bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary diversity and its correlates among pregnant adolescent girls in Ghana
Authors: Gyimah Linda A. , Annan Reginald A. , Apprey Charles , Edusei Anthony K. , Aduku Linda Esi , Asamoah-Boakye Odeafo , Azanu Wisdom , Lutterodt Herman
Published: August 2020

Background

Dietary diversity, a qualitative measure of dietary intake, which reflects the variety of foods consumed has been recommended to assuage nutritional problems related to insufficient micronutrients and food insecurity. To better understand the underlying factors for poor birth outcomes in Ghana, we assessed factors associated with dietary diversity among rural and urban pregnant adolescents in the Ashanti Region of Ghana.

Methods

As part of a larger longitudinal cohort of 416 pregnant adolescents, the FAO women’s dietary diversity index was used to determine dietary diversity score (DDS) of the participants from a 3-day repeated 24-hour dietary recall data. The household hunger scale (HHS) and lived poverty index (LPI) were used to determine hunger and socioeconomic status. Eating behavior and socio-demographic data were gathered using interviewer-administered questionnaires.

Results

The mean DDS for participants was 4.3 but 59.7% of participants were below the minimum DD. More rural (67.1%) than urban dwellers (53.9%) had inadequate DDS (p=0.008). Urban dwelling adolescents recorded higher odds for adequate DD (OR=1.8 CI =1.0-2.8, p=0.034) compared to the rural respondents. Other factors associated with higher odds for adequate DD are income (OR=12.1, p = 0.043, 95%CI= 1.1-136.8), moderate (OR=2.1, p = 0.019, 95%CI=1.1-3.8) and high LPI (OR=2.2, p=0.007, 95%CI=1.2-3.9), practicing food aversion (OR=1.6, p = 0.046, 95%CI= 1.0-2.4), and pica (OR 1.6, p =0.043, 95%CI= 1.0-2.5).

Conclusions

Low DD is common among pregnant adolescents in this study and associated with poverty, food insecurity, rural living, pica practice, and food aversions. Livelihood support for pregnant teenagers and nutrition education are recommended interventions to improve dietary quality and limit the consequences of poor dietary diversity.
Children’s Anxiety and Physical Activity during COVID-19 in Relation to Prenatal Exposure to Gestational Diabetes
Authors: Alves Jasmin M. , Yunker Alexandra G. , DeFendis Alexis , Xiang Anny H. , Page Kathleen A.
Published: August 2020

Research goal

Assess the relationships between anxiety levels, physical activity and in utero exposure to Gestational Diabetes mellitus (GDM) in children age 9 to 15, during the coronavirus disease 2019 (COVID-19) pandemic.

Methods

During the COVID-19 pandemic, participants completed phone call or video calls with study personnel where they were asked to report on their physical activity and anxiety levels using the 24-hour physical activity recall and the State-Trait Anxiety Inventory for Children. GDM-exposure was assessed using electronic medical records.

Results

Children who reported higher levels of moderate to vigorous physical activity or vigorous physical activity, reported lower anxiety symptoms. Children exposed to GDM in utero reported higher anxiety scores and lower engagement in vigorous physical activity compared to unexposed children. Moreover, the pathway through which children exposed to GDM in utero, reported higher anxiety was partially explained by reduced engagement in vigorous physical activity (75%, p=0.05).

Conclusions

Engaging in physical activity during the COVID-19 pandemic may be beneficial for reducing anxiety, particularly among children exposed to GDM in utero, who are at increased risk for adverse psychological outcomes.
Automated measurement of the foveal avascular zone in healthy eyes on Heidelberg Spectralis Optical Coherence Tomography Angiography
Authors: Gutierrez-Benitez Laura , Palomino Yolanda , Casas Noe , Asaad Mouafk
Published: August 2020

Purpose

To develop and evaluate an automated method to measure the foveal avascular zone (FAZ) area in healthy eyes on Heidelberg Spectralis Optical Coherence Tomography Angiography (HS-OCTA). This method is referred to as the modified Kanno-Saitama macro (mKSM) and it is an evolution of the original Kanno-Saitama macro (KSM) approach.

Methods

This cross-sectional study included 29 eyes of 25 healthy volunteers who underwent HS-OCTA at the macular area twice at the same time. Regardless of the quality of the images, all of them were included. Macular data on the superficial vascular plexus, intermediate capillary plexus and deep capillary plexus were processed by mKSM. The FAZ area was measured twice automatically using the mKSM and KSM and twice manually by two independent examiners.

Results

From 174 images, KSM could not measure correctly 31% while mKSM could successfully measure all of them. Intrascan intraclass coefficient ranged from 0,948 to 0,993 for manual measurements and was 1 for mKSM method, which means that mKSM FAZ area value is always the same for the same OCTA image. Despite that the difference between human examiners is smaller than between human examiners and mKSM according to Bland-Altman plots, the scatterplots show a strong correlation between human and automatic measurements. The best results are obtained in intermediate capillary plexus.

Conclusions

With mKSM, the automated determination of the FAZ area in HS-OCTA is feasible and less human-dependent. It solves the inability of KSM to measure the FAZ area in suboptimal quality images which are frequent in daily clinical practice. Therefore, the mKSM processing could contribute to our understanding of the three vascular plexuses.
Genetic and Phenotypic Evidence for the Causal Relationship Between Aging and COVID-19
Authors: Ying Kejun , Zhai Ranran , Pyrkov Timothy V. , Mariotti Marco , Fedichev Peter O. , Shen Xia , Gladyshev Vadim N.
Published: August 2020

Epidemiological studies have revealed that the elderly and those with co-morbidities are most susceptible to COVID-19. To understand the genetic link between aging and the risk of COVID-19, we conducted a multi-instrument Mendelian randomization analysis and found that the genetic variation that leads to a longer lifespan is significantly associated with a lower risk of COVID-19 infection. The odds ratio is 0.32 (95% CI: 0.18 to 0.57; P = 1.3 × 10-4) per additional 10 years of life, and 0.62 (95% CI: 0.51 to 0.77; P = 7.2 × 10-6) per unit higher log odds of surviving to the 90th percentile age. On the other hand, there was no association between COVID-19 susceptibility and healthspan (the lifespan free of the top seven age-related morbidities). To examine the relationship at the phenotypic level, we applied various biological aging clock models and detected an association between the biological age acceleration and future incidence and severity of COVID-19 infection for all subjects as well as for the individuals free of chronic disease. Biological age acceleration was also significantly associated with the risk of death in COVID-19 patients. Our findings suggest a causal relationship between aging and COVID-19, defined by genetic variance, the rate of aging, and the burden of chronic diseases.
Predation impacts late but not early community assembly in model marine biofilms
Authors: Tobias-Hünefeldt Sven P. , Wenley Jess , Baltar Federico , Morales Sergio E.
Published: August 2020

Bottom-up selection plays an important role in microbial community assembly but is unable to account for all observed variance. Other processes like top-down selection (e.g. predation) may be partially responsible for the unexplained variance. However, top-down processes often remain unexplored, especially in interaction with bottom-up selective pressures. We utilised anin situmarine biofilm model system to test the effects of bottom-up (i.e. substrate properties) and top-down (i.e. predator exclusion via 100 µm mesh) selective pressures on community assembly over time (56 days). Community compositions were monitored using 16S and 18S rRNA amplicon sequencing. Wooden substrates promoted heterotrophic growth, while the inert substrates’ (i.e., plastic, glass, tile) lack of degradable material selected for autotrophs. Early wood communities contained 9-50% more mixotrophs and heterotrophs (e.g. Proteobacteria and Euglenozoa) compared to inert substrates. Inert substrates instead showed twice the autotrophic (e.g. Cyanobacteria and Ochrophyta) abundance. Late communities differed mainly due to exclusion status, as large predators preferably pruned heterotrophs. This resulted in the autotrophic domination of native communities, while high heterotrophic abundance characterised exclusive conditions. Top-down control through exclusion increased explainable variance by 18-53%, depending on community age, leading to increased understanding of the underlying ecological framework that guides microbial community assembly.
Molecular markers characterization determining cell fate specification in an adult neurogenesis model ofAlzheimer’s disease
Authors: Blanco-Luquin Idoia , Cabello Juan , Urdánoz-Casado Amaya , Acha Blanca , Gómez-Orte Eva Ma , Roldan Miren , Pérez-Rodríguez Diego R. , Mendioroz Maite
Published: August 2020

Adult hippocampal neurogenesis (AHN) study is still a challenge. In addition to methodological difficulties is the controversy of results derived of human or animal system approaches. In view of the proven link between AHN and learning and memory impairment, we generated a straightforwardin vitromodel to recapitulate adult neurogenesis in the context of Alzheimer’s disease (AD).

Neural progenitor cells (NPCs) monolayer culture was differentiated for a period of 29 days and Aβ peptide 1-42 was administered once a week. mRNA expression ofNEUROD1, NCAM1, TUBB3, RBFOX3, CALB1andGFAPgenes was determined by RT-qPCR.

Phenotypic changes were observed during directed differentiation. Except forGFAPandCALB1, these changes correlated with altered expression profile of all genes since 9 days. OnlyTUBB3expression remained constant whileNEUROD1, NCAM1andRBFOX3expression increased over time. Moreover, Aβ treated NPCs showed transient decreases of mRNA expression forNCAM1, TUBB3andRBFOX3genes at 9 or 19 days.

Ourin vitrohuman NPCs model is framed within the multistep process of AHN in the SGZ of the DG. Remarkably, its transcriptional assessment might reflect alterations detected in AD human patients, deepening our understanding of the disorder and possibly of its pathogenesis.

SUMMARY STATEMENT

Transcriptional profile of a number of genes recapitulating particular stages of Adult hippocampal neurogenesis in the context of Alzheimer’s disease
Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer
Authors: Iqbal Mohammad Askandar , Siddiqui Shumaila , Ur Rehman Asad , Siddiqui Farid Ahmad , Singh Prithvi , Kumar Bhupender , Saluja Daman
Published: August 2020

Striking similarity exists between metabolic changes associated with embryogenesis and tumorigenesis. Chromobox proteins-CBX2/4/6/7/8, core components of canonical polycomb repressor complex 1 (cPRC1), play essential roles in embryonic development and aberrantly expressed in breast cancer. Understanding how altered CBX expression relates to metabolic reprogramming in breast cancer may reveal vulnerabilities of therapeutic pertinence. Using transcriptomic and metabolomic data from breast cancer patients (N>3000 combined), we performed pathway-based analysis and identified outstanding roles of CBX2 and CBX7 in positive and negative regulation of glucose metabolism, respectively. Genetic ablation experiments validated the contrasting roles of two isoforms in cancer metabolism and cell growth. Furthermore, we provide evidence for the role of mTORC1 signaling in mediating contrary effects of CBX2 and CBX7 on breast cancer metabolism. Underpinning the biological significance of metabolic roles, CBX2 and CBX7 were found to be the most up- and down-regulated isoforms, respectively, in breast tumors compared to normal tissues. Moreover, CBX2 and CBX7 expression (not other isoforms) correlated strongly, but oppositely, with breast tumor subtype aggressiveness and the proliferation markers. Consistently, genomic data also showed higher amplification frequency of CBX2, not CBX7, in breast tumors. Highlighting the clinical significance of findings, disease-specific survival and drug sensitivity analysis revealed that CBX2 and CBX7 predicted patient outcome and sensitivity to FDA-approved clinical drugs. In summary, this work identifies novel cross-talk between CBX2/7 and breast tumor metabolism, and the results presented may have implications in strategies targeting breast cancer.
Lamin-related congenital muscular dystrophy alters mechanical signaling and skeletal muscle growth
Authors: Owens Daniel J. , Messéant Julien , Moog Sophie , Viggars Mark , Ferry Arnaud , Mamchaoui Kamel , Lacène Emmanuelle , Roméro Norma , Brull Astrid , Bonne Gisèle , Butler-Browne Gillian , Coirault Catherine
Published: August 2020

Background

Laminopathies are a clinically heterogeneous group of disorders caused by mutations in theLMNAgene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated withLMNAmutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, andLMNA-related congenital muscular dystrophy (LMNA-CMD). Although the exact pathophysiological mechanisms responsible forLMNA-CMD are not yet understood, severe contracture and muscle atrophy suggest that impair skeletal muscle growth may contribute to the disease severity.

Methods

We used human muscle stem cells (MuSCs) carrying 4 differentLMNAmutations and two mouse models of muscle laminopathies, representing a spectrum of disease severity, to investigate the ability of skeletal muscle to differentiate and to hypertrophy in response to mechanical challenges. We extended these finding to individuals withLMNA-related muscular dystrophy using muscle biopsies.

Results

In vitro, we observe impaired myogenic differentiation with disorganized cadherin/β catenin adhesion complexes in MuSCs carryingLMNA-CMD. We show that skeletal muscle fromLmna-CMD mice is unable to hypertrophy in response to functional overload, due to defective accretion of activated MuSCs, defective protein synthesis and defective remodeling of the neuro-muscular junction. Moreover, stretched myotubes and overloaded muscle fibers withLMNA-CMD mutations display aberrant mechanical regulation of the Yes-Associated Protein (YAP), a key sensor and mediator of mechanical cues. We also observe defects in MuSC activation and YAP signaling in muscle biopsies fromLMNA-CMD patients. These phenotypes are not recapitulated in closely-related EDMD models.

Conclusions

Combining studiesin vitro,in vivoand patient samples, we find thatLMNA-CMD mutations interfere with mechano-signaling pathways in skeletal muscle, implicating defective skeletal muscle growth as a pathogenic contributor for the severity ofLMNA-related muscular dystrophy.
Effect of pancreatic lipase inhibitor and sorbent of lipids on cholesterolaemia and faecal output of fat in rats
Authors: Marounek Milan , Volek Zdeněk , Taubner Tomáš , Dušková Dagmar , Czauderna Marian
Published: August 2020

Obesity and high cholesterolaemia are major health problems in industrialized countries. The effects of the antiobesity drug orlistat at 0.3 g kg-1and amidated alginate at 40 g kg-1on serum and hepatic cholesterol and the faecal output of fat and sterols were compared in female rats. Rats were fed diets containing cholesterol and palm fat at 10 and 70 g kg-1, respectively. Palm fat was provided by coconut meal. Amidated alginate (the octadecylamide of alginic acid) is a sorbent of lipids, and orlistat (tetrahydrolipstatin) is an inhibitor of pancreatic lipase. Both agents significantly increased the faecal loss of fat, orlistat, however, did not significantly decrease serum total cholesterol and its effect on hepatic cholesterol was less pronounced. Amidated alginate at 40 g kg-1significantly decreased serum total cholesterol, LDL cholesterol, hepatic cholesterol, and hepatic lipids, and increased the faecal output of fat and coprostanol (a metabolite of cholesterol). Both orlistat and amidated alginate modified the fatty acid profile in excreted lipids. The concentration of saturated fatty acids decreased and the concentration of unsaturated fatty acids increased. Despite different modes of action, orlistat and amidated alginate were equally efficient in the removing dietary fat from the body. Amidated alginate, however, was more active in the control of serum and hepatic lipid metabolism.
Expression and distribution of synaptotagmin isoforms in the zebrafish retina
Authors: Henry Diane , Joselevitch Christina , Matthews Gary G. , Wollmuth Lonnie P.
Published: August 2020

Synaptotagmins belong to a large family of proteins. While various synaptotagmins have been implicated as Ca2+sensors for vesicle replenishment and release at conventional synapses, their roles at retinal ribbon synapses remain incompletely understood. Zebrafish is a widely used experimental model for retinal research. We therefore investigated the homology between human, rat, mouse, and zebrafish synaptotagmins 1 to 10 using a bioinformatics approach. We also characterized the expression and distribution of various synaptotagmin (syt) genes in the zebrafish retina using RT-PCR andin situhybridization, focusing on the family members whose products likely underlie Ca2+-dependent exocytosis in the central nervous system (synaptotagmins 1, 2, 5 and 7). We find that most zebrafish synaptotagmins are well conserved and can be grouped in the same classes as mammalian synaptotagmins, based on crucial amino acid residues needed for coordinating Ca2+binding and determining phospholipid binding affinity. The only exception is synaptotagmin 1b, which lacks 34 amino acid residues in the C2B domain and is therefore unlikely to bind Ca2+there. Additionally, the products of zebrafishsyt5aandsyt5bgenes share identity with mammalian class 1 and 5 synaptotagmins. Zebrafishsyt1,syt2,syt5andsyt7paralogues are found in the zebrafish brain, eye, and retina, exceptingsyt1b, which is only present in the brain. The complementary expression pattern of the remaining paralogues in the retina suggests thatsyt1aandsyt5amay underlie synchronous release andsyt7aandsyt7bmay mediate asynchronous release or other Ca2+dependent processes in different types of retinal neurons.
3D quantification of zebrafish cerebrovascular architecture by automated image analysis of light sheet fluorescence microscopy datasets
Authors: Kugler E. C. , Frost J. , Silva V. , Plant K. , Chhabria K. , Chico T. J.A. , Armitage P. A.
Published: August 2020

Zebrafish transgenic lines and light sheet fluorescence microscopy allow in-depth insights into vascular developmentin vivoand 3D. However, robust quantification of the zebrafish cerebral vasculature in 3D remains a challenge, and would be essential to describe the vascular architecture. Here, we report an image analysis pipeline that allows 3D quantification of the total or regional zebrafish brain vasculature. This is achieved by landmark- or object-based inter-sample registration and extraction of quantitative parameters including vascular volume, surface area, density, branching points, length, radius, and complexity. Application of our analysis pipeline to a range of sixteen genetic or pharmacological manipulations shows that our quantification approach is robust, allows extraction of biologically relevant information, and provides novel insights into vascular biology. To allow dissemination, the code for quantification, a graphical user interface, and workflow documentation are provided. Together, we present the first 3D quantification approach to assess the whole 3D cerebrovascular architecture in zebrafish.
Particulate Matter emission sources and meteorological parameters combine to shape the airborne microbiome communities in the Ligurian coast, Italy
Authors: Palladino Giorgia , Morozzi Pietro , Biagi Elena , Brattich Erika , Turroni Silvia , Rampelli Simone , Tositti Laura , Candela Marco
Published: August 2020

Here we explore how the chemical composition of particulate matter (PM) and meteorological conditions combine in shaping the air microbiome in a heavily inhabited industrial urban settlement. During the observation time, the air microbiome was highly dynamic, fluctuating between different compositional states, likely resulting from the aerosolization of different microbiomes emission sources. This dynamic process depends on the combination of local meteorological parameters and particle emission sources, which may affect the prevalent aerosolized microbiomes. In particular, we showed that, in the investigated area, industrial emissions and winds blowing from the inlands combine with an airborne microbiome that includes faecal microbiomes components, suggesting multiple citizens’ exposure to both chemicals and microorganisms of faecal origin, as related to landscape exploitation and population density. In conclusion, our findings support the need to include monitoring of the air microbiome compositional structure as a relevant factor for the final assessment of local air quality.
Predicting Residues Involved in Anti-DNA Autoantibodies with Limited Neural Networks
Authors: St.Clair Rachel , Teti Michael , Pavlovic Mirjana , Hahn William , Barenholtz Elan
Published: August 2020

Computer-aided rational vaccine design (RVD) and synthetic pharmacology are rapidly developing fields that leverage existing datasets for developing compounds of interest. Computational proteomics utilizes algorithms and models to probe proteins for functional prediction. A potentially strong target for such a computational approach is autoimmune antibodies which are the result of broken tolerance in the immune system where it cannot distinguish “self” from “non-self” resulting in attack of its own structures (proteins and DNA, mainly). The information on structure, function and pathogenicity of autoantibodies may assist in engineering RVD against autoimmune diseases. Current computational approaches exploit large datasets curated with extensive domain knowledge, most of which include the need for many computational resources and have been applied indirectly to problems of interest for DNA, RNA, and monomer protein binding. Here, we present a novel method for discovering potential binding sites. We employed long short-term memory (LSTM) models trained on FASTA primary sequences directly to predict protein binding in DNA-binding hydrolytic antibodies (abzymes). We also employed CNN models applied to the same dataset. While the CNN model outperformed the LSTM on the primary task of binding prediction, analysis of internal model representations of both models showed that the LSTM models highlighted sub-sequences that were more strongly correlated with sites known to be involved in binding. These results demonstrate that analysis of internal processes of recurrent neural network models may serve as a powerful tool for primary sequence analysis.
SNPC-1.3 is a sex-specific transcription factor that drives male piRNA expression inC. elegans
Authors: Choi Charlotte P. , Tay Rebecca J. , Starostik Margaret R. , Feng Suhua , Moresco James J. , Montgomery Brooke E. , Xu Emily , Hammonds Maya A. , Schatz Michael C. , Montgomery Taiowa A. , Yates John R. , Jacobsen Steven E. , Kim John K.
Published: August 2020

Piwi-interacting RNAs (piRNAs) play essential roles in silencing repetitive elements to promote fertility in metazoans. Studies in worms, flies, and mammals reveal that piRNAs are expressed in a sex-specific manner. However, the mechanisms underlying this sex-specific regulation are unknown. Here we identify SNPC-1.3, a variant of a conserved subunit of the snRNA activating protein complex, as a male-specific piRNA transcription factor inC. elegans. Binding of SNPC-1.3 at male piRNA loci drives spermatogenic piRNA transcription and requires the core piRNA transcription factor SNPC-4. Loss ofsnpc-1.3leads to depletion of male piRNAs and defects in male-dependent fertility. Furthermore, TRA-1, a master regulator of sex determination, binds to thesnpc-1.3promoter and represses its expression during oogenesis. Loss of TRA-1 targeting causes ectopic expression ofsnpc-1.3and male piRNAs during oogenesis. Thus, sexual dimorphic regulation ofsnpc-1.3coordinates male and female piRNA expression during germline development.
SVCollector: Optimized sample selection for cost-efficient long-read population sequencing
Authors: Ranallo-Benavidez T. Rhyker , Lemmon Zachary , Soyk Sebastian , Aganezov Sergey , Salerno William J. , McCoy Rajiv C. , Lippman Zachary B. , Schatz Michael C. , Sedlazeck Fritz J.
Published: August 2020

An increasingly important scenario in population genetics is when a large cohort has been genotyped using a low-resolution approach (e.g. microarrays, exome capture, short-read WGS), from which a few individuals are selected for resequencing using a more comprehensive approach, especially long-read sequencing. The subset of individuals selected should ensure that the captured genetic diversity is fully representative and includes variants across all subpopulations. For example, human variation has historically been focused on individuals with European ancestry, but this represents a small fraction of the overall diversity.

To address this goal, SVCollector (https://github.com/fritzsedlazeck/SVCollector) identifies the optimal subset of individuals for resequencing. SVCollector analyzes a population-level VCF file from a low resolution genotyping study. It then computes a ranked list of samples that maximizes the total number of variants present from a subset of a given size. To solve this optimization problem, SVCollector implements a fast greedy heuristic and an exact algorithm using integer linear programming. We apply SVCollector on simulated data, 2504 human genomes from the 1000 Genomes Project, and 3024 genomes from the 3K Rice Genomes Project and show the rankings it computes are more representative than widely used naive strategies. Notably, we show that when selecting an optimal subset of 100 samples in these two cohorts, SV-Collector identifies individuals from every subpopulation while naive methods yield an unbalanced selection. Finally, we show the number of variants present in cohorts of different sizes selected using this approach follows a power-law distribution that is naturally related to the population genetic concept of the allele frequency spectrum, allowing us to estimate the diversity present with increasing numbers of samples.
Behavioral correlates of cortical semantic representations modeled by word vectors
Authors: Nishida Satoshi , Blanc Antione , Maeda Naoya , Kado Masataka , Nishimoto Shinji
Published: August 2020

The quantitative modeling of semantic representations in the brain plays a key role in understanding the neural basis of semantic processing. Previous studies have demonstrated that word vectors, which were originally developed for use in the field of natural language processing, provide a powerful tool for such quantitative modeling. However, whether semantic representations revealed by the word vector-based models actually capture our perception of semantic information remains unclear, as there has been no study explicitly examining the behavioral correlates of the modeled semantic representations. To address this issue, we compared the semantic structure of nouns and adjectives estimated from word vector-based brain models with that evaluated from human behavior. The brain models were constructed using voxelwise modeling to predict the functional magnetic resonance imaging (fMRI) response to natural movies from semantic contents in each movie scene through a word vector space. The semantic dissimilarity of word representations was then evaluated using the brain models. Meanwhile, data on human behavior reflecting the perception of semantic dissimilarity between words were collected in psychological experiments. We found a significant correlation between brain model- and behavior-derived semantic dissimilarities of words. This finding suggests that semantic representations in the brain modeled via word vectors appropriately capture our perception of word meanings.

Author summery

Word vectors, which have been originally developed in the field of engineering (natural language processing), have been extensively leveraged in neuroscience studies to model semantic representations in the human brain. These studies have attempted to model brain semantic representations by associating them with the meanings of thousands of words via a word vector space. However, there has been no study explicitly examining whether the modeled semantic representations actually capture our perception of semantic information. To address this issue, we compared the semantic representational structure of words estimated from word vector-based brain models with that evaluated from behavioral data in psychological experiments. The results revealed a significant correlation between these model- and behavior-derived semantic representational structures of words. This indicates that the brain semantic representations modeled using word vectors actually reflect the human perception of word meanings. Our findings contribute to the establishment of word vector-based brain modeling as a useful tool in studying human semantic processing.
Gluconeogenic Enzyme PCK1 Deficiency Is Critical for CHK2 O-GlcNAcylation and Hepatocellular Carcinoma Growth upon Glucose Deprivation
Authors: Xiang Jin , Chen Chang , Liu Rui , Gou Dongmei , Chang Lei , Deng Haijun , Gao Qingzhu , Zhang Wanjun , Tuo Lin , Pan Xuanming , Liang Li , Xia Jie , Huang Luyi , Huang Ailong , Wang Kai , Tang Ni
Published: August 2020

Elevated hexosamine-biosynthesis pathway (HBP) activity and O-GlcNAcylation are emerging hallmarks of hepatocellular carcinoma (HCC). Inhibiting O-GlcNAcylation could be a promising anti-cancer strategy. Here, we investigate this possibility and demonstrate that deficiency of phosphoenolpyruvate carboxykinase 1 (PCK1), a rate-limiting enzyme in gluconeogenesis, promotes O-GlcNAcylation and hepatoma cell proliferation under low-glucose conditions. PCK1 loss results in oxaloacetate accumulation and AMPK inactivation, promoting uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) synthesis and CHK2 threonine 378 O-GlcNAcylation and counteracting its ubiquitination and degradation. O-GlcNAcylation also promotes CHK2-dependent Rb phosphorylation and HCC cell proliferation. Therefore, blocking HBP-mediated O-GlcNAcylation suppresses tumor progression in liver-specificPck1-knockout mice. We reveal a link between PCK1 depletion and hyper-O-GlcNAcylation that underlies HCC oncogenesis and suggest therapeutic targets for HCC that act by inhibiting O-GlcNAcylation.
Wrong person, place and time: viral load and contact network structure predict SARS-CoV-2 transmission and super-spreading events
Authors: Goyal Ashish , Reeves Daniel B. , Cardozo-Ojeda E. Fabian , Schiffer Joshua T. , Mayer Bryan T.
Published: August 2020

SARS-CoV-2 is difficult to contain because many transmissions occur during the pre-symptomatic phase of infection. Moreover, in contrast to influenza, while most SARS-CoV-2 infected people do not transmit the virus to anybody, a small percentage secondarily infect large numbers of people. We designed mathematical models of SARS-CoV-2 and influenza which link observed viral shedding patterns with key epidemiologic features of each virus, including distributions of the number of secondary cases attributed to each infected person (individual R0) and the duration between symptom onset in the transmitter and secondarily infected person (serial interval). We identify that people with SARS-CoV-2 or influenza infections are usually contagious for fewer than one day congruent with peak viral load several days after infection, and that transmission is unlikely below a certain viral load. SARS-CoV-2 super-spreader events with over 10 secondary infections occur when an infected person is briefly shedding at a very high viral load and has a high concurrent number of exposed contacts. The higher predisposition of SARS-CoV-2 towards super-spreading events is not due to its 1-2 additional weeks of viral shedding relative to influenza. Rather, a person infected with SARS-CoV-2 exposes more people within equivalent physical contact networks than a person infected with influenza, likely due to aerosolization of virus. Our results support policies that limit crowd size in indoor spaces and provide viral load benchmarks for infection control and therapeutic interventions intended to prevent secondary transmission.

One Sentence Summary

We developed a coupled within-host and between-host mathematical model to identify viral shedding levels required for transmission of SARS-CoV-2 and influenza, and to explain why super-spreading events occur more commonly during SARS-CoV-2 infection.
Mapping access to basic hygiene services in low- and middle-income countries: A cross-sectional case study of geospatial disparities
Authors: Yu Weiyu , Bain Robert E. S. , Yu Jie , Alegana Victor , Dotse-Gborgbortsi Winfred , Lin Yi , Wright Jim A.
Published: August 2020

Handwashing with water and soap, is among the most a cost-effective interventions to improve public health. Yet billions of people globally lacking handwashing facilities with water and soap on premises, with gaps particularly found in low- and middle-income countries. Targeted efforts to expand access to basic hygiene services require data at geospatially explicit scales. Drawing on country-specific cross-sectional Demographic and Health Surveys with georeferenced hygiene data, we developed an ensemble model to predict the prevalence of basic hygiene facilities in Malawi, Nepal, Nigeria, Pakistan and Uganda. The ensemble model was based on a multiple-level stacking structure, where five predictive modelling algorithms were used to produce sub-models, and a random forest model was used to generalise the final predictions. An inverse distance weighted interpolation was incorporated in the random forest model to account for spatial autocorrelation. Local coverage and a local dissimilarity index were calculated to examine the geographic disparities in access. Our methodology produced robust outputs, as evidenced by performance evaluations (all R2were above 0.8 with the exception of Malawi where R2= 0.6). Among the five study countries, Pakistan had the highest overall coverage, whilst Malawi had the poorest coverage. Apparent disparities in basic hygiene services were found across geographic locations and between urban and rural settings. Nigeria had the highest level of inequalities in basic hygiene services, whilst Malawi showed the least segregation between populations with and without basic hygiene services. Both educational attainment and wealth were important predictors of the geospatial distribution of basic hygiene services. By producing geospatially explicit estimates of the prevalence of handwashing facilities with water and soap, this study provides a means of identifying geographical disparities in basic hygiene services. The method and outputs can be useful tools to identify areas of low coverage and to support efficient and precise targeting of efforts to scale up access to handwashing facilities and shift social and cultural norms on handwashing.
Implementing integrated care pilot projects in hospital settings – an exploration of disruptive practices
Authors: Mansfield Elizabeth , Sandercock Jane , Dowedoff Penny , Martel Sara , Marcinow Michelle , Shulman Richard , Parks Sheryl , Peters Mary-Lynn , Versloot Judith , Kerr Jason , Zenlea Ian
Published: August 2020

Purpose

In Canada, integrated care pilot projects are often implemented as a local reform strategy to improve the quality of patient care and system efficiencies. In the qualitative study reported here, the authors explored the experiences of healthcare professionals when first implementing integrated care pilot projects, bringing together physical and mental health services, in a community hospital setting.

Design/methodology/approach

Engaging a qualitative descriptive study design, semi-structured interviews were conducted with 24 healthcare professionals who discussed their experiences with implementing three integrated care pilot projects one year following project launch. The thematic analysis captured early implementation issues and was informed by an institutional logics framework.

Findings

Three themes highlight disruptions to established logics reported by healthcare professionals during the early implementation phase: (1) integrated care practices increased workload and impacted clinical workflows; (2) integrating mental and physical health services altered patient and healthcare provider relationships; and (3) the introduction of integrated care practices disrupted healthcare team relations.

Originality/value

Study findings highlight the importance of considering existing logics in healthcare settings when planning integrated care initiatives. While integrated care pilot projects can contribute to organizational, team and individual practice changes, the priorities of healthcare stakeholders, relational work required and limited project resources can create significant implementation barriers.
Individual-focused transformational leadership and employee strengths use: the roles of positive affect and core self-evaluation
Authors: Ding He , Lin Xinqi
Published: August 2020

Purpose

Through the lens of affective events theory, this study sought to investigate the associations of individual-focused transformational leadership, namely individualized consideration and intellectual stimulation, with employee strengths use (ESU) and the mediating role of positive affect and the moderating role of core self-evaluation (CSE) in these associations.

Design/methodology/approach

The authors collected data by a three-wave research design. Hypotheses were examined with a sample of 178 employees working in various organizations in China.

Findings

The results revealed that both individualized consideration and intellectual stimulation have positive relationships with ESU and positive affect partially mediates these two relationships. Contrary to our hypotheses, CSE negatively moderated the relationship of intellectual stimulation with positive affect and the mediational effect of positive affect on the relationship between intellectual stimulation and ESU. However, CSE did not moderate the relationships between individualized consideration, positive affect and ESU.

Originality/value

This study was the first to empirically examine the relationships of individualized consideration and intellectual stimulation with ESU and the mediating effect of positive affect and the moderating effect of CSE on these relationships.
Blast Suppression Foam, Aqueous Gel Blocks, and their Effect on Subsequent Analysis of Forensic Evidence*
Authors: Monson Keith L. , Kyllonen Kelsey M. , Leggitt Jeffrey L. , Edmiston Kelli E. , Justus Calvin R. , Kavlick Mark F. , Phillip Maria , Roberts Maria A. , Shegogue Candie W. , Watts Gabriel D.
Published: August 2020

In addition to having blast mitigation properties, aqueous foam concentrate AFC‐380 blast suppression foam is designed to capture aerosolized chemical, biological, and radioactive particles during render‐safe procedures of explosive devices. Exposure to aqueous environments and surfactants may negatively affect forensic evidence found at the scene, but the effects of AFC‐380 foam and aqueous gel on the preservation and subsequent analysis of forensic evidence have not previously been investigated. Sebaceous finger and palm prints and DNA samples on paper, cardboard, tape, and various metal and plastic items, along with hairs, carpet and yarn fibers, and inks and documents, were exposed to AFC‐380 foam. Similar mock evidence was also exposed to a superabsorbent gel of the type found in aqueous gel blocks used for shrapnel containment. Exposure to foam or aqueous gel was associated with a dilution effect for recovered DNA samples, but quality of the samples was not substantially affected. In contrast, exposure to AFC‐380 foam or gel was detrimental to development of latent finger and palm prints on any substrate. Neither the hair nor the fiber samples were affected by exposure to either the foam or gel. Indented writing on the document samples was detrimentally affected by foam or gel exposure, but not inks and toners. The results from this study indicate that most types of forensic evidence recovered after being exposed to aqueous gel or blast suppression foam can be reliably analyzed, but latent finger and palm prints may be adversely affected.
miR‐138 and miR‐193 target long non‐coding RNA UCA1 to inhibit cell proliferation, migration, and invasion of lung cancer
Authors: Xun Guangsu , Ma Ming , Li Bing , Zhao Song
Published: August 2020

Background

Long non‐coding RNA‐urothelial carcinoma associated 1 (LncRNA‐UCA1) is a crucial oncogene that is deregulated in many types of cancers. However, the mechanism of UCA1 function, especially for its posttranscriptional regulation in lung cancer, remains unclear.

Methods

miRCode was used to predict potential miRNA candidates that might target UCA1. The targets of miR‐138 and miR‐193 on UCA1 and CDK6 were verified by luciferase reporter analysis. Western blotting was used to detect protein levels. The RNA level was evaluated using quantitative real‐time polymerase chain reaction (PCR). Proliferation, wound healing, and transwell invasion assays were performed to assess cell proliferation and invasion abilities. Correlations between miR‐138 or miR‐193 and UCA1 in lung cancer tissues was assessed using quantitative real‐time PCR.

Results

miR‐138 and miR‐193 specifically targeted and regulated lncRNA‐UCA1. MiR‐138 and miR‐193 both suppressed cell proliferation and cell cycle progression. Moreover, miR‐138 and miR‐193 inhibited cell migration and invasion. Overexpression of UCA1 reversed the proliferation, migration, and invasion suppression effects of miR‐138 or miR‐193. Furthermore, miR‐138/193 affected the expression of UCA1 downstream genes. UCA1 regulated the expression of CDK6 as a miR‐138 and miR‐193 common target. In human lung cancer tissues, our study showed a significant negative correlation between miR‐138 or miR‐193 and UCA1 in lung cancer tissues.

Conclusions

Our results demonstrated that miR‐138 and miR‐193 affect cell function by directly targeting and regulating UCA1 in lung cancer.
Chronic nicotine impairs sparse motor learning via striatal fast‐spiking parvalbumin interneurons
Authors: Kim Baeksun , Im Heh‐In
Published: August 2020

Nicotine can diversely affect neural activity and motor learning in animals. However, the impact of chronic nicotine on striatal activity in vivo and motor learning at long‐term sparse timescale remains unknown. Here, we demonstrate that chronic nicotine persistently suppresses the activity of striatal fast‐spiking parvalbumin interneurons, which mediate nicotine‐induced deficit in sparse motor learning. Six weeks of longitudinal in vivo single‐unit recording revealed that mice show reduced activity of fast‐spiking interneurons in the dorsal striatum during chronic nicotine exposure and withdrawal. The reduced firing of fast‐spiking interneurons was accompanied by spike broadening, diminished striatal delta oscillation power, and reduced sample entropy in local field potential. In addition, chronic nicotine withdrawal impaired motor learning with a weekly sparse training regimen but did not affect general locomotion and anxiety‐like behavior. Lastly, the excitatory DREADD hM3Dq‐mediated activation of striatal fast‐spiking parvalbumin interneurons reversed the chronic nicotine withdrawal‐induced deficit in sparse motor learning. Taken together, we identified that chronic nicotine withdrawal impairs sparse motor learning via disruption of activity in striatal fast‐spiking parvalbumin interneurons. These findings suggest that sparse motor learning paradigm can reveal the subtle effect of nicotine withdrawal on motor function and that striatal fast‐spiking parvalbumin interneurons are a neural substrate of nicotine's effect on motor learning.
Mechanisms of spindle assembly and size control
Authors: Guilloux Gabriel , Gibeaux Romain
Published: August 2020

The spindle is crucial for cell division by allowing the faithful segregation of replicated chromosomes to daughter cells. Proper segregation is ensured only if microtubules (MTs) and hundreds of other associated factors interact to assemble this complex structure with the appropriate architecture and size. In this review, we describe the latest view of spindle organisation as well as the molecular gradients and mechanisms underlying MT nucleation and spindle assembly. We then discuss the overlapping physical and molecular constraints that dictate spindle morphology, concluding with a focus on spindle size regulation.
Evaluation of the role of thyroid scintigraphy in the differential diagnosis of thyrotoxicosis
Authors: Perdomo Carolina M. , García‐Goñi Marta , Sancho Lidia , J. Paricio José , Lozano María D. , de la Higuera Magdalena , Currás María , Arbizu Javier , Galofré Juan C.
Published: August 2020

Objective

A differential diagnosis of thyrotoxicosis is crucial as the treatment of the main causes of this condition can vary significantly. Recently published diagnostic guidelines on thyrotoxicosis embrace the presence of thyrotropin receptor (TSH‐R) antibodies (TRAb) as the primary and most important diagnostic step. The application of diagnostic algorithms to aid in the treatment of hyperthyroidism supports using thyroid radionuclide scintigraphy (TRSt) in baffling clinical scenarios, when TRAb are absent or when third‐generation TRAb are not available. First‐generation TRAb measurement may have limitations. Consequently, patients with thyrotoxicosis and first‐generation TRAb results may be misdiagnosed and consequently improperly treated. Our purpose was to compare first‐generation TRAb values to TRSt in the differential diagnosis of hyperthyroidism.

Methods

We conducted a retrospective study of 201 untreated outpatients with overt or subclinical hyperthyroidism on whom first‐generation TRAb and TRSt had been performed at the time of diagnosis. Histological specimens were analysed in patients who had previously undergone thyroid surgery at our centre. SPSS 20.0 was used in statistical analysis.

Results

Seventy‐three out of 201 (36.3%) patients had positive TRAb. A diffuse uptake was present in 83.5% (61/73), whereas 13.7% (10/73) had a heterogeneous uptake and 2.7% (2/73) had an absent uptake. Thirty out of 91 (33%) patients with diffuse uptake were negative for positive TRAb and were diagnosed with Graves’ disease. Analysis of 37 histological specimens indicated that TRSt had greater accuracy (81% vs 75.7%) and specificity (79.2% vs 57.1%) when compared to TRAb in the differential diagnosis of thyrotoxicosis. However, TRSt sensitivity was inferior to TRAb (84.6% vs 92.3%).

Conclusions

Our study endorses that initial differential diagnosis of thyrotoxicosis should not be based solely on first‐generation TRAb as this approach may leave nearly 20% of the patients misdiagnosed and, consequently, improperly treated. Our results underscore that thyroid scintigraphy should also be performed when only first‐generation TRAb assays are available during the initial differential diagnosis of thyrotoxicosis.