bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic model for overall survival of head and neck cancer patients in the palliative phase
Authors: Hoesseini Arta , Sewnaik Aniel , van den Besselaar Boyd N. , Zhang Jang , van Leeuwen Nikki , Hardillo Jose A. , Baatenburg de Jong Robert Jan , Offerman Marinella P. J. 
Published: February 2024

Abstract
Background
Patients with head and neck squamous cell carcinoma (HNSCC) enter the palliative phase when cure is no longer possible or when they refuse curative treatment. The mean survival is five months, with a range of days until years. Realistic prognostic counseling enables patients to make well-considered end-of-life choices. However, physicians tend to overestimate survival. The aim of this study was to develop a prognostic model that calculates the overall survival (OS) probability of palliative HNSCC patients.

Methods
Patients diagnosed with incurable HNSCC or patients who refused curative treatment for HNSCC between January 1st 2006 and June 3rd 2019 were included (n = 659). Three patients were lost to follow-up. Patients were considered to have incurable HNSCC due to tumor factors (e.g. inoperability with no other curative treatment options, distant metastasis) or patient factors (e.g. the presence of severe comorbidity and/or poor performance status).Tumor and patients factors accounted for 574 patients. An additional 82 patients refused curative treatment and were also considered palliative. The effect of 17 candidate predictors was estimated in the univariable cox proportional hazard regression model. Using backwards selection with a cut-off P-value < 0.10 resulted in a final multivariable prediction model. The C-statistic was calculated to determine the discriminative performance of the model. The final model was internally validated using bootstrapping techniques.

Results
A total of 647 patients (98.6%) died during follow-up. Median OS time was 15.0 weeks (95% CI: 13.5;16.6). Of the 17 candidate predictors, seven were included in the final model: the reason for entering the palliative phase, the number of previous HNSCC, cT, cN, cM, weight loss in the 6 months before diagnosis, and the WHO performance status. The internally validated C-statistic was 0.66 indicating moderate discriminative ability. The model showed some optimism, with a shrinkage factor of 0.89.

Conclusion
This study enabled the development and internal validation of a prognostic model that predicts the OS probability in HNSCC patients in the palliative phase. This model facilitates personalized prognostic counseling in the palliative phase. External validation and qualitative research are necessary before widespread use in patient counseling and end-of-life care.
JianPiYiShen formula prevents cisplatin-induced acute kidney injury in mice by improving necroptosis through MAPK pathway
Authors: Li Zhongtang , He Riming , Liu Jiahui , Jin Xiaoming , Jiang Beibei , Lao Yunlan , Yang Shudong 
Published: February 2024

Abstract
Background
Acute kidney injury (AKI), characterized by necroptosis and activation of MAPK pathway, causes sudden declines in renal function. To date, efficacious treatments are lacking. JianPiYiShen Formula (JPYSF) has a protective effect on the kidneys. The aim of this study is to explore the mechanism of JPYSF in cisplatin-induced AKI.

Methods
Male C57/BL6J mice were divided into control group, cisplatin group and cisplatin + JPYSF group. Before establishing the model, the cisplatin + JPYSF group was administered JPYSF (18.35 g/kg/day) by gavage for 5 consecutive days. A single intraperitoneal injection of cisplatin (20 mg/kg) was used to establish AKI model. Measurement of renal function and H&E staining were performed to assess renal damage. WB, PCR, TUNEL staining and immunohistochemistry were used to detect related indicators of mitochondrial function, oxidative stress, necroptosis, inflammation and MAPK pathway. And one-way analysis of variance was used to compare group differences.

Results
Compared with the cisplatin group, JPYSF can attenuate AKI, reflected by the decrease in Scr and BUN levels, the improvement of renal tubular injury, and the downregulation of NGAL and KIM1. Cisplatin can induce mitochondrial dysfunction and oxidative stress, triggering necroptosis. In this study, JPYSF improved mitochondrial dysfunction to enhance oxidative stress, as manifested by upregulation of OPA1, PGC-1α, SOD and CAT, and downregulation of DRP1 and MFF. Then JPYSF showed a significant protective effect in necroptosis, as embodied by reduced number of TUNEL-positive cells, decreased the gene expression of RIPK3 and MLKL, as well as downregulation the proteins expression of P-RIPK1, P-RIPK3, and P-MLKL. Moreover, necroptosis can aggravate inflammation. JPYSF ameliorated inflammation by improving inflammatory and anti-inflammatory indexes, including downregulation of TNF-α, IL-6, MCP-1 and LY6G, and upregulation of IL-10. In addition, JPYSF also inhibited MAPK pathway to improve necroptosis by decreasing the expression of P-JNK and P-ERK.

Conclusion
Our data showed that JPYSF prevents cisplatin-induced AKI by improving necroptosis through MAPK pathway, which is related to the improvement of mitochondrial dysfunction, oxidative stress, and inflammation.
Anti-psoriatic characteristics of ROCEN (topical Arthrocen) in comparison with Cyclosporine A in a murine model
Authors: Goudarzi Ramin , Min-Ho Kim  , Partoazar Alireza 
Published: February 2024

AbstractTopical ROCEN (Roc), liposomal arthrocen hydrogel, is a robust anti-inflammatory formulation which has been developed for skin diseases such as eczema. Therefore, we aimed to evaluate the efficacy of Roc 2% on the healing of imiquimod (Imiq)-induced psoriasis in a mouse model. Psoriasis was induced by applying Imiq topically to the mice's back skin once daily for five consecutive days. Moreover, a group of animal experiments was treated with Cyclosporine A (CsA), as a standard drug, for comparison with Roc treated group. The efficacy of Roc on skin lesions was evaluated by employing Psoriasis Area and Severity Index (PASI) scores. Subsequently, the skin samples were assessed using Baker’s scoring system and Masson's trichrome staining, immunohistochemistry, and real-time PCR analysis. The observational and histopathological results indicated that topical application of Roc significantly reduced the PASI and Baker’s scores in the plaque-type psoriasis model. Moreover, biochemical assessments showed that Roc suppressed significantly the increase of IL-17, IL-23, and TNF-α cytokines gene expression in the lesion site of psoriatic animals. In conclusion topical Roc 2% could significantly alleviate major pathological aspects of Imiq-induced psoriasis through inflammation inhibition which was comparable to the CsA drug. The beneficial outcomes of Roc application in the psoriasis model suggest its potential usage in complementary medicine.
The moderating effect of perceived organizational support on presenteeism related to the inclusive leadership
Authors: Wang Ting , Qin Hui , Zhang Ziqi , Qin Yonghao 
Published: February 2024

Abstract
Aim
This study aimed to assess inclusive leadership and presenteeism among clinical nurses and to examine the moderating effect of perceived organizational support on presenteeism related to the inclusive leadership among nurses.

Background
Nurses’ presenteeism has become common. In hospitals, inclusive leadership is an acknowledged leadership style that has a positive influence on nurses. However, little emphasis has been paid to research on their relationships and moderating effect.

Methods
A cross-sectional study was undertaken to assess 2222 nurses using a general information questionnaire, Stanford Presenteeism Scale (SPS-6), Perceived Organisational Support Scale, and Inclusive Leadership Scale. Study variables were analyzed using descriptive statistics, correlation, and structural equation modelling (SEM).

Results
Presenteeism was relatively severe among clinical nurses. There were correlations between inclusive leadership, perceived organizational support and presenteeism. Perceived organizational support moderated the relationship between inclusive leadership and presenteeism.

Discussion and conclusion
Nursing managers should actively adopt an inclusive leadership style and improve nurses' sense of perceived organizational support to improve clinical nurses' presenteeism behaviors.

Implications for nursing policy and practice
Healthcare organizations and nursing managers should pay attention to the psychological needs of their nurses, provide complete understanding and support, encourage staff to actively participate in their work and contribute new ideas and opinions, reduce the incidence of presenteeism, and improve nurses' sense of well-being at work.
Biomechanical effects of cranial closing wedge osteotomy on joint stability in normal canine stifles: an ex vivo study
Authors: Shimada Masakazu , Huang Chenxu , Yamakawa Satoshi , Fujie Hiromichi , Murakami Sawako , Kanno Nobuo , Hara Yasushi 
Published: February 2024

Abstract
Background
Cranial closing wedge osteotomy (CCWO) is a functional stabilisation technique for cranial cruciate ligament (CrCL) ruptures. This biomechanical study aimed to evaluate the influence of CCWO on the stability of the stifle joint.
Eighteen Beagle stifle joints were divided into two groups: control and CCWO. The stifle joints were analyzed using a six-degree-of-freedom robotic joint biomechanical testing system. The joints were subjected to 30 N in the craniocaudal (CrCd) drawer and proximal compression tests and 1 Nm in the internal–external (IE) rotation test. Each test was performed with an extension position, 135°, and 120° of joint angle.

Results
The stifle joints were tested while the CrCLs were intact and then transected.
In the drawer test, the CCWO procedure, CrCL transection, and stifle joint flexion increased CrCd displacement. The CCWO procedure and CrCL transection showed an interaction effect. In the compression test, the CCWO procedure decreased and CrCL transection and stifle joint flexion increased displacement. In the IE rotation test, CCWO, CrCL transection, and stifle joint flexion increased the range of motion.

Conclusions
CCWO was expected to provide stability against compressive force but does not contribute to stability in the drawer or rotational tests. In the CCWO-treated stifle joint, instability during the drawer test worsened with CrCL transection. In other words, performing the CCWO procedure when the CrCL function is present is desirable for stabilizing the stifle joint.
Identification of circRNA-associated ceRNA networks in the longissimus dorsi of yak under different feeding systems
Authors: Ma Xiaoming , Guo Xian , Yongfu La , Wang Tong , Bao Pengjia , Chu Min , Wu Xiaoyun , Yan Ping , Liang Chunnian 
Published: February 2024

AbstractBackgroundYaks (Bos grunniens), prized for their ability to thrive in high-altitude environments, are indispensable livestock in the plateau region. Modifying their feeding systems holds significant promise for improving their growth and meat quality. Tenderness, a key determinant of yak meat quality and consumer appeal, is demonstrably influenced by dietary regimen. Indoor feeding regimes have been shown to enhance tenderness by lowering shear stress and optimizing pH values. CircRNAs, well-known modulators of circulatory function, also play a crucial role in skeletal muscle development across various animal species. However, their functional significance in yak skeletal muscle remains largely unexplored.ResultsIn this study, we identified a total of 5,534 circRNAs within the longissimus dorsi muscle, and we found 51 differentially expressed circRNAs (20 up-regulated and 31 down-regulated) between the two feeding groups. Constructing a comprehensive ceRNA network illuminated intricate regulatory mechanisms, withPGPand circRNA_0617 converging on bta-miR-2285q, mirrored byKLF15/circRNA_0345/bta-miR-20b andCTSF/circRNA_0348/bta-miR-146a. These findings shed light on the potential of circRNAs to influence yak muscle development and meat quality, offering valuable insights for future research.ConclusionsThis investigation unraveled a complex interaction network between circRNAs、mRNAs and miRNAs in yak skeletal muscle. We further elucidated the target genes regulated by these target genes within the network, offering valuable insights into the potential regulatory mechanisms governing muscle development and meat quality-related traits in yaks.
Intra-breath changes in respiratory mechanics are sensitive to history of respiratory illness in preschool children: the SEPAGES cohort
Authors: Siroux Valérie , Boudier Anne , Lyon-Caen Sarah , Quentin Joane , Gioria Yoann , Hantos Zoltán , Slama Rémy , Pin Isabelle , Bayat Sam 
Published: February 2024

Abstract
Background
Intra-breath oscillometry has been proposed as a sensitive means of detecting airway obstruction in young children. We aimed to assess the impact of early life wheezing and lower respiratory tract illness on lung function, using both standard and intra-breath oscillometry in 3 year old children.

Methods
History of doctor-diagnosed asthma, wheezing, bronchiolitis and bronchitis and hospitalisation for respiratory problems were assessed by questionnaires in 384 population-based children. Association of respiratory history with standard and intra-breath oscillometry parameters, including resistance at 7 Hz (R7), frequency-dependence of resistance (R7 − 19), reactance at 7 Hz (X7), area of the reactance curve (AX), end-inspiratory and end-expiratory R (ReI, ReE) and X (XeI, XeE), and volume-dependence of resistance (ΔR = ReE-ReI) was estimated by linear regression adjusted on confounders.

Results
Among the 320 children who accepted the oscillometry test, 281 (88%) performed 3 technically acceptable and reproducible standard oscillometry measurements and 251 children also performed one intra-breath oscillometry measurement. Asthma was associated with higher ReI, ReE, ΔR and R7 and wheezing was associated with higher ΔR. Bronchiolitis was associated with higher R7 and AX and lower XeI and bronchitis with higher ReI. No statistically significant association was observed for hospitalisation.

Conclusions
Our findings confirm the good success rate of oscillometry in 3-year-old children and indicate an association between a history of early-life wheezing and lower respiratory tract illness and lower lung function as assessed by both standard and intra-breath oscillometry. Our study supports the relevance of using intra-breath oscillometry parameters as sensitive outcome measures in preschool children in epidemiological cohorts.
Association of the triglyceride-glucose index with all-cause and cardiovascular mortality in patients with cardiometabolic syndrome: a national cohort study
Authors: Liu Quanjun , Zhang Yeshen , Chen Shuhua , Xiang Hong , Ouyang Jie , Liu Huiqin , Zhang Jing , Chai Yanfei , Zhan Zishun , Gao Peng , Zhang Xiao , Fan Jianing , Zheng Xinru , Zhang Zhihui , Lu Hongwei 
Published: February 2024

Abstract
Objective
This study aimed to evaluate the association of triglyceride-glucose (TyG) index with all-cause and cardiovascular mortality risk among patients with cardiometabolic syndrome (CMS).

Methods
We performed a cohort study of 5754 individuals with CMS from the 2001–2018 National Health and Nutrition Examination Survey. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate Cox proportional hazards regression models assessed the associations between TyG index and mortality . Non-linear correlations and threshold effects were explored using restricted cubic splines and a two-piecewise Cox proportional hazards model.

Results
Over a median follow-up of 107 months, 1201 all-cause deaths occurred, including 398 cardiovascular disease-related deaths. The multivariate Cox proportional hazards regression model showed a positive association between the TyG index and all-cause and cardiovascular mortality. Each one-unit increase in the TyG index was associated with a 16% risk increase in all-cause mortality (HR: 1.16, 95% CI 1.03, 1.31, P = 0.017) and a 39% risk increase in cardiovascular mortality (HR: 1.39, 95% CI 1.14, 1.71, P = 0.001) after adjusting for confounders. The restricted cubic splines revealed a U-shaped association between the TyG index and all-cause (P for nonlinear < 0.001) and cardiovascular mortality (P for nonlinear = 0.044), identifying threshold values (all-cause mortality: 9.104; cardiovascular mortality: 8.758). A TyG index below these thresholds displayed a negative association with all-cause mortality (HR: 0.58, 95% CI 0.38, 0.90, P = 0.015) but not with cardiovascular mortality (HR: 0.39, 95% CI 0.12, 1.27, P = 0.119). Conversely, a TyG index exceeding these thresholds was positively associated with all-cause and cardiovascular mortality (HR: 1.35, 95% CI 1.17, 1.55, P < 0.001; HR: 1.54, 95% CI 1.25, 1.90, P < 0.001, respectively). Notably, a higher TyG index (≥ threshold values) was significantly associated with increased mortality only among individuals aged under 55 compared to those with a lower TyG index (< threshold values).

Conclusions
The TyG index demonstrated a U-shaped correlation with all-cause and cardiovascular mortality in individuals with CMS. The thresholds of 9.104 and 8.758 for all-cause and cardiovascular mortality, respectively, may be used as intervention targets to reduce the risk of premature death and cardiovascular disease.
Intensive lifestyle intervention in type 2 diabetes and risk of incident coronary artery disease for the common haptoglobin phenotypes: the Look AHEAD study
Authors: Warren Rachel A. , Bancks Michael P. , Carew Allie S. , Levy Andrew P. , Sapp John , Bahnson Judy , Lewis Cora E. , Rimm Eric B. , Espeland Mark A. , Cahill Leah E. 
Published: February 2024

Abstract
Background
Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) participants with the haptoglobin (Hp) 2-2 phenotype only. It remains unknown whether Hp phenotype modifies the effect of an intensive lifestyle intervention (ILI) on CAD in type 2 diabetes.

Methods
Haptoglobin phenotype was measured in 4542 samples from the Action for Health in Diabetes (Look AHEAD) study. Cox regression models assessed the effect of ILI (focused on weight loss from caloric restriction and physical activity) versus diabetes support and education (DSE) on CAD events in each phenotype group, and within pre-specified subgroups including race/ethnicity, sex, history of cardiovascular disease, diabetes medication use, and diabetes duration.

Results
1590 (35%) participants had the Hp2-2 phenotype. The ILI did not lower glycated hemoglobin (%HbA1c) to < 6.5% in either phenotype, with a peak significant difference between treatment arms of 0.5% [non-Hp2-2] and 0.6% [Hp2-2]. The cumulative CAD incidence was 13.4% and 13.8% in the DSE arm and 12.2% and 13.6% in the ILI arm for non-Hp2-2 and Hp2-2 groups, respectively. Compared to DSE, the ILI was not associated with CAD among participants without (HR = 0.95, 95% CI 0.78–1.17) or with (0.89, 0.68–1.19) the Hp2-2 phenotype (p-interaction between Hp phenotype and ILI = 0.58). After Bonferroni correction, there were no significant results among any subgroups.

Conclusions
Hp phenotype did not modify the effect of the weight loss ILI on risk of CAD in Look AHEAD, potentially because it did not substantially impact glycemic control among participants with or without the Hp2-2 phenotype. Further research is needed to determine if these results are conclusive.
High-throughput screening of catalytically active inclusion bodies using laboratory automation and Bayesian optimization
Authors: Helleckes Laura Marie , Küsters Kira , Wagner Christian , Hamel Rebecca , Saborowski Ronja , Marienhagen Jan , Wiechert Wolfgang , Oldiges Marco 
Published: February 2024

Abstract
Background
In recent years, the production of inclusion bodies that retain substantial catalytic activity was demonstrated. These catalytically active inclusion bodies (CatIBs) are formed by genetic fusion of an aggregation-inducing tag to a gene of interest via short linker polypeptides. The resulting CatIBs are known for their easy and cost-efficient production, recyclability as well as their improved stability. Recent studies have outlined the cooperative effects of linker and aggregation-inducing tag on CatIB activities. However, no a priori prediction is possible so far to indicate the best combination thereof. Consequently, extensive screening is required to find the best performing CatIB variant.

Results
In this work, a semi-automated cloning workflow was implemented and used for fast generation of 63 CatIB variants with glucose dehydrogenase of Bacillus subtilis (BsGDH). Furthermore, the variant BsGDH-PT-CBDCell was used to develop, optimize and validate an automated CatIB screening workflow, enhancing the analysis of many CatIB candidates in parallel. Compared to previous studies with CatIBs, important optimization steps include the exclusion of plate position effects in the BioLector by changing the cultivation temperature. For the overall workflow including strain construction, the manual workload could be reduced from 59 to 7 h for 48 variants (88%). After demonstration of high reproducibility with 1.9% relative standard deviation across 42 biological replicates, the workflow was performed in combination with a Bayesian process model and Thompson sampling. While the process model is crucial to derive key performance indicators of CatIBs, Thompson sampling serves as a strategy to balance exploitation and exploration in screening procedures. Our methodology allowed analysis of 63 BsGDH-CatIB variants within only three batch experiments. Because of the high likelihood of TDoT-PT-BsGDH being the best CatIB performer, it was selected in 50 biological replicates during the three screening rounds, much more than other, low-performing variants.

Conclusions
At the current state of knowledge, every new enzyme requires screening for different linker/aggregation-inducing tag combinations. For this purpose, the presented CatIB toolbox facilitates fast and simplified construction and screening procedures. The methodology thus assists in finding the best CatIB producer from large libraries in short time, rendering possible automated Design-Build-Test-Learn cycles to generate structure/function learnings.
Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infection
Authors: Zhang Furui , Ni Linhan , Zhang Zhen , Luo Xuegang , Wang Xuequan , Zhou Wenmiao , Chen Jiale , Liu Jing , Qu Yuliang , Liu Kunmei , Guo Le 
Published: February 2024

Abstract
Background
Helicobacter pylori (H. pylori) causes chronic gastric disease. An efficient oral vaccine would be mucosa-targeted and offer defense against colonization of invasive infection in the digestive system. Proteolytic enzymes and acidic environment in the gastrointestinal tract (GT) can, however, reduce the effectiveness of oral vaccinations. For the creation of an edible vaccine, L. lactis has been proposed as a means of delivering vaccine antigens.

Results
We developed a plSAM (pNZ8148-SAM) that expresses a multiepitope vaccine antigen SAM-WAE containing Urease, HpaA, HSP60, and NAP extracellularly (named LL-plSAM-WAE) to increase the efficacy of oral vaccinations. We then investigated the immunogenicity of LL-plSAM-WAE in Balb/c mice. Mice that received LL-plSAM-WAE or SAM-WAE with adjuvant showed increased levels of antibodies against H. pylori, including IgG and sIgA, and resulted in significant reductions in H. pylori colonization. Furthermore, we show that SAM-WAE and LL-plSAM-WAE improved the capacity to target the vaccine to M cells.

Conclusions
These findings suggest that recombinant L. lactis could be a promising oral mucosa vaccination for preventing H. pylori infection.