bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Accuracy of Simple Postoperative AKI Risk (SPARK) Classification and General Surgery AKI (GS AKI) Index in Predicting Postoperative Acute Kidney Injury among Patients Undergoing Non-Cardiac Surgery at a Tertiary Hospital in the Philippines
Authors: Te Michelle Wendy , Robles Demi Sarah , Boado Carlo Antonio , Naidas Oscar 
Published: April 2022

AbstractBackgroundPostoperative AKI is a significant postoperative complication. Clinical risk prediction models are lacking for patients undergoing non-cardiac surgery. SPARK Classification and GS AKI Index are tools that have shown fair discriminative ability to predict post-operative AKI in non-cardiac surgery and have external validation in their original cohorts. There is no study that compares the diagnostic accuracy of both tools.ObjectivesThis study aims to compare the diagnostic accuracy of SPARK Classification vs GS-AKI Risk Index in predicting post-operative AKI among patients who will undergo non-cardiac surgery at a tertiary hospital in the Philippines.MethodsThis is a cross-sectional study, including adult patients who underwent non-cardiac surgeries from January 2019 to July 2021. The individual risk of post-operative AKI for both models were determined. Descriptive data was described using t-test and logistic regression. Measures of accuracy were described using sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio, and discriminative ability using concordance (c) statistic.ResultsOf the 340 patients in this study, 77 (22.65%) developed post-operative AKI and 24 (7.06%) developed critical AKI. Based on demographic data, older age, pre-existing renal disease, longer duration of surgery, anemia, hypoalbuminemia, and hyponatremia were associated with higher incidence of post-operative AKI. SPARK had a sensitivity ranging from 17-43% and specificity ranging from 58-93% for Class B to C. GS AKI had a sensitivity ranging from 10-26% and specificity ranging from 61-97% for Class I to V. SPARK had a discriminative power (c statistic) ranging from 0.46 to 0.61 while GS AKI had a discriminative power ranging from 0.41 to 0.54.ConclusionBased on this study, there is an association between higher risk classification in both SPARK and GS AKI and postoperative AKI. However, both clinical prediction models demonstrate poor discriminative power to predict post-operative AKI.
Toxicity of extracellular alpha-synuclein is independent of intracellular alpha-synuclein
Authors: Dening Yanina , Straßl Theresa , Ruf Viktoria , Dirscherl Petra , Chovsepian Alexandra , Stievenard Alicia , Khairnar Amit , Schmidt Felix , Giesert Florian , Herms Jochen , Levin Johannes , Dieterich Marianne , Falkai Peter , Weisenhorn Daniela Vogt , Wurst Wolfgang , Giese Armin , Pan-Montojo Francisco 
Published: April 2022

AbstractParkinson′s disease (PD) pathology progresses throughout the nervous system affecting numerous neuronal structures. It has been postulated that the progression of the pathology is based on a prion-like disease mechanism partly due to the seeding effect of endocytosed alpha-synuclein (ASYN) on the endogenous ASYN. The appearance of the pathology in dopaminergic neurons leads to neuronal cell death and motor symptoms. However, the effect on other neuronal structures is more inconsistent, leading to a higher variability in the prevalence of non-motor symptoms. Thus, the sensitivity to the pathology seems to vary among neuronal subtypes. Here, we analyzed the role of endogenous ASYN in the progression of PD-like pathology and the effect of monomeric and oligomeric ASYN as well as paraquat and rotenone on primary enteric, dopaminergic and cortical neurons from wild-type mice. Our results showed that pathology progression did not occur in the absence of endogenous ASYN and that dopaminergic neurons were more sensitive to ASYN and rotenone when compared to all other neuronal subtypes. Remarkably, the toxic effect of ASYN was independent of the presence of endogenous ASYN and directly related to the disturbance of the mitochondrial membrane potential. Thus, we suggest that the interaction between ASYN and mitochondria plays an important role in the toxicity of trans-synaptically transported ASYN and in the progression of PD pathology. These results question the prion-disease hypothesis and propose that endocytosed ASYN impairs the host′s mitochondrial function thereby also contributing to PD-pathology progression.
Transmission of SARS-CoV-2 in standardised First Few X cases and household transmission investigations: a systematic review and meta-analysis
Authors: Lewis Hannah C , Marcato Adrian J , Meagher Niamh , Valenciano Marta , Villanueva-Cabezas Juan-Pablo , Spirkoska Violeta , Fielding James E , Karahalios Amalia , Subissi Lorenzo , Nardone Anthony , Cheng Brianna , Rajatonirina Soatiana , Okeibunor Joseph , Aly Eman A , Barakat Amal , Jorgensen Pernille , Azim Tasnim , Wijesinghe Pushpa Ranjan , Le Linh-Vi , Rodriguez Angel , Vicari Andrea , Van Kerkhove Maria , McVernon Jodie , Pebody Richard , Price David J , Bergeri Isabel ,   the Unity Studies Collaborator Group
Published: April 2022

AbstractWe aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines.We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for ‘Unity-aligned’ First Few X cases (FFX) and HHTIs published between 1 December 2019 and 26 July 2021. Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses.Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by Unity Studies collaborators) were retained in the systematic review and 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2%–90% (95% prediction interval: 3%–71%; I2=99.7%); I2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates.FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.
Inferring the true number of SARS-CoV-2 infections in Japan
Authors: McKenzie Lauren , Shoukat Affan , Wong Kai On , Itahashi Koju , Yasuda Eiji , Demarsh Alex , Khan Kamran 
Published: April 2022

AbstractIntroductionIn Japan, as of December 31, 2021, more than 1.73 million laboratory-confirmed cases have been reported. However, the actual number of infections is likely to be under-ascertained due to the epidemiological characteristics such as mild and subclinical infections and limited testing availability in the early days of the pandemic. In this study, we infer the true number of infections in Japan between January 16, 2020, and December 31, 2021, using a statistical modelling framework that combines data on reported cases and fatalities.MethodsWe used reported daily COVID-19 deaths stratified into 8 distinct age-groups and age-specific infection fatality ratios (IFR) to impute the true number of infections. Estimates of IFR were informed from published studies as well seroprevalence studies conducted in Japan. To account for the uncertainty in IFR estimates, we sampled values from relevant distributions.ResultsWe estimated that as of December 31, 2021, 2.90 million (CrI: 1.77 to 4.27 million) people had been infected in Japan, which is 1.68 times higher than the 1.73 million reported cases. Our meta-analysis confirmed that these findings were consistent with the intermittent seroprevalence studies conducted in Japan.ConclusionsWe have estimated that a substantial number of COVID-19 infections in the country were unreported, particularly in adults. Our approach provides a more realistic assessment of the true underlying burden of COVID-19. The results of this study can be used as fundamental components to strengthen population health control and surveillance measures.
Viability of AMURA biomarkers from single-shell diffusion MRI in Migraine Clinical Studies
Authors: Martín-Martín Carmen , Planchuelo-Gómez Álvaro , Guerrero Ángel L. , García-Azorín David , Tristán-Vega Antonio , de Luis García Rodrigo , Aja-Fernández Santiago 
Published: April 2022

AbstractDiffusion Tensor Imaging (DTI) is the most employed method to assess white matter properties using quantitative parameters derived from diffusion MRI, but it presents known limitations that restricts the evaluation of complex structures. The objective of this study was the assessment of complementary diffusion measures extracted with a novel approach, Apparent Measures Using Reduced Acquisitions (AMURA), in comparison with DTI in clinical studies. Fifty healthy controls, 51 episodic migraine and 56 chronic migraine patients underwent single-shell diffusion MRI. Three DTI-based and eight AMURA-based parameters were compared between groups with tract-based spatial statistics. On the other hand, following a region-based analysis, the measures were assessed for multiple subsamples with diverse reduced sample sizes and their stability was evaluated with the coefficient of quartile variation. Compared to DTI, statistically significant differences in additional regions and group comparisons were found with AMURA-based measures. Additionally, some AMURA-based measures showed a remarkable discriminative power for quite reduced sample size and, simultaneously, lower stability (higher coefficient of quartile variation) than DTI-based measures. These findings suggest that AMURA presents favorable characteristics to identify differences of specific microstructural properties between clinical groups in regions with complex fiber architecture and lower dependency on the sample size or assessing technique than DTI.
Near-neutral pH increased n-caprylate production in a microbiome with product inhibition of methanogenesis
Authors: Palomo-Briones Rodolfo , Xu Jiajie , Spirito Catherine M. , Usack Joseph G. , Trondsen Lauren H. , Guzman Juan J. L. , Angenent Largus T. 
Published: April 2022

AbstractThe pH is a critical parameter in chain-elongating bioreactors, affecting: (1) the concentration of inhibitory undissociated carboxylic acids, which in turn affects the efficiency of product extraction; (2) the thermodynamics; and (3) the kinetics. Here, we examined the effect of five different pH levels (5.5 to 7.0) on n-caprylate (C8) production using an anaerobic sequencing batch reactor (ASBR) with continuous membrane-based liquid-liquid extraction (pertraction). We found that the product spectrum was directed by pH: mildly acidic pH (5-6) led to n-caproate (C6) production, while near-neutral and neutral pH (6.75-7) favored n-caprylate production. In particular, the pH of 6.75 led to the maximum values of volumetric n-caprylate production rate (75.6 ± 0.6 mmol C L−1 d−1; 0.06 g L−1 d−1) and n-caprylate concentration in the fermentation broth (420 mM C; 7.57 g L−1). Given that methane production remained low at near-neutral and neutral pH, we theorized that the high concentration of undissociated n-caprylic acid (5.71 mM C) inhibited methanogenesis. We then demonstrated such an inhibitory effect at neutral pH in: (1) microcosm experiments; and (2) the continuous bioreactor by adding methanogenic sludge. Furthermore, 16S rRNA gene sequencing analysis revealed that near-neutral and neutral pH led to more diverse microbial communities than at mildly-acidic pH. For the first time, we report predominant n-caprylate production in a microbiome at near-neutral and neutral pH conditions where methanogenesis was controlled by the inhibitory effects of undissociated n-caprylic acid. At the same time, extraction of this species occurred even at near-neutral and neutral pH.
Modulation of Receptor-like Trans-Membrane Kinase 1 nuclear localisation by DA1 peptidases in Arabidopsis
Authors: Gu Benguo , Dong Hui , Smith Caroline , Bevan Michael W. 
Published: April 2022

AbstractThe activities of proteins can depend on their cleavage, which influences their cellular location, stability and functions. The cleavage of intracellular domains of Receptor -Like Kinases (RLK) has an important functional role in the transduction of signals from the cell surface to the nucleus in many organisms. However, the peptidases that catalyse protein cleavage during signal transduction remain poorly understood despite their crucial roles in diverse signalling processes. Here we report in the flowering plant Arabidopsis thaliana that members of the DA1 family of ubiquitin-regulated Zn metallopeptidases cleave the cytoplasmic kinase domain of TransMembrane Kinase 1 (TMK1), releasing it for nuclear localisation where it represses auxin-responsive cell growth during apical hook formation by phosphorylation and stabilisation of the transcriptional repressors IAA32 and IAA34. Mutations in DA1 family members exhibited reduced apical hook formation, and DA1 family mediated cleavage of TMK1 was promoted by auxin treatment. Expression of the DA1 family - generated intracellular kinase domain of TMK1 by an auxin-responsive promoter fully restored apical hook formation in a tmk1 mutant, establishing the function of DA1 family peptidase activities in TMK1-mediated differential cell growth and apical hook formation. DA1 family peptidase activity therefore modulates TMK1 kinase activity between a membrane location where it stimulates acid cell growth and initiates an auxin-dependent kinase cascade controlling cell proliferation in lateral roots and a nuclear localisation where it represses auxin mediated gene expression and growth.
Simultaneous adjustments of major mitochondrial pathways through redox regulation of dihydrolipoamide dehydrogenase (mtLPD1)
Authors: Timm Stefan , Klaas Nicole , Niemann Janice , Jahnke Kathrin , Alseekh Saleh , Zhang Youjun , Souza Paulo V.L. , Hou Liang-Yu , Geigenberger Peter , Daloso Danilo M. , Fernie Alisdair R. , Hagemann Martin 
Published: April 2022

AbstractThioredoxins (TRX) are pivotal for the redox regulation of enzyme activities to adjust metabolic fluxes towards environmental changes. Previous reports demonstrated TRXo1andh2impact on mitochondrial metabolism including photorespiration and the tricarboxylic acid (TCA) cycle. Here, we aimed to unravel potential specificities between regulation modes of both TRXs, especially under conditions with short-term changes in photorespiration. Therefore, short-term metabolite responses of singleTRXmutants were analyzed after exposure to altered CO2/O2ratios during darkness and illumination. This approach was complemented by comprehensive characterization of multiple Arabidopsis mutants lacking either one or bothTRXin the wild-type Arabidopsis or the glycine decarboxylase (GDC) T-protein knock down line (gldt1). The results provided evidence for additive effects of combined TRXo1andh2deficiency to suppress growth, photosynthesis and mitochondrial metabolism. Quantification of pyrimidine nucleotides in conjunction with metabolite and13C-labelling approaches revealed a rather uniform impact on mitochondrial dihydrolipoamide dehydrogenase (mtLPD1) dependent pathways. Biochemical analysis of recombinant mtLPD1 demonstrated its inhibition by NADH, pointing at an additional measure to fine-tune it’sin vivoactivity. Collectively, we propose that TRXo1andh2contribute to the communication of altered subcellular redox-states through direct and indirect regulation of mtLPD1. This regulation module might represent a common intercept for simultaneous adjustments in the operation of photorespiration, the TCA-cycle and the degradation of branched chain amino acids.One-sentence summaryRedox regulation of mitochondrial dihydrolipoamide dehydrogenase (mtLPD1) simultaneously modulates photorespiration, the tricarboxylic acid (TCA)-cycle and branched chain amino acid (BCAA) degradation in response to rapid environmental changes.
Melanization is an important antifungal defense mechanism in Galleria mellonella hosts
Authors: Smith Daniel F. Q. , Dragotakes Quigly , Kulkarni Madhura , Hardwick J. Marie , Casadevall Arturo 
Published: April 2022

SummaryA key component of insect immunity is melanin encapsulation of microbes. Melanization is also a part of an immune process known as nodulation, which occurs when insect hemocytes surround microbes and produce melanin. Insect nodules are analogous to mammalian immune granulomas. Melanin is believed to kill microbes through the production of toxic intermediates and oxidative damage. However, it is unclear to what extent immune melanin is directly fungicidal during infections of insect hosts. We reported previously that C. neoformans cells are encapsulated with host-derived melanin within hemocyte nodules. Here we report an association between melanin-based immune responses by Galleria mellonella wax moth larvae and fungal cell death of C. neoformans during infection. To monitor melanization in situ, we applied a tissue-clearing technique to G. mellonella larvae, revealing that nodulation occurs throughout the organism. Further, we developed a protocol for time-lapse microscopy of extracted hemolymph following exposure to fungal cells, which allowed us to visualize and quantify the kinetics of the melanin-based immune response. Using this technique, we found evidence that cryptococcal melanins and laccase enhance immune melanization in hemolymph. We used these techniques to also study the fungal pathogen Candida albicans infections of G. mellonella. We find that the yeast form of C. albicans was the primary targets of host melanization, while filamentous structures were melanin-evasive. Approximately 23% of melanin-encapsulated C. albicans yeast survive and break through the encapsulation. Overall, our results provide direct evidence that the melanization reaction functions as a direct antifungal mechanism in insect hosts.
A brain-inspired object-based attention network for multi-object recognition and visual reasoning
Authors: Adeli Hossein , Ahn Seoyoung , Zelinsky Gregory J. 
Published: April 2022

AbstractThe visual system uses sequences of selective glimpses to objects to support goal-directed behavior, but how is this attention control learned? Here we present an encoder-decoder model inspired by the interacting bottom-up and top-down visual pathways making up the recognitionattention system in the brain. At every iteration, a new glimpse is taken from the image and is processed through the “what” encoder, a hierarchy of feedforward, recurrent, and capsule layers, to obtain an object-centric (object-file) representation. This representation feeds to the “where” decoder, where the evolving recurrent representation provides top-down attentional modulation to plan subsequent glimpses and impact routing in the encoder. We demonstrate how the attention mechanism significantly improves the accuracy of classifying highly overlapping digits. In a visual reasoning task requiring comparison of two objects, our model achieves near-perfect accuracy and significantly outperforms larger models in generalizing to unseen stimuli. Our work demonstrates the benefits of object-based attention mechanisms taking sequential glimpses of objects.
Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature upon SARS-CoV-2 sensing by monocytes in COVID-19
Authors: Maher Allison K. , Burnham Katie L. , Jones Emma , Baillon Laury , Selck Claudia , Giang Nicolas , Argüello Rafael , Short Charlotte-Eve , Quinlan Rachael , Barclay Wendy S. , Cooper Nichola , Taylor Graham P. , Davenport Emma E. , Dominguez-Villar Margarita 
Published: April 2022

AbstractAlterations in the myeloid immune compartment have been observed in COVID-19, but the specific mechanisms underlying these impairments are not completely understood. Here we examined the functionality of classical CD14+monocytes as a main myeloid cell component in well-defined cohorts of patients with mild and moderate COVID-19 during the acute phase of infection and compared them to that of healthy individuals. We found thatex vivoisolated CD14+monocytes from mild and moderate COVID-19 patients display specific patterns of costimulatory and inhibitory receptors that clearly distinguish them from healthy monocytes, as well as altered expression of histone marks and a dysfunctional metabolic profile. Decreased NFκB activation in COVID-19 monocytesex vivois accompanied by an intact type I IFN antiviral response. Subsequent pathogen sensingex vivoled to a state of functional unresponsiveness characterized by a defect in pro-inflammatory cytokine expression, NFκB-driven cytokine responses and defective type I IFN response in moderate COVID-19 monocytes. Transcriptionally, COVID-19 monocytes switched their gene expression signature from canonical innate immune functions to a pro-thrombotic phenotype characterized by increased expression of pathways involved in hemostasis and immunothrombosis. In response to SARS-CoV-2 or other viral or bacterial components, monocytes displayed defects in the epigenetic remodelling and metabolic reprogramming that usually occurs upon pathogen sensing in innate immune cells. These results provide a potential mechanism by which innate immune dysfunction in COVID-19 may contribute to disease pathology.
Dominance vs. epistasis: the biophysical origins and plasticity of genetic interactions within and between alleles
Authors: Xie Xuan , Lehner Ben , Li Xianghua 
Published: April 2022

AbstractA central challenge in genetics, evolutionary biology and biotechnology is to understand and predict how mutations combine to alter phenotypes, including molecular activities, fitness and disease. In diploid organisms, two mutations in the same gene can either combine on the same chromosome or on different chromosomes, with interactions between the mutations quantified as epistasis and dominance, respectively. However, a direct comparison of the extent, sign and stability of interactions within and between alleles is lacking. Here we show that, even in the simplest biophysical systems, interactions between mutations are frequent, context-dependent and different when variants are combined within and between alleles. Whereas protein folding alone generates epistasis, the addition of a single molecular interaction is sufficient to cause dominance. Epistasis and dominance interactions change quantitatively, qualitatively and differently as a system becomes more complicated or the conditions change. Altering the concentration of a ligand can, for example, switch an allele from dominant to recessive. Our results show that epistasis and dominance should be widely expected in even the simplest biological systems but also reinforce the view that they are plastic system properties and so a formidable challenge to predict. Accurate prediction of epistasis and dominance will require either detailed mechanistic understanding and experimental parameterization or brute-force measurement and learning.