bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose approach matter? A meta-analysis of outcomes following transfemoral versus transapical transcatheter aortic valve replacement
Authors: Guo Ruikang , Xie Minghui , Yim Wai Yen , Wu Wenconghui , Jiang Weiwei , Wang Yin , Hu Xingjian
Published: July 2021

Background

Transcatheter aortic valve replacement (TAVR) has gained increasing acceptance for patients with aortic disease. Both transfemoral (TF-TAVR) and transapical (TA-TAVR) approach were widely adopted while their performances are limited to a few studies with controversial results. This meta-analysis aimed to compare the mortality and morbidity of complications between TF- versus TA-TAVR based on the latest data.

Methods

Electronic databases were searched until April 2021. RCTs and observational studies comparing the outcomes between TF-TAVR versus TA-TAVR patients were included. Heterogeneity assumption was assessed by an I2 test. The pooled odds ratios(OR) or mean differences with corresponding 95% confidence intervals (CI) were used to evaluate the difference for each end point using a fixed-effect model or random-effect model based on I2 test.

Results

The meta-analysis included 1 RCT and 20 observational studies, enrolling 19,520 patients (TF-TAVR, n = 11,986 and TA-TAVR, n = 7,534). Compared with TA-TAVR, TF-TAVR patients showed significantly lower rate of postoperative in-hospital death (OR = 0.67, 95% CI 0.59–0.77, P < 0.001) and 1-year death (OR = 0.53, 95% CI 0.41–0.69, P < 0.001). Incidence of major bleeding and acute kidney injury were lower and length of hospital stay was shorter, whereas those of permanent pacemaker and major vascular complication were higher in TF-TAVR patients. There were no significant differences between TF-TAVR versus TA-TAVR for stroke and mid-term mortality.

Conclusions

There were fewer early deaths in patients with transfemoral approach, whereas the number of mid-term deaths and stroke was not significantly different between two approaches. TF-TAVR was associated with lower risk of bleeding, acute kidney injury as well as shorter in-hospital stay, but higher incidence of vascular complication and permanent pacemaker implantation.
Importance of confirming the underlying diagnosis in patients with myocardial infarction and non-obstructive coronary arteries (MINOCA): a single-centre retrospective cohort study
Authors: Pustjens T. F. S. , Meerman A. , Vranken N. P. A. , Ruiters A. W. , Gho B. , Stein M. , Ilhan M. , Veenstra L. , Winkler P. , Lux Á. , Rasoul S. , van ‘t Hof A. W. J.
Published: July 2021

Background

Many patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) are discharged without a known aetiology for their clinical presentation. This study sought to assess the effect of this ‘indeterminate MINOCA’ diagnosis on the prevalence of recurrent cardiovascular events and presentations to the Cardiac Emergency Department (CED).

Methods

We retrospectively analysed all patients meeting the diagnostic MINOCA criteria presenting at a large secondary hospital between January 2017 and April 2019.

Participants

Patients were divided into the (1) ‘indeterminate MINOCA’, or (2) ‘MINOCA with diagnosis’ group. The primary outcome was the occurrence of major adverse cardiac events (MACE) defined as the composite of all-cause mortality, non-fatal myocardial infarction, stroke and any revascularisation procedure. Secondary outcomes were all recurrent visits at the CED, and MACE including unplanned cardiac hospitalisation.

Results

In 62/198 (31.3%) MINOCA patients, a conclusive diagnosis was found (myocardial infarction, (peri)myocarditis, cardiomyopathy, or miscellaneous). MINOCA patients with a confirmed diagnosis were younger compared to those with an indeterminate diagnosis (56.7 vs. 62.3 years,p = 0.007), had higher maximum troponin-T [238 ng/L vs. 69 ng/L,p < 0.001] and creatine kinase (CK) levels [212U/L vs. 152U/L,p = 0.007], and presented more frequently with electrocardiographic signs of ischaemia (71.0% vs. 47.1%,p = 0.002). Indeterminate MINOCA patients more often showed recurrent CED presentations (36.8% vs. 22.6%,p = 0.048), however the occurrence of cardiovascular events was equal (8.8 vs. 8.1%,p = 0.86). Multivariable analysis showed that elevated levels of troponin-T and CK, ST-segment deviation on electrocardiography, reduced left ventricular ejection fraction, regional wall motion abnormalities, and performance of additional examination methods were independent predictors for finding the underlying MINOCA cause.

Conclusions

Only in one-third of MINOCA patients a conclusive diagnosis for the acute presentation was identified. Recurrent CED visits were more often observed in the indeterminate MINOCA group, while the occurrence of cardiovascular events was similar across groups.

Trial registration

Retrospectively registered
Proteomic analysis identifies deregulated metabolic and oxidative-associated proteins in Italian intrahepatic cholangiocarcinoma patients
Authors: Cavalloni Giuliana , Peraldo-Neia Caterina , Massa Annamaria , Bergamini Carlo , Trentini Alessandro , De Rosa Giovanni , Daniele Lorenzo , Ciccosanti Fabiola , Cervellati Carlo , Leone Francesco , Aglietta Massimo
Published: July 2021

Background

Cholangiocarcinoma (CCA) is an aggressive disease with poor prognosis. A molecular classification based on mutational, methylation and transcriptomic features could allow identifying tailored therapies to improve CCA patient outcome. Proteomic remains partially unexplored; here, we analyzed the proteomic profile of five intrahepatic cholangiocarcinoma (ICC) derived from Italian patients undergone surgery and one normal bile duct cell line.

Methods

Proteome profile was investigated by using 2D electrophoresis followed by Mass Spectrometry (MS). To validate proteomic data, the expression of four overexpressed proteins (CAT, SOD, PRDX6, DBI/ACBP) was evaluated by immunohistochemistry in an independent cohort of formalin fixed, paraffin-embedded (FFPE) ICC tissues. We also compared proteomic data with those obtained by transcriptomic profile evaluated by microarray analysis of the same tissues.

Results

We identified 19 differentially expressed protein spots, which were further characterized by MS; 13 of them were up- and 6 were down-regulated in ICC. These proteins are mainly involved in redox processes (CAT, SODM, PRDX2, PRDX6), in metabolism (ACBP, ACY1, UCRI, FTCD, HCMS2), and cell structure and organization (TUB2, ACTB). CAT is overexpressed in 86% of patients, PRDX6 in 73%, SODM in 100%, and DBI/ACBP in 81% compared to normal adjacent tissues. A concordance of 50% between proteomic and transcriptomic data was observed.

Conclusions

This study pointed out that the impairment of the metabolic and antioxidant systems, with a subsequent accumulation of free radicals, might be a key step in CCA development and progression.
Prediction of lymphovascular space invasion using a combination of tenascin-C, cox-2, and PET/CT radiomics in patients with early-stage cervical squamous cell carcinoma
Authors: Li Xiaoran , Xu Chen , Yu Yang , Guo Yan , Sun Hongzan
Published: July 2021

Background

Lymphovascular space invasion is an independent prognostic factor in early-stage cervical cancer. However, there is a lack of non-invasive methods to detect lymphovascular space invasion. Some researchers found that Tenascin-C and Cyclooxygenase-2 was correlated with lymphovascular space invasion. Radiomics has been studied as an emerging tool for distinguishing tumor pathology stage, evaluating treatment response, and predicting prognosis. This study aimed to establish a machine learning model that combines radiomics based on PET imaging with tenascin-C (TNC) and cyclooxygenase-2 (COX-2) for predicting lymphovascular space invasion (LVSI) in patients with early-stage cervical cancer.

Methods

One hundred and twelve patients with early-stage cervical squamous cell carcinoma who underwent PET/CT examination were retrospectively analyzed. Four hundred one radiomics features based on PET/CT images were extracted and integrated into radiomics score (Rad-score). Immunohistochemical analysis was performed to evaluate TNC and COX-2 expression. Mann-Whitney U test was used to distinguish differences in the Rad-score, TNC, and COX-2 between LVSI and non-LVSI groups. The correlations of characteristics were tested by Spearman analysis. Machine learning models including radiomics model, protein model and combined model were established by logistic regression algorithm and evaluated by ROC curve. Pairwise comparisons of ROC curves were tested by DeLong test.

Results

The Rad-score of patients with LVSI was significantly higher than those without. A significant correlation was shown between LVSI and Rad-score (r = 0.631, p < 0.001). TNC was correlated to both the Rad-score (r = 0.244, p = 0.024) and COX-2 (r = 0.227, p = 0.036). The radiomics model had the best predictive performance among all models in training and external dataset (AUCs: 0.914, 0.806, respectively, p < 0.001). However, in testing dataset, the combined model had better efficiency for predicting LVSI than other models (AUCs: 0.801 vs. 0.756 and 0.801 vs. 0.631, respectively).

Conclusion

The machine learning model of the combination of PET radiomics with COX-2 and TNC provides a new tool for detecting LVSI in patients with early-stage cervical cancer. In the future, multicentric studies on larger sample of patients will be used to test the model.

Trial registration

This is a retrospective study and there is no experimental intervention on human participants. The Ethics Committee has confirmed that retrospectively registered is not required.
Mental health and its association with coping strategies and intolerance of uncertainty during the COVID-19 pandemic among the general population in Saudi Arabia: cross-sectional study
Authors: AlHadi Ahmad N. , Alarabi Mohammed A. , AlMansoor Khulood M.
Published: July 2021

Background

The COVID-19 pandemic has had a major impact on people’s lives globally. The outbreak in Saudi Arabia worsened when the number of cases and deaths rose in March and April of 2020, leading to a national lockdown. This study aimed to assess the factors associated with mental health symptoms in a sample of people residing in Saudi Arabia during the COVID-19 pandemic.

Methods

We conducted an observational cross-sectional study using an online survey distributed via social media, completed by 3032 respondents from all Saudi regions. We collected demographic data, illness history, and scores of validated self-report scales to assess mental health symptoms, intolerance of uncertainty, and coping strategies.

Results

In total, respondents indicated moderate to very severe symptoms during the pandemic as follows: 20.9% for depression, 17.5% for anxiety, and 12.6% for stress. Younger age, female gender, and history of mental illness were associated with higher levels of depression, anxiety, stress, and insomnia. Intolerance of uncertainty and certain coping strategies (such as denial or self-blame) were associated with more severe symptoms.

Conclusions

Mental health is a key concern during the COVID-19 pandemic, especially for the identified vulnerable groups. Agencies concerned with mental health during crises may use the studied associated factors of mental health symptoms to generate targeted policies or interventions.
Opioid use disorder treatment disruptions during the early COVID-19 pandemic and other emergent disasters: a scoping review addressing dual public health emergencies
Authors: Henderson Rita , McInnes Ashley , Mackey Leslee , Bruised Head Myles , Crowshoe Lindsay , Hann Jessica , Hayward Jake , Holroyd Brian R. , Lang Eddy , Larson Bonnie , Leonard Ashley Jane , Persaud Steven , Raghavji Khalil , Sarin Chris , Virani Hakique , Wadsworth Iskotoahka William , Whitman Stacey , McLane Patrick
Published: July 2021

Background

During public health emergencies, people with opioid use disorder (PWOUD) may be particularly impacted. Emergent disasters such as the COVID-19 pandemic disrupt already-strained harm reduction efforts and treatment availability. This study aims to answer three research questions. How do public health emergencies impact PWOUD? How can health systems respond to novel public health emergencies to serve PWOUD? How can the results of this scoping review be contextualized to the province of Alberta to inform local stakeholder responses to the pandemic?

Methods

We conducted a scoping review using the 6-stage Arksey and O’Malley framework to analyse early-pandemic and pre-pandemic disaster literature. The results of the scoping review were contextualized to the local pandemic response, through a Nominal Group Technique (NGT) process with frontline providers and stakeholders in Alberta, Canada.

Results

Sixty one scientific journal articles and 72 grey literature resources were included after full-text screening. Forty sources pertained to early COVID-19 responses, and 21 focused on OUD treatment during other disasters. PWOUD may be more impacted than the general population by common COVID-19 stressors including loss of income, isolation, lack of rewarding activities, housing instability, as well as fear and anxiety. They may also face unique challenges including threats to drug supplies, stigma, difficulty accessing clean substance use supplies, and closure of substance use treatment centres. All of these impacts put PWOUD at risk of negative outcomes including fatal overdose. Two NGT groups were held. One group (n = 7) represented voices from urban services, and the other (n = 4) Indigenous contexts. Stakeholders suggested that simultaneous attention to multiple crises, with adequate resources to allow attention to both social and health systems issues, can prepare a system to serve PWOUD during disasters.

Conclusion

This scoping review and NGT study uncovers how disasters impact PWOUD and offers suggestions for better serving PWOUD.
Sexual behaviour, human papillomavirus and its vaccine: a qualitative study of adolescents and parents in Andalusia
Authors: González-Cano María , Garrido-Peña Francisco , Gil-Garcia Eugenia , Lima-Serrano Marta , Cano-Caballero María Dolores
Published: July 2021

Background

Human papillomavirus (HPV) is one of the most common sexually transmitted infections and can be prevented by vaccination. The purpose of this study is to gain a better understanding, by analysing interview responses of adolescents and parents, of how adolescent sexual behaviour is approached in families, how widespread knowledge about HPV is in Andalusia, the autonomous region with the lowest vaccination rate in Spain, as well as to learn more about the interviewees’ position regarding vaccination.

Methods

A qualitative study by means of 15 focus groups of adolescents (N = 137, aged 14–17 years) and five focus groups of parents with children of those ages (N = 37) was conducted in the provinces of Granada, Seville and Jaén (Andalusia, Spain). The audio data were transcribed verbatim, coded and analysed thematically using NVIVO-10 software.

Results

There were three major results: (1) There is a lack of communication between adolescents and parents regarding sexual behaviour; (2) In both groups, scarce knowledge about HPV and vaccination was found; (3) Parents mistrust vaccination due to a lack of qualified and verified information about its benefits.

Conclusions

Healthy adolescent sexual behaviour is aided by communication within the family. Families need more information based on the evidence about HPV and vaccination. Health professionals are a key element in this process.
Chronic respiratory disease disparity between American Indian/Alaska Native and white populations, 2011–2018
Authors: Laffey Kimberly G. , Nelson Alfreda D. , Laffey Matthew J. , Nguyen Quynh , Sheets Lincoln R. , Schrum Adam G.
Published: July 2021

Background

American Indian/Alaska Native (AI/AN) populations have been disproportionately affected by chronic respiratory diseases for reasons incompletely understood. Past research into disease disparity using population-based surveys mostly focused on state-specific factors. The present study investigates the independent contributions of AI/AN racial status and other socioeconomic/demographic variables to chronic respiratory disease disparity in an 11-state region with historically high AI/AN representation. Using data from the Behavioral Risk Factor Surveillance System (BRFSS) spanning years 2011–2018, this work provides an updated assessment of disease disparity and potential determinants of respiratory health in AI/AN populations.

Methods

This cross-sectional study used data from the BRFSS survey, 2011–2018. The study population included AI/AN and non-Hispanic white individuals resident in 11 states with increased proportion of AI/AN individuals. The yearly number of respondents averaged 75,029 (62878–87,350) which included approximately 5% AI/AN respondents (4.5–6.3%). We compared the yearly adjusted prevalence for chronic respiratory disease, where disease status was defined by self-reported history of having asthma and/or chronic obstructive pulmonary disease (COPD). Multivariable logistic regression was performed to determine if being AI/AN was independently associated with chronic respiratory disease. Covariates included demographic (age, sex), socioeconomic (marital status, education level, annual household income), and behavioral (smoking, weight morbidity) variables.

Results

The AI/AN population consistently displayed higher adjusted prevalence of chronic respiratory disease compared to the non-Hispanic white population. However, the AI/AN race/ethnicity characteristic was not independently associated with chronic respiratory disease (OR, 0.93; 95% CI, 0.79–1.10 in 2017). In contrast, indicators of low socioeconomic status such as annual household income of <$10,000 (OR, 2.02; 95% CI, 1.64–2.49 in 2017) and having less than high school education (OR, 1.37; 95% CI, 1.16–1.63 in 2017) were positively associated with disease. These trends persisted for all years analyzed.

Conclusions

This study highlighted that AI/AN socioeconomic burdens are key determinants of chronic respiratory disease, in addition to well-established risk factors such as smoking and weight morbidity. Disease disparity experienced by the AI/AN population is therefore likely a symptom of disproportionate socioeconomic challenges they face. Further promotion of public health and social service efforts may be able to improve AI/AN health and decrease this disease disparity.
Association of pelvic inflammatory disease (PID) with ovarian cancer: a nationwide population-based retrospective cohort study from Taiwan
Authors: Chang Cherry Yin-Yi , Lin Kent Yu-Hsien , Huang Chien-Chu , Lin Wu-Chou
Published: July 2021

Background

Pelvic inflammatory disease (PID) is an important health issue for women. Infection and inflammation play an important role in carcinogenesis and PID has been reported to be associated with ovarian cancer in some small scale studies.

Aim

We sought to determine whether PID is associated with an elevated risk of ovarian cancer in Asian women.

Methods

Using data from Taiwan’s National Health Insurance Research Database (NHIRD), our retrospective cohort study included women diagnosed with PID (cases) between the years of 2000 till 2012. Each case was matched with two women without PID (controls) by age and the year of first entry into the database. Both study cohorts were followed-up until the first event of ovarian cancer, withdrawal from the NHI program, death, or the end of the study period (December 31, 2012). Cox proportional hazards regression models were used to estimate crude and adjusted hazard ratios (HRs and aHRs) with their corresponding 95% confidence intervals (95% CIs) for the association of PID and ovarian cancer risk, with and without adjusting for potential confounders.

Results

During an approximate 10 years of follow-up, cases were significantly more likely than controls to develop ovarian cancer (incidence rates of 0.27 and 0.16 per 1,000 person-years, respectively; P < 0.001). Women with a history of PID had a 1.49-fold elevated risk for ovarian cancer (aHR, 1.49; 95% CI, 1.21–1.84; P < 0.001).

Conclusion

Our study evidence supports the contention that PID increases the risk of developing ovarian cancer among Taiwanese women. Gynecologists should undertake careful assessments and closely follow patients with PID, who are at long-term risk of developing ovarian cancer. Our findings need further verification in other international cohorts.
Outcomes of blended learning for capacity strengthening of health professionals in Guinea
Authors: Millimouno Tamba Mina , Delamou Alexandre , Kourouma Karifa , Kolié Jean Michel , Béavogui Abdoul Habib , Roegiers Sara , Garcia Marlon , Tsunami Carlos Kiyan , Van Bastelaere Stefaan , Van Damme Wim , Delvaux Thérèse
Published: July 2021

Background

Quality human resources constitute an essential pillar of an effective health system. This paper analyzes the outcomes of blended learning for post-Ebola capacity strengthening of health professionals in Guinea.

Methods

Two courses lasting 3 months each (7–8 modules) were developed and implemented: one in Primary Health Care (eSSP) and the other in Sexual and Reproductive Health Services Management (eSSR). Both eSSP and eSSR courses were offered online on the Moodle platform, followed by a face-to-face capacity-building workshop. A cross-sectional study using a mixed-methods approach was conducted in 2018–19. As outcomes, we described learners’ sociodemographic characteristics, course completion and success, and perceptions of the courses and support from the instructors, analyzed the factors associated with learners’ successful completion and reported on learners’ feedback on their blended learning experience. Quantitative data were analyzed using the STATA 15 software, and qualitative data were analyzed through content analysis.

Results

Overall, 282 health professionals were enrolled for both eSSP and eSSR courses. The completion rate was 69.5% (196/282). The success rate for learners who completed the courses was 80% (156/196), and the overall success rate for enrollees was 55% (156/282). The dropout and abstention rates were 22 and 9%, respectively. On both eSSP and eSSR courses, the success rate of women enrolled was higher than or equal to men’s. The success rate of medical doctors enrolled (53% for eSSP and 67% for eSSR) was higher than for other health professionals, in particular nurses (9% for eSSP) and midwives (40% for eSSR). Course type was associated with success (AOR = 1.93; 95% CI = 1.15–3.24). Most learners strongly agreed that the courses are relevant for targeted health professionals (81 to 150/150), pdf course materials are well-structured and useful (105/150), the content of the modules is relevant, comprehensible, and clear (90/150), self-assessment quizzes are helpful (105/150), summative assessment assignments are relevant (90/150), the course administrators and IT manager were responsive to learners’ concerns (90/150), they will recommend the courses to colleagues and friends (120/150).

Conclusion

Two blended courses for capacity strengthening of health professionals were successfully developed and implemented in Guinea.
Characterization of DNA lesions associated with cell-free DNA by targeted deep sequencing
Authors: Shin Seung-Ho , Park Woong-Yang , Park Donghyun
Published: July 2021

Background

Recently, a next-generation sequencing (NGS)-based method has been used for the successful detection of circulating tumor DNA (ctDNA) in various cancer types. Thus, the use of NGS on liquid biopsies will improve cancer diagnosis and prognosis. However, the low-allelic fraction of ctDNA poses a challenge for the sensitive and specific detection of tumor variants in cell-free DNA (cfDNA). To distinguish true variants from false positives, the characteristics of errors that occur during sample preparation and sequencing need to be elucidated.

Methods

We generated capture-based targeted deep sequencing data from plasma cfDNA and peripheral blood leucocyte (PBL) gDNA to profile background errors. To reveal cfDNA-associated DNA lesions, background error profiles from two sample types were compared in each nucleotide substitution class.

Results

In this study, we determined the prevalence of single nucleotide substitutions in cfDNA sequencing data to identify DNA damage preferentially associated with cfDNA. On comparing sequencing errors between cfDNA and cellular genomic DNA (gDNA), we observed that the total substitution error rates in cfDNA were significantly higher than those in gDNA. When the substitution errors were divided into 12 substitution error classes, C:G>T:A substitution errors constituted the largest difference between cfDNA and gDNA samples. When the substitution error rates were estimated based on the location of DNA-fragment substitutions, the differences in error rates of most substitution classes between cfDNA and gDNA samples were observed only at the ends of the DNA fragments. In contrast, C:G>T:A substitution errors in the cfDNA samples were not particularly associated with DNA-fragment ends. All observations were verified in an independent dataset.

Conclusions

Our data suggested that cytosine deamination increased in cfDNA compared to that in cellular gDNA. Such an observation might be due to the attenuation of DNA damage repair before the release of cfDNA and/or the accumulation of cytosine deamination after it. These findings can contribute to a better understanding of cfDNA-associated DNA damage, which will enable the accurate analysis of somatic variants present in cfDNA at an extremely low frequency.
Analysis of therapeutic targets and prognostic biomarkers of CXC chemokines in cervical cancer microenvironment
Authors: Kong Weina , Zhao Gang , Chen Haixia , Wang Weina , Shang Xiaoqian , Sun Qiannan , Guo Fan , Ma Xiumin
Published: July 2021

Background

The tumor microenvironment (TME) has received an increasing amount of attention. CXC chemokines can regulate immune cell transport and tumor cell activity to exert anti-tumor immunity. However, studies on the expression and prognosis of CXC chemokines in cervical cancer (CC) are more limited.

Methods

The study investigated the role of CXC chemokines in TME of CC by using public databases. Moreover, quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) of CXC chemokines were performed to further verify.

Results

The transcriptional levels of CXCL1/3/5/6/8/9/10/11/13/16/17 in CC tissues were significantly elevated while the transcriptional levels of CXCL12/14 were significantly reduced. We reached a consistent conclusion that the expression of CXCL9/10/11/13 was verified by quantitative real-time PCR and immunohistochemistry. Moreover, CC patients with low transcriptional levels of CXCL1/2/3/4/5/8 were significantly associated with longer overall survival (OS). The CCL family was related to CXC chemokines neighboring alteration. RELA, NFKB1, LCK and PAK2 were the key transcription factors and kinase targets of CXC chemokines, respectively. We also found there were significant correlations between the expression of CXCL9/10/11 and the infiltration of immune cells (CD8+ T cell, CD4+ T cell, neutrophils and dendritic cells).

Conclusions

In brief, we conducted a comprehensive analysis of CXC chemokines via clinical data and some online public databases. Our results may provide a new idea for the selection of immunotherapeutic targets and prognostic biomarkers for cervical cancer.
Midazolam increases cisplatin-sensitivity in non-small cell lung cancer (NSCLC) via the miR-194-5p/HOOK3 axis
Authors: Sun Tingting , Chen Jing , Sun Xuechao , Wang Guonian
Published: July 2021

Backgrounds

As previously reported, midazolam anesthesia exerts tumor-suppressing effects in non-small cell lung cancer (NSCLC), but the regulating effects of this drug on cisplatin-resistance in NSCLC have not been studied. Thus, we designed this study to investigate this issue and preliminarily delineate the potential molecular mechanisms.

Methods

We performed MTT assay and trypan blue staining assay to measure cell proliferation and viability. Cell apoptosis was examined by FCM. qRT-PCR and immunoblotting were performed to determine the expression levels of genes. The targeting sites between genes were predicted by bioinformatics analysis and were validated by dual-luciferase reporter gene system assay. Mice tumor-bearing models were established and the tumorigenesis was evaluated by measuring tumor weight and volume. Immunohistochemistry (IHC) was used to examine the pro-proliferative Ki67 protein expressions in mice tumor tissues.

Results

The cisplatin-resistant NSCLC (CR-NSCLC) cells were treated with high-dose cisplatin (50 μg/ml) and low-dose midazolam (10 μg/ml), and the results showed that midazolam suppressed cell proliferation and viability, and promoted cell apoptosis in cisplatin-treated CR-NSCLC cells. In addition, midazolam enhanced cisplatin-sensitivity in CR-NSCLC cell via modulating the miR-194-5p/hook microtubule-tethering protein 3 (HOOK3) axis. Specifically, midazolam upregulated miR-194-5p, but downregulated HOOK3 in the CR-NSCLC cells, and further results validated that miR-194-5p bound to the 3’ untranslated region (3’UTR) of HOOK3 mRNA for its inhibition. Also, midazolam downregulated HOOK3 in CR-NSCLC cells by upregulating miR-194-5p. Functional experiments validated that both miR-194-5p downregulation and HOOK3 upregulation abrogated the promoting effects of midazolam on cisplatin-sensitivity in CR-NSCLC cells.

Conclusions

Taken together, this study found that midazolam anesthesia reduced cisplatin-resistance in CR-NSCLC cells by regulating the miR-194-5p/HOOK3 axis, implying that midazolam could be used as adjuvant drug for NSCLC treatment in clinical practices.
Factors affecting job choice among physician anesthesia providers in Uganda: a survey of income composition, discrete choice experiment, and implications for the decision to work rurally
Authors: Law Tyler J. , Subhedar Shivani , Bulamba Fred , O’Hara Nathan N. , Nabukenya Mary T. , Sendagire Cornelius , Hewitt-Smith Adam , Lipnick Michael S. , Tumukunde Janat
Published: July 2021

Background

One of the biggest barriers to accessing safe surgical and anesthetic care is lack of trained providers. Uganda has one of the largest deficits in anesthesia providers in the world, and though they are increasing in number, they remain concentrated in the capital city. Salary is an oft-cited barrier to rural job choice, yet the size and sources of anesthesia provider incomes are unclear, and so the potential income loss from taking a rural job is unknown. Additionally, while salary augmentation is a common policy proposal to increase rural job uptake, the relative importance of non-monetary job factors in job choice is also unknown.

Methods

A survey on income sources and magnitude, and a Discrete Choice Experiment examining the relative importance of monetary and non-monetary factors in job choice, was administered to 37 and 47 physician anesthesiologists in Uganda, between May–June 2019.

Results

No providers worked only at government jobs. Providers earned most of their total income from a non-government job (50% of income, 23% of working hours), but worked more hours at their government job (36% of income, and 44% of working hours). Providers felt the most important job attributes were the quality of the facility and scope of practice they could provide, and the presence of a colleague (33% and 32% overall relative importance). These were more important than salary and living conditions (14% and 12% importance).

Conclusions

No providers accepted the salary from a government job alone, which was always augmented by other work. However, few providers worked only nongovernment jobs. Non-monetary incentives are powerful influencers of job preference, and may be leveraged as policy options to attract providers. Salary continues to be an important driver of job choice, and jobs with fewer income generating opportunities (e.g. private work in rural areas) are likely to need salary augmentation to attract providers.
Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells
Authors: Li Xiaopeng , Ma Guilin , Guo Wenjie , Mu Ning , Wang Yingying , Liu Xiangguo , Su Ling
Published: July 2021

Background

Hhex(human hematopoietically expressed homeobox), also known as PRH, is originally considered as a transcription factor to regulate gene expression due to its homebox domain. Increasing studies show that Hhex plays a significant role in development, including anterior–posterior axis formation, vascular development and HSCs self-renewal etc. Hhex is linked to many diseases such as cancers, leukemia, and type-2 diabetes. Although Hhex is reported to inhibit cell migration and invasion of breast and prostate epithelial cells by upregulating Endoglin expression, the effect and molecular mechanism for lung cancer cell motility regulation remains elusive.

Methods

Human non-small cell lung cancer cells and HEK293FT cells were used to investigate the molecular mechanism of Hhex regulating lung cancer cell migration by using Western blot, immunoprecipitation, wound-healing scratch assay, laser confocal.

Results

Our data indicated that Hhex could inhibit cell migration and cell protrusion formation in lung cancer cells. In addition, Hhex inhibited CFL1 phosphorylation to keep its F-actin-severing activity. RHOGDIA was involved in Hhex-induced CFL1 phosphorylation regulation. Hhex enhanced RHOGDIA interaction with RHOA/CDC42, thus maintaining RHOA/CDC42 at an inactive form.

Conclusion

Collectively, these data indicate that Hhex inhibited the activation of RHOA/CDC42 by enhancing interaction of RHOGDIA with RHOA/CDC42, and then RHOA/ CDC42-p-CFL1 signaling pathway was blocked. Consequently, the formation of Filopodium and Lamellipodium on the cell surface was suppressed, and thus the ability of lung cancer cells to migrate was decreased accordingly. Our findings show Hhex plays an important role in regulating migration of lung cancer cells and may provide a potential target for lung cancer therapy.
Technology-supported sitting balance therapy versus usual care in the chronic stage after stroke: a pilot randomized controlled trial
Authors: Thijs Liselot , Voets Eline , Wiskerke Evelien , Nauwelaerts Thomas , Arys Yves , Haspeslagh Harold , Kool Jan , Bischof Patrick , Bauer Christoph , Lemmens Robin , Baumgartner Daniel , Verheyden Geert
Published: July 2021

Background

Technology development for sitting balance therapy and trunk rehabilitation is scarce. Hence, intensive one-to-one therapist-patient training is still required. We have developed a novel rehabilitation prototype, specifically aimed at providing sitting balance therapy. We investigated whether technology-supported sitting balance training was feasible and safe in chronic stroke patients and we determined whether clinical outcomes improved after a four-week programme, compared with usual care.

Methods

In this parallel-group, assessor-blinded, randomized controlled pilot trial, we divided first-event chronic stroke participants into two groups. The experimental group received usual care plus additional therapy supported by rehabilitation technology, consisting of 12 sessions of 50 min of therapy over four weeks. The control group received usual care only. We assessed all participants twice pre-intervention and once post-intervention. Feasibility and safety were descriptively analysed. Between-group analysis evaluated the pre-to-post differences in changes in motor and functional outcomes.

Results

In total, 30 participants were recruited and 29 completed the trial (experimental group: n = 14; control group: n = 15). There were no between-group differences at baseline. Therapy was evaluated as feasible by participants and therapist. There were no serious adverse events during sitting balance therapy. Changes in clinical outcomes from pre- to post-intervention demonstrated increases in the experimental than in the control group for: sitting balance and trunk function, evaluated by the Trunk Impairment Scale (mean points score (SD) 7.07 (1.69) versus 0.33 (2.35);p < 0.000); maximum gait speed, assessed with the 10 Metre Walk Test (mean gait speed 0.16 (0.16) m/s versus 0.06 (0.06) m/s;p = 0.003); and functional balance, measured using the Berg balance scale (median points score (IQR) 4.5 (5) versus 0 (4);p = 0.014).

Conclusions

Technology-supported sitting balance training in persons with chronic stroke is feasible and safe. A four-week, 12-session programme on top of usual care suggests beneficial effects for trunk function, maximum gait speed and functional balance.

Trial Registration:ClinicalTrials.gov identifier: NCT04467554,https://clinicaltrials.gov/ct2/show/NCT04467554, date of Registration: 13 July 2020.
Geriatric depression and quality of life in North Shoa Zone, Oromia region: a community cross-sectional study
Authors: Jemal Kemal , Hailu Dejene , Tesfa Bikila , Lama Tasfaye , Kinati Tadele , Mengistu Endeshaw
Published: July 2021

Introduction

Depression and low quality of life are severe conditions that lead to disability and mortality, common in high and low-resourced countries. Therefore, this study aimed to assess geriatric depression, quality of life, and associated factors among elderly persons in the low-resource country.

Methods

A community-based cross-sectional study was used from March to April 2020. The depression and quality of life were assessed using the standardized and pre-tested geriatric depression scale (GDS) and the World Health Organization Quality Of Life (WHOQOL)-BREF, respectively. A multi-stage sampling technique was employed to select woreda and study participants. For data input and analysis, Epi-data version 4.3 and SPSS version 23 were utilized, consecutively. Bivariable and multivariable in the logistic regression analysis were done, and significance was determined at the odds ratio with a 95% confidence interval andPvalue < 0.05.

Results

A total of 822 elderly persons participated in face to face interviewed-administered questionnaire. More than half 54.5% (n = 448) of elderly persons had depression and 51.8% (n = 426) of elderly participants had low quality of life. Advanced age, single participants, not having a formal education, living alone, and having chronic diseases were significantly associated with both the depression symptoms and low overall WHOQOL-BREF. Depression was correlated with low quality of life.

Conclusion

We found that elderly persons have a high risk of depression symptoms and a low quality of life. The Ethiopian Ministry of Health should develop psychological interventions, providing ongoing education for the elderly, and monitoring the health of the elderly population to address the specific needs of elderly persons who have been impacted by the aging process.
Ethnobotany of the Aegadian Islands: safeguarding biocultural refugia in the Mediterranean
Authors: La Rosa Alfonso , Cornara Laura , Saitta Alessandro , Salam Akram M. , Grammatico Santo , Caputo Marco , La Mantia Tommaso , Quave Cassandra L.
Published: July 2021

Background

The Aegadian Islands are located west of Trapani, Sicily. Once the site of bountiful tuna fisheries and fruit orchards (plums, peaches, apricots), grapevines, prickly pears, and grains, the local economy is now based on tourism, and many traditional agricultural and maritime practices have been abandoned. In this study, we aimed to evaluate the state of traditional ecological knowledge (TEK) concerning the use of wild and cultivated plants and fungi for human health, food, maritime, and agricultural purposes on the islands of Levanzo, Favignana, and Marettimo and compare present-day practices with those documented in the past.

Methods

In-depth semi-structured interviews were conducted in Italian with 48 participants with prior informed consent from May 2016 to July 2017 and October 2018. Herbarium voucher specimens of wild species were collected for herbarium deposit. A rigorous literature review of scientific and other local reports on TEK of wild flora and their application in food, health, and household applications was undertaken for the purpose of comparing findings from this field study with prior reports.

Results

A total of 122 plant and five fungal taxa representing 54 families were cited for 355 uses. Among the most pervasive species in the landscape, Agave americana and A. sisalana had diverse applications in the past, which ranged from cordage for agricultural and maritime applications to tools for sewing, eating land snails, and constructing furniture. Fields of Ferula communis also dominate the landscape, and the dry stems were used extensively in furniture making; this species also serves as an environmental indicator for the location of the most preferred edible mushrooms, Pleurotus eryngii var. ferulae. Other important flora included topical medicinal applications of Glaucium flavum for hematomas and Artemisia arborescens for ritual bathing of newborns.

Conclusion

While many plant-based traditions have disappeared from daily practice, especially those related to traditional fishing and health practices, they remain in the memories of the eldest subset of the population. Documenting this knowledge before it disappears from oral history is a key factor in reducing loss of TEK and biocultural diversity, safeguarding the role of the Aegadian Islands as biocultural refugia.
Functional and mutational analysis after radiation and cetuximab treatment on prostate carcinoma cell line DU145
Authors: Schneider Raik , Gademann Günther , Ochel Hans-Joachim , Neumann Karsten , Jandrig Burkhard , Hass Peter , Walke Mathias , Schostak Martin , Brunner Thomas , Christoph Frank
Published: July 2021

Background

Epidermal Growth Factor Receptor is often overexpressed in advanced prostate carcinoma. In-vitro-studies in prostate carcinoma cell line DU145 have demonstrated increased sensibility to radiation after cetuximab treatment, but clinical data are not sufficient to date.

Methods

We analyzed effects of radiation and cetuximab in DU145 and A431 using proliferation, colony-forming-unit- and annexin-V-apoptosis-assays. Changes in protein expression of pEGFR and pERK1/2 after radiation and cetuximab treatment were analyzed. Using NGS we also investigated the impact of cetuximab long-term treatment.

Results

Cell counts in DU145 were reduced by 44% after 4 Gy (p = 0.006) and 55% after 4 Gy and cetuximab (p < 0.001). The surviving fraction (SF) was 0.69 after 2 Gy, 0.41 after 4 Gy and 0.15 after 6 Gy (each p < 0.001). Cetuximab treatment did not alter significantly growth reduction in 4 Gy radiated DU145 cells, p > 0.05 or SF, p > 0.05, but minor effects on apoptotic cell fraction in DU145 were detected. Using western blot, there were no detectable pEGFR and pERK1/2 protein signals after cetuximab treatment. No RAS mutation or HER2 amplification was detected, however a TP53 gen-mutation c.820G > T was found.

Conclusions

Radiation inhibits cell-proliferation and colony-growth and induces apoptosis in DU145. Despite blocking MAP-Kinase-pathway using cetuximab, no significant radiation-sensitizing-effect was detected. Cetuximab treatment did not induce resistance-mutations. Further research must clarify which combination of anti-EGFR treatment strategies can increase radiation-sensitizing-effects.
Interfractional target changes in brain metastases during 13-fraction stereotactic radiotherapy
Authors: Uto Megumi , Ogura Kengo , Katagiri Tomohiro , Takehana Keiichi , Mizowaki Takashi
Published: July 2021

Background

The risk for radiation necrosis is lower in fractionated stereotactic radiotherapy (SRT) than in conventional radiotherapy, and 13-fraction SRT is our method of choice for the treatment of brain metastases ≥ around 2 cm or patients who are expected to have a good prognosis. As 13-fraction SRT lasts for at least 17 days, adaptive radiotherapy based on contrast-enhanced mid-treatment magnetic resonance imaging (MRI) is often necessary for patients undergoing 13-fraction SRT. In this study, we retrospectively analyzed interfractional target changes in patients with brain metastases treated with 13-fraction SRT.

Methods

Our analyses included data from 23 patients and 27 metastatic brain lesions treated with 13-fraction SRT with dynamic conformal arc therapy. The peripheral dose prescribed to the planning target volume (PTV) was 39–44.2 Gy in 13-fractions. The gross tumor volume (GTV) of the initial SRT plan (initial GTV), initial PTV, and modified GTV based on the mid-treatment MRI scan (mid-treatment GTV) were assessed.

Results

The median initial GTV was 3.8 cm3 and the median time from SRT initiation to the mid-treatment MRI scan was 6 days. Compared to the initial GTV, the mid-treatment GTV increased by more than 20% in five lesions and decreased by more than 20% in five lesions. Interfractional GTV volume changes of more than 20% were not significantly associated with primary disease or the presence of cystic components/necrosis. The mid-treatment GTV did not overlap perfectly with the initial PTV in more than half of the lesions.

Conclusions

Compared to the initial GTV, the mid-treatment GTV changed by more than 20% in almost one-third of lesions treated with 13-fraction SRT. As SRT usually generates a steep dose gradient as well as increasing the maximum dose of PTV compared to conventional radiotherapy, assessment of the volume and locational target changes and adaptive radiotherapy should be considered as the number of fractions increases.
Implementation of Enhanced Recovery After Surgery (ERAS) protocol for elderly patients receiving surgery for intertrochanteric fracture: a propensity score-matched analysis
Authors: Zhu Wenhao , Yan Yinjie , Sun Yijin , Fan Zhaoxiang , Fang Niangkang , Zhang Yunlu , Yin Mengchen , Wan Hongbo , Mo Wen , Lu Wei , Wu Xuequn
Published: July 2021

Purpose

Enhanced Recovery After Surgery (ERAS) is a multimodal approach to perioperative care that aims to reduce patient perioperative complications, accelerate patient recovery, and improve patient satisfaction by refining and optimizing all perioperative management processes. By comparing two groups of patients before and after the implementation of ERAS for intertrochanteric fracture (ITF) with a matching analysis of propensity score (PS), we aimed to demonstrate that the implementation of ERAS protocol shortens the length of hospital stay (LOS), reduces pain, decreases the incidence of postoperative complications, and promotes functional recovery of the joint.

Methods

We selected 2 periods of 1 year, before (n=98patients) and after ERAS implementation (n=92patients). Data were collected on patient demographics, operative and perioperative details, LOS, VAS score, Harris score, and 30-day complications. ERAS-trained nurses are engaged to support patients at each step of the pre/per/postoperative process, including completing a satisfaction survey, with the help of a mobile app. PS analyses were used for dealing with confounding bias in this retrospective observational study.

Results

After PS matching, the outcomes of 124 well-balanced pairs of patients were compared (conventional vs ERAS). LOS was significantly reduced from 24.3±3.9 to 15.2±2.9 days (P<0.001). With the same preoperative VAS scores, we found that patients in the ERAS group had significantly lower postoperative VAS scores than those in the conventional group at days 3 and 7 (P<0.001), but the difference was not statistically significant at day 14. patients in the ERAS group had higher Harris scores than those in the conventional group at 1 and 3 months, but the difference was not significant at 6 months. In addition, we found that only one patient in the ERAS group developed complications, while nine patients in the conventional group developed different complications. There was no significant difference concerning the satisfaction survey.

Conclusion

The introduction of ERAS for ITF in our institution has resulted in a significant decrease in LOS, alleviated patient pain, promoted early recovery of patient’s hip function while effectively preventing complications, and obtained patient satisfaction.