bluuebunny/crossref_metadata_2025 huggingface dataset:
Tools to measure barriers to medication management capacity in older adults: a scoping review
Authors: Baby Bincy , McKinnon Annette , Patterson Kirk , Patel Hawa , Sharma Rishabh , Carter Caitlin , Griffin Ryan , Burns Catherine , Chang Feng , Guilcher Sara JT , Lee Linda , Fadaleh Sara Abu , Patel Tejal
Published: March 2024

Background

Medication management capacity is a crucial component of medication adherence, particularly among older adults. Various factors, including physical abilities, cognitive functions, sensory capabilities, motivational, and environmental factors, influence older adults' ability to manage medications. It is, therefore, crucial to identify appropriate tools that allow clinicians to determine which factors may impact medication management capacity and, consequently, nonadherence to medications.

Purpose

1)To identify tools that measure physical, cognitive, sensory (vision, hearing, touch), motivational, and environmental barriers to medication self-management in older adults, and 2) to understand the extent to which these tools assess various barriers.

Methods

The scoping review was conducted using Arksey and O'Malley's scoping review framework and the PRISMA Extension for Scoping Reviews checklist. In June 2022, the relevant literature was identified by searching PubMed (MEDLINE), Ovid Embase, Ovid IPA, EBSCOhost CINAHL, APA PsycINFO, and Scopus.

Results and discussion

In total, 7235 studies were identified. Following the removal of duplicates, 4607 articles were screened by title and abstract, of which 4253 did not meet the inclusion criteria. Three reviewers reviewed the full texts of the remaining 354 articles; among them, 41 articles, 4 theses and 1 conference abstract met the inclusion criteria. From the included studies, 44 tools were identified that measured a combination of physical, cognitive, sensory, motivational, and environmental barriers (n=19) or only cognition (n=13), vision (n=5), environmental factors (n=3), auditory (n=1), and motivational factors (n=1). The review also examined the psychometric properties of the identified tools and found that most of them had reported validity and reliability data. Several tools have demonstrated promise in assessing a combination of barriers with validity and reliability. These tools include the Self-Medication Assessment Tool (SMAT), ManageMed Screening (MMS), Self-Medication Risk Assessment Tool (RAT), HOME-Rx revised, and Medication Management Ability Assessment (MMAA).

Conclusion

This scoping review identified 44 validated tools to measure various challenges that older adults encounter with medication management. However, no tool measures all five barriers (physical, cognitive, sensory, motivational, and environmental) to medication-taking at home. Therefore, utilizing a combination of tools would be most appropriate to measure these different aspects comprehensively. Further research is needed to develop a new comprehensive tool that simultaneously measures various barriers to medication self-management.
Assessing the use of anti-PD1 monotherapy as adjuvant therapy and determinants of treatment choice in stage III cutaneous melanoma in the US
Authors: Whitman Eric D. , Totev Todor I. , Jiang Shan , da Costa Wilson L. , Grebennik Dmitri , Wang Hongjue , Boca Andra-Ecaterina , Ayyagari Rajeev
Published: March 2024

Background

The objective of this study was to describe real-world adjuvant therapy (AT) use by disease substage and assess determinants of treatment choice among patients with stage III melanoma.

Methods

This non-interventional retrospective study included survey responses and data from patient records provided by US medical oncologists. Survey responses, patient demographic/clinical characteristics, treatment utilization, and reasons for treatment were reported descriptively. The association between patient and disease characteristics and AT selection was assessed using logistic and multinomial regression models, overall and stratified by AJCC8 substage (IIIA vs. IIIB/C/D) and type of AT received (anti-PD1 monotherapy, BRAF/MEK, no AT), respectively.

Results

In total 152 medical oncologists completed the survey and reviewed the charts of 507 patients (168 stage IIIA; 339 stages IIIB/IIIC/IIID); 405 (79.9%) patients received AT (360/405 (88.9%) received anti-PD1 therapy; 45/405 (11.1%) received BRAF/MEK therapy). Physicians reported clinical guidelines (61.2%), treatment efficacy (37.5%), and ECOG performance status (31.6%) as drivers of AT prescription. Patient-level data confirmed that improving patient outcomes (79%) was the main reason for anti-PD1 prescription; expected limited treatment benefit (37%), patient refusal (36%), and toxicity concerns (30%) were reasons for not prescribing AT. In multivariable analyses stage IIIB/IIIC/IIID disease significantly increased the probability of receiving AT (odds ratio [OR] 1.74) and anti-PD1 therapy (OR 1.82); ECOG 2/3 and Medicaid/no insurance decreased the probability of AT receipt (OR 0.37 and 0.42, respectively) and anti-PD1 therapy (OR 0.41 and 0.42, respectively) among all patients and patients with stage IIIA disease.

Conclusion

Most patients were given AT with a vast majority treated with an anti-PD1 therapy. Physician- and patient-level evidence confirmed the impact of disease substage on AT use, with stage IIIA patients, patients without adequate insurance coverage, and worse ECOG status having a lower probability of receiving AT.
Optimizing care for children with difficult-to-treat and severe asthma through specialist paediatric asthma centres: expert practical experience and advice
Authors: Pijnenburg M. W. , Rubak S. , Skjerven H. O. , Verhulst S. , Elenius V. , Hugen C. , Jauhola O. , Kempeneers C. , Melén E. , Reier Nilsen T. , Rutjes N. W. , Ruotsalainen M. , Schaballie H. , Zwitserloot A. M. , Proesmans M. , Mäkelä M. J.
Published: March 2024

Severe asthma in children carries an unacceptable treatment burden, yet its rarity means clinical experience in treating it is limited, even among specialists. Practical guidance is needed to support clinical decision-making to optimize treatment for children with this condition.

This modified Delphi convened 16 paediatric pulmonologists and allergologists from northern Europe, all experienced in treating children with severe asthma. Informed by interviews with stakeholders involved in the care of children with severe asthma (including paediatricians, nurses and carers), and an analysis of European guidelines, the experts built a consensus focused on the gaps in existing guidance. Explored were considerations for optimizing care for patients needing biologic treatment, and for selecting home or hospital delivery of biologics. This consensus is aimed at clinicians in specialist centres, as well as general paediatricians, paediatric allergologists and paediatric pulmonologists who refer children with the most severe asthma to specialist care. Consensus is based on expert opinion and is intended for use alongside published guidelines.

Our discussions revealed three key facets to optimizing care. Firstly, early asthma detection in children presenting with wheezing and/or dyspnoea is vital, with a low threshold for referral from primary to specialist care. Secondly, children who may need biologics should be referred to and managed by specialist paediatric asthma centres; we define principles for the specialist team members, tests, and expertise necessary at such centres, as well as guidance on when homecare biologics delivery is and is not appropriate. Thirdly, shared decision-making is essential at all stages of the patient’s journey: clear, concise treatment plans are vital for patient/carer self-management, and structured processes for transition from paediatric to adult services are valuable. The experts identified the potential for specialist paediatric asthma nurses to play a significant role in facilitating multidisciplinary working.

Through this project is agreed a framework of practical advice to optimize the care of children with severe asthma. We encourage clinicians and policymakers to implement this practical advice to enhance patient care.
The effect of the Yara smartphone application on anxiety, sleep quality, and suicidal thoughts in patients with major depressive disorder in Iran: a randomized controlled trial
Authors: Soltani Zeinab , Parizad Naser , Radfar Moloud , Alinejad Vahid , Arzanlo Mohammad , Haghighi Mahmonir
Published: March 2024

Background

Depression is one of the most common mental disorders that leads to anxiety, sleep disturbances, and suicidal thoughts. Due to the high cost of treatment and the reluctance of many patients to seek medical help, major depressive disorder (MDD) is becoming more prevalent. Therefore, alternative methods like smartphone applications can help prevent and improve depression symptoms. The present study aimed to determine the effect of the newly developed Yara smartphone application on anxiety, sleep quality, and suicidal thoughts in patients with MDD.

Methods

This randomized controlled trial with a pretest-posttest design was conducted on Iranian patients with MDD in 2022. Sixty-four patients were recruited using convenience sampling and randomly assigned to two control and intervention groups. The intervention was conducted using the Yara smartphone application for three months. Data were collected using the Spielberger State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), and Beck Scale for Suicidal Ideation (BSSI). Data were first entered into IBM SPSS Statistics for Windows, version 22 (IBM Corp., Armonk, N.Y., USA) and then analyzed using descriptive and analytical statistics.

Results

There was no statistically significant difference in the mean score of anxiety and sleep quality between the intervention and control groups before the intervention (p ≥ .05). However, this difference in the mean score of anxiety and sleep quality was statistically significant in the two groups after the intervention (p < .05). The results showed no statistically significant difference in the mean score of suicidal thoughts between the two groups before and after the intervention (p ≥ .05). The use of the Yara smartphone application had a significant positive effect on anxiety and sleep quality in depressed patients (p < .001). At the same time, it had no significant effect on suicidal thoughts (p ≥ .05).

Conclusion

Considering the positive effect of using the Yara smartphone application on reducing anxiety and improving sleep quality in depressed patients, this application can help alleviate the problems of depressed patients alongside existing treatment methods. Thus, this application is recommended for this group of patients in psychiatric clinics and departments. The Yara application's effectiveness was not approved on suicidal thoughts in this study so that further investigation would be necessary.

Trial Registration

Iranian Registry of Clinical Trial approval code (IRCT# IRCT20131112015390N7).
Psychometric analysis and linguistic adaptation of the Persian version of Contraceptive Self-Efficacy Scale (CSES-P)
Authors: Azari Nadereh , Mahmoodi Hassan , Mousavi Saeed , Mirghafourvand Mojgan , Keikhaee Razieh , Shaghaghi Abdolreza
Published: March 2024

Background

This study was aimed to test adaptability of the Contraceptive Self-Efficacy Scale (CSES) for use on Persian-speaking women of reproductive age.

Method

A preliminary draft of the Contraceptive Self Efficacy Scale (CSES) was prepared according to the standard translation/back translation procedures and an expert panel appraised its content and face validities. The approved draft was tested on 400 randomly selected women of reproductive age (15–49 years) at the 29th Bahman Hospital of in Tabriz, the capital city of East Azerbaijan province, North West of Iran from May to August 2018. The exploratory and confirmatory factor analysis (EFA, CFA) was carried out to verify the implicit factor structure of the CSES for use on Persian-speaking women of fertile age. The Cronbach’s α and Interclass Correlation coefficients were estimated for internal consistency and accuracy assessment of the instrument.

Results

This translated scale indicated good internal consistency (0.9) and reliability (0.9). A four-factor solution best fitted the study data and the estimated fit indices were in the acceptable range (chi square/ degree of freedom = 2.956, the Root Mean Square Error of Approximation = 0.070, Confirmatory Fit Index = 0.667, The Tucker-Lewis Index = 0.599).

Conclusion

The CSES-P can be considered as a potentially valid and reliable tool to assess contraceptive self-efficacy among Persian-speaking women. The CSES-P is a general instrument to measure overall contraceptive self-efficacy of the Iranian reproductive age women and it would also be fascinating to work on method specific self-efficacy tools in future.
Efficient hip joint distraction using the AO large femoral distractor in treating acetabular fractures associated with marginal impaction and intraarticular incarcerated fragments
Authors: Badran Mahmoud , Khalifa Ahmed A. , Fergany Ali , Ibrahim Bahaaeldin , Moustafa Mohamed , Adem Ephrem , Gilyen Botond , Farouk Osama
Published: March 2024

Purpose

The results after acetabular fracture are primarily related to the quality of articular reduction. Using the AO large femoral distractor, incarcerated fragments can be easily removed, and marginally impacted fragments can be elevated under direct visualization without further re-dislocating the joint. The current study aimed to evaluate our early results of using the AO large femoral distractor as an assisting tool during ORIF of acetabular fractures associated with marginal impaction or intraarticular incarcerated fragments.

Methods

Eighteen patients were included in this retrospective case series study diagnosed with an acetabular fracture associated with either marginal impaction injury or an intraarticular incarcerated fragment. On a usual operative table, all patients were operated upon in a prone position through the Kocher Langenbeck approach. The AO large femoral distractor was used to facilitate hip joint distraction. Postoperative fracture reduction and joint clearance were assessed in the immediate postoperative CT scans.

Results

The average age of the patients was 30 ± 8.2 years; 13 (72.2%) were males. All cases had a posterior wall fracture, and it was associated with transverse fractures, posterior column fractures, and T-type fractures in five (27.8%), two (11.1%), and one (5.6%) patients, respectively. Intraarticular incarcerated fragments were present in 13 (72.2%) cases and marginal impaction in five (27.8%). Fracture reduction measured on the postoperative CT scans showed an anatomical reduction in 14 (77.8%) patients, imperfect in four (22.2%), and complete clearance of the hip joint of any incarcerated fragments.

Conclusion

The use of the AO large femoral distractor is a reliable and reproducible technique that can be applied to assist in the removal of incarcerated intraarticular fragments and to ease the reduction of marginally impacted injuries associated with acetabular fractures.
Radiation safety compliance awareness among healthcare workers exposed to ionizing radiation
Authors: Allam Shaimaa Mohamed Elghareeb , Algany Mohamed Mustafa Abd , Khider Yasmin Ibrahim Abdelkader
Published: March 2024

Background

In recent years, there has been a marked growth in the use of ionizing radiation in medical imaging for both diagnosis and therapy, which in turn has led to increased radiation exposure among healthcare workers.

Aim

The purpose of this study was to assess the level of safety compliance awareness among healthcare workers exposed to ionizing radiation.

Research design

A descriptive cross-sectional design was used for this investigation.

Setting

This study was conducted online, using social media sites such as WhatsApp, Instagram, and Facebook.

Subjects

A purposive sample of 384 Egyptian healthcare workers was enrolled in the current study.

Tool

A safety compliance awareness questionnaire was used in this study to collect pertinent data.

Results

The result of this study showed that 65.4% and 64.1% of the studied sample chose the correct answers that mammography and CT scans involve the use of x-rays. However, 64.3% and 67.2% of the studied sample chose the wrong answers, saying that MRI and Ultrasound involve the use of X-rays. Moreover, 47.14%, 43.5%, and 57% of the studied sample never used a dosimeter, did not follow dosimeter controls, and did not wear a lead collar.

Conclusion

Most of the healthcare workers studied had poor knowledge about radiation exposure safety. Moreover, most of the healthcare workers in the current study demonstrated inadequate practice compliance concerning radiation protection procedures.

Recommendation

Should encourage hospital training programs to include radiation safety topics in their training plans for healthcare workers.
Global job satisfaction and fluctuation among community general practitioners: a systematic review and meta-analysis
Authors: Deng Qilin , Liu Yifang , Cheng Ziyi , Wang Qi , Liu Junan
Published: March 2024

Introduction

Community General Practitioners (CGPs) are crucial to primary healthcare worldwide. Their job satisfaction significantly impacts the quality and accessibility of healthcare. However, a comprehensive global perspective on this issue remains absent, necessitating this systematic review and meta-analysis.

Methods

This systematic review and meta-analysis sourced literature from PubMed, Web of Science, CNKI, and Wanfang, up to June 14, 2023. Of the 2,742 identified studies, 100 articles were selected for meta-analysis to assess satisfaction levels, and 97 studies were chosen for comparative analysis of influential factors. We employed both meta-analytic and comparative analytic methodologies, focusing on varying geographical, economic, and temporal contexts.

Results

The pooled rate and corresponding 95% confidence interval (CI) for job satisfaction among CGPs was 70.82% (95%CI: 66.62–75.02%) globally. Studies utilizing 5-point score scale obtained a random effect size of 3.52 (95%CI: 3.43–3.61). Diverse factors influenced satisfaction, with remuneration and working conditions being predominant. A noticeable decline in job satisfaction has been observed since the coronavirus disease 2019 outbreak, with satisfaction rates dropping from an average of 72.39% before 2009 to 63.09% in those published after 2020.

Conclusions

The downward trend in CGPs’ job satisfaction is concerning and warrants urgent attention from policymakers, especially in regions with an acute shortage of CGPs. The findings from this comprehensive review and meta-analysis provide essential insights for informed healthcare policy-making. It highlights the urgency of implementing strategies to enhance CGP satisfaction, thereby improving the effectiveness of primary healthcare systems globally.
Exploring healthcare provider retention in a rural and frontier community in Northern Idaho
Authors: Moore Jonathan D. , Lords Allie M. , Casanova Madeline P. , Reeves Ashley J. , Lima Ann , Wilkinson Cody , Deming Sarah M. , Baker Russell T.
Published: March 2024

Background

A shortage of healthcare providers, particularly in primary care and mental health, exists in the predominately rural state of Idaho. There are also barriers to retaining healthcare providers to work in rural and remote communities. Limited research using U.S. samples has explored factors that may affect the retention of healthcare providers in rural areas. Additionally, due to differences between communities, it is important to conduct community-level investigations to better understand how these factors may affect retention in rural areas. Therefore, the purpose of this study was to explore factors affecting healthcare provider retention in a rural community in Northern Idaho.

Methods

A modified version of the Nursing Community Apgar Questionnaire (NCAQ) was completed by 30 healthcare providers in a rural and frontier community in Northern Idaho to assess factors influencing healthcare provider retention. Factors were classified into classes including geographic, economic, scope of practice, medical support, and facility and community support classes. Retention factors were assessed on their perceived importance to retention as well as whether they were perceived as an advantage or challenge to retention based on Likert scales. A “Community Apgar” score was also created by combining the importance and advantage/challenge factors.

Results

Overall, items in the medical support group had the highest importance of any other class and included factors such as nursing workforce. Additionally, the facility and community support class, which included factors such as televideo support, was rated the highest advantage class and had the highest Apgar score, indicating it contained the factor that healthcare providers identified as the most important advantage (i.e., medical reference resources).

Conclusion

Our study identified multiple factors that healthcare providers deemed as important advantages or disadvantages to retaining healthcare providers in rural areas. Overall, facility and community support factors were found to have the highest advantage in the retention of rural providers. Rural healthcare organizations looking to increase healthcare provider retention should target retention efforts towards these factors. Additional research should also be conducted on other rural samples across the U.S. to make comparisons of findings.
Association of TRAIL receptor with phosphatase SHP-1 enables repressing T cell receptor signaling and T cell activation through inactivating Lck
Authors: Chyuan I-Tsu , Liao Hsiu-Jung , Tan Tse-Hua , Chuang Huai-Chia , Chu Yu-Chuan , Pan Meng-Hsun , Wu Chien-Sheng , Chu Ching-Liang , Sheu Bor-Ching , Hsu Ping-Ning
Published: March 2024

Background

T cell receptor (TCR) signaling and T cell activation are tightly regulated by gatekeepers to maintain immune tolerance and avoid autoimmunity. The TRAIL receptor (TRAIL-R) is a TNF-family death receptor that transduces apoptotic signals to induce cell death. Recent studies have indicated that TRAIL-R regulates T cell-mediated immune responses by directly inhibiting T cell activation without inducing apoptosis; however, the distinct signaling pathway that regulates T cell activation remains unclear. In this study, we screened for intracellular TRAIL-R-binding proteins within T cells to explore the novel signaling pathway transduced by TRAIL-R that directly inhibits T cell activation.

Methods

Whole-transcriptome RNA sequencing was used to identify gene expression signatures associated with TRAIL-R signaling during T cell activation. High-throughput screening with mass spectrometry was used to identify the novel TRAIL-R binding proteins within T cells. Co-immunoprecipitation, lipid raft isolation, and confocal microscopic analyses were conducted to verify the association between TRAIL-R and the identified binding proteins within T cells.

Results

TRAIL engagement downregulated gene signatures in TCR signaling pathways and profoundly suppressed phosphorylation of TCR proximal tyrosine kinases without inducing cell death. The tyrosine phosphatase SHP-1 was identified as the major TRAIL-R binding protein within T cells, using high throughput mass spectrometry-based proteomics analysis. Furthermore, Lck was co-immunoprecipitated with the TRAIL-R/SHP-1 complex in the activated T cells. TRAIL engagement profoundly inhibited phosphorylation of Lck (Y394) and suppressed the recruitment of Lck into lipid rafts in the activated T cells, leading to the interruption of proximal TCR signaling and subsequent T cell activation.

Conclusions

TRAIL-R associates with phosphatase SHP-1 and transduces a unique and distinct immune gatekeeper signal to repress TCR signaling and T cell activation via inactivating Lck. Thus, our results define TRAIL-R as a new class of immune checkpoint receptors for restraining T cell activation, and TRAIL-R/SHP-1 axis can serve as a potential therapeutic target for immune-mediated diseases.
Regulation mechanism and bioactivity characteristic of surfactin homologues with C14 and C15 fatty acid chains
Authors: Su Yumeng , Gao Ling , Li Chenyu , Wang Liang , Zhou Huimin , Zhang Chenhao , Xia Xiaole
Published: March 2024

Background

Surfactin, a green lipopeptide bio-surfactant, exhibits excellent surface, hemolytic, antibacterial, and emulsifying activities. However, a lack of clear understanding of the synthesis regulation mechanism of surfactin homologue components has hindered the customized production of surfactin products with different biological activities.

Results

In this study, exogenous valine and 2-methylbutyric acid supplementation significantly facilitated the production of C14–C15 surfactin proportions (up to 75% or more), with a positive correlation between the homologue proportion and fortified concentration. Subsequently, the branched-chain amino acid degradation pathway and the glutamate synthesis pathway are identified as critical pathways in regulating C14–C15 surfactin synthesis by transcriptome analysis. Overexpression of genes bkdAB and glnA resulted in a 1.4-fold and 1.3-fold increase in C14 surfactin, respectively. Finally, the C14-rich surfactin was observed to significantly enhance emulsification activity, achieving an EI24 exceeding 60% against hexadecane, while simultaneously reducing hemolytic activity. Conversely, the C15-rich surfactin demonstrated an increase in both hemolytic and antibacterial activities.

Conclusion

This study presents the first evidence of a potential connection between surfactin homologue synthesis and the conversion of glutamate and glutamine, providing a theoretical basis for targeting the synthesis regulation and structure–activity relationships of surfactin and other lipopeptide compounds.

Graphical Abstract
Implementation of post-discharge malaria chemoprevention (PDMC) in Benin, Kenya, Malawi, and Uganda: stakeholder engagement meeting report
Authors: Hill Jenny ,   PDMC Saves Lives Consortium, Accrombessi Manfred , Briand Valérie , Dhabangi Aggrey , Hill Jenny , Hoyt Jenna , Idro Richard , Khairallah Carole , Kariuki Simon , ter Kuile Feiko O. , Kwambai Titus , Luty Adrian J. F. , Manda-Taylor Lucinda , Massougbodji Achille , Otieno Juliet , Phiri Kamija S. , Rosu Laura , Rujumba Joseph , Seddon Tracy , Tangara Brian , Vincent Jeanne Perpétue , Worrall Eve
Published: March 2024

A Stakeholder engagement meeting on the implementation of post-discharge malaria chemoprevention (PDMC) in Benin, Kenya, Malawi, and Uganda was held in Nairobi, Kenya, on 27 September 2023. Representatives from the respective National Malaria Control Programmes, the World Health Organization (WHO) Geneva, Africa Regional and Kenya offices, research partners, non-governmental organizations, and the Medicines for Malaria Venture participated. PDMC was recommended by the WHO in June 2022 and involves provision of a full anti-malarial treatment course at regular intervals during the post-discharge period in children hospitalized with severe anaemia in areas of moderate-to-high malaria transmission. The WHO recommendation followed evidence from a meta-analysis of three clinical trials and from acceptability, delivery, cost-effectiveness, and modelling studies. The trials were conducted in The Gambia using monthly sulfadoxine-pyrimethamine during the transmission season, in Malawi using monthly artemether-lumefantrine, and in Kenya and Uganda using monthly dihydroartemisinin-piperaquine, showing a significant reduction in all-cause mortality by 77% (95% CI 30–98) and a 55% (95% CI 44–64) reduction in all-cause hospital readmissions 6 months post-discharge. The recommendation has not yet been implemented in sub-Saharan Africa. There is no established platform for PDMC delivery. The objectives of the meeting were for the participating countries to share country contexts, plans and experiences regarding the adoption and implementation of PDMC and to explore potential delivery platforms in each setting. The meeting served as the beginning of stakeholder engagement within the PDMC Saves Lives project and will be followed by formative and implementation research to evaluate alternative delivery strategies in selected countries. Meeting highlights included country consensus on use of dihydroartemisinin-piperaquine for PDMC and expansion of the target group to "severe anaemia or severe malaria", in addition to identifying country-specific options for PDMC delivery for evaluation in implementation research. Further exploration is needed on whether the age group should be extended to school-age children.
The serum soluble ASGR1 concentration is elevated in patients with coronary artery disease and is associated with inflammatory markers
Authors: Luo Qin , Chen Jingfei , Yi Yanfeng , Wu Panyun , Su Yingjie , Chen Zhangling , Aydemir Hacı Ahmet , Tang Jianjun , Fang Zhenfei , Luo Fei
Published: March 2024

Background and aims

Current research has suggested that asialoglycoprotein receptor 1 (ASGR1) is involved in cholesterol metabolism and is also related to systemic inflammation. This study aimed to assess the correlation between the serum soluble ASGR1 (sASGR1) concentration and inflammatory marker levels. Moreover, the second objective of the study was to assess the association between sASGR1 levels and the presence of coronary artery disease (CAD).

Methods

The study subjects included 160 patients who underwent coronary angiography. Ninety patients were diagnosed with CAD, while seventy age- and sex-matched non-CAD patients served as controls. We measured the serum sASGR1 levels using an ELISA kit after collecting clinical baseline characteristics.

Results

Patients with CAD had higher serum sASGR1 levels than non-CAD patients did (P < 0.0001). sASGR1 was independently correlated with the risk of CAD after adjusting for confounding variables (OR = 1.522, P = 0.012). The receiver operating characteristic (ROC) curve showed that sASGR1 had a larger area under the curve (AUC) than did the conventional biomarkers apolipoprotein B (APO-B) and low-density lipoprotein cholesterol (LDL-C). In addition, multivariate linear regression models revealed that sASGR1 is independently and positively correlated with high-sensitivity C-reactive protein (CRP) (β = 0.86, P < 0.001) and WBC (β = 0.13, P = 0.004) counts even after adjusting for lipid parameters. According to our subgroup analysis, this relationship existed only for CAD patients.

Conclusion

Our research demonstrated the link between CAD and sASGR1 levels, suggesting that sASGR1 may be an independent risk factor for CAD. In addition, this study provides a reference for revealing the potential role of sASGR1 in the inflammation of atherosclerosis.
Opportunities for cancer prevention at syringe services programs: acceptability of HPV self-sampling and vaccination among people who inject drugs
Authors: Hinkes Samuel , Ciraldo Katrina , Kobetz Erin , Bartholomew Tyler S. , Rinehart Sarah , Siringo Nicolette , Barnett Rebecca , Godbole Neha , Jeanty Frantzia , Frederick Morgan , Tookes Hansel E.
Published: March 2024

Introduction

Despite having a high risk of acquiring sexually transmitted infections, people who inject drugs (PWID) often do not receive recommended HPV screenings due to barriers to healthcare. Guideline-based cervical HPV screening and vaccination can prevent cervical cancer. Low-cost, low-barrier methods for cancer screening and prevention are important for vulnerable communities such as PWID.

Methods

We examined acceptability of HPV self-sampling at a syringe services program (SSP). Participants with a cervix (n = 49) participated in patient education followed by a survey to assess willingness to perform HPV self-sampling versus standard of care.

Results

59% found self-sampling to be acceptable, citing privacy, ease, and quickness. Among those opting for HPV screening delivered by a provider (n = 16), participants cited concerns about adequate sampling (81%) and test accuracy (75%). Notably, only 18% of participants reported complete HPV vaccination.

Conclusion

Cervical HPV self-sampling was acceptable to PWID. SSP-based efforts to provide preventative health services could place tools for cancer screening into the hands of PWID, a need-to-reach community.
Prophylaxis with enoxaparin and antithrombin III in drug-induced coagulation alterations in childhood leukemia: a retrospective experience of 20 years
Authors: Salvador Christina , Salvador Robert , Kropshofer Gabriele , Meister Bernhard , Rock Marie , Obexer Petra , Hetzer Benjamin , Rabensteiner Evelyn , Crazzolara Roman
Published: March 2024

Background

Thromboembolic complications are well known in the treatment of childhood acute lymphoblastic leukemia. Over the years it has not been possible to reach a consensus on a possible prophylaxis of thromboembolic events during intensive therapy. Only the administration of enoxaparin was able to achieve evidence in the literature to date.

Methods

In this retrospective study, 173 childhood leukemia patients were treated over 20 years with a thromboembolic prophylaxis including enoxaparin and AT III during induction therapy with L-asparaginase and cortisone.

Results

We here report the effectiveness of administration of enoxaparin and AT III in childhood leukemia, showing a strikingly low prevalence of deep vein thrombosis (2.9%). Especially in adolescent patients, a particularly great need for AT III was demonstrated.

Conclusions

We recommend thromboembolic prophylaxis with enoxaparin and AT III substitution during induction/reinduction therapy with L-asparaginase and glucocorticosteroids, especially from adolescence onwards.
Rolapitant treats lung cancer by targeting deubiquitinase OTUD3
Authors: Du Tongde , Gu Quan , Zhang Yonghui , Gan Yujie , Liang Rongrui , Yang Wenzhu , Lu Ya , Xu Chenxin , Wu Jianzhong , Ma Rong , Cao Haixia , Jiang Jingwei , Wang Juan , Feng Jifeng
Published: March 2024

Background

Lung cancer is cancer with the highest morbidity and mortality in the world and poses a serious threat to human health. Therefore, discovering new treatments is urgently needed to improve lung cancer prognosis. Small molecule inhibitors targeting the ubiquitin-proteasome system have achieved great success, in which deubiquitinase inhibitors have broad clinical applications. The deubiquitylase OTUD3 was reported to promote lung tumorigenesis by stabilizing oncoprotein GRP78, implying that inhibition of OTUD3 may be a therapeutic strategy for lung cancer.

Results

In this study, we identified a small molecule inhibitor of OTUD3, Rolapitant, by computer-aided virtual screening and biological experimental verification from FDA-approved drugs library. Rolapitant inhibited the proliferation of lung cancer cells by inhibiting deubiquitinating activity of OTUD3. Quantitative proteomic profiling indicated that Rolapitant significantly upregulated the expression of death receptor 5 (DR5). Rolapitant also promoted lung cancer cell apoptosis through upregulating cell surface expression of DR5 and enhanced TRAIL-induced apoptosis. Mechanistically, Rolapitant directly targeted the OTUD3-GRP78 axis to trigger endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-DR5 signaling, sensitizing lung cancer cells to TRAIL-induced apoptosis. In the vivo assays, Rolapitant suppressed the growth of lung cancer xenografts in immunocompromised mice at suitable dosages without apparent toxicity.

Conclusion

In summary, the present study identifies Rolapitant as a novel inhibitor of deubiquitinase OTUD3 and establishes that the OTUD3-GRP78 axis is a potential therapeutic target for lung cancer.
Osteofibrous dysplasia: a narrative review
Authors: Liu Rui , Tong Linjian , Wu Haiyang , Guo Qiang , Xu Lixia , Sun Zhiming , Yan Hua
Published: March 2024

Osteofibrous dysplasia (OFD) is a rare, benign, self-limited bone disorder with a relatively low incidence, accounting for approximately 0.2% of all primary bone tumors. It was frequently found intra-cortical of the mid-shaft of the tibia. OFD can also occur in other skeletal regions, including the fibula, ulna, radius, femur, humerus, ischium, rib, tarsus, metatarsals, vertebral, and capitate. OFD can present with asymptomatic, mass, pain, swelling, deformity, and even pathological fracture. OFD might be misdiagnosed as adamantinoma (AD) and because they are three subtypes origin from the same family of bone tumors and have similar imaging features. Moreover, pathology could provide evidence for an accurate diagnosis of OFD, but misdiagnosis may occur due to small sampling materials. To date, few studies have comprehensively introduced the epidemiology, clinical manifestations, pathogenesis, radiological features, pathology, and treatment for OFD. We herein discuss clinical signs, diagnosis methods, and treatment options of OFD to improve the understanding of OFD, which is helpful for accurate diagnosis and appropriate treatment.
Deep learning in cancer genomics and histopathology
Authors: Unger Michaela , Kather Jakob Nikolas
Published: March 2024

Histopathology and genomic profiling are cornerstones of precision oncology and are routinely obtained for patients with cancer. Traditionally, histopathology slides are manually reviewed by highly trained pathologists. Genomic data, on the other hand, is evaluated by engineered computational pipelines. In both applications, the advent of modern artificial intelligence methods, specifically machine learning (ML) and deep learning (DL), have opened up a fundamentally new way of extracting actionable insights from raw data, which could augment and potentially replace some aspects of traditional evaluation workflows. In this review, we summarize current and emerging applications of DL in histopathology and genomics, including basic diagnostic as well as advanced prognostic tasks. Based on a growing body of evidence, we suggest that DL could be the groundwork for a new kind of workflow in oncology and cancer research. However, we also point out that DL models can have biases and other flaws that users in healthcare and research need to know about, and we propose ways to address them.
Peptidoglycan in osteoarthritis synovial tissue is associated with joint inflammation
Authors: Holub Meaghan N , Wahhab Amanda , Rouse Joseph R , Danner Rebecca , Hackner Lauren G , Duris Christine B , McClune Mecaila E , Dressler Jules M , Strle Klemen , Jutras Brandon L , Edelstein Adam I , Lochhead Robert B
Published: March 2024

Objectives

Peptidoglycan (PG) is an arthritogenic bacterial cell wall component whose role in human osteoarthritis is poorly understood. The purpose of this study was to determine if PG is present in synovial tissue of osteoarthritis patients at the time of primary total knee arthroplasty (TKA), and if its presence is associated with inflammation and patient reported outcomes.

Methods

Intraoperative synovial tissue and synovial fluid samples were obtained from 56 patients undergoing primary TKA, none of whom had history of infection. PG in synovial tissue was detected by immunohistochemistry (IHC) and immunofluorescence microscopy (IFM). Synovial tissue inflammation and fibrosis were assessed by histopathology and synovial fluid cytokine quantification. Primary human fibroblasts isolated from arthritis synovial tissue were stimulated with PG to determine inflammatory cytokine response.

Results

A total of 33/56 (59%) of primary TKA synovial tissue samples were positive for PG by IHC, and PG staining colocalized with markers of synovial macrophages and fibroblasts by IFM. Synovial tissue inflammation and elevated IL-6 in synovial fluid positively correlated with PG positivity. Primary human fibroblasts stimulated with PG secreted high levels of IL-6, consistent with ex vivo findings. Interestingly, we observed a significant inverse correlation between PG and age at time of TKA, indicating younger age at time of TKA was associated with higher PG levels.

Conclusion

Peptidoglycan is commonly found in synovial tissue from patients undergoing TKA. Our data indicate that PG may play an important role in inflammatory synovitis, particularly in patients who undergo TKA at a relatively younger age.
Utility of the Venous Excess Ultrasound (VEXUS) score to track dynamic change in volume status in patients undergoing fluid removal during haemodialysis – the ACUVEX study
Authors: Wong Adrian , Olusanya Olusegun , Watchorn Jim , Bramham Kate , Hutchings Sam
Published: March 2024

Background

The use of ultrasound assessment, including the Venous Excess Ultrasound (VEXUS) score, is increasingly being utilised as part of fluid status assessment in clinical practice. We aimed to evaluate the ability of the VEXUS score to track fluid removal during the course of the dialysis session and explore the relationship between traditional measures of fluid status and venous congestion.

Methods

Single-centre, observational study in patients undergoing intermittent haemodialysis, who presented above their target dry weight. Patients had serial assessment using VEXUS, lung ultrasound and selected echocardiographic measures, before, during and after fluid removal.

Results

Amongst 33 patients analysed, 5 (15%) had an elevated VEXUS score (> 0). There was no difference in starting weight, dry weight or amount of fluid removed in patients with a normal VEXUS score and those with an elevated VEXUS score. In all patients with elevated VEXUS scores, the degree of venous congestion improved during the course of fluid removal. All patients with an elevated VEXUS score had evidence of both right and left ventricular systolic impairment.

Conclusion

In patients with ESRF undergoing haemodialysis, the incidence of venous congestion as measured by the VEXUS is low. In patients with elevated VEXUS scores, removal of fluid through haemodialysis improves the venous congestion score. The pattern of LV and RV systolic dysfunction suggests that VEXUS may be a reflection of cardiac failure rather than venous volume status.

Trial registration

Ethical approval was provided by South Central-Berkshire Research and Ethics Committee and registered on clinicaltrials.org (IRAS305720). Trial registration: ISRCTN14351189 – Retrospectively registered on 30/11/2023.
Elevated tryptase level in a child with idiopathic anaphylaxis: a case of hereditary alpha-tryptasemia
Authors: Le Blanc Vicky , Watson Wade T. A.
Published: March 2024

Hereditary alpha-tryptasemia (HαT) is an autosomal dominant disorder estimated to affect 5% of the population. High baseline tryptase level is a consistent finding, but there is a great variability of clinic manifestations, including no symptoms at all. We describe a case of HαT in a 5 years 8 months old girl manifesting with idiopathic anaphylaxis and elevated baseline tryptase level. As more cases of HαT are described, a better understanding of the clinical phenotype will be acquired.
The paradox of MRI for breast cancer screening: high-risk and dense breasts—available evidence and current practice
Authors: Sardanelli Francesco , Magni Veronica , Rossini Gabriele , Kilburn-Toppin Fleur , Healy Nuala A. , Gilbert Fiona J.
Published: March 2024

In the mid-1990s, the identification of BRCA1/2 genes for breast cancer susceptibility led to testing breast MRI accuracy in screening women at increased risk. From 2000 onwards, ten intraindividual comparative studies showed the marked superiority of MRI: the sensitivity ranged 25−58% for mammography, 33−52% for ultrasound, 48−67% for mammography plus ultrasound, and 71−100% for MRI; specificity 93–100%, 91–98%, 89–98%, and 81–98%, respectively. Based on the available evidence, in 2006–2007, the UK National Institute for Clinical Excellence and the American Cancer Society recommended MRI screening of high-risk women, followed by other international guidelines. Despite evidence-based medicine ideally requiring randomised controlled trials (RCTs) for policy changes regarding screening procedures, breast MRI for high-risk screening was adopted in many countries worldwide. In 2019, the results of the “DENSE” RCT were published in favour of breast MRI screening of women with extremely dense breasts compared to mammography alone, showing a reduction of more than 80% of the interval cancer rate in women who attended MRI screening. Even though international recommendations in favour of this practice were issued, substantial obstacles still prevent health systems from adopting breast MRI for screening women with extremely dense breasts. A paradox is evident: we adopted a screening procedure without evidence from RCTs, and now that we have this level-1 evidence for the same procedure, we fail to do so. This critical review tries to explain the differences between the two cases, as examples of the complex pathways of translating radiological research into everyday practice.

Critical relevance statement The high-level evidence in favour of breast MRI screening of women with extremely dense breasts is failing to persuade policy makers to translate this into clinical practice.

Key points

• Breast MRI screening of high-risk women was adopted on basis of the evidence provided by test accuracy comparative studies showing an MRI performance greatly superior to that of mammography.

• Breast MRI screening of women with extremely dense breasts has not been adopted although the evidence of a large reduction in interval cancer rate from a RCT.

• We illustrate the differences between the two cases, as an example of the complex ways of translation of radiological research in clinical practice according to the EBM theory.

Graphical Abstract
Adipose-derived stem cell-based optimization strategies for musculoskeletal regeneration: recent advances and perspectives
Authors: Yuan Chenrui , Song Wei , Jiang Xiping , Wang Yifei , Li Chenkai , Yu Weilin , He Yaohua
Published: March 2024

Musculoskeletal disorders are the leading causes of physical disabilities worldwide. The poor self-repair capacity of musculoskeletal tissues and the absence of effective therapies have driven the development of novel bioengineering-based therapeutic approaches. Adipose-derived stem cell (ADSC)-based therapies are being explored as new regenerative strategies for the repair and regeneration of bone, cartilage, and tendon owing to the accessibility, multipotency, and active paracrine activity of ADSCs. In this review, recent advances in ADSCs and their optimization strategies, including ADSC-derived exosomes (ADSC-Exos), biomaterials, and genetic modifications, are summarized. Furthermore, the preclinical and clinical applications of ADSCs and ADSC-Exos, either alone or in combination with growth factors or biomaterials or in genetically modified forms, for bone, cartilage, and tendon regeneration are reviewed. ADSC-based optimization strategies hold promise for the management of multiple types of musculoskeletal injuries. The timely summary and highlights provided here could offer guidance for further investigations to accelerate the development and clinical application of ADSC-based therapies in musculoskeletal regeneration.

Graphical abstract