Primary Site Research Articles

Short-term results of a multicenter study based on a modified N7 induction regimen combined with arsenic trioxide in the treatment of children with high-risk neuroblastoma

Objective: To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB). Methods: This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children's Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children's Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher's exact test. Results: Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion: ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Glucocorticoids induce a maladaptive epithelial stress response to aggravate acute kidney injury.

Acute kidney injury (AKI) is a frequent and challenging clinical condition associated with high morbidity and mortality and represents a common complication in critically ill patients with COVID-19. In AKI, renal tubular epithelial cells (TECs) are a primary site of damage, and recovery from AKI depends on TEC plasticity. However, the molecular mechanisms underlying adaptation and maladaptation of TECs in AKI remain largely unclear. Here, our study of an autopsy cohort of patients with COVID-19 provided evidence that injury of TECs by myoglobin, released as a consequence of rhabdomyolysis, is a major pathophysiological mechanism for AKI in severe COVID-19. Analyses of human kidney biopsies, mouse models of myoglobinuric and gentamicin-induced AKI, and mouse kidney tubuloids showed that TEC injury resulted in activation of the glucocorticoid receptor by endogenous glucocorticoids, which aggravated tubular damage. The detrimental effect of endogenous glucocorticoids on injured TECs was exacerbated by the administration of a widely clinically used synthetic glucocorticoid, dexamethasone, as indicated by experiments in mouse models of myoglobinuric- and folic acid-induced AKI, human and mouse kidney tubuloids, and human kidney slice cultures. Mechanistically, studies in mouse models of AKI, mouse tubuloids, and human kidney slice cultures demonstrated that glucocorticoid receptor signaling in injured TECs orchestrated a maladaptive transcriptional program to hinder DNA repair, amplify injury-induced DNA double-strand break formation, and dampen mTOR activity and mitochondrial bioenergetics. This study identifies glucocorticoid receptor activation as a mechanism of epithelial maladaptation, which is functionally important for AKI.

Bladder transitional cell carcinoma anatomic primary site as a predictor of survival and mortality: a population-based retrospective cohort study

Background: Bladder cancer is a heterogeneous disease with varying prognostic outcomes based on the primary tumor site within the bladder. This study aims to evaluate the impact of tumor location on overall survival and cancer-specific survival in bladder cancer patients. Methods: The authors conducted a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results database. Patients with primary transitional cell carcinoma of the bladder were categorized based on their tumor locations. Survival outcomes were assessed using Kaplan–Meier analysis and Cox proportional hazards regression models, adjusted for age, sex, race, cancer stage, and treatment modalities. Additionally, binary logistic regression models were employed to predict overall mortality (OM) and cancer-specific mortality (CSM) at 1, 5, and 10 years. Results: The study included 107 909 patients diagnosed with primary bladder cancer between 2000 and 2021. Significant differences in survival outcomes were observed across different tumor sites. Bladder cancer originating in the urachus had the worst OS before 100 months and the worst CSS overall. Tumors in the anterior wall showed the worst OS after 100 months. In the Cox multivariable analysis, anterior wall tumors were associated with a 1.513-fold increased risk of death compared to lateral wall tumors. The binary logistic regression models showed that anterior wall tumors predicted the highest OM and CSM at 1-year, while urachal tumors had the worst outcomes at 5 and 10 years. Conclusions: The primary site of bladder cancer is a significant predictor of survival outcomes, with tumors in the urachus and anterior wall associated with a poorer prognosis. These findings underscore the importance of considering tumor location in the prognosis and management of bladder cancer. Future studies should aim to validate these findings in more diverse populations and explore the underlying biological mechanisms that drive these differences.

From Headache to Handled: Advanced In-Basket Management System in Primary Care Clinics Reduces Provider Workload Burden and Self-Reported Burnout.

The electronic health record (EHR) has been associated with provider burnout, exacerbated by increasing In-Basket burden. We sought to study the impact of implementing a team-based approach to In-Basket management on a series of primary care ambulatory sites. We performed a workflow analysis of the transition to the Advanced In-Basket Management (AIM) nurse team triage for six family medicine clinic locations in a large health system. We abstracted and analyzed associated provider workflow metrics from our EHR. We conducted a postintervention provider survey on satisfaction with the AIM project and provider burnout. The AIM project was implemented in six family medicine clinics after provider townhalls and workgroup development. A nurse team curriculum was created using the principles of "maturing the message" before sending it to a provider and "only handle it once" to improve response efficiency. Provider workload metrics abstracted from the EHR demonstrated 12.2 fewer In-Basket messages per provider per day (p < 0.05), 6.3 fewer minutes per provider per day worked outside scheduled hours (p < 0.05), 3.5 fewer minutes spent in the In-Basket per provider per day (p < 0.05), but 13.7 more seconds spent per completed message per provider (p = 0.017), likely attributable to increased message complexity. Sixty-four percent of providers reported no burnout symptoms in a postintervention survey, 56% agreed that the AIM project reduced their burnout, and approximately 70% of providers agreed that the AIM project was acceptable and appropriate for their clinic. The AIM project demonstrates team-based nurse In-Basket triage is possible to implement across multiple primary care sites, is an acceptable intervention for providers, can reduce provider workload burden and self-reported provider burnout.

Management of de novo Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) and the role of Radiotherapy: A Consensus by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

Prostate cancer treatments paradigms are in continuous evolution, especially in metastatic setting. In this context, the Genito-Urinary (GU) Group of Italian Association of Radiotherapy and Clinical Oncology (AIRO) aimed to create a Consensus on radiotherapy indication in de novo metastatic hormone sensitive prostate cancer both on primary tumour and metastatic sites. A panel of experts, involved in clinical management of prostate cancer, through the estimate-talk-estimate (ETE) method, developed a list of items and correspondent statements on the identified topic. Seven conclusive items were identified with 12 statements about the chosen topic, radiotherapy in metastatic hormone sensitive prostate cancer on primary tumour and metastatic sites. This consensus might help clinicians in prostate cancer managing in daily clinical practice.

Risk Factors for Locoregional Relapse After Segmentectomy: Supplementary Analysis of the JCOG0802/WJOG4607L Trial

IntroductionThe JCOG0802/WJOG4607L trial revealed superior overall survival in segmentectomy compared with lobectomy for small-peripheral NSCLC. Nevertheless, locoregional relapse (LR) is a major issue for segmentectomy. An ad hoc supplementary analysis aimed to determine the risk factors for LR and the degree of advantages of segmentectomy on the basis of primary tumor sites. MethodsParticipants in multi-institutional and intergroup, open-label, phase 3 randomized controlled trial in Japan were enrolled from August 10, 2009, to October 21, 2014. Risk factors for LR after segmentectomy and clinical features following the primary tumor site were investigated. ResultsOf 1105 patients, 576 and 529 underwent lobectomy and segmentectomy, respectively. The primary tumor site for segmentectomy was the left upper division, left lingular segment, left S6, left basal segment, right upper lobe, right S6, or right basal segment. Multivariable analysis in the segmentectomy group revealed that pure-solid appearance on thin-section computed tomography (OR = 3.230; 95% confidence interval [CI]: 1.559–6.690; p = 0.0016), margin distance less than the tumor size (OR = 2.682; 95% CI: 1.350–5.331; p = 0.0049), and male sex (OR = 2.089; 95% CI: 1.047–4.169; p = 0.0366) were significantly associated with LR. Patients with left lingular segment tumors (OR = 4.815; 95% CI: 1.580–14.672) tended to experience LR more frequently than those with left upper division tumors, although primary tumor sites were not statistically significant. ConclusionsThin-section computed tomography findings and margin distance are important factors to avoid LR in segmentectomy.

Cancer as an Independent Mortality Risk in Chronic Thromboembolic Pulmonary Hypertension

BackgroundThe management of chronic thromboembolic pulmonary hypertension (CTEPH) has advanced significantly in recent years, thereby improving patient prognosis. However, the impact of cancer on the outcomes of patients with CTEPH under current treatment remains unclear. This study aimed to investigate the prevalence of cancer in patients with CTEPH and determine how comorbid cancer affects their prognosis and clinical course. MethodsData from an ongoing Japanese prospective cohort study were analyzed. Prevalence and primary cancer sites were evaluated. The association of a history of cancer with a composite endpoint, including all-cause death, lung transplantation, and worsening of CTEPH, as well as venous thromboembolism and bleeding events, was assessed. ResultsOf the 1,270 patients in the cohort, 134 (10.6%) had a history of cancer, with the most common primary sites being the breast in women and the prostate in men. The incidence of composite outcome and all-cause death was higher in those with a history of cancer (p<0.001, log-rank test). In the Cox proportional hazard model, age- and sex-adjusted hazard ratios for the composite outcome and all-cause death were 2.69 (95% confidence interval, 1.48–4.89, p=0.001) and 4.25 (95% confidence interval, 1.98–9.10, p<0.001), respectively, for patients with a history of cancer. No significant differences in venous thromboembolism and bleeding events were observed between patients with and those without a history of cancer. ConclusionsA history of cancer, with a prevalence of 10.6%, is an independent risk factor for mortality in patients with CTEPH undergoing the currently recommended treatment.

Peptide receptor radionuclide therapy for ectopic Cushing’s syndrome caused by metastatic neuroendocrine neoplasia

Background: Metastatic gastroenteropancreatic neuroendocrine neoplasia (GEPNEN) can cause ectopic Cushing’s syndrome (ECS). ECS is highly morbid and medical therapy is complex and can be ineffective. Patients unsuitable for bilateral adrenalectomy (BA) have dismal outcomes. Peptide receptor radionuclide therapy (PRRT) is a rational option for hormone and disease control in ECS caused by NEN with high somatostatin receptor (SSTR) expression. Aim: To describe characteristics and outcomes of patients with ECS treated with PRRT. Methods: Single-centre, retrospective analysis of imaging, biochemistry and outcomes of seven consecutive patients with ECS caused by metastatic GEPNEN treated with PRRT from 2006-2023. Results: Patients were aged 17–75 (female n=6). The primary site was pancreas (5/7) and rectum (2/7). Six patients were on medical therapy for ECS at baseline (one previous BA). A median of 34.4GBq of [177Lu]Lu-DOTA-octreotate was given. [90Y]Y-DOTA-octreotate (one patient) and [111In]In-octreotide (one patient) was also used. Five patients had radiosensitising chemotherapy. Five patients had a flare of ECS within one week of PRRT cycle 1 (PRRT-C1). Following PRRT-C1, 5/7 patients had complete biochemical resolution of ECS at 1.5–6 months (four ongoing; one recurred after 12 months and had elective BA at 18 months). Best metabolic response on [18F]F-FDG PET/CT: Four patients had a complete metabolic response (CMR), one had a partial metabolic response. PFS was 3–208 months. Two patients progressed at first follow-up. The longest ECS remission and CMR continues at &gt;17 years. Conclusion: PRRT can be effective for ECS caused by metastatic SSTR-positive GEPNEN and should be considered in its treatment algorithm.

Time toxicity faced by patients with advanced cancer across primary cancer sites.

268 Background: Time toxicity, defined as the burden of time for patients interacting with the health care systems, is particularly important for patients with limited life expectancy. Little is known about the relative impact of time toxicity among different cancer types at the end of life. This study examines median contact days for inpatient, outpatient, and home health services among different primary cancer types for patients with advanced cancer with limited prognosis. Methods: A retrospective cohort analysis was performed on patients with advanced (stage 4) cancer who died within one year of diagnosis at Kaiser Permanente Northern California between January 1, 2015, and June 30, 2023. Time toxicity was defined as comprehensive contact days with healthcare system over the course of patients’ survival period between cancer diagnosis and death (i.e., contact days divided by survival or contact %). Types of contact included institutional stay (emergency department visit, hospitalization, skilled nursing facility, rehabilitation); outpatient visits (ambulatory care, labs, imaging); and in-home care (home-health, home hospice, telephone and virtual visit). The study quantified overall median contact % and contact % by specific care settings, stratified by cancer primary site. Results: The study included 10102 patients. The median age at diagnosis was 74 years with 47% female. Patients were predominantly white (65%), followed by Asian (12%), Hispanic (12%), and black (8%). The median Elixhauser comorbidity score was 4. With the exception of head and neck cancers, most cancers had higher contact % near diagnosis and at end of life (U-shaped curve). Head and neck cancers had the highest percent of patients undergoing surgery (36%) and radiation (52%), which may explain its sinuosity-like curve with a rapid increase of weekly contact % after diagnosis (a small peak), followed by rapid decrease and another increase by the end of their life. Survival days were comparatively long for head and neck cancers (158 days, IQR: 84-265) and short for thoracic (80 days, IQR: 35-166) and upper gastrointestinal cancers (80 days, IQR: 38-173). Malignant hematology patients had notably higher comprehensive contact % (74%, IQR: 47-100) which was driven primarily by emergency room department visits and hospital stays (p&lt;0.001 for all contact types). Conclusions: The study highlights the high burden of time toxicity in patients with advanced cancer with limited prognosis. The significant variations in time toxicity among different cancer types, especially in malignant hematology and head and neck patients, emphasize the need to tailor goals of care discussions for patients with cancer at the end of life. By focusing on reducing unwanted time toxicity, healthcare providers can enhance the quality of life for patients with cancer, ensuring more efficient and patient-centered care delivery.

Piloting a patient navigation programme for individuals living with dementia, their care partners and members of the care team: protocol for a mixed-methods evaluation

IntroductionInternationally, the number of individuals living with dementia continues to rise. Individuals living with dementia, their care partners and their care team face many barriers and challenges to accessing dementia...

Unpacking the Theatre-Religion Dialectic: Siting Christianity’s Mary Magdalene

In this article, we focus on the portrayal of Mary Magdalene in the rock opera Jesus Christ Superstar as a case study to offer insights into the dialectical relationship between theatre and religion. This allows us to better understand the difficulties and limits involved as one attempts to challenge or confront the other. Drawing on the framework of ideological sites, particularly the anthropological distinction between primary and secondary sites, we provide a valuable explanation as to why, despite the endeavours at redressing them, misconceptions about Mary Magdalene continue to exist. We close with a discussion of metatheatre and extract guidelines on how a metatheatrical critique of received understandings about Mary might be conceived.

Selective adsorption of oxidized yeast glucan for Pb2+: Influencing factors, adsorption site and mechanism

This work investigated the influencing factors and mechanism of Pb2+ adsorbed by oxidized yeast glucan (OYG). Firstly, OYG showed greater Pb2+ adsorption performance than yeast glucan, and the adsorption capacity was greater with the oxidation degree increased. The optimal pH range for Pb2+ adsorption was 6–7. The adsorption capacity of Pb2+ reached its maximum of 86.68 and 96.88 mg/g for 20 mg of OYG1 and OYG2, respectively. In addition, OYG exhibited selective adsorption, with adsorption capacity in the order: Pb2+ > Cd2+ > Cu2+ > Ca2+. Then adsorption isotherm was established by fitting Langmuir and Freundlich isotherm adsorption models. Freundlich model could better fit the adsorption process of lead by OYG, indicating that the adsorption process was heterogeneous. According to the Langmuir model, the maximum lead adsorption capacities of OYG1 and OYG2 at 298 K were 100.70 and 131.06 mg/g, respectively. Thermodynamic data indicated a spontaneous endothermic process (ΔG < 0, ΔH > 0), accompanied by increased system disorder (ΔS > 0), involving physical and chemical adsorptions. Finally, FT-IR and XPS results revealed -COOH and -OH were the primary adsorption sites in OYG, and the interaction between these groups and Pb2+ was mainly achieved by electrostatic interaction (or ion-dipole interaction).

Preparation of vascularized forearm dermal fat flap and repairing of donor site

Objective:This study prepared vascularized dermal fat flaps and introduced a local split-thickness skin graft from an in situ cutaneous area cutaneous area to manage forearm flap donor sites and evaluated the esthetic and functional outcomes post-operatively. From July 2020 to June 2023, 13 patients with soft tissue defects in Oral and Maxillary Area were repaired with tvascular forearm dermal fat flap. There were 8 males and 5 females, aged from 42-71 years. The flaps ranged from 8 cm×7 cm to 7 cm×5 cm in size. The donor site defects were covered by local split-thickness skin graft from the in situ skins. The color matching degree, surgical scars, ranges of wrist movement and hand sensations in donor forearms were assessed at 6 months after surgery. Results:The tvascular forearm dermal fat flaps for 15 cases all survived. All the local split-thickness skin grafts transplanted with this technique showed primary healing. The follow-up period for 6 months, Donor site exhibited suitabler color matching and there was not severe complications. Conclusion:The vascularized dermal fat flap provides an alternative to conventional forearm flap harvest, which enables primary donor site closure with reduced rates of delayed donor site healing. The vascularized dermal fat flap is a relatively reliable repair method for soft defects in Oral and Maxillary Area.

50 years in the making: acp3U, an amino-acid-containing nucleoside, links N-glycans and RNA in glycoRNA

In a recent publication in Cell, Xie etal.1 report a sensitive and scalable method for the detection and characterization of native glycoRNAs and identify acp3U, an abundant modified nucleoside discovered 50 years ago in tRNAPhe, as one of the primary attachment sites for N-glycans.

Time toxicity of lutetium-177 treatment in gastroenteropancreatic neuroendocrine tumours

Objectives: We aim to investigate the time toxicity of patients with gastroenteropancreatic-neuroendocrine tumours treated with lutetium-177 Dotatate in a single institution. Design: This is a retrospective cohort study. Methods: All patients with gastroenteropancreatic-neuroendocrine tumours treated with lutetium-177 Dotatate in the Alexander Fleming Institute were included. Our primary endpoint was to evaluate time toxicity, which accounted for every day that the patient had contact with any department of any healthcare institution. Results: Our cohort included 21 patients with metastatic disease, female sex 86%, and had a median age of 55 (IQR 44-63). The primary tumour site was small intestine in 47.6% of the cases. The median number of previous systemic treatments for advanced disease was 2 (IQR 2 - 3). The overall response rate was 19%, and 66.6% had disease clinical benefit. The median calculated 'time toxicity' was 11 days (IQR 8-18), representing 5.7% of the total treatment duration. The main contributors to time-toxicity included infusion days, blood draws, radiological scans, and hospitalizations (median 4 days for each). Conclusion: Lutetium-177 Dotatate treatment for gastroenteropancreatic-neuroendocrine tumours was associated with a low time toxicity, excellent tolerability, good response and a prolonged PFS, of which the median was not reached in the short follow-up we present. Newer treatments with different mechanisms of action provide longer survivals and widen the landscape of choices. Understanding new clinical endpoints is important for the transition into a more modern clinical practice, strengthening personalised and patient-oriented strategies.

EP.03G.01 Comparison of Tumor Immune Microenvironments Between Primary and Metastatic Sites in Non-Small Cell Lung Cancer

EP.03G.01 Comparison of Tumor Immune Microenvironments Between Primary and Metastatic Sites in Non-Small Cell Lung Cancer

Leveraging a geographic information system (GIS) to identify lung cancer care disparities and opportunities in rural Appalachia.

78 Background: The Rural Appalachian Lung Cancer Screening Initiative is led by the Association of Cancer Care Centers (ACCC) and patient advocacy partners. Recognized by the White House Cancer Moonshot, this initiative seeks to improve lung cancer screening rates by partnering with health systems in rural Appalachia to develop and implement interventions. An 11-county region bordering West Virginia, Virginia, and Kentucky has significantly higher mortality and lung cancer incidence rates than the national rates of 35.0 and 54.0 per 100,000 people, respectively (Table 1). This region was identified as the focus area for the initiative with participation from health systems in Pike County, KY, and Buchanan County, VA. Methods: To understand availability of local resources, ACCC developed an interactive GIS tool that identifies screening and referral locations as well as essential services in the region. Lung cancer screening sites, oncology services, mammography locations, critical access hospitals, NCI-designated cancer centers, federally qualified health centers (FQHCs) and look-alikes, rural health clinics, and primary care/general health services were identified from publicly available data and data requested from state departments of health. Facilities were contacted to verify services when unclear. STATA 18 was used to combine and clean data for upload to Google MyMaps, creating an interactive map. Results: Of the 11 counties, all contain at least 1 FQHC or primary care site. However, 5 of the counties do not have lung cancer screening sites and 7 of the counties do not have oncology service sites (Table). The closest NCI-designated cancer centers to the participating sites are over 140 miles away. Conclusions: While there is a notable presence of primary care, access to lung cancer screening and oncology care is limited. Sites can utilize this map to inform development of interventions by considering potential geographical challenges, identifying referral sites, outreach opportunities, and partners to facilitate lung cancer screening and education. Further, these methods are replicable, and can be used to inform current access to care and improve equitable delivery of lung cancer screening in regions across the U.S. Distribution of lung cancer mortality, incidence, and infrastructure within initiative focus region. Region Mortality*(per 100,000) Incidence*(per 100,000) # Lung Cancer Screening Sites # Oncology Services Sites KY (1 county) 70 109.3 2 2 VA (6 counties) 45.0 – 61.4 42.9 – 68.6 4 3 WV (4 counties) 57.6 – 74.8 100.4 – 111.5 1 0 *Lung &amp; Bronchus, 2016-2020 age-adjusted death rates (KY, VA, WV) and incidence rates (KY, WV). Lung &amp; Bronchus, 2015-2019 age-adjusted incidence rate (VA). Source: statecancerprofiles.cancer.gov.

Development of a predictive model for patients with bone metastases referred to palliative radiotherapy: Secondary analysis of a multicenter study (the PRAIS trial).

The decision to administer palliative radiotherapy (RT) to patients with bone metastases (BMs), as well as the selection of treatment protocols (dose, fractionation), requires an accurate assessment of survival expectancy. In this study, we aimed to develop three predictive models (PMs) to estimate short-, intermediate-, and long-term overall survival (OS) for patients in this clinical setting. This study constitutes a sub-analysis of the PRAIS trial, a longitudinal observational study collecting data from patients referred to participating centers to receive palliative RT for cancer-induced bone pain. Our analysis encompassed 567 patients from the PRAIS trial database. The primary objectives were to ascertain the correlation between clinical and laboratory parameters with the OS rates at three distinct time points (short: 3 weeks; intermediate: 24 weeks; prolonged: 52 weeks) and to construct PMs for prognosis. We employed machine learning techniques, comprising the following steps: (i) identification of reliable prognostic variables and training; (ii) validation and testing of the model using the selected variables. The selection of variables was accomplished using the LASSO method (Least Absolute Shrinkage and Selection Operator). The model performance was assessed using receiver operator characteristic curves (ROC) and the area under the curve (AUC). Our analysis demonstrated a significant impact of clinical parameters (primary tumor site, presence of non-bone metastases, steroids and opioid intake, food intake, and body mass index) and laboratory parameters (interleukin 8 [IL-8], chloride levels, C-reactive protein, white blood cell count, and lymphocyte count) on OS. Notably, different factors were associated with the different times for OS with only IL-8 included both in the PMs for short- and long-term OS. The AUC values for ROC curves for 3-week, 24-week, and 52-week OS were 0.901, 0.767, and 0.806, respectively. We successfully developed three PMs for OS based on easily accessible clinical and laboratory parameters for patients referred to palliative RT for painful BMs. While our findings are promising, it is important to recognize that this was an exploratory trial. The implementation of these tools into clinical practice warrants further investigation and confirmation through subsequent studies with separate databases.

Instability and Evolution of Shocked Clouds Formed by Orthogonal Collisions between Magnetized Filamentary Molecular Clouds

Filamentary molecular clouds are recognized as primary sites for the formation of stars. Specifically, regions characterized by the overlapping point of multiple filaments, known as hub regions, are often associated with active star formation. However, the formation mechanism of this hub structure is not well understood. Therefore, to understand the formation mechanism and star formation in hub structures, as a first step, we investigate the orthogonal collisions between two filaments using three-dimensional ideal magnetohydrodynamical simulations. As a model of initial filaments, we use an infinitely long filament in magnetohydrostatic equilibrium under a global magnetic field running perpendicular to the filament axis. Two identical equilibrium filaments, sharing the same magnetic flux, are arranged with their long axes perpendicular to each other and given an initial velocity perpendicular to their long axes to replicate an orthogonal collision. We find three types of evolution after the shocked cloud is formed: collapse, stable, and expansion modes. The energy balance just after the filaments completely collide explains the future evolution of the shocked cloud. If the magnitude of gravitational energy is larger than the sum of the kinetic, thermal, and magnetic energies, the shocked cloud evolves in collapse mode. If the magnitude of gravitational energy is less than the sum of these energies, the cloud evolves in stable mode when the kinetic energy is relatively small and in expansion mode when the kinetic energy is sufficiently large.

A Novel Etanercept-loaded Nano-emulsion for Targeted Treatment of Inflammatory Arthritis via Draining Lymph Node.

Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD), and the global incidence rate is 0.5 ~ 1%. Existing medications might reduce symptoms, however, there is no known cure for this illness. Etanercept (EN) can competitively inhibit TNF-α binding to the TNF receptor on the cell surface to treat RA. However, subcutaneous injection of free EN predisposes to systemic distribution and induces immune system hypofunction. Draining lymph nodes (LNs) play a significant role in the onset, maintenance, and progression of RA as they are the primary sites of aberrant immune response and inflammatory cytokine production. The purpose of this study was to successfully treat RA with etanercept by encapsulating it in nanoemulsions (NEs/EN) and then delivering it specifically to draining LNs. The EN-loaded NEs were prepared by high-pressure homogenization method and modified with DSPE-mPEG2000 and Ca(OH)2. A novel nano-emulsion (NE) was constructed to deliver EN (NE/EN) to RA-draining LNs. To decrease aggregation and load EN, DSPE-mPEG2000 and Ca(OH)2 were successively decorated on the surface of the lipid injectable emulsions. The hydrodynamic diameter and morphology of NEs/EN were investigated by using a laser particle size analyzer and transmission electron microscopy, respectively. The in vivo fluorescence imaging system was used to study the in vivo LN targeting ability of the formulation. In the therapeutic experiment, NEs/EN was subcutaneously administrated to inhibit the development of the mouse arthritis model. Circular dichroism spectrum and L929 cell experiment confirmed that NEs encapsulation had no impact on the biological activity of EN. In vivo investigation on collagen-induced arthritis (CIA) mouse model showed that NEs/EN have good inguinal lymph node targeting capabilities, as well as, anti-inflammatory effect against RA. Compared with the free group, the paw thickness and arthritic score in NEs/EN group were significantly alleviated. Moreover, the concentration of pro-inflammatory cytokines TNF-α and IL-1β in NEs/EN-treated mice was lower than that in free EN. NEs/EN effectively improve the effectiveness of EN in the treatment of RA. Our work provides an experimental foundation for expanding the clinical application of EN.