bluuebunny/crossref_metadata_2025 huggingface dataset:
Inverse tides in pulsating binary stars
Authors: Fuller Jim
Published: November 2020

In close binary stars, the tidal excitation of pulsations typically dissipates energy, causing the system to evolve towards a circular orbit with aligned and synchronized stellar spins. However, for stars with self-excited pulsations, we demonstrate that tidal interaction with unstable pulsation modes can transfer energy in the opposite direction, forcing the spins of the stars away from synchronicity, and potentially pumping the eccentricity and spin–orbit misalignment angle. This ‘inverse’ tidal process only occurs when the tidally forced mode amplitude is comparable to the mode’s saturation amplitude, and it is thus most likely to occur in main-sequence gravity mode pulsators with orbital periods of a few days. We examine the long-term evolution of inverse tidal action, finding the stellar rotation rate can potentially be driven to a very large or very small value, while maintaining a large spin–orbit misalignment angle. Several recent asteroseismic analyses of pulsating stars in close binaries have revealed extremely slow core rotation periods, which we attribute to the action of inverse tides.
Sweat Equity in U.S. Private Business*
Authors: Bhandari Anmol , McGrattan Ellen R
Published: November 2020

We develop a theory of sweat equity—the value of business owners’ time and expenses to build customer bases, client lists, and other intangible assets. We discipline the theory using data from U.S. national accounts, business censuses, and brokered sales to estimate a value for sweat equity in the private business sector equal to 1.2 times U.S. GDP, which is about the same magnitude as the value of fixed assets in use in these businesses. For a typical owner, 26% of the sweat equity is transferable through inheritance or sale. The equity values are positively correlated with business incomes and standard measures of markups based on accounting data, but not with owners’ financial assets or standard measures of business total factor productivity. We use our theory to show that abstracting from sweat activity leads to a significant understatement of the effects of lowering business income tax rates on private business activity for both the extensive and intensive margins. Despite finding larger responses, our model’s implied tax elasticities of establishments and owner hours are in line with empirical estimates in the public finance literature. Allowing for financial constraints and superstar firms does not overturn our main findings.
Use of a Modal Model in Predicting Propagation from a Point Source Over Grooved Ground
Authors: Mellish Steve , Taherzadeh Shahram , Attenborough Keith
Published: November 2020

Regularly spaced low walls and rectangular lattices on a hard ground have been investigated as a means for reducing noise levels from surface transport. Predictions of the insertion loss of such surfaces has involved the use of computationally intensive numerical methods such as the Boundary Element Method (BEM) or Finite difference techniques (FDTD and PSTD). By considering point-to-point propagation above regularly spaced acoustically hard grooves with rectangular cross sections, a modal model used hitherto to predict electromagnetic and ultrasonic surface waves is adapted to derive an effective impedance for such a grooved surface. When this effective impedance is used in the classical theory for propagation from a point source above an impedance plane, the modal model enables predictions of excess attenuation spectra that compare closely with those obtained by numerical methods but take a fraction of the time. Also the modal method is extended to predict excess attenuation spectra above phase gradient metasurfaces with porous material in each constituent groove.
Cochrane Schizophrenia Group’s Study-Based Register of Randomized Controlled Trials: Development and Content Analysis
Authors: Shokraneh Farhad , Adams Clive E
Published: November 2020

Background

Study-based registers facilitate systematic reviews through shortening the process for review team and reducing considerable waste during the review process. Such a register also provides new insights about trends of trials in a sub-specialty. This paper reports development and content analysis of Cochrane Schizophrenia Group’s Study-Based Register.

Methods

The randomized controlled trials were collected through systematic searches of major information sources. Data points were extracted, curated and classified in the register. We report trends using regression analyses in Microsoft Excel and we used GIS mapping (GunnMap 2) to visualize the geographical distribution of the origin of schizophrenia trials.

Results

Although only 17% of trials were registered, the number of reports form registered trials is steadily increasing and registered trials produce more reports. Clinical trial registers are main source of trial reports followed by sub-specialty journals. Schizophrenia trials have been published in 23 languages from 90 countries while 105 nations do not have any reported schizophrenia trials. Only 9.7% of trials were included in at least one Cochrane review. Pharmacotherapy is the main target of trials while trials targeting psychotherapy are increasing in a continuous rate. The number of people randomized in trials is on average 114 with 60 being the most frequent sample size.

Conclusions

Curated datasets within the register uncover new patterns in data that have implications for research, policy, and practice for testing new interventions in trials or systematic reviews.
Triple Canal Occlusion for the Treatment of Intractable Menière's Disease
Authors: Gill Charn , Muzaffar Jameel , Kumar Raghu , Irving Richard
Published: November 2020

Objective:

Menière's disease can be a debilitating condition but in most cases the symptoms are controlled by lifestyle changes and medical management. However, some patients remain symptomatic despite medical treatment and have the option of more invasive surgical treatments. Surgical intervention for Menière's includes a range of interventions from grommet insertion, intratympanic steroids/Gentamicin, endolymphatic sac decompression, labyrinthectomy, and vestibular neurectomy. A recently described technique involves the occlusion of all three semi-circular canals as an alternative in intractable Menière's disease.

Study Design:

This is a case series of three patients who underwent triple canal occlusion for the treatment of intractable Menière's disease.

Setting:

Patients were selected from those who were referred to Queen Elizabeth Hospital in Birmingham, a tertiary referral center.

Patients:

Patients who were severely symptomatic despite medical treatment who were considering ablative therapy were offered the option of triple canal occlusion as an alternative.

Intervention:

We report a series of Menière's patients treated by triple canal occlusion, describe the rationale behind this intervention, the surgical technique, and preliminary results.

Main Outcome Measure:

Each patient was followed up for a minimum of 2 years following the procedure. The main outcomes measures were the class of vertigo control and hearing threshold levels according to the American Academy of Otolaryngology–Head and Neck Surgery guidelines.

Results:

Of the three patients, two were men and one was woman, the age range was 45 years to 61 years old. Two patients with unilateral disease achieved class A control whereas one patient with bilateral disease achieved class B control. Two patients who underwent the procedure had little or no effect to their hearing on the treated side however one patient suffered a 30 dB hearing loss on the operative side.

Conclusions:

Based on our limited experience and the early reports in the literature we consider that there are potential patient benefits for triple canal occlusion for intractable Menière's disease as an alternative to vestibular neurectomy due to the reduced morbidity and long-term efficacy.
Middle Ear Viral Load Considerations in the COVID-19 Era: A Systematic Review
Authors: Liaw Jeffrey , Saadi Robert , Patel Vijay A. , Isildak Huseyin
Published: November 2020

Objective:

To systematically review the available medical literature to investigate the viral load in the middle ear and mastoid cavity and the potential risk of exposure to airborne viruses during otologic surgery.

Data Sources:

PubMed, MEDLINE, and Cochrane databases.

Study Selection:

This review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Protocol.

Data Extraction:

Using the Boolean method and relevant search term combinations for terms “mastoid,” “middle ear,” “virus,” “exposure” “COVID-19” “SARS-CoV-2.” PubMed, MEDLINE, and Cochrane databases were queried. A total of 57 abstracts were identified and screened by two independent reviewers. Following inclusion and exclusion criteria, 18 studies were selected for the final analysis.

Data Synthesis:

Due to the heterogeneity of clinical data, a meta-analysis was not feasible.

Results:

Rhinovirus, followed by respiratory syncytial virus are reported to be the most prevalent viruses in MEF samples but formal statistical analysis is precluded by the heterogeneity of the studies. Drilling was identified to have the highest risk for aerosol generation and therefore viral exposure during otologic Surgery.

Conclusions:

The medical literature has consistently demonstrated the presence of nucleic acids of respiratory viruses involving the middle ear, including SARS-CoV2 in a recent postmortem study. Although no in vivo studies have been conducted, due to the likely risk of transmission, middle ear and mastoid procedures, particularly involving the use of a drill should be deferred, if possible, during the pandemic and enhanced personal protective equipment (PPE) used if surgery is necessary.
Endocannabinoid system and cannabis hyperemesis syndrome: a narrative update
Authors: Perisetti Abhilash , Goyal Hemant
Published: November 2020

Cannabis use has been increasing in the United States and throughout the world. It is derived from one of the earliest plants cultivated by humans – Cannabis sativa. Cannabis (also called marijuana) is the most commonly used psychoactive substance worldwide. The cannabis plant has more than 400 chemicals, of which more than 100 cannabinoids (such as cannabigerol, cannabidiol, and cannabinol) have been identified. The endocannabinoid system (ECS) plays an essential role in the effects of cannabis on end organs. Although cannabis use has been reported for many decades, some of its unique adverse effects of nausea, vomiting, and abdominal pain, termed as cannabis hyperemesis syndrome (CHS), were noted recently. The legal status of cannabis in the United States has been rapidly changing from state to state. The incidence of CHS is expected to rise with rising access to cannabis in the United States. Furthermore, CHS is frequently underdiagnosed due to a lack of uniform criteria, subjective nature of symptoms, and overlap with cyclical vomiting syndrome (CVS). Understanding the ECS and its role in biphasic response (proemetic and antiemetic) of CHS is critical to explain its pathophysiology. As the use of cannabis increases globally, awareness of CHS is warranted for early recognition and prompt treatment to avoid complications. We describe the putative mechanism of CHS with an overview of the clinical features in these patients. Furthermore, we highlight the differences between CHS and CVS with important differentials to consider. We provide a narrative update on the current evidence on CHS pathophysiology, diagnosis, treatment, and identifying research gaps.
Risk factors and clinical characteristics of early-onset colorectal cancer vs. late-onset colorectal cancer: a case-case study
Authors: Di Leo Milena , Zuppardo Raffaella A. , Puzzono Marta , Ditonno Ilaria , Mannucci Alessandro , Antoci Graziana , Russo Raucci Annalisa , Patricelli Maria G. , Elmore Ugo , Tamburini Andrea M. , Albarello Luca , Azzolini Francesco , Bonura Giuliano F. , Esposito Dario , Fanti Lorella , Notaristefano Chiara , Viale Edi , Perea Josè , Testoni Pier A. , Rosati Riccardo , Cavestro Giulia M.
Published: November 2020

Background and objectives

Early-onset colorectal cancer (eoCRC), defined as colorectal cancer (CRC) before the age of 50 is increasing in incidence. We evaluated exogenous and endogenous risk factors, and clinical features of eoCRC, compared to late-onset CRC (loCRC).

Methods

In this retrospective case-case study, patients were prospectively enrolled from 2015 to 2018. We collected clinical features (age, sex, time from symptom onset to diagnosis, symptoms, family history, smoking and alcohol habits, diabetes, BMI, and genetic analysis) and tumor characteristics. Independent risk factors for eoCRC and odds ratios (ORs) were identified.

Results

Fifty-four eoCRCs and 494 loCRCs were enrolled. Patients with eoCRC experienced longer delay time from symptom onset to diagnosis: 40.7% were diagnosed within 6 months from symptoms onset, compared to 85.6% of patients with loCRC (P < 0.0001). They differed for sex, presence of symptoms, family history, smoking habit, alcohol intake, and BMI. Rectal localization was more closely associated with eoCRC (64.8%) than loCRC (34.5%, P < 0.0001). Family history of CRC was associated with eoCRC (OR = 8.8). When family history occurred with hereditary cancer syndromes, the OR for eoCRC increased to 21.

Conclusion

In young adults with alarming symptoms, CRC must be suspected to avoid delay time from symptom onset to diagnosis and genetic risk assessment has to be evaluated. Smoking habits, alcohol intake, and BMI are not associated with eoCRC.
Better Nurse Staffing Is Associated With Survival for Black Patients and Diminishes Racial Disparities in Survival After In-Hospital Cardiac Arrests
Authors: Brooks Carthon Margo , Brom Heather , McHugh Matthew , Sloane Douglas M. , Berg Robert , Merchant Raina , Girotra Saket , Aiken Linda H.
Published: November 2020

Background:

Racial disparities in survival among patients who had an in-hospital cardiac arrest (IHCA) have been linked to hospital-level factors.

Objectives:

To determine whether nurse staffing is associated with survival disparities after IHCA.

Research Design:

Cross-sectional data from (1) the American Heart Association’s Get With the Guidelines-Resuscitation database; (2) the University of Pennsylvania Multi-State Nursing Care and Patient Safety Survey; and (3) The American Hospital Association annual survey. Risk-adjusted logistic regression models, which took account of the hospital and patient characteristics, were used to determine the association of nurse staffing and survival to discharge for black and white patients.

Subjects:

A total of 14,132 adult patients aged 18 and older between 2004 and 2010 in 75 hospitals in 4 states.

Results:

In models that accounted for hospital and patient characteristics, the odds of survival to discharge was lower for black patients than white patients [odds ratio (OR)=0.70; 95% confidence interval (CI), 0.61–0.82]. A significant interaction was found between race and medical-surgical nurse staffing for survival to discharge, such that each additional patient per nurse lowered the odds of survival for black patients (OR=0.92; 95% CI, 0.87–0.97) more than white patients (OR=0.97; 95% CI, 0.93–1.00).

Conclusions:

Our findings suggest that disparities in IHCA survival between black and white patients may be linked to the level of medical-surgical nurse staffing in the hospitals in which they receive care and that the benefit of being admitted to hospitals with better staffing may be especially pronounced for black patients.
Respiratory Pathogen Detection in Pediatric Patients Intubated for Presumed Infection
Authors: Jamieson Nathan , Akande Manzilat , Karsies Todd , Smith Rachel M. , Kline David , Spencer Sandra P.
Published: November 2020

Objectives

Respiratory syncytial virus (RSV) in pediatric patients has been associated with low risk of concomitant bacterial infection. However, in children with severe disease, it occurs in 22% to 50% of patients. As viral testing becomes routine, bacterial codetections are increasingly identified in patients with non-RSV viruses. We hypothesized, among patients intubated for respiratory failure secondary to suspected infection, there are similar rates of codetection between RSV and non-RSV viral detections.

Methods

This retrospective chart review, conducted over a 5-year period, included all patients younger than 2 years who required intubation secondary to respiratory failure from an infectious etiology in a single pediatric emergency department. Patients intubated for noninfectious causes were excluded.

Results

We reviewed 274 patients, of which 181 had positive viral testing. Of these, 48% were RSV-positive and 52% were positive for viruses other than RSV. Codetection of bacteria was found in 76% (n = 65; 95% confidence interval [CI], 66%, 84%) of RSV-positive patients and 66% (n = 63, 95% CI: 57%, 76%) of patients positive with non-RSV viruses. Among patients with negative viral testing, 33% had bacterial growth on lower respiratory culture. Male sex was the only patient-related factor associated with increased odds of codetection (odds ratio [OR], 2.2; 95% CI, 1.08–4.38). The odds of codetection between RSV-positive patients and non-RSV viruses were not significantly different (OR, 1.3; 95% CI, 0.62–2.71).

Conclusions

Bacterial codetection is common and not associated with anticipated patient-related factors or with a specific virus. These results suggest consideration of empiric antibiotics in infants with respiratory illness requiring intubation.
Using Informatics to Build a Digital Health Footprint of Patients Living With Inherited Metabolic Disorders Identified by Newborn Screening
Authors: Singh Rani H. , Brown Sheereen J. , Hale Piper M. , Narlow Kristen , Gurung Saran , Salvatore Mary L. , Tchamako Jimica K.
Published: November 2020

Newborn screening is a process identifying people with inherited metabolic disorders (IMDs) at birth, but these patients are often lost to follow-up, and limited data on their long-term needs are available to advocate for policies that will help this vulnerable community. Using informatics best practices, the Medical Nutrition Therapy for Prevention (MNT4P) program and the Public Health Informatics Institute successfully deployed a minimally viable product—that is, the most basic working version that is scalable—allowing for lifelong patient follow-up and outcome and needs tracking, and that can address national data gaps. The new system offers a HIPAA-compliant, efficient record-keeping system that allows data standardization and harmonization. MNT4P staff have transitioned completely away from former manual processes and are relying on this system to log and track patient information. Other programs serving patient populations burdened with rare, marginalized diseases also may benefit from this work.
Prostate Cancer Liver Metastases Presenting as Relatively Photopenic Lesions on 18F-Fluciclovine PET/CT
Authors: Baiomy Ali , Martiniova Lucia , Efstathiou Eleni , Schuster David M. , Ravizzini Gregory
Published: November 2020

A 66-year-old man with prostate adenocarcinoma status post radical retropubic prostatectomy and bilateral pelvic lymph node dissection, followed by salvage external beam radiation therapy to the prostate bed 1 year after surgery. Over the course of 17 years, the patient underwent multiple lines of systemic treatment for recurrent disease. He was referred for restaging 18F-fluciclovine PET/CT due to rising serum prostate-specific antigen levels. Contrast-enhanced 18F-fluciclovine PET/CT images demonstrated multiple new liver metastases, which were relatively photopenic in comparison with the physiologic radiotracer activity in the surrounding normal liver parenchyma.
Widespread Glial Activation in Primary Progressive Multiple Sclerosis Revealed by 18F-PBR06 PET
Authors: Singhal Tarun , Rissanen Eero , Ficke John , Cicero Steven , Carter Kelsey , Weiner Howard L.
Published: November 2020

A 64-year-old man with primary progressive multiple sclerosis (Expanded Disability Status Scale 3.5) underwent PET using 18F-PBR06, a second-generation 18-kDa translocator protein ligand targeting activated brain microglia and astrocytes. Voxel-by-voxel statistical comparison of patient’s PET images (acquired 60–90 minutes postinjection) with a healthy control data set was performed to generate a 3-dimensional z-score map of increased radiotracer uptake, which showed widespread increased glial activation in normal-appearing cerebral white matter, white matter lesional and perilesional areas, brainstem and cerebellum. In contrast, patient’s 3-T MRI scan showed only a few small white matter brain lesions without contrast enhancement.
Assessment of Central Nervous System Lymphoma Based on CXCR4 Expression In Vivo Using 68Ga-Pentixafor PET/MRI
Authors: Starzer Angelika M. , Berghoff Anna S. , Traub-Weidinger Tatjana , Haug Alexander R. , Widhalm Georg , Hacker Marcus , Rausch Ivo , Preusser Matthias , Mayerhoefer Marius E.
Published: November 2020

Purpose of the Report

18F-FDG PET is limited for assessment of central nervous system lymphoma (CNSL) due to physiologic tracer accumulation in the brain. We prospectively evaluated the novel PET tracer 68Ga-pentixafor, which targets the C-X-C chemokine receptor 4 (CXCR4), for lesion visualization and response assessment of CNSL.

Materials and Methods

Seven CNSL patients underwent 68Ga-pentixafor PET/MRI with contrast enhancement (CE-MRI) and diffusion-weighted sequences. The accuracy of 68Ga-pentixafor PET for CNSL lesion detection relative to the CE-MRI reference standard was determined. Standardized uptake values (SUVmean and SUVmax), PET-based (PTV) and MRI-based (VOLMRI) tumor volumes, and apparent diffusion coefficients (ADCs) were assessed, and correlation coefficients were calculated. Three SUVmax thresholds (41%, 50%, and 70%) were evaluated for PTV definitions (PTV41%, PTV50%, and PTV70%) and tested against VOLMRI using paired sample t tests.

Results

Twelve 68Ga-pentixafor PET/MRI examinations (including 5 follow-up scans) of 7 patients were evaluated. 68Ga-pentixafor PET demonstrated 18 lesions, all of which were confirmed by CE-MRI; there were no false-positive lesions on PET (accuracy, 100%). PTV41% showed the highest concordance with lesion morphology, with no significant difference compared with VOLMRI (mean difference, −0.24 cm3; P = 0.45). The correlation between ADCmean and SUVmean41% (r = 0.68) was moderate. Changes in PTV41% on follow-up PET/MRI showed the same trend as VOLMRI changes, including progression of 1 lesion each in patient 1 (+456.0% PTV41% and +350.8% VOLMRI) and patient 3 (+110.4% PTV41% and +85.1% VOLMRI).

Conclusions

68Ga-pentixafor PET may be feasible for assessment and follow-up of CNSL. Future studies need to focus on testing its clinical value to distinguish between glioma and CNSL, and between radiation-induced inflammation and viable residual tumor.
Quantitative Features From CHO PET Distinguish the WHO Grades of Primary Diffuse Glioma
Authors: Kong Ziren , Jiang Chendan , Liu Delin , Chen Wenlin , Ma Wenbin , Cheng Xin , Wang Yu
Published: November 2020

Purpose

The aim of this study was to investigate the quantitative 18F-fluoroethylcholine (CHO) PET characteristics for differentiating lower-grade glioma (LGG) from glioblastoma (GBM).

Patients and Methods

Thirty-nine patients who underwent CHO PET with histopathologically confirmed primary diffuse glioma were prospectively enrolled. The 3-dimensional region of interest was semiautomatically defined based on the SUV threshold, and a total of 74 quantitative features, including 13 shape features, 31 SUV-based features, and 30 normalized SUV-based features, were calculated. Wilcoxon rank sum test, receiver operating characteristic curve, and correlation coefficient analyses were applied to select independent representative features, and patient prognosis was stratified by the World Health Organization (WHO) grade and CHO features.

Results

A total of 89.2% of the quantitative features were significantly different between LGG and GBM, and the SUV-based features displayed higher area under the receiver operating characteristic curve (AUC) values than the other feature groups. Among the 5 traditional features, the SUVmax and the total lesion CHO uptake were the most distinguishing, with AUCs of 0.880 and 0.860 (0.938 and 0.927 after reclassification of 2 outliers), respectively, both of which could also stratify patient prognosis better than WHO grade. Five alternative features, including 2 shape features and 3 SUV-based features, were considered representative, with AUCs ranging from 0.754 to 0.854.

Conclusions

Quantitative features from CHO PET are reliable in determining the WHO grade of primary diffuse gliomas. Our findings suggest that GBM has a larger volume, a more spherical shape, higher choline activity in most interval segments, and a more symmetrical distribution than LGG.
Liver Transplantation for Intrahepatic Cholangiocarcinoma: A Meta-analysis and Meta-regression of Survival Rates
Authors: Ziogas Ioannis A. , Giannis Dimitrios , Economopoulos Konstantinos P. , Hayat Muhammad H. , Montenovo Martin I. , Matsuoka Lea K. , Alexopoulos Sophoclis P.
Published: November 2020

Background.

Intrahepatic cholangiocarcinoma (iCCA) is a contraindication to liver transplantation in most centers worldwide. Therefore, only a few such cases have been performed in each individual center, and the need for a systematic review and meta-analysis to cumulatively pool these results is apparent.

Methods.

A systematic literature review was conducted using the MEDLINE and Cochrane Library databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement (end-of-search date: May 29, 2020). Meta-analyses of proportions were conducted to pool the overall survival (OS), recurrence-free survival (RFS), and overall recurrence rates using the random-effects model. Meta-regression was used to examine cirrhosis and incidental diagnosis as confounders on OS and RFS.

Results.

Eighteen studies comprising 355 patients and a registry study of 385 patients were included. The pooled 1-, 3-, and 5-y OS rates were 75% (95% CI, 64%-84%), 56% (95% CI, 46%-67%), and 42% (95% CI, 29%-55%), respectively. The pooled 1-, 3-, and 5-y RFS rates were 70% (95% CI, 63%-75%), 49% (95% CI, 41%-57%), and 38% (95% CI, 27%-50%), respectively. Cirrhosis was positively associated with RFS, while incidental diagnosis was not. Neither cirrhosis nor incidental diagnosis was associated with OS. The pooled overall recurrence rate was 43% (95% CI, 33%-53%) over a mean follow-up of 40.6 ± 37.7 mo. Patients with very early (single ≤2 cm) iCCA exhibited superior pooled 5-y RFS (67%; 95% CI, 47%-86%) versus advanced iCCA (34%; 95% CI, 23%-46%).

Conclusions.

Cirrhotics with very early iCCA or carefully selected patients with advanced iCCA after neoadjuvant therapy may benefit from liver transplantation under research protocols.
Characteristics, Trends, and Outcomes of Liver Transplantation for Primary Sclerosing Cholangitis in Female Versus Male Patients: An Analysis From the European Liver Transplant Registry
Authors: Berenguer Marina , Di Maira Tommaso , Baumann Ulrich , Mirza Darius F. , Heneghan Michael A. , Klempnauer Jurgen L. , Bennet William , Ericzon Bo-Goran , Line Pål-Dag , Lodge Peter A. , Zieniewicz Krzysztof , Watson Christopher J. E. , Metselaar Herold J. , Adam René , Karam Vincent , Aguilera Victoria
Published: November 2020

Background.

The influence of sex on primary sclerosing cholangitis (PSC), pre- and postliver transplantation (LT) is unclear. Aims are to assess whether there have been changes in incidence, profile, and outcome in LT-PSC patients in Europe with specific emphasis on sex.

Methods.

Analysis of the European Liver Transplant Registry database (PSC patients registered before 2018), including baseline demographics, donor, biochemical, and clinical data at LT, immunosuppression, and outcome.

Results.

European Liver Transplant Registry analysis (n = 6463, 32% female individuals) demonstrated an increasing number by cohort (1980–1989, n = 159; 1990–1999, n = 1282; 2000–2009, n = 2316; 2010–2017, n = 2549) representing on average 4% of all transplant indications. This increase was more pronounced in women (from 1.8% in the first cohort to 4.3% in the last cohort). Graft survival rate at 1, 5, 10, 15, 20, and 30 y was 83.6%, 70.8%, 57.7%, 44.9%, 30.8%, and 11.6%, respectively. Variables independently associated with worse survival were male sex, donor and recipient age, cholangiocarcinoma at LT, nondonation after brain death donor, and reduced size of the graft. These findings were confirmed using a more recent LT population closer to the current standard of care (LT after the y 2000).

Conclusions.

An increasing number of PSC patients, particularly women, are being transplanted in European countries with better graft outcomes in female recipients. Other variables impacting outcome include donor and recipient age, cholangiocarcinoma, nondonation after brain death donor, and reduced graft size.
Heart Donation From Donors After Controlled Circulatory Death
Authors: Anguela-Calvet Laura , Moreno-Gonzalez Gabriel , Sbraga Fabrizio , Gonzalez-Costello Jose , Tsui Steven , Oliver-Juan Eva
Published: November 2020

The gold-standard therapy for advanced-stage heart failure is cardiac transplantation. Since the first heart transplant in 1967, the majority of hearts transplanted came from brain death donors. Nevertheless, in recent years, the option of donation after circulatory death (DCD) is gaining importance to increase donor pool. Currently, heart-transplant programs using controlled donation after circulatory death (cDCD) have been implemented in the United Kingdom, Belgium, Australia, United States of America, and, recently, in Spain. In this article, we performed a concise review of the literature in heart cDCD; we summarize the pathophysiology involved in ischemia and reperfusion injury during this process, the different techniques of heart retrieval in cDCD donors, and the strategies that can be used to minimize the damage during retrieval and until transplantation. Heart transplant using DCD hearts is in continuous improvement and must be implemented in experienced cardiac transplant centers.
Early chains of transmission of COVID-19 in France
Authors: Paireau Juliette , Mailles Alexandra , Eisenauher Catherine , de Laval Franck , Delon François , Bosetti Paolo , Salje Henrik , Pontiès Valérie , Cauchemez Simon
Published: November 2020

Introduction

SARS-CoV-2, which causes COVID-19, has spread rapidly across the world. A dedicated surveillance system was implemented in France in January 2020 to improve early detection of cases and their contacts and limit secondary transmission. Our objective was to use contact-tracing data collected during this initial phase of the epidemic to better characterize SARS-CoV-2 transmission.

Methods

We analysed data collected during contact tracing and retrospective epidemiological investigations in France from 24 January to 30 March 2020. We assessed the secondary clinical attack rate and characterized the risk of a contact becoming a case. We described chains of transmission and estimated key parameters of spread.

Results

Over the study period, 6,082 contacts of 735 confirmed cases were traced. The overall secondary clinical attack rate was 4.1% (95%CI 3.6-4.6) and increased with age of the index case and of the contact. Family contacts were at higher risk of becoming cases (adjusted odds ratio 2.1 (95%CI 1.4-3.0)) while nosocomial contacts were at lower risk (adjusted odds ratio 0.3 (95%CI 0.1-0.7)), compared to coworkers/friends. We identified 328 infector/infectee pairs, 49% of which were family members. The distribution of secondary cases was highly over-dispersed with 80% of secondary cases being caused by 10% of cases. The mean serial interval was 5.1 days (interquartile range 2-8 days) in contact-tracing pairs where late transmission events may be censored, and 6.8 (3-8) days in pairs investigated retrospectively.

Conclusion

This study contributes to improving our knowledge of SARS-CoV-2 transmission, such as the importance of superspreading events. Contact-tracing data are challenging to collect but are key to better understand emerging pathogens.

Funding statement

This work was supported by the LabEx “Integrative Biology of Emerging Infectious Diseases (IBEID)” (Grant Number ANR-10-LABX-62-IBEID), Santé Publique France, the INCEPTION project (PIA/ANR-16-CONV-0005), and the European Union’s Horizon 2020 research and innovation program under grants 101003589 (RECOVER) and 874735 (VEO).
Risk of evolutionary escape from neutralizing antibodies targeting SARS-CoV-2 spike protein
Authors: Van Egeren Debra , Novokhodko Alexander , Stoddard Madison , Tran Uyen , Zetter Bruce , Rogers Michael , Pentelute Bradley L. , Carlson Jonathan M. , Hixon Mark , Joseph-McCarthy Diane , Chakravarty Arijit
Published: November 2020

As many prophylactics targeting SARS-CoV-2 are aimed at the spike protein receptor-binding domain (RBD), we examined the risk of immune evasion from previously published RBD-targeting neutralizing antibodies (nAbs). Epitopes for RBD-targeting nAbs overlap one another substantially and can give rise to escape mutants with ACE2 affinities comparable to wild type that still infect cells in vitro. We used evolutionary modeling to predict the frequency of immune escape before and after the widespread presence of nAbs due to vaccines, passive immunization or natural immunity. Our modeling suggests that SARS-CoV-2 mutants with one or two mildly deleterious mutations are expected to exist in high numbers due to neutral genetic variation, and consequently resistance to single or double antibody combinations can develop quickly under positive selection.

One Sentence Summary

SARS-CoV-2 will evolve quickly to evade widely deployed spike RBD-targeting monoclonal antibodies, requiring combinations that rely on at least three antibodies targeting distinct epitopes to suppress viral immune evasion.
Magnaporthe oryzaepopulations in Sub-Saharan Africa are diverse and show signs of local adaptation
Authors: Onaga Geoffrey , Suktrakul Worrawit , Wanjiku Margaret , Quibod Ian Lorenzo , Entfellner Jean-Baka Domelevo , Bigirimana Joseph , Habarugira George , Murori Rosemary , Asea Godfrey , Ismail Abdelbagi M. , Jantasuriyarat Chatchawan , Oliva Ricardo
Published: November 2020

Rice blast caused byMagnaporthe oryzaeis one of the most economically damaging diseases of rice worldwide. The disease originated in Asia but was detected for the first time in Sub-Saharan Africa (SSA) around 100 years ago. Despite its importance, the evolutionary processes involved in shaping the population structure ofM. oryzaein SSA remain unclear. In this study, we investigate the population history ofM. oryzaeusing a combined dataset of 180 genomes. Our results show that SSA populations are more diverse than earlier perceived, and harbor all genetic groups previously reported in Asia. WhileM. oryzaepopulations in SSA and Asia draw from the same genetic pools, both are experiencing different evolutionary trajectories resulting from unknown selection pressures or demographic processes. The distribution of rare alleles, measured as Tajima’sDvalues, show significant differences at the substructure level. Genome-wide analysis indicates potential events of population contraction strongly affectingM. oryzaein SSA. In addition, the distribution and haplotype diversity of effectors might suggest a process of local adaptation to SSA conditions. These findings provide additional clues about the evolutionary history ofM. oryzaeoutside the center of origin and help to build customized disease management strategies.
More than the sum of its parts: Merging network psychometrics and network neuroscience with application in autism
Authors: Bathelt Joe , Geurts Hilde M. , Borsboom Denny
Published: November 2020

Network approaches that investigate the interaction between symptoms and behaviours have opened new ways of understanding psychological phenomena in health and disorder in recent years. In parallel, network approaches that characterise the interaction between brain regions have become the dominant approach to understanding brain function in neuroimaging research. Combining these parallel approaches would enable new insights into the interaction between behaviours and their brain-level correlates. In this paper, we introduce a methodology for combining network psychometrics and network neuro-science. This approach utilises the information from the psychometric network to obtain neural correlates that are associated with each node in the psychometric network (network-based regression). Moreover, we combine the behavioural variables and their neural correlates in a joint network to characterise their interactions. We illustrate the approach by highlighting the interaction between the triad of autistic traits and their resting-state functional connectivity associations. To this end, we utilise data from 172 male autistic participants (10-21 years) from the autism brain data exchange (ABIDE, ABIDE-II) that completed resting-state fMRI and were assessed using the autism diagnostic interview (ADI-R). Our results indicate that the network-based regression approach can uncover both unique and shared neural correlates of behavioural measures. In addition, because the shared variance between behavioural measures is controlled for in the approach, the methodology enables us to isolate mechanisms at the brain-level that are unique to particular behavioural variables. For instance, our example analysis indicates that the overlap between communication and social difficulties is not reflected in the overlap between their functional brain correlates.
Temporal dynamics of implicit memory underlying serial dependence
Authors: Bilacchi Cristiano Moraes , Sirius Esaú Ventura Pupo , Cravo André Mascioli , de Azevedo Neto Raymundo Machado
Published: November 2020

Serial dependence is the effect in which the immediately preceding trial influences participants' responses to the current stimulus. But for how long does this bias last in the absence of interference from other stimuli? Here, we had 20 healthy young adult participants (12 women) perform a coincident timing task using different inter-trial intervals to characterize the serial dependence effect as the time between trials increases. Our results show that serial dependence abruptly decreases from 0.1 s to 1 s inter-trial interval, but it remains pronounced after that for up to 8 s. In addition, participants' response variability slightly decreases over longer intervals. We discuss these results in light of recent models suggesting that serial dependence might rely on a short-term memory trace kept through changes in synaptic weights, which might explain its long duration and apparent stability over time.
Fast neutron mutagenesis in soybean creates frameshift mutations
Authors: Wyant Skylar R. , Rodriguez M. Fernanda , Carter Corey K. , Parrott Wayne A. , Jackson Scott A. , Stupar Robert M. , Morrell Peter L.
Published: November 2020

The mutagenic effects of ionizing radiation have been used for decades to create novel variants in experimental populations. Fast neutron (FN) bombardment as a mutagen has been especially widespread in plants, with extensive reports describing the induction of large structural variants, i.e., deletions, insertions, inversions, and translocations. However, the full spectrum of FN-induced mutations is poorly understood. We contrast small insertions and deletions (indels) observed in 27 soybean lines subject to FN irradiation with the standing indels identified in 107 diverse soybean lines. We use the same populations to contrast the nature and context (bases flanking a nucleotide change) of single nucleotide variants. The accumulation of new single nucleotide changes in FN lines is marginally higher than expected based on spontaneous mutation. In FN treated lines and in standing variation, C→T transitions and the corresponding reverse complement G→A transitions are the most abundant and occur most frequently in a CpG local context. These data indicate that most SNPs identified in FN lines are likely derived from spontaneous de novo processes in generations following mutagenesis, rather than from the FN irradiation mutagen. However, small indels in FN lines differ from standing variants. Short insertions, from 1 – 6 base pairs, are less abundant than in standing variation. Short deletions are more abundant and prone to induce frameshift mutations that should disrupt the structure and function of encoded proteins. These findings indicate that FN irradiation generates numerous small indels, increasing the abundance of loss of function mutations that will impact single genes.

Significance Statement

Irradiation mutagenesis is commonly viewed as a method to induce large structural variants in genomes. We also find enrichment in small insertion and deletion (indel) variants. The radiation-mutagenized lines averaged 32 indels per line, far exceeding the number estimated to occur by spontaneous processes, indicating that these arose from the irradiation treatment. Nevertheless, naturally-occurring standing variation among soybean accessions is still four orders of magnitude higher than the level of diversity introduced by mutagenesis. Induced mutations from any source are likely to constitute a relatively small portion of the genetic variation present in crop species. However, irradiation mutagenesis is useful for altering genomes by introducing small indels into single genes or disrupting gene clusters by creating structural variants.
Genomic analyses of high-grade neuroendocrine gynecological malignancies reveal a unique mutational landscape and therapeutic vulnerabilities
Authors: Mahdi Haider , Joehlin-Price Amy , Dowlati Afshin , Abbas Ata
Published: November 2020

The high-grade neuroendocrine carcinoma of gynecologic origin (NEC-GYN) is a highly aggressive cancer affecting young women. The clinical management of NEC-GYN is often extrapolated from their counterpart, small cell carcinoma of the lung (SCLC), but, unfortunately, they have limited effect. In our NEC-GYN cohort, median progression-free survival (PFS) and overall survival (OS) were 1 and 12 months, respectively, indicating their highly lethal nature. Our comprehensive genomic analyses unveiled that NEC-GYN harbors a higher mutational burden with distinct mutational landscapes from SCLC. We identified 14 cancer driver genes (FDR <0.01) including the most frequently alteredKMT2C(100%),KNL1(100%),NCOR2(100%), andCCDC6(93%) genes. Transcriptomic analyses identified several novel gene fusions in NEC-GYN. Furthermore, NEC-GYN exhibited a highly immunosuppressive state and uniquely belonged to theYAP1high molecular subtype that promotes multidrug resistance. Our study suggests an urgent need to reevaluate the therapeutic options and targets for NEC-GYN.
AbaM Regulates Quorum Sensing, Biofilm Formation and Virulence inAcinetobacter baumannii
Authors: López-Martín Mario , Dubern Jean-Frédéric , Alexander Morgan R. , Williams Paul
Published: November 2020

Acinetobacter baumanniipossesses a single divergentluxR/luxI-type quorum sensing (QS) locus namedabaR/abaI. This locus also contains a third gene located betweenabaRandabaIwhich we termabaMthat codes for an uncharacterized member of the RsaM protein family known to regulateN-acylhomoserine lactone (AHL) dependent QS in other β- and γ-proteobacteria. Here we show that disruption ofabaMvia a T26 insertion inA. baumanniistrain AB5075 resulted in increased production of N-(3-hydroxydodecanoyl)-L-homoserine lactone (OHC12) and enhanced surface motility and biofilm formation. In contrast to the wild type andabaI::T26 mutant, the virulence of theabaM::T26 mutant was completely attenuated in a Galleria mellonella infection model. Transcriptomic analysis of theabaM::T26 mutant revealed thatabaMdifferentially regulates at least 76 genes including thecsupilus operon and the acinetin 505 lipopeptide biosynthetic operon, that are involved in surface adherence, biofilm formation and virulence. A comparison of the wild type,abaM::T26 andabaI::T26 transcriptomes, indicates thatabaMregulates ~21% of the QS regulon including the csu operon. Moreover, the QS genes (abaI/abaR) were among the most upregulated in theabaM::T26 mutant.A. baumannii lux-basedabaMreporter gene fusions revealed thatabaMexpression is positively regulated by QS but negatively auto-regulated. Overall, the data presented in this work demonstrates thatabaMplays a central role in regulatingA. baumanniiQS, virulence, surface motility and biofilm formation.

IMPORTANCE

Acinetobacter baumanniis a multi-antibiotic resistant pathogen of global healthcare importance. UnderstandingAcinetobactervirulence gene regulation could aid the development of novel anti-infective strategies. InA. baumannii, theabaRandabaIgenes that code for the receptor and synthase components of anN-acylhomoserine (AHL) lactone-dependent quorum sensing system (QS) are separated byabaM. Here we show that although mutation ofabaMincreased AHL production, surface motility and biofilm development, it resulted in the attenuation of virulence.abaMwas found to control both QS-dependent and QS-independent genes. The significance of this work lies in the identification ofabaM, an RsaM ortholog known to control virulence in plant pathogens, as a modulator of virulence in a human pathogen.
Accuracy, Clinical Utility and Usability Study of a Wireless Self-Guided Fetal Heart Rate Monitor
Authors: Porter Paul , Muirhead Fleur , Brisbane Joanna , Schneider Brooke , Choveaux Jennifer , Bear Natasha , Carson Jennie , Jones Kym , Silva Desiree , Neppe Cliff
Published: November 2020

Objective

To evaluate the accuracy, reliability, clinical utility, and usability of HeraBEAT, a wireless fetal and maternal heart rate monitor (HBM) when used by clinicians and pregnant women to monitor fetal heart rate (FHR).

Methods

We recruited women aged 18 years or older with a singleton pregnancy of ≥12 weeks gestation. FHR recordings were performed using the HBM and cardiotocography (CTG) to determine comparative accuracy. The HBM was then used by clinicians and participants in the antenatal clinic with the latter then using the device unassisted to record at home. The women rated the HBM using the System Usability Scale (SUS).

Results

A total of 81 participants provided 126 recordings for analysis. The accuracy of the HBM was excellent compared with CTG, with limits of agreement (95%) between −1.5 and +0.9 beats per minute (bpm) and a mean difference of −0.29 bpm. The FHR was detected on 100% of occasions by clinicians (52 recordings) and participants when used in the clinic (42 recordings) and at home (32 recordings). Home users took an average of 1.1 minutes to detect the FHR and recorded a continuous trace of >1 minute in 94% of occasions, with an average total trace time of 4.4 minutes. The FHR trace was deemed to be clinically useful in 100% of clinician recordings and 97% of home recordings. There was no effect from body mass index, gestational age, pregnancy history, or placental position. The HBM ranked in the 96–100th percentile on the SUS for usability and learnability.

Conclusions

The HBM was accurate and easy for clinicians and participants to use. The data recorded at home was equivalent to that obtained in the clinic using current assessment protocols for low-risk pregnancies, allowing the device to be used in telehealth consultations.

Clinical Trial Registration

Australian New Zealand Clinical Trial Registry, https://www.anzctr.org.au ACTRN12620000739910.