bluuebunny/crossref_metadata_2025 huggingface dataset:
Revealing the Active Compounds and Mechanism of Banxia Xiexin Decoction Against Gastric Ulcer by Network Pharmacology and Molecular Docking
Authors: Ji Wanli , Zhuang Xiaoyu , Hu Cheng , Zhang Yifan
Published: August 2022

Gastric ulcer (GU) is a clinically common gastrointestinal disease with a long disease course that frequently reoccurs. Banxia Xiexin decoction (BXD), a traditional Chinese medicine prescription, has a prominent protective effect against GU. Nonetheless, the therapeutic mechanisms of BXD against GU remain elusive. In this study, a rat model of GU was established by gavage with 95% ethanol, and BXD significantly attenuated the inflammatory effect of GU in rats. An “active ingredient–target” interaction and GU protein–protein interaction networks were constructed based on system biology, which could screen out the crucial active ingredients. The target protein–protein interaction network for the BXD treatment of GU was constructed to identify the key target proteins with network topology parameters. The DAVID database was then used to perform Gene Ontology and Kyoto encyclopedia of genes and genomes enrichment analysis on the proteins targeted by BXD in the treatment of GU. Finally, molecular docking technology was used to study the interactions between key active ingredients and core target proteins. A total of 89 active ingredients of BXD were screened and 63 target proteins of BXD in the treatment of GU were identified. Through the analysis of protein–protein interaction and the active ingredient–target protein network diagram, it was found that tumor necrosis factor-α(TNF-α), AKT1, and PTGS2 may play a key role in the treatment of GU by BXD. Molecular docking showed that these 3 core target proteins had a good affinity with the main components of BXD, including baicalein, norwogonin, and skullcapflavone II. The mechanism of BXD against GU may involve the inhibition of inflammatory response and oxidative stress, involving signaling pathways such as TNF, hypoxia-inducible factor-1, and mitogen-activated protein kinase. Network pharmacology and molecular docking technology indicated the key active ingredients, target proteins, and signal pathways that may be the biological basis of BXD in the treatment of GU.
Therapeutic potential of epiphyseal growth plate cells for bone regeneration in an osteoporosis model
Authors: Baek Inho , Bello Alvin Bacero , Jeon Jieun , Arai Yoshie , Cha Byung-Hyun , Kim Byoung Ju , Lee Soo-Hong
Published: August 2022

Bone growth occurs in the epiphyseal growth plate (EGP) and epiphyseal growth plate cells (EGPCs) exist in EGP. EGPCs, including skeletal stem cells (SSCs), are cells that induce bone growth and development through endochondral ossification. Recently, the superiority of bone regeneration through endochondral ossification has been reported. Our study compared EGPCs with bone marrow-derived mesenchymal stem cells (BM-MSCs) and suggested the therapeutic potential of new bone regeneration. In this study, we analyzed the characteristics between EGPCs and BM-MSCs based on morphological characteristics and molecular profiles. EGPCs expressed chondrogenic and osteogenic markers higher than BM-MSCs. Additionally, in co-culture with BM-MSCs, EGPCs induced an increase in chondrogenic, osteogenic, and hypertrophic markers of BM-MSCs. Finally, EGPCs induced higher bone regeneration than BM-MSCs in the osteoporosis model. Overall, we suggest the possibility of EGPCs as cell therapy for effective bone regeneration.
Cutaneous sarcoidosis in eyebrows cosmetically pigmented with microblading method: A case report and review of the literature
Authors: Spurr Alison , Hanna Nardin , Colantonio Sophia
Published: August 2022

Microblading is a novel method of semi-permanent makeup, which has achieved popularity in the last few years. We present the case of a patient who developed cutaneous sarcoidosis after microblading of her eyebrows. A 45-year-old female presented with a 6-month history of pruritic erythematous granulomatous plaques on bilateral eyebrows corresponding to the site of microblading 1.5 years prior. A tissue biopsy was preformed which was consistent with cutaneous sarcoidosis. An extensive work-up including assessment by respirology, rheumatology, and ophthalmology did not reveal any evidence of systemic sarcoidosis. The patient was treated with intralesional triamcinolone injections and tacrolimus ointment twice daily, with complete resolution. To our knowledge, this is the first case of cutaneous sarcoidosis associated with microblading in the literature. Dermatologists should be aware of popular and novel cosmetic procedures and the potential complications that arise from these interventions.
When Birds of a Feather Instagram Together: Debating the Image of Islam in Echo Chambers and Through Trench Warfare on Social Media
Authors: Aydin Zeynep , Fuess Albrecht , Förster Marcel , Sunier Thijl
Published: August 2022

Social media contributions surrounding the Charlie Hebdo attacks have been key in the creation and evolution of the image of Islam online. While the attacks were seen as an affront to French values and ways of life, online exchanges have traveled around the globe. Especially with social media platforms, such as Twitter and Instagram, offering immediate translations of captions has increased the reach of posts immensely. Specifically, hashtag use has the ability to transcend national boundaries and helps in the creation of echo chambers and or fuels trench warfare online. This article extends on this work by examining how the image of Islam is transmitted and changed on Instagram through the use of the hashtag #CharlieHebdo. Specifically, the following three primary research questions are examined: (1) How does hashtag co-occurrence, in the discussion surrounding Charlie Hebdo, indicate echo chamber behavior? (2) How does trench warfare impact the debate surrounding the image of Islam within the #CharlieHebdo conversation? (3) Which categories can posts be put into based on other hashtags that are used simultaneously? To answer these questions, Instagram posts, posted nearly 6 years after the Charlie Hebdo attack was perpetrated in Paris and during the time of the trials of the suspects took place, are used as a case study. It was found that Islamophobia within the Charlie Hebdo debate online indeed indicates echo chamber behavior. The significance of this study was found to be two-fold. First, it extends the research on detecting echo chamber behavior through social network analysis and sentiment analysis of co-used hashtags. Second, it highlights the fact that trench warfare is a well understood tactic by Instagram users, for the hijacking of hashtags, and the role it plays in the polarization of hashtag communities.
Comparison of precise and approximated building height: Estimation from number of building storeys and spatial variations in the Tokyo metropolitan region
Authors: Usui Hiroyuki
Published: August 2022

Precise building height is indispensable for evaluating variability in building heights. However, relevant data are not always available. Conventionally, building height is approximated as the product of the number of building storeys and floor height, called approximated building height. However, there is no consensus on how floor height, a key determinant of approximated building height, should be set. In Japan, increasingly precise building height data are becoming available as an open 3D urban model. This provides the motivation for answering the following research questions, in the context of the Tokyo metropolitan region: (1) What is the difference between approximated and precise building height? (2) How should we set floor height to minimise the difference between approximated and precise building height? The results show that (1) the average difference is −3.46 m if floor height, c, is 5 m, −0.87 m if c is 4 m and 1.71 m if c is 3 m; (2) c = 4 can effectively estimate building height from the number of storeys; and (3) the greatest difference between approximated and precise building height is spatially clustered where commercial zones and industrial zones are allocated, with their degree being dependent on how floor height is set. Furthermore, it is found that (1) in commercial zones and industrial districts, the optimal floor height, defined as the optimal solution which minimises the sum of squared differences between approximated and precise building height, is greater than 4 m; (2) in mid/high rise residential districts, the optimal floor height ranges from 3 to 3.4 m; and (3) in low-rise residential districts, the optimal floor height ranges from 3.5 to 3.9 m. The findings of this paper can help urban planners find the optimal floor height in each district and understand spatial variations in building and floor heights.
Avoid or seek light – a randomized crossover fMRI study investigating opposing treatment strategies for photophobia in migraine
Authors: Matt Eva , Aslan Tuna , Amini Ahmad , Sariçiçek Kardelen , Seidel Stefan , Martin Paul , Wöber Christian , Beisteiner Roland
Published: August 2022

Background

Photophobia, the aberrantly increased sensitivity to light, is a common symptom in migraine patients and light discomfort is frequently found as a trigger for migraine attacks. In behavioral studies, planned exposure to light was found to reduce headache in migraine patients with photophobia, potentially by increasing habituation to this migraine trigger. Here, we aimed to elucidate neurophysiological mechanisms of light exposure versus light deprivation in migraine patients using functional magnetic resonance imaging (fMRI).

Methods

Ten migraine patients (9 female, age = 28.70 ± 8.18 years) and 11 healthy controls (9 female, age = 23.73 ± 2.24 years) spent one hour on 7 consecutive days exposed to flashing light (Flash) or darkness (Dark) using a crossover design with a wash-out period of 3 months. Study participants kept a diary including items on interictal and ictal photophobia, presence and severity of headache 7 days before, during and 7 days after the interventions. One week before and one day after both interventions, fMRI using flickering light in a block design was applied. Functional activation was analyzed at whole-brain level and habituation of the visual cortex (V1) was modeled with the initial amplitude estimate and the corrected habituation slope.

Results

Mean interictal photophobia decreased after both interventions, but differences relative to the baseline did not survive correction for multiple comparisons. At baseline, flickering light induced activation in V1 was higher in the patients compared to the controls, but activation normalized after the Flash and the Dark interventions. V1 habituation indices correlated with headache frequency, headache severity and ictal photophobia. In the Flash condition, the individual change of headache frequency relative to the baseline corresponded almost perfectly to the change of the habituation slope compared to the baseline.

Conclusions

On average, light exposure did not lead to symptom relief, potentially due to the short duration of the intervention and the high variability of the patients’ responses to the intervention. However, the strong relationship between visual cortex habituation and headache symptoms and its modulation by light exposure might shed light on the neurophysiological basis of exposure treatment effects.

Trial registration

NCT05369910 (05/06/2022, retrospectively registered).
Twinkle twinkle brittle star: the draft genome of Ophioderma brevispinum (Echinodermata: Ophiuroidea) as a resource for regeneration research
Authors: Mashanov Vladimir , Machado Denis Jacob , Reid Robert , Brouwer Cory , Kofsky Janice , Janies Daniel A.
Published: August 2022

Background

Echinoderms are established models in experimental and developmental biology, however genomic resources are still lacking for many species. Here, we present the draft genome of Ophioderma brevispinum, an emerging model organism in the field of regenerative biology. This new genomic resource provides a reference for experimental studies of regenerative mechanisms.

Results

We report a de novo nuclear genome assembly for the brittle star O. brevispinum and annotation facilitated by the transcriptome assembly. The final assembly is 2.68 Gb in length and contains 146,703 predicted protein-coding gene models. We also report a mitochondrial genome for this species, which is 15,831 bp in length, and contains 13 protein-coding, 22 tRNAs, and 2 rRNAs genes, respectively. In addition, 29 genes of the Notch signaling pathway are identified to illustrate the practical utility of the assembly for studies of regeneration.

Conclusions

The sequenced and annotated genome of O. brevispinum presented here provides the first such resource for an ophiuroid model species. Considering the remarkable regenerative capacity of this species, this genome will be an essential resource in future research efforts on molecular mechanisms regulating regeneration.
Assessment of DNA methylation in porcine immune cells reveals novel regulatory elements associated with cell-specific gene expression and immune capacity traits
Authors: Corbett Ryan J. , Luttman Andrea M. , Herrera-Uribe Juber , Liu Haibo , Raney Nancy E. , Grabowski Jenna M. , Loving Crystal L. , Tuggle Christopher K. , Ernst Catherine W.
Published: August 2022

Background

Genetics studies in the porcine immune system have enhanced selection practices for disease resistance phenotypes and increased the efficacy of porcine models in biomedical research; however limited functional annotation of the porcine immunome has hindered progress on both fronts. Among epigenetic mechanisms that regulate gene expression, DNA methylation is the most ubiquitous modification made to the DNA molecule and influences transcription factor binding as well as gene and phenotype expression. Human and mouse DNA methylation studies have improved mapping of regulatory elements in these species, but comparable studies in the pig have been limited in scope.

Results

We performed whole-genome bisulfite sequencing to assess DNA methylation patterns in nine pig immune cell populations: CD21+ and CD21− B cells, four T cell fractions (CD4+, CD8+, CD8+CD4+, and SWC6γδ+), natural killer and myeloid cells, and neutrophils. We identified 54,391 cell differentially methylated regions (cDMRs), and clustering by cDMR methylation rate grouped samples by cell lineage. 32,737 cDMRs were classified as cell lowly methylated regions (cLMRs) in at least one cell type, and cLMRs were broadly enriched in genes and regions of intermediate CpG density. We observed strong correlations between differential methylation and expression across immune cell populations, with cell-specific low methylation disproportionately impacting genes exhibiting enriched gene expression in the same cell type. Motif analysis of cLMRs revealed cell type-specific enrichment of transcription factor binding motifs, indicating that cell-specific methylation patterns may influence accessibility by trans-acting factors. Lastly, cDMRs were enriched for immune capacity GWAS SNPs, and many such overlaps occurred within genes known to influence immune cell development and function (CD8B, NDRG1).

Conclusion

Our DNA methylation data improve functional annotation of the porcine genome through characterization of epigenomic regulatory patterns that contribute to immune cell identity and function, and increase the potential for identifying mechanistic links between genotype and phenotype.
Effects of berberine hydrochloride on immune response in the crab Charybdis japonica
Authors: Gao Tian-heng , Han Ming-ming , Zhou Hui , Zhu Chen-xi , Yang Ying , Zuraini Zakaria , Guo Yan-Xia , Jiang Qi-chen
Published: August 2022

Berberine hydrochloride is the main effective component of Coptis spp. used in Chinese herbal medicine and its underlying molecular mechanisms, responsible for inducing effects in crustacean species, are not fully understood. In this study, the molecular response of the crab Charybdis japonica to berberine hydrochloride exposure was studied using transcriptome sequencing. The survival rate, gene expression and activities of several immune enzymes were measured after berberine hydrochloride treatments, with or without injection of the pathogenic bacterium Aeromonas hydrophila. A total of 962 differentially expressed genes (464 up-regulated and 498 down-regulated) were observed during exposure to 100 mg/L of berberine hydrochloride and in the control group after 48 h. Enrichment analysis revealed that these genes are involved in metabolism, cellular processes, signal transduction and immune functions, indicating that exposure to berberine hydrochloride activated the immune complement system. This bioactive compound simultaneously activated fibrinogen beta (FGB), fibrinogen alpha (FGA), alpha-2-macroglobulin (A2M), kininogen (KNG), fibrinogen gamma chain (FGB), alpha-2-HS-glycoprotein (AHSG), caspase-8 (CASP8), cathepsin L (CTSL), adenylate cyclase 3 (Adcy3) and MMP1. Its action could significantly increase the survival rate of the crabs injected with A. hydrophila and promote the activity of LZM, Caspas8, FGA, ACP and AKP in the hepatopancreas. When A. hydrophila was added, the neutralization of 300 mg/L berberine hydrochloride maximized the activities of Caspas8, LZM, ACP and AKP. Our results provide a new understanding of the potential effects of berberine hydrochloride on the immune system mechanisms in crustaceans.
Homocysteine is related to enlarged perivascular spaces in the brainstem in patients with isolated pontine infarction
Authors: Fu Yunting , Yun Wenwei , Zhang Zhixiang , Ma Yi , Xiao Lulu , Zhang Min , Zhu Wusheng
Published: August 2022

Background

Homocysteine is correlated with several imaging features of cerebral small vessel disease including white matter hyperintensities, lacunes, and enlarged perivascular spaces (EPVS) in the basal ganglia. However, little is known about EPVS in the brainstem. This study aimed to investigate the correlation between serum total homocysteine (tHcy) and EPVS in the brainstem in patients with acute isolated pontine infarction.

Methods

Consecutive patients with isolated pontine infarction were retrospectively enrolled. Clinical characteristics and laboratory tests including tHcy were recorded. Imaging markers of cerebral small vessel disease including EPVS in the basal ganglia (BG-EPVS), EPVS in the centrum semiovale, and EPVS in the midbrain or pons (brainstem-EPVS) were assessed using conventional magnetic resonance imaging. The relation between tHcy and EPVS of different parts in the brain was analyzed using univariate and multivariate regression model.

Results

A total of 227 patients were included (mean age 67.10 ± 9.38 years, male sex 58.6%). The frequencies of brainstem-EPVS and moderate to severe BG-EPVS accounted for 40.1% (91/227) and 40.5% (92/227) respectively. After controlling for confounding factors, multivariate logistic regression analyses showed that tHcy was an independent risk factor for both moderate to severe BG-EPVS (P = 0.003, P for trend < 0.001) and the presence of brainstem-EPVS (P < 0.001, P for trend < 0.001) in a dose-dependent manner. Furthermore, multivariate linear regression model indicated that the presence of brainstem-EPVS (β = 0.264, 95% confidence interval = 0.143-0.402, P < 0.001) and the severity of BG-EPVS (β = 0.162, 95% confidence interval = 0.024-0.197, P = 0.013) were positively associated with serum tHcy.

Conclusions

Serum tHcy is correlated with brainstem-EPVS and BG-EPVS dose-dependently. This study may support a contributing role for homocysteine in the pathophysiology of EPVS in the brainstem and the basal ganglia.
COVID-19 vaccine adoption and hesitancy among older Veterans
Authors: Wyte-Lake Tamar , Levy Cari , Hovsepian Sona , Mudoh Yvonne , Schmitz Cheryl , Dobalian Aram
Published: August 2022

Background

Older adults are particularly at risk for severe illness or death from COVID-19. Accordingly, the Veterans Health Administration (VA) has prioritized this population group in its COVID-19 vaccination strategy. This study examines the receptivity of Veterans enrolled in the VA’s Geriatric Patient Aligned Care Team (GeriPACT) to receiving the COVID-19 vaccine. GeriPACT is an outpatient primary care program that utilizes multi-disciplinary teams to provide health services to older Veterans.

Methods

We conducted semistructured interviews with 42 GeriPACT-enrolled Veterans from five states. Participants were asked to identify barriers to vaccine acceptance. We gathered data from January-March 2021 and analyzed them using qualitative methods.

Results

Both White and African American GeriPACT Veterans had minimal vaccine hesitancy towards the COVID-19 vaccine. On-line registration and ineligibility of a spouse/caregiver for vaccination were primary barriers to early vaccination.

Conclusions

As the first wave of early adopters of the COVID-19 vaccination effort nears completion, targeted strategies are needed to understand and respond to vaccine hesitancy to lower the risk of subsequent waves of infections. The 2021 SAVE LIVES Act, begins to address identified vaccination barriers by permitting vaccination of Veteran spouses and caregivers, but consideration must be given to creating alternatives to on-line registration and allowing spouses and caregivers to register for appointments together.
Environmental and personal factors for osteoporosis or osteopenia from a large health check-up database: a retrospective cohort study in Taiwan
Authors: Chung Ping-Chen , Chan Ta-Chien
Published: August 2022

Background

Osteoporosis is an important public health issue in aging societies because of its associated morbidity, mortality, and decreased quality of life. The study aims to identify the association of low bone mineral density, including osteoporosis and osteopenia, with environmental and personal factors.

Methods

The data of participants aged ≥ 20 years with multiple visits were obtained from a health check-up database in Taiwan from 2008 to 2016. Multivariable logistic regressions were performed to identify the selected factors associated with low bone mineral density for multiple visit data.

Results

A total of 194,910 participants with 359,943 visits were included in this study. The prevalence of low bone mineral density (BMD) in the study population was 10.6% (n = 20.615). Older women, ever and current smokers (odds ratio (OR) = 1.04 [95% confidence interval (CI) = 1.01, 1.08]), or participants who were underweight (OR = 1.72 [1.64, 1.81]), consumed a vegetarian diet (OR = 1.32 [1.25, 1.39]), or had higher triglyceride levels (OR = 1.04 [1.01, 1.06]) were significantly associated with a higher risk of low BMD. Participants who had higher educational years (OR = 0.43 [0.41, 0.46]), higher physical activity (OR = 0.93 [0.89, 0.97]), appropriate sleep duration and better quality (OR = 0.98 [0.97, 0.99]), dairy intake (≥ 1 slice of yogurt or cheese/week, OR = 0.97 [0.95, 0.99]), higher uric acid (OR = 0.93 [0.91, 0.95]), higher walkability (OR = 0.997 [0.995,0.999]), and higher solar radiation exposure (OR = 0.997 [0.97,0.99]) were significantly associated with a lower risk of low BMD.

Conclusion

Interventions in different directions, such as having better health behaviors, increasing sun exposure, and residing in a highly walkable environment, are beneficial for reducing the risk of low BMD.
Acceptance and experience of digital dental technology, burnout, job satisfaction, and turnover intention for Taiwanese dental technicians
Authors: Teng Tang-Yun , Wu Ju-Hui , Lee Chen-Yi
Published: August 2022

Background

Digital dental technology (DDT) has progressed and been introduced to Taiwan in the recent years, gradually changing the industry ecology. Many studies have demonstrated that DDT is more accurate and faster than conventional dental technology. However, there is a paucity of research exploring dental technicians’ perspectives on digital dental techniques, and their burnout, job satisfaction, and turnover intention.

Methods

This cross-sectional survey with convenience sampling was conducted at the conference venue of the Taiwan Association of Dental Technology to investigate the perspectives of dental technicians. We used the snowballing method in this study; two sampling methods were adopted, a convenience sampling of dental technicians to complete a survey, followed by asking the survey participants of the convenience sample to invite their colleagues to participate in the online survey. The survey questionnaire included questions on demographics, work-related information, acceptance and experiences of dental technicians toward DDT, occupational burnout, job satisfaction, and turnover intention. Regression models were used to determine the predictors of job satisfaction and determinants of turnover intention.

Results

In total, 341 valid questionnaires were obtained. Overall, the participants reported long working hours (95.5%), positive score on the DDT acceptance scale, moderate job satisfaction, higher personal burnout, and work burnout, along with lower over-commitment. Among them, 32.9% and 28.2% reported the intention to leave their organization and profession, respectively. The stepwise multiple regression model revealed that higher work burnout decreased job satisfaction, while higher DDT acceptance and position as employer increased job satisfaction. The binary logistic regression models revealed that geographical area of workplace, work burnout, and job satisfaction were significant predictors of turnover intentions.

Conclusions

Many Taiwanese dental technicians reported turnover intentions and higher burnout. With the trend of digitalization in the dental industry, even though most dental technicians had a positive outlook toward DDT, its influence on job satisfaction appears limited. Retaining good and professional talents required of a dental technician is crucial, especially as Taiwan’s dental care becomes increasingly specialized. Strategies for improving the work environment and occupational health of dental technicians should thus be the focus of future studies.
Griottes: a generalist tool for network generation from segmented tissue images
Authors: Ronteix Gustave , Aristov Andrey , Bonnet Valentin , Sart Sebastien , Sobel Jeremie , Esposito Elric , Baroud Charles N.
Published: August 2022

Background

Microscopy techniques and image segmentation algorithms have improved dramatically this decade, leading to an ever increasing amount of biological images and a greater reliance on imaging to investigate biological questions. This has created a need for methods to extract the relevant information on the behaviors of cells and their interactions, while reducing the amount of computing power required to organize this information.

Results

This task can be performed by using a network representation in which the cells and their properties are encoded in the nodes, while the neighborhood interactions are encoded by the links. Here, we introduce Griottes, an open-source tool to build the “network twin” of 2D and 3D tissues from segmented microscopy images. We show how the library can provide a wide range of biologically relevant metrics on individual cells and their neighborhoods, with the objective of providing multi-scale biological insights. The library’s capacities are demonstrated on different image and data types.

Conclusions

This library is provided as an open-source tool that can be integrated into common image analysis workflows to increase their capacities.
Associations of genetically predicted IL-6 signaling with cardiovascular disease risk across population subgroups
Authors: Georgakis Marios K. , Malik Rainer , Richardson Tom G. , Howson Joanna M. M. , Anderson Christopher D. , Burgess Stephen , Hovingh G. Kees , Dichgans Martin , Gill Dipender
Published: August 2022

Background

Interleukin 6 (IL-6) signaling is being investigated as a therapeutic target for atherosclerotic cardiovascular disease (CVD). While changes in circulating high-sensitivity C-reactive protein (hsCRP) are used as a marker of IL-6 signaling, it is not known whether there is effect heterogeneity in relation to baseline hsCRP levels or other cardiovascular risk factors. The aim of this study was to explore the association of genetically predicted IL-6 signaling with CVD risk across populations stratified by baseline hsCRP levels and cardiovascular risk factors.

Methods

Among 397,060 White British UK Biobank participants without known CVD at baseline, we calculated a genetic risk score for IL-6 receptor (IL-6R)-mediated signaling, composed of 26 variants at the IL6R gene locus. We then applied linear and non-linear Mendelian randomization analyses exploring associations with a combined endpoint of incident coronary artery disease, ischemic stroke, peripheral artery disease, aortic aneurysm, and cardiovascular death stratifying by baseline hsCRP levels and cardiovascular risk factors.

Results

The study participants (median age 59 years, 53.9% females) were followed-up for a median of 8.8 years, over which time a total of 46,033 incident cardiovascular events occurred. Genetically predicted IL-6R-mediated signaling activity was associated with higher CVD risk (hazard ratio per 1-mg/dL increment in absolute hsCRP levels: 1.11, 95% CI: 1.06–1.17). The increase in CVD risk was linearly related to baseline absolute hsCRP levels. There was no evidence of heterogeneity in the association of genetically predicted IL-6R-mediated signaling with CVD risk when stratifying the population by sex, age, body mass index, estimated glomerular filtration rate, or systolic blood pressure, but there was evidence of greater associations in individuals with low-density lipoprotein cholesterol ≥ 160 mg/dL.

Conclusions

Any benefit of inhibiting IL-6 signaling for CVD risk reduction is likely to be proportional to absolute reductions in hsCRP levels. Therapeutic inhibition of IL-6 signaling for CVD risk reduction should therefore prioritize those individuals with the highest baseline levels of hsCRP.
Risk of hip fracture in meat-eaters, pescatarians, and vegetarians: results from the UK Women’s Cohort Study
Authors: Webster James , Greenwood Darren C. , Cade Janet E.
Published: August 2022

Background

The risk of hip fracture in women on plant-based diets is unclear. We aimed to investigate the risk of hip fracture in occasional meat-eaters, pescatarians, and vegetarians compared to regular meat-eaters in the UK Women’s Cohort Study and to determine if potential associations between each diet group and hip fracture risk are modified by body mass index (BMI).

Methods

UK women, ages 35–69 years, were classified as regular meat-eaters (≥ 5 servings/week), occasional meat-eaters (< 5 servings/week), pescatarian (ate fish but not meat), or vegetarian (ate neither meat nor fish) based on a validated 217-item food frequency questionnaire completed in 1995–1998. Incident hip fractures were identified via linkage to Hospital Episode Statistics up to March 2019. Cox regression models were used to estimate the associations between each diet group and hip fracture risk over a median follow-up time of 22.3 years.

Results

Amongst 26,318 women, 822 hip fracture cases were observed (556,331 person-years). After adjustment for confounders, vegetarians (HR (95% CI) 1.33 (1.03, 1.71)) but not occasional meat-eaters (1.00 (0.85, 1.18)) or pescatarians (0.97 (0.75, 1.26)) had a greater risk of hip fracture than regular meat-eaters. There was no clear evidence of effect modification by BMI in any diet group (p-interaction = 0.3).

Conclusions

Vegetarian women were at a higher risk of hip fracture compared to regular meat-eaters. Further research is needed to confirm this in men and non-European populations and to identify factors responsible for the observed risk difference. Further research exploring the role of BMI and nutrients abundant in animal-sourced foods is recommended.

Trial registration

ClinicalTrials.gov, NCT05081466
Synergistic effects on itaconic acid production in engineered Aspergillus niger expressing the two distinct biosynthesis clusters from Aspergillus terreus and Ustilago maydis
Authors: Wang Yaqi , Guo Yufei , Cao Wei , Liu Hao
Published: August 2022

Background

Itaconic acid (IA) is a versatile platform chemical widely used for the synthesis of various polymers and current methods for IA production based on Aspergillus terreus fermentation are limited in terms of process efficiency and productivity. To construct more efficient IA production strains, A. niger was used as a chassis for engineering IA production by assembling the key components of IA biosynthesis pathways from both A. terreus and Ustilago maydis.

Results

Recombinant A. niger S1596 overexpressing the A. terreus IA biosynthesis genes cadA, mttA, mfsA produced IA of 4.32 g/L, while A. niger S2120 overexpressing the U. maydis IA gene cluster adi1, tad1, mtt1, itp1 achieved IA of 3.02 g/L. Integration of the two IA production pathways led to the construction of A. niger S2083 with IA titers of 5.58 g/L. Increasing cadA copy number in strain S2083 created strain S2209 with titers of 7.99 g/L and deleting ictA to block IA degradation in S2209 created strain S2288 with IA titers of 8.70 g/L. Overexpressing acoA to enhance the supply of IA precursor in strain S2288 generated strain S2444 with IA titers of 9.08 g/L in shake flask.

Conclusion

Recombinant A. niger overexpressing the U. maydis IA biosynthesis pathway was capable of IA accumulation. Combined expression of the two IA biosynthesis pathways from A. terreus and U. maydis in A. niger resulted in much higher IA titers. Furthermore, increasing cadA copy number, deleting ictA to block IA degradation and overexpressing acoA to enhance IA precursor supply all showed beneficial effects on IA accumulation.
A novel quantitative prognostic model for initially diagnosed non-small cell lung cancer with brain metastases
Authors: Li Xiaohui , Gu Wenshen , Liu Yijun , Wen Xiaoyan , Tian Liru , Yan Shumei , Chen Shulin
Published: August 2022

Background

The prognosis of non-small cell lung cancer (NSCLC) with brain metastases (BMs) had been researched in some researches, but the combination of clinical characteristics and serum inflammatory indexes as a noninvasive and more accurate model has not been described.

Methods

We retrospectively screened patients with BMs at the initial diagnosis of NSCLC at Sun Yat-Sen University Cancer Center. LASSO-Cox regression analysis was used to establish a novel prognostic model for predicting OS based on blood biomarkers. The predictive accuracy and discriminative ability of the prognostic model was compared to Adjusted prognostic Analysis (APA), Recursive Partition Analysis (RPA), and Graded Prognostic Assessment (GPA) using concordance index (C-index), time-dependent receiver operating characteristic (td-ROC) curve, Decision Curve Analysis(DCA), net reclassification improvement index (NRI), and integrated discrimination improvement index (IDI).

Results

10-parameter signature's predictive model for the NSCLC patients with BMs was established according to the results of LASSO-Cox regression analysis. The C-index of the prognostic model to predict OS was 0.672 (95% CI = 0.609 ~ 0.736) which was significantly higher than APA,RPA and GPA. The td-ROC curve and DCA of the predictive model also demonstrated good predictive accuracy of OS compared to APA, RPA and GPA. Moreover, NRI and IDI analysis indicated that the prognostic model had improved prediction ability compared with APA, RPA and GPA.

Conclusion

The novel prognostic model demonstrated favorable performance than APA, RPA, and GPA for predicting OS in NSCLC patients with BMs.
Sequential acid/reduction response of triblock copolymeric nanomicelles to release camptothecin and toll-like receptor 7/8 agonist for orchestrated chemoimmunotherapy
Authors: Ge Xiaoyan , Hao Yanyun , Li Hui , Zhao Huajun , Liu Yang , Liu Yutong , Li Xia , Chen Hongfei , Zou Jing , Zhang Shiying , Huang Lingling , Shan Gang , Zhang Zhiyue
Published: August 2022

Background

Immunosuppressive tumor immune microenvironment (TIME) lowers immunotherapy effectiveness. Additionally, low penetration efficiency and unpredictable drug release in tumor areas restrict tumor therapy.

Methods

A triblock copolymeric micelle (NanoPCPT+PIMDQ) was developed to carry the chemotherapeutic drug camptothecin (CPT) and the TLR7/8 agonist 1-(4-(aminomethyl)benzyl)-2-butyl-1H-imidazo[4,5-c] quinoline-4-amine (IMDQ) to achieve deep tumor penetration and on-demand drug release by responding to acid and reduction stimuli sequentially. The synergistic antitumour efficacy of NanoPCPT+PIMDQ was assessed both in vitro and in vivo.

Results

NanoPCPT+PIMDQ is composed of a hydrophilic PEG(polyethylene glycol) outer layer, an acid-sensitive EPEMA middle layer, and a drug inner core. Upon intratumoral injection, (i) NanoPCPT+PIMDQ first responds to the acidic tumor microenvironment and disintegrates to PIMDQ and PCPT, penetrating deep regions of the tumor; (ii) tumor cells are killed by the released CPT; (iii) DCs are activated by PIMDQ to increase the infiltration of cytotoxic T lymphocyte (CTL); and (iv) both downregulated Foxp3+ Tregs by CPT and repolarized M2 macrophages by PIMDQ can relieve the TIME.

Conclusion

This pH/GSH-responsive triblock polymer-drug conjugate reduces immunosuppression and enhances the infiltration of CTLs by codelivering CPT and IMDQ in a controllable manner, providing a promising platform for synergistic tumor chemoimmunotherapy.
Black phosphorous nanomaterials as a new paradigm for postoperative tumor treatment regimens
Authors: Hou Yanhua , Fei Yang , Liu Zehong , Liu Yingqi , Li Menghuan , Luo Zhong
Published: August 2022

Surgery is currently a mainstream treatment modality for various solid tumor indications. However, aggressive resection of tumor tissues frequently causes postoperative complications, which severely undermine the well-being of patients. Moreover, the residue tumor cells may substantially increase the risk of local and distant tumor relapse. The recent development in black phosphorus (BP)-based nanomaterials offers a promising opportunity to address these clinical challenges. BP is an emerging nanomaterial with excellent biocompatibility and versatile functionality, which has already demonstrated great potential for a variety of biomedical applications including tumor therapy and tissue engineering. In this review, the recent advances in BP-based nanobiomaterials for the post-surgery treatment of solid tumor have been summarized, while specific emphasis was placed on their capability to continuously inhibit residue tumor growth at the surgery site as well as stimulating various healing mechanisms, aiming to preventing tumor relapse while promoting the healing of surgery-induced traumatic soft/hard tissue injuries. It is anticipated that the nanoengineered BP-based materials may open new avenues to tackle those clinical challenges in surgical treatment of solid tumors.
Investing for population mental health in low and middle income countries—where and why?
Authors: Freeman Melvyn
Published: August 2022

Background

Policy makers intent on improving population mental health are required to make fundamental decisions on where to invest resources to achieve optimal outcomes. While research on the effectiveness and efficiency of interventions is critical to such choices, including clinical outcomes and return on investment, in the “real world” of policy making other concerns invariably also play a role. Politics, history, community awareness and demands for care, understanding of etiology, severity of condition and local circumstances are all critical. Policy makers should not merely rely on previous allocations, but need to take active decisions regarding the proportion of resources that should be allocated to particular interventions to achieve optimum outcomes. Given that scientific evidence is only one of the reasons informing such decisions, it is necessary to have clear and informed reasons for allocations and for making cases for new mental health investments.

Main body

Investment allocations are unlikely to ever be an exact science. Alternatives therefore need to be rationally weighed up and reasoned decisions made based on this. Using prevalence data and the distribution of mental health resources in South Africa as a backdrop and proxy, investment proposals are made for LMICs with due consideration given to inter alia the social determinants of mental health, the needs and potential benefits of investments in people with severe verses common mental disorder, mental health promotion and disease prevention and to other areas that may impact on population mental health, such as management.

Conclusion

Based on a range of arguments, it is proposed that mental health investments should follow the following approach. A mental health-in-all-policies method must be adopted. There should be no more than a 20% gap in the humane and human rights oriented care, treatment and rehabilitation of people with severe mental disorder. A minimum additional amount of 10% of the amount spent on severe mental disorder should be allocated to treating people with common mental disorder. Screening for mental disabilities should take place within all chronic care services. A minimum of 3% of the budget spent on severe mental disorder should be spent on promotion and prevention programmes. An additional 1% of the allocation for severe mental disorder should be provided for managing/driving the mental health programme.
A novel 1,3,4-thiadiazole modified chitosan: synthesis, characterization, antimicrobial activity, and release study from film dressings
Authors: Mohamed Ahmad E. , Elgammal Walid E. , Dawaba Aya M. , Ibrahim Ahmed G. , Fouda Amr , Hassan Saber M.
Published: August 2022

Herein, two new polymers designated as Cs-EATT and Cs-BATT have been synthesized via linking the chitosan with the synthesized 1,3,4-thiadiazole compounds. They were characterized using 1H,13C-NMR, FT-IR, TGA, Elemental analysis, Mass spectrum, and UV–vis spectrophotometer. The synthesized polymers exhibit high activity to control the growth of pathogenic bacteria (S. aureus, B. subtilis, E. coli, and P. aeruginosa), and unicellular fungi (C. albicans). The MIC values were in the range of 25–100 µg mL–1 for Cs-EATT and 25–200 µg mL–1 for Cs-BATT with varied clear zones. The new polymers were mixed with three film-forming agents: polyvinyl alcohol, hydroxyethyl cellulose, and carboxymethyl cellulose to form six film dressings designated as E1, E2, and E3 for Cs-EATT, and B1, B2, and B3 for Cs-BATT, respectively. The evaluation of film dressings showed that the formed films had transparency, uniformity, homogeneity, elasticity, and non-irritation pH values for skin within the normal range. The maximum percentages of Cs-E/B-ATT content were recorded for film dressings E2 and B2, with values of 92.5% and 94.9%, respectively. Also, the release percentages varied according to film dressing formulation, with values in the ranges of 83.88–93.2% for Cs-EATT and (87.7–97.35%) for Cs-EATT after 9 h.
Noonan syndrome with RAF1 gene mutations in a newborn with cerebral haemorrhage
Authors: Lan Junwei , Zeng Tianbao , Liu Sheng , Lan Juhong , Qian Lijun
Published: August 2022

Background

Noonan syndrome is an autosomal dominant genetic disorder that can occur in men and women and has a sporadic or family history. NS can lead to abnormal bleeding, but cerebral haemorrhage is rare. This is the first case of cerebral haemorrhage with a RAF1 gene mutation that originated in the neonatal period.

Case presentation

This case presents a newborn with a RAF1 gene mutation resulting in NS complicated with an abnormality of chromosome 46, X, del (Y) (q12). In the course of treatment, the baby's breathing suddenly increased. After an MRI examination of the skull, haemorrhaging was found in multiple parts of the brain.

Conclusions

After symptomatic treatment, the baby recovered well, but the main cause of cerebral haemorrhage was not found.
Comparing an optimised physiotherapy treatment package with usual physiotherapy care for people with tennis elbow — protocol for the OPTimisE pilot and feasibility randomised controlled trial
Authors: Bateman M. , Saunders B. , Littlewood C. , Davis D. , Beckhelling J. , Cooper K. , Skeggs A. , Foster N. E. , Vicenzino B. , Hill J. C.
Published: August 2022

Background

Physiotherapy is recommended for people with tennis elbow, but whilst a wide array of treatments is available, the optimal approach remains uncertain. We have therefore recently developed an optimised physiotherapy treatment package for tennis elbow based on a synthesis of the evidence, patient input and clinical consensus. It consists of detailed advice and education, a structured progressive exercise programme and provision of a counter-force elbow brace. Here, we report the protocol for our multicentre pilot and feasibility randomised controlled trial (RCT) designed to (a) examine the feasibility of our optimised physiotherapy treatment package and (b) to pilot trial processes for a future fully powered RCT to test clinical and cost-effectiveness compared with usual physiotherapy treatment.

Methods

A multicentre pilot and feasibility RCT will be conducted across three sites in England, recruiting up to 50 patients (or for a maximum of 12 months). Participants with tennis elbow, identified from physiotherapy clinic waiting lists and general practice surgeries, will be randomly allocated to receive the optimised physiotherapy treatment package or usual physiotherapy care. Analysis will focus on feasibility measures including consent rate, intervention fidelity, follow-up rate and outcome completion rate. A nested qualitative study will explore the acceptability of the study processes and patient and physiotherapist experiences of the new optimised intervention.

Discussion

This study will determine the feasibility of a new optimised physiotherapy treatment package for people with tennis elbow and pilot the processes for a future fully powered RCT. In the longer term, this treatment package may provide superior clinical outcomes for patients, in terms of pain and quality of life, and be more cost-effective for the health service.

Trial registration

Registered with the ISRCTN database 19/7/2021, https://www.isrctn.com/ISRCTN64444585