bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of occlusal canting identifying tool: verification, reliability and validation assessment
Authors: Alhuwaish Hessah A. , Almoammar Khalid A. , Fakhouri Abdulaziz S.
Published: January 2024

Introduction

Occlusal cant (OC) is a malocclusion trait that lacks accurate clinical assessment methods. The occlusal canting identifying tool (OCIT) was invented and patented as a clinical tool to accurately identify and quantify the degree of maxillary OC. This study aimed to 1) develop a prototype of the OCIT, 2) verify the functionality of the OCIT and 3) assess the validity and reliability of the OCIT.

Materials and methods

A patented OCIT design was revised, and the dimensions were finalized, followed by a three-dimensional conceptual prototype design that was reviewed and approved by the inventors. Verification was performed using a digital angle gauge to determine the accuracy of the bubble level as well as the angle between the bite plate and the protractor. For laboratory validation, 40 orthodontists measured the simulated OC at (0°, 2°, 4°, 6° and 8°) on five phantom heads using the OCIT. A reliability assessment of the tool was performed in three occasions by one orthodontist using the same laboratory settings.

Results

The OCIT was prototyped from a medical-grade stainless steel alloy (316 L). Verification assessment revealed that the accuracy error of the bubble level (0.316° ± 0.028°) was statistically significant but clinically insignificant, while that of the angle between the bite plate and protractor (0.100° ± 0.050°) was statistically insignificant. Validation assessment showed high validity of the OCIT with no statistically significant difference between the OCIT and the reference values, having more errors in identifying smaller OC degrees compared to larger OC degrees. The intraclass correlation coefficient indicated the high reliability of the OCIT.

Conclusion

The OCIT was verified and proven to be a valid and reliable clinical tool that accurately evaluates the degree of OC.
Exploring the alignment between paramedicine's professional capabilities and competency frameworks for current and evolving scopes of practice: a literature review
Authors: Weber Anthony , Devenish Scott , Lam Louisa
Published: January 2024

Background

To adequately prepare graduates for the dynamic demands of paramedic practice, adopting a contemporary educational approach is essential. This involves collaborating to identify crucial competencies through input from industry stakeholders, experienced practitioners, and discipline-specific experts. Accreditation assumes a central role within this framework, serving as a cornerstone to ensure that paramedicine curricula align with paramedics' diverse and evolving professional roles.

Methods

A narrative review of the literature and a directed search of grey literature were performed to identify specific developments in paramedicine competencies and scope of practice and mapped to the professional capabilities published by the Paramedicine Board of Australia. In determining a competency map and accreditation’s role in a competency framework specific to current and evolving paramedic practice, key documents were analysed using a qualitative approach based on content analysis to identify common traits among documents, countries and other professions.

Results

The review process identified 278 themes that were further allocated to 22 major analytical groupings. These groupings could further be mapped to previously reported cognitive, technical, integrative, context, relationship, affective/moral competencies and habits of mind. At the same time, the highest-rated groupings were key competencies of intellectual skills, safety, accountability, clinical decision-making, professionalism, communications, team-based approach and situational awareness. Two groups were represented in the literature but not in the professional capabilities, namely Health and Social continuum and self-directed practice.

Conclusions

This review highlights the importance of measuring and validating the professional capabilities of Paramedicine Practitioners. The study explores various metrics and competency frameworks used to assess competency, comparing them against national accreditation schemes' professional capability standards. The findings suggest that accreditation frameworks play a crucial role in improving the quality of paramedicine practice, encompassing intellectual skills, safety, accountability, clinical decision-making, professionalism, communication, teamwork, and situational awareness.
Job preferences of master of public health students in China: a discrete choice experiment
Authors: Luo Nansheng , Bai Ru , Sun Yu , Li Xueying , Liu Libing , Xu Xin , Liu Li
Published: January 2024

Background

The shortage of public health personnel and the uneven distribution between urban and rural areas are thorny issues in China. Master of public health (MPH) is an integral part of public health human resources in the future, and it is of far-reaching significance to discuss their work preferences. The present study wants to investigate the job preference of MPH, understand the relative importance of different job attributes, and then put forward targeted incentive measures.

Methods

Discrete choice experiment (DCE) was used to evaluate the job preference of MPHs in two medical colleges in Liaoning Province. Attributes include employment location, bianzhi, working environment, career development prospects, work value and monthly income. Thirty-six choice sets were developed using a fractional factorial design. Mixed logit models were used to analysis the DCE data.

Results

The final sample comprised 327 MPHs. All the attributes and levels included in the study are statistically significant. Monthly income is the most important factor for MPHs. For non-economic factors, they value career development prospects most, followed by the employment location. Respondents’ preferences are heterogeneous and influenced by individual characteristics. Subgroup analysis showed that respondents from different family backgrounds have different job preferences. Policy simulation suggested that respondents were most sensitive to a salary increase, and the combination of several non-economic factors can also achieve the same effect.

Conclusions

Economic factors and non-economic factors significantly affect the job preference of MPHs. To alleviate the shortage and uneven distribution of public health personnel, more effective policy intervention should comprehensively consider the incentive measures of the work itself and pay attention to the individual characteristics and family backgrounds of the target object.
Predatory publishing in medical education: a rapid scoping review
Authors: Tomlinson Owen W
Published: January 2024

Background

Academic publishing is a cornerstone of scholarly communications, yet is unfortunately open to abuse, having given rise to ‘predatory publishers’– groups that employ aggressive marketing tactics, are deficient in methods and ethics, and bypass peer review. Preventing these predatory publishers from infiltrating scholarly activity is of high importance, and students must be trained in this area to increase awareness and reduce use. The scope of this issue in the context of medical students remains unknown, and therefore this sought to examine the breadth of the current literature base.

Methods

A rapid scoping review was undertaken, adhering to adapted PRISMA guidelines. Six databases (ASSIA, EBSCO, Ovid, PubMed, Scopus, Web of Science) were systematically searched for content related to predatory publishing and medical students. Results were single-screened, facilitated by online reviewing software. Resultant data were narratively described, with common themes identified.

Results

After searching and screening, five studies were included, representing a total of 1338 students. Two predominant themes– understanding, and utilisation– of predatory publishers was identified. These themes revealed that medical students were broadly unaware of the issue of predatory publishing, and that a small number have already, or would consider, using their services.

Conclusion

There remains a lack of understanding of the threat that predatory publishers pose amongst medical students. Future research and education in this domain will be required to focus on informing medical students on the issue, and the implication of engaging with predatory publishers.
Challenges and promising solutions to engaging patients in healthcare implementation in the United States: an environmental scan
Authors: Woodward Eva N. , Castillo Andrea Isabel Melgar , True Gala , Willging Cathleen , Kirchner JoAnn E.
Published: January 2024

Background

One practice in healthcare implementation is patient engagement in quality improvement and systems redesign. Implementers in healthcare systems include clinical leadership, middle managers, quality improvement personnel, and others facilitating changes or adoption of new interventions. Patients provide input into different aspects of health research. However, there is little attention to involve patients in implementing interventions, especially in the United States (U.S.), and this might be essential to reduce inequities. Implementers need clear strategies to overcome challenges, and might be able to learn from countries outside the U.S.

Methods

We wanted to understand existing work about how patients are being included in implementation activities in real world U.S. healthcare settings. We conducted an environmental scan of three data sources: webinars, published articles, and interviews with implementers who engaged patients in implementation activities in U.S. healthcare settings. We extracted, categorized, and triangulated from data sources the key activities, recurring challenges, and promising solutions using a coding template.

Results

We found 27 examples of patient engagement in U.S. healthcare implementation across four webinars, 11 published articles, and seven interviews, mostly arranging patient engagement through groups and arranging processes for patients that changed how engaged they were able to be. Participants rarely specified if they were engaging a population experiencing healthcare inequities. Participants described eight recurring challenges; the two most frequently identified were: (1) recruiting patients representative of those served in the healthcare system; and (2) ensuring processes for equitable communication among all. We matched recurring challenges to promising solutions, such as logistic solutions on how to arrange meetings to enhance engagement or training in inclusivity and power-sharing.

Conclusion

We clarified how some U.S. implementers are engaging patients in healthcare implementation activities using less and more intensive engagement. It was unclear whether reducing inequities was a goal. Patient engagement in redesigning U.S. healthcare service delivery appears similar to or less intense than in countries with more robust infrastructure for this, such as Canada and the United Kingdom. Challenges were common across jurisdictions, including retaining patients in the design/delivery of implementation activities. Implementers in any region can learn from those in other places.
Assessing the contributions of an urban population health initiative to shift political priority towards cardiovascular health: three case studies from Brazil, Mongolia and Senegal
Authors: Saric Jasmina , Aerts Ann , Anne Malick , Barboza Joseph , Boch Johannes , Dashdorj Naranjargal , McGhie Diana Vaca , Santana Adela , Shellaby Jason T. , Rollemberg Suely Miya Shiraishi , Silveira Mariana , Steinmann Peter , Cobos Daniel
Published: January 2024

Background

The urban population health initiative was designed as a multidisciplinary, multisector programme to address cardiovascular (CV) disease, specifically hypertension and its underlying causes in the cities of Ulaanbaatar, Mongolia; Dakar, Senegal; and São Paulo, Brazil. This article aims to provide an overview of the history and dynamics of CV disease policy making in the three countries, to present the policy reform contributions of the initiative and its role in the policy agenda-setting framework/process in each country and to identify the enablers and challenges to the initiative for doing so.

Methods

A qualitative case study was conducted for each setting from November 2020 to January 2021, comprised of a document review, semi-structured in-depth interviews and unstructured interviews with stakeholders involved in the initiative. The literature review included documents from the initiative and the peer-reviewed and grey literature with a total of 188 documents screened. Interviews were conducted with 21 stakeholders. Data collection and thematic analysis was guided by (i) the Kingdon multiple streams conceptual framework with the main themes being CV disease problems, policy, politics and the role of policy entrepreneurs; and (ii) the study question inquiring on the role of the urban population health initiative at the CV disease policy level and enabling and challenging factors to advancing CV disease policy. Data were thematically analysed using the Framework Method.

Results

Each setting was characterized by a high hypertension and CV disease burden combined with an aware and proactive political environment. Policy outcomes attributed to the initiative were updating the guidelines and/or algorithms of care for hypertension and including revised physical and nutritional education in school curricula, in each city. Overall, the urban health initiative’s effects in the policy arena, were most prominent in Mongolia and Senegal, where the team effectively acted as policy entrepreneur, promoting the solutions/policies in alignment with the most pressing local problems and in strong involvement with the political actors. The initiative was also involved in improving access to CV disease drugs at primary health levels. Its success was influenced by the local governance structures, the proximity of the initiative to the policy makers and the local needs. In Brazil, needs were expressed predominantly in the clinical practice.

Conclusions

This multi-country experience shows that, although the policy and political environment plays its role in shaping initiatives, often the local priority needs are the driving force behind wider change.
First experiences of a hospital-based 3D printing facility – an analytical observational study
Authors: Kveller Christian , Jakobsen Anders M. , Larsen Nicoline H. , Lindhardt Joakim L. , Baad-Hansen Thomas
Published: January 2024

Purpose

To identify the clinical impact and potential benefits of in-house 3D-printed objects through a questionnaire, focusing on three principal areas: patient education; interdisciplinary cooperation; preoperative planning and perioperative execution.

Materials and methods

Questionnaires were sent from January 2021 to August 2022. Participants were directed to rate on a scale from 1 to 10.

Results

The response rate was 43%. The results of the rated questions are averages. 84% reported using 3D-printed objects in informing the patient about their condition/procedure. Clinician-reported improvement in patient understanding of their procedure/disease was 8.1. The importance of in-house placement was rated 9.2. 96% reported using the 3D model to confer with colleagues. Delay in treatment due to 3D printing lead-time was 1.8. The degree with which preoperative planning was altered was 6.9. The improvement in clinician perceived preoperative confidence was 8.3. The degree with which the scope of the procedure was affected, in regard to invasiveness, was 5.6, wherein a score of 5 is taken to mean unchanged. Reduction in surgical duration was rated 5.7.

Conclusion

Clinicians report the utilization of 3D printing in surgical specialties improves procedures pre- and intraoperatively, has a potential for increasing patient engagement and insight, and in-house location of a 3D printing center results in improved interdisciplinary cooperation and allows broader access with only minimal delay in treatment due to lead-time.
Ultrasonography, computed tomography and magnetic resonance imaging of the dromedary camel distal limbs
Authors: Nahas Ayman El , Almohamad Zakriya , Hagag Usama
Published: January 2024

Background

Lameness associated with the distal limb region in dromedary camels is quiet prevalent. The diagnosis of lameness relies on a comprehensive orthopedic examination conjugated with an appropriate imaging modality to achieve a decisive diagnosis. Using of modern imaging tools provoked a significant breakthrough in the diagnosis of lameness. Ultrasonography (US) is widely established in dromedaries, whereas computed tomography (CT) and magnetic resonance imaging (MRI) are gaining popularity. CT provides a considerably higher bone detail than any other imaging modality. US and MRI continue to be the best options for soft tissue imaging. A truthful assessment of the clinical US, CT and MRI images dictates a comprehensive familiarity with the standard US, CT and MRI tissue deviations. Accordingly, our purposes were to present a full MRI protocol for investigating the dromedary camel distal limbs as well as comparing and illustrating the merits of using MRI, CT and US for evaluation of the front and hind distal limbs in 10 healthy lameness free dromedary camel cadavers. The limbs were scanned via a high-field 1.5 Tesla MRI magnet and a multi-detector CT scanner then subjected to a systematic US examination in both longitudinal and transverse planes. The obtained MRI, CT and US images were evaluated, correlated and compared.

Results

CT and MRI eliminated the structural superimposition in the dromedary camel distal limbs and afforded assessment of minute ligamentous and tendentious structures that were inaccessible by US including the axial collateral ligaments, ligaments supporting the proximal sesamoid bones and the palmar/plantar aspects of the inter-phalangeal joints. US and MRI were appreciated for the assessment of the articular cartilage that was not visible on the plain CT images.

Conclusions

CT and MRI accurately identified and characterized bones and soft tissues constituting the dromedary camel distal limbs. US was appreciated for assessment of soft tissues, articular cartilage and bone contours. CT and MRI may be considered when US results are inconclusive or to evaluate the unreachable parts of the camel distal limbs. Images presented in this study could be used as a reference standard for evaluating dromedary camel distal limb diseases.
Assessing the protection elicited by virus-like particles expressing the RSV pre-fusion F and tandem repeated G proteins against RSV rA2 line19F infection in mice
Authors: Kim Min-Ju , Chu Ki Back , Lee Su-Hwa , Mao Jie , Eom Gi-Deok , Yoon Keon-Woong , Moon Eun-Kyung , Quan Fu-Shi
Published: January 2024

Excessive pulmonary inflammation is the hallmark of respiratory syncytial virus (RSV) infection hindering efficacious RSV vaccine development. Yet, the vast majority of the experimental RSV vaccine studies use laboratory-adapted RSV strains that do not reflect the highly pathogenic and inflammatory nature of the virus found in clinical settings. Here, we re-evaluated the protective efficacy of the virus-like particle (VLP) vaccine co-expressing the pre-fusion (pre-F) protein and G protein with tandem repeats (Gt) reported in our previous study against the recombinant RSV rA2-line19F strain, which inflicts severe mucus production and inflammation in mice. VLP vaccine immunization elicited virus-specific serum antibody responses that mediated RSV rA2-line19F virus neutralization. VLP vaccine immunization promoted Th1 immune response development in the spleens and CD8 + T cell influx into the lungs of mice, which are essential for efficient viral clearance and dampened inflammatory response. When compared to the VLPs expressing only the pre-F antigen, those co-expressing both pre-F and Gt antigens conferred better protection in mice against rA2-line19F challenge infection. Overall, our data suggest that the pre-clinical VLP vaccine co-expressing RSV pre-F and Gt antigens can effectively protect mice against RSV strains that resemble pathogenic clinical isolates.
Reflective questioning to guide socially just global health reform: a narrative review and expert elicitation
Authors: Lebu Sarah , Musoka Lena , Graham Jay P.
Published: January 2024

Recent research has highlighted the impacts of colonialism and racism in global health, yet few studies have presented concrete steps toward addressing the problems. We conducted a narrative review to identify published evidence that documented guiding frameworks for enhancing equity and inclusion in global health research and practice (GHRP). Based on this narrative review, we developed a questionnaire with a series of reflection questions related on commonly reported challenges related to diversity, inclusion, equity, and power imbalances. To reach consensus on a set of priority questions relevant to each theme, the questionnaire was sent to a sample of 18 global health experts virtually and two rounds of iterations were conducted. Results identified eight thematic areas and 19 reflective questions that can assist global health researchers and practitioners striving to implement socially just global health reforms. Key elements identified for improving GHRP include: (1) aiming to understand the historical context and power dynamics within the areas touched by the program; (2) promoting and mobilizing local stakeholders and leadership and ensuring measures for their participation in decision-making; (3) ensuring that knowledge products are co-produced and more equitably accessible; (4) establishing a more holistic feedback and accountability system to understand needed reforms based on local perspectives; and (5) applying systems thinking to addressing challenges and encouraging approaches that can be sustained long-term. GHRP professionals should reflect more deeply on how their goals align with those of their in-country collaborators. The consistent application of reflective processes has the potential to shift GHRP towards increased equity.
The role of rapid syndromic diagnostic testing of gastrointestinal pathogens as a clinical decision support tool in a pediatric emergency department
Authors: Kang Hyun Mi , Yoo In Hyuk , Jeong Dae Chul
Published: January 2024

Purpose

This study aimed to investigate the role of rapid syndromic diagnostic testing of gastrointestinal pathogens as a clinical decision support tool in a pediatric emergency department (ED) by comparing clinical decision and patient outcome parameters pre- and post-implementation.

Methods

This was a big data analytical study of children < 18 years old without any underlying diseases, that visited the ED with acute moderate to severe diarrhea during a 34-month period from 2018 to 2022 using Seoul St. Mary’s hospital’s healthcare corporate data warehouse to retrieve demographic, clinical, and laboratory parameters. Outcome measures pre- and post-implementation of a rapid syndromic multiplex gastrointestinal panel (GI panel) were compared.

Results

A total of 4,184 patients’ data were included in the analyses. Broad spectrum antibiotics were prescribed at a significantly lower rate to patients presenting with acute infectious diarrhea at discharge from the ED (9.9% vs 15.8%, P < 0.001) as well as upon admission (52.2% vs 66.0%, P < 0.001) during the post-implementation period compared to the pre-implementation period. Although the duration of ED stay was found to be significantly longer (6.5 vs 5.5 h, P < 0.0001), the rate of ED revisit due to persistent or aggravated symptoms was significantly lower (Δ in intercept, β = -0.027; SE = 0.013; P = 0.041), and the admission rate at follow up after being discharged from the ED shown to be significantly lower during the post-implementation period compared to the pre-implementation period (0.8% vs. 2.1%, P = 0.001, respectively). No significant difference in disease progression was observed (P = 1.000).

Conclusion

Using the GI panel in the ED was shown to decrease broad spectrum antibiotic prescribing practices and reduce revisits or admission at follow up by aiding clinical decisions and improving patient outcome.
Therapeutic challenges in peripheral T-cell lymphoma
Authors: Luan Yunpeng , Li Xiang , Luan Yunqi , Luo Junyu , Dong Qinzuo , Ye Shili , Li Yuejin , Li Yanmei , Jia Lu , Yang Jun , Yang Dong-Hua
Published: January 2024

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of hematological malignancies. Compared to our knowledge of B-cell tumors, our understanding of T-cell leukemia and lymphoma remains less advanced, and a significant number of patients are diagnosed with advanced stages of the disease. Unfortunately, the development of drug resistance in tumors leads to relapsed or refractory peripheral T-Cell Lymphomas (r/r PTCL), resulting in highly unsatisfactory treatment outcomes for these patients. This review provides an overview of potential mechanisms contributing to PTCL treatment resistance, encompassing aspects such as tumor heterogeneity, tumor microenvironment, and abnormal signaling pathways in PTCL development. The existing drugs aimed at overcoming PTCL resistance and their potential resistance mechanisms are also discussed. Furthermore, a summary of ongoing clinical trials related to PTCL is presented, with the aim of aiding clinicians in making informed treatment decisions.
Association between antithrombotic therapy and mortality in patients hospitalized for COVID‑19
Authors: Wang Xing , Chen Wuqian , Guo Jiulin , Qiu Xingyu , You Chao , Ma Lu
Published: January 2024

Background

The prothrombotic state is a common abnormality in patients with coronavirus disease 2019 (COVID-19). However, there is controversy over the use of anticoagulants, especially oral anticoagulants (OAC) due to limited studies. We sought to evaluate the association between antithrombotic therapy on mortality and clinical outcomes in patients hospitalized for COVID-19 through propensity score matching (PSM) analysis.

Methods

A retrospective cohort study was performed to include adult patients with COVID-19 in a university hospital. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) admission, mechanical ventilation, and acute kidney injury (AKI) during hospitalization. PSM was used as a powerful tool for matching patients’ baseline characteristics. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated from the models.

Results

Of 4,881 COVID-19 patients during the study period, 690 (14.1%) patients received antithrombotic therapy and 4,191 (85.9%) patients were under no antithrombotic therapy. After adjustment with multivariate regression analysis, patients receiving OAC, compared with those who did not receive any antithrombotic therapy, had significantly lower odds for in-hospital mortality (aOR: 0.46. 95% CI: 0.24 to 0.87; P= 0.017). PSM analysis observed similar results (aOR: 0.35. 95% CI: 0.19 to 0.61; P< 0.001). Moreover, in critically ill patients who received mechanical ventilation, antithrombotic treatment (aOR: 0.54. 95% CI: 0.32 to 0.89; P= 0.022) was associated with reduced risk of mortality.

Conclusions

The application OACs was associated with reduced hospital mortality and mechanical ventilation requirement in COVID-19 patients. Besides, antithrombotic treatment was associated with a reduction in in-hospital mortality among critically ill COVID-19 patients who required mechanical ventilation.
SB431542 partially inhibits high glucose-induced EMT by restoring mitochondrial homeostasis in RPE cells
Authors: Cao Jingjing , Jiao Mingfei , Kou Zhenyu , Han Feifei , Dong Lijie
Published: January 2024

Background

The epithelial–mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells participated in the development of retinal fibrosis. SB431542 is a small molecule inhibitor with inhibitory effects on the ALK4, ALK5 and ALK7. Our study aimed to explore the effect of SB431542 on the EMT of RPE cells and to provide new ideas for the treatment of retinal fibrosis.

Methods

We performed fundus fluorescein angiography, optical coherence tomography and hematoxylin–eosin staining in vivo to observe the effect of SB431542 on choroidal neovascularization (CNV)-induced retinopathy. The proliferation, migration, cytoskeleton, adhesion, reactive oxygen species (ROS), mitochondrial morphology and membrane potential of RPE cells were observed in vitro through fluorescein diacetate staining, Cell Counting Kit-8 experiment, wound healing assay, phalloidin staining, immunofluorescence, MitoSOX, DCFH-DA, MitoTracker and JC-10 staining. Western blot, reverse transcription quantitative and immunofluorescence were used to detect the expression of EMT–related markers, pERK1/2, pGSK3β and β-catenin.

Results

SB431542 significantly alleviated retinopathy in the CNV model. The proliferation, migration and adhesion in RPE cells decreased to a certain extent in SB431542 treatment. SB431542 partially normalized the structure of RPE cells. The expression levels of E-cadherin increased, while the expression levels of laminin and N-cadherin decreased with SB431542 treatment. SB431542 reduced the production of total ROS, mitochondrial SOX and recovered the mitochondrial membrane potential to a certain degree. In addition, our study showed that SB431542 downregulated the phosphorylation of ERK1/2, GSK3β and the expression of β-catenin.

Conclusion

SB431542 improved EMT in RPE cells by maintaining mitochondrial homeostasis via the ERK1/2 and GSK3β/β-catenin pathways.

Graphical Abstract

SB431542 inhibits EMT in RPE cells under high glucose conditions.
Translational medicine for acute lung injury
Authors: Zhang Jianguo , Guo Yumeng , Mak Michael , Tao Zhimin
Published: January 2024

Acute lung injury (ALI) is a complex disease with numerous causes. This review begins with a discussion of disease development from direct or indirect pulmonary insults, as well as varied pathogenesis. The heterogeneous nature of ALI is then elaborated upon, including its epidemiology, clinical manifestations, potential biomarkers, and genetic contributions. Although no medication is currently approved for this devastating illness, supportive care and pharmacological intervention for ALI treatment are summarized, followed by an assessment of the pathophysiological gap between human ALI and animal models. Lastly, current research progress on advanced nanomedicines for ALI therapeutics in preclinical and clinical settings is reviewed, demonstrating new opportunities towards developing an effective treatment for ALI.
Cervical lymphoepithelioma-like carcinoma with deficient mismatch repair and loss of SMARCA4/BRG1: a case report and five related cases
Authors: Miyama Yu , Kato Tomomi , Sato Masayasu , Yabuno Akira , Hasegawa Kosei , Yasuda Masanori
Published: January 2024

Background

We encountered a cervical lymphoepithelial carcinoma (LEC) possessing a predominantly solid architecture with deficient mismatch repair (dMMR) and loss of expression of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complex subunit. This is the first case report of LEC with dMMR and loss of SWI/SNF complex subunit.

Case presentation

A 34-year-old woman presented at our hospital with menstrual irregularities and abnormal vaginal bleeding. Magnetic resonance imaging revealed an exophytic mass in the posterior uterine cervix. Biopsy specimens confirmed squamous cell carcinoma with a 2018 International Federation of Gynecology and Obstetrics (FIGO) uterine cervical cancer stage of IB2. In a subsequent conization specimen, the tumor appeared exophytic. Microscopically, the tumor cells formed a predominant solid architecture. Abundant lymphocytic infiltration was observed. The pathological diagnosis indicated human papillomavirus (HPV)-associated squamous cell carcinoma with LEC pattern and pT1b2. Immunohistochemically, high programmed death-ligand 1 (PD-L1) expression, dMMR, and loss of the switch/sucrose non-fermentable family-related, matrix-associated, actin-dependent regulator of chromatin subfamily member 4 (SMARCA4)/BRG1, an SWI/SNF complex subunit, were observed. The patient underwent a radical hysterectomy and is alive without disease one year and five months later. Our analysis of five additional LEC cases revealed a consistent association with high-risk HPV and elevated PD-L1 expression. In addition to the present case, another patient exhibited dMMR. The SWI/SNF complex was retained except in the present case. The prognosis was favorable in all cases.

Conclusions

This unique case of LEC with dMMR suggests a distinct clinical entity with potential immunotherapy implications. Analysis of the other five LEC cases revealed that LEC was immune hot, and immune checkpoint inhibitors may be effective. The two dMMR cases showed loss of MLH1 and PMS2 expressions, and prominently high tumor PD-L1 expression. In those cases, dMMR might have contributed to the morphological characteristics of LEC.
Translation and validation of the Breastfeeding Motivation Scale in China
Authors: Yu Yanfei , Zhang Lu , Liu Ying , Zhang Lan , Guo Nafei
Published: January 2024

Background

There are several versions of the Breastfeeding Motivation Scale (BMS), which have been shown to measure maternal breastfeeding motivation, but there is not a Chinese version yet. The study aimed to translate the BMS into Chinese and subsequently assess its psychometric properties among Chinese mothers during the postpartum period.

Methods

The study was composed of two phases. The translation of BMS closely followed the principals of good practices. Phase 1 included a comprehensive translation, back-translation, cross-cultural adaptation, and pretest to develop the Chinese version of the BMS. From 1 December 2021 to 1 July 2022, the Chinese version of the BMS was administered to 206 postnatal mothers in our maternity wards to assess its psychometric properties. Phase 2 involved psychometric property testing, including testing of the internal consistency, test–retest reliability, content validity, construct validity, convergent validity and discriminant validity.

Results

Minor modifications in four items were recommended after translations. The Cronbach's α coefficient of the Chinese version of the BMS was .887, and the intraclass correlation coefficient was .897 (P < 0.001). The model fit was acceptable (χ2/df = 2.40, P < 0.001, RMSEA = 0.08, CFI = 0.91, IFI = 0.92 and TLI = 0.90) according to the confirmatory factor analysis. The composite reliability values corresponding to each latent variable were 0.733 ~ 0.926, and the average variance extracted values were 0.476 ~ 0.653. The correlations among the five measured variables were all lower than .85 and the square roots of average variance extracted from the variable were greater than the interconstruct correlations among the five measured variables in the model.

Conclusions

The Chinese version of the BMS has good reliability and validity and provides a reliable assessment tool for measuring maternal breastfeeding motivation. It also provides support to develop culturally sensitive interventions for Chinese mothers’ who are breastfeeding.
Comparing the effects of decreasing prescription opioid shipments and the release of an abuse deterrent OxyContin formulation on opioid overdose fatalities in WV: an interrupted time series study
Authors: Lundstrom Eric W. , Dai Zheng , Groth Caroline P. , Hendricks Brian , Winstanley Erin L. , Abate Marie , Smith Gordon S.
Published: January 2024

Introduction

The 2010 release of an abuse deterrent formulation (ADF) of OxyContin, a brand name prescription opioid, has been cited as a major driver for the reduction in prescription drug misuse and the associated increasing illicit opioid use and overdose rates. However, studies of this topic often do not account for changes in supplies of other prescription opioids that were widely prescribed before and after the ADF OxyContin release, including generic oxycodone formulations and hydrocodone. We therefore sought to compare the impact of the ADF OxyContin release to that of decreasing prescription opioid supplies in West Virginia (WV).

Methods

Opioid tablet shipment and overdose data were extracted from The Washington Post ARCOS (2006–2014) and the WV Forensic Drug Database (2005–2020), respectively. Locally estimated scatterplot smoothing (LOESS) was used to estimate the point when shipments of prescription opioids to WV began decreasing, measured via dosage units and morphine milligram equivalents (MMEs). Interrupted time series analysis (ITSA) was used to compare the impact LOESS-identified prescription supply changes and the ADF OxyContin release had on prescription (oxycodone and hydrocodone) and illicit (heroin, fentanyl, and fentanyl analogues) opioid overdose deaths in WV. Model fit was compared using Akaike Information Criteria (AIC).

Results

The majority of opioid tablets shipped to WV from 2006 to 2014 were generic oxycodone or hydrocodone, not OxyContin. After accounting for a 6-month lag from ITSA models using the LOESS-identified change in prescription opioid shipments measured via dosage units (2011 Q3) resulted in the lowest AIC for both prescription (AIC = -188.6) and illicit opioid-involved overdoses (AIC = -189.4), indicating this intervention start date resulted in the preferred model. The second lowest AIC was for models using the ADF OxyContin release as an intervention start date.

Discussion

We found that illicit opioid overdoses in WV began increasing closer to when prescription opioid shipments to the state began decreasing, not when the ADF OxyContin release occurred. Similarly, the majority of opioid tablets shipped to the state for 2006–2014 were generic oxycodone or hydrocodone. This may indicate that diminishing prescription supplies had a larger impact on opioid overdose patterns than the ADF OxyContin release in WV.
Evaluation of PTV margins with daily iterative online adaptive radiotherapy for postoperative treatment of endometrial and cervical cancer: a prospective single-arm phase 2 study
Authors: Wang Guangyu , Wang Zhiqun , Guo Yuping , Zhang Yu , Qiu Jie , Hu Ke , Li Jing , Yan JunFang , Zhang Fuquan
Published: January 2024

Background

To determine the optimal planning target volume (PTV) margins for adequate coverage by daily iterative cone-beam computed tomography (iCBCT)-guided online adaptive radiotherapy (oART) in postoperative treatment of endometrial and cervical cancer and the benefit of reducing PTV margins.

Methods

Fifteen postoperative endometrial and cervical cancer patients treated with daily iCBCT-guided oART were enrolled in this prospective phase 2 study. Pre- and posttreatment iCBCT images of 125 fractions from 5 patients were obtained as a training cohort, and clinical target volumes (CTV) were contoured separately. Uniform three-dimensional expansions were applied to the PTVpre to assess the minimum margin required to encompass the CTVpost. The dosimetric advantages of the proposed online adaptive margins were compared with conventional margin plans (7–15 mm) using an oART emulator in another cohort of 125 iCBCT scans. A CTV-to-PTV expansion was verified on a validation cohort of 253 fractions from 10 patients, and further margin reduction and acute toxicity were studied.

Results

The average time from pretreatment iCBCT to posttreatment iCBCT was 22 min. A uniform PTV margin of 5 mm could encompass nodal CTVpost in 100% of the fractions (175/175) and vaginal CTVpost in 98% of the fractions (172/175). The margin of 5 mm was verified in our validation cohort, and the nodal PTV margin could be further reduced to 4 mm if ≥ 95% CTV coverage was predicted to be achieved. The adapted plan with a 5 mm margin significantly improved pelvic organ-at-risk dosimetry compared with the conventional margin plan. Grade 3 toxicities were observed in only one patient with leukopenia, and no patients experienced acute urinary toxicity.

Conclusion

In the postoperative treatment of endometrial and cervical cancer, oART could reduce PTV margins to 5 mm, which significantly decrease the dose to critical organs at risk and potentially lead to a lower incidence of acute toxicity.
Anatomic distribution of basivertebral foramen with a magistral form in vertebral bodies of T10~L5 and its clinical significance for extensive epidural cement leakage in cement-augmented pedicle screw fixation: a multicenter case–control study
Authors: Yu Weibo , Cai Daozhang , Yao Zhensong , Zhang Haiyan , Jiang Xiaobing
Published: January 2024

Background

There are no reports discussing anatomic distribution of basivertebral foramen (BVF) in the osteoporotic vertebral body, which is critical in the analysis of the risk of epidural cement leakage (ECL) after cement-augmented pedicle screw fixation (CAPSF).

Methods

371 osteoporotic patients using 1898 cement-augmented screws were included. Preoperative computed tomography (CT) was used to determine the frequency, width, height, and depth of magistral BVF in T10~L5. Additionally, we measured the distance between BVF and the left/right borders of vertebral body as well as the distance between BVF and upper/lower endplates. Following CAPSF, the severity of ECL and the position of pedicle screws were determined by postoperative CT. Finally, significant risk factors for extensive ECL were identified through binary logistic regression analysis.

Results

Of 2968 vertebral bodies ranging from T10 to L5, 801 (42.2%) had a magistral BVF. From T10 to L5, the frequency of magistral BVF appeared to gradually increase. The magistral BVF was much closer to the upper endplate and the depth accounted for about a quarter of anteroposterior diameter of vertebral body. Overall, there were 19 patients (5.1%) and 32 screws (1.7%) with extensive ECL, nine of whom had neurological symptoms. The independent risk factors for extensive ECL were the magistral BVF (OR = 8.62, P < 0.001), more volume of cement injected (OR = 1.57, P = 0.031), reduced distance from screw tip to vertebral midline (OR = 0.76, P = 0.003) and vertebral posterior wall (OR = 0.77, P < 0.001) respectively.

Conclusion

When planning a CAPSF procedure, it is important to consider anatomical distribution of BVF and improve screw implantation methods.
m6A-modified circARHGAP12 promotes the aerobic glycolysis of doxorubicin-resistance osteosarcoma by targeting c-Myc
Authors: Zhang Dawei , Guo Qingzhu , You Kemin , Zhang Yi , Zheng Yao , Wei Tao
Published: January 2024

Chemotherapy resistance accompanied by energy metabolism abnormality functions as one of the main reasons for treatment failure and poor prognosis. However, the function of N6-methyladenosine (m6A)-modified circular RNA (circRNA) on osteosarcoma (OS) is still unclear. Here, present research investigated the potential role and mechanism of circARHGAP12 on OS doxorubicin (Dox) resistance and aerobic glycolysis. Results indicated that circARHGAP12 was a novel m6A-modified circRNA, which was up-regulated in OS cells. Overexpression of circARHGAP12 promoted the Dox resistance half-maximal inhibitory concentration (IC50) and aerobic glycolysis (glucose uptake, lactate and ATP production) in OS cells (Saos-2/Dox, MG63/Dox). Mechanistically, m6A-modified circARHGAP12 could bind with c-Myc mRNA through m6A-dependent manner, thereby enhancing the c-Myc mRNA stability. Thus, these findings revealed the critical function of circARHGAP12 on OS Dox-resistance and aerobic glycolysis. Taken together, our study demonstrated a critical function of circARHGAP12 on OS chemotherapy resistance and energy metabolism abnormality, providing critical roles on OS treatment.
Contribution of genetic variants to congenital heart defects in both singleton and twin fetuses: a Chinese cohort study
Authors: Lin Shaobin , Shi Shanshan , Lu Jian , He Zhiming , Li Danlun , Huang Linhuan , Huang Xuan , Zhou Yi , Luo Yanmin
Published: January 2024

Background

The contribution of genetic variants to congenital heart defects (CHDs) has been investigated in many postnatal cohorts but described in few prenatal fetus cohorts. Overall, specific genetic variants especially copy number variants (CNVs) leading to CHDs are somewhat diverse among different prenatal cohort studies. In this study, a total of 1118 fetuses with confirmed CHDs were recruited from three units over a 5-year period, composing 961 of singleton pregnancies and 157 of twin pregnancies. We performed chromosomal microarray analysis on all cases to detect numerical chromosomal abnormalities (NCAs) and pathogenic/likely pathogenic CNVs (P/LP CNVs) and employed whole-exome sequencing for some cases without NCAs and P/LP CNVs to detect P/LP sequence variants (P/LP SVs).

Results

Overall, NCAs and P/LP CNVs were identified in 17.6% (197/1118) of cases, with NCA accounting for 9.1% (102/1118) and P/LP CNV for 8.5% (95/1118). Nonisolated CHDs showed a significantly higher frequency of NCA than isolated CHD (27.3% vs. 4.4%, p < 0.001), but there was no significant difference in the frequency of P/LP CNVs between isolated and nonisolated CHD (11.7% vs. 7.7%). A total of 109 P/LP CNVs were identified in 95 fetuses, consisting of 97 (89.0%) de novo, 6 (5.5%) parental inherited and 6 (5.5%) with unavailable parental information. The 16p11.2 proximal BP4-BP5 deletion was detected in 0.9% (10/1118) of all cases, second only to the most common 22q11.21 proximal A-D deletion (2.1%, 23/1118). Most of the 16p11.2 deletions (8/10) detected were de novo, and were enriched in CHD cases compared with a control cohort from a previous study. Additionally, SV was identified in 12.9% (8/62) of cases without NCA and P/LP CNV, most of which were de novo with autosomal dominant inheritance.

Conclusions

Our cohort study provides a deep profile of the contribution of genetic variants to CHDs in both singleton and twin fetuses; NCA and P/LP CNV contribute to 9.1% and 8.5% of CHD in fetuses, respectively. We confirmed the 16p11.2 deletion as a CHD-associated hotspot CNV, second only to the 22q11.21 deletion in frequency. Most 16p11.2 deletions detected were de novo. Additionally, P/LP SV was identified in 12.9% (8/62) of fetuses without NCA or P/LP CNV.
The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors
Authors: Wei Qing , Li Peijing , Yang Teng , Zhu Jiayu , Sun Lu , Zhang Ziwen , Wang Lu , Tian Xuefei , Chen Jiahui , Hu Can , Xue Junli , Ma Letao , Shimura Takaya , Fang Jianmin , Ying Jieer , Guo Peng , Cheng Xiangdong
Published: January 2024

Antibody-drug conjugates (ADCs) represent an important class of cancer therapies that have revolutionized the treatment paradigm of solid tumors. To date, many ongoing studies of ADC combinations with a variety of anticancer drugs, encompassing chemotherapy, molecularly targeted agents, and immunotherapy, are being rigorously conducted in both preclinical studies and clinical trial settings. Nevertheless, combination therapy does not always guarantee a synergistic or additive effect and may entail overlapping toxicity risks. Therefore, understanding the current status and underlying mechanisms of ADC combination therapy is urgently required. This comprehensive review analyzes existing evidence concerning the additive or synergistic effect of ADCs with other classes of oncology medicines. Here, we discuss the biological mechanisms of different ADC combination therapy strategies, provide prominent examples, and assess their benefits and challenges. Finally, we discuss future opportunities for ADC combination therapy in clinical practice.