bluuebunny/crossref_metadata_2025 huggingface dataset:
Circ_0064288 acts as an oncogene of hepatocellular carcinoma cells by inhibiting miR-335-5p expression and promoting ROCK1 expression
Authors: Nie Yingying , Zhu Xuedan , Bu Nan , Jiang Yang , Su Yue , Pan Keming , Li Shanshan
Published: March 2022

Background

Reportedly, circular RNA (circRNA) is a key modulator in the development of human malignancies. This work is aimed to probe the expression pattern, biological effects and mechanism of circ_0064288 on hepatocellular carcinoma (HCC) progression.

Methods

The differentially expressed circRNA was screened by analyzing the expression profiles of circRNAs in HCC tissues and normal tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of circ_0064288, miR-335-5p and Rho associated coiled-coil containing protein kinase 1 (ROCK1) mRNA in HCC specimens. After circ_0064288 was overexpressed or knocked down in HCC cells, cell growth was detected by the CCK-8 experiment, and cell migration was evaluated using Transwell experiment and scratch healing experiment. The targeting relationship between miR-335-5p and circ_0064288 and ROCK1 mRNA was predicted and verified using bioinformatic analysis and dual-luciferase reporter gene experiments, respectively. Western blot was executed to examine ROCK1 protein expression in HCC cells.

Results

Circ_0064288 and ROCK1 expression was up-modulated in HCC, while miR-335-5p was down-modulated. High circ_0064288 expression was associated with shorter survival time of HCC patients. It was also revealed that circ_0064288 overexpression remarkably enhanced HCC cell growth and migration, while knockdown of circ_0064288 induced opposite effects. Additionally, circ_0064288 could competitively bind with miR-335-5p thereby up-modulate ROCK1 expression. MiR-335-5p overexpression partly counteracted the effect of circ_0064288 overexpression on HCC cells.

Conclusion

Circ_0064288 facilitates HCC cell growth and migration by modulating the miR-335-5p/ROCK1 axis.
Compliance of functional exercises in school-age children with limb fractures: implication for nursing countermeasures
Authors: Liu Hui , Wang Yun , Li Mengya , Chen Dan , Tang Yuping
Published: March 2022

Background

Functional exercises is very essential to the recovery of patients with fracture. We aimed to evaluate the compliance of functional exercises in school-age children with limb fracture, to provide evidence to the clinical management and nursing care of children with limb fracture.

Methods

School-age children with limb fractures treated in our hospital from January 1, 2020 to June 30, 2021 were selected. The characteristics and postoperative functional exercise compliance of included children were analyzed. Pearson correlation and Logistic regression analysis were conducted to analyze the influencing factors of compliance to functional exercises.

Results

A total of 328 children with limb fracture were included, the incidence of compliance to functional exercise was only 35.98%. Pearson correlation analysis showed that age(r = 0.707), only child of family(r = 0.537), guardians(r = 0.642) and type of temperament(r = 0.635) were correlated with compliance to functional exercises in school-age children with limb fractures (all p < 0.05). Logistic regression analysis indicated that age ≤ 10y (OR2.913, 95%CI2.091 ~ 3.611), only child of family (OR2.006, 95%CI1.683 ~ 2.558), guarded by grandparents (OR1.512, 95%CI1.201 ~ 2.118), non-easy-going temperament (OR4.127, 95%CI3.811 ~ 4.902) were the influencing factors of non-compliance to functional exercises in children with limb fracture (all p < 0.05).

Conclusions

School-age children have poor compliance with functional exercises after limb fractures, and there are many influencing factors. For children with those risks, health care providers should actively intervene in nursing to improve children’s exercise compliance and the rehabilitation effect.
An atypical case of Kawasaki disease with severe pneumonia in a neonate
Authors: Kawamura Yoshiki , Miura Hiroki , Saito Kazuyoshi , Kanno Takayuki , Yokoyama Tadafumi , Aizawa Yuta , Yoshikawa Tetsushi
Published: March 2022

Background

Kawasaki disease (KD) is an acute, febrile, systemic vasculitis of unknown etiology that primarily affects the coronary arteries and generally occurs at around 1 year of age. Although the diagnosis of KD is generally not difficult, it is challenging in cases of incomplete KD lacking characteristic clinical manifestations. The incidence of incomplete KD is higher in infants younger than 6 months of age. Pneumonia is an extremely rare complication of KD and can be misinterpreted as atypical pneumonia rather than KD. Herein, we report a neonate with atypical KD and severe pneumonia who required mechanical ventilation.

Case presentation

Japanese one-month-old infant had only fever and rash on admission (day 1), and he was transferred to the intensive care unit for severe pneumonia on day 2. Although pneumonia improved following intensive care, he was diagnosed with KD on day 14 because of emerging typical clinical manifestations such as fever, bulbar nonexudative conjunctival injection, desquamation of the fingers, and coronary artery aneurysm. KD symptoms improved after three doses of intravenous immunoglobulin plus cyclosporine. However, small coronary aneurysms were present at the time of discharge. In a retrospective analysis, no pathogens were detected by multiplex real-time PCR in samples collected at admission, and the serum cytokine profile demonstrated prominent elevation of IL-6 as well as elevation of neopterin, sTNF-RI, and sTNF-RII, which suggested KD.

Conclusions

The patient’s entire clinical course, including the severe pneumonia, was caused by KD. As in this case, neonatal KD may exhibit atypical manifestations such as severe pneumonia requiring mechanical ventilation.
Social inequalities in healthcare utilization during Ecuadorian healthcare reform (2007–2017): a before-and-after cross-sectional study
Authors: Quizhpe Edy , Teran Enrique , Pulkki-Brännström Anni-Maria , San Sebastián Miguel
Published: March 2022

Background

Limited research is available about the impact of healthcare reforms on healthcare utilization according to socioeconomic group. Although most health reforms in Latin America have focused on reducing the gap between the most advantaged and disadvantaged groups and improving the quality of health services, the available information has shown limited progress. Therefore, this study assessed whether the recent Ecuadorian healthcare reform (2007–2017) contributed to decreasing the socioeconomic inequalities in healthcare utilization.

Methods

We used data from the National Living Standards Measurement surveys conducted in 2006 and 2014. Unmet healthcare needs (UHCN) were used as the dependent variable and proxy for difficulties in accessing health services. Place of residence, ethnicity, education and wealth were selected as indicators of socioeconomic status. The slope and relative inequality indexes were calculated for adult men and women for each period and socioeconomic variable. A multiplicative interaction term between midpoint scores and time was applied to estimate changes in inequalities over time. Sample weights were applied to all analyses, and 95% confidence intervals were calculated to assess statistical significance in the regression analysis.

Results

In 2006, the poor, Indigenous, those living in rural areas and with low education had lower access to health services. In 2014, the overall prevalence of UHCN decreased from 27 to 18% and was higher in women than men. Statistically significant reductions of refraining were observed in absolute and relative terms in all social groups, both in men and women.

Conclusions

Our results showed remarkable and significant decreases in inequalities in all examined socioeconomic groups in absolute and relative terms in this period. Although a new model of healthcare was established to achieve universal health coverage, its performance must be continuously evaluated and monitored with specific indicators. Further studies are also needed to identify the main barriers that contribute to UHCN among socially disadvantaged groups.
Nutrition standards for the charitable food system: challenges and opportunities
Authors: Levi Ronli , Schwartz Marlene , Campbell Elizabeth , Martin Katie , Seligman Hilary
Published: March 2022

Food insecurity is associated with increased risk of chronic disease and poor dietary intake. The United States charitable food system, a complex network of food banks, pantries and congregate meal sites, provides food for millions of low-income households each year. Food banks and pantries play a critical role in supporting food security and are an important contributor to dietary intake for its clients. In recent years, there has been an increased focus on sourcing and supplying more nutritious foods within the charitable food system. Despite this, there is a lack of alignment in how the charitable food system defines and tracks the nutritional quality of food.

In 2019, Healthy Eating Research convened a panel of nutrition, charitable food system and food policy experts to create a set of evidence-based nutrition standards. Standards were developed based on a review of the literature and existing nutrition ranking systems, while also considering the operational needs and capacity of the charitable food system. The panel provided recommendations for eleven distinct food categories: fruits and vegetables, grains, protein, dairy, non-dairy alternatives, beverages, mixed dishes, processed and packaged snacks, desserts, condiments and cooking staples, and other miscellaneous items. Products are ranked into three tiers, choose often (green), choose sometimes (yellow) or choose rarely (red), based on designated saturated fat, sodium, and added sugar thresholds. This paper outlines the expert panel’s approach and summarizes the barriers and opportunities for implementing these standards across the charitable food system.
Respiratory symptoms and lung function among inmates in a Nigerian prison: a cross sectional study
Authors: Eze Joy Nkiru , Ozoh Obianuju Beatrice , Otuu Fred Chibuisi , Shu Elvis Neba , Anyaehie Bond Ugochukwu
Published: March 2022

Background

Prisoners in low- and middle-income countries are vulnerable to poor lung health from multiple adverse conditions confronted within the prison such as overcrowding, poor ventilation and exposure to second hand smoke. Evidence for poor lung health in this disadvantaged group is needed to inform policy on prison conditions in this region. We assessed the respiratory symptoms and lung function measured by spirometry among prisoners in Enugu, Nigeria and explored the associations between them.

Methods

This was a cross‑sectional study among prison inmates aged 16–76 years. We assessed frequency of respiratory symptoms in the preceding one-year, previous respiratory diagnosis, tobacco smoking status and spirometry. The relationships between respiratory symptoms, smoking status and spirometry pattern were determined using the Chi‑square test.

Results

Of 245 participants, 170 (69.4%) reported at least one respiratory symptom. In all, 214 (87.3%) performed spirometry and 173 (80.8%) had good quality spirometry tests. Using the Global Lung Function Initiative (GLI) predicted values for ‘African Americans’, spirometry results were abnormal in 41 (23.7%) of the participants and when the GLI reference values for ‘Other’ ethnic groups was applied, 78 (45.1%) had abnormal results. Restrictive impairment was most common occurring in 21 (12.1%) and 59 (34.1%) respectively based on the two reference values, and obstructive pattern was found in 18 (10.4%) and 13 (7.5%) respectively. There was no significant association between abnormal spirometry pattern and presence of respiratory symptoms or smoking status. No previous diagnosis for asthma, or bronchitis/chronic obstructive pulmonary disease (COPD) had been made in any of the participants.

Conclusions

We reported high rates of respiratory symptoms and abnormal lung function with under-diagnosis of chronic respiratory diseases among inmates in Enugu prison. The restrictive abnormalities based on GLI equations remain unexplained. There is need for improvement in prison facilities that promote lung health and enhanced access to diagnosis and treatment of respiratory non-communicable disease.
Poorer sleep quality in patients with chronic temporomandibular disorders compared to healthy controls
Authors: Lee Yeon-Hee , Auh Q-Schick , An Jung-Sub , Kim Tae
Published: March 2022

Objectives

This study aimed to investigate and compare sleep quality between patients with chronic temporomandibular disorder and healthy controls, and to analyze the association of sleep quality with disease characteristics, obstructive sleep apnea risk factors, and excessive daytime sleepiness.

Methods

Chronic temporomandibular disorder patients (n = 503, mean age: 33.10 ± 13.26 years, 333 females) and 180 age- and sex-matched healthy controls (mean age: 32.77 ± 12.95 years, 116 females) were included, who completed well-organized clinical report and answered questions on sleep quality (Pittsburgh Sleep Quality Index), sleep apnea risk factors (STOP-Bang questionnaire), and excessive daytime sleepiness (Epworth sleepiness scale).

Results

Mean global Pittsburgh Sleep Quality Index scores were significantly higher in the patients (6.25 ± 2.77) than in healthy controls (3.84 ± 2.29) (p <  0.001). Poor sleep was significantly more prevalent in the patient group (56.9%) than in healthy controls (22.2%) (p <  0.001). Compared with healthy controls, chronic temporomandibular disorder patients had a higher likelihood of obstructive sleep apnea (STOP-Bang total score ≥ 3; 7.2% vs. 16.1%; p <  0.01) and higher excessive daytime sleepiness (Epworth sleepiness scale score ≥ 10; 12.8% vs. 19.7%; p <  0.05). Age (odds ratio = 2.551; p <  0.001), female sex (odds ratio = 1.885; p = 0.007), total Epworth sleepiness scale score (odds ratio = 1.839; p = 0.014), and headache attributed to temporomandibular disorder (odds ratio = 1.519; p = 0.049) were the most powerful predictors of poor sleep (global Pittsburgh Sleep Quality Index score ≥ 5) in chronic temporomandibular disorder patients.

Conclusion

Chronic temporomandibular disorder patients had markedly impaired sleep quality than healthy controls. Poorer sleep in patients with chronic temporomandibular disorder was associated with a variety of clinical factors, including a higher likelihood of excessive daytime sleepiness, older age, female gender, higher Epworth sleepiness scale scores, and the presence of headache attributed to temporomandibular disorder.
The impact of pain on quality of life in patients with osteoarthritis: a cross-sectional study from Palestine
Authors: Shalhoub Mojahed , Anaya Mohammad , Deek Soud , Zaben Anwar H. , Abdalla Mazen A. , Jaber Mohammad M. , Koni Amer A. , Zyoud Sa’ed H.
Published: March 2022

Background

Osteoarthritis is one of the most common musculoskeletal problems. Pain is the most common complaint and the most significant cause of decreased health-related quality of life (HRQOL) among osteoarthritic patients. The objectives of this study were to assess the impact of pain on quality of life among patients with osteoarthritis and to assess the association of sociodemographic and clinical factors with HRQOL.

Methods

Using a cross-sectional study design, we collected data from osteoarthritis patients in orthopedic outpatient clinics from four hospitals in the Palestine-West bank between November 2020 and March 2021. We used the Brief Pain Inventory (BPI) scale to assess pain and the Quality of Life scale five dimensions (EQ-5D) with the visual analog scale of the European Quality of Life (EQ-VAS) to assess HRQOL.

Results

In our study, 196 patients composed the final sample, with an average of 60.12 ± 13.63 years. The medians for the EQ-5D score and EQ-VAS score were 0.72 (0.508–0.796) and 70 (55–85), respectively. The pain severity score was found to have a significant negative association with both the EQ-5D and EQ-VAS scores with r of − 0.620, p <  0.001, and − 0.554, p <  0.001, respectively. Similar associations were found between pain interference score and both EQ-5D (r = − 0.822, p <  0.001) and EQ-VAS scores (r = − 0.609, p <  0.001). Multiple regression analysis showed that participants with higher educational level (p = 0.028), less diseased joints (p = 0.01), shorter duration of disease (p = 0.04), and lesser pain severity and interference scores (both with p < 0.001) had significantly higher HRQOL scores.

Conclusions

We found that many variables have a significant negative impact on HRQOL among patients with osteoarthritis. Our finding provides a well-founded database to use by clinicians and healthcare professionals who work with patients with osteoarthritis, as well as educational and academic institutions.
Cross-cultural adaptation of a Spanish version of a previously validated HPV survey that evaluates dental students’ knowledge, perception and clinical practices in Latin America
Authors: Pinzon Lilliam M. , Velazquez Alan , Rutkoski Holdunn , Tay Djin L. , Martel Lara , Drury Carmen , Ayres Shauna , Dixon Barbara , Winkler James R. , Kepka Deanna
Published: March 2022

Background

The global incidence of oropharyngeal cancer (OPC) is increasing. Dental professionals play a key role in the detection of oral lesions that could lead to cancer. However, scientific-based HPV-OPC visual inspection guidelines are underdeveloped and HPV knowledge and awareness has been reported to be low among dental students and professionals. The present study adapted and performed pretesting of a multi-scale survey evaluating knowledge, perceptions, and clinical practices regarding HPV and HPV-OPC for Latin American Spanish-speaking populations.

Methods

A previously developed questionnaire for English-speaking dental students was translated to Spanish. The questionnaire was administered to first year dental students at two Latin American universities with dental programs. Internal consistencies were measured using Cronbach Alpha. Analyses were conducted in SAS Version 9.4.

Results

Data from a total of 114 students, a majority of the which were female (61%), and Hispanic/Latino(a)/Spanish (91%). The HPV, HPV-OPC, and HPV vaccine knowledge subscales demonstrated good internal consistency, the Cronbach’s alpha was 0.83, 0.75, and 0.86 respectively. The Barriers subscale had a Cronbach’s alpha of 0.93, showing excellent internal consistency. The Clinical Procedures subscale, focused on factors surrounding dental students’ hypothetical clinical practice procedures, had a Cronbach’s alpha of 0.86. The Scope of Practice scale had a Cronbach’s alpha of 0.93.

Conclusions

Ultimately, this survey demonstrated reliability and applicability for the assessment of dental students’ knowledge, perceptions, and clinical practices regarding HPV and HPV-OPC in Latin America.
Nurses’ experiences with continuous vital sign monitoring on the general surgical ward: a qualitative study based on the Behaviour Change Wheel
Authors: Leenen J. P. L. , Dijkman E. M. , van Hout A. , Kalkman C. J. , Schoonhoven L. , Patijn G. A.
Published: March 2022

Background

To support early recognition of clinical deterioration on a general ward continuous vital signs monitoring (CMVS) systems using wearable devices are increasingly being investigated. Although nurses play a crucial role in successful implementation, reported nurse adoption and acceptance scores vary significantly. In-depth insight into the perspectives of nurses regarding CMVS is lacking. To this end, we applied a theoretical approach for behaviour change derived from the Behaviour Change Wheel (BCW).

Aim

To provide insight in the capability, opportunity and motivation of nurses working with CMVS, in order to inform future implementation efforts.

Methods

A qualitative study was conducted, including twelve nurses of a surgical ward in a tertiary teaching hospital with previous experience of working with CMVS. Semi-structured interviews were audiotaped, transcribed verbatim, and analysed using thematic analysis. The results were mapped onto the Capability, Opportunity, Motivation – Behaviour (COM-B) model of the BCW.

Results

Five key themes emerged. The theme ‘Learning and coaching on the job’ linked to Capability. Nurses favoured learning about CVSM by dealing with it in daily practice. Receiving bedside guidance and coaching was perceived as important. The theme ‘interpretation of vital sign trends’ also linked to Capability. Nurses mentioned the novelty of monitoring vital sign trends of patients on wards. The theme ‘Management of alarms’ linked to Opportunity. Nurses perceived the (false) alarms generated by the system as excessive resulting in feelings of irritation and uncertainty. The theme ‘Integration and compatibility with clinical workflow’ linked to Opportunity. CVSM was experienced as helpful and easy to use, although integration in mobile devices and the EMR was highly favoured and the management of clinical workflows would need improvement. The theme ‘Added value for nursing care’ linked to Motivation. All nurses recognized the potential added value of CVSM for postoperative care.

Conclusion

Our findings suggest all parts of the COM-B model should be considered when implementing CVSM on general wards. When the themes in Capability and Opportunity are not properly addressed by selecting interventions and policy categories, this may negatively influence the Motivation and may compromise successful implementation.
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

Background

Unfortunately, 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 text

There 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.

Conclusion

Antimicrobial 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

Nanocarriers 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

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

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

Obesity 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

Background

Ambient 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.

Results

Short-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).

Conclusion

Exposure 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

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

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

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

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

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
‘The Drug Survey App’: a protocol for developing and validating an interactive population survey tool for drug use among Aboriginal and Torres Strait Islander Australians
Authors: Conigrave James H. , Wilson Scott , Conigrave Katherine M. , Chikritzhs Tanya , Hayman Noel , Dawson Angela , Ali Robert , Perry Jimmy , Fitts Michelle S. , Degenhardt Louisa , Doyle Michael , Egert Sonya , Slade Tim , Ezard Nadine , Dzidowska Monika , Lee K. S. Kylie
Published: March 2022

Background

Disadvantage and transgenerational trauma contribute to Aboriginal and Torres Strait Islander (Indigenous) Australians being more likely to experience adverse health consequences from alcohol and other drug use than non-Indigenous peoples. Addressing these health inequities requires local monitoring of alcohol and other drug use. While culturally appropriate methods for measuring drinking patterns among Indigenous Australians have been established, no similar methods are available for measuring other drug use patterns (amount and frequency of consumption). This paper describes a protocol for creating and validating a tablet-based survey for alcohol and other drugs (“The Drug Survey App”).

Methods

The Drug Survey App will be co-designed with stakeholders including Indigenous Australian health professionals, addiction specialists, community leaders, and researchers. The App will allow participants to describe their drug use flexibly with an interactive, visual interface. The validity of estimated consumption patterns, and risk assessments will be tested against those made in clinical interviews conducted by Indigenous Australian health professionals. We will then trial the App as a population survey tool by using the App to determine the prevalence of substance use in two Indigenous communities.

Discussion

The App could empower Indigenous Australian communities to conduct independent research that informs local prevention and treatment efforts.
Alignment between vertical and horizontal coordination for food quality and safety in Indonesian vegetable chains
Authors: Widadie Fanny , Bijman Jos , Trienekens Jacques
Published: March 2022

This study explores the alignment between vertical coordination (VC) and horizontal coordination (HC) in Indonesian vegetable value chains. This alignment helps buyers to design efficient coordination mechanisms with regard to the production of safe and high-quality vegetables. We use a qualitative approach and describe five vegetable value chains featuring VC and HC. Within-case and cross-case analyses have been performed to develop propositions. The empirical study finds that there is a diverse combination of VC and HC mechanisms in Indonesian vegetable value chains. Strong VC correlates with high food quality and safety standards that farmers have to meet. The presence of HC through a producer organisation (PO) reduces the need for strict VC mechanisms. When VC is combined with HC through a PO, efficiency of quality and safety control increases and coordination costs decrease, ensuring better compliance with food quality and safety requirements.