Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcomes in Patients With Lung Adenocarcinoma With Transformation to Small Cell Lung Cancer After EGFR Tyrosine Kinase Inhibitors Resistance: A Systematic Review and Pooled Analysis

Background Lung adenocarcinoma can transform into small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. Approximately 3% to 10% of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) could transform to SCLC. This phenomenon has been described in several case reports and small patient series. However, the characteristics and treatment outcomes of this population have not been comprehensively reported, and their clinical course is poorly characterized. Methods We performed a systematic review of the published literature to summarize the clinical and pathological features and prognosis of the reported cases and analyzed the demographics, disease features, and outcomes. Results A total of 72 patients (50 females and 22 males) initially diagnosed with lung adenocarcinoma were included. EGFR mutations included 19-deletion (75%), L858R (22%), and G719X (3%). All patients received EGFR-TKIs before SCLC transformation. The median time from diagnosis to transformation was 20.5 months (95% CI, 15.45 to 26.55 months). Of the 67 patients with post-translational gene test results, 58 maintained their EGFR mutation, and only 1 of 18 with prior T790M positivity retained T790M mutation. After the pathological transformation, both conventional chemotherapy regimen and chemotherapy combined targeted therapy yielded high response rates. The disease control rate of first-line therapy after transformation was 76%, while the objective response rate was 48%. The median overall survival (OS) since diagnosis was 27 months (95% CI, 22.90 to 31.10 months), whereas median OS since SCLC transformation was 8.5 months (95% CI, 5.50 to 11.60 months). Conclusion The prognosis of transformed SCLC is worse than primary SCLC. The response rate to conventional chemotherapy was high. However, the progression-free survival and OS after transformation were short and the prognosis was poor with first-line therapies. New therapies are needed in the management of transformed SCLC.
Lipoic Acid-Coated Silver Nanoparticles: Biosafety Potential on the Vascular Microenvironment and Antibacterial Properties

Purpose: To study and compare the antibacterial properties and the potential cytotoxic effects of commercially available uncoated silver nanoparticles (AgNPs) with lipoic acid coated silver nanoparticles (AgNPsLA) developed by our group. The antibacterial, cytotoxic, and hemolytic properties of those NPs were assessed with the main objective of investigating if AgNPsLA could maintain their antibacterial properties while improving their biosafety profile over uncoated AgNPs within the blood vessel’s microenvironment. Methods: Comercially available uncoated 2.6 nm AgNPs and 2.5 nm AgNPsLA synthesized and characterized as previously described by our group, were used in this study. Antimicrobial activity was assessed on a wide range of pathogens and expressed by minimal inhibitory concentrations (MIC). Assessment of cytotoxicity was carried out on human umbilical vein endothelial cells (HUVEC) using an MTT test. Detection of reactive oxygen species, cell apoptosis/necrosis in HUVEC, and measurement of mitochondrial destabilization in HUVEC and platelets were performed by flow cytometry. The potential harmful effect of nanoparticles on red blood cells (RBCs) was investigated measuring hemoglobin and LDH released after exposure to NPs. Transmission electron microscopy was also used to determine if AgNPs and AgNPsLA could induce any ultrastructural changes on HUVEC cells and Staphylococcus aureus bacteria. Results: AgNPs and AgNPsLA had antimicrobial properties against pathogens associated with catheter-related bloodstream infections. AgNPs, in contrast to AgNPsLA, induced ROS production and apoptosis in HUVEC, ultrastructural changes in HUVEC and S. aureus, depolarization of mitochondrial membrane in HUVEC and platelets, and also hemolysis. Conclusion: AgNPsLA synthesized by our group have antimicrobial activity and a better biosafety profile than uncoated AgNPs of similar size. Those observations are of critical importance for the future in vivo investigations and the potential application of AgNPsLA in medical devices for human use.
Blood Group O Protect End-Stage Renal Disease Patients With Dialysis From Coronary Artery Disease

Objective Our study aims to investigate the role of the ABO blood group in the development and severity of coronary artery disease (CAD) in end-stage renal disease (ESRD) patients with dialysis. Methods A total of 408 ESRD patients with dialysis between January 2010 and December 2020 were enrolled including 204 patients diagnosed with CAD undergoing coronary angiography for the first time, and baseline characteristics as well as Gensini score (GS) were collected. Logistic regression analysis and linear regression analysis were performed to evaluate the relation of ABO blood types to the risk and severity of CAD, respectively. Results Blood group O frequency was significantly low in dialysis ESRD patients with CAD (25 vs. 38.24%) compared with the non-CAD patients and multivariable logistic regression showed blood group O was negatively associated with the risk of CAD [adjusted odds ratio (OR) = 0.33, 95% CI = 0.19–0.60, p < 0.001] as well as the GS tertiles (adjusted OR = 0.23, 95% CI = 0.11–0.49, p < 0.001) compared with A blood group. Blood group A, B, and AB were positively associated with the high Gensini tertile compared with O blood group (adjusted OR = 4.26, 95% CI = 2.03–8.93, p < 0.001; adjusted OR = 2.39, 95% CI = 1.11–5.13, p < 0.05; adjusted OR = 4.33, 95% CI = 1.40–13.35, P < 0.05). Similarly, multivariable linear regression results revealed O blood type was negatively associated with the GS (β = −26.129, 95% CI = −40.094 to −12.164, p < 0.001). Conclusion This case-control study demonstrated that blood group O was a potential independent protective factor for the risk and severity of CAD in ESRD patients with dialysis.
Genetic Parameter Estimation and Genome-Wide Association Study-Based Loci Identification of Milk-Related Traits in Chinese Holstein

Accurately estimating the genetic parameters and revealing more genetic variants underlying milk production and quality are conducive to the genetic improvement of dairy cows. In this study, we estimate the genetic parameters of five milk-related traits of cows—namely, milk yield (MY), milk fat percentage (MFP), milk fat yield (MFY), milk protein percentage (MPP), and milk protein yield (MPY)—based on a random regression test-day model. A total of 95,375 test-day records of 9,834 cows in the lower reaches of the Yangtze River were used for the estimation. In addition, genome-wide association studies (GWASs) for these traits were conducted, based on adjusted phenotypes. The heritability, as well as the standard errors, of MY, MFP, MFY, MPP, and MPY during lactation ranged from 0.22 ± 0.02 to 0.31 ± 0.04, 0.06 ± 0.02 to 0.15 ± 0.03, 0.09 ± 0.02 to 0.28 ± 0.04, 0.07 ± 0.01 to 0.16 ± 0.03, and 0.14 ± 0.02 to 0.27 ± 0.03, respectively, and the genetic correlations between different days in milk (DIM) within lactations decreased as the time interval increased. Two, six, four, six, and three single nucleotide polymorphisms (SNPs) were detected, which explained 5.44, 12.39, 8.89, 10.65, and 7.09% of the phenotypic variation in MY, MFP, MFY, MPP, and MPY, respectively. Ten Kyoto Encyclopedia of Genes and Genomes pathways and 25 Gene Ontology terms were enriched by analyzing the nearest genes and genes within 200 kb of the detected SNPs. Moreover, 17 genes in the enrichment results that may play roles in milk production and quality were selected as candidates, including CAMK2G, WNT3A, WNT9A, PLCB4, SMAD9, PLA2G4A, ARF1, OPLAH, MGST1, CLIP1, DGAT1, PRMT6, VPS28, HSF1, MAF1, TMEM98, and F7. We hope that this study will provide useful information for in-depth understanding of the genetic architecture of milk production and quality traits, as well as contribute to the genomic selection work of dairy cows in the lower reaches of the Yangtze River.
Ethanol- and Cigarette Smoke-Related Alternations in Oral Redox Homeostasis

Alcohol abuse as well as smoking cigarettes has been proven to negatively affect the oral environment. The aim of this work was to provide a systematic review of the literature on the influence of ethanol and cigarette smoking on oral redox homeostasis. A search was performed for scientific articles indexed in the PubMed, Medline and Web of Science databases. We identified 32,300 articles, of which 54 were used for the final review, including the results from 2000 to 2021. Among the publications used to write this article, n = 14 were related to the influence of alcohol consumption (clinical studies n = 6, experimental studies n = 8) and n = 40 were related to the influence of smoking (clinical studies n = 33, experimental studies n = 7) on oral redox homeostasis. The reviewed literature indicates that alcohol abusers and smokers are more likely to suffer from salivary gland dysfunction, as well as develop precancerous lesions due to DNA damage. Compared to alcohol abstainers and non-smokers, alcohol drinkers and smokers are also characterized by a deterioration in periodontal health measured by various indicators of periodontal status. In summary, alcohol abuse and smoking are associated with disrupted oral redox homeostasis, which may lead not only to tooth loss, but also contribute to various adverse effects related to mental health, digestive processes and chronic inflammation throughout the human body.
Enhanced Immunomodulatory Effect of Intravenous Immunoglobulin by Fc Galactosylation and Nonfucosylation

Intravenous immunoglobulin (IVIG) is used as an immunomodulatory agent in the treatment of various autoimmune/inflammatory diseases although its mechanism of action remains elusive. Recently, nonfucosylated IgG has been shown to be preferentially bound to Fcγ receptor IIIa (FcγRIIIa) on circulating natural killer cells; therefore, we hypothesized that nonfucosylated IVIG may modulate immune responses through FcγRIIIa blockade. Here, homogeneous fucosylated or nonfucosylated glycoforms of normal polyclonal IgG bearing sialylated, galactosylated or nongalactosylated Fc oligosaccharides were generated by chemoenzymatic glycoengineering to investigate whether the IgG glycoforms can inhibit antibody-dependent cellular cytotoxicity (ADCC). Among the six IgG glycoforms, galactosylated, nonfucosylated IgG [(G2)2] had the highest affinity to FcγRIIIa and 20 times higher potency to inhibit ADCC than native IgG. A pilot study of IVIG treatment in mice with collagen antibody-induced arthritis highlighted the low-dose (G2)2 glycoform of IVIG (0.1 g/kg) as an effective immunomodulatory agent as the 10-fold higher dose of native IVIG. These preliminary results suggest that the anti-inflammatory activity of IVIG is in part mediated via activating FcγR blockade by galactosylated, nonfucosylated IgG and that such nonfucosylated IgG glycoforms bound to FcγRs on immune cells play immunomodulatory roles in health and disease. This study provides insights into improved therapeutic strategies for autoimmune/inflammatory diseases using glycoengineered IVIG and recombinant Fc.
Cell-Free Fat Extract Prevents Tail Suspension–Induced Bone Loss by Inhibiting Osteocyte Apoptosis

Introduction: As the space field has developed and our population ages, people engaged in space travel and those on prolonged bed rest are at increasing risk for bone loss and fractures. Disuse osteoporosis occurs frequently in these instances, for which the currently available anti-osteoporosis agents are far from satisfactory and have undesirable side effects. CEFFE is a cell-free fraction isolated from nanofat that is enriched with a variety of growth factors, and we aim to investigate its potential therapeutic effects on disuse osteoporosis. Methods: A tail suspension–induced osteoporosis model was applied in this study. Three weeks after tail suspension, CEFFE was intraperitoneally injected, and PBS was used as a control. The trabecular and cortical bone microstructures of the tibia in each group were assessed by μCT after 4 weeks of administration. Osteocyte lacunar-canalicularity was observed by HE and silver staining. In vitro, MLO-Y4 cell apoptosis was induced by reactive oxygen species (ROSUP). TUNEL staining and flow cytometry were used to detect apoptosis. CCK-8 was used to detect cell proliferation, and Western blotting was used to detect MAPK signaling pathway changes. Results: CEFFE increased the bone volume (BV/TV) and trabecular number (Tb.N) of the trabecular bone and increased the thickness of the cortical bone. HE and silver staining results showed that CEFFE reduced the number of empty lacunae and improved the lacuna-canalicular structure. CEFFE promoted osteocyte proliferative capacity in a dose-dependent manner. CEFFE protected MLO-Y4 from apoptosis by activating the serine/threonine-selective protein kinase (ERK) signaling pathways. Conclusion: CEFFE attenuated immobilization-induced bone loss by decreasing osteocyte apoptosis. CEFFE increased the survival of osteocytes and inhibited osteocyte apoptosis by activating the ERK signaling pathway in vitro.
Sa12b Improves Biological Activity of Human Degenerative Nucleus Pulposus Mesenchymal Stem Cells in a Severe Acid Environment by Inhibiting Acid-Sensitive Ion Channels

Sa12b is a wasp peptide that can inhibit acid-sensitive ion channels (ASICs). The biological effects of nucleus pulposus mesenchymal stem cells (NP-MSCs) have not been investigated. Therefore, this study investigated the effect of Sa12b on the biological activity of NP-MSCs through ASICs in the acidic environment of intervertebral disc degeneration (IVDD). In this study, NP-MSCs were isolated from the nucleus pulposus (NP) in patients who underwent lumbar disc herniation surgery, identified by flow cytometry and tertiary differentiation, and cultured in vitro in an acidic environment model of IVDD with a pH of 6.2. Proliferation, and apoptosis were observed after different Sa12b concentrations were added to P2 generation NP-MSCs. The Ca2+ influx was detected using flow cytometry and laser confocal scanning microscopy, and qPCR was used to detect the relative expression of stem cell–associated genes (Oct4, Nanog, Jag1, and Notch1), the relative expression of extracellular matrix (ECM)–associated genes (collagen II, aggrecan, and SOX-9), and the relative expression of genes encoding ASICs (ASIC1, ASIC2, ASIC3, and ASIC4). Western blotting was used to detect the protein expression of collagen II and aggrecan in different treatment groups. Cells isolated and cultured from normal NP were spindle-shaped and adherent, and they exhibited expansion in vitro. Flow cytometry results showed that the cells exhibited high expression of CD73 (98.1%), CD90 (97.5%), and CD105 (98.3%) and low expression of HLA-DR (0.93%), CD34 (2.63%), and CD45 (0.33%). The cells differentiated into osteoblasts, adipocytes, and chondrocytes. According to the International Society for Cellular Therapy criteria, the isolated and cultured cells were NP-MSCs. With an increase in Sa12b concentration, the cell proliferation rate of NP-MSCs increased, and the apoptosis rate decreased significantly, reaching the optimal level when the concentration of Sa12b was 8 μg/μl. When the Sa12b concentration was 8 μg/μl and contained the ASIC non-specific inhibitor amiloride, the Ca2+ influx was the lowest, followed by that when the Sa12b concentration was 8 μg/μl. The Ca2+ influx was the highest in the untreated control group. qPCR results showed that as the concentration of Sa12b increased, the relative expression of Oct4, Nanog, Jag1, Notch1, collagen II, aggrecan, and SOX-9 increased, while that of ASIC1, ASIC2, ASIC3, and ASIC4 decreased. The difference was statistically significant (p < 0.05). In conclusion, Sa12b can improve the biological activity of NP-MSCs in severely acidic environments of the intervertebral disc by reducing Ca2+ influx via AISC inhibition and, probably, the Notch signaling pathway. This study provides a new approach for the biological treatment of IVDD. Inhibition of AISCs by Sa12b may delay IVDD and improve low back pain.
Comparative Transcriptional Analysis Identified Characteristic Genes and Patterns in HIV-Infected Immunological Non-Responders

Purpose The incomplete immune reconstitution is a complex phenomenon among human immunodeficiency virus (HIV)-infected patients despite the fact that they have achieved persistent viral suppression under the combined antiretroviral therapy. This study aims to screen and verify the immunological characteristics and underlying mechanisms of immunological non-responders (INRs). Methods The RNA-seq and the differentially expressed genes (DEGs) analysis were used to explore potential characteristics among INRs. Gene Ontology (GO) enrichment, ingenuity pathway analysis (IPA) analysis, Gene set enrichment analysis (GSEA) analysis, and the weighted gene co-expression network analysis (WGCNA) were used to explore the potential mechanism. The transcriptional meta-analysis was used to analyze the external efficiency. Results The RNA-seq identified 316 DEGs among INRs. The interferon signaling pathway was enriched via GO and IPA analysis among DEGs. The combined GSEA and WGCNA analysis confirmed that the IFN response was more correlated with INR. Furthermore, IFI27 (IFN-α Inducible Protein 27, also known as ISG12) was chosen based on combined DEG analysis, WGCNA analysis, and the transcriptional meta-analysis conducted on other published datasets about INRs. The expression of IFI27 was significantly negatively correlated with the CD4+ T-cell counts of PLWH, and the predictive efficiency of IFI27 level in distinguishing PLWH with poor immune recovery was also with significant power (AUC = 0.848). Conclusion The enhanced expression of IFI27 and the IFN response pathway are among the important immunological characteristics of INRs and exhibited promising efficiency as biomarkers for CD4+ T-cell recovery.
Development and Validation of a CT-Based Radiomics Nomogram for Predicting Postoperative Progression-Free Survival in Stage I–III Renal Cell Carcinoma

Background Many patients experience recurrence of renal cell carcinoma (RCC) after radical and partial nephrectomy. Radiomics nomogram is a newly used noninvasive tool that could predict tumor phenotypes. Objective To investigate Radiomics Features (RFs) associated with progression-free survival (PFS) of RCC, assessing its incremental value over clinical factors, and to develop a visual nomogram in order to provide reference for individualized treatment. Methods The RFs and clinicopathological data of 175 patients (125 in the training set and 50 in the validation set) with clear cell RCC (ccRCC) were retrospectively analyzed. In the training set, RFs were extracted from multiphase enhanced CT tumor volume and selected using the stability LASSO feature selection algorithm. A radiomics nomogram final model was developed that incorporated the RFs weighted sum and selected clinical predictors based on the multivariate Cox proportional hazard regression. The performances of a clinical variables-only model, RFs-only model, and the final model were compared by receiver operator characteristic (ROC) analysis and DeLong test. Nomogram performance was determined and validated with respect to its discrimination, calibration, reclassification, and clinical usefulness. Results The radiomics nomogram included age, clinical stage, KPS score, and RFs weighted sum, which consisted of 6 selected RFs. The final model showed good discrimination, with a C-index of 0.836 and 0.706 in training and validation, and good calibration. In the training set, the C-index of the final model was significantly larger than the clinical-only model (DeLong test, p = 0.008). From the clinical variables-only model to the final model, the reclassification of net reclassification improvement was 18.03%, and the integrated discrimination improvement was 19.08%. Decision curve analysis demonstrated the clinical usefulness of the radiomics nomogram. Conclusion The CT-based RF is an improvement factor for clinical variables-only model. The radiomics nomogram provides individualized risk assessment of postoperative PFS for patients with RCC.
Cognitive and Linguistic Effects of Working Memory Training in Children With Corresponding Deficits

Working memory training has been found to result in improvements on tasks similar to those involved in the training (near transfer) but show limited impact on everyday skills such as language or academic abilities (far transfer). Previous research has largely focused on those with a broad range of skills, and examined group level responses. This study uses a single subject design to examine the effect of working memory training on both working memory and related domains in children with working memory impairment. Seven children (8–11 years old) with a working memory impairment completed 20 sessions of computerized working memory intervention. Data revealed near transfer for all participants. Evidence of far transfer to improvements in language, reading, or math was observed for approximately half of the participants on individual measures. Three participants showed convincing but modest training effects across multiple measures. A combination of factors appeared to influence far transfer including age, training intensity, and baseline measures.
Identification of a Novel Nomogram to Predict Progression Based on the Circadian Clock and Insights Into the Tumor Immune Microenvironment in Prostate Cancer

Background Currently, the impact of the circadian rhythm on the tumorigenesis and progression of prostate cancer (PCA) has yet to be understood. In this study, we first established a novel nomogram to predict PCA progression based on circadian clock (CIC)-related genes and provided insights into the tumor immune microenvironment. Methods The TCGA and Genecards databases were used to identify potential candidate genes. Lasso and Cox regression analyses were applied to develop a CIC-related gene signature. The tumor immune microenvironment was evaluated through appropriate statistical methods and the GSCALite database. Results Ten genes were identified to construct a gene signature to predict progression probability for patients with PCA. Patients with high-risk scores were more prone to progress than those with low-risk scores (hazard ratio (HR): 4.11, 95% CI: 2.66-6.37; risk score cut-off: 1.194). CLOCK, PER (1, 2, 3), CRY2, NPAS2, RORA, and ARNTL showed a higher correlation with anti-oncogenes, while CSNK1D and CSNK1E presented a greater relationship with oncogenes. Overall, patients with higher risk scores showed lower mRNA expression of PER1, PER2, and CRY2 and higher expression of CSNK1E. In general, tumor samples presented higher infiltration levels of macrophages, T cells and myeloid dendritic cells than normal samples. In addition, tumor samples had higher immune scores, lower stroma scores and lower microenvironment scores than normal samples. Notably, patients with higher risk scores were associated with significantly lower levels of neutrophils, NK cells, T helper type 1, and mast cells. There was a positive correlation between the risk score and the tumor mutation burden (TMB) score, and patients with higher TMB scores were more prone to progress than those with lower TMB scores. Likewise, we observed similar results regarding the correlation between the microsatellite instability (MSI) score and the risk score and the impact of the MSI score on the progression-free interval. We observed that anti-oncogenes presented a significantly positive correlation with PD-L1, PD-L2, TIGIT and SIGLEC15, especially PD-L2. Conclusion We identified ten prognosis-related genes as a promising tool for risk stratification in PCA patients from the fresh perspective of CIC.