bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of CYP24A1 with survival and drug resistance in clinical cancer patients: a meta-analysis
Authors: Zeng Rui , Li Hua , Jia Lingyan , Lee Sau Har , Jiang Rilei , Zhang Yujia , Hu Xudong , Ye Tingjie , Wang Xiaoling , Yan Xiaofeng , Lu Yanlin , Sun Zhumei , Xu Jiatuo , Xu Wei
Published: December 2022

Background

Acquired chemo-drug resistance constantly led to the failure of chemotherapy for malignant cancers, consequently causing cancer relapse. Hence, identifying the biomarker of drug resistance is vital to improve the treatment efficacy in cancer. The clinical prognostic value of CYP24A1 remains inconclusive, hence we aim to evaluate the association between CYP24A1 and the drug resistance in cancer patients through a meta-analysis approach.

Method

Relevant studies detecting the expression or SNP of CYP24A1 in cancer patients up till May 2022 were systematically searched in four common scientific databases including PubMed, EMBASE, Cochrane library and ISI Web of Science. The pooled hazard ratios (HRs) indicating the ratio of hazard rate of survival time between CYP24A1high population vs CYP24A1low population were calculated. The pooled HRs and odds ratios (ORs) with 95% confidence intervals (CIs) were used to explore the association between CYP24A1’s expression or SNP with survival, metastasis, recurrence, and drug resistance in cancer patients.

Result

Fifteen studies were included in the meta-analysis after an initial screening according to the inclusion and exclusion criteria. There was a total of 3784 patients pooled from all the included studies. Results indicated that higher expression or SNP of CYP24A1 was significantly correlated with shorter survival time with pooled HRs (95% CI) of 1.21 (1.12, 1.31), metastasis with pooled ORs (95% CI) of 1.81 (1.11, 2.96), recurrence with pooled ORs (95% CI) of 2.14 (1.45, 3.18) and drug resistance with pooled HRs (95% CI) of 1.42 (1.17, 1.68). In the subgroup analysis, cancer type, treatment, ethnicity, and detection approach for CYP24A1 did not affect the significance of the association between CYP24A1 expression and poor prognosis.

Conclusion

Findings from our meta-analysis demonstrated that CYP24A1’s expression or SNP was correlated with cancer progression and drug resistance. Therefore, CYP24A1 could be a potential molecular marker for cancer resistance.
A cervical cancer biorepository for pharmacogenomics research in Zimbabwe
Authors: Kuguyo Oppah , Chambwe Nyasha , Nhachi Charles F. B. , Tsikai Nomsa , Dandara Collet , Matimba Alice
Published: December 2022

Background

Research infrastructures such as biorepositories are essential to facilitate genomics and its growing applications in health research and translational medicine in Africa. Using a cervical cancer cohort, this study describes the establishment of a biorepository consisting of biospecimens and matched phenotype data for use in genomic association analysis and pharmacogenomics research.

Method

Women aged > 18 years with a recent histologically confirmed cervical cancer diagnosis were recruited. A workflow pipeline was developed to collect, store, and analyse biospecimens comprising donor recruitment and informed consent, followed by data and biospecimen collection, nucleic acid extraction, storage of genomic DNA, genetic characterization, data integration, data analysis and data interpretation. The biospecimen and data storage infrastructure included shared -20 °C to -80 °C freezers, lockable cupboards, secured access-controlled laptop, password protected online data storage on OneDrive software. The biospecimen or data storage, transfer and sharing were compliant with the local and international biospecimen and data protection laws and policies, to ensure donor privacy, trust, and benefits for the wider community.

Results

This initial establishment of the biorepository recruited 410 women with cervical cancer. The mean (± SD) age of the donors was 52 (± 12) years, comprising stage I (15%), stage II (44%), stage III (47%) and stage IV (6%) disease. The biorepository includes whole blood and corresponding genomic DNA from 311 (75.9%) donors, and tumour biospecimens and corresponding tumour DNA from 258 (62.9%) donors. Datasets included information on sociodemographic characteristics, lifestyle, family history, clinical information, and HPV genotype. Treatment response was followed up for 12 months, namely, treatment-induced toxicities, survival vs. mortality, and disease status, that is disease-free survival, progression or relapse, 12 months after therapy commencement.

Conclusion

The current work highlights a framework for developing a cancer genomics cohort-based biorepository on a limited budget. Such a resource plays a central role in advancing genomics research towards the implementation of personalised management of cancer.
Corneal endothelial ring following the implantation of toric implantable collamer lenses with a central hole: a case report
Authors: Zhu Jun , Dai Qi , Ye Yu-feng
Published: December 2022

Background

To report a case of a corneal endothelial ring after toric implantable collamer lens (TICL, V4C) implantation in the right eye of a patient.

Case presentation

A 36-year-old woman with refractive errors of -8.00 DS/-2.00 DC * 8° in the right eye and − 6.50 DS/-1.75 DC * 177° in the left eye developed a corneal endothelial ring in the right eye on the first day after receiving TICLs implantation for treatment of high myopic astigmatism, which has not been previously reported as a complication of ICLs implantation. At 1 day postoperatively, the uncorrected distance visual acuity (UDVA) was 20/16, the intraocular pressure as measured by non-contact tonometry was 16.9 mmHg, and the vault as measured by anterior segment optical coherence tomography was 1238 μm. The eye was quiet and there was no unusual anterior chamber reaction. However, slit-lamp examination revealed an endothelial annular lesion of approximately 0.4 mm in diameter in the central part of the cornea, which was gray-white in color. The shape of the ring was the same as that of the central hole of the TICL. Specular microscopy showed that the mean endothelial cell density (ECD) of the ring significantly decreased to 1442 ± 263 cells/mm2, while the other part was still normal (2852 ± 103 cells/mm2). After 9 days of corticosteroid treatment and intense lubrication, the patient had a clear cornea, increased ECD (1532 ± 653 cells/mm2), and a good UDVA (20/16).

Conclusion

This case suggests that a few hours after ICL V4C implantation, with a large vault, corneal displacement caused by an air puff would make the endothelium close to or even contact the ICL, producing a corneal endothelial ring. After ruling out various possible factors, we speculated that the endothelial ring was developed due to the non-contact tonometer air puff before slit-lamp evaluation, and this phenomenon was recorded by Corvis, which confirmed that the cornea could come in contact with the ICL due to gas shock. This “contact” may cause transient corneal endothelial damage.
Negative experiences, social exclusion and unwanted attention on social media: exploring the association with adolescent alcohol use
Authors: Ranganath Priya , Hjetland Gunnhild Johnsen , Finserås Turi Reiten , Brunborg Geir Scott , Hesse Morten , Skogen Jens Christoffer
Published: December 2022

Background

Adolescents’ presence on Social Media (SoMe) facilitates peer connections making them susceptible to peer-influences and approval. Negative experiences on SoMe can affect adolescent stress and wellbeing, impelling their use of alcohol. This paper provides a novel understanding of the relationship between negative experiences on SoMe and key indicators of alcohol use in adolescents.

Methods

Data was collected from upper secondary school students (n = 3528, ages 16–19, 45% boys) in Bergen (Norway) using a web-based questionnaire during school-hours in 2020 and 2021. Dependent variables were alcohol consumption, binge drinking and scoring ≥ 2 points on the CRAFFT instrument screening for substance use problems in adolescents. Independent variables were two scales indicating “negative acts and exclusion” and “unwanted attention from others”. Covariates included age, gender, country of birth and subjective socioeconomic status. Results are presented as relative risk ratios (RRR), odds ratios (OR) and incidence rate ratios (IRR) with 95% confidence intervals.

Results

Using multinomial logistic regression models, “negative acts and exclusion” and “unwanted attention” were positively associated with trying alcohol (OR: 1.50 (95% CI 1.28–1.76) and 1.86 (95% CI 1.66–2.09) respectively, both p ≤ 0.001), with frequency and amount of alcohol consumed. Findings from logistic regression models indicated that “negative acts and exclusion” and “unwanted attention” were positively associated with i. CRAFFT-caseness (OR: 2.13 and 1.86) and ii. frequent binge drinking (OR: 1.55 and 1.89).

Conclusion

Both exclusion and unwanted attention on SoMe were associated with indicators of problematic drinking, including frequency, quantity, and consequences related to alcohol.
Cultural adaptation and validation of the SPICT-ES™ instrument to identify palliative care needs in Chilean older adults
Authors: Farfán-Zuñiga Ximena , Zimmermann-Vildoso Melissa
Published: December 2022

Introduction

Chile presents a context of an aging population and increased life expectancy, leading to many older adults (OA) needing palliative care (PC) during the course of their illness. The SPICT-ES™ is an instrument used to clinically evaluate patients with advanced chronic illness (ACI) to detect PC needs. Validating this instrument in Chile will allow for early detection of OA at risk of clinical deterioration who require this care.

Objective

Adapt and validate the SPICT-ES™ instrument to identify PC needs among OA in Chile.

Methodology

Study following quantitative design – cross-sectional, descriptive, and developed in three stages: cultural adaptation by expert judgment; preliminary test of the SPICT-ESCH instrument to evaluate reliability and application of the SPICT-ESCH in 292 patients, to determine internal consistency and stability of the instrument. This study was done between January 2019 and July 2021. Participants in the study were nurses and OA from 5 health centers in Santiago, Chile. This study was approved by the Ethics Committee of Universidad de los Andes.

Results

In the cultural adaptation with content validity, following expert judgment, all items were kept. Semantic modifications were made on only three of them. A Lawshe coefficient of 84% which determined SPICT-ESCH as an acceptable instrument for the following stages of validation and reliability. The pilot for the new version in Chile, SPICT-ESCH, determined stability and consistency over time, with a Pearson correlation coefficient (ρ) of 0.9167 (p < 0.0001). In the final application of the instrument, to fortify the psychometric evaluation (n = 292) we identified 53.4% positive SPICT-ESCH. The logistical model via OR (< 0.001) showed that the items predicted the positivity of the instrument. The internal consistency obtained was 0.8662, confirming a correlation and intercorrelation between items. 100% of nurses evaluated the SPICT-ESCH as a useful and feasible instrument.

Conclusion

SPICT-ESCH includes all the relevant indicators for adequate clinical identification of PC needs among the Chilean OA population, who could Benefit from the early introduction of palliative support contributing to their quality of life.
Investigating the structural validity and reliability of the sexual health literacy for adults (SHELA) questionnaire among a sample of women in Qazvin, Iran
Authors: Panahi Rahman , Dehghankar Leila , Amjadian Mohiadin
Published: December 2022

Background

The correct measurement of sexual health literacy requires an instrument with desirable psychometric properties and fitness to the sociocultural context. Despite acceptable psychometric properties of the sexual health literacy for adults questionnaire in the mixed population of men and women, the validity and reliability of this questionnaire in the female population were not determined. Therefore, considering differences in the study population, this study aimed to determine the structural validity and reliability of the questionnaire among women.

Methods

The present study was a methodological and psychometric study of instruments conducted among 310 women referring to healthcare centers in Qazvin, Iran in 2020. Sampling was done using a one-step cluster method. We used Cronbach's alpha coefficient, Pearson correlation coefficient, and confirmatory and exploratory factor analyses to determine the reliability, convergence validity, and construct validity of the questionnaire respectively. Also, the Sexual Quality of Life-Female questionnaire (SQOL-F) and the Female Sexual Function Index (FSFI) were used to evaluate the convergence validity. Data were analyzed using SPSS 20, and STATA 13.

Results

Exploratory factor analysis identified three factors including, “reading and understanding”, “evaluation and application of information”, and “skills of access” which together accounted for 70.85% of the whole variance. Based on the results of confirmatory factor analysis, this questionnaire had overall goodness of fit too. (RMSEA = 0.071, CFI = 0.928, TLI = 0.919, SRMR = 0.041, X2/df = 2.501). Convergent validity of the questionnaire showed a correlation of 0.121–0.243 between the questionnaire's dimensions with the FSFI and the SQOL-F questionnaires respectively. Also, the results showed that the questionnaire had proper internal consistency (Cronbach’s alpha was 0.981) for measuring sexual health literacy in women.

Conclusions

The 39-item sexual health literacy assessment questionnaire consisting of 3 factors in the present study was endowed with sufficient validity and reliability, and it can be used for precisely assessing women’s sexual health literacy.
Malignant perivascular epithelioid cell tumor (PEComa) of the uterus
Authors: Cao Bo , Huang Yi
Published: December 2022

Background

Perivascular epithelioid cell tumors (PEComas) of the uterus is a rare type of mesenchymal tumors associated with myelomelanocytic differentiation and distinctive histological appearances. So far, the reported cases of uterine PEComas are usually benign. Documented malignant cases with aggressive behavior appear to be less common.

Case presentation

We report a 37-year-old female who received abdominal hysterectomy for uterine tumor in a local hospital. She was diagnosed with uterine leiomyosarcoma and referred to Hubei Cancer Hospital. Her histological slides were reviewed and immunohistochemical staining for specific markers of epithelial, melanocytic, myoid and some others were analyzed. The pathologic diagnosis was malignant uterine PEComa. Systematic imaging of the patient further revealed an abdominal para-aortic mass. She received pelvic and para-aortic lymph node dissection. Postoperative histology revealed para-aortic lymph nodal metastasis of malignant uterine PEComa. She received 8 cycles of chemotherapy after surgery. The chemotherapy regiment was epirubicin plus ifosfamide The patient is free of recurrence and metastasis 6 years after surgical resection.

Conclusion

Uterine PEComas are indistinguishable from other uterine tumors such as leiomyoma and leiomyosarcoma before pathologic diagnosis could be made. For patients with malignant uterine PEComas, removal of both primary lesions and metastatic foci, if any, needs to be attempted. Postoperative chemotherapy or radiotherapy should also be considered in patients with distant metastases or positive lymph nodes.
First evaluation of an app to optimize and organize the processes and assessments in dental clinical courses
Authors: Goob Janosch , Possert Philipp , Klören Markus , Erdelt Kurt , Güth Jan-Frederik , Edelhoff Daniel , Liebermann Anja
Published: December 2022

Background

Digital teaching and learning tools, such as computer/mobile apps, are becoming an important factor in modern university education. The objective of our study was to introduce, analyze, and assess an organization and dual assessment app for clinical courses in dental medicine.

Methods

This was a survey-based study of dental students from the clinical study phase (4th/5th year; 8th/10th semester) of a department of prosthetic dentistry at a German university hospital about the benefits of a novel web-based and mobile app for organization and dual assessment of dental clinical courses. A total of eight questions were answered in an anonymous online survey. Data were analyzed using the Kolmogorov-Smirnov test, followed by an exploratory data analysis (α < 0.05).

Results

The app was given an average grade of 2.4, whereby 56.9% of the respondents rated the app with a grade of 2 (2 = good). In all, 94.6% of the study participants had not experienced any technical problems when using the app. Concerning the assessment, teaching doctor assessment (51.5 [IQR: 44.0]) was rated significantly better (p = 0.002) than self-assessment (39.5 [IQR: 32.8]).

Conclusions

This investigation evaluated a newly introduced app to optimize dental clinical course workflows and assessment. The organizational feature was rated as good, while the daily self- and teaching doctor assessments were evaluated as less important. The results outline how the use of app technologies can provide an infrastructure for managing organization and daily assessments in dental education.
New graduate registered nurses’ professional competence and the impact of preceptors’ education intervention: a quasi-experimental longitudinal intervention study
Authors: Lindfors Kirsi , Flinkman Mervi , Kaunonen Marja , Huhtala Heini , Paavilainen Eija
Published: December 2022

Aims and objectives

The aim of this quasi-experimental longitudinal intervention study was to investigate new graduate nurses’ professional competence development after preceptors’ participation in an education intervention.

Background

New graduate registered nurses are expected to be competent in many areas of nursing. Expectations that are sometimes unrealistic may cause a sense of inadequacy and stress, and this may in turn prevent them from fully deploying their competencies. Competence development is related to practice environment, occupational commitment, empowerment, and work experience. Orientation or transition programs have been designed to ensure new graduate nurses’ competence, and preceptors and preceptorship could also have significant influence on their competence development.

Design

A quasi-experimental longitudinal intervention study.

Methods

The data was collected from October 2015 to November 2017. Participating wards were randomized into intervention and control groups. The intervention group preceptors had an eight-hour education intervention that focused on new employees’ orientation, particularly from new graduates’ point of view. Wards in the control group continued to precept as before. The Nurse Competence Scale was used for new graduates’ self-assessment at baseline and at three-month and nine-month follow-up. This study is reported in accordance with the TREND Statement Checklist.

Results

The education intervention aimed at preceptors did not have impact on the intervention group NGRNs’ competence development. There were no statistically significant differences between the groups and effect size remained small.

Conclusions

The preceptors’ education intervention was not effective enough to develop new graduates’ professional competence so that it would have differed from that of the graduates receiving conventional orientation at the university hospital. This study confirmed that competence development is a complex and multidimensional phenomenon and organizations should invest in new graduate registered nurses’ competence development during their early career. Preceptors’ education and development of preceptorship and transition programs are an important part of overall competence development in complex health care environments.

Trial registration

Retrospectively registered
The comparative effectiveness of Core versus Core+Enhanced implementation strategies in a randomized controlled trial to improve substance use treatment receipt among justice-involved youth
Authors: Knight Danica K. , Belenko Steven , Dennis Michael L. , Wasserman Gail A. , Joe George W. , Aarons Gregory A. , Bartkowski John P. , Becan Jennifer E. , Elkington Katherine S. , Hogue Aaron , McReynolds Larkin S. , Robertson Angela A. , Yang Yang , Wiley Tisha R. A.
Published: December 2022

Background

Most justice-involved youth are supervised in community settings, where assessment and linkage to substance use (SU) treatment services are inconsistent and fragmented. Only 1/3 of youth with an identified SU need receive a treatment referral and even fewer initiate services. Thus, improving identification and linkage to treatment requires coordination across juvenile justice (JJ) and behavioral health (BH) agencies. The current study examines the comparative effectiveness of two bundled implementation intervention strategies for improving SU treatment initiation, engagement, and continuing care among justice-involved youth supervised in community settings. Exploration, Preparation, Implementation, Sustainment (EPIS) served as the conceptual framework for study design and selection/timing of implementation intervention components, and the BH Services Cascade served as the conceptual and measurement framework for identifying and addressing gaps in service receipt.

Methods

Part of a larger Juvenile-Justice Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS) Cooperative, this study involved a multisite, cluster-randomized control trial where sites were paired then randomly assigned to receive Core (training teams on the BH Services Cascade and data-driven decision making; supporting goal selection) or Core+Enhanced (external facilitation of implementation teams) intervention components. Youth service records were collected from 20 JJ community supervision agencies (in five states) across five study phases (baseline, pre-randomization, early experiment, late experiment, maintenance). Implementation teams comprised of JJ and BH staff collaboratively identified goals along the BH Cascade and used data-driven decision-making to implement change.

Results

Results suggest that Core intervention components were effective at increasing service receipt over time relative to baseline, but differences between Core and Core+Enhanced conditions were non-significant. Time to service initiation was shorter among Core+Enhanced sites, and deeper Cascade penetration occurred when external facilitation (of implementation teams) was provided. Wide variation existed in the degree and nature of change across service systems.

Conclusions

Findings demonstrate the criticality of early EPIS phases, demonstrating that strategies provided during the formative exploration and preparation phases produced some improvement in service receipt, whereas implementation-focused activities produced incremental improvement in moving youth farther along the Cascade.
Molecular characterization and antiviral effects of canine interferon regulatory factor 1 (CaIRF1)
Authors: Hao Xiangqi , Chen Hui , Li Yanchao , Chen Bo , Liang Weifeng , Xiao Xiangyu , Zhou Pei , Li Shoujun
Published: December 2022

Background

Interferon regulatory factor 1 (IRF1) is an important transcription factor that activates the type I interferon (IFN-I) response and plays a vital role in the antiviral immune response. Although IRF1 has been identified in several mammals, little information related to its function in canines has been described.

Results

In this study, canine IRF1 (CaIRF1) was cloned. After a series of bioinformatics analyses, we found that the CaIRF1 protein structure was similar to that of other animal IRF1 proteins, including a conserved DNA-binding domain (DBD), an IRF-association domain 2 (IAD2) domain and two nuclear localization signals (NLSs). An indirect immunofluorescence assay (IFA) revealed that CaIRF1 was mainly distributed in the nucleus. Overexpression of CaIRF1 in Madin-Darby canine kidney cells (MDCK) induced high levels of interferon β (IFNβ) and IFN-stimulated response element (ISRE) promoter activation and induced interferon-stimulated gene (ISG) expression. Subsequently, we assayed the antiviral activity of CaIRF1 against vesicular stomatitis virus (VSV) and canine parvovirus type-2 (CPV-2) in MDCK cells. Overexpression of CaIRF1 effectively inhibited the viral yields of VSV and CPV-2, while knocking down of CaIRF1 expression mildly increased viral gene copies.

Conclusions

CaIRF1 is involved in the cellular IFN-I signaling pathway and plays an important role in the antiviral response.
Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry
Authors: Miravitlles Marc , Turner Alice M. , Torres-Duran María , Tanash Hanan , Rodríguez-García Carlota , López-Campos José Luis , Chlumsky Jan , Guimaraes Catarina , Rodríguez-Hermosa Juan Luis , Corsico Angelo , Martinez-González Cristina , Hernández-Pérez José María , Bustamante Ana , Parr David G. , Casas-Maldonado Francisco , Hecimovic Ana , Janssens Wim , Lara Beatriz , Barrecheguren Miriam , González Cruz , Stolk Jan , Esquinas Cristina , Clarenbach Christian F.
Published: December 2022

Background

Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history.

Methods

The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 μM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022.

Results

A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%).

Conclusions

EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function.

Trial registrationwww.clinicaltrials.gov (ID: NCT04180319)
Financial burden and health-seeking behaviors related to chronic diseases under the National Health Insurance Scheme in Bolikhamxay Province, Lao PDR: a cross-sectional study
Authors: Ito Tomoo , Kounnavong Sengchanh , Miyoshi Chiaki
Published: December 2022

Background

Chronic diseases pose a serious threat to health and longevity worldwide. As chronic diseases require long periods of treatment and may become serious conditions, the ensuing financial burden is often worse than that for non-chronic diseases. In 2016, the Lao PDR implemented the National Health Insurance (NHI) system, which covers select provinces. However, data on health service accessibility and the financial burden on households, especially those with chronically ill members covered by the NHI, are scarce.

Methods

This study used a cross-sectional design. Data collection was conducted in Bolikhamxay province (population = 273,691), from January 15 to February 13, 2019. In total, 487 households, selected through stratified random sampling, were surveyed via questionnaire-based interviews. Healthcare service usage and financial burden were examined.

Results

A total of 370 households had at least one member with self-reported health issues within the last 3 months prior to the interview, while 170 had at least one member with a chronic condition. More than 75% of the households accessed a health facility when a member experienced health problems. The majority of households (43.2%) spent the maximum value covered by the NHI, but households in the second largest group (21.4%) spent 10 times the maximum value covered by the NHI. The prevalence of catastrophic health expenditure (i.e., health-related expenditure equivalent to > 20% of total income) was 25.9% (20% threshold) and 16.2% (40% threshold). Through logistic regression, we found that the major factors determining financial catastrophes owing to health problems were household members with chronic illness, hospitalization, household poverty status, household size (for both the 20 and 40% thresholds), visiting a private facility (20% threshold), and distance from the province to the referral hospital (40% threshold).

Conclusions

The NHI system has had a positive effect on households’ access to health facilities. However, catastrophic health expenditure remains high, especially among chronically ill patients. Facilities under the NHI system should be improved to provide more services, including care for chronic conditions.
SPTBN1 abrogates renal clear cell carcinoma progression via glycolysis reprogramming in a GPT2-dependent manner
Authors: Wu Jiajin , Miao Chenkui , Wang Yuhao , Wang Songbo , Wang Zhongyuan , Liu Yiyang , Wang Xiaoyi , Wang Zengjun
Published: December 2022

Background

Renal clear cell carcinoma (ccRCC) is the most prevalent tumors worldwide. Discovering effective biomarkers is essential to monitor the prognosis and provide alternative clinical options. SPTBN1 is implicated in various cancerous processes. However, its role in ccRCC remains unelucidated. This study intends to explore the biological function and mechanism of SPTBN1 in ccRCC.

Methods

Single-cell and bulk RNA-seq, tissue microarray, real-time quantitative PCR, and western blotting were applied to verify the expression and predictive value of SPTBN1 in ccRCC. Gain or loss of functional ccRCC cell line models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Actinomycin D experiment, RNA immunoprecipitation (RIP), specific inhibitors, and rescue experiments were carried out to define the molecular mechanisms.

Results

SPTBN1 was down-regulated in ccRCC and knockdown of SPTBN1 displayed a remarkably oncogenic role both in vitro and in vivo; while overexpressing SPTBN1 reversed this effect. SPTBN1 mediated ccRCC progression via the pathway of glutamate pyruvate transaminase 2 (GPT2)-dependent glycolysis. The expression of GPT2 was significantly negatively correlated with that of SPTBN1. As an RNA binding protein SPTBN1, regulated the mRNA stability of GPT2.

Conclusion

Our research demonstrated that SPTBN1 is significantly down-regulated in ccRCC. SPTBN1 knockdown promotes ccRCC progression via activating GPT2-dependent glycolysis. SPTBN1 may serve as a therapeutic target for the treatment of ccRCC.
Evidence for objects of implementation in healthcare: considerations for Implementation Science and Implementation Science Communications
Authors: Wensing Michel , Sales Anne , Aarons Gregory A. , Xu Dong , Wilson Paul
Published: December 2022

The journals Implementation Science and Implementation Science Communications are focused on the implementation of evidence into healthcare practice and policy. This editorial offers reflections on how we handle this as editors. Studies that focus on the simultaneous implementation of implementation objects and (technological or other) structures to enable their implementation are considered on a case-by-case basis regarding their contribution to implementation science. Studies on implementation objects with limited, mixed, or of out-of-context evidence are considered if the evidence for key components of the object of interest is sufficiently robust. We follow GRADE principles in our assessment of the certainty of research findings for health-related interventions in individuals. Adapted thresholds apply to evidence for population health interventions, organizational changes, health reforms, health policy innovations, and medical devices. The added value of a study to the field of implementation science remains of central interest for our journals.
Prioritizing evidence-based practices for acute respiratory distress syndrome using digital data: an iterative multi-stakeholder process
Authors: Ervin Jennifer N. , Dibble Millie R. , Rentes Victor C. , Sjoding Michael W. , Gong Michelle N. , Hough Catherine L. , Iwashyna Theodore J. , Sales Anne E.
Published: December 2022

Background

Evidence-based practices (EBPs) for patients receiving invasive mechanical ventilation vary in the quality of their underlying evidence and ease of implementation.

Research question

How do researchers and clinicians prioritize EBPs to help guide clinical decision-making and focus implementation efforts to improve patient care using existing, validated measures?

Study design and methods

We developed a 4-step rapid method using existing criteria to prioritize EBPs associated with lower mortality and/or shorter duration of invasive mechanical ventilation for patients suffering from acute respiratory failure or acute respiratory distress syndrome. Using different types of data including surveys, we (1) identified relevant EBPs, (2) rated EBPs using the Guideline Implementability Appraisal (GLIA) tool, (3) surveyed practicing ICU clinicians from different hospital systems using a subset of GLIA criteria, and (4) developed metrics to assess EBP performance. In this paper, we describe steps 2 and 3.

Results

In step 2, we prioritized 11 EBPs from an initial list of 30, using surveys and ratings among a small group of clinician researchers. In step 3, 42 clinicians from 8 different hospital systems provided assessments of these 11 EBPs which inform the final step of metric development.

Interpretation

Our prioritization process allowed us to identify 11 EBPs out of a larger group that clinicians perceive is most likely to help optimize invasive mechanical ventilation and improve the outcomes of this vulnerable patient population. While this method was developed in critical care related to adults receiving invasive mechanical ventilation, it is adaptable to other health contexts.
Efficacy analysis of a double-Schanz screw external fixator combined with anti-rotating Kirschner wire in the treatment of proximal humerus fractures in skeletally immature patients
Authors: Wang Qian , Wang Yu , Zhao Huai , Kong Qingzhu , Zhao Jingxin , jin Yu
Published: December 2022

Objectives

The objective of this study is to evaluate the efficacy of a double-Schanz screw external fixator combined with anti-rotating Kirschner wire in the treatment of displaced Salter–Harris type II proximal humerus fractures in skeletally immature patients.

Methods

A retrospective analysis was performed on 22 cases of displaced Salter–Harris type II proximal humerus fractures in skeletally immature patients who were treated with a double-Schanz screw external fixator combined with anti-rotating Kirschner wire. Patients included were the Neer–Horowitz (N–H) type 2, 3, and 4 of fracture. The basic information of the patients was recorded, fracture healing and shoulder range of motion were assessed at the last follow-up visit. The disabilities of the arm, hand (DASH) score and Constant—Murley score of the shoulder were performed to observe the occurrence of complications.

Results

The mean age at the time of surgery was 12.41 years, and all patients completed a median follow-up of 18.18 months. There were two cases of N–H type 2, 12 cases of N–H type 3, and eight cases of N–H type 4 among the patients. At the last follow-up, all patients were able to achieve pain-free shoulder movement. There was no significant difference in shoulder function between the injured side and the uninjured side. The DASH score mean was 2.43 (95% CI 1.44–3.52). The constant score mean was 98.55 (95% CI 97.73–99.27). All patients returned to their pre-injury daily life and physical activities, and there was no significant difference in bilateral limb length at the last follow-up (p < 0.05). The most common complication of double-Schanz screw external fixator combined with anti-rotating Kirschner wire surgery was pin tract infection, which occurred in 5 cases (22.7%). There were no complications such as deep infections, vascular and nerve damage, failure of fixation, secondary fracture displacement, non-union of fracture, osteonecrosis of the humerus, joint stiffness, rotator cuff weakness and limb deformity.

Conclusion

The double-Schanz screw external fixator combined with anti-rotating Kirschner wire is a safe and effective treatment for displaced Salter–Harris type II proximal humerus fractures in skeletally immature patients over the age of 10 years.
Febrile infection-related Epilepsy Syndrome (FIRES): a severe encephalopathy with status epilepticus. Literature review and presentation of two new cases
Authors: Pavone Piero , Corsello Giovanni , Raucci Umberto , Lubrano Riccardo , Parano Enrico , Ruggieri Martino , Greco Filippo , Marino Silvia , Falsaperla Raffaele
Published: December 2022

FIRES is defined as a disorder that requires a prior febrile infection starting between 2 weeks and 24 h before the onset of the refractory status epilepticus with or without fever at the onset of status epilepticus. The patients, previously normal, present in the acute phase recurrent seizures and status epilepticus followed by a severe course with usually persistent seizures and residual cognitive impairment. Boundary with “new onset refractory status epilepticus (NORSE) has not clearly established. Pathogenetic hypothesis includes inflammatory or autoimmune mechanism with a possible genetic predisposition for an immune response dysfunction.

Various types of treatment have been proposed for the treatment of the acute phase of the disorder to block the rapid seizures evolution to status epilepticus and to treat status epilepticus itself. Prognosis is usually severe both for control of the seizures and for cognitive involvement.

FIRES is an uncommon but severe disorder which must be carefully considered in the differential diagnosis with other epileptic encephalopathy.
Continuous bladder urinary oxygen tension as a new tool to monitor medullary oxygenation in the critically ill
Authors: Hu Raymond T. , Lankadeva Yugeesh R. , Yanase Fumitake , Osawa Eduardo A. , Evans Roger G. , Bellomo Rinaldo
Published: December 2022

Acute kidney injury (AKI) is common in the critically ill. Inadequate renal medullary tissue oxygenation has been linked to its pathogenesis. Moreover, renal medullary tissue hypoxia can be detected before biochemical evidence of AKI in large mammalian models of critical illness. This justifies medullary hypoxia as a pathophysiological biomarker for early detection of impending AKI, thereby providing an opportunity to avert its evolution. Evidence from both animal and human studies supports the view that non-invasively measured bladder urinary oxygen tension (PuO2) can provide a reliable estimate of renal medullary tissue oxygen tension (tPO2), which can only be measured invasively. Furthermore, therapies that modify medullary tPO2 produce corresponding changes in bladder PuO2. Clinical studies have shown that bladder PuO2 correlates with cardiac output, and that it increases in response to elevated cardiopulmonary bypass (CPB) flow and mean arterial pressure. Clinical observational studies in patients undergoing cardiac surgery involving CPB have shown that bladder PuO2 has prognostic value for subsequent AKI. Thus, continuous bladder PuO2 holds promise as a new clinical tool for monitoring the adequacy of renal medullary oxygenation, with its implications for the recognition and prevention of medullary hypoxia and thus AKI.
Exploring functional protein covariation across single cells using nPOP
Authors: Leduc Andrew , Huffman R. Gray , Cantlon Joshua , Khan Saad , Slavov Nikolai
Published: December 2022

Background

Many biological processes, such as cell division cycle and drug resistance, are reflected in protein covariation across single cells. This covariation can be quantified and interpreted by single-cell mass spectrometry with sufficiently high throughput and accuracy.

Results

Here, we describe nPOP, a method that enables simultaneous sample preparation of thousands of single cells, including lysing, digesting, and labeling individual cells in volumes of 8–20 nl. nPOP uses piezo acoustic dispensing to isolate individual cells in 300 pl volumes and performs all subsequent sample preparation steps in small droplets on a fluorocarbon-coated glass slide. Protein covariation analysis identifies cell cycle dynamics that are similar and dynamics that differ between cell types, even within subpopulations of melanoma cells delineated by markers for drug resistance priming. Melanoma cells expressing these markers accumulate in the G1 phase of the cell cycle, display distinct protein covariation across the cell cycle, accumulate glycogen, and have lower abundance of glycolytic enzymes. The non-primed melanoma cells exhibit gradients of protein abundance, suggesting transition states. Within this subpopulation, proteins functioning in oxidative phosphorylation covary with each other and inversely with proteins functioning in glycolysis. This protein covariation suggests divergent reliance on energy sources and its association with other biological functions. These results are validated by different mass spectrometry methods.

Conclusions

nPOP enables flexible, automated, and highly parallelized sample preparation for single-cell proteomics. This allows for quantifying protein covariation across thousands of single cells and revealing functionally concerted biological differences between closely related cell states. Support for nPOP is available at https://scp.slavovlab.net/nPOP.
How do we know a treatment is good enough? A survey of non-inferiority trials
Authors: Attard Naomi , Totton Nikki , Gillies Katie , Goulao Beatriz
Published: December 2022

Background

Non-inferiority and equivalence trials aim to determine whether a new treatment is good enough (non-inferior) or as good as (equivalent to) another treatment. To inform the decision about non-inferiority or equivalence, a margin is used. We aimed to identify the current methods used to determine non-inferiority or equivalence margins, as well as the main challenges and suggestions from trialists.

Methods

We developed an online questionnaire that included both closed and open-ended questions about methods to elicit non-inferiority or equivalence margins, underlying principles, and challenges and suggestions for improvement. We recruited trialists with experience of determining a margin by contacting corresponding authors for non-inferiority or equivalence trials. We used descriptive statistics and content analysis to identify categories in qualitative data.

Results

We had forty-one responses, all from non-inferiority trials. More than half of the trials were non-pharmacological (n = 21, 51%), and the most common primary outcome was clinical (n = 29, 71%). The two most used methods to determine the margin were as follows: a review of the evidence base (n = 27, 66%) and opinion seeking methods (n = 24, 59%). From those using reviews, the majority used systematic reviews or reviews of multiple RCTs to determine the margin (n = 17, 63%). From those using opinion seeking methods, the majority involved clinicians with or without other professionals (n = 19, 79%). Respondents reported that patients’ opinions on the margin were sought in four trials (16%). Median confidence in overall quality of the margin was 5 out of 7 (maximum confidence); however, around a quarter of the respondents were “completely unconfident” that the margin reflected patient’s views. We identified “stakeholder involvement” as the most common category to determine respondent’s confidence in the quality of the margins and whether it reflected stakeholder’s views. The most common suggestion to improve the definition of margins was “development of methods to involve stakeholders,” and the most common challenge identified was “communication of margins.”

Conclusions

Responders highlighted the need for clearer guidelines on defining a margin, more and better stakeholder involvement in its selection, and better communication tools that enable discussions about non-inferiority trials with stakeholders. Future research should focus on developing best practice recommendations.
A savings intervention to reduce men’s engagement in HIV risk behaviors: study protocol for a randomized controlled trial
Authors: Egbe Teniola I. , Omollo Ouma Dan , Wesonga Julius Oduor , Bair Elizabeth F. , Chakrabarti Averi , Putt Mary E. , Celum Connie L. , Camlin Carol S. , Napierala Sue , Agot Kawango , Thirumurthy Harsha
Published: December 2022

Background

In much of eastern and southern Africa, the incidence of HIV and other sexually transmitted infections (STIs) remains high despite the scale-up of promising biomedical and behavioral interventions. Studies have documented the crucial role of transactional sex—the exchange of money, material support, or goods, in sexual relationships—and heavy alcohol use in contributing to men’s and women’s health outcomes. Existing policy responses to this challenge have largely focused on women, through the provision of pre-exposure prophylaxis (PrEP) or structural interventions such as education subsidies and cash transfers. However, the effectiveness of these interventions has been hindered by the relative lack of interventions and programs targeting men’s behavior. We describe the protocol for a study that will test an economic intervention designed to reduce men’s engagement in HIV/STI-related risk behaviors in Kenya.

Methods

We will conduct a randomized controlled trial among income-earning men in Kenya who are aged 18–39 years and self-report alcohol use and engagement in transactional sex. The study will enroll 1500 participants and randomize them to a control group or savings group. The savings group will receive access to a savings account that includes lottery-based incentives to save money regularly, opportunities to develop savings goals/strategies, and text message reminders about their savings goals. The control group will receive basic health education. Over a period of 24 months, we will collect qualitative and quantitative data from participants and a subset of their female partners. Participants will also be tested for HIV and other STIs at baseline, 12, and 24 months.

Discussion

The findings from this study have the potential to address a missing element of HIV/STI prevention efforts in sub-Saharan Africa by promoting upstream and forward-looking behavior and reducing the risk of acquiring HIV/STIs in a high HIV/STI burden setting. If this study is effective, it is an innovative approach that could be scaled up and could have great potential for scientific and public health impact in Kenya.

Trial registration

ClinicalTrials.govNCT05385484. Registered on May 23, 2022