bluuebunny/crossref_metadata_2025_split huggingface dataset:
TLR7 agonist, DSP-0509, with radiation combination therapy enhances anti-tumor activity and modulates T cell dependent immune activation
Authors: Ota Yosuke , Inagaki Ryosaku , Nagai Yasuhiro , Hirose Yuko , Murata Masashi , Yamamoto Setsuko 
Published: July 2024

Abstract
Background
TLR7 is a key player in the antiviral immunity. TLR7 signaling activates antigen-presenting cells including DCs and macrophages. This activation results in the adaptive immunity including T cells and B cells. Therefore, TLR7 is an important molecule of the immune system. Based on these observations, TLR7 agonists considered to become a therapy weaponize the immune system against cancer. Radiation therapy (RT) is one of the standard cancer therapies and is reported to modulate the tumor immune response. In this study, we aimed to investigate the anti-tumor activity in combination of TLR7 agonist, DSP-0509, with RT and underlying mechanism.

Result
We showed that anti-tumor activity is enhanced by combining RT with the TLR7 agonist DSP-0509 in the CT26, LM8, and 4T1 inoculated mice models. We found that once- weekly (q1w) dosing of DSP-0509 rather than biweekly (q2w) dosing is needed to achieve superior anti-tumor activities in CT26 model. Spleen cells from the mice in RT/DSP-0509 combination treatment group showed increased tumor lytic activity, inversely correlated with tumor volume, as measured by the chromium-release cytotoxicity assay. We also found the level of cytotoxic T lymphocytes (CTLs) increased in the spleens of completely cured mice. When the mice completely cured by combination therapy were re-challenged with CT26 cells, all mice rejected CT26 cells but accepted Renca cells. This rejection was not observed with CD8 depletion. Furthermore, levels of splenic effector memory CD8 T cells were increased in the combination therapy group. To explore the factors responsible for complete cure by combination therapy, we analyzed peripheral blood leukocytes (PBLs) mRNA from completely cured mice. We found that Havcr2low, Cd274low, Cd80high, and Il6low were a predictive signature for the complete response to combination therapy. An analysis of tumor-derived mRNA showed that combination of RT and DSP-0509 strongly increased the expression of anti-tumor effector molecules including Gzmb and Il12.

Conclusion
These data suggest that TLR7 agonist, DSP-0509, can be a promising concomitant when used in combination with RT by upregulating CTLs activity and gene expression of effector molecules. This combination can be an expecting new radio-immunotherapeutic strategy in clinical trials.
Effect of seed priming with auxin on ROS detoxification and carbohydrate metabolism and their relationship with germination and early seedling establishment in salt stressed maize
Authors: Ellouzi Hasna , Ben Slimene Debez Imen , Amraoui Souhir , Rabhi Mokded , Hanana Mohsen , Alyami Nouf M. , Debez Ahmed , Abdelly Chedly , Zorrig Walid 
Published: July 2024

AbstractAs crucial stages in the plant ontogeny, germination and seedling establishment under adverse conditions greatly determine staple crop growth and productivity. In the context of green technologies aiming to improve crop yield, seed priming is emerging as an effective approach to enhance seed vigor and germination performance under salt stress. In this study, we assess the efficiency of seed priming with indole-3-acetic acid (IAA) in mitigating the adverse effects of salt stress on maize (Zea mays L.) seedlings during germination and early seedling stages. In unprimed seeds, salt stress reduced germination indices, and seedling (both radicle and coleoptile) growth, together with decreased tissue hydration. However, seed priming using IAA significantly improved maize salt response, as reflected by the increased seed germination dynamics, early seedling establishment, and water status. Besides, seedlings from IAA-primed seeds showed a higher activity of α-amylase, resulting in increased sugar contents in roots and coleoptiles of salt-stressed plants. Further, IAA-seed priming stimulated the accumulation of endogenous IAA in salt-stressed seedlings, in concomitance with a significant effect on reactive oxygen species detoxification and lipid peroxidation prevention. Indeed, our data revealed increased antioxidant enzyme activities, differentially regulated in roots and coleoptiles, leading to increased activities of the antioxidant enzymes (SOD, CAT and GPX). In summary, data gained from this study further highlight the potential of IAA in modulating early interactions between multiple signaling pathways in the seed, endowing maize seedlings with enhanced potential and sustained tolerance to subsequent salt stress.
Remimazolam protects the liver from ischemia-reperfusion injury by inhibiting the MAPK/ERK pathway
Authors: Shi Yanhua , Deng Housheng , Zhang Zhiming , Zhu Xiaoling , Zeng Zhiqin 
Published: July 2024

Abstract
Background
Ischemia-reperfusion (I/R) injury is a major factor in liver damage following hepatic resection and liver transplantation, with anesthetics demonstrating the ability to shield organs from this type of injury.

Methods
Hypoxia-reoxygenation (H/R) was used to create in vitro I/R hepatocyte cell injury models. The CCK-8 assay, flow cytometer, LDH assay, and ELSIA were utilized to assess hepatocyte injury. The in vivo I/R injury rat model was then built. HE and TUNEL staining were used to assess liver tissue damage. Western-blot was applied to assess the activation of the MAPK/ERK pathway.

Results
Remimazolam (RMZL) remarkably improved cell viability and decreased apoptosis in H/R-induced hepatocyte injury. RMZL reduced the release of H/R-induced inflammatory mediators (TNF-α and IL-6) as well as LDH levels. We also discovered that RMZL inhibited p38 and ERK1/2 phosphorylation in vivo and in vitro. The stimulation of MAPK/ERK, on the other hand, abolished RMZL’s anti-inflammation effects in H/R-induced hepatocyte injury. Furthermore, RMZL reduced liver tissue injury in I/R rats.

Conclusion
RMZL prevented hepatic I/R damage by inhibiting MAPK/ERK signaling.
Psychometric properties of the Fraboni scale of ageism (FSA) applied to long-term caregivers in nursing homes
Authors: Li Jie , Dong Ziyan , Xie Wen , Yang Liuqing , Qi Xiaojing 
Published: July 2024

Abstract
Background
The aging society has resulted in enormous demand for long-term care services. However, ageism is a common phenomenon in long-term care facilities, which not only hinders the quality of care for the recipients but also negatively influences caregivers’ well-being. In this paper, we first applied the Fraboni Scale of Ageism (FSA) to evaluate its reliability and construct validity among Chinese long-term caregivers in nursing homes. This study could contribute to assessing the prevalence of ageism in Chinese long-term caregivers, prompting facilities and the government to recognize the issue of ageism and explore necessary interventions to reduce ageism in long-term caregivers.

Methods
This is a cross-sectional study. We recruited 392 long-term caregivers using a convenience sampling strategy in nursing homes from two cities in Chinese central and northern regions. Parameters included the demographic characteristics, Cronbach’s alpha coefficients, and intraclass correlation coefficient. The construct validity was conducted by exploratory factor analysis and confirmatory factor analysis.

Results
The Cronbach’s alpha of FSA (Chinese version) was 0.856 and ICC was 0.871. The factor analysis identified 3 principal factors, explaining 43.95% of the total variance. The 3-factor model was confirmed to fit by confirmatory factor analysis.

Conclusions
The findings confirm that the FSA is easy to use and has good psychometric properties. This study will contribute to improving the condition of ageism, thereby improving the quality of care for the elderly and retention of professional talents in the LTC system.
Advancing ASD identification with neuroimaging: a novel GARL methodology integrating Deep Q-Learning and generative adversarial networks
Authors: Zhou Yujing , Jia Guangbo , Ren Yingtong , Ren Yingxin , Xiao Zhifeng , Wang Yinmei 
Published: July 2024

AbstractAutism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects an individual's behavior, speech, and social interaction. Early and accurate diagnosis of ASD is pivotal for successful intervention. The limited availability of large datasets for neuroimaging investigations, however, poses a significant challenge to the timely and precise identification of ASD. To address this problem, we propose a breakthrough approach, GARL, for ASD diagnosis using neuroimaging data. GARL innovatively integrates the power of GANs and Deep Q-Learning to augment limited datasets and enhance diagnostic precision. We utilized the Autistic Brain Imaging Data Exchange (ABIDE) I and II datasets and employed a GAN to expand these datasets, creating a more robust and diversified dataset for analysis. This approach not only captures the underlying sample distribution within ABIDE I and II but also employs deep reinforcement learning for continuous self-improvement, significantly enhancing the capability of the model to generalize and adapt. Our experimental results confirmed that GAN-based data augmentation effectively improved the performance of all prediction models on both datasets, with the combination of InfoGAN and DQN's GARL yielding the most notable improvement.
Prevalence and clinical correlates of abnormal lipid metabolism in older Chinese patients with first-episode drug-naïve major depressive disorder
Authors: Huang Xiao , Yuan Sun M. M. , Zhang Xiang-Yang 
Published: July 2024

Abstract
Background
Older major depressive disorder (MDD) patients have more complex clinical symptoms and higher abnormal lipid metabolism (ALM) rates. This study aimed to compare clinical differences between those with and without ALM in a sample of older first-episode drug naïve (FEDN) patients.

Methods
We recruited 266 older MDD patients. Socio-demographic variables, clinical data, and lipid parameters were obtained. The Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the positive subscale of the Positive and Negative Syndrome Scale (PANSS-P) were conducted to evaluate patients’ depression, anxiety and psychotic symptoms, respectively.

Results
In this study, we found that the prevalence of comorbid ALM was 86.1% in older MDD patients. Compared with the non-abnormal lipid metabolism (NALM) group, the ALM group had a higher duration of illness, higher clinical global impression of severity scale (CGI-S) and HAMD scores, higher thyroid stimulating hormone (TSH) and glucose levels. Logistic regression analysis indicated that duration of illness (OR = 1.11, P = 0.023, 95%CI = 1.015–1.216) and CGI-S score (OR = 2.28, P = 0.014, 95%CI = 1.18–4.39) were associated with ALM in older MDD patients.

Conclusion
The importance of regular lipid assessment in older MDD patients needs to be taken into account.
Effect of exercise and manual therapy or kinesiotaping on sEMG and pain perception in chronic low back pain: a randomized trial
Authors: Blanco-Giménez P , Vicente-Mampel J. , Gargallo P , Maroto-Izquierdo S , Martín-Ruíz J , Jaenada-Carrilero E , Barrios C 
Published: July 2024

AbstractThe importance of incorporating lumbo-pelvic stability core and controlling motor exercises in patients with chronic low back pain (CLBP) reinforces the use of strategies to improve biopsychosocial beliefs by reducing biomedical postulations. However, clinical practice guidelines recommend multimodal approaches incorporating exercise and manual therapy (MT), and instead reject the application of kinesiotape (KT) in isolation. Therefore, the objectives of this study were to analyze the effects of 12 weeks of exercises combined with MT or KT on perceived low back pain using the visual analog scale (VAS) and muscle electric activity measured with electromyography (EMG) of the rectus abdominis and multifidus in CLBP (mild disability) and to explore the relationship between the rectus abdominis and multifidus ratios and pain perception after intervention. A blinded, 12-week randomized controlled trial (RCT) was carried out, involving three parallel groups of patients with CLBP. The study was registered at Clinicaltrial.gov and assigned the identification number NCT05544890 (19/09/22). The trial underwent an intention-to-treat analysis. The primary outcome revealed a multimodal treatment program supplemented by additional therapies such as MT and KT, resulting in significant reductions in perceived low back pain. The subjective assessment of individuals with CLBP indicated no discernible distinction between exclusive core stability exercises and control-motor training when combined with MT or KT. Notably, our findings demonstrated positive alterations in both the mean and peak EMG values of the right rectus abdominis in the exercise group, suggesting a beneficial impact on muscle activation. This study focused on assessing the activation levels of the trunk musculature, specifically the rectus abdominis (RA) and multifidus (MF), in individuals with CLBP exhibiting mild disability according to the Oswestry Disability Index. Importantly, improvements in the VAS values were observed independently of changes in muscle electrical activity.
Maxillary labial frenectomy: a randomized, controlled comparative study of two blue (445 nm) and infrared (980 nm) diode lasers versus surgical scalpel
Authors: Sobouti Farhad , Moallem Savasari Aryousha , Aryana Mehdi , Hakimiha Neda , Dadgar Sepideh 
Published: July 2024

Abstract
Background
This study aimed to compare the intra and postoperative complications of frenectomy procedure with a surgical scalpel versus 445 nm and 980 nm diode lasers.

Methods
This randomized controlled clinical trial was conducted on 174 patients requiring maxillary labial frenectomy. After completion of fixed orthodontic treatment and primary closure of maxillary diastema, the patients were randomly assigned into three groups (n = 58): group 1 (frenectomy via 445 nm diode laser, continuous-wave, 1.5 W), group 2 (frenectomy via 980 nm laser, continuous-wave, 1.7 W), and control group (V-Y plasty technique via scalpel). Intra-operative bleeding, discomfort in chewing and speaking, pain, and tissue healing were compared among the groups immediately, at 7 and 30 days postoperatively using the Kruskal-Wallis, Mann-Whitney, and Chi-square tests.

Results
Pain scores were significantly lower in group 1 compared to group 2 (immediately and day 7, P < 0.05). Significant faster tissue healing at days 7 and 30 were observed in group 1 compared to group 2 (P < 0.05). Group 1 was superior to the control group regarding lower intraoperative bleeding, discomfort in chewing and speaking (immediately and day 7), lower pain (immediately and day 7), and tissue healing (day 7) (P < 0.05 for all). Group 2 was significantly superior to the control group in lower intraoperative bleeding, discomfort in chewing and speaking (immediately and day 7), and better tissue healing (day 7) (P < 0.05 for all).

Conclusions
In conclusion, diode laser frenectomy resulted in significantly lower intra and postoperative complications compared to the scalpel. Moreover, 445 nm diode laser showed significantly superior effects compared to 980 nm diode laser.

Trial registration
The study protocol was registered on 29.10.2022 at the Iranian Registry of Clinical Trials (www.irct.ir) (registration number: IRCT20220630055326N1).
Dementia patients in palliative care according to data from the German National Hospice and Palliative Care Register (2009–2021)
Authors: Donath Carolin , Ostgathe Christoph , Heckel Maria 
Published: July 2024

Abstract
Background
People with dementia are less in focus of palliative care research than other patient groups even though the awareness of their palliative and end-of-life care needs is rising. Empirical data analyses on people with dementia in palliative care services are lacking.

Aim
To explore the prevalence of dementia diagnoses as per the ICD criteria among users of various palliative care settings and to compare use of palliative services, care pathways, and outcomes in people with and without a dementia diagnosis.

Design
We conducted retrospective analysis of dementia diagnoses as per ICD (F00-F03/G30) in the German National Hospice and Palliative Care Register between 2009 and 2021. The analysis used methods of descriptive and inferential statistics, including the Bonferroni correction for alpha error inflation.

Setting/participants
We limited the analysis to the subsample of people aged over 64.

Results
The prevalence of dementia in the different settings of palliative care was lower than in the age-comparable population: Of the 69,116 data sets included in the analysis, a small minority (3.3%) was coded with dementia as the principal diagnosis. Among patients on inpatient palliative care wards, 0.8% (148 of 19,161) had a dementia diagnosis, as did 2.2% (52 of 2,380) of those under hospital palliative care support teams and 4.3% (2,014 of 46,803) of those receiving specialized palliative care at home.

Conclusions
The records of the German National Hospice and Palliative Care Register suggest that the prevalence of dementia is lower than one might expect from general population data, though numbers are in line with international studies on proportion of dementia patients receiving palliative care. Future research could usefully examine whether this discrepancy stems either from omissions in coding dementia as patients’ principal diagnosis respectively from lapses in documentation of a dementia diagnosis previously made, or from barriers to accessing palliative care services or even displays being excluded from palliative care when trying to access it.

Trial registration
No registration.
Nonlinear association between visceral adipose tissue area and remnant cholesterol in US adults: a cross-sectional study
Authors: Gu Xi , Wang Xun , Wang Sujie , Shen Ying , Lu Leiqun 
Published: July 2024

Abstract
Background
Excessive visceral adipose tissue (VAT) is associated with a spectrum of diseases, including diabetes, cancer, and cardiovascular diseases. Remnant cholesterol (RC), denoting cholesterol within triglyceride-rich lipoproteins and their metabolic byproducts, has been identified as a key contributor to cardiovascular diseases and related mortality. However, the association between the VAT and RC remains unclear. In this study, the objective is to provide new evidence regarding the association between VAT and RC concentrations.

Methods
4727 individuals aged 18–59 were selected from the National Health and Nutrition Examination Survey conducted between 2011 and 2018 as study participants. This study utilized several weighted linear regression models and a restricted cubic spline (RCS) to explore the association and potential nonlinearities between VAT and RC. Subgroup analyses were performed to determine the consistency of findings.

Results
The mean VAT value was 103.82 ± 1.42 cm2, and the median RC value was 18 mg/dl. VAT demonstrated a positive association with RC in a fully adjusted model, with a β and 95% confidence interval (CI) of 0.09 (0.08, 0.11) after adjustment for potential confounders. Analysis using RCS revealed a nonlinear association between the VAT area and RC (P < 0.001 for nonlinearity). Adjusted two-piecewise regression models demonstrated β coefficients of 0.13 (95%CI: 0.11 ~ 0.16, P < 0.001) for RC in individuals with VAT < 143 cm2, and 0.02 (95%CI: -0.01 ~ 0.06, P = 0.15) for those with VAT ≥ 143 cm2. Interactions were observed among the body mass index (BMI) subgroup; the β coefficients for RC were 0.14 (95%CI: 0.12 ~ 0.16) in those with BMI < 30 kg/m2 and 0.05 (95%CI:0.04 ~ 0.07) in those with BMI ≥ 30 kg/m2, with a P-value of < 0.001 for interaction.

Conclusions
This study identified a nonlinear association between VAT and RC in American adults. Reducing the VAT area may be beneficial in lowering RC concentration, particularly when VAT is < 143 cm2 and those with a BMI < 30 kg/m2.
Screening high-risk individuals for primary gastric carcinoma: evaluating overall survival probability score in the presence and absence of lymphatic metastasis post-gastrectomy
Authors: Qu Wenqing , Li Ling , Ma Jinfeng , Li Yifan 
Published: July 2024

Abstract
Objective
The aim of this study was to develop and validate prognostic models for predicting overall survival in individuals with gastric carcinoma, specifically focusing on both negative and positive lymphatic metastasis.

Methods
A total of 1650 patients who underwent radical gastric surgery at Shanxi Cancer Hospital between May 2002 and December 2020 were included in the analysis. Multiple Cox Proportional Hazards analysis was performed to identify key variables associated with overall survival in both negative and positive lymphatic metastasis cases. Internal validation was conducted using bootstrapping to assess the prediction accuracy of the models. Calibration curves were used to demonstrate the accuracy and consistency of the predictions. The discriminative abilities of the prognostic models were evaluated and compared with the 8th edition of AJCC-TNM staging using Harrell’s Concordance index, decision curve analysis, and time-dependent receiver operating characteristic curves.

Results
The nomogram for node-negative lymphatic metastasis included variables such as age, pT stage, and maximum tumor diameter. The C-index for this model in internal validation was 0.719, indicating better performance compared to the AJCC 8th edition TNM staging. The nomogram for node-positive lymphatic metastasis included variables such as gender, age, maximum tumor diameter, neural invasion, Lauren classification, and expression of Her-2, CK7, and CD56. The C-index for this model was 0.674, also outperforming the AJCC 8th edition TNM staging. Calibration curves, time-dependent receiver operating characteristic curves, and decision curve analysis for both nomograms demonstrated excellent prediction ability. Furthermore, significant differences in prognosis between low- and high-risk groups supported the models’ strong risk stratification performance.

Conclusion
This study provides valuable risk stratification models for lymphatic metastasis in gastric carcinoma, encompassing both node-positive and negative cases. These models can help identify low-risk individuals who may not require further intervention, while high-risk individuals can benefit from targeted therapies aimed at addressing lymphatic metastasis.