bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine
Authors: Miao Sai-Nan , Chai Meng-Qi , Liu Xiang-Yu , Wei Cheng-Yu , Zhang Cun-Cun , Sun Ning-Ning , Fei Qing-Ze , Peng Lin-Lin , Qiu Huan
Published: April 2024

Background and purpose

In recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression.

Method

C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR.

Results

This study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression.

Conclusion

Exercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice.
Brain structural alterations associated with impulsiveness in male violent patients with schizophrenia
Authors: Lu Juntao , Gou Ningzhi , Sun Qiaoling , Huang Ying , Guo Huijuan , Han Dian , Zhou Jiansong , Wang Xiaoping
Published: April 2024

Background

Violence in schizophrenia (SCZ) is a phenomenon associated with neurobiological factors. However, the neural mechanisms of violence in patients with SCZ are not yet sufficiently understood. Thus, this study aimed to explore the structural changes associated with the high risk of violence and its association with impulsiveness in patients with SCZ to reveal the possible neurobiological basis.

Method

The voxel-based morphometry approach and whole-brain analyses were used to measure the alteration of gray matter volume (GMV) for 45 schizophrenia patients with violence (VSC), 45 schizophrenia patients without violence (NSC), and 53 healthy controls (HC). Correlation analyses were used to examine the association of impulsiveness and brain regions associated with violence.

Results

The results demonstrated reduced GMV in the right insula within the VSC group compared with the NSC group, and decreased GMV in the right temporal pole and left orbital part of superior frontal gyrus only in the VSC group compared to the HC group. Spearman correlation analyses further revealed a positive correlation between impulsiveness and GMV of the left superior temporal gyrus, bilateral insula and left medial orbital part of the superior frontal gyrus in the VSC group.

Conclusion

Our findings have provided further evidence for structural alterations in patients with SCZ who had engaged in severe violence, as well as the relationship between the specific brain alterations and impulsiveness. This work provides neural biomarkers and improves our insight into the neural underpinnings of violence in patients with SCZ.
Risk of diabetes and expected years in life without diabetes among adults from an urban community in India: findings from a retrospective cohort
Authors: Sharma Palak , Dilip T.R. , Kulkarni Anjali , Mishra Udaya Shankar , Shejul Yogesh
Published: April 2024

Background

Diabetes prevalence has increased over the past few decades, and the shift of the burden of diabetes from the older population to the younger population has increased the exposure of longer durations in a morbid state. The study aimed at ascertaining the likelihood of progression to diabetes and to estimate the onset of diabetes within the urban community of Mumbai.

Methods

This study utilized an observational retrospective non-diabetic cohort comprising 1629 individuals enrolled in a health security scheme. Ten years of data were extracted from electronic medical records, and the life table approach was employed to assess the probability of advancing to diabetes and estimate the expected number of years lived without a diabetes diagnosis.

Results

The study revealed a 42% overall probability of diabetes progression, with age and gender variations. Males (44%) show higher probabilities than females (40%) of developing diabetes. Diabetes likelihood rises with age, peaking in males aged 55–59 and females aged 65–69. Males aged 30–34 exhibit a faster progression (10.6 years to diagnosis) compared to females (12.3 years).

Conclusion

The study’s outcomes have significant implications for the importance of early diabetes detection. Progression patterns suggest that younger cohorts exhibit a comparatively slower rate of progression compared to older cohorts.
Evaluation of the effect of chemical disinfection and ultraviolet disinfection on the dimensional stability of polyether impression material: an in-vitro study
Authors: Joshi Snehal , Madhav V. N.V , Saini Ravinder S. , Gurumurthy Vishwanath , Alshadidi Abdulkhaliq Ali F. , Aldosari Lujain Ibrahim N. , Okshah Abdulmajeed , Mosaddad Seyed Ali , Heboyan Artak
Published: April 2024

Background

Various methods, chemical and physical, disinfect dental impressions. Common chemicals include 1% Sodium Hypochlorite and 2% glutaraldehyde, while UV radiation is a prevalent physical method. Few studies compare their effects on dimensional stability in polyether impressions. This study aims to assess such stability using different disinfection methods. Therefore, this study was planned to evaluate the dimensional stability of polyether impression material using different disinfection methods.

Methods

This in vitro study compared the effects of chemical disinfectants (1% Sodium Hypochlorite and 2% glutaraldehyde) and UV irradiation on the dimensional stability of polyether impression material. Groups A, B, C, and D, each with ten samples (N = 10), were studied. Group A was untreated (control). Group B was treated with 2% glutaraldehyde for 20 min, Group C with 1% Sodium Hypochlorite for 20 min, and Group D with UV rays for 20 min. A pilot milling machine drill was used to make four parallel holes labeled A, B, C, and D in the anterior and premolar regions from right to left. After sequential drilling, four implant analogs were positioned using a surveyor for accuracy. Ten open-tray polyether impressions were made and treated as described in the groups, followed by pouring the corresponding casts. Distortion values for each disinfection method were measured using a coordinate measuring machine capable of recording on the X- and Y-axes.

Results

A comprehensive analysis was conducted using the one-way ANOVA test for distinct groups labeled A, B, C, and D, revealing significant differences in the mean distances for X1, X2, X4, X5, and X6 among the groups, with p-values ranging from 0.001 to 0.000. However, no significant differences were observed in X3. Notably, mean distances for the Y variables exhibited substantial differences among the groups, emphasizing parameter variations, with p-values ranging from 0.000 to 0.033. The results compared the four groups using the one-way ANOVA test, revealing statistically significant distance differences for most X and Y variables, except for X3 and Y4. Similarly, post-hoc Tukey’s tests provided specific pairwise comparisons, underlining the distinctions between group C and the others in the mean and deviation distances for various variables on both the X- and Y-axes.

Conclusions

This study found that disinfection with 1% sodium hypochlorite or UV rays for 20 min maintained dimensional stability in polyether impressions.
Identifying subgroups in heart failure patients with multimorbidity by clustering and network analysis
Authors: Martins Catarina , Neves Bernardo , Teixeira Andreia Sofia , Froes Miguel , Sarmento Pedro , Machado Jaime , Magalhães Carlos A. , Silva Nuno A. , Silva Mário J. , Leite Francisca
Published: April 2024

This study presents a workflow for identifying and characterizing patients with Heart Failure (HF) and multimorbidity utilizing data from Electronic Health Records. Multimorbidity, the co-occurrence of two or more chronic conditions, poses a significant challenge on healthcare systems. Nonetheless, understanding of patients with multimorbidity, including the most common disease interactions, risk factors, and treatment responses, remains limited, particularly for complex and heterogeneous conditions like HF. We conducted a clustering analysis of 3745 HF patients using demographics, comorbidities, laboratory values, and drug prescriptions. Our analysis revealed four distinct clusters with significant differences in multimorbidity profiles showing differential prognostic implications regarding unplanned hospital admissions. These findings underscore the considerable disease heterogeneity within HF patients and emphasize the potential for improved characterization of patient subgroups for clinical risk stratification through the use of EHR data.
Olfactory bulb anomalies in KBG syndrome mouse model and patients
Authors: Goodkey Kara , Wischmeijer Anita , Perrin Laurence , Watson Adrianne E. S. , Qureshi Leenah , Cordelli Duccio Maria , Toni Francesco , Gnazzo Maria , Benedicenti Francesco , Elmaleh-Bergès Monique , Low Karen J. , Voronova Anastassia
Published: April 2024

ANKRD11 (ankyrin repeat domain 11) is a chromatin regulator and the only gene associated with KBG syndrome, a rare neurodevelopmental disorder. We have previously shown that Ankrd11 regulates murine embryonic cortical neurogenesis. Here, we show a novel olfactory bulb phenotype in a KBG syndrome mouse model and two diagnosed patients. Conditional knockout of Ankrd11 in murine embryonic neural stem cells leads to aberrant postnatal olfactory bulb development and reduced size due to reduction of the olfactory bulb granule cell layer. We further show that the rostral migratory stream has incomplete migration of neuroblasts, reduced cell proliferation as well as aberrant differentiation of neurons. This leads to reduced neuroblasts and neurons in the olfactory bulb granule cell layer. In vitro, Ankrd11-deficient neural stem cells from the postnatal subventricular zone display reduced migration, proliferation, and neurogenesis. Finally, we describe two clinically and molecularly confirmed KBG syndrome patients with anosmia and olfactory bulb and groove hypo-dysgenesis/agenesis. Our report provides evidence that Ankrd11 is a novel regulator of olfactory bulb development and neuroblast migration. Moreover, our study highlights a novel clinical sign of KBG syndrome linked to ANKRD11 perturbations in mice and humans.
Shared genetic architecture between autoimmune disorders and B-cell acute lymphoblastic leukemia: insights from large-scale genome-wide cross-trait analysis
Authors: Yu Xinghao , Chen Yiyin , Chen Jia , Fan Yi , Lu Huimin , Wu Depei , Xu Yang
Published: April 2024

Background

To study the shared genetic structure between autoimmune diseases and B-cell acute lymphoblastic leukemia (B-ALL) and identify the shared risk loci and genes and genetic mechanisms involved.

Methods

Based on large-scale genome-wide association study (GWAS) summary-level data sets, we observed genetic overlaps between autoimmune diseases and B-ALL, and cross-trait pleiotropic analysis was performed to detect shared pleiotropic loci and genes. A series of functional annotation and tissue-specific analysis were performed to determine the influence of pleiotropic genes. The heritability enrichment analysis was used to detect crucial immune cells and tissues. Finally, bidirectional Mendelian randomization (MR) methods were utilized to investigate the casual associations.

Results

Our research highlighted shared genetic mechanisms between seven autoimmune disorders and B-ALL. A total of 73 pleiotropic loci were identified at the genome-wide significance level (P < 5 × 10–8), 16 of which had strong evidence of colocalization. We demonstrated that several loci have been previously reported (e.g., 17q21) and discovered some novel loci (e.g., 10p12, 5p13). Further gene-level identified 194 unique pleiotropic genes, for example IKZF1, GATA3, IKZF3, GSDMB, and ORMDL3. Pathway analysis determined the key role of cellular response to cytokine stimulus, B cell activation, and JAK-STAT signaling pathways. SNP-level and gene-level tissue enrichment suggested that crucial role pleiotropic mechanisms involved in the spleen, whole blood, and EBV-transformed lymphocytes. Also, hyprcoloc and stratified LD score regression analyses revealed that B cells at different developmental stages may be involved in mechanisms shared between two different diseases. Finally, two-sample MR analysis determined causal effects of asthma and rheumatoid arthritis on B-ALL.

Conclusions

Our research proved shared genetic architecture between autoimmune disorders and B-ALL and shed light on the potential mechanism that might involve in.
Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus
Authors: Bi Jiao , Zheng Mei , Li Ke , Sun Siwei , Zhang Zihang , Yan Nana , Li Xueping
Published: April 2024

Background

Compelling evidence suggests that calcium/phosphorus homeostasis-related parameters may be linked to diabetes mellitus and cardiovascular events. However, few studies have investigated the association of fibroblast growth factor 23 (FGF23), α-klotho and FGF23/α-klotho ratio with atherosclerosis in patients with type 2 diabetes mellitus (T2DM).

Objective

This study was designed to evaluate whether FGF23, α-klotho and FGF23/α-klotho ratio are associated with T2DM and further to explore the relationships between these three factors and atherosclerosis in Chinese patients with T2DM.

Methods

Serum FGF23 and α-klotho levels were measured via an enzyme-linked immunosorbent assay (ELISA) kit, and the carotid intima-media thickness (CIMT) was assessed via high-resolution color Doppler ultrasonography. The associations of serum FGF23, α-klotho and FGF23/α-klotho ratio with atherosclerosis in T2DM patients were evaluated using multivariable logistic regression models.

Results

This cross-sectional study involved 403 subjects (207 with T2DM and 196 without T2DM), 41.7% of the patients had atherosclerosis, and 67.2% of the carotid intima were thickened to a thickness greater than 0.9 mm. Compared with those in the lowest tertile, higher tertiles of FGF23 levels and FGF23/α-klotho ratio were positively associated with T2DM after adjusting for covariates, and serum α-klotho concentration was inversely correlated with T2DM (all P values < 0.01). Moreover, elevated serum FGF23 levels and FGF23/α-klotho ratio were positively associated with CIMT and carotid atherosclerosis in T2DM patients (all P values < 0.01). Further spline analysis similarly revealed linear dose‒response relationship (all P values < 0.01). And there was still significant differences in CIMT and carotid atherosclerosis between the highest group of α-klotho and the reference group in T2DM patients (P values = 0.05).

Conclusions

T2DM was positively linearly related to serum FGF23 concentration and FGF23/α-klotho ratio, and negatively correlated with serum α-klotho concentration. Furthermore, both FGF23 and FGF23/α-klotho ratio were positively correlated with CIMT and atherosclerosis in T2DM patients, while α-klotho was inversely correlated with both CIMT and atherosclerosis, although the associations were not completely significant. Prospective exploration and potential mechanisms underlying these associations remain to be further elucidated.
Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors
Authors: Chen Tong , Wang Mingzhao , Chen Yanchao , Liu Yutao
Published: April 2024

The application of chimeric antigen receptor (CAR) T cells in the management of hematological malignancies has emerged as a noteworthy therapeutic breakthrough. Nevertheless, the utilization and effectiveness of CAR-T cell therapy in solid tumors are still limited primarily because of the absence of tumor-specific target antigen, the existence of immunosuppressive tumor microenvironment, restricted T cell invasion and proliferation, and the occurrence of severe toxicity. This review explored the history of CAR-T and its latest advancements in the management of solid tumors. According to recent studies, optimizing the design of CAR-T cells, implementing logic-gated CAR-T cells and refining the delivery methods of therapeutic agents can all enhance the efficacy of CAR-T cell therapy. Furthermore, combination therapy shows promise as a way to improve the effectiveness of CAR-T cell therapy. At present, numerous clinical trials involving CAR-T cells for solid tumors are actively in progress. In conclusion, CAR-T cell therapy has both potential and challenges when it comes to treating solid tumors. As CAR-T cell therapy continues to evolve, further innovations will be devised to surmount the challenges associated with this treatment modality, ultimately leading to enhanced therapeutic response for patients suffered solid tumors.
Seasonal extreme temperatures and short-term fine particulate matter increases pediatric respiratory healthcare encounters in a sparsely populated region of the intermountain western United States
Authors: Landguth Erin L. , Knudson Jonathon , Graham Jon , Orr Ava , Coyle Emily A. , Smith Paul , Semmens Erin O. , Noonan Curtis
Published: April 2024

Background

Western Montana, USA, experiences complex air pollution patterns with predominant exposure sources from summer wildfire smoke and winter wood smoke. In addition, climate change related temperatures events are becoming more extreme and expected to contribute to increases in hospital admissions for a range of health outcomes. Evaluating while accounting for these exposures (air pollution and temperature) that often occur simultaneously and may act synergistically on health is becoming more important.

Methods

We explored short-term exposure to air pollution on children’s respiratory health outcomes and how extreme temperature or seasonal period modify the risk of air pollution-associated healthcare events. The main outcome measure included individual-based address located respiratory-related healthcare visits for three categories: asthma, lower respiratory tract infections (LRTI), and upper respiratory tract infections (URTI) across western Montana for ages 0–17 from 2017–2020. We used a time-stratified, case-crossover analysis with distributed lag models to identify sensitive exposure windows of fine particulate matter (PM2.5) lagged from 0 (same-day) to 14 prior-days modified by temperature or season.

Results

For asthma, increases of 1 µg/m3 in PM2.5 exposure 7–13 days prior a healthcare visit date was associated with increased odds that were magnified during median to colder temperatures and winter periods. For LRTIs, 1 µg/m3 increases during 12 days of cumulative PM2.5 with peak exposure periods between 6–12 days before healthcare visit date was associated with elevated LRTI events, also heightened in median to colder temperatures but no seasonal effect was observed. For URTIs, 1 unit increases during 13 days of cumulative PM2.5 with peak exposure periods between 4–10 days prior event date was associated with greater risk for URTIs visits that were intensified during median to hotter temperatures and spring to summer periods.

Conclusions

Delayed, short-term exposure increases of PM2.5 were associated with elevated odds of all three pediatric respiratory healthcare visit categories in a sparsely population area of the inter-Rocky Mountains, USA. PM2.5 in colder temperatures tended to increase instances of asthma and LRTIs, while PM2.5 during hotter periods increased URTIs.
Triglyceride-glucose index predicts postoperative delirium in elderly patients with type 2 diabetes mellitus: a retrospective cohort study
Authors: Sun Miao , Liu Min , Zhang Faqiang , Sang Lijuan , Song Yuxiang , Li Peng , Liu Siyuan , Yang Huikai , Ma Libin , Cao Jiangbei , Mi Weidong , Ma Yulong
Published: April 2024

Background

Postoperative delirium (POD) is more prevalent among elderly patients with type 2 diabetes mellitus (T2DM). Insulin resistance (IR) can be assessed using the triglyceride-glucose (TyG) index, a novel biomarker. This study aims to investigate the predictive potential of the TyG index for POD in elderly patients with T2DM.

Materials and methods

Elderly patients (≥ 65) with T2DM who underwent non-neurosurgery and non-cardiac surgery were enrolled. Univariate and multivariate logistic regression analyses were conducted to assess the association between the TyG index and POD. Additionally, subgroup analyses were performed to compare the sex-specific differences in the predictive ability of the TyG index for POD.

Results

A total of 4566 patients were included in this retrospective cohort. The receiver operating characteristic (ROC) curve analysis determined the optimal cut-off value for the TyG index to be 8.678. In the univariate model, a TyG index > 8.678 exhibited an odds ratio (OR) of 1.668 (95% CI: 1.210–2.324, P = 0.002) for predicting POD. In the multivariate regression models, the ORs were 1.590 (95% CI: 1.133–2.252, P < 0.008), 1.661 (95% CI: 1.199–2.325, P < 0.003), and 1.603 (95% CI: 1.137–2.283, P = 0.008) for different models. Subgroup analyses demonstrated that the predictive ability of the TyG index was more pronounced in females compared to males.

Conclusion

The TyG index shows promise as a novel biomarker for predicting the occurrence of POD in elderly surgical patients with T2DM.
A pH-responsive nanoplatform with dual-modality imaging for enhanced cancer phototherapy and diagnosis of lung metastasis
Authors: Yuan Mujie , Han Zeyu , Li Yan , Zhan Xin , Sun Yong , He Bin , Liang Yan , Luo Kui , Li Fan
Published: April 2024

To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis.
Impact of doxorubicin-loaded ferritin nanocages (FerOX) vs. free doxorubicin on T lymphocytes: a translational clinical study on breast cancer patients undergoing neoadjuvant chemotherapy
Authors: Sevieri Marta , Andreata Francesco , Mainini Francesco , Signati Lorena , Piccotti Francesca , Truffi Marta , Bonizzi Arianna , Sitia Leopoldo , Pigliacelli Claudia , Morasso Carlo , Tagliaferri Barbara , Corsi Fabio , Mazzucchelli Serena
Published: April 2024

Despite the advent of numerous targeted therapies in clinical practice, anthracyclines, including doxorubicin (DOX), continue to play a pivotal role in breast cancer (BC) treatment. DOX directly disrupts DNA replication, demonstrating remarkable efficacy against BC cells. However, its non-specificity toward cancer cells leads to significant side effects, limiting its clinical utility. Interestingly, DOX can also enhance the antitumor immune response by promoting immunogenic cell death in BC cells, thereby facilitating the presentation of tumor antigens to the adaptive immune system. However, the generation of an adaptive immune response involves highly proliferative processes, which may be adversely affected by DOX-induced cytotoxicity. Therefore, understanding the impact of DOX on dividing T cells becomes crucial, to deepen our understanding and potentially devise strategies to shield anti-tumor immunity from DOX-induced toxicity. Our investigation focused on studying DOX uptake and its effects on human lymphocytes. We collected lymphocytes from healthy donors and BC patients undergoing neoadjuvant chemotherapy (NAC). Notably, patient-derived peripheral blood mononuclear cells (PBMC) promptly internalized DOX when incubated in vitro or isolated immediately after NAC. These DOX-treated PBMCs exhibited significant proliferative impairment compared to untreated cells or those isolated before treatment initiation. Intriguingly, among diverse lymphocyte sub-populations, CD8 + T cells exhibited the highest uptake of DOX. To address this concern, we explored a novel DOX formulation encapsulated in ferritin nanocages (FerOX). FerOX specifically targets tumors and effectively eradicates BC both in vitro and in vivo. Remarkably, only T cells treated with FerOX exhibited reduced DOX internalization, potentially minimizing cytotoxic effects on adaptive immunity.

Our findings underscore the importance of optimizing DOX delivery to enhance its antitumor efficacy while minimizing adverse effects, highlighting the pivotal role played by FerOX in mitigating DOX-induced toxicity towards T-cells, thereby positioning it as a promising DOX formulation. This study contributes valuable insights to modern cancer therapy and immunomodulation.
The value of admission avoidance: cost-consequence analysis of one-year activity in a consolidated service
Authors: Hernandez Carme , Herranz Carme , Baltaxe Erik , Seijas Nuria , González-Colom Rubèn , Asenjo Maria , Coloma Emmanuel , Fernandez Joaquim , Vela Emili , Carot-Sans Gerard , Cano Isaac , Roca Josep , Nicolas David
Published: April 2024

Background

Many advantages of hospital at home (HaH), as a modality of acute care, have been highlighted, but controversies exist regarding the cost-benefit trade-offs. The objective is to assess health outcomes and analytical costs of hospital avoidance (HaH-HA) in a consolidated service with over ten years of delivery of HaH in Barcelona (Spain).

Methods

A retrospective cost-consequence analysis of all first episodes of HaH-HA, directly admitted from the emergency room (ER) in 2017–2018, was carried out with a health system perspective. HaH-HA was compared with a propensity-score-matched group of contemporary patients admitted to conventional hospitalization (Controls). Mortality, re-admissions, ER visits, and direct healthcare costs were evaluated.

Results

HaH-HA and Controls (n = 441 each) were comparable in terms of age (73 [SD16] vs. 74 [SD16]), gender (male, 57% vs. 59%), multimorbidity, healthcare expenditure during the previous year, case mix index of the acute episode, and main diagnosis at discharge. HaH-HA presented lower mortality during the episode (0 vs. 19 (4.3%); p < 0.001). At 30 days post-discharge, HaH-HA and Controls showed similar re-admission rates; however, ER visits were lower in HaH-HA than in Controls (28 (6.3%) vs. 34 (8.1%); p = 0.044). Average costs per patient during the episode were lower in the HaH-HA group (€ 1,078) than in Controls (€ 2,171). Likewise, healthcare costs within the 30 days post-discharge were also lower in HaH-Ha than in Controls (p < 0.001).

Conclusions

The study showed higher performance and cost reductions of HaH-HA in a real-world setting. The identification of sources of savings facilitates scaling of hospital avoidance.

Registration

ClinicalTrials.gov (26/04/2017; NCT03130283).
Effects of red meat taxes and warning labels on food groups selected in a randomized controlled trial
Authors: Willits-Smith Amelia , Taillie Lindsey Smith , Jaacks Lindsay M. , Frank Sarah M. , Grummon Anna H.
Published: April 2024

Background

High consumption of red and processed meat contributes to both health and environmental harms. Warning labels and taxes for red meat reduce selection of red meat overall, but little is known about how these potential policies affect purchases of subcategories of red meat (e.g., processed versus unprocessed) or of non-red-meat foods (e.g., cheese, pulses) relevant to health and environmental outcomes. This study examined consumer responses to warning labels and taxes for red meat in a randomized controlled trial.

Methods

In October 2021, we recruited 3,518 US adults to complete a shopping task in a naturalistic online grocery store. Participants were randomly assigned to one of four arms: control (no warning labels or tax), warning labels only (health and environmental warning labels appeared next to products containing red meat), tax only (prices of products containing red meat were increased 30%) or combined warning labels + tax. Participants selected items to hypothetically purchase, which we categorized into food groups based on the presence of animal- and plant-source ingredients (e.g., beef, eggs, pulses), meat processing level (e.g., processed pork versus unprocessed pork), and meat species (e.g., beef versus pork). We assessed the effects of the warning labels and tax on selections from each food group.

Results

Compared to control, all three interventions led participants to select fewer items with processed meat (driven by reductions in processed pork) and (for the tax and warning labels + tax interventions only) fewer items with unprocessed meat (driven by reductions in unprocessed beef). All three interventions also led participants to select more items containing cheese, while only the combined warning labels + tax intervention led participants to select more items containing processed poultry. Except for an increase in selection of pulses in the tax arm, the interventions did not affect selections of fish or seafood (processed or unprocessed), eggs, or plant-based items (pulses, nuts & seeds, tofu, meat mimics, grains & potatoes, vegetables).

Conclusions

Policies to reduce red meat consumption are also likely to affect consumption of other types of foods that are relevant to both health and environmental outcomes.

Trial registration

NCT04716010 on www.clinicaltrials.gov.
Quinic acid regulated TMA/TMAO-related lipid metabolism and vascular endothelial function through gut microbiota to inhibit atherosclerotic
Authors: Jin Qiao , Zhang Chiyuan , Chen Ran , Jiang Luping , Li Hongli , Wu Pengcui , Li Liang
Published: April 2024

Background

Quinic acid (QA) and its derivatives have good lipid-lowering and hepatoprotective functions, but their role in atherosclerosis remains unknown. This study attempted to investigate the mechanism of QA on atherogenesis in Apoe−/− mice induced by HFD.

Methods

HE staining and oil red O staining were used to observe the pathology. The PCSK9, Mac-3 and SM22a expressions were detected by IHC. Cholesterol, HMGB1, TIMP-1 and CXCL13 levels were measured by biochemical and ELISA. Lipid metabolism and the HMGB1-SREBP2-SR-BI pathway were detected by PCR and WB. 16 S and metabolomics were used to detect gut microbiota and serum metabolites.

Results

QA or low-frequency ABX inhibited weight gain and aortic tissue atherogenesis in HFD-induced Apoe−/− mice. QA inhibited the increase of cholesterol, TMA, TMAO, CXCL13, TIMP-1 and HMGB1 levels in peripheral blood of Apoe−/− mice induced by HFD. Meanwhile, QA or low-frequency ABX treatment inhibited the expression of CAV-1, ABCA1, Mac-3 and SM22α, and promoted the expression of SREBP-1 and LXR in the vascular tissues of HFD-induced Apoe−/− mice. QA reducedStreptococcus_danieliaeabundance, and promotedLactobacillus_intestinalisandIleibacterium_valensabundance in HFD-induced Apoe−/− mice. QA altered serum galactose metabolism, promoted SREBP-2 and LDLR, inhibited IDOL, FMO3 and PCSK9 expression in liver of HFD-induced Apoe−/− mice. The combined treatment of QA and low-frequency ABX regulated microbe-related Glycoursodeoxycholic acid and GLYCOCHENODEOXYCHOLATE metabolism in HFD-induced Apoe−/− mice. QA inhibited TMAO or LDL-induced HCAECs damage and HMGB1/SREBP2 axis dysfunction, which was reversed by HMGB1 overexpression.

Conclusions

QA regulated the gut-liver lipid metabolism and chronic vascular inflammation of TMA/TMAO through gut microbiota to inhibit the atherogenesis in Apoe−/− mice, and the mechanism may be related to the HMGB1/SREBP2 pathway.
A P2RY12 deficiency results in sex-specific cellular perturbations and sexually dimorphic behavioral anomalies
Authors: Uweru Ogochukwu J. , Okojie Akhabue K. , Trivedi Aparna , Benderoth Jordan , Thomas Lauren S. , Davidson Georgia , Cox Kendall , Eyo Ukpong B.
Published: April 2024

Microglia are sexually dimorphic, yet, this critical aspect is often overlooked in neuroscientific studies. Decades of research have revealed the dynamic nature of microglial-neuronal interactions, but seldom consider how this dynamism varies with microglial sex differences, leaving a significant gap in our knowledge. This study focuses on P2RY12, a highly expressed microglial signature gene that mediates microglial-neuronal interactions, we show that adult females have a significantly higher expression of the receptor than adult male microglia. We further demonstrate that a genetic deletion of P2RY12 induces sex-specific cellular perturbations with microglia and neurons in females more significantly affected. Correspondingly, female mice lacking P2RY12 exhibit unique behavioral anomalies not observed in male counterparts. These findings underscore the critical, sex-specific roles of P2RY12 in microglial-neuronal interactions, offering new insights into basal interactions and potential implications for CNS disease mechanisms.

Graphical Abstract
Immunotherapy with an antibody against CD1d modulates neuroinflammation in an α-synuclein transgenic model of Lewy body like disease
Authors: Iba Michiyo , Kwon Somin , Kim Changyoun , Szabo Marcell , Horan-Portelance Liam , Lopez-Ocasio Maria , Dagur Pradeep , Overk Cassia , Rissman Robert A. , Masliah Eliezer
Published: April 2024

The neuroinflammatory process in synucleinopathies of the aging population such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) involves microglial activation as well as infiltration of the CNS by T cells and natural killer T cells (NKTs). To evaluate the potential of targeting NKT cells to modulate neuroinflammation, we treated α-syn transgenic (tg) mice (e.g.: Thy1 promoter line 61) with an antibody against CD1d, which is a glycoprotein expressed in antigen presenting cells (APCs). CD1d-presented lipid antigens activate NKT cells through the interaction with T cell receptor in NKTs, resulting in the production of cytokines. Thus, we hypothesized that blocking the APC-NKT interaction with an anti-CD1d antibody might reduce neuroinflammation and neurodegeneration in models of DLB/PD. Treatment with the anti-CD1d antibody did not have effects on CD3 (T cells), slightly decreased CD4 and increased CD8 lymphocytes in the mice. Moreover, double labeling studies showed that compared to control (IgG) treated α-syn tg mice, treatment with anti-CD1d decreased numbers of CD3/interferon γ (IFN γ)-positive cells, consistent with NKTs. Further double labeling studies showed that CD1d-positive cells co-localized with the astrocytes marker GFAP and that anti-CD1d antibody reduced this effect. While in control α-syn tg mice CD3 positive cells were near astrocytes, this was modified by the treatment with the CD1d antibody. By qPCR, levels of IFN γ, CCL4, and interleukin-6 were increased in the IgG treated α-syn tg mice. Treatment with CD1d antibody blunted this cytokine response that was associated with reduced astrocytosis and microgliosis in the CNS of the α-syn tg mice treated with CD1d antibody. Flow cytometric analysis of immune cells in α-syn tg mice revealed that CD1d-tet + T cells were also increased in the spleen of α-syn tg mice, which treatment with the CD1d antibody reduced. Reduced neuroinflammation in the anti-CD1d-treated α-syn tg mice was associated with amelioration of neurodegenerative pathology. These results suggest that reducing infiltration of NKT cells with an antibody against CD1d might be a potential therapeutical approach for DLB/PD.
Analysis of ischemic stroke-mediated effects on blood–brain barrier properties along the arteriovenous axis assessed by intravital two-photon imaging
Authors: Protzmann Jil , Jung Felix , Jakobsson Lars , Fredriksson Linda
Published: April 2024

Early breach of the blood–brain barrier (BBB) and consequently extravasation of blood-borne substances into the brain parenchyma is a common hallmark of ischemic stroke. Although BBB breakdown is associated with an increased risk of cerebral hemorrhage and poor clinical prognosis, the cause and mechanism of this process are largely unknown. The aim of this study was to establish an imaging and analysis protocol which enables investigation of the dynamics of BBB breach in relation to hemodynamic properties along the arteriovenous axis. Using longitudinal intravital two-photon imaging following photothrombotic induction of ischemic stroke through a cranial window, we were able to study the response of the cerebral vasculature to ischemia, from the early critical hours to the days/weeks after the infarct. We demonstrate that disruption of the BBB and hemodynamic parameters, including perturbed blood flow, can be studied at single-vessel resolution in the three-dimensional space as early as 30 min after vessel occlusion. Further, we show that this protocol permits longitudinal studies on the response of individual blood vessels to ischemia over time, thus enabling detection of (maladaptive) vascular remodeling such as intussusception, angiogenic sprouting and entanglement of vessel networks. Taken together, this in vivo two-photon imaging and analysis protocol will be useful in future studies investigating the molecular and cellular mechanisms, and the spatial contribution, of BBB breach to disease progression which might ultimately aid the development of new and more precise treatment strategies for ischemic stroke.
Pelvic target volume inter-fractional motion during radiotherapy for cervical cancer with daily iterative cone beam computed tomography
Authors: Zeng Zheng , Zhu Jiawei , Wang Zhiqun , Wang Guangyu , Yan Junfang , Zhang Fuquan
Published: April 2024

Background

Tumor regression and organ movements indicate that a large margin is used to ensure target volume coverage during radiotherapy. This study aimed to quantify inter-fractional movements of the uterus and cervix in patients with cervical cancer undergoing radiotherapy and to evaluate the clinical target volume (CTV) coverage.

Methods

This study analyzed 303 iterative cone beam computed tomography (iCBCT) scans from 15 cervical cancer patients undergoing external beam radiotherapy. CTVs of the uterus (CTV-U) and cervix (CTV-C) contours were delineated based on each iCBCT image. CTV-U encompassed the uterus, while CTV-C included the cervix, vagina, and adjacent parametrial regions. Compared with the planning CTV, the movement of CTV-U and CTV-C in the anterior-posterior, superior-inferior, and lateral directions between iCBCT scans was measured. Uniform expansions were applied to the planning CTV to assess target coverage.

Results

The motion (mean ± standard deviation) in the CTV-U position was 8.3 ± 4.1 mm in the left, 9.8 ± 4.4 mm in the right, 12.6 ± 4.0 mm in the anterior, 8.8 ± 5.1 mm in the posterior, 5.7 ± 5.4 mm in the superior, and 3.0 ± 3.2 mm in the inferior direction. The mean CTV-C displacement was 7.3 ± 3.2 mm in the left, 8.6 ± 3.8 mm in the right, 9.0 ± 6.1 mm in the anterior, 8.4 ± 3.6 mm in the posterior, 5.0 ± 5.0 mm in the superior, and 3.0 ± 2.5 mm in the inferior direction. Compared with the other tumor (T) stages, CTV-U and CTV-C motion in stage T1 was larger. A uniform CTV planning treatment volume margin of 15 mm failed to encompass the CTV-U and CTV-C in 11.1% and 2.2% of all fractions, respectively. The mean volume change of CTV-U and CTV-C were 150% and 51%, respectively, compared with the planning CTV.

Conclusions

Movements of the uterine corpus are larger than those of the cervix. The likelihood of missing the CTV is significantly increased due to inter-fractional motion when utilizing traditional planning margins. Early T stage may require larger margins. Personal radiotherapy margining is needed to improve treatment accuracy.
Comparison of early patient-reported outcomes between uniportal thoracoscopic segmentectomy and wedge resection for peripheral small-sized non-small-cell lung cancer
Authors: Zhao Yingzhi , Liu Wenwu , Gao Xin , Zhang Kaixin , Dai Wei , Wei Xing , Zheng Haoqian , Lei Cheng , Yu Hongfan , Shi Qiuling , Li Qiang , Xie Tianpeng
Published: April 2024

Background

Analysis of patient-reported outcomes (PROs) offers valuable insights into distinguishing the effects of closely related medical procedures from the patient’s perspective. In this study we compared symptom burden in patients undergoing uniportal thoracoscopic segmentectomy and wedge resection for peripheral small-sized non-small cell lung cancer (NSCLC).

Methods

This study included patients with peripheral NSCLC from an ongoing longitudinal prospective cohort study (CN-PRO-Lung 3) who underwent segmentectomy or wedge resection with tumor diameter ≤ 2 cm and consolidation tumor ratio (CTR) ≤ 0.5. PROs data were collected using the Perioperative Symptom Assessment for Lung Surgery questionnaire pre-operatively, daily post-surgery up to the fourth hospitalization day, and weekly post-discharge up to the fourth week. Propensity score matching and a generalized estimation equation model were employed to compare symptom severity. In addition, short-term clinical outcomes were compared.

Results

In total, data of 286 patients (82.4%) undergoing segmentectomy and 61 patients (17.6%) undergoing wedge resection were extracted from the cohort. No statistically significant differences were found in the proportion of moderate-to-severe symptoms and mean scores for pain, cough, shortness of breath, disturbed sleep, fatigue, drowsiness, and distress during the 4-day postoperative hospitalization or the 4-week post-discharge period before or after matching (all p > 0.05). Compared with segmentectomy, wedge resection showed better short-term clinical outcomes, including shorter operative time (p = 0.001), less intraoperative bleeding (p = 0.046), and lower total hospital costs (p = 0.002).

Conclusions

The study findings indicate that uniportal thoracoscopic segmentectomy and wedge resection exert similar early postoperative symptom burden in patients with peripheral NSCLC (tumor diameter ≤ 2 cm and CTR ≤ 0.5).

Clinical trial registration

Not applicable.
Surgical strategy for intravenous leiomyomatosis spreading from uterine to the right atrium presenting with recurrent syncope
Authors: He Gengxu , Yao Tong , Zhao Lei , Geng Hong , Ji Qiang , Zuo Kun , Luo Yuanzhi , Zhou Kai
Published: April 2024

Uterine leiomyoma invading internal iliac vein and consequently disseminating into the right atrium is an extremely rare condition, and surgical strategy is controversial. Here, we reported a specific case with successful surgical resection through one-stage total hysterectomy, bilateral oophorectomy, and the intracardiovascular lesion. This procedure would be an optimal choice for uterine leiomyoma invading inferior vena cava and spreading to right atrium.
Impact of Long-COVID in children: a large cohort study
Authors: Hersh Ziv , Weisband Yiska Loewenberg , Bogan Ariel , Leibovich Adir , Obolski Uri , Nevo Daniel , Gilad-Bachrach Ran
Published: April 2024

Background

The impact of long-term Coronavirus disease 2019 (COVID-19) on the pediatric population is still not well understood. This study was designed to estimate the magnitude of COVID-19 long-term morbidity 3–6 months after the date of diagnosis.

Methods

A retrospective study of all Clalit Health Services members in Israel aged 1–16 years who tested positive for SARS-CoV-2 between April 1, 2020 and March 31, 2021. Controls, who had no previous diagnosis of COVID-19, were one-to-one matched to 65,548 COVID-19-positive children and teens, and were assigned the infection dates of their matches as their index date. Matching included age, sex, socio-economic score, and societal sector. Individuals were excluded from the study if they had severe medical conditions before the diagnosis such as cancer, diabetes, chronic respiratory diseases, and/or abnormal physiological development. Generalized Estimating Equations were used to estimate the associations between COVID-19 and the use of medical services. The analysis focused on the 3–6 months after the infection date. Adjustments were made for demographics and for the use of medical services 6–12 and 3–6 months before the infection date. The latter was necessary because of observed disparities in medical service utilization between the groups before the COVID-19 diagnosis, despite the matching process.

Results

Statistically significant differences were only found for referrals for mental health services [adjusted relative-risk (RR) 1·51, 95%CI 1·15 − 1·96; adjusted risk-difference (RD) 0·001, 95%CI 0·0006 − 0·002], and medication prescriptions of any kind (RR 1·03, 95%CI 1·01–1·06; RD 0·01 95%CI 0·004 − 0·02).

Conclusions

The significant increase in medication prescriptions and mental health service referrals support the hypothesis that COVID-19 is associated with long-lasting morbidities in children and adolescents aged 1–16 years. However, the risk difference in both instances was small, suggesting a minor impact on medical services.