bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum carcinoembryonic antigen and carbohydrate antigen 19-9 as preoperative diagnostic biomarkers of extrahepatic bile duct cancer
Authors: Kim Hyeong Seok , Han Youngmin , Kang Jae Seung , Kang Yoon Hyung , Lee Mirang , Sohn Hee Ju , Kim Hongbeom , Kwon Wooil , Jang Jin-Young
Published: December 2021

Background

Serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have been proposed as useful preoperative biomarkers of extrahepatic bile duct cancer (EBDC). This study investigated the accuracy of CEA and CA19-9 for preoperative diagnosis of EBDC.

Methods

Patients who underwent surgery for EBDC at a tertiary centre between 1995 and 2018 were studied, and those with concurrent hepatobiliary diseases (including gallbladder cancer, intraductal papillary mucinous neoplasms of pancreas), which could affect CEA or CA19-9 levels, were excluded. The control group included patients who underwent cholecystectomy for benign gallbladder diseases during the same period. Diagnostic accuracy was determined using sensitivity, specificity and area under the receiver operating characteristic curve (AUC).

Results

After excluding 23 patients, 687 patients (488 men and 199 women, mean age 65.8 years) were compared with the control group of 2310 patients. Median CEA and CA19-9 levels were 1.8 μg/l and 47.0 kU/l in patients with EBDC. CEA (cut-off 5.0 μg/l) showed AUC of 0.541, sensitivity 9.0 per cent and specificity 99.2 per cent, whereas CA19-9 (cut-off 37.0 kU/l) showed AUC of 0.753, sensitivity 56.2 per cent and specificity 94.5 per cent. Sensitivity of CA19-9 was lower in early (T stages 0–II) than advanced (T stages III and IV) cancer (47.0 versus 64.9 per cent), and also lower in N0 stage cancer than lymph node metastasis (50.1 versus 68.8 per cent).

Conclusion

Serum CEA and CA19-9 showed low sensitivity limiting their usefulness as diagnostic biomarkers of EBDC.
Tenofovir Alafenamide Plasma Concentrations Are Reduced in Pregnant Women Living With Human Immunodeficiency Virus (HIV): Data From the PANNA Network
Authors: Bukkems Vera E , Necsoi Coca , Hidalgo Tenorio Carmen , Garcia Coral , Alba Alejandre Irene , Weiss Fabian , Lambert John S , van Hulzen Astrid , Richel Olivier , te Brake Lindsey H M , van der Meulen Eric , Burger David , Konopnicki Deborah , Colbers Angela
Published: December 2021

Background

Tenofovir alafenamide (TAF), a prodrug of tenofovir (TFV), is included in the majority of the recommended first-line antiretroviral regimens for patients living with human immunodeficiency virus (HIV), but there are limited data on TAF use in pregnant women. We aimed to examine the plasma pharmacokinetics of TAF and TFV in pregnant women from Europe.

Methods

Pregnant women living with HIV were included from treatment centers across Europe, and intensive pharmacokinetic sampling in the third trimester and postpartum was performed. Pharmacokinetic parameters of TAF and TFV were determined with noncompartmental analysis. The proportion of women with a TAF area under the curve (AUClast) below the target of 53.1 ng∗h/mL was determined. Clinical efficacy and safety outcome parameters were reported.

Results

In total, 20 pregnant women living with HIV were included. At the third trimester, geometric mean TAF AUClast and Cmax were decreased by 46% and 52%, respectively, compared with postpartum. TFV AUC0-24h, Cmax, and Ctrough decreased by 33%, 30%, and 34%, respectively. The proportion of women with a TAF AUClast < 53.1 ng∗h/mL was 6% at third trimester and 0% postpartum. One out of 20 women had a viral load > 50 copies/mL at third trimester and no mother-to-child transmission occurred.

Conclusions

TAF plasma concentrations were reduced by about half in women living with HIV during third trimester of pregnancy but remained above the predefined efficacy target in the majority of the pregnant women. TFV concentrations were reduced by approximately 30% during third trimester. Despite the observed exposure decrease, high virologic efficacy was observed in this study.
Circulating Ubiquitous RNA, A Highly Predictive and Prognostic Biomarker in Hospitalized Coronavirus Disease 2019 (COVID-19) Patients
Authors: Bruneau Thomas , Wack Maxime , Poulet Geoffroy , Robillard Nicolas , Philippe Aurélien , Puig Pierre Laurent , Bélec Laurent , Hadjadj Jérôme , Xiao Wenjin , Kallberg Julia Linnea , Kernéis Solen , Diehl Jean Luc , Terrier Benjamin , Smadja David M , Taly Valerie , Veyer David , Péré Hélène
Published: December 2021

Background

Approximately 15–30% of hospitalized coronavirus disease 2019 (COVID-19) patients develop acute respiratory distress syndrome, systemic tissue injury, and/or multi-organ failure leading to death in around 45% of cases. There is a clear need for biomarkers that quantify tissue injury, predict clinical outcomes, and guide the clinical management of hospitalized COVID-19 patients.

Methods

We herein report the quantification by droplet-based digital polymerase chain reaction (ddPCR) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia and the plasmatic release of a ubiquitous human intracellular marker, the ribonuclease P (RNase P) in order to evaluate tissue injury and cell lysis in the plasma of 139 COVID-19 hospitalized patients at admission.

Results

We confirmed that SARS-CoV-2 RNAemia was associated with clinical severity of COVID-19 patients. In addition, we showed that plasmatic RNase P RNAemia at admission was also highly correlated with disease severity (P < .001) and invasive mechanical ventilation status (P < .001) but not with pulmonary severity. Altogether, these results indicate a consequent cell lysis process in severe and critical patients but not systematically due to lung cell death. Finally, the plasmatic RNase P RNA value was also significantly associated with overall survival.

Conclusions

Viral and ubiquitous blood biomarkers monitored by ddPCR could be useful for the clinical monitoring and the management of hospitalized COVID-19 patients. Moreover, these results could pave the way for new and more personalized circulating biomarkers in COVID-19, and more generally in infectious diseases, specific from each patient organ injury profile.
Time to Flexible Sigmoidoscopy or Colonoscopy in Patients Admitted With Ulcerative Colitis Has Decreased From 2012 to 2018
Authors: Bali Aman S , Picco Michael F , Hashash Jana G , Farraye Francis A , Kröner Paul T
Published: December 2021

Background

Early endoscopic evaluation of patients with ulcerative colitis (UC) enables assessment of disease activity and accurate diagnosis based on exclusion of other similarly presenting conditions including infections. Early endoscopy is also associated with improved outcomes of patients with active UC. The aim of this study was determining temporal trends in endoscopy in patients with UC over a 7-year period from 2012 to 2018.

Methods

Retrospective cohort study using the National Inpatient Sample 2012–2018. Patients admitted with ICD-9–10 principal codes for UC were included. Early endoscopy using flexible sigmoidoscopy (FS) or colonoscopy was defined as performed within 48 hours of admission. The primary outcome was trends in endoscopy timing. Secondary outcomes were inpatient morbidity, mortality, length of stay (LOS), and hospitalization charges/costs comparing patients undergoing early vs nonearly endoscopy using multivariable regression.

Results

Of 222 460 patients hospitalized with UC, 5900 (2.7%) underwent FS and 43 345 (19.5%) underwent colonoscopy. The rate of endoscopy increased from 3.9% (2.3% early) to 39.3% (23.3% early) from 2012 to 2018 (P < .01). Early endoscopy was associated with statistically significant decreased mortality, shock, multiorgan failure, and intensive care unit odds, as well as decreased resource utilization and LOS.

Conclusions

In patients hospitalized with UC, early endoscopy rates were low but performed more frequently from 2012 to 2018. This may reflect increasing awareness of improved outcomes from earlier disease staging and/or diagnosis. Early endoscopy was associated with decreased resource utilization and hospitalization-related outcomes, highlighting the importance of early endoscopy in patients admitted with UC.
Slow periodic oscillation without radiation damping: new evolution laws for rate and state friction
Authors: Mizushima Ryo , Hatano Takahiro
Published: December 2021

The dynamics of sliding friction is mainly governed by the frictional force. Previous studies have shown that the laboratory-scale friction is well described by an empirical law stated in terms of the slip velocity and the state variable. The state variable represents the detailed physicochemical state of the sliding interface. Despite some theoretical attempts to derive this friction law, there has been no unique equation for time evolution of the state variable. Major equations known to date have their own merits and drawbacks. To shed light on this problem from a new aspect, here we investigate the feasibility of periodic motion without the help of radiation damping. Assuming a patch on which the slip velocity is perturbed from the rest of the sliding interface, we prove analytically that three major evolution laws fail to reproduce stable periodic motion without radiation damping. Furthermore, we propose two new evolution equations that can produce stable periodic motion without radiation damping. These two equations are scrutinized from the viewpoint of experimental validity and the relevance to slow earthquakes.
An interactive video increasing French students’ mental health literacy: a mixed-methods randomized controlled pilot study
Authors: Queroue Marine , Pouymayou Aude , Pereira Edwige , Tzourio Christophe , González-Caballero Juan Luis , Montagni Ilaria
Published: December 2021

Mental health literacy (MHL) is a determinant of psychological well-being in young people. A randomized controlled design was used to evaluate the appreciation and effectiveness of an interactive video on French University students’ MHL (knowledge about depression and suicidal behavior, mental health help-seeking behaviors, stigma and misconceptions about mental health). At the baseline, all participants (n = 101) completed a questionnaire including several scales on MHL. One month after, participants were randomly assigned to two homogeneous groups (intervention, n = 50 or control, n = 51) and again completed the questionnaire on MHL. Through a mixed-methods approach, semi-structured interviews were also conducted with the intervention group to collect information on the appreciation of the interactive video. Quantitative data indicated that MHL scores increased or remained stable in the intervention group. Comparison with the control group and multivariate logistic regression models did not show statistically significant differences, due to the small sample of the study. According to qualitative data, users appreciated the content and the format of the intervention. It was suggested that the video could be disseminated in other University campuses in France and internationally to promote MHL among students.
An evaluation of information sharing schemes to identify what motivates fishers to share catch information
Authors: Calderwood Julia , Marshall C Tara , Haflinger Karl , Alfaro-Shigueto Joanna , Mangel Jeffrey C , Reid David G
Published: December 2021

Avoiding unwanted catches and reducing discards is an important objective of fisheries management. Fishers can avoid unwanted catches to some extent by improving selectivity of their fishing operations. This can be achieved through technical measures and gear modifications but also by adjusting when and where fishing takes place. Having access to real-time information, as provided through information sharing within a fleet, can help fishers avoid unwanted catches. Yet, there often remains a reluctance to share catch information with others. This paper compiles information from 15 case study examples of existing information sharing schemes in fisheries throughout the world. We compare the structure and operation of each of these schemes and determine what motivated participants to join and share potentially sensitive catch information. While there is no one-size-fits-all approach to designing and implementing information sharing schemes in fisheries, this paper highlights how industry and stakeholder support is often important, and understanding the needs, concerns, and motivations of any group of fishers is fundamental in developing and expanding such approaches.
Psilocybin Therapy of Psychiatric Disorders Is Not Hampered by hERG Potassium Channel–Mediated Cardiotoxicity
Authors: Hackl Benjamin , Todt Hannes , Kubista Helmut , Hilber Karlheinz , Koenig Xaver
Published: December 2021

Psilocybin, a hallucinogen contained in “magic” mushrooms, holds great promise for the treatment of various psychiatric disorders, and early clinical trials are encouraging. Adverse cardiac events after intake of high doses of psilocybin and a trial reporting QT interval prolongation in the electrocardiogram attributed to the drug’s main metabolite, psilocin, gave rise to safety concerns. Here we show that clinical concentrations of psilocin do not cause significant human ether-a-go-go-related gene (hERG) potassium channel inhibition, a major risk factor for adverse cardiac events. We conclude that hERG channel blockage by psilocin is not liable for psilocybin- associated cardiotoxic effects.
Finite-time stabilization of nonlinear polytopic systems: a control Lyapunov function approach
Authors: Kumar Soni Sandeep , Kamal Shyam , Ghosh Sandip , Olaru Sorin
Published: December 2021

This paper addresses the finite-time stabilization of nonlinear polytopic systems. Sufficient conditions are proposed for the existence of a continuous time-invariant finite-time stabilizing state feedback controller through a robust control Lyapunov function. It is shown that the obtained sufficient condition is also necessary if there exists a state feedback controller such that the closed-loop system has a robust Lyapunov function for all possible uncertainties. Finally, to verify the efficacy of the proposed control design, a numerical example is presented.
Impact of Dapivirine and Placebo Vaginal Rings on the Microbiota of Adolescent, Lactating, and Postmenopausal Females
Authors: Austin Michele N , Meyn Leslie A , Avolia Hilary A , Petrina Melinda A , Cosentino Lisa A , Alphonse Calins , Chen Beatrice A , Bunge Katherine , Noguchi Lisa , Beigi Richard , Squires Kathleen , Hillier Sharon L
Published: December 2021

Background

A 25-mg dapivirine vaginal ring has been demonstrated to reduce risk of human immunodeficiency virus (HIV) acquisition in nonpregnant adult women. In this secondary analysis of studies conducted in US adolescent, lactating, and postmenopausal females, vaginal microbiota was assessed prior to and after ring use, and between dapivirine and placebo ring users.

Methods

Vaginal fluid swabs were collected before and after product use for the evaluation of microbiota using Nugent criteria, quantitative culture, and quantitative polymerase chain reaction.

Results

Vaginal ring use did not impact bacterial vaginosis prevalence among the 3 populations and was associated with minimal shifts in microbiota. Adolescents in both arms demonstrated an increased prevalence of Lactobacillus crispatus and a decrease in quantity of Megasphaera lornae. Postmenopausal active and placebo ring users demonstrated an increased prevalence of lactobacilli and non-albicans yeast, while dapivirine ring users demonstrated an increased prevalence of Candida albicans and increased quantity of group B Streptococcus and non-albicans yeasts. Prevotella species were increased in lactating women, whereas Prevotella timonensis increased in prevalence and concentration among adolescent and postmenopausal females and Prevotella bivia increased in prevalence among adolescent dapivirine ring users.

Conclusions

Dapivirine vaginal ring use was associated with minimal changes in the vaginal microbiota that are likely not clinically significant.
Migrating a research data warehouse to a public cloud: challenges and opportunities
Authors: Kahn Michael G , Mui Joyce Y , Ames Michael J , Yamsani Anoop K , Pozdeyev Nikita , Rafaels Nicholas , Brooks Ian M
Published: December 2021

Objective

Clinical research data warehouses (RDWs) linked to genomic pipelines and open data archives are being created to support innovative, complex data-driven discoveries. The computing and storage needs of these research environments may quickly exceed the capacity of on-premises systems. New RDWs are migrating to cloud platforms for the scalability and flexibility needed to meet these challenges. We describe our experience in migrating a multi-institutional RDW to a public cloud.

Materials and Methods

This study is descriptive. Primary materials included internal and public presentations before and after the transition, analysis documents, and actual billing records. Findings were aggregated into topical categories.

Results

Eight categories of migration issues were identified. Unanticipated challenges included legacy system limitations; network, computing, and storage architectures that realize performance and cost benefits in the face of hyper-innovation, complex security reviews and approvals, and limited cloud consulting expertise.

Discussion

Cloud architectures enable previously unavailable capabilities, but numerous pitfalls can impede realizing the full benefits of a cloud environment. Rapid changes in cloud capabilities can quickly obsolete existing architectures and associated institutional policies. Touchpoints with on-premise networks and systems can add unforeseen complexity. Governance, resource management, and cost oversight are critical to allow rapid innovation while minimizing wasted resources and unnecessary costs.

Conclusions

Migrating our RDW to the cloud has enabled capabilities and innovations that would not have been possible with an on-premises environment. Notwithstanding the challenges of managing cloud resources, the resulting RDW capabilities have been highly positive to our institution, research community, and partners.
Early specialized palliative care for patients with metastatic lung cancer receiving chemotherapy: a feasibility study of a nurse-led screening-triggered programme
Authors: Matsumoto Yoshihisa , Umemura Shigeki , Okizaki Ayumi , Fujisawa Daisuke , Kobayashi Naoko , Tanaka Yuko , Sasaki Chiyuki , Shimizu Ken , Ogawa Asao , Kinoshita Hiroya , Uchitomi Yosuke , Yoshiuchi Kazuhiro , Matsuyama Yutaka , Morita Tatsuya , Goto Koichi , Ohe Yuichiro
Published: December 2021

Background

Strategies to implement early specialized palliative care have not yet been established. The present study investigated the feasibility of a nurse-led, screening-triggered early specialized palliative care intervention programme and obtained data to design a randomized controlled trial.

Methods

Patients with metastatic lung cancer undergoing first-line platinum-based chemotherapy were eligible. The intervention consisted of (1) a questionnaire-based screening programme and (2) advanced-level nurse counselling and care coordination with interdisciplinary team approach. The primary endpoint was the completion rate of the assessment questionnaire after the second course of first-line chemotherapy (T2). Secondary endpoints included changes in Functional Assessment of Cancer Therapy-Lung scores, depression and anxiety rates based on the Patient Health Questionnaire 9 and the Hospital Anxiety and Depression Scale, and the contents of specialized palliative care.

Results

A total of 50 patients were enrolled between August 2012 and March 2014. Median age was 66 years (range, 40–78 year) and 84% were male. A total of 38 patients had stage IV non-small cell lung carcinoma and 12 had extensive disease small-cell lung carcinoma. The completion rate was 70% (95% confidence interval 56.0–81.0). The median duration between baseline and T2 was 53 days. Improvement from baseline were observed at T2 in Functional Assessment of Cancer Therapy-Lung scores (86.0 ± 18.1 vs 94.9 ± 18.2, P = 0.057), depression (16.0 vs 5.7%; P = 0.26) and anxiety (32.0 vs 22.9%; P = 0.65); however, these results were not statistically significant.

Conclusions

This early specialized palliative care intervention is feasible and could be useful in improving patients’ quality of life. The present results justify the initiation of a randomized control trial.
Fungal oxysterol-binding protein-related proteins promote pathogen virulence and activate plant immunity
Authors: Chen Meng-Meng , Yang Si-Ru , Wang Jian , Fang Ya-Li , Peng You-Liang , Fan Jun
Published: December 2021

Oxysterol-binding protein-related proteins (ORPs) are a conserved class of lipid transfer proteins that are closely involved in multiple cellular processes in eukaryotes, but their roles in plant–pathogen interactions are mostly unknown. We show that transient expression of ORPs of Magnaporthe oryzae (MoORPs) in Nicotiana benthamina plants triggered oxidative bursts and cell death; treatment of tobacco Bright Yellow-2 suspension cells with recombinant MoORPs elicited the production of reactive oxygen species. Despite ORPs being normally described as intracellular proteins, we detected MoORPs in fungal culture filtrates and intercellular fluids from barley plants infected with the fungus. More importantly, infiltration of Arabidopsis plants with recombinant Arabidopsis or fungal ORPs activated oxidative bursts, callose deposition, and PR1 gene expression, and enhanced plant disease resistance, implying that ORPs may function as endogenous and exogenous danger signals triggering plant innate immunity. Extracellular application of fungal ORPs exerted an opposite impact on salicylic acid and jasmonic acid/ethylene signaling pathways. Brassinosteroid Insensitive 1-associated Kinase 1 was dispensable for the ORP-activated defense. Besides, simultaneous knockout of MoORP1 and MoORP3 abolished fungal colony radial growth and conidiation, whereas double knockout of MoORP1 and MoORP2 compromised fungal virulence on barley and rice plants. These observations collectively highlight the multifaceted role of MoORPs in the modulation of plant innate immunity and promotion of fungal development and virulence in M. oryzae.
Plant iron nutrition: the long road from soil to seeds
Authors: Murgia Irene , Marzorati Francesca , Vigani Gianpiero , Morandini Piero
Published: December 2021

Iron (Fe) is an essential plant micronutrient since many cellular processes including photosynthesis, respiration, and the scavenging of reactive oxygen species depend on adequate Fe levels; however, non-complexed Fe ions can be dangerous for cells, as they can act as pro-oxidants. Hence, plants possess a complex homeostatic control system for safely taking up Fe from the soil and transporting it to its various cellular destinations, and for its subcellular compartmentalization. At the end of the plant’s life cycle, maturing seeds are loaded with the required amount of Fe needed for germination and early seedling establishment. In this review, we discuss recent findings on how the microbiota in the rhizosphere influence and interact with the strategies adopted by plants to take up iron from the soil. We also focus on the process of seed-loading with Fe, and for crop species we also consider its associated metabolism in wild relatives. These two aspects of plant Fe nutrition may provide promising avenues for a better comprehension of the long pathway of Fe from soil to seeds.
Fatty alcohol oxidase 3 (FAO3) and FAO4b connect the alcohol- and alkane-forming pathways in Arabidopsis stem wax biosynthesis
Authors: Yang Xianpeng , Cui Lili , Li Shipeng , Ma Changle , Kosma Dylan K , Zhao Huayan , Lü Shiyou
Published: December 2021

The alcohol- and alkane-forming pathways in cuticular wax biosynthesis are well characterized in Arabidopsis. However, potential interactions between the two pathways remain unclear. Here, we reveal that mutation of CER4, the key gene in the alcohol-forming pathway, also led to a deficiency in the alkane-forming pathway in distal stems. To trace the connection between the two pathways, we characterized two homologs of fatty alcohol oxidase (FAO), FAO3 and FAO4b, which were highly expressed in distal stems and localized to the endoplasmic reticulum. The amounts of waxes from the alkane-forming pathway were significantly decreased in stems of fao4b and much lower in fao3 fao4b plants, indicative of an overlapping function for the two proteins in wax synthesis. Additionally, overexpression of FAO3 and FAO4b in Arabidopsis resulted in a dramatic reduction of primary alcohols and significant increases of aldehydes and related waxes. Moreover, expressing FAO3 or FAO4b led to significantly decreased amounts of C18–C26 alcohols in yeast co-expressing CER4 and FAR1. Collectively, these findings demonstrate that FAO3 and FAO4b are functionally redundant in suppressing accumulation of primary alcohols and contributing to aldehyde production, which provides a missing and long-sought-after link between these two pathways in wax biosynthesis.
Molybdenum: More than an essential element
Authors: Huang Xin-Yuan , Hu Da-Wei , Zhao Fang-Jie
Published: December 2021

Molybdenum (Mo) is an essential element for almost all living organisms. After being taken up into the cells as molybdate, it is incorporated into the molybdenum cofactor, which functions as the active site of several molybdenum-requiring enzymes and thus plays crucial roles in multiple biological processes. The uptake and transport of molybdate is mainly mediated by two types of molybdate transporters. The homeostasis of Mo in plant cells is tightly controlled, and such homeostasis likely plays vital roles in plant adaptation to local environments. Recent evidence suggests that Mo is more than an essential element required for plant growth and development; it is also involved in local adaptation to coastal salinity. In this review, we summarize recent research progress on molybdate uptake and transport, molybdenum homeostasis network in plants, and discuss the potential roles of the molybdate transporter in plant adaptation to their local environment.
The effect of dwarf galaxies on the tidal tails of globular clusters
Authors: El-Falou Nada , Webb Jeremy J
Published: December 2021

The tidal tails of globular clusters have been shown to be sensitive to the external tidal field. We investigate how Galactic globular clusters with observed tails are affected by satellite dwarf galaxies by simulating tails in galaxy models with and without dwarf galaxies. The simulations indicate that tidal tails can be subdivided into three categories based on how they are affected by dwarf galaxies: (1) dwarf galaxies perturb the progenitor cluster’s orbit (NGC 4590, Pal 1, Pal 5), (2) dwarf galaxies perturb the progenitor cluster’s orbit and individual tail stars (NGC 362, NGC 1851, NGC 4147, NGC 5466, NGC 7492, Pal 14, Pal 15), and (3) dwarf galaxies negligibly affect tidal tails (NGC 288, NGC 5139, NGC 5904, Eridanus). Perturbations to a cluster’s orbit occur when dwarf galaxies pass within its orbit, altering the size and shape of the orbital and tail path. Direct interactions between one or more dwarf galaxies and tail stars lead to kinks and spurs, however we find that features are more difficult to observe in projection. We further find that the tails of Pal 5 are shorter in the galaxy model with dwarf galaxies as it is closer to apocentre, which results in the tails being compressed. Additional simulations reveal that differences between tidal tails in the two galaxy models are primarily due to the Large Magellanic Cloud. Understanding how dwarf galaxies affect tidal tails allows for tails to be used to map the distribution of matter in dwarf galaxies and the Milky Way.
Reconstructing orbits of galaxies in extreme regions (ROGER) – II: reliability of projected phase-space in our understanding of galaxy populations
Authors: Coenda Valeria , Rios Martín de los , Muriel Hernán , Cora Sofía A , Martínez Héctor J , Ruiz Andrés N , Vega-Martínez Cristian A
Published: December 2021

We connect galaxy properties with their orbital classification by analysing a sample of galaxies with stellar mass M⋆ ≥ 108.5h−1M⊙ residing in and around massive and isolated galaxy clusters with mass M200 > 1015h−1M⊙ at redshift z = 0. The galaxy population is generated by applying the semi-analytic model of galaxy formation sag on the cosmological simulation MultiDark Planck 2. We classify galaxies considering their real orbits (3D) and their projected phase-space position using the roger  code (2D). We define five categories: cluster galaxies, galaxies that have recently fallen into a cluster, backsplash galaxies, infalling galaxies, and interloper galaxies. For each class, we analyse the 0.1(g − r) colour, the specific star formation rate (sSFR), and the stellar age, as a function of the stellar mass. For the 3D classes, we find that cluster galaxies have the lowest sSFR, and are the reddest and the oldest, as expected from environmental effects. Backsplash galaxies have properties intermediate between the cluster and recent infaller galaxies. For each 2D class, we find an important contamination by other classes. We find it necessary to separate the galaxy populations in red and blue to perform a more realistic analysis of the 2D data. For the red population, the 2D results are in good agreement with the 3D predictions. Nevertheless, when the blue population is considered, the 2D analysis only provides reliable results for recent infallers, infalling galaxies and interloper galaxies.
Rapid turn-on of a luminous X-ray source in the candidate Lyman continuum emitting galaxy Tol 0440-381
Authors: Kaaret P , Bluem J , Prestwich A H
Published: December 2021

Chandra observations of the nearby candidate Lyman continuum (LyC) emitting galaxy Tol 0440-381 show brightening of an X-ray source by at least a factor of 4 to a luminosity of $1.6 \times 10^{40} \rm \, erg \, s^{-1}$ over 3.8 d. The X-ray emission likely arises from either a low-luminosity active galactic nucleus or an ultraluminous X-ray source. The properties of the X-ray source are similar to those found in Haro 11 and Tololo 1247-232, the only other LyC emitting galaxies that have been resolved in X-rays. All three galaxies host luminous, variable, and hard-spectrum X-ray sources that are likely accretion-powered. Accretion on to compact objects produces powerful outflows and ionizing radiation that could help enable LyC escape.
Caught in motion: human NTHL1 undergoes interdomain rearrangement necessary for catalysis
Authors: Carroll Brittany L , Zahn Karl E , Hanley John P , Wallace Susan S , Dragon Julie A , Doublié Sylvie
Published: December 2021

Base excision repair (BER) is the main pathway protecting cells from the continuous damage to DNA inflicted by reactive oxygen species. BER is initiated by DNA glycosylases, each of which repairs a particular class of base damage. NTHL1, a bifunctional DNA glycosylase, possesses both glycolytic and β-lytic activities with a preference for oxidized pyrimidine substrates. Defects in human NTHL1 drive a class of polyposis colorectal cancer. We report the first X-ray crystal structure of hNTHL1, revealing an open conformation not previously observed in the bacterial orthologs. In this conformation, the six-helical barrel domain comprising the helix-hairpin-helix (HhH) DNA binding motif is tipped away from the iron sulphur cluster-containing domain, requiring a conformational change to assemble a catalytic site upon DNA binding. We found that the flexibility of hNTHL1 and its ability to adopt an open configuration can be attributed to an interdomain linker. Swapping the human linker sequence for that of Escherichia coli yielded a protein chimera that crystallized in a closed conformation and had a reduced activity on lesion-containing DNA. This large scale interdomain rearrangement during catalysis is unprecedented for a HhH superfamily DNA glycosylase and provides important insight into the molecular mechanism of hNTHL1.
Foster thy young: enhanced prediction of orphan genes in assembled genomes
Authors: Li Jing , Singh Urminder , Bhandary Priyanka , Campbell Jacqueline , Arendsee Zebulun , Seetharam Arun S , Wurtele Eve Syrkin
Published: December 2021

Proteins encoded by newly-emerged genes (‘orphan genes’) share no sequence similarity with proteins in any other species. They provide organisms with a reservoir of genetic elements to quickly respond to changing selection pressures. Here, we systematically assess the ability of five gene prediction pipelines to accurately predict genes in genomes according to phylostratal origin. BRAKER and MAKER are existing, popular ab initio tools that infer gene structures by machine learning. Direct Inference is an evidence-based pipeline we developed to predict gene structures from alignments of RNA-Seq data. The BIND pipeline integrates ab initio predictions of BRAKER and Direct inference; MIND combines Direct Inference and MAKER predictions. We use highly-curated Arabidopsis and yeast annotations as gold-standard benchmarks, and cross-validate in rice. Each pipeline under-predicts orphan genes (as few as 11 percent, under one prediction scenario). Increasing RNA-Seq diversity greatly improves prediction efficacy. The combined methods (BIND and MIND) yield best predictions overall, BIND identifying 68% of annotated orphan genes, 99% of ancient genes, and give the highest sensitivity score regardless dataset in Arabidopsis. We provide a light weight, flexible, reproducible, and well-documented solution to improve gene prediction.
Development of a genome-targeting mutator for the adaptive evolution of microbial cells
Authors: Eom Ga-eul , Lee Hyunbin , Kim Seokhee
Published: December 2021

Methods that can randomly introduce mutations in the microbial genome have been used for classical genetic screening and, more recently, the evolutionary engineering of microbial cells. However, most methods rely on either cell-damaging agents or disruptive mutations of genes that are involved in accurate DNA replication, of which the latter requires prior knowledge of gene functions, and thus, is not easily transferable to other species. In this study, we developed a new mutator for in vivo mutagenesis that can directly modify the genomic DNA. Mutator protein, MutaEco, in which a DNA-modifying enzyme is fused to the α-subunit of Escherichia coli RNA polymerase, increases the mutation rate without compromising the cell viability and accelerates the adaptive evolution of E. coli for stress tolerance and utilization of unconventional carbon sources. This fusion strategy is expected to accommodate diverse DNA-modifying enzymes and may be easily adapted to various bacterial species.
The consequences of the Trade and Cooperation Agreement for the UK’s international trade
Authors: Fusacchia Ilaria , Salvatici Luca , Winters L Alan
Published: December 2021

We analyse the likely trade effects of the Trade and Cooperation Agreement (TCA), which defines the post-Brexit trading environment between the United Kingdom (UK) and the European Union (EU). We apply a computable general equilibrium model and focus on trade in value added rather than just the gross values of exports and imports. We describe the TCA and estimate its effects on the costs of conducting UK–EU trade, including various non-tariff barriers in both goods and services. We suggest that the TCA will reduce UK trade significantly: total exports by around 7 per cent and imports by around 14 per cent. In terms of value added (i.e. incomes generated), textiles and vehicles, both of which trade extensively with the EU, suffer heavily, as do services which trade significantly with the EU, face large increases in trade barriers, and experience declining demand from other sectors as those sectors’ exports fall. Such inter-industry linkages spread the losses from Brexit widely through the economy.
CHEST CT USAGE IN COVID-19 PNEUMONIA: MULTICENTER STUDY ON RADIATION DOSES AND DIAGNOSTIC QUALITY IN BRAZIL
Authors: Bernardo Monica , Homayounieh Fatemeh , Cuter Maria Cristina Rodel , Bellegard Luiz Mário , Oliveira Junior Homero Medeiros , Buril Gabriela Oliveira , de Melo Tapajós Juliana Santana , Sales Danilo Moulin , de Moura Carvalho Luiz Claudio , Alves Pinto Débora , Varella Ricardo , Tapajós Luciano Leitão , Ebrahimian Shadi , Vassileva Jenia , Kalra Mannudeep K , Khoury Helen Jamil
Published: December 2021

We assessed variations in chest CT usage, radiation dose and image quality in COVID-19 pneumonia. Our study included all chest CT exams performed in 533 patients from 6 healthcare sites from Brazil. We recorded patients’ age, gender and body weight and the information number of CT exams per patient, scan parameters and radiation doses (volume CT dose index—CTDIvol and dose length product—DLP). Six radiologists assessed all chest CT exams for the type of pulmonary findings and classified CT appearance of COVID-19 pneumonia as typical, indeterminate, atypical or negative. In addition, each CT was assessed for diagnostic quality (optimal or suboptimal) and presence of artefacts. Artefacts were frequent (367/841), often related to respiratory motion (344/367 chest CT exams with artefacts) and resulted in suboptimal evaluation in mid-to-lower lungs (176/344) or the entire lung (31/344). There were substantial differences in CT usage, patient weight, CTDIvol and DLP across the participating sites.
Identification of a novel SARS-CoV-2 P.1 sub-lineage in Brazil provides new insights about the mechanisms of emergence of variants of concern
Authors: Gräf Tiago , Bello Gonzalo , Venas Taina Moreira Martins , Pereira Elisa Cavalcante , Paixão Anna Carolina Dias , Appolinario Luciana Reis , Lopes Renata Serrano , Mendonça Ana Carolina Da Fonseca , da Rocha Alice Sampaio Barreto , Motta Fernando Couto , Gregianini Tatiana Schäffer , Salvato Richard Steiner , Fernandes Sandra Bianchini , Rovaris Darcita Buerger , Cavalcanti Andrea Cony , Leite Anderson Brandão , Riediger Irina , Debur Maria do Carmo , Bernardes André Felipe Leal , Ribeiro-Rodrigues Rodrigo , Grinsztejn Beatriz , Alves do Nascimento Valdinete , de Souza Victor Costa , Gonçalves Luciana , da Costa Cristiano Fernandes , Mattos Tirza , Dezordi Filipe Zimmer , Wallau Gabriel Luz , Naveca Felipe Gomes , Delatorre Edson , Siqueira Marilda Mendonça , Resende Paola Cristina
Published: December 2021

One of the most remarkable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) features is the significant number of mutations they acquired. However, the specific factors that drove the emergence of such variants since the second half of 2020 are not fully resolved. In this study, we describe a new SARS-CoV-2 P.1 sub-lineage circulating in Brazil, denoted here as Gamma-like-II, that as well as the previously described lineage Gamma-like-I shares several lineage-defining mutations with the VOC Gamma. Reconstructions of ancestor sequences support that most lineage-defining mutations of the Spike (S) protein, including those at the receptor-binding domain (RBD), accumulated at the first P.1 ancestor. In contrast, mutations outside the S protein were mostly fixed at subsequent steps. Our evolutionary analyses estimate that P.1-ancestral strains carrying RBD mutations of concern probably circulated cryptically in the Amazonas for several months before the emergence of the VOC Gamma. Unlike the VOC Gamma, the other P.1 sub-lineages displayed a much more restricted dissemination and accounted for a low fraction (<2 per cent) of SARS-CoV-2 infections in Brazil in 2021. The stepwise diversification of lineage P.1 through multiple inter-host transmissions is consistent with the hypothesis that partial immunity acquired from natural SARS-CoV-2 infections in heavily affected regions might have been a major driving force behind the natural selection of some VOCs. The lag time between the emergence of the P.1 ancestor and the expansion of the VOC Gamma and the divergent epidemic trajectories of P.1 sub-lineages support a complex interplay between the emergence of mutations of concern and viral spread in Brazil.
Polerovirus genomic variation
Authors: LaTourrette Katherine , Holste Natalie M , Garcia-Ruiz Hernan
Published: December 2021

The polerovirus (family Solemoviridae, genus Polerovirus) genome consists of single-, positive-strand RNA organized in overlapping open reading frames (ORFs) that, in addition to others, code for protein 0 (P0, a gene silencing suppressor), a coat protein (CP, ORF3), and a read-through domain (ORF5) that is fused to the CP to form a CP-read-through (RT) protein. The genus Polerovirus contains twenty-six virus species that infect a wide variety of plants from cereals to cucurbits, to peppers. Poleroviruses are transmitted by a wide range of aphid species in the genera Rhopalosiphum, Stiobion, Aphis, and Myzus. Aphid transmission is mediated both by the CP and by the CP-RT. In viruses, mutational robustness and structural flexibility are necessary for maintaining functionality in genetically diverse sets of host plants and vectors. Under this scenario, within a virus genome, mutations preferentially accumulate in areas that are determinants of host adaptation or vector transmission. In this study, we profiled genomic variation in poleroviruses. Consistent with their multifunctional nature, single-nucleotide variation and selection analyses showed that ORFs coding for P0 and the read-through domain within the CP-RT are the most variable and contain the highest frequency of sites under positive selection. An order/disorder analysis showed that protein P0 is not disordered. In contrast, proteins CP-RT and virus protein genome-linked (VPg) contain areas of disorder. Disorder is a property of multifunctional proteins with multiple interaction partners. The results described here suggest that using contrasting mechanisms, P0, VPg, and CP-RT mediate adaptation to host plants and to vectors and are contributors to the broad host and vector range of poleroviruses. Profiling genetic variation across the polerovirus genome has practical applications in diagnostics, breeding for resistance, and identification of susceptibility genes and contributes to our understanding of virus interactions with their host, vectors, and environment.
Correlation Between Cerebral Tissue Oxygen Saturation and Oxygen Extraction Fraction During Anesthesia: Monitoring Cerebral Metabolic Demand-supply Balance During Vasopressor Administration
Authors: Koch Klaus U. , Zhao Xu , Mikkelsen Irene K. , Espelund Ulrick S. , Aanerud Joel , Rasmussen Mads , Meng Lingzhong
Published: December 2021

Background:

The speculation that cerebral tissue oxygen saturation (SctO2) measured using tissue near-infrared spectroscopy reflects the balance between cerebral metabolic rate of oxygen and cerebral oxygen delivery has not been validated. Our objective was to correlate SctO2 with cerebral oxygen extraction fraction (OEF) measured using positron emission tomography; OEF is the ratio between cerebral metabolic rate of oxygen and cerebral oxygen delivery and reflects the balance between these 2 variables.

Materials and Methods:

This cohort study was based on data collected in a previously published trial assessing phenylephrine versus ephedrine treatment in anesthetized patients undergoing brain tumor surgery. The variables of interest were measured twice over the healthy hemisphere before surgery: the first measurement performed after anesthesia induction and the second measurement performed after induction of a ∼20% increase in blood pressure using either phenylephrine or ephedrine.

Results:

Data from 24 patients were analyzed. The overall vasopressor-induced relative changes in SctO2 (ΔSctO2) and OEF (ΔOEF) were 3.16% [interquartile range, −0.73% to 6.04%] and −12.5% [interquartile range, −24.0% to −6.19%], respectively. ΔSctO2 negatively correlated with ΔOEF after phenylephrine treatment (Spearman rank correlation coefficient [r
s]=–0.76; P=0.007), ephedrine treatment (r
s=–0.76; P=0.006), and any treatment (r
s=–0.79; P<0.001). ΔSctO2 significantly associated with ΔOEF based on multivariable analysis with ΔOEF, relative changes in mean arterial pressure, arterial blood oxygen tension, and the bispectral index as covariates (P=0.036).

Conclusions:

The negative correlation between changes in SctO2 and OEF suggests that SctO2 may reflect the cerebral metabolic demand-supply balance during vasopressor treatment. The generalizability of our findings in other clinical scenarios remains to be determined.
Effect of the Number, Size, and Location of Cannulated Screws on the Incidence of Avascular Necrosis of the Femoral Head in Pediatric Femoral Neck Fractures: A Review of 153 Cases
Authors: Wang Wentao , Li Yiqiang , Xiong Zhu , Guo Yueming , Li Ming , Mei Haibo , Shao Jingfan , Li Jin , Canavese Federico , Chen Shunyou
Published: December 2021

Background:

The correlation between the number, size, and location of cannulated screws and the incidence of avascular necrosis (AVN) in children with femoral neck fractures treated surgically is uncertain.

Methods:

We retrospectively reviewed 153 children (mean age: 10.6±3.7 y) with femoral neck fractures treated by internal fixation with 2 (n=112) or 3 (n=41) cannulated screws. The severity of initial displacement was divided into incomplete (type I) and complete (type II, angulation <50 degrees; type III, angulation >50 degrees) fractures. The diameter of the screw was measured and recorded as a percentage of the femoral neck width. The distance (D) between the mid-point of each screw at the base (B) of the femoral neck and at the tip (T) of each screw and the superior and anterior cortices of the femoral neck, respectively, were measured on anteroposterior (AP) and lateral (L) radiographs. Values were expressed as the ratio between the measured distance and the width of the femoral neck (BDAP%, TDAP%, BDL%, and TDL%). The correlation between the number, size, and location of the screws and AVN was analyzed.

Results:

Patients with type II of initial displacement treated with 2 cannulated screws had a lower AVN rate (21.4%) than those treated with 3 screws (44.8%) (P=0.027). Screw diameter (19%) in patients with AVN was larger than (17%) in patients without AVN (P<0.001); patients with AVN had a lower BDAP% (48.6%) than those without AVN (56.4%) (P<0.001). Screw size and BDAP% were risk factors for AVN (P<0.05). Further, screw diameter >16.5% and BDAP% <51.6% of the femoral neck width were the cutoff values for an increased AVN rate (P<0.05).

Conclusions:

Patients treated with 2 cannulated screws showed a lower rate of AVN than patients treated with 3 screws. Screws of larger size and screws closer to the piriformis fossa on AP radiographs increased the risk of AVN in children with femoral neck fractures treated surgically.

Level of Evidence:

Level III.