bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disulfidptosis-related signature predicts prognosis and characterizes the immune microenvironment in hepatocellular carcinoma
Authors: Tang Jun , Peng Xintong , Xiao Desheng , Liu Shuang , Tao Yongguang , Shu Long 
Published: January 2024

Abstract
Background
Disulfidptosis is a type of programmed cell death caused by excessive cysteine-induced disulfide bond denaturation leading to actin collapse. Liver cancer has a poor prognosis and requires more effective intervention strategies. Currently, the prognostic and therapeutic value of disulfidptosis in liver cancer is not clear.

Methods
We investigated the features of 16 disulfidptosis-related genes (DRGs) of HCC patients in the TCGA and classified the patients into two disulfidptosis pattern clusters by consensus clustering analysis. Then, we constructed a prognostic model using LASSO Cox regression. Next, the microenvironment and drug sensitivity were evaluated. Finally, we used qPCR and functional analysis to verify the reliability of hub DRGs.

Results
Most of the DRGs showed significantly higher expression in cancer tissues than in adjacent tissues. Our prognostic model, the DRG score, can well predict the survival of HCC patients. There were significant differences in survival, features of the microenvironment, effects of immunotherapy, and drug sensitivity between the high- and low-DRG score groups. Ultimately, we demonstrated that a few hub DRGs have differential mRNA expression between liver cancer cells and normal cells and that the protective gene LCAT can inhibit liver cancer metastasis in vitro.

Conclusion
We established a novel risk model based on DRG scores to predict HCC patient prognosis, drug sensitivity and immunotherapy efficacy, which provides new insight into the relationship between disulfidptosis and HCC and provides valuable assistance for the personalized treatment of HCC.
Upregulation of TTK expression is associated with poor prognosis and immune infiltration in endometrial cancer patients
Authors: Du Hongxiang , Zhang Li , Chen Jia , Chen Xinyi , Qiang Ronghui , Ding Xiaoyi , Wang Yilang , Yang Xiaoqing 
Published: January 2024

Abstract
Background
Threonine and tyrosine kinase (TTK) is associated with invasion and metastasis in various tumors. However, the prognostic importance of TTK and its correlation with immune infiltration in endometrial cancer (EC) remain unclear.

Methods
The expression profile of TTK was analyzed using data from The Cancer Genome Atlas (TCGA) and the Clinical Proteome Cancer Analysis Consortium (CPTAC). TTK protein and mRNA levels were verified in EC cell lines. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of TTK to distinguish between normal and EC tissues. K-M survival analysis was also conducted to evaluate the impact of TTK on survival outcomes. Protein‒protein interaction (PPI) networks associated with TTK were explored using the STRING database. Functional enrichment analysis was performed to elucidate the biological functions of TTK. TTK mRNA expression and immune infiltration correlations were examined using the Tumor Immune Estimation Resource (TIMER) and the Tumor-Immune System Interaction Database (TISIDB).

Results
TTK expression was significantly greater in EC tissues than in adjacent normal tissues. Higher TTK mRNA expression was associated with tumor metastasis and advanced TNM stage. The protein and mRNA expression of TTK was significantly greater in tumor cell lines than in normal endometrial cell lines. ROC curve analysis revealed high accuracy (94.862%), sensitivity (95.652%), and specificity (94.894%) of TTK in differentiating EC from normal tissues. K-M survival analysis demonstrated that patients with high TTK expression had worse overall survival (OS) and disease-free survival (DFS) rates. Correlation analysis revealed that TTK mRNA expression was correlated with B cells and neutrophils.

Conclusion
TTK upregulation is significantly associated with poor survival outcomes and immune infiltration in patients with EC. TTK can serve as a potential biomarker for poor prognosis and a promising immunotherapy target in EC. Further investigation of the role of TTK in EC may provide valuable insights for therapeutic interventions and personalized treatment strategies.
Baseline susceptibility of Anopheles gambiae to clothianidin in northern Ghana
Authors: Pambit Zong Cosmos M. , Coleman Sylvester , Mohammed Abdul Rahim , Owusu-Asenso Christopher M. , Akuamoah-Boateng Yaw , Sraku Isaac K. , Attah Simon K. , Cui Liwang , Afrane Yaw A. 
Published: January 2024

Abstract
Background
Clothianidin, an insecticide with a novel mode of action, has been deployed in the annual indoor residual spraying programme in northern Ghana since March 2021. To inform pragmatic management strategies and guide future studies, baseline data on local Anopheles gambiae sensu lato (s.l.) susceptibility to the clothianidin insecticide were collected in Kpalsogu, a village in the Northern region, Ghana.

Methods
Phenotypic susceptibility of An. gambiae mosquitoes to clothianidin was assessed using the World Health Organization (WHO) insecticide resistance monitoring bioassay. The WHO cone bioassays were conducted on mud and cement walls sprayed with Sumishield 50 wettable granules (WG) (with clothianidin active ingredient). Daily mortalities were recorded for up to 7 days to observe for delayed mortalities. Polymerase chain reaction (PCR) technique was used to differentiate the sibling species of the An. gambiae complex and also for the detection of knock down resistance genes (kdr) and the insensitive acetylcholinesterase mutation (ace-1).

Results
The WHO susceptibility bioassay revealed a delayed killing effect of clothianidin. Mosquitoes exposed to the cone bioassays for 5 min died 120 h after exposure. Slightly higher mortalities were observed in mosquitoes exposed to clothianidin-treated cement wall surfaces than mosquitoes exposed to mud wall surfaces. The kdr target-site mutation L1014F occurred at very high frequencies (0.89–0.94) across all vector species identified whereas the ace-1 mutation occurred at moderate levels (0.32–0.44). Anopheles gambiae sensu stricto was the most abundant species observed at 63%, whereas Anopheles arabiensis was the least observed at 9%.

Conclusions
Anopheles gambiae s.l. mosquitoes in northern Ghana were susceptible to clothianidin. They harboured kdr mutations at high frequencies. The ace-1 mutation occurred in moderation. The results of this study confirm that clothianidin is an effective active ingredient and should be utilized in malaria vector control interventions.
Anopheles arabiensis continues to be the primary vector of Plasmodium falciparum after decades of malaria control in southwestern Ethiopia
Authors: Eligo Nigatu , Wegayehu Teklu , Pareyn Myrthe , Tamiru Girum , Lindtjørn Bernt , Massebo Fekadu 
Published: January 2024

Abstract
Background
Investigating the species distribution and their role in malaria transmission is important as it varies from place to place and is highly needed to design interventions appropriate to the site. The current study aimed to investigate the Anopheles mosquito species distribution and their infection rate in southwestern Ethiopia.

Methods
The study was conducted in 14 malaria-endemic kebeles (the smallest administrative unit), which were situated in eight different malaria-endemic districts and four zones in southwestern Ethiopia. Ten per cent of households in each village were visited to collect adult mosquitoes using Centers for Disease Control and Prevention (CDC) light traps. The larval and pupal collection was done from breeding sites within the villages, and reared to adults. Female mosquitoes were morphologically identified. The head and thorax of adult Anopheles mosquitoes were tested for circumsporozoite proteins (CSPs) using ELISA. At the same time, legs, wings, and abdomen were used to identify sibling species using PCR targeting the rDNA intergenic spacers region for species typing of the Anopheles funestus group and the internal transcribed spacer 2 region genes for Anopheles gambiae complex.

Results
A total of 1445 Anopheles mosquitoes comprising eight species were collected. Of 813 An. gambiae complex tested by PCR, 785 (97%) were Anopheles arabiensis, and the remaining 28 (3%) were not amplified. There were 133 An. funestus group captured and tested to identify the species, of which 117 (88%) were positive for Anopheles parensis, and 15 (11%) were not amplified. A single specimen (1%) showed a band with a different base pair length from the known An. funestus group species. Sequencing revealed this was Anopheles sergentii. Among 1399 Anopheles tested for CSPs by ELISA, 5 (0.4%) An. arabiensis were positive for Plasmodium falciparum and a single (0.07%) was positive for Plasmodium vivax.

Conclusions
Anopheles arabiensis continues to play the principal role in malaria transmission despite implementing indoor-based interventions for decades. Sequencing results suggest that An. sergentii was amplified by the An. funestus group primer, producing PCR amplicon size of different length. Therefore, relying solely on amplifying a specific gene of interest in grouping species could be misleading, as different species may share the same gene.
Group-based trajectory models of integrated vaccine delivery and equity in low- and middle-income countries
Authors: Ravi Sanjana J. , Vecino-Ortiz Andrés I. , Potter Christina M. , Merritt Maria W. , Patenaude Bryan N. 
Published: January 2024

Abstract
Background
Integrated vaccine delivery – the linkage of routine vaccination with provision of other essential health services – is a hallmark of robust primary care systems that has been linked to equitable improvements in population health outcomes.

Methods
We gathered longitudinal data relating to routine immunization coverage and vaccination equity in 78 low- and middle-income countries that have ever received support from Gavi, the Vaccine Alliance, using multiple imputation to handle missing values. We then estimated several group-based trajectory models to describe the relationship between integrated vaccine delivery and vaccination equity in these countries. Finally, we used multinomial logistic regression to identify predictors of group membership.

Results
We identified five distinct trajectories of geographic vaccination equity across both the imputed and non-imputed datasets, along with two and four trajectories of socioeconomic vaccination equity in the imputed and non-imputed datasets, respectively. Integration was associated with reductions in the slope index of inequality of measles vaccination in the countries analyzed. Integration was also associated with an increase in the percentage of districts reporting high measles vaccination coverage.

Conclusions
Integrated vaccine delivery is most strongly associated with improvements in vaccination equity in settings with high baseline levels of inequity. Continued scholarship is needed to further characterize the relationship between integration and health equity, as well as to improve measurement of vaccination coverage and integration.
Hepcidin deficiency impairs hippocampal neurogenesis and mediates brain atrophy and memory decline in mice
Authors: Bai Xue , Wang Bing , Cui Yiduo , Tian Siqi , Zhang Yi , You Linhao , Chang Yan-Zhong , Gao Guofen 
Published: January 2024

Abstract
Background
Hepcidin is the master regulator of iron homeostasis. Hepcidin downregulation has been demonstrated in the brains of Alzheimer’s disease (AD) patients. However, the mechanism underlying the role of hepcidin downregulation in cognitive impairment has not been elucidated.

Methods
In the present study, we generated GFAP-Cre-mediated hepcidin conditional knockout mice (HampGFAP cKO) to explore the effect of hepcidin deficiency on hippocampal structure and neurocognition.

Results
We found that the HampGFAP cKO mice developed AD-like brain atrophy and memory deficits. In particular, the weight of the hippocampus and the number of granule neurons in the dentate gyrus were significantly reduced. Further investigation demonstrated that the morphological change in the hippocampus of HampGFAP cKO mice was attributed to impaired neurogenesis caused by decreased proliferation of neural stem cells. Regarding the molecular mechanism, increased iron content after depletion of hepcidin followed by an elevated level of the inflammatory factor tumor necrosis factor-α accounted for the impairment of hippocampal neurogenesis in HampGFAP cKO mice. These observations were further verified in GFAP promoter-driven hepcidin knockdown mice and in Nestin-Cre-mediated hepcidin conditional knockout mice.

Conclusions
The present findings demonstrated a critical role for hepcidin in hippocampal neurogenesis and validated the importance of iron and associated inflammatory cytokines as key modulators of neurodevelopment, providing insights into the potential pathogenesis of cognitive dysfunction and related treatments.

Graphical Abstract
Exercise-induced modulation of myokine irisin on muscle-bone unit in the rat model of post-traumatic osteoarthritis
Authors: Shang Xingru , Hao Xiaoxia , Hou Wenjie , Liu Jiawei , Chi Ruimin , Deng Xiaofeng , Pan Chunran , Xu Tao 
Published: January 2024

Abstract
Background and aim
Post-traumatic osteoarthritis (PTOA) is a subtype of osteoarthritis (OA). Exercise may produce and release the myokine irisin through muscle fiber contraction. However, the effect of exercise-promoted irisin production on the internal interactions of the muscle–bone unit in PTOA studies remains unclear.

Methods
Eighteen 8-week-old Sprague–Dawley (SD) rats were randomly divided into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). The PTOA model was established by transection of anterior cruciate ligament (ACLT) and destabilization of medial meniscus (DMM). After 4 weeks of modeling, the PTOA/TW group underwent treadmill exercise (15 m/min, 30 min/d, 5 d/ week, 8 weeks), and the other two groups were free to move in the cage. Evaluation and correlation analysis of muscle, cartilage, subchondral bone and serological indexes were performed after euthanasia.

Results
Eight weeks of treadmill exercise effectively alleviated the trauma-induced OA phenotype, thereby maintaining cartilage and subchondral bone integrity in PTOA, and reducing quadriceps atrophy and myofibril degradation. Exercise reversed the down-regulated expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and fibronectin type III structural domain protein 5 (FNDC5) in muscle tissue of PTOA rats, and increased the blood irisin level, and the irisin level was positively correlated with the expression of PGC-1α and FNDC5. In addition, correlation analysis showed that irisin metabolism level was strongly negatively correlated with Osteoarthritis Research Society International (OARSI) and subchondral bone loss, indicating that irisin may be involved in cartilage biology and PTOA-related changes in cartilage and subchondral bone. Moreover, the metabolic level of irisin was strongly negatively correlated with muscle fiber cross-sectional area (CSA), Atrogin-1 and muscle ring-finger protein-1(MuRF-1) expression, suggesting that irisin may alleviate muscle atrophy through autocrine action.

Conclusion
Treadmill exercise can alleviate the atrophy and degeneration of muscle fibers in PTOA rats, reduce the degradation of muscle fibrin, promote the expression of serum irisin, and alleviate the degeneration of articular cartilage and subchondral bone loss in PTOA rats. These results indicate that treadmill exercise can affect the process of PTOA by promoting the expression of myokine irisin in rat muscle–bone unit.
Impact of feed, light and access to manipulable material on tail biting in pigs with intact tails
Authors: Wallgren Per , Johansson Magnus , Wallgren Torun , Susic Zeljko , Sigfridson Kerstin , Johansson Sven-Erik 
Published: January 2024

Abstract
Background
Tail biting (TB) is a welfare issue with economic consequences due to infections and ill-thrift. This study aimed to reduce tail injuries in a high-performing non-tail-docking pig herd.

Results
During eleven years preceding the trial, the annual incidence of tail injuries registered at slaughter in pigs from the herd increased from 3% (equivalent to the national mean) to 10%. It was positively correlated to a high weight gain and negatively correlated to daylight length.
The overall incidence of tail injuries during the four years preceding the trial was 9.2% with significant differences between four identically structured buildings for fatteners (I < II < III < IV).
The feed was enriched with amino acids, minerals and fibres. The buildings used different illumination strategies, I: standard fluorescent tubes with an invisible flickering light of 30–40% for 14 h daily, II: non-flickering led light for 14 h daily, III (control) and IV: standard fluorescent tubes for 2 h daily. IV had free access to manipulable material (hay-silage), while I–III was offered 100–200 g daily.
During the adaptation period (6 months), the incidence of tail injuries decreased significantly in all buildings to a mean of 5.4%. The largest decrease (from 11.4 to 4.3%) was obtained in IV.
During the trial period (12 months), the mean incidence of tail injuries decreased in all groups to a mean of 3.0%. There were no differences in treatment incidences of individual pigs due to TB between groups, but the use of enriched pellets due to TB in pens was lowest in II. The low incidence of tail injuries was retained during the post-trial period (6 months) when all buildings used artificial illumination for two hours per day.

Conclusions
The incidence of TB in fast growing non-tail-docked pigs in the herd was successfully reduced by supplementing the feed with amino acids, minerals, vitamins and fibres. Additional manipulable material accelerated that process and non-flickering illumination may have had an impact in preventing TB.
The results obtained do not support the need for tail-docking of pigs, provided that the needs of the pigs in terms of feed ingredients, stocking density and access to manipulable materials are fulfilled.
Natural killer cells drive 4-1BBL positive uveal melanoma towards EMT and metastatic disease
Authors: Neo Shi Yong , Oliveira Mariana M. S. , Tong Le , Chen Yi , Chen Ziqing , Cismas Sonia , Burduli Nutsa , Malmerfelt Anna , Teo Joey Kay Hui , Lam Kong-Peng , Alici Evren , Girnita Leonard , Wagner Arnika K. , Westerberg Lisa S. , Lundqvist Andreas 
Published: January 2024

Abstract
Background
Inflammation in the eye is often associated with aggravated ocular diseases such as uveal melanoma (UM). Poor prognosis of UM is generally associated with high potential of metastatic liver dissemination. A strong driver of metastatic dissemination is the activation of the epithelial-mesenchymal transition (EMT) regulating transcription factor ZEB1, and high expression of ZEB1 is associated with aggressiveness of UM. While ZEB1 expression can be also associated with immune tolerance, the underlying drivers of ZEB1 activation remain unclear.

Methods
Transcriptomic, in vitro, ex vivo, and in vivo analyses were used to investigate the impact on clinical prognosis of immune infiltration in the ocular tumor microenvironment. A metastatic liver dissemination model of was developed to address the role of natural killer (NK) cells in driving the migration of UM.

Results
In a pan-cancer TCGA analysis, natural killer (NK) cells were associated with worse overall survival in uveal melanoma and more abundant in high-risk monosomy 3 tumors. Furthermore, uveal melanoma expressed high levels of the tumor necrosis factor superfamily member 4-1BB ligand, particularly in tumors with monosomy 3 and BAP1 mutations. Tumors expressing 4-1BB ligand induced CD73 expression on NK cells accompanied with the ability to promote tumor dissemination. Through ligation of 4-1BB, NK cells induced the expression of the ZEB1 transcription factor, leading to the formation of liver metastasis of uveal melanoma.

Conclusions
Taken together, the present study demonstrates a role of NK cells in the aggravation of uveal melanoma towards metastatic disease.
The E3 ligase NEURL3 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma by promoting vimentin degradation
Authors: Zhou Shi-Qing , Feng Ping , Ye Ming-Liang , Huang Sheng-Yan , He Shi-Wei , Zhu Xun-Hua , Chen Jun , Zhang Qun , Li Ying-Qing 
Published: January 2024

Abstract
Background
Metastasis has emerged as the major reason of treatment failure and mortality in patients with nasopharyngeal carcinoma (NPC). Growing evidence links abnormal DNA methylation to the initiation and progression of NPC. However, the precise regulatory mechanism behind these processes remains poorly understood.

Methods
Bisulfite pyrosequencing, RT-qPCR, western blot, and immunohistochemistry were used to test the methylation and expression level of NEURL3 and its clinical significance. The biological function of NEURL3 was examined both in vitro and in vivo. Mass spectrometry, co-immunohistochemistry, immunofluorescence staining, and ubiquitin assays were performed to explore the regulatory mechanism of NEURL3.

Results
The promoter region of NEURL3, encoding an E3 ubiquitin ligase, was obviously hypermethylated, leading to its downregulated expression in NPC. Clinically, NPC patients with a low NEURL3 expression indicated an unfavorable prognosis and were prone to develop distant metastasis. Overexpression of NEURL3 could suppress the epithelial mesenchymal transition and metastasis of NPC cells in vitro and in vivo. Mechanistically, NEURL3 promoted Vimentin degradation by increasing its K48-linked polyubiquitination at lysine 97. Specifically, the restoration of Vimentin expression could fully reverse the tumor suppressive effect of NEURL3 overexpression in NPC cells.

Conclusions
Collectively, our study uncovers a novel mechanism by which NEURL3 inhibits NPC metastasis, thereby providing a promising therapeutic target for NPC treatment.