bluuebunny/crossref_metadata_2025 huggingface dataset:
Loneliness and academic performance mediates the relationship between fear of missing out and smartphone addiction among Iranian university students
Authors: Alinejad Vahid , Parizad Naser , Yarmohammadi Malakeh , Radfar Moloud
Published: August 2022

Background

Fear of missing out (FoMO) can increase loneliness and smartphone addiction and decrease academic performance in university students. Most studies investigated the relationship between FoMO and smartphone addiction in developed countries, and no studies were found to examine this association in Iran. The mediating role of loneliness and academic performance in the relationship between FoMO and smartphone addiction is unclear. This study investigated the relationship between FoMO and smartphone addiction and the mediating role of loneliness and academic performance in this relationship in Iranian university students.

Methods

In this cross-sectional study, 447 students from Urmia University of Medical Sciences were investigated. Data were collected using demographic questionnaires, Przybylski's FoMO scale, Pham and Taylor's academic performance questionnaire, Russell's loneliness scale, and Kwon's smartphone addiction scale. Data were analyzed using SPSS ver. 23 and SmartPLS ver. 2.

Results

FoMO had a positive and direct association with smartphone addiction (β = 0.315, t-value = 5.152, p < 0.01). FoMO also had a positive and direct association with students’ loneliness (β = 0.432, t-value = 9.059, p < 0.01) and a negative and direct association with students' academic performance (β = -0.2602, t-value = 4.201, p < 0.01). FoMO indirectly associated with smartphone addiction through students' loneliness (β = 0.311, t-value = 5.075, p < 0.01), but academic performance was not mediator of smartphone addiction (β = 0.110, t-value = 1.807, p > 0.05). FoMO also indirectly correlated with academic performance through students' loneliness (β =—0.368, t-value = 6.377, p < 0.01).

Conclusions

FoMO can be positively associated with students' smartphone addiction, and loneliness is an important mediator of this association. Since smartphone addiction could harm students' academic performance, thus, healthcare administrators should reduce students' loneliness and improve their academic performance by adopting practical strategies to help students to manage their time and control their smartphone use. Holding self-management skills classes, keeping students on schedule, turning off smartphone notifications, encouraging students to engage in sports, and participating in group and family activities will help manage FoMO and loneliness.
Adolescent mobile phone addiction during the COVID-19 pandemic predicts subsequent suicide risk: a two-wave longitudinal study
Authors: Li Gangqin , Conti Aldo Alberto , Qiu Changjian , Tang Wanjie
Published: August 2022

Both the rate of mobile phone addiction and suicidality among adolescents have increased during the pandemic lockdown. However, the relationship between mobile phone addiction and suicide risk and the underlying psychological mechanisms remains unknown. This study examined the associations between mobile phone addiction in adolescents during the first month of lockdown and the suicide risk in the subsequent five months. A two-wave short-term longitudinal web-based survey was conducted on 1609 senior high school students (mean age = 16.53 years, SD = 0.97 years; 63.5% female). At Time 1 (T1), the severity of mobile phone addiction and basic demographic information was collected from Feb 24 to 28, 2020 in Sichuan Province, China (at the pandemic’s peak). Five months later, between July 11 and July 23 (Time 2, T2), mobile phone addiction, daytime sleepiness, depression, and suicidality were measured within the past five months. The regression analysis revealed that mobile phone addiction during quarantine directly predicted suicidality within the next five months, even after controlling for the effect of depression and daytime sleepiness. Meanwhile, mobile phone addiction at T1 also indirectly predicted suicidality at T2, with depression and daytime sleepiness mediating this association. Programs targeting improvement of daytime sleepiness and depressive symptoms may be particularly effective in reducing suicide risk among adolescents with mobile phone addiction.
Consumer-driven strategies towards a resilient and sustainable food system following the COVID-19 pandemic in Australia
Authors: Kent Katherine , Gale Fred , Penrose Beth , Auckland Stuart , Lester Elizabeth , Murray Sandra
Published: August 2022

Background

The COVID-19 pandemic and associated public health restrictions temporarily disrupted food supply chains around the world and changed the way people shopped for food, highlighting issues with food systems resilience and sustainability. The aim of this study was to explore consumer-driven strategies towards a more resilient and sustainable food system in Australia, learning from experiences during the beginning of the COVID-19 pandemic.

Methods

During May–June 2020, a cross-sectional, online survey was conducted in Tasmania, Australia in a non-random sample of adults aged 18 years and over. The survey collected demographic data and posted the open-ended question: “How could Tasmania’s food system be better prepared for a disaster in the future?” Descriptive statistics were used to analyse the demographic data and thematic analysis was employed to analyse the qualitative data.

Results

Survey respondents (n = 698) were predominantly female (79%), over 55 years of age (48%), university educated (70%) and living with dependents (45%). Seven key themes were identified: (i) balance food exports with local needs; (ii) strengthen local food systems; (iii) increase consumer awareness of food supply chains; (iv) build collaboration and connection in the food system; (v) embed clear contingency arrangements; (vi) support community capacity building and individual self-sufficiency; and (vii) the food system coped well.

Conclusions

The consumer-driven strategies identified indicate multiple opportunities to increase resilience and sustainability in the food system to avoid future supply disruptions. Our findings indicate that considerable popular support for more resilient, local and sustainable food systems may be emerging from the COVID-19 pandemic.
Identification of HMGB2 associated with proliferation, invasion and prognosis in lung adenocarcinoma via weighted gene co-expression network analysis
Authors: Qiu Xie , Liu Wei , Zheng Yifan , Zeng Kai , Wang Hao , Sun Haijun , Dai Jianhua
Published: August 2022

Background

High mobility group protein B2 (HMGB2) is a multifunctional protein that plays various roles in different cellular compartments. Moreover, HMGB2 serves as a potential prognostic biomarker and therapeutic target for lung adenocarcinoma (LUAD).

Methods

In this study, the expression pattern, prognostic implication, and potential role of HMGB2 in LUAD were evaluated using the integrated bioinformatics analyses based on public available mRNA expression profiles from The Cancer Genome Atlas and Gene Expression Omnibus databases, both at the single-cell level and the tissue level. Further study in the patient-derived samples was conducted to explore the correlation between HMGB2 protein expression levels with tissue specificity, (tumor size-lymph node-metastasis) TNM stage, pathological grade, Ki-67 status, and overall survival. In vitro experiments, such as CCK-8, colony-formation and Transwell assay, were performed with human LUAD cell line A549 to investigate the role of HMGB2 in LUAD progression. Furthermore, xenograft tumor model was generated with A549 in nude mice.

Results

The results showed that the HMGB2 expression was higher in the LUAD samples than in the adjacent normal tissues and was correlated with high degree of malignancy in different public data in this study. Besides, over-expression of HMGB2 promoted A549 cells proliferation and migration while knocking down of HMGB2 suppressed the tumor promoting effect.

Conclusions

Our study indicated that HMGB2 was remarkably highly expressed in LUAD tissues, suggesting that it is a promising diagnostic and therapeutic marker for LUAD in the future.
Outpatient palliative care during the COVID-19 pandemic: a retrospective single centre analysis in Germany
Authors: Behnke Jonas , Arndt Philipp Friedrich , Cekay Michael John , Berthold Daniel , Herentin Birgit , Dumitrascu Rio , Sibelius Ulf , Eul Bastian
Published: August 2022

Background

The coronavirus disease 2019 (COVID-19) pandemic has challenged health care systems worldwide. In Germany, patients in a palliative care setting have the opportunity to receive treatment by a specialised mobile outpatient palliative care team (OPC). The given retrospective single centre analysis describes the use of OPC structures for terminally ill COVID-19 patients during the height of the pandemic in Germany and aims to characterise this exceptional OPC patient collective.

Methods

First, death certificates were analysed in order to collect data about the place of death of all deceased COVID-19 patients (n = 471) within our local governance district. Second, we investigated whether advance care planning structures were established in local nursing homes (n = 30) during the height of the COVID-19 pandemic in 2020. Third, we examined patient characteristics of COVID-19 negative (n = 1579) and COVID-19 positive (n = 28) patients treated by our tertiary care centre guided OPC service.

Results

The analysis of death certificates in our local district revealed that only 2.1% of all deceased COVID-19 patients had succumbed at their home address (n = 10/471). In contrast, 34.0% of COVID-19 patients died in nursing homes (n = 160/471), whereas 63.5% died in an inpatient hospital setting (n = 299/471). A large proportion of these hospitalised patients died on non-intensive care unit wards (38.8%). Approximately 33.0% of surveyed nursing homes had a palliative care council service and 40.0% of them offered advance care planning (ACP) structures for their nursing home residents. In our two OPC collectives we observed significant differences concerning clinical characteristics such as the Index of Eastern Cooperative Oncology Group [ECOG] (p = 0.014), oncologic comorbidity (p = 0.004), as well as referrer and primary patient location (p = 0.001, p = 0.033).

Conclusions

Most COVID-19 patients in our governance district died in an inpatient setting. However, the highest number of COVID-19 patients in our governance district who died in an outpatient setting passed away in nursing homes where palliative care structures should be further expanded. COVID-19 patients who died under the care of our OPC service had considerably fewer oncologic comorbidities. Finally, to relieve conventional health care structures, we propose the expansion of established OPC structures for treating terminally ill COVID-19 patients.
Standardizing evaluation of patient-specific 3D printed models in surgical planning: development of a cross-disciplinary survey tool for physician and trainee feedback
Authors: Schlegel Lauren , Ho Michelle , Fields J. Matthew , Backlund Erik , Pugliese Robert , Shine Kristy M.
Published: August 2022

Background

3D printed models are becoming increasingly popular in healthcare as visual and tactile tools to enhance understanding of anatomy and pathology in medical trainee education, provide procedural simulation training, and guide surgical procedures. Patient-specific 3D models are currently being used preoperatively for trainee medical education in planning surgical approaches and intraoperatively to guide decision-making in several specialties. Our study group utilized a modified Delphi process to create a standardized assessment for trainees using patient-specific 3D models as a tool in medical education during pre-surgical planning.

Methods

A literature review was conducted to identify survey questions administered to clinicians in published surgical planning studies regarding the use of patient-specific 3D models. A core study team reviewed these questions, removed duplicates, categorized them, mapped them to overarching themes, and, where applicable, modified individual questions into a form generalizable across surgical specialties. The core study panel included a physician, physician-scientist, social scientist, engineer/medical student, and 3D printing lab manager. A modified Delphi process was then used to solicit feedback on the clarity and relevance of the individual questions from an expert panel consisting of 12 physicians from specialties including anesthesiology, emergency medicine, radiology, urology, otolaryngology, and obstetrics/gynecology. When the Radiological Society of North America (RSNA)/American College of Radiology (ACR) 3D Printing Registry Data Dictionary was released, additional survey questions were reviewed. A final cross-disciplinary survey of the utility of 3D printed models in surgical planning medical education was developed.

Results

The literature review identified 100 questions previously published in surveys assessing patient-specific 3D models for surgical planning. Following the review, generalization, and mapping of survey questions from these studies, a list of 24 questions was generated for review by the expert study team. Five additional questions were identified in the RSNA/ACR 3D Printing Registry Data Dictionary and included for review. A final questionnaire consisting of 20 questions was developed.

Conclusions

As 3D printed models become more common in medical education, the need for standardized assessment is increasingly essential. The standardized questionnaire developed in this study reflects the interests of a variety of stakeholders in patient-specific 3D models across disciplines.
Factor structure of the Maslach Burnout Inventory Human Services Survey in Spanish urgency healthcare personnel: a cross-sectional study
Authors: Forné Carles , Yuguero Oriol
Published: August 2022

Background

The Maslach Burnout Inventory (MBI) is an instrument commonly used to evaluate burnout syndrome. The goal of the present study was to assess the internal reliability and the performance of the items and the subscales of the MBI-HSS (the version for professionals working in human services) by validating its factorial structure in Spanish urgency healthcare personnel.

Methods

Cross-sectional study including 259 healthcare emergency professionals (physicians and nurses) in the Spanish health region of Lleida and the Pyrenees. Burnout was measured using the Spanish validated version of the MBI-HSS. Internal reliability was estimated using Cronbach’s alpha coefficient. The sampling adequacy was assessed using the Kaiser-Meyer-Olkin measure along with the Bartlett’s test of sphericity. A principal axis exploratory factor analysis with an oblique transformation of the solution and a confirmatory factor analysis with maximum likelihood estimation were performed. Goodness-of-fit was assessed by means of the chi-square ratio by the degrees of freedom, the standardized root mean square residual (SRMR), the root mean square error of approximation (RMSEA), the Tucker-Lewis Index (TLI) and the comparative fit index (CFI).

Results

The three subscales showed good internal reliability with Cronbach’s alpha coefficients exceeding the critical value of 0.7. Exploratory factor analysis revealed five factors with eigenvalues greater than 1. Nevertheless, confirmatory factor analysis showed a relatively satisfactory fit of the three-factor structure (χ2/df = 2.6, SRMR = 0.07, RMSEA = 0.08, TLI = 0.87, CFI = 0.89), which was improved when several items were removed (χ2/df = 1.7, SRMR = 0.04, RMSEA = 0.05, TLI = 0.97, CFI = 0.98).

Conclusions

Although it is necessary exploring new samples to get to more consistent conclusions, the MBI-HSS is a reliable and factorially valid instrument to evaluate burnout syndrome in health professionals from the Spanish emergency services.
Maternal smoking during pregnancy and type 1 diabetes in the offspring: a nationwide register-based study with family-based designs
Authors: Wei Yuxia , Andersson Tomas , Edstorp Jessica , Löfvenborg Josefin E. , Talbäck Mats , Feychting Maria , Carlsson Sofia
Published: August 2022

Background

Maternal smoking during pregnancy was reported to be associated with a reduced risk of type 1 diabetes in the offspring. We investigated whether this association is consistent with a causal interpretation by accounting for familial (shared genetic and environmental) factors using family-based, quasi-experimental designs.

Methods

We included 2,995,321 children born in Sweden between 1983 and 2014 and followed them for a diagnosis of type 1 diabetes until 2020 through the National Patient, Diabetes and Prescribed Drug Registers. Apart from conducting a traditional cohort study, we performed a nested case–control study (quasi-experiment) comparing children with type 1 diabetes to their age-matched siblings (or cousins). Information on maternal smoking during pregnancy was retrieved from the Swedish Medical Birth Register. Multivariable adjusted Cox proportional hazards regression and conditional logistic regression were used.

Results

A total of 18,617 children developed type 1 diabetes, with a median age at diagnosis of 9.4 years. The sibling and cousin comparison design included 14,284 and 7988 of these children, respectively. Maternal smoking during pregnancy was associated with a 22% lower risk of offspring type 1 diabetes in the full cohort (hazard ratio 0.78, 95% confidence interval [CI] 0.75–0.82). The corresponding odds ratio was 0.78 (95% CI 0.69–0.88) in the sibling and 0.72 (95% CI 0.66–0.79) in the cousin comparison analysis.

Conclusions

This nationwide, family-based study provides support for a protective effect of maternal smoking on offspring type 1 diabetes. Mechanistic studies are needed to elucidate the underlying pathways behind this link.
Different serotypes of Escherichia coli flagellin exert identical adjuvant effects
Authors: Pang Shengmei , Wu Wenwen , Liu Qinfang , Zhu Guoqiang , Duan Qiangde
Published: August 2022

Bacterial flagellin is a potent powerful adjuvant, which exerts its adjuvant activity by activating the Toll-like receptor 5 (TLR5) signaling pathway to induce host pro-inflammatory responses. Flagellin of Salmonella typhimurium (S. typhimurium) has shown strong adjuvant effects for a variety of vaccine candidates, however, the adjuvanticity of different serotypes of Escherichia coli (E. coli) flagellin (FliC) is unclear. To explore the adjuvant activity of different serotypes of E. coli flagellin, FliCH1, FliCH7, and FliCH19 recombinant flagellins were prokaryotically-expressed and purified. The adjuvanticity of three recombinant flagellins was evaluated by analyzing their abilities to induce the IL-8 production in human colorectal adenocarcinoma (Caco-2) cells and the immune responses to co-administrated FaeG antigen in mice. Sequence analysis showed that the N-and C-terminal regions are highly conserved, whereas the central region is hypervariable. The TLR5 recognized site is identical among these three serotypes of flagellins. Coomassie blue staining SDS-PAGE showed the molecular mass of FliCH1, FliCH7, and FliCH19 recombinant flagellin are 66 kDa, 64 kDa, and 68 kDa, which can be recognized by anti-FliCH1, FliCH7, and FliCH19 serum, respectively. Moreover, the flagellin serotypes induced similar levels of IL-8 and TNF-α production in Caco-2 cells, anti-FaeG specific IgG antibodies in mice, and IL-4 production in mice spleen cells. Our results indicated that E. coli flagellins can be an adjuvant for vaccine candidates and that different serotypes of E. coli flagellins possess identical adjuvant effects.
Breakfast in the Philippines: food and diet quality as analyzed from the 2018 Expanded National Nutrition Survey
Authors: Angeles-Agdeppa Imelda , Custodio Ma. Rosel S. , Toledo Marvin B.
Published: August 2022

Background

The quality of foods taken during breakfast could contribute in shaping diet quality. This study determined the regularity of breakfast consumption and breakfast quality based on the food, energy and nutrient intakes of Filipinos.

Materials and methods

Data from the 2018 Expanded National Nutrition Survey (ENNS) was extracted for analysis. There were 63,655 individuals comprising about 14,013 school-aged children (6–12 years old), 9,082 adolescents (13–18 years old), 32,255 adults (19–59 years old), and 8,305 elderly (60 years old and above). Two-day non-consecutive 24-h food recalls were used to measure food and nutrient intakes. Diet quality was measured using Nutrient-Rich Food Index (NRF) 9.3. The sample was stratified by age group and NRF9.3 tertiles.

Results and findings

Results showed that 96 – 98% Filipinos across age groups were consuming breakfast. Children age 6–12 years have the highest NRF9.3 average score (417), followed by the elderly (347), adolescents (340), and adults (330). These scores were very low in comparison with the maximum possible NRF score which is 900. The essential nutrient intakes of respondents were significantly higher among those with the healthiest breakfast diet (Tertile 3) compared to those with the poorest breakfast diet (Tertile 1). However, participants in the healthiest breakfast diet did not meet 20% of the recommendations for calcium, fiber, vitamin C, and potassium.

Conclusion and recommendations

This study revealed that majority of the population are regular breakfast consumers. However, the breakfast consumed regularly by Filipinos were found to be nutritionally inadequate. And even those classified under Tertile 3 which were assumed as having a better quality of breakfast were still found to have nutrient inadequacies. Thus, the study suggests that Filipinos must consume a healthy breakfast by including nutrient-dense foods such as fruits, vegetables, whole grains, fresh meat, and milk to provide at least 20–25% of the daily energy and nutrient intakes.
Nanobiotics against antimicrobial resistance: harnessing the power of nanoscale materials and technologies
Authors: Chakraborty Nayanika , Jha Diksha , Roy Indrajit , Kumar Pradeep , Gaurav Shailendra Singh , Marimuthu Kalisvar , Ng Oon-Tek , Lakshminarayanan Rajamani , Verma Navin Kumar , Gautam Hemant K.
Published: August 2022

Given the spasmodic increment in antimicrobial resistance (AMR), world is on the verge of “post-antibiotic era”. It is anticipated that current SARS-CoV2 pandemic would worsen the situation in future, mainly due to the lack of new/next generation of antimicrobials. In this context, nanoscale materials with antimicrobial potential have a great promise to treat deadly pathogens. These functional materials are uniquely positioned to effectively interfere with the bacterial systems and augment biofilm penetration. Most importantly, the core substance, surface chemistry, shape, and size of nanomaterials define their efficacy while avoiding the development of AMR. Here, we review the mechanisms of AMR and emerging applications of nanoscale functional materials as an excellent substitute for conventional antibiotics. We discuss the potential, promises, challenges and prospects of nanobiotics to combat AMR.

Graphical Abstract
Cost-effectiveness of integrated disease management for high risk, exacerbation prone, patients with chronic obstructive pulmonary disease in a primary care setting
Authors: Scarffe Andrew D. , Licskai Christopher J. , Ferrone Madonna , Brand Kevin , Thavorn Kednapa , Coyle Doug
Published: August 2022

Background

We evaluate the cost-effectiveness of the ‘Best Care’ integrated disease management (IDM) program for high risk, exacerbation prone, patients with chronic obstructive pulmonary disease (COPD) compared to usual care (UC) within a primary care setting from the perspective of a publicly funded health system (i.e., Ontario, Canada).

Methods

We conducted a model-based, cost-utility analysis using a Markov model with expected values of costs and outcomes derived from a Monte-Carlo Simulation with 5000 replications. The target population included patients started in GOLD II with a starting age of 68 years in the trial-based analysis. Key input parameters were based on a randomized control trial of 143 patients (i.e., UC (n = 73) versus IDM program (n = 70)). Results were shown as incremental cost per quality-adjusted life year (QALY) gained.

Results

The IDM program for high risk, exacerbation prone, patients is dominant in comparison with the UC group. After one year, the IDM program demonstrated cost savings and improved QALYs (i.e., UC was dominated by IDM) with a positive net-benefit of $5360 (95% CI: ($5175, $5546) based on a willingness to pay of $50,000 (CAN) per QALY.

Conclusions

This study demonstrates that the IDM intervention for patients with COPD in a primary care setting is cost-effective in comparison to the standard of care. By demonstrating the cost-effectiveness of IDM, we confirm that investment in the delivery of evidence based best practices in primary care delivers better patient outcomes at a lower cost than UC.
LncRNA GAS6-AS1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating TRIM14 through miR-370-3p/miR-1296-5p and FUS
Authors: Chen Qing , Zhou Lin , Ma De , Hou Juan , Lin Yuxin , Wu Jie , Tao Min
Published: August 2022

Background

Long non-coding RNAs (lncRNAs) are essential regulators of tumorigenesis and the development of colorectal cancer (CRC). Here, we aimed to investigate the role of lncRNA GAS6-AS1 in CRC and its potential mechanisms.

Methods

Bioinformatics analyses evaluated the level of GAS6-AS1 in colon cancer, its correlation with clinicopathological factors, survival curve and diagnostic value. qRT-PCR were performed to detect the GAS6-AS1 level in CRC samples and cell lines. The CCK8, EdU, scratch healing, transwell assays and animal experiments were conducted to investigate the function of GAS6-AS1 in CRC. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene analyses were carried out to reveal interaction between GAS6-AS1, TRIM14, FUS, and miR-370-3p/miR-1296-5p.

Results

GAS6-AS1 was greatly elevated in CRC and positively associated with unfavorable prognosis of CRC patients. Functionally, GAS6-AS1 positively regulates CRC proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and induces CRC growth and metastasis in vivo. Moreover, GAS6-AS1 exerted oncogenic function by competitively binding to miR-370-3p and miR-1296-5p, thereby upregulating TRIM14. Furthermore, we verified that GAS6-AS1 and TRIM14 both interact with FUS and that GAS6-AS1 stabilized TRIM14 mRNA by recruiting FUS. Besides, rescue experiments furtherly demonstrated that GAS6-AS1 facilitate progression of CRC by regulating TRIM14.

Conclusion

Collectively, these findings demonstrate that GAS6-AS1 promotes TRIM14-mediated cell proliferation, migration, invasion, and EMT of CRC via ceRNA network and FUS-dependent manner, suggesting that GAS6-AS1 could be utilized as a novel biomarker and therapeutic target for CRC.
Identification of immune-related key genes in the peripheral blood of ischaemic stroke patients using a weighted gene coexpression network analysis and machine learning
Authors: Zheng Peng-Fei , Chen Lu-Zhu , Liu Peng , Pan Hong Wei , Fan Wen-Juan , Liu Zheng-Yu
Published: August 2022

Background

The immune system plays a vital role in the pathological process of ischaemic stroke. However, the exact immune-related mechanism remains unclear. The current research aimed to identify immune-related key genes associated with ischaemic stroke.

Methods

CIBERSORT was utilized to reveal the immune cell infiltration pattern in ischaemic stroke patients. Meanwhile, a weighted gene coexpression network analysis (WGCNA) was utilized to identify meaningful modules significantly correlated with ischaemic stroke. The characteristic genes correlated with ischaemic stroke were identified by the following two machine learning methods: the support vector machine-recursive feature elimination (SVM-RFE) algorithm and least absolute shrinkage and selection operator (LASSO) logistic regression.

Results

The CIBERSORT results suggested that there was a decreased infiltration of naive CD4 T cells, CD8 T cells, resting mast cells and eosinophils and an increased infiltration of neutrophils, M0 macrophages and activated memory CD4 T cells in ischaemic stroke patients. Then, three significant modules (pink, brown and cyan) were identified to be significantly associated with ischaemic stroke. The gene enrichment analysis indicated that 519 genes in the above three modules were mainly involved in several inflammatory or immune-related signalling pathways and biological processes. Eight hub genes (ADM, ANXA3, CARD6, CPQ, SLC22A4, UBE2S, VIM and ZFP36) were revealed to be significantly correlated with ischaemic stroke by the LASSO logistic regression and SVM-RFE algorithm. The external validation combined with a RT‒qPCR analysis revealed that the expression levels of ADM, ANXA3, SLC22A4 and VIM were significantly increased in ischaemic stroke patients and that these key genes were positively associated with neutrophils and M0 macrophages and negatively correlated with CD8 T cells. The mean AUC value of ADM, ANXA3, SLC22A4 and VIM was 0.80, 0.87, 0.91 and 0.88 in the training set, 0.85, 0.77, 0.86 and 0.72 in the testing set and 0.87, 0.83, 0.88 and 0.91 in the validation samples, respectively.

Conclusions

These results suggest that the ADM, ANXA3, SLC22A4 and VIM genes are reliable serum markers for the diagnosis of ischaemic stroke and that immune cell infiltration plays a crucial role in the occurrence and development of ischaemic stroke.
Molecular evolutionary process of advanced gastric cancer during sequential chemotherapy detected by circulating tumor DNA
Authors: Xi Wenqi , Zhou Chenfei , Xu Fei , Sun Debin , Wang Shengzhou , Chen Yawei , Ji Jun , Ma Tao , Wu Junwei , Shangguan Chengfang , Zhu Zhenggang , Zhang Jun
Published: August 2022

Background

Efficacy of conventional sequential chemotherapy paradigm for advanced gastric cancer (AGC) patients has largely plateaued. Dynamic molecular changes during and after sequential chemotherapy have not been fully delineated. We aimed to profile the molecular evolutionary process of AGC patients during sequential chemotherapy by next generation sequencing (NGS) of plasma circulating tumor DNA (ctDNA).

Methods

A total of 30 chemo-naïve patients who were diagnosed with unresectable advanced or metastatic stomach adenocarcinoma were enrolled. All patients received sequential chemotherapy regimens following the clinical guideline. One hundred and eight serial peripheral blood samples were collected at baseline, radiographical assessment and disease progression. Plasma ctDNA was isolated and a customized NGS panel was used to detect the genomic features of ctDNA including single nucleotide variants (SNVs) and gene-level copy number variations (CNVs). KEGG pathway enrichment analysis was performed.

Results

Platinum-based combination chemotherapy was administrated as first-line regimen. Objective response rate was 50% (15/30). Patients with higher baseline values of copy number instability (CNI), CNVs and variant allel frequency (VAF) were more sensitive to platinum-based first-line regimens. Tumor mutation burden (TMB), CNI and CNV burden at partial response and stable disease were significantly lower than those at baseline, where at progressive disease they recovered to baseline levels. Dynamic change of TMB (ΔTMB) was correlated with progression-free survival of first-line treatment. Fluctuating changes of SNVs and gene-level CNVs could be observed during sequential chemotherapy. Under the pressure of conventional chemotherapy, the number of novel gene-level CNVs were found to be higher than that of novel SNVs. Such novel molecular alterations could be enriched into multiple common oncologic signaling pathways, including EGFR tyrosine kinase inhibitor resistance and platinum drug resistance pathways, where their distributions were found to be highly heterogenous among patients. The impact of subsequent regimens, including paclitaxel-based and irinotecan-based regimens, on the molecular changes driven by first-line therapy was subtle.

Conclusion

Baseline and dynamic changes of genomic features of ctDNA could be biomarkers for predicting response of platinum-based first-line chemotherapy in AGC patients. After treatment with standard chemotherapy regimens, convergent oncologic pathway enrichment was identified, which is yet characterized by inter-patient heterogenous gene-level CNVs.
Sensory neuron dysfunction in orthotopic mouse models of colon cancer
Authors: Balogh Mihály , Zhang Jixiang , Gaffney Caitlyn M. , Kalakuntla Neha , Nguyen Nicholas T. , Trinh Ronnie T. , Aguilar Clarissa , Pham Hoang Vu , Milutinovic Bojana , Nichols James M. , Mahalingam Rajasekaran , Shepherd Andrew J.
Published: August 2022

Reports of neurological sequelae related to colon cancer are largely restricted to rare instances of paraneoplastic syndromes, due to autoimmune reactions. Systemic inflammation associated with tumor development influences sensory neuron function in other disease models, though the extent to which this occurs in colorectal cancer is unknown. We induced orthotopic colorectal cancer via orthotopic injection of two colorectal cancer cell lines (MC38 and CT26) in two different mouse strains (C57BL/6 and Balb/c, respectively). Behavioral tests of pain sensitivity and activity did not detect significant alterations in sensory sensitivity or diminished well-being throughout tumor development. However, immunohistochemistry revealed widespread reductions in intraepidermal nerve fiber density in the skin of tumor-bearing mice. Though loss of nerve fiber density was not associated with increased expression of cell injury markers in dorsal root ganglia, lumbar dorsal root ganglia neurons of tumor-bearing animals showed deficits in mitochondrial function. These neurons also had reduced cytosolic calcium levels in live-cell imaging and reduced spontaneous activity in multi-electrode array analysis. Bulk RNA sequencing of DRGs from tumor-bearing mice detected activation of gene expression pathways associated with elevated cytokine and chemokine signaling, including CXCL10. This is consistent with the detection of CXCL10 (and numerous other cytokines, chemokines and growth factors) in MC38 and CT26 cell-conditioned media, and the serum of tumor-bearing mice. Our study demonstrates in a pre-clinical setting that colon cancer is associated with latent sensory neuron dysfunction and implicates cytokine/chemokine signaling in this process. These findings may have implications for determining risk factors and treatment responsiveness related to neuropathy in colorectal cancer.
A cross-sectional study examining consideration of self-managed abortion among people seeking facility-based care in the United States
Authors: Ralph Lauren , Ehrenreich Katherine , Kaller Shelly , Biggs M. Antonia
Published: August 2022

Introduction

With increasing restrictions on abortion across the United States, we sought to understand whether people seeking abortion would consider ending their pregnancy on their own if unable to access a facility-based abortion.

Methods

From January to June 2019, we surveyed patients seeking abortion at 4 facilities in 3 US states. We explored consideration of self-managed abortion (SMA) using responses to the question: “Would you consider ending this pregnancy on your own if you are unable to obtain care at a health care facility?” We used multivariable Poisson regression to assess associations between individual sociodemographic, pregnancy and care-seeking characteristics and prevalence of considering SMA. In bivariate Poisson models, we also explored whether consideration of SMA differed by specific obstacles to abortion care.

Results

One-third (34%) of 741 participants indicated they would definitely or probably consider ending the pregnancy on their own if unable to obtain care at a facility. Consideration of SMA was higher among those who reported no health insurance (adjusted prevalence ratio [aPR] = 1.66; 95% Confidence Interval [CI] 1.12–2.44), described the pregnancy as unintended (aPR = 1.53; 95% CI 1.08–2.16), were seeking abortion due to concerns about their own physical or mental health (aPR = 1.50, 95% CI 1.02, 2.20), or experienced obstacles that delayed their abortion care seeking (aPR = 2.26, 95% CI 1.49, 3.40). Compared to those who would not consider SMA, participants who would consider SMA expressed higher difficulty finding an abortion facility (35 vs. 27%, p = 0.019), figuring out how to get to the clinic (29 vs 21%, p = 0.021) and needing multiple clinic visits (23 vs 17%, p = 0.044).

Conclusions.

One in three people seeking facility-based abortion would consider SMA if unable to obtain abortion care at a facility. As abortion access becomes increasingly restricted in the US, SMA may become more common. Future research should continue to monitor people’s consideration and use of SMA and ensure that they have access to safe and effective methods.
Effects of hawthorn seed oil on plasma cholesterol and gut microbiota
Authors: Kwek Erika , Yan Chi , Ding Huafang , Hao Wangjun , He Zouyan , Liu Jianhui , Ma Ka Ying , Zhu Hanyue , Chen Zhen-Yu
Published: August 2022

Background

Hypercholesterolemia and gut microbiota dysbiosis are associated with the risk of cardiovascular diseases. Hawthorn fruits has shown to be cardioprotective and hypocholesterolemic. However, no studies to date have studied the biological activity of hawthorn seed oil (HSO). The present study was to investigate if HSO could favourably reduce plasma cholesterol and modulate gut microbiota in hypercholesterolemia hamsters.

Methods

Golden Syrian hamsters (age, 8 weeks) were randomly divided into five groups (n = 8, each) and fed one of the following five diets, namely a non-cholesterol diet, a high cholesterol diet containing 0.15% cholesterol (HCD); a HCD diet with addition of 4.75% HSO (LHSO), a HCD diet with addition of 9.5% HSO (HHSO), a HCD diet with addition of 0.50% cholestyramine as positive control diet. After 6-week dietary intervention, plasma lipids, inflammatory markers, atherosclerosis plaque, hepatic and fecal lipids were quantified. Microbiota in fresh feces were analysed by sequencing 16S rRNA genes, while RT-PCR and Western blot analyses were employed to quantify the expression of genes involved in cholesterol homeostasis.

Results

HSO at a dose of 9.5% HSO could decrease plasma cholesterol and non-HDL-cholesterol by 15%. Additionally, both HSO experimental groups also suppressed mRNA of 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMG-CoA-R). Supplementation of HSO at 4.75% could significantly increase the excretion of fecal acidic sterols, accompanied by elevation of short-chain fatty acid levels in feces. The analyses of gut microbiome indicated that HSO supplementation could selectively alter the genera abundance of gut bacteria that were correlated with cholesterol metabolism including unclassified_f__Christensenellaceae, Ruminococcaceae_NK4A214_ group, norank_o_Gastranaerophilales, Faecalibaculum, Peptococcus, norank_f__Clostridiales_vadinBB60_group and Ruminococcus_2.

Conclusions

HSO supplementation was able to decrease plasma cholesterol by favourably modulating gut microbiota composition and gut-derived metabolites associated with cholesterol regulation.

Graphical Abstract
The optimal screw-hole positions of the eccentric revision cup based on a morphological study
Authors: Zhang Yanchao , Ma Haiyang , Liu Yang , Shen Junmin , Zhang Bohan , Zhou Yonggang
Published: August 2022

Background

Bridging bone defects in revision total hip arthroplasty is a challenge to orthopedic surgeons. The eccentric revision cup is a progression of jumbo cup. Our aim is to confirm the optimal screw-hole positions of the eccentric revision cup by morphological measurements of three-dimensional pelvic reconstruction.

Methods

Eighty CT images were converted to virtual three-dimensional bones. After simulating the surgery procedure, all available screw holes were inserted with the screws in virtual. By measuring the length of the screw in the pelvic bone, we determined the rich bone stock area. Then the screw holes were designed according to the characteristics of bone stock distribution. The peripheral screw-hole cluster and inner screw-hole cluster were studied respectively.

Results

For peripheral screw-hole cluster, five screw holes were evenly distributed between point A and point B in the thicker rim. For inner screw-hole cluster, screw hole 1 and screw hole 2 are the recommended inner screw holes.

Conclusion

The eccentric revision cup has inherited the strengths of jumbo cup besides several unique advantages, including using the peripheral screws enhancing primary stability; decreasing the shift of hip rotation center and restoring biomechanical function; reducing the risk of dislocation because of the smaller head-cup differences; increasing the contact area between the outer cup and the host bone while maintaining a normal inclination of the inner cup. In this study, we confirmed the optimal screw-hole positions of the eccentric revision cup by surgical simulation and morphological measurement. However, biomechanical tests are still being further explored.
A new perspective on NO pathway in sepsis and ADMA lowering as a potential therapeutic approach
Authors: Singh Jaipal , Lee Young , Kellum John A.
Published: August 2022

The nitric oxide pathway plays a critical role in vascular homeostasis. Increased levels of systemic nitric oxide (NO) are observed in preclinical models of sepsis and endotoxemia. This has led to the postulation that vasodilation by inducible nitric oxide synthase (iNOS) generated NO may be a mechanism of hypotension in sepsis. However, contrary to the expected pharmacological action of a nitric oxide synthase (NOS) inhibitor, clinical studies with L-NAME produced adverse cardiac and pulmonary events, and higher mortality in sepsis patients. Thus, the potential adverse effects of NO in human sepsis and shock have not been fully established. In recent years, the emerging new understanding of the NO pathway has shown that an endogenously produced inhibitor of NOS, asymmetric dimethylarginine (ADMA), a host response to infection, may play an important role in the pathophysiology of sepsis as well as organ damage during ischemia–reperfusion. ADMA induces microvascular dysfunction, proinflammatory and prothrombotic state in endothelium, release of inflammatory cytokines, oxidative stress and mitochondrial dysfunction. High levels of ADMA exist in sepsis patients, which may produce adverse effects like those observed with L-NAME. Several studies have demonstrated the association of plasma ADMA levels with mortality in sepsis patients. Preclinical studies in sepsis and ischemia–reperfusion animal models have shown that lowering of ADMA reduced organ damage and improved survival. The clinical finding with L-NAME and the preclinical research on ADMA “bed to bench” suggest that ADMA lowering could be a potential therapeutic approach to attenuate progressive organ damage and mortality in sepsis. Testing of this approach is now feasible by using the pharmacological molecules that specifically lower ADMA.
Molecular profiling of human non-small cell lung cancer by single-cell RNA-seq
Authors: Li Qingqing , Wang Rui , Yang Zhenlin , Li Wen , Yang Jingwei , Wang Zhijie , Bai Hua , Cui Yueli , Tian Yanhua , Wu Zixin , Guo Yuqing , Xu Jiachen , Wen Lu , He Jie , Tang Fuchou , Wang Jie
Published: August 2022

Background

Lung cancer, one of the most common malignant tumors, exhibits high inter- and intra-tumor heterogeneity which contributes significantly to treatment resistance and failure. Single-cell RNA sequencing (scRNA-seq) has been widely used to dissect the cellular composition and characterize the molecular properties of cancer cells and their tumor microenvironment in lung cancer. However, the transcriptomic heterogeneity among various cancer cells in non-small cell lung cancer (NSCLC) warrants further illustration.

Methods

To comprehensively analyze the molecular heterogeneity of NSCLC, we performed high-precision single-cell RNA-seq analyses on 7364 individual cells from tumor tissues and matched normal tissues from 19 primary lung cancer patients and 1 pulmonary chondroid hamartoma patient.

Results

In 6 of 16 patients sequenced, we identified a significant proportion of cancer cells simultaneously expressing classical marker genes for two or even three histologic subtypes of NSCLC—adenocarcinoma (ADC), squamous cell carcinoma (SCC), and neuroendocrine tumor (NET) in the same individual cell, which we defined as mixed-lineage tumor cells; this was verified by both co-immunostaining and RNA in situ hybridization. These data suggest that mixed-lineage tumor cells are highly plastic with mixed features of different types of NSCLC. Both copy number variation (CNV) patterns and mitochondrial mutations clearly showed that the mixed-lineage and single-lineage tumor cells from the same patient had common tumor ancestors rather than different origins. Moreover, we revealed that patients with high mixed-lineage features of different cancer subtypes had worse survival than patients with low mixed-lineage features, indicating that mixed-lineage tumor features were associated with poorer prognosis. In addition, gene signatures specific to mixed-lineage tumor cells were identified, includingAKR1B1. Gene knockdown and small molecule inhibition ofAKR1B1can significantly decrease cell proliferation and promote cell apoptosis, suggesting thatAKR1B1plays an important role in tumorigenesis and can serve as a candidate target for tumor therapy of NSCLC patients with mixed-lineage tumor features.

Conclusions

In summary, our work provides novel insights into the tumor heterogeneity of NSCLC in terms of the identification of prevalent mixed-lineage subpopulations of cancer cells with combined signatures of SCC, ADC, and NET and offers clues for potential treatment strategies in these patients.