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Abstract Background Reproducibility is a fundamental requirement in scientific experiments. Some recent publications have claimed that microarrays are unreliable because lists of differentially expressed genes (DEGs) are not reproducible in similar experiments. Meanwhile, new statistical methods for identifying DEGs continue to appear in the scientific literature. The resultant variety of existing and emerging methods exacerbates confusion and continuing debate in the microarray community on the appropriate choice of methods for identifying reliable DEG lists. Results Using the data sets generated by the MicroArray Quality Control (MAQC) project, we investigated the impact on the reproducibility of DEG lists of a few widely used gene selection procedures. We present comprehensive results from inter-site comparisons using the same microarray platform, cross-platform comparisons using multiple microarray platforms, and comparisons between microarray results and those from TaqMan – the widely regarded "standard" gene expression platform. Our results demonstrate that (1) previously reported discordance between DEG lists could simply result from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion with a non-stringent P-value cutoff filtering, the DEG lists become much more reproducible, especially when fewer genes are selected as differentially expressed, as is the case in most microarray studies; and (3) the instability of short DEG lists solely based on P-value ranking is an expected mathematical consequence of the high variability of the t-values; the more stringent the P-value threshold, the less reproducible the DEG list is. These observations are also consistent with results from extensive simulation calculations. Conclusion We recommend the use of FC-ranking plus a non-stringent P cutoff as a straightforward and baseline practice in order to generate more reproducible DEG lists. Specifically, the P-value cutoff should not be stringent (too small) and FC should be as large as possible. Our results provide practical guidance to choose the appropriate FC and P-value cutoffs when selecting a given number of DEGs. The FC criterion enhances reproducibility, whereas the P criterion balances sensitivity and specificity.

Background: Awareness of the characteristics of glial fibrillary acidic protein autoantibody (GFAP-IgG) associated myelitis facilitates early diagnosis and treatment. We explored features in GFAP-IgG myelitis and compared them with those in myelitis associated with aquaporin-4 IgG (AQP4-IgG) and myelin oligodendrocyte glycoprotein IgG (MOG-IgG). Methods: We retrospectively reviewed data from patients with GFAP-IgG myelitis at the First Affiliated Hospital of Zhengzhou University and Henan Children's Hospital from May 2018 to May 2023. AQP4-IgG and MOG-IgG myelitis patients served as controls. Results: Thirty-four patients with GFAP-IgG myelitis were included (15 women, 12 children; median age at onset, 28.5 years). Over half experienced prodromal symptoms and required intensive care support. The median Expanded Disability Status Scale (EDSS) score was 4 at admission and 0 at final follow-up (median, 20 months). Cerebrospinal fluid (CSF) analysis showed markedly elevated leukocyte counts in 23 patients, elevated total protein in 28 patients, and decreased glucose levels in 9 patients. Longitudinally sagittal T2 and gadolinium-enhancing spinal cord lesions were detected. Features favoring GFAP-IgG over the other types included presence of fever and neck stiffness, requirement of intensive care and mechanical ventilation, higher monocyte-to-lymphocyte ratio (MLR), presence of hyponatremia, markedly elevated CSF leukocyte counts, increased CSF total protein levels, and decreased CSF glucose levels. Imaging findings more common in GFAP-IgG than in AQP4-IgG myelitis were longer diseased segments, central canal enhancement, and gadolinium-enhancing brain lesions. Higher EDSS scores at discharge distinguished GFAP-IgG from MOG-IgG. Conclusion: Clinical, laboratory, imaging, and outcome variables facilitate differential diagnosis of myelitis subtypes. [ABSTRACT FROM AUTHOR]

Routinely monitoring viral rebound (VR) is important in the life course of people with HIV (PWH). This study examined risk factors for time to the first VR, the number of VRs and their association with VR history in men who have sex with men (MSM). It includes 8176 adult PWH diagnosed from January 2005 to December 2018, followed until July 2021. We used the Cox model for time to the first VR, the Poisson model for a number of VRs, and logistic regression for VR history in MSM. Younger individuals (50–59 years vs 18–29 years, aHR: 0.43, 95% CI: [0.34, 0.55]) were more likely to experience VR. Black individuals (Black vs White, IRR: 1.61, 95% CI [1.38, 1.88]) had more VR, while MSM (MSM vs Heterosexual, IRR: 0.68, 95% CI: [0.57, 0.81]) was negatively associated with number of VsR. Furthermore, individuals engaging illicit drug use (IDU) (aOR: 1.50, 95% CI: [1.03, 2.17]) were more likely to experience VR in the MSM subgroup. This study highlighted the alarming risk factors related to VR among PWH. Tailored intervention should also be deployed for young, Black MSM patients with substance use for more effective and targeted public health strategies concerning VR. [ABSTRACT FROM AUTHOR]

Maintaining retention in care (RIC) for people living with HIV (PLWH) helps achieve viral suppression and reduce onward transmission. This study aims to identify the best machine learning model that predicts the RIC transition over time. Extracting from the enhanced HIV/AIDS reporting system, this study included 9765 PLWH from 2005 to 2020 in South Carolina. Transition of RIC was defined as the change of RIC status in each two–year time window. We applied seven classifiers, such as Random Forest, Support Vector Machine, eXtreme Gradient Boosting and Long–short–term memory, for each lagged response to predict the subsequent year's RIC transition. Classification performance was assessed using balanced prediction accuracy, the area under the curve (AUC), recall, precision and F1 scores. The proportion of the four categories of RIC transition was 13.59%, 29.78%, 9.06% and 47.57%, respectively. Support Vector Machine was the best approach for every lag model based on both the F1 score (0.713, 0.717 and 0.719) and AUC (0.920, 0.925 and 0.928). The findings could facilitate the risk augment of PLWH who are prone to follow–up so that clinicians and policymakers could come up with more specific strategies and relocate resources for intervention to keep them sustained in HIV care. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the effects of elevated KDM4D expression and potential therapeutic effects of Lycium barbarum polysaccharide (LBP) on pterygium. Methods: The expression levels of KDM4D in the primary pterygium (n = 29) and normal conjunctiva (n = 14) were detected by immunohistochemistry. The effects of KDM4D on pterygium fibroblasts were detected by the CCK-8 assay, liquid chromatography-mass spectrometry assay, flow cytometry, and scratch wound healing assay. The relative expression of KDM4D in pterygium fibroblasts stimulated by interleukin (IL)-1β, IL-6, IL-8, and LBP was detected by quantitative real-time PCR and Western blot. The effects of LBP on pterygium fibroblasts were detected using flow cytometry and scratch wound healing assays. Results: The expression level of KDM4D in pterygium was higher than that in normal conjunctiva. KDM4D increased the cell viability of pterygium fibroblasts. The differentially expressed genes identified in the LM-MS assay enriched in "actin filament organization" and "apoptosis." KDM4D promoted migration and inhibited apoptosis of pterygium fibroblasts in vitro. Inflammatory cytokines, including IL-1β, IL-6, and IL-8, enhanced the expression of KDM4D in pterygium fibroblasts. LBP inhibited the expression of KDM4D in pterygium fibroblasts and decreased their cell viability. Moreover, LBP attenuated the KDM4D effects on migration and apoptosis of pterygium fibroblasts. Conclusions: Elevated KDM4D expression is a risk factor for pterygium formation. LBP inhibits the expression of KDM4D in pterygium fibroblasts and may be a potential drug for delaying pterygium development. [ABSTRACT FROM AUTHOR]

Periacetabular osteotomy (PAO) is an effective technique to treat symptomatic hip dysplasia. However, following PAO, some patients still experience persistent pain or development of hip arthritis, requiring total hip arthroplasty (THA). Issues such as whether patients with PAO are necessarily at increased risk of post‐THA complications and revision of the prosthesis remain debatable. The purpose of this study was to evaluate the biomechanical influence of PAO on the acetabulum after THA by finite element analysis. Eight patients with developmental dysplasia of the hip (DDH) diagnosed in the Fourth Medical Center of the PLA General Hospital were enrolled in this research. Patient‐specific hip joint models were reconstructed from computed tomography scans, and the hip prosthesises, were established via computer‐aided design (CAD) modeling technology. The finite element analysis was conducted to compare the surface and internal stress through the process mapping of the model due to the THA. Compared with the THA after PAO, the position of the high‐stress area of the acetabular fossa of patients without PAO decreased, and the high‐stress area developed toward the lower edge of the acetabulum. Although the high‐stress area of the suprapubic branch did not change significantly, the peak stress was higher (t =.00237). The analysis of the section plane showed that the high‐stress area of cancellous bone had a large distribution. The acetabular size and vertical distance of rotation center (VDRC) were significantly correlated with the maximum postoperative acetabular equivalent stress (p =.011, p =.001). In the Post group, both the horizontal distance of rotation center (HDRC) and A‐ASA were significantly correlated with postoperative maximal acetabular equivalent stress, with a significance of 0.014 and 0.035, respectively. The risk of postoperative prosthetic revision following THA is not increased by PAO, although the risk of postoperative suprapubic branch fracture is increased. [ABSTRACT FROM AUTHOR]

The pathogenesis of systemic lupus erythematosus (SLE) is closely associated with aberrant immune system. Here, the aim of our study was to explore the regulation of cucurbitacin IIb (CuIIb) to Th17/Treg cells in SLE. Compared with normal mice, the percentage of Treg cells was downregulated in SLE mouse model, and Th17 was upregulated. Meantime, the production of Treg‐related transcription factor (foxp3) in SLE model mouse was reduced, and the production of Th17‐related transcription factor (RORγt) was increased. After treatment with CuIIb, the percentage of Treg cells in SLE mice was partly upregulated, and Th17 cells percentage was downregulated. The expression of foxp3 and RORγt in SLE mice were promoted and inhibited by CuIIb treatment, respectively. SLE‐induced kidney injury also was improved by CuIIb treatment. In vitro, we demonstrated again that CuIIb upregulated the percentage of Treg cells in lymphocytes from SLE mice, and downregulated the percentage of Th17 cells. Highly expressed IL‐6 and IL17, and lowly expressed IL‐10 and TGF‐β in lymphocytes from SLE mice were repressed and facilitated by CuIIb treatment, respectively. Overall, our data proved that CuIIb improved kidney injury in SLE mice through balancing the percentage of Th17 and Treg cells. Our data provided a reliable evidence to support the potential of CuIIb in SLE treatment. [ABSTRACT FROM AUTHOR]

Deconjugation of bile salts in vivo not only promotes the cholesterol metabolism of the host, but also provides cellular carbon, nitrogen and sulphur for some probiotics. In this study, the gene of BSH from Bifidobacterium bifidum (ATCC 29521) was amplified and expressed using glutathione S-transferase (GST) Gene Fusion System. The enzyme was purified in a mild conditions without denaturation and renaturation, and the molecular mass was estimated to be 35 kDa. The optimum pH for the enzyme catalysis was 5.5. The BSH enzyme was stable from 37 to 57 °C. In addition, this enzyme was completely inhibited by Cu2+, while many other metal ions only gave moderate inhibition. Hydrolysis efficiency of BSH was quantified in two ways: ninhydrin colouration method and high-performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD). The hydrolysis process was clearly observed through real-time picture monitoring. The activity of BSH on glycine-conjugated bile salts was better than on taurine-conjugated bile salts. The proportion of hydrolysis for both sodium glycochenodeoxycholate (GCDCA) and sodium glycoursodeoxycholate (GUDCA) were more than 90% in 60 min. However, the proportion of hydrolysis for sodium taurochenodeoxycholate (TCDCA) and sodium tauroursodeoxycholate (TUDCA) were only 68% and 43% at the same condition. The study of this paper provides a better choice for hydrolysis of glycine-conjugated bile salts. The specificity of BSH was high for glycine-conjugated bile salts. Hydrolysis process of bile acid was obtained through real-time picture monitoring. Hydrolysis efficiency of BSH was quantified in two ways: ninhydrin colouration method and HPLC-ELSD. [ABSTRACT FROM AUTHOR]

Although many organic molecules found commonly in the atmosphere are known to be surface-active in aqueous solutions, their effects on the mechanisms underlying haze formation remain unclear. In this paper, based on a simple thermodynamic analysis, we report that the adsorption of amphiphilic organics alone not only lowers the surface tension, but also unexpectedly stabilizes nanodroplets of specific size under water vapor supersaturation. Then we determine how various factors, including relative humidity, water activity effect due to dissolution of inorganic components as well as surface tension effect due to surface adsorption of organic components, cooperatively induce the stability of nanodroplets. The nanodroplet stability behaviors not captured in the current theory would change the formation mechanism of haze droplets, from the hygroscopic growth pathway to a nonclassical two-step nucleation pathway. [ABSTRACT FROM AUTHOR]

Purpose: Although retinoblastoma is rare but can be deadly in some severe cases. To find novel therapeutic targets for retinoblastoma, we explored the potential role of lncRNA NKILA in retinoblastoma. Results: We found that, comparing to healthy controls, NKILA was downregulated, while lncRNA XIST was upregulated in plasma of retinoblastoma patients and they were inversely correlated. Downregulation of NKILA distinguished early-stage patients from healthy controls. Overexpression of lncRNA NKILA mediated the downregulation of XIST in retinoblastoma cells, while XIST overexpression failed to significantly affect NKILA. Overexpression of NKILA resulted in decreased, while XIST overexpression resulted in increased proliferation, migration and invasion rates of retinoblastoma cells. In addition, rescue experiment showed that XIST overexpression attenuated the effects of NKILA overexpression on cancer cell behaviors. Conclusions: Therefore, NKILA inhibits retinoblastoma possibly by downregulating XIST, but the causality has not been fully validated. [ABSTRACT FROM AUTHOR]

The dysregulation of microRNAs (miRNAs/miRs) has become increasingly recognized as a primary feature of retinoblastoma (RB). Furthermore, miRNAs have been demonstrated to be involved in the occurrence and development of RB. Therefore, it is crucial to investigate the expression profile and roles of miRNAs in RB in order to identify potential therapeutic targets to treat patients with RB. The expression profile and biological roles of miRNA-504 (miR-504) have been reported in numerous types of human cancer; however, the roles of miR-504 in RB remain unknown. In the present study, it was demonstrated that miR-504 expression was significantly decreased in RB tissues and cell lines. Functional analysis identified that resumption of miR-504 expression suppressed cell proliferation and invasion in RB. Furthermore, astrocyte elevated gene-1 (AEG-1) was determined to be a direct target of miR-504 in RB, and a negative correlation between miR-504 and AEG-1 mRNA expression levels was observed in RB tissues. Additionally, the tumor-suppressing effects of miR-504 overexpression in RB cells could be rescued by AEG-1 upregulation. In conclusion, these results indicated a significant role of the miR-504/AEG-1 pathway in inhibiting the aggressiveness of RB, suggesting that this miRNA may be employed as a therapeutic target for the treatment of patients with this disease. [ABSTRACT FROM AUTHOR]