Effects of one-week bilateral cerebellar iTBS on resting-state functional brain network and multi-task attentional performance in healthy individuals: A randomized, sham-controlled trial.

BACKGROUND: Cerebellar intermittent theta burst stimulation (iTBS) modulates the excitability of the cerebral cortex and may enhance attentional performance. To date, few studies have conducted iTBS on healthy subjects for one week and used electroencephalography (EEG) to investigate the effect of multiple stimulation sessions on resting-state functional brain networks and the daily stimulation effect on attentional performance. METHODS: 16 healthy subjects participated in a one-week experiment, receiving bilateral cerebellar iTBS or sham stimulation and engaging in multi-task attentional training. The primary measures were the one-week attentional performance and pre- and post-experiment resting-state EEG activities. Amplitude Envelope Correlation (AEC) was used to construct the functional connectivity in the eye-open (EO) and eye-closed (EC) phases. RESULTS: At least three sessions of iTBS were required to enhance multi-task performance significantly, whereas only one or two sessions failed to elicit the improvement. Compared with the control group, iTBS induced significant changes in PSD, AEC functional connectivity, and AEC network properties during the EO phase, while it had little effect during the EC phase. During the EO phase, the network property changes of the iTBS subject were correlated with improved attentional performance. CONCLUSION: The multi-task performance requires multiple stimulations to enhance. iTBS affects the resting-state alpha band brain activities during the EO rather than the EC phase. The AEC network properties may serve as a biomarker to assess the attentional potential of healthy subjects.

Case report and literature review: Orally ingested toothpick perforating the lower rectum.

Introduction: Most foreign bodies (FBs) can spontaneously pass through the gastrointestinal tract. Sharp FBs are believed to be able to puncture any part of the gastrointestinal tract, causing perforation and potentially secondary damage to adjacent organs. Case description: A 44-year-old man complained of having persistent dull pain in the perianal region. He was diagnosed with a toothpick impacted into the wall of the lower rectum after accepting a digital rectal examination of the lower rectum and a pelvic computed tomography (CT). The surgeon extracted the FB using vascular forceps guided by the operator's index finger. The patient was discharged after intravenous ceftriaxone was given for 6 days. A follow-up pelvic CT performed 2 weeks after surgery revealed that the perirectal fat and muscles had already normalized. Conclusion: A systematic review of relevant literature from the past decade was performed to summarize the imaging features of an orally ingested toothpick perforating the gastrointestinal tract. The location of abdominal pain is an important clue for the diagnosis of toothpick perforation, and a CT examination is recommended as the first option for the detection of an ingested toothpick. Determining the location of the toothpick perforation and assessing the severity of local inflammation are important bases for the selection of treatment.

Nano-Engineering Strategies for Tumor-Specific Therapy.

Nanodelivery systems (NDSs) provide promising prospects for decreasing drug doses, reducing side effects, and improving therapeutic effects. However, the bioapplications of NDSs are still compromised by their fast clearance, indiscriminate biodistribution, and limited tumor accumulation. Hence, engineering modification of NDSs aiming at promoting tumor-specific therapy and avoiding systemic toxicity is usually needed. An NDS integrating various functionalities, including flexible camouflage, specific biorecognition, and sensitive stimuli-responsiveness, into one sequence would be "smart" and highly effective. Herein, we systematically summarize the related principles, methods, and progress. At the end of the review, we predict the obstacles to precise nanoengineering and prospects for the future application of NDSs.

Metal-polyphenol "prison" attenuated bacterial outer membrane vesicle for chemodynamics promoted in situ tumor vaccines.

As natural adjuvants, the bacterial outer membrane vesicles (OMV) hold great potential in cancer vaccines. However, the inherent immunotoxicity of OMV and the rarity of tumor-specific antigens seriously hamper the clinical translation of OMV-based cancer vaccines. Herein, metal-phenolic networks (MPNs) are used to attenuate the toxicity of OMV, meanwhile, provide tumor antigens via the chemodynamic effect induced immunogenic cell death (ICD). Specifically, MPNs are assembled on the OMV surface through the coordination reaction between ferric ions and tannic acid. The iron-based "prison" is locally collapsed in the tumor microenvironment (TME) with both low pH and high ATP features, and thus the systemic toxicity of OMV is significantly attenuated. The released ferric ions in TME promote the ICD of cancer cells through Fenton reaction and then the generation of abundant tumor antigens, which can be used to fabricate in-situ vaccines by converging with OMV. Together with the immunomodulatory effect of OMV, potent tumor repression on a bilateral tumor model is achieved with good biosafety.

Review Article Imaging Evaluation for the Size of Saccular Intracranial Aneurysm.

BACKGROUND: In addition to evaluate the morphologic characteristics of intracranial aneurysms, the dimension of the aneurysm is an important parameter for selecting treatment strategies, determining follow-up period, and predicting the risk of rupture. High-resolution vessel wall imaging has an increasingly dominant role in measuring aneurysm size and assessing the risk of rupture accurately. The size of saccular intracranial aneurysm may play an important role as a predictor of the rupture risk. With the rapid improvement in radiological techniques, different noninvasive imaging methods have respective characteristics in saccular intracranial aneurysms (sIA) measurement and morphologic description. Although most studies believe that the larger the aneurysm, the higher the risk of rupture, there is still a synergistic effect of multiple factors (such as location, morphology, history of aneurysmal subarachnoid hemorrhage, and even patient factors) to explain the rupture of small aneurysms. METHODS: A literature search was performed of intracranial aneurysm size and risk of rupture. RESULTS: The specificity and sensitivity of different imaging methods for evaluating intracranial aneurysms varied based on sizes. Rupture risk of aneurysms was associated with multiple factors. A comprehensive assessment that considered aneurysm size in conjunction with other relevant factors would be helpful in guiding options of management. CONCLUSIONS: Accurate measurement of the dimension of sIA is an important basis in the selection of appropriate treatment including intravascular intervention or surgical clipping, as well as for determining the follow-up cycles for conservative or postoperative treatment. A uniform definition of sIA size is recommended to facilitate the integration of similar studies and to accomplish rapid and effective screening of cases in sIA treatment.

Distant Metastasis is the Dominant Cause of Treatment Failure after Lateral Lymph Node Dissection in Patients with Lateral Lymph Node Metastasis: Results of the Large Multicenter Lateral Node Study in China.

Background: Lateral lymph node (LLN) metastases (LLNM) are often associated with poor prognosis. This study aimed to investigate the prognostic significance and postoperative recurrence pattern in rectal cancer patients with LLNM after LLN dissection (LLND). Materials and Methods: This is a multicenter retrospective case-control study where propensity score-matched (PSM) analysis was introduced. From January 2012 to December 2019, 259 patients with clinical suspicion of LLNM who underwent LLND without neoadjuvant therapy were included in the study. They were divided into the negative (n = 197) and positive (n = 62) LLN groups. Primary endpoints were 3-year recurrence-free survival (RFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). Results: After PSM, the DMFS rate in the positive LLN group was significantly worse (67.9 vs. 52.5%, P = 0.012). Pathological LLNM (HR, 3.07; 95% CI, 1.55-6.05; P = 0.001) were independent prognostic factors for DMFS. Patients in the positive LLN group had a higher proportion of distant metastases in all recurrence patterns (92.3% vs 82.6%). Among patients with LLN metastasis, metastases to the common iliac and external iliac arteries were the independent prognostic factor for DMFS (HR: 2.85; 95% CI, 1.31-4.67; P = 0.042). No significant different was observed for prognosis between patients with metastases to the obturator or internal iliac vessels and patients with a N2b stage. Conclusion: Distant metastasis is the main cause of treatment failure after LLND in patients with LLNM. Because of the low completion rate of adjuvant chemotherapy, preoperative chemotherapy or total neoadjuvant therapy may be considered before LLND. In addition, patients with metastasis to external iliac and common iliac vessels have an extremely poor prognosis, and systemic chemotherapy instead of LLND should be recommended.

Color-changing fluorescent DNA probe containing solvatochromic Dansyl-nucleoside surrogate for sensing local variation of DNA duplex.

A novel Dansyl-nucleoside surrogate (Dns) based on (±)-trans-4-(hydroxymethyl) piperidin-3-ol was designed and synthesized. The Dns exhibited excellent solvatochromic properties. About 90 nm of red-shift accompanied color change from green to orange could be achieved with an increase of solvent polarity. The Dns was incorporated into oligodeoxynucleotide by phosphoroamidite chemistry. Two kinds of Dns-incorporated fluorescent DNA probes were designed and synthesized for sensing variation of DNA duplexes based on color-changing manner. As a result, the color-changing DNA probe not only can detect complementary oligonucleotide, but also can distinguish mismatch flanked in Dansyl/nucleobase pair by naked eye. Moreover, the change of fluorescence color of sample solutions could be captured by smartphone, and the photographs could be digitalized by image-processing software. Thus, the Dns-incorporated fluorescent DNA probe is expected to open the way to point-of-care assays in the future.

Optimal futures hedging strategies based on an improved kernel density estimation method.

In this paper, we study the hedging effectiveness of crude oil futures on the basis of the lower partial moments (LPMs). An improved kernel density estimation method is proposed to estimate the optimal hedge ratio. We investigate crude oil price hedging by contributing to the literature in the following twofold: First, unlike the existing studies which focus on univariate kernel density method, we use bivariate kernel density to calculate the estimated LPMs, wherein the two bandwidths of the bivariate kernel density are not limited to the same, which is our main innovation point. According to the criterion of minimizing the mean integrated square error, we derive the conditions that the optimal bandwidths satisfy. In the process of derivation, we make a distribution assumption locally in order to simplify calculation, but this type of local distribution assumption is far better than global distribution assumption used in parameter method theoretically and empirically. Second, in order to meet the requirement of bivariate kernel density for independent random variables, we adopt ARCH models to obtain the independent noises with related to the returns of crude oil spot and futures. Genetic algorithm is used to tune the parameters that maximize quasi-likelihood. Empirical results reveal that, at first, the hedging strategy based on the improved kernel density estimation method is of highly efficiency, and then it achieves better performance than the hedging strategy based on the traditional parametric method. We also compare the risk control effectiveness of static hedge ratio vs. time-varying hedge ratio and find that static hedging has a better performance than time-varying hedging.

Comprehensive analysis to identify DLEU2L/TAOK1 axis as a prognostic biomarker in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors that are harmful to human health. Increasing evidence has underscored the critical role of the competitive endogenous RNA (ceRNA) regulatory networks among various human cancers. However, the complexity and behavior characteristics of the ceRNA network in HCC were still unclear. In this study, we aimed to clarify a phosphatase and tensin homolog (PTEN)-related ceRNA regulatory network and identify potential prognostic markers associated with HCC. The expression profiles of three RNAs (long non-coding RNAs [lncRNAs], microRNAs [miRNAs], and mRNAs) were extracted from The Cancer Genome Atlas (TCGA) database. The DLEU2L-hsa-miR-100-5p/ hsa-miR-99a-5p-TAOK1 ceRNA network related to the prognosis of HCC was obtained by performing bioinformatics analysis. Importantly, we identified the DLEU2L/TAOK1 axis in the ceRNA by using correlation analysis, and it appeared to become a clinical prognostic model by Cox regression analysis. Furthermore, methylation analyses suggested that the abnormal upregulation of the DLEU2L/TAOK1 axis likely resulted from hypomethylation, and immune infiltration analysis showed that the DLEU2L/TAOK1 axis may have an impact on the changes in the tumor immune microenvironment and the development of HCC. In summary, the current study constructing a ceRNA-based DLEU2L/TAOK1 axis might be a novel important prognostic factor associated with the diagnosis and prognosis of HCC.

The role of UGT1A1 (c.-3279 T > G) gene polymorphisms in neonatal hyperbilirubinemia susceptibility.

BACKGROUND: Neonatal hyperbilirubinemia (NNH) is a common disease in newborns. This research study aimed to assess the associations between uridine diphospho-glucuronate-glucuronosyltransferase 1A1 (UGT1A1, c.-3279 T > G) polymorphisms and NNH risk. METHODS: We searched PubMed, the Cochrane Library, and the Embase electronic databases. All published eligible studies before July 1, 2019, were searched for this meta-analysis. RESULTS: We identified 7 independent studies including 1560 cases. The data showed that in the general population, compared with the GT + GG vs TT and GG vs TT, c.-3279 T > G (rs4124874) was significantly related to a higher NNH risk (GG vs TT: OR = 1.865, 95% CI: 1.031-3.373, P = 0.039; GT + GG vs TT: OR = 1.331, 95% CI: 1.055-1.679, P = 0.016). Although not statistically significant, the data showed that c.3279 T > G had a tendency to be associated with NNH under the allele model and GG vs GT + TT in the overall population (G vs T: OR = 1.288, 95% CI: 0.982-1.689, P = 0.067; GG vs TT + GT: OR = 1.583, 95% CI: 0.947-2.647, P = 0.080). CONCLUSION: The UGT1A1 gene c.-3279 T > G (rs4124874) polymorphism increased susceptibility to NNH, especially for the comparison of GT + GG vs TT and GG vs TT. In the future, we can use homozygous state of the UGT1A1 gene c.-3279 T > G (rs4124874) polymorphism for the diagnosis and screening of molecular biomarkers in NNH patients.

Evaluating the predictive factors for anastomotic leakage after total laparoscopic resection with transrectal natural orifice specimen extraction for colorectal cancer.

BACKGROUND: Natural orifice specimen extraction (NOSE) surgery has been widely implemented in colorectal cancer surgery due to its good short-term efficacy. However, anastomotic leakage (AL) is a serious postoperative complication in colorectal cancer, and the risk factors for this complication after NOSE surgery have rarely been investigated. The aim of this study was to explore the predictive factors for AL after laparoscopic resection with transrectal NOSE for rectal cancer and sigmoid colon cancer. METHODS: A total of 208 patients who underwent total laparoscopic resection with transrectal NOSE for rectal cancer and sigmoid colon cancer from January 2014 to June 2019 were systematically reviewed. Univariate and multivariate analyses were performed to identify the relevant risk factors. RESULTS: The rate of AL was 10.1% (21 of 208 patients). The univariate analyses showed that male sex (85.7% vs 57.8%, P = .013), the distance from the anal verge (10.5 vs 14.5 cm, P = .011), and a duration of operation ≥140 min (71.4% vs 29.4%, P<.001) were associated with an increased incidence of AL. The multivariate analysis showed that a duration of operation ≥140 min (OR = 5427, 95% CI = 1.355-21.727, P = .017) was an independent risk factor for AL. CONCLUSION: A duration of operation ≥140 min is a possible risk factor for AL after total laparoscopic resection with transrectal NOSE for colorectal cancer.

Kirigami-Based Highly Stretchable Thin Film Solar Cells That Are Mechanically Stable for More than 1000 Cycles.

Exploiting stretchable solar cells that can accommodate large strain and feature high cyclic mechanical endurance is challenging for wearable and skin-interfaced electronics application. In this work, we demonstrated such solar cells using the kirigami design. Experiments and mechanical simulations showed that the kirigami structure effectively imparted stretchability to perovskite solar cells (PSCs) through out-of-plane deformation, which significantly reduced the stress in devices. The kirigami-based PSCs with optimal geometric parameters exhibited high mechanical deformability, including stretchability (strain up to 200%), twistability (angle up to 450°), and bendability (radius down to 0.5 mm). More importantly, the kirigami PSCs revealed high mechanical endurance with almost unchanged performance even after 1000 repetitive stretching, twisting, and bending cycles. This kirigami design for stretchable PSCs presented here provides a promising strategy to achieve high deformability for solar cells as well as other optoelectronic devices.

Rheological behaviors of microbial polysaccharides with different substituents in aqueous solutions: Effects of concentration, temperature, inorganic salt and surfactant.

Rheological behaviors of microbial polysaccharides with different substituents in aqueous solutions have been systematically investigated. Both the saccharide side chains and acetyl substituents improve the gelation of welan gum (WG), diutan gum (DG) and gellan gum (GG) in pure water at 25 °C. For the polysaccharides with saccharide side chains (WG and DG), the relationship between the apparent viscosity and concentration conforms to the linear equation, while that of the polysaccharide with acetyl (GG) is exponential. More importantly, the roles of substituents on the stability of the molecular conformation of polysaccharides are significantly depended on the surrounding environment. Disaccharide side chains promote the stability of helical conformation and gel aggregates of GG at high temperature (85 °C) or in the presence of inorganic salts with the ionic strength of 2.0 mol L-1. The stability of gel structure containing acetyl (GG) shows higher temperature/salt sensitivity. Additionally, deacylated gellan gum (GG(d)) solutions transform into hydrogels in the presence of dodecyltrimethylammonium bromide (DTAB). This study will help to obtain a better understanding on the rheological properties of polysaccharides with respect to the conformation and applications.