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Background: Health-related quality of life (HRQoL) is a predictor of treatment outcomes in cancer patients. This study aimed to evaluate the effect of pretreatment HRQoL on treatment tolerance and survival outcomes in patients with HNC planned for concurrent chemoradiotherapy (CCRT) in Taiwan. Methods: This study included 461 patients with HNC planned for definitive CCRT at three medical centers in Taiwan between August 2017 and December 2018. HRQoL was assessed using the QLQ-HN35 one week before the initiation of CCRT. Patients were grouped based on the sum scores of QLQ-HN35 (

Background/purpose: This study addresses the delicate balance between healthcare personnel burnout and medical accessibility in the context of endovascular thrombectomy (EVT) services in urban areas. We aimed to determine the minimum number of hospitals providing EVT on rotation each day without compromising patient access. Methods: Employing an optimization model, we developed shift schedules based on patient coverage rates and volumes during the pre-pandemic (2016–2018) and pandemic (2019–2021) periods. Starting with a minimum of two hospitals on duty per day, we gradually increased to a maximum of eight. Patient coverage rates, defined as the proportion of patients meeting bypass criteria and transported to rotating hospitals capable of EVT, were the primary outcomes. Sensitivity analyses explored the impact of varying patient transport intervals and accumulating patients over multiple years. Results: Results from 7024 patient records revealed patient coverage rates of 92.5% (standard deviation [SD] 2.8%) during the pre-pandemic and 91.4% (SD 2.8%) during the pandemic, with at least two rotating hospitals daily. No significant differences were observed between schedules based on the highest patient volume and coverage rate months. A patient coverage rate of 98.99% was achieved with four rotating hospitals per day during the pre-pandemic period, with limited improvement beyond this threshold. Changing patient transport intervals and accumulating patients over six years (p = 0.83) had no significant impact on coverage rates. Conclusion: Our optimization model supports reducing the number of daily rotating hospitals by half while preserving a balance between patient accessibility and alleviating strain on medical teams.

Background: This study aims to determine whether end-stage renal disease (ESRD) is a true contraindication for extracorporeal membrane oxygenation in adult patients. Materials and methods: Adult patients who received VA-ECMO at National Taiwan University Hospital between January 2010 and December 2021 were included. Patients who received regular dialysis before the index admission were included in the ESRD group. The primary outcome was in-hospital mortality. Results: 1341 patients were included in the analysis, 121 of whom had ESRD before index admission. The ESRD group was older (62.3 versus 56.8 years; P

Background: Acute myeloid leukemia (AML) is a hematological malignancy with a heterogeneous prognosis. Novel markers are required to accurately assess the prognosis and formulate treatment plans. Methods: The association of ARHGAP family genes with prognostic value in acute myeloid leukemia (AML) was assessed using public databases (CCLE, GEPIA, TCGA, and GEO). Results: Elevated expression of ARHGAP43 (SH3BP1) was associated with poor prognosis in patients with acute myeloid leukemia. ARHGAP43 (SH3BP1) expression was higher in the poor/adverse prognosis (P

Abstract Ischemic heart disease is the most prevalent cause of death worldwide affecting both the gender of all age groups. The high mortality rate is due to damage of myocardial tissue that emanates at the time of myocardial ischemia and re-oxygenation, thus averting reperfusion injury is recognized as a potential way to reduce acute cardiac injury and subsequent mortality. Flavonoids are polyphenol derivatives of plant origin and empirical shreds of evidence substantiate their numerous activities such as antioxidant, anti-inflammatory, anti-apoptotic, and anti-thrombotic activity, leading to their role in cardio protection. Recent investigations have unveiled the capacity of flavonoids to impede pivotal regulatory enzymes, signaling molecules, and transcription factors that orchestrate the mediators participating in the inflammatory cascade. The present comprehensive review, dwells on the preclinical studies on the effectiveness of flavonoids from the year 2007 to 2023, for the prevention and therapeutics for myocardial ischemia-reperfusion injury. Graphical Abstract

Abstract Background Vision impairment and blindness are significant global public health challenges, particularly in low- and middle-income countries, where access to eye care services remains limited. India has significantly reduced the prevalence of Blindness and Vision Impairment (VI) over the last two decades. This was achieved with the help of greater investments towards blindness control programs. The use of utility values helps in conducting economic evaluations of various eye health programs and empirically justify investing in these programs. This study aimed to estimate utility values for various childhood eye conditions in central India using the EuroQol-Five-Dimension-Youth (EQ-5D-Y) instrument. Methods This is a before and after study with data collected at two time points for few participants and at only one time point for others. This study was undertaken at Shri Sadguru Netra Chikitsalaya (SNC) and included children representing central and north India. Participants were randomly sampled in the hospital. After comprehensive eye examination, participants completed the EuroQol-Five-Dimension-Youth (EQ-5D-Y) questionnaire along with EuroQol Visual Analogue Scale (EQ VAS) measurement to elicit their health state for their condition which was repeated after six months post-intervention to measure the change in utility value. We have used Indonesian value set to analyze the preference scores of each dimension of EQ-5D-Y. Results Utility values of 16 eye conditions were estimated at baseline and seven conditions were followed up for post-intervention utility value estimation. There is a statistically significant improvement in the utility values post-intervention amongst six conditions. Blindness and Pediatric cataract had the greatest change (0.23 and 0.2 respectively) in utility value whereas mild Vision Impairment (VI) showed the least change (0.02) in the utility value post-intervention. Blindness had the lowest baseline (0.62) and post-intervention (0.85) utility value. Conclusion The utility values estimated in this study showed that generic measures such as EQ-5D-Y may be used to elicit health states for various eye conditions amongst children. These estimates are helpful in undertaking cost-utility analyses of eye health programs and interventions aimed at these eye conditions.

Abstract Introduction This study comprehensively investigates the changes in healthcare utilization among chronic patients with regular outpatient visits to hospitals after the occurrence of Covid-19. The research examines whether patients altered their originally regular medical attendance frequencies due to the pandemic and explores potential negative impacts on the health conditions of those irregular attendees post-pandemic. Methods Data for this study were sourced from a database at a medical center in Taiwan. The subjects were chronic patients with regular hospital outpatient visits before the Covid-19 outbreak. The study tracked medical utilization patterns from 2017 to 2022 for different patient characteristics and outpatient behaviors, employing statistical methods such as Repeated Measures ANOVA and Generalized Estimating Equation to analyze changes in healthcare utilization and health status during the post-pandemic period. Results The results reveal that, compared to the regular group, chronic patients with irregular outpatient visits during the post-pandemic period exhibited a decrease of 5.85 annual outpatient visits, a reduction of NT$20,290.1 in annual medical expenses, and a significantly higher abnormality rate in average biochemical test results by 0.9%. Conclusions The findings contribute to understanding the impact of the Covid-19 pandemic on healthcare utilization and health conditions among outpatient chronic disease populations. In response to the new medical landscape in the post-pandemic era, proactive suggestions are made, including providing telemedicine outpatient services and referral-based medical care to meet the needs of the target population, ensuring a continuous and reassuring healthcare model for chronic patients, and mitigating the operational impacts of public health emergencies on hospitals.

Abstract Objective To estimate the economic impact for the society, generated as a consequence of the onset of loss of vision and irreversible legal blindness, for the main ophthalmologic diseases in Spain: glaucoma, diabetic retinopathy (DR), diabetic macular edema (DME), age-related macular degeneration (AMD) and high myopia (HM). Methods A cost analysis model was developed to estimate the economic burden of glaucoma, DR, DME, AMD and HM over a 10-year time horizon (2021-2030), from a societal perspective in Spain. The epidemiological and economic parameters used in the model were obtained through a literature review. Prevalence, incidence, and progression stages were used to establish the epidemiological flows. Annual costs per patient from publications were included and classified into direct healthcare, direct non-healthcare and indirect costs. Costs from other countries were converted based on purchasing-power-parity (€EUR, PPP). Epidemiological parameters about population and cost results were validated by a panel of experts. All costs were adjusted to euros, 2021 (€, 2021), and using the Consumer Price Index (CPI) of the last 10 years, extrapolated to 2030 euros (€, 2030). Results It was estimated that the total population of patients with the main diseases pathologies (glaucoma, DR, DME, AMD and HM) will increase to 7.99 million patients by 2030, representing an increase of 103%. The total cost by 2030 of all pathologies would amount to 99.8 billion euros. Direct non-healthcare costs account for the largest item (44%), followed by loss of productivity costs (38%), and direct healthcare costs (18%). The pathologies with the highest cumulative costs will be glaucoma (€33.6 billion) and DME (€19.8 billion).The greatest increment costs compared to 2021 will likely be generated by pathologies related to diabetes mellitus, such as DR (703%) and DME (317%). Conclusions Knowing the costs associated with the pathologies that generate loss of vision and irreversible legal blindness is essential to understand the socioeconomic impact associated with these pathologies. Furthermore, the high cost of treating these diseases makes necessary to coordinate efforts between administrations, together with the support of patient associations, to meet their needs.

Abstract We investigate the factors that influence the variance in hospital charges and inpatient care for kidney transplant cases in the US. Using the AHRQ’s (Agency for Healthcare Research and Quality) HCUP’s (Hospital Cost and Utilization Project) NIS (National Inpatient Sample) database, we find that variance in hospital charges and inpatient care is driven by patient demographics and hospital variables. We find that variance in hospital charges and inpatient care is determined by patient-specific factors including age, gender, race, and income, and hospital factors such as size, type, and location. Our results provide a deeper understanding of the non-clinical factors that impact hospital charges and inpatient care for kidney transplant patients.

Abstract Background Rape is one of the trauma incidents with the highest risk of subsequent post-traumatic stress disorder. Early interventions, such as prolonged exposure therapy (PE), have shown promise in preventing PTSD following a sexual assault. The primary objective of this internal pilot trial was to examine the feasibility of the EIR study protocol, which used modified prolonged exposure therapy (mPE) as a preventive intervention after rape. Methods This parallel two-arm clinical pilot study involved three sexual assault centers (SACs) in Trondheim, Oslo, and Vestfold, with data collected between June 2022 and March 2023. Women seeking assistance at one of these three SACs within 72 h after rape or attempted rape received acute medical treatment and forensic examinations. Women who wanted further psychosocial treatment were, if eligible and consenting, recruited to complete baseline assessments and a clinical interview before being randomized to one of two study arms. The intervention group prescribed up to five sessions of modified PE (mPE) in addition to treatment as usual (TAU), starting within the first 14 days after the rape incident, followed by weekly sessions. The other group received TAU. The present pilot evaluation is based on 22 participants, i.e., nine mPE + TAU and 13 TAU alone. Primary outcomes were predefined progression criteria regarding recruitment, retention, intervention implementation, a harm reporting system, and applying biological measurements and actigraphy. Results During the 6-month recruitment period, 235 women visited the three SACs. After eligibility screening and consent, 22 (9.4%) women were randomized. Three months later, 14 (63.6%) participants completed the final assessments. Intervention implementation was successful using trained SAC personnel to deliver mPE. The harm reporting system was used according to the study’s plan, and adverse and serious adverse events were detected during the trial. The biological measurements and actigraphy had substantial missing data but were still considered usable for statistical analyses. Conclusion It may be feasible to conduct a full-scale RCT of early intervention after rape by comparing mPE + TAU to TAU alone. Minor design refinements were made to the protocol to enhance the main study outcome. Trial registration ClinicalTrials.gov Identifier: NCT05489133. Registered on 15 July 2022, retrospectively.

Abstract Rheumatoid arthritis (RA) remains a challenging chronic autoimmune disorder characterized by persistent joint inflammation and damage. While modern regenerative strategies, encompassing cell/stem cell-based therapies, gene therapy, and tissue engineering, have advanced tissue repair efforts, a definitive cure for RA remains elusive. Consequently, there is growing interest in developing targeted therapies that directly address the underlying mechanisms driving RA pathogenesis, such as extracellular vesicles (EVs). These small membrane-bound particles can modulate immune responses within the inflammatory microenvironment of damaged cartilage. To launch the clinical potential of EVs, they can be isolated from various cell types through several techniques. EVs can carry various bioactive molecules and anti-inflammatory or pro-regenerative drugs, deliver them directly to the affected joints, and affect the behavior of injured cells, making them a compelling choice for targeted therapy and drug delivery in RA patients. However, there are still several challenges and limitations associated with EV-based therapy, including the absence of standardized protocols for EV isolation, characterization, and delivery. This review provides a comprehensive overview of the cellular sources of EVs in RA and delves into their therapeutic potential and the hurdles they must overcome.

Abstract Background Primary human hepatocytes (PHHs) are highly valuable for drug-metabolism evaluation, liver disease modeling and hepatocyte transplantation. However, their availability is significantly restricted due to limited donor sources, alongside their constrained proliferation capabilities and reduced functionality when cultured in vitro. To address this challenge, we aimed to develop a novel method to efficiently expand PHHs in vitro without a loss of function. Methods By mimicking the in vivo liver regeneration route, we developed a two-step strategy involving the de-differentiation/expansion and subsequent maturation of PHHs to generate abundant functional hepatocytes in vitro. Initially, we applied SiPer, a prediction algorithm, to identify candidate small molecules capable of activating liver regenerative transcription factors, thereby formulating a novel hepatic expansion medium to de-differentiate PHHs into proliferative human hepatic progenitor-like cells (ProHPLCs). These ProHPLCs were then re-differentiated into functionally mature hepatocytes using a new hepatocyte maturation condition. Additionally, we investigated the underlying mechanism of PHHs expansion under our new conditions. Results The novel hepatic expansion medium containing hydrocortisone facilitated the de-differentiation of PHHs into ProHPLCs, which exhibited key hepatic progenitor characteristics and demonstrated a marked increase in proliferation capacity compared to cells cultivated in previously established expansion conditions. Remarkably, these subsequent matured hepatocytes rivaled PHHs in terms of transcriptome profiles, drug metabolizing activities and in vivo engraftment capabilities. Importantly, our findings suggest that the enhanced expansion of PHHs by hydrocortisone may be mediated through the PPARα signaling pathway and regenerative transcription factors. Conclusions This study presents a two-step strategy that initially induces PHHs into a proliferative state (ProHPLCs) to ensure sufficient cell quantity, followed by the maturation of ProHPLCs into fully functional hepatocytes to guarantee optimal cell quality. This approach offers a promising means of producing large numbers of seeding cells for hepatocyte-based applications.

Abstract Background Mesenchymal stem cells (MSCs) possess powerful immunomodulatory ability. This study aimed to assess the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UMSCs) in patients with ulcerative colitis (UC) and to explore the potential mechanisms. Methods This prospective, self-controlled clinical study was conducted at Henan Provincial People’s Hospital. Patients with moderate-to-severe active UC, unresponsive to traditional drugs were continuously enrolled from September 2018 to March 2023. UMSCs were administered intravenously monthly for two months at a cell dosage of 1 × 106 per kg. The primary outcome was a clinical response at 2 months. The levels of cytokines and progerin in the plasma of the patients were analyzed using enzyme-linked immunosorbent assay kits, and longitudinal data was analyzed using generalized estimation equation. Results Forty-one patients were enrolled and received UMSC therapy. At 2 months, 73.2% (30/41) of patients achieved a clinical response, and 41.5% (17/41) achieved a clinical remission. At 6 months, 2 patients were lost to follow-up; the corresponding figures were 70.0% (25/41) and 34.2% (14/41), respectively. After UMSC therapy, the Mayo score, Mayo endoscopy score, mean and maximum values of Ulcerative Colitis Endoscopic Index of Severity and Nancy index were significantly reduced compared with baseline values. Additionally, the levels of progerin and inflammatory markers, such as interleukin (IL)-1β, IL-6, IL-8, IL-12, and IL-17 A decreased, while hemoglobin, albumin, and IL-10/IL-17 A ratio increased, particularly in the response group. Multiple stepwise logistic regression analysis showed age was an independent risk factor affecting efficacy (odds ratio, 0.875 (95% confidence interval (0.787, 0.972)); the area under the receiver operating characteristic curve for age was 0.79. No serious adverse events were observed during or after UMSC therapy. Conclusion UMSCs are safe and effective for patients with UC, with age being an independent risk factor affecting efficacy. Mechanistically, UMSC treatment may ameliorate cell senescence and suppress the secretion of pro-inflammatory cytokines. Trial registration The study was retrospectively registered at www.chictr.org.cn/ (ChiCTR1900026035) on September 18, 2019.

Abstract Background Atrial fibrillation has an estimated prevalence of 1.5–2%, making it the most common cardiac arrhythmia. The processes that cause and sustain the disease are still not completely understood. An association between atrial fibrillation and systemic, as well as local, inflammatory processes has been reported. However, the exact mechanisms underlying this association have not been established. While it is understood that inflammatory macrophages can influence cardiac electrophysiology, a direct, causative relationship to atrial fibrillation has not been described. This study investigated the pro-arrhythmic effects of activated M1 macrophages on human induced pluripotent stem cell (hiPSC)-derived atrial cardiomyocytes, to propose a mechanistic link between inflammation and atrial fibrillation. Methods Two hiPSC lines from healthy individuals were differentiated to atrial cardiomyocytes and M1 macrophages and integrated in an isogenic, pacing-free, atrial fibrillation-like coculture model. Electrophysiology characteristics of cocultures were analysed for beat rate irregularity, electrogram amplitude and conduction velocity using multi electrode arrays. Cocultures were additionally treated using glucocorticoids to suppress M1 inflammation. Bulk RNA sequencing was performed on coculture-isolated atrial cardiomyocytes and compared to meta-analyses of atrial fibrillation patient transcriptomes. Results Multi electrode array recordings revealed M1 to cause irregular beating and reduced electrogram amplitude. Conduction analysis further showed significantly lowered conduction homogeneity in M1 cocultures. Transcriptome sequencing revealed reduced expression of key cardiac genes such as SCN5A, KCNA5, ATP1A1, and GJA5 in the atrial cardiomyocytes. Meta-analysis of atrial fibrillation patient transcriptomes showed high correlation to the in vitro model. Treatment of the coculture with glucocorticoids showed reversal of phenotypes, including reduced beat irregularity, improved conduction, and reversed RNA expression profiles. Conclusions This study establishes a causal relationship between M1 activation and the development of subsequent atrial arrhythmia, documented as irregularity in spontaneous electrical activation in atrial cardiomyocytes cocultured with activated macrophages. Further, beat rate irregularity could be alleviated using glucocorticoids. Overall, these results point at macrophage-mediated inflammation as a potential AF induction mechanism and offer new targets for therapeutic development. The findings strongly support the relevance of the proposed hiPSC-derived coculture model and present it as a first of its kind disease model.

Abstract Background The immunomodulatory oligodeoxynucleotide (ODN) IMT504 might harbor antifibrotic properties within the liver. Methods Fibrosis models were induced in mice through thioacetamide (TAA) administration and bile-duct ligation. Cre-loxP mice were utilized to identify GLAST + Wnt1 + bone marrow stromal progenitors (BMSPs) and to examine their contribution with cells in the liver. In vivo and in vitro assays; flow-cytometry, immunohistochemistry, and qPCR were conducted. Results IMT504 demonstrated significant inhibition of liver fibrogenesis progression and reversal of established fibrosis. Early responses to IMT504 involved the suppression of profibrogenic and proinflammatory markers, coupled with an augmentation of hepatocyte proliferation. Additionally, this ODN stimulated the proliferation and mobilization of GLAST + Wnt1 + BMSPs, likely amplifying their contribution with endothelial- and hepatocytes-like cells. Moreover, IMT504 significantly modulated the expression levels of Wnt ligands and signaling pathway/target genes specifically within GLAST + Wnt1 + BMSPs, with minimal impact on other BMSPs. Intriguingly, both IMT504 and conditioned media from IMT504-pre-treated GLAST + Wnt1 + BMSPs shifted the phenotype of fibrotic macrophages, hepatic stellate cells, and hepatocytes, consistent with the potent antifibrotic effects observed. Conclusion In summary, our findings identify IMT504 as a promising candidate molecule with potent antifibrotic properties, operating through both direct and indirect mechanisms, including the activation of GLAST + Wnt1 + BMSPs.

Abstract Background Understanding the lineage differentiation of human prostate not only is crucial for basic research on human developmental biology but also significantly contributes to the management of prostate-related disorders. Current knowledge mainly relies on studies on rodent models, lacking human-derived alternatives despite clinical samples may provide a snapshot at certain stage. Human embryonic stem cells can generate all the embryonic lineages including the prostate, and indeed a few studies demonstrate such possibility based on co-culture or co-transplantation with urogenital mesenchyme into mouse renal capsule. Methods To establish a stepwise protocol to obtain prostatic organoids in vitro from human embryonic stem cells, we apply chemicals and growth factors by mimicking the regulation network of transcription factors and signal transduction pathways, and construct cell lines carrying an inducible NKX3-1 expressing cassette, together with three-dimensional culture system. Unpaired t test was applied for statistical analyses. Results We first successfully generate the definitive endoderm, hindgut, and urogenital sinus cells. The embryonic stem cell-derived urogenital sinus cells express prostatic key transcription factors AR and FOXA1, but fail to express NKX3-1. Therefore, we construct NKX3-1-inducible cell line by homologous recombination, which is eventually able to yield AR, FOXA1, and NKX3-1 triple-positive urogenital prostatic lineage cells through stepwise differentiation. Finally, combined with 3D culture we successfully derive prostate-like organoids with certain structures and prostatic cell populations. Conclusions This study reveals the crucial role of NKX3-1 in prostatic differentiation and offers the inducible NKX3-1 cell line, as well as provides a stepwise differentiation protocol to generate human prostate-like organoids, which should facilitate the studies on prostate development and disease pathogenesis.

Abstract Background Periodontal ligament stem cells (PDLSCs) are important seed cells in tissue engineering and clinical applications. They are the priority receptor cells for sensing various mechanical stresses. Yes-associated protein (YAP) is a recognized mechanically sensitive transcription factor. However, the role of YAP in regulating the fate of PDLSCs under tension stress (TS) and its underlying mechanism is still unclear. Methods The effects of TS on the morphology and fate of PDLSCs were investigated using fluorescence staining, transmission electron microscopy, flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). Then qRT-PCR, western blotting, immunofluorescence staining and gene knockdown experiments were performed to investigate the expression and distribution of YAP and its correlation with PDLSCs proliferation. The effects of cytoskeleton dynamics on YAP nuclear translocation were subsequently explored by adding cytoskeleton inhibitors. The effect of cytoskeleton dynamics on the expression of the LINC complex was proved through qRT-PCR and western blotting. After destroying the LINC complex by adenovirus, the effects of the LINC complex on YAP nuclear translocation and PDLSCs proliferation were investigated. Mitochondria-related detections were then performed to explore the role of mitochondria in YAP nuclear translocation. Finally, the in vitro results were verified by constructing orthodontic tooth movement models in Sprague-Dawley rats. Results TS enhanced the polymerization and stretching of F-actin, which upregulated the expression of the LINC complex. This further strengthened the pull on the nuclear envelope, enlarged the nuclear pore, and facilitated YAP’s nuclear entry, thus enhancing the expression of proliferation-related genes. In this process, mitochondria were transported to the periphery of the nucleus along the reconstructed microtubules. They generated ATP to aid YAP’s nuclear translocation and drove F-actin polymerization to a certain degree. When the LINC complex was destroyed, the nuclear translocation of YAP was inhibited, which limited PDLSCs proliferation, impeded periodontal tissue remodeling, and hindered tooth movement. Conclusions Our study confirmed that appropriate TS could promote PDLSCs proliferation and periodontal tissue remodeling through the mechanically driven F-actin/LINC complex/YAP axis, which could provide theoretical guidance for seed cell expansion and for promoting healthy and effective tooth movement in clinical practice.

Abstract Background Chronic lung disease of prematurity, called bronchopulmonary dysplasia (BPD), lacks effective therapies, stressing the need for preclinical testing systems that reflect human pathology for identifying causal pathways and testing novel compounds. Alveolar organoids derived from human pluripotent stem cells (hPSC) are promising test platforms for studying distal airway diseases like BPD, but current protocols do not accurately replicate the distal niche environment of the native lung. Herein, we investigated the contributions of cellular constituents of the alveolus and fetal respiratory movements on hPSC-derived alveolar organoid formation. Methods Human PSCs were differentiated in 2D culture into lung progenitor cells (LPC) which were then further differentiated into alveolar organoids before and after removal of co-developing mesodermal cells. LPCs were also differentiated in Transwell® co-cultures with and without human fetal lung fibroblast. Forming organoids were subjected to phasic mechanical strain using a Flexcell® system. Differentiation within organoids and Transwell® cultures was assessed by flow cytometry, immunofluorescence, and qPCR for lung epithelial and alveolar markers of differentiation including GATA binding protein 6 (GATA 6), E-cadherin (CDH1), NK2 Homeobox 1 (NKX2-1), HT2-280, surfactant proteins B (SFTPB) and C (SFTPC). Results We observed that co-developing mesenchymal progenitors promote alveolar epithelial type 2 cell (AEC2) differentiation within hPSC-derived lung organoids. This mesenchymal effect on AEC2 differentiation was corroborated by co-culturing hPSC-NKX2-1+ lung progenitors with human embryonic lung fibroblasts. The stimulatory effect did not require direct contact between fibroblasts and NKX2-1+ lung progenitors. Additionally, we demonstrate that episodic mechanical deformation of hPSC-derived lung organoids, mimicking in situ fetal respiratory movements, increased AEC2 differentiation without affecting proximal epithelial differentiation. Conclusion Our data suggest that biophysical and mesenchymal components promote AEC2 differentiation within hPSC-derived distal organoids in vitro.

Abstract Background Reduction of adult hippocampal neurogenesis is an early critical event in Alzheimer’s disease (AD), contributing to progressive memory loss and cognitive decline. Reduced levels of the nucleoporin 153 (Nup153), a key epigenetic regulator of NSC stemness, characterize the neural stem cells isolated from a mouse model of AD (3×Tg) (AD-NSCs) and determine their altered plasticity and gene expression. Methods Nup153-regulated mechanisms contributing to NSC function were investigated: (1) in cultured NSCs isolated from AD and wild type (WT) mice by proteomics; (2) in vivo by lentiviral-mediated delivery of Nup153 or GFP in the hippocampus of AD and control mice analyzing neurogenesis and cognitive function; (3) in human iPSC-derived brain organoids obtained from AD patients and control subjects as a model of neurodevelopment. Results Proteomic approach identified Nup153 interactors in WT- and AD-NSCs potentially implicated in neurogenesis regulation. Gene ontology (GO) analysis showed that Nup153-bound proteins in WT-NSCs were involved in RNA metabolism, nuclear import and epigenetic mechanisms. Nup153-bound proteins in AD-NSCs were involved in pathways of neurodegeneration, mitochondrial dysfunction, proteasomal processing and RNA degradation. Furthermore, recovery of Nup153 levels in AD-NSCs reduced the levels of oxidative stress markers and recovered proteasomal activity. Lentiviral-mediated delivery of Nup153 in the hippocampal niche of AD mice increased the proliferation of early progenitors, marked by BrdU/DCX and BrdU/PSANCAM positivity and, later, the integration of differentiating neurons in the cell granule layer (BrdU/NeuN+ cells) compared with GFP-injected AD mice. Consistently, Nup153-injected AD mice showed an improvement of cognitive performance in comparison to AD-GFP mice at 1 month after virus delivery assessed by Morris Water Maze. To validate the role of Nup153 in neurogenesis we took advantage of brain organoids derived from AD-iPSCs characterized by fewer neuroepithelial progenitor loops and reduced differentiation areas. The upregulation of Nup153 in AD organoids recovered the formation of neural-like tubes and differentiation. Conclusions Our data suggest that the positive effect of Nup153 on neurogenesis is based on a complex regulatory network orchestrated by Nup153 and that this protein is a valuable disease target.

Abstract Diabetic foot ulcers (DFUs) are chronic wounds and one of the most common complications of diabetes, imposing significant physical and mental burdens on patients due to their poor prognosis and treatment efficacy. Adipose-derived stem cells (ADSCs) have been proven to promote wound healing, with studies increasingly attributing these beneficial effects to their paracrine actions. Consequently, research on ADSC secretome as a novel and promising alternative for DFU treatment has been extensively conducted. This article provides a comprehensive review of the mechanisms underlying refractory DFU wounds, the secretome of ADSCs, and its role in promoting wound healing in diabetes foot ulcers. And the review aims to provide reliable evidence for the clinical application of ADSC secretome in the treatment of refractory DFU wounds.

Abstract Background Burn trauma is one of the major causes of morbidity and mortality worldwide. The standard management of burn wounds consists of early debridement, dressing changes, surgical management, and split-thickness skin autografts (STSGs). However, there are limitations for the standard management that inclines us to find alternative treatment approaches, such as innovative cell-based therapies. We aimed to systematically review the different aspects of cell-based treatment approaches for burn wounds in clinical trials. Methods A systematic search through PubMed, Medline, Embase, and Cochrane Library databases was carried out using a combination of keywords, including “Cell transplantation”, “Fibroblast”, “Keratinocyte”, “Melanocyte”, or “Stem Cell” with “Burn”, “Burn wound”, or “Burn injury”. Firstly, titles and abstracts of the studies existing in these databases until “February 2024” were screened. Then, the selected studies were read thoroughly, and considering the inclusion and exclusion criteria, final articles were included in this systematic review. Moreover, a manual search was performed through the reference lists of the included studies to minimize the risk of missing reports. Results Overall, 30 clinical trials with 970 patients were included in our study. Considering the type of cells, six studies used keratinocytes, nine used fibroblasts, eight used combined keratinocytes and fibroblasts, one study used combined keratinocytes and melanocytes, five used combined keratinocytes and fibroblasts and melanocytes, and one study used mesenchymal stem cells (MSCs). Evaluation of the preparation type in these studies showed that cultured method was used in 25 trials, and non-cultured method in 5 trials. Also, the graft type of 17 trials was allogeneic, and of 13 other trials was autologous. Conclusions Our study showed that employing cell-based therapies for the treatment of burn wounds have significant results in clinical studies and are promising approaches that can be considered as alternative treatments in many cases. However, choosing appropriate cell-based treatment for each burn wound is essential and depends on the situation of each patient.

Abstract Background Inflammation-induced testicular damage is a significant contributing factor to the increasing incidence of infertility. Traditional treatments during the inflammatory phase often fail to achieve the desired fertility outcomes, necessitating innovative interventions such as cell therapy. Methods We explored the in vivo properties of intravenously administered Sertoli cells (SCs) in an acute lipopolysaccharide (LPS)-induced inflammatory mouse model. Infiltrating and resident myeloid cell phenotypes were assessed using flow cytometry. The impact of SC administration on testis morphology and germ cell quality was evaluated using computer-assisted sperm analysis (CASA) and immunohistochemistry. Results SCs demonstrated a distinctive migration pattern, importantly they preferentially concentrated in the testes and liver. SC application significantly reduced neutrophil infiltration as well as preserved the resident macrophage subpopulations. SCs upregulated MerTK expression in both interstitial and peritubular macrophages. Applied SC treatment exhibited protective effects on sperm including their motility and kinematic parameters, and maintained the physiological testicular morphology. Conclusion Our study provides compelling evidence of the therapeutic efficacy of SC transplantation in alleviating acute inflammation-induced testicular damage. These findings contribute to the expanding knowledge on the potential applications of cell-based therapies for addressing reproductive health challenges and offer a promising approach for targeted interventions in male infertility.

Abstract Background In 2016, a voluntary National Healthy Food and Drink Policy was released to improve the healthiness of food and drinks for sale in New Zealand health sector organisations. The Policy aims to role model healthy eating and demonstrate commitment to health and well-being of hospital staff and visitors and the general public. This study aimed to understand the experiences of hospital food providers and public health dietitians/staff in implementing the Policy, and identify tools and resources needed to assist with the implementation. Methods A maximum variation purposive sampling strategy (based on a health district’s population size and food outlet type) was used to recruit participants by email. Video conference or email semi-structured interviews included 15 open-ended questions that focused on awareness, understanding of, and attitudes towards the Policy; level of support received; perceived customer response; tools and resources needed to support implementation; and unintended or unforeseen consequences. Data was analysed using a reflexive thematic analysis approach. Results Twelve participants (eight food providers and four public health dietitians/staff) were interviewed; three from small ( 300,000 people) health districts. There was agreement that hospitals should role model healthy eating for the wider community. Three themes were identified relating to the implementation of the Policy: (1) Complexities of operating food outlets under a healthy food and drink policy in public health sector settings; (2) Adoption, implementation, and monitoring of the Policy as a series of incoherent ad-hoc actions; and (3) Policy is (currently) not achieving the desired impact. Concerns about increased food waste, loss of profits and an uneven playing field between food providers were related to the voluntary nature of the unsupported Policy. Three tools could enable implementation: a digital monitoring tool, a web-based database of compliant products, and customer communication materials. Conclusions Adopting a single, mandatory Policy, provision of funding for implementation actions and supportive tools, and good communication with customers could facilitate implementation. Despite the relatively small sample size and views from only two stakeholder groups, strategies identified are relevant to policy makers, healthcare providers and public health professionals.

Abstract Background Food insecurity has involved more than 750 million individuals worldwide. The association of food insecurity with socio-economic factors is also undeniable demand more consideration. Food insecurity will become a global priority by 2030. This systematic review and meta-analysis examined current literature concerning the association between food insecurity and psychological distress. Methods Relevant researches were identified by searching databases including PubMed, EMBASE, Scopus, and Web of Science, ProQuest, and Cochrane Library up to June 2024 without language limitation. Then a snowball search was conducted in the eligible studies. The quality assessment was made through Newcastle–Ottawa Scale. Results Data were available from 44 cross-sectional articles for systematic review and 17 eligible articles for meta-analysis with 2,267,012 and 1,953,636 participants, respectively. Findings support the growing segment of literature on the association between food insecurity and psychological distress. The highly represented groups were households with low income. Psychological and diabetic distress was directly associated with food insecurity as it increased the odds of distress to 329% (OR: 3.29; 95% CI: 2.46–4.40). Sleep problems, anxiety, depression, lower life satisfaction, obesity, and a higher rate of smoking were among the secondary outcomes. Conclusion Food insecurity was a common stressor that can have a negative impact on psychological well-being and even physical health. The findings should be considered in the public health and making policy-making process.

Abstract Background People living with obesity receive treatment services from health professionals for their weight or other health needs. In order for the students of the Faculty of Health Sciences, who will be a member of the health team in the future, to raise awareness of the society, it is necessary to first determine their obesity prejudices and eating habits. Methods The study is a cross-sectional and descriptive research. The study data were collected from 406 students studying at the Faculty of Health Sciences by online questionnaire method using a personal characteristics identification form, GAMS 27-Obesity Bias Scale and University Students Eating Behavior Scale (USEBS). The data were analyzed with SPSS 26 statistical software. Results In this study, all students were found to be prone to prejudice according to the mean total score of the Obesity Bias Scale and Obesity Bias Scale was higher in female students studying in perfusion department. In the sub-dimensions of the University Students Eating Behavior Scale, the enjoyment of food score was found to have the highest mean score. Conclusion According to the results of the study, there is a need to develop educational planning that will both increase the awareness of university students about the relationship between eating behaviors and obesity and eliminate obesity prejudice tendencies due to the fact that they are educated to provide services in the field of health.

Abstract Background Ethiopia is reported to have one of the highest prevalence of underweight among lactating mothers in Africa. In our study setting, the nutritional report from the district health office showed a high number of underweight lactating mothers and recurrent malnutrition problems. However, the determinants of underweight among lactating mothers were not well understood in our study setting. The study aimed to assess the determinants of underweight among lactating mothers in public health facilities of Siraro District, Southern Ethiopia. Methods Unmatched case control study was conducted among 390 (130 cases and 260 controls) lactating mothers in public health facilities of Siraro District from April 30 to May 30/2022. Cases were lactating mothers with BMI

Abstract Background Primary hypogonadism is a recognised complication in survivors of testicular cancer. However, secondary hypogonadism can result from other causes that suppress the hypothalamic-pituitary axis, including obesity, high dose glucocorticoids, chronic end organ failure, and diabetes. The aim of this study was to explore low total serum testosterone in Australian survivors of testicular cancer and examine associations with body mass index, age, and prior chemotherapy use. Methods Clinical data including height, weight, diagnosis, treatment, and hormonal evaluations during follow-up were extracted from the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Chemocog study (2007-2012), accompanied by data from two Australian, high-volume testicular cancer centres included in the iTestis testicular cancer registry (2012-2019). Low testosterone was defined by a serum concentration of testosterone (T) 8 IU/L, otherwise as secondary. Results Two hundred eighty-five individuals with either stage 1 or advanced testicular cancer were included. Of these, 105 (37%) were treated with orchidectomy and chemotherapy. Forty-nine (17%) met criteria for low testosterone during follow-up: 21 (43%) had primary and 27 (55%) had secondary low testosterone. Survivors of testicular cancer with higher body mass index were more likely to display low testosterone, both primary (p = 0.032) and secondary (p = 0.028). Our data did not show evidence of an association between older age or chemotherapy use and low testosterone in our cohort. Conclusions Low total serum testosterone was common in survivors of testicular cancer, and associated with a higher body mass index prior to orchidectomy, suggesting that elevated body mass index may contribute to low testosterone in this population, and that body weight, diet, and exercise should be addressed in testicular cancer follow-up.

Abstract Background Early detection through screening dramatically improves lung cancer survival rates, including among war Veterans, who are at heightened risk. The effectiveness of low dose computed tomography scans in lung cancer screening (LCS) prompted the Veteran’s Affairs Lung Precision Oncology Program (VA LPOP) to increase screening rates. We aimed to develop an adaptive population health tool to determine adequate resource allocation for the program, with a specific focus on primary care providers, nurse navigators, and radiologists. Methods We developed a tool using C + + that uses inputs that represents the process of the VA LCS program in Ann Arbor, Michigan to calculate FTEs of human resource needs to screen a given population. Further, we performed a sensitivity analysis to understand how resource needs are impacted by changes in population, screening eligibility, and time allocated for the nurse navigators’ tasks. Results Using estimates from the VA LCS Program as demonstrative inputs, we determined that the greatest number of full-time equivalents required were for radiologists, followed by nurse navigators and then primary care providers, for a target population of 75,000. An increase in the population resulted in a linear increase of resource needs, with radiologists experiencing the greatest rate of increase, followed by nurse navigators and primary care providers. These resource requirements changed with primary care providers, nurse navigators and radiologists demonstrating the greatest increase when 1–20, 20–40 and > 40% of Veterans accepted to be screened respectively. Finally, when increasing the time allocated to check eligibility by the nurse navigator from zero to three minutes, there was a linear increase in the full-time equivalents required for the nurse navigator. Conclusion Variation of resource utilization demonstrated by our user facing tool emphasizes the importance of tailored strategies to accommodate specific population demographics and downstream work. We will continue to refine this tool by incorporating additional variability in system parameters, resource requirements following an abnormal test result, and resource distribution over time to reach steady state. While our tool is designed for a specific program in one center, it has wider applicability to other cancer screening programs.

Abstract Introduction Healthy School Recognized Campus (HSRC) is a Texas A&M AgriLife Extension initiative that promotes the delivery of multiple evidence-based physical activity and nutrition programs in schools. Simultaneous delivery of programs as part of HSRC can result in critical implementation challenges. The study examines how the inner setting constructs from the Consolidated Framework for Implementation Research (CFIR) impact HSRC program delivery. Methods We surveyed (n = 26) and interviewed (n = 20) HSRC implementers (n = 28) to identify CFIR inner setting constructs related to program acceptability, appropriateness, and feasibility. Using a concurrent mixed-methods design, we coded interviews using the CFIR codebook, administered an inner setting survey, tested for relationships between constructs and implementation outcomes via chi-square tests, and compared quantitative and qualitative results. Results Stakeholders at schools that implemented one program vs. more than one program reported no differences in acceptability, appropriateness, or feasibility outcomes (p > .05); however, there was a substantial difference in reported program minutes (1118.4 ± 951.5 vs. 2674.5 ± 1940.8; p = .036). Available resources and leadership engagement were related to HSRC acceptability (r = .41; p = .038 and r = .48; p = .012, respectively) and appropriateness (r = .39; p = .046 and r = 0.63; p = .001, respectively). Qualitative analyses revealed that tangible resources (e.g., curriculum, a garden) enabled implementation, whereas intangible resources (e.g., lack of time) hindered implementation. Participants also stressed the value of buy-in from many different stakeholders. Quantitative results revealed that implementation climate was related to HSRC acceptability (r = .46; p = .018), appropriateness (r = .50; p = .009), and feasibility (r = .55; p = .004). Learning climate was related to HSRC appropriateness (r = .50; p = .009). However, qualitative assessment of implementation climate subconstructs showed mixed perspectives about their relationship with implementation, possibly due to differences in the compatibility/priority of different programs following COVID-19. Networks/communication analysis showed that schools have inner and outer circles of communication that can either benefit or hinder implementation. Conclusion Few differences were found by the number of programs delivered. Implementation climate (i.e., compatibility, priority) and readiness for implementation (i.e., resources and leadership engagement) were important to HSRC implementation. Strategies that focus on reducing time-related burdens and engaging stakeholders may support HSRC’s delivery. Other constructs (e.g., communication, access to knowledge) may be important to the implementation of HSRC but need further exploration.

Abstract Background The direct and indirect costs of chronic kidney disease (CKD) are substantial and increase over time. Concerns regarding our capacity to manage the financial burden that CKD) places on patients, caregivers, and society are raised by its increasing prevalence and progression. Lack of awareness of CKD’s economic effects is a major reason that lawmakers and administrators pay little attention to this chronic illness. Objective We aimed to analyze the direct burden of CKD across Asian countries and evaluate the main cost drivers among all mentioned cost centers in previous studies. Methodology Related works evaluating the expenditures of CKD from the perspective of the patient were interpreted by a thorough search of PUBMED and GOOGLE SCHOLAR. Results Country-wise, in Asia, the direct mean average medical costs in RRT patients were reported in 8 studies as $4574, $18668, $2901, $6848, $16669, $3489, $5945, and $6344 in Singapore, Korea, Taiwan, China, Jordan, Vietnam, Lebanon, and India respectively and the direct mean average medical costs in non-RRT patients were reported in six studies as $3412, $2241, $4534, $290 and $1500 in Singapore, Japan, China, Vietnam, and India respectively. Conclusion Hemodialysis is the main cost driver having an average mean cost of $23,358 per patient per year while the average mean cost of disease management is $4977 per patient per year. More research is needed to understand the specific economic challenges disadvantaged populations face, including the impact of income, education, and access to healthcare resources on the financial burden of CKD.

Abstract Background Treatment cost and high prevalence of Poly Cystic Ovarian Syndrome (PCOS) is a very challenging issue globally. Due to this reason; current study was conducted to determine pharmaco-economy of conventional and non-conventional treatments for the management of PCOS. Methods Prospective Cross-Sectional study was conducted in the metropolitan city of Karachi from January – December 2019. Primary data of 200 PCOS patients were collected from different hospitals and clinics. An instrument was used to collect data pertaining to the direct and indirect cost associated with the disease management. Collected data was analyzed by the tools for cost analysis and software called Statistical Package of Social Sciences (SPSS) – 22. Results In Cost Minimization Analysis (CMA); Allopathic treatment [Mean cost/month: PKR:4479.32 ± 350.95 (USD:27.46 ± 2.15)], Herbal treatment [Mean cost/month: PKR:1527.78 ± 78.15 (USD:9.37 ± 0.48)], Combination treatment [Mean cost/month: PKR:2803.09 ± 654.22 (USD:17.18 ± 4.01)], and Homoeopathic treatment [Mean cost/month: PKR:976.95 ± 46.19 (USD:5.99 ± 0.28)]. Incremental cost/month for Allopathic treatment is 358%, Herbal treatment is 56%, Combination treatment is 187%. In Cost Effectiveness Analysis (CEA); Allopathic treatment (Incremental cost-effectiveness ratio/month: 1334.24), Herbal treatment (Incremental cost-effectiveness ratio/month: 936.41), Combination treatment (Incremental cost-effectiveness ratio/month: 1017.09). Due to lowest cost of Homeopathic treatment, cost of Homeopathic treatment was considered as a threshold value. In-direct cost/month of Allopathic treatment is PKR:593.33 ± 24.00 (USD:3.64 ± 0.15), Herbal treatment is PKR:307.84 ± 26.69 (USD:1.89 ± 0.16), Combination treatment is PKR:409.09 ± 45.63 (USD:2.51 ± 0.28) and Homoeopathic treatment is PKR:300.00 ± 26.39 (USD:1.84 ± 0.16). Conclusion The most cost-effective is treatment is Homeopathic; Herbal treatment is second most cost-effective option for the treatment of PCOS. Lowest direct and indirect costs and short treatment duration collaboratively lessen the %incremental cost per year and incremental cost effectiveness ratio per year.

Abstract Background Since December 2021, Wuxi, China has offered a two-dose human papillomavirus (HPV) vaccination to 14-year-old females for free. This study evaluated the costs and benefits of this vaccination scheduled in the Expanded Program on Immunization in Wuxi from the perspective of the cities’ demographic characteristics, economic development, and policy support. Methods The model-based economic evaluation used TreeAge Pro software to construct a decision tree-Markov model for the vaccination strategy in which 100,000 14-year-old females received two doses of bivalent HPV vaccine or no vaccination. Costs and effects of the strategy were assessed from a societal perspective through literature research and data obtained from the Wuxi Centre for Disease Control and Prevention. Univariate, multivariate, and probabilistic sensitivity analyses assessed the stability of the findings. Results The cost of the bivalent HPV vaccine in Wuxi is 711.3 CNY. The two-dose of bivalent HPV vaccine for 100,000 14-year-old females would cost an additional 658,016 CNY compared to no vaccination, but would result in 1,960 Quality Adjustment Years of Life (QALYs). Using the per capita gross domestic product of 187,415 CNY in 2021 in Wuxi as the willingness-to-pay threshold, the vaccination strategy costs 3,357.37 CNY per QALY gained, which is much lower than the threshold, suggesting that it is a very cost-effective strategy. In addition, the vaccine strategy reduced the incidence of cervical cancer by 300 cases and cervical cancer deaths by 181 cases, representing a benefit-cost ratio of 2.86 (> 1) when health output outcomes were measured in monetary terms. These results suggested that the vaccination strategy was advantageous. Sensitivity analyses showed that changes in the parameters did not affect the conclusions and that the findings were robust. Conclusions Compared to no vaccination, the delivery of two doses of bivalent HPV vaccine for 14-year-old females was a more highly cost-effective and optimal strategy.

Abstract Background The National Institute for Health and Care Excellence (NICE) recommend that men with prostate cancer on androgen deprivation therapy (ADT) are offered twice weekly supervised aerobic and resistance exercise to address side effects of treatment. However, supervised exercise is not routinely offered in standard clinical practice. The STAMINA programme grant for applied research (PGfAR) has been designed to evaluate whether this recommendation can be delivered within standard NHS care. This paper describes how future implementation of NICE recommendations within the NHS was explored during complex intervention development to enable evaluation of a lifestyle intervention. Methods Two stakeholder workshops were conducted to explore factors pertinent to future implementation of the STAMINA Lifestyle intervention (SLI). Normalisation Process Theory (NPT) provided the theoretical framework for discussion and analysis. Stakeholder workshop 1 focussed on intervention coherence and buy-in. Stakeholder workshop 2 explored barriers and facilitators for embedding SLI into the context of the NHS, with delivery partner Nuffield Health, in the future. Results Workshops were attended by healthcare professionals (n = 16), exercise professionals (n = 17), members of public involved in PPI including patients (n = 12), health psychologists (n = 2), clinical commissioners (n = 4), cancer charities (n = 3), a cancer alliance (n = 1) and health economist (n = 1). Stakeholders agreed that professional training packages should emphasise the uniqueness of the SLI and underpinning theory and evidence (Coherence). To further engagement, the use of STAMINA champions and information about the delivery partner were recommended to enhance confidence and knowledge (Cognitive participation). Furthermore, a simple communication (Collective Action) and progress reporting system (Reflexive Monitoring) was suggested to fit into existing infrastructure within the NHS and community partner. Conclusions Application of NPT within two stakeholder workshops enhanced complex intervention development. Context-specific strategies to support implementation of SLI within the context of a trial were proposed, sensed-checked, and considered acceptable. The organisational implications of embedding and sustaining the intervention in preparation for wider NHS roll-out were considered (if proven to be effective) and will be explored in the qualitative component of a process evaluation underpinned by NPT. Trial registration (ISRCTN: 46385239 ). Registered on July 30, 2020.

Abstract Background Our research team partnered with primary care and quality improvement staff in Federally Qualified Community Health Centers (CHCs) to develop Partnered and Equity Data-Driven Implementation (PEDDI) to promote equitable implementation of evidence-based interventions. The current study used a human-centered design methodology to evaluate the usability of PEDDI and generate redesign solutions to address usability issues in the context of a cancer screening intervention. Methods We applied the Cognitive Walkthrough for Implementation Strategies (CWIS), a pragmatic assessment method with steps that include group testing with end users to identify and prioritize usability problems. We conducted three facilitated 60-min CWIS sessions with end users (N = 7) from four CHCs that included scenarios and related tasks for implementing a colorectal cancer (CRC) screening intervention. Participants rated the likelihood of completing each task and identified usability issues and generated ideas for redesign solutions during audio-recorded CWIS sessions. Participants completed a pre-post survey of PEDDI usability. Our research team used consensus coding to synthesize usability problems and redesign solutions from transcribed CWIS sessions. Results Usability ratings (scale 0–100: higher scores indicating higher usability) of PEDDI averaged 66.3 (SD = 12.4) prior to the CWIS sessions. Scores averaged 77.8 (SD = 9.1) following the three CWIS sessions improving usability ratings from “marginal acceptability” to “acceptable”. Ten usability problems were identified across four PEDDI tasks, comprised of 2–3 types of usability problems per task. CWIS participants suggested redesign solutions that included making data fields for social determinants of health and key background variables for identifying health equity targets mandatory in the electronic health record and using asynchronous communication tools to elicit ideas from staff for adaptations. Conclusions Usability ratings indicated PEDDI was in the acceptable range following CWIS sessions. Staff identified usability problems and redesign solutions that provide direction for future improvements in PEDDI. In addition, this study highlights opportunities to use the CWIS methodology to address inequities in the implementation of cancer screening and other clinical innovations in resource-constrained healthcare settings.

Abstract Background Presence of Germline mutations in the BRCA1 and BRCA2 genes is the most significant epidemiological factor for breast cancer (BC), where germline BRCA1 (gBRCA 1) mutation increases the risk for BC by 59–87% and gBRCA 2 mutation increases the risk by 38–80%. In this retrospective study, we have analyzed NGS-based genetic data for samples received at our laboratory for genetic testing over a three-year period to understand the prevalence and pattern if any of BRCA1 and BRCA2 mutations in Indian breast cancer patients. Results BRCA gene sequencing using NGS was performed in 395 consecutive cases of BC referred for testing to our lab between 2021 and 2023. Genetic analysis of mutations BRCA 1 and BRCA 2 genes resulted in 115 (29%) positive patients. Out of 115 patients, 79 reported BRCA1 mutations, whereas 36 had BRCA2 mutations. Exon 10 (57.3%) of BRCA1 and exon 11 (52%) of BRCA2 were the most mutated exons observed in this study. The c.1961delA (26.4%) variant, followed by the c.68_69delAG (22.7%) variant in BRCA1, and the c.6373delA (20.5%) variant in BRCA2, were the most common mutations found in our study. Our data shows positive correlation of younger age group (20–45 years) with BRCA positive status (Chi-square p value = 0.001). Conclusion BRCA mutation prevalence was 29.1% in our data which is higher than Western countries. Based on our findings BRCA screening looks imperative for women with BC especially younger women (

Abstract Background Acute myeloid leukemia (AML) is a clonal disorder arising from the differentiation arrest of myeloid precursor and malignant proliferation of a bone marrow derived, self-renewing stem or progenitor cells inside the bone marrow (BM) and blood due to numerous genetic mutations. Some mutations can also adjust DNA methylation and may play a critical function in pathogenesis in Cytogenetically Normal Acute Myeloid Leukemia (CN-AML). Somatic mutations in DNMT3a were pronounced in approximately 20% and ∼30–35% of overall AML and CN-AML, respectively. Most DNMT3a mutations in AML have been observed to be heterozygous, A missense mutation, R882, located inside Hot spot exon 23, has been found to be the maximum common mutation. This is a preliminary study conducted on 20 adult Egyptian patients newly diagnosed as AML where Sanger sequencing of Hotspot Exon 23 of DNMT3a gene was performed on their initial bone marrow samples and were followed up to 3 months post-induction therapy. Only De Novo AML patients were included in our study. Results Our results revealed that overall DNMT3a mutations were present in 25% of our patients, 10% having the R882 (rs147001633) mutation being 5% R882C and 5% R882H. Immunophenotyping analysis among Mutated DNMT3a (R882 and Non R882) and Wild DNMT3a revealed that AML markers exhibited no significant differences except for myeloperoxidase positivity which was significant among the groups (0.050). Regarding cytogenetics, only one case of the mutated DNMT3a had positive FISH inv (16), where the rest were FISH negative. After 28 days of induction, 75% of all our patients achieved complete response (CR), 20% achieve partial response (PR) out of which 75% are DNMT3a mutated. After 3 months follow-up, 10% of all patients faced mortality where 5% was DNMT3a wild type (died due to treatment-related mortality) and 5% was R882 mutated DNMT3a. Conclusion DNMT3a mutations are present in 25% (5/20) of our AML patients, with 10% (2/20) having the R882 mutation being 5% (1/20) R882C and 5% (1/20) R882H. R882 mutation is associated with resistance to chemotherapy, and poorer outcomes, highlighting its poorer prognostic significance in AML.

Abstract Background Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive oral cancer with a poor prognosis. Its polygenic risk is likely influenced by complex transcriptional disorders involving networks of co-expressed and functionally related genes, though such investigations are limited in OSCC. Methods We analyzed the GSE37991 dataset, comprising 40 OSCC and 40 normal oral tissue samples from the Gene Expression Omnibus. Tumor-specific modules were identified using weighted correlation network analysis (WGCNA), leading to the selection of hub mRNAs and lncRNAs. These lncRNAs were used to construct lncRNA–mRNA and competing endogenous RNA networks. We further examined the expression profiles and survival data of these genes from the Cancer Genome Atlas. Prognostic markers were identified and validated through 5-year survival analysis and Cox proportional hazards modeling. RT-qPCR was used to validate the expression levels in clinical OSCC tissues. Results We identified 1847 differentially expressed genes in OSCC tissues. WGCNA revealed four OSCC-specific modules, screening 120 hub mRNAs and five hub lncRNAs. Two prognostic markers (AQP5, IL-26) from hub mRNAs and three (FRMD5, INHBB, GUCY1A3) from the lncRNA–mRNA network were associated with survival. Validation showed lower expression of AQP5 and GUCY1A3, and higher expression of FRMD5 and INHBB in OSCC compared to normal tissues. Conclusion This study enhances our understanding of transcriptional dysregulation in OSCC and may highlights AQP5, IL-26, FRMD5, INHBB, and GUCY1A3 as promising prognostic biomarkers.

Abstract Introduction Occupational therapy has been underdeveloped and often neglected in the global health workforce agenda, contrasting with the global rise of population needs for services. The World Federation of Occupational Therapists (WFOT) is utilizing a research-based, multi-step process for developing a Global Strategy for strengthening the occupational therapist workforce. A multi-pronged scoping review, situational analysis, and expert input process enabled the drafting of a provisional Global Strategy. Here, feedback on that draft from representatives of WFOT member organizations was obtained and analyzed as one key intermediate step toward shaping the in-developing Strategy’s content and structure. Methods Two-phased, mixed-methods consultation consisting of: (1) online survey with score ratings and comments on the utility of each strategy and (2) four in-person focus groups discussions on low-scoring items involving a total of 76 representatives of WFOT member organizations. The focus group discussions were analyzed using an inductive thematic analysis approach. Results Strategies involving ‘task shifting/task sharing’ or the ‘harmonization of workforce data-collection requirements’ received the lowest scores in the initial survey and were thereby addressed in the focus groups discussions. The overarching theme of the focus groups was the need to: “clarify, specify, and contextualize the strategies”, including: (1) “clarify the terminology and specify the application”, for example, describe the meaning of task shifting, specify which tasks can (and cannot) be shifted and to whom, to address concerns regarding scope-of-practice, service demand, and safety; and (2) “outline the context of need and the context for the implementation” of the strategies, elucidating why the strategies are needed and how they can be feasibly implemented across the different jurisdictional contexts. Conclusion Within a mixed-methods consultation, WFOT representatives identified challenging topics on the draft workforce strategies and suggested methods to improve the Global Strategy, its acceptability, and implementation. The terms ‘task shifting/task sharing’ raised the greatest discussion among the profession leaders, when the strategy was not sufficiently clarified, specified, or contextualized.

Abstract Background Neurofibromatosis type 1 (NF1), an autosomal dominant disorder, characterized by a spectrum of diverse neurocutaneous manifestations, is caused by heterozygous pathogenic variants in NF1 gene. While patients with NF1 often exhibit characteristic features, atypical phenotypes can arise, necessitating consideration of differential diagnoses or concurrent pathologies. Case presentation A seven-year-old boy with suspected NF1 underwent clinical evaluation. He presented hallmark café-au-lait spots, axillary freckling, and neurofibromas. Neuroimaging revealed a cranial plexiform neurofibroma. Additionally, he exhibited attention-deficit hyperactivity disorder and developmental delay. Genetic testing identified an Alu insertion variant within the NF1 gene, and subsequent array comparative genomic hybridization detected a 16p13.11 duplication. Conclusions This case underscores the intricate molecular bases of NF1 by identifying a rare Alu insertion variant. The patient's neurocognitive challenges and dysmorphic features prompted exploration of a potential overlapping genetic condition. Coexisting genetic disorders have been documented in NF1 patients, emphasizing the necessity of discerning atypical manifestations. The observed 16p13.11 duplication likely contributes to the patient's phenotype, enhancing the precision of diagnosis, prognosis, and genetic counseling.

Abstract Background The effectiveness of eLearning in enhancing healthcare professionals’ capacity has received substantial attention globally. This review sought to synthesis evidence on the effectiveness of various types of eLearning programmes, and the facilitators and barriers to its use. Methods The review was guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four main databases (PubMed, Web of Science, JSTOR, and Scopus) in July 2023 and 44 articles met the eligibility criteria and were included in the review. The JBI critical appraisal checklist was used to appraise the methodological quality of the studies. The data were examined using narrative review to determine the effectiveness of the intervention as well as the barriers and facilitators to its use. Results This review found that asynchronous, synchronous, blended, and self-learning methodologies are effective eLearning approaches for continuous professional development. Previous positive experiences, user-friendly interfaces and relevance of the eLearning content to daily practice are critical elements that facilitate eLearning usage. Poor computer competence and literacy, lack of personal computers and high family duties were the main personal factors that hindered eLearning use. Some systemic barriers included; heavy workloads, shortage of specialised eLearning facilitators poor management involvement, and technical inadequacies within the ICT departments. Environmental issues such as poor infrastructure, including limited internet and frequent power outages acted as barriers. Conclusion The review highlights the effectiveness of various eLearning approaches among health professionals and presents the disparities between developing and developed economies in relation to the facilitators and barriers.

Abstract Background The genetic code for every organism is stored in biomolecules the deoxyribonucleic acid (DNA) and the ribonucleic acid (RNA). In higher organisms, DNA is found inside the nucleus while RNA is found outside the nucleus. While gene, which is directly responsible for the coding of proteins which are needed by the organism, constitutes only around one per cent of DNA, the remaining 99 per cent is noncoding. Coding RNA generally refers to mRNA that encodes protein, noncoding RNAs  act as cellular regulators without encoding proteins. Main text Although two-thirds of the human genome get transcribed, only 2% of the transcribed genome encodes proteins. It has been found that the remaining gets converted into long ncRNA and other ncRNAs. Noncoding RNA molecules known right from the early days of molecular biology are molecules like tRNA and rRNA. Long ncRNAs (lncRNA) were thought of as transcriptional noise even in the genomic era, but it has been found that they act as regulators at different levels of gene expression including chromatin organisation, transcriptional regulation and post-transcriptional control. This means that long ncRNAs control all stages of cell biogenesis and have critical roles in cell development and diseases. As much as they are vital to the development, evidence from research proves that mutations and dysregulations of these long ncRNA molecules are linked to diverse human diseases ranging from neuro-degeneration to cancers. Conclusion The noncoding gene which was largely ignored in the initial days of molecular biology has come to the centre space after the prime role it occupies in the various stages of biogenesis of organisms has come to light. The study of such molecules is vital and central in molecular biology today and they are immensely researched in drug discovery too.

Abstract Background Gallbladder cancer (GBC) is an infrequent type of malignant neoplasm worldwide. There are a number of risk factors that increase a person's likelihood of developing GBC. Gallbladder inflammatory (GID) diseases including cholelithiasis increase the risk of GBC, and this is further complicated by the fact that Helicobacter pylori (H. pylori) infection is extremely common in gastrointestinal tract in India. Since both miR 499 and H. pylori infection are found to be linked with tumor progression and metastasis, therefore there is a possibility that H. pylori might be involved in inflammation via dysregulation of miR 499. The study was designed to investigate the association of miR 499 expressions with H. pylori infection and their correlation with clinicopathological parameters of GBC. Material and methods The hundred three tissue samples used in this study are categorized into GID (n = 55) and GBC (n = 48). The expression of miR-499 was examined by using the Livak method for relative gene expression analysis. The presence/absence of H. pylori infection was examined by RT-PCR (Liferiver Helicobacter pylori RT-PCR Kit). Results Helicobacter pylori infection and GBC/GID cases were not significantly correlated. Decreased expression of miR 499 was observed in GBC (1.6 fold) as compared to GID patients (P

Abstract Background Kenya grapples with a paradox; severe public sector workforce shortages co-exist with rising unemployment among healthcare professionals. Medical schools have increased trainee outputs, but only 45% of newly qualified/registered doctors were absorbed by the public sector during 2015–2018. In such a context, we explore what influences doctors’ career choices at labour market entry, specifically understanding the role of public service motivation (PSM). Methods We conducted a cross-sectional and prospective study of interns and recently graduated doctors to examine PSM, their intention to work in the public sector and their final employment sector and status. We surveyed them on their PSM and job intentions and conducted a prospective follow-up survey of the interns, around one year later, to understand their employment status. Findings We recruited 356 baseline participants and followed up 76 out of 129 eligible interns. The overall PSM score was high among all participants (rated 4.50/5.00) irrespective of sector preferences. 48% (171/356) of the participants preferred to work in the public sector immediately after internship, alongside 16% (57/356) preferring direct entry into specialist training—commonly in the public sector. Only 13% (46/356) and 7% (25/365) preferred to work in the private or faith-based sector. Despite the high proportion of interns preferring public sector jobs, only 17% (13/76) were employed in the public sector at follow-up and 13% (10/76) were unemployed, due to lack of job availability. Conclusion High PSM scores irrespective of sector preferences suggest that doctors are generally committed to serving the ‘public good’. Many intended to work in the public sector but were unable to due to lack of job opportunities. Policymakers have an opportunity to tackle workforce gaps in the public sector as young doctors continue to express a preference for such work. To do this they should prioritise creating adequate and sustainable job opportunities.

Abstract Background Malnutrition in the elderly places a significant burden on healthcare, social, and aged-care systems, yet it often remains undiagnosed and untreated. This study aims to evaluate family physicians' knowledge and attitudes towards the diagnosis and treatment of malnutrition in the elderly. Methods Based on a literature review, an online questionnaire was developed, comprised of seven knowledge-related items and eight attitude-related questions regarding malnutrition in elderly populations. We also assessed the feasibility of including two malnutrition screening questions in regular clinic visits for individuals aged ≥ 70 years. Results Surveys were completed by 126 physicians (35% response rate), mean age 47.2 ± 12.6 years; 15.6 ± 12.5 years of practice; 67% females; and 92% board-certified family physicians. Moreover, 77.6% agreed that diagnosing malnutrition is important in patients with decreased appetite. Most respondents demonstrated knowledge of nutritional screening principles (63.5%) and recognized that even obese elderly individuals could be malnourished (83.2%). There was partial agreement (60%) that normal BMI values in the elderly differ from those in younger populations. Almost complete agreement was seen for incorporating two nutritional status questions in medical visits (91%), with physicians expressing willingness to receive training in malnutrition identification and screening tools. Despite challenges such as time constraints and limited knowledge, participants were open to conducting biannual malnutrition risk screening for elderly patients. Conclusion We recommend malnutrition screening in primary care followed by malnutrition diagnosis and referral of malnourished patients to the proper intervention.

Abstract Background Women in the sex trade encounter significant challenges in obtaining reproductive healthcare. Reports of reproductive healthcare for women in the sex trade center on the prevention and termination of pregnancies, yet most women in the sex trade globally experience full term pregnancies and bear children. This study aimed to explore barriers and enabling factors to providing reproductive healthcare for women in the sex trade in Israel. Methods We conducted a qualitative study utilizing a grounded theory method. Data were collected through semi-structured interviews, conducted between June 2021 and July 2022. Interviews were conducted with practitioners in healthcare settings (n = 20), practitioners in social services settings (n = 15), and women in the sex trade who received reproductive health care-related medical services (n = 13) in Israel. The interviews were audiotaped, transcribed, and thematically analyzed. Results The findings indicated a multilayered structure of healthcare system-related factors and women-related factors. Stigma was noted as a multidimensional barrier, reflected in service providers’ attitude towards women in the sex trade, impairing the patient-provider relationship and impeding women’s help-seeking. However, the creation of a relationship of trust between the women and healthcare providers enabled better health outcomes. Conclusions Based on the findings, we propose recommendations for designing and implementing reproductive healthcare services for women in the sex trade. The recommendations offer to (a) include women with lived experiences in planning and providing reproductive healthcare services, (b) adopt a trauma-informed approach, (c) emphasize nonjudgmental care, (d) train healthcare providers to reduce stigma and bias, and (e) enhance the affordability of health services for women experiencing marginalization.

Abstract Background Missing data are common in observational studies and often occur in several of the variables required when estimating a causal effect, i.e. the exposure, outcome and/or variables used to control for confounding. Analyses involving multiple incomplete variables are not as straightforward as analyses with a single incomplete variable. For example, in the context of multivariable missingness, the standard missing data assumptions (“missing completely at random”, “missing at random” [MAR], “missing not at random”) are difficult to interpret and assess. It is not clear how the complexities that arise due to multivariable missingness are being addressed in practice. The aim of this study was to review how missing data are managed and reported in observational studies that use multiple imputation (MI) for causal effect estimation, with a particular focus on missing data summaries, missing data assumptions, primary and sensitivity analyses, and MI implementation. Methods We searched five top general epidemiology journals for observational studies that aimed to answer a causal research question and used MI, published between January 2019 and December 2021. Article screening and data extraction were performed systematically. Results Of the 130 studies included in this review, 108 (83%) derived an analysis sample by excluding individuals with missing data in specific variables (e.g., outcome) and 114 (88%) had multivariable missingness within the analysis sample. Forty-four (34%) studies provided a statement about missing data assumptions, 35 of which stated the MAR assumption, but only 11/44 (25%) studies provided a justification for these assumptions. The number of imputations, MI method and MI software were generally well-reported (71%, 75% and 88% of studies, respectively), while aspects of the imputation model specification were not clear for more than half of the studies. A secondary analysis that used a different approach to handle the missing data was conducted in 69/130 (53%) studies. Of these 69 studies, 68 (99%) lacked a clear justification for the secondary analysis. Conclusion Effort is needed to clarify the rationale for and improve the reporting of MI for estimation of causal effects from observational data. We encourage greater transparency in making and reporting analytical decisions related to missing data.

Abstract Background Early identification of children at high risk of developing myopia is essential to prevent myopia progression by introducing timely interventions. However, missing data and measurement error (ME) are common challenges in risk prediction modelling that can introduce bias in myopia prediction. Methods We explore four imputation methods to address missing data and ME: single imputation (SI), multiple imputation under missing at random (MI-MAR), multiple imputation with calibration procedure (MI-ME), and multiple imputation under missing not at random (MI-MNAR). We compare four machine-learning models (Decision Tree, Naive Bayes, Random Forest, and Xgboost) and three statistical models (logistic regression, stepwise logistic regression, and least absolute shrinkage and selection operator logistic regression) in myopia risk prediction. We apply these models to the Shanghai Jinshan Myopia Cohort Study and also conduct a simulation study to investigate the impact of missing mechanisms, the degree of ME, and the importance of predictors on model performance. Model performance is evaluated using the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). Results Our findings indicate that in scenarios with missing data and ME, using MI-ME in combination with logistic regression yields the best prediction results. In scenarios without ME, employing MI-MAR to handle missing data outperforms SI regardless of the missing mechanisms. When ME has a greater impact on prediction than missing data, the relative advantage of MI-MAR diminishes, and MI-ME becomes more superior. Furthermore, our results demonstrate that statistical models exhibit better prediction performance than machine-learning models. Conclusion MI-ME emerges as a reliable method for handling missing data and ME in important predictors for early-onset myopia risk prediction.

Abstract The inability to correctly account for unmeasured confounding can lead to bias in parameter estimates, invalid uncertainty assessments, and erroneous conclusions. Sensitivity analysis is an approach to investigate the impact of unmeasured confounding in observational studies. However, the adoption of this approach has been slow given the lack of accessible software. An extensive review of available R packages to account for unmeasured confounding list deterministic sensitivity analysis methods, but no R packages were listed for probabilistic sensitivity analysis. The R package unmconf implements the first available package for probabilistic sensitivity analysis through a Bayesian unmeasured confounding model. The package allows for normal, binary, Poisson, or gamma responses, accounting for one or two unmeasured confounders from the normal or binomial distribution. The goal of unmconf is to implement a user friendly package that performs Bayesian modeling in the presence of unmeasured confounders, with simple commands on the front end while performing more intensive computation on the back end. We investigate the applicability of this package through novel simulation studies. The results indicate that credible intervals will have near nominal coverage probability and smaller bias when modeling the unmeasured confounder(s) for varying levels of internal/external validation data across various combinations of response-unmeasured confounder distributional families.

Abstract Background A dramatic decline in mental health of people worldwide in the early COVID-19 pandemic years has not recovered. In rural and remote Australia, access to appropriate and timely mental health services has been identified as a major barrier to people seeking help for mental ill-health. From 2020 to 2021 a care navigation model, Navicare, was co-designed with rural and remote communities in the Greater Whitsunday Region of Central Queensland in Australia. The Exploration, Preparation, Implementation and Sustainment (EPIS) framework was used to design and guide multiple aspects of a multisite study, The Bridging Study, to evaluate the implementation of Navicare in Australia. Methods A community-engaged hybrid effectiveness-implementation study design will focus on the tailored implementation of Navicare at three new sites as well as monitoring implementation at an existing site established since 2021. Study outcomes assessed will include sustained access as the co-primary outcome (measured using access to Navicare mental health referral services) and Proctor’s Implementation Outcomes of feasibility, acceptability, appropriateness, adoption, fidelity, implementation cost, and sustainability. Data collection for the implementation evaluation will include service usage data, community consultations, interviews, and workshops; analysed using mixed methods and guided by EPIS and other implementation frameworks. Pre-post effectiveness and cost-consequence study components are embedded in the implementation and sustainment phases, with comparison to pre-implementation data and value assessed for each EPIS phase using hospital, service, and resource allocation data. A scaling up strategy will be co-developed using a national roundtable forum in the final year of the study. Qualitative exploration of other aspects of the study (e.g., mechanisms of action and stakeholder engagement) will be conducted. Discussion Our study will use tailoring to local sites and a community-engaged approach to drive implementation of a mental health care navigation service in rural and remote Australia, with expected benefits to mental healthcare access. This approach is consistent with policy recommendations nationally and internationally as building blocks for rural health including the World Health Organization Framework for Action on Strengthening Health Systems to Improve Health Outcomes. Trial registration Prospectively registered on April 2, 2024, on the Australian New Zealand Clinical Trials Registry, no. ACTRN12624000382572. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386665&isReview=true .

Abstract Background Chronic, non-malignant diseases (CNMD) like chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) and dementia in advanced stages are very burdensome for patients. Timely palliative care with strong collaboration between general practitioners (GPs) and specialist palliative home care (SPHC) teams can reduce symptom burden, hospitalization rates, hospitalization costs and overall healthcare costs. The KOPAL-study on strengthening interprofessional collaboration for patients with palliative care needs tested the effect of an intervention comprising of a SPHC nurse assessment and an interprofessional case conference. This qualitative evaluative study explores patients’, proxies’ and their associates’ motivation to participate in the KOPAL-study and views on the (benefits of the) intervention. Methods We interviewed 13 male and 10 female patients as well as 14 proxies of patients with dementia and six associates of study participants using a semi-structured interview guide. All interviews were digitally recorded, transcribed verbatim and analysed with deductive-inductive qualitative content analysis. Results Motivation for participation was driven by curiosity, the aim to please the GP or to support research, respectively to help other patients. Few interviewees pointed out to have expected positive effects for themselves. The nurse visit was evaluated very positively. Positive changes concerning health care or quality of life were reported sparsely. Most study participants did not prepare for the SPHC nurse assessment. They had no expectations concerning potential benefits of such an assessment, the interdisciplinary case conference and an early integration of palliative care. The majority of interviewees reported that they did not talk about the nurse visit and the interprofessional case conference with their GPs. Conclusion Our results lead to the conclusion that SPHC nurses can serve as an advocate for the patient and thereby support the patients’ autonomy. GPs should actively discuss the results of the interdisciplinary case conference with patients and collaboratively decide on further actions. Patient participation in the interdisciplinary case conference could be another way to increase the effects of the intervention by empowering patients to not just passively receive the intervention. Trial registration DRKS00017795 German Clinical Trials Register, 17Nov2021, version 05.