bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial therapies for prevention of recurrent acute exacerbations of COPD (AECOPD): beyond the guidelines
Authors: Brennan Michelle , McDonnell M. J. , Harrison M. J. , Duignan N. , O’Regan A. , Murphy D. M. , Ward C. , Rutherford R. M. 
Published: March 2022

AbstractBackgroundUnfortunately, many COPD patients continue to exacerbate despite good adherence to GOLD Class D recommended therapy. Acute exacerbations lead to an increase in symptoms, decline in lung function and increased mortality rate. The purpose of this review is to do a literature search for any prophylactic anti-microbial treatment trials in GOLD class D patients who ‘failed’ recommended therapy and discuss the role of COPD phenotypes, lung and gut microbiota and co-morbidities in developing a tailored approach to anti-microbial therapies for high frequency exacerbators.Main textThere is a paucity of large, well-conducted studies in the published literature to date. Factors such as single-centre, study design, lack of well-defined controls, insufficient patient numbers enrolled and short follow-up periods were significant limiting factors in numerous studies. One placebo-controlled study involving more than 1000 patients, who had 2 or more moderate exacerbations in the previous year, demonstrated a non-significant reduction in exacerbations of 19% with 5 day course of moxifloxacillin repeated at 8 week intervals. InPseudomonas aeruginosa(Pa) colonised COPD patients, inhaled antimicrobial therapy using tobramycin, colistin and gentamicin resulted in significant reductions in exacerbation frequency. Viruses were found to frequently cause acute exacerbations in COPD (AECOPD), either as the primary infecting agent or as a co-factor. However, other, than the influenza vaccination, there were no trials of anti-viral therapies that resulted in a positive effect on reducing AECOPD. Identifying clinical phenotypes and co-existing conditions that impact on exacerbation frequency and severity is essential to provide individualised treatment with targeted therapies. The role of the lung and gut microbiome is increasingly recognised and identification of pathogenic bacteria will likely play an important role in personalised antimicrobial therapies.ConclusionAntimicrobial therapeutic options in patients who continue to exacerbate despite adherence to guidelines-directed therapy are limited. Phenotyping patients, identification of co-existing conditions and assessment of the microbiome is key to individualising antimicrobial therapy. Given the impact of viruses on AECOPD, anti-viral therapeutic agents and targeted anti-viral vaccinations should be the focus of future research studies.
Exosomes as bio-inspired nanocarriers for RNA delivery: preparation and applications
Authors: Amiri Ala , Bagherifar Rafieh , Ansari Dezfouli Ehsan , Kiaie Seyed Hossein , Jafari Reza , Ramezani Reihaneh 
Published: March 2022

AbstractNanocarriers as drug/biomolecule delivery systems have been significantly developed during recent decades. Given the stability, reasonable delivery efficiency, and safety of nanocarriers, there are several barriers in the fulfillment of successful clinical application of these delivery systems. These challenges encouraged drug delivery researchers to establish innovative nanocarriers with longer circulation time, high stability, and high compatibility. Exosomes are extracellular nanometer-sized vesicles released through various cells. These vesicles serve as nanocarriers, possessing great potential to overcome some obstacles encountered in gene and drug delivery due to their natural affinity to recipient cells and the inherent capability to shuttle the genes, lipids, proteins, and RNAs between cells. So far, there has been a lot of valuable research on drug delivery by exosomes, but research on RNA delivery, especially mRNA, is very limited. Since mRNA-based vaccines and therapies have recently gained particular prominence in various diseases, it is essential to find a suitable delivery system due to the large size and destructive nature of these nucleic acids. That's why we're going to take a look at the unique features of exosomes and their isolation and loading methods, to embrace this idea that exosome-mediated mRNA-based therapies would be introduced as a very efficient strategy in disease treatment within the near future.Graphical Abstract
Potential benefit of osimertinib plus bevacizumab in leptomeningeal metastasis with EGFR mutant non-small-cell lung cancer
Authors: Yi Yali , Cai Jing , Xu Peng , Xiong Le , Lu Zhiqin , Zeng Zhimin , Liu Anwen 
Published: March 2022

Abstract
Background
EGFR-mutant non-small cell lung cancer (NSCLC) is prone to leptomeningeal metastasis (LM) after Tyrosine kinase inhibitors (TKIs) treatment. Our previous study suggested that osimertinib plus bevacizumab was safe and effective in LM from EGFR-mutant NSCLC. This study aimed to compare the efficacy of osimertinib plus bevacizumab with osimertinib in EGFR-mutant NSCLC patients with LM.

Methods
We retrospectively reviewed the data from 27 LM patients with EGFR-mutant NSCLC who received osimertinib with or without bevacizumab at the Second Affiliated Hospital of Nanchang University. Next, we investigated the antitumor efficacy of osimertinib plus bevacizumab in an LM xenograft model using the H1975 (EGFR exon20 T790M and exon21 L858R) cell line. We examined the ability of osimertinib plus bevacizumab compared with osimertinib to penetrate the blood–brain barrier (BBB) and explored the potential mechanism.

Results
Our retrospective study observed the improved survival of LM patients in osimertinib plus bevacizumab group. The median overall survival (OS) of the patients who received osimertinib and bevacizumab (n = 16) compared with osimertinib group (n = 11) was 18.0 months versus 13.7 months (log-rank test, p = 0.046, HR = 2.867, 95% CI 1.007–8.162). The median intracranial Progression-free Survival (iPFS) was 10.6 months versus 5.5 months (log-rank test, p = 0.037, HR = 3.401, 95% CI 1.079–10.720). In the LM xenograft model with H1975 cells, the combined treatment significantly increased the effective intracranial concentration of osimertinib, modulated the level of E-cadherin and downregulated the levels of EGFR and downstream signaling pathways including p-AKT and reduced tumor microvessel density (TMD), indicated that combined osimertinib with bevacizumab may exhibit a synergistic effect in EGFR-mutant LM model possibly by modulating the level of E-cadherin.

Conclusions
Our findings indicate the potential benefit of osimertinib plus bevacizumab in LM with EGFR-mutant NSCLC, and more larger sample size research are still needed.
Homer1 promotes the conversion of A1 astrocytes to A2 astrocytes and improves the recovery of transgenic mice after intracerebral hemorrhage
Authors: Fei Xiaowei , Dou Ya-nan , Wang Li , Wu Xiuquan , Huan Yu , Wu Shuang , He Xin , Lv Weihao , Wei Jialiang , Fei Zhou 
Published: March 2022

Abstract
Background
Inflammation induced by intracerebral hemorrhage (ICH) is one of the main causes of the high mortality and poor prognosis of patients with ICH. A1 astrocytes are closely associated with neuroinflammation and neurotoxicity, whereas A2 astrocytes are neuroprotective. Homer scaffolding protein 1 (Homer1) plays a protective role in ischemic encephalopathy and neurodegenerative diseases. However, the role of Homer1 in ICH-induced inflammation and the effect of Homer1 on the phenotypic conversion of astrocytes remain unknown.

Methods
Femoral artery autologous blood from C57BL/6 mice was used to create an ICH model. We use the A1 phenotype marker C3 and A2 phenotype marker S100A10 to detect astrocyte conversion after ICH. Homer1 overexpression/knock-down mice were constructed by adeno-associated virus (AAV) infection to explore the role of Homer1 and its mechanism of action after ICH. Finally, Homer1 protein and selumetinib were injected into in situ hemorrhage sites in the brains of Homer1flox/flox/Nestin-Cre+/− mice to study the efficacy of Homer1 in the treatment of ICH by using a mouse cytokine array to explore the potential mechanism.

Results
The expression of Homer1 peaked on the third day after ICH and colocalized with astrocytes. Homer1 promotes A1 phenotypic conversion in astrocytes in vivo and in vitro. Overexpression of Homer1 inhibits the activation of MAPK signaling, whereas Homer1 knock-down increases the expression of pathway-related proteins. The Homer1 protein and selumetinib, a non-ATP competitive MEK1/2 inhibitor, improved the outcome in ICH in Homer1flox/flox/Nestin-Cre+/− mice. The efficacy of Homer1 in the treatment of ICH is associated with reduced expression of the inflammatory factor TNFSF10 and increased expression of the anti-inflammatory factors activin A, persephin, and TWEAK.

Conclusions
Homer1 plays an important role in inhibiting inflammation after ICH by suppressing the A1 phenotype conversion in astrocytes. In situ injection of Homer1 protein may be a novel and effective method for the treatment of inflammation after ICH.
Drug dosing in hospitalized obese patients with COVID-19
Authors: Barletta Jeffrey F. , Erstad Brian L. 
Published: March 2022

AbstractObesity is highly prevalent in hospitalized patients admitted with COVID-19. Evidence based guidelines are available for COVID-19-related therapies but dosing information specific to patients with obesity is lacking. Failure to account for the pharmacokinetic alterations that exist in this population can lead to underdosing, and treatment failure, or overdosing, resulting in an adverse effect. The objective of this manuscript is to provide clinicians with guidance for making dosing decisions for medications used in the treatment of patients with COVID-19. A detailed literature search was conducted for medications listed in evidence-based guidelines from the National Institutes of Health with an emphasis on pharmacokinetics, dosing and obesity. Retrieved manuscripts were evaluated and the following prioritization strategy was used to form the decision framework for recommendations: clinical outcome data > pharmacokinetic studies > adverse effects > physicochemical properties. Most randomized controlled studies included a substantial number of patients who were obese but few had large numbers of patients more extreme forms of obesity. Pharmacokinetic data have described alterations with volume of distribution and clearance but this variability does not appear to warrant dosing modifications. Future studies should provide more information on size descriptors and stratification of data according to obesity and body habitus.
Graphic Abstract
Increases in ambient air pollutants during pregnancy are linked to increases in methylation of IL4, IL10, and IFNγ
Authors: Aguilera Juan , Han Xiaorui , Cao Shu , Balmes John , Lurmann Fred , Tyner Tim , Lutzker Liza , Noth Elizabeth , Hammond S. Katharine , Sampath Vanitha , Burt Trevor , Utz P. J. , Khatri Purvesh , Aghaeepour Nima , Maecker Holden , Prunicki Mary , Nadeau Kari 
Published: March 2022

AbstractBackgroundAmbient air pollutant (AAP) exposure is associated with adverse pregnancy outcomes, such as preeclampsia, preterm labor, and low birth weight. Previous studies have shown methylation of immune genes associate with exposure to air pollutants in pregnant women, but the cell-mediated response in the context of typical pregnancy cell alterations has not been investigated. Pregnancy causes attenuation in cell-mediated immunity with alterations in the Th1/Th2/Th17/Treg environment, contributing to maternal susceptibility. We recruited women (n = 186) who were 20 weeks pregnant from Fresno, CA, an area with chronically elevated AAP levels. Associations of average pollution concentration estimates for 1 week, 1 month, 3 months, and 6 months prior to blood draw were associated with Th cell subset (Th1, Th2, Th17, and Treg) percentages and methylation of CpG sites (IL4,IL10, IFNγ,andFoxP3). Linear regression models were adjusted for weight, age, season, race, and asthma, using aQvalue as the false-discovery-rate-adjustedp-value across all genes.ResultsShort-term and mid-term AAP exposures to fine particulate matter (PM2.5), nitrogen dioxide (NO2) carbon monoxide (CO), and polycyclic aromatic hydrocarbons (PAH456) were associated with percentages of immune cells. A decrease in Th1 cell percentage was negatively associated with PM2.5(1 mo/3 mo:Q < 0.05), NO2(1 mo/3 mo/6 mo:Q < 0.05), and PAH456(1 week/1 mo/3 mo:Q < 0.05). Th2 cell percentages were negatively associated with PM2.5(1 week/1 mo/3 mo/6 mo:Q < 0.06), and NO2(1 week/1 mo/3 mo/6 mo:Q < 0.06). Th17 cell percentage was negatively associated with NO2(3 mo/6 mo:Q < 0.01), CO (1 week/1 mo:Q < 0.1), PM2.5(3 mo/6 mo:Q < 0.05), and PAH456(1 mo/3 mo/6 mo:Q < 0.08). Methylation of theIL10gene was positively associated with CO (1 week/1 mo/3 mo:Q < 0.01), NO2(1 mo/3 mo/6 mo:Q < 0.08), PAH456(1 week/1 mo/3 mo:Q < 0.01), and PM2.5(3 mo:Q = 0.06) whileIL4gene methylation was positively associated with concentrations of CO (1 week/1 mo/3 mo/6 mo:Q < 0.09). Also,IFNγgene methylation was positively associated with CO (1 week/1 mo/3 mo:Q < 0.05) and PAH456(1 week/1 mo/3 mo:Q < 0.06).ConclusionExposure to several AAPs was negatively associated with T-helper subsets involved in pro-inflammatory and anti-inflammatory responses during pregnancy. Methylation ofIL4, IL10, andIFNγ geneswith pollution exposure confirms previous research. These results offer insights into the detrimental effects of air pollution during pregnancy, the demand for more epigenetic studies, and mitigation strategies to decrease pollution exposure during pregnancy.
Signal enhancement ratio of CE-MRI: a potential biomarker of survival after hepatic arterial infusion chemotherapy in biliary tract cancers
Authors: Zheng Kanglian , Fu Shijie , Leng Boyu , Cui Yong , Yang Renjie , Cao Guang , Xu Liang , Li Wen-Qing , Li Ying , Zhu Xu , Gao Song , Liu Peng , Wang Xiaodong 
Published: March 2022

Abstract
Background
The association of contrast-enhanced MRI (CE-MRI) and the overall survival (OS) of biliary tract cancers (BTC) is ambiguous. Thus, the aim of this study is to evaluate the value of signal enhancement ratio (SER) and its early change in CE-MRI as biomarkers of survival after hepatic arterial infusion chemotherapy (HAIC) in BTC.

Results
One hundred and two BTC patients treated via HAIC with 3cir-OFF regimen between January 2011 and June 2020 were enrolled in this retrospective study. The median progression-free survival (PFS) and OS were 9.8 months [range 1.5–83.3 months, 95% confidence interval (CI) 7.789–11.811] and 14.2 months (range 1.8–83.3 months, 95% CI: 11.106–17.294), respectively. The cutoff value of SER before HAIC (SER0) was 1.04, and both median PFS and OS in the SER0 ≥ 1.04 group were longer than in the SER0 < 1.04 group (median PFS: 10.5 vs. 8.5 months, p = 0.027; median OS: 23.9 vs. 12.3 months, p < 0.001). The median OS in the ΔSER > 0 group was longer than in the ΔSER < 0 group (17.3 versus 12.8 months, p = 0.029 (ΔSER means the change of SER after two cycles of HAIC). Multivariate analysis showed SER0 (p = 0.029) and HAIC treatment cycle (p = 0.002) were independent predictors of longer survival.

Conclusions
SER in CE-MRI before HAIC (SER0) is a potential biomarker for the prediction of survival after HAIC in advanced BTC.
Quantitative measurements of esophageal varices using computed tomography for prediction of severe varices and the risk of bleeding: a preliminary study
Authors: Wan Shang , He Yuhao , Zhang Xin , Wei Yi , Song Bin 
Published: March 2022

Abstract
Background
We aimed to assess whether the quantitative parameters of esophageal varices (EV) based on computed tomography (CT) can noninvasively predict severe EV and the risk of esophageal variceal bleeding (EVB).

Methods
A total of 136 endoscopically confirmed EV patients were included in this retrospective study and were divided into a non-conspicuous (mild-to-moderate EV, n = 30) and a conspicuous EV group (severe EV, n = 106), a bleeding (n = 89) and a non-bleeding group (n = 47). EV grade (EVG), EV diameter (EVD), cross-sectional surface area (CSA), EV volume (EVV), spleen volume (SV), splenic vein (SNV), portal vein (PV), diameter of left gastric vein (DLGV), and the opening type of LGV were measured independently using 3D-slicer. Univariate and multivariate logistic analysis were used to determine the independent factors and the receiver operating characteristic (ROC) curves were performed to evaluate the diagnostic performance.

Results
The difference of EVG, EVD, CSA, EVV, DLGV, SNV between the conspicuous and non-conspicuous EV group were statistically significant (p < 0.05), area under the curves (AUCs) of them for predicting severe EV were 0.72, 0.772, 0.704, 0.768, 0.707, 0.65, with corresponding sensitivities of 70.3%, 63.5%, 50%, 74.3%, 52.7%, 48.6%, specificities of 71.4%, 85.7%, 100%, 71.4%, 81%, 81%, respectively. EVG, CSA (odds ratio 3.258, 95% CI 1.597–6.647; 1.029, 95% CI 1.008–1.050) were found to be independent predictive factors. However, there was no significant difference of the included indices between the bleeding and non-bleeding group (p > 0.05).

Conclusions
CT can be used as a noninvasive method to predict the severity of EV, which may reduce the invasive screening of endoscopy.
Using online spaces to recruit Kenyan queer womxn and trans men in restrictive offline settings
Authors: Haase Stephanie , Zweigenthal Virginia , Müller Alex 
Published: March 2022

Abstract
Background
Understanding and addressing healthcare and service delivery inequalities is essential to increase equity and overcome health disparities and service access discrimination. While tremendous progress has been made towards the inclusion of sexual and gender minorities in health and other research, gaps still exist. Innovative methods are needed to close these. This case study describes and reflects on using online-based data collection to ascertain sexual health decision-making and health service utilisation among Kenyan queer womxn and trans men.

Methods
Case study
The study used a mixed-methods approach in two phases with triangulated quantitative and qualitative elements. Both elements used web-based technology to gather data.

Results
Using online spaces to recruit and collect data from queer womxn and trans men exceeded expectations. A total of 360 queer womxn and trans men responded to the digitally distributed survey, and 33 people, queer womxn and trans men, as well as key informants, participated in the interviews, which were primarily conducted on Zoom and Skype. The case study analyses the risks and benefits of this approach and concludes that online sampling approaches can mitigate risks and enable effective and safe sampling of a marginalised group in a restrictive legal setting: Kenyan queer womxn and trans men.

Conclusion
Using online spaces when researching marginalised populations could effectively overcome risks around stigma, discrimination and violence. It could be an effective way to understand these populations’ healthcare needs better. Factors contributing to success included building trusting relationships with key members of the community, strategic and opportune timing, a nuanced understanding of the mobile landscape, and carefully chosen safety and security measures. However, it should be noted that conducting research online could increase the risk of further marginalising and excluding those without access to web-based technology.
Association between divorce and access to healthcare services among married immigrants: propensity score approaches
Authors: Bae Suyeong , Graham James E. , Nam Sanghun , Hong Ickpyo 
Published: March 2022

Abstract
Background
While divorce is a social determinant of health among married immigrants in Korea, its association with access to healthcare services is unclear. Given the rapid increase in the number of married immigrants in Korea, research is needed to improve minority groups’ access to healthcare services. Here, we examined healthcare service utilization among married immigrants.

Methods
We retrieved 11,778 adults from the 2018 Korea National Multicultural Family Survey. We analyzed whether the sex of divorced immigrants is associated with healthcare access using multivariable logistic regression analysis. Further, we analyzed the association between divorce and access to healthcare services among married immigrants using propensity score matching methods.

Results
There were 691 (5.8%) divorced immigrants in the data set. The married male immigrants had no association between divorce status and healthcare access (adjusted odds ratio [OR] = 1.05, 95% confidence interval [CI] = 0.55–2.03, p = 0.8620). Divorced immigrants were less likely to receive healthcare services than married immigrants (adjusted OR = 1.42, 95% CI = 1.07–1.88).

Conclusion
Our findings revealed that divorce increases the risk of limited access to healthcare services among married immigrants. Policymakers and healthcare providers should be aware of these potential disparities in this vulnerable minority population.
Using intervention mapping for hookah smoking cessation: a quasi-experimental evaluation
Authors: Dadipoor Sakineh , Heyrani Ali , Mirzaei-Alavijeh Mehdi , Aghamolaei Teamur , Ghaffari Mohtasham , Ghanbarnejad Amin 
Published: March 2022

Abstract
Background
The present study aimed to evaluate the results of a theory-based and systematic intervention on Hookah Tobacco Smoking (HTS) cessation in women local to Bandar Abbas, Iran.

Methods
In the present quasi-experimental research, we used an intervention mapping approach to develop, implement, and evaluate an education and training course as our intervention. Applying the results of a systematic review and two prior local qualitative studies, we identified six HTS determinants and set goals for the intervention. We selected 212 eligible women through systematic stratified random sampling and enrolled them in control and intervention groups. The course was presented to the intervention group in 17 sessions for four months. The educational material was developed to address the goals of the intervention, improve HTS determinants, and change the HTS behavior. We used a questionnaire to collect data on participants’ characteristics, HTS behavior, and detailed determinants of HTS in the control and intervention groups at the beginning of the study, at the end of the intervention, and at three- and six- months follow-up. All work done in the study was guided by ethical considerations.

Results
The results showed no significant difference between women enrolled in control and intervention groups regarding participants’ characteristics and HTS behavior. At baseline, there were no differences between groups for six determinants of HTS (knowledge, attitude, social norms, self-efficacy, habit, and intention). At the end of the intervention and at three and six months follow-up, the women in the intervention group had significantly better results in all six domains, compared with those in the control group. The rate of HTS abstinence at the end of the intervention and at the three- and six-month follow-ups was 61.3%, 48.5%, and 45.5% for the intervention and 16%, 14.4%, and 10% for the control groups, respectively.

Conclusions
HTS is a complicated behavior, and its cessation is hard. However, Intervention Mapping (IM) can be a powerful integrative, purposeful, theory-based, and participation-based method to reduce or cease HTS. This method should be tested in other settings.
Trial registration: IRCT20190126042494N1, Registered 3.3.2019. https://en.irct.ir/trial/37129