bluuebunny/crossref_metadata_2025 huggingface dataset:
LKB1 expression and the prognosis of lung cancer
Authors: Lin Chunxuan , Lin Xiaochun , Lin Kunpeng , Tan Jialiang , Wei Chenggong , Liu Taisheng
Published: November 2021

Background:

In the past few decades, many lines of evidence implicate the importance of liver kinase B1 (LKB1) as a tumor suppressor gene in the development and progression of solid tumours. However, the prognostic and clinicopathological value of LKB1 in patients with lung cancer are controversial. This article aimed to investigate the latest evidence on this question.

Methods:

A systematic literature searched in the PubMed, Web of Science, Embase, Cochrane library, Scopus until September 20, 2020. The association between overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), clinicopathological features and LKB1 were analysed by meta-analysis.

Results:

Eleven studies including 1507 patients were included in this meta-analysis. The pooled results revealed that low LKB1 expression was significantly associated with poor overall survival (OS) (HR = 1.67, 95% CI: 1.07–2.60, P = .024) in lung cancer. However, no association was found between LKB1 expression and DFS/PFS (HR = 1.29, 95% CI: 0.70–2.39, P = .410). Pooled results showed that low LKB1 expression was associated with histological differentiation (poor vs moderate or well, OR = 4.135, 95% CI:2.524–6.774, P < .001), nodal metastasis (absent vs present, OR = 0.503, 95% CI: 0.303–0.835, P = .008) and smoking (yes vs no, OR = 1.765, 95% CI: 1.120–2.782, P = .014).

Conclusion:

These results suggest that low expression of LKB1 can be considered as a unfavorable prognostic biomarker for human lung cancer, which should be further researched.
An unusual huge thymoma composed of sclerosing thymoma and type AB thymoma
Authors: Jiang Yu-ting , Zhang Tian-yue , Guo Dan-dan , Li Rui
Published: November 2021

Rationale:

Sclerosing thymoma (ST) is quite a rare disease, as denoted in previous literature. Less than 20 cases of ST have been reported to date. However, the combined thymoma, composed of both type AB thymoma and ST, has never been described before.

Patient concerns:

The subject, a 49-year-old woman, came in with the chief complaint of cough for 10 days.

Diagnoses:

Both the contrast-enhanced computed tomography scan and the ultrasonography showed a huge mass located in the right thoracic cavity with inhomogeneous contrast accompanied by the invasion of the pericardium and pleura. Subsequently, computed tomography-guided core-needle biopsy revealed type B2 thymoma, and type AB thymoma could not be excluded. Based on postsurgical histopathology and immunohistochemical finding, this tumor was given the final diagnosis of ST and type AB thymoma.

Interventions:

After 6 months of adjuvant chemotherapy and local radiotherapy, total thymectomy was performed.

Outcomes:

The patient has been duly followed up for 1 year without any tumor recurrence.

Lessons:

ST is a very rare mediastinal neoplasm. Moreover, ST in combination with AB thymoma and affecting a large area, is unprecedented. Whether radiotherapy and chemotherapy have a certain effect on ST requires further investigation. In addition, due to the unclear recurrence rate of ST, long-term follow-up evaluation seems necessary.
Bilateral widespread segmental swelling on nerve sonography in multifocal acquired demyelinating sensory and motor neuropathy
Authors: Hsieh Wan-Jen , Chang Kai-Chieh , Hsueh Hsueh-Wen , Chao Chi-Chao , Hsieh Sung-Tsang
Published: November 2021

Introduction:

Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) is an asymmetric immune-related neuropathy with conduction block. We report 2 MADSAM cases with detailed clinical, electrophysiological, and sonography profiles.

Patient concerns and diagnosis:

Two cases presented with patchy sensorimotor impairment in both clinical and electrophysiological findings. Notably, nerve ultrasound demonstrated multifocal nerve enlargement not only at sites of conduction blockade but also at the unaffected contralateral sites. Interestingly, in our first case, focal radial nerve enlargement was observed prior to the clinical manifestations, suggesting nerve dynamic pathogenesis with variable clinical significance.

Interventions and outcomes:

The first patient was initially treated with prednisolone, however, 3 months after steroid therapy, her symptoms progressed. After treatment with intravenous immunoglobulin for 3 months, the symptoms stabilized. The second patient showed improvement after 2 months of prednisolone treatment.

Conclusion:

These observations suggest a more widespread pathomechanism underlying MADSAM, and ultrasound may detect nerve lesions earlier than clinical electrophysiology studies, and is warranted for early detection and thorough documentation of nerve pathology.
Synergistic effects of herbal medicines and anticancer drugs
Authors: Cheon Chunhoo
Published: November 2021

Background:

An increasing number of studies have been reporting combination therapy using herbal medicines and anticancer drugs, and the synergistic effects of this combination have gained much attention across the medical community. In this study, we will review and summarize all published studies that have investigated the synergistic interaction between herbal medicines and anticancer drugs.

Methods:

We will search the PubMed, Embase, and Cochrane Library databases. Studies investigated the synergistic interaction between herbal medicines and anticancer drugs will be included. The selection and extraction process will be performed by 2 independent reviewers, and we will perform qualitative synthesis.

Discussion:

The present study is being performed to investigate the herbal medicines and anticancer drugs that are used concomitantly, and to determine the combinations that are expected to show a synergistic effect. This knowledge will provide new insights into the possible role of herbal medicines in anticancer treatment.

Review registration:

Trial registration: OSF Registration number: DOI 10.17605/OSF.IO/H5QS9.
insideOutside: an accessible algorithm for classifying interior and exterior points, with applications in embryology
Authors: Strawbridge Stanley E. , Kurowski Agata , Corujo-Simon Elena , Fletcher Alastair N. , Nichols Jennifer , Fletcher Alexander G.
Published: November 2021

A crucial aspect of embryology is relating the position of individual cells to the broader geometry of the embryo. A classic example of this is the first cell-fate decision of the mouse embryo, where interior cells become inner cell mass and exterior cells become trophectoderm. Fluorescent labelling, imaging, and quantification of tissue-specific proteins have advanced our understanding of this dynamic process. However instances arise where these markers are either not available, or not reliable, and we are left only with the cells’ spatial locations. Therefore, a simple, robust method for classifying interior and exterior cells of an embryo using spatial information is required. Here, we describe a simple mathematical framework and an unsupervised machine learning approach, termedinsideOutside, for classifying interior and exterior points of a three-dimensional point-cloud, a common output from imaged cells within the early mouse embryo. We benchmark our method against other published methods to demonstrate that it yields greater accuracy in classification of nuclei from the pre-implantation mouse embryos and greater accuracy when challenged with local surface concavities. We have made MATLAB and Python implementations of the method freely available. This method should prove useful for embryology, with broader applications to similar data arising in the life sciences.
Hierarchical organization of rhesus macaque behavior
Authors: Voloh Benjamin , Eisenreich Benjamin R. , Maisson David J-N. , Ebitz R. Becket , Park Hyun Soo , Hayden Benjamin Y. , Zimmermann Jan
Published: November 2021

Primatologists, psychologists and neuroscientists have long hypothesized that primate behavior is highly structured. However, fully delineating that structure has been impossible due to the difficulties of precision behavioral tracking. Here we analyzed a dataset consisting of continuous measures of the 3D position of fifteen body landmarks from two male rhesus macaques (Macaca mulatta) performing three different tasks in a large unrestrained environment over many hours. Using an unsupervised embedding approach on the tracked joints, we identified commonly repeated pose patterns, which we call postures. We found that macaques’ behavior is characterized by 49 distinct identifiable postures, lasting an average of 0.6 seconds each. We found evidence that behavior is hierarchically organized, in that transitions between poses tend to occur within larger modules, which correspond to intuitively identifiably actions; these actions are in turn organized hierarchically. Our behavioral decomposition allows us to identify universal (cross-individual and cross-task) and unique (specific to each individual and task) principles of behavior. These results demonstrate the hierarchical nature of primate behavior and provide a method for the automated “ethogramming” of primate behavior.
NAD precursors cycle between host tissues and the gut microbiome
Authors: Chellappa Karthikeyani , McReynolds Melanie R. , Lu Wenyun , Zeng Xianfeng , Makarov Mikhail , Hayat Faisal , Mukherjee Sarmistha , Bhat Yashaswini R. , Lingala Siddharth R. , Shima Rafaella T. , Descamps Hélène C. , Cox Timothy , Ji Lixin , Jankowski Connor , Chu Qingwei , Davidson Shawn M. , Thaiss Christoph A. , Migaud Marie E. , Rabinowtiz Joshua D. , Baur Joseph A.
Published: November 2021

Nicotinamide adenine dinucleotide (NAD) is an essential redox cofactor in both mammals and microbes. Here we use isotope tracing to investigate the precursors supporting NAD synthesis in the gut microbiome. We find that preferred dietary NAD precursors are absorbed in the proximal part of the gastrointestinal tract and not available to microbes in the distal gut. Instead, circulating host nicotinamide enters the gut lumen and supports gut microbiome NAD synthesis. In addition, the microbiome converts nicotinamide, originating from the host circulation, into nicotinic acid. Host tissues uptake and utilize this microbiome-derived nicotinic acid for NAD synthesis, maintaining circulating nicotinic acid levels even in the absence of dietary consumption. Moreover, the main route from oral nicotinamide riboside, a widely used nutraceutical, to host NAD is via conversion into nicotinic acid by the gut microbiome. Thus, NAD precursors cycle between the host and gut microbiome to maintain NAD homeostasis.
A Thin-Film Lubrication Model for Biofilm Expansion Under Strong Adhesion
Authors: Tam Alexander K. Y. , Harding Brendan , Green J. Edward F. , Balasuriya Sanjeeva , Binder Benjamin J.
Published: November 2021

Understanding microbial biofilm growth is important to public health, because biofilms are a leading cause of persistent clinical infections. In this paper, we develop a thin-film model for microbial biofilm growth on a solid substratum to which it adheres strongly. We model biofilms as two-phase viscous fluid mixtures of living cells and extracellular fluid. The model tracks the movement, depletion, and uptake of nutrients explicitly, and incorporates cell proliferation via a nutrient-dependent source term. Notably, our thin-film reduction is two-dimensional and includes the vertical dependence of cell volume fraction. Numerical solutions show that this vertical dependence is weak for biologically-feasible parameters, reinforcing results from previous models in which this dependence was neglected. We exploit this weak dependence by writing and solving a simplified one-dimensional model that is computationally more efficient than the full model. We use both the one and two-dimensional models to predict how model parameters affect expansion speed and biofilm thickness. This analysis reveals that expansion speed depends on cell proliferation, nutrient availability, cell–cell adhesion on the upper surface, and slip on the biofilm–substratum interface. Our numerical solutions provide a means to qualitatively distinguish between the extensional flow and lubrication regimes, and quantitative predictions that can be tested in future experiments.
The stochastic logistic model with correlated carrying capacities reproduces beta-diversity metrics of microbial communities
Authors: Zaoli Silvia , Grilli Jacopo
Published: November 2021

The large taxonomic variability of microbial community composition is a consequence of the combination of environmental variability, mediated through ecological interactions, and stochasticity. Most of the analysis aiming to infer the biological factors determining this difference in community structure start by quantifying how much communities are similar in their composition, trough beta-diversity metrics. The central role that these metrics play in microbial ecology does not parallel with a quantitative understanding of their relationships and statistical properties. In particular, we lack a framework that reproduces the empirical statistical properties of beta-diversity metrics. Here we take a macroecological approach and introduce a model to reproduce the statistical properties of community similarity. The model is based on the statistical properties of individual communities and on a single tunable parameter, the correlation of species’ carrying capacities across communities, which sets the difference of two communities. The model reproduces quantitatively the empirical values of several commonly-used beta-diversity metrics, as well as the relationships between them. In particular, this modeling framework naturally reproduces the negative correlation between overlap and dissimilarity, which has been observed in both empirical and experimental communities and previously related to the existence of universal features of community dynamics. In this framework, such correlation naturally emerges due to the effect of random sampling.

AUTHORS SUMMARY

Several biological and ecological forces shape the composition of microbial communities. But also contingency and stochasticity play an important role. Comparing communities, identifying which conditions are similar in communities with similar species composition, allows to identify which forces shape their structure. Here we introduce a modeling framework which reproduces the statistical features of community similarity. We identify a single relevant parameter that captures in a single number the multidimensional nature of similarity in community composition. These results set the basis for a quantitative, and predicting, theory of the statistical properties of microbial communities.
The haplotype-resolved chromosome pairs and transcriptome of a heterozygous diploid African cassava cultivar
Authors: Qi Weihong , Lim Yi-Wen , Patrignani Andrea , Schläpfer Pascal , Bratus-Neuenschwander Anna , Grüter Simon , Chanez Christelle , Rodde Nathalie , Prat Elisa , Vautrin Sonia , Fustier Margaux-Alison , Pratas Diogo , Schlapbach Ralph , Gruissem Wilhelm
Published: November 2021

Background

Cassava (Manihot esculenta) is an important clonally propagated food crop in tropical and sub-tropical regions worldwide. Genetic gain by molecular breeding is limited because cassava has a highly heterozygous, repetitive and difficult to assemble genome.

Findings

Here we demonstrate that Pacific Biosciences high-fidelity (HiFi) sequencing reads, in combination with the assembler hifiasm, produced genome assemblies at near complete haplotype resolution with higher continuity and accuracy compared to conventional long sequencing reads. We present two chromosome scale haploid genomes phased with Hi-C technology for the diploid African cassava variety TME204. Genome comparisons revealed extensive chromosome re-arrangements and abundant intra-genomic and inter-genomic divergent sequences despite high gene synteny, with most large structural variations being LTR-retrotransposon related. Allele-specific expression analysis of different tissues based on the haplotype-resolved transcriptome identified both stable and inconsistent alleles with imbalanced expression patterns, while most alleles expressed coordinately. Among tissue-specific differentially expressed transcripts, coordinately and biasedly regulated transcripts were functionally enriched for different biological processes. We use the reference-quality assemblies to build a cassava pan-genome and demonstrate its importance in representing the genetic diversity of cassava for downstream reference-guided omics analysis and breeding.

Conclusions

The haplotype-resolved genome allows the first systematic view of the heterozygous diploid genome organization in cassava. The completely phased and annotated chromosome pairs will be a valuable resource for cassava breeding and research. Our study may also provide insights into developing cost-effective and efficient strategies for resolving complex genomes with high resolution, accuracy and continuity.
Transcriptomic and proteomic analysis of marine nematodeLitoditis marinaacclimated to different salinities
Authors: Xie Yusu , Zhang Liusuo
Published: November 2021

Salinity is a critical abiotic factor for all living organisms. The ability to adapt to different salinity environments determines an organism’s survival and ecological niches.Litoditis marinais a euryhaline marine nematode widely distributed in coastal ecosystems all over the world, although numerous genes involved in its salinity response have been reported, the adaptive mechanisms underlying its euryhalinity remain unexplored. Here, we utilized worms which have been acclimated to either low salinity or high salinity conditions and evaluated their basal gene expression at both transcriptomic and proteomic levels. We found that several conserved regulators, including osmolytes biosynthesis genes, transthyretin-like family genes, V-type H+-transporting ATPase and potassium channel genes, were involved in both short-term salinity stress response and long-term acclimation processes. In addition, we identified genes related to cell volume regulation, such as actin regulatory genes, Rho family small GTPases and diverse ion transporters, might contribute to hyposaline acclimation, while the glycerol biosynthesis genesgpdh-1andgpdh-2accompanied hypersaline acclimation inL. marina. Furthermore,gpdh-2might play an essential role in transgenerational inheritance of osmotic stress protection inL. marinaas in its relative nematodeCaenorhabditis elegans. Hereby, this study paves the way for further in-depth exploration on adaptive mechanisms underlying euryhalinity, and may also contribute to the studies of healthy ecosystems in the context of global climate change.
Meta-Research: A Poor Research Landscape Hinders the Progression of Knowledge and Treatment of Reproductive Diseases
Authors: Mercuri Natalie D , Cox Brian J
Published: November 2021

Reproductive diseases have gone under the radar for many years, resulting in insufficient diagnostics and treatments. Infertility rates are rising, preeclampsia claims over 70 000 maternal and 500 000 neonatal lives globally per year, and endometriosis affects 10% of all reproductive-aged women but is often undiagnosed for many years. Changes in policy have been enacted to mitigate the gender inequality in research investigators and subjects of medical research. However, the disparities in reproductive research advancement still exist. Here, we analyzed the reproductive science research landscape in attempt to quantify the gravity of the current situation. We find that non-reproductive organs are annually researched 5-20 times more than reproductive organs leading to an exponentially increasing relative knowledge gap in reproductive sciences. Additionally, reproductive organs (breast and prostate) are mainly researched when there is a disease-focus, leading to a lack of basic understanding of the reproductive organs. This gap in knowledge affects reproductive syndromes, as well as other bodily systems and research areas, such as cancer biology and regenerative medicine. Action must be taken by current researchers, funding organizations, and educators to combat this longstanding disregard of reproductive science.
MTD: a unique pipeline for host and meta-transcriptome joint and integrative analyses of RNA-seq data
Authors: Wu Fei , Liu Yao-Zhong , Ling Binhua
Published: November 2021

RNA-seq data contains not only host transcriptomes but also non-host information that comprises transcripts from active microbiota in the host cells. Therefore, joint and integrative analyses of both host and meta-transcriptome can reveal gene expression of microbial community in a given sample as well as the correlative and interactive dynamics of host response to the microbiome. However, there are no convenient tools that can systemically analyze host-microbiota interactions by simultaneously quantifying host and meta-transcriptome in the same sample at the tissue and the single-cell level, which poses a challenge for interested researchers with a limited expertise in bioinformatics. Here, we developed a software pipeline that can comprehensively and synergistically analyze and correlate the host and meta-transcriptome in a single sample using bulk and single-cell RNA-seq data. This pipeline, named MTD, can extensively identify and quantify microbiome, including viruses, bacteria, protozoa, fungi, plasmids, and vectors in the host cells and correlate the microbiome with the host transcriptome. MTD is easy to install and run, involving only a few lines of simple commands. It empowers researchers with unique genomics insights into host immune responses to microorganisms.
Trait Association and Prediction Through Integrative K-mer Analysis
Authors: He Cheng , Washburn Jacob D. , Hao Yangfan , Zhang Zhiwu , Yang Jinliang , Liu Sanzhen
Published: November 2021

Genome-wide association study (GWAS) with single nucleotide polymorphisms (SNPs) has been widely used to explore genetic controls of phenotypic traits. Here we employed an GWAS approach using k-mers, short substrings from sequencing reads. Using maize cob and kernel color traits, we demonstrated that k-mer GWAS can effectively identify associated k-mers. Co-expression analysis of kernel color k-mers and pathway genes directly found k-mers from causal genes. Analyzing complex traits of kernel oil and leaf angle resulted in k-mers from both known and candidate genes. Evolution analysis revealed most k-mers positively correlated with kernel oil were strongly selected against in maize populations, while most k-mers for upright leaf angle were positively selected. In addition, phenotypic prediction of kernel oil, leaf angle, and flowering time using k-mer data showed at least a similarly high prediction accuracy to the standard SNP-based method. Collectively, our results demonstrated the bridging role of k-mers for data integration and functional gene discovery.
The relationship between land cover and microbial community composition in European lakes
Authors: Sperlea Theodor , Philip Schenk Jan , Dreßler Hagen , Beisser Daniela , Hattab Georges , Boenigk Jens , Heider Dominik
Published: November 2021

Microbes such as bacteria, archaea, and protists are essential for element cycling and ecosystem functioning, but many questions central to the understanding of the role of microbes in ecology are still open. Here, we analyze the relationship between lake microbiomes and the land cover surrounding the lakes. By applying machine learning methods, we quantify the covariance between land cover categories and the microbial community composition recorded in the largest amplicon sequencing dataset of European lakes available to date. We identify microbial bioindicators for these land cover categories. Combining land cover and physico-chemical bioindicators identified from the same amplicon sequencing dataset, we develop two novel similarity metrics that facilitate insights into the ecology of the lake microbiome. We show that the bioindicator network, i.e., the graph linking OTUs indicative of the same environmental parameters, corresponds to microbial co-occurrence patterns. Taken together, we demonstrate the strength of machine learning approaches to identify correlations between microbial diversity and environmental factors, potentially opening new approaches to integrate environmental molecular diversity into monitoring and water quality assessments.
Quantifying asymmetry in non-symmetrical morphologies, with an example from Cetacea
Authors: Coombs Ellen. J. , Felice Ryan. N.
Published: November 2021

1. Three-dimensional measurements of morphology are key to gaining an understanding of a species’ biology and to answering subsequent questions regarding the processes of ecology (or palaeoecology), function, and evolution. However, the collection of morphometric data is often focused on methods designed to produce data on bilaterally symmetric morphologies which may mischaracterise asymmetric structures.

2. Using 3D landmark and curve data on 3D surface meshes of specimens, we present a method for first quantifying the level of asymmetry in a specimen and second, accurately capturing the morphology of asymmetric specimens for further geometric analyses.

3. We provide an example of the process from initial landmark placement, including details on how to place landmarks to quantify the level of asymmetry, and then on how to use this information to accurately capture the morphology of asymmetric morphologies or structures. We use toothed whales (odontocetes) as a case study and include examples of the consequences of mirroring landmarks and curves, a method commonly used in bilaterally symmetrical specimens, on asymmetric specimens.

4. We conclude by presenting a step-by-step method to collecting 3D landmark data on asymmetric specimens. Additionally, we provide code for placing landmarks and curves on asymmetric specimens in a manner designed to both save time and ultimately accurately quantify morphology. This method can be used as a first crucial step in morphometric analyses of any biological specimens by assessing levels of asymmetry and then if required, accurately quantifying this asymmetry. The latter not only saves the researcher time, but also accurately represents the morphology of asymmetric structures.
Kinetic networks identify Twist2 as a key regulatory node in adipogenesis
Authors: Dutta Arun B. , Lank Daniel S. , Przanowska Róża K. , Przanowski Piotr , Wang Lixin , Nguyen Bao , Walavalkar Ninad M. , Duarte Fabiana M. , Guertin Michael J.
Published: November 2021

Adipocytes contribute to metabolic disorders such as obesity, diabetes, and atherosclerosis. Prior characterizations of the transcriptional network driving adipogenesis overlook transiently acting transcription factors (TFs), genes, and regulatory elements that are essential for proper differentiation. Moreover, traditional gene regulatory networks provide neither mechanistic details about individual RE-gene relationships nor temporal information needed to define a regulatory hierarchy that prioritizes key regulatory factors. To address these shortcomings, we integrate kinetic chromatin accessibility (ATAC-seq) and nascent transcription (PRO-seq) data to generate temporally resolved networks that describe TF binding events and resultant effects on target gene expression. Our data indicate which TF families cooperate with and antagonize each other to regulate adipogenesis. Compartment modeling of RNA polymerase density quantifies how individual TFs mechanistically contribute to distinct steps in transcription. Glucocorticoid receptor activates transcription by inducing RNA polymerase pause release while SP and AP1 factors affect RNA polymerase initiation. We identifyTwist2as a previously unappreciated effector of adipocyte differentiation. We find that TWIST2 acts as a negative regulator of 3T3-L1 and primary preadipocyte differentiation. We confirm thatTwist2knockout mice have compromised lipid storage within subcutaneous and brown adipose tissue. Previous phenotyping ofTwist2knockout mice and Setleis syndrome (Twist2-/-) patients noted deficiencies in subcutaneous adipose tissue. This network inference framework is a powerful and general approach for interpreting complex biological phenomena and can be applied to a wide range of cellular processes.
Assessing the Use of Prescription Drugs in Obese Respondents in the National Health and Nutrition Examination Survey
Authors: Barrett Laura A. , Xing Aiwen , Sheffler Julia , Steidley Elizabeth , Adam Terrence J. , Zhang Rui , He Zhe
Published: November 2021

Introduction

Obesity is a common disease and a known risk factor for many other conditions such as hypertension, type 2 diabetes, and cancer. Treatment options for obesity include lifestyle changes, pharmacotherapy, and surgical interventions such as bariatric surgery. In this study, we examine the use of prescription drugs and dietary supplements by the individuals with obesity.

Methods

We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) data 2003-2014. We used multivariate logistic regression to analyze the correlations of demographics and obesity status with the use of prescription drugs and dietary supplement use. We also built machine learning models to classify prescription drug and dietary supplement use using demographic data and obesity status.

Results

Individuals with obesity are more likely to take cardiovascular agents (OR=1.265, 95% CI 1.222-1.311) and metabolic agents (OR=1.398, 95% CI 1.343-1.456) than individuals without obesity. The best performing model for classifying prescription drug use had the accuracy of 74.5% and the AUROC of 0.817.

Conclusions

This study can inform clinical practice and patient education of the use of prescription drugs and dietary supplements and their correlation with obesity.
The clinical efficacy of faecal microbiota transplantation: An umbrella review of randomized controlled trials
Authors: Liu Nanyang , Zhang Tingting , Sun Jiahui , Fu Jianhua , Li Hao
Published: November 2021

INTRODUCTION

Faecal microbiota transplantation (FMT) therapeutic strategy has been associated with positive outcomes in multiple diseases. We conducted an umbrella review of the meta-analysis to summarize the available evidence and assess its credibility.

METHODS

We evaluated a meta-analysis of randomized controlled trials that investigated the efficacy and safety of FMT for any condition. We used the random-effects model to obtain estimates and corresponding 95% confidence intervals, heterogeneity estimates, and small-study effects. We used AMSTAR 2 to assess methodological quality and GRADE tools to grade the evidence.

RESULTS

Seven meta-analyses with a total of 33 outcomes were included in the current umbrella review to evaluate the efficacy and safety of FMT. Overall, there is a moderate certainty of evidence supporting the associations of the use of FMT with better clinical remission in patients with Clostridium difficile infection (RR = 1.74; 95% CI: 1.37-2.22) and inflammatory bowel disease (RR = 1.70; 95% CI: 1.12-2.56). A very low certainty evidence supports the use of FMT to treat antibiotic-resistant bacteria (RR = 5.67; 95% CI: 2.20-14.63) and functional constipation (RR = 1.35; 95% CI: 1.14-1.60) but does not support irritable bowel syndrome (RR = 1.08; 95% CI: 0.65-1.77).

DISCUSSION

The umbrella review of the current meta-analysis demonstrates that FMT intervention is associated with positive outcomes for several diseases. However, the credibility of the evidence is not high. Further high-quality randomized controlled trials should be carried out to improve the strength and credibility of the evidence base.
The distinct effects of MEK and GSK3 inhibition upon the methylome and transcriptome of mouse embryonic stem cells
Authors: Spindel Julia , Krueger Christel , Krueger Felix , Papachristou Evangelia K , Kishore Kamal , D'Santos Clive S , Reik Wolf
Published: November 2021

Mouse embryonic stem cells (mESCs) were first cultured in vitro in serum-containing medium with leukaemia inhibitory factor, in which they exhibit heterogeneous expression of both pluripotency and some early differentiation markers. Over the last decade, however, it has become commonplace to grow mESCs with inhibitors of MEK and GSK3 signalling, which together elicit a more homogeneously 'naive' state of pluripotency. Whilst 2i/L-cultured mESCs have been shown to be globally hypomethylated, a comprehensive understanding of the distinct effects of these signalling inhibitors upon the DNA methylome is still lacking. Here we carried out whole genome bisulphite and RNA sequencing of mESCs grown with MEK or GSK3 inhibition alone, including different time points and concentrations of MEK inhibitor treatment. This demonstrated that MEK inhibition causes a dose-dependent impairment of maintenance methylation via loss of UHRF1 protein, as well as rapid impairment of de novo methylation. In contrast, GSK3 inhibition triggers impairment of de novo methylation alone, and consequent hypomethylation is enriched at enhancers with a 2i/L-specific chromatin signature and coincides with upregulation of nearby genes. Our study provides detailed insights into the epigenetic and transcriptional impacts of inhibiting MEK or GSK3 signalling in mouse pluripotent cells.
The critical role of the ventral temporal lobe in word retrieval
Authors: Snyder Kathryn M. , Forseth Kiefer J. , Donos Cristian , Rollo Patrick S. , Fischer-Baum Simon , Breier Joshua , Tandon Nitin
Published: November 2021

Deficits in word retrieval are a hallmark of a variety of neurological illnesses spanning from dementia to traumatic injuries. The role of the dominant temporal lobe in fluent naming has been characterized by lesional analyses, functional imaging, and intracranial recordings, but limitations of each of these measures preclude a clear assessment of which specific constituent of the temporal lobe is critical for naming. We studied a large cohort of patients undergoing surgical resections or laser ablations of the dominant temporal lobe for medically intractable epilepsy (n=95). These techniques are exceedingly effective for seizure control but often result in language declines, particularly in confrontation naming, which can be socio-economically disabling. We used a multivariate voxel-based lesion symptom mapping analysis to localize brain regions significantly associated with visual object naming deficits. We observed that posterior inferior temporal regions, centered around the middle fusiform gyrus, were significantly associated with a decline in confrontation naming. Furthermore, we found that the posterior margin of anterior temporal lobectomies was linearly correlated to a decline in visual naming with a clinically significant decline occurring once the resection extended 6 cm from the anterior tip of the temporal lobe. We integrated these findings with electrocorticography during naming in a subset of this population and found that the majority of cortical regions whose resection was associated with a significant decline overlapped with regions that were functionally most active prior to articulation. Importantly, these loci coincide with the sites of susceptibility artifacts during echo-planar imaging, which explains why this region has not previously been implicated. Taken together, these data highlight the crucial contribution of the posterior ventral temporal cortex in lexical access and its important role in the pathophysiology of anomia following temporal lobe resections. Surgical strategies, including the use of laser ablation to target the medial temporal lobe as well as microsurgical approaches, should attempt to preserve this region to mitigate postoperative language deficits.
Impact of the COVID-19 pandemic on community antibiotic prescribing and stewardship: a qualitative interview study with general practitioners in England
Authors: Borek Aleksandra J. , Maitland Katherine , McLeod Monsey , Campbell Anne , Hayhoe Benedict , Butler Christopher C. , Morrell Liz , Roope Laurence , Holmes Alison , Walker A. Sarah , Tonkin-Crine Sarah
Published: November 2021

The COVID-19 pandemic has had a profound impact on the delivery of primary care services. We aimed to identify general practitioners’ (GPs’) perceptions and experiences of how the COVID-19 pandemic influenced antibiotic prescribing and antimicrobial stewardship (AMS) in general practice in England. Twenty-four semi-structured interviews were conducted with 18 GPs at two time-points: autumn 2020 (14 interviews) and spring 2021 (10 interviews). Interviews were audio-recorded, transcribed and analysed thematically, taking a longitudinal approach. Participants reported a lower threshold for antibiotic prescribing (and fewer consultations) for respiratory infections and COVID-19 symptoms early in the pandemic, then returning to more usual (pre-pandemic) prescribing. They perceived less impact on antibiotic prescribing for urinary and skin infections. Participants perceived the changing ways of working and consulting (e.g., proportions of remote and in-person consultations), and the changing patient presentations and GP workload as influencing the fluctuations in antibiotic prescribing. This was compounded by decreased engagement with, and priority of, AMS due to COVID-19-related urgent priorities. Re-engagement with AMS is needed, e.g., through reviving antibiotic prescribing feedback and targets/incentives. While the pandemic disrupted the usual ways of working, it also produced opportunities, e.g., for re-organising ways of managing infections and AMS in the future.
Childhood Immuno-metabolic Markers and Risk of Depression and Psychosis in Adulthood: A Prospective Birth Cohort Study
Authors: Donnelly NA , Perry BI , Jones HJ , Khandaker GM
Published: November 2021

Background

Metabolic and inflammatory disorders commonly co-occur with depression and psychosis, with emerging evidence implicating immuno-metabolic dysfunction in their aetiology. Previous studies have reported metabolic dysfunction and inflammation in adults with depression and psychosis. However, longitudinal studies testing the direction of association, and the effects of different dimensions of early-life immuno-metabolic dysfunction on adult psychopathology, are limited.

Methods

Using data from 3875 birth cohort participants we examined longitudinal associations of three metabolic hormones (leptin, adiponectin, insulin) at age 9 with risks for depression- and psychosis-spectrum outcomes at age 24. In addition, using nine immuno-metabolic biomarkers, we constructed an exploratory bifactor model showing a general immuno-metabolic factor and three specific factors (adiposity, inflammation, and insulin resistance), which were also used as exposures.

Results

Childhood leptin was associated with adult depressive episode (adjusted odds ratio (aOR)=1.28; 95% CI, 1.00-1.64) and negative symptoms (aOR=1.12; 95% CI, 1.05-1.20). The general immuno-metabolic factor was associated with depressive symptoms (aOR=1.05; 95% CI, 1.01-1.08) and psychotic experiences (aOR=1.20; 95% CI, 1.01-1.42). The adiposity factor was associated with negative symptoms (aOR=1.07; 95% CI 1.02-1.12). All associations tended to be stronger in women, though 95% credible intervals overlapped with that for men. In women, the inflammatory factor was associated with depressive episode (aOR=1.23; 95% CI, 1.01-1.47) and atypical depressive symptoms (aOR=1.10; 95% CI, 1.02-1.19).

Conclusions

While general immuno-metabolic dysfunction in childhood may contribute to risks for both psychotic and depressive symptoms in adulthood, childhood adiposity and inflammation are linked to affective (depressive, atypical, and negative) symptoms.
When less is more – A fast TurboID KI approach for high sensitivity endogenous interactome mapping
Authors: Stockhammer Alexander , Spalt Carissa , Benz Laila S. , Harel Shelly , Natalia Vini , Wiench Lukas , Freund Christian , Kuropka Benno , Bottanelli Francesca
Published: November 2021

In recent years, proximity labelling has established itself as an unbiased and powerful approach to map the interactome of specific proteins. While physiological expression of the labelling enzyme is beneficial for the mapping of interactors, generation of the desired cell lines remains time-consuming and challenging. Using our established pipeline for the rapid generation of C- and N-terminal CRISPR-Cas9 knock-ins (KIs) based on antibiotic selection, we were able to compare the performance of commonly used labelling enzymes when endogenously expressed. Endogenous tagging of the μ subunit of the AP-1 complex with TurboID allowed identification of known interactors and cargo proteins that simple overexpression of a labelling enzyme fusion protein could not reveal. We used the KI-strategy to compare the interactome of the different adaptor protein (AP) complexes and clathrin and were able to assemble lists of potential interactors and cargo proteins that are specific for each sorting pathway. Our approach greatly simplifies the execution of proximity labelling experiments for proteins in their native cellular environment and allows going from CRISPR transfection to mass spectrometry analysis and interactome data in just over a month.
Simulation of particles screening in pulsating negative pressure shale shaker by coupling CFD and DEM
Authors: Yin Peng , Hou Yongjun , Wu Xianjin
Published: November 2021

Purpose

The purpose of this paper is to obtain the combination of working parameters suitable for pulsating negative pressure shale shaker through simulation, which is conducive to efficient recovery of clean drilling fluid and relatively dry cuttings.

Design/methodology/approach

Shale shaker is still one of the main equipment in solid–solid and solid–liquid separation processes in drilling industry. This research is based on a new drilling fluids circulation treatment device, namely pulsating negative pressure shale shaker. In this work, a numerical study of particle flow and separation in the pulsating negative pressure shale shaker is carried out by coupling computational fluid dynamics/discrete element method (CFD-DEM). The effect of vibration parameters and negative pressure parameters are studied in terms of conveyance velocity and percent through screen.

Findings

The results show that, conveyance velocity of particle is mainly affected by vibration parameters, negative pressure in pulsating form can effectively prevent cuttings from sticking to the screen. Vibration parameters and pulsating airflow velocity peak have great influence on percent through screen, while vibration frequency and screen slope have influence on the time when the percent through screen reaches stability.

Originality/value

In this paper, the authors put forward a new kind of drilling waste fluid treatment equipment, and focused on the study of particle movement law. The results have important guiding significance for the selection of structural design parameters and rational use of equipment. In addition, the new device provides a new idea for solid–liquid separation method, which is one of the hot topics in current research.
Modularity of total hip prosthesis and its tribological implications
Authors: Badita Liliana-Laura , Florescu Virgil , Tiganesteanu Constantin , Capitanu Lucian
Published: November 2021

Purpose

The study aims to analyze the fretting phenomenon, manifested at the taper junctions of modular total hip prostheses (THP). Modularity of prostheses implies the micro-movement occurrence. Fractures can arise as a result of the fretting cracking of the prostheses components, affecting durability of modular THPs. Fretting corrosion is associated with the decrease in the clinical acceptance of hip modular implants.

Design/methodology/approach

Starting from the fretting phenomenon influence on modularity, monoblock THPs and prostheses with modular femoral head recovered from some review surgeries were investigated. Modular prostheses have a taper junction femoral head – femoral stem neck. Investigation consisted in the analysis of fretting wear and fretting corrosion, of the femoral heads’ taper and of the femoral stems’ trunnions.

Findings

The main result was that the micro-movement that provokes the fretting of the femoral head-femoral stem taper junction analyzed does not have the same direction. It is manifesting in the direction of the axis of the femoral head taper, around this axis or as a composed movement. The authors suspect that this is due to the different design of the taper. In this way, the inclination of the stem’s trunnion into the head hole has a different angular misalignment and may cause greater damages of the taper.

Originality/value

This result can be a starting point from the improvement of the future taper junctions design that will improve the quality, durability and modularity of THPs.
Effect of quality of governance on the relationship between illicit financial flows and economic growth
Authors: Mohd Padil Hazlina , Kasim Eley Suzana , Mohd Razali Fazlida , Atan Ruhaya , Aminullah Haziq
Published: November 2021

Purpose

The purpose of this paper is twofold. First, the study aims to examine the direct effect of illicit financial flows (IFF) and quality of governance (QoG) on economic growth. Second, this study seeks to examine the moderating effect of QoG on the economic consequences of IFF.

Design/methodology/approach

This study collected data from nine The Association of Southeast Asian Nations (ASEAN) countries for the period of 10 years from 2008 to 2019. The study concerned an analysis of the testing of a conceptual framework which based on secondary data which may lack a comprehensive substantiation on the grounds of measurement theory. A partial least squares (PLS) modelling using the SmartPLS 3.2.8 version was used as a statistical tool to examine the measurement and structural model.

Findings

Key findings provide empirical support on the effect of IFF and QoG on economic growth. It also confirmed that QoG significantly moderated the relationship between IFF and economic growth by reducing the negative impact of IFF on economic growth.

Practical implications

Immediate corrective action needs to be implemented by policymakers of ASEAN countries to strengthen QoG to effectively curb IFF activities.

Originality/value

This study provides current empirical evidence on the relationship of IFF, QoG and economic growth within ASEAN countries.