bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vibration therapy as an effective approach to improve bone healing in diabetic rats
Authors: Campos Maysa S. , Volpon José B. , Ximenez João Paulo B. , Franttini Ana Paula , Dalloul Christopher E. , Sousa-Neto Manoel D. , Silva Raquel A. , Kacena Melissa A. , Zamarioli Ariane 
Published: August 2022

ObjectiveTo investigate the effects of vibration therapy on fracture healing in diabetic and non-diabetic rats.Methods148 rats underwent fracture surgery and were assigned to four groups: (1) SHAM: weight-matched non-diabetic rats, (2) SHAM+VT: non-diabetic rats treated with vibration therapy (VT), (3) DM: diabetic rats, and (4) DM+VT: diabetic rats treated with VT. Thirty days after diabetes induction with streptozotocin, animals underwent bone fracture, followed by surgical stabilization. Three days after bone fracture, rats began VT. Bone healing was assessed on days 14 and 28 post-fracture by serum bone marker analysis, and femurs collected for dual-energy X-ray absorptiometry, micro-computed tomography, histology, and gene expression.ResultsOur results are based on 88 animals. Diabetes led to a dramatic impairment of bone healing as demonstrated by a 17% reduction in bone mineral density and decreases in formation-related microstructural parameters compared to non-diabetic control rats (81% reduction in bone callus volume, 69% reduction in woven bone fraction, 39% reduction in trabecular thickness, and 45% in trabecular number). These changes were accompanied by a significant decrease in the expression of osteoblast-related genes (Runx2, Col1a1, Osx), as well as a 92% reduction in serum insulin-like growth factor I (IGF-1) levels. On the other hand, resorption-related parameters were increased in diabetic rats, including a 20% increase in the callus porosity, a 33% increase in trabecular separation, and a 318% increase in serum C terminal telopeptide of type 1 collagen levels. VT augmented osteogenic and chondrogenic cell proliferation at the fracture callus in diabetic rats; increased circulating IGF-1 by 668%, callus volume by 52%, callus bone mineral content by 90%, and callus area by 72%; and was associated with a 19% reduction in circulating receptor activator of nuclear factor kappa beta ligand (RANK-L).ConclusionsDiabetes had detrimental effects on bone healing. Vibration therapy was effective at counteracting the significant disruption in bone repair induced by diabetes, but did not improve fracture healing in non-diabetic control rats. The mechanical stimulus not only improved bone callus quality and quantity, but also partially restored the serum levels of IGF-1 and RANK-L, inducing bone formation and mineralization, thus creating conditions for adequate fracture repair in diabetic rats.
Antiosteoporosis and bone protective effect of dieckol against glucocorticoid-induced osteoporosis in rats
Authors: Wang Hao , Yang Leigang , Chao Junwei 
Published: August 2022

BackgroundGlucocorticoids (GCs) induce osteoporosis, which results in fractures in the bond, causing significant morbidity. In the conducted study, we examined the antiosteoporosis effect of dieckol against GC-induced osteoporosis in rats.MethodsSprague–Dawley (SD) rats were used for the current study and dexamethasone (2.5 mg/kg) induced osteoporosis in the rats that received the dieckol (test) and alendronate (standard) for 20 weeks. Bone turnover parameters, microCT, antioxidant, inflammatory cytokines, nutrient, and hormones parameters.ResultsDieckol noticeably suppressed the body weight and boosted the uterine and vagina weight. Dieckol considerably altered the level of trabecular number (Tb. N), the bone volume to total volume (BV/TV), trabecular separation (Tb.Sp), bone surface to bone volume (BS/BV), and t​r​a​b​e​c​u​l​a​r thickness (Tb.Th). Dieckol noticeably (P &lt; 0.001) elevated the level of osteocalcin (OC) and alleviated the level of bone Gla protein (BGP), acid phosphatase (ACP), alkaline phosphatase (ALP), and β-CTx. Dieckol markedly boosted the level of malondialdehyde (MDA) and suppressed the level of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) along with the suppression of inflammatory cytokines like TNF-α, IL-1β, and IL-6. Dieckol remarkably increased the level of calcium, potassium, magnesium, and 25 (OH) vitamin D. Dieckol substantially (P &lt; 0.001) boosted the level of estradiol and alleviated the level of parathyroid hormone and tartrate-resistant acid phosphatase (TRAP). Dieckol also suppressed the level of receptor activator of nuclear factor κB ligand (RANKL) and boosted the level of osteoprotegerin (OPG).ConclusionTaken together, our data suggest that dieckol demonstrated the anti-osteoporosis effect against GC-induced osteoporosis in rats.
Prevalence and clinical characteristics of Crooke’s cell adenomas in 101 patients with T-PIT-positive pituitary adenomas: Case series and literature review
Authors: Zhu Dimin , Wang Zongming , Tian Tian , Wu Xinyi , He Dongsheng , Zhu Yonghong , Liu Dawei , Wang Haijun 
Published: August 2022

PurposeWe aimed to perform a retrospective analysis of a rare subtype of corticotroph adenoma, Crooke’s cell adenoma, to better understand its clinical features.MethodsWe collected T-PIT-positive pituitary adenomas and screened Crooke’s cell adenomas from January 2020 to December 2021 in our center. Case reports of such tumors were also collected through a literature search. Clinical data such as biochemical tests, imaging examinations, and pathological data of the above cases were analyzed.ResultsA total of 101 T-PIT-positive patients were treated in our center in the last 2 years, and 4 were finally pathologically diagnosed with Crooke’s cell adenomas. All of these patients were male with elevated adrenocorticotropic hormone levels, and 50.0% presented with hypercortisolemia, Cushing’s syndrome, visual impairment, and headache. The tumor diameter was significantly larger in these 4 patients (37.0 mm) than in the other patients (26.0 mm), and their tumor invasive behavior was more pronounced. Cases reported in the literature were mainly female (72.8%), and the clinical presentation was also dominated by Cushing’s syndrome (65.1%) and hormonal dysfunction. Tumors were more common as macroadenomas (33.2 mm) and suprasellar growths (63.8%). The tumor recurrence rate was as high as 55.6%, with 6 cases progressing to pituitary carcinomas and 7.7% of tumor-related deaths. Our further integrated analysis of our center and reported cases revealed that gender, Cushing’s syndrome, visual dysfunction, hormonal disorders, and tumor growth characteristics were statistically different in different tumor categories.ConclusionCrooke’s cell adenoma is a tumor subtype with obvious clinical aggressive behavior, and an in-depth analysis of its clinical characteristics may assist in developing a comprehensive treatment plan.
Deep learning reveals cuproptosis features assist in predict prognosis and guide immunotherapy in lung adenocarcinoma
Authors: Li Gang , Luo Qingsong , Wang Xuehai , Zeng Fuchun , Feng Gang , Che Guowei 
Published: August 2022

BackgroundCuproptosis is a recently found non-apoptotic cell death type that holds promise as an emerging therapeutic modality in lung adenocarcinoma (LUAD) patients who develop resistance to radiotherapy and chemotherapy. However, the Cuproptosis’ role in the onset and progression of LUAD remains unclear.MethodsCuproptosis-related genes (CRGs) were identified by a co-expression network approach based on LUAD cell line data from radiotherapy, and a robust risk model was developed using deep learning techniques based on prognostic CRGs and explored the value of deep learning models systematically for clinical applications, functional enrichment analysis, immune infiltration analysis, and genomic variation analysis.ResultsA three-layer artificial neural network risk model was constructed based on 15 independent prognostic radiotherapy-related CRGs. The risk model was observed as a robust independent prognostic factor for LUAD in the training as well as three external validation cohorts. The patients present in the low-risk group were found to have immune “hot” tumors exhibiting anticancer activity, whereas the high-risk group patients had immune “cold” tumors with active metabolism and proliferation. The high-risk group patients were more sensitive to chemotherapy whereas the low-risk group patients were more sensitive to immunotherapy. Genomic variants did not vary considerably among both groups of patients.ConclusionOur findings advance the understanding of cuproptosis and offer fresh perspectives on the clinical management and precision therapy of LUAD.
Identification of fragmented cropland in arid and semiarid sandy areas: a case study of horqin left rear banner
Authors: Sang Zhiting , Liang Jie , Zheng Huihui , Wang Kaige , Xu Yan , Liu Yibin 
Published: August 2022

The sustainable development and utilization of sandy areas in arid and semiarid regions is of strategic importance to ensure both food and ecological security. The unique geographical environment of these areas and uncontrolled exploitation by farmers lead to large amounts of fragmented cropland. Despite government management, the quantity and distribution of these fragmented croplands is unknown, and accurate identification of the region’s fragmented croplands can provide data to support the sustainable use of sandy areas. We propose a method for identifying fragmented cropland based on scale transformation. Small-scale fragmented cropland is approximately represented at larger scales, so we apply small-scale high-resolution remote sensing images to identify features and obtain information at a large scale, i.e., the ratio of fragmented cropland area. By correcting the cropland areas identified from low-resolution remote sensing images and using them as the basis for the resulting calculation, more accurate identification can be 1 at a large scale. In this study, this method was applied based on remote sensing images with 0.54 and 30 m resolutions that were acquired during the same period, using Horqin Zuoyihou Banner as the study area. The results showed that (1) there was 13,637.08 hm2 of fragmented cropland in Horqin Zuoyihou Banner due to precipitation and terrain topography, mainly in the central and western regions and 2) identification at the sample point scale and plot scale were positively correlated in area and showed a consistent distribution. Therefore, accurate and efficient identification of fragmented cropland can be achieved through scale transformation.
Phosphatidylinositol glycan anchor biosynthesis, class C is a prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma
Authors: Zhao Qian , Shen Chuan , Wei Junwei , Zhao Caiyan 
Published: August 2022

Background and aims: The exact function of Phosphatidylinositol Glycan Anchor Biosynthesis, Class C (PIGC) gene has yet to be elucidated. In the study, we attempted to clarify the correlations of PIGC to prognosis and tumor-infiltrating lymphocytes in hepatocellular carcinoma (HCC).Methods:PIGC expression was analyzed via the Oncomine database, Gene Expression Profiling Interactive Analysis, Hepatocellular carcinoma data base, Human Protein Atlas database and Tumor Immune Estimation Resource (TIMER). We showed the correlation of PIGC with the clinical characteristics using UALCAN. We evaluated the influence of PIGC on clinical prognosis using Kaplan-Meier plotter databases. And co-expressed genes with PIGC and its regulators were identified using LinkedOmics. The correlations between PIGC and cancer immune infiltrates were investigated via TIMER. We analyzed the drug sensitivity and immunotherapy response via R package.Results:PIGC was found up-regulated in tumor tissues in multiple HCC cohorts, also increased in HCC patient with different clinical characteristics. High PIGC expression was associated with poorer overall survival. PIGC expression showed a strong positive association with the expression of ACBD6, a strong negative association with AGXT212. The cell components and distribution in treatment and non-treatment of HCC patients were quite distinct, which may reveal the relationship between the immunotherapy with tumor microenvironment. Notably, PIGC expression was positively correlated with infiltrating levels of immune cells.Conclusion: These findings suggest that PIGC is correlated with prognosis and immune infiltrating in HCC, which can be used as a prognostic biomarker for determining prognosis, laying a foundation for further study of the immune regulatory role of PIGC in HCC.
Comprehensive analysis of the prognostic and immunotherapeutic implications of STAT family members in human colorectal cancer
Authors: Li Dingchang , Jiao Yanan , Gao Wenxing , Hu Shidong , Li Dingling , Zhao Wen , Chen Peng , Jin Lujia , Zhao Yingjie , Ma Zhaofu , Wu Xiansheng , Yan Yang , Sun Wen , Du Xiaohui , Dong Guanglong 
Published: August 2022

Background: Colorectal cancer (CRC) is the third most prevalent cancer worldwide and the second leading cause of cancer mortality. Signal transducer and activator of transcription (STAT) proteins are a group of transcription factors implicated in cell signal transduction and gene transcription in several cancer types. However, the level of expression, genetic alterations, and biological function of different STATs, as well as their prognostic and immunotherapeutic value in CRC remain unclear.Methods: The mRNA and protein expression levels, genetic alterations, prognostic value, gene–gene and protein–protein interaction networks, and biological function of STATs in CRC were studied using the GEPIA, HPA, cBioPortal, PrognoScan, Kaplan–Meier plotter, GeneMANIA, STRING, and Metascape databases. The expression of STATs in CRC was confirmed using immunohistochemistry (IHC). Finally, the relationship between STAT expression and immune infiltration as well as immunotherapy-associated indicators was also investigated.Results: The expression levels of STAT2/5A/5B are downregulated in CRC, and the STAT1/3/4/5B expressions were significantly associated with the tumor stage of patients with CRC. The abnormal expression of STAT2/4/5B in patients with CRC is related to the prognosis of patients with CRC. The STATs and their neighboring proteins are primarily associated with lymphocyte activation, cytokine-mediated signaling pathways, positive regulation of immune response, regulation of cytokine production, and growth hormone receptor signaling pathways in cancer. The expression of STATs was significantly associated with immune infiltration and immunotherapy response-associated indicators.Conclusion: This study may help further understand the molecular mechanism of CRC and provide new prognostic biomarkers and immunotherapy targets in patients with CRC.
Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon
Authors: Ayoub Carine , Azar Yara , Maddah Dina , Ghaleb Youmna , Elbitar Sandy , Abou-Khalil Yara , Jambart Selim , Varret Mathilde , Boileau Catherine , El Khoury Petra , Abifadel Marianne 
Published: August 2022

Familial chylomicronemia syndrome is a rare autosomal recessive disorder of lipoprotein metabolism characterized by the presence of chylomicrons in fasting plasma and an important increase in plasma triglycerides (TG) levels that can exceed 22.58 mmol/l. The disease is associated with recurrent episodes of abdominal pain and pancreatitis, eruptive cutaneous xanthomatosis, lipemia retinalis, and hepatosplenomegaly. A consanguineous Syrian family who migrated to Lebanon was referred to our laboratory after perceiving familial chylomicronemia syndrome in two children. The LPL and PCSK9 genes were sequenced and plasma PCSK9 levels were measured. Sanger sequencing of the LPL gene revealed the presence of the p.(Val227Phe) pathogenic variant in exon 5 at the homozygous state in the two affected children, and at the heterozygous state in the other recruited family members. Interestingly, PCSK9 levels in homozygous carriers of the p.(Val227Phe) were ≈50% lower than those in heterozygous carriers of the variant (p-value = 0.13) and ranged between the 5th and the 7.5th percentile of PCSK9 levels in a sample of Lebanese children of approximately the same age group. Moreover, this is the first reported case of individuals carrying simultaneously an LPL pathogenic variant and PCSK9 variants, the L10 and L11 leucine insertion, which can lower and raise low-density lipoprotein cholesterol (LDL-C) levels respectively. TG levels fluctuated concomitantly between the two children, were especially high following the migration from a country to another, and were reduced under a low-fat diet. This case is crucial to raise public awareness on the risks of consanguineous marriages to decrease the emergence of inherited autosomal recessive diseases. It also highlights the importance of the early diagnosis and management of these diseases to prevent serious complications, such as recurrent pancreatitis in the case of familial hyperchylomicronemia.
CX3CL1-induced CD16+ monocytes extravasation in myeloperoxidase-ANCA-associated vasculitis correlates with renal damage
Authors: Tang Jiale , Liao Zhonghua , Luo Liying , Deng Shuanglinzi , Jiang Yuanyuan , Wang Fangyuan , Hu Xinyue , Yin Hongling , Gong Guanghui , Feng Juntao , Li Xiaozhao 
Published: August 2022

BackgroundMonocytes are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Monocyte/macrophages are the dominant infiltrating cells in the glomeruli of patients with myeloperoxidase-AAV (MPO-AAV). However, how human monocyte subsets extravasate to the kidney in MPO-AAV with renal damage is unclear.Methods30 MPO-AAV patients with renal damage and 22 healthy controls were enrolled in this study. Monocyte subsets and monocyte-related chemokines in the blood and kidneys of MPO-AAV patients were detected. The chemoattractant activity of the CX3CL1-CX3CR1 axis on CD16+ monocytes was observed. The effect of MPO-ANCA on the migration of CD16+ monocytes to human glomerular endothelial cells (HGECs) was detected by flow cytometry and transwell migration assay.ResultsCompared with controls, CD16+ monocytes were significantly decreased in the blood and increased in the glomeruli of MPO-AAV patients with renal damage. The level of CX3CL1, but not CCL2, was significantly increased in the plasma of MPO-AAV patients. CX3CL1 co-localized with glomerular endothelial cells in MPO-AAV patients with renal damage. Moreover, we initially found that MPO-ANCA promotes an increase of the chemokine CX3CL1 on HGECs, imposing recruitment on CD16+ monocytes. Finally, the percentage of CD16+ monocytes in the blood was found to be positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with urinary protein creatinine ratio in MPO-AAV patients with renal damage. Furthermore, the urinary protein creatinine ratio was positively correlated with the infiltrating of CD14+ and CD16+ cells in the kidneys.ConclusionEnhanced extravasation of CD16+ monocytes to the kidney via the CX3CL1-CX3CR1 axis may be involved in renal damage in MPO-AAV.
Association of longitudinal platelet count trajectory with ICU mortality: A multi-cohort study
Authors: Chen Jiajin , Gao Xi , Shen Sipeng , Xu Jingyuan , Sun Zhe , Lin Ruilang , Dai Zhixiang , Su Li , Christiani David C. , Chen Feng , Zhang Ruyang , Wei Yongyue 
Published: August 2022

ObjectivePlatelet (PLT) engages in immune and inflammatory responses, all of which are related to the prognosis of critically ill patients. Although thrombocytopenia at ICU admission contributes to in-hospital mortality, PLT is repeatedly measured during ICU hospitalization and the role of longitudinal PLT trajectory remains unclear. We aimed to identify dynamic PLT trajectory patterns and evaluate their relationships with mortality risk and thrombocytopenia.MethodsWe adopted a three-phase, multi-cohort study strategy. Firstly, longitudinal PLT trajectory patterns within the first four ICU days and their associations with 28-day survival were tested in the eICU Collaborative Research Database (eICU-CRD) and independently validated in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Secondly, the relationships among PLT trajectory patterns, thrombocytopenia, and 28-day mortality were explored and validated. Finally, a Mortality GRade system for ICU dynamically monitoring patients (Mortality-GRID) was developed to quantify the mortality risk based on longitudinal PLT, which was further validated in the Molecular Epidemiology of Acute Respiratory Distress Syndrome (MEARDS) cohort.ResultsA total of 35,332 ICU patients were included from three cohorts. Trajectory analysis clustered patients into ascending (AS), stable (ST), or descending (DS) PLT patterns. DS patients with high baseline PLT decline quickly, resulting in poor prognosis. AS patients have low baseline PLT but recover quickly, favoring a better prognosis. ST patients maintain low PLT, having a moderate prognosis in between (HRSTvsAS = 1.26, 95% CI: 1.14–1.38, P = 6.15 × 10−6; HRDSvsAS = 1.58, 95% CI: 1.40–1.79, P = 1.41 × 10−13). The associations remained significant in patients without thrombocytopenia during the entire ICU hospitalization and were robust in sensitivity analyses and stratification analyses. Further, the trajectory pattern was a warning sign of thrombocytopenia, which mediated 27.2% of the effects of the PLT trajectory on 28-day mortality (HRindirect = 1.11, 95% CI: 1.06–1.17, P = 9.80 × 10−6). Mortality-GRID well predicts mortality risk, which is in high consistency with that directly estimated in MEARDS (r = 0.98, P = 1.30 × 10−23).ConclusionLongitudinal PLT trajectory is a complementary predictor to baseline PLT for patient survival, even in patients without risk of thrombocytopenia. Mortality-GRID could identify patients at high mortality risk.