bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of the relative abundance of rodents in landscapes dominated by Eucalyptus plantations
Authors: Teixeira Daniela , Magalhães Ana , Ares-Pereira Guilherme , Lima Cátia , Castro Guilherme , Camarinha Cláudia , Fonseca Carlos , Rosalino Luís Miguel
Published: March 2022

Forestry plantations have increased considerably over recent decades to fulfil human demand for wood, pulp and paper. Eucalyptus globulus Labill is one of the most abundant plantation species, particularly in Europe, where its largest presence is in Portugal. Furthermore, plantations in Mediterranean areas, such as Portugal, frequently suffer from forest fires, and thus it is crucial to understand their impacts on vertebrates. This is especially relevant for some species, like small mammals, that use landscapes at smaller scales for which even small changes in forest cover may have a profound effect. In this study, we evaluate the effects of several environmental, disturbance and habitat drivers on the relative abundance of rodents (Muridae) in Eucalyptus plantations in central Portugal. Specimen capture took place across two seasons and at eight study sites representing six different stages of Eucalyptus plantations and two native forests from 2019 to 2020. Using a structural equation modelling approach, we show that the relative abundance of rodents was promoted by recent wildfire events and was higher in areas where carnivores and wild boar were more abundant. By contrast, abundant deer and increased percentages of herbaceous or litter cover and bare soil limited the abundance of rodents. We did not detect a significant relationship between Eucalyptus plantations and the relative abundance of rodents. The presence of other species, either by direct contact (carnivores) or by inducing habitat changes (ungulates), and vegetation structure, likely linked to plantation management or fire regime, are the more important factors dictating the population dynamics of rodents across plantation forests in central Portugal.
Data-adaptive global full-waveform inversion
Authors: Thrastarson Solvi , van Herwaarden Dirk-Philip , Krischer Lion , Boehm Christian , van Driel Martin , Afanasiev Michael , Fichtner Andreas
Published: March 2022

We present a novel approach to global-scale full-waveform inversion (FWI) that can reduce computational cost by over an order of magnitude, compared to previously published methods, without sacrificing physical and mathematical rigour. This is based on data-adaptation, and thereby application-oriented specialization, on two complementary levels. On the simulation level, we exploit the approximate azimuthal symmetry of seismic wavefields by implementing wavefield-adapted meshes and discrete adjoints, thereby lowering numerical simulation cost. On the measurement level, we use a quasi-stochastic approach where variable mini-batches of data are used during an iterative misfit minimization in order to promote a parsimonious exploitation of data. In addition to the methodological developments, we present an inversion of long-period (100–200 s) seismic waveforms from 1179 earthquakes for 3-D whole-mantle structure. The computational cost of the 72 iterations in the inversion approximately equals one third of a single iteration using an FWI approach with widely used cubed-sphere-based meshes and non-stochastic gradient optimization. The resulting LOng-Wavelength earth model (LOWE) constitutes the first global FWI constructed entirely from a spherically symmetric initial mantle structure. While mostly serving as a showcase for the method, LOWE contains a wealth of regional-scale structures that compare well to earlier tomographic images. Being conservatively smooth and based on minimal assumptions, it may therefore serve as starting model for future inversions at shorter period or smaller scales.
Doege Potter syndrome presenting as multiple fibrous tumours of the chest
Authors: Donato Britton B , Sewell Marisa A , Sen Ayan , Beamer Staci E
Published: March 2022

Doege Potter syndrome is a rare condition causing non-islet cell paraneoplastic hypoglycaemia associated with fibrous tumours, which can be both benign and malignant. The vast majority are solitary and located within the chest. Non-islet cell tumour-induced hypoglycaemia, as in Doege Potter syndrome, is quite rare and occurs around 4 times less often than islet cell-associated paraneoplastic hypoglycaemia. We present a case of Doege Potter syndrome with severe hypoglycaemia in conjunction with multiple recurrent fibrous tumours of the lung and pleura.
Saudi pharmacy students’ perceived knowledge and attitude on their role in public health services
Authors: Alfadl Abubakr Abdelraouf , Siddeeg Khalid , Anaam Mohammed Saif , Alharbi Rakan A , Aljutayli Meshal A , Alsaeed Hamad M
Published: March 2022

Objectives

This study aimed to explore the preparedness of pharmacy students to actively participate in public health services by examining their attitude towards and knowledge about the national public health programmes (NPHPs).

Methods

A cross-sectional study was conducted using an online questionnaire survey of the students in Unaizah College of Pharmacy (UCP) and College of Pharmacy Main Campus (CPMC), Qassim University, between October 2019 and February 2020.

Key findings

A total of 100 out of 125 students responded to the questionnaire at a response rate of 80%. While the majority (77%) of the participants agreed on the necessity for pharmacists to know about the NPHPs, 71% reported they did not learn about National Health Policy in their pharmacy curriculum. Also, a small number of pharmacy students, at 16%, believed that their current knowledge about the NPHPs was sufficient or very sufficient. Lastly, 81% of the participants felt that they had an important or very important role to play in the NPHPs.

Conclusions

The majority of the participants expressed interest in more education on public health during their pharmacy education. Their interest supports the advancement of public health education to facilitate greater involvement of pharmacists in public health services.
Decolonization of Postcolonial Africa: A Structural Justice Project More Radical than Transitional Justice
Authors: Sesay Mohamed
Published: March 2022

This article seeks to contribute to the debate as to whether the field of transitional justice can or should take on decolonization as one of its desired goals. I argue that efforts to incorporate decolonization within the normative and functional remit of the field are politically, practically and conceptually untenable. In addition to the high implausibility of the field undertaking self-radicalization within the existing (neo)liberal Euro-American order, transitional justice is based on principles of responsibility and accountability that are fundamentally different from decolonization construed as structural justice. In particular, whereas transitional justice is essentially an intervention to restore the integrity of the existing normative and social order, the decolonization project seeks to interrogate and dismantle some parts of the system being legitimated, if not the entire system. Therefore, framing such a project as transitional justice risks depoliticizing and minimizing its socially transformative essence which is long established in the history of political liberation movements of the postcolony. Although this is a case study of Sierra Leone’s almost 20-year experience of transitional justice, I aim to connect the field with the recent critical turn to the decolonization of postcolonial Africa.
In vivo efficacy of WCK 6777 (ertapenem/zidebactam) against carbapenemase-producing Klebsiella pneumoniae in the neutropenic murine pneumonia model
Authors: Gethers Matthew , Chen Iris , Abdelraouf Kamilia , Nicolau David P
Published: March 2022

Objectives

Ertapenem has proven to be an effective antimicrobial; however, increasing enzyme-mediated resistance has been noted. Combination with zidebactam, a β-lactam enhancer, is restorative. Human-simulated regimens (HSRs) of ertapenem and zidebactam alone and in combination (WCK 6777; 2 g/2 g q24h) were assessed for efficacy against carbapenemase-producing Klebsiella pneumoniae (CP-KP) in the pneumonia model.

Methods

Infected ICR mice were rendered neutropenic and exposed to various doses of ertapenem and zidebactam alone and in combination to develop the HSRs that were subsequently confirmed in additional pharmacokinetic studies. Twenty-one CP-KP (KPC or OXA-48-like producers) with WCK 6777 MICs of 1–8 mg/L were utilized. Mice were treated for 24 h with saline or HSRs of ertapenem, zidebactam and WCK 6777. Efficacy was defined as change in mean lung bacterial density relative to 0 h.

Results

Confirmatory pharmacokinetic analysis showed agreement between predicted human exposures (%fT>MIC) and those achieved in vivo for all three HSRs. The 0 h bacterial density across all isolates was 6.69 ± 0.31 log10 cfu/lungs. At 24 h, densities increased by 2.57 ± 0.50, 2.2 ± 0.60 and 2.05 ± 0.71 log10 cfu/lungs in the 24 h control, ertapenem HSR and zidebactam HSR groups, respectively. Overall, 18/21 of the isolates exposed to the WCK 6777 HSR displayed a killing profile that exceeded the translational benchmark for efficacy of a 1 log10 cfu reduction. Among the remaining three isolates, two displayed ∼0.5 log10 kill and stasis was observed in the third.

Conclusions

Human-simulated exposures of WCK 6777 demonstrated potent in vivo activity against CP-KP, including those with WCK 6777 MICs up to 8 mg/L.
Spatio-Temporal Dynamics of a Dieldrin Resistance Gene in Aedes albopictus and Culex quinquefasciatus Populations From Reunion Island
Authors: Lebon Cyrille , Alout Haoues , Zafihita Stanislas , Dehecq Jean-Sébastien , Weill Mylène , Tortosa Pablo , Atyame Célestine
Published: March 2022

The control of mosquito populations using insecticides is increasingly threatened by the spread of resistance mechanisms. Dieldrin resistance, conferred by point mutations in the Rdl gene encoding the γ-aminobutyric acid receptor, has been reported at high prevalence in mosquito populations in response to selective pressures. In this study, we monitored spatio-temporal dynamics of the resistance-conferring RdlR allele in Aedes (Stegomyia) albopictus (Skuse, 1895) and Culex (Culex) quinquefasciatus (Say, 1823) populations from Reunion Island. Specimens of both mosquito species were sampled over a 12-month period in three cities and in sites located at lower (<61 m) and higher (between 503 and 564 m) altitudes. Mosquitoes were genotyped using a molecular test detecting the alanine to serine substitution (A302S) in the Rdl gene. Overall, the RdlR frequencies were higher in Cx. quinquefasciatus than Ae. albopictus. For both mosquito species, the RdlR frequencies were significantly influenced by location and altitude with higher RdlR frequencies in the most urbanized areas and at lower altitudes. This study highlights environmental factors that influence the dynamics of insecticide resistance genes, which is critical for the management of insecticide resistance and the implementation of alternative and efficient vector control strategies.
Anti-inflammatory, anti-oxidant and anti-apoptotic effects of olive leaf extract in cardiac tissue of diabetic rats
Authors: Asghari Ali Akbar , Mahmoudabady Maryam , Shabab Sadegh , Niazmand Saeed
Published: March 2022

Objectives

Inflammatory process and apoptosis are involved in the pathogenesis of cardiac injury and oxidative damage caused by diabetes mellitus. The cardioprotective effects of standardized aqueous ethanolic olive leaf extract (OLE), metformin (as a cardiovascular protective agent) and valsartan (as an angiotensin receptor blocker) in the streptozotocin-induced diabetic rats were evaluated.

Methods

Wistar rats divided into control, diabetic, OLE-treated (100, 200 and 400 mg/kg), metformin (300 mg/kg)-treated, valsartan (30 mg/kg)-treated and metformin/valsartan-treated diabetic groups. Biochemical parameters, including malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activates, and the total contents of thiol were measured, and histopathological and gene expression studies were done on cardiac tissues. Fasting blood sugar (FBS) and cardiac injury markers were examined in serum.

Key findings

FBS; the serum levels of lactate dehydrogenase (LDH), creatine kinase-muscle/brain (CK-MB), aspartate aminotransferase (AST); and heart tissue MDA levels due to diabetes were significantly alleviated by OLE treatment (effect size; ηp2 = 0.934, 0.888, 0.848, 0.888 and 0.879, respectively), and SOD and CAT activity and the thiol content in heart tissue were significantly increased (effect size; ηp2 = 0.770, 0.749 and 0.753, respectively). Interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and the number of infiltrating inflammatory cells were reduced in cardiac tissues of OLE-treated groups compared with the diabetic rats (effect size; ηp2 = 0.969 and 0.949, respectively). OLE up-regulated BCL2 gene expression and down-regulated BAX gene expression in cardiac tissue (effect size; ηp2= 0.490 and 0.522, respectively).

Conclusion

OLE in a dose-dependent manner ameliorates cardiac damage in diabetic cardiomyopathy, perhaps through attenuating inflammation, oxidative stress and apoptosis.
Interactions of melatonin, reactive oxygen species, and nitric oxide during fruit ripening: an update and prospective view
Authors: Corpas Francisco J , Rodríguez-Ruiz Marta , Muñoz-Vargas María A , González-Gordo Salvador , Reiter Russel J , Palma José M
Published: March 2022

Fruit ripening is a physiological process that involves a complex network of signaling molecules that act as switches to activate or deactivate certain metabolic pathways at different levels, not only by regulating gene and protein expression but also through post-translational modifications of the involved proteins. Ethylene is the distinctive molecule that regulates the ripening of fruits, which can be classified as climacteric or non-climacteric according to whether or not, respectively, they are dependent on this phytohormone. However, in recent years it has been found that other molecules with signaling potential also exert regulatory roles, not only individually but also as a result of interactions among them. These observations imply the existence of mutual and hierarchical regulations that sometimes make it difficult to identify the initial triggering event. Among these ‘new’ molecules, hydrogen peroxide, nitric oxide, and melatonin have been highlighted as prominent. This review provides a comprehensive outline of the relevance of these molecules in the fruit ripening process and the complex network of the known interactions among them.
Absorption variability of the highly obscured active galactic nucleus NGC 4507
Authors: Jana Arghajit , Ricci Claudio , Naik Sachindra , Tanimoto Atsushi , Kumari Neeraj , Chang Hsiang-Kuang , Nandi Prantik , Chatterjee Arka , Safi-Harb Samar
Published: March 2022

We present a detailed study of the highly obscured active galaxy NGC 4507, performed using four Nuclear Spectroscopic Telescope Array (NuSTAR) observations carried out between May and August in 2015 (∼130 ks in total). Using various phenomenological and physically motivated torus models, we explore the properties of the X-ray source and those of the obscuring material. The primary X-ray emission is found to be non-variable, indicating a stable accretion during the period of the observations. We find the equatorial column density of the obscuring materials to be ∼2 × 1024 cm−2 while the line-of-sight column density to be ∼7–8 × 1023 cm−2. The source is found to be deeply buried with the torus covering factor of ∼0.85. We observe variability in the line-of-sight column density on a time-scale of <35 d. The covering factor of the Compton-Thick material is found to be ∼0.35 in agreement with the results of recent X-ray surveys. From the variability of the line-of-sight column density, we estimate that the variable absorbing material is likely located either in the BLR or in the torus.
The OmegaWhite survey for short-period variable stars – VI. Open clusters
Authors: Toma R , Ramsay G , Jeffery C S , Macfarlane S A , Woudt P , Groot P J
Published: March 2022

Using light curves with ∼3 min cadence and a duration of 2 h made using the OmegaWhite survey, we present the results of a search for short-period variable stars in the field of 20 open clusters. We identified 92 variable stars in these fields. Using a range of cluster member catalogues and Gaia EDR3 data, we have determined that 10 are cluster members and 2 more are probable members. Based on their position on the Gaia HRD and their photometric periods, we find that most of these are δ Sct stars. We obtained low-resolution optical spectroscopy of some of these cluster members and field stars. We discuss the cluster variable stars in the context of δ Sct stars in other open clusters.
Stellar proper motions in the outskirts of classical dwarf spheroidal galaxies withGaiaEDR3
Authors: Qi Yuewen , Zivick Paul , Pace Andrew B , Riley Alexander H , Strigari Louis E
Published: March 2022

We use Gaia EDR3 data to identify stars associated with six classical dwarf spheroidals (dSphs) (Draco, Ursa Minor, Sextans, Sculptor, Fornax, Carina) at their outermost radii, beyond their nominal King stellar limiting radius. For all of the dSphs examined, we find radial velocity matches with stars residing beyond the King limiting radius and with ${\gt}50{{\ \rm per\ cent}}$ astrometric probability (four in Draco, two in Ursa Minor, eight in Sextans, two in Sculptor, 12 in Fornax, and five in Carina), indicating that these stars are associated with their respective dSphs at high probability. We compare the positions of our candidate ‘extra-tidal’ stars with the orbital tracks of the galaxies, and identify stars, both with and without radial velocity matches, that are consistent with lying along the orbital track of the satellites. However, given the small number of candidate stars, we cannot make any conclusive statements about the significance of these spatially correlated stars. Cross matching with publicly available catalogues of RR Lyrae, we find one RR Lyrae candidate with ${\gt}50{{\ \rm per\ cent}}$ astrometric probability outside the limiting radius in each of Sculptor and Fornax, two such candidates in Draco, nine in Ursa Minor, seven in Sextans, and zero in Carina. Follow-up spectra on all of our candidates, including possible metallicity information, will help confirm association with their respective dSphs, and could represent evidence for extended stellar haloes or tidal debris around these classical dSphs.
The dependence of theoretical synthetic spectra on α-enhancement in young, binary stellar populations
Authors: Byrne C M , Stanway E R , Eldridge J J , McSwiney L , Townsend O T
Published: March 2022

The enhancement of α elements such as oxygen is an important phase in the chemical evolution of the early Universe, with nebular material becoming enriched in these elements sooner than iron. Here, we present models which incorporate stellar spectra with α-enhanced compositions, focusing on the impact on the integrated light of young stellar populations, including those with large binary star fractions using the Binary Populations and Spectral Synthesis (bpass) framework, while using Solar-scaled stellar evolution models. We find that broad spectrum outputs such as production of ionizing flux, the ultraviolet spectral slope and optical colours are only weakly affected by a change in $[\alpha /\rm {Fe}]$. A number of features such as ultraviolet line indices (e.g. at 1719 and 1853 Å) and optical line indices (such as MgB) are sensitive to such changes in composition for a continuously star-forming population and a single starburst population respectively. We find that at ages of more than 1 Gyr, α-enhanced stellar populations appear bluer than their Solar-scaled counterparts, and show expected sensitivity of optical line indices to composition, in agreement with previous work. The ultraviolet stellar absorption lines are relatively insensitive to subtleties in the abundances ratios, although with sufficient measurement precision, a combination of UV line indices may enable a simultaneous measurement of total metallicity mass fraction and $[\alpha /\rm {Fe}]$ in young stellar populations. The output models are designated as bpass v2.3 and made available to the community with the aim of assisting interpretation of observations of high-redshift galaxies with the James Webb Space Telescope.
Predictions for complex distributions of stellar elemental abundances in low-mass galaxies
Authors: Patel Preet B , Loebman Sarah R , Wetzel Andrew , Faucher-Giguère Claude-André , El-Badry Kareem , Bailin Jeremy
Published: March 2022

We investigate stellar elemental abundance patterns at $z$ = 0 in eight low-mass ($M_{*}=10^{6}{-}10^{9}\ \text{M}_{\odot }$) galaxies in the Feedback in Realistic Environments cosmological simulations. Using magnesium (Mg) as a representative α-element, we explore stellar abundance patterns in magnesium-to-iron ([Mg/Fe]) versus iron-to-hydrogen ([Fe/H]), which follow an overall monotonic trend that evolved slowly over time. Additionally, we explore three notable secondary features in enrichment (in three different case-study galaxies) that arise from a galaxy merger or bursty star formation. First, we observe a secondary track with a lower [Mg/Fe] than the main trend. At $z$ = 0, stars from this track are predominantly found within 2–6 kpc of the centre; they were accreted in a 1:3 total-mass-ratio merger ∼0.4 Gyr ago. Second, we find a distinct elemental bimodality that forms following a strong burst in star formation in a galaxy at $t_{\text{lookback}}\, \sim 10$ Gyr. This burst quenched star formation for ∼0.66 Gyr, allowing Type Ia supernovae to enrich the system with iron (Fe) before star formation resumed. Third, we examine stripes in enrichment that run roughly orthogonal to the dominant [Mg/Fe] versus [Fe/H] trend; these stripes correspond to short bursts of star formation during which core-collapse supernovae enrich the surrounding medium with Mg (and Fe) on short time-scales. If observed, these features would substantiate the utility of elemental abundances in revealing the assembly and star-formation histories of dwarf galaxies. We explore the observability of these features for upcoming spectroscopic studies. Our results show that precise measurements of elemental abundance patterns can reveal critical events in the formation histories of low-mass galaxies.
AI-driven spatio-temporal engine for finding gravitationally lensed type Ia supernovae
Authors: Kodi Ramanah Doogesh , Arendse Nikki , Wojtak Radosław
Published: March 2022

We present a spatio-temporal AI framework that concurrently exploits both the spatial and time-variable features of gravitationally lensed supernovae in optical images to ultimately aid in future discoveries of such exotic transients in wide-field surveys. Our spatio-temporal engine is designed using recurrent convolutional layers, while drawing from recent advances in variational inference to quantify approximate Bayesian uncertainties via a confidence score. Using simulated Young Supernova Experiment (YSE) images of lensed and non-lensed supernovae as a showcase, we find that the use of time-series images adds relevant information from time variability of spatial light distribution of partially blended images of lensed supernova, yielding a substantial gain of around 20 per cent in classification accuracy over single-epoch observations. Preliminary application of our network to mock observations from the Legacy Survey of Space and Time (LSST) results in detections with accuracy reaching around 99 per cent. Our innovative deep learning machinery is versatile and can be employed to search for any class of sources that exhibit variability both in flux and spatial distribution of light.
Genetic code degeneracy is established by the decoding center of the ribosome
Authors: Ye Shixin , Lehmann Jean
Published: March 2022

The degeneracy of the genetic code confers a wide array of properties to coding sequences. Yet, its origin is still unclear. A structural analysis has shown that the stability of the Watson–Crick base pair at the second position of the anticodon–codon interaction is a critical parameter controlling the extent of non-specific pairings accepted at the third position by the ribosome, a flexibility at the root of degeneracy. Based on recent cryo-EM analyses, the present work shows that residue A1493 of the decoding center provides a significant contribution to the stability of this base pair, revealing that the ribosome is directly involved in the establishment of degeneracy. Building on existing evolutionary models, we show the evidence that the early appearance of A1493 and A1492 established the basis of degeneracy when an elementary kinetic scheme of translation was prevailing. Logical considerations on the expansion of this kinetic scheme indicate that the acquisition of the peptidyl transferase center was the next major evolutionary step, while the induced-fit mechanism, that enables a sharp selection of the tRNAs, necessarily arose later when G530 was acquired by the decoding center.
ChIP-Atlas 2021 update: a data-mining suite for exploring epigenomic landscapes by fully integrating ChIP-seq, ATAC-seq and Bisulfite-seq data
Authors: Zou Zhaonan , Ohta Tazro , Miura Fumihito , Oki Shinya
Published: March 2022

ChIP-Atlas (https://chip-atlas.org) is a web service providing both GUI- and API-based data-mining tools to reveal the architecture of the transcription regulatory landscape. ChIP-Atlas is powered by comprehensively integrating all data sets from high-throughput ChIP-seq and DNase-seq, a method for profiling chromatin regions accessible to DNase. In this update, we further collected all the ATAC-seq and whole-genome bisulfite-seq data for six model organisms (human, mouse, rat, fruit fly, nematode, and budding yeast) with the latest genome assemblies. These together with ChIP-seq data can be visualized with the Peak Browser tool and a genome browser to explore the epigenomic landscape of a query genomic locus, such as its chromatin accessibility, DNA methylation status, and protein–genome interactions. This epigenomic landscape can also be characterized for multiple genes and genomic loci by querying with the Enrichment Analysis tool, which, for example, revealed that inflammatory bowel disease-associated SNPs are the most significantly hypo-methylated in neutrophils. Therefore, ChIP-Atlas provides a panoramic view of the whole epigenomic landscape. All datasets are free to download via either a simple button on the web page or an API.
Mechanisms of myostatin and activin A accumulation in chronic kidney disease
Authors: Bataille Stanislas , Dou Laetitia , Bartoli Marc , Sallée Marion , Aniort Julien , Ferkak Borhane , Chermiti Rania , McKay Nathalie , Da Silva Nathalie , Burtey Stéphane , Poitevin Stéphane
Published: March 2022

Background

Myostatin and activin A induce muscle wasting by activating the ubiquitin proteasome system and inhibiting the Akt/mammalian target of rapamycin pathway. In chronic kidney disease (CKD), myostatin and activin A plasma concentrations are increased, but it is unclear if there is increased production or decreased renal clearance.

Methods

We measured myostatin and activin A concentrations in 232 CKD patients and studied their correlation with estimated glomerular filtration rate (eGFR). We analyzed the myostatin gene (MSTN) expression in muscle biopsies of hemodialysis (HD) patients. We then measured circulating myostatin and activin A in plasma and the Mstn and Inhba expression in muscles, kidney, liver and heart of two CKD mice models (adenine and 5/6 nephrectomy models). Finally, we analyzed whether the uremic toxin indoxyl sulfate (IS) increased Mstn expression in mice and cultured muscle cells.

Results

In patients, myostatin and activin A were inversely correlated with eGFR. MSTN expression was lower in HD patients’ muscles (vastus lateralis) than in controls. In mice with CKD, myostatin and activin A blood concentrations were increased. Mstn was not upregulated in CKD mice tissues. Inha was upregulated in kidney and heart. Exposure to IS did not induce Mstn upregulation in mouse muscles and in cultured myoblasts and myocytes.

Conclusion

During CKD, myostatin and activin A blood concentrations are increased. Myostatin is not overproduced, suggesting only an impaired renal clearance, but activin A is overproduced in the kidney and heart. We propose to add myostatin and activin A to the list of uremic toxins.
TERT promoter C228T mutation in neural progenitors confers growth advantage following telomere shortening in vivo
Authors: Miki Shunichiro , Koga Tomoyuki , Mckinney Andrew M , Parisian Alison D , Tadokoro Takahiro , Vadla Raghavendra , Marsala Martin , Hevner Robert F , Costello Joseph F , Furnari Frank
Published: March 2022

Background

Heterozygous TERT (telomerase reverse transcriptase) promoter mutations (TPMs) facilitate TERT expression and are the most frequent mutation in glioblastoma (GBM). A recent analysis revealed this mutation is one of the earliest events in gliomagenesis. However, no appropriate human models have been engineered to study the role of this mutation in the initiation of these tumors.

Method

We established GBM models by introducing the heterozygous TPM in human induced pluripotent stem cells (hiPSCs) using a two-step targeting approach in the context of GBM genetic alterations, CDKN2A/B and PTEN deletion, and EGFRvIII overexpression. The impact of the mutation was evaluated through the in vivo passage and in vitro experiment and analysis.

Results

Orthotopic injection of neuronal precursor cells (NPCs) derived from hiPSCs with the TPM into immunodeficient mice did not enhance tumorigenesis compared to TERT promoter wild type NPCs at initial in vivo passage presumably due to relatively long telomeres. However, the mutation recruited GA-Binding Protein and engendered low-level TERT expression resulting in enhanced tumorigenesis and maintenance of short telomeres upon secondary passage as observed in human GBM. These results provide the first insights regarding increased tumorigenesis upon introducing a TPM compared to isogenic controls without TPMs.

Conclusion

Our novel GBM models presented the growth advantage of heterozygous TPMs for the first time in the context of GBM driver mutations relative to isogenic controls, thereby allowing for the identification and validation of TERT promoter-specific vulnerabilities in a genetically accurate background.
Heterologous expression reveals that GABA does not directly inhibit the vacuolar anion channel AtALMT9
Authors: Jaślan Justyna , De Angeli Alexis
Published: March 2022

GABA, a molecule involved in the regulation of the stomata aperture and drought tolerance does not modify vacuolar anion fluxes mediated by the anion channel AtALMT9.
The impact of drought-induced root and root hair shrinkage on root–soil contact
Authors: Duddek Patrick , Carminati Andrea , Koebernick Nicolai , Ohmann Luise , Lovric Goran , Delzon Sylvain , Rodriguez-Dominguez Celia M , King Andrew , Ahmed Mutez Ali
Published: March 2022

Although root hairs significantly increased root–soil contact, in maize, their shrinkage during soil drying is initiated at relatively high soil matric potentials (between −10 and −310 kPa).
Zombies at Large? Corporate Debt Overhang and the Macroeconomy
Authors: Jordà Òscar , Kornejew Martin , Schularick Moritz , Taylor Alan M
Published: March 2022

Debt overhang is associated with higher financial fragility and slower recovery from recession. However, while household credit booms have been extensively documented to have this property, we find that corporate debt does not fit the same pattern. Newly collected data on nonfinancial business liabilities for 18 advanced economies over the past 150 years shows that, in the aggregate, greater frictions in corporate debt resolution make for slower recoveries, with weak investment and more persistent “zombie firms” and that this is an important factor in explaining the difference in outcomes relative to household credit booms.
Clinical and laboratory characteristics of dengue and COVID-19 coinfected patients in Dhaka, Bangladesh
Authors: Hannan Tabiha Binte , Hossain Zazeba , Hasan Md Nazmul , Khan Abed Hussain , Alam Md Rafiqul , Rahman Md Mujibur , Arafat Shohael Mahmud , Chowdhury Fazle Rabbi
Published: March 2022

Background

Dengue–COVID-19 coinfection is one of the greatest emerging challenges in dengue-endemic areas during the continuing pandemic. With coinciding clinical and laboratory pictures, early diagnosis becomes burdensome, with management discrepancy.

Methods

A descriptive study was performed on dengue–COVID-19 coinfected patients during July–August 2021 for an overview of disease progression, severity and outcome. A total of 11 patients who were positive for dengue NS1 and/or antidengue IgM were included in this study.

Results

In total, 45.5% patients developed severe COVID-19 disease, 45.5% patients developed group B dengue fever and 9% patients developed group C dengue fever. Concurrent severity of both diseases was seen to be rare, except for in one patient.

Conclusion

Early diagnosis and compatible management still stand as basic principles to prevent fatality and morbidity.
The observed relationship between the degree of parasite aggregation and the prevalence of infection within human host populations for soil-transmitted helminth and schistosome infections
Authors: Kura Klodeta , Truscott James E , Collyer Benjamin S , Phillips Anna , Garba Amadou , Anderson Roy M
Published: March 2022

Background

Soil-transmitted helminths (STH) and schistosome parasites are highly aggregated within the human population. The probability distribution of worms per person is described well by the negative binomial probability distribution with aggregation parameter, k, which varies inversely with parasite clustering. The relationship between k and prevalence in defined populations subject to mass drug administration is not well understood.

Methods and Results

We use statistical methods to estimate k using two large independent datasets for STH and schistosome infections from India and Niger, respectively, both of which demonstrate increased aggregation of parasites in a few hosts, as the prevalence of infections declines across the dataset.

Conclusions

A greater attention needs to be given in monitoring and evaluation programmes to find and treat the remaining aggregates of parasites.
Arthrodesis of the Distal Tibiofibular Joint: A Review of the Literature and Evidence-based Guidelines
Authors: Pisaniello Jade L. , Beamond Ben , Alder-Price Angela C. , Proudman Charlotte , Rackham Matthew
Published: March 2022

Distal tibiofibular joint (DTFJ) arthrodesis has been proposed as a motion-preserving salvage option in cases of chronic syndesmotic disruption and degeneration. It is an uncommonly performed procedure with few cases reported in the literature. The aim of this study was to conduct a review of the literature in order to examine the appropriate indications, operative techniques, and outcomes. The authors’ also present a case for inclusion. Twenty cases of DTFJ arthrodesis were identified for inclusion. Nine operations were performed in males and 11 in females. The average patient age was 41.1 years. The indication for all arthrodeses was chronic pain±instability. Symptoms were a result of disruption of the DTFJ secondary to: (a) previous fracture malunion (n=12), (b) soft tissue injury (n=6), or (c) osteochondroma (n=2). DTFJ arthrodesis has been successfully utilized in cases of syndesmosis disruption secondary to osteochondroma, fracture and soft tissue injury in low-demand and high-demand adult patients of any age and activity level. Arthrodesis can be performed through an anterior or lateral ankle approach. Fixation with 2×3.5 mm screws across the DTFJ impacted with autologous bone graft provides sufficient fixation. Patient should nonweight bear on an immobilized ankle for a minimum of 6 weeks, or until bony union is evident on imaging.

Level of Evidence: Diagnostic Level IV.
Factors Related to Passive Social Withdrawal and Active Social Avoidance in Schizophrenia
Authors: Farina Emily A. , Assaf Michal , Corbera Silvia , Chen Chi-Ming
Published: March 2022

Social withdrawal in schizophrenia may be a result of “passive” motivation (reduced drive to engage) or “active” motivation (increased drive to avoid). We conducted a cross-sectional, between-subjects study using self-report measures and social cognition tasks to evaluate the relationships between motivational subtypes, social abilities, and social functioning in schizophrenia spectrum (n = 52, ages 19–34). Regression models showed significant differences in passive and active withdrawal. Passive, but not active, motivation predicted social functioning as measured by a clinical interview. This suggests that motivation, especially passive type, plays an important role in social withdrawal in schizophrenia. However, on a self-report measure of social functioning, neither passive nor active motivation predicted outcomes, suggesting a potential disconnect between observer versus self-report measures when assessing social motivation. Furthermore, performance on tasks of social abilities did not predict motivation, which supports the idea that motivation is distinct from social ability and should be specifically addressed in treatment.
Protein Phosphatase PPM1B Inhibits Gastric Cancer Progression and Serves as a Favorable Prognostic Biomarker
Authors: Li Riheng , Dou Jian , Bai Tianliang , Cai Bindan , Liu Yabin
Published: March 2022

Background:

Protein phosphatase PPM1B, also named as PP2Cβ, is a member of serine/threonine phosphatase family. Dysregulated expression of PPM1B has been reported in several malignancies; nevertheless, its role in gastric cancer remains unknown. Here, we aimed to initially investigate the expression and function of PPM1B in gastric adenocarcinoma.

Methods:

We firstly evaluated the protein expression of PPM1B in our enrolled retrospective cohort (n=161) via immunohistochemistry staining. Univariate and multivariate analyses were conducted to assess its prognostic value. Cellular experiments and xenografts in mice model were also performed to validate the role of PPM1B in gastric adenocarcinoma progression.

Results:

The advanced tumor stage was characterized with a lower PPM1B level. Lower PPM1B was associated with poor prognosis in both The Cancer Genome Atlas (TCGA) dataset and our cohort (P<0.05). Furthermore, Cox regression analysis demonstrated that PPM1B was a novel independent prognostic factor for gastric adenocarcinoma patients (hazard ratio=0.35, P=0.001). Finally, cellular and xenografts data confirmed that overexpressing PPM1B can remarkably attenuated gastric adenocarcinoma growth.

Conclusion:

Low expression of PPM1B may be a potential molecular marker for poor prognosis in gastric adenocarcinoma.
Comparison of Antibodies to Detect Uroplakin in Urothelial Carcinomas
Authors: Kristoffersen Heidi L. , Røge Rasmus , Nielsen Søren
Published: March 2022

Immunohistochemistry for Uroplakin (UP) II and III is used to determine urothelial origin of carcinomas of unknown primary site and are especially valuable to differentiate urothelial carcinomas (UCs) from lung squamous cell carcinomas and prostate carcinomas. In the Nordic immunohistochemical Quality Control assessment scheme, only 45% of the participants obtained a sufficient staining result for UP. Primary antibodies (Abs) against UPII were most successful with a pass rate of 86%. No Abs against UPIII provided sufficient staining results. A comparative study was carried out on a larger cohort of tissue samples with optimized methods for the UPII mouse monoclonal antibody (mmAb) clone BC21, UPIII mmAb clone AU-1, and rabbit monoclonal antibody (rmAb) clone SP73 to evaluate the performance in a standardized way. Tissue microarrays containing 58 UCs, 111 non-UCs, and 20 normal tissues were included. The UP stains were evaluated by using H-score. Based on H-scores, samples were categorized as high-expressor (150 to 300), moderate-expressor (10 to 149), low-expressor (1 to 9), and negative (<1). The UPII mmAb clone BC21 obtained a significant higher analytical sensitivity of 69% for UCs compared with the UPIII Abs mmAb clone AU-1 and rmAb clone SP73 with 19% and 29%, respectively. No high-expressor UCs were seen for the UPIII Abs, whereas 13% of the positive UCs obtained an H-score >150 for the UPII Ab. The 2 UPIII Abs gave an analytical specificity of 100% compared with 97% for the UPII Ab being positive in 2 ovarian carcinomas and 1 cervical squamous cell carcinoma.
Association Between Subjective-Objective Discrepancy of Sleeping Time and Health-Related Quality of Life: A Community-Based Polysomnographic Study
Authors: Cho Seo-Eun , Kang Jae Myeong , Ko Kwang-Pil , Lim Weon-Jeong , Redline Susan , Winkelman John W. , Kang Seung-Gul
Published: March 2022

Objective

This study aimed to investigate the existence of a difference in quality of life (QOL) between individuals with and without significant subjective-objective discrepancy (SOD) in total sleep time (TST).

Methods

From the Sleep Heart Health Study 2, 2540 individuals who had completed polysomnography, a morning sleep survey, and the 36-item Short-Form Health Survey (SF-36) were included in the analyses. The participants were classified as normoestimators (estimation of TST <±60 minutes), underestimators (underestimation of TST ≥60 minutes), or overestimators (overestimation of TST ≥60 minutes). The standardized SF-36 QOL scores were compared among the three groups. An adjusted partial correlation analysis was conducted between SOD and QOL.

Results

Of the 2540 participants, 1617 (63.7%), 433 (17.0%), and 490 (19.3%) were assigned to the normoestimator, underestimator, and overestimator groups, respectively. The bodily pain and social functioning components of the SF-36 score were significantly lower in the underestimators than in the normoestimators, whereas the physical functioning component was significantly lower in the overestimators than in the normoestimators. The absolute value of SOD in the TST showed a significant negative correlation with the physical and mental components of the SF-36.

Conclusions

QOL was significantly better in the normoestimator than in the other groups and linearly correlated with the absolute value of SOD. This study suggests that a high prevalence of positive and negative sleep misperception in a community population can be a potential factor associated with poor QOL and potential comorbidities.
Impact of an Enhanced Patient Care Intervention on Viral Suppression Among Patients Living With HIV in Kenya
Authors: Wachira Juddy , Genberg Becky , Mwangi Ann , Chemutai Diana , Braitstein Paula , Galarraga Omar , Siika Abraham , Wilson Ira
Published: March 2022

Background:

Effective patient-centered interventions are needed to promote patient engagement in HIV care. We assessed the impact of a patient-centered intervention referred to as enhanced patient care (EPC) on viral suppression among unsuppressed patients living with HIV in Kenya.

Setting:

Two rural HIV clinics within the Academic Model Providing Access to Health care.

Methods:

This was a 6-month pilot randomized control trial. The EPC intervention incorporated continuity of clinician–patient relationships, enhanced treatment dialog, and improved patients' clinic appointment scheduling. Provider–patient communication training was offered to all clinicians in the intervention site. We targeted 360 virally unsuppressed patients: (1) 240 in the intervention site with 120 randomly assigned to provider–patient communication (PPC) training + EPC and 120 to PPC training + standard of care (SOC) and (2) 120 in the control site receiving SOC. Logistic regression analysis was applied using R (version 3.6.3).

Results:

A total of 328 patients were enrolled: 110 (92%) PPC training + EPC, 110 (92%) PPC training + SOC, and 108 (90%) SOC. Participants' mean age at baseline was 48 years (SD: 12.05 years). Viral suppression 6 months postintervention was 84.4% among those in PPC training + EPC, 83.7% in PPC training + SOC, and 64.4% in SOC (P ≤ 0.001). Compared with participants in PPC training + EPC, those in SOC had lower odds of being virally suppressed 6 months postintervention (odds ratio = 0.36, 95% confidence interval: 0.18 to 0.72).

Conclusions:

PPC training may have had the greatest impact on patient viral suppression. Hence, adequate training and effective PPC implementation strategies are needed.
Traumatic brain injury patients with platelet inhibition receiving platelet transfusion demonstrate decreased need for neurosurgical intervention and decreased mortality
Authors: Miles M. Victoria P. , Hicks R. Chace , Parmer Hunter , Brown Caroline , Edwards Abigail , Stewart Kathryn , Gao Lani , Maxwell Robert
Published: March 2022

BACKGROUND

Platelet dysfunction is known to occur in patients with traumatic brain injury (TBI), and the correction of platelet dysfunction may prevent hemorrhagic progression in TBI. Thromboelastography with platelet mapping (TEG-PM; Haemonetics) evaluates the degree of platelet function inhibition through the adenosine diphosphate (ADP) and arachidonic acid (AA) pathways. We hypothesized that ADP and AA inhibition would improve with the transfusion of platelets in patients with TBI.

METHODS

A retrospective review was conducted at a Level I trauma center of all patients presenting with TBI from December 2019 to December 2020. Per a practice management guideline, a platelet mapping assay was obtained on all patients with TBI upon admission. If ADP or AA was found to be inhibited (>60%), the patient was transfused 1 unit of platelets and a repeat platelet mapping assay was ordered. Demographic data, laboratory values, and outcomes were analyzed.

RESULTS

Over the 13-month study period, 453 patients with TBI underwent TEG-PM with a protocol adherence rate of 66.5% resulting in a total of 147 patients who received platelets for ADP and/or AA inhibition; of those, 107 underwent repeat TEG-PM after platelets were administered. With the administration of platelets, ADP (p < 0.0001), AA (p < 0.0001), and MA (p = 0.0002) all significantly improved. Of 330 patients with TBI not taking antiplatelet medications, 50.9% showed inhibition in ADP and/or AA. If AA or ADP inhibition was noted on admission, mortality was increased (p = 0.0108). If ADP improved with platelet administration, the need for neurosurgical intervention was noted to decrease (p = 0.0182).

CONCLUSION

Patients with TBI and platelet inhibition may benefit from the administration of platelets to correct platelet dysfunction. Thromboelastography with platelet mapping may be implemented in the initial workup of patients presenting with TBI to assess platelet dysfunction and provide prognostic information, which may guide treatment.

LEVEL OF EVIDENCE

Therapeutic / Care Management, level III.