bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global adverse events reported for direct-acting antiviral therapies for the treatment of hepatitis C: an analysis of the World Health Organization VigiBase
Authors: Hayes Kaleen N. , Burkard Theresa , Weiler Stefan , Tadrous Mina , Burden Andrea M. 
Published: April 2021

Background
Direct-acting antivirals (DAAs) have transformed the treatment of hepatitis C infection (HCV) globally. Exploratory studies to identify potential rare adverse drug events associated with DAAs to optimize their use are scarce.

Objective
We aimed to describe the most common serious DAA-associated adverse drug reaction (ADR) reports overall and by DAA regimen.

Methods
We conducted a cross-sectional analysis of post-market ADRs associated with DAA therapy using VigiBase, the global database of the WHO Programme for International Drug Monitoring. Reports occurring between 2013 and 2020 in which an eligible DAA brand or regimen was reported as the suspect drug were included and described. Reports of concomitant ribavirin or interferon use were excluded. The top 25 events for all reports where the outcome was indicated as ‘serious’ or ‘life-threatening’ were described overall and by drug regimen.

Results
We identified 56 636 global ADR reports [45% women, 38% ledipasvir/sofosbuvir use, 67% from USA/Canada, average patient age 57 (SD 13) years]. Overall, 3.8% of reports described a life-threatening event or death. Unexpected ADRs included major pulmonary (dyspnea, pneumonia, and respiratory failure) and cardiac (myocardial infarction and cardiac arrest) events.

Comment
When examining all serious ADRs for DAAs globally, unexpected pulmonary and cardiac events were identified and may be of interest for further research on DAA safety. Future studies must examine population-level risk of ADRs for DAA therapies while accounting for confounding by indication, comorbidities, and stage of HCV disease.
Competing tissue-specific functions for the Tribbles-1 plasma lipid associated locus
Authors: Hu Krista Y. , Bauer Robert C. 
Published: April 2021

Purpose of review
The pseudokinase Tribbles-1 (TRIB1) remains the focus of intense research since genome-wide association studies (GWAS) associated it with multiple cardiometabolic traits in humans, including plasma lipids and atherosclerosis. This review highlights recent advances in understanding the function of TRIB1 and what outstanding questions remain.

Recent findings
Studies performed in a myeloid-specific Trib1 mouse model show that Trib1 contributes to foam cell formation, underscoring the importance of continued research into tissue-specific functions of TRIB1. Investigations of TRIB1 function in a 3D hepatic organoid model demonstrate that hepatic TRIB1 functions elucidated in mouse models are recapitulated in these organoid systems. Lastly, a recent study showed berberine, an existing lipid-lowering drug, to be acting via a TRIB1-dependent mechanism, highlighting both a novel regulator of TRIB1 expression and the potential of studying TRIB1 through existing therapeutics.

Summary
TRIB1 remains one of the more fascinating loci to arise from cardiometabolic GWAS, given the constellation of traits it associates with. As genetic studies continue to link TRIB1 to metabolic phenotypes, more functional research on tissue-specific TRIB1, regulation of TRIB1 and its function in current therapies, as well as the reproduction of results from mice in human contexts are all necessary to increase our understanding of TRIB1 and its relevance.
A 3-Year-Old Girl With Recent Onset of Seizures and Asymmetric Hypermetabolic Activity on 18F-FDG PET/CT
Authors: Hayrapetian Artineh , Dambroz Andrezza , Seyedroudbari Ameen , Schelbert Heinrich , Gupta Pawan 
Published: April 2021

Abstract
A 3-year-old, previously healthy girl started having clusters of seizures, not responsive to multiple antiepileptic medications. High-dose prednisone and intravenous immunoglobulin could partially control the seizures. Lumbar puncture and CT were normal. An MRI showed right hemispheric injury and atrophy compatible with clinical suspicion of Rasmussen encephalitis. Neurological 18F-FDG PET/CT demonstrated asymmetric hypermetabolic activity in the right frontal and parietal lobes compatible with active inflammation. The patient underwent a right functional hemispherectomy, which confirmed clinical suspicion of Rasmussen encephalitis. During the follow-up, the patient has continued to take phenobarbital and levetiracetam (Keppra), with no recurrence of seizures.
Shimia sediminis sp. nov., a bacterium isolated from marine sediment in the East China Sea
Authors: Zhu Suting , Chen Can , Cheng Yuping , Guo Chaobo , Peng Nan , Zhang Weiyan , He Shan 
Published: April 2021

A Gram-stain-negative, ovoid-shaped, motile and strictly aerobic bacterium, designated ZQ172T, was isolated from marine sediment sampled on Zhoushan Island located in the East China Sea. Strain ZQ172T grew optimally at temperatures of 25–30 °C, at NaCl concentration of 2.0 % (w/v) and at pH 7.0–8.5. Catalase and oxidase activities, urease, and nitrate reduction were positive. Indole production, methyl red reaction, H2S production and hydrolysis of gelatin, starch, casein and Tweens 20, 40, 60 and 80 were negative. The major cellular fatty acid was summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c). The only respiratory quinone was ubiquinone-10. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidylcholine. Comparative analysis of the 16S rRNA gene sequence showed highest similarities to

Shimia aestuarii

JC2049T (97.5 %),

Shimia abyssi

JAMH 043T (97.5 %) and

Shimia thalassica

CECT 7735T (97.3 %). Phylogenetic analyses indicated that strain ZQ172T clustered with the genus

Shimia

and was closely related to

Shimia thalassica

CECT 7735T. The average nucleotide identity and digital DNA–DNA hybridization values between strain ZQ172T and related species of the genus

Shimia

were well below the threshold limit for prokaryotic species delineation. The DNA G+C content was 59.6 mol%. Based on its phenotypic, chemotaxonomic and genotypic data, strain ZQ172T is considered to be a representative of a novel species in the genus

Shimia

, for which the name Shimia sediminis sp. nov. is proposed. The type strain is ZQ172T (=KCTC 62578T=MCCC 1K03531T).
Facilitation of sensory axon conduction to motoneurons during cortical or sensory evoked primary afferent depolarization (PAD) in humans
Authors: Metz K. , Concha-Matos I. , Li Y. , Afsharipour B. , Thompson C.K. , Negro F. , Bennett DJ. , Gorassini MA. 
Published: April 2021

AbstractSensory and corticospinal (CST) pathways activate spinal GABAergic interneurons with axo-axonic connections onto proprioceptive (Ia) afferents that depolarize these afferents (termed primary afferent depolarization, PAD). In rodents sensory-evoked PAD is produced by GABAAreceptors at nodes of Ranvier in Ia-afferents, rather than at presynaptic terminals, and facilitates action potential propagation to motoneurons by preventing branch point failures, rather than causing presynaptic inhibition. Here we examined if PAD likewise facilitates the Ia-afferent mediated H-reflex in humans by evoking PAD with both sensory and CST stimulation. H-reflexes in several lower limb muscles were facilitated by prior conditioning from low-threshold proprioceptive, cutaneous or CST pathways, with a similar time course (∼200 ms) to the PAD measured in rodent Ia-afferents. Long trains of repeated cutaneous or proprioceptive afferent stimulation produced long-lasting facilitation of the H-reflex for up to 2 minutes, consistent with the tonic depolarization of rodent Ia-afferents mediated by nodal 5-GABA receptors for similar stimulation trains. Facilitation of the conditioned H-reflexes was not mediated by direct facilitation of the motoneurons because isolated stimulation of sensory or CST pathways did not modulate the firing rate of tonically activated motor units in tested muscles. Furthermore, cutaneous conditioning increased the firing probability of a single motor unit during the H-reflex without increasing its firing rate at this time, indicating that the underlying excitatory postsynaptic potential (EPSP) was more probable, but not larger. These results are consistent with sensory and CST pathways activating nodal GABAAreceptors that reduce intermittent failure of action potentials propagating into Ia-afferent branches.Key Points SummaryThe control of posture and movement requires peripheral sensory feedback, which was previously thought to be inhibited by specialized GABAergic neurons in the spinal cord.Based on new findings in rodents, we provide evidence in humans that sensory and corticospinal pathways that likely activate these GABAergic pathways facilitate, rather than inhibit, the flow of sensory feedback in afferents that carry information about body position, movement and effort.These new findings of how sensory and descending pathways facilitate this sensory feedback to spinal motor neurons can now be applied to people with injury to the brain or spinal cord where these GABA neurons are affected, allowing us to understand how altered sensory control may affect residual motor function and the production of involuntary muscle spasticity.
Caerin 1.1 and 1.9 peptides from Australian tree frog inhibit antibiotic-resistant bacteria growth in a murine skin infection model
Authors: Chen Shu , Zhang Pingping , Xiao Liyin , Liu Ying , Wu Kuihai , Ni Guoying , Li Hejie , Wang Tianfang , Wu Xiaolian , Chen Guoqiang , Liu Xiaosong 
Published: April 2021

AbstractHost-defence caerin 1.9 peptide was originally isolated from skin secretion of Australian tree frog, and inhibits the growth of a wide range of bacteriain vitro. In this study, we demonstrated that caerin 1.9 shows high bioactivity against several bacteria strains, such asStaphylococcus aureus, Acinetobacter Baumannii, methicillin-resistantStaphylococcus aureus(MRSA), andStreptococcus hemolyiicus in vitro. Importantly, unlike antibiotic Tazocin, caerin 1.9 does not induce bacterial resistance after 30 rounds ofin vitroculture. Moreover, caerin 1.1, another peptide of caerin family, has additive antibacterial effect when used together with caerin 1.9. Furthermore, caerin 1.1 and 1.9 prepared in the form of a temperature sensitive gel inhibitMRSAgrowth in skin bacterial infection model of two murine strains. These results indicate that caerin 1.1 and 1.9 may have the advantage than conventional antibiotics against bacterial infection of skin.
Effects of TeaCrine® (theacrine), Dynamine™ (methylliberine), and caffeine on gamer psychomotor performance in a first-person shooter video game scenario
Authors: La Monica Michael B. , Listman Jennifer B. , Donovan Ian , Johnson Taylor E. , Heeger David J. , Mackey Wayne E 
Published: April 2021

AbstractPurposeTo compare the effects of purported cognitive enhancing dietary bioactive ingredients on subjective and objective measures of cognitive and motor performance during a first-person shooter video game.MethodsUsing a placebo-controlled crossover design, nine healthy men (23.4±5.7 yr, 178.9±5.8cm, 86.0±17.1kg) completed four 20-minute gaming sessions designed to assess cognitive, motor, and perceptual skills via artificial intelligence-driven battery of tasks (Aim Lab). Participants ingested either a placebo (PL), caffeine (CAFF), or caffeine + methylliberine (Dynamine™) + theacrine (TeaCrine®) (CMT). Before and after each gaming session participants rated various feelings of affect. Data were analyzed using mixed factorial ANOVA, bootstrapping post-hoc tests with 95% confidence intervals, and effect sizes.ResultsCompared to PL, self-assessed performance was significantly increased in CMT vs. PL (p=0.035) and self-assessed jitteriness was increased by CAFF vs. PL (p=0.043). CMT was associated with a greater improvement of participants’ visuo-spatial working memory from baseline vs. PL (p=0.04) and CAFF (p=0.033). CAFF had a greater decrease in reaction time for false alarms (indicating diminished cognitive control) from baseline vs. PL (p=0.002) and CMT (p=0.001) and a greater increase for time on target tracking vs. PL (p=0.008) and CMT (p=0.047). Compared to PL, CMT was associated with a greater decrease in median kill time (indicating improved speed) (p=0.017). Compared to PL, systolic blood pressure was significantly increased by CAFF (p=0.025) and CMT (p=0.020) but remained within normal limits.ConclusionsAcute CMT supplementation improved cognitive and motor abilities in recreational gamers. The addition of theacrine and methylliberine to caffeine may lessen some undesirable effects of isolated caffeine ingestion on cognitive control and jitteriness.
Smc3 acetylation, Pds5 and Scc2 control the translocase activity that establishes cohesin dependent chromatin loops
Authors: Bastié Nathalie , Chapard Christophe , Dauban Lise , Gadal Olivier , Beckouёt Frederic , Koszul Romain 
Published: April 2021

ABSTRACTChromosome spatial organization and dynamics influence DNA-related metabolic processes. SMC complexes like cohesin are essential instruments of chromosome folding. Cohesin-dependent chromatin loops bring together distal loci to regulate gene transcription, DNA repair and V(D)J recombination processes. Here we characterize further the roles of members of the cohesin holocomplex in regulating chromatin loop expansion, showing that Scc2, which stimulates cohesin ATPase activity, is essential for the translocation process required to extend DNA loop length. Eco1-dependent acetylation of Smc3 during S phase counteracts this activity through the stabilization of Pds5, to finely tune loop sizes and stability during G2. Inhibiting Pds5 in G2 leads to a strong enlargement of pre-established, stable DNA loops, in a Scc2-dependent manner. Altogether, the study strongly supports a Scc2-mediated translocation process driving expansion of DNA loops in living cells.
An ELISA-based method for rapid genetic screens inDrosophila
Authors: Jay Taylor R , Kang Yunsik , Jefferson Amanda , Freeman Marc R 
Published: April 2021

AbstractDrosophila is a powerful model in which to perform genetic screens, but screening assays that are both rapid and can be used to examine a wide variety of cellular and molecular pathways are limited.Drosophilaoffer an extensive toolbox of GFP-based transcriptional reporters, GFP-tagged proteins, and driver lines which can be used to express GFP in numerous subpopulations of cells. Thus, a tool that can rapidly and quantitatively evaluate GFP levels inDrosophilatissue would provide a broadly applicable screening platform. To quantify GFP levels fromDrosophilalysates, we developed a GFP-based ELISA assay. We demonstrate that this assay can detect membrane localized GFP in a variety of neuronal and glial cell populations and validate that it can identify genes that change the morphology of these cells. This assay was also able to detect STAT transcriptional activity after injury. We found that this assay can detect endogenously GFP-tagged proteins, including Draper and Cryptochrome, and it is able to report developmental and circadian changes in the expression of these proteins. Finally, we validated that the assay can be used to detect changes in synapse elimination upon genetic manipulation of astrocytes. We then used the assay to perform a small-scale screen, which identified Syntaxins as novel regulators of astrocyte-mediated synapse elimination. Together, these studies establish an ELISA as a rapid, easy and quantitativein vivoscreening method to assay a wide breadth of fundamental questions in neurobiology.Significance StatementForward genetic screens inDrosophilahave played an integral role in elucidating the cellular and molecular pathways that govern almost every facet of biology. However, current screening methods inDrosophilaare either fast, but limited in their specificity for particular pathways or processes, or rely on imaging, which requires substantial expertise, time, and cost. We have developed a rapid GFP-based ELISA screening method that, when paired with the wealth of GFP-based genetic tools already available inDrosophila, can be used to screen for regulators of many subpopulations of cells, transcriptional programs and levels of thousands of different proteins. Using this assay, we have identified a novel family of genes required for astrocytes to mediate developmental synapse elimination. This technique provides a screening platform that is fast, accessible, and broadly applicable to many pathways and processes, makingDrosophilaan even more powerful screening tool.
Integrated cycles for urban biomass as a strategy to promote a CO2-neutral society – a feasibility study
Authors: Meinusch Nicole , Kramer Susanne , Körner Oliver , Wiese Jürgen , Seick Ingolf , Beblek Anita , Berges Regine , Illenberger Bernhard , Illenberger Marco , Uebbing Jennifer , Wolf Maximilian , Saake Gunter , Benndorf Dirk , Reichl Udo , Heyer Robert 
Published: April 2021

AbstractProgressive global warming is one of the biggest challenges civilization is facing today. The establishment of a carbon dioxide (CO2)-neutral society based on sustainable value creation cycles is required to stop this development. The Integrated Cycles for Urban Biomass (ICU) concept is a new concept towards a CO2-neutral society. The integration of closed biomass cycles into residential buildings enable efficient resource utilization and avoid transport of biowaste. In this scenario, biowaste is degraded on-site into biogas that is converted into heat and electricity. The liquid fermentation residues are upgraded by nitrification processes (e.g., by a soiling®-process, EP3684909A1) to refined fertilizer, which can be used subsequently in house-internal gardens to produce fresh food for residents.Whereas this scenario sounds promising, comprehensive evaluations of produced amounts of biogas and food, saved CO2and costs as well as social-cultural aspects are lacking. To assess these points, a feasibility study was performed, which estimated the material and energy flows based on simulations of the biogas process and food production.The calculations show that a residential complex with 100 persons can generate 21 % of the annual power (electrical and heat) consumption from the accumulated biowaste. The nitrogen (N) in the liquid fermentation residues enables the production of up to 6.3 t of fresh mass of lettuce per year in a 70 m2professional hydroponic production area. The amount of produced lettuce corresponds to the amount of calories required to feed four persons for one year. Additionally, due to the reduction of biowaste transport and the in-house food and fertilizer production, 6 468 kg CO2-equivalent (CO2-eq) per year are saved compared to a conventional building. While the ICU concept is technically feasible, its costs are still 1.5 times higher than the revenues. However, the model predictions show that the ICU concept becomes economically feasible in case food prices further increase and ICU is implemented at larger scale, e.g.; at the district level. Finally, this study demonstrates that the ICU implementation can be a worthwile contribution towards a sustainable CO2-neutral society and enable to decrease the demand for agricultural land.
Anisotropic poroviscoelastic medium: reflection of inhomogeneous waves at the plane boundary with restricted seepage of pore fluid
Authors: Sharma M. D. 
Published: April 2021

ABSTRACTAn attenuating wave field in an anisotropic poroviscoelastic medium is represented through the three‐dimensional inhomogeneous propagation of four bulk waves. Propagation of each wave is governed by a complex slowness vector, which specifies its phase direction, phase velocity and coefficients for homogeneous/inhomogeneous attenuation. Partially opened surface pores restrict the seepage of pore fluid at the boundary. A generalized reflection phenomenon is illustrated for incidence of inhomogeneous waves at this boundary. Horizontal slowness of this incidence derives the slowness vectors of four inhomogeneous waves reflected into the medium. Slowness vectors and polarizations of incident and reflected waves are used to calculate the amplitudes, phase shifts and energy fluxes of reflected waves in comparison to the incident wave. A particular example illustrates the numerical implementation of the derived mathematical model for anisotropic poroviscoelastic reflection.
An unusual case of suicide: Near decapitation by a modified table saw
Authors: Simon Gábor , Heckmann Veronika 
Published: April 2021

AbstractTable saws are dangerous tools able to create severe injuries. In accidental injuries, the most commonly injured body parts are fingers (85.9%) while amputations occur in 10% of cases. Accidental neck or head injuries account for only 3.1% of all injuries. Table saws cause nearly half of all saw‐related amputations. There are approximately 30,000 cases of table saw‐related injuries in the United States annually, but only a few table saw‐related suicides have been reported in the scientific literature. In regard to suicides, usually the head or the neck is targeted. Usually, only the soft tissues of the neck are injured because the blade height limits the cutting depth and the victim falls down from the table saw before complete transection. A rare case of suicide committed by a modified table saw that resulted in near decapitation is presented. Previously reported cases of suicides by table saw are also reviewed.
Effects of polymyxin B hemoperfusion in patients with sepsis requiring continuous hemodiafiltration: Analysis of a nationwide administrative database in Japan
Authors: Fujimori Kenji , Tarasawa Kunio , Fushimi Kiyohide 
Published: April 2021

AbstractThis study investigated sepsis patients' current status with continuous hemodiafiltration (CHDF) with or without polymyxin B hemoperfusion (PMX). We identified 17 367 adult sepsis patients treated with CHDF and PMX using the Japanese diagnosis procedure combination (DPC) database from April 2016 to March 2019. More than half of the patients in this category resulted in death in the hospital, which means that patients in this group were critically ill. Among the patients who received CHDF, the 28‐day survival rate of PMX‐treated patients was significantly higher than that of non‐treated patients, after adjusting the patient background by propensity score matching (69.5% vs. 65.4%, p < 0.0001). Furthermore, the length of hospital stay and intensive care unit stay was significantly shorter in PMX‐treated patients than that of non‐treated patients. These results suggest that PMX may provide benefits to patients with severe sepsis requiring CHDF.