bluuebunny/crossref_metadata_2025 huggingface dataset:
Salvage ablation for locally recurrent prostate cancer
Authors: Lomas Derek J. , Woodrum David A. , Mynderse Lance A.
Published: March 2021

Purpose of review

This review aims to summarize the latest evidence for the use of salvage ablation of localized prostate cancer recurrences after primary therapy radiotherapy or prostatectomy.

Recent findings

Savage ablation represents a treatment option in select patients with localized recurrences following primary therapy of prostate cancer. Following radiotherapy, salvage cryotherapy and high-intensity focused ultrasound (HIFU) demonstrate encouraging oncologic outcomes. Biochemical recurrence-free survival ranged from 71% at 2 years to 44.2% at 10 years for cryotherapy and from 51% at 5 years to 28.7% at 10 years for HIFU. Rates of adverse effects appear to be more favorable with ablation compared to salvage surgery. Focal salvage ablation may offer a further balance between oncologic control and adverse effects. Following radical prostatectomy, recent data on the use of salvage ablation of local recurrences are less robust with only a few small studies published in the last 2 years.

Salvage ablation is an option for localized disease recurrences following primary treatment. Its role is most established for postradiation recurrence. It can also be utilized in postprostatectomy recurrence, although published data is more limited. Future studies are needed to further explore the role of ablation in both cohorts.
Withdrawal of Combination Immunotherapy in Paediatric Inflammatory Bowel Disease—An International Survey of Practice
Authors: Meredith Joseph , Henderson Paul , Wilson David C. , Van Limbergen Johan , Wine Eytan , Russell Richard K.
Published: March 2021

Objectives:

To assess current practices around the use of combination immunosuppression in paediatric inflammatory bowel disease (PIBD) with a focus on the subsequent withdrawal process.

Methods:

A web‐based, 43‐question survey.

Results:

Surveys were completed by 70 paediatric gastroenterologists (PGs) from 27 nations across Europe, North America, Oceania and Asia from 62 centres covering approximately 15,000 PIBD patients (median of 200 patients [interquartile range (IQR) 130–300] per centre). Routine use of co‐immunosuppression was significantly higher with infliximab (IFX) versus adalimumab (ADL) ([61/70, 87.1%] compared with [23/70, 32.9%]; P < 0.01). Thiopurines (azathioprine [AZA] or 6‐mercaptopurine) were the preferred option overall for co‐immunosuppression. They were favoured with either IFX or ADL (76% and 77%, respectively) and in both ulcerative colitis (UC) and Crohn disease (CD) (84% and 69%) compared with methotrexate (MTX).

Immunomodulators were the preferred choice as the initial drug to be withdrawn from the combination therapy rather than anti‐tumour necrosis factor‐alpha (anti‐TNFα) therapy (59/67, 88% [P < 0.01]). The most common withdrawal time was after 6–12 months, with this decision usually based on clinical assessment rather than a scheduled withdrawal time (51/67, 76% vs 16/67, 24%). Indicators of mucosal healing and therapeutic drug monitoring results tended to be the most important “clinical factors” in the withdrawal decision (P = 0.05).

Conclusion:

Most PG's favour initial withdrawal of immunomodulator (usually thiopurines) rather than biologic therapy in the step‐down process, usually after 6–12 months based on sustained clinical remission. This survey precedes an in‐depth, multicentre study of clinical outcomes of withdrawal of co‐immunosuppression in PIBD.
Positive Emotion Dysregulation Identifies Trauma-Exposed Community Individuals at Risk for Suicide and Nonsuicidal Self-Injury
Authors: Raudales Alexa M. , Darosh Angela G. , Contractor Ateka A. , Schatten Heather T. , Dixon-Gordon Katherine L. , Weiss Nicole H.
Published: March 2021

Emotion dysregulation is associated with increased risk for suicidal thoughts and behaviors (STBs) and nonsuicidal self-injury (NSSI). However, research in this area has focused almost exclusively on dysregulation stemming from negative emotions. The present study aimed to address this gap in the literature by examining the associations between the specific domains of positive emotion dysregulation and both STBs and NSSI. Participants included 397 trauma-exposed community adults (M
age = 35.95; 57.7% female; 76.8% White). Results demonstrated significant associations between positive emotion dysregulation and both STBs and NSSI. In particular, higher levels of nonacceptance of positive emotions were found to be significantly related to risk for STBs (versus no risk), higher severity of STBs, and history of NSSI (versus no history). Findings suggest positive emotion dysregulation may play an important role in the etiology and treatment of both STBs and NSSI among trauma-exposed individuals.
Coagulations Studies Do Not Correlate With Each Other or With Hematologic Complications During Pediatric Extracorporeal Membrane Oxygenation*
Authors: Deshpande Shyam J. , Vitali Sally , Thiagarajan Ravi , Brediger Steven , McManus Michael , Geva Alon
Published: March 2021

OBJECTIVES:

Anticoagulation plays a key role in the management of children supported with extracorporeal membrane oxygenation. However, the ideal strategy for monitoring anticoagulation remains unclear. Our objective was to evaluate the utility of laboratory measures of anticoagulation in pediatric extracorporeal membrane oxygenation.

DESIGN:

Retrospective cohort study.

SETTING:

Quaternary care academic children’s hospital.

PATIENTS:

Children in a noncardiac PICU cannulated to extracorporeal membrane oxygenation in 2010—2016.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Demographic data, laboratory values, and heparin doses were extracted from the enterprise data warehouse. Primary diagnoses, indications for cannulation, hemorrhagic and thrombotic complications, and survival outcomes were abstracted from the local registry used for Extracorporeal Life Support Organization reporting. Statistical models accounting for repeated measures using generalized estimating equations were constructed to evaluate correlations between heparin doses and laboratory values; among laboratory values; and between heparin dose or laboratory values and clinical outcomes. One hundred thirty-three unique patients—78 neonates and 55 older patients—were included in the study. There was no significant association between antifactor Xa level, activated partial thromboplastin time, activated clotting time, or heparin dose with hemorrhage or thrombosis (odds ratio ≅ 1 for all associations). There was weak-to-moderate correlation between antifactor Xa, activated partial thromboplastin time, and activated clotting time in both neonates and older pediatric patients (R
2 < 0.001 to 0.456). Heparin dose correlated poorly with laboratory measurements in both age groups (R
2 = 0.010–0.063).

CONCLUSIONS:

In children supported with extracorporeal membrane oxygenation, heparin dose correlates poorly with common laboratory measures of anticoagulation, and these laboratory measures correlate poorly with each other. Neither heparin dose nor laboratory measures correlate with hemorrhage or thrombosis. Further work is needed to identify better measures of anticoagulation in order to minimize morbidity and mortality associated with extracorporeal membrane oxygenation.
Diffuse Tract Damage Correlates With Global Cognitive Impairment in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: A Tract-Based Spatial Statistics Study
Authors: Zhang Qi , Wang Dongdong , Wu Shiman , Ren Yan , Li Yajie , Zhang Junhai , Feng Xiaoyuan
Published: March 2021

Purpose

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial arteriopathy characterized by recurrent lacunar stroke, migraine, and depression. The mechanism of cognitive dysfunction in CADASIL is still uncertain. The aim of this study was to use tract-based spatial statistics (TBSS) to map voxelwise the spatial distribution of brain microstructural change revealed by DTI-derived indices in patients with CADASIL to further study the underlying neuropsychopathological mechanism of CADASIL.

Method

Twelve patients with CADASIL and 11 age-, sex-matched healthy controls underwent magnetic resonance imaging at 3 T. Then we evaluated DTI-derived indices (fractional anisotropy [FA], mode of anisotropy [MO], mean diffusivity [MD], axial diffusivity [AD] and radial diffusivity [RD]) of brain white matter (WM) between CADASIL patients and healthy subjects through TBSS.

Results

Compared with healthy controls, patients with CADASIL showed extensive decreased FA, MO and increased RD, AD, and MD throughout the entire brain (mainly the WM of the temporal poles, inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corpus callosum, uncinate fasciculus, internal capsule, external capsule, corona radiata, thalamic radiation, and cingulum). Furthermore, these WM microstructural alterations were significantly correlated with cognitive scores and Scheltens scores. Decreased FA values and MO values were positively correlated with Montreal Cognitive Assessment scores in CADASIL patients. Increased AD, RD, and MD values were significantly negatively correlated with Montreal Cognitive Assessment scores.

Conclusions

Widespread WM abnormalities were clearly shown in CADASIL by using TBSS. Severity of microstructural changes correlates significantly with extension of T2 hyperintensity. Moreover, WM microstructural damage and cognitive impairment were significantly correlated. This study indicated that WM tract damage plays an important role in cognitive impairment in CADASIL.
Importance of Thalamostriatal Pathway Associated With Neurocognitive Dysfunctions in Children With Neurofibromatosis Type 1: Diffusion Tensor Imaging Findings
Authors: Cesme Dilek Hacer , Aydin Sinem , Alkan Alpay , Gultekin Mehmet Ali , Peker Abdusselim Adil , Toprak Mekiya Filiz , Iscan Akin
Published: March 2021

Objective

To determine whether there is a difference between healthy control group and children with neurofibromatosis type 1 (NF1) in terms of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values in different regions of the brain associated with neurocognitive functions and to investigate the correlation between diffusion tensor imaging parameters and neurocognitive dysfunctions.

Methods

The study included 28 children with NF1 and 21 controls. Nine distinct areas related to cognitive functions were selected for the analysis. The ADC and FA values were compared.

Results

There was a significant difference between NF1 and healthy control in terms of ADC values obtained from all areas. The ADC values at obtained from thalamus and striatum were positively correlated with the full-scale intelligence quotient (IQ), verbal IQ, and performance IQ.

Conclusions

We are speculated that the development of microstructural damage in the thalamostriatal pathway may lead to neurocognitive dysfunction.
Standing Waves on Computed Tomography Angiography in Multiple Vessels in a Young Trauma Patient
Authors: Rasheed Amer , White Sarah B. , Bhalla Manav
Published: March 2021

Standing waves are a phenomenon of uncertain etiology seen on imaging. We present the first case demonstrating standing waves on computed tomography angiography in multiple vessels in a single patient with imaging evidence of resolution in some of the vessels. Our case further supports the literature that standing waves are a physiologic phenomenon, likely because of flow mechanics, rather than modality.
Utility of Radial Scanning for the Identification of Arterial Hypervascularity of Hepatocellular Carcinoma on Gadoxetic Acid–Enhanced Magnetic Resonance Images
Authors: Narita Keigo , Nakamura Yuko , Higaki Toru , Nishihara Takashi , Harada Kuniaki , Takizawa Masahiro , Shirase Ryuji , Bito Yoshitaka , Akagi Motonori , Honda Yukiko , Iida Makoto , Awai Kazuo
Published: March 2021

Objectives

This study aimed to compare the accuracy of assessing the arterial hypervascularity of hepatocellular carcinoma (HCC) on dynamic computed tomography (CT) scans and gadoxetic acid (EOB)–enhanced magnetic resonance imaging (MRI) scans performed with radial sampling.

Methods

We studied the images of 40 patients with hypervascular HCC. A radiologist recorded the standard deviation of the attenuation (or the signal intensity [SI]) in subcutaneous fat tissue as the image noise (N) and calculated the contrast-to-noise ratio (CNR) as follows: (CNR) = (n-ROIT − n-ROIL)/N, where n-ROIT is the mean attenuation (or SI) of the tumor divided by the mean attenuation (or SI) of the aorta and n-ROIL is the mean attenuation (or SI) of the liver parenchyma divided by the mean attenuation (or SI) of the aorta.

Results

The CNR was significantly higher on EOB-enhanced MRI than on dynamic CT scans.

Conclusions

For the assessment of HCC vascularity, EOB-enhanced MRI scans acquired with radial sampling were more accurate than dynamic CT images.
Incidence of COVID-19 in 902 Patients With Immunomediated Inflammatory Diseases Treated With Biologics and Targeted Synthetic Disease-Modifying Antirheumatic Drugs—Findings From the BIOCOVID Study
Authors: Muñoz-Fernández Santiago , Cebrian Laura , Thuissard Israel John , Steiner Martina , García-Yubero Cristina , Esteban Ana Victoria , Sánchez Fernando , Gómez Alejandro , Matías Maria Angeles , Cobo-Ibáñez Tatiana , Esteban Mar , Manceñido Noemí , Pajares Ramón , Arribas María Rosario , Martínez Alicia , Andreu Cristina , Esteban Concepción , Romero Liz , Navío Teresa
Published: March 2021

Objectives

The aim of this study was to examine the incidence of coronavirus disease 2019 (COVID-19) among patients with immunomediated inflammatory diseases (IMIDs) treated with biologic or targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) and to evaluate the influence of either IMIDs or related therapies on the incidence and evolution of COVID-19.

Methods

This observational, cross-sectional study was conducted from January 31, 2020, to May 15, 2020. Data of 902 patients were obtained from clinical records in hospitals, primary care units, and community pharmacies. Inclusion criteria were adults with IMIDs treated with bDMARDs or tsDMARDs who started therapy 3 months prior to study commencement. Patients with poor adherence to treatments were excluded. COVID-19 was classified as “definitive” (severe acute respiratory syndrome coronavirus 2 polymerase chain reaction [PCR]–positive), “possible” (characteristic symptoms and negative PCR), and “suspected” (characteristic symptoms but PCR not performed).

Results

COVID-19 was diagnosed in 70 patients (11 definitive, 19 possible, and 40 suspected). The cumulative incidence of definitive COVID-19 was 1.2%. When considering all cases, the incidence was 7.8%. Patients on biosimilars tumor necrosis factor blockers were more likely to have a diagnosis of COVID-19 (odds ratio, 2.308; p < 0.001). Patients on anti–B-cell therapies had a lower incidence of infections (p = 0.046). Low rates of hospitalization (14.3%), pneumonia (14.3%), death (2.9%), or thrombosis (2.9%) were observed, and 94.3% of patients recovered.

Conclusions

The cumulative incidence of confirmed cases of COVID-19 was similar to the general population, with generally low hospitalization, intensive care management, and mortality rates. COVID-19 incidence was less frequent in patients with more severe immunosuppression.
Patient Characteristics Independently Associated With Knee Osteoarthritis Symptom Severity at Initial Orthopedic Consultation
Authors: Schwartzberg Harel G. , Roy Ryan , Wilson Kyle , Starring Hunter , Leonardi Claudia , Bronstone Amy , Dasa Vinod
Published: March 2021

Background/Objective

The objective of this study was to identify patient and disease characteristics associated with the symptomatic severity of knee osteoarthritis (OA) at the time of initial knee OA diagnosis by an orthopedist.

Methods

This medical records review included patients initially diagnosed with knee OA during 2016 to 2017 by a single orthopedic surgeon in a university-based tertiary care setting. All variables were assessed at first OA diagnosis. Main outcomes were subscales of the Knee Injury and Osteoarthritis Outcome Score–Pain, other Symptoms, knee-related quality of life, and function in daily living. Multivariable regression analyses examined the following predictors of main outcomes: sex, race, age, insurance type, body mass index, Charlson comorbidity index, and radiographic OA severity (Kellgren-Lawrence grade).

Results

Of the 559 patients included in the study, most were African American (52.1%), female (71.7%), and had severe radiographic OA (Kellgren-Lawrence grade, 4; 68.7%). Female sex, African American racial/ethnic group, Medicaid insurance, younger age, and severe radiographic OA were independently statistically significantly associated with worse symptoms, pain, and function (p < 0.05 for all). Body mass index and Charlson comorbidity index were not statistically significant predictors of any outcome.

Conclusions

This study identified disparities in the perception of knee OA problems at initial orthopedist diagnosis based on sex, age, race, insurance, and radiographic OA severity. Because most of these variables are also associated with more rapid progression of OA, identifying their biopsychosocial underpinnings may help determine which interventions are most likely to redress these disparities and delay progression to end-stage knee OA.
Persistent Nontumoral High-Amino-Acid Uptake on Brain [11C]Methionine PET/CT in a Patient After Combined Glioma Treatment
Authors: Skvortsova Tatiana Yu. , Savintceva Zhanna I. , Zhavoronkova Anastasia S. , Gurchin Alexander F. , Andropova Polina L.
Published: March 2021

A 44-year-old man after combined left temporal low-grade glioma treatment presented with daily multiple series of seizures. MRI demonstrated diffuse cortical swelling in the left frontal lobe with intensive gyral enhancement. PET with [11C]methionine (PET-MET) revealed increased radiotracer uptake strictly confined to the cortical ribbon of the left cerebral hemisphere, which persisted for 3 months. Tumor recurrence was suggested, and biopsy was performed. No evidence of recurrent tumor was found. During a 2-year follow-up, a diffuse gyral enhancement in the left hemisphere has persisted on MRI; PET has shown high [11C]methionine uptake in the left frontal and parietal cortex with gradual positive dynamics.
Double Trigger Wrist Caused by 2 Flexor Tendon Sheath Giant Cell Tumors
Authors: Ghieh Fadi , Karami Reem , Atallah Georgio , Bakhach Joseph
Published: March 2021

Trigger finger is a relatively common condition affecting the smooth gliding of tendons in the hand. When this entity affects the gliding motion of the wrist, it is termed as trigger wrist. In this article, we report the extremely rare case of a double trigger wrist caused by 2 tendon sheath tumors resulting in 2 trigger points in the motion of the wrist and carpal tunnel syndrome. The patient was managed with surgical excision of the tumors and release of the flexor retinaculum with resolution of symptoms.
ECT Utilization in the Treatment of Catatonic Patients in the United States
Authors: Trivedi Chintan , Manikkara Geetha , Zhang Mingxu , Mansuri Zeeshan , Jain Shailesh
Published: March 2021

Introduction

Primary objective was to evaluate baseline characteristics for catatonic patients treated with and without electroconvulsive therapy (ECT). We also studied the trends of ECT utilization in catatonia patients.

Methods

The Nationwide Inpatient Sample data were used to compare patients and hospital-level characteristics between catatonic patients treated with and without ECT in the United States. Multivariate and trend analysis were performed.

Results

Electroconvulsive therapy was performed in 8.3% in patients with the diagnosis of catatonia (n = 24,311; mean age, 43.1; 38% White; 52.1% male). Racially, more patients in the ECT group were White (47% vs 38%) and had a comorbid diagnosis of major depressive disorder. In the multivariate analysis, the odds of receiving ECT was more with increase in age (P = 0.007). Urban area hospitals had 3 times higher odds of receiving ECT (P = 0.001) compared with rural hospitals. The odds of receiving ECT for catatonia were the highest for large bed hospitals compared with small/medium size (P < 0.001). In the trend analysis, catatonia patients undergoing ECT decreased initially from 7.0% in 2002 to 2005 to 5.2% in 2006 to 2009. After that, there was an upward trend with 10.6% patients undergoing ECT in the quarter 2014 to 2017. There was an upward trend in ECT utilization for catatonic patients with comorbid bipolar disorders and psychotic disorders.

Conclusions

Electroconvulsive therapy is underutilized for catatonia treatment in the United States. White catatonic patients are most likely to get ECT at an urban large bed hospital. In recent years, there is an upward trend in the use of ECT. Additional controlled clinical trials are warranted.
Marinomonas algicola sp. nov. and Marinomonas colpomeniae sp. nov., isolated from marine macroalgae
Authors: Sun Xiao-Meng , Chen Cui , Xue Zhao , He Xiao-Yan , Liu Ning-Hua , Chen Xiu-Lan , Zhang Yu-Zhong , Fan Shou-Jin , Zhang Xi-Ying
Published: March 2021

Two Gram-stain-negative, aerobic, rod-shaped bacteria, polar flagellated, designated strains SM2066Tand SM1966T, were respectively isolated from the surfaces ofColpomenia sinuosaandUlva pertusamacroalgae collected off the coastal areas of Rongcheng, PR China. Strain SM2066Tgrew at 8–37 °C and with 0.5–7.0 % (w/v) NaCl, while strain SM1966Tgrew at 5–30 °C and with 0.5–8.5% (w/v) NaCl. Both of them reduced nitrate to nitrite and required Na+for growth but neither of them hydrolysed starch and DNA. Phylogenetic analysis based on 16S rRNA gene and single-copy orthologous cluster sequences revealed that both strains SM2066Tand SM1966Twere affiliated with the genusMarinomonasbut formed distinct phylogenetic branches from knownMarinomonasspecies, respectively sharing the highest 16S rRNA gene sequence similarities with type strains ofMarinomonas ushuaiensis(97.9 %) andMarinomonas blandensis(96.7 %). The digital DNA–DNA hybridization and average nucleotide identity values between strains SM2066Tand SM1966Tand type strains of closely relatedMarinomonasspecies were all below 22.9 and 79.9 mol%, respectively. The major fatty acids of the two strains were summed feature 3 (C16 : 1 ω6c/C16 : 1 ω7c), summed feature 8 (C18 : 1 ω7c) and C16 : 0, with their predominant polar lipids being phosphatidylethanolamine and phosphatidylglycerol, and their sole respiratory quinone being Q-8. The genomic DNA G+C contents of strains SM2066Tand SM1966Tdetermined from genomic sequences were 40.3 and 41.6 mol%, respectively. On the basis of the polyphasic evidence presented in this study, strains SM2066Tand SM1966Tare considered to represent two novel species within the genusMarinomonas, for which the namesMarinomonas colpomeniaesp. nov. andMarinomonas algicolasp. nov. are proposed. The type strains are SM2066T(=MCCC 1K04390T= KCTC 82372T) and SM1966T(=MCCC 1K04387T= KCTC 72848T), respectively.
Evidence for microbiome-dependent chilling tolerance in sorghum
Authors: Erlandson Sonya , Bheemanahalli Raju , Narayana Nisarga Kodadinne , Johnson Marina , Graham Christopher , Jagadish S. V. Krishna , Subramanian Senthil
Published: March 2021

Early season chilling stress is a major constraint on sorghum production in temperate climates. Chilling-tolerant sorghum is an active area of development, but the potential for early season microbial-enhanced chilling tolerance in sorghum has not yet been explored. In this study, we characterized traits of field-grown sorghum accessions in response to chilling and non-chilling temperatures and the corresponding cohorts of phyllosphere fungal and bacterial taxa. Further, we characterized the effects of chilling temperatures and microbial inoculation on sorghum accession traits in a growth chamber experiment. By comparing sorghum trait responses under chilling stress with and without soil microbial inoculation, we were able to detect a potential microbe-dependent sorghum response to chilling stress. Four sorghum genotypes showed a negative response to chilling stress with vs. without microbial inoculation, while five sorghum accessions show increased shoot biomass or leaf area under chilling stress when inoculated with a soil microbiome. These differential responses provides opportunities to exploit beneficial microbial taxa for enhancing early-stage chilling tolerance in sorghum, with a potential to be extended to other crops.
Tetraspanin immunocapture phenotypes extracellular vesicles according to biofluid source but may limit identification of multiplexed cancer biomarkers
Authors: Mizenko Rachel R. , Brostoff Terza , Rojalin Tatu , Koster Hanna J. , Swindell Hila S. , Leiserowitz Gary S. , Wang Aijun , Carney Randy P.
Published: March 2021

Tetraspanin expression of extracellular vesicles (EVs) is often used as a surrogate for their general detection and classification from background contaminants. This common practice typically assumes a consistent expression of tetraspanins across EV sources, thus obscuring subpopulations of variable or limited tetraspanin expression. While some recent studies indicate differential expression of tetraspanins across bulk isolated EVs, here we present analysis of single EVs isolated using various field-standard methods from a variety ofin vitroandin vivosources to identify distinct patterns in colocalization of tetraspanin expression. We report an optimized method for the use of antibodycapture single particle interferometric reflectance imaging sensing (SP-IRIS) and fluorescence detection to identify subpopulations according to tetraspanin expression and compare our findings with nanoscale flow cytometry. Using SP-IRIS and immunofluorescence, we report that tetraspanin profile is consistent from a given EV source regardless of isolation method, but that tetraspanin profiles are distinct across various sources. Tetraspanin profiles as measured by flow cytometry do not share similar trends, suggesting that limitations in subpopulation detection significantly impact apparent protein expression. We further analyzed tetraspanin expression of single EVs captured non-specifically, revealing that tetraspanin capture can bias the apparent multiplexed tetraspanin profile. Finally, we demonstrate that this bias can have significant impact on diagnostic sensitivity for tumor-associated EV surface markers. Our findings may reveal key insights into the complexities of the EV biogenesis and signaling pathways and better inform EV capture and detection platforms for diagnostic or other downstream use.
Genomic evaluation ofBordetella spp. originating from Australia
Authors: Fong Winkie , Timms Verlaine , Sim Eby , Sintchenko Vitali
Published: March 2021

Bordetella pertussisis the primary causative agent of pertussis, a highly infectious respiratory disease associated with prolonged coughing episodes. Pertussis infections are typically mild in adults, however in neonates, infections can be fatal. Despite successful vaccine uptake, the disease is re-emerging across the globe, therefore it is critical to determine the mechanism by whichB. pertussisis escaping vaccination control. Studies have suggested that significant changes have occurred inB. pertussisgenomes in response to whole cell and acellular vaccines. Continued molecular monitoring is therefore crucial for public health surveillance.

High-resolution molecular surveillance ofB. pertussiscan be achieved through the sequencing of the whole genome. In public health laboratories, whole genome sequencing is primarily performed by short-read sequencing technologies as they are most cost-effective. However short read sequencing does not resolve the extensive genomic rearrangement evident inBordetellagenomes. This is because repeat regions present inBordetellagenomes are collapsed by downstream analysis. For example, theB. pertussisgenome contains more than 200 copies of the IS481insertion element, hence assemblies generally consist of >200 contigs. Advancements in long-read technologies however increase the potential to circularise and close genomes by bridging the locations of the IS481insertion element.

In this study, we aimed to contextualise theBordetellaspp. circulating in NSW, Australia and assess their relationship with global isolates utilising core genome, SNP and structural clustering analysis using long read technology. We report five closed genomes ofBordetellaspp. isolated from Australian patients. Two of the threeB. pertussisclosed isolates, were unique with their own genomic structure, while the other structurally clustered with global isolates. We found that AustralianB. holmesiiandB. parapertussisstrains cluster with global isolates and do not appear to be unique to Australia. Australian draftB. holmesiiSNP analysis showed that between 1999 and 2007, isolates were relatively similar, however post-2012, isolates were distinct from each other. The closed isolates can also be used as high-quality reference sequences for both surveillance and other investigations into pertussis spread.
Apparent diet digestibility of captive colobines in relation to stomach types with special reference to fibre digestion
Authors: Hoshino Satoru , Seino Satoru , Funahashi Takashi , Hoshino Tomonori , Clauss Marcus , Mastuda Ikki , Yayota Masato
Published: March 2021

Colobine monkeys are known for the anatomical complexity of their stomachs, making them distinct within the primate order. Amongst foregut fermenters, they appear peculiar because of the occurrence of two different stomach types, having either three (‘tripartite’) or four (‘quadripartite’, adding the praesaccus) chambers. The functional differences between tri and quadripartite stomachs largely remain to be explained. In this study, we aim to compare the apparent digestibility (aD) in tripartite and quadripartite colobines. Hence, we measured the aD in two colobine species,Nasalis larvatus(quadripartite) andTrachypithecus cristatus(tripartite), in two zoos. We also included existing colobine literature data on the aD and analysed whether the aD of fibre components is different between the stomach types to test the hypothesis of whether quadripartite colobines show higher aD of fibre components than tripartite colobines did. Our captiveN. larvatusspecimen had a more distinctively varying nutrient intake across seasons with a larger seasonal variation in aD than that of a pair ofT. cristatus, which mostly consumed commercial foods with a lower proportion of browse and less seasonal variation. We observed higher aD of dry matter (DM), neutral detergent fibre (NDF) and acid detergent fibre (ADF) in theN. larvatusspecimen, suggesting a higher gut capacity ofN. larvatusprovided by the additional praesaccus forestomach chamber. Based on the analysis of literature data for aD, we also found that quadripartite species achieved higher fibre digestibility at similar dietary fibre levels compared with tripartite species, supporting the hypothesis that the additional gut capacity offered by the praesaccus facilitates a longer retention and hence more thorough microbial fermentation of plant fibre.
Development and Validation of LAMP Primer Sets for Rapid and Correct Identification of Aspergillus fumigatus Carrying the cyp51A TR46 Azole Resistance Gene
Authors: Trabasso Plinio , Matsuzawa Tetsuhiro , Arai Teppei , Hagiwara Daisuke , Mikami Yuzuru , Moretti Maria Luiza , Watanabe Akira
Published: March 2021

Infections due to triazole resistant Aspergillus fumigatus are increasingly reported worldwide and are associated with treatment failure and mortality. The principal class of azole resistant isolates is characterized by the presence of tandem repeats of 34 bp or 46 bp (TR34 or TR46) within the promoter region of the cyp51A gene. Loop-mediated isothermal amplification (LAMP) is a widely used nucleic acid amplification system with high rapidity and specificity. In this paper, we report a new LAMP assay method to detect the 46 bp tandem repeat insertion in the cyp51A gene promoter region, named TR46-LAMP assay, based on the use of a newly designed specific LAMP primer sets. TR46 is a high-prevalence allele which is associated with the occurrence of multi-triazole resistance of A. fumigatus in patients as well as isolates from the environment. This newly designed TR46-LAMP assay was validated as a useful method for specific detection of azole-resistant A. fumigatus isolates bearing TR462 as well as TR463 in cyp51A gene promoter region. It could also differentiate azole-resistant isolates of TR46 tandem repeats from those with TR34 tandem repeats in cyp51A genes. These results showed this TR46-LAMP method is specific, rapid, and also provides crucial insights to enable development of novel antifungal therapeutic strategies against severe fungal infections due to A. fumigatus with TR46 tandem repeats.
Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell epitope mapping
Authors: Schreibing Felix , Hannani Monica , Ticconi Fabio , Fewings Eleanor , Nagai James S , Begemann Matthias , Kuppe Christoph , Kurth Ingo , Kranz Jennifer , Frank Dario , Anslinger Teresa M , Ziegler Patrick , Kraus Thomas , Enczmann Jürgen , Balz Vera , Windhofer Frank , Balfanz Paul , Kurts Christian , Marx Gernot , Marx Nikolaus , Dreher Michael , Schneider Rebekka K , Saez-Rodriguez Julio , Costa Ivan , Kramann Rafael
Published: March 2021

The current COVID-19 pandemic represents a global challenge. A better understanding of the immune response against SARS-CoV-2 is key to unveil the differences in disease severity and to develop future vaccines targeting novel SARS-CoV-2 variants. Feature barcode technology combined with CITE-seq antibodies and DNA-barcoded peptide-MHC I Dextramer reagents enabled us to identify relevant SARS-CoV-2-derived epitopes and compare epitope-specific CD8+T cell populations between mild and severe COVID-19. We identified a strong CD8+T cell response against an S protein-derived epitope. CD8+effector cells in severe COVID-19 displayed hyperactivation, T cell exhaustion and were missing characteristics of long-lived memory T cells. We identify A*0101 WTAGAAAYY as an immunogenic CD8+T cell epitope with the ability to drive clonal expansion. We provide an in-depth characterization of the CD8+T cell-mediated response to SARS-CoV-2 infection which will be relevant for the development of molecular and targeted therapies and potential adjustments of vaccination strategies.
Paralogous gene modules derived from ancient hybridization drive vesicle traffic evolution in yeast
Authors: Purkanti Ramya , Thattai Mukund
Published: March 2021

Modules of interacting proteins regulate vesicle budding and fusion in eukaryotes. Distinct paralogous copies of these modules act at distinct sub-cellular locations. The processes by which such large gene modules are duplicated and retained remain unclear. Here we show that interspecies hybridization is a potent source of paralogous gene modules. We study the dynamics of paralog doublets derived from the 100-million-year-old hybridization event that gave rise to the whole genome duplication clade of budding yeast. We show that paralog doublets encoding vesicle traffic proteins are convergently retained across species. Vesicle coats and adaptors involved in secretory and early-endocytic pathways are retained as doublets, while tethers and other machinery involved in intra-Golgi traffic and later endocytic steps are reduced to singletons. These patterns reveal common selective pressures that have sculpted traffic pathways in diverse yeast species. They suggest that hybridization may have played a pivotal role in the expansion of the endomembrane system.
The connectome spectrum as a canonical basis for a sparse representation of fast brain activity
Authors: Rué-Queralt Joan , Glomb Katharina , Pascucci David , Tourbier Sebastien , Carboni Margherita , Vulliémoz Serge , Plomp Gijs , Hagmann Patric
Published: March 2021

The functional organization of neural processes is constrained by the brain’ s intrinsic structural connectivity. Here, we explore the potential of exploiting this structure in order to improve the signal representation properties of brain activity and its dynamics. Using a multi-modal imaging dataset (electroencephalography, structural MRI and diffusion MRI), we represent electrical brain activity at the cortical surface as a time-varying composition of harmonic modes of structural connectivity. The harmonic modes are termed connectome harmonics, and their representation is known as the connectome spectrum of the signal. We found that: first, the brain activity signal is more compactly represented by the connectome spectrum than by the traditional area-based representation; second, the connectome spectrum characterizes fast brain dynamics in terms of signal broadcasting profile, revealing different temporal regimes of integration and segregation that are consistent across participants. And last, the connectome spectrum characterises fast brain dynamics with fewer degrees of freedom than area-based signal representations. Specifically, we show that with the connectome spectrum representation, fewer dimensions are needed to capture the differences between low-level and high-level visual processing, and the topological properties of the signal. In summary, this work provides statistical, functional and topological evidence supporting that by accounting for the brain’ s structural connectivity fosters a more comprehensive understanding of large-scale dynamic neural functioning.
Geroprotective effects ofAronia melanocarpafruit extract onDrosophila melanogaster
Authors: Platonova Elena Y. , Zemskaya Nadezhda V. , Shaposhnikov Mikhail V. , Golubev Denis A. , Kukuman Daria V. , Pakshina Natalya R. , Ulyasheva Natalia S. , Punegov Vasily V. , Patov Sergey A. , Moskalev Alexey A.
Published: March 2021

Aging and its consequences is one of the main problems of humanity. Phytochemicals such as polyphenols, flavonoids, anthocyanins have great potential as geroprotectors. Plants including Aronia used as dietary supplements are an excellent source of these compounds. We have studied the effects of the ethanol extract from Aronia fruits onDrosophila melanogasterlifespan, locomotor activity, stress resistance (oxidative stress, heat shock and starvation). And also, in order to reveal the influence of Aronia extract applied to different life cycles ofDrosophila melanogaster, we selected different dietary schemes for imago: throughout life, during the first two weeks (1 – 2) and during average age (4 – 6 weeks). It was revealed that the ethanol extract of chokeberry increases the median life expectancy in males and females by 5% whenDrosophila melanogasteris added to the diet for 4 – 6 weeks of life. This suggests that intervention even in old age is sufficient to increase lifespan. In addition, no harmful effects of ABE on locomotor activity were found as an indicator of fly health. We showed that Aronia extract increased stress resistance to hyperthermia and oxidative stress. At the same time, Aronia extract did not significantly affect the resistance of flies to starvation. ABE supplementation has increased expression of heat shock proteins (Hsp27, Hsp68, Hsp83), oxidative stress resistance genes (Keap1, NRF, Sod1), some circadian clock genes (Clk, per) and gene of longevitySirt1.
A Machine Learning Approach to Unmask Novel Gene Signatures and Prediction of Alzheimer’s Disease Within Different Brain Regions
Authors: Sharma Abhibhav , Dey Pinki
Published: March 2021

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder whose aetiology is currently unknown. Although numerous studies have attempted to identify the genetic risk factor(s) of AD, the interpretability and/or the prediction accuracies achieved by these studies remained unsatisfactory, reducing their clinical significance. Here, we employ the ensemble of random-forest and regularized regression model (LASSO) to the AD-associated microarray datasets from four brain regions - Prefrontal cortex, Middle temporal gyrus, Hippocampus, and Entorhinal cortex- to discover novel genetic biomarkers through a machine learning-based feature-selection classification scheme. The proposed scheme unrevealed the most optimum and biologically significant classifiers within each brain region, which achieved by far the highest prediction accuracy of AD in 5-fold cross-validation (99% average). Interestingly, along with the novel and prominent biomarkers including CORO1C, SLC25A46, RAE1, ANKIB1, CRLF3, PDYN, numerous non-coding RNA genes were also observed as discriminator, of which AK057435 and BC037880 are uncharacterized long non-coding RNA genes.
Genome-wide identification of genetic requirements ofPseudomonas aeruginosaPAO1 for rat cardiomyocyte (H9C2) infection by insertion sequencing
Authors: Ranjani Jothi , Sivakumar Ramamoorthy , Gunasekaran Paramasamy , Rajendhran Jeyaprakash
Published: March 2021

Pseudomonas aeruginosais the major infectious agent among Gram-negative bacteria which causes both acute and chronic infections without any tissue specificity. Infections due toP. aeruginosaare hard to treat, as it entails various strategies like virulence factors synthesis, drug efflux systems & resistance and protein secretion systems during pathogenesis. Despite extensive research inPseudomonaspathogenesis, novel drug targets and potential therapeutic strategies are inevitable. In this study, we investigated the genetic requirements ofP.aeruginosaPAO1 for rat cardiomyocyte (H9C2) infection by insertion sequencing (INSeq). A mutant library comprising ~70,000 mutants of PAO1 was generated and the differentiated form of H9C2 cells (d-H9C2) was infected with the library. The infected d-H9C2 cells were maintained with antibiotic-protection and without any antibiotics in the growth media for 24 h. Subsequently, DNA library for INSeq was prepared, sequenced and fitness analysis was performed. A-One hundred and thirteen mutants were negatively selected in the infection condition with antibiotic-protection, whereas 143 mutants were negatively selected in antibiotic-free condition. Surprisingly, a higher number of mutants showed enriched fitness than the mutants of reduced fitness during the infection. We demonstrated that the genes associated with flagella and T3SS are important for adhesion and invasion of cardiomyocytes, while pili and proteases are conditionally essential during host cell lysis.

Take away

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Fitness ofP.aeruginosamutants were analyzed during cardiomyocyte infection

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Genes involve amino acid transport & metabolism and signal transduction are important during intracellular lifestyle

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OMVs play a crucial role during infection and pathogenesis

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Flagella and T3SS are conditionally essential for adhesion and invasion, whereas pili and proteases are conditionally essential during host cell lysis
Dopaminergic signaling supports auditory social learning
Authors: Paraouty Nihaad , Rizzuto Catherine R. , Sanes Dan H.
Published: March 2021

Explicit rewards are commonly used to reinforce a behavior, a form of learning that engages the dopaminergic neuromodulatory system. In contrast, skill acquisition can display dramatic improvements from a social learning experience, even though the observer receives no explicit reward. Here, we test whether a dopaminergic signal contributes to social learning in naïve gerbils that are exposed to, and learn from, a skilled demonstrator performing an auditory discrimination task. Following five exposure sessions, naïve observer gerbils were allowed to practice the auditory task, and their performance was assessed across days. We first tested the effect of an explicit food reward in the observer’s compartment that was yoked to the demonstrator’s performance during exposure sessions. Naïve observer gerbils with the yoked reward learned the discrimination task significantly faster, as compared to unrewarded observers. The effect of this explicit reward was abolished by administration of a D1/D5 dopamine receptor antagonist during the exposure sessions. Similarly, the D1/D5 antagonist reduced the rate of learning in unrewarded observers. To test whether a dopaminergic signal was sufficient to enhance social learning, we administered a D1/D5 receptor agonist during the exposure sessions in which no reward was present, and found that the rate of learning occurred significantly faster. Finally, a quantitative analysis of observer vocalizations and movements during the exposure sessions suggest behavioral strategies that contribute to social learning. Together, these results are consistent with a dopamine-dependent reward signal during social learning.
Novel anti-repression mechanism of H-NS proteins by a phage “early protein”
Authors: Bdira Fredj Ben , Qin Liang , Volkov Alexander N. , Lippa Andrew M. , Erkelens Amanda M. , Bowring Nicholas , Boyle Aimee L. , Ubbink Marcellus , Dove Simon L. , Dame Remus T.
Published: March 2021

H-NS family proteins, bacterial xenogeneic silencers, play central roles in genome organization and in the regulation of foreign genes. It is thought that gene repression is directly dependent on the DNA binding modes of H-NS family proteins. These proteins form lateral protofilaments along DNA. Under specific environmental conditions they switch to bridging two DNA duplexes. This switching is a direct effect of environmental conditions on electrostatic interactions between the oppositely charged DNA binding and N-terminal domains of H-NS proteins. ThePseudomonaslytic phage LUZ24 encodes the early protein gp4, which modulates the DNA binding and function of the H-NS family protein MvaT ofPseudomonas aeruginosa. However, the mechanism by which gp4 modulates MvaT activity remains elusive. In this study, we show that gp4 specifically interferes with the formation and stability of the bridged MvaT-DNA complex. Structural investigations suggest that gp4 acts as an “electrostatic zipper” between the oppositely charged domains of MvaT protomers, and stabilizes a structure resembling their “half-open” conformation, resulting in relief of gene silencing and adverse effects onP. aeruginosagrowth. The ability to control H-NS conformation and thereby its impact on global gene regulation and growth might open new avenues to fightPseudomonasmultidrug resistance.
Modulation of early level EEG signatures by distributed facial emotion cues
Authors: Costa Diana , Dias Camila , Sousa Teresa , Estiveira João , Castelhano João , Figueiredo Verónica , Pereira Andreia , Castelo-Branco Miguel
Published: March 2021

Face perception plays an important role in our daily social interactions, as it is essential to recognize emotions. The N170 Event Related Potential (ERP) component has been widely identified as a major face-sensitive neuronal marker. However, despite extensive investigations conducted to examine this electroencephalographic pattern, there is yet no agreement regarding its sensitivity to the content of facial expressions.

Here, we aim to clarify the EEG signatures of the recognition of facial expressions by investigating ERP components that we hypothesize to be associated with this cognitive process. We asked the question whether the recognition of facial expressions is encoded by the N170 as weel as at the level of P100 and P250. In order to test this hypothesis, we analysed differences in amplitudes and latencies for the three ERPs, in a sample of 20 participants. A visual paradigm requiring explicit recognition of happy, sad and neutral faces was used. The facial cues were explicitly controlled to vary only regarding mouth and eye components. We found that non neutral emotion expressions elicit a response difference in the amplitude of N170 and P250. In contrast with the P100, there by excluding a role for low level factors.

Our study brings new light to the controversy whether emotional face expressions modulate early visual response components, which have been often analysed apart. The results support the tenet that neutral and emotional faces evoke distinct N170 patterns, but go further by revealing that this is also true for P250, unlike the P100.