bluuebunny/crossref_metadata_2025 huggingface dataset:
Emu oil and grape seed extract reduce tumour burden and disease parameters in murine colitis-associated colorectal cancer
Authors: Chartier Lauren C , Howarth Gordon S , Trinder Debbie , Mashtoub Suzanne
Published: September 2020

Ulcerative colitis is an incurable condition whereby patients are at an increased risk of developing colorectal cancer (CRC). We aimed to investigate the combination of Emu oil (EO) and grape seed extract (GSE) in an azoxymethane (AOM)/dextran sulphate sodium (DSS) model of colitis-associated CRC (CA-CRC). C57BL/6 mice (n = 10/group) were injected i.p. with saline or AOM (7.4 mg/kg) and underwent three DSS/water cycles. Mice were orally-gavaged thrice weekly with water (80 μl), EO (80 μl), GSE (80 μl; 400 mg/kg) or combined EO/GSE (160 μl). Mice were euthanized on day 63. AOM/DSS induced significant bodyweight loss (max −21%) and increased disease activity index (DAI) (max +83%) throughout the trial (P < 0.05). EO (max −53%), GSE (max −51%) and EO/GSE (max −71%) reduced DAI scores in AOM/DSS mice in all DSS cycles (P < 0.05). EO/GSE-treatment in AOM/DSS mice resulted in further DAI reduction compared with EO (max −62%) and GSE (max −71%) alone (P < 0.05). AOM/DSS mice presented with severe colonoscopically-assessed colitis at all time-points, which was reduced by EO, GSE and EO/GSE (P < 0.05). EO, GSE and EO/GSE reduced the number of colonic tumours compared with AOM/DSS controls (P < 0.05). Myeloperoxidase (acute inflammation) and fluorescein isothiocyanate-dextran levels (intestinal permeability) were increased in AOM/DSS controls (P < 0.05). EO (−58%) and EO/GSE (−77%) reduced fluorescein isothiocyanate-dextran compared with AOM/DSS controls (P < 0.05), with no effect on myeloperoxidase. Histologically-assessed severity scores were increased in the distal colon of AOM/DSS mice compared with saline (P < 0.05), with no effect observed following treatment. The combination of EO and GSE improved clinical indicators and reduced colonic tumours in AOM/DSS treated mice, suggesting potential in CA-CRC management.
Alteration of fecal microbiota by fucoxanthin results in prevention of colorectal cancer in AOM/DSS mice
Authors: Terasaki Masaru , Uehara Osamu , Ogasa Shinya , Sano Taishi , Kubota Atsuhito , Kojima Hiroyuki , Tanaka Takuji , Maeda Hayato , Miyashita Kazuo , Mutoh Michihiro
Published: September 2020

Fucoxanthin (Fx), a marine carotenoid found in edible brown algae, is well known for having anticancer properties. The gut microbiota has been demonstrated as a hallmark for colorectal cancer progression in both humans and rodents. However, it remains unclear whether the gut microbiota is associated with the anticancer effect of Fx. We investigated the chemopreventive potency of Fx and its effect on gut microbiota in a mouse model of inflammation-associated colorectal cancer (by azoxymethane/dextran sulfate sodium treatment). Fx administration (30 mg/kg bw) during a 14 week period significantly inhibited the multiplicity of colorectal adenocarcinoma in mice. The number of apoptosis-like cleaved caspase-3high cells increased significantly in both colonic adenocarcinoma and mucosal crypts. Fx administration significantly suppressed Bacteroidlales (f_uc; g_uc) (0.3-fold) and Rikenellaceae (g_uc) (0.6-fold) and increased Lachnospiraceae (g_uc) (2.2-fold), compared with those of control mice. Oral administration of a fecal suspension obtained from Fx-treated mice, aimed to enhance Lachnospiraceae, suppress the number of colorectal adenocarcinomas in azoxymethane/dextran sulfate sodium-treated mice with a successful increase in Lachnospiraceae in the gut. Our findings suggested that an alteration in gut microbiota by dietary Fx might be an essential factor in the cancer chemopreventive effect of Fx in azoxymethane/dextran sulfate sodium-treated mice.
A study of the immune infiltrate and patient outcomes in esophageal cancer
Authors: Conroy Melissa J , Kennedy Susan A , Doyle Suzanne L , Hayes Brian , Kavanagh Maria , van der Stok Eric P , O’Sullivan Katie , Cathcart Mary-Clare , Reynolds John V , Lysaght Joanne
Published: September 2020

Objectives

Cancer patient outcomes and selection for novel therapies are heavily influenced by the immune contexture of the tumor microenvironment. Esophageal cancer is associated with poor outcomes. In contrast to colorectal cancer, where the immunoscore is increasingly used in prognostic staging, little is known about the immune cell populations in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (SCC), and their clinical significance.

Methods

Tissue microarrays were constructed from resected tumor tissue of 72 EAC patients and 23 SCC patients. Immunohistochemical staining of CD3, CD8, CD56, CD68, CD45RO, CD69, IFN-γ, IL-10, IL-4, IL-17, TGF-β, FOXP3 and CD107a was performed. Positivity was examined in both the stromal and epithelial compartments. Statistical analysis was performed to identify differences in immune cell infiltration and functional phenotypes between cancer subtypes and tissue compartments.

Results

This study identified that esophageal tumors are enriched with CD45RO+ and CD8+ cells and such positivity is significantly higher in SCC compared with EAC. Furthermore, the expression of CD45RO positively correlates with that of CD8 within the tumors of both patient cohorts, suggesting a dominance of memory cytotoxic T cells. This is supported by strong positivity of degranulation marker CD107a in the stromal compartment of EAC and SCC tumors. Cytokine staining revealed a mixed pro- and anti-inflammatory profile within EAC tumors.

Conclusions

Esophageal tumors are enriched with memory cytotoxic T cells. Applying these measurements to a larger cohort will ascertain the clinical utility of assessing specific lymphocyte infiltrates in EAC and SCC tumors with regards to future immunotherapy use, patient prognosis and outcomes.
How Ambient Environment Influences Olfactory Orientation in Search and Rescue Dogs
Authors: Jinn Judy , Connor Erin G , Jacobs Lucia F
Published: September 2020

Under natural conditions, an animal orienting to an air-borne odor plume must contend with the shifting influence of meteorological variables, such as air temperature, humidity, and wind speed, on the location and the detectability of the plume. Despite their importance, the natural statistics of such variables are difficult to reproduce in the laboratory and hence few studies have investigated strategies of olfactory orientation by mobile animals under different meteorological conditions. Using trained search and rescue dogs, we quantified the olfactory orientation behaviors of dogs searching for a trail (aged 1–3 h) of a hidden human subject in a natural landscape, under a range of meteorological conditions. Dogs were highly successful in locating the human target hidden 800 m from the start location (93% success). Humidity and air temperature had a significant effect on search strategy: as air conditions became cooler and more humid, dogs searched significantly closer to the experimental trail. Dogs also modified their speed and head position according to their search location distance from the experimental trail. When close to the trail, dogs searched with their head up and ran quickly but when their search took them farther from the trail, they were more likely to search with their nose to the ground, moving more slowly. This study of a mammalian species responding to localized shifts in ambient conditions lays the foundation for future studies of olfactory orientation, and the development of a highly tractable mammalian species for such research.
Dynamics of the Decay of Human Immunodeficiency Virus (HIV) RNA and Distribution of Bictegravir in the Genital Tract and Rectum in Antiretroviral-naive Adults Living With HIV–1 Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (Spanish HIV/AIDS Research Network, PreEC/RIS 58)
Authors: Imaz Arkaitz , Tiraboschi Juan M , Niubó Jordi , Martinez-Picado Javier , Cottrell Mackenzie L , Domingo Pere , Chivite Ivan , Negredo Eugenia , Schauer Amanda , Van Horne Brian , Morenilla Sandra , Urrea Víctor , Silva-Klug Ana , Scévola Sofía , Garcia Benito , Kashuba Angela D M , Podzamczer Daniel
Published: September 2020

Background

The pharmacokinetics of bictegravir (BIC) and its association with the decay of human immunodeficiency virus (HIV)–1 RNA in genital fluids and the rectum have not yet been addressed.

Methods

We conducted a prospective, multicenter study of antiretroviral-naive people living with HIV-1 and initiating BIC/emtricitabine (FTC)/tenofovir alafenamide (TAF). HIV-1 RNA was measured (limit of quantification, 40 copies/mL) in blood plasma (BP), seminal plasma (SP), rectal fluid (RF), and cervicovaginal fluid (CVF) at baseline; Days 3, 7, 14, and 28; and Weeks 12 and 24. Total and protein-unbound BIC concentrations at 24 hours postdose (C24h) were quantified in BP, SP, CVF and rectal tissue (RT) on Day 28 and Week 12 using a validated liquid chromatography-tandem mass spectrometry assay.

Results

The study population comprised 15 males and 8 females. In SP, RF, and CVF, the baseline HIV-1 RNA was >40 copies/mL in 12/15, 13/15, and 4/8 individuals, respectively, with medians of 3.54 (2.41–3.79), 4.19 (2.98–4.70), and 2.56 (1.61–3.56) log10 copies/mL, respectively. The initial decay slope was significantly lower in SP than in RF and BP. The time to undetectable HIV-1 RNA was significantly shorter in SP and RF than in BP. All women achieved undetectable HIV-1 RNA in CVF at Day 14. The median total BIC concentrations in SP, RT, and CVF were 65.5 (20.1–923) ng/mL, 74.1 (6.0–478.5) ng/g, and 61.6 (14.4–1760.2) ng/mL, respectively, representing 2.7%, 2.6%, and 2.8% of the BP concentration, respectively, while the protein-unbound fractions were 51.1%, 44.6%, and 42.6%, respectively.

Conclusions

BIC/FTC/TAF led to rapid decay of HIV-1 RNA in genital and rectal fluids. Protein-unbound BIC concentrations in SP, RT, and CVF highly exceeded the half-maximal effective concentration (EC50) value (1.1 ng/mL).

Clinical Trials Registration

EudraCT 2018-002310-12.
The silent presence of Mycoplasma hominis in patients with prostate cancer
Authors: Saadat Saman , Karami Pezhman , Jafari Mohammad , Kholoujini Mahdi , Rikhtegaran Tehrani Zahra , Mohammadi Younes , Alikhani Mohammad Yousef
Published: September 2020

Background

Mycoplasma hominis, an opportunistic pathogen in human genitourinary tract, can cause chronic infection in the prostate. Intracellular survival of M. hominis leads to a prolonged presence in the host cells that can affect the cell's biological cycle. In the present study, we aimed to evaluate the frequency of M. hominis DNA in prostate tissue of Iranian patients with prostate cancer (PCa) in comparison to a control group with benign prostatic hyperplasia (BPH).

Methods

This research was a retrospective case-control study using 61 archived formalin-fixed paraffin-embedded (FFPE) blocks of prostate tissue from patients with PCa and 70 FFPE blocks of patients with BPH. Real-time PCR, targeting two different genes, 16S rRNA and yidC, in the M. hominis genome was performed for all specimens.

Results

Out of 61 blocks of prostate biopsy from patients with PCa, eight samples (13%) were positive for M. hominis, while the bacterium was not detected in any of the 70 blocks of patients with BPH (P value, 0.002).

Conclusions

The high frequency of M. hominis in patients with PCa likely shows a hidden role of the organism in prostate cancer during its chronic, apparently silent and asymptomatic colonization in prostate.
Simulation of multi-angle fractured uranium deposits by neutron logging
Authors: Zhang Xueang , Yang Zhichao , Li Xiaoyan
Published: September 2020

Uranium is an important energy material and a key exploration object in the field of radioactive geophysical exploration. Through field study, it was found that fractured uranium is one of the most abundant sources of uranium, therefore it is an important target of energy geophysical exploration. However, the fractured structure increases the difficulty of uranium exploration and analysis. Therefore, in order to identify the distribution and analyse the content of fractured uranium deposits, it is necessary to study the influence of fracture parameters on the occurrence state of uranium ore and its manifestation status in neutron logging response. Considering the fracture structure from different aspects, this study simulated the uranium ore occurrence state in the pore-fracture medium environment and obtained corresponding logging response results by setting two fracture parameters (number density and angle). The study generated several findings, namely: (1) high angle and high porosity fracture type uranium strata have the greatest influence on thermal neutrons; (2) under the condition of high porosity, the neutron energy spectrum displays a dispersion peak and moves towards the high energy region. It is noteworthy that in a high number density environment, medium-low angle uranium ore has the strongest thermal neutron absorption in a low energy range. (3) energy decay rate is the highest in the high angle fracture environment and (4) the higher the density of the fracture number, the more susceptible the counting is to the influence of the angle factor. These findings can be used to quantitatively analyse the effects of fracture parameters on uranium deposits. These results have important guiding significance to the evaluation of a fractured uranium reservoir.
Anatomy of the Italian occupational structure: concentrated power and distributed knowledge
Authors: Cetrulo Armanda , Guarascio Dario , Virgillito Maria Enrica
Published: September 2020

Which type of work do Italians perform? In this contribution, we aim at detecting the anatomy of the Italian occupational structure by taking stock of a micro-level dataset registering the task content, the execution of procedures, the knowledge embedded in the work itself, called ICP (Indagine Campionaria sulle Professioni), the latter being comparable to the U.S. O*NET dataset. We perform an extensive empirical investigation moving from the micro to the macro level of aggregation. Our results show that the Italian occupational structure is strongly hierarchical, with the locus of power distinct by the locus of knowledge generation. It is also weak in terms of collaborative and worker involvement practices, and possibility to be creative. Our analysis allows to pinpoint the role exerted by hierarchical structures, decision-making autonomy, and knowledge as the most relevant attributes characterizing the division of labor.
Prevalence of cystic echinococcosis and associated risk factors among humans in Khartoum State, Central Sudan
Authors: Ahmed Mohamed E , Abdalla Sara Siddig , Adam Ibrahim A , Grobusch Martin P , Aradaib Imadeldin E
Published: September 2020

Background

Hydatid disease or cystic echinococcosis (CE) is caused by the larval stages of the cestode parasite Echinococcus granulosus. The objectives of this study were to estimate the prevalence of seropositivity and to identify the risk factors associated with the disease among humans in Khartoum State, Central Sudan.

Methods

A cross-sectional study was conducted between November 2017 and April 2018. A total of 305 randomly selected consenting participants from three localities were included in the current investigation using a multistage probability sampling method. An in-house enzyme-linked immunosorbent assay was used to detect immunoglobulin G antibodies to E. granulosus. The χ2 test and logistic regression analysis were used to determine the risk factors associated with CE seropositivity.

Results

A seroprevalence of 6.5% (20/305) was recorded among humans in Khartoum State, Central Sudan. Age (odds ratio [OR] 16.61 [confidence interval {CI} 2.21 to 117.92], p=0.006), locality (OR 3.08 [CI 1.42 to 22.54], p=0.011) and contact with dogs (OR 2.34 [CI 0.026 to 0.646], p=0.013) were recorded as potential risk factors for seropositivity to CE in the study area.

Conclusions

The seroprevalence of CE (6.5%) is high among humans in Khartoum State, Central Sudan. Improved surveillance is necessary to optimize control and prevention strategies for CE as an important neglected zoonotic disease among the human population in the study area of Central Sudan.
Financial Literacy and Intra-household Decision Making: Evidence from Rwanda
Authors: Grohmann Antonia , Schoofs Annekathrin
Published: September 2020

Research has consistently shown that women’s involvement in household decision making positively affects household outcomes such as nutrition and education of children. Is financial literacy a determinant for women to participate in intra-household decision making? Using data on savings groups in Rwanda, we examine this relationship and show that women with higher financial literacy are more involved in financial and expenditure decisions. Instrumental variable estimations suggest a causal link. For this reason, we perform a decomposition analysis breaking down the gender gap in financial literacy into differences based on observed socio-demographic and psychological characteristics and differences in returns on these characteristics. Our results show high explanatory power by education, happiness, symptoms of depression and openness but also suggest that a substantial fraction can be explained by differences in returns. We argue that this results from a strong role of society and culture.
Reduced Water Negatively Impacts Social Bee Survival and Productivity Via Shifts in Floral Nutrition
Authors: Wilson Rankin Erin E , Barney Sarah K , Lozano Giselle E
Published: September 2020

Pollinators provide a key ecosystem service vital for the survival and stability of the biosphere. Identifying factors influencing the plant–pollinator mutualism and pollinator management is necessary for maintaining a healthy ecosystem. Since healthy beehives require substantial amounts of carbohydrates (nectar) and protein (pollen) from forage plants such as clover, we must assess how resources offered by plants change under limited water conditions in order to fully understand how drought modifies the pollination mutualism. Here we document how reduced water availability leads to decreased nectar quality and quantity and decreased protein quality of pollen. Furthermore, we provide conclusive evidence that these lower quality resources lead to decreased survival and productivity in both developing honey bees (Hymenoptera: Apidae) and bumble bees (Hymenoptera: Apidae). The results emphasize the importance of the nutritional effects of reduced water on bees when predicting shifts of pollination mutualisms under climate change.
Treatment patterns in pancreatic cancer patients based on a hospital claims database in Japan
Authors: Suzuki Toshiaki , Kawai Sayo , Ueno Makoto , Lin Yingsong , Kikuchi Shogo
Published: September 2020

Background

Pancreatic cancer treatment is evolving, but few studies have examined a nationwide trend in the treatment patterns. The purpose of this study was to clarify real-world treatment patterns for pancreatic cancer in Japan.

Methods

This retrospective study examined the treatment patterns among 68 479 patients, who had pancreatic cancer diagnosis in Medical Data Vision claims database from 2010 to 2018. We extracted relevant data on treatment options, including chemotherapy, surgery and their combination. For patients who had undergone chemotherapy, we sought to analyse the use of different chemotherapy regimens. In addition, we examined the trend in treatment patterns by age group (<59, 60–69, 70–79, ≥80).

Results

The trend in treatment options of pancreatic cancer remained stable from 2010 to 2018, with chemotherapy being the most common therapeutic option and surgery performed in approximately half that of chemotherapy. On the other hand, the use of chemotherapy regimen had changed during the same period. Although gemcitabine was the most commonly administrated single-agent regimen in 2010, gemcitabine + nab-paclitaxel was the most frequently used therapeutic agent in 2018. In the older age groups (age ≥80), the majority of patients was untreated (supposedly received supportive care), and the use of conventional regimens such as gemcitabine or S-1 was common among those undergoing chemotherapy.

Conclusions

Although chemotherapy has been the main treatment option for pancreatic cancer, the regimens of choice have increased significantly during the last decade. With accumulating evidence on combination chemotherapy, treatment options may further evolve in the future.
Treatment Burden for Pediatric Eosinophilic Esophagitis: A Cross-Sectional Survey of Carers
Authors: Hannan Nicole , McMillan Sara S , Tiralongo Evelin , Steel Amie
Published: September 2020

Objective

To investigate treatment burden and impact on health-related quality of life (HRQoL) for children with eosinophilic esophagitis (EoE) and their carers.

Methods

An Australian cross-sectional online survey of carers of children aged 18 years and under with EoE between September 2018 to February 2019.

Results

Of 181 complete responses, more than half of carers experienced reduced HRQoL since their child’s diagnosis. Reported mean out-of-pocket expenditure for healthcare utilization (practitioner visits and treatment) was AUD$3064.3 annually. Backwards stepwise linear regression models showed that reduced ability to manage on income and missing more than one workday in the previous 30 days were significant predictors of lower carer HRQoL. Ability to manage on the current income described as “difficult some of the time,” “difficult all of the time,” and “impossible” were associated with lower child HRQoL. When compared with EoE diagnosis between 13 and 23 months of age, diagnosis between 2 and 4 years was a significant predictor of lowered child HRQoL.

Conclusions

Pediatric EoE in Australia leads to high treatment burden for carers. Changes in carer employment and income manageability can negatively impact carer psychosocial wellbeing. Carers of children with EoE need to be informed about available financial and social support to reduce treatment-related burden and improve the quality of life of both the carer and child.
Voluminous schwannoma type ‘ancient’ of the cervicothoracic district removed through a cervicotomic approach
Authors: Testori Alberto , Alloisio Marco , Cariboni Umberto , Costa Francesco , Voulaz Emanuele , Bottoni Edoardo , De Simone Matilde , Rahal Daoud , Cioffi Ugo
Published: September 2020

Schwannomas are generally benign tumors, well delimited, resulting from nerve sheaths that are frequently found in the thorax, mainly in the posterior mediastinum. We report a 58-year-old patient who carried out investigations following the appearance of a large right supraclavicular cervical mass associated with anisocoria and eyelid ptosis, histologically diagnosed as ancient schwannoma, completely removed through a cervicotomic approach without opening the chest.
The many facets of protein ubiquitination and degradation in plant root iron-deficiency responses
Authors: Spielmann Julien , Vert Grégory
Published: September 2020

Organisms need to deal with the absolute requirement for metals and also their possible toxicity. This is achieved through an intricate network of signaling pathways that are integrated to ultimately fine-tune iron uptake and metabolism. The mechanisms by which plants cope with iron limitation and the associated genomic responses are well characterized. On top of this transcriptional cascade is another level of regulation involving the post-translational protein modification and degradation. The ubiquitination and/or degradation of several transcription factors in the iron-deficiency signaling pathways and metal transporters has recently come to light. In this review we discuss the mechanisms and possible roles of protein modification and turnover in the regulation of root iron-deficiency responses. We also highlight the tight coupling between metal sensing by E3 ubiquitin ligases or bifunctional transporters and protein degradation.
Presumption of Marriage in Uganda
Authors: Mujuzi Jamil Ddamulira
Published: September 2020

Case law, amongst other sources, shows that many people in Uganda are living together as husband and wife although they are not married. Unlike legislation in other African countries such as Tanzania and Malawi, in Uganda, the pieces of legislation governing marriages are silent on the issue of presumption of marriage. Likewise, unlike in Kenya and South Africa where legislation does not provide for presumption of marriage but courts have held that such a presumption exists based on long cohabitation, Ugandan courts, the High Court, and the Court of Appeal, have held that Ugandan law does not recognise marriage based on long cohabitation (marriage by repute). However, courts will presume the existence of a marriage where a marriage ceremony took place. Since 2003, attempts to enact legislation to provide for the presumption of marriage in Uganda have not been successful. In this article, the author argues that there is still room for the Supreme Court to hold, on the basis of common law, that Ugandan law recognises the principle of presumption of marriage. This recognition would also be in line with Uganda’s international law obligation as the Committee on the Elimination of Discrimination against Women has called upon States Parties to CEDAW to enact legislation giving effect to de facto unions. The author relies on case law and legislation from some African countries to suggest ways in which the Supreme Court could deal with the issue of presumption of marriage.
Stellar masses of giant clumps in CANDELS and simulated galaxies using machine learning
Authors: Huertas-Company Marc , Guo Yicheng , Ginzburg Omri , Lee Christoph T , Mandelker Nir , Metter Maxwell , Primack Joel R , Dekel Avishai , Ceverino Daniel , Faber Sandra M , Koo David C , Koekemoer Anton , Snyder Gregory , Giavalisco Mauro , Zhang Haowen
Published: September 2020

A significant fraction of high redshift star-forming disc galaxies are known to host giant clumps, whose nature and role in galaxy evolution are yet to be understood. In this work, we first present a new method based on neural networks to detect clumps in galaxy images. We use this method to detect clumps in the rest-frame optical and UV images of a complete sample of ∼1500 star forming galaxies at 1 < z < 3 in the CANDELS survey as well as in images from the VELA zoom-in cosmological simulations. We show that observational effects have a dramatic impact on the derived clump properties leading to an overestimation of the clump mass up to a factor of 10, which highlights the importance of fair comparisons between observations and simulations and the limitations of current HST data to study the resolved structure of distant galaxies. After correcting for these effects with a mixture density network, we estimate that the clump stellar mass function follows a power law down to the completeness limit (107 solar masses) with the majority of the clumps being less massive than 109 solar masses. This is in better agreement with recent gravitational lensing based measurements. The simulations explored in this work overall reproduce the shape of the observed clump stellar mass function and clumpy fractions when confronted under the same conditions, although they tend to lie in the lower limit of the confidence intervals of the observations. This agreement suggests that most of the observed clumps are formed in situ.
MeerKAT’s discovery of a radio relic in the bimodal merging cluster A2384
Authors: Parekh V , Thorat K , Kale R , Hugo B , Oozeer N , Makhathini S , Kleiner D , White S V , Józsa G I G , Smirnov O , van der Heyden K , Perkins S , Andati L , Ramaila A , Ramatsoku M
Published: September 2020

We present the discovery of a single radio relic located at the edge of the galaxy cluster A2384, using the MeerKAT radio telescope. A2384 is a nearby (z = 0.092), low-mass, complex bimodal, merging galaxy cluster that displays a dense X-ray filament (∼700 kpc in length) between A2384(N; northern cluster) and A2384(S; southern cluster). The origin of the radio relic is puzzling. Using the MeerKAT observation of A2384, we estimate that the physical size of the radio relic is 824 × 264 kpc2 and that it is a steep spectrum source. The radio power of the relic is $P_{1.4\mathrm{GHz}}\, \sim$ (3.87 ± 0.40) × 1023 W Hz−1. This radio relic could be the result of shock wave propagation during the passage of the low-mass A2384(S) cluster through the massive A2384(N) cluster, creating a trail appearing as a hot X-ray filament. In the previous GMRT 325 MHz observation, we detected a peculiar FR I radio galaxy interacting with the hot X-ray filament of A2384, but the extended radio relic was not detected; it was confused with the southern lobe of the FR I galaxy. This newly detected radio relic is elongated and perpendicular to the merger axis, as seen in other relic clusters. In addition to the relic, we notice a candidate radio ridge in the hot X-ray filament. The physical size of the radio ridge source is ∼182 × 129 kpc2. Detection of the diffuse radio sources in the X-ray filament is a rare phenomenon, and could be a new class of radio source found between the two merging clusters of A2384(N) and A2384(S).
Calibrating the BHB star distance scale and the halo kinematic distance to the Galactic Centre
Authors: Utkin Nikita D , Dambis Andrei K
Published: September 2020

We report the first determination of the distance to the Galactic Centre based on the kinematics of halo objects. We apply the statistical-parallax technique to the sample of ∼2500 blue horizontal branch (BHB) stars compiled by Xue et al. to simultaneously constrain the correction factor to the photometric distances of BHB stars as reported by those authors and the distance to the Galactic Centre to find R = 8.2 ± 0.6 kpc. We also find that the average velocity of our BHB star sample in the direction of Galactic rotation, V0 = −240 ± 4 km s−1, is greater by about 20 km s−1 in absolute value than the corresponding velocity for halo RR Lyrae type stars (V0 = −222 ± 4 km s−1) in the Galactocentric distance interval from 6 to 18 kpc, whereas the total (σV) and radial (σr) velocity dispersion of the BHB sample are smaller by about 40–45 km s−1 than the corresponding parameters of the velocity dispersion ellipsoid of halo RR Lyrae type variables. The velocity dispersion tensor of halo BHB stars proved to be markedly less anisotropic than the corresponding tensor for RR Lyrae type variables: the corresponding anisotropy parameter values are equal to βBHB = 0.51 ± 0.02 and βRR = 0.71 ± 0.03, respectively.
Star formation in CALIFA survey perturbed galaxies – I. Effects of tidal interactions
Authors: Morales-Vargas A , Torres-Papaqui J P , Rosales-Ortega F F , Sánchez S F , Chow-Martínez M , Ortega-Minakata R A , Trejo-Alonso J J , Robleto-Orús A C , Romero-Cruz F J , Neri-Larios D M ,   (The CALIFA Survey Collaboration)
Published: September 2020

We explore the effects of tidal interactions on star formation (SF) by analysing a sample of CALIFA survey galaxies. The sample consists of tidally and non-tidally perturbed galaxies whose star-forming regions are paired at the closest stellar mass surface densities, even between the same galaxy types. The regions are then compared, both on the resolved star-formation main sequence (SFMS) plane and in annular property profiles. Star-forming regions in tidally perturbed galaxies exhibit flatter SFMS slopes compared to star-forming regions in non-tidally perturbed galaxies. Despite the fact that the annular profiles show star-forming regions in tidally perturbed galaxies as being mostly older, their SF properties are never reduced against those of non-tidally perturbed galaxies. Star-forming regions in non-tidally perturbed galaxies are better candidates for SF suppression (quenching). The lowered SF with increasing stellar mass density in tidally perturbed galaxies may suggest a lower dependence of SF on stellar mass. Though the SFMS slopes, either flatter or steeper, are found independent of stellar mass density, the effect of global stellar mass cannot be ignored when distinguishing between galaxy types. Since a phenomenon or property other than local/global stellar mass may be taking part in the modulation of SF, the integrated SF properties are related to the tidal perturbation parameter. We find weak, but detectable, positive correlations for perturbed galaxies suggesting that tidal perturbations induced by close companions increase the gas accretion rates of these objects.
Base pairing, structural and functional insights into N4-methylcytidine (m4C) and N4,N4-dimethylcytidine (m42C) modified RNA
Authors: Mao Song , Sekula Bartosz , Ruszkowski Milosz , Ranganathan Srivathsan V , Haruehanroengra Phensinee , Wu Ying , Shen Fusheng , Sheng Jia
Published: September 2020

The N4-methylation of cytidine (m4C and m42C) in RNA plays important roles in both bacterial and eukaryotic cells. In this work, we synthesized a series of m4C and m42C modified RNA oligonucleotides, conducted their base pairing and bioactivity studies, and solved three new crystal structures of the RNA duplexes containing these two modifications. Our thermostability and X-ray crystallography studies, together with the molecular dynamic simulation studies, demonstrated that m4C retains a regular C:G base pairing pattern in RNA duplex and has a relatively small effect on its base pairing stability and specificity. By contrast, the m42C modification disrupts the C:G pair and significantly decreases the duplex stability through a conformational shift of native Watson-Crick pair to a wobble-like pattern with the formation of two hydrogen bonds. This double-methylated m42C also results in the loss of base pairing discrimination between C:G and other mismatched pairs like C:A, C:T and C:C. The biochemical investigation of these two modified residues in the reverse transcription model shows that both mono- or di-methylated cytosine bases could specify the C:T pair and induce the G to T mutation using HIV-1 RT. In the presence of other reverse transcriptases with higher fidelity like AMV-RT, the methylation could either retain the normal nucleotide incorporation or completely inhibit the DNA synthesis. These results indicate the methylation at N4-position of cytidine is a molecular mechanism to fine tune base pairing specificity and affect the coding efficiency and fidelity during gene replication.
iModulonDB: a knowledgebase of microbial transcriptional regulation derived from machine learning
Authors: Rychel Kevin , Decker Katherine , Sastry Anand V , Phaneuf Patrick V , Poudel Saugat , Palsson Bernhard O
Published: September 2020

Independent component analysis (ICA) of bacterial transcriptomes has emerged as a powerful tool for obtaining co-regulated, independently-modulated gene sets (iModulons), inferring their activities across a range of conditions, and enabling their association to known genetic regulators. By grouping and analyzing genes based on observations from big data alone, iModulons can provide a novel perspective into how the composition of the transcriptome adapts to environmental conditions. Here, we present iModulonDB (imodulondb.org), a knowledgebase of prokaryotic transcriptional regulation computed from high-quality transcriptomic datasets using ICA. Users select an organism from the home page and then search or browse the curated iModulons that make up its transcriptome. Each iModulon and gene has its own interactive dashboard, featuring plots and tables with clickable, hoverable, and downloadable features. This site enhances research by presenting scientists of all backgrounds with co-expressed gene sets and their activity levels, which lead to improved understanding of regulator-gene relationships, discovery of transcription factors, and the elucidation of unexpected relationships between conditions and genetic regulatory activity. The current release of iModulonDB covers three organisms (Escherichia coli, Staphylococcus aureus and Bacillus subtilis) with 204 iModulons, and can be expanded to cover many additional organisms.
BiG-FAM: the biosynthetic gene cluster families database
Authors: Kautsar Satria A , Blin Kai , Shaw Simon , Weber Tilmann , Medema Marnix H
Published: September 2020

Computational analysis of biosynthetic gene clusters (BGCs) has revolutionized natural product discovery by enabling the rapid investigation of secondary metabolic potential within microbial genome sequences. Grouping homologous BGCs into Gene Cluster Families (GCFs) facilitates mapping their architectural and taxonomic diversity and provides insights into the novelty of putative BGCs, through dereplication with BGCs of known function. While multiple databases exist for exploring BGCs from publicly available data, no public resources exist that focus on GCF relationships. Here, we present BiG-FAM, a database of 29,955 GCFs capturing the global diversity of 1,225,071 BGCs predicted from 209,206 publicly available microbial genomes and metagenome-assembled genomes (MAGs). The database offers rich functionalities, such as multi-criterion GCF searches, direct links to BGC databases such as antiSMASH-DB, and rapid GCF annotation of user-supplied BGCs from antiSMASH results. BiG-FAM can be accessed online at https://bigfam.bioinformatics.nl.
Evolution of body composition and wasting indicators by time of day of haemodialysis
Authors: Carrero Juan J , Zawada Adam M , Wolf Melanie , Stuard Stefano , Canaud Bernard , Gauly Adelheid , Winter Anke C , Fouque Denis
Published: September 2020

Background

It has been a long-standing clinical concern that haemodialysis (HD) patients on afternoon shifts (ASs) are more prone to protein-energy wasting (PEW) than those on morning shifts (MSs), as their dialysis scheme and post-dialysis symptoms may interfere with meal intake. We evaluated the effect of time of day of HD on the evolution of body composition changes and PEW surrogates.

Methods

We conducted a retrospective study among 9.963 incident HD patients treated in NephroCare centres (2011–16); data were routinely collected in the European Clinical Database. The course of multi-frequency bioimpedance determined lean and fat tissue indices (LTI and FTI) between patients in MSs/ASs over 2 years were compared with linear mixed models. Secondary PEW indicators were body mass index, albumin, creatinine index and normalized protein catabolic rate. Models included fixed (age, sex, vascular access and diabetes mellitus) and random effects (country and patient).

Results

Mean baseline LTI and FTI were comparable between MSs (LTI: 12.5 ± 2.9 kg/m2 and FTI: 13.7 ± 6.0 kg/m2) and ASs (LTI: 12.4 ± 2.9 kg/m2 and FTI: 13.2 ± 6.1 kg/m2). During follow-up, LTI decreased and FTI increased similarly, with a mean absolute change (baseline to 24 months) of −0.3 kg/m2 for LTI and +1.0 kg/m2 for FTI. The course of these malnutrition indicators did not differ between dialysis shifts (P for interaction ≥0.10). We also did not observe differences between groups for secondary PEW indicators.

Conclusions

This study suggests that a dialysis shift in the morning or in the afternoon does not impact the long-term nutritional status of HD patients. Regardless of time of day of HD, patients progressively lose muscle mass and increase body fat.
Les soins complets de l’enfant ayant la paralysie cérébrale et capable de marcher (GMFCS I et II) : une perspective canadienne
Authors: Kawamura Anne , Makino Amber , McLeod Scott
Published: September 2020

La paralysie cérébrale (PC), qui est l’incapacité physique la plus fréquente au Canada, touche de deux à trois personnes sur 1 000. Au cours de leur carrière, les pédiatres verront et soigneront à coup sûr des enfants ayant la PC et leur famille. Le pédiatre général joue un rôle crucial dans les soins de l’enfant ayant la PC, qu’il s’agisse de poser le diagnostic ou d’assurer l’accès à une maison médicale (medical home), de garantir la coordination des soins ou de donner des conseils et des soins préventifs pour assurer sa santé et son bien-être. La fiche de santé et de bien-être en cas de PC qui accompagne le présent point de pratique peut aider à la fois le praticien et la famille de l’enfant à explorer des aspects essentiels de la santé, du fonctionnement, de la participation aux activités et du bien-être. Cette fiche peut être utilisée conjointement avec d’autres guides de promotion de la santé fondés sur des données probantes, comme le Relevé postnatal Rourke et le Relevé médical Greig, pour renseigner les cliniciens qui s’occupent d’enfants ayant la PC et capables de marcher (niveaux I et II du système de classification de la fonction motrice globale) sur des troubles et des domaines de santé particuliers.
Potato Virus X Vector-Mediated DNA-Free Genome Editing in Plants
Authors: Ariga Hirotaka , Toki Seiichi , Ishibashi Kazuhiro
Published: September 2020

Genome editing technology is important for plant science and crop breeding. Genome-edited plants prepared using general CRISPR-Cas9 methods usually contain foreign DNA, which is problematic for the production of genome-edited transgene-free plants for vegetative propagation or highly heterozygous hybrid cultivars. Here, we describe a method for highly efficient targeted mutagenesis in Nicotiana benthamiana through the expression of Cas9 and single-guide (sg)RNA using a potato virus X (PVX) vector. Following Agrobacterium-mediated introduction of virus vector cDNA, >60% of shoots regenerated without antibiotic selection carried targeted mutations, while ≤18% of shoots contained T-DNA. The PVX vector was also used to express a base editor consisting of modified Cas9 fused with cytidine deaminase to introduce targeted nucleotide substitution in regenerated shoots. We also report exogenous DNA-free genome editing by mechanical inoculation of virions comprising the PVX vector expressing Cas9. This simple and efficient virus vector-mediated delivery of CRISPR-Cas9 could facilitate transgene-free gene editing in plants.
Local Rapid Exhumation and Fast Cooling in a Long-lived Paleoproterozoic Orogeny
Authors: Zou Yi , Chu Xu , Li Qiuli , Mitchell Ross N , Zhai Mingguo , Zou Xinyu , Zhao Lei , Wang Yuquan , Liu Bo
Published: September 2020

The exhumation and cooling rates of high-grade metamorphic rocks are crucial for inferring orogenic processes and understanding the regimes of heat transport in the Earth’s crust. Quantification of these rates remains challenging for Precambrian terranes, because the temporal resolution of geochronology becomes coarser in deeper geological time. This limitation is partly reflected by a striking lack of Proterozoic or older short-duration events (<10 Myr); most documented cases of fast metamorphism are confined to the Phanerozoic. In this study, we use garnet geospeedometry to explore the metamorphic rates of Paleoproterozoic high-grade rocks from two representative areas within the long-lived (1·95–1·80 Ga) Jiao-Liao-Ji orogenic belt, North China Craton. The pelitic granulites in the Taipingzhuang area record high-pressure granulite-facies (HPG) metamorphism of ∼12 kbar and ∼800 °C, followed by a fast decompression-cooling to ∼5 kbar and ∼600 °C within ∼5 Myr, at c. 1·87 Ga. The pelitic granulites in the Rizhuang area document a brief (<1 Myr) thermal excursion to ultrahigh-temperature (UHT) metamorphism of ∼8 kbar and ∼940 °C at c. 1·85 Ga, followed by a fast cooling to ∼600 °C within 1–5 Myr. In light of available geological data, the fast decompression-cooling of HPG granulites is interpreted as the syn-collisional exhumation of thickened lower crustal segments at c. 1·87 Ga, most probably through tectonic extrusion. The thermal excursion transiently reaching UHT conditions is inferred to be triggered by localized syn-metamorphic mafic intrusions in association with magmatic underplating during post-collisional extension at c. 1·85 Ga. These metamorphic pulses were interspersed within the protracted Paleoproterozoic orogenesis and require geodynamic processes resembling modern plate tectonics. Notably, these ancient rapid events are beyond the temporal resolution of commonly used in situ geochronology, which tends to yield apparent longer durations given errors and uncertainties. We therefore note that most ancient metamorphic rates might be underestimated using geochronological data, and recommend garnet geospeedometry as a promising alternative approach. The largely similar rates recorded by Paleoproterozoic and Phanerozoic orogens, as well as high-pressure metamorphism at 1·9–1·8 Ga, support the operation of modern plate tectonics in Paleoproterozoic time.
The impact of disease severity and duration on cost, early retirement and ability to work in rheumatoid arthritis in Europe: an economic modelling study
Authors: Galloway James , Capron Jean-Philippe , De Leonardis Francesco , Fakhouri Walid , Rose Alison , Kouris Ilias , Burke Tom
Published: September 2020

Objective

RA is a progressive, chronic autoimmune disease. We summarize the impact of disease activity as measured by the DAS in 28 joints (DAS28-CRP scores) and pain on productivity and ability to work using the Work Productivity and Activity Impairment questionnaire (WPAI) scores, in addition to the impact of disease duration on the ability to work.

Methods

Data were drawn from the Burden of RA across Europe: a Socioeconomic Survey (BRASS), a European cross-sectional study in RA. Analyses explored associations between DAS28-CRP score and disease duration with stopping work because of RA, and regression analyses assessed impacts of pain and DAS28-CRP on early retirement and WPAI.

Results

Four hundred and seventy-six RA specialist clinicians provided information on 4079 adults with RA, of whom 2087 completed the patient survey. Severe disease activity was associated with higher rates of stopping work or early retirement attributable to RA (21%) vs moderate/mild disease (7%) or remission (8%). Work impairment was higher in severe (67%) or moderate RA (45%) compared with low disease activity [LDA (37%)] or remission (28%). Moreover, patients with severe (60%) or moderate pain (48%) experienced increased work impairment [mild (34%) or no pain (19%)]. Moderate to severe pain is significant in patients with LDA (35%) or remission (22%). A statistically significant association was found between severity, duration and pain vs work impairment, and between disease duration vs early retirement.

Conclusion

Results demonstrate the high burden of RA. Furthermore, subjective domains, such as pain, could be as important as objective measures of RA activity in affecting the ability to work.
Cyclical Fluctuations, Financial Shocks, and the Entry of Fast-Growing Entrepreneurial Startups
Authors: Albert Christoph , Caggese Andrea
Published: September 2020

We analyze a multiyear, multicountry entrepreneurship survey with more than one million observations to identify startups with low and high growth potential. We confirm the validity of these ex ante measures with ex post firm-level information on employment growth. We find that negative aggregate financial shocks reduce all startup types, but their effect is significantly stronger for startups with high growth potential, especially when GDP growth is low. Our results uncover a new composition of entry channel that significantly reduces employment growth and is potentially important for explaining slow recoveries after financial crises.