bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validation of Lactate Metabolism-Related lncRNA Signature as a Prognostic Model for Lung Adenocarcinoma
Authors: Mai Shijie , Liang Liping , Mai Genghui , Liu Xiguang , Diao Dingwei , Cai Ruijun , Liu Le 
Published: March 2022

BackgroundLung cancer has been a prominent research focus in recent years due to its role in cancer-related fatalities globally, with lung adenocarcinoma (LUAD) being the most prevalent histological form. Nonetheless, no signature of lactate metabolism-related long non-coding RNAs (LMR-lncRNAs) has been developed for patients with LUAD. Accordingly, we aimed to develop a unique LMR-lncRNA signature to determine the prognosis of patients with LUAD.MethodThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to derive the lncRNA expression patterns. Identification of LMR-lncRNAs was accomplished by analyzing the co-expression patterns between lncRNAs and LMR genes. Subsequently, the association between lncRNA levels and survival outcomes was determined to develop an effective signature. In the TCGA cohort, Cox regression was enlisted to build an innovative signature consisting of three LMR-lncRNAs, which was validated in the GEO validation cohort. GSEA and immune infiltration analysis were conducted to investigate the functional annotation of the signature and the function of each type of immune cell.ResultsFourteen differentially expressed LMR-lncRNAs were strongly correlated with the prognosis of patients with LUAD and collectively formed a new LMR-lncRNA signature. The patients could be categorized into two cohorts based on their LMR-lncRNA signatures: a low-risk and high-risk group. The overall survival of patients with LUAD in the high-risk group was considerably lower than those in the low-risk group. Using Cox regression, this signature was shown to have substantial potential as an independent prognostic factor, which was further confirmed in the GEO cohort. Moreover, the signature could anticipate survival across different groups based on stage, age, and gender, among other variables. This signature also correlated with immune cell infiltration (including B cells, neutrophils, CD4+ T cells, CD8+ T cells, etc.) as well as the immune checkpoint blockade target CTLA-4.ConclusionWe developed and verified a new LMR-lncRNA signature useful for anticipating the survival of patients with LUAD. This signature could give potentially critical insight for immunotherapy interventions in patients with LUAD.
The Effects of 12-Weeks Whey Protein Supplements on Markers of Bone Turnover in Adults With Abdominal Obesity – A Post Hoc Analysis
Authors: Fuglsang-Nielsen Rasmus , Rakvaag Elin , Vestergaard Peter , Hermansen Kjeld , Gregersen Søren , Starup-Linde Jakob 
Published: March 2022

BackgroundWhile osteoporosis is characterized by skeletal fragility due to increased bone turnover and low bone mineral density (BMD), subjects with abdominal obesity and type-2 diabetes have increased risk of bone fractures despite low bone turnover and increased BMD. Diets with increased protein content are reported to increase bone turnover in healthy adults and may be a point of interest in preserving bone strength in subjects with abdominal obesity and/or type-2 diabetes.MethodsWe examined the effect of 12-weeks dietary intervention on bone turnover in 64 adults with abdominal obesity using data from the MERITS trial. The trial was a randomized, controlled, double blinded study in which participants were allocated to receive either 60 g/d of whey protein hydrolysate or maltodextrin in combination with either high (30 g/d) or low dietary fiber intake (10 g/d). Primarily, we assessed changes in plasma markers of bone turnover Procollagen type 1 N-terminal propeptide (p1NP), C-terminal telopeptide type-1 collagen (CTX), and parathyroid hormone (PTH) within the four intervention groups. In addition, we measured u-calcium and u-carbamide excretion, 25(OH)D, and BMD by whole body DXA scans. Finally, we compared changes in insulin resistance (Homeostasis-model assessment of insulin resistance, HOMA-IR) with changes in bone turnover markers.The trial was registered at www.clinicaltrials.gov as NCT02931630.ResultsSixty-four subjects were included in the study. We did not find any effect of twelve weeks of high protein or high fiber intake on plasma levels of P1NP or CTX. There was a nonsignificant positive association between protein intake and PTH levels (p=0.06). U-calcium and u-carbamide increased in both protein groups. There was a positive association between change in HOMA-IR and PTH (p=0.042), while changes in P1NP and CTX did not associate to changes in HOMA-IR.ConclusionTwelve weeks of increased whey protein intake in subjects with abdominal obesity did not affect markers of bone turnover significantly, although tended to increase PTH levels. Dietary fiber intake did not affect bone turnover. We report a positive association between change in HOMA-IR and PTH supporting a hypothesis of insulin resistance as a potential key factor in the expanding field of bone fragility in T2D subjects.
Predictive Effect of Triglyceride Glucose−Related Parameters, Obesity Indices, and Lipid Ratios for Diabetes in a Chinese Population: A Prospective Cohort Study
Authors: Li Xiaotong , Sun Mengzi , Yang Yixue , Yao Nan , Yan Shoumeng , Wang Ling , Hu Wenyu , Guo Ruirui , Wang Yuxiang , Li Bo 
Published: March 2022

ObjectiveThe purpose of this study was to evaluate the association between triglyceride glucose (TyG) index and new-onset diabetes under different glycemic states and to compare the predictive value of TyG−related parameters, obesity indices, and lipid ratios for new-onset diabetes.MethodsData were collected from the China Health and Retirement Longitudinal Study (CHARLS), consisting of 6,258 participants aged ≥45 years. Participants were grouped according to their glycemic states. Cox proportional hazards models and restricted cubic spline regression were used to explore the association between TyG index and diabetes. Cox proportional hazard models were applied to confirm the predictive value of the optimal marker. Receiver operating characteristic (ROC) curves were used to compare the predictive value.ResultsTyG index was positively correlated with the risk of diabetes (hazard ratio (HR), 1.75; 95% confidence interval (CI), 1.56–1.97), and the linear association existed (p &lt; 0.001). The highest correlation with diabetes was visceral adiposity index (VAI) (HR, 2.04; 95% CI, 1.44–2.90) in normal fasting glucose (NFG) group and TyG-body mass index (TyG-BMI) (HR, 2.53; 95% CI, 1.97–3.26) in impaired fasting glucose (IFG) group. The largest area under curve (AUC) was observed in TyG-waist-to-height ratio (TyG-WHtR) in the NFG group (AUC, 0.613; 95% CI, 0.527–0.700), and TyG-BMI had the highest AUC in the IFG group (AUC, 0.643; 95% CI, 0.601–0.685).ConclusionThe association between TyG index and new-onset diabetes was positive and linear. TyG-WHtR was a clinically effective marker for identifying the risks of diabetes in the NFG group and TyG-BMI was an effective marker to predict diabetes in the IFG group.
Comparative Analysis of Differentially Mutated Genes in Non-Muscle and Muscle-Invasive Bladder Cancer in the Chinese Population by Whole Exome Sequencing
Authors: Wang Fangming , Dong Xiying , Yang Feiya , Xing Nianzeng 
Published: March 2022

Objective: To characterize the spectra of mutations in non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) in the Chinese population to identify any mutational features and find potential therapeutic targets.Materials and methods: We collected fresh bladder tumor samples from NMIBC (n = 9) and MIBC patients (n = 11) along with adjacent normal bladder tissue specimen and peripheral blood sample. Using whole exome sequencing (WES), we analyzed the mutation spectra of those NMIBC and MIBC bladder cancer (BCa) specimen.Results: Our results demonstrated that 95% of BCa patients (19/20) had varying degrees of driver gene mutations, FGFR3 (45%), KMT2D (40%), PIK3CA (35%), ARID1A (20%), EP300 (20%), KDM6A (20%), KMT2C (20%), and STAG2 (20%) were the most frequently mutated genes in BCa patients. NMIBC and MIBC exhibited different genomic alterations. FGFR3 (67%), PIK3CA (56%), and RHOB (44%) were the most frequently mutated genes in NMIBC patients. Of note, RHOB mutation only occurred in NMIBC, whereas mutations of KMT2D (55%), TP53 (36%) and KMT2B (27%) were frequently detected in MIBC, and TP53 and KMT2B mutation only occurred in MIBC. The frequency of mutations in DNA-damage repair (DDR) gene was higher in MIBC than that in NMIBC (91 vs 78%, 6.2 vs 2.4 gene mutations per patient). Copy number alterations (CNAs) occurred at more diverse chromosomal locations in NMIBC, but the CNA burden was higher in MIBC [9.01 (2.07–31.51) vs 4.98 (0.99–9.73) mutations/Mb]., the trend of which was consistent with the tumor mutation burden (TMB) [8.26 (4.63–21.84) vs 5.58 (3.87–9.58) mutations/Mb]. Among the current set of single-base substitution (SBS) signatures including SBS 1, 2, 5, 13, and 40, we identified one differently expressed signature between NMIBC and MIBC patients: SBS13.Conclusions: There were different gene mutational characteristics and signatures between NMIBC and MIBC in the Chinese population. Frequency of DDR, CNA burden and TMB were higher in MIBC. Our analysis revealed that several genes in NMIBC did not overlap with those reported in MIBC, suggesting that a fraction of NMIBC and MIBC likely developed secondary to different precursor lesions.
Clinical and Genetic Features of Chinese Adult Patients With Chronic Non-Bacterial Osteomyelitis: A Single Center Report
Authors: Zhao Mengzhu , Wu Di , Yu Keyi , Shen Min 
Published: March 2022

ObjectivesChronic non-bacterial osteomyelitis (CNO) is a rare polygenic autoinflammatory bone disease. We aimed to characterize the clinical manifestations and gene variants of Chinese adult patients with CNO.MethodsBy reviewing data of all CNO patients being diagnosed and followed up at the Center for Adult Autoinflammation Diseases, Department of Rheumatology, Peking Union Medical College Hospital, clinical and genetic features of these patients were evaluated and concluded.ResultsThe median age of disease onset was 19 (6-64) years old, and adult-onset was observed in 6 (60%) patients. The mean time of diagnosis delay was 92 ± 78 months. The common symptoms were bone pain (10, 100%), fever (9, 90%), and arthritis (6, 60%). In total, there were 54 skeletal lesions, and each patient had no less than 2 lesions. The most frequently affected sites included lower limbs (20.5%), mandible, vertebrae and pelvis (17.5%, separately). Variants of 4 genes were detected in our study including COL1A1, PSTPIP1, LRP5 and CLCN7. In seven patients who were treated with combination therapy containing tumor necrosis factor (TNF) α inhibitors, five (55.6%) had a complete response and 2 (44.4%) had a partial response.ConclusionThis is the first and largest case series of CNO in the Chinese adult patients. Four novel genetic mutations potentially associated with CNO were identified. Notably, CNO should be considered in the differential diagnosis of adult patients with long disease course and recurrent multifocal osteomyelitis of unknown cause, and these patients might benefit from combination therapy containing TNFα inhibitors.
Natural Killer Cells Infiltration in the Joints Exacerbates Collagen-Induced Arthritis
Authors: Wu Lisheng , Wang Ran , Zhou Yi , Zhao Di , Chen Feilong , Wu Xianghui , Chen Xiaoguang , Chen Shixian , Li Juan , Zhu Junqing 
Published: March 2022

IntroductionThe role of natural killer (NK) cells in rheumatoid arthritis remains controversial. We aimed to assess the role of NK cells in the pathogenesis of rheumatoid arthritis.Materials and MethodsThe percentage of NK cells in the peripheral blood, spleen, lymph nodes and inflamed paws from collagen-induced arthritis mice were examined through the disease progression. Correlation between the proportion of NK cells and subsets with arthritis score, histopathological changes, and bone destruction were evaluated. Adoptive cell transfer was performed to determine the effect of NKp46+NK cells on arthritis development, and the role of receptor NKp46 was explored with NKp46 knockout mice.ResultsThe percentage of NK cells in peripheral blood decreased at the late stage of the disease and negatively correlated with arthritis score. NK cells increased in the inflamed paws during arthritis development and were positively associated with arthritis score, histopathological change, and bone destruction. Adoptive transfer of NKp46+NK cells before disease onset resulted in increased NK cells infiltration in the joints, higher incidence of arthritis, more severe clinical symptoms, and more pronounced joint inflammation and bone damage. NKp46 deficiency had no significant influence on the incidence and severity of arthritis in collagen-induced arthritis mice.ConclusionsNK cell infiltration in the joints positively correlates with arthritis progression, inflammation, and bone destruction. The pathogenic role of NK cells in rheumatoid arthritis may be independent of the receptor NKp46.
A Risk Model Developed Based on Necroptosis Predicts Overall Survival for Hepatocellular Carcinoma and Identification of Possible Therapeutic Drugs
Authors: Li Zedong , Fang Jianyu , Chen Sheng , Liu Hao , Zhou Jun , Huang Jiangsheng , Liu Sushun , Peng Yu 
Published: March 2022

BackgroundNecroptosis is a form of regulatory cell death (RCD) that attracts and activates immune cells, resulting in pro-tumor or anti-tumor effects. The purpose of this study was to investigate genes associated with necroptosis, to construct a risk score for predicting overall survival in patients with hepatocellular carcinoma, and to find potentially effective drugs.MethodsThe three algorithms ssGSEA, EPIC, and ESTIMATE were used to quantify the immune cell infiltration of the samples, differentially expressed genes (DEGs) analysis, and weighted gene co-expression network analysis were used to screen necroptosis related genes. Variables were screened according to random survival forest analysis, and combinations with significant p-values and a low number of genes were defined as prognostic signatures by using log-rank test after gene combination. Based on the sensitivity data of PRISM and CTRP2.0 datasets, we predicted the potential therapeutic agents for high-NRS patients.ResultsSeven genes such as TOP2A were used to define necroptosis-related risk score (NRS). The prognostic value of risk score was further validated, where high NRS was identified as a poor prognostic factor and tended to have higher grades of histologic grade, pathologic stage, T stage, BCLC, CLIP, and higher AFP. Higher NRS was also negatively correlated with the abundance of DCs, Neutrophils, Th17 cells, Macrophages, Endothelial, and positively correlated with Th2 cells. Necroptosis is often accompanied by the release of multiple cytokines, and we found that some cytokines were significantly correlated with both NRS and immune cells, suggesting that necroptosis may affect the infiltration of immune cells through cytokines. In addition, we found that TP53 mutations were more common in samples with high NRS, and these mutations may be associated with changes in NRS. Patients with high NRS may be more sensitive to gemcitabine, and gemcitabine may be an effective drug to improve the prognosis of patients with high NRS, which may play a role by inhibiting the expression of TOP2A.ConclusionsWe constructed a necroptosis-related scoring model to predict OS in HCC patients, and NRS was associated with immune response, TP53 mutation, and poor clinical classification in HCC patients. In addition, gemcitabine may be an effective drug for high-NRS patients.
Spin Properties and Metal-Semiconductor Transition of Nitrogen-Containing Zigzag Graphyne Nanoribbon Caused by Magnetic Atom Doping
Authors: Min Zi-Cong , Peng Xiao-Fang , Tan Shi-Hua 
Published: March 2022

In this study, the density function theory (DFT) was used to study the influence of the magnetic atoms (Fe, Co, Ni) doping on the electrical properties of nitrogen-containing zigzag graphyne-like nanoribbon (N-ZGyNR). The results show that, by doping different atoms into the natural “holes” of N-ZGyNR, the changes in the structure, magnetic moment distribution and electrical properties of N-ZGyNR are different. Due to the incomplete saturation of the edge C atoms, the initial N-ZGyNR presents metallicity and spin degeneracy. The doping of Fe atoms will cause the C-C bond in N-ZGyNR to be completely broken, resulting in structural distortion, and about 0.8e- will transfer from Fe to N-ZGyNR. Compared with Fe doping, Co/Ni doping has a smaller effect on the N-ZGyNR and will not cause structural distortion, but will redistribute the spin charge in N-ZGyNR, thereby forming a band gap of 60 meV near the Fermi level to realize the transition of metal-semiconductor. The above results show that the electrical properties of N-ZGyNR can be controlled by magnetic atom doping, and the metal-semiconductor transition can be realized by Co/Ni doping, which provides a new alternative for spintronic devices.
Shedding of SARS-CoV-2 for 85 Days in COVID-19 Patients With Type 2 Diabetes Mellitus and Lung Metastasis: A Case Report
Authors: Wu Xiaoheng , Shen Min , Quan Hui , Zhang Xianqin , Xu Fengcheng , Li Juan , He Miao , Pan Dongmei , Cao Ling , Yue Changwu , Liu Tianhu , Jia Xu 
Published: March 2022

BackgroundCOVID-19 (coronavirus disease 2019) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seriously endangers people's lives. The variation in SARS-CoV-2 makes the research and development of vaccines and specific drugs particularly important. However, the prevention and diagnosis of COVID-19 cannot be underestimated in the control of the epidemic.Case PresentationWe introduced a 65-year-old female patient who was diagnosed with COVID-19. The SARS-CoV-2 nucleic acid test result of this patient was positive again during treatment. It took 85 days from the first symptom to the final cure. According to the known reports, she is currently the patient with the longest virus shedding in Sichuan Province, China. Due to the patient's special condition, she was treated in four hospitals before and after, and she was diagnosed with type 2 diabetes mellitus (T2DM) and right lung metastatic adenocarcinoma. We fully introduced the patient's epidemiological history, diagnosis, testing, and treatment process. The patient was finally discharged from the hospital under the treatment of antiviral, hypoglycaemic, anti-anxiety, and a combination of Chinese and Western medicine.ConclusionsThe epidemic is still rampant, and we should not relax our efforts in the prevention and control of viruses. For the elderly, especially those who are suffering from complications or vulnerable to diseases, it is recommended to extend the observation time. Additionally, medical workers should pay attention to the mental state of patients.
The Cropping Obstacle of Garlic Was Associated With Changes in Soil Physicochemical Properties, Enzymatic Activities and Bacterial and Fungal Communities
Authors: Yu Jinyang , Liu Yihao , Wang Zuyu , Huang Xiaohui , Chai Dan , Gu Yunfu , Zhao Ke , Yu Xiumei , Shuai Zhengbin , Liu Hanjun , Zhang Xiaoping , Penttinen Petri , Chen Qiang 
Published: March 2022

AimsIn garlic cultivation, long-time monoculture has resulted in continuous-cropping obstacles. However, the cause has not been studied to date.MethodsWe analyzed soils from garlic fields in Pengzhou, China, to determine continuous-cropping obstacle related changes in soil physicochemical properties and enzyme activities, and in the diversity and composition of bacterial and fungal communities. Furthermore, we examined the relationships between soil properties and the bacterial and fungal communities.ResultsThe soil pH and the soil catalase, urease, invertase, and polyphenol oxidase activities were lower in the cropping obstacle soil than in the healthy control soil. The richness and diversity of the bacteria were lower in the cropping obstacle soil than in the control. The bacterial and fungal communities in the cropping obstacle soil were clearly different from those in the control soil. The differences in bacterial communities between the cropping obstacle soil and the control soil were associated with differences in pH and available potassium content. The taxa with higher relative abundances in the cropping obstacle soils included potential plant pathogens and the taxa with lower relative abundances included potential plant growth promoters.ConclusionThe enrichment of plant pathogens and the depletion of plant growth promoting fungi may have contributed to the poor growth of garlic in the cropping obstacle soil. The enzyme activity and microbial community differences were associated with acidification that was likely an important factor in the deterioration of the soil ecological environment and the garlic cropping obstacle. The results provide information to guide agricultural practices in cultivating garlic.
Inactivation of Fluorescent Lipid Bilayers by Irradiation With 300 keV Electrons Using Liquid Cell Transmission Electron Microscopy
Authors: Moser Trevor , Evans James E. 
Published: March 2022

Liquid cell transmission electron microscopy allows for imaging of samples in a fully hydrated state at high resolution and has the potential for visualizing static or dynamic biological structures. However, the ionizing nature of the electron beam makes it difficult to discern real physiological dynamics from radiation induced artifacts within liquid cell samples. Electron flux thresholds for achieving high resolution structures from biological samples frozen in ice have been described extensively by the cryo-electron microscopy field, while electron flux thresholds which do not result in a functional change for biological samples within the hydrated environment of a transmission electron microscope liquid cell is less clear. Establishing these functional thresholds for biologically relevant samples is important for accurate interpretation of results from liquid cell experiments. Here we demonstrate the electron damage threshold of fluorescently tagged lipid bilayers by quantifying the change in fluorescence before and after electron exposure. We observe the reduction of fluorescent signal in bilayers by 25% after only 0.0005 e−/Å2 and a reduction of over 90% after 0.01 e−/Å2. These results indicate that the loss of function occurs at irradiation thresholds far below a typical single high resolution (scanning) transmission electron microscopy image and orders of magnitude below fluxes used for preserving structural features with cryo-electron microscopy.