bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dementia Prediction in Older People through Topic-cued Spontaneous Conversation
Authors: Rutkowski Tomasz M. , Abe Masato S. , Tokunaga Seiki , Otake-Matsuura Mihoko 
Published: May 2021

AbstractAn increase in dementia cases is producing significant medical and economic pressure in many communities. This growing problem calls for the application of AI-based technologies to support early diagnostics, and for subsequent non-pharmacological cognitive interventions and mental well-being monitoring. We present a practical application of a machine learning (ML) model in the domain known as ‘AI for social good’. In particular, we focus on early dementia onset prediction from speech patterns in natural conversation situations. This paper explains our model and study results of conversational speech pattern-based prognostication of mild dementia onset indicated by predictive Mini-Mental State Exam (MMSE) scores. Experiments with elderly subjects are conducted in natural conversation situations, with four members in each study group. We analyze the resulting four-party conversation speech transcripts within a natural language processing (NLP) deep learning framework to obtain conversation embedding. With a fully connected deep learning model, we use the conversation topic changing distances for subsequent MMSE score prediction. This pilot study is conducted with Japanese elderly subjects within a healthy group. The best median MMSE prediction errors are at the level of 0.167, with a median coefficient of determination equal to 0.330 and a mean absolute error of 0.909. The results presented are easily reproducible for other languages by swapping the language model in the proposed deep-learning conversation embedding approach.
Predicting bloodstream infection outcome using machine learning
Authors: Zoabi Yazeed , Kehat Orli , Lahav Dan , Weiss-Meilik Ahuva , Adler Amos , Shomron Noam 
Published: May 2021

AbstractBloodstream infections (BSI) are a main cause of infectious disease morbidity and mortality world-wide. Early prediction of patients at high risk of poor outcomes of BSI is important for earlier decision making and effective patient stratification. We developed electronic medical record-based machine learning models that predict patient outcomes of BSI. The area under the receiver-operating characteristics curve was 0.82 for a full featured inclusive model, and 0.81 for a compact model using only 25 features. Our models were trained, using electronic medical records that include demographics, blood tests, and the medical and diagnosis history of 7,889 hospitalized patients diagnosed with BSI. Among the implications of this work is implementation of the models as a basis for selective rapid microbiological identification, toward earlier administration of appropriate antibiotic therapy. Additionally, our models may help reduce the development of BSI and its associated adverse health outcomes and complications.
Association of C-reactive protein and Interleukin-6 single nucleotide polymorphisms with preterm labour: results of a pilot study
Authors: Sato Akira , Miura Hiroshi , Onodera Yohei , Shirasawa Hiromitu , Kameyama Saeko , Fujishima Akiko , Kikuti Yuko , Goto Mayumi , Sato Toshiharu , Terada Yukihiro 
Published: May 2021

AbstractPreterm labour (PTL) can be described as an inflammatory event. C-reactive protein (CRP) and Interleukin-6 (IL-6) are key members of the innate immune response that play major roles in inflammation. The main objective of this case-control study was to determine the association of specific CRP and IL-6 polymorphisms with PTL. The study was carried out in a total of 31 Japanese women with PTL and 28 control women with normal pregnancy. Four SNPs in the CRP gene (rs1800947, rs3091244, rs2794521, and rs3093059) and two SNPs in the IL-6 gene (rs2097677 and rs1800795) were genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Biochemical parameters were assayed and cervical length measurements were performed with ultrasound sonography. There were no significant differences in inflammatory markers, including white blood cell count, CRP, neutrophil elastase in cervical mucous, and foetal fibronectin in vaginal discharge, between the PTL and control groups. The frequency of rs1800947 minor allele (G) was significantly higher in the PTL group than in the control group. This finding has not been previously reported. We suggest that mutations in rs1800947 may lead to PTL. Thus, the rs1800947 SNP may be useful as a genetic marker for PTL risk assessment in pregnant women.
Frequent suboptimal thermocycler ramp rate usage negatively impacts MTBDRsl performance for second-line drug resistant tuberculosis diagnosis
Authors: Derendinger Brigitta , de Vos Margaretha , Pillay Samantha , Venter Rouxjeane , Metcalfe John , Ghebrekristos Yonas , Minnies Stephanie , Dolby Tania , Beylis Natalie , Warren Robin , Theron Grant 
Published: May 2021

AbstractStrengthening the detection of second-line drug-resistance is a key tuberculosis (TB) control priority. The performance of MTBDRplus, a multidrug-resistant (MDR)-TB assay is reduced when suboptimal ramp rates are used. We investigated ramp rate’s effect on MTBDRsl; the most widely-used molecular second-line drug-resistant TB assay.We tested 52 smear-negative Xpert MTB/RIF Ultra-positive sputa and a Mycobacterium tuberculosis (Mtb) dilution series at manufacturer-recommended (2.2°C/s) or most common suboptimal ramp rate (4.0°C/s; identified via an earlier survey). Mtb-complex DNA (TUB-band)-positivity, indeterminate rates, fluoroquinolone- and second-line injectable-resistance accuracy, banding differences and, separately, inter-reader variability were assessed.39% of re-surveyed laboratories (5/13) did not use the manufacturer-recommended MTBDRsl ramp rate. On sputum, this ramp rate improved indeterminates vs. 4.0°C/s (0/52 vs. 7/51; p=0.006), false drug-resistance calls (0/104 vs. 6/102; p=0.013), and incorrect banding calls (0/1300 vs. 55/1275; p<0.001). Valid results (neither TUB-negative, indeterminate, nor any false drug-resistance calls) (52/52 vs. 41/51; p=0.001) on sputa hence improved by +21% (95% CI: 8-34%) with optimal ramp rate usage. Suboptimal ramp rate increased banding call inter-reader variability [52/1300 (4%) vs. 34/1300 (3%); p=0.030] on sputa but not dilution series; highlighting the importance of using clinical specimens for assay performance evaluations.Suboptimal ramp rate contributes to poor MTBDRsl performance. Ramp rate correction will improve second-line drug-resistant TB diagnoses. Laboratories must ensure the optimal manufacturer-recommended ramp rate is used.
Changes in the urinary proteome in rats with regular swimming exercise
Authors: Meng Wenshu , Xu Dan , Meng Yunchen , Zhang Weinan , Zhen Zhiping , Gao Youhe 
Published: May 2021

AbstractPurposeUrine can sensitively reflect early pathophysiological changes in the body. The purpose of this study was to determine whether the urine proteome could reflect changes in regular swimming exercise.MethodsIn this study, experimental rats were subjected to daily moderate-intensity swimming exercise for 7 weeks. Urine samples were collected at weeks 2, 5, and 7 and were analyzed by using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).ResultsUnsupervised clustering analysis of all urinary proteins identified at week 2 showed that the swimming group was distinctively different from the control group. Compared to the control group, a total of 112, 61 and 44 differential proteins were identified in the swimming group at weeks 2, 5 and 7, respectively. Randomized grouping statistical analysis showed that more than 85% of the differential proteins identified in this study were caused by swimming exercise rather than random allocation. According to the Human Protein Atlas, the differential proteins that have human orthologs were strongly expressed in the liver, kidney and intestine. Functional annotation analysis revealed that these differential proteins were involved in glucose metabolism and immunity-related pathways.ConclusionOur results revealed that the urinary proteome could reflect significant changes following regular swimming exercise. These findings may suggest an approach to monitoring whether the amount of exercise is appropriate.
A mutation-selection model of protein evolution under persistent positive selection
Authors: Tamuri Asif U. , dos Reis Mario 
Published: May 2021

We use first principles of population genetics to model the evolution of proteins under persistent positive selection (PPS). PPS may occur when organisms are subjected to persistent environmental change, during adaptive radiations, or in host-pathogen interactions. Our mutation-selection model indicates protein evolution under PPS is an irreversible Markov process, and thus proteins under PPS show a strongly asymmetrical distribution of selection coefficients among amino acid substitutions. Our model shows the criteria ω > 1 (where ω is the ratio of non-synonymous over synonymous codon substitution rates) to detect positive selection is conservative and indeed arbitrary, because in real proteins many mutations are highly deleterious and are removed by selection even at positively-selected sites. We use a penalized-likelihood implementation of our model to successfully detect PPS in plant RuBisCO and influenza HA proteins. By directly estimating selection coefficients at protein sites, our inference procedure bypasses the need for using ω as a surrogate measure of selection and improves our ability to detect molecular adaptation in proteins.Significance StatementUnderstanding how natural selection acts on proteins is important as it can inform studies from adaptive radiations to host-pathogen co-evolution. Traditionally, selection on proteins is inferred indirectly by measuring the non-synonymous to synonymous rate ratio, ω, with ω > 1, = 1, and < 1 indicating positive (adaptive) selection, neutral evolution, and negative (purifying) selection respectively. However, the theoretical underpinnings of this ratio are not well understood. Here we use first-principles of population genetics to work out how persistent changes in selection affect protein evolution and we use our new model to detect adaptive sites in plant and influenza proteins. We show measuring selection directly improves detection of adaptation in proteins.
Possible Implications of AlphaFold2 for Crystallographic Phasing by Molecular Replacement
Authors: McCoy Airlie J. , Sammito Massimo D. , Read Randy J. 
Published: May 2021

AbstractThe AlphaFold2 results in the 14th edition of Critical Assessment of Structure Prediction (CASP14) showed that accurate (low root-mean-square deviation) in silico models of protein structure domains are on the horizon, whether or not the protein is related to known structures through high- coverage sequence similarity. As highly accurate models become available, generated by harnessing the power of correlated mutations and deep learning, one of the aspects of structural biology to be impacted will be methods of phasing in crystallography. We here use the data from CASP14 to explore the prospect for changes in phasing methods, and in particular to explore the prospects for molecular replacement phasing using in silico models.SynopsisWe discuss the implications of the AlphaFold2 protein structure modelling software for crystallographic phasing strategies.
Mechanism of the Switch from NO to H2O2 in Endothelium-Dependent Vasodilation in Diabetes
Authors: Juguilon Cody , Wang Zhiyuan , Wang Yang , Jamaiyar Anurag , Xu Yanyong , Enrick Molly , Gadd James , Chen Chwen-Lih W. , Pu Autumn , Kolz Chris , Ohanyan Vahagn , Chen Yeong-Renn , Zhang Yanqiao , Chilian William M , Yin Liya 
Published: May 2021

AbstractCoronary microvascular dysfunction is prevalent among diabetics and is correlated with cardiac mortality. Compromised endothelial-dependent dilation (EDD) is an early event in the progression of diabetes, but the mechanisms remain incompletely understood. Nitric oxide (NO) is the major endothelium-dependent vasodilatory metabolite in the healthy coronary circulation, but switches to hydrogen peroxide (H2O2) in coronary artery disease (CAD) patients. Because diabetes is a major risk factor for CAD we hypothesized that a similar switch from NO-to-H2O2 occurs in diabetes. Methods: Vasodilation was measured ex vivo in isolated coronary arteries from wild type (WT) and microRNA-21 (miR-21) null mice fed chow or high fat and sugar diet, and LepR null (db/db) mice using myography. Myocardial blood flow (MBF), blood pressure, and heart rate were measured in vivo using contrast echocardiography and a solid-state pressure sensor catheter. RNA from coronary arteries, endothelial cells and hearts were analyzed via qPCR for gene expression and protein expression was assessed via Western-Blot analyses. Superoxide was detected via electron paramagnetic resonance (EPR). Results: 1) Ex vivo coronary EDD and in vivo MBF was impaired in diabetes. 2) L-NAME (NO-synthase inhibitor) inhibited ex vivo coronary EDD and in vivo MBF in WT, while PEG-catalase (H2O2 scavenger) inhibited diabetic EDD ex vivo and MBF in vivo. 5) miR-21 deficiency blocked the NO-to-H2O2 switch and prevented diabetic vasodilation impairments. 6) Diabetic mice displayed increased serum NO and H2O2, upregulated mRNA expression of Sod1, Sod2, iNos, and Cav-1, and downregulated Pgc-1α. Deficiency of miR-21 reversed these changes. 7) miR-21 deficiency increased PGC1α, PPARα and eNOS protein and reduced detection of endothelial superoxide. Conclusions: Diabetics exhibit an NO-to-H2O2 switch in the mediator of EDD coronary dilation, which contributed to microvascular dysfunction and is mediated by miR-21. This study represents the first mouse model recapitulating the NO-to-H2O2 switch seen in CAD patients.
Somatic structural variant formation is guided by and influences genome architecture
Authors: Sidiropoulos Nikos , Mardin Balca R. , Rodríguez-González F. Germán , Garg Shilpa , Stütz Adrian M. , Korbel Jan O. , Aiden Erez Lieberman , Weischenfeldt Joachim 
Published: May 2021

AbstractThe occurrence and formation of genomic structural variants (SV) is known to be influenced by the 3D chromatin architecture, but the extent and magnitude has been challenging to study. Here, we apply Hi-C to study chromatin organization before and after induction of chromothripsis in human cells. We use Hi-C to manually assemble the derivative chromosomes following the massive complex rearrangements, which allowed us to study the sources of SV formation and their consequences on gene regulation. We observe an action-reaction interplay whereby the 3D chromatin architecture directly impacts on the location and formation of SVs. In turn, the SVs reshape the chromatin organization to alter the local topologies, replication timing and gene regulation in cis. We show that genomic compartments and replication timing are important determinants for juxtaposing distant loci to form SVs across 30 different cancer types with a pronounced abundance of SVs between early replicating regions in uterine cancer. We find that SVs frequently occur at 3D loop-anchors, cause compartment switching and changes in replication timing, and that this is a major source of SV-mediated effects on nearby gene expression changes.
Evolutionary coexistence in a fluctuating environment by specialization on resource level
Authors: Wortel Meike T. 
Published: May 2021

AbstractMicrobial communities in fluctuating environments, such as the human gut or repeated dilutions in the laboratory, contain a wealth of diversity. Diversity contributes to the stability and function of communities and is maintained by underlying mechanisms. When nutrient levels fluctuate over time, one possibly relevant mechanism is that types specialize on low and high nutrient levels. The relevance of this process is supported by observations of coexistence in the laboratory, and by simple models, that show that negative frequency dependence of two such types can stabilize coexistence. However, as microbial populations are often large and numerous, they evolve. Our aim is to determine what happens when species can evolve; whether evolutionary branching can create diversity or whether evolution will destabilize coexistence.We derive the selection coefficient in fluctuating environments and use adaptive dynamics to find that evolutionary stable coexistence requires a special type of trade-off between growth at low and high nutrients. We do not find support for the necessary trade-off in data available for the bacterium Escherichia coli and the yeast Saccharomyces cerevisiae on glucose. However, this type data is scarce, and might exist for other species or in different conditions. Moreover, we do find evidence for the right trade-off and evolutionarily stable coexistence of the two species together. Since we find this coexistence in the scarce data that is available, we predict that specialization on resource level is a relevant mechanism for species diversity in microbial communities in fluctuating environments in natural settings.
The Global Protein-RNA Interaction map of Epithelial Splicing Regulatory Protein 1 defines a post-transcriptional program that is essential for epithelial cell function
Authors: Peart Natoya J. , Hwang Jae Yeon , Quesnel- Vallières Mathieu , Sears Matthew J. , Yang Yuequin , Stoilov Peter , Barash Yoseph , Park Juw Won , Carstens Russ P. 
Published: May 2021

SummaryThe epithelial splicing regulatory proteins, ESRP1 and ESRP2 are essential for mammalian development through regulation of a global program of alternative splicing of genes involved in maintenance of epithelial cell function. To further inform our understanding of the molecular functions of ESRP1 we performed enhanced crosslinking immunoprecipitation coupled with high throughput sequencing (eCLIP) in epithelial cells of mouse epidermis. The genome-wide binding sites of ESRP1 were integrated with RNA-Seq analysis of alterations in splicing and total gene expression that result from epidermal ablation of Esrp1 and Esrp2. These studies demonstrated that ESRP1 functions in splicing regulation occur primarily through direct binding in a position-dependent manner to either promote exon inclusion or skipping. In addition, we also identified widespread binding of ESRP1 in 3’ and 5’ untranslated regions (UTRs) of genes involved in epithelial cell function suggesting that its post-transcriptional functions extend beyond splicing regulation.
Deciphering ion transport and ATPase coupling in the intersubunit tunnel of KdpFABC
Authors: Silberberg Jakob M , Corey Robin A , Hielkema Lisa , Stock Charlott , Stansfeld Phillip J , Paulino Cristina , Hänelt Inga 
Published: May 2021

AbstractKdpFABC, a high-affinity K+ pump, combines the ion channel KdpA and the P-type ATPase KdpB to secure survival at K+ limitation. Here, we apply a combination of cryo-EM, biochemical assays, and MD simulations to illuminate the mechanisms underlying transport and the coupling to ATP hydrolysis. We unambiguously show that ions are transported via an intersubunit tunnel through KdpA and KdpB. At the subunit interface, the tunnel is constricted by a phenylalanine, which, by polarized cation-π stacking, controls K+ entry into the canonical substrate binding site (CBS) of KdpB. Within the CBS, ATPase coupling is mediated by the charge distribution between an aspartate and a lysine. Interestingly, individual elements of the ion translocation mechanism of KdpFABC identified here are conserved among a wide variety of P-type ATPases from different families. This leads us to the hypothesis that KdpB might represent an early descendant of a common ancestor of cation pumps.
Hybridization and range expansion in tamarisk beetles (Diorhabda spp.) introduced to North America for classical biological control
Authors: Stahlke Amanda R. , Bitume Ellyn V. , Ozsoy A. Zeynep , Bean Dan W. , Veillet Anne , Clark Meaghan I. , Clark Eliza I. , Moran Patrick , Hufbauer Ruth A. , Hohenlohe Paul A. 
Published: May 2021

AbstractWith the global rise of human-mediated translocations and invasions, it is critical to understand the genomic consequences of hybridization and mechanisms of range expansion. Conventional wisdom is that high genetic drift and loss of genetic diversity due to repeated founder effects will constrain introduced species. However, reduced genetic variation can be countered by behavioral aspects and admixture with other distinct populations. As planned invasions, classical biological control (biocontrol) agents present important opportunities to understand the mechanisms of establishment and spread in a novel environment. The ability of biocontrol agents to spread and adapt, and their effects on local ecosystems, depends on genomic variation and the consequences of admixture in novel environments. Here we use a biocontrol system to examine the genome-wide outcomes of introduction, spread, and hybridization in four cryptic species of a biocontrol agent, the tamarisk beetle (Diorhabda carinata, D. carinulata, D. elongata, and D. sublineata), introduced from six localities across Eurasia to control the invasive shrub tamarisk (Tamarix spp.) in western North America. We assembled a de novo draft reference genome and applied RADseq to over 500 individuals from laboratory cultures, the native ranges, and across the introduced range. Despite evidence of a substantial genetic bottleneck among D. carinulata in N. America, populations continue to establish and spread, possibly due to aggregation behavior. We found that D. carinata, D. elongata, and D. sublineata hybridize in the field to varying extents, with D. carinata x D. sublineata hybrids being the most abundant. Genetic diversity was greater at sites with hybrids, highlighting potential for increased ability to adapt and expand. Our results demonstrate the complex patterns of genomic variation that can result from introduction of multiple ecotypes or species for biocontrol, and the importance of understanding them to predict and manage the effects of biocontrol agents in novel ecosystems.
Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2
Authors: Israelow Benjamin , Mao Tianyang , Klein Jonathan , Song Eric , Menasche Bridget , Omer Saad B. , Iwasaki Akiko 
Published: May 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 160 million infections and more than 3 million deaths worldwide. While effective vaccines are currently being deployed, the adaptive immune determinants which promote viral clearance and confer protection remain poorly defined. Using mouse models of SARS-CoV-2, we demonstrate that both humoral and cellular adaptive immunity contributes to viral clearance in the setting of primary infection. Furthermore, we find that either convalescent mice, or mice that receive mRNA vaccination are protected from both homologous infection and infection with a variant of concern, B.1.351. Additionally, we find this protection to be largely mediated by antibody response and not cellular immunity. These results highlight the in vivo protective capacity of antibodies generated to both vaccine and natural infection.One-Sentence SummaryDefining the roles of humoral and cellular adaptive immunity in viral clearance and protection from SARS-CoV-2 and a variant of concern.