bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal conduction effects on formation of chromospheric solar tadpole-like jets
Authors: Navarro Anamaría , Lora-Clavijo F D , Murawski K , Poedts Stefaan
Published: November 2020

We measure the effects of non-isotropic thermal conduction on generation of solar chromospheric jets through numerical simulations carried out with the use of one fluid magnetohydrodynamics (MHD) code magnus. Following the work of Srivastava et al. (2018), we consider the atmospheric state with a realistic temperature model and generate the ejection of plasma through a gas pressure driver operating in the top chromosphere. We consider the magnetic field mimicking a flux tube and perform parametric studies by varying the magnetic field strength and the amplitude of the driver. We find that in the case of thermal conduction the triggered jets exhibit a considerably larger energy and mass fluxes and their shapes are more collimated and penetrate more the solar corona than for the ideal MHD equations. Low magnetic fields allow these jets to be more energetic, and larger magnetic fields decrease the enhancement of mass and energy due to the inclusion of the thermal conductivity.
mirisim: a simulator for the Mid-Infrared Instrument on JWST
Authors: Klaassen P D , Geers V C , Beard S M , O’Brien A D , Cossou C , Gastaud R , Coulais A , Schreiber J , Kavanagh P J , Topinka M , Azzollini R , De Meester W , Bouwman J , Glasse A C H , Glauser A M , Law D R , Cracraft M , Murray K , Sargent B , Jones O C , Wright G S
Published: November 2020

The Mid-Infrared Instrument (MIRI) on the James Webb Space Telescope (JWST), has imaging, four coronagraphs, and both low and medium resolution spectroscopic modes. Being able to simulate MIRI observations will help commissioning of the instrument, as well as get users familiar with representative data. We designed the MIRI instrument simulator (mirisim) to mimic the on-orbit performance of the MIRI imager and spectrometers using the Calibration Data Products (CDPs) developed by the MIRI instrument team. The software incorporates accurate representations of the detectors, slicers, distortions, and noise sources along the light path including the telescope’s radiative background and cosmic rays. The software also includes a module that enables users to create astronomical scenes to simulate. mirisim is a publicly available python package that can be run at the command line, or from within python. The outputs of mirisim are detector images in the same uncalibrated data format that will be delivered to MIRI users. These contain the necessary metadata for ingestion by the JWST calibration pipeline.
Polarization of accreting X-ray pulsars. I. A new model
Authors: Caiazzo Ilaria , Heyl Jeremy
Published: November 2020

A new window is opening in high-energy astronomy: X-ray polarimetry. With many missions currently under development and scheduled to launch as early as 2021, observations of the X-ray polarization of accreting X-ray pulsars will soon be available. As polarization is particularly sensitive to the geometry of the emission region, the upcoming polarimeters will shed new light on the emission mechanism of these objects, provided that we have sound theoretical models that agree with current spectroscopic and timing observation and that can make predictions of the polarization parameters of the emission. We here present a new model for the polarized emission of accreting X-ray pulsars in the accretion column scenario that for the first time takes into account the macroscopic structure and dynamics of the accretion region and the propagation of the radiation towards the observer, including relativistic beaming, gravitational lensing, and quantum electrodynamics. In this paper, we present all the details of the model, while in a companion paper, we apply our model to predict the polarization parameters of the bright X-ray pulsar Hercules X-1.
Polarization of accreting X-ray pulsars – II. Hercules X-1
Authors: Caiazzo Ilaria , Heyl Jeremy
Published: November 2020

We employ our new model for the polarized emission of accreting X-ray pulsars to describe the emission from the luminous X-ray pulsar Hercules X-1. In contrast with previous works, our model predicts the polarization parameters independently of spectral formation, and considers the structure and dynamics of the accretion column, as well as the additional effects on propagation due to general relativity and quantum electrodynamics. We find that our model can describe the observed pulse fraction and the pulse shape of the main peak, as well as the modulation of the cyclotron line with phase. We pick two geometries, assuming a single accretion column or two columns at the magnetic poles, that can describe current observations of pulse shape and cyclotron modulation with phase. Both models predict a high polarization fraction, between 60 and 80 per cent in the 1–10 keV range, that is phase and energy dependent, and that peaks at the same phase as the intensity. The phase and energy dependence of the polarization fraction and of the polarization angle can help discern between the different geometries.
The rocky road to quiescence: compaction and quenching of quasar host galaxies at z ∼ 2
Authors: Stacey H R , McKean J P , Powell D M , Vegetti S , Rizzo F , Spingola C , Auger M W , Ivison R J , van der Werf P P
Published: November 2020

We resolve the host galaxies of seven gravitationally lensed quasars at redshift 1.5–2.8 using observations with the Atacama Large (sub)Millimetre Array. Using a visibility plane lens modelling technique, we create pixellated reconstructions of the dust morphology, and CO line morphology and kinematics. We find that the quasar hosts in our sample can be distinguished into two types: (1) galaxies characterized by clumpy, extended dust distributions (Reff ∼ 2 kpc) and mean star formation rate (SFR) surface densities comparable to sub-mm-selected dusty star-forming galaxies (ΣSFR ∼ 3  M⊙ yr−1 kpc−2 ) and (2) galaxies that have sizes in dust emission similar to coeval passive galaxies and compact starbursts (Reff ∼ 0.5 kpc), with high mean SFR surface densities (ΣSFR = 400–4500  M⊙ yr−1 kpc−2 ) that may be Eddington-limited or super-Eddington. The small sizes of some quasar hosts suggest that we observe them at a stage in their transformation into compact spheroids via dissipative contraction, where a high density of dynamically unstable gas leads to efficient star formation and black hole accretion. For the one system where we probe the bulk of the gas reservoir, we find a gas fraction of just 0.06 ± 0.04 and a depletion time-scale of 50 ± 40 Myr, suggesting it is transitioning into quiescence. In general, we expect that the extreme level of star formation in the compact quasar host galaxies will rapidly exhaust their gas reservoirs and could quench with or without help from active galactic nucleus feedback.
GTRD: an integrated view of transcription regulation
Authors: Kolmykov Semyon , Yevshin Ivan , Kulyashov Mikhail , Sharipov Ruslan , Kondrakhin Yury , Makeev Vsevolod J , Kulakovskiy Ivan V , Kel Alexander , Kolpakov Fedor
Published: November 2020

The Gene Transcription Regulation Database (GTRD; http://gtrd.biouml.org/) contains uniformly annotated and processed NGS data related to gene transcription regulation: ChIP-seq, ChIP-exo, DNase-seq, MNase-seq, ATAC-seq and RNA-seq. With the latest release, the database has reached a new level of data integration. All cell types (cell lines and tissues) presented in the GTRD were arranged into a dictionary and linked with different ontologies (BRENDA, Cell Ontology, Uberon, Cellosaurus and Experimental Factor Ontology) and with related experiments in specialized databases on transcription regulation (FANTOM5, ENCODE and GTEx). The updated version of the GTRD provides an integrated view of transcription regulation through a dedicated web interface with advanced browsing and search capabilities, an integrated genome browser, and table reports by cell types, transcription factors, and genes of interest.
tRNA import across the mitochondrial inner membrane inT. bruceirequires TIM subunits but is independent of protein import
Authors: Shikha Shikha , Huot Jonathan L , Schneider André , Niemann Moritz
Published: November 2020

Mitochondrial tRNA import is widespread, but mechanistic insights of how tRNAs are translocated across mitochondrial membranes remain scarce. The parasitic protozoan T. brucei lacks mitochondrial tRNA genes. Consequently, it imports all organellar tRNAs from the cytosol. Here we investigated the connection between tRNA and protein translocation across the mitochondrial inner membrane. Trypanosomes have a single inner membrane protein translocase that consists of three heterooligomeric submodules, which all are required for import of matrix proteins. In vivo depletion of individual submodules shows that surprisingly only the integral membrane core module, including the protein import pore, but not the presequence-associated import motor are required for mitochondrial tRNA import. Thus we could uncouple import of matrix proteins from import of tRNAs even though both substrates are imported into the same mitochondrial subcompartment. This is reminiscent to the outer membrane where the main protein translocase but not on-going protein translocation is required for tRNA import. We also show that import of tRNAs across the outer and inner membranes are coupled to each other. Taken together, these data support the ‘alternate import model’, which states that tRNA and protein import while mechanistically independent use the same translocation pores but not at the same time.
Association of circulating cardiac biomarkers with electrocardiographic abnormalities in chronic kidney disease
Authors: Kula Alexander J , Katz Ronit , Zelnick Leila R , Soliman Elsayed , Go Alan , Shlipak Michael , Deo Rajat , Ky Bonnie , DeBoer Ian , Anderson Amanda , Christenson Rob , Seliger Stephen L , Defilippi Chris , Feldman Harold I , Wolf Myles , Kusek John , Shafi Tariq , He Jiang , Bansal Nisha
Published: November 2020

Background

Among patients with chronic kidney disease (CKD), the circulating cardiac biomarkers soluble ST2 (SST2), galectin-3, growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-T (hsTnT) possibly reflect pathophysiologic processes and are associated with clinical cardiovascular disease. Whether these biomarkers are associated with electrocardiographic findings is not known. The aim of this study was to test the association between serum cardiac biomarkers and the presence of electrocardiographic changes potentially indicative of subclinical myocardial disease in patients with CKD.

Methods

We performed a cross-sectional analysis using 3048 participants from the Chronic Renal Insufficiency Cohort (CRIC) without atrial fibrillation, atrioventricular block, bundle branch block or a pacemaker at the baseline visit. Using logistic regression, we tested the association of each of the five cardiac biomarkers with baseline electrocardiogram (ECG) findings: PR interval >200 ms, QRS interval >100 ms and a prolonged QTc interval. Models were adjusted for demographic variables, measures of kidney function, prevalent cardiovascular disease and cardiovascular risk factors.

Results

In adjusted models, hsTnT levels associated with prolonged PR {odds ratio [OR] 1.23 [95% confidence interval (CI) 1.08–1.40]}, QRS [OR 1.28 (95% CI 1.16–1.42)] and QTc [OR 1.94 (95% CI 1.50–2.51)] intervals. NT-proBNP levels were associated with prolonged QRS [OR 1.11 (95% CI 1.06–1.16)] and QTc [OR 1.82 (95% CI 1.58–2.10)] intervals. SST2, galectin-3 and GDF-15 were not significantly associated with any of the ECG parameters.

Conclusions

hsTnT and NT-proBNP were associated with ECG measures indicative of subclinical myocardial dysfunction. These results may support future research investigating the significance of myocardial ischemia and volume overload in the pathogenesis of dysfunctional myocardial conduction in CKD.
Menthol and Mint Cigarettes and Cigars: Initiation and Progression in Youth, Young Adults and Adults in Waves 1–4 of the PATH Study, 2013–2017
Authors: Villanti Andrea C , Johnson Amanda L , Halenar Michael J , Sharma Eva , Cummings K Michael , Stanton Cassandra A , Delnevo Cristine D , Wackowski Olivia A , Bansal-Travers Maansi , Pearson Jennifer L , Abrams David B , Niaura Raymond S , Fong Geoffrey T , Elton-Marshall Tara , Hatsukami Dorothy , Trinidad Dennis R , Kaufman Annette , Sawdey Michael D , Taylor Ethel V , Slavit Wendy I , Rass Olga , Compton Wilson M , Hyland Andrew
Published: November 2020

Introduction

This study examined in youth (12–17 years), young adults (18–24 years), and adults (25+ years): (1) the prevalence of the first menthol cigarette and menthol/mint cigar use among new tobacco users; (2) association between the first menthol/mint use, subsequent tobacco use, and nicotine dependence ~1 year later compared with the first non-menthol/mint use.

Aims and Methods

Longitudinal analysis of data from Waves 1 to 4 of the Population Assessment of Tobacco and Health (PATH) Study (2013–2017; 10 086 youth and 21 281 adults). Main outcome measures were past 12-month and past 30-day cigarette and cigar use, and nicotine dependence.

Results

Youth and young adult new cigarette users are more likely to smoke a menthol cigarette or indicate that they do not know the flavor compared with adults aged 25+. A greater proportion of adults aged 25+ first used menthol/mint-flavored cigars (13.4%) compared with youth (8.5%) and young adults (7.4%). Among young adults, first use of a menthol cigarette is associated with past 12-month use of cigarettes at the subsequent wave and first use of any menthol/mint-flavored cigars is associated with past 30-day use of these products at the subsequent wave in both youth and young adults. In youth and adults, there were no significant relationships between first use of a menthol/mint cigarette or cigar and nicotine dependence scores at a subsequent wave in multivariable analyses.

Conclusions

The first use of menthol/mint cigarettes and cigars is associated with subsequent cigarette and cigar use in young people aged 12–24.

Implications

This study examined the relationship between initiation with menthol cigarettes and menthol/mint cigars, subsequent tobacco use, and nicotine dependence in US youth, young adults, and adults who participated in Waves 1–4 of the Population Assessment of Tobacco and Health study. New use of menthol cigarettes was associated with greater past 12-month cigarette use in young adults and new use of menthol/mint-flavored cigars was associated with greater past 30-day cigar use in youth and young adults compared with non-menthol use. Initiation with menthol/mint cigarette and cigar products may lead to subsequent use of those products.
Assessment of Testing and Treatment of Asymptomatic Bacteriuria Initiated in the Emergency Department
Authors: Petty Lindsay A , Vaughn Valerie M , Flanders Scott A , Patel Twisha , Malani Anurag N , Ratz David , Kaye Keith S , Pogue Jason M , Dumkow Lisa E , Thyagarajan Rama , Hsaiky Lama M , Osterholzer Danielle , Kronick Steven L , McLaughlin Elizabeth , Gandhi Tejal N
Published: November 2020

Background

Reducing antibiotic use in patients with asymptomatic bacteriuria (ASB) has been inpatient focused. However, testing and treatment is often started in the emergency department (ED). Thus, for hospitalized patients with ASB, we sought to identify patterns of testing and treatment initiated by emergency medicine (EM) clinicians and the association of treatment with outcomes.

Methods

We conducted a 43-hospital, cohort study of adults admitted through the ED with ASB (February 2018–February 2020). Using generalized estimating equation models, we assessed for (1) factors associated with antibiotic treatment by EM clinicians and, after inverse probability of treatment weighting, (2) the effect of treatment on outcomes.

Results

Of 2461 patients with ASB, 74.4% (N = 1830) received antibiotics. The EM clinicians ordered urine cultures in 80.0% (N = 1970) of patients and initiated treatment in 68.5% (1253 of 1830). Predictors of EM clinician treatment of ASB versus no treatment included dementia, spinal cord injury, incontinence, urinary catheter, altered mental status, leukocytosis, and abnormal urinalysis. Once initiated by EM clinicians, 79% (993 of 1253) of patients remained on antibiotics for at least 3 days. Antibiotic treatment was associated with a longer length of hospitalization (mean 5.1 vs 4.2 days; relative risk = 1.16; 95% confidence interval, 1.08–1.23) and Clostridioides difficile infection (CDI) (0.9% [N = 11] vs 0% [N = 0]; P = .02).

Conclusions

Among hospitalized patients ultimately diagnosed with ASB, EM clinicians commonly initiated testing and treatment; most antibiotics were continued by inpatient clinicians. Antibiotic treatment was not associated with improved outcomes, whereas it was associated with prolonged hospitalization and CDI. For best impact, stewardship interventions must expand to the ED.
Gender economics: an assessment
Authors: Sevilla Almudena
Published: November 2020

Concerns about gender equality have jumped to the forefront of public debate in recent years, and Gender Economics is slowly affirming its place as a major field of study. This assessment examines where we are in terms of gender equality. It reviews the theoretical foundations that can explain existing inequalities, and documents the empirical findings supported by the theories, identifying avenues for future research and providing a fruitful framework to think about the effectiveness of policies and interventions targeting gender inequality. In doing so, I provide the foundations against which the contributions in this issue can be placed.
Exploring the Development, Validity, and Utility of the Short-Form Version of the CHoice of Outcome In Cbt for PsychosEs: A Patient-Reported Outcome Measure of Psychological Recovery
Authors: Webb Rebecca , Bartl Gergely , James Bryony , Skan Rosie , Peters Emmanuelle , Jones Anna-Marie , Garety Philippa , Kuipers Elizabeth , Hayward Mark , Greenwood Kathryn
Published: November 2020

The original CHoice of Outcome In Cbt for psychosEs (CHOICE) measure was designed in collaboration with experts by experience as a patient-reported “Psychological Recovery” outcome measure for cognitive-behavioral therapy for psychosis (CBTp). A short version (CHOICE-SF) was developed to use as a brief outcome measure, with a focus on sensitivity to change, for use in future research and practice. CHOICE-SF was developed and validated using 3 separate samples, comprising 640 service users attending 1 of 2 transdiagnostic clinics for (1) CBTp or (2) therapies for voice hearing or (3) who took part in the treatment as usual arm of a trial. In the initial subsample of 69 participants, items from the original CHOICE measure with medium to large effect sizes for change pre- to post-CBTp were retained to form the CHOICE-SF. Internal consistency, construct validity, and sensitivity to change were confirmed, and the factor structure was examined in 242 participants. Specificity was confirmed by comparison with 44 participants who completed CHOICE at 2 time points but did not receive therapy. Validation of CHOICE-SF was carried out by confirming factor structure and sensitivity to change in a new sample of 354 and a subsample of 51 participants, respectively. The CHOICE-SF comprised 11 items and 1 additional personal goal item. A single-factor structure was confirmed, with high internal consistency, construct validity, and sensitivity to change. The CHOICE-SF is a brief, psychometrically robust measure to assess change following psychological therapies in research and clinical practice for people with psychosis and severe mental illness.
The Color Line in Southeastern Europe: A Du Boisian Analysis of the Yugoslav Region
Authors: Kuperberg Jeremy
Published: November 2020

Sociologists apply the theory and methods of W.E.B. Du Bois to cases of widely-understood racial difference, often using the historical black-white divide of the United States as a default case. As a result, there is a dearth of Du Boisian analysis of phenomena that are primarily conceptualized using non-racial categories such as nation, ethnicity, or class. However, Du Bois's theories and the racialized structures they address are global in scope. This article uses Du Boisian theory to examine identity discourse surrounding the Yugoslav region, an ostensibly white space at the blurred border of Europe and historical empire. This article places Du Bois in conversation with critical Balkan scholarship to reveal the ways in which South Slavic populations experience unique versions of racialized double consciousness, despite assumptions of whiteness. This framing illuminates the presence of race and empire otherwise obscured in discussions of historical conflict. We can better understand the relevance of a global Du Boisian project if we reject the assumption that processes of racialization map neatly onto bounded populations or geographic spaces.
Bottleneck, Isolate, Amplify, Select (BIAS) as a mechanistic framework for intracellular population dynamics of positive-sense RNA viruses
Authors: Qu Feng , Zheng Limin , Zhang Shaoyan , Sun Rong , Slot Jason , Miyashita Shuhei
Published: November 2020

Many positive-sense RNA viruses, especially those infecting plants, are known to experience stringent, stochastic population bottlenecks inside the cells they invade, but exactly how and why these populations become bottlenecked are unclear. A model proposed ten years ago advocates that such bottlenecks are evolutionarily favored because they cause the isolation of individual viral variants in separate cells. Such isolation in turn allows the viral variants to manifest the phenotypic differences they encode. Recently published observations lend mechanistic support to this model and prompt us to refine the model with novel molecular details. The refined model, designated Bottleneck, Isolate, Amplify, Select (BIAS), postulates that these viruses impose population bottlenecks on themselves by encoding bottleneck-enforcing proteins (BNEPs) that function in a concentration-dependent manner. In cells simultaneously invaded by numerous virions of the same virus, BNEPs reach the bottleneck-ready concentration sufficiently early to arrest nearly all internalized viral genomes. As a result, very few (as few as one) viral genomes stochastically escape to initiate reproduction. Repetition of this process in successively infected cells isolates viral genomes with different mutations in separate cells. This isolation prevents mutant viruses encoding defective viral proteins from hitchhiking on sister genome-encoded products, leading to the swift purging of such mutants. Importantly, genome isolation also ensures viral genomes harboring beneficial mutations accrue the cognate benefit exclusively to themselves, leading to the fixation of such beneficial mutations. Further interrogation of the BIAS hypothesis promises to deepen our understanding of virus evolution and inspire new solutions to virus disease mitigation.
A Pilot Trial Examining the Merits of Combining Amantadine and Repetitive Transcranial Magnetic Stimulation as an Intervention for Persons With Disordered Consciousness After TBI
Authors: Bender Pape Theresa L. , Herrold Amy A. , Livengood Sherri L. , Guernon Ann , Weaver Jennifer A. , Higgins James P. , Rosenow Joshua M. , Walsh Elyse , Bhaumik Runa , Pacheco Marilyn , Patil Vijaya K. , Kletzel Sandra , Conneely Mark , Bhaumik Dulal K. , Mallinson Trudy , Parrish Todd
Published: November 2020

Objective:

Report pilot findings of neurobehavioral gains and network changes observed in persons with disordered consciousness (DoC) who received repetitive transcranial magnetic stimulation (rTMS) or amantadine (AMA), and then rTMS+AMA.

Participants:

Four persons with DoC 1 to 15 years after traumatic brain injury (TBI).

Design:

Alternate treatment-order, within-subject, baseline-controlled trial.

Main Measures:

For group and individual neurobehavioral analyses, predetermined thresholds, based on mixed linear-effects models and conditional minimally detectable change, were used to define meaningful neurobehavioral change for the Disorders of Consciousness Scale-25 (DOCS) total and Auditory-Language measures. Resting-state functional connectivity (rsFC) of the default mode and 6 other networks was examined.

Results:

Meaningful gains in DOCS total measures were observed for 75% of treatment segments and auditory-language gains were observed after rTMS, which doubled when rTMS preceded rTMS+AMA. Neurobehavioral changes were reflected in rsFC for language, salience, and sensorimotor networks. Between networks interactions were modulated, globally, after all treatments.

Conclusions:

For persons with DoC 1 to 15 years after TBI, meaningful neurobehavioral gains were observed after provision of rTMS, AMA, and rTMS+AMA. Sequencing and combining of treatments to modulate broad-scale neural activity, via differing mechanisms, merits investigation in a future study powered to determine efficacy of this approach to enabling neurobehavioral recovery.
Safety Considerations for the Use of Transcranial Magnetic Stimulation as Treatment for Coma Recovery in People With Severe Traumatic Brain Injury
Authors: Kletzel Sandra L. , Aaronson Alexandra L. , Guernon Ann , Carbone Christina , Chaudhry Noor , Walsh Elyse , Conneely Mark , Patil Vijaya , Roth Elliott , Steiner Monica , Pacheco Marilyn , Rosenow Joshua , Bender Pape Theresa L.
Published: November 2020

Objective:

For persons in states of disordered consciousness (DoC) after severe traumatic brain injury (sTBI), we report cumulative findings from safety examinations, including serious adverse events (AEs) of a repetitive transcranial magnetic stimulation (rTMS) parameter protocol in 2 different studies.

Participants:

Seven persons in states of DoC after sTBI with widespread neuropathology, but no large lesions in proximity to the site of rTMS. One participant had a ventriculoperitoneal shunt with programmable valve.

Methods:

Two clinical trials each providing 30 rTMS sessions to the right or left dorsolateral prefrontal cortex, involving 300 to 600 pulses over 1 or 2 sessions daily. One study provided concomitant amantadine. Safety indicators monitored related to sleep, temperature, blood pressure, skin integrity, sweating, weight loss, infections, and seizure.

Results:

Average changes for monitored indicators were of mild severity, with 75 nonserious AEs and 1 serious AE (seizure). The participant incurring a seizure resumed rTMS while taking antieplieptics without further seizure activity.

Conclusions:

Considering elevated risks for this patient population and conservative patient selection, findings indicate a relatively safe profile for the specified rTMS protocols; however, potential for seizure induction must be monitored. Future research for this population can be broadened to include patients previously excluded on the basis of profiles raising safety concerns.
SYSTEMIC FACTORS AND EARLY TREATMENT RESPONSE TO INTRAVITREAL INJECTION FOR DIABETIC MACULAR EDEMA
Authors: Hwang Hyeseong , Lee Hwanho , Kim Jin Young , Lee Suhwan , Seo Eoi Jong , Chae Ju Byung , Kim Dong Yoon
Published: November 2020

Purpose:

To investigate the effect of systemic factors on early treatment response to intravitreal bevacizumab injection (IVBI) and intravitreal dexamethasone implant (IVDI) in patients with diabetic macular edema (DME).

Methods:

We reviewed the medical records of 117 treatment naïve DME patients who underwent IVBI. We divided the patients according to their IVBI response. An IVDI was performed in patients with poor response to IVBIs. We investigated the various systemic factors of diabetic patients and examined the relationship between systemic factors and the treatment response to IVBI and IVDI.

Results:

In a total of 117 treatment naïve DME eyes, 61 eyes (52.14%) were classified as IVBI responders. An IVDI was performed in 23 of 56 eyes with poor response to IVBI, and 17 eyes (73.91%) had a good response. Among various systemic factors of patients with diabetes, renal function (blood urea nitrogen, creatinine, and estimated glomerular filtration rate) showed a significant negative correlation with central subfield retinal thickness improvement after treatment (P < 0.05). However, there was no difference in HbA1C levels regarding the treatment response to IVBI and IVDI.

Conclusion:

Renal function was significantly worse in patients with a poor response to IVBI and IVDI. Renal function could be used as a possible predictor for treatment response in certain patients with DME. Furthermore, for patients with DME with poor responses to anti–vascular endothelial growth factor or steroid treatments, assessment of renal function could help explain the poor treatment response.
Discrepancy between the results of one-stage and chromogenic factor VIII:C assays in patients with mild/moderate hemophilia A
Authors: Vosough Fatemeh , Ahmadinejad Minoo , Toogeh Gholamreza , Karimi Katayoun , Homayoun Sanaz , Managhchi Mohammad Reza , Arabkhazaeli Ali
Published: November 2020

Diagnosis of hemophilia A is generally based on the measurement of plasma factor VIII activity (FVIII:C) using the one-stage assay (OSA) or the two-stage chromogenic substrate assay (CSA). The results of these methods show considerable discrepancy in about one-third of non-severe hemophilia A patients. The aim of this study was to assess the prevalence of FVIII:C assay discrepancy in non-severe hemophilia A patients in Iran and the relationship between the bleeding tendency with the level of FVIII:C by each method. Patients registered as mild or moderate hemophilia A in hemophilia clinic of Imam Khomeini Hospital were included. In each patient, FVIII:C level was assessed using one-stage (FVIII:C1) and chromogenic (FVIII:CR) methods. Assay discrepancy was defined as a two-fold or greater difference between the results of two assays. Bleeding tendency of the patients was recorded based on ‘ISTH-BAT’. Sixty male patients were eligible for the study. The levels of FVIII:C1 was higher than FVIII:CR in 90% of patients. Assay discrepancy was seen in 41 (68%) patients. The classification of hemophilia A in 23 (38%) patients was modified by chromogenic method. No significant correlation was noted between the results of ISTH BAT with FVIII:C levels of each method. Regarding the prevalence of FVIII:C assay discrepancy in 2/3 of our non-severe hemophilia A patients, high rate of disease severity modification by chromogenic method and no significant relation between the clinical bleeding phenotype with any method, the authors highly recommend to perform both FVIII:C assays for the diagnosis and classification of non-severe hemophilia A.
Cognitive Remediation for Inpatients With Schizophrenia
Authors: Buonocore Mariachiara , Agostoni Giulia , Bechi Margherita , Inguscio Emanuela , Gritti Davide , Anchora Lavinia , Spangaro Marco , Cocchi Federica , Bianchi Laura , Guglielmino Carmelo , Sormani Marika , Russotti Massimiliano , Bosia Marta , Cavallaro Roberto
Published: November 2020

Computer-assisted cognitive remediation (CACR) is a computer-based rehabilitation treatment aimed at improving cognition and at developing strategies that can be applied to various functional areas. Different protocols are currently used with great variability over the intensity and duration of treatments. In this study, we evaluated the effects of a brief and intensive CACR training (i.e., 15 sessions for 3 weeks) on cognitive domains, as well as the durability of cognitive gains and their generalization to functional areas, 3 months after CACR training. Thirty-eight patients with schizophrenia were recruited and assessed for psychopathology, cognitive performance, and functioning before the rehabilitative intervention. Patients were reassessed for cognition after CACR rehabilitation. Moreover, a subsample of 13 patients was evaluated for cognition and functioning 3 months after CACR completion. Results show significant improvements in multiple cognitive domains after CACR. Furthermore, 3 months after CACR completion, significant improvements were also detected in executive functions and daily functioning. This study suggests that a brief and intense CACR training is effective on cognitive and functional domains and that it could be feasible and affordable for health care services, thus offering patients the best options for fulfilling recovery goals.
Identification of Immunohistochemical Reagents for In Situ Protein Expression Analysis of Coronavirus-associated Changes in Human Tissues
Authors: Szabolcs Matthias , Sauter Jennifer L. , Frosina Denise , Geronimo Jerica A. , Hernandez Enmily , Selbs Elena , Rapkiewicz Amy V. , Rekhtman Natasha , Baine Marina K. , Jäger Elke , Travis William D. , Jungbluth Achim A.
Published: November 2020

We studied the suitability of commercially available monoclonal antibodies (mAbs) for the immunohistochemical (IHC) detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in standard archival specimens. Antibodies were screened on HEK293 cells transfected with viral nucleoprotein, S1 subunit and S2 subunit of spike protein and on untransfected cells, as well as a panel of normal tissue. Lung tissue with presence of SARS-CoV2 confirmed by in situ hybridization (ISH) was also used. A total of 7 mAbs were tested: (1) mAb 001 (Sino Biological, 40143-R001), (2) mAb 007 (Sino Biological, 40150-R007), (3) mAb 019 (Sino Biological, 40143-R019), (4) mAb 1A9 (GeneTex, GTX632604), (5) mAb ABM19C9 (Abeomics, 10-10007), (6) FIPV3-70 (Santa Cruz, SC-65653), and (7) mAb 6F10 (BioVision, A2060). Only 2 mAbs, clone 001 to the nucleoprotein and clone 1A9 to the S2 subunit spike protein displayed specific immunoreactivity. Both clones showed strong staining in the acute phase of COVID-19 pneumonia, mostly in areas of acute diffuse alveolar damage, but were not completely congruent. Viral protein was also found in kidney tubules, endothelia of multiple organs and a nasal swab of a patient with persistent SARS-CoV2 infection. The other tested reagents were either poorly reactive or demonstrated nonspecific staining in tissues and lesions not infected by SARS-CoV2. Our study demonstrates that rigid specificity testing is mandatory for the evaluation of mAbs to SARS-CoV2 and that clones 001 to nucleoprotein and 1A9 to S2 subunit spike protein are useful for the in situ detection of SARS-CoV2.
HER2 Mutated and Nonmutated Non–small Cell Lung Carcinomas Can Harbor Heterogeneous HER2 Gene Amplification and HER2 Protein Expression
Authors: Castillon Marine , Bourhis Amélie , Quintin-Roué Isabelle , Uguen Arnaud
Published: November 2020

Molecular analyses have become mandatory for treatment choices in patients with advanced non–small cell lung cancers (NSCLC). Among them, HER2 gene mutation, HER2 gene amplification, and HER2 protein expression consist in potential targets of various treatments. Tumor heterogeneity and overlapping of molecular alterations may cause dilemmas in treatment choices but to date there are few that reported about HER2 with discrepant data. We led a retrospective study evaluating HER2 protein expression and HER2 gene/chromosome 17 copy number variations across different tumor areas and samples from patients with advanced NSCLC harboring HER2 gene mutations and other oncogenic mutations. Among patients with HER2-mutated (10 patients) and nonmutated lung adenocarcinomas (10 patients), we observed frequent heterogeneous HER2 protein expression with no correlation with HER2 gene copy number variations. HER2 gene amplification was observed in 6 patients (3 HER2-mutated and 3 HER2-nonmutated), but with intrasample heterogeneity in 2 cases and intersample heterogeneity in another case. Our small case series emphasizes the potential overlapping and spatial heterogeneity of HER2 alterations in NSCLC, which must be taken into account as a limitation in building predictive strategies accompanying the development of anti-HER2 therapeutic strategies in patients with advanced NSCLC.
Influence of Sex and Age on Ratings of Confidence and Relevance in Continuing Certification Longitudinal Assessment
Authors: Kinney Carolyn L. , Raddatz Mikaela M. , Robinson Lawrence R.
Published: November 2020

Objective

Longitudinal assessments use spaced repetition of items to facilitate learning. Algorithms selecting repetition items can prioritize various properties for future presentation. The purpose of this pilot study was to evaluate the relationship between participant ratings of item-specific confidence and/or practice relevance and participant age, sex, and response correctness.

Design

This is a prospective quality improvement study of 403 American Board of Physical Medicine and Rehabilitation diplomates with time-limited certificates. Participants answered 20 items quarterly over four quarters, rating each item on its relevance to their practice and their confidence in their response.

Results

The relationship between sex and ratings of response confidence was significant, with women less likely than men to be confident in their responses, regardless of correctness. Younger physicians were significantly more confident in their responses and rated items as more practice relevant.

Conclusions

Women physicians were less confident than men in their item-specific confidence ratings, regardless of correctness, on the American Board of Physical Medicine and Rehabilitation continuing certification longitudinal knowledge assessment. Older physicians were less confident in their responses than younger physicians. The findings supported the American Board of Physical Medicine and Rehabilitation prioritization of response correctness and practice relevance, rather than response confidence, to select items for spaced repetition in American Board of Physical Medicine and Rehabilitation’s continuing certification longitudinal assessment.
Metformin Inhibits Transforming Growth Factor β–Induced Fibrogenic Response of Human Dermal Fibroblasts and Suppresses Fibrosis in Keloid Spheroids
Authors: Jeon Hong Bae , Roh Hyun , Ahn Hyo Min , Lee Ju Hee , Yun Chae Ok , Roh Tai Suk , Lee Won Jai
Published: November 2020

Accumulation of excessive extracellular matrix (ECM) and aberrant transforming growth factor β (TGF-β) signaling pathway function can be potential therapeutic targets for keloid treatment. In this study, we examined the antifibrotic effect of metformin as a suppressor of TGF-β signaling pathways in human dermal fibroblasts (HDFs) and keloid spheroids. Human dermal fibroblasts were stimulated with TGF-β (10 ng/mL) and treated with metformin (10 mM). The mRNA and protein expression of ECM components were evaluated by quantitative polymerase chain reaction, western blot, and immunofluorescence assay. In addition, we immunohistochemically examined the expression levels of ECM proteins in keloid spheroids. After addition of metformin (10 mM), collagen types I and III and elastin mRNA levels were significantly decreased in HDFs, and collagen type I protein level was significantly decreased. In addition, the expression levels of collagen types I and III, fibronectin, and elastin were significantly reduced in keloid spheroids after treatment with metformin (100 mM). Collagen types I and III and p-Smad2/3 complex proteins were decreased in metformin-treated keloid spheroids. These findings indicated that metformin inhibits the expression of ECM components in TGF-β–stimulated HDFs and keloid spheroids. Therefore, we suggest the potential of metformin as an effective agent for the treatment of keloids.
COVID-19 in Lung Transplant Recipients
Authors: Messika Jonathan , Eloy Philippine , Roux Antoine , Hirschi Sandrine , Nieves Ana , Le Pavec Jérôme , Sénéchal Agathe , Saint Raymond Christel , Carlier Nicolas , Demant Xavier , Le Borgne Aurélie , Tissot Adrien , Debray Marie-Pierre , Beaumont Laurence , Renaud-Picard Benjamin , Reynaud-Gaubert Martine , Mornex Jean-François , Falque Loïc , Boussaud Véronique , Jougon Jacques , Mussot Sacha , Mal Hervé ,   for the French Group of Lung Transplantation
Published: November 2020

Background.

A concern about the susceptibility of immunocompromised patients to the worldwide pandemic of coronavirus disease 2019 (COVID-19) has been raised. We aimed at describing COVID-19 infections in the French cohort of lung transplant (LT) patients.

Methods.

Multicenter nationwide cohort study of all LT recipients with COVID-19 diagnosed from March 1 to May 19, 2020. Recipient main characteristics and their management were retrieved. Hospitalization characteristics, occurrence of complications and survival were analyzed.

Results.

Thirty-five LT patients with a COVID-19 infection were included. Median age was 50.4 (40.6–62.9) years, 16 (45.7%) were female, and 80% were double-LT recipients. Infection was community-acquired in 25 (71.4%). Thirty-one (88.6%) required hospitalization, including 13 (41.9%) in the intensive care unit. The main symptoms of COVID-19 were fever, cough, and diarrhea, present in 71.4%, 54.3%, and 31.4% of cases, respectively. Extension of pneumonia on chest CT was moderate to severe in 51.4% of cases. Among the 13 critically ill patients, 7 (53.9%) received invasive mechanical ventilation. Thrombotic events occurred in 4 patients. Overall survival rate was 85.7% after a median follow-up of 50 days (41.0–56.5). Four of 5 nonsurvivors had had bronchial complications or intensification of immunosuppression in the previous weeks. On univariate analysis, overweight was significantly associated with risk of death (odds ratio, 16.0; 95% confidence interval, 1.5-170.6; P = 0.02).

Conclusions.

For the 35 LT recipients with COVID-19, the presentation was severe, requiring hospitalization in most cases, with a survival rate of 85.7%.
Unraveling the Crucial Roles of FoxP3+ Regulatory T Cells in Vascularized Composite Allograft Tolerance Induction and Maintenance
Authors: Anggelia Madonna Rica , Cheng Hui-Yun , Chuang Wen-Yu , Hsieh Yun-Huan , Wang Aline Yen Ling , Lin Chih-Hung , Wei Fu-Chan , Brandacher Gerald , Lin Cheng-Hung
Published: November 2020

Background.

The role of regulatory T cells (Treg) in tolerance induction of vascularized composite allotransplantation (VCA) remains unclear. This study was designed to examine characteristics of Treg after VCA and their capacity to rescue allografts from rejection.

Methods.

Osteomyocutaneous allografts were transplanted from Balb/c to C57BL/6 mice. All mice received costimulatory blockade and a short course of rapamycin. To elucidate the role of Treg for tolerance induction, Treg depletion was performed at postoperative day (POD) 0, 30, or 90. To assess capacity of Treg to rescue allografts from rejection, an injection of 2 × 106 Treg isolated from tolerant mice was applied.

Results.

Eighty percent of VCA recipient mice using costimulatory blockade and rapamycin regimen developed tolerance. The tolerant recipients had a higher ratio of circulating Treg to effector T cells and elevated interleukin-10 at POD 30. A significantly higher rejection rate was observed when Treg were depleted at POD 30. But Treg depletion at POD 90 had no effect on tolerance. Treg from tolerant recipients showed stronger suppressive potential and the ability to rescue allografts from rejection. Furthermore, transplanted Treg-containing skin grafts from tolerant mice delayed rejection elicited by adoptively transferred effector T cells to Rag2–/– mice.

Conclusions.

Circulating Treg are crucial for inducing VCA tolerance in the early posttransplant phase, and allograft-residing Treg may maintain tolerance. Treg may, therefore, serve as a potential cellular therapeutic to improve VCA outcomes.
Summary of International Recommendations for Donation and Transplantation Programs During the Coronavirus Disease Pandemic
Authors: Weiss Matthew J. , Lalani Jehan , Patriquin-Stoner Chelsea , Dieudé Mélanie , Hartell David , Hornby Laura , Shemie Sam D. , Wilson Lindsay , Mah Allison
Published: November 2020

Background.

The COVID-19 pandemic has disrupted all aspects of the international organ donation and transplantation (ODT) system. Multiple organizations have developed guidance, but to date, no comparative summary has emerged to understand differences in existing recommendations.

Methods.

We developed and applied a comparative methodology to a convenience sample of recommendations available on The Transplantation Society website. Document types were classified according to characteristics such as type of organization (eg, governing body or professional society) and geographic region. Recommendations were grouped according to content, and summaries were posted on a public website. This process is ongoing and will be updated as new recommendations become available.

Results.

Eighteen documents were extracted in the initial review. All documents were based on expert opinion, and none described a formal literature review or adherence with clinical guideline development processes. Recommendation categories included screening of potential donors, risk assessment of potential recipients, posttransplant risk, living/paired donation, protection of ODT professionals, and ethics/logistics. While many documents included similar recommendations, such as the need to screen and test patients who are potential donors, there was variation on some topics. Type of recommended laboratory testing varied with 64% recommending nasopharyngeal swabs, 43% oropharyngeal, and 24% bronchial aspirates. Updated results are available at https://cdtrp.ca/en/covid-19-international-recommendations-for-odt/

Conclusions.

The current state of COVID-19 ODT recommendations is limited to expert opinion. Substantial variation exists regarding recommendations, which are based on emerging but currently low-quality evidence. This summary of existing recommendations will serve to inform priorities for evidence-based recommendations.
Central and peripheral stress-induced epigenetic mechanisms of resilience
Authors: Dudek Katarzyna Anna , Kaufmann Fernanda Neutzling , Lavoie Olivier , Menard Caroline
Published: November 2020

Purpose of review

Resilience is an adaptation process presented by an individual despite facing adversities. Epigenetic changes, such as histone acetylation/methylation and DNA methylation, have been demonstrated to mediate stress response. In this review, we summarize recent findings on epigenetic mechanisms contributing to stress resilience.

Recent findings

: Epigenetic modifications of genes involved in synaptic plasticity, endocrine, immune, and vascular systems are linked to resilience. For instance, increased DNA methylation of the nonneuronal growth factor Gdnf in specific brain regions promotes stress resilience. Additionally, high DNA methylation at the glucocorticoid receptor gene was associated with resilience in both rodents and humans. At the immune level, chronic stress induces increased DNA methylation at IL6 gene, a mediator of stress vulnerability. Moreover, epigenetic adaptations of the blood--brain barrier have been recently associated with stress resilience, which could lead to innovative therapeutic approaches to treat depression.

Identification of both central and peripheral epigenetic changes promoting stress resilience represent promising novel targets in the development of preventive and personalized medicine. Nevertheless, more research is needed to establish sex specific differences and to identify novel epigenetic mechanisms, such as serotonylation and dopaminylation, that hold great promises for the field of psychiatry.