bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an Extended Cardiovascular SOFA Score Component Reflecting Cardiac Dysfunction with Improved Survival Prediction in Sepsis: An Exploratory Analysis in the Sepsis and Elevated Troponin (SET) Study
Authors: Lörstad S. , Wang Y. , Tehrani S. , Shekarestan S. , Åstrand P. , Gille-Johnson P. , Jernberg T. , Persson J.
Published: October 2024

Introduction

The cardiovascular component of the Sequential Organ Failure Assessment (SOFA) score does not correspond with contemporary clinical practice in sepsis or identify impaired cardiac function. Our aim was to develop a modified cardiovascular SOFA component that reflects cardiac dysfunction and improves the SOFA score's 30-day mortality discrimination.

Methods

A cohort of sepsis patients from a previous study was divided into a training (n = 250) and test cohort (n = 253). Nine widely available measures of cardiovascular function were screened for association with 30-day mortality using natural cubic spline. High-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP) and heart rate (HR) were transformed into ordinal variables (0-4 points). The presence of atrial fibrillation (AF) was assigned two points. The SOFA score was extended by adding the variable points in different weights and combinations. The best-performing cardiac-extended model (CE-SOFA) was evaluated in the test cohort. Improved prognostic discrimination and calibration were assessed using logistic regression, area under receiver operating characteristic curves (AUC), Net Reclassification Improvement (NRI) index, and DeLong and Hoshmer-Lemeshow tests.

Results

In the training cohort, all differently weighted and combined models using hs-cTnT, NT-proBNP and AF points added to the SOFA score showed improved discriminative ability (AUC 0.67-0.75) compared to the SOFA score (AUC 0.62; NRI P < .001; DeLong P ≤ .001). In the test cohort, CE-SOFA demonstrated improved 30-day mortality discrimination compared to the SOFA score (AUC 0.72 vs 0.68), exhibiting good calibration and significantly improved discrimination using the NRI index ( P = .009) but not the DeLong test ( P = .142).

Conclusions

The CE-SOFA model reflects cardiac dysfunction and improves 30-day mortality discrimination in sepsis. External validation is the next step to further substantiate a revised cardiovascular component in a future SOFA 2.0.
Progressive damage analysis of green composite laminates subjected to in-plane crashworthiness
Authors: Giammaria Valentina , Del Bianco Giulia , Fiumarella Dario , Ciardiello Raffaele , Vigna Lorenzo , Boria Simonetta , Scattina Alessandro , Belingardi Giovanni , Castorani Vincenzo
Published: October 2024

In this paper the initiation and propagation of delamination in thin-walled green composite structures were studied. In particular, laminates of flax and hemp fibers with epoxy resin were investigated from experimental and numerical points of view, using the finite element code LS-DYNA. First, an experimental campaign was conducted using DCB and 4ENF tests to obtain the values of the interlaminar fracture modes, required for the cohesive fracture modeling. In addition, in-plane crashworthiness tests were performed on composite plates to analyze the damage of the specimens, under both quasi-static and dynamic conditions. A trigger mechanism was considered to help delamination to start and to ensure the most progressive crushing possible. The predominant damage mode was splaying, but some ply fragmentation in the middle layers and some buckling phenomena were also observed. In general, more stable progressive crushing was observed under dynamic conditions than under quasi-static ones, even if a reduction in terms of absorbed energy was obtained by moving to the dynamic condition. The numerical predictions showed a good agreement with the experimental reference results, validating the current framework for crashworthiness analysis of green composite structures.
Study on Action and Mechanism of Potentilla discolor Bunge using Patch-Clamp to Explore the Effect of the Main Components of Potentilla discolor Bunge on Myocardial Cell Membranes
Authors: Dang Yanxin , Zhao Wenjie , Li Xiaohan , Chen Yongchao , Liu Jie , Li Lin , Xie Minzhen , Chen Zhouxiu , Gu Siqi , Wang Qi , Liu Guijun
Published: October 2024

Background

Potentilla discolor Bunge (PDB) is a plant of the Rosaceae family. A wide range of pharmacological activities, such as antibacterial, hypoglycemic, and others, can be achieved through its chemical components, which include terpenes, steroids, polyphenols, and flavonoids. However, the effects of the herb on the heart are unclear.

Objectives

To explore the effect of the main components of PDB on myocardial cell membranes.

Materials and Methods

We investigated the role of different concentrations of PDB in cardiomyocytes by evaluating myocardial electrical activity. We used high-performance liquid chromatography to analyze the components. Patch-clamp experiments were conducted to detect the drugs’ impact on the ion channels of cardiomyocytes.

Results

PDB regulated 14 potential metabolites in mice. Interestingly, quercetin exerts certain effects on the heart by acting on the inositol phosphate metabolism pathway. Quercetin is a monomer compound that can enhance the activity of IK1 on the myocardium membrane.

Conclusion

This study showed that monomeric compounds of PDB can significantly enhance IK1 activity and influence ion channels in a concentration-dependent manner.
Aberrant CD45 Immunoreactivity in Neuroendocrine Neoplasms: A Diagnostic Pitfall—Report of 10 Specimens and Clinical Recommendations
Authors: Pantanowitz Joshua , Huang Tao , Cantley Richard , Mehra Rohit , Pantanowitz Liron
Published: October 2024

Leukocyte common antigen (LCA), or CD45, is classically thought of as a leukocyte-exclusive protein, and as such, CD45 immunohistochemistry (IHC) is often used as a key differentiator between non-Hodgkin lymphomas (NHLs) and morphologically similar neuroendocrine neoplasms (NENs). Herein, we report our experience regarding aberrant CD45 immunoreactivity in a series of NENs. A natural language search was used to retrieve desired archival patient files. All prior NENs which had a positive neuroendocrine diagnosis or IHC results (synaptophysin, chromogranin, CD56, and/or neuron-specific enolase), as well as CD45 staining performed, were reviewed for possible CD45 positivity ( n = 686). Among these 686 NENs, 10 were aberrantly positive for CD45 staining. CD45 showed nuclear, cytoplasmic, and/or membranous staining in tumor cells. The significance of such staining is unclear. Albeit for a minority of patients, pathologists should be aware that NENs may aberrantly stain with CD45 and thereby pose a diagnostic pitfall. Therefore, broadening routine IHC panels is recommended to differentiate NENs more clearly from NHLs.
Change in Talar Axial Rotation and Pain Intensity Following Correction of Progressive Collapsing Foot Deformity
Authors: DiGiovanni Grace M. , El Masry Seif , Jones Agnes , Kim Jaeyoung , Deland Jonathan T. , Ellis Scott J. , Conti Matthew S.
Published: October 2024

Background:

The talus is more internally rotated within the ankle mortise in progressive collapsing foot deformity (PCFD) patients. However, no studies have investigated the change in talar axial rotation (AR) in PCFD postoperatively. The primary aim was to investigate the change in talar AR following PCFD reconstruction. Secondary aims were to determine whether talar AR changes were associated with other radiographic measurements or specific procedures, and whether postoperative talar AR was associated with 2-year patient-reported outcome scores.

Methods:

Twenty-seven patients older than 18 years who underwent flexible PCFD reconstruction with preoperative and at least 5-month postoperative weightbearing computed tomographic (WBCT) scans and radiographs and had preoperative and at least 2-year postoperative PROMIS scores were included. Patients with talonavicular fusions were excluded. Talar AR was the angle between the transmalleolar axis and talar axis on WBCT scans, with smaller angles representing more internal rotation as described by Kim et al. Hindfoot moment arm, Meary angle, fibulocalcaneal and talocalcaneal distance, subtalar middle facet uncoverage, and talonavicular angle were measured on radiographs.

Results:

Postoperative talar AR was 49.7 degrees (IQR, 45.9, 57.3), which was more externally rotated than preoperative AR by a median of 8.3 degrees (IQR, 2.2, 15.7) ( P > .001). The change in talar AR was not associated with changes in any radiographic parameter. Increasing external talar AR was associated with an increase in postoperative PROMIS pain intensity ( rs = 0.38, 95% CI 0.00, 0.67). Lateral column lengthening and subtalar fusion procedures were not associated with changes in talar AR ( P > .10).

Conclusion:

PCFD reconstruction results in external rotation of the talus within the ankle mortise. Kim et al found that control patients had approximately 40 to 60 degrees of talar AR, which is similar to this study’s corrected position of the talus. However, increasing talar external rotation resulted in worse postoperative PROMIS pain intensity, suggesting the possibility of overcorrecting the internal AR deformity.
Socio-ethical challenges and opportunities for advancing diversity, equity, and inclusion in digital medicine
Authors: Paccoud Ivana , Leist Anja K. , Schwaninger Isabel , van Kessel Robin , Klucken Jochen
Published: October 2024

Digitalization in medicine offers a significant opportunity to transform healthcare systems by providing novel digital tools and services to guide personalized prevention, prediction, diagnosis, treatment and disease management. This transformation raises a number of novel socio-ethical considerations for individuals and society as a whole, which need to be appropriately addressed to ensure that digital medical devices (DMDs) are widely adopted and benefit all patients as well as healthcare service providers. In this narrative review, based on a broad literature search in PubMed, Web of Science, Google Scholar, we outline five core socio-ethical considerations in digital medicine that intersect with the notions of equity and digital inclusion: (i) access, use and engagement with DMDs, (ii) inclusiveness in DMD clinical trials, (iii) algorithm fairness, (iv) surveillance and datafication, and (v) data privacy and trust. By integrating literature from multidisciplinary fields, including social, medical, and computer sciences, we shed light on challenges and opportunities related to the development and adoption of DMDs. We begin with an overview of the different types of DMDs, followed by in-depth discussions of five socio-ethical implications associated with their deployment. Concluding our review, we provide evidence-based multilevel recommendations aimed at fostering a more inclusive digital landscape to ensure that the development and integration of DMDs in healthcare mitigate rather than cause, maintain or exacerbate health inequities.
Redesigning Dynamic components for additive manufacturing using topology optimization
Authors: Patham K. Fathima
Published: October 2024

Direct digital manufacturing (DDM) is the technology that provides the possibility of producing the final product directly from the 3D CAD model without the aid of any additional tools. Additive manufacturing is the main element of DDM for producing end-user products. The layer-on-layer creation of the product using additive manufacturing provides a lot of design freedom. The layer-on-layer production methodology enables the possibility of producing products with complex and freeform geometries. The layer-on-layer technology allows the material deposition only on the required spots, and hence a significant weight reduction is obtained during the manufacturing of products. Complex geometrical structures with light weight are the greatest interest of the aerospace, spacecraft, and automobile industries. Therefore, these industries have completely relied on novel lightweight materials for producing lightweight structures until now. However, novel lightweight materials are highly expensive and increase the cost of the products significantly. Recent studies show that additive manufacturing helps in producing lightweight structures with high structural stability without the need for expensive lightweight materials. The complete redesign of aircraft, spacecraft, and automobiles suitable for additive manufacturing increases the possibility of producing lightweight structures with high structural stability. The generative design method created for additive manufacturing opens up enormous design possibilities, but the complete redesign of the aircraft or spacecraft would take a few decades. Until then, redesigning and replacing some aerospace components are the most efficient way to achieve the goals in a certain percentage. This study aims to explore the possibilities of implementing DDM for small and medium manufacturing firms by combining the advances of computer application software, topology optimization, and additive manufacturing. The main classifications of aerospace components are static and dynamic.
Influences of Global Health Initiatives in Plastic and Reconstructive Surgical Residents
Authors: Gandhikumar Tiffany , David Lisa
Published: October 2024

Purpose:

Over the last decade there is an increased awareness that the need for surgical care in under-resourced countries is contributing to significant health inequities and financial hardship across the globe. Plastic surgery has long been recognized as a surgical discipline that has been successful in deploying resources to help address these inequities but to be sustainable there must be a lasting commitment through teaching and education. The purpose of this study is to answer the question “In plastic and reconstructive surgical residents, how does participation in global health initiatives influence independent clinical practice and their perceptions of global health?”

Methods:

A survey was administered through Redcap to 59 total eligible current or previous Wake Forest School of Medicine plastic and reconstructive surgical residents.

Results:

About 33 out of 34 participants have had some kind of global health exposure with the majority being through mission trips, volunteering, and external rotations. There was a 33.3% improvement in awareness of global surgical disease burden ( P = .000093 < .05), 23.5% improvement in obligations to create global change ( P = .00021 < .05), 26.3% improvement in comfortability with language and cultural barriers ( P = .0013 < .05), and 20.9% improvement in doctor-patient relationships with patients of differing backgrounds ( P = .0019 < .05) when comparing participant’s views prior and after residency training. Overall, participants were inclined to continue with global health initiatives in the future as 75.8% see themselves participating in another global health experience and 90.9% believed participating in global health has an impact on independent clinical practice and professional development post-residency.

Conclusions:

Global health initiatives within surgical residency curriculums have had tremendous effects on the perceptions of global health amongst plastic and reconstructive surgical residents, which may improve physician shortage and global health needs in the future.
The enhanced antibacterial and antibiofilm properties of titanium dioxide nanoparticles biosynthesized by multidrug-resistant Pseudomonas aeruginosa
Authors: Haji Sayran Hamad , Ganjo Aryan R. , Faraj Tola A. , Fatah Mohammed H. , Smail Sakar B.
Published: October 2024

The emergence of Multidrug-resistant (MDR) bacteria are becoming a major worldwide health concern, encouraging the development effective alternatives to conventional antibiotics. The study identified P. aeruginosa and assessed its antimicrobial sensitivity using the Vitek-2 system. Carbapenem-resistant genes were detected through Polymerase chain reaction (PCR). MDR- P. aeruginosa isolates were used to biosynthesize titanium dioxide nanoparticles (TiO2NPs) and characterized using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM). A study involving 78 P. aeruginosa isolates revealed that 85.8% were MDR, with meropenem and amikacin showing effectiveness against 70% of the isolates. The most prevalent carbapenemase gene was blaOXA-48, present in 83% of the isolates. Majority of the isolates formed biofilms, and biosynthesized TiO2NPs were able to reduce biofilm formation by 94%. TiO2NPs exhibited potent antibacterial action against MDR-Gram-negative bacilli pathogens and showed synergistic activity with antibiotics, particularly piperacillin, with a significant fold increase in areas (283%). A new local strain of P. aeruginosa, identified as ON678251 in the World GenBank, was found capable of producing TiO2NPs. Our findings demonstrate the potential of biosynthesized TiO2NPs to manage antibiotic resistance and regulate the formation of biofilms. This presents a promising direction for the creation of novel antimicrobial agents or substitutes for use in clinical settings, particularly in the management of isolates capable of resisting multiple drugs.
Sleep quality disparities in different pregnancy trimesters in low- and middle-income countries: a systematic review and meta-analysis
Authors: Mislu Esuyawkal , Kumsa Henok , Tadesse Shimelis , Arage Mulugeta Wodaje , Susu Belay , Ayele Mulat , Chane Fiker
Published: October 2024

Introduction

Sleep is a crucial determinant of maternal and fetal health, significantly impacting the well-being of both the mother and her developing fetus. Poor sleep quality, characterized by difficulties in falling asleep or staying asleep, can cause poor pregnancy outcome. Conversely, studies came with inconsistent result in the prevalence of poor sleep quality in different trimester of pregnancy. Therefore, this systematic review and meta-analysis study aimed to compare the prevalence of poor sleep quality in different trimesters.

Method

A systematic review and meta-analysis were done on published studies. Electronic data base search was done from PubMed, Hinari, Medline and Google Scholar. Data were extracted with Excel and the analysis were done using STATA version 17. Publication bias was assessed both graphically and statistically. I-square test was used to identify heterogeneity.

Result

In this meta-analysis, 38 studies that measured poor sleep quality using the Pittsburg Sleep Quality Index (PSQI ≥ 5) were included. The pooled prevalence of poor sleep quality was identified as 37.46% (95% CI: 29.26, 45.67) in the first trimester, 47.62% (95% CI: 42.23, 53.02) in the second trimester, and 60.05% (95% CI: 51.32, 68.78) in the third trimester.

Conclusion

This study identified a significant discrepancy in the prevalence of poor sleep quality, which increases as gestational age advances. Therefore, this discrepancy should be addressed, and additional support should be provided to pregnant women to help them achieve adequate sleep, especially as gestational age advances.
HELLP syndrome and associated factors among pregnant women with preeclampsia/eclampsia at a referral hospital in southwestern Uganda: a cross-sectional study
Authors: Abdullahi Fadumo Mohamed , Tornes Yarine Fajardo , Migisha Richard , Kalyebara Paul Kato , Tibaijuka Leevan , Ngonzi Joseph , Kayondo Musa , Byamukama Onesmus , Turanzomwe Stuart , Rwebazibwa Joseph , Ainomugisha Brenda , Kajabwangu Rogers , Mugyenyi Godfrey R. , Lugobe Henry Mark
Published: October 2024

Background

Hemolysis Elevated Liver Enzymes Low Platelets (HELLP) syndrome, a complication of preeclampsia/eclampsia, is associated with severe maternal morbidity and mortality. In resource-limited settings, such as Uganda, gaps in routine laboratory assessments may lead to underdetection of HELLP syndrome. This study determined the prevalence and factors associated with HELLP syndrome among pregnant women with preeclampsia/eclampsia at Mbarara Regional Referral Hospital (MRRH), southwestern Uganda.

Methods

A cross-sectional study was conducted at the high-risk ward of the MRRH from December 2022 to June 2023. Pregnant women diagnosed with preeclampsia or eclampsia were enrolled consecutively. Participants’ sociodemographic and clinical data were collected using an interviewer-administered questionnaire. The diagnosis of complete HELLP syndrome was made based on the Tennessee classification: aspartate aminotransferase enzyme ≥ 70 IU/L, platelet counts < 100,000 cells/µL, and serum lactate dehydrogenase enzyme ≥ 600 IU/L. We used multivariable modified Poisson regression analysis to determine factors associated with HELLP syndrome.

Results

A total of 129 participants with a mean age of 28 ± 6.6 years were enrolled in the study. The prevalence of HELLP syndrome was 18.6% (n = 24; 95% CI: 12.7–26.3%). Independent factors associated with HELLP syndrome were maternal age (adjusted prevalence ratio [aPR]: 4.96; 95% CI: 1.57–15.65; for mothers aged < 20 years compared to those aged 20–34 years), the presence of epigastric pain (aPR: 5.89; 95% CI: 1.41–14.63), and referral from other health facilities (aPR: 3.14; 95% CI: 1.27–7.72).

Conclusion

Approximately 2 of the 10 women who presented with preeclampsia or eclampsia had HELLP syndrome. It is more common among teenage mothers, those with a history of epigastric pain and those referred from lower health facilities. Incorporating routine laboratory testing for HELLP syndrome in the diagnostic protocol for preeclampsia or eclampsia, especially among adolescent mothers, those experiencing epigastric pain, and those referred from lower health facilities, could enhance timely detection and management of mothers with preeclampsia whose pregnancies are complicated by HELLP syndrome.
Access to healthcare services during the COVID-19 pandemic: a cross-sectional analysis of income and user-access across 16 economically diverse countries
Authors: Abel Zachary D. V. , Roope Laurence S. J. , Duch Raymond , Clarke Philip M.
Published: October 2024

Background

National health systems have different strengths and resilience levels. During the COVID-19 pandemic, resources often had to be reallocated and this impacted the availability of healthcare services in many countries. To date there have been few quantitative contemporary studies of inequalities in access to healthcare within and between countries.

In this study, we aim to compare inequality within and between 16 economically diverse countries.

Methods

Online surveys were conducted on 22 150 adults in 16 countries across six continents in 2022. Quota sampling and post-stratification weighting was used to obtain an age, gender, geographically, and educationally representative sample. The study assesses the differences in challenges in access to healthcare during the pandemic (for GP, surgical/clinical and digital GP services) using country-specific expanded health-needs-adjusted Erreygers’ concentration indices and compares these values between countries using a Spearman’s rank correlation coefficient.

Results

Results show wide variation in income-related challenges in access within countries for different types of care. For example, Erreygers’ concentration index for digital services in Colombia exhibited highly regressive inequality at 0·17, compared to Japan with an index of -0·15. Inequalities between countries were also evident, with Spearman rank coefficients of -0·69 and -0·65 (p-values of 0·003 and 0·006) for digital and surgical access, indicating that lower income countries had greater inequality in healthcare access challenges.

Conclusion

During the pandemic, inequalities in challenges to accessing healthcare were greatest in low and middle-income countries. Digital technologies offer a reasonable means to address some of this inequality if adequate support is provided and accessible digital infrastructure exists.
Risk factors and clinical impact of seroma formation following laparoscopic inguinal hernia repair: a retrospective study
Authors: Xie Hong-yang , Chen Bin , Shen Jie , Wang Yi-ping , Shen Wei-cai , Dai Chun-shan
Published: October 2024

Background

Although laparoscopic inguinal hernia repair (LIHR) has advantages over open surgery, postoperative seroma formation remains an issue. This study aimed to investigate the risk factors and clinical outcomes of seroma formation in patients undergoing LIHR.

Methods

From January 2016 to March 2023, clinical data of patients who underwent LIHR were retrospectively analyzed. Patients who developed seroma and those who did not were classified into the seroma and non-seroma groups, respectively. The demographic and clinical characteristics were compared between the two groups. Univariate and multivariate logistic regression analyses were performed for variables of interest. The receiver operating characteristic curve was used to evaluate the risk factors of the binary logistic model, and the cutoff value for each risk factor was obtained.

Results

Data of 128 patients were evaluated. Compared with patients in the non-seroma group, those in the seroma group had a higher body mass index (BMI) (P < 0.001), more direct hernias (P < 0.001), larger hernial orifice size (P < 0.001), more laparoscopic total extraperitoneal hernioplasty (TEP) (P < 0.001), more frequent reduction of hernial sac (P = 0.011), and lower preoperative serum albumin level (PSAL) (P < 0.001). Multivariate logistic regression analyses performed on these variables showed that high BMI (P = 0.005), large hernial orifice (P = 0.001), TEP (P = 0.033), and low PSAL (P = 0.009) were risk factors for seroma formation. Compared with the non-seroma group, the seroma group exhibited a higher numerical rating scale score for postoperative pain (P < 0.001), and longer hospital stays (P = 0.032).

Conclusions

BMI (> 24.5 kg/m2), hernial orifice size (> 2.5 cm), TEP, and PSAL (< 32.5 g/L) were independent risk factors of postoperative seroma formation in patients who underwent LIHR. Although most seromas resolve spontaneously without surgical intervention, seroma formation results in increased patient pain and prolonged hospital stay.
Effect of preparation design on fracture resistance of molars restored with occlusal veneers of different CAD-CAM materials: an in vitro study
Authors: Taha Ahmed Ismail , Hafez Mona Elshirbini
Published: October 2024

Background

Occlusal veneer had been evaluated for mechanical properties using lithium disillicate. However, studies evaluating the mechanical properties of occlusal veneer with different preparation designs and ceramic materials are lacking. So, this in vitro study aimed to evaluate the fracture resistance of occlusal veneers with two designs fabricated from two different ceramic materials.

Material and methods

Fourty mandibular third molars were distributed to 2 groups (n = 20) according to preparation design: group (O) anatomical occlusal reduction and group (OA) anatomical occlusal and 1 mm axial reduction. Each group was additionally subdivided into two subgroups (n = 10) according to ceramic materials; in subgroup X, lithium disilicate (e.max CAD, Ivoclar AG, Schaan, Liechtenstein) was used, and in subgroup S, zirconia-reinforced lithium silicate (ZLS) (Vita Suprinity, VitaZahnfabrik, Bad Säckingen, Germany) was used. All specimens were cemented with a light-cure resin cement (Choice 2, Bisco, Schaumburg, USA). 5000 thermocycles were applied to all specimens with both temperatures of 5 °C and 55 °C in two water baths; the dwell time was 30s at each bath, and the transfer time was 10s. Then all specimens were subjected to a fatigue simulation under dynamic loading of 200 N for 250,000 cycles. A universal testing machine (5500R/1123, Instron, Norwood, USA) was used to evaluate the fracture strength with a crosshead speed of 1 mm/min. All data were analyzed statistically by using a two-way ANOVA, and for some violations of assumptions, these results were compared with those obtained by the nonparametric test (Scheirer Ray Hare) (α = 0.05).

Results

A statistically significantly higher fracture resistance in the ‘OA’ (3389 N) compared to the ‘O’ (2787 N) group regardless of the ceramic material (P < .001) and a statistically significantly higher fracture resistance in the ‘X’ (3295 N) compared to the ‘S’ (2881 N) regardless of the preparation design (P = .015).

Conclusions

For occlusal veneers, all preparation designs and materials (such as Vita Suprinity and e.max CAD) had clinically acceptable fracture resistance values that were greater than the maximal biting forces. On the other hand, the e.max CAD with occlusal veneer, including axial reduction design, demonstrated the maximum fracture resistance value. Finally, no relationship between fracture strength and mode of failure was found.
Acknowledgement and use of advance care directives and goals of care by emergency department staff: a mixed method post intervention study
Authors: Osman Abdi D. , Howell Jocelyn , Yeoh Michael , Lam Louisa , Jones Daryl , Braitberg George
Published: October 2024

Introduction

Advance Care Planning (ACP) refers to a process that includes Advance Care Directives (ACD) and Goals of Care (GOC), a practice widely used for over three decades. Following the findings of an audit and a cross-sectional study in 2019 and 2021 respectively, we implemented several educational and other interventional strategies aimed at enhancing staff awareness and emphasizing the importance of recognizing and documenting of ACD/GOC. The aim of this study was to evaluate the acknowledgement and use of ACD and GOC by Emergency Department (ED) staff following these interventions.

Method

We used a mixed methods approach, incorporating both observational and cross-sectional designs with reflexive thematic analysis. Data extraction for the observational study took place between 1st April and 30th June 2023 focusing on a target population of randomly sampled adults aged ≥ 65 years. Demographics and other ACD and GOC related patients’ clinical data were collected. Data collection for the cross-sectional study occurred between 19th July and 13th September 2023 targeting all ED staff. Information gathered included demographics, awareness about ACD and GOC, including storage location and implementation, as well as knowledge of Medical Treatment decision Makers (MTDM), a jurisdictional term identifying a person legally appointed to make healthcare decisions on behalf of someone who lacks decision-making capacity and other Victorian State legislative requirements were collected.

Results

In the observational period, 22,335 patients attended the ED and 19% (n = 6546) qualified for inclusion from which a sample of 308 patients were randomly extracted. We found ACD documents were noted in the medical records of 6.5% of the sample, fewer than 8% identified in our previous study. There was no correlation between ACD record availability and age (p = 0.054; CI ranging from − 0.065 to 7.768). The response rate for the cross-sectional survey was 12% (n = 340) in contrast to earlier study with 28% (n = 476) respondents. Staff knowledge and familiarity with ACD was 25% and GOC 45%.

Conclusion

After implementing interventions in staff education and ACP awareness, we found that ACD documentation did not improve. However, GOC documentation increased in the context of heightened institutional awareness and integration into the Electronic Medical Records (EMR).
Cervical cancer screening delay and associated factors among women with HIV in Lesotho: a mixed-methods study
Authors: Harder Michelle T. , Mokete Moliehi , Chammartin Frédérique , Lerotholi Malebanye , Motaboli Lipontso , Kopo Mathebe , Kao Mpho , Mokebe Moleboheng , Chejane Ntoiseng , Mahlatsi Palesa , Nyakane Morongoe , Tarumbiswa Tapiwa , Labhardt Niklaus D. , Tschumi Nadine , Belus Jennifer M.
Published: October 2024

Background

Cervical cancer is the fourth most common cancer in women worldwide, and women with human immunodeficiency virus (HIV) are particularly at risk of developing it. Regular screening effectively prevents morbidity and mortality. This mixed-methods study quantitatively assessed cervical cancer screening uptake and qualitatively explored the process of undergoing cervical cancer screening to understand possible reasons for delayed screening among women with HIV in Lesotho.

Methods

Between October 2020 and March 2022, the Viral load Triggered ART care in Lesotho (VITAL) trial enrolled women aged 18 years and older with HIV who were taking antiretroviral therapy (ART). Cervical cancer screening delay was defined as reporting a screening that occurred more than two years ago or never having been screened. Cervical cancer screening uptake and the association between screening delay and sociodemographic variables were assessed using a multivariable mixed-effects logistic regression model accounting for clustering at clinic level. In-depth interviews were conducted with 16 women to obtain information on awareness, perceptions, and barriers to cervical cancer screening and were analyzed using thematic analysis.

Results

Quantitative data were available for 3790 women. Among them, cervical cancer screening was delayed in 1814 (47.9%), including 1533 (40.5%) who were never screened. Compared to women aged 25 to 39 years, women aged 18 to 24 years (adjusted odds ratio (aOR) 2.8; 95% confidence interval (CI) 2.1–3.7), women aged 40 to 59 years (aOR 1.3; CI 1.1–1.6), and women older than 60 years (aOR 3.9; CI 3.0-5.1) were at higher risk of screening delay. Furthermore, time on ART below 6 months (aOR 1.6; CI 1.1–2.3) compared to above 6 months was associated with screening delay. Qualitative data identified limited awareness of cervical cancer risks and screening guidelines, misconceptions and fears created by the influence of other women’s narratives, and low internal motivation as the main barriers to screening uptake.

Conclusions

Cervical cancer screening delay was common. Limited personal awareness and motivation as well as the negative influence of other women were the primary internal barriers to cervical cancer screening. Awareness and screening campaigns in Lesotho should consider these factors.

Trial registration

clinicaltrials.gov, NCT04527874, August 27, 2020.
VEGF-dependent testicular vascularisation involves MEK1/2 signalling and the essential angiogenesis factors, SOX7 and SOX17
Authors: Blücher Rheannon O. , Lim Rachel S. , Ritchie Matthew E. , Western Patrick S.
Published: October 2024

Background

Abnormalities of in utero testis development are strongly associated with reproductive health conditions, including male infertility and testis cancer. In mouse testes, SOX9 and FGF9 support Sertoli cell development, while VEGF signalling is essential for the establishment of vasculature. The mitogen-activated protein kinase (MAPK) pathway is a major signalling cascade, essential for cell proliferation, differentiation and activation of Sry during primary sex-determination, but little is known about its function during fetal testis morphogenesis. We explored potential functions of MAPK signalling immediately after the establishment of testis cords in embryonic day (E)12.5 Oct4-eGFP transgenic mouse testes cultured using a MEK1/2 inhibitor.

Results

RNA sequencing in isolated gonadal somatic cells identified 116 and 114 differentially expressed genes after 24 and 72 h of MEK1/2 inhibition, respectively. Ingenuity Pathway Analysis revealed an association of MEK1/2 signalling with biological functions such as angiogenesis, vasculogenesis and cell migration. This included a failure to upregulate the master transcriptional regulators of vascular development, Sox7 and Sox17, VEGF receptor genes, the cell adhesion factor gene Cd31 and a range of other endothelial cell markers such as Cdh5 (encoding VE-cadherin) and gap junction genes Gja4 and Gja5. In contrast, only a small number of Sertoli cell enriched genes were affected. Immunofluorescent analyses of control testes revealed that the MEK1/2 downstream target, ERK1/2 was phosphorylated in endothelial cells and Sertoli cells. Inhibition of MEK1/2 eliminated pERK1/2 in fetal testes, and CD31, VE-cadherin, SOX7 and SOX17 and endothelial cells were lost. Consistent with a role for VEGF in driving endothelial cell development in the testis, inhibition of VEGFR also abrogated pERK1/2 and SOX7 and SOX17 expressing endothelial cells. Moreover, while Sertoli cell proliferation and localisation to the testis cord basement membrane was disrupted by inhibition of MEK1/2, it was unaffected by VEGFR inhibition. Instead, inhibition of FGF signalling compromised Sertoli cell proliferation and localisation to the testis cord basement membrane.

Conclusions

Together, our data highlight an essential role for VEGF-dependent MEK1/2 signalling in promoting vasculature and indicate that FGF signalling through MEK1/2 regulates Sertoli cell organisation in the developing mouse testis.
Ciliary body myxoid epithelioid sarcoma in a cat: a case report
Authors: Leis Marina L , Sayi Soraya , Grahn Bruce H
Published: October 2024

Background

The majority of primary, intraocular tumors in cats originate from the uvea and include feline diffuse iris melanoma, lymphoma, and iridociliary epithelial adenoma or adenocarcinoma. In this case report, we describe for the first time the clinical, histological, and immunohistochemical findings of a rare myxoid intraocular neoplasm arising from the ciliary body in a cat.

Case presentation

A 14-year-old, female, spayed domestic shorthaired cat was presented for evaluation of discolouration of the right eye. Upon examination, a clear to light whitish-tan, bubble-shaped intraocular mass adherent to the inferior ciliary body and extending into the anterior chamber was noted. Within five weeks, the tumor was significantly larger and the eye had developed secondary glaucoma so was enucleated. Light microscopic examination of the globe revealed a multinodular, hypocellular neoplasm arising from the ciliary body composed of interwoven spindle cells embedded in abundant amounts of a lightly basophilic myxoid matrix. Neoplastic cells exhibited strong immunoreactivity for cytokeratin while also showing moderate to strong immunoreactivity to vimentin. A diagnosis was therefore made of an unusual intraocular myxoid epithelioid sarcoma arising from the ciliary body.

Conclusions

Although apparently exceedingly rare, epithelioid myxosarcoma should be included as a differential diagnosis for intraocular tumors in cats and they represent a clinical, histologic, and immunohistochemical diagnostic challenge. Early surgical intervention should be considered to prevent local invasion and ascension to the brain.
Pulmonary artery mass with PIK3CA mutation after orthotopic heart transplantation
Authors: Son Andre Y. , Clark Aaron J. , Alexiev Borislav A. , Pham Duc Thinh
Published: October 2024

Background

Patients can develop de novo malignancies following orthotopic heart transplantation. However, vascular tumors are not commonly described in this population.

Case presentation

We present a 69-year-old female with a history of orthotopic heart transplantation for chemotherapy-induced cardiomyopathy who developed an incidental pulmonary artery mass six years after her transplantation. Given concerns for malignancy, the patient underwent an operative excisional biopsy through a left anterior mini-thoracotomy with femoral artery and vein cannulation for cardiopulmonary bypass. The mass was determined to be a non-malignant vascular overgrowth with PIK3CA mutation.

Conclusion

We present the case of an unusual pulmonary artery mass with PIK3CA mutation found in a post heart transplant patient. We were able to spare her the morbidity of a redo-sternotomy by excising the mass via a minimally invasive left anterior thoracotomy approach.
Preclinical investigations and a first-in-human phase 1a trial of JS007, a novel anti-CTLA-4 antibody, in patients with advanced solid tumors
Authors: Zhou Chenfei , Jiang Jinling , Xiang Xiaojun , Liu Hongli , Wu Guowu , Zeng Ruichao , Lu Tong , Zhang Mengqi , Shen Yuteng , Hong Min , Zhang Jun
Published: October 2024

Background

Blocking cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) shows substantial antitumor efficacy. Here, we report the preclinical data and outcomes of a first-in-human phase 1a trial of JS007, a novel anti-CTLA-4 antibody, in advanced solid tumors.

Methods

In preclinical studies, both in vitro characteristics and in vivo characteristics of JS007 were investigated. The clinical trial included a dose escalation phase and a dose expansion phase. Eligible patients with previously treated advanced solid tumors were enrolled. In the dose escalation phase, JS007 was administered intravenously every 3 weeks at doses of 0.03, 0.3, 1, 3, and 10 mg/kg. Then, 3 and 10 mg/kg were chosen for the dose expansion phase. The primary endpoints included the maximum tolerated dose (MTD) of JS007 based on dose-limiting toxicities (DLTs) and safety.

Results

JS007 could effectively bind to CTLA-4 and induce an immune response in vitro. Potent in vivo antitumor activity of JS007 was observed. Increased T cell infiltration and T regulatory (Treg) cell depletion in tumor microenvironment of cancer cell xenografts were detected after treated with JS007. Pharmacological analysis in experimental animals showed a dose-proportional increase in exposure. In the clinical trial, a total of 28 patients were treated with JS007 across 5 dose levels. No DLTs occurred. The MTD did not reach at the highest dose tested (10 mg/kg). Twenty-three (82.1%) patients experienced at least one treatment-related adverse event (TRAE). The incidence of Grade ≥ 3 TRAEs was 28.6% (8/28) with alanine aminotransferase increase (7.1%, 2/28) being the most frequently reported TRAE. No severe immune-related adverse event (irAE) occurred. Pharmacological profiles of JS007 in patients were similar to those in animal models. Serum concentration of JS007 showed a dose-dependent escalation, and the half-life of JS007 was 9.4 ~ 12.2 days. Treatment-induced anti-drug antibody was detected in 2 patients. The disease control rate was 50% (14/28), and the median overall survival was 14.7 months.

Conclusions

JS007 preliminarily demonstrates good tolerance and encouraging antitumor activity in patients with previously treated advanced solid tumors.

Trial registration

ClinicalTrials.gov identifier: NCT05049265 (Sep 20, 2021).
Effects of lactic acid bacteria and cellulase additives on the fermentation quality, antioxidant activity, and metabolic profile of oat silage
Authors: Wang Xin , Liu Han , Wang Yuan , Lin Yanli , Ni Kuikui , Yang Fuyu
Published: October 2024

Oats (Avena sativa L.) are rich in nutrients and bioactive compounds, serving as a roughage source for ruminants. This study investigated the impact of lactic acid bacteria (LAB), cellulase (M), and their combinations (LM) on the fermentation quality and metabolic compounds of oat silage. Results demonstrated that all additive treatments significantly increased lactic acid content compared to the control group (P < 0.05), with the lactic acid bacteria treatment group exhibiting the lowest pH value (P < 0.05). Analysis of antioxidant activity and metabolites in oat silage over 60 days revealed 374 differential metabolites with 113 up-regulated and 261 down-regulated, and all treatment groups showing higher antioxidant activity than raw oat materials (P < 0.05). Although no significant differences in antioxidant activity were observed among the various treatment groups in this experiment, notable changes in metabolic pathways were identified. Furthermore, two metabolites (carboxylic acids and derivatives and benzene and substituted derivatives) were identified through non-targeted metabolomics technology, both of which are strongly associated with the antioxidant activity of oat silage. This finding provides a theoretical basis for the efficient use of oat silage in animal husbandry.

Graphical abstract
The fundamentals of a parental peer-to-peer support program in the NICU: a scoping review
Authors: Pascual A. , Wielenga J. M. , Ruhe K. , van Kaam A. H. , Denswil N. P. , Maaskant J. M.
Published: October 2024

Purpose and background

Parental peer support is part of the Family Integrated Care model in NICUs. However, little attention has been devoted to the specific content and organization of parental peer support programs. This scoping review aimed to identify (1) the preferred content of a parental peer support intervention, (2) the organizational processes, and (3) the suggested educational curriculum for peer support providers within existing programs in neonatal care.

Discussion

Parental peer support programs have the goal to provide emotional support, information and assistance, and are to empower parents in the NICU. To achieve these goals, veteran parents receive training in communication skills, roles and boundaries, mental health, (non)medical aspects in the NICU and post-discharge preparation. Data on the organizational components remain limited. Hence, the question remains how the organization of a parental peer support program, and the training and supervision of veteran parents should be managed.

Implications for research and practice

This scoping review provides a variety of aspects that should be considered when developing and implementing a parental peer support program in the NICU. Program development preferably involves NICU staff at an early stage. Future research should focus on the support of diverse populations in terms of culture, social economic status and gender, and on the effects of parental peer support on parent and infant.