bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term Results of Combined Trabeculotomy-Trabeculectomy in Primary Congenital Glaucoma from a Tertiary Eye Care Center in Tunisia
Authors: Malek Ines , Sayadi Jihene , Choura Racem , Mekni Manel , Rayhane Haythem , Khairallah Moncef , Nacef Leila
Published: August 2022

Objective

To report the long-term visual and surgical outcomes of combined trabeculotomy–trabeculectomy (CTT) as the initial glaucoma surgery in children with primary congenital glaucoma (PCG).

Methods

Prospective analysis of children who underwent primary CTT for PCG between January 2010 and December 2019. The main outcome measures were intraocular pressure (IOP) reduction, corneal clarity, success rate, complications, refractive errors and visual acuities (VA).

Results

A total of 98 eyes of 62 patients were enrolled. At last follow-up, mean IOP reduced from 22.68±3.99 mmHg to 9.75±3.88 mmHg (P<0.0001). Complete success rate was 91.6%, 88.4%, 84.7%, 71.6%, 59.7%, and 54.3%, respectively at first, second, fourth, sixth, eighth, and tenth year. Follow-up averaged 42.06±28.36 months. Preoperatively, 72 eyes (73.5%) had significant corneal haze, 84.7% among them achieved normal corneal transparency. Among the sight-threatening complications, endophthalmitis was encountered in one eye. Myopia was the most common refractive error (80.6%). Data on Snellen VA were available for 53.2% of the patients. 33.3% of patients achieved normal VA (VA ≥ 6/12), 21.2% had mild visual impairment (VI), 9.1% had moderate VI, 21.2% had severe VI, and 15.2% were blind. The failure rate was statistically correlated to the early disease onset (<3 months) and to preoperative corneal clouding (p=0.022 and p=0.037, respectively). Two critical time points were identified: within the first year and around the sixth year (28.6 and 25% of surgical failures, respectively).

Conclusion

Primary CTT seems to be an optimal procedure in a population with advanced disease at presentation, problematic follow-ups, and limited resources.

Summary box

What is already known on this topic

Primary congenital glaucoma (PCG) is the most common type of childhood glaucoma. Surgery is the main therapeutic option with the goal of permanently controlling IOP and preserving visual function. Several surgical procedures are available. Each approach has its potential benefits and risks. The optimum first-line surgery is debated.

What this study adds?

PCG in Tunisian children seems to be characterized by a high prevalence of inherited and advanced form of the disease.

Challenges in the management of PCG in Tunisia include remoteness of care facilities and poor compliance to follow-up.

Primary combined trabeculotomy-trabeculectomy allowed in the current study satisfactory long-term IOP control and reasonable visual outcome. The overall incidence of serious complications was low.

How this study might affect research, practice or policy

CTT may be the optimal primary surgical procedure for the management of PCG in Tunisia and all other developing countries. Future research with a larger sample size and preferably randomized clinical trials that focus exclusively on the severe presentation of the disease are required.
Direct utility of natural history data in analysis of clinical trials: Propensity match-based analysis of Omaveloxolone in Friedreich ataxia using the FA-COMS dataset
Authors: Lynch David R , Goldsberry Angie , Rummey Christian , Farmer Jennifer , Boesch Sylvia , Delatycki Martin B. , Giunti Paola , Hoyle J. Chad , Mariotti Caterina , Mathews Katherine D. , Nachbauer Wolfgang , Perlman Susan , Subramony S.H. , Wilmot George , Zesiewicz Theresa , Weissfeld Lisa , Meyer Colin
Published: August 2022

Rationale

The natural history of Friedreich Ataxia (FRDA) is being investigated in a multi-center longitudinal study designated the Friedreich Ataxia Clinical Outcome Measures Study (FA-COMS). To understand the utility of this natural history dataset in analysis of clinical trials, we performed a propensity-matched comparison of the data from the open-label MOXIe Extension (omaveloxolone) with that from FA-COMS.

Methods

All MOXIe Extension patients who had at least one post-baseline assessment were matched to FA-COMS patients using logistic regression to estimate propensity scores based on multiple covariates: sex, baseline age, age of onset, baseline modified Friedreich Ataxia Rating scale (mFARS) score, and baseline gait score. Selection of covariates was based on clinical relevance (i.e., factors considered prognostic for disease progression) and availability. The change from baseline in mFARS at Year 3 for the MOXIe Extension patients compared to the matched FA-COMS patients was analyzed as the primary efficacy endpoint using mixed model repeated measures analysis.

Results

Data from the MOXIe Extension show that omaveloxolone provides persistent benefit over three years when compared to an untreated, rigorously matched cohort from FA-COMS. At each year, and in all analysis populations, patients in the MOXIe Extension experienced a smaller change from baseline in mFARS score than the matched FA-COMS patients. In the Primary Pooled Population (136 patients in each group) by Year 3, patients in the FA-COMS matched set progressed 6.6 points whereas patients treated with omaveloxolone in MOXIe Extension progressed 3 points (difference =-3.6; nominal p value =0.0001). Thus, progression in mFARS was slowed by 55% with omaveloxolone treatment.

Conclusions

These results suggest a clinically meaningful slowing of FRDA progression with omaveloxolone, and consequently details how propensity-matched analysis contributes to the understanding of the effects of therapeutic agents. This demonstrates the direct value of natural history studies in the evaluation of clinical trials.
Scalable variational inference for low-rank spatio-temporal receptive fields
Authors: Duncker Lea , Ruda Kiersten M. , Field Greg D. , Pillow Jonathan W.
Published: August 2022

An important problem in systems neuroscience is to characterize how a neuron integrates sensory inputs across space and time. The linear receptive field provides a mathematical characterization of this weighting function, and is commonly used to quantify neural response properties and classify cell types. However, estimating receptive fields is difficult in settings with limited data and correlated or high-dimensional stimuli. To overcome these difficulties, we propose a hierarchical model designed to flexibly parameterize low-rank receptive fields. The model includes Gaussian process priors over spatial and temporal components of the receptive field, encouraging smoothness in space and time. We also propose a new temporal prior called temporal relevance determination (TRD), which imposes a variable degree of smoothness as a function of time lag. We derive a scalable algorithm for variational Bayesian inference for both spatial and temporal receptive field components and hyperparameters. The resulting estimator scales to high-dimensional settings in which full-rank maximum likelihood or a posteriori estimates are intractable. We evaluate our approach on neural data from rat retina and primate cortex, and show that it substantially out-performs a variety of existing estimators. Our modeling approach will have useful extensions to a variety of other high-dimensional inference problems with smooth or low-rank structure.
Context-independent scaling of neural responses to task difficulty in the multiple-demand network
Authors: Wen Tanya , Egner Tobias
Published: August 2022

The multiple-demand (MD) network is sensitive to many aspects of cognitive demand, showing increased activation with more difficult tasks. However, it is currently unknown whether the MD network is modulated by the context in which task difficulty is experienced. Using fMRI, we examined MD network responses to low, medium, and high difficulty arithmetic problems within two cued contexts, an easy versus a hard set. The results showed that MD activity varied reliably with the absolute difficulty of a problem, independent of the context in which the problem was presented. Similarly, MD activity during task execution was independent of the difficulty of the previous trial. Representational similarity analysis further supported that representational distances in the MD network were consistent with a context-independent code. Finally, we identified several regions outside the MD network that showed context-dependent coding, including the inferior parietal lobule, paracentral lobule, posterior insula, and large areas of the visual cortex. In sum, cognitive effort is processed by the MD network in a context-independent manner. We suggest that this absolute coding of cognitive demand in the MD network reflects the limited range of task difficulty that can be supported by the cognitive apparatus.
Multiplex PCR Assay for Clade-typing Salmonella Enteritidis
Authors: Gallichan Sarah , Perez-Sepulveda Blanca M. , Feasey Nicholas A. , Hinton Jay C. D. , Thomas Juno , Smith Anthony Marius
Published: August 2022

2.

Salmonella Enteritidis is one of the most commonly reported serovars of non-typhoidal Salmonella causing human disease and is responsible for both gastroenteritis and invasive non-typhoidal Salmonella (iNTS) disease worldwide. Whole-genome sequence (WGS) comparison of Salmonella Enteritidis isolates from across the world have identified three distinct clades, named Global Epidemic, Central/East African and West African, all of which have been implicated in epidemics: the Global Epidemic clade was linked to poultry-associated gastroenteritis, while the two African clades were related to iNTS disease. However, the distribution and epidemiology of these clades across Africa is poorly understood because identification of these clades currently requires whole genome sequencing capacity. Here, we report a sensitive, time- and cost-effective real-time PCR assay capable of differentiating between the Salmonella Enteritidis clades to facilitate surveillance and to inform public health responses.

3.

Impact statement

Challenges in the diagnosis and treatment of invasive Salmonella Enteritidis (S. Enteritidis) bloodstream infections in sub–Saharan Africa are responsible for a case fatality rate of approximately 15% (12). It is important to identify distinct clades of S. Enteritidis in diagnostic laboratories in the African setting to determine whether particular outbreaks are associated with different health outcomes. Here, we have described the development of a high-quality molecular classification assay for the clade-typing of S. Enteritidis that is ideal for use in public health laboratories in resource-limited settings.
Self-testing for proteinuria in pregnancy: a systematic review and meta-analysis
Authors: Yeh Ping Teresa , Rhee Dong Keun , Kennedy Caitlin Elizabeth , Zera Chloe A. , Tunçalp Özge , Lucido Briana , Narasimhan Manjulaa
Published: August 2022

Background

Self-testing for proteinuria may help identify preeclampsia risk during pregnancy, increase end-user empowerment, and reduce burden on health systems. We conducted this systematic review of the impact of proteinuria self-testing during pregnancy to expand the evidence base for the World Health Organization consolidated guideline on self-care interventions.

Methods

We comprehensively searched for articles comparing the effect of proteinuria self-testing with clinic-based testing among pregnant individuals receiving antenatal care on the following outcomes: maternal mortality or near-miss; adverse pregnancy outcomes; eclampsia or pre-eclampsia; long-term diseases; follow-up care and appropriate management; self-efficacy, self-determination, autonomy, and empowerment; mental health and well-being; adverse events and social harms; device-related issues; intra-uterine growth restriction; preterm birth; and stillbirth or perinatal death. After abstract screening and full-text review, we systematically extracted data using standardized forms and summarized the relative risks of outcomes between self-testing and clinic-based testing for proteinuria. We also assessed values and preferences and costs of self-testing.

Results

Three publications were identified for the effectiveness review; two for values/preferences, and none for the cost review, mostly from high-income countries. Overall, there was no statistically significant difference between self-testing and inpatient care for proteinuria among women with hypertension for any of the outcomes with data available. In general, both women and providers were supportive of proteinuria self-testing because it allows a greater role in self-care and fewer clinic visits, though some emphasized the need to train end-users for proper testing and appropriate follow-up actions.

Conclusions

Very limited evidence suggests that self-testing for proteinuria results in comparable maternal and fetal outcomes as provider-testing for hypertensive pregnant individuals, and is generally acceptable to end-users and providers despite some concerns. No evidence of effectiveness was available for the general pregnant population. This evidence base supports its feasibility as an additional option for identifying individuals at risk of preeclampsia.

Systematic review registration number

PROSPERO CRD42021233845
Methylation of the glucocorticoid receptor gene (NR3C1) in dyads mother-child exposed to intimate partner violence in Cameroon: Association with anxiety symptoms
Authors: Wadji Dany Laure , Morina Naser , Martin-Soelch Chantal , Wicky Chantal
Published: August 2022

Background

The glucocorticoid receptor (GR), which is encoded by theNR3C1(Nuclear Receptor Subfamily 3 Group C Member 1) gene plays an important role in the modulation of the hypothalamic-pituitary-adrenal (HPA) axis activity by providing feedback regulation which allows termination of the stress response. Little is known about epigenetic programming at the level of NGFI-A putative binding site (CpG) of theNR3C1exon 1F in dyads mother-child exposed to intimate partner violence (IPV) more specifically in an unstudied region such as the Sub-Saharan Africa where levels of violence are very high.

Objective

ExamineNR3C1exon 1F methylation in response to IPV and possible association with cortisol concentration and mental health.

Method

We recruited 20 mother–child dyads exposed to IPV and a control group of 20 mother–child dyads not exposed to IPV. We administered self-reported questionnaires to measure mother’s mental health and collected saliva samples for cortisol dosage and bisulfite sequencing of DNA methylation.

Results

Regarding the mothers, our results showed a significant difference in methylation level at CpG 16-21 sites of theNR3C1exon 1F promoter region between the groups. In the exposed group as compared to the control group, there was a significant positive association between the level of methylation at CpG 16-21 sites and mother’s mental health in particular anxiety symptoms. However, we did not find any significant correlation between methylation level and cortisol concentration. In children, we did not find any significant result.

Conclusion

This study highlights a NGFI-A putative binding site (CpG 16-21) that is more methylated in mothers exposed to IPV and which may have the potential to confer vulnerability for psychopathologies.
Effect of Acute Cardiovascular Exercise on Cerebral Blood Flow: A Systematic Review
Authors: Mulser Lisa , Moreau David
Published: August 2022

A single bout of cardiovascular exercise can have a cascade of physiological effects, including increased blood flow to the brain. This effect has been documented across multiple modalities, yet studies have reported mixed findings. Here, we systematically review evidence for the acute effect of cardiovascular exercise on cerebral blood flow across a range of neuroimaging techniques and exercise characteristics. Based on 52 studies and a combined sample size of 1,174 individuals, our results indicate that the acute effect of cardiovascular exercise on cerebral blood flow generally follows an inverted U-shaped relationship, whereby blood flow increases early on but eventually decreases as exercise continues. However, we also find that this effect is not uniform across studies, instead varying across a number of key variables including exercise characteristics, brain regions, and neuroimaging modalities. As the most comprehensive synthesis on the topic to date, this systematic review sheds light on the determinants of exercise-induced change in cerebral blood flow, a necessary step toward personalized interventions targeting brain health across a range of populations.
A pan-cancer analysis of the oncogenic role of COVID-19 risk gene Leucine Zipper Transcription Factor-Like Protein 1 (LZTFL1) in human tumors
Authors: Mo Jihao , Zhang Zhenzhen , Wang Daping , Su Mingqin , Hu Jian , Liu Yakun , Wang Lei , Wang Meimei
Published: August 2022

Population-based studies showed that COVID-19 infection causes higher death rate in cancer patients. However, the molecular mechanism of COVID-19 with cancer is still largely unknown. Here we analyzed the Leucine Zipper Transcription Factor-Like Protein 1 (LZTFL1) which is the most significant gene associated with COVID-19. First, we explored the potential oncogenic roles of LZTFL1 through transcriptome data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. LZTFL1 is significantly low expressed in 11 of 34 kinds of cancers we analyzed. Consistent with the mRNA expression data, the protein expression of LZTFL1 in lung adenocarcinoma (LUAD), clear cell renal cell carcinoma (ccRCC), Uterine corpus endometrial carcinoma (UCEC), and ovarian cancer (OV) patients are significantly decreased compared to healthy tissues. The survival analysis from the Kidney renal clear cell carcinoma (KIRC), Rectum adenocarcinoma (READ), and Uveal Melanoma (UVM), the LZTFL1 high expression group have a significantly higher survival rate compared to the low expression group. Taken together, LZTFL1 acts as a cancer suppressor gene for several cancers. Moreover, LZTFL1 expression was associated with the cancer-associated fibroblast infiltration in several tumors including Bladder Urothelial Carcinoma (BLCA), Breast invasive carcinoma (BRCA), Esophageal carcinoma (ESCA), Head and Neck squamous cell carcinoma (HNSC), Lung squamous cell carcinoma (LUSC), and Pancreatic adenocarcinoma (PAAD). Gene ontology analysis showed that cilium organization, positive regulation of establishment of protein localization to telomere and SRP-dependent cotranslational protein targeting to the membrane were involved in the function mechanisms related to LZTFL1. Our studies offer a relatively comprehensive understanding of the oncogenic roles of LZTFL1 across different kinds of tumors.
Syncope and subsequent traffic crash: A responsibility analysis
Authors: Staples John A , Erdelyi Shannon , Merchant Ketki , Yip Candace , Khan Mayesha , Redelmeier Donald A , Chan Herbert , Brubacher Jeffrey R
Published: August 2022

Background

Physicians are often asked to counsel patients about driving safety after syncope, yet little empirical data guides such advice.

Methods

We identified a population-based retrospective cohort of 9,507 individuals with a driver license who were discharged from any of six urban emergency departments (EDs) with a diagnosis of ‘syncope and collapse’. We examined all police-reported crashes that involved a cohort member as a driver and occurred between 1 January 2010 and 31 December 2016. We categorized crash-involved drivers as ‘responsible’ or ‘non-responsible’ for their crash using detailed police-reported crash data and a validated responsibility scoring tool. We then used logistic regression to test the hypothesis that recent syncope was associated with driver responsibility for crash.

Results

Over the 7-year study interval, cohort members were involved in 475 police-reported crashes: 210 drivers were deemed responsible and 133 drivers were deemed non-responsible for their crash; the 132 drivers deemed to have indeterminate responsibility were excluded from further analysis. An ED visit for syncope occurred in the three months leading up to crash in 11 crash-responsible drivers and in 5 crash-non-responsible drivers, suggesting that recent syncope was not associated with driver responsibility for crash (adjusted odds ratio, 1.31; 95%CI, 0.40-4.74; p=0.67). However, all drivers with cardiac syncope were deemed responsible, precluding calculation of an odds ratio for this important subgroup.

Conclusions

Recent syncope was not significantly associated with driver responsibility for traffic crash. Clinicians and policymakers should consider these results when making fitness-to-drive recommendations after syncope.

Key Messages

What is already known on this topic: Clinicians are often asked to counsel patients about driving safety after syncope, yet little empirical data guides such advice.

What this study adds: In contrast to prior studies, we found no significant association between an emergency department visit for syncope and driver responsibility for a subsequent motor vehicle crash.

How this study might affect research, practice or policy: These findings might reassure clinicians, patients and policymakers that current driving restrictions after first-episode syncope adequately mitigate the risk of subsequent crash.
Principles of metabolome conservation in animals
Authors: Liska Orsolya , Boross Gábor , Rocabert Charles , Szappanos Balázs , Tengölics Roland , Papp Balázs
Published: August 2022

Metabolite concentrations shape cellular physiology and disease susceptibility, yet the general principles governing metabolome evolution are largely unknown. Here we introduce a measure of conservation of individual metabolite concentrations among related species. By analysing multispecies metabolome datasets in mammals and fruit flies, we show that conservation varies extensively across metabolites. Three major functional properties, metabolite abundance, essentiality and association with human diseases predict conservation, highlighting a striking parallel between the evolutionary forces driving metabolome and protein sequence conservation. Metabolic network simulations recapitulated these general patterns, and revealed that abundant metabolites are highly conserved due to their strong coupling to key metabolic fluxes in the network. This study uncovers simple rules governing metabolic evolution in animals and implies that most metabolome differences between species are permitted, rather than favored by selection. More broadly, our work paves the way towards using evolutionary information to discover biomarkers, as well as to detect pathogenic metabolome alterations in individual patients.
A cell-autonomous role for primary cilia in long-range commissural axon guidance
Authors: Dumoulin Alexandre , Wilson Nicole H. , Tucker Kerry L. , Stoeckli Esther T.
Published: August 2022

Ciliopathies are characterized by the absence or dysfunction of primary cilia. Despite the fact that cognitive impairments are a common feature of ciliopathies, how cilia dysfunction affects neuronal development has not been characterized in detail. Here, we show that the primary cilium is required cell-autonomously by neurons during neural circuit formation. In particular, the primary cilium is crucial during axonal pathfinding for the switch in responsiveness of axons at a choice point, or intermediate target. Utilizing animal models and in vivo, ex vivo, as well as in vitro experiments, we provide evidence for a critical role of the primary cilium in long-range axon guidance. The primary cilium on the cell body of commissural neurons transduces long-range guidance signals sensed by growth cones navigating an intermediate target. In extension of our finding that Shh is required for the rostral turn of post-crossing commissural axons, we show here that the cilium is required for a transcriptional change of axon guidance receptors, which in turn mediate the repulsive response to floorplate-derived Shh shown by post-crossing commissural axons.
Bioinformatics analysis in identifying significantly expressed immune related genes in influenza A virus infection
Authors: Olaniyi Ayinde , Oluwabunmi Alabi , Oluwatobi Oguntoye
Published: August 2022

This study is done to identify significantly expressed genes of influenza A virus infection in human, facilitated by the idea of checking for the presence of immune related genes in these significantly expressed genes, followed by the analysis of their potential mechanism and pathway. Considering the usage of microarray dataset, the gene expression profile GSE66597 was downloaded from the gene expression omnibus(GEO) database, and then a subsequent generation of differentially expressed genes(DEGs) using the GEO2R tool. A total of 1107 genes was generated with 703 upregulated and 404 downregulated genes. The protein-protein interaction (PPI) network was constructed using string and Cytoscape software which resulted in generating the core genes, hub genes, and bottleneck genes. Subsequent Venn diagram analysis finally gave the six candidate genes CRP, CCL5, IL17A, STAT1, CD34, SPI1, subjected to gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) for enrichment and pathway analysis respectively. Out of the initial six candidate genes, four of these genes CRP, CCL5, IL17A, are immune related, and initiated particularly by the presence of influenza A virus.
The High-quality genome assembly of Lactarius hatsudake
Authors: Shen Airong , Luo Chen , Zeng Liangbin , Li Jilie
Published: August 2022

Lactarius hatsudake is a species of Lactarius commonly found in pine forests, is edible with a delicious and nutritious fruiting body and exhibits medicinal properties. It is an ideal natural multi-functional food with bioactive components including fungal polysaccharides, crude fiber, unsaturated fatty acids, nucleic acid derivatives, various amino acids, and vitamins. However, biological and genomic analyses of this mycorrhizal mushroom is sparse, thereby hindering large-scale cultivation. Previously, we isolated and screened L. hatsudake JH5 strains and have been applied our garnered knowledge to the large-scale cultivation of mycorrhizal seedlings. In this study we produced a high-quality genome assembly of L. hatsudake JH5 by combining Illumina paired-end (PE) and PacBio single molecule real-time (SMRT) sequencing which resulted in PacBio SMRT reads of 7.67Gb and Illumina Pair-End (PE) reads of 1560Mb. Based on the distribution of k-mer frequencies, the genome size of this strain was estimated to be 63.84Mb (1.14% heterozygosity). Based on de novo genome assembly, a final genome size was determined to be 73.16 Mb, with scaffold N50 of 223.2 kb and N90 of 54.5 kb, and a GC content of 54.38%. BUSCO assessment showed that genome completeness was 89.0%. The N50 length of the JH5 genome was 43.62% longer than that of the previously published L. hatsudake MG20 genome. This high-quality L. hatsudake genome assembly will facilitate research on the functional genome, molecular breeding, yield enhancement and sustainability of L. hatsudake cultivation.
Hepatic MCPIP1 protein levels are reduced in NAFLD patients and are predominantly expressed in cholangiocytes and liver endothelium
Authors: Pydyn Natalia , Kadluczka Justyna , Major Piotr , Hutsch Tomasz , Wołoszyn Kinga , Malczak Piotr , Radkowiak Dorota , Budzynski Andrzej , Miekus Katarzyna , Jura Jolanta , Kotlinowski Jerzy
Published: August 2022

Nonalcoholic fatty liver disease (NAFLD) is characterized by the excessive accumulation of fat in hepatocytes. NAFLD can range from simple steatosis to the aggressive form called nonalcoholic steatohepatitis (NASH), which is characterized by both fatty liver and liver inflammation. Without proper treatment, NAFLD may further progress to lifethreatening complications, such as fibrosis, cirrhosis or liver failure. Monocyte chemoattractant protein-induced protein 1 (MCPIP1, alias Regnase 1) is a negative regulator of inflammation, acting through the cleavage of transcripts coding for proinflammatory cytokines and the inhibition of NFκB activity.

In this study, we investigated MCPIP1 expression in the liver and peripheral blood mononuclear cells (PBMCs) collected from a cohort of 36 control and NAFLD patients hospitalized due to bariatric surgery or primary inguinal hernia laparoscopic repair. Based on liver histology data (H&E and Oil Red O staining), 12 patients were classified into the nonalcoholic fatty liver (NAFL) group, 19 into the NASH group and 5 into the control (non-NAFLD) group. Biochemical characterization of patient plasma was followed by expression analysis of genes regulating inflammation and lipid metabolism. The MCPIP1 protein level was reduced in the livers of NAFL and NASH patients in comparison to non-NAFLD control individuals. Additionally, in all groups of patients, immunohistochemical staining showed that the expression of MCPIP1 was higher in the portal fields and bile ducts in comparison to the liver parenchyma and central vein. The liver MCPIP1 protein level negatively correlated with hepatic steatosis but not with patient BMI or any other analyte. The MCPIP1 level in PBMCs did not differ between NAFLD patients and control patients. Similarly, in patients’ PBMCs there were no differences in the expression of genes regulating β-oxidation (ACOX1, CPT1A, and ACC1) and inflammation (TNF, IL1B, IL6, IL8, IL10, and CCL2), or transcription factors controlling metabolism (FAS, LCN2, CEBPB, SREBP1, PPARA, and PPARG).

We have demonstrated that MCPIP1 protein levels are reduced in NAFLD patients, but further research is needed to investigate the specific role of MCPIP1 in NAFL initiation and the transition to NASH.
DeepGAMI: Deep biologically guided auxiliary learning for multimodal integration and imputation to improve phenotype prediction
Authors: Chandrashekar Pramod Bharadwaj , Wang Jiebiao , Hoffman Gabriel E. , He Chenfeng , Jin Ting , Alatkar Sayali , Khullar Saniya , Bendl Jaroslav , Fullard John F. , Roussos Panagiotis , Wang Daifeng
Published: August 2022

Genotype-phenotype association is found in many biological systems, such as brain-related diseases and behavioral traits. Despite the recent improvement in the prediction of phenotypes from genotypes, they can be further improved and explainability of these predictions remains challenging, primarily due to complex underlying molecular and cellular mechanisms. Emerging multimodal data enables studying such mechanisms at different scales from genotype to phenotypes involving intermediate phenotypes like gene expression. However, due to the black-box nature of many machine learning techniques, it is challenging to integrate these multi-modalities and interpret the biological insights in prediction, especially when some modality is missing. Biological knowledge has recently been incorporated into machine learning modeling to help understand the reasoning behind the choices made by these models.

To this end, we developed DeepGAMI, an interpretable deep learning model to improve genotype-phenotype prediction from multimodal data. DeepGAMI uses prior biological knowledge to define the neural network architecture. Notably, it embeds an auxiliary-learning layer for cross-modal imputation while training the model from multimodal data. Using this pre-trained layer, we can impute latent features of additional modalities and thus enable predicting phenotypes from a single modality only. Finally, the model uses integrated gradient to prioritize multimodal features and links for phenotypes. We applied DeepGAMI to multiple emerging multimodal datasets: (1) population-level genotype and bulk-tissue gene expression data for predicting schizophrenia, (2) population-level genotype and gene expression data for predicting clinical phenotypes in Alzheimer’s Disease, (3) gene expression and electrophysiological data of single neuronal cells in the mouse visual cortex, and (4) cell-type gene expression and genotype data for predicting schizophrenia. We found that DeepGAMI outperforms existing state-of-the-art methods and provides a profound understanding of gene regulatory mechanisms from genotype to phenotype, especially at cellular resolution. DeepGAMI is an open-source tool and is available at https://github.com/daifengwanglab/DeepGAMI.
In-vivo Measurement of Radio Frequency Electric Fields in Mice Brain
Authors: Yaghmazadeh Omid , Schoenhardt Seth , Sarabandi Arya , Sabet Ali , Sabet Kazem , Safari Fatemeh , Alon Leeor , Buzsáki György
Published: August 2022

With development of novel technologies, radio frequency (RF) energy exposure is expanding at various wavelengths and power levels. These developments necessitate updated approaches of RF measurements in complex environments, particularly in live biological tissue. In this study, we introduce a technique for direct in-vivo measurement of electric fields in living tissue. Proof of principle in-vivo electric field measurements were conducted in rodent brains using Bismuth Silicon Oxide (BSO) crystals exposed to varying levels of RF energy. Electric field measurements were calibrated and verified using in-vivo temperature measurements using optical temperature fibers alongside electromagnetic field simulations of a transverse electromagnetic (TEM) cell.

SIGNIFICANCE

Accurate dosimetry of the absorbed radio frequency (RF) electric fields (E-Fields) by the live tissue is the keystone of environmental health considerations for this type of ever-growing non-ionizing radiation energy. The complexity of biological tissue and technical difficulties have made direct measurement of E-fields in live tissue challenging leading to application of ex-vivo and in-silico approaches. Here, we present a novel method for in-vivo direct measurement of RF E-fields in anesthetized mice brain using electro-optic sensors.
Changes in active-site geometry on X-ray photoreduction of a lytic polysaccharide monooxygenase active-site copper and saccharide binding
Authors: Tandrup Tobias , Muderspach Sebastian J. , Banerjee Sanchari , Santoni Gianluca , Ipsen Johan Ø. , Hernández-Rollán Cristina , Nørholm Morten H. H. , Johansen Katja S. , Meilleur Flora , Lo Leggio Leila
Published: August 2022

The recently discovered lytic polysaccharide monooxygenases (LPMOs) are Cu-containing enzymes capable of degrading polysaccharide substrates oxidatively. The generally accepted first step in the LPMO reaction is the reduction of the active-site metal ion from Cu2+ to Cu+. Here we have used a systematic diffraction data collection method to monitor structural changes in two AA9 LPMOs, one from Lentinus similis (LsAA9_A) and one from Thermoascus aurantiacus (TaAA9_A), as the active-site Cu is photoreduced in the X-ray beam. For LsAA9_A, the protein produced in two different recombinant systems was crystallized to probe the effect of post-translational modifications and different crystallization conditions on the active site and metal photoreduction. We can recommend that crystallographic studies of AA9 LPMOs wishing to address the Cu2+ form use a total X-ray dose below 3 × 104 Gy, while the Cu+ form can be attained using 1 × 106 Gy. In all cases, we observe the transition from a hexacoordinated Cu site with two solvent-facing ligands to a T-shaped geometry with no exogenous ligands, and a clear increase of the θ2 parameter and a decrease of the θ3 parameter by averages of 9.2° and 8.4°, respectively, but also a slight increase in θT. Thus, the θ2 and θ3 parameters are helpful diagnostics for the oxidation state of the metal in a His-brace protein. On binding of cello-oligosaccharides to LsAA9_A, regardless of the production source, the θT parameter increases, making the Cu site less planar, while the active-site Tyr—Cu distance decreases reproducibly for the Cu2+ form. Thus, the θT increase found on copper reduction may bring LsAA9_A closer to an oligosaccharide-bound state and contribute to the observed higher affinity of reduced LsAA9_A for cellulosic substrates.
The temperature-dependent conformational ensemble of SARS-CoV-2 main protease (Mpro)
Authors: Ebrahim Ali , Riley Blake T. , Kumaran Desigan , Andi Babak , Fuchs Martin R. , McSweeney Sean , Keedy Daniel A.
Published: August 2022

The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or Mpro, is a promising target for the development of novel antiviral therapeutics. Previous X-ray crystal structures of Mpro were obtained at cryogenic temperature or room temperature only. Here we report a series of high-resolution crystal structures of unliganded Mpro across multiple temperatures from cryogenic to physiological, and another at high humidity. We interrogate these data sets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a perturbation-dependent conformational landscape for Mpro, including a mobile zinc ion interleaved between the catalytic dyad, mercurial conformational heterogeneity at various sites including a key substrate-binding loop, and a far-reaching intramolecular network bridging the active site and dimer interface. Our results may inspire new strategies for antiviral drug development to aid preparation for future coronavirus pandemics.
Impact of critical pedagogy on professional learning for post-16 education
Authors: Conn Carmel , Mahoney Neil , Multani Yasmeen , Rees Jodie
Published: August 2022

Purpose

Professional learning has been highlighted as critical to improvement in educational practice for Autistic learners. Empirical evidence about what is effective for professional learning in education suggests it is a “bottom-up” process of intellectual, practical and emotional engagement and application of new knowledge to specific contexts. The purpose of this study was to gather information about postgraduate professional learning that sought to combine lived experience with reflection on practice in a critical pedagogy approach for practitioners working with Autistic learners in post-16 education.

Design/methodology/approach

Participants in the study represented all further education (FE) colleges in Wales and included experienced teachers and leaders, most of whom have a role focused on inclusion and learning support within their setting. Two phases of data collection were carried out, namely, a baseline survey (n = 36) and follow-up interviews (n = 15) at the end of the year of study. Interviews explored personal experiences of learning, knowledge and beliefs about practice and change in this respect and professionals’ priorities for the development of practice.

Findings

Findings present information gathered from the interviews and indicate that the course did not provide practitioners with new knowledge about autism but supported the development of more nuanced understandings of autism and more professional confidence about practice. However, familiarisation with lived experience and critical reflection on practice were described as supporting the questioning of basic assumptions and greater appreciation of the nature of difference for Autistic learners.

Originality/value

Study findings reframe what should be considered the focus of support practices for Autistic learners in FE.
Corporate social responsibility and public diplomacy as formulas to reduce hate speech on social media in the fake news era
Authors: Doncel-Martín Israel , Catalan-Matamoros Daniel , Elías Carlos
Published: August 2022

Purpose

Analyse the presence of hate speech in society, placing special emphasis on social media. In this sense, the authors strive to build a formula to moderate this type of content, in which platforms and public institutions cooperate, from the fields of corporate social responsibility and public diplomacy, respectively.

Design/methodology/approach

To this aim, it is important to focus efforts on the creation of counter-narratives; the establishment of content moderation guidelines, which are not necessarily imposed by unilateral legislation; the promotion of suitable scenarios for the involvement of civil society; transparency on the part of social media companies; and supranational cooperation that is as transnational as possible. To exemplify the implementation of initiatives against hate speech, two cases are analysed that are paradigmatic for assuming two effective approaches to the formula indicated by the authors.

Findings

The authors analyse, in the case of the European Union, its “Code of conduct to counteract illegal online hate speech”, which included the involvement of different social media companies. And in the case of Canada, the authors discuss the implementation of the bill to include a definition of hate speech and the establishment of specific sanctions for this in the Canadian Human Rights Act and the Canadian Penal Code.

Originality/value

The case of the European Union was a way of seeking consensus with social media companies without legislation, while the case of Canada involved greater legislative and penalisation. Two ways of seeking the same goal: curbing hate speech.
Heavy lifting: authentic talent development and leadership obtainment for Black women state legislators
Authors: Wrighten Jatia
Published: August 2022

Purpose

The purpose of this paper is to apply a novel intersectional framework, the heavy lifter theory, to leadership attainability in state legislatures. It is a logical and unique way to examine the gender ascription of Black women. This work helps to shed light on the political behavior of Black women, the institutional obstacles they face, and the lasting power of ancestral talent development.

Design/methodology/approach

One way to examine this intersectional theory, as it relates to Black women and authentic talent development in a sociocultural context, is an examination of leadership attainment in state legislatures. The specific research question was: What is the probability that Black women will attain leadership in state legislatures in comparison to Black men and white women? This study used panel data that have individual-level data on state legislators from 2007 to 2014 and applied a logistic regression and a predictive probability.

Findings

Intersectionality, measured as the interaction term between sex and race, increases the probability of Black women earning formal leadership positions in state legislatures. In addition, Black women attain leadership positions at higher rates than both Black men and white women.

Originality/value

This research presents a historical context by which to understand and examine the gendered nature of the ascription process of Black women. Specifically, their experience as a marginalized group burdened them with the duty of the heavy lifter. Although being the heavy lifter is a burden, this focus on Black women’s ability to thrive under constant discrimination in the form of racism and sexism should give scholars pause. In looking at Black women legislators’ ability to gain leadership, the heavy lifter identity can potentially be a vehicle through which Black women legislators can find a sense of purpose and both psychological and social strength to forge their own unexpected path.
Defects in Malaysian hospital buildings
Authors: Jesumoroti Christtestimony , Olanrewaju AbdulLateef , Khor Soo Cheen
Published: August 2022

Purpose

Hospital building maintenance management constitutes a pertinent issue of global concern for all healthcare stakeholders. In Malaysia, the maintenance management of hospital buildings is instrumental to the Government’s goal of providing efficient healthcare services to the Government's citizenry. However, there is a paucity of studies that have comprehensively explored all dimensions of hospital building defects in relation to maintenance management. Consequently, this study seeks to evaluate the defects of hospital buildings in Malaysia with the aim of proffering viable solutions for the rectification and prevention of the issue.

Design/methodology/approach

The study utilised a quantitative approach for data collection.

Findings

The findings indicated that cracked floors, floor tile failures, wall tiles failure, blocked water closets, and damaged windows were some of the flaws that degrade hospital buildings. The study’s outcomes reveal that defects not only deface the aesthetic appearance of hospital buildings but also inhibit the functionality of the buildings and depreciate the overall satisfaction.

Research limitations/implications

Considering the indispensable role of hospital buildings in the grand scheme of healthcare service provision and ensuring the well-being of people, the issue of defects necessitates an urgent re-evaluation of the maintenance management practices of hospital buildings in Malaysia. Previous studies on the maintenance management of hospital buildings in Malaysia have focused primarily on design, safety, and construction.

Practical implications

This is particularly important because defects in hospital buildings across the country have recently led to incessant ceiling collapses, fire outbreaks, ceiling, roof collapses, and other structural failures. These problems are typically the result of poor maintenance management, exacerbated by poor design and construction. These disasters pose significant risks to the lives of hospital building users.

Originality/value

This study offers invaluable insights for maintenance organisations and maintenance department staff who are genuinely interested in improving hospital buildings’ maintenance management to optimise staff's performance and enhance the user satisfaction of hospital buildings in Malaysia and globally.
Linking environmental knowledge, environmental responsibility, altruism, and intention toward green hotels through ecocentric and anthropocentric attitudes
Authors: Patwary Ataul Karim , Rasoolimanesh S. Mostafa , Rabiul Md Karim , Aziz Roslizawati Che , Hanafiah Mohd Hafiz
Published: August 2022

Purpose

This study aims to examine the effects of environmental knowledge, perceived environmental responsibility and altruism on tourist’s intention to stay in green hotels. In addition, the mediating role played by tourists’ attitudes, including ecocentric and anthropocentric attitudes, is explored.

Design/methodology/approach

Data were collected from 393 international tourists in Malaysia. This study followed a cross-sectional approach and applied the partial least squares – structural equation modelling using SmartPLS version 3 software to analyse the data and test the hypotheses.

Findings

The results indicated that environmental knowledge, altruism, environmental responsibility and ecocentric and anthropocentric attitudes positively influence tourists’ intention to stay in green hotels. Ecocentric attitudes mediate environmental knowledge, altruism, environmental responsibility and intention to stay in green hotels. However, environmental knowledge and altruism do not influence anthropocentric attitudes. Likewise, anthropocentric attitudes do not mediate the relationship between environmental knowledge, altruism, perceived environmental responsibility and intention to stay in green hotels.

Research limitations/implications

This study posed several theoretical and practical implications that will benefit future researchers and practitioners while exploring tourists’ behaviour in a green hotel context.

Originality/value

This study makes a unique and significant contribution by including ecocentric and anthropocentric attitudes in a unified model underpinned by the Theory of Planned Behaviour and the Value-Basis Theory.