bluuebunny/crossref_metadata_2025 huggingface dataset:
Induced pluripotent stem cell-derived cells model brain microvascular endothelial cell glucose metabolism
Authors: Weber Callie M. , Moiz Bilal , Zic Sophia M. , Alpízar Vargas Viviana , Li Andrew , Clyne Alisa Morss
Published: December 2022

Glucose transport from the blood into the brain is tightly regulated by brain microvascular endothelial cells (BMEC), which also use glucose as their primary energy source. To study how BMEC glucose transport contributes to cerebral glucose hypometabolism in diseases such as Alzheimer’s disease, it is essential to understand how these cells metabolize glucose. Human primary BMEC (hpBMEC) can be used for BMEC metabolism studies; however, they have poor barrier function and may not recapitulate in vivo BMEC function. iPSC-derived BMEC-like cells (hiBMEC) are readily available and have good barrier function but may have an underlying epithelial signature. In this study, we examined differences between hpBMEC and hiBMEC glucose metabolism using a combination of dynamic metabolic measurements, metabolic mass spectrometry, RNA sequencing, and Western blots. hiBMEC had decreased glycolytic flux relative to hpBMEC, and the overall metabolomes and metabolic enzyme levels were different between the two cell types. However, hpBMEC and hiBMEC had similar glucose metabolism, including nearly identical glucose labeled fractions of glycolytic and TCA cycle metabolites. Treatment with astrocyte conditioned media and high glucose increased glycolysis in both hpBMEC and hiBMEC, though hpBMEC decreased glycolysis in response to fluvastatin while hiBMEC did not. Together, these results suggest that hiBMEC can be used to model cerebral vascular glucose metabolism, which expands their use beyond barrier models.
Four-dimensional measurement of root system development using time-series three-dimensional volumetric data analysis by backward prediction
Authors: Teramoto Shota , Uga Yusaku
Published: December 2022

Background

Root system architecture (RSA) is an essential characteristic for efficient water and nutrient absorption in terrestrial plants; its plasticity enables plants to respond to different soil environments. Better understanding of root plasticity is important in developing stress-tolerant crops. Non-invasive techniques that can measure roots in soils nondestructively, such as X-ray computed tomography (CT), are useful to evaluate RSA plasticity. However, although RSA plasticity can be measured by tracking individual root growth, only a few methods are available for tracking individual roots from time-series three-dimensional (3D) images.

Results

We developed a semi-automatic workflow that tracks individual root growth by vectorizing RSA from time-series 3D images via two major steps. The first step involves 3D alignment of the time-series RSA images by iterative closest point registration with point clouds generated by high-intensity particles in potted soils. This alignment ensures that the time-series RSA images overlap. The second step consists of backward prediction of vectorization, which is based on the phenomenon that the root length of the RSA vector at the earlier time point is shorter than that at the last time point. In other words, when CT scanning is performed at time point A and again at time point B for the same pot, the CT data and RSA vectors at time points A and B will almost overlap, but not where the roots have grown. We assumed that given a manually created RSA vector at the last time point of the time series, all RSA vectors except those at the last time point could be automatically predicted by referring to the corresponding RSA images. Using 21 time-series CT volumes of a potted plant of upland rice (Oryza sativa), this workflow revealed that the root elongation speed increased with age. Compared with a workflow that does not use backward prediction, the workflow with backward prediction reduced the manual labor time by 95%.

Conclusions

We developed a workflow to efficiently generate time-series RSA vectors from time-series X-ray CT volumes. We named this workflow 'RSAtrace4D' and are confident that it can be applied to the time-series analysis of RSA development and plasticity.
Ethnic and racial-specific differences in levels of centrosome-associated mitotic kinases, proliferative and epithelial-to-mesenchymal markers in breast cancers
Authors: Rivera-Rivera Yainyrette , Vargas Geraldine , Jaiswal Neha , Núñez-Marrero Angel , Li Jiannong , Chen Dung-Tsa , Eschrich Steven , Rosa Marilin , Johnson Joseph O. , Dutil Julie , Chellappan Srikumar P. , Saavedra Harold I.
Published: December 2022

Molecular epidemiology evidence indicates racial and ethnic differences in the aggressiveness and survival of breast cancer. Hispanics/Latinas (H/Ls) and non-Hispanic Black women (NHB) are at higher risk of breast cancer (BC)-related death relative to non-Hispanic white (NHW) women in part because they are diagnosed with hormone receptor-negative (HR) subtype and at higher stages. Since the cell cycle is one of the most commonly deregulated cellular processes in cancer, we propose that the mitotic kinases TTK (or Mps1), TBK1, and Nek2 could be novel targets to prevent breast cancer progression among NHBs and H/Ls. In this study, we calculated levels of TTK, p-TBK1, epithelial (E-cadherin), mesenchymal (Vimentin), and proliferation (Ki67) markers through immunohistochemical (IHC) staining of breast cancer tissue microarrays (TMAs) that includes samples from 6 regions in the Southeast of the United States and Puerto Rico -regions enriched with NHB and H/L breast cancer patients. IHC analysis showed that TTK, Ki67, and Vimentin were significantly expressed in triple-negative (TNBC) tumors relative to other subtypes, while E-cadherin showed decreased expression. TTK correlated with all of the clinical variables but p-TBK1 did not correlate with any of them. TCGA analysis revealed that the mRNA levels of multiple mitotic kinases, including TTK, Nek2, Plk1, Bub1, and Aurora kinases A and B, and transcription factors that are known to control the expression of these kinases (e.g. FoxM1 and E2F1-3) were upregulated in NHBs versus NHWs and correlated with higher aneuploidy indexes in NHB, suggesting that these mitotic kinases may be future novel targets for breast cancer treatment in NHB women.
Extended treatment of multimodal cognitive behavioral therapy in children and adolescents with obsessive–compulsive disorder improves symptom reduction: a within-subject design
Authors: Adam Julia , Goletz Hildegard , Dengs Stefanie , Klingenberger Nora , Könnecke Sonja , Vonderbank Christina , Hautmann Christopher , Hellmich Martin , Plück Julia , Döpfner Manfred
Published: December 2022

Background

Based on the current state of research regarding the treatment in pediatric obsessive–compulsive disorder (OCD), cognitive behavioral therapy (CBT) (in severe cases with additional pharmacotherapy) is considered as the first-line treatment according to internationally recognized guidelines. Research is mostly based on randomized controlled trials (RCTs; efficacy research). Thus, examined treatment conditions, especially the treatment duration, and patients’ characteristics do not necessarily correspond to those found within routine care. Studies showed CBT packages as a whole to be efficacious, but less is known about the effects of individual CBT components. Furthermore, effects on comorbid symptoms or psychosocial impairment have been often neglected and different rater perspectives have been hardly considered in previous research.

Methods

This effectiveness study aimed to examine the effects of multimodal CBT in children, adolescents, and young adults (age 6–20 years) with OCD (n = 38) within routine care. Effects on obsessive–compulsive and co-existing symptoms were evaluated in a within-subject design by comparing changes during the assessment phase with 12-week standard treatment and with individually tailored extended treatment. Additionally, within the standard treatment, non-exposure treatment was compared to exposure treatment. Multi-informant assessment was applied, and the analyses included multilevel modeling and t-tests for pre-post comparisons.

Results

During the standard treatment and extended treatment, obsessive–compulsive symptoms, strain, and functional impairment significantly decreased. Moreover, a significant reduction of overall comorbid symptoms emerged, particularly regarding internalizing symptoms, including anxiety and depression. Comparisons of treatment components indicated that adding exposure with response prevention (ERP) has an additional positive effect. Clinical improvement and remission rates increased considerably when more treatment sessions were provided.

Conclusions

These results suggest that improvement after an initial 12-week course of treatment may not allow for the prediction of non-responders/non-remitters and for the termination of treatment. Overall, the findings show that results from randomized controlled trials are transferrable to routine care.

Trial registration number This study was registered retrospectively at the German Clinical Trials Register (https://drks.de/search/de/trial/DRKS00030050).
Robust and rigorous identification of tissue-specific genes by statistically extending tau score
Authors: Lüleci Hatice Büşra , Yılmaz Alper
Published: December 2022

Objectives

In this study, we aimed to identify tissue-specific genes for various human tissues/organs more robustly and rigorously by extending the tau score algorithm.

Introduction

Tissue-specific genes are a class of genes whose functions and expressions are preferred in one or several tissues restrictedly. Identification of tissue-specific genes is essential for discovering multi-cellular biological processes such as tissue-specific molecular regulations, tissue development, physiology, and the pathogenesis of tissue-associated diseases.

Materials and Methods

Gene expression data derived from five large RNA sequencing (RNA-seq) projects, spanning 96 different human tissues, were retrieved from ArrayExpress and ExpressionAtlas. The first step is categorizing genes using significant filters and tau score as a specificity index. After calculating tau for each gene in all datasets separately, statistical distance from the maximum expression level was estimated using a new meaningful procedure. Specific expression of a gene in one or several tissues was calculated after the integration of tau and statistical distance estimation, which is called as extended tau approach. Obtained tissue-specific genes for 96 different human tissues were functionally annotated, and some comparisons were carried out to show the effectiveness of the extended tau method.

Results and Discussion

Categorization of genes based on expression level and identification of tissue-specific genes for a large number of tissues/organs were executed. Genes were successfully assigned to multiple tissues by generating the extended tau approach as opposed to the original tau score, which can assign tissue specificity to single tissue only.
Evaluation of carotid intima media thickness in children with idiopathic nephrotic syndrome
Authors: Kamel Ashraf Sayed , AlGhawass Mohamed Mohamed Ezzat , Sayed Muhammad Adel , Roby Sara Aly
Published: December 2022

Background

Nephrotic syndrome is the one of the commonest renal disorders in children. Children with nephrotic syndrome (NS) are at a high risk of atherosclerosis due to hyperlipidemia, hypertension. Carotid intima media thickness (CIMT) is a surrogate marker for atherosclerosis. This study aimed to evaluate the carotid intima media thickness in children with nephrotic syndrome and its relation to different risk factors.

Methods

This is an observational case control study that included forty children with nephrotic syndrome and thirty healthy children as controls. The inclusion criteria were: age of 2 years or more with disease duration of minimum of 1 year and glomerular filtration rate > 90 mL/min/1.73m2. CIMT was assessed by ultrasound. Lipid profile, protein/creatinine ratio in urine and kidney function tests were done.

Results

The mean CIMT (mm) was significantly higher in patients with NS (0.477 ± 0.04) compared to controls (0.39 ± 0.03) (P < 0.001) even when compared across different age groups. 60% of patients had received non-steroid immunosuppressive therapy. CIMT was significantly higher in patients receiving non-steroid immunosuppressive therapy than those receiving steroids alone. Subsequently, CIMT had significant positive correlation to duration of the disease (p = 0.05), body mass index (BMI) (p = 0.03), number of relapses (p = 0.01) and diastolic blood pressures (p = 0.003).

Conclusion

Children with NS had significantly higher CIMT than control group. CIMT was positively correlated to disease duration, number of relapses and BMI. It was significantly higher among patients receiving non-steroid immunosuppressive therapy than those receiving steroids alone.
The awareness and acceptance of anti-COVID 19 vaccination in adolescence
Authors: Cupertino Vita , Bozzola Elena , De Luca Giampaolo , Del Giudice Emanuela , De Martino Giuseppe , Cannataro Piero , Tozzi Alberto Eugenio , Corsello Giovanni
Published: December 2022

Background

COVID-19 had devastating effects on children’s and adolescents’ life, including neuropsychological impairment, discontinuation of social life and education.

Since June 2021, antiCOVID19 vaccination has become available to adolescents in Italy up to 12 years and since December 2021 to children aged more than 5 years. The pediatric population represents a challenging target for vaccination. Aim of the study is to perform a survey among adolescents to explore factors associated with COVID 19 immunization and their perceptions about COVID-19 vaccines.

Methods

Italian students aged 10–17 years were invited to participate in an anonymous online survey regarding their immunization against COVID-19 and their opinion on the immunization practice through a web link to the questionnaire. The study period was March-June 2022. Statistical analysis was performed with SPSS v 21.

Results

In the study period, 895 students entered the survey. A total of 87.3% of respondents were immunized against SARS-CoV2. The most important predictors of being immunized against SARS-CoV2 were having both parents immunized (p < 0, 001) and being aged over 12 years. In the unvaccinated group, the decision was mostly influenced by the family (65.8%). Regardless the immunization status, respondents were willing to receive information about COVID 19 vaccination mostly by their family doctor (51.8%) and at school (28.9%).

Conclusions

Parents’ decisions and attitudes strongly affected the immunization status of adolescents.

Students’ willing to receive COVID 19 vaccine information by family doctors and at school, underline the potential role of paediatricians and school educators in contributing to an increased vaccine coverage among the paediatric age.
New roles for AP-1/JUNB in cell cycle control and tumorigenic cell invasion via regulation of cyclin E1 and TGF-β2
Authors: Pérez-Benavente Beatriz , Fathinajafabadi Alihamze , de la Fuente Lorena , Gandía Carolina , Martínez-Férriz Arantxa , Pardo-Sánchez José Miguel , Milián Lara , Conesa Ana , Romero Octavio A. , Carretero Julián , Matthiesen Rune , Jariel-Encontre Isabelle , Piechaczyk Marc , Farràs Rosa
Published: December 2022

Background

JUNB transcription factor contributes to the formation of the ubiquitous transcriptional complex AP-1 involved in the control of many physiological and disease-associated functions. The roles of JUNB in the control of cell division and tumorigenic processes are acknowledged but still unclear.

Results

Here, we report the results of combined transcriptomic, genomic, and functional studies showing that JUNB promotes cell cycle progression via induction of cyclin E1 and repression of transforming growth factor (TGF)-β2 genes. We also show that high levels of JUNB switch the response of TGF-β2 stimulation from an antiproliferative to a pro-invasive one, induce endogenous TGF-β2 production by promoting TGF-β2 mRNA translation, and enhance tumor growth and metastasis in mice. Moreover, tumor genomic data indicate that JUNB amplification associates with poor prognosis in breast and ovarian cancer patients.

Conclusions

Our results reveal novel functions for JUNB in cell proliferation and tumor aggressiveness through regulation of cyclin E1 and TGF-β2 expression, which might be exploited for cancer prognosis and therapy.
Cluster randomised control trial protocol for estimating the effectiveness and cost-effectiveness of a complex intervention to increase care home staff influenza vaccination rates compared to usual practice (FLUCARE)
Authors: Patel Amrish , Sims Erika , Blacklock Jeanette , Birt Linda , Bion Veronica , Clark Allan , Griffiths Alys , Guillard Cecile , Hammond Amber , Holland Richard , Jones Andy , Jones Liz , Katangwe-Chigamba Thando , Pitcher Jennifer , Ruby Po , Scott Sion , Wagner Adam P. , Ahmed Saiqa , Baqir Wasim , Cook Luke , Dean Tony , Wright David
Published: December 2022

The care home staff influenza vaccination rate in England is significantly lower than the 75% World Health Organisation recommendation. This represents a substantial potential for resident harm. Barriers to staff vaccination stem from individual and organisational levels. Existing interventions address some but not all barriers and are not underpinned by behavioural science theory. This study aims to estimate the effectiveness and cost-effectiveness of a theory-informed intervention to improve care home staff vaccination rates compared to routine practice.

Set in care homes with both nursing and residential focus, and a range of ownership status, only homes providing long stay care to older people with a staff vaccination rate below 40% are eligible to participate. Participation expressions of interest will be sought using a variety of approaches prior to seeking consent.

The primary outcome measure is the proportion of staff vaccinated at 6 months, with secondary outcome measures being proportion vaccinated at 3 months, numbers of staff sick days, general practitioner and nurse visits to care home, care home resident hospitalisations and mortality.

Based on the assumptions that the mean cluster (care home) size is 54 staff, a coefficient of variation of 0.48, control vaccination rate is 55%, intervention 75%, intra-cluster correlation coefficient of 0.2 and with 90% power, and 20% attrition, we require 39 care homes per arm.

Blocked randomisation will be at the level of care home, stratified by the proportion of non-white care home staff, and implemented by Norwich Clinical Trials Unit.

The intervention comprises co-designed information videos and posters, provision of in-house staff vaccination clinics, and incentive scheme and monthly data collection on trial outcomes. Beyond usual practice, the control arm will additionally contribute monthly data.

Data will be collected at the start, monthly and at 6 months, and analysis will be blind to allocation. Statistical analysis will use the intention-to-treat principle with the difference in vaccination rates between groups compared using a random effect logistic regression model at the staff-level.

This will be the first study to use a theory-informed intervention designed to comprehensively address identified barriers to care home staff influenza vaccination.

Trial registration: ISRCTN ISRCTN22729870. Registered on 24 August 22. Secondary identifiers: R209939, IRAS 316820, CPMS 53812.
Novel alendronate-CGS21680 conjugate reduces bone resorption and induces new bone formation in post-menopausal osteoporosis and inflammatory osteolysis mouse models
Authors: Larrañaga-Vera Ane , Toti Kiran S. , Flatow James S. , Haraczy Alexandra J. , Warnick Eugene , Rao Harsha , Gao Zhan-Guo , Sussman Sarah M. , Mediero Aranzazu , Leucht Philipp , Jacobson Kenneth A. , Cronstein Bruce N.
Published: December 2022

Loss of bone is a common medical problem and, while it can be treated with available therapies, some of these therapies have critical side effects. We have previously demonstrated that CGS21680, a selective A2A adenosine receptor agonist, prevents bone loss, but its on-target toxicities (hypotension, tachycardia) and frequent dosing requirements make it unusable in the clinic. We therefore generated a novel alendronate-CGS21680 conjugate (MRS7216), to target the agonist to bone where it remains for long periods thereby diminishing the frequency of administration and curtailing side effects. MRS7216 was synthesized from CGS21680 by sequential activation of the carboxylic acid moiety and reacting with an appropriate amino acid (PEG, alendronic acid) under basic conditions. MRS7216 was tested on C57BL/6J (WT) mice with established osteoporosis (OP) and WT or A2A KO mice with wear particle-induced inflammatory osteolysis (OL). Mice were treated weekly with MRS7216 (10mg/kg). Bone formation was studied after in vivo labeling with calcein/Alizarin Red, and μCT and histology analyses were performed. In addition, human primary osteoblasts and osteoclasts were cultured using bone marrow discarded after hip replacement. Receptor binding studies demonstrate that MRS7216 efficiently binds the A2A adenosine receptor. MRS7216-treated OP and OL mice had significant new bone formation and reduced bone loss compared to vehicle or alendronate-treated mice. Histological analysis showed that MRS7216 treatment significantly reduced osteoclast number and increased osteoblast number in murine models. Interestingly, cultured human osteoclast differentiation was inhibited, and osteoblast differentiation was stimulated by the compound indicating that MRS7216 conjugates represent a novel therapeutic approach to treat osteoporosis and osteolysis.
Effect of arm movement and task difficulty level on balance performance in healthy children: are there sex differences?
Authors: Muehlbauer Thomas , Hill Mathew W. , Schedler Simon
Published: December 2022

Objective

In children, studies have shown that balance performance is worse in boys compared to girls and further studies revealed inferior performance when arm movement was restricted during balance assessment. However, it remains unclear whether restriction of arm movement during balance testing differentially affects children’s balance performance (i.e., boys more than girls). Thus, we compared the influence of arm movement on balance performance in healthy boys versus girls (mean age: ~ 11.5 years) while performing balance tasks with various difficulty level.

Results

In nearly all tests, balance performance (i.e., timed one-legged stance, 3-m beam walking backward step number, Lower Quarter Y-Balance test reach distance) was significantly worse during restricted compared to free arm movement but without any differences between sexes or varying levels of task difficulty. These findings indicated that balance performance is negatively affected by restriction of arm movement, but this does not seem to be additionally influenced by children’s sex and the level of task difficulty.
Strongyloidiasis infection in a borderline lepromatous leprosy patient with adrenocorticoid insufficiency undergoing corticosteroid treatment: a case report
Authors: Morel Rumala , Maddumabandara Kusala , Amarasinghe Nisansala , Amarangani Sujeewa , Amarasinghe Anjalie , Gunathilaka Mihiri , Wathsala Gayani , Bandara Lakmalee , Wijesundara Sunil , Gunaratne Nilupuli , Waduge Roshitha , Medagama Arjuna
Published: December 2022

Background

Strongyloidiasis is a soil-transmitted helminthiasis mainly caused by Strongyloides stercoralis. It is endemic to the tropics and subtropics. Sri Lanka has a 0–1.6% prevalence rate. S. stercoralis infection was identified in a 33-year-old Sri Lankan male patient treated with corticosteroids for borderline lepromatous leprosy with adrenocortical dysfunction.

Case presentation

In March 2020, a 33-year-old Sri Lankan (Sinhalese) male patient presented with watery diarrhea, lower abdominal pain, and post-prandial abdominal fullness. Previously, he was diagnosed with borderline lepromatous leprosy and was treated with rifampicin, clofazimine, and prednisolone 60 mg daily since July 2019. After developing gastrointestinal symptoms, he had defaulted leprosy treatment including the prednisolone for 3 months. Duodenal biopsy revealed numerous intraepithelial nematodes within the lumina of glands in the duodenum whose appearance favored Strongyloides. Fecal wet smear revealed numerous Strongyloidis stercoralis L1 rhabditiform larvae. Larval tracks were seen in the agar plate culture. L3 filariform larvae of Strongyloidis stercoralis were seen in the Harada–Mori culture.

In addition, the short synacthen test revealed adrenocortical insufficiency, and oral hydrocortisone and fludrocortisone were started with albendazole treatment against strongyloidiasis. Fecal wet smear and culture repeated after treatment with albendazole were negative for Strongyloidis stercoralis. The patient was discharged in July 2020 on oral hydrocortisone. One month later his condition was reviewed and the repeated fecal wet smear and agar plate culture was normal. He is being followed up every 3 months.

Conclusion

This is the first case of strongyloidiasis diagnosed in a patient with borderline lepromatous leprosy from Sri Lanka. The patient manifested symptoms of strongyloidiasis while on high-dose steroid therapy for his lepromatous reaction. Subsequently, the patient not only discontinued his steroid therapy, but also developed adrenocortical insufficiency as a complication of leprosy. Therefore, although diagnosis of strongyloidiasis was delayed, his subsequent low steroid levels probably protected him from disseminated disease. This is an interesting case where symptomatic strongyloidiasis was diagnosed in a patient who was initially treated with high-dose steroids but subsequently developed adrenocortical insufficiency. We emphasize the need to screen all patients prior to the commencement of immunosuppressive therapy.
Quantifying headphone listening experience in virtual sound environments using distraction
Authors: Rane Milap , Coleman Philip , Mason Russell , Bech Søren
Published: December 2022

Headphones are commonly used in various environments including at home, outside and on public transport. However, the perception and modelling of the interaction of headphone audio and noisy environments is relatively unresearched. This work investigates the headphone listening experience in noisy environments using the perceptual attributes of distraction and quality of listening experience. A virtual sound environment was created to simulate real-world headphone listening, with variations in foreground sounds, background contexts and busyness, headphone media content and simulated active noise control. Listening tests were performed, where 15 listeners rated both distraction and quality of listening experience across 144 stimuli using a multiple-stimulus presentation. Listener scores were analysed and compared to a computational model of listener distraction. The distraction model was found to be a good predictor of the perceptual distraction rating, with a correlation of 0.888 and an RMSE of 13.4%, despite being developed to predict distraction in the context of audio-on-audio interference in sound zones. In addition, perceived distraction and quality of listening experience had a strong negative correlation of − 0.953. Furthermore, the busyness and type of the environment, headphone media, loudness of the foreground sound and active noise control on/off were significant factors in determining the distraction and quality of listening experience scores.
Can new healthy luxury food products accelerate short food supply chain formation via social media marketing in high-income countries?
Authors: Wiedenroth Christoph F. , Otter Verena
Published: December 2022

Social media marketing is a promising tool for successful product placement of new healthy luxury food products, a subcategory of superfoods. Despite its growing popularity, no studies have investigated how social media marketing affects consumers’ quality perception process for such superfoods and whether this provides opportunities for farmers to gain a competitive advantage in direct marketing channels. Therefore, we integrate media richness theory into the food quality guidance model, compile a data set of 697 German fruit consumers from May to June 2020, and analyze this sample via partial least square analysis. Results show that social media marketing is a viable tool for new healthy luxury food products if media content is highly experience providing. Furthermore, it offers opportunities for the formation of shorter food supply chains as farmers could, through the provision of engaging social media marketing content, sell new healthy luxury food products directly to the final consumer. This research provides implications to farmers, retailers and policy makers to exploit the social media marketing potential of new healthy luxury food products.
Reproducible and opposing gut microbiome signatures distinguish autoimmune diseases and cancers: a systematic review and meta-analysis
Authors: Islam Md Zohorul , Tran Melissa , Xu Tao , Tierney Braden T. , Patel Chirag , Kostic Aleksandar David
Published: December 2022

Background

The gut microbiome promotes specific immune responses, and in turn, the immune system has a hand in shaping the microbiome. Cancer and autoimmune diseases are two major disease families that result from the contrasting manifestations of immune dysfunction. We hypothesized that the opposing immunological profiles between cancer and autoimmunity yield analogously inverted gut microbiome signatures. To test this, we conducted a systematic review and meta-analysis on gut microbiome signatures and their directionality in cancers and autoimmune conditions.

Methodology

We searched PubMed, Web of Science, and Embase to identify relevant articles to be included in this study. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements and PRISMA 2009 checklist. Study estimates were pooled by a generic inverse variance random-effects meta-analysis model. The relative abundance of microbiome features was converted to log fold change, and the standard error was calculated from the p-values, sample size, and fold change.

Results

We screened 3874 potentially relevant publications. A total of 82 eligible studies comprising 37 autoimmune and 45 cancer studies with 4208 healthy human controls and 5957 disease cases from 27 countries were included in this study. We identified a set of microbiome features that show consistent, opposite directionality between cancers and autoimmune diseases in multiple studies. Fusobacterium and Peptostreptococcus were the most consistently increased genera among the cancer cases which were found to be associated in a remarkable 13 (+0.5 log fold change in 5 studies) and 11 studies (+3.6 log fold change in 5 studies), respectively. Conversely, Bacteroides was the most prominent genus, which was found to be increased in 12 autoimmune studies (+0.2 log fold change in 6 studies) and decreased in six cancer studies (−0.3 log fold change in 4 studies). Sulfur-metabolism pathways were found to be the most frequent pathways among the member of cancer-increased genus and species.

Conclusions

The surprising reproducibility of these associations across studies and geographies suggests a shared underlying mechanism shaping the microbiome across cancers and autoimmune diseases.
Dynamics of rice microbiomes reveal core vertically transmitted seed endophytes
Authors: Zhang Xiaoxia , Ma Yi-Nan , Wang Xing , Liao Kaiji , He Shanwen , Zhao Xia , Guo Hebao , Zhao Dongfang , Wei Hai-Lei
Published: December 2022

Background

Plants and their associated microbiota constitute an assemblage of species known as holobionts. The plant seed microbiome plays an important role in nutrient uptake and stress attenuation. However, the core vertically transmitted endophytes remain largely unexplored.

Results

To gain valuable insights into the vertical transmission of rice seed core endophytes, we conducted a large-scale analysis of the microbiomes of two generations of six different rice varieties from five microhabitats (bulk soil, rhizosphere, root, stem, and seed) from four geographic locations. We showed that the microhabitat rather than the geographic location and rice variety was the primary driver of the rice microbiome assemblage. The diversity and network complexity of the rice-associated microbiome decreased steadily from far to near the roots, rice exterior to interior, and from belowground to aboveground niches. Remarkably, the microbiomes of the roots, stems, and seeds of the rice interior compartments were not greatly influenced by the external environment. The core bacterial endophytes of rice were primarily comprised of 14 amplicon sequence variants (ASVs), 10 of which, especially ASV_2 (Pantoea) and ASV_48 (Xanthomonas), were identified as potentially vertically transmitted taxa because they existed across generations, were rarely present in exterior rice microhabitats, and were frequently isolated from rice seeds. The genome sequences of Pantoea and Xanthomonas isolated from the parental and offspring seeds showed a high degree of average nucleotide and core protein identity, indicating vertical transmission of seed endophytes across generations. In silico prediction indicated that the seed endophytes Pantoea and Xanthomonas possessed streamlined genomes with short lengths, low-complexity metabolism, and various plant growth-promoting traits. We also found that all strains of Pantoea and Xanthomonas exhibited cellulase activity and produced indole-3-acetic acid. However, most strains exhibited insignificant antagonism to the major pathogens of rice, such as Magnaporthe oryzae and X. oryzae pv. oryzae.

Conclusion

Overall, our study revealed that microhabitats, rather than site-specific environmental factors or host varieties, shape the rice microbiome. We discovered the vertically transmitted profiles and keystone taxa of the rice microbiome, which led to the isolation of culturable seed endophytes and investigation of their potential roles in plant-microbiome interactions. Our results provide insights on vertically transmitted microbiota and suggest new avenues for improving plant fitness via the manipulation of seed-associated microbiomes.
Functional noninvasive detection of glycolytic pancreatic ductal adenocarcinoma
Authors: Heid Irina , Münch Corinna , Karakaya Sinan , Lueong Smiths S. , Winkelkotte Alina M. , Liffers Sven T. , Godfrey Laura , Cheung Phyllis F. Y. , Savvatakis Konstantinos , Topping Geoffrey J. , Englert Florian , Kritzner Lukas , Grashei Martin , Tannapfel Andrea , Viebahn Richard , Wolters Heiner , Uhl Waldemar , Vangala Deepak , Smeets Esther M. M. , Aarntzen Erik H. J. G. , Rauh Daniel , Weichert Wilko , Hoheisel Jörg D. , Hahn Stephan A. , Schilling Franz , Braren Rickmer , Trajkovic-Arsic Marija , Siveke Jens T.
Published: December 2022

Background

Pancreatic ductal adenocarcinoma (PDAC) lacks effective treatment options beyond chemotherapy. Although molecular subtypes such as classical and QM (quasi-mesenchymal)/basal-like with transcriptome-based distinct signatures have been identified, deduced therapeutic strategies and targets remain elusive. Gene expression data show enrichment of glycolytic genes in the more aggressive and therapy-resistant QM subtype. However, whether the glycolytic transcripts are translated into functional glycolysis that could further be explored for metabolic targeting in QM subtype is still not known.

Methods

We used different patient-derived PDAC model systems (conventional and primary patient-derived cells, patient-derived xenografts (PDX), and patient samples) and performed transcriptional and functional metabolic analysis. These included RNAseq and Illumina HT12 bead array, in vitro Seahorse metabolic flux assays and metabolic drug targeting, and in vivo hyperpolarized [1-13C]pyruvate and [1-13C]lactate magnetic resonance spectroscopy (HP-MRS) in PDAC xenografts.

Results

We found that glycolytic metabolic dependencies are not unambiguously functionally exposed in all QM PDACs. Metabolic analysis demonstrated functional metabolic heterogeneity in patient-derived primary cells and less so in conventional cell lines independent of molecular subtype. Importantly, we observed that the glycolytic product lactate is actively imported into the PDAC cells and used in mitochondrial oxidation in both classical and QM PDAC cells, although more actively in the QM cell lines. By using HP-MRS, we were able to noninvasively identify highly glycolytic PDAC xenografts by detecting the last glycolytic enzymatic step and prominent intra-tumoral [1-13C]pyruvate and [1-13C]lactate interconversion in vivo.

Conclusion

Our study adds functional metabolic phenotyping to transcriptome-based analysis and proposes a functional approach to identify highly glycolytic PDACs as candidates for antimetabolic therapeutic avenues.
Assessing the impact of the Royal Canadian Mounted Police (RCMP) protocol and Emotional Resilience Skills Training (ERST) among diverse public safety personnel
Authors: Carleton R. Nicholas , McCarron Michelle , Krätzig Gregory P. , Sauer-Zavala Shannon , Neary J. Patrick , Lix Lisa M. , Fletcher Amber J. , Camp Ronald D. , Shields Robyn E. , Jamshidi Laleh , Nisbet Jolan , Maguire Kirby Q. , MacPhee Renée S. , Afifi Tracie O. , Jones Nicholas A. , Martin Ronald R. , Sareen Jitender , Brunet Alain , Beshai Shadi , Anderson Gregory S. , Cramm Heidi , MacDermid Joy C. , Ricciardelli Rosemary , Rabbani Rasheda , Teckchandani Taylor A. , Asmundson Gordon J. G.
Published: December 2022

Background

Public safety personnel (PSP; e.g., border services personnel, correctional workers, firefighters, paramedics, police, public safety communicators) are frequently exposed to potentially psychologically traumatic events. Such events contribute to substantial and growing challenges from posttraumatic stress injuries (PTSIs), including but not limited to posttraumatic stress disorder.

Methods

The current protocol paper describes the PSP PTSI Study (i.e., design, measures, materials, hypotheses, planned analyses, expected implications, and limitations), which was originally designed to evaluate an evidence-informed, proactive system of mental health assessment and training among Royal Canadian Mounted Police for delivery among diverse PSP (i.e., firefighters, municipal police, paramedics, public safety communicators). Specifically, the PSP PTSI Study will: (1) adapt, implement, and assess the impact of a system for ongoing (i.e., annual, monthly, daily) evidence-based assessments; (2) evaluate associations between demographic variables and PTSI; (3) longitudinally assess individual differences associated with PTSI; and, (4) assess the impact of providing diverse PSP with a tailored version of the Emotional Resilience Skills Training originally developed for the Royal Canadian Mounted Police in mitigating PTSIs based on the Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders. Participants are assessed pre- and post-training, and then at a follow-up 1-year after training. The assessments include clinical interviews, self-report surveys including brief daily and monthly assessments, and daily biometric data. The current protocol paper also describes participant recruitment and developments to date.

Discussion

The PSP PTSI Study is an opportunity to implement, test, and improve a set of evidence-based tools and training as part of an evidence-informed solution to protect PSP mental health. The current protocol paper provides details to inform and support translation of the PSP PTSI Study results as well as informing and supporting replication efforts by other researchers.

Trial registration

Hypotheses Registration: aspredicted.org, #90136. Registered 7 March 2022—Prospectively registered. Trial registration: ClinicalTrials.gov, NCT05530642. Registered 1 September 2022—Retrospectively registered. The subsequent PSP PTSI Study results are expected to benefit the mental health of all participants and, ultimately, all PSP.
Chromatin state distribution of residue-specific histone acetylation in early myoblast differentiation
Authors: Li Yuan , Khilji Saadia , Mach Yan Z. , Chen Jihong , Li Qiao
Published: December 2022

Dynamic changes in epigenetic landscape reflect a critical command of lineage-specific gene expression. In an effort to discern the epigenetic regulatory networks of myogenic differentiation, we have used systematic and integrative approaches to explore multi-omics datasets on global myogenic gene expression, histone acetylation and acetyltransferase occupancy in view of distinct chromatin states. In this brief report, we discuss experimental design and provide a comprehensive assessment regarding data quality control, filtering and processing. We also define a gene-level overlap between RNA-seq and ChIP-seq datasets through integrative analyses to offer strategies for future use of the data. Furthermore, our analyses generate a blueprint on chromatin state distribution of residue-specific histone acetylation and concomitant association with histone acetyltransferase p300 in committed skeletal myoblasts and differential histone acetylation signatures at the onset of myoblast differentiation. These datasets can be further utilized to delineate the function of muscle-specific regulatory elements governed by other muscle myogenic regulators or signaling molecules.
Analysis of volatile compounds of black bean, mung bean, and soybean extracts prepared with distillation under reduced pressure–continuous liquid–liquid extraction and hot water extraction
Authors: Han Eunji , Ahn Hyunwoo , Lee Seongho , Lee Kwang-Geun
Published: December 2022

In this study, volatile compounds of various beans (black bean, mung bean, and soybean) were analyzed on the basis of particle sizes and extraction temperatures by two extraction methods, namely, distillation under reduced pressure–continuous liquid–liquid extraction (DRP–LLE) and hot water extraction (HWE). The experimental results confirmed the presence of 10 volatile components. The five major volatile compounds were hexanal, 2-methyl-1-butanol, 1-hexanol, 1-octen-3-ol and benzaldehyde. The highest total volatile compound concentrations in the extracts of black bean, mung bean, and soybean using DRP–LLE were obtained at 60 °C and 355–500 μm, 60 °C and 500–710 μm, and 50 °C and 355–500 μm, respectively. For the same particle size, the total volatile compound concentrations in the extracts of black bean, mung bean, and soybean obtained by HWE at 70 °C were 2–3 times significantly higher than those obtained at 90 °C. Moreover, the highest total volatile compound concentration was obtained in the black bean extract by HWE at 500–710 μm, while the lowest total volatile compound concentration in the soybean extract was obtained by HWE at 500–710 μm. The total concentrations of volatiles in the black bean and soybean extracts obtained by DRP–LLE were significantly higher than those obtained by HWE.
Clinical pharmacists in primary care general practices: evaluation of current workforce and their distribution
Authors: Chopra Elisha , Choudhary Tanvi , Hazen Ankie , Shrestha Sunil , Dehele Inderpal , Paudyal Vibhu
Published: December 2022

Background

General practices in primary care across England are increasingly employing clinical pharmacists to help tackle the workforce crisis and alleviate pressure. Clinical pharmacists can provide administrative and clinical duties, including non-medical prescribing, advice on polypharmacy and medicines optimisation. The aim of this study was to investigate the distribution of clinical pharmacists in general practice across England, and explore the relationship between the distribution and regional demography.

Methods

This study used publicly available government database from various sources pertaining to primary care general practice workforce and population demographics of England. The number and distribution of pharmacists working within general practices in England were analysed and compared across practices considering general practitioner (GP), nurse and patient population in the practices, patients age ≥ 65 years and over and the Index of Multiple Deprivation (IMD) scores.

Results

Twenty two percentage (1469 of 6674) of practices in England were found to have access to a clinical pharmacist, equating to 1358 full-time equivalent (FTE) pharmacists and a mean pharmacist FTE of 10.07 (95% CI 8.40, 11.75, SD = 9.84) per Clinical Commissioning Group (CCG). A significant relationship between pharmacist FTE and the number of patients 65 years and older [r (132) = 0.75, P < 0.001)] was observed; however, the distribution was not related to population deprivation scores.

Conclusions

Approximately one in five general practices in England have access to a clinical pharmacist. Further research is needed to ensure wider and equitable distribution based on workforce needs and practice population demography.
Pharmacist management of atrial fibrillation in UK primary care: a qualitative study
Authors: Al-Arkee Shahd , Mason Julie , Lindenmeyer Antje , Jalal Zahraa
Published: December 2022

Background

Atrial fibrillation (AF) affects up to 2% of the UK population. AF is a potentially long-term condition that needs management, and as such primary care pharmacists may have a substantial role in supporting the management of AF.

Objectives

This study aims to explore the role of primary care pharmacists, working in community pharmacies and general practices (GPs), in supporting the management of AF. Furthermore, this study investigates pharmacists’ confidence in their knowledge and their attitudes towards incorporating AF-associated mobile apps use into their current practice.

Methods

A qualitative study was conducted, using one-to-one semi-structured, audio-recorded interviews with primary care pharmacists. The topic guide was developed based on pharmacy visits and included the most relevant constructs from the ‘consolidated framework for implementation research (CFIR)’. All interviews were audio-recorded, transcribed verbatim and thematically analysed until saturation was achieved, guided by Braun and Clarke’s 6-step research method. This study was given a favourable opinion on 5 September 2019 by the University of Birmingham (UOB) Research Ethics Committee (Reference ERN_19-0908).

Results

Thematic saturation was achieved after 11 interviews with primary care pharmacists (seven community pharmacists, and four GP pharmacists). Three main themes emerged relating to (1) the clinical role of pharmacists in the management of AF; (2) knowledge and awareness; and (3) prioritisation of resources. The first highlighted that primary care pharmacists were an underutilised resource within AF management. The second demonstrated that pharmacists, especially those based in the community, felt a lack of confidence in their knowledge of AF and its management, mainly community pharmacists due to other roles taking precedence over clinical roles. Both community and GP pharmacists expressed the need to have further training in this therapeutic area to be able to effectively support patients with AF. The third shed light on the pharmacists’ views relating to the technological revolution in healthcare. Pharmacists expressed an interest in using apps to support their current practice.

Conclusions

Primary care pharmacists supported an extended care to AF management from screening to consultations, yet the provision of such services remains limited and inconsistent. Future research should focus on understanding the ways in which pharmacists’ role can be adapted toward greater involvement in clinical care.