On Ridge Estimation in High-dimensional Rotationally Sparse Linear Regression

Recently, deep neural networks have been found to nearly interpolate training data but still generalize well in various applications. To help understand such a phenomenon, it has been of interest to analyze the ridge estimator and its interpolation limit in high-dimensional regression models. For this motivation, we study the ridge estimator in a rotationally sparse setting of high-dimensional linear regression, where the signal of a response is aligned with a small number, $d$, of covariates with large or spiked variances, compared with the remaining covariates with small or tail variances, \textit{after} an orthogonal transformation of the covariate vector. We establish high-probability upper and lower bounds on the out-sample and in-sample prediction errors in two distinct regimes depending on the ratio of the effective rank of tail variances over the sample size $n$. The separation of the two regimes enables us to exploit relevant concentration inequalities and derive concrete error bounds without making any oracle assumption or independent components assumption on covariate vectors. Moreover, we derive sufficient and necessary conditions which indicate that the prediction errors of ridge estimation can be of the order $O(\frac{d}{n})$ if and only if the gap between the spiked and tail variances are sufficiently large. We also compare the orders of optimal out-sample and in-sample prediction errors and find that, remarkably, the optimal out-sample prediction error may be significantly smaller than the optimal in-sample one. Finally, we present numerical experiments which empirically confirm our theoretical findings

Influence of Anodic Oxidation Parameters of TiO₂Nanotube Arrays on Morphology and Photocatalytic Performance

Titanium dioxide nanotube arrays (TNTAs) were fabricated by electrochemical anodization of Ti foils. The effects of electrolyte, applied voltage, duration of anodic oxidation to morphology, and photocatalytic performance of TNTAs were investigated. TNTAs formed in electrolyte of glycol and DMSO tend to grow along radial direction with flimsy tube wall and weak adhesion on Ti substrate. Those in glycerol, however, easily achieve balance between growth rate and corrosion rate, form orderly arranged array of nanotubes with uniform diameter, moderate length, and strong adhesiveness with substrates then. Although the photocatalytic activity of Rh B degradation on TNTAs prepared in glycol and DMSO is higher than those prepared in glycerol, their convenience of recycling and recovery shows the opposite. The optimality condition of anodic oxidation for TNTAs with good morphology and photocatalytic performance was present, which may have potential application in the synthesis of composite nanoarrays.</jats:p

Prognostic significance and immune microenvironment infiltration patterns of hypoxia and endoplasmic reticulum stress-related genes in gastric cancer

BackgroundGastric cancer (GC) is a prevalent malignant neoplasm within the digestive system, accounting for approximately 740,000 deaths globally each year, significantly impacting patients' quality of life and survival rates. The objective of this investigation was to elucidate the expression patterns of Hypoxia and Endoplasmic Reticulum Stress-related Differentially Expressed Genes (HERSRDEGs) in GC and their association with prognostic outcomes of the patients.MethodsUtilizing The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, GC datasets were retrieved, and standard normalization was performed. Differential expression analysis was conducted using DESeq2, while somatic mutations and copy number variations were examined using maftools and GISTIC2.0. Spearman's correlation assessed the interplay between HERSRDEGs across datasets. Functional enrichment analyses were carried out using clusterProfiler for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, alongside Gene Set Enrichment Analysis (GSEA). A prognostic risk model was obtained by utilizing univariate Cox regression analysis with a survival R package. We employed RT-qPCR to validate the mRNA expression levels of five model genes that impact the prognostic risk of gastric cancer in human gastric adenocarcinoma tissues.ResultsThe acquired data revealed 19 HERSRDEGs including ANGPT2, CXCL8, and AURKA exhibiting significant variation in expression between GC and controls. In the Cox regression analysis, a total of five genes—ANGPT2, CD36, EGR1, NOX4, TLR2—emerged as statistically significant, correlating strongly with overall survival. A LASSO regression model featuring ANGPT2, CD36, and NOX4 yielded a risk score formula capable of predicting patient outcomes. Furthermore, multivariate Cox regression analysis highlighted RiskScore, age and stage as significant survival predictors. The analysis of immune infiltration revealed notable differences in the populations of immune cells, such as Natural Killer cells and T-helper cells, when comparing high-risk and low-risk groups.ConclusionIn conclusion, this investigation elucidates the involvement of HERSRDEGs in GC progression and their potential as prognostic biomarkers

Dai-Huang-Fu-Zi-Tang Alleviates Intestinal Injury Associated with Severe Acute Pancreatitis by Regulating Mitochondrial Permeability Transition Pore of Intestinal Mucosa Epithelial Cells

Objective. The aim of the present study was to examine whether Dai-Huang-Fu-Zi-Tang (DHFZT) could regulate mitochondrial permeability transition pore (MPTP) of intestinal mucosa epithelial cells for alleviating intestinal injury associated with severe acute pancreatitis (SAP). Methods. A total of 72 Sprague-Dawley rats were randomly divided into 3 groups (sham group, SAP group, and DHFZT group, n=24 per group). The rats in each group were divided into 4 subgroups (n=6 per subgroup) accordingly at 1, 3, 6, and 12 h after the operation. The contents of serum amylase, D-lactic acid, diamine oxidase activity, and degree of MPTP were measured by dry chemical method and enzyme-linked immunosorbent assay. The change of mitochondria of intestinal epithelial cells was observed by transmission electron microscopy. Results. The present study showed that DHFZT inhibited the openness of MPTP at 3, 6, and 12 h after the operation. Meanwhile, it reduced the contents of serum D-lactic acid and activity of diamine oxidase activity and also drastically relieved histopathological manifestations and epithelial cells injury of intestine. Conclusion. DHFZT alleviates intestinal injury associated SAP via reducing the openness of MPTP. In addition, DHFZT could also decrease the content of serum diamine oxidase activity and D-lactic acid after SAP

Case report: Treatment of Wilson’s disease by human amniotic fluid administration

BackgroundWilson’s disease (WD) is not an uncommon genetic disease in clinical practice. However, the current WD therapies have limitations. The effectiveness of stem cell therapy in treating WD has yet to be verified, although a few animal studies have shown that stem cell transplantation could partially correct the abnormal metabolic phenotype of WD. In this case report, we present the therapeutic effect of human amniotic fluid containing stem cells in one WD patient.Case presentationA 22-year-old Chinese woman was diagnosed with WD 1 year ago in 2019. The available drugs were not effective in managing the progressive neuropsychiatric symptoms. We treated the patient with pre-cultured human amniotic fluid containing stem cells. Amniotic fluid was collected from pregnant women who underwent induced labor at a gestational age of 19–26 weeks, and then, the fluid was cultured for 2 h to allow stem cell expansion. Cultured amniotic fluid that contained amniotic fluid derived stem cells (AFSC) in the range of approximately 2.8–5.5 × 104/ml was administrated by IV infusion at a rate of 50–70 drops per minute after filtration with a 300-mu nylon mesh. Before the infusion of amniotic fluid, low-molecular-weight heparin and dexamethasone were successively administrated. The patient received a total of 12 applications of amniotic fluid from different pregnant women, and the treatment interval depended on the availability of amniotic fluid. The neuropsychiatric symptoms gradually improved after the stem cell treatment. Dystonia, which included tremor, chorea, dysphagia, dysarthria, and drooling, almost disappeared after 1.5 years of follow-up. The Unified Wilson’s Disease Rating Scale score of the patient decreased from 72 to 10. Brain magnetic resonance imaging (MRI) showed a reduction in the lesion area and alleviation of damage in the central nervous system, along with a partial recovery of the lesion to the normal condition. The serum ceruloplasmin level was elevated from undetectable to 30.8 mg/L, and the 24-h urinary copper excretion decreased from 171 to 37 μg. In addition, amniotic fluid transplantation also alleviates hematopoietic disorders. There were no adverse reactions during or after amniotic fluid administration.ConclusionAmniotic fluid administration, through which stem cells were infused, significantly improves the clinical outcomes in the WD patient, and the finding may provide a novel approach for managing WD effectively

Phylogeography and biological characterization of H12N2 virus isolated from whooper swan in Central China

Wild birds and waterfowl serve as the natural reservoirs of avian influenza viruses (AIVs). When AIVs originating from wild birds cross species barriers to infect mammals or humans, they pose a significant threat to public health. The H12 subtype of AIVs primarily circulates in wild birds, with relatively few isolates reported worldwide, and the evolutionary and biological characteristics of H12 subtype AIVs remain largely unknown. In this study, we analyzed the spatiotemporal distribution of H12 subtype AIVs worldwide and conducted a comprehensive investigation into the evolutionary and biological characteristics of an H12N2 virus isolated from a whooper swan in Central China. Phylogenetic analysis revealed that the H12N2 isolate belongs to the Eurasian lineage, with its HA gene likely originating from a duck-derived H12N5 virus and its NA gene potentially derived from an H9N2 virus, indicating that it is a complex reassorted virus. Animal experiments in domestic ducks and chickens demonstrated that the virus replicates at low levels in the respiratory tract of poultry and exhibits moderate horizontal transmission in ducks. However, it is capable of efficient horizontal transmission in chickens. Mouse infection experiments revealed that the virus could be detected in the nasal turbinates and lungs of mice, indicating that the H12N2 virus can infect mice without prior adaptation. In vitro studies revealed that the virus replicates efficiently in MDCK cells, with significantly higher titers than those in DF1 cells. These findings, combined with the mouse infection results, suggest that the H12N2 virus poses a potential risk of mammalian infection. This study provides valuable insights regarding the characteristics of the H12N2 virus and highlights the importance of ongoing surveillance and risk assessment of AIVs originating from wild birds

Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas

The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030