bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal Exposure to Opioids and Neurodevelopmental Disorders in Children: A Bayesian Mediation Analysis
Authors: Wang Shuang , Puggioni Gavino , Wu Jing , Meador Kimford J , Caffrey Aisling , Wyss Richard , Slaughter Jonathan L , Suzuki Etsuji , Ward Kristina E , Lewkowitz Adam K , Wen Xuerong
Published: September 2023

This study explores natural direct and joint natural indirect effects (JNIE) of prenatal opioid exposure on neurodevelopmental disorders (NDDs) in children mediated through pregnancy complications, major and minor congenital malformations, and adverse neonatal outcomes, using Medicaid claims linked to vital statistics in Rhode Island, United States, 2008–2018. A Bayesian mediation analysis with elastic net shrinkage prior was developed to estimate mean time to NDD diagnosis ratio using posterior mean and 95% credible intervals (CrIs) from Markov chain Monte Carlo algorithms. Simulation studies showed desirable model performance. Of 11,176 eligible pregnancies, 332 had ≥2 dispensations of prescription opioids anytime during pregnancy, including 200 (1.8%) having ≥1 dispensation in the first trimester (T1), 169 (1.5%) in the second (T2), and 153 (1.4%) in the third (T3). A significant JNIE of opioid exposure was observed in each trimester (T1, JNIE = 0.97, 95% CrI: 0.95, 0.99; T2, JNIE = 0.97, 95% CrI: 0.95, 0.99; T3, JNIE = 0.96, 95% CrI: 0.94, 0.99). The proportion of JNIE in each trimester was 17.9% (T1), 22.4% (T2), and 56.3% (T3). In conclusion, adverse pregnancy and birth outcomes jointly mediated the association between prenatal opioid exposure and accelerated time to NDD diagnosis. The proportion of JNIE increased as the timing of opioid exposure approached delivery.
Machine learning-based quantification for disease uncertainty increases the statistical power of genetic association studies
Authors: Park Jun Young , Lee Jang Jae , Lee Younghwa , Lee Dongsoo , Gim Jungsoo , Farrer Lindsay , Lee Kun Ho , Won Sungho
Published: September 2023

Motivation

Allowance for increasingly large samples is a key to identify the association of genetic variants with Alzheimer’s disease (AD) in genome-wide association studies (GWAS). Accordingly, we aimed to develop a method that incorporates patients with mild cognitive impairment and unknown cognitive status in GWAS using a machine learning-based AD prediction model.

Results

Simulation analyses showed that weighting imputed phenotypes method increased the statistical power compared to ordinary logistic regression using only AD cases and controls. Applied to real-world data, the penalized logistic method had the highest AUC (0.96) for AD prediction and weighting imputed phenotypes method performed well in terms of power. We identified an association (P<5.0×10-8) of AD with several variants in the APOE region and rs143625563 in LMX1A. Our method, which allows the inclusion of individuals with mild cognitive impairment, improves the statistical power of GWAS for AD. We discovered a novel association with LMX1A.

Availability and implementation

Simulation codes can be accessed at https://github.com/Junkkkk/wGEE_GWAS.
Towards precise PICO extraction from abstracts of randomized controlled trials using a section-specific learning approach
Authors: Hu Yan , Keloth Vipina K , Raja Kalpana , Chen Yong , Xu Hua
Published: September 2023

Motivation

Automated extraction of population, intervention, comparison/control, and outcome (PICO) from the randomized controlled trial (RCT) abstracts is important for evidence synthesis. Previous studies have demonstrated the feasibility of applying natural language processing (NLP) for PICO extraction. However, the performance is not optimal due to the complexity of PICO information in RCT abstracts and the challenges involved in their annotation.

Results

We propose a two-step NLP pipeline to extract PICO elements from RCT abstracts: (i) sentence classification using a prompt-based learning model and (ii) PICO extraction using a named entity recognition (NER) model. First, the sentences in abstracts were categorized into four sections namely background, methods, results, and conclusions. Next, the NER model was applied to extract the PICO elements from the sentences within the title and methods sections that include >96% of PICO information. We evaluated our proposed NLP pipeline on three datasets, the EBM-NLPmod dataset, a randomly selected and re-annotated dataset of 500 RCT abstracts from the EBM-NLP corpus, a dataset of 150 Coronavirus Disease 2019 (COVID-19) RCT abstracts, and a dataset of 150 Alzheimer’s disease (AD) RCT abstracts. The end-to-end evaluation reveals that our proposed approach achieved an overall micro F1 score of 0.833 on the EBM-NLPmod dataset, 0.928 on the COVID-19 dataset, and 0.899 on the AD dataset when measured at the token-level and an overall micro F1 score of 0.712 on EBM-NLPmod dataset, 0.850 on the COVID-19 dataset, and 0.805 on the AD dataset when measured at the entity-level.

Availability and implementation

Our codes and datasets are publicly available at https://github.com/BIDS-Xu-Lab/section_specific_annotation_of_PICO.
DeepMHCI: an anchor position-aware deep interaction model for accurate MHC-I peptide binding affinity prediction
Authors: Qu Wei , You Ronghui , Mamitsuka Hiroshi , Zhu Shanfeng
Published: September 2023

Motivation

Computationally predicting major histocompatibility complex class I (MHC-I) peptide binding affinity is an important problem in immunological bioinformatics, which is also crucial for the identification of neoantigens for personalized therapeutic cancer vaccines. Recent cutting-edge deep learning-based methods for this problem cannot achieve satisfactory performance, especially for non-9-mer peptides. This is because such methods generate the input by simply concatenating the two given sequences: a peptide and (the pseudo sequence of) an MHC class I molecule, which cannot precisely capture the anchor positions of the MHC binding motif for the peptides with variable lengths. We thus developed an anchor position-aware and high-performance deep model, DeepMHCI, with a position-wise gated layer and a residual binding interaction convolution layer. This allows the model to control the information flow in peptides to be aware of anchor positions and model the interactions between peptides and the MHC pseudo (binding) sequence directly with multiple convolutional kernels.

Results

The performance of DeepMHCI has been thoroughly validated by extensive experiments on four benchmark datasets under various settings, such as 5-fold cross-validation, validation with the independent testing set, external HPV vaccine identification, and external CD8+ epitope identification. Experimental results with visualization of binding motifs demonstrate that DeepMHCI outperformed all competing methods, especially on non-9-mer peptides binding prediction.

Availability and implementation

DeepMHCI is publicly available at https://github.com/ZhuLab-Fudan/DeepMHCI.
Brain tumour genetic network signatures of survival
Authors: Ruffle James K , Mohinta Samia , Pombo Guilherme , Gray Robert , Kopanitsa Valeriya , Lee Faith , Brandner Sebastian , Hyare Harpreet , Nachev Parashkev
Published: September 2023

Tumour heterogeneity is increasingly recognized as a major obstacle to therapeutic success across neuro-oncology. Gliomas are characterized by distinct combinations of genetic and epigenetic alterations, resulting in complex interactions across multiple molecular pathways. Predicting disease evolution and prescribing individually optimal treatment requires statistical models complex enough to capture the intricate (epi)genetic structure underpinning oncogenesis.

Here, we formalize this task as the inference of distinct patterns of connectivity within hierarchical latent representations of genetic networks. Evaluating multi-institutional clinical, genetic and outcome data from 4023 glioma patients over 14 years, across 12 countries, we employ Bayesian generative stochastic block modelling to reveal a hierarchical network structure of tumour genetics spanning molecularly confirmed glioblastoma, IDH-wildtype; oligodendroglioma, IDH-mutant and 1p/19q codeleted; and astrocytoma, IDH-mutant.

Our findings illuminate the complex dependence between features across the genetic landscape of brain tumours and show that generative network models reveal distinct signatures of survival with better prognostic fidelity than current gold standard diagnostic categories.
SOCS1 acts as a ferroptosis driver to inhibit the progression and chemotherapy resistance of triple-negative breast cancer
Authors: Wang Yiding , Pang Xiaoling , Liu Yuexin , Mu Guiling , Wang Qian
Published: September 2023

Objectives

Ferroptosis is involved in many types of cancers, including triple-negative breast cancer (TNBC). Suppressor of cytokine signaling 1 (SOCS1) has recently been implicated as a regulator of ferroptosis. We aim to explore whether targeting SOCS1 is a potential therapeutic strategy for TNBC therapy.

Methods

Stable cell lines were constructed using lentivirus transfection. Cell viability was determined using CCK-8 and cell colony formation assays, respectively. Assays including lactate dehydrogenase release, lipid peroxidation and malondialdehyde assays were conducted to evaluate ferroptosis. Real-time quantitative polymerase chain reaction and western blotting were performed to evaluate mRNA and protein expression, respectively. A xenograft animal model was established by subcutaneous injection of cells into the flank.

Results

Our results showed that SOCS1 overexpression inhibited cell proliferation and induced ferroptosis in TNBC cells, while SOCS1 knockdown promoted cell proliferation and reduced ferroptosis. We also found that SOCS1 regulated ferroptosis by modulating GPX4 expression. Furthermore, SOCS1 regulated cisplatin resistance in TNBC cells by promoting ferroptosis. Our in vivo data suggested that SOCS1 regulated tumor growth and cisplatin resistance in vivo.

Conclusions

SOCS1 inhibits the progression and chemotherapy resistance of TNBC by regulating GPX4 expression.
The impact of perioperative non-steroidal anti-inflammatory drugs use on pleurodesis following thoracic surgery
Authors: Kutywayo Kudzayi , Habib Akolade A , Caruana Edward J
Published: September 2023

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: in patients who have had {visceral and parietal pleural symphysis}, {do NSAIDs reduce} {the efficacy of pleurodesis}? Sixteen papers were discovered in the search. Of these, 3 human studies were included in the analysis. None showed a significantly higher rate of pleurodesis failure in patients given perioperative NSAIDs. The results from the largest study met criteria for noninferiority. Within the constraints of the study, the results suggest that systemic administration of nonsteroidal anti-inflammatory medication in the perioperative period does not necessarily attenuate effective pleurodesis. However, further study is needed as there is a clear paucity of human-based studies.
Long-term outcomes of the classic Konno–Rastan procedure in paediatric and adult patients: impact of aortic annulus size on patient outcomes
Authors: Amirghofran Ahmad Ali , Salimi Maryam , Kamran Hooman , Bazrafshan Hamed , Navaei Mohammad Rafati , Shokrollahi Ali , Nirooei Elahe , Edraki Mohammadreza , Amoozgar Hamid , Ajami Gholamhossein , Arabi Hamid
Published: September 2023

OBJECTIVES

The classic Konno–Rastan procedure may yield different outcomes regarding aortic annulus diameters ≤15 mm and larger. Focusing on the effect of the diameter of the aortic annulus, we described the long-term outcomes of our patients.

METHODS

The outcomes of paediatric and adult patients who underwent surgery from 2000 to 2021 were studied retrospectively. The patient population was divided into 2 groups with aortic annulus diameters ≤15 mm and >15, and the outcomes were compared between the 2 groups.

RESULTS

A total of 48 patients, with a mean age of 12.24 ± 9.42 years (2–53 years) and a median follow-up duration of 8 years (7 months to 20 years) with an IQR of 5.5, were enrolled. The mean peak instantaneous pressure gradient was 78.97 ± 25.29 mmHg, which decreased to 21.43 mmHg (P-value = 0.012). The maximum left ventricular outflow tract gradient at the last follow-up was 28.21 mmHg, with the exception of 1 case with a gradient of 68.45 mmHg. The mean diameter of the aortic annulus was 15.34 ± 3.87 mm (8–23 mm), and the mean prosthetic valve size was 20.31 mm, which was 5 mm (33%) larger than the native annulus diameter. The overall mortality rate was 6.3%, with 1 death in the hospital and 2 in the first year after the surgery. The major complication rate, including mortality, heart block and reintervention, was higher in patients with ≤15 mm annulus (P-value = 0.028.) However, there was no difference between the 2 groups in follow-up. Four (8%) late cardiac reoperations were performed, none of which were related to our surgeries.

CONCLUSIONS

Kono–Rastan surgery for patients with aortic valve diameter of ≤15 mm can be performed with acceptable long-term outcomes.
Multinational corporations’ capital allocation decisions across asymmetric risk locations: intertemporal equilibrium and optimal transitional adjustment paths
Authors: Fedderke Johannes W , Luiz John M , Barnard Helena
Published: September 2023

Multinational corporations operate across locations with different risk profiles. We examine how multinational corporations address the optimal allocation of capital across multiple locations and analyse the transition path to the intertemporal equilibrium. Our model considers returns, risks and adjustment costs to reflect the dynamics of allocating capital assets across locations over time, as well as the mix of assets across locations in equilibrium. Variational calculus is employed to show that the model confirms standard expectations that where a location’s rates of return on assets increase, or adjustment costs decrease, equilibrium capital allocation and transitional capital flows to that location will increase. Symmetrically, rising (falling) risk increases (decreases) the proportion of the capital asset holdings of a location. The crucial insight is that for the transitional dynamics to intertemporal equilibrium, the optimal relative capital flow response to changes in risk can generate relative portfolio allocations that may initially move in the opposite direction to that implied by the stock equilibrium. Specifically, an increase in risk for the high-risk location may initially result in an increase in the relative capital asset flow to the high-risk location relative to the low-risk location. Empirical research must account for the possibility of non-monotonicity in asset allocation flows to avoid misspecification. Moreover, policy makers will have to anticipate possible pressure for reversal resulting from short-term worsening capital flows. These reflections are mirrored in recent research calls for separating structural and transition effects of institutional change on the investment decisions by multinational corporations.
The right to terminate pregnancy (abortion): reflections from Turkey
Authors: Şenol Hatice Kübra Ercoşkun , Ercoşkun Pelin
Published: September 2023

In this article, the right to terminate pregnancy is discussed comparatively in terms of the situation in Turkey and the rest of the world. We have concluded that certain minimum conditions must be met to be able to talk about the full recognition of this right. Recognizing that pregnancy can be terminated voluntarily is the most important of these conditions. Just as the period in which this right can be exercised should not be kept short, it should also be accepted that it can only be used based on the will of a pregnant person who has the power of discernment. In addition, certain obligations must be avoided, such as receiving counseling services before the termination of pregnancy and then waiting for a certain period of time to pass. In cases where pregnancy can be terminated because of an anomaly, a disease, or a crime, it is important to make clear arrangements that will not make practitioners, especially physicians, hesitate to perform such a procedure. Finally, the State must never forget that it is obliged to organize services for the termination of pregnancies in a way that is easily accessible to everyone who may need this procedure.
SWOT: Analysis of Strategic Approaches in Total Force Fitness and Whole Health Summit
Authors: Triscari Craig A , Rutherford Ronald B , DiMercurio Carlo , Franzos M Alaric
Published: September 2023

Leaders and subject matter experts from the Department of Defense (DoD), Department of Veterans Affairs, and other organizations participated in the Total Force Fitness (TFF) and Whole Health Summit. TFF and Whole Health Summit are holistic programs designed to maximize performance and resilience through interventions across multiple domains of health, wellness, and preparedness. Findings generated from the Summit were collected and categorized using a tool known as a Strengths–Weaknesses–Opportunities–Threats (SWOT) analysis. The SWOT analysis highlighted key beneficial points regarding implementation of TFF–Whole Health principles including (1) a strong history of collaboration between the DoD and Department of Veterans Affairs, (2) a potential boost to recruitment and retention, and (3) better support for military-to-civilian transition. Risks identified ranged from policy limitations to program development within a fiscally constrained environment. The SWOT analysis can focus future efforts.
Do funding modes matter? A multilevel analysis of funding allocation mechanisms on university research performance
Authors: Zacharewicz Thomas , Pulido Pavón Noemi , Palma Martos Luis Antonio , Lepori Benedetto
Published: September 2023

Over the last decades, most EU countries have profoundly reshaped their public research funding systems by shifting from traditional institutional block-funding towards more project-based mechanisms. The main rationale underlying this evolution builds on the assumption that project funding would foster research performance through the introduction of competitive allocation mechanisms. In contrast with the general increase of project funding, evidence is mixed regarding a positive effect of competitive funding mechanisms on research performance, as some studies find a positive impact, other a negative one or no impact. Differences also appear across studies regarding research actors, funding streams, and research outputs considered. This article integrates these different approaches through a multilevel design gathering funding inputs for 10 countries and 148 universities between 2011 and 2019 and assesses their impact on the quantity and quality of publications. Results highlight no impact of national and university-level competitive funding mechanisms on universities highly cited publications and no clear effect on the quantity of publications.
Management of adult-onset Still's disease: evidence- and consensus-based recommendations by experts
Authors: Leavis Helen L , van Daele Paul L A , Mulders-Manders Catharina , Michels Renée , Rutgers Abraham , Legger Elizabeth , Bijl Marc , Hak Elisabeth A , Lam-Tse Wai-Kwan , Bonte-Mineur Femke , Fretter Peter , Simon Anna , van Paassen Pieter , van der Goes Marlies C , Flendrie Marcel , Vercoutere Ward , van Lieshout Antoine W T , Leek Arjen , Vastert Sebastiaan J , Tas Sander W
Published: September 2023

Objectives

Adult-onset Still’s disease (AOSD) is a rare condition characterized by fevers, rash, and arthralgia/arthritis; most doctors treating AOSD in the Netherlands treat <5 patients per year. Currently, there is no internationally accepted treatment guideline for AOSD. The objectives of this study were to conduct a Delphi panel aimed at reaching consensus about diagnostic and treatment strategies for patients with AOSD and to use the outcomes as a basis for a treatment algorithm.

Methods

The Delphi panel brought together 18 AOSD experts: rheumatologists, internists and paediatricians. The Delphi process consisted of three rounds. In the first two rounds, online lists of questions and statements were completed. In the third round, final statements were discussed during a virtual meeting and a final vote took place. Consensus threshold was set at 80%. Two targeted literature searches were performed identifying the level of evidence of the consensus-based statements.

Results

Consensus was reached on 29 statements, including statements related to diagnosis and diagnostic tests, definition of response and remission, the therapy, the use of methotrexate and tapering of treatment. The panel consented on reduction of the use of glucocorticoids to avoid side effects, and preferred the use of biologics over conventional treatment. The role of IL-1 and IL-6 blocking agents was considered important in the treatment of AOSD.

Conclusion

In this Delphi panel, a high level of consensus was achieved on recommendations for diagnosis and therapy of AOSD that can serve as a basis for a treatment guideline.
Abstract 20 Long-Term Follow-Up of Cryopreserved Umbilical Cord Tissue as a Source of Mesenchymal Stem Cells
Authors: Rico Jessica Patiño , Raffo Diego , Romaso Karen , Neira Celeste , Sasso Diego Fernandez
Published: September 2023

Introduction

Mesenchymal stem cells (MSCs) can differentiate into various cell types and exhibit immunomodulatory and paracrine effects. The cryopreservation of umbilical cord tissue as a viable source of MSCs has great potential for the field of regenerative medicine. We previously demonstrated that it is feasible to cryopreserve umbilical cord tissue cut into small fragments measuring 2 to 5 mm in length and obtain viable cells by thawing them between 30 and 60 days after freezing.

Objectives

We aim to assess the condition of previously frozen samples for periods exceeding one year and analyze the data obtained from the cryopreservation of new samples.

Methods

A total of 834 new samples were frozen with our protocol for umbilical cord tissue cryopreservation. These Samples were thawed after obtaining microbiological contamination results of each sample. Additionally, a group of 100 samples that have been kept frozen for at least one year were selected to be thawed to assess the viability of the tissue frozen for extended periods of time. All cultures were maintained and the days to reach confluence were registered.

Results

The microbial analysis of the group of 834 new samples showed similar microbial profile and risk factors to those previously reported by us, with higher contamination frequencies associated with vaginal delivery and samples obtained by less experienced personnel in the operating room. Moreover, similar to our previous reports, the most frequent microorganism detected in contaminated samples were Staphylococcus sp, Escherichia Coli, Enterococcus sp and Streptocuccus sp. The group of 100 samples that were kept frozen for a minimum period of one year were thawed to assess if we could obtain viable cells from them. All cell cultures obtained from the thawed tissue were successful, reaching confluence between days 18 and 23, which is consistent with our previously observed timings.

Discussion

New cryopreserved tissue samples, and samples frozen for more than one year had viable cells that can be expanded as a source of MSCs. Microbial profile of those samples showed association with sample collection conditions at the operating room indicating that proper training of the personnel is the key to reduce contamination rates.
Abstract 25 Cord Blood Mononuclear Cells and Cord Blood Plasma Alter Human Cardiac Endothelial Cell Angiogenic Sprouting and Growth In Vitro
Authors: Chuang Angela , Angerosa Julie , Tian Pei , Elwood Ngaire , Brizard Christian , Pepe Salvatore
Published: September 2023

Introduction

The mononuclear cell fraction of human placental cord blood (CBMNC) comprises immune cells, hematopoietic, mesenchymal and other stem or progenitor cells. CBMNCs are proposed to afford therapeutic benefit based on their paracrine release of multiple cytokines, growth factors and other proteins that stimulate signalling for wound healing, including attenuation of inflammation and fibrosis. Whether CBMNCs augment angiogenic sprouting and tube formation by endothelial cells in human ventricular myocardium is not well characterised.

Objectives

The aim of this study was to investigate the in vitro influence of CBMNCs on endothelial cell angiogenic-like growth.

Methods

A tube formation assay for human donor primary ventricular myocardium microvascular endothelial cells (HMVECs), (3 female donors, age 48-50 yrs, 3 replicates per treatment group) was established using Matrigel-coated 96-well plates (62,500-78,125 cells/cm2). Cells from passage 5-8 were used for all experiments.. Angiogenic processes, as characterized by endothelial sprouting followed by tube extension into honeycomb-like mesh structures, were imaged over 24 hours. HMVECs were treated with CBMNCs at a concentration of 1:10 (MNC:HMVEC) or cord blood plasma (1μg/μL) at 0h, 3h, or 6h after the HMVECs were seeded. The cells were visualized by phase contrast microscope and images (4x magnification) were analysed using the Angiogenesis Analyzer plugin in FIJI ImageJ. Size exclusion chromatography and multiplex ELISAs were performed to determine the presence of analytes in media collected from each well.

Results

CBMNC-treated HMVECs exhibited greater average total elongated branching length and more tube-like structured meshes, compared to untreated controls. MMP-1, MMP-2, MMP-9, MMP-10, TIMP-1, TIMP-2, angiopoietin-2, EGF, endoglin, endothelin-1, FGF-2, follistatin, HB-EGF, IL-8, PLGF, VEGF-A, and VEGF-C were detected in extracellular media during in vitro tube formation. With CBMNC treatment, only MMP-9 was increased by 475.94%, whereas angiopoietin-2, follistatin, and PLGF levels were decreased by 27.90%, 15.90%, and 26.18% respectively. In contrast, CB plasma-treated HMVECs did not form tube sprouts, instead an intense endothelial cell proliferation was observed which was associated with increased MMP-2, MMP-9, endothelin-1 and IL-8 levels with decreased angiopoietin-2, HB-EGF, PLGF, and endoglin levels.

Discussion

CBMNC treatment enhanced pro-angiogenic processes in HMVECs in vitro through increased branching and network formation, whereas CB plasma evoked cell proliferation.
Abstract 27 Secretome of Umbilical Cord Mesenchymal Stem Cells: Potential Effects on Melanoma
Authors: Fernandes Pablo , Gomes Andreia , Coelho Pedro
Published: September 2023

Introduction

Melanoma, a tumor resulting from the malignant transformation of melanocytes, is characterized by its aggressive nature and propensity to metastasize. Current treatment options for advanced melanoma are limited and mostly ineffective, highlighting the need for novel therapeutic approaches. Mesenchymal stem cells (MSCs) have increased considerable attention due to their anti-cancer and immunomodulatory properties. In particular, human umbilical cord MSCs (hUCMSCs) have shown promise in various therapeutic applications.

Objectives

The objective of this research was to assess and understand the potential therapeutic effects of conditioned media (CM) derived from hUCMSCs on melanoma cells in vitro.

Methods

hUCMSC, isolated from the umbilical cord of seven healthy neonates by enzymatic digestion followed by direct plastic adherence method, were cultivated and their CM stored for subsequent assays. Then, malignant melanoma B16F10 cells were treated using a final concentration of 100% of hUCMSC-CM for 24 hours. Afterward, their viability, adhesion, and motility were accessed by MTT, crystal violet, and scratch wound healing assays, respectively.

Results

The MTT assay showed the inhibition of B16F10 cell viability in all treated groups compared to the control group (32%; p<0,05 vs control, n=7). Moreover, crystal violet staining revealed that hUCMSC-CM enhanced the adhesion capacity of melanoma cells by 16% (p<0,05 vs control, n=7). In terms of motility, the hUCMSC-CM reduced migration by 24% (p<0,05 vs control, n=7) after 24 hours.

Discussion

Our results suggest that hUCMSCs may exhibit dual effects on melanoma cells. On one hand, certain factors produced by hUCMSCs have shown potential in reducing the viability and motility of B16F10 melanoma cells, indicating a potential therapeutic benefit. On the other hand, it has also been observed that CM of hUCMSCs can increase the adhesion capacity of melanoma cells.

While hUCMSC-released factors may exhibit beneficial effects on melanoma cells, further research and clinical trials are needed to establish their safety, efficacy, and optimal therapeutic protocols for malignant melanoma.
Volatile anesthetic isoflurane exposure facilitates Enterococcus biofilm infection
Authors: Maisat Wiriya , Yuki Koichi
Published: September 2023

Enterococcus faecalis (E. faecalis) is one of the major pathogenic bacteria responsible for surgical site infections. Biofilm infections are major hospital‐acquired infections. Previous studies suggested that ions could regulate biofilm formation in microbes. Volatile anesthetics, frequently administered in surgical setting, target ion channels. Here, we investigated the role of ion channels/transporters and volatile anesthetics in the biofilm formation by E. faecalis MMH594 strain and its ion transporter mutants. We found that a chloride transporter mutant significantly reduced biofilm formation compared to the parental strain. Downregulation of teichoic acid biosynthesis in the chloride transporter mutant impaired biofilm matrix formation and cellular adhesion, leading to mitigated biofilm formation. Among anesthetics, isoflurane exposure enhanced biofilm formation in vitro and in vivo. The upregulation of de novo purine biosynthesis pathway by isoflurane exposure potentially enhanced biofilm formation, an essential process for DNA, RNA, and ATP synthesis. We also demonstrated that isoflurane exposure to E. faecalis increased cyclic‐di‐AMP and extracellular DNA production, consistent with the increased purine biosynthesis. We further showed that isoflurane enhanced the enzymatic activity of phosphoribosyl pyrophosphate synthetase (PRPP‐S). With the hypothesis that isoflurane directly bound to PRPP‐S, we predicted isoflurane binding site on it using rigid docking. Our study provides a better understanding of the underlying mechanisms of E. faecalis biofilm formation and highlights the potential impact of an ion transporter and volatile anesthetic on this process. These findings may lead to the development of novel strategies for preventing E. faecalis biofilm formation and improving patient outcomes in clinical settings.
Facet Joint Morphology and Tropism in Adolescents
Authors: Ishihama Yoshihiro , Tezuka Fumitake , Manabe Hiroaki , Morimoto Masatoshi , Yamashita Kazuta , Sakai Toshinori , Sairyo Koichi
Published: September 2023

Study Design.

A cross-sectional and observational study.

Objective.

To investigate the incidence of bidirectional lumbar facet tropism and its relationship with lumbar spine disease in adolescents.

Summary of Background Data.

There is limited information on facet joint asymmetry in the sagittal plane in adolescents.

Materials and Methods:

The orientation of all lumbar facet joints was measured in the bidirectional planes on computed tomographic images for 191 patients with low back pain. The patients were divided into 4 groups according to age (<15 or ≥15 yr) and sex. The facet joint angle and tropism rate were compared among the groups. Facet tropism was defined as a difference in bilateral angle of >10° in the axial plane and >5° in the sagittal plane. Facet joint orientation was compared among groups using a one-way analysis of variance and Tukey honestly significant difference test or Games-Howell post hoc test and the incidence of facet tropism using the Kruskal-Wallis test with Bonferroni correction. The association of facet tropism with disease was investigated further by analyzing facet joint orientation and the incidence of facet tropism in 116 patients with single-level lumbar disease.

Results.

Facet tropism was observed in 8.7% of axial views and 7.5% of sagittal views. The incidence of axial facet tropism was significantly higher in male patients aged ≥15 years, especially at L4/5. Facet joint morphology in the axial plane was more coronal at L3/4 and L4/5 in male patients ≥15 years than in those <15 years. Facet joint morphology in the sagittal plane was unchanged at around 15 years of age in both sexes. Axial facet tropism was found at L4/5 in 55.6% of patients with herniated nucleus pulposus. There was a significant difference in sagittal facet orientation in patients with spondylolysis at L5. The facet angle was significantly larger in patients with L5 spondylolysis at L3/4 and L4/5.

Conclusions.

Facet tropism in adolescents is similar in the axial and sagittal planes. Facet tropism and specific morphology may be related to lumbar disk herniation and spondylolysis in this age group.
Cardiotoxicity of Breast Cancer Chemotherapy
Authors: Roberts Sacha A. , Frishman William H.
Published: September 2023

Breast cancer is one of the leading causes of malignancy affecting women in the United States. Although many effective treatments are available, most come with notable side effects that providers and patients must take into consideration. Various classes of chemotherapeutic agents, including anthracyclines and human epidermal growth factor receptor-2 antagonists, are known to be toxic to myocardial tissue. In this review article, we discuss what is reported in the literature regarding the cardiotoxicity of these agents as well as how to monitor and prevent cardiac injury and dysfunction.
Cardiovascular Health Behavior Prediction Model in Patients With Type 2 Diabetes
Authors: Lee Sun Kyung , Hwang Seon Young
Published: September 2023

Background

To prevent cardiovascular disease in adults with type 2 diabetes, it is necessary to identify the factors that affect cardiovascular health behavior.

Objective

The aim of this study was to verify the causal relationship between illness perception and diabetes knowledge as cognitive representations, depression as emotional representations, self-efficacy as cognitive coping, and oral health and cardiovascular health behaviors as behavioral coping strategies. A hypothetical model was established based on a literature review and the self-regulation model.

Methods

In this study, a cross-sectional survey design was used, and the participants were adults 30 years or older who had been given a diagnosis of type 2 diabetes for more than 6 months and were recruited from South Korea. Data from 272 participants were collected through face-to-face interviews or Google surveys in 2021, and analyzed using SPSS 25.0 and AMOS 22.0.

Results

Oral health behavior (β = 0.26, P < .001) and self-efficacy (β = 0.16, P = .048) had a direct effect on cardiovascular health behavior, and illness perception (β = 0.24, P = .018) and depression (β = −0.25, P < .001) had an indirect effect through self-efficacy (β = 0.24, P = .016), with a total explanatory power of 19.1%. Oral health behavior was directly affected by illness perception and self-efficacy, and self-efficacy was directly affected by illness perception, diabetes knowledge, and depression (P < .05).

Conclusion

To practice cardiovascular health behaviors in adults with diabetes, self-efficacy for diabetes management should be enhanced. To this end, it is necessary to increase illness perception and knowledge, and reduce depression through cardiovascular disease prevention education for them, and the importance of oral health behaviors should also be emphasized.
A Standard Practice Protocol for Addressing Depression in a Hospice Setting
Authors: Williams Beth A. , Cormack Carrie L.
Published: September 2023

Depression can worsen physical suffering and psychiatric distresses in individuals with life-limiting illnesses and is associated with increased rates of pain, fatigue, dyspnea, and worse survival outcomes. Evidence supports protocol development to address depression in the hospice setting using validated screening tools and a process for referral and treatment. After protocol development and integration of validated screening tools into the electronic medical record, newly admitted patients meeting inclusion criteria were screened during the social workers' initial psychosocial assessment. Patients were referred for pharmacological and nonpharmacological treatment strategies based on the severity of depression detailed in the protocol. Of all patients who met inclusion criteria, 100% were screened using the Patient Health Questionnaire-2 with 52% being identified as having some severity of depression, 26% being appropriately referred for treatment, and 50% receiving a pharmacological strategy, whereas 26% received nonpharmacological strategies. There was a statistically significant difference in severity of depression found between those identified as having a depressed mood preintervention and those with some severity of depression using a validated screening tool postintervention. Implementing a standardized practice protocol to address depression in a hospice setting allowed for consistent evaluation through the use of validated screening tool(s) and increased recognition of those with symptoms of depression.
The Difference in Time to Discharge Between Daytime and Nighttime Administration of Ketamine in Children
Authors: Choi Kang , Yu Woosung
Published: September 2023

Objective

The objective of this study was to compare the time to discharge between daytime and nighttime ketamine administration to children undergoing primary facial repair in the emergency department (ED).

Methods

This retrospective, cross-sectional study was performed in a sample of children aged younger than 18 years and requiring sedation for primary facial repair in 2019. Children who received ketamine for reasons other than facial repair were excluded. All patients were initially injected with 4 mg/kg of ketamine intramuscularly and additionally injected if sedation failed. The time of injection and awakening were recorded in the electronic medical record system by nurses in charge, and the level of wakefulness was determined with a postanesthesia discharge scoring system administered by physicians.

Results

A total of 562 cases of ketamine administration were divided into 2 groups: daytime and nighttime. We defined daytime and nighttime as 8 a.m. and 8 p.m./sunrise and sunset, respectively. They found that there were no significant differences between 2 groups in each standard (95% confidence interval, −4.55–4.55; P = 0.877 and 95% confidence interval, −6.41–2.41; P = 0.487, respectively)

Conclusions

The findings of the study suggest that the time of ketamine injection has no relationship to duration of sedation for primary facial repair in children.
The Use of Urinary Bladder Matrix for Reconstructing Avulsed Traumatic Soft Tissue Injuries to the Maxillofacial Region
Authors: Amin Dina , Marwan Hisham , Rowan Brian , Abramowicz Shelly , Zaid Waleed
Published: September 2023

Introduction:

The purpose of the study was to provide an overview of our initial experience utilizing urinary bladder matrix (UBM) for reconstructing avulsed injuries resulting from trauma.

Materials and Methods:

This retrospective case series evaluated patients presented with avulsed soft tissue injuries to the head and neck who underwent reconstruction with UBM. Patients were treated by Oral and Maxillofacial Surgery Service in Louisiana State University Health Sciences Center (Baton Rouge, LA). Descriptive variables were collected. Descriptive statistics were calculated.

Results:

Eight patients (mean age 55.8 y) met our inclusion criteria. Wounds were located in the scalp (n=2, 25%), mandible (n=2, 25%), upper eyelid (n=1, 12.5%), cheek (n=1, 12.5%), nose (n=1, 12.5%), or neck (n=1, 12.5%). The depth of the wound extended from the skin to the subcutaneous tissue (n=1, 12.5%), muscle (n=2, 25%), bone (n=3, 37.5%), and/or cartilage (n=1, 12.5%). The mean wound diameter was 47.9 cm2 (range 17–85 cm2). Wounds were classified as acute (n=6, 75%) or chronic wounds (n=2, 25%). At 6 months, all patients had achieved complete healing with no need for additional surgical procedures (n=8, 100%) with a mean healing time of 36.5 days (range 14–90 d).

Conclusion:

Urinary bladder matrix minimize donor-side morbidity, eliminates contraction, and offers a wide range of product sizes to cover a wide range of maxillofacial soft tissue defects in a single-stage manner.
Implication of lipid turnover for the control of energy balance
Authors: Bernard S. , Spalding K. L.
Published: September 2023

The ongoing obesity epidemic is a consequence of a progressive energy imbalance. The energy-balance model (EBM) posits that obesity results from an excess in food intake and circulating fuels. A reversal in causality has been proposed recently in the form of the carbohydrate–insulin model (CIM), according to which fat storage drives energy imbalance. Under the CIM, dietary carbohydrates shift energy use in favour of storage in adipose tissue. The dynamics of lipid storage and mobilization could, therefore, be sensitive to changes in carbohydrate intake and represent a measurable component of the CIM. To characterize potential changes in lipid dynamics induced by carbohydrates, mathematical models were used. Here, we propose a coherent mathematical implementation of the CIM-energy deposition model (CIM-EDM), which includes lipid turnover dynamics. Using lipid turnover data previously obtained by radiocarbon dating, we build two cohorts of virtual patients and simulate lipid dynamics during ageing and weight loss. We identify clinically testable lipid dynamic parameters that discriminate between the CIM-EDM and an energy in, energy out implementation of the EBM (EBM-IOM). Using a clinically relevant two-month virtual trial, we additionally identify scenarios and propose mechanisms whereby individuals may respond differently to low-carbohydrate diets.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part II)’.
Carbohydrate-insulin model: does the conventional view of obesity reverse cause and effect?
Authors: Ludwig David S.
Published: September 2023

Conventional obesity treatment, based on the First Law of Thermodynamics, assumes that excess body fat gain is driven by overeating, and that all calories are metabolically alike in this regard. Hence, to lose weight one must ultimately eat less and move more. However, this prescription rarely succeeds over the long term, in part because calorie restriction elicits predictable biological responses that oppose ongoing weight loss. The carbohydrate-insulin model posits the opposite causal direction:
overeating doesn't drive body fat increase; instead, the process of storing excess fat drives overeating
. A diet high in rapidly digestible carbohydrates raises the insulin-to-glucagon ratio, shifting energy partitioning towards storage in adipose, leaving fewer calories for metabolically active and fuel sensing tissues. Consequently, hunger increases, and metabolic rate slows in the body's attempt to conserve energy. A small shift in substrate partitioning though this mechanism could account for the slow but progressive weight gain characteristic of common forms of obesity. From this perspective, the conventional calorie-restricted, low-fat diet amounts to symptomatic treatment, failing to target the underlying predisposition towards excess fat deposition. A dietary strategy to lower insulin secretion may increase the effectiveness of long-term weight management and chronic disease prevention.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part II)’.
Models of body weight and fatness regulation
Authors: Speakman John R. , Hall Kevin D.
Published: September 2023

Body weight and fatness appear to be regulated phenomena. Several different theoretical models are available to capture the essence of this idea. These include the set-point, dynamic equilibrium, adiposity force, control theory-settling point, Hall–Guo, operation point and dual intervention point (DIP) models. The set-point model posits a single reference point around which levels of fat are regulated. The dynamic equilibrium model suggests that the apparent regulation of body fat around a reference point is an illusion owing to the necessary impacts of weight change on energy expenditure. Control theory focuses on the importance of feedback gain and suggests set-point and dynamic equilibrium are ends of a continuum of feedback gain. Control theory models have also been called ‘settling point’ models. The Hall–Guo, operation point and DIP models also bring together the set-point and dynamic equilibrium ideas into a single framework. The DIP proposes a zone of indifference where dynamic equilibrium ‘regulation’ predominates, bounded by upper and lower intervention points beyond which physiological mechanisms are activated. The drifty gene hypothesis is an idea explaining where this individual variation in the upper intervention point might come from. We conclude that further experiments to test between the models are sorely required.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part II)’.
Searching for Strep A in the clinical environment during a human challenge trial: a sub-study protocol
Authors: Enkel Stephanie L. , Hla Thel K. , Wong Bernadette , Pickering Janessa , Barnett Timothy C. , Thomas Hannah M. M. , Lansbury Nina , Carapetis Jonathan R. , Manning Laurens , Bowen Asha C.
Published: September 2023

Introduction
Streptococcus pyogenes (also known as Group A Streptococcus, Strep A) is an obligate human pathogen with significant global morbidity and mortality. Transmission is believed to occur primarily between individuals via respiratory droplets, however knowledge about other potential sources of transmission via aerosols or the environment is limited. Such knowledge is required to design optimal interventions to control transmission, particularly in endemic settings. We aimed to detail experimental methodology to assess the transmission potential of Strep A in a clinical environment.
Materials and methods
We will examine potential sources of transmission in up to 20 participants recruited to the Controlled human infection for penicillin against Streptococcus pyogenes (CHIPS) Trial. Three approaches to understanding transmission will be used: the use of selective agar settle plates to capture possible droplet or airborne spread of Strep A; measurement of the possible distance of Strep A droplet spread during conversation; and environmental swabbing of personal and common high-touch items to detect the presence of Strep A on hard and soft surfaces. All methods are designed to allow for an assessment of transmission potential by symptomatic, asymptomatic, and non-cases. Ethical approval has been obtained through Bellberry Human Research Ethics Committee (Approval 2021-03-295). Trial Registration number: ACTRN12621000751875.
Discussion
Any results elicited from these experiments will be of benefit to the scientific literature in improving our knowledge of opportunities to prevent Strep A transmission as a direct component of the primordial prevention of rheumatic fever. Findings will be reported at local, national, and international conferences and in peer-reviewed journals.