bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles of hypoxic environment and M2 macrophage-derived extracellular vesicles on the progression of non-small cell lung cancer
Authors: Chu Xiao , Wang Zetian , Wang Weiqing , Liu Wenjing , Cao Yunyun , Feng Liang 
Published: July 2023

Abstract
Background
Hypoxia contributes to the development of invasive and metastatic cancer cells, and is detrimental to cancer treatment. This study aimed to explore the molecular mechanisms by which hypoxic microenvironments affect hypoxic non-small cell lung cancer (NSCLC) development and the effects of M2 macrophage-derived extracellular vesicles (EVs) on NSCLC cells.

Methods
A549 cells were cultured in an anoxic incubator for 48 h to construct hypoxic A549 cells, and then normal and hypoxic A549 cells were harvested for RNA sequencing. Next, THP-1 cells were used to induce M2 macrophages, and EVs were isolated from THP-1 cells and M2 macrophages. Cell counting kit-8 and transwell assays were used to determine the viability and migration of hypoxic A549 cells, respectively.

Results
After sequencing, 2426 DElncRNAs and 501 DEmiRNAs were identified in normal A549 cells and hypoxic A549 cells. These DElncRNAs and DEmiRNAs were significantly enriched in “Wnt signaling pathway,” “Hippo signaling pathway,” “Rap1 signaling pathway,” “calcium signaling pathway,” “mTOR signaling pathway,” and “TNF signaling pathway.” Subsequently, ceRNA networks consisting of 4 lncRNA NDRG1 transcripts, 16 miRNAs and 221 target mRNAs were built, and the genes in the ceRNA networks were significantly associated with “Hippo signaling pathway” and “HIF-1 signaling pathway.” EVs were successfully extracted from THP-1 cells and M2 macrophages, and M2 macrophage-derived EVs significantly enhanced the viability and migration of hypoxic A549 cells. Finally, M2 macrophage-derived EVs further upregulated the expression of NDRG1-009, NDRG1-006, VEGFA, and EGLN3, while downregulating miR-34c-5p, miR-346, and miR-205-5p in hypoxic A549 cells.

Conclusions
M2 macrophage-derived EVs may worsen the progression of NSCLC in a hypoxic microenvironment by regulating the NDRG1-009-miR-34c-5p-VEGFA, NDRG1-006-miR-346-EGLN3, NDRG1-009-miR-205-5p-VEGFA, and Hippo/HIF-1 signaling pathways.
Epicardial adipose tissue in patients with chronic obstructive pulmonary disease: systematic review with meta‑analysis and trial sequential analysis
Authors: Lan Yi , Ma Qianli , Luo Guangming , Yang Heping , Li Yingrui , Zhang Qiao 
Published: July 2023

Abstract
Background
Limited data suggest that chronic obstructive pulmonary disease (COPD) patients have pathologic elevated epicardial adipose tissue (EAT), which is splanchnic fat tissue with anti-inflammatory properties and regulating free fatty acids functions. Therefore, there is a need for meta-analysis to explore the relationship between EAT and COPD.

Methods
Online databases were systematically searched for studies about EAT in COPD patients published up to October 5th, 2022. The EAT data of the COPD patient group and the control group were included. Trial sequential analysis (TSA) and meta-analysis were applied to assess the difference in EAT between patients with and without COPD. TSA software and Stata 12.0 were used in all statistical analyses.

Results
The final analysis included 5 studies (n = 596 patients). COPD patients had significantly more EAT than control subjects (SMD: 0.0.802; 95% CI: 0.231, 1.372; P = 0.006; TSA-adjusted 95% CI 1.20, 1.80; P < 0.0001). And higher CRP levels in COPD patients than non-COPD patients, whereas triglycerides and LDL were not significantly different between patients with and without COPD.

Conclusion
EAT is abnormally elevated in COPD patients, which may be related to systemic inflammatory responses in COPD.

PROSPERO number
CRD42021228273.
The knowledge, attitudes and behaviors of hospital nurses on smoking cessation interventions: a cross-sectional study
Authors: Čivljak Marta , Ačkar Lovro , Puljak Livia 
Published: July 2023

Abstract
Background
Smoking is a major public health problem in Croatia. It is unknown to what extent nurses in Croatia use interventions for smoking cessation to help their patients. This study aimed to analyze the knowledge, attitudes and behaviors of hospital nurses on smoking cessation interventions.

Methods
We conducted a cross-sectional study in Zagreb, Croatia, in 2022 on a convenient sample of hospital nurses. We collected data with a questionnaire that included sociodemographic questions and questions about the frequency of implementation of 5 A’s (Ask, Advise, Assess, Assist, Arrange) interventions for smoking cessation during their work using the Helping Smokers Quit (HSQ) survey, participants’ attitudes and knowledge about smoking cessation skills and the smoking status of the nurses.

Results
There were 824 nurses employed in the targeted departments; 258 nurses participated in the study (response rate: 31%). Among them, 43% responded that they always ask patients about their use of tobacco products. Only 2.7% indicated that they always help the patient to stop smoking. Very few (2%) attended any training in the past two years about helping patients to quit smoking, and 82% never had such training. 44% of the included nurses were smokers. Nurses who smoked stated more frequently than nonsmokers they should not be role models for their patients by avoiding smoking (P 0.001). Additionally, patients were less frequently questioned about their inability to stop smoking by nurses who smoked than nurses who did not smoke (P = 0.010).

Conclusion
Even though smoking cessation interventions delivered by nurses were proven effective, such interventions are used by a small number of surveyed nurses. A small number of nurses have received training to help them support smokers in quitting. The high smoking prevalence among nurses may impact their attitudes and the implementation of workplace smoking cessation efforts.
Responsive and resilient healthcare? ‘Moments of Resilience’ in post-hospitalisation services for COVID-19
Authors: Overton Charlotte , Emerson Tristan , A Evans Rachael , Armstrong Natalie 
Published: July 2023

Abstract
Background
COVID-19 caused disruption to healthcare services globally, resulting in high numbers of hospital admissions and with those discharged often requiring ongoing support. Within the UK, post-discharge services typically developed organically and were shaped over time by local need, funding, and government guidance. Drawing on the Moments of Resilience framework, we explore the development of follow-up services for hospitalised patients by considering the links between resilience at different system levels over time. This study contributes to the resilient healthcare literature by providing empirical evidence of how diverse stakeholders developed and adapted services for patients following hospitalisation with COVID-19 and how action taken at one system level influenced another.

Methods
Qualitative research comprising comparative case studies based on interviews. Across three purposively selected case studies (two in England, one in Wales) a total of 33 semi-structured interviews were conducted with clinical staff, managers and commissioners who had been involved in developing and/or implementing post-hospitalisation follow-up services. The interviews were audio-recorded and professionally transcribed. Analysis was conducted with the aid of NVivo 12.

Results
Case studies demonstrated three distinct examples of how healthcare organisations developed and adapted their post-discharge care provision for patients, post-hospitalisation with COVID-19. Initially, the moral distress of witnessing the impact of COVID-19 on patients who were being discharged coupled with local demand gave clinical staff the impetus to take action. Clinical staff and managers worked closely to plan and deliver organisations’ responses. Funding availability and other contextual factors influenced situated and immediate responses and structural adaptations to the post-hospitalisation services. As the pandemic evolved, NHS England and the Welsh government provided funding and guidance for systemic adaptations to post-COVID assessment clinics. Over time, adaptations made at the situated, structural, and systemic levels influenced the resilience and sustainability of services.

Conclusions
This paper addresses understudied, yet inherently important, aspects of resilience in healthcare by exploring when and where resilience occurs across the healthcare system and how action taken at one system level influenced another. Comparison across the case studies showed that organisations responded in similar and different ways and on varying timescales to a disruption and national level strategies.
Genetically mimicked effects of ASGR1 inhibitors on all-cause mortality and health outcomes: a drug-target Mendelian randomization study and a phenome-wide association study
Authors: Yang Guoyi , Schooling C. Mary 
Published: July 2023

AbstractBackgroundAsialoglycoprotein receptor 1 (ASGR1) is emerging as a potential drug target to reduce low-density lipoprotein (LDL)-cholesterol and coronary artery disease (CAD) risk. Here, we investigated genetically mimicked ASGR1 inhibitors on all-cause mortality and any possible adverse effects.MethodsWe conducted a drug-target Mendelian randomization study to assess genetically mimicked effects of ASGR1 inhibitors on all-cause mortality and 25a priorioutcomes relevant to lipid traits, CAD, and possible adverse effects, i.e. liver function, cholelithiasis, adiposity and type 2 diabetes. We also performed a phenome-wide association study of 1951 health-related phenotypes to identify any novel effects. Associations found were compared with those for currently used lipid modifiers, assessed using colocalization, and replicated where possible.ResultsGenetically mimicked ASGR1 inhibitors were associated with a longer lifespan (3.31 years per standard deviation reduction in LDL-cholesterol, 95% confidence interval 1.01 to 5.62). Genetically mimicked ASGR1 inhibitors were inversely associated with apolipoprotein B (apoB), triglycerides (TG) and CAD risk. Genetically mimicked ASGR1 inhibitors were positively associated with alkaline phosphatase, gamma glutamyltransferase, erythrocyte traits, insulin-like growth factor 1 (IGF-1) and C-reactive protein (CRP), but were inversely associated with albumin and calcium. Genetically mimicked ASGR1 inhibitors were not associated with cholelithiasis, adiposity or type 2 diabetes. Associations with apoB and TG were stronger for ASGR1 inhibitors compared with currently used lipid modifiers, and most non-lipid effects were specific to ASGR1 inhibitors. The probabilities for colocalization were > 0.80 for most of these associations, but were 0.42 for lifespan and 0.30 for CAD. These associations were replicated using alternative genetic instruments and other publicly available genetic summary statistics.ConclusionsGenetically mimicked ASGR1 inhibitors reduced all-cause mortality. Beyond lipid-lowering, genetically mimicked ASGR1 inhibitors increased liver enzymes, erythrocyte traits, IGF-1 and CRP, but decreased albumin and calcium.
Dobutamine-induced alternations in cerebral blood flow of healthy adults: a 3D pseudocontinuous arterial spin labeling study
Authors: Zhang Tingting , Niu Haijun , Liu Yawen , Cai Linkun , Liu Dong , Zhao Erwei , Li Min , Liu Wenjuan , Li Jing , Qiao PengGang , Zheng Wei , Ren Pengling , Wang Zhenchang 
Published: July 2023

Abstract
Background
It is unclear whether dobutamine, commonly used clinically in echocardiography and short-term congestive heart failure treatment for promoting increased myocardial contractility, affects brain microcirculatory behavior. Cerebral microcirculation plays an important role in ensuring adequate oxygen transport. Therefore, we investigated the effects of dobutamine on cerebral hemodynamics.

Methods
Forty-eight healthy volunteers without cardiovascular or cerebrovascular disease underwent MRI to obtain cerebral blood flow (CBF) maps using 3D pseudocontinuous arterial spin labeling before and during the dobutamine stress test. Additionally, cerebrovascular morphology was obtained based on 3D-time-off-light (3D-TOF) magnetic resonance angiography (MRA). Electrocardiogram, heart rate (HR), respiration rate (RR), blood pressure, and blood oxygen were simultaneously recorded before and during dobutamine injection and during recovery (not during MRI). The anatomic features of the circle of Willis and the basilar artery (BA) diameter were assessed on MRA images by two radiologists with extensive neuroimaging experience. Binary logistic regression was used to test for the independent determinants of CBF changes.

Results
HR, RR, systolic (SBP), and diastolic blood pressure (DBP) significantly increased after dobutamine infusion. Blood oxygen levels remained similar. Compared to the CBF in the resting state, the CBF values exhibited significantly lower CBF levels in both grey matter and white matter. Furthermore, compared with the CBF in the resting state, that in the stress state was decreased in the anterior circulation, mainly in the frontal lobe (voxel level P < 0.001, pixel level P < 0.05). Logistic regression showed that body mass index (BMI; odds ratio [OR] 5.80, 95% confidence interval [CI] 1.60–21.01, P = 0.008], resting SBP (OR 0.64, 95% CI 0.45–0.92, P = 0.014), and BA diameter (OR 11.04, 95% CI 1.05–116.53, P = 0.046) were significantly associated with frontal lobe CBF changes.

Conclusions
Dobutamine-induced stress significantly decreased CBF in the frontal lobe anterior circulation. Individuals with a high BMI and low SBP during the dobutamine stress test are more likely to have a stress-induced CBF decrease. Thus, attention should be paid to blood pressure, BMI, and cerebrovascular morphology of patients undergoing dobutamine stress echocardiography or those receiving intensive care or anesthesia.
Progressive trajectories of schizophrenia across symptoms, genes, and the brain
Authors: Jiang Sisi , Huang Huan , Zhou Jingyu , Li Hechun , Duan Mingjun , Yao Dezhong , Luo Cheng 
Published: July 2023

Abstract
Background
Schizophrenia is characterized by complex psychiatric symptoms and unclear pathological mechanisms. Most previous studies have focused on the morphological changes that occur over the development of the disease; however, the corresponding functional trajectories remain unclear. In the present study, we aimed to explore the progressive trajectories of patterns of dysfunction after diagnosis.

Methods
Eighty-six patients with schizophrenia and 120 healthy controls were recruited as the discovery dataset. Based on multiple functional indicators of resting-state brain functional magnetic resonance imaging, we conducted a duration-sliding dynamic analysis framework to investigate trajectories in association with disease progression. Neuroimaging findings were associated with clinical symptoms and gene expression data from the Allen Human Brain Atlas database. A replication cohort of patients with schizophrenia from the University of California, Los Angeles, was used as the replication dataset for the validation analysis.

Results
Five stage-specific phenotypes were identified. A symptom trajectory was characterized by positive-dominated, negative ascendant, negative-dominated, positive ascendant, and negative surpassed stages. Dysfunctional trajectories from primary and subcortical regions to higher-order cortices were recognized; these are associated with abnormal external sensory gating and a disrupted internal excitation–inhibition equilibrium. From stage 1 to stage 5, the importance of neuroimaging features associated with behaviors gradually shifted from primary to higher-order cortices and subcortical regions. Genetic enrichment analysis identified that neurodevelopmental and neurodegenerative factors may be relevant as schizophrenia progresses and highlighted multiple synaptic systems.

Conclusions
Our convergent results indicate that progressive symptoms and functional neuroimaging phenotypes are associated with genetic factors in schizophrenia. Furthermore, the identification of functional trajectories complements previous findings of structural abnormalities and provides potential targets for drug and non-drug interventions in different stages of schizophrenia.
Neutralizing antibody levels associated with injectable and aerosolized Ad5-nCoV boosters and BA.2 infection
Authors: Wang Fuzhen , Huang Baoying , Deng Yao , Zhang Shaobai , Liu Xiaoqiang , Wang Lei , Liu Qianqian , Zhao Li , Tang Lin , Wang Wenling , Wang Xiaoqi , Ye Fei , Hu Weijun , Yang Haitao , Wang Siquan , Ren Jiao , Liu Xiaoyu , Wang Cangning , Guan Xuhua , Wang Ruize , Zheng Yan , Zhang Xianfeng , Zheng Hui , Wu Dan , An Zhijie , Xu Wenbo , Rodewald Lawrence E. , Gao George F. , Yin Zundong , Tan Wenjie 
Published: July 2023

Abstract
Background
Several COVID-19 vaccines are in widespread use in China. Few data exist on comparative immunogenicity of different COVID-19 vaccines given as booster doses. We aimed to assess neutralizing antibody levels raised by injectable and inhaled aerosolized recombinant adenovirus type 5 (Ad5)-vectored COVID-19 vaccine as a heterologous booster after an inactivated COVID-19 vaccine two-dose primary series.

Methods
Using an open-label prospective cohort design, we recruited 136 individuals who had received inactivated vaccine primary series followed by either injectable or inhaled Ad5-vectored vaccine and measured neutralizing antibody titers against ancestral SARS-CoV-2 virus and Omicron BA.1 and BA.5 variants. We also measured neutralizing antibody levels in convalescent sera from 39 patients who recovered from Omicron BA.2 infection.

Results
Six months after primary series vaccination, neutralizing immunity against ancestral SARS-CoV-2 was low and neutralizing immunity against Omicron (B.1.1.529) was lower. Boosting with Ad5-vectored vaccines induced a high immune response against ancestral SARS-CoV-2. Neutralizing responses against Omicron BA.5 were ≥ 80% lower than against ancestral SARS-CoV-2 in sera from prime-boost subjects and in convalescent sera from survivors of Omicron BA.2 infection. Inhaled aerosolized Ad5-vectored vaccine was associated with greater neutralizing titers than injectable Ad5-vectored vaccine against ancestral and Omicron SARS-CoV-2 variants.

Conclusions
These findings support the current strategy of heterologous boosting with injectable or inhaled Ad5-vectored SARS-CoV-2 vaccination of individuals primed with inactivated COVID-19 vaccine.
Family history and breast cancer risk for Asian women: a systematic review and meta-analysis
Authors: Wang Heran , MacInnis Robert J. , Li Shuai 
Published: July 2023

Abstract
Background
Studies of women of European ancestry have shown that the average familial relative risk for first-degree relatives of women with breast cancer is approximately twofold, but little is known for Asian women. We aimed to provide evidence for the association between family history and breast cancer risk for Asian women by systematically reviewing published literature.

Methods
Studies reporting the familial relative risk of breast cancer for Asian women were searched in three online databases and complemented by a manual search. Odds ratios (ORs) for the association between family history and breast cancer risk were pooled across all included studies and by subgroups in terms of the type of family history, age, menopausal status and geographical region.

Results
The pooled OR for women who have a first-degree relative with breast cancer was 2.46 (95% confidence interval [CI]: 2.03, 2.97). There was no evidence that the familial risk differed by the type of affected relative (mother versus sisters), the woman’s age (< 50 years versus ≥ 50 years), menopausal status (pre versus post) and geographical region (East and Southeast Asia versus other regions) (all P > 0.3). The pooled ORs for women of Asian ancestry with a family history in any relative were similar for those living in non-Asian countries (2.26, 95% CI: 1.42, 3.59) compared with those living in Asian countries (2.18, 95% CI: 1.85, 2.58).

Conclusions
Family history of breast cancer is associated with an approximately twofold relative risk of breast cancer for Asian women, which is of similar magnitude to that observed for women of European ancestry. This implies that similar familial factors are implicated in breast cancer risk between women of European and Asian ancestries. Genetic factors are likely to play a substantial role in explaining the breast cancer familial risk for Asian women, as similar risks were observed across different living environments and cultures.
Evaluation of post-acute care and one-year outcomes among Medicare beneficiaries with hip fractures: a retrospective cohort study
Authors: Riester Melissa R. , Beaudoin Francesca L. , Joshi Richa , Hayes Kaleen N. , Cupp Meghan A. , Berry Sarah D. , Zullo Andrew R. 
Published: July 2023

Abstract
Background
Post-acute care (PAC) services after hospitalization for hip fracture are typically provided in skilled nursing facilities (SNFs), inpatient rehabilitation facilities (IRFs), or at home via home health care (HHC). Little is known about the clinical course following PAC for hip fracture. We examined the nationwide burden of adverse outcomes by PAC setting in the year following discharge from PAC for hip fracture.

Methods
This retrospective cohort included Medicare Fee-for-Service beneficiaries > 65 years who received PAC services in U.S. SNFs, IRFs, or HHC following hip fracture hospitalization between 2012 and 2018. Individuals who had a fall-related injury (FRI) during PAC or received PAC services in multiple settings were excluded. Primary outcomes included FRIs, all-cause hospital readmissions, and death in the year following discharge from PAC. Cumulative incidences and incidence rates for adverse outcomes were reported by PAC setting. Exploratory analyses examined risk ratios and hazard ratios between settings before and after inverse-probability-of-treatment-weighting, which accounted for 43 covariates.

Results
Among 624,631 participants (SNF, 67.78%; IRF, 16.08%; HHC, 16.15%), the mean (standard deviation) age was 82.70 (8.26) years, 74.96% were female, and 91.30% were non-Hispanic White. Crude incidence rates (95%CLs) per 1000 person-years were highest among individuals receiving SNF care for FRIs (SNF, 123 [121, 123]; IRF, 105 [102, 107]; HHC, 89 [87, 91]), hospital readmission (SNF, 623 [619, 626]; IRF, 538 [532, 544]; HHC, 418 [414, 423]), and death (SNF, 167 [165, 169]; IRF, 47 [46, 49]; HHC, 55 [53, 56]). Overall, rates of adverse outcomes generally remained higher among SNF care recipients after covariate adjustment. However, inferences about the group with greater adverse outcomes differed for FRIs and hospital readmissions based on risk ratio or hazard ratio estimates.

Conclusions
In this retrospective cohort study of individuals hospitalized for hip fracture, rates of adverse outcomes in the year following PAC were common, especially among SNF care recipients. Understanding risks and rates of adverse events can inform future efforts to improve outcomes for older adults receiving PAC for hip fracture. Future work should consider calculating risk and rate measures to assess the influence of differential time under observation across PAC groups.