bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploration of understanding of integrated care from a public health perspective: A scoping review
Authors: Noor Fadumo , Gulis Gabriel , Karlsson Leena Eklund 
Published: July 2023

Background: Many health care systems attempt to develop an integrated care approach that is a whole population health-oriented system. However, knowledge of strategies to support this effort are scarce and fragmented. The aim of the current paper is to investigate existing concepts of integrated care and their elements from a public health perspective and to propose an elaborated approach that could be applied to explore the public health orientation of integrated care. Design and methods: We applied a scoping review approach. A literature search was conducted in Embase, Medline, CINAHL, Scopus and Web of Science for the period 2000–2020 yielding 16 studies for inclusion. Results: Across the papers, 14 frameworks were identified. Nine of these referred to the Chronic Care Model (CCM). Service delivery, person-centeredness, IT systems design and utilization and decision support were identified as the core elements of most of the included frameworks. The descriptions of these elements were mainly clinical-oriented focusing particularly on clinical care processes and treatment of diseases instead of wider determinants of population health. Conclusions: A synthesized model is proposed that emphasizes the importance of mapping the unique needs and characteristics of the population it aims to serve, leans on the social determinants approach with a commitment to individual and community empowerment, health literacy and suggests reorienting services to meet the expressed needs of the population.
Prevalence and Risk Factors of Glenoid Bone Loss in Combined Shoulder Instability in Young, Active-Duty Military Patients
Authors: Green Clare K. , Scanaliato John P. , Turner Robert C. , Sandler Alexis B. , Dunn John C. , Parnes Nata 
Published: July 2023

Background: US military servicemembers experience higher rates of posterior and combined-type instability as compared with their nonmilitary peers. Purpose: (1) To determine the prevalence of glenoid bone loss (GBL) in young, active-duty military patients with combined-type shoulder instability who underwent operative shoulder stabilization; (2) to evaluate whether GBL is associated with differences in postoperative outcomes; and (3) to identify factors associated with larger defects. Study Design: Case series; Level of evidence, 4. Methods: This study included active-duty military patients who underwent primary surgical shoulder stabilization for combined anterior and posterior capsulolabral tears between January 2012 and December 2018. Preoperative magnetic resonance arthrograms were used to calculate anterior, posterior, and total GBL using the “perfect circle” technique. We recorded patient characteristics, revisions, complications, return to duty, range of motion, and scores on multiple outcome measures (visual analog scale for pain, Single Assessment Numeric Evaluation, American Shoulder and Elbow Surgeons, and Rowe). GBL prevalence was compared by time to surgery, glenoid version, history of trauma, and number of anchors used for labral repair. Outcome scores, return to active duty, and revision procedures were compared by degree of anterior or posterior GBL: <13.5% (mild) versus ≥13.5% (subcritical). Results: GBL was noted in 28 (77.8%) of the 36 patients. Nineteen (52.8%) patients had anterior GBL, 18 (50.0%) had posterior, and 9 (25.0%) had combined. Four (11.1%) patients had subcritical anterior or posterior GBL. Increased posterior GBL was associated with history of trauma ( P = .041), time to surgery >12 months ( P = .024), and glenoid retroversion ≥9° ( P = .010); increased total GBL was associated with longer time to surgery ( P = .023) and labral repair requiring >4 anchors ( P = .012); and increased anterior GBL was associated with labral repair requiring >4 anchors ( P = .011). There were statistically significant improvements on all outcome measures, with no changes in range of motion postoperatively. No significant difference on any outcome score was observed between patients with mild and subcritical GBL. Conclusion: In our analysis, 78% of patients had appreciable GBL, suggesting that GBL is highly prevalent in this patient population. Longer time to surgery, traumatic cause, significant glenoid retroversion, and large labral tears were identified as risk factors for increased GBL.
Longitudinal effects of elexacaftor/tezacaftor/ivacaftor on sputum viscoelastic properties, airway infection and inflammation in patients with cystic fibrosis
Authors: Schaupp Laura , Addante Annalisa , Völler Mirjam , Fentker Kerstin , Kuppe Aditi , Bardua Markus , Duerr Julia , Piehler Linus , Röhmel Jobst , Thee Stephanie , Kirchner Marieluise , Ziehm Matthias , Lauster Daniel , Haag Rainer , Gradzielski Michael , Stahl Mirjam , Mertins Philipp , Boutin Sébastien , Graeber Simon Y. , Mall Marcus A. 
Published: July 2023

BackgroundRecent studies demonstrated that the triple combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI) improves lung function and reduces pulmonary exacerbations in cystic fibrosis (CF) patients with at least oneF508delallele. However, effects of ETI on downstream consequences of CFTR dysfunction,i.e.abnormal viscoelastic properties of airway mucus, chronic airway infection and inflammation have not been studied. The aim of this study was to determine the longitudinal effects of ETI on airway mucus rheology, microbiome and inflammation in CF patients with one or twoF508delalleles aged ≥12 years throughout the first 12 months of therapy.MethodsIn this prospective observational study, we assessed sputum rheology, the microbiome, inflammation markers and proteome before and 1, 3 and 12 months after initiation of ETI.ResultsIn total, 79 patients with CF and at least oneF508delallele and 10 healthy controls were enrolled in this study. ETI improved the elastic modulus and viscous modulus of CF sputum at 3 and 12 months after initiation (all p<0.01). Furthermore, ETI decreased the relative abundance ofPseudomonas aeruginosain CF sputum at 3 months and increased the microbiome α-diversity at all time points.In addition, ETI reduced interleukin-8 at 3 months (p<0.05) and free neutrophil elastase activity at all time points (all p<0.001), and shifted the CF sputum proteome towards healthy.ConclusionsOur data demonstrate that restoration of CFTR function by ETI improves sputum viscoelastic properties, chronic airway infection and inflammation in CF patients with at least oneF508delallele over the first 12 months of therapy; however, levels close to healthy were not reached.
Hyperpolarised xenon-129 diffusion-weighted magnetic resonance imaging for assessing lung microstructure in idiopathic pulmonary fibrosis
Authors: Eaden James A. , Weatherley Nicholas D. , Chan Ho-Fung , Collier Guilhem , Norquay Graham , Swift Andrew J. , Rajaram Smitha , Smith Laurie J. , Bartholmai Brian J. , Bianchi Stephen M. , Wild Jim M. 
Published: July 2023

BackgroundHyperpolarised 129-xenon (129Xe) magnetic resonance imaging (MRI) shows promise in monitoring the progression of idiopathic pulmonary fibrosis (IPF) due to the lack of ionising radiation and the ability to quantify functional impairment. Diffusion-weighted (DW)-MRI with hyperpolarised gases can provide information about lung microstructure. The aims were to compare129Xe DW-MRI measurements with pulmonary function tests (PFTs), and to assess whether they can detect early signs of disease progression in patients with newly diagnosed IPF.MethodsThis is a prospective, single-centre, observational imaging study of patients presenting with IPF to Northern General Hospital (Sheffield, UK). Hyperpolarised129Xe DW-MRI was performed at 1.5 T on a whole-body General Electric HDx scanner and PFTs were performed on the same day as the MRI scan.ResultsThere was an increase in global129Xe apparent diffusion coefficient (ADC) between the baseline and 12-month visits (mean 0.043 cm2·s−1, 95% CI 0.040–0.047 cm2·s−1versusmean 0.045 cm2·s−1, 95% CI 0.040–0.049 cm2·s−1; p=0.044; n=20), with no significant change in PFTs over the same time period. There was also an increase in129Xe ADC in the lower zone (p=0.027), and an increase in129Xe mean acinar dimension in the lower zone (p=0.033) between the baseline and 12-month visits.129Xe DW-MRI measurements correlated strongly with diffusing capacity of the lung for carbon monoxide (% predicted), transfer coefficient of the lung for carbon monoxide (KCO) andKCO(% predicted).Conclusions129Xe DW-MRI measurements appear to be sensitive to early changes of microstructural disease that are consistent with progression in IPF at 12 months. As new drug treatments are developed, the ability to quantify subtle changes using129Xe DW-MRI could be particularly valuable.
Antibiotics in pregnancy influence nasal microbiome and respiratory morbidity in infancy
Authors: Rüttimann Céline , Nissen-Kratzert Annika , Mostacci Nadja , Künstle Noëmi , Marten Andrea , Gisler Amanda , Bacher Katharina , Yammine Sophie , Steinberg Ruth , Schulzke Sven , Röösli Martin , Latzin Philipp , Hilty Markus , Frey Urs , Gorlanova Olga 
Published: July 2023

BackgroundThe effects of prenatal antibiotic exposure on respiratory morbidity in infancy and the involved mechanisms are still poorly understood. We aimed to examine whether prenatal antibiotic exposure in the third trimester is associated with nasal microbiome and respiratory morbidity in infancy and at school age, and whether this association with respiratory morbidity is mediated by the nasal microbiome.MethodsWe performed 16S ribosomal RNA gene sequencing (regions V3–V4) on nasal swabs obtained from 296 healthy term infants from the prospective Basel–Bern birth cohort (BILD) at age 4–6 weeks. Information about antibiotic exposure was derived from birth records and standardised interviews. Respiratory symptoms were assessed by weekly telephone interviews in the first year of life and a clinical visit at age 6 years. Structural equation modelling was used to test direct and indirect associations accounting for known risk factors.Resultsα-Diversity indices were lower in infants with antibiotic exposure compared to nonexposed infants (e.g.Shannon index p-value 0.006). Prenatal antibiotic exposure was also associated with a higher risk of any, as well as severe, respiratory symptoms in the first year of life (risk ratio 1.38, 95% CI 1.03–1.84; adjusted p-value (padj)=0.032 and risk ratio 1.75, 95% CI 1.02–2.97; padj=0.041, respectively), but not with wheeze or atopy in childhood. However, we found no indirect mediating effect of nasal microbiome explaining these clinical symptoms.ConclusionPrenatal antibiotic exposure was associated with lower diversity of nasal microbiome in infancy and, independently of microbiome, with respiratory morbidity in infancy, but not with symptoms later in life.
The impact of emphysema heterogeneity on treatment response after endobronchial valve treatment
Authors: Roodenburg Sharyn A. , Klooster Karin , Slebos Dirk-Jan , Hartman Jorine E. 
Published: July 2023

BackgroundLung volume reduction with endobronchial valves can significantly improve functional outcomes in patients with advanced emphysema. The extent and spatial distribution pattern of emphysema shows considerable heterogeneity, which might affect response to endobronchial valve treatment. Our aim was to study the effect of emphysema heterogeneity on change in clinical outcomes after endobronchial valve treatment.MethodsData were collected from our national registry of patients who received endobronchial valve treatment between 2016 and 2020. We assessed the association between the heterogeneity index, absolute difference in destruction between the target and ipsilateral lobe, and relative change in forced expiratory volume in 1 s (FEV1), residual volume (RV), St George's Respiratory Questionnaire (SGRQ) and 6-min walk distance (6MWD) at 6-week, 6-month and 12-month follow-up.ResultsIn total, 236 patients were included. Heterogeneity index was significantly associated with improvements in FEV1, RV and 6MWD at all follow-up visits, and in SGRQ at the 6- and 12-month follow-up visits. The majority of patients, independent of heterogeneity index, showed clinically meaningful improvements based on minimal important difference thresholds.ConclusionsHeterogeneity index influences the degree of clinical improvement after endobronchial valve treatment where in general a more heterogeneous distribution translates to larger improvements. However, patients with a more homogeneous distribution also showed clinically meaningful improvements. Therefore, we believe emphysema heterogeneity alone should not be used as a decisive patient selection criterion, but should be weighed in the context of all other relevant patient and target lobe characteristics when deciding on a patient's treatment eligibility.
Development of a risk score to increase detection of severe alpha-1 antitrypsin deficiency
Authors: Riley E. Leonard , Brunson J. Cory , Eydgahi Soroush , Brantly Mark L. , Lascano Jorge E. 
Published: July 2023

BackgroundAlpha-1 antitrypsin deficiency (AATD) is an under-recognised genetic cause of chronic obstructive lung disease, and many fewer cases than estimated have been identified. Can a reported respiratory and hepatic disease history from a large AATD testing database be used to stratify a person's risk of severe AATD?MethodsWe analysed data extracted from the AATD National Detection Program. Demographics and medical history were evaluated to predict AATD PI*ZZ genotype. Logistic regression and integer programming models identified predictors and obtained risk scores. These were internally validated on a subset of the data.ResultsOut of 301 343 subjects, 1529 (0.5%) had PI*ZZ genotype. Predictors of severe AATD were asthma, bronchitis, emphysema, allergies, bronchiectasis, family history of AATD, cirrhosis, hepatitis and history of abnormal liver function tests. The derived model establishes a subject's risk of severe AATD, and scores ≥0 had an estimated risk of 0.41%, sensitivity 84.62% and specificity 24.32%. A model simulating guideline recommendations had an estimated risk of 0.51% with a sensitivity of 37.98% and specificity 46.60%. By recommending screening for scores ≥0, we estimate that more subjects would be screened (75.7%versus53.4%) and detected (84.6%versus58.2%) compared to a guideline-simulated model.ConclusionThis medical history risk model is a useful predictive tool to detect subjects at greater risk of having severe AATD and improves sensitivity of detection. Scores <0 are at lower risk and may need not be screened; testing is recommended for scores ≥0 and consistent with current guidelines.
Roles of protein post-translational modifications in glucose and lipid metabolism: mechanisms and perspectives
Authors: Yang Yu-Hang , Wen Ri , Yang Ni , Zhang Tie-Ning , Liu Chun-Feng 
Published: July 2023

AbstractThe metabolism of glucose and lipids is essential for energy production in the body, and dysregulation of the metabolic pathways of these molecules is implicated in various acute and chronic diseases, such as type 2 diabetes, Alzheimer’s disease, atherosclerosis (AS), obesity, tumor, and sepsis. Post-translational modifications (PTMs) of proteins, which involve the addition or removal of covalent functional groups, play a crucial role in regulating protein structure, localization function, and activity. Common PTMs include phosphorylation, acetylation, ubiquitination, methylation, and glycosylation. Emerging evidence indicates that PTMs are significant in modulating glucose and lipid metabolism by modifying key enzymes or proteins. In this review, we summarize the current understanding of the role and regulatory mechanisms of PTMs in glucose and lipid metabolism, with a focus on their involvement in disease progression associated with aberrant metabolism. Furthermore, we discuss the future prospects of PTMs, highlighting their potential for gaining deeper insights into glucose and lipid metabolism and related diseases.
CKM and TERT dual promoters drive CRISPR–dCas9 to specifically inhibit the malignant behavior of osteosarcoma cells
Authors: Hu Yawei , Zhang Hao , Guo Zengfeng , Zhou Jianhua , Zhang Wang , Gong Ming , Wu Jiawen 
Published: July 2023

AbstractImprovements in treatment and chemotherapy have increased the survival rate of osteosarcoma, but overall efficacy remains low, highlighting the need for new gene therapy methods. Clustered regularly interspaced short palindromic repeats–deactivated Cas9 (CRISPR–dCas9) technology offers a promising strategy, but targeting osteosarcoma cells precisely is a challenge. We designed a system to achieve specific expression of CRISPR–dCas9–KRAB in osteosarcoma cells by using the creatine kinase muscle (CKM) promoter to drive dCas9–KRAB and the telomerase reverse transcriptase (TERT) promoter to drive single guide (sg)RNA expression. We inhibited the MDM2 proto-oncogene using this system in vitro, which efficiently inhibited the malignant behavior of osteosarcoma cells and induced apoptosis without affecting normal cells. In vivo experiments demonstrated that this system effectively inhibited the growth of subcutaneously transplanted tumors in nude mice. These findings provide a new method for precise identification and intervention of osteosarcoma with significant implications for the development of gene therapy methods for other cancers. Future research should focus on optimizing this system for clinical translation.
Varicella zoster virus-associated non-necrotizing retinitis: case report
Authors: Rym Maamouri , Yasmine Houman , Marwa Abdelaziz , Imen Helal , Monia Cheour 
Published: July 2023

Abstract
Purpose
To describe clinical features and the course of a case of non-necrotizing herpetic retinitis secondary to Varicella zoster virus (VZV).

Materiel and methods
A single case report documented with multimodal imaging.

Results
A 52-year-old female patient with a past medical history of diabetes mellitus who presented with painful red right eye (OD). Ophthalmic examination showed perilimbal conjunctival nodule, granulomatous anterior uveitis, sectoral iris atrophy and increased intraocular pressure. Fundus examination in OD revealed posterior multifocal retinitis. Left eye examination was unremarkable. Polymerase chain reaction (PCR) of aqueous humor sample confirmed the presence of VZV DNA. Systemic antiviral therapy allowed the improvement of intraocular inflammation and disappearance of the retinal non necrotizing retinitis after one year of regular follow-up.

Conclusion
Non-necrotizing retinitis is an underdiagnosed form of VZV ocular infection.
AMEND: active module identification using experimental data and network diffusion
Authors: Boyd Samuel S. , Slawson Chad , Thompson Jeffrey A. 
Published: July 2023

AbstractBackgroundMolecular interaction networks have become an important tool in providing context to the results of various omics experiments. For example, by integrating transcriptomic data and protein–protein interaction (PPI) networks, one can better understand how the altered expression of several genes are related with one another. The challenge then becomes how to determine, in the context of the interaction network, the subset(s) of genes that best captures the main mechanisms underlying the experimental conditions. Different algorithms have been developed to address this challenge, each with specific biological questions in mind. One emerging area of interest is to determine which genes are equivalently or inversely changed between different experiments. The equivalent change index (ECI) is a recently proposed metric that measures the extent to which a gene is equivalently or inversely regulated between two experiments. The goal of this work is to develop an algorithm that makes use of the ECI and powerful network analysis techniques to identify a connected subset of genes that are highly relevant to the experimental conditions.ResultsTo address the above goal, we developed a method called Active Module identification using Experimental data and Network Diffusion (AMEND). The AMEND algorithm is designed to find a subset of connected genes in a PPI network that have large experimental values. It makes use of random walk with restart to create gene weights, and a heuristic solution to the Maximum-weight Connected Subgraph problem using these weights. This is performed iteratively until an optimal subnetwork (i.e., active module) is found. AMEND was compared to two current methods, NetCore and DOMINO, using two gene expression datasets.ConclusionThe AMEND algorithm is an effective, fast, and easy-to-use method for identifying network-based active modules. It returned connected subnetworks with the largest median ECI by magnitude, capturing distinct but related functional groups of genes. Code is freely available athttps://github.com/samboyd0/AMEND.
Genome-wide identification, characterization and transcriptional profile of the SWEET gene family in Dendrobium officinale
Authors: Hao Li , Shi Xin , Qin Shunwang , Dong Jiahong , Shi Huan , Wang Yuehua , Zhang Yi 
Published: July 2023

Abstract
Background
Dendrobium officinale Kimura et Migo (D. officinale) is a well-known traditional Chinese medicine with high content polysaccharides in stems. The SWEET (Sugars Will Eventually be Exported Transporters) family is a novel class of sugar transporters mediating sugar translocation among adjacent cells of plants. The expression patterns of SWEETs and whether they are associated with stress response in D. officinale remains uncovered.

Results
Here, 25 SWEET genes were screened out from D. officinale genome, most of which typically contained seven transmembrane domains (TMs) and harbored two conserved MtN3/saliva domains. Using multi-omics data and bioinformatic approaches, the evolutionary relationship, conserved motifs, chromosomal location, expression patterns, correlationship and interaction network were further analyzed. DoSWEETs were intensively located in nine chromosomes. Phylogenetic analysis revealed that DoSWEETs were divided into four clades, and conserved motif 3 specifically existed in DoSWEETs from clade II. Different tissue-specific expression patterns of DoSWEETs suggested the division of their roles in sugar transport. In particular, DoSWEET5b, 5c, and 7d displayed relatively high expression levels in stems. DoSWEET2b and 16 were significantly regulated under cold, drought, and MeJA treatment, which were further verified using RT-qPCR. Correlation analysis and interaction network prediction discovered the internal relationship of DoSWEET family.

Conclusions
Taken together, the identification and analysis of the 25 DoSWEETs in this study provide basic information for further functional verification in D. officinale.