bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumorigenic circulating tumor cells from xenograft mouse models of non-metastatic NSCLC patients reveal distinct single cell heterogeneity and drug responses
Authors: Suvilesh Kanve N. , Nussbaum Yulia I. , Radhakrishnan Vijay , Manjunath Yariswamy , Avella Diego M. , Staveley-O’Carroll Kevin F. , Kimchi Eric T. , Chaudhuri Aadel A. , Shyu Chi-Ren , Li Guangfu , Pantel Klaus , Warren Wesley C. , Mitchem Jonathan B. , Kaifi Jussuf T.
Published: March 2022

Background

Circulating tumor cells (CTCs) are liquid biopsies that represent micrometastatic disease and may offer unique insights into future recurrences in non-small cell lung cancer (NSCLC). Due to CTC rarity and limited stability, no stable CTC-derived xenograft (CDX) models have ever been generated from non-metastatic NSCLC patients directly. Alternative strategies are needed to molecularly characterize CTCs and means of potential future metastases in this potentially curable patient group.

Methods

Surgically resected NSCLC primary tumor tissues from non-metastatic patients were implanted subcutaneously in immunodeficient mice to establish primary tumor patient-derived xenograft (ptPDX) models. CTCs were isolated as liquid biopsies from the blood of ptPDX mice and re-implanted subcutaneously into naïve immunodeficient mice to generate liquid biopsy CTC-derived xenograft (CDX) tumor models. Single cell RNA sequencing was performed and validated in an external dataset of non-xenografted human NSCLC primary tumor and metastases tissues. Drug response testing in CDX models was performed with standard of care chemotherapy (carboplatin/paclitaxel). Blockade of MYC, which has a known role in drug resistance, was performed with a MYC/MAX dimerization inhibitor (10058-F4).

Results

Out of ten ptPDX, two (20%) stable liquid biopsy CDX mouse models were generated. Single cell RNA sequencing analysis revealed an additional regenerative alveolar epithelial type II (AT2)-like cell population in CDX tumors that was also identified in non-xenografted NSCLC patients’ metastases tissues. Drug testing using these CDX models revealed different treatment responses to carboplatin/paclitaxel. MYC target genes and c-MYC protein were upregulated in the chemoresistant CDX model, while MYC/MAX dimerization blocking could overcome chemoresistance to carboplatin/paclitaxel.

Conclusions

To overcome the lack of liquid biopsy CDX models from non-metastatic NSCLC patients, CDX models can be generated with CTCs from ptPDX models that were originally established from patients’ primary tumors. Single cell analyses can identify distinct drug responses and cell heterogeneities in CDX tumors that can be validated in NSCLC metastases tissues. CDX models deserve further development and study to discover personalized strategies against micrometastases in non-metastatic NSCLC patients.
Interaction of lncRNA MIR100HG with hnRNPA2B1 facilitates m6A-dependent stabilization of TCF7L2 mRNA and colorectal cancer progression
Authors: Liu Hao , Li Danxiu , Sun Lina , Qin Hongqiang , Fan Ahui , Meng Lingnan , Graves-Deal Ramona , Glass Sarah E. , Franklin Jeffrey L. , Liu Qi , Wang Jing , Yeatman Timothy J. , Guo Hao , Zong Hong , Jin Shuilin , Chen Zhiyu , Deng Ting , Fang Ying , Li Cunxi , Karijolich John , Patton James G. , Wang Xin , Nie Yongzhan , Fan Daiming , Coffey Robert J. , Zhao Xiaodi , Lu Yuanyuan
Published: March 2022

Background

Epithelial-to-mesenchymal transition (EMT) is a process linked to metastasis and drug resistance with non-coding RNAs (ncRNAs) playing pivotal roles. We previously showed that miR-100 and miR-125b, embedded within the third intron of the ncRNA host gene MIR100HG, confer resistance to cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in colorectal cancer (CRC). However, whether the MIR100HG transcript itself has a role in cetuximab resistance or EMT is unknown.

Methods

The correlation between MIR100HG and EMT was analyzed by curating public CRC data repositories. The biological roles of MIR100HG in EMT, metastasis and cetuximab resistance in CRC were determined both in vitro and in vivo. The expression patterns of MIR100HG, hnRNPA2B1 and TCF7L2 in CRC specimens from patients who progressed on cetuximab and patients with metastatic disease were analyzed by RNAscope and immunohistochemical staining.

Results

The expression of MIR100HG was strongly correlated with EMT markers and acted as a positive regulator of EMT. MIR100HG sustained cetuximab resistance and facilitated invasion and metastasis in CRC cells both in vitro and in vivo. hnRNPA2B1 was identified as a binding partner of MIR100HG. Mechanistically, MIR100HG maintained mRNA stability of TCF7L2, a major transcriptional coactivator of the Wnt/β-catenin signaling, by interacting with hnRNPA2B1. hnRNPA2B1 recognized the N6-methyladenosine (m6A) site of TCF7L2 mRNA in the presence of MIR100HG. TCF7L2, in turn, activated MIR100HG transcription, forming a feed forward regulatory loop. The MIR100HG/hnRNPA2B1/TCF7L2 axis was augmented in specimens from CRC patients who either developed local or distant metastasis or had disease progression that was associated with cetuximab resistance.

Conclusions

MIR100HG and hnRNPA2B1 interact to control the transcriptional activity of Wnt signaling in CRC via regulation of TCF7L2 mRNA stability. Our findings identified MIR100HG as a potent EMT inducer in CRC that may contribute to cetuximab resistance and metastasis by activation of a MIR100HG/hnRNPA2B1/TCF7L2 feedback loop.
Nanoarchitectured prototypes of mesoporous silica nanoparticles for innovative biomedical applications
Authors: Kankala Ranjith Kumar , Han Ya-Hui , Xia Hong-Ying , Wang Shi-Bin , Chen Ai-Zheng
Published: March 2022

Despite exceptional morphological and physicochemical attributes, mesoporous silica nanoparticles (MSNs) are often employed as carriers or vectors. Moreover, these conventional MSNs often suffer from various limitations in biomedicine, such as reduced drug encapsulation efficacy, deprived compatibility, and poor degradability, resulting in poor therapeutic outcomes. To address these limitations, several modifications have been corroborated to fabricating hierarchically-engineered MSNs in terms of tuning the pore sizes, modifying the surfaces, and engineering of siliceous networks. Interestingly, the further advancements of engineered MSNs lead to the generation of highly complex and nature-mimicking structures, such as Janus-type, multi-podal, and flower-like architectures, as well as streamlined tadpole-like nanomotors. In this review, we present explicit discussions relevant to these advanced hierarchical architectures in different fields of biomedicine, including drug delivery, bioimaging, tissue engineering, and miscellaneous applications, such as photoluminescence, artificial enzymes, peptide enrichment, DNA detection, and biosensing, among others. Initially, we give a brief overview of diverse, innovative stimuli-responsive (pH, light, ultrasound, and thermos)- and targeted drug delivery strategies, along with discussions on recent advancements in cancer immune therapy and applicability of advanced MSNs in other ailments related to cardiac, vascular, and nervous systems, as well as diabetes. Then, we provide initiatives taken so far in clinical translation of various silica-based materials and their scope towards clinical translation. Finally, we summarize the review with interesting perspectives on lessons learned in exploring the biomedical applications of advanced MSNs and further requirements to be explored.

Graphical Abstract
Platinum prodrug nanoparticles inhibiting tumor recurrence and metastasis by concurrent chemoradiotherapy
Authors: Jiang Wei , Wei Lulu , Chen Bing , Luo Xingyu , Xu Peipei , Cai Jianfeng , Hu Yong
Published: March 2022

Background

Although concurrent chemoradiotherapy (CRT), as one of the most effective antineoplastic therapies in clinic, can successfully inhibit the growth of tumor cells, a risk of developing secondary tumor is still an insurmountable barrier in clinical practice.

Results

Herein, a new platinum prodrug composed of tannic acid (TA) and Pt2+ (TA-Pt) complex film was synthesized on the surface of Fe2O3 nanoparticles (NPs) with excellent stability and biocompatibility for enhanced CRT. In this system, TA-Pt complex could respond to the tumor acidic microenvironment and damage the DNA of tumor cells. Moreover, the internal iron core not only improved the effect of subsequent radiotherapy (RT), but also disrupted the iron balance in cells, inducing intracellular ferroptosis and eliminating apoptosis-resistant cells. In vitro and vivo experimental results indicated that more than 90% of tumor cells were depleted and more than 75% of the cured tumor-bearing mice evinced no recurrence or metastasis.

Conclusions

This work offered a new idea for combining the effective chemotherapy, RT and ferroptosis therapy to enhance the curative effect of CRT and inhibit tumor recurrence and metastasis.

Graphical Abstract
Comparison of the extraperitoneal and transperitoneal routes for permanent colostomy: a meta-analysis with RCTs and systematic review
Authors: Luo Jinlong , Singh Dujanand , Zhang Faqiang , Yang Xinting , Zha Xiaoying , Jiang Huaiwu , Yang Lie , Yang Hua
Published: March 2022

Aim

To assess the efficacy of extraperitoneal colostomy (EPC) in preventing stoma-related complications.

Background

Transperitoneal colostomy (TPC) is a widely used surgical approach. However, TPCs have been reported to have increased risks of stoma-related complications, such as parastomal hernias, stomal retraction, and stomal prolapse. The purpose of EPC is to reduce these complications. However, there is still a lack of evidence-based studies.

Materials and methods

MEDLINE, EMBASE, Web of Science, Scopus, MOOSE, PubMed, Google Scholar, Baidu Scholar, and the Cochrane Library were searched to conduct a systematic review and meta-analysis with RCTs. The meta-analysis was performed with RevMan 5.4 software.

Results

This study included 5 eligible RCTs. Compared with the TPC group, the EPC group had lower incidence rates of parastomal hernias (RR, 0.14; 95% CI, 0.04–0.52, P = 0.003, I2 = 0%) and stomatal prolapse (RR, 0.27; 95% CI, 0.08–0.95, P = 0.04, I2 = 0%), but a higher rate of defecation sensation (RR, 3.51; 95% CI, 2.47–5.0, P < 0.00001, I2 = 37%). No statistically significant differences were observed in stoma retraction, colostomy construction time, stoma ischemia, or stoma necrosis.

Conclusion

Extraperitoneal colostomies are associated with lower rates of postoperative complications than transperitoneal colostomies. A randomized controlled trial meta-analysis found that permanent colostomies after abdominoperineal resection resulted in better outcomes.
Feasibility of dpFAMM flap in tongue reconstruction after facial vessel ligation and radiotherapy—case presentation
Authors: Gontarz Michał , Bargiel Jakub , Gąsiorowski Krzysztof , Marecik Tomasz , Szczurowski Paweł , Zapała Jan , Wyszyńska-Pawelec Grażyna
Published: March 2022

Background

Salvage surgery with reconstruction of the second and next primary tongue cancer remains difficult, especially after earlier neck dissection and radiotherapy. In the current report, we describe the feasibility of the extended, double-pedicled facial artery musculomucosal (dpFAMM) flap in the reconstruction of the patient with second primary tongue squamous cell carcinoma, after facial vessel ligation and radiotherapy.

Case presentation

An 81-year-old female patient was operated on due to tongue squamous cell carcinoma (SCC) on the left side T3N1M0 in 2019. Bilateral selective neck dissection with tongue reconstruction was performed by island FAMM flap. The patient also suffered from synchronous mucinous breast carcinoma treated with tamoxifen. The second primary SCC of the tongue on the opposite (right) side was detected in 2020. The patient did not agree to surgical treatment; therefore, radiotherapy was performed. The local recurrence of the tongue cancer of the right side was treated surgically in 2021. Salvage surgery comprised hemiglossectomy and dpFAMM flap reconstruction with uneventful postoperative follow-up.

Conclusions

This case presentation proved that dpFAMM flap can be used in salvage surgery and reconstruction even in patients after ligation of facial vessels, irradiation, and in the course of hormone therapy. The flap is easy to handle, has good vascularity, and comprises a predictable method of reconstruction, especially for patients with severe comorbidities.
What makes community health worker models for tuberculosis active case finding work? A cross-sectional study of TB REACH projects to identify success factors for increasing case notifications
Authors: Dam Thu A. , Forse Rachel J. , Tran Phuong M. T. , Vo Luan N. Q. , Codlin Andrew J. , Nguyen Lan P. , Creswell Jacob
Published: March 2022

Background

In the field of tuberculosis (TB), Community Healthcare Workers (CHWs) have been engaged for advocacy, case detection, and patient support in a wide range of settings. Estimates predict large-scale shortfalls of healthcare workers in low- and middle-income settings by 2030 and strategies are needed to optimize the health workforce to achieve universal availability and accessibility of healthcare. In 2018, the World Health Organization (WHO) published guidelines on best practices for CHW engagement, and identified remaining knowledge gaps. Stop TB Partnership’s TB REACH initiative has supported interventions using CHWs to deliver TB care in over 30 countries, and utilized the same primary indicator to measure project impact at the population-level for all TB active case finding projects, which makes the results comparable across multiple settings. This study compiled 10 years of implementation data from the initiative’s grantee network to begin to address key knowledge gaps in CHW networks.

Methods

We conducted a cross-sectional study analyzing the TB REACH data repository (n = 123) and primary survey responses (n = 50) of project implementers. We designed a survey based on WHO guidelines to understand projects’ practices on CHW recruitment, training, activities, supervision, compensation, and sustainability. We segmented projects by TB notification impact and fitted linear random-effect regression models to identify practices associated with higher changes in notifications.

Results

Most projects employed CHWs for advocacy alongside case finding and holding activities. Model characteristics associated with higher project impact included incorporating e-learning in training and having the prospect of CHWs continuing their responsibilities at the close of a project. Factors that trended towards being associated with higher impact were community-based training, differentiated contracts, and non-monetary incentives.

Conclusion

In line with WHO guidelines, our findings emphasize that successful implementation approaches provide CHWs with comprehensive training, continuous supervision, fair compensation, and are integrated within the existing primary healthcare system. However, we encountered a great degree of heterogeneity in CHW engagement models, resulting in few practices clearly associated with higher notifications.
Performance of the Mexican nursing labor market: a repeated cross-sectional study, 2005–2019
Authors: Nigenda Gustavo , Serván-Mori Edson , Fuentes-Rivera Evelyn , Aristizabal Patricia , Zárate-Grajales Rosa Amarilis
Published: March 2022

Background

The close link between human resources for health and the performance of health systems calls for a comprehensive study of the labor market. This paper proposes a performance metric for the nursing labor market, measures its magnitude and analyzes its predictors over the last 15 years.

Design and methods

A repeated cross-sectional analysis using data from the quarterly population-based National Survey of Occupation and Employment 2005–2019 (ENOE in Spanish). An aggregate total of 19,311 Mexican nurses (population N = 4,816,930) was analyzed. Nursing labor market performance was defined as the level of non-precarious employment of nurses in the health sector. After describing the sociodemographic, labor and contextual characteristics of the nurses surveyed, we identified the key correlates of market performance using repeated cross-sectional multiple logistic regression analysis. We then estimated the adjusted prevalence of market performance according to the survey period and socioeconomic region of residence.

Results

The exogenous indicators analyzed shed light on various aspects of the market structure. Unemployment remained stable at 5% during the period examined, but underemployment rose by 26% and precarious employment, our endogenous indicator, also grew significantly. On the whole, our indicators revealed a notable deterioration in the structure of the nursing labor market; they varied by age and sex as well as between public and private institutions. Although the steepest deterioration occurred in the private sector, we observed an increase in precarious jobs among public institutions formerly protective of employment conditions.

Conclusions

The deterioration of the labor market jeopardizes the ability of nursing professionals to participate in the market as well as to obtain secure jobs once they do enter. The Mexican Health System suffers from a chronic dearth of nurses, reducing its capacity to achieve its core objectives including enhanced coverage and increased effectiveness. Nursing workforce planning requires a context where the conditions in which the market currently operates, and its potential deterioration are considered.
Assessing changes in knowledge, attitudes, and intentions to use family planning after watching documentary and drama health education films: a qualitative study
Authors: Mubangizi Vincent , Plastow Jane , Nakaggwa Florence , Nahabwe Haven , Natukunda Sylvia , Atim Fiona , Mawere Brenda , Laughton Matthew , Muller Ingrid , Owokuhaisa Judith , Coates Sabine , Chambers Isabella , Goodhart Clare , Willcox Merlin
Published: March 2022

Background

There is a paucity of literature on the effectiveness of drama or documentary films in changing knowledge, beliefs, attitudes, and behavior of people towards family planning. This study aimed to compare and assess the acceptability of health promotion films based on documentary or drama, and their effect on knowledge, attitudes, and intention to use family planning.

Methods

We developed short documentary and drama films about contraceptive implants, using the person-based approach. Their acceptability was assessed in focus group discussions with younger women below 23 years, women over 23 years, men of reproductive age, and health workers in four different areas of Uganda (Bwindi/Kanungu, Walukuba/Jinja, Kampala, and Mbarara). Transcripts of the focus group discussions were analyzed using thematic analysis, to generate themes and examine the key issues. We assessed changes in knowledge, attitudes, and intentions to use family planning after watching the films.

Results

Sixteen focus groups with 150 participants were carried out. Participants said that the documentary improved their knowledge and addressed their fears about side effects, myths, and implant insertion. The drama improved their attitudes towards the implant and encouraged them to discuss family planning with their partner. The final versions of the documentary and the drama films were equally liked.

Conclusions

Viewing a short documentary on the contraceptive implant led to positive changes in knowledge, while a short drama improved attitudes and intentions to discuss the implant with their partner. The drama and documentary have complementary features, and most participants wanted to see both.
Herpesviruses and their genetic diversity in the blood virome of healthy individuals: effect of aging
Authors: Autio Arttu , Kettunen Jalmari , Nevalainen Tapio , Kimura Bryn , Hurme Mikko
Published: March 2022

Background

As we age, the functioning of the human immune system declines. The results of this are increases in morbidity and mortality associated with infectious diseases, cancer, cardiovascular disease, and neurodegenerative disease in elderly individuals, as well as a weakened vaccination response. The aging of the immune system is thought to affect and be affected by the human virome, the collection of all viruses present in an individual. Persistent viral infections, such as those caused by certain herpesviruses, can be present in an individual for long periods of time without any overt pathology, yet are associated with disease in states of compromised immune function. To better understand the effects on human health of such persistent viral infections, we must first understand how the human virome changes with age. We have now analyzed the composition of the whole blood virome of 317 individuals, 21–70 years old, using a metatranscriptomic approach. Use of RNA sequencing data allows for the unbiased detection of RNA viruses and active DNA viruses.

Results

The data obtained showed that Epstein-Barr virus (EBV) was the most frequently expressed virus, with other detected viruses being herpes simplex virus 1, human cytomegalovirus, torque teno viruses, and papillomaviruses. Of the 317 studied blood samples, 68 (21%) had EBV expression, whereas the other detected viruses were only detected in at most 6 samples (2%). We therefore focused on EBV in our further analyses. Frequency of EBV detection, relative EBV RNA abundance and the genetic diversity of EBV was not significantly different between age groups (21–59 and 60–70 years old). No significant correlation was seen between EBV RNA abundance and age. Deconvolution analysis revealed a significant difference in proportions of activated dendritic cells, macrophages M1, and activated mast cells between EBV expression positive and negative individuals.

Conclusions

As it is likely that the EBV RNA quantified in this work is derived from reactivation of the latent EBV virus, these data suggest that age does not affect the rate of reactivation nor the genetic landscape of EBV. These findings offer new insight on the genetic diversity of a persistent EBV infection in the long-term.
Sexual dimorphism in ritualized agonistic behaviour, fighting ability and contest costs of Sus scrofa
Authors: Camerlink Irene , Farish Marianne , Arnott Gareth , Turner Simon P.
Published: March 2022

Background

Sexual selection has driven sexual dimorphism in agonistic behaviour in many species. Agonistic behaviour is fundamentally altered by domestication and captivity, but it is unclear whether ancestral sex differences remain. We aimed to evaluate the effect of sex on agonistic behaviour, fighting ability and contest costs. We studied this in domestic pigs (Sus scrofa) where aggression compromises welfare, and sexual dimorphism in aggression has been inconclusively demonstrated. Behaviour and physiology of 827 male and female juvenile pigs were studied during resident-intruder tests and dyadic contests at various ages, while accounting for the relative body weight difference between the opponents.

Results

Males won in 79% of contests against females, even when at a large weight disadvantage. The effect of sex increased with age, with males having a 138 times higher likelihood of winning than females when 13 weeks old. In dyadic contests, males invested more time in non-damaging agonistic display behaviour and took longer before escalating into damaging aggression. Males showed ritualized display that included foaming from the mouth and piloerection of the neck hair, which was nearly always absent in females. Contest costs in terms of contest duration, blood lactate and skin lesions where higher for males, especially when fighting another male.

Conclusions

Profound sex differences were present for agonistic behaviour, fighting ability and contest costs, and became more pronounced as animals got older. Males invested more in ritualized display before escalating into costly fights, whereas females attacked sooner but also terminated contests more rapidly and with fewer costs. The sexual dimorphism in agonistic behaviour in juvenile domestic pigs is in line with the evolutionary relevance for females’ maternal defence and males’ competition for females.
Diagnostic waste: whose responsibility?
Authors: Street Alice , Vernooij Eva , Rogers Mohamed Hashim
Published: March 2022

Waste management is notably absent from current discussions about efforts to improve access to diagnostics in low-and middle-income Countries (LMICs). Yet an increase in testing will inevitably lead to an increase in diagnostic waste, especially since many of the diagnostic tests designed for use in LMICs are single-use point-of-care tests. Diagnostic waste poses a threat to both human and environmental health. In this commentary we draw on our experience of diagnostic waste management in Sierra Leone and review current evidence on: the volume and impact of diagnostic waste in LMICs, existing health-care waste management capacity in LMICs, established national and international policies for improving health-care waste management, and opportunities for strengthening policy in this area. We argue that questions of safe disposal for diagnostics should not be an afterthought, only posed once questions of access have already been addressed. Moreover, responsibility for safe disposal of diagnostic waste should not fall solely on national health systems by default. Instead, consideration of the end-life of diagnostic products must be fully integrated into the diagnostic access agenda and greater pressure should be placed on manufacturers to take responsibility for the full life-cycle of their products.
A hybrid CNN–SVM classifier for weed recognition in winter rape field
Authors: Tao Tao , Wei Xinhua
Published: March 2022

Background

Weed recognition is key for automatic weeding, which is a challenging problem. Weed recognition is mainly based on different features of crop images. The extracted image features mainly include color, texture, shape, etc. The designed features depend on manual work, which is blind to some extent. Meanwhile these features have poor generalization performance on a sample set. The final discrimination results tend to have a greater difference. The current study proposed a deep convolutional neural network (CNN) with support vector machine (SVM) classifier which aims to improve the classification accuracy of winter rape seeding and weeds in fields.

Results

The VGG network model was adopted, which received a true color image (224 × 224 pixels) of rape/weed as the input. The proposed VGG-SVM model was able to identify rape/weeds with average accuracies of 99.2% in the training procedures and 92.1% in the test procedures, respectively. A comparative experiment was conducted using the proposed VGG-SVM model and five other methods. The proposed VGG-SVM model obtained a higher classification accuracy, greater robustness and real time.

Conclusions

The VGG-SVM weed classification model proposed in this study is effective. The model can be further applied to the recognition of multi-sample mixed crop images in fields.
Impact of an addiction medicine consult team intervention in a Canadian inner city hospital on acute care utilization: a pragmatic quasi-experimental study
Authors: Salvalaggio Ginetta , Dong Kathryn A. , Hyshka Elaine , McCabe Christopher , Nixon Lara , Rosychuk Rhonda J. , Dmitrienko Klaudia , Krajnak Judith , Mrklas Kelly , Wild T. Cameron
Published: March 2022

Background

Inner city patients have a higher illness burden and need for care, but experience more unmet care needs. Hospital Addiction Medicine Consult Teams (AMCTs) are a promising emerging intervention. The objective of this study was to assess the impact of a Canadian AMCT-like intervention for inner city patients on reduction in high emergency department (ED) use, hospital admission, and inpatient length of stay.

Methods

Using a community-engaged, two-arm, pre-post, longitudinal quasi-experimental study design, 572 patients reporting active substance use, unstable housing, unstable income, or a combination thereof (302 at intervention site, 270 at control sites) were enrolled. Survey and administrative health service data were collected at baseline, six months post-enrolment, and 12 months post-enrolment. Multivariable regression models tested the intervention effect, adjusting for clinically important covariables (inpatient status at enrolment, medical complexity, age, gender, Indigenous identity, shelter use, opioid use).

Results

Initial bivariable analyses demonstrated an intervention effect on reduction in admissions and length of stay, however, this effect was no longer significant after adjusting for covariables. There was no evidence of reduction in high ED use on either bivariable or subsequent multivariable analysis.

Conclusions

After adjusting for covariables, no AMCT intervention effect was detected for reduction in high ED use, inpatient admission, or hospital length of stay. Further research is recommended to assess other patient-oriented intervention outcomes.
Effectiveness of a multifaceted implementation strategy for improving adherence to the guideline for prevention of mental ill-health among school personnel in Sweden: a cluster randomized trial
Authors: Toropova Anna , Björklund Christina , Bergström Gunnar , Elinder Liselotte Schäfer , Stigmar Kjerstin , Wåhlin Charlotte , Jensen Irene , Kwak Lydia
Published: March 2022

Background

There is limited research on prevention of mental ill-health of school personnel and the systematic management of school work environments. The aim of this study was to assess the effectiveness of implementing the guideline recommendations for the prevention of mental ill-health in schools, in particular, whether there was a difference in adherence to guideline recommendations between a multifaceted (group 1) and single implementation strategy (group 2) from baseline to 6 and to 12 months.

Method

We conducted a cluster-randomized controlled trial with a 6- and 12-month follow-up. Data was collected from nearly 700 participants in 19 Swedish schools. Participants were school personnel working under the management of a school principal. The single implementation strategy consisted of one educational meeting, while the multifaceted implementation strategy comprised an educational meeting, an ongoing training in the form of workshops, implementation teams and Plan-Do-Study-Act cycles. Adherence was measured with a self-reported questionnaire. Generalized Linear Mixed Models were used to assess the difference between groups in adherence to the guideline between baseline, 6-, and 12-months follow-up.

Results

There were no statistically significant differences between the groups in improvements in adherence to the guideline between baseline, 6-, and 12-months follow-up. However, among those schools that did not undergo any organizational changes during the 12 months of the study significant differences between groups were observed at 12 months for one of the indicators.

Conclusions

The multifaceted strategy was no more effective than the single strategy in improving guideline adherence. There are some limitations to the study, such as the measurement of the implementation outcome measure of adherence. The outcome measure was developed in a systematic manner by the research team, assessing specific target behaviors relevant to the guideline recommendations, however not psychometrically tested, which warrants a careful interpretation of the results.

Trial registration

ClinicalTrials.gov, 150571. Registered 12 September 2017.
De-implementing low-value care in cancer care delivery: a systematic review
Authors: Alishahi Tabriz Amir , Turner Kea , Clary Alecia , Hong Young-Rock , Nguyen Oliver T. , Wei Grace , Carlson Rebecca B. , Birken Sarah A.
Published: March 2022

Background

Accumulating evidence suggests that interventions to de-implement low-value services are urgently needed. While medical societies and educational campaigns such as Choosing Wisely have developed several guidelines and recommendations pertaining to low-value care, little is known about interventions that exist to de-implement low-value care in oncology settings. We conducted this review to summarize the literature on interventions to de-implement low-value care in oncology settings.

Methods

We systematically reviewed the published literature in PubMed, Embase, CINAHL Plus, and Scopus from 1 January 1990 to 4 March 2021. We screened the retrieved abstracts for eligibility against inclusion criteria and conducted a full-text review of all eligible studies on de-implementation interventions in cancer care delivery. We used the framework analysis approach to summarize included studies’ key characteristics including design, type of cancer, outcome(s), objective(s), de-implementation interventions description, and determinants of the de-implementation interventions. To extract the data, pairs of authors placed text from included articles into the appropriate cells within our framework. We analyzed extracted data from each cell to describe the studies and findings of de-implementation interventions aiming to reduce low-value cancer care.

Results

Out of 2794 studies, 12 met our inclusion criteria. The studies covered several cancer types, including prostate cancer (n = 5), gastrointestinal cancer (n = 3), lung cancer (n = 2), breast cancer (n = 2), and hematologic cancers (n = 1). Most of the interventions (n = 10) were multifaceted. Auditing and providing feedback, having a clinical champion, educating clinicians through developing and disseminating new guidelines, and developing a decision support tool are the common components of the de-implementation interventions. Six of the de-implementation interventions were effective in reducing low-value care, five studies reported mixed results, and one study showed no difference across intervention arms. Eleven studies aimed to de-implement low-value care by changing providers’ behavior, and 1 de-implementation intervention focused on changing the patients’ behavior. Three studies had little risk of bias, five had moderate, and four had a high risk of bias.

Conclusions

This review demonstrated a paucity of evidence in many areas of the de-implementation of low-value care including lack of studies in active de-implementation (i.e., healthcare organizations initiating de-implementation interventions purposefully aimed at reducing low-value care).
Characteristics of locoregional extension of unilateral nasopharyngeal carcinoma and suggestions for clinical target volume delineation
Authors: Wu Zheng , Zhang Lin , He Qian , Li Feiping , Ma Hongzhi , Zhou Yujuan , Wang Hui , Han Yaqian
Published: March 2022

Background

To summarize the characteristics of local invasion and distribution of metastatic lymph nodes in unilateral nasopharyngeal carcinoma (NPC) by magnetic resonance imaging (MRI) to provide references for the optimization of clinical target volume.

Methods

MRI and clinical data of 176 cases of unilateral NPC admitted to the Hunan Cancer Hospital from January 2019 to December 2019 were collected. Unilateral NPC was defined as a lesion confined to the one side of the nasopharynx and had not exceeded the midline as judged by MRI.

Results

Ipsilateral levator veli muscle (63.1%, 111/176), tensor veli palatini muscle (55.7%, 98/176), parapharyngeal space (50.0%, 88/176), and prevertebral muscle (43.7%, 77/176) were more likely to be invaded. Contralateral parapharyngeal space and skull base foramina were not invaded. All local invasions presented as continuous invasion from gross lesions and discontinuous invasions were not observed. The overall lymph node metastatic rate was 89.8% (158/176), of which bilateral metastasis accounted for 56.3% (89/158), and ipsilateral metastasis accounted for 88.1% (155/176), which was higher than the contralateral metastatic rate (55.4%, 94/176) (P < 0.001). The most common regions of lymph node metastasis were level IIb (82.4%), VIIa (69.9%), IIa (54.0%), and III (54.0%). Only one patient had skipping lymph node metastasis (0.6%).

Conclusion

Local invasion of unilateral NPC was characterized by continuous invasion from proximal to distal sites, and lymph node metastasis occurred from the upper to lower neck. Contralateral parapharyngeal space and skull base foramina had a very low probability of invasion, and routine prophylactic radiation may not be necessary.
Dosimetric benefit of MR-guided online adaptive radiotherapy in different tumor entities: liver, lung, abdominal lymph nodes, pancreas and prostate
Authors: Nierer Lukas , Eze Chukwuka , da Silva Mendes Vanessa , Braun Juliane , Thum Patrick , von Bestenbostel Rieke , Kurz Christopher , Landry Guillaume , Reiner Michael , Niyazi Maximilian , Belka Claus , Corradini Stefanie
Published: March 2022

Background

Hybrid magnetic resonance (MR)-Linac systems have recently been introduced into clinical practice. The systems allow online adaption of the treatment plan with the aim of compensating for interfractional anatomical changes. The aim of this study was to evaluate the dose volume histogram (DVH)-based dosimetric benefits of online adaptive MR-guided radiotherapy (oMRgRT) across different tumor entities and to investigate which subgroup of plans improved the most from adaption.

Methods

Fifty patients treated with oMRgRT for five different tumor entities (liver, lung, multiple abdominal lymph nodes, pancreas, and prostate) were included in this retrospective analysis. Various target volume (gross tumor volume GTV, clinical target volume CTV, and planning target volume PTV) and organs at risk (OAR) related DVH parameters were compared between the dose distributions before and after plan adaption.

Results

All subgroups clearly benefited from online plan adaption in terms of improved PTV coverage. For the liver, lung and abdominal lymph nodes cases, a consistent improvement in GTV coverage was found, while many fractions of the prostate subgroup showed acceptable CTV coverage even before plan adaption. The largest median improvements in GTV near-minimum dose (D98%) were found for the liver (6.3%, p < 0.001), lung (3.9%, p < 0.001), and abdominal lymph nodes (6.8%, p < 0.001) subgroups. Regarding OAR sparing, the largest median OAR dose reduction during plan adaption was found for the pancreas subgroup (-87.0%). However, in the pancreas subgroup an optimal GTV coverage was not always achieved because sparing of OARs was prioritized.

Conclusion

With online plan adaptation, it was possible to achieve significant improvements in target volume coverage and OAR sparing for various tumor entities and account for interfractional anatomical changes.
Risk factors of vertebral re-fracture after PVP or PKP for osteoporotic vertebral compression fractures, especially in Eastern Asia: a systematic review and meta-analysis
Authors: Dai Chuanqiang , Liang Gang , Zhang Youshu , Dong Yao , Zhou Xiaodan
Published: March 2022

Objective

Percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) have been widely used to treat osteoporotic vertebral compression fractures (OVCF), but the risk of vertebral re-fracture after PVP/PKP remains controversial. This study aims to investigate the incidence and risk factors of vertebral re-fracture after PVP/PKP.

Methods

Relevant literatures published up to November 2021 were collected from PubMed, Embase and Web of Science. A meta-analysis was performed to extract data associated with risk factors of SVCF following the PRISMA guidelines. Also, pooled odds ratio (OR) or weighted mean difference (WMD) with 95% confidence interval (CI) was calculated.

Results

A total of 23 studies, encompassing 9372 patients with OVCF, met the inclusion criteria. 1255 patients (13.39%) suffered re-fracture after PVP/PKP surgery. A total of 22 studies were from Eastern Asia and only 1 study was from Europe. Female sex (OR = 1.34, 95%CI 1.09–1.64, P = 0.006), older age (WMD = 2.04, 95%CI 0.84–3.24, P = 0.001), lower bone mineral density (BMD, WMD = − 0.38, 95%CI − 0.49–0.26, P < 0.001) and bone cement leakages (OR = 2.05, 95% CI 1.40–3.00, P < 0.001) increased the risk of SVCF. The results of subgroup analysis showed the occurrence of re-fracture was significantly associated with gender (P = 0.002), age (P = 0.001) and BMD (P < 0.001) in Eastern Asia. Compared with the unfractured group, anterior-to-posterior vertebral body height ratio (AP ratio, WMD = 0.06, 95%CI 0.00–0.12, P = 0.037) and visual analog scale score (VAS, WMD = 0.62, 95%CI 0.09–1.15, P = 0.022) were higher in the refracture group, and kyphotic angle correction ratio (Cobb ratio, WMD = − 0.72, 95%CI − 1.26–0.18, P = 0.008) was smaller in Eastern Asia. In addition, anti-osteoporosis treatment (OR = 0.40, 95% CI 0.27–0.60, P < 0.001) could be a protective factor.

Conclusion

The main factors associated with re-fracture after PVP/PKP are sex, age, bone mineral density, AP ratio, Cobb ratio, VAS score, bone cement leakage and anti-osteoporosis treatment, especially in Eastern Asia.
MiR-206 improves intervertebral disk degeneration by targeting GJA1
Authors: Zhou Peng , Xu Peng , Yu Wantao , Li Huan
Published: March 2022

Background

A large amount of evidence suggested that miRNA was involved in the progression of intervertebral disk degeneration (IDD). The purpose of our study was to explore the function and potential mechanism of miR-206/GJA1 axis in IDD.

Methods

IDD nucleus pulposus (NP) cell model was established through treatment of LPS. IDD rat model was established by annulus fibrosus puncture. The expression of miR-206 and GJA1 was detected by RT-PCR, apoptosis was evaluated by flow cytometry or TUNEL, inflammatory factors were tested by ELISA, extracellular matrix related protein expression was detected by western blot, and HE and safranin-O staining were used to assess the pathological changes of IDD.

Results

GJA1 was found to be highly expressed in IDD tissues and LPS-induced NP cells. Down regulation of GJA1 reduced inflammatory factors, inhibited apoptosis and enhanced extracellular matrix in LPS-induced NP cells. MiR-206 was downregulated in IDD tissues and directly targeted GJA1, and the expression of miR-206 was negatively correlated with the expression of GJA1 in IDD tissues. Further, it was demonstrated that overexpression of miR-206 could attenuate LPS-induced NP cell injury by targeting GJA1. In vivo, the upregulation of miR-206 improved IDD and reduced NP cell apoptosis.

Conclusion

Our study showed that miR-206 reduced the level of inflammatory factors, restrained NP cell apoptosis and increases extracellular matrix by targeting GJA1. These data suggested that miR-206/GJA1 might be potential therapeutic targets for IDD.
Central acetabular osteophytes (CAO) are more prevalent in the borderline developmental dysplastic hip (BDDH) patients: a propensity-score matched CT study
Authors: Yang Fan , Huang Hong-Jie , He Zi-Yi , Xu Yan , Zhang Xin , Wang Jian-Quan
Published: March 2022

Background

The acetabular fossa often showing the first signs of degeneration, Central acetabular osteophytes (CAO) have been increasingly recognized during hip arthroscopy. The purpose of this study was to investigate the condition of CAO in BDDH hips and compare cotyloid fossa size between the BDDH and the non-BDDH hips on CT images.

Methods

We performed a retrospective analysis of prospectively collected data of hip CT images of FAI or labral injury patients. A 1:2 propensity-score matched observational study comparing the linear length of cotyloid fossa was analyzed. Cotyloid fossa width (CFW) and cotyloid notch width (CNW) were measured on axial images, cotyloid fossa height (CFH) and cotyloid fossa depth (CFD) were measured on coronal images. Within the CAO patients, we performed central acetabular decompression (CAD) and then observed the morphology change in fossa.

Results

Propensity-score matching yielded 61 BDDH hips and 122 non-BDDH hips. BDDH hips had a higher prevalence of CAO and a decreased linear length of cotyloid fossa (CFW, CFH and CNW). In the BDDH group, 33 hips underwent CAD, postoperative CFW, CFH and CNW were significantly increased (p < .001 for all), and had no statistical difference compared with the non-BDDH hips (p = .193, p = .132, p = .421, respectively).

Conclusion

BDDH hips had a significantly higher prevalence of CAO than adequate acetabular coverage hips. After the procedure of CAD, BDDH hips were found to have acetabular parameters (CFW, CFH, CNW) and were restored to that of the control hips.
Efficacy of direct anterior approach combined with direct posterior approach in Pipkin IV femoral head fractures
Authors: Liu Bo , Zhao Binghao , Zhang Qingsong
Published: March 2022

Objective

The study aimed to explore the efficacy of direct anterior approach combined with direct posterior approach in Pipkin IV femoral head fractures.

Methods

The study enrolled 64 patients with Pipkin IV femoral head fractures who were treated at our hospital between March 2019 and April 2020. They were assigned to the control group and the study group using the random number table method with 32 patients in each group and received treatment by the direct anterior approach and treatment by the direct anterior approach combined with the direct posterior approach. The operative time, intraoperative estimated blood loss, postoperative drainage time, drainage volume, time to partial and full weight-bearing, total length of hospital stay and the levels of hemoglobin (Hb) and hematocrit (Hct) in the two groups were compared, and severity of pain and hip function at different time points postoperatively were observed, and the occurrences of complications were compared.

Results

There was no statistical difference in the operative time and intraoperative estimated blood loss between the two groups (P > 0.05). Compared with the control group, the study group had shorter postoperative drainage time, lower drainage volume, shorter time to partial and full weight-bearing, and shorter total length of hospital stay, and the difference was statistically different (P < 0.05). There was no significant difference in Hb and Hct levels between the two groups before surgery (P > 0.05). The levels of Hb and Hct in both groups at postoperative day (POD) 1 were lower than those before surgery, and the levels of Hb and Hct in the study group were significantly higher than those in the control group (P < 0.05). Compared with the control group, the study group had significantly less severe pain at POD 1 and 7 and 1, 3 and 6 months postoperatively (P < 0.05). Compared with the control group, the study group had significantly better hip function at 3, 6 and 12 months postoperatively (P < 0.05). All patients were followed up for 12 months, and 1 case of ectopic ossification appeared in both groups 3 months postoperatively, both Brooker grade I. No special treatment was provided as it did not interfere with the mobility of the hip and caused no apparent discomfort in the patients. In the current study, no incision infection, ischemic necrosis of the femoral head, breakage of the internal fixation device, fracture nonunion and loss of fracture reduction and other complications were reported in any patients.

Conclusion

Direct anterior approach combined with direct posterior approach in Pipkin IV femoral head fractures does not increase operative time and intraoperative estimated blood loss but can lessen severity of pain and promote functional recovery of the hip, leading to a favorable prognosis while not increasing the incidence of complications.