paper, we investigate the effects of DINGs on background radio emission using theoretical DING models. We find that complex structures of galaxy result in complicated depolarization features and Faraday dispersion functions (FDFs), but, for the features of depolarizations and FDFs, the global component of magnetic fields is important. We show the simplest results with ring magnetic field in the galactic disk. We find that the degree of depolarization significantly depends on the inclination angle and the impact parameter of the DING. We found that the larger the standard deviation, the more likely it is that depolarization will occur. The FDF represents the rotation measure (RM) structure within the beam. The FDF exhibits multi-components due mainly to the RM structure within the beam and the fraction of the DING that covers the background emission (the filling factor). The peak Faraday depth of the FDF is different from the beam-averaged RM of the DING. The Monte Carlo simulations indicate that a DING’s contribution to the standard deviation of observed RMs follows σRM ∝ 1/(1 + z)k with k ∼ 2.7 and exhibits a steeper redshift dependence than the wavelength squared. DINGs will have a significant impact on RM catalogs created by future survey projects such as the Square Kilometer Array (SKA) and SKA Precursor/Pathfinder.
Evaluation of Anterior Coverage in Children With Developmental Dysplasia of the Hip Using Transverse Magnetic Resonance Imaging at 2 Years Is Predictive of Future Radiographic Coverage
Authors: Tsukagoshi Yuta , Kamada Hiroshi , Takeuchi Ryoko , Tomaru Yohei , Nakagawa Shogo , Kimura Mio , Aiba Shutaro , Shimada Hayato , Ikezawa Yoshiyasu , Yamazaki Masashi
Published: June 2022

Background:

Although normal anterior acetabular coverage provides stability to the hip, acetabular retroversion leads to femoroacetabular impingement related to hip osteoarthritis. Previous studies have focused on acetabular version and anteroposterior coverage in children with developmental dysplasia of the hip (DDH); however, the correlation between anteroposterior coverage and acetabular development is unclear. We measured anteroposterior acetabular coverage in DDH patients using transverse magnetic resonance imaging (MRI) and subsequent bony acetabular growth, and evaluated the correlation of those findings.

Methods:

We evaluated 37 DDH (dislocations) in 36 patients who underwent MRI at 2 years of age. The mean age was 2.2±0.3 years at the time of MRI (1.6±0.4 y after reduction) and 6.0±0.1 years at the time of plain radiography for the Severin classification. On MRI scans, we measured the cartilaginous center-edge angle (CCEA) and cartilaginous acetabular-head index (CAHI) in the coronal plane and the anterior and posterior cartilaginous center-edge angles (AC-CEA and PC-CEA, respectively) in the transverse plane. Severin I or II was defined as a good outcome and III or IV as a poor outcome.

Results:

In the evaluations conducted at 2 years of age, the mean CCEA, CAHI, AC-CEA, and PC-CEA were 14±9 degrees, 66%±10%, 39±8 degrees, and 77±7 degrees, respectively; the CEA at 6 years of age was 13±7 degrees. Twelve and 25 hips were classified in the good and poor outcome groups, respectively. Although CCEA, CAHI, and AC-CEA were significantly associated with the outcome in a single regression analysis (P<0.05), only AC-CEA was significant in the multiple regression analysis with a stepwise selection method (P=0.018). The cutoff AC-CEA value for a good outcome was 38 degrees (sensitivity, 67%; specificity, 68%) using a receiver operating characteristic curve.

Conclusions:

Among MRI findings for acetabular cartilaginous morphology, AC-CEA was strongly associated with the outcome. Anteroposterior coverage was correlated with bony acetabular growth in childhood, and anterior coverage was particularly important for subsequent acetabular growth.

Level of Evidence:

Level IV—case series.
Rationale, Criteria, and Impact of Identifying Extreme Risk in Patients with Atherosclerotic Cardiovascular Disease
Authors: Zeng Yuhong , Zhao Dong
Published: June 2022

Assessment of the overall risk of atherosclerotic cardiovascular disease (ASCVD) is the first step in managing dyslipidemia and is an important reference for the target and intensity of treatment. Recently, different guidelines and consensuses on the management of this condition have successively recommended further risk stratification among patients with ASCVD, and a new “extreme risk” category has been proposed to identify patients who may obtain greater benefit from more intensive lipid-lowering therapy. The definition and terminology of extreme risk varies among different guidelines and consensuses; however, they all recommended an aggressive lipid-lowering therapeutic approach and/or a more stringent low-density lipoprotein cholesterol target for patients at extreme risk. Regardless of the definitions, this general approach may have a remarkable effect on the treatment of this condition in clinical practice. To help clinicians and patients to better understand the new strategy for the secondary prevention of ASCVD, this review provides a summary highlighting the necessity of further risk stratification among ASCVD patients, how patients at extreme risk can be identified, and the potential impact of applying the new “extreme risk” category in clinical practice.