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Elevated serum corin concentrations in patients with cardiac diseases have been associated with adverse cardiovascular events and progressive renal dysfunction. This study aimed to determine the role of serum corin levels in predicting the incidence of acute kidney injury (AKI) and mortality in critically ill patients admitted to intensive care units (ICUs). We screened 323 patients admitted to the ICU in our institution from May 2018 through December 2019. After excluding patients receiving renal replacement therapy, 288 subjects were enrolled. Cases were divided equally into high (n = 144) and low (n = 144) corin groups according to median serum corin levels, using 910 pg/mL as the cut-off point. Patient characteristics and comorbidities were collected from medical records. The primary outcome was AKI within 48 h after ICU admission, while the secondary outcome was all-cause of mortality within 1 year. Compared with the low corin group, patients in the high corin group had higher prevalence rates of diabetes, cirrhosis, and nephrotoxic agent exposure; higher Sequential Organ Failure Assessment scores, white blood cell counts, proteinuria, and serum N-terminal pro-brain natriuretic peptide levels; but had lower initial estimated glomerular filtration rates. Furthermore, elevated serum corin was associated with higher risks of AKI within 48h of ICU admission (43.1% vs. 18.1%, p < 0.001) and all-cause mortality within one year (63.9% vs. 50.0%, p = 0.024). High corin level showed strongly positive results as an independent predictor of AKI (OR 2.15, 95% CI 1.11-4.19, p = 0.024) but not for the all-cause mortality after adjusting for confounding factors in multivariate analyses. Elevated circulating corin predicted AKI in critically ill patients, but did not predict all-cause mortality within 1 year. As a key enzyme in renin-angiotensin-aldosterone system, corin expression may be regulated through a feedback loop following natriuretic peptide resistance and desensitization of natriuretic peptide receptors in different critically ill status., (© 2024. The Author(s).)

Our study aimed to compare bone scintigraphy and dual-layer detector spectral CT (DLCT) with multiphase contrast enhancement for the diagnosis of osteoblastic bone lesions in patients with prostate cancer. The patients with prostate cancer and osteoblastic bone lesions detected on DLCT were divided into positive bone scintigraphy group (pBS) and negative bone scintigraphy group (nBS) based on bone scintigraphy. A total of 106 patients (57 nBS and 49 pBS) was included. The parameters of each lesion were measured from DLCT including Hounsfield unit (HU), 40-140 keV monochromatic HU, effective nuclear numbers (Z eff ), and Iodine no water (InW) value in non-contrast phase (N), the arterial phase (A), and venous phase (V). The slope of the spectral curve at 40 and 100 keV, the different values of the parameters between A and N phase (A-N), V and N phase (V-N), and hybrid prediction model with multiparameters were used to differentiate pBS from nBS. Receiver operating characteristic analysis was performed to compare the area under the curve (AUC) for differentiating the pBS group from the nBS group. The value of conventional HU values, slope, and InW in A-N and V-N, and hybrid model were significantly higher in the pBS group than in the nBS group. The hybrid model of all significant parameters had the highest AUC of 0.988, with 95.5% sensitivity and 94.6% specificity. DLCT with arterial contrast enhancement phase has the potential to serve as an opportunistic screening tool for detecting positive osteoblastic bone lesions, corresponding to those identified in bone scintigraphy., (© 2024. The Author(s).)

Knowledge regarding the ligament footprints in the canine stifle is essential for biomechanical modeling of the joint and patient-specific surgical planning for anatomical ligament reconstruction. The present study aimed to establish and evaluate deformable shape templates (DSTs) of the femur and tibia with footprints of the cruciate and collateral ligaments embedded for the noninvasive estimation of ligament footprint positions. To this end, a data set of computed tomography (CT)-derived surface models of the femur and tibia were established and used to build statistical shape models (SSMs). The contours of the stifle ligaments were obtained from CT scans of 27 hindlimb specimens with radio-opaque markings on the ligament footprints. The DST, constructed by embedding averaged footprint contours into the SSM, was used to estimate subject-specific ligament footprints in a leave-one-out cross-validation framework. The DST predictions were compared with those derived from radio-opaque-marked footprints. The results showed that the averaged Euclidean distances between the estimated and reference footprint centroids were less than 1.2 mm for the cruciate ligaments and 2.0 mm for the collateral ligaments. The DST appeared to provide a feasible alternative approach for noninvasively estimating the footprints of the stifle ligaments in vivo., (© 2024. The Author(s).)

Myocardial perfusion imaging (MPI) is a clinical tool which can assess the heart's perfusion status, thereby revealing impairments in patients' cardiac function. Within the MPI modality, the acquired three-dimensional signals are typically represented as a sequence of two-dimensional grayscale tomographic images. Here, we proposed an end-to-end survival training approach for processing gray-scale MPI tomograms to generate a risk score which reflects subsequent time to cardiovascular incidents, including cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke (collectively known as Major Adverse Cardiovascular Events; MACE) as well as Congestive Heart Failure (CHF). We recruited a total of 1928 patients who had undergone MPI followed by coronary interventions. Among them, 80% (n = 1540) were randomly reserved for the training and 5- fold cross-validation stage, while 20% (n = 388) were set aside for the testing stage. The end-to-end survival training can converge well in generating effective AI models via the fivefold cross-validation approach with 1540 patients. When a candidate model is evaluated using independent images, the model can stratify patients into below-median-risk (n = 194) and above-median-risk (n = 194) groups, the corresponding survival curves of the two groups have significant difference (P < 0.0001). We further stratify the above-median-risk group to the quartile 3 and 4 group (n = 97 each), and the three patient strata, referred to as the high, intermediate and low risk groups respectively, manifest statistically significant difference. Notably, the 5-year cardiovascular incident rate is less than 5% in the low-risk group (accounting for 50% of all patients), while the rate is nearly 40% in the high-risk group (accounting for 25% of all patients). Evaluation of patient subgroups revealed stronger effect size in patients with three blocked arteries (Hazard ratio [HR]: 18.377, 95% CI 3.719-90.801, p < 0.001), followed by those with two blocked vessels at HR 7.484 (95% CI 1.858-30.150; p = 0.005). Regarding stent placement, patients with a single stent displayed a HR of 4.410 (95% CI 1.399-13.904; p = 0.011). Patients with two stents show a HR of 10.699 (95% CI 2.262-50.601; p = 0.003), escalating notably to a HR of 57.446 (95% CI 1.922-1717.207; p = 0.019) for patients with three or more stents, indicating a substantial relationship between the disease severity and the predictive capability of the AI for subsequent cardiovascular inciidents. The success of the MPI AI model in stratifying patients into subgroups with distinct time-to-cardiovascular incidents demonstrated the feasibility of proposed end-to-end survival training approach., (© 2024. The Author(s).)

Metabolism of haem by-products such as bilirubin by humans and their gut microbiota is essential to human health, as excess serum bilirubin can cause jaundice and even neurological damage. The bacterial enzymes that reduce bilirubin to urobilinogen, a key step in this pathway, have remained unidentified. Here we used biochemical analyses and comparative genomics to identify BilR as a gut-microbiota-derived bilirubin reductase that reduces bilirubin to urobilinogen. We delineated the BilR sequences from similar reductases through the identification of key residues critical for bilirubin reduction and found that BilR is predominantly encoded by Firmicutes species. Analysis of human gut metagenomes revealed that BilR is nearly ubiquitous in healthy adults, but prevalence is decreased in neonates and individuals with inflammatory bowel disease. This discovery sheds light on the role of the gut microbiome in bilirubin metabolism and highlights the significance of the gut-liver axis in maintaining bilirubin homeostasis., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Dengue virus (DENV) infection remains a challenging health threat worldwide. Ubiquitin-specific protease 18 (USP18), which preserves the anti-interferon (IFN) effect, is an ideal target through which DENV mediates its own immune evasion. However, much of the function and mechanism of USP18 in regulating DENV replication remains incompletely understood. In addition, whether USP18 regulates DENV replication merely by causing IFN hyporesponsiveness is not clear. In the present study, by using several different approaches to block IFN signaling, including IFN neutralizing antibodies (Abs), anti-IFN receptor Abs, Janus kinase inhibitors and IFN alpha and beta receptor subunit 1 (IFNAR1)knockout cells, we showed that USP18 may regulate DENV replication in IFN-associated and IFN-unassociated manners. Localized in mitochondria, USP18 regulated the release of mitochondrial DNA (mtDNA) to the cytosol to affect viral replication, and mechanisms such as mitochondrial reactive oxygen species (mtROS) production, changes in mitochondrial membrane potential, mobilization of calcium into mitochondria, 8-oxoguanine DNA glycosylase 1 (OGG1) expression, oxidation and fragmentation of mtDNA, and opening of the mitochondrial permeability transition pore (mPTP) were involved in USP18-regulated mtDNA release to the cytosol. We therefore identify mitochondrial machineries that are regulated by USP18 to affect DENV replication and its association with IFN effects., (© 2023. The Author(s).)

We report on the structural properties of Bi thin films grown on (111) Si substrates with a thickness of 22-30 BL. HRXRD and EBSD measurements show that these Bi films are mainly composed of twinning grains in the (0003) direction. The grain size can be as large as tens of microns. From a double-peak (01[Formula: see text]4) φ-scan, we found two pairs of twinning phases coexisting with a rotation angle of ~ 3.6°. We proposed a coincidence site lattice model based on preferential close-packed sites for Bi atoms on Si (111) surface to explain the coexistence of the rotation phases in the quasi-van der Waals epitaxy. From the measured lattice constants c and a of our samples, along with the data from the literature, we derived a c-a relation: (c-c 0 ) = - 2.038(a-a 0 ), where c 0 and a 0 are the values of bulk Bi. The normalized position of the second basis atom in the unit cell x, in these strained Bi films is found very close to that of bulk Bi, indicating that the strain does not disturb the Peierls distortion of the lattice. The fixed ratio of bilayer thickness to lattice constant c, reveals that the elastic properties of covalent-bonded bilayer dominate those of Bi crystal., (© 2023. The Author(s).)

Peierls transition that modifies electronic band structure has attracted intensive attention in solid state physics. In the present work, we report that a photonic analog of Peierls transition has been observed in a 1-D triangular metal diaphragm array, where the photonic bandgap structures have been designed at will by adjusting periodically metal diaphragm positions. It is shown by the numerical analysis that the transmission and radiation effect of the present periodic metal structure designed through the Peierls transition rule exhibits the behavior significantly different from an original periodic structure with each unit cell containing a metal diaphragm. The near- and far-field measurement results are in good agreement with our theoretical simulation. The present effect of photonic Peierls transition can serve as a working mechanism for designing new types of guided wave devices. It can be seen that the photonic Peierls transition would be one of the simplest ways for modifying the transport characteristics of electromagnetic waves in periodic structures., (© 2023. Springer Nature Limited.)

Since a planar periodic transmission line can suppress drastically the electromagnetic coupling, it would be advantageous to use such a kind of transmission lines in solving the problem of miniaturization of circuit area. By adjusting the lattice constants and geometric parameters of periodic microstrip lines, a time domain characteristic impedance that is the same as that of conventional microstrip lines (CMLs) can be achieved. Such periodic microstrip lines can therefore be used to trick high-speed digital signals, causing a digital signal to misjudge the time domain characteristic impedance of the transmission lines. The theoretical analysis has been verified by our experimental measurement results. Besides, a specific expression for the characteristic impedance of lossless periodic artificial materials is deduced by a circuit model and a standard of misidentification for the characteristic impedance of periodic microstrip lines is given for the digital signals., (© 2023. Springer Nature Limited.)

Occurrence of amyloid-β (Aβ) aggregation in brain begins before the clinical onset of Alzheimer's disease (AD), as preclinical AD. Studies have reported that sleep problems and autonomic dysfunction associate closely with AD. However, whether they, especially the interaction between sleep and autonomic function, play critical roles in preclinical AD are unclear. Therefore, we investigated how sleep patterns and autonomic regulation at different sleep-wake stages changed and whether they were related to cognitive performance in pathogenesis of AD mice. Polysomnographic recordings in freely-moving APP/PS1 and wild-type (WT) littermates were collected to study sleep patterns and autonomic function at 4 (early disease stage) and 8 months of age (advanced disease stage), cognitive tasks including novel object recognition and Morris water maze were performed, and Aβ levels in brain were measured. APP/PS1 mice at early stage of AD pathology with Aβ aggregation but without significant differences in cognitive performance had frequent sleep-wake transitions, lower sleep-related delta power percentage, lower overall autonomic activity, and lower parasympathetic activity mainly during sleep compared with WT mice. The same phenomenon was observed in advanced-stage APP/PS1 mice with significant cognitive deficits. In mice at both disease stages, sleep-related delta power percentage correlated positively with memory performance. At early stage, memory performance correlated positively with sympathetic activity during wakefulness; at advanced stage, memory performance correlated positively with parasympathetic activity during both wakefulness and sleep. In conclusion, sleep quality and distinction between wake- and sleep-related autonomic function may be biomarkers for early AD detection., (© 2023. The Author(s).)

Peace of mind (PoM) is an index of mental health in Asian culture and emphasizes low arousal, happiness, harmony, and an internal state of peacefulness. While previous studies have found that mindful self-awareness can contribute to PoM, regular physical activity (PA) is also an important factor contributing to one's PoM due to its function in promoting one's resilience. The study aims to investigate a hypothetical model that assumes PA is associated with resilience while controlling for mindful self-awareness, contributing to PoM. The PoM scale, Connor-Davidson Resilience Scale, Chinese translation of Mindful Attention Awareness Scale, and PA self-report questionnaire were used. A path analysis was applied to test the association between these variables and the mediating role of resilience. A total of 436 students from a university in Taiwan were recruited; the mean age was 20.87, with 46.3% female and 73.6% engaging in over 150 min/week of moderate PA. Gender and age negatively correlated with PA. After controlling for age and gender, there was no direct effect of physical activity on PoM; both mindful self-awareness and PA predict resilience, which in turn predicts PoM, suggesting that both cognitive (i.e., mindful self-awareness) and PA are important to cultivate resilience and thus PoM., (© 2023. The Author(s).)

It is debatable whether external forcing can change the state of the climate. By investigating decadal changes with and without including the 1990s stratospheric volcanic aerosols, we explored the volcanic eruptions contribution to decadal climate regime shifts occurring in boreal winter over the North Pacific. The volcanic eruptions contribution can be characterized as a series of rapid changes, including the strengthening and poleward shift of the midlatitude westerly jet stream. In addition to the short-lived radiative effects primarily induced by the 1991 Mount Pinatubo eruption, the volcanically driven decadal change can be observed in the mid-to-late 1990s, suggesting a time-lagged characteristic of the volcanic climate impact. Compared with the decadal change irrelevant to volcanic eruption, the decadal state more dramatically enters into the next phase when volcanic forcing is included. The climate oscillation-related pattern shifts that occurred across the 1990s can provide insights into volcanically induced changes in decadal atmospheric circulation., (© 2023. The Author(s).)

High-grade liver laceration is a common injury with bleeding as the main cause of death. Timely resuscitation and hemostasis are keys to the successful management. The impact of in-hospital trauma system on the quality of resuscitation and management in patients with traumatic high-grade liver laceration, however, was rarely reported. We retrospectively reviewed the impact of team-based approach on the quality and outcomes of high-grade traumatic liver laceration in our hospital. Patients with traumatic liver laceration between 2002 and 2020 were enrolled in this retrospective study. Inverse probability of treatment weighting (IPTW)-adjusted analysis using the propensity score were performed. Outcomes before the trauma team establishment (PTTE) and after the trauma team establishment (TTE) were compared. A total of 270 patients with liver trauma were included. After IPTW adjustment, interval between emergency department arrival and managements was shortened in the TTE group with a median of 11 min (p < 0.001) and 28 min (p < 0.001) in blood test reports and duration to CT scan, respectively. Duration to hemostatic treatments in the TTE group was also shorter by a median of 94 min in patients receiving embolization (p = 0.012) and 50 min in those undergoing surgery (p = 0.021). The TTE group had longer ICU-free days to day 28 (0.0 vs. 19.0 days, p = 0.010). In our study, trauma team approach had a survival benefit for traumatic high-grade liver injury patients with 65% reduction of risk of death within 72 h (Odds ratio (OR) = 0.35, 95% CI = 0.14-0.86) and 55% reduction of risk of in-hospital mortality (OR = 0.45, 95% CI = 0.23-0.87). A team-based approach might contribute to the survival benefit in patients with traumatic high-grade liver laceration by facilitating patient transfer from outside the hospital, through the diagnostic examination, and to the definitive hemostatic procedures., (© 2023. The Author(s).)

The injury severity score (ISS) is used in daily practice to evaluate the severity of trauma patients; however, the score is not always consistent with the prognosis. After injury, systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) are related to the prognosis of trauma patients. We aimed to evaluate the associations between the immune response and prognosis in trauma patients. Patients who admitted to the Trauma Intensive Care Unit (ICU) were eligible. Whole blood samples were collected at admission, and then 6, 12, 24, 48 and 72 h after admission. Natural killer (NK) cells, lymphocyte subset population and cytokines release were identified using flow cytometry. We grouped patients by their ISS (≤ 25 and > 25 as very severe injury) and ICU stay (≤ 10 days as a short ICU stay and > 10 days as a long ICU stay) for evaluation. Fifty-three patients were enrolled. ICU stay but not ISS was close correlated with activity daily living (ADL) at discharge. Patients with a long ICU stay had an immediate increase in NK cells followed by lymphopenia which persisted for 48 h. Immediate activation of CD8 + T cells and then exhaustion with a higher programmed cell death-1 (PD-1) expression and suppression of CD4 + T cells with a shift to an anti-inflammatory Th2 phenotype were also observed in the patients with a long ICU stay. When the patients were grouped by ISS, the dynamics of immune responses were inconsistent to those when the patients were grouped by ICU stay. Immune responses are associated with the prognosis of trauma patients, however the currently used clinical parameters may not accurately reflect immune responses. Further investigations are needed to identify accurate predictors of prognosis in trauma patients., (© 2023. The Author(s).)

Chinese hamster ovary (CHO) cell lines are widely used to manufacture biopharmaceuticals. However, CHO cells are not an optimal expression host due to the intrinsic plasticity of the CHO genome. Genome plasticity can lead to chromosomal rearrangements, transgene exclusion, and phenotypic drift. A poorly understood genomic element of CHO cell line instability is extrachromosomal circular DNA (eccDNA) in gene expression and regulation. EccDNA can facilitate ultra-high gene expression and are found within many eukaryotes including humans, yeast, and plants. EccDNA confers genetic heterogeneity, providing selective advantages to individual cells in response to dynamic environments. In CHO cell cultures, maintaining genetic homogeneity is critical to ensuring consistent productivity and product quality. Understanding eccDNA structure, function, and microevolutionary dynamics under various culture conditions could reveal potential engineering targets for cell line optimization. In this study, eccDNA sequences were investigated at the beginning and end of two-week fed-batch cultures in an ambr ® 250 bioreactor under control and lactate-stressed conditions. This work characterized structure and function of eccDNA in a CHO-K1 clone. Gene annotation identified 1551 unique eccDNA genes including cancer driver genes and genes involved in protein production. Furthermore, RNA-seq data is integrated to identify transcriptionally active eccDNA genes., (© 2023. The Author(s).)

The vaping of electronic cigarettes (E-cigarettes) has recently emerged as a popular alternative to traditional cigarette smoking, but its association with bladder cancer (BC) risk remains to be established. BC patients exhibit high rates of recurrent disease, possibly as a consequence of the field cancerization effect. We have shown that BC-derived extracellular vesicles (BCEVs) can permanently alter recipient urothelial cells in predisposed fields such that they become fully transformed malignant cells. To model the role that BCEVs may play in this potentially oncogenic setting, we treated TCCSUP BC cells with cigarette smoke extract, unflavored E-liquid, or menthol flavored E-liquid. Those treated BCEVs were then tested for their tumorigenic potential. We found that these smoking- and E-cigarette-related BCEVs were able to promote oxidative stress, inflammatory signaling, and DNA damage in recipient SV-HUC urothelial cells. Strikingly, menthol E-liquid-induced BCEVs significantly increased rates of malignant urothelial cell transformation. While further in vivo validation of the simultaneous effects of E-liquid and E-liquid-induced BCEVs on field cancerization is needed, these data highlight the possibility that E-cigarettes may compound user risk in a manner that can contribute to higher rates of BC incidence or recurrence., (© 2023. The Author(s).)

This study was to determine the significance of factors considered for the measurement accuracy of personal dosimeter in dosimetry services such as dosimetry service, irradiation category, years of use and readout frequency. The investigation included management information questionnaire, on-site visit and blind test. The blind test with random selected personal badge was used in inter-comparison of eight dosimetry services, and the test results followed ANSI/HPS N13.11 criteria. This study also analyzed the measurement deviations if they felt in the criteria of ICRP 75 or not. One-way ANOVA tests were used to analyze the significant difference of the measurement deviations in different dosimetry services, irradiation categories, and years of use. Simple linear-regression test was performed for the significance of the prediction model between measurement deviations and readout frequencies. All visited dosimetry services followed the proper statue of basic management and passed the performance check of the tolerance level. The average deviations corresponding to category I, category II deep dose, and category II shallow dose were 6.08%, 9.49%, and 10.41% respectively. There had significant differences of measurement deviation in different dosimetry services (p < 0.0001) and irradiation categories (p = 0.016) but no significant difference in years of use (p = 0.498). There was no significance in the linear-regression model between measurement deviation and badge readout frequencies. Based on the regular calibration of the personal dosimeter, the deviation of the measured value is mainly affected by different dosimetry services and irradiation categories; and there shows no significant influence by years of use and readout frequency., (© 2022. The Author(s).)

Delayed bleeding is a major issue in patients with high-grade splenic injuries who receive non-operative management (NOM). While only few studies addressed the clinical manifestations of delayed bleeding in these patients. We reviewed the patients with high-grade splenic injuries presented with delayed bleeding, defined as the need for salvage procedures following NOM. There were 138 patients received NOM in study period. Fourteen of 107 patients in the SAE group and 3 of 31 patients in the non-embolization group had delayed bleeding. Among the 17 delayed bleeding episodes, 6 and 11 patients were salvaged by splenectomy and SAE, respectively. Ten (58.9%, 10/17) patients experienced bleeding episodes in the intensive care unit (ICU), whereas seven (41.1%, 7/17) experienced those in the ward or at home. The clinical manifestations of delayed bleeding were a decline in haemoglobin levels (47.1%, 8/17), hypotension (35.3%, 6/17), tachycardia (47.1%, 8/17), new abdominal pain (29.4%, 5/17), and worsening abdominal pain (17.6%, 3/17). For the bleeding episodes detected in the ICU, a decline in haemoglobin (60%, 6/10) was the main manifestation. New abdominal pain (71.43%, 5/7) was the main presentation when the patients left the ICU. In conclusion, abdominal pain was the main early clinical presentation of delayed bleeding following discharge from the ICU or hospital., (© 2022. The Author(s).)

To determine whether body composition indices interact with age and gender as a predictor of all-cause mortality, 1200 participants at least 40 years of age were recruited in 2009 and 2010. A multi-frequency bioelectrical impedance analysis device was used to measure each participant's body composition indices, including the fat mass index (FMI), fat free mass index (FFMI), skeletal muscle mass index (SMMI), and visceral fat area index (VFAI). A baseline questionnaire was used to collect demographic information about lifestyle habits, socioeconomic status, and medical conditions. All claimed records of death from 2009 to 2018 in the National Health Insurance Research Databank were identified. The all-cause mortality rate was 8.67% after a mean follow-up period of 5.86 ± 2.39 person-years. The Cox proportional hazard model analysis showed significantly negative associations between FFMI or SMMI with all-cause mortality in the total group and those aged ≥ 65 y/o. The FFMI and SMMI were negative predictors of mortality in both genders. The FMI and VFAI were positive predictors of mortality exclusively in females. In conclusion, the SMMI is a better predictor of mortality than the BMI, FMI, and FFMI, especially in older adults. A higher fat mass or visceral fat distribution may predict higher mortality in females., (© 2022. The Author(s).)

Predictors of needle-knife pre-cut papillotomy (NKP) failure for patients with difficult biliary cannulation has not been reported. Between 2004 and 2016, 390 patients with difficult biliary cannulation undergoing NKP were included in this single-center study. Following NKP, deep biliary cannulation failed in 95 patients (24.4%, NKP-failure group) and succeeded in 295 patients (75.6%, NKP-success group). Patient and technique factors were used to identify the predictors of initial NKP failure. Compared with the NKP-success group, periampullary diverticulum (28.4% vs. 18%, p = 0.028), surgically altered anatomy (13.7% vs. 7.1%, p = 0.049), number of cases performed by less experienced endoscopists, and bleeding during NKP (38.9% vs. 3.4%, p < 0.001), were significantly more frequent in the NKP-failure group. On multivariate analysis, surgically altered anatomy (OR 2.374, p = 0.045), endoscopists' experience (OR 3.593, p = 0.001), and bleeding during NKP (OR 21.18, p < 0.001) were significantly associated with initial failure of NKP. In conclusion, NKP is a highly technique-sensitive procedure, as endoscopists' experience, bleeding during NKP, and surgically altered anatomy were predictors of initial NKP failure., (© 2022. The Author(s).)

In this retrospective, multicenter study, we determined the predictive value of imaging biomarkers in diabetic macular edema (DME) outcomes following dexamethasone (DEX) implant(s). Sixty-seven eyes of 47 patients' best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography (OCT) before and after intravitreal DEX implants were evaluated. Baseline imaging biomarkers were graded using fundus photography and OCT, and the predictive value of biomarkers for significant treatment effects at six months was analyzed. Six months after 2.0 ± 0.8 (mean ± SD) DEX implants, 35 (52%) and 16 (24%) eyes had CFT reduction ≥ 10% from baseline and decreased to < 300 µm, respectively. BCVA improved ≥ 3 lines in 15 (22%) and remained stable in 38 (57%) eyes. At six months, eyes with severe intraretinal cyst (IRC), abundant hyperreflective dots (HRD), and moderate or severe hard exudate had a significantly higher chance of CFT reduction ≥ 10%. Eyes with abundant HRD at baseline and those underwent three DEX implants were more likely to achieve CFT < 300 µm. Eyes with DME and severe IRC, abundant HRD, or moderate-to-severe hard exudate at baseline were more likely to show a significant reduction in CFT six months after DEX implant., (© 2022. The Author(s).)

We aim to assess the changes in sexual function and vaginal topography using 3-D transperineal ultrasound in stress-incontinent women treated with Er:YAG vaginal laser. Two hundred and twenty women with stress urinary incontinence (SUI) treated with Er:YAG laser were recruited. Assessment before and 6 months after the treatment included vaginal topography using 3-D transperineal ultrasound and sexual function using female sexual function index questionnaire (FSFI). A total of 50 women with complete data showed that the symptomatic improvement was noted in 37 (74%) women. After Er:YAG vaginal laser treatment, significantly decreased width and cross-sectional area in proximal, middle, and distal vagina were found in women with SUI. Nearly all of the domains of FSFI improved significantly after the vaginal laser treatment, except sexual desire. In conclusion, 3-D transperineal ultrasound can be used to conduct vaginal topography. After Er:YAG vaginal laser treatment, the anatomical changes of vaginal shrinkage and the improvement of female sexual function were both noted. The favorable outcome of sexual function partly related to the tightening of vagina, as evidenced by the measurements of the 3-D transperineal ultrasound., (© 2022. The Author(s).)

Spinal metastasis from malignant primary brain tumors (MPBTs) in pediatric patients is rare and often appears as enhancing lesions on MRI. However, some indolent enhancing spinal lesions (IESLs) resulting from previous treatment mimic metastasis on MRI, leading to unnecessary investigation and treatment. In 2005-2020, we retrospectively enrolled 12 pediatric/young patients with clinical impression of spinal metastasis and pathological diagnosis of their spinal lesions. Three patients had MPBT with IESL, and 9 patients had malignant tumors with metastases. The histopathologic diagnosis of IESL was unremarkable marrow change. We evaluated their MRI, CT, and bone scan findings. The following imaging findings of IESL vs. spinal metastasis were noted: (1) IESLs appeared round/ovoid (3/3, 100%), whereas spinal metastasis appeared irregular (9/9, 100%) (P = 0.005); (2) target-shaped enhancement was noted in (3/3, 100%) vs. (0/9, 0%) of cases, respectively (P = 0.005); (3) pathologic fracture of the vertebral body was noted in (1/3, 33.3%) vs. (9/9, 100%) of cases, respectively (P = 0.045); (4) expansile vertebral shape was noted in (0/3, 0%) vs. (9/9, 100%) of cases, respectively (P = 0.005); (5) obliteration of the basivertebral vein was noted in (0/3, 0%) vs. (9/9, 100%) of cases, respectively (P = 0.005); and (6) osteoblastic change on CT was noted in (3/3, 100%) vs. (2/9, 22.2%) of cases, respectively (P = 0.034). IESL in pediatric patients with MPBT can be differentiated from metastasis based on their imaging characteristics. We suggest close follow-up rather than aggressive investigation and treatment for IESL., (© 2022. The Author(s).)

Ever more stringent regulations on greenhouse gas emissions from transportation motivate efforts to revisit materials used for vehicles 1 . High-strength aluminium alloys often used in aircrafts could help reduce the weight of automobiles, but are susceptible to environmental degradation 2,3 . Hydrogen 'embrittlement' is often indicated as the main culprit 4 ; however, the exact mechanisms underpinning failure are not precisely known: atomic-scale analysis of H inside an alloy remains a challenge, and this prevents deploying alloy design strategies to enhance the durability of the materials. Here we performed near-atomic-scale analysis of H trapped in second-phase particles and at grain boundaries in a high-strength 7xxx Al alloy. We used these observations to guide atomistic ab initio calculations, which show that the co-segregation of alloying elements and H favours grain boundary decohesion, and the strong partitioning of H into the second-phase particles removes solute H from the matrix, hence preventing H embrittlement. Our insights further advance the mechanistic understanding of H-assisted embrittlement in Al alloys, emphasizing the role of H traps in minimizing cracking and guiding new alloy design., (© 2022. The Author(s).)

The effect of precession on paleoclimate changes depends on eccentricity. However, whether and to what degree eccentricity relates to millennial-scale monsoonal changes remain unclear. By investigating climate simulations with a fixed precession condition of 9 ka before the present, we explored the potential influence of eccentricity on early-Holocene changes in the Afro-Asian summer monsoons. Compared with the lower eccentricity of the present day, higher eccentricity in the early Holocene strengthened the continental summer monsoons, Pacific anticyclone, and Hadley circulation, particularly over the ocean. Over Africa, the eccentricity-induced "dry-gets-wetter" condition could be related to the Green Sahara, suggesting a superimposed effect of precession. Over the western Pacific, the tropical response to eccentricity may have been competitive in terms of what an extremely high obliquity may have caused. A downscaled modulation of eccentricity in relation to precession and obliquity cannot be ignored when paleomonsoon records are studied. Regarding early-Holocene monsoonal changes in South Asia, however, a high eccentricity may have had only a secondary effect on enhancing the monsoonal precipitation in the southern edge of the Tibetan Plateau, exhibiting the weak power of candle-like heating. This suggested that sizable monsoonal changes over the northern Indian Ocean and India-Pakistan region are unrelated to early-Holocene eccentricity., (© 2021. The Author(s).)

Phosphate has been linked to higher cardiovascular (CV) risk. However, whether phosphate is associated with poor outcomes for patients with coronary artery disease (CAD) after percutaneous coronary interventions (PCIs) remained undetermined. 2,894 CAD patients (2,220 male, aged 71.6 ± 12.2), who received PCI at TVGH from 2006 to 2015, with phosphate measurement, were enrolled. The primary outcome was the composite of major adverse CV events [MACE, comprising of CV death, nonfatal MI, and nonfatal stroke] and heart failure hospitalization (HHF). The key secondary outcome was MACE. There was a J-curve association between phosphate and CV events after adjusted for comorbidities and renal function. Phosphate around 3.2 ± 0.1 mg/dL was associated with the lowest CV risk. In Cox analysis, each 1 mg/dL increases in phosphate was associated with a higher risk of MACE + HHF (HR: 1.12, 95% CI: 1.05-1.21): CV death (HR: 1.37, 95% CI: 1.22-1.55) and HHF (HR: 1.12, 95% CI: 1.02-1.23). Subgroup analyses showed more prominent association between phosphate and MACE + HHF in male, age > 65, bare-metal stents (BMSs), LVEF < 50%, eGFR < 60, LDL > 70 mg/dL, and emergent PCI. Phosphate has a significant association with the risk of CV events in CAD patients undergoing PCI that was independent of comorbidities and renal function., (© 2021. The Author(s).)

The association among sugar sweetened beverages (SSB) consumption, addiction and depression in adults, children and adolescents is widely reported. Dieting patterns during pregnancy is complicated by maternal fetal concerns. Specifically, restrained use of SSB might be potentially a source of perinatal distress. The current study modified diagnostic criteria for Substance Use Disorder (SUD) in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), into SSB-specific questions to assess SSB use tendency. Edinburgh Postpartum Depression Scores (EPDS) is used to assess maternal distress during pregnancy. One hundred and ninety-six consecutive pregnant women receiving antenatal care at Kaohsiung Medical University Hospital were invited to participate in this study. In the first trimester, 46.6% of women had none or 1 DSM-5 symptom, 27.0% had 2-3 symptoms, while 26.4% had ≥ 4 symptoms. The mean numbers of DSM-5 symptoms in each trimester were found to be 2.5 ± 2.25, 2.6 ± 2.45, 2.4 ± 2.43 for the first, second and third trimester, respectively, p = 0.750. While EPDS score showed no difference among DSM-5 symptoms 0-1, 2-3 and ≥ 4 groups in the first trimester (8.1 ± 4.59, 8.4 ± 5.00, 8.8 ± 4.82, p = 0.343), women with ≥ 4 DSM-symptoms was found significantly higher EPDS scores than those with < 4 DSM-symptoms in the second (7.2 ± 4.81, 7.7 ± 4.98, 8.8 ± 4.33, p = 0.030) and third trimester (6.8 ± 5.00, 7.2 ± 4.63, 8.7 ± 5.24, p = 0.019). The relationship remained significant after adjusting for covariates including actual SSB amount consumed (adjusted β = 0.25 with 95% confident interval (CI) 0.04-0.45 and 0.21 with 95% CI 0.04-0.38 for the second and third trimesters, respectively). Overall, the study is the first to characterize the positive relationship between SSB use tendency and antenatal distress in pregnancy, independent of actual SSB amount consumed. The observational nature of the study design precludes inferences of its underlying socio-psychomotor mechanisms, although restrained SSB use in pregnancy is suspected to contribute. The novel employment of modified SSB-specific DSM-5 scores and EPDS in this setting is feasible and further validation is promising. With better understanding and awareness, pregnant women with increased SSB use tendency should be properly counseled with special attention to their mental state., (© 2021. The Author(s).)

Endoscopic retrograde cholangiopancreatography is not always successful even with needle knife precut sphincterotomy (NKPS). How to manage these patients with initial NKPS failure has not been well studied. We report the outcomes of patients who received endoscopic and non-endoscopic rescue treatment after the initial NKPS failure. During the 15 years from 2004 to 2018, 87 patients with initial NKPS failure received interval endoscopic treatment (IET group, n = 43), percutaneous transhepatic biliary drainage (PTBD group, n = 25), or bile duct surgery (BDS group, n = 19) were retrospectively studied. Compared with the PTBD group, the prevalence of choledocholithiasis was higher (69.8% vs. 16.0%, p < 0.001), and malignant bile duct stricture were lower (20.9% vs. 76.0%, p < 0.001) in the IET group. Furthermore, the IET group had a significantly longer time interval between the first and second treatment procedures (4 days vs. 2 days, p = 0.001), a lower technique success rate (79.1% vs. 100%, p = 0.021), and a shorter length of hospital stay (7 days vs. 18 days, p < 0.001). Compared to the BDS group, the only significant finding was that the patients in the IET group were older. Although not statistically significant, the complication rate was lowest in the IET group (7.0%) while highest in the BDS group (15.8%). Complications in the IET group were also mild, as compared with the other two groups. In conclusion, IET should be considered after initial failed NKPS for deep biliary cannulation before contemplating more invasive treatment such as BDS. PTBD may be the alternative therapy for patients with malignant biliary obstruction., (© 2021. The Author(s).)

Inconsistent results have been reported for the association between alcohol use and pancreatic cancer, particularly at low levels of alcohol consumption. Individuals genetically susceptible to the carcinogenic effect of alcohol might have higher pancreatic cancer risk after drinking alcohol. The current study investigated the association between alcohol use and pancreatic cancer with 419 pancreatic cancer cases and 963 controls recruited by a hospital-based case-control study in Taiwan. Gene-environment interaction between alcohol use and polymorphisms of two ethanol-metabolizing genes, ADH1B and ALDH2, on pancreatic risk was evaluated. Our results showed no significant association between alcohol drinking and an increased pancreatic cancer risk, even at high levels of alcohol consumption. Even among those genetically susceptible to the carcinogenic effect of alcohol (carriers of ADH1B*2/*2(fast activity) combined with ALDH2*1/*2(slow activity) or ALDH2*2/*2(almost non-functional)), no significant association between alcohol use and pancreatic cancer was observed. Overall, our results suggested that alcohol drinking is not a significant contributor to the occurrence of pancreatic cancer in Taiwan., (© 2021. The Author(s).)

Severe extracranial carotid stenosis (SECS) patients may present with nonspecific neurological symptoms that require intracranial magnetic resonance imaging (MRI) and time-of-flight (TOF)-MR angiography (MRA) to exclude intracranial pathology. Recognition of SECS on intracranial TOF-MRA findings is beneficial to provide a prompt carotid imaging study and aggressive stroke prevention. Patients with SECS (January 2016 to May 2019) undergoing percutaneous transluminal angioplasty and stenting (PTAS) were included. Differences in normalized signal intensities (SR ICA ) and diameters (D ICA ) between bilateral petrous internal carotid arteries (ICAs) were calculated 1 cm from the orifice. A hypothesized criterion describing the opacification grades (G OPH ) of bilateral ophthalmic arteries was proposed. We correlated SR ICA (p = 0.041), D ICA (p = 0.001) and G OPH (p = 0.012), with the severity of extracranial carotid stenosis on digital subtractive angiography (DSA) in the examined group (n = 113), and all showed statistical significance in predicting percentages of ICA stenosis. The results were further validated in another patient group with SECS after radiation therapy (n = 20; p = 0.704 between the actual and predicted stenosis grades). Our findings support the evaluation of the signal ratio and diameter of intracranial ICA on TOF-MRA to achieve early diagnosis and provide appropriate management of SECS.

Increased blood pressure (BP) caused by exposure to cold temperatures can partially explain the increased incidence of cardiovascular events in winter. However, the physiological mechanisms involved in cold-induced high BP are not well established. Many studies have focused on physiological responses to severe cold exposure. In this study, we aimed to perform a comprehensive analysis of cardiovascular autonomic function and sleep patterns in rats during exposure to mild cold, a condition relevant to humans in subtropical areas, to clarify the physiological mechanisms underlying mild cold-induced hypertension. BP, electroencephalography, electromyography, electrocardiography, and core body temperature were continuously recorded in normotensive Wistar-Kyoto rats over 24 h. All rats were housed in thermoregulated chambers at ambient temperatures of 23, 18, and 15 °C in a randomized crossover design. These 24-h physiological recordings either with or without sleep scoring showed that compared with the control temperature of 23 °C, the lower ambient temperatures of 18 and 15 °C not only increased BP, vascular sympathetic activity, and heart rate but also decreased overall autonomic activity, parasympathetic activity, and baroreflex sensitivity in rats. In addition, cold exposure reduced the delta power percentage and increased the incidence of interruptions during sleep. Moreover, a correlation analysis revealed that all of these cold-induced autonomic dysregulation and sleep problems were associated with elevation of BP. In conclusion, mild cold exposure elicits autonomic dysregulation and poor sleep quality, causing BP elevation, which may have critical implications for cold-related cardiovascular events.

Keloid is a skin disease characterized by exaggerated scar formation, excessive fibroblast proliferation, and excessive collagen deposition. Cancers commonly arise from a fibrotic microenvironment; e.g., hepatoma arises from liver cirrhosis, and oral cancers arise from submucosal fibrosis. As keloids are a prototypic fibroproliferative disease, this study investigated whether patients with keloids have an increased cancer risk. In a matched, population-based study, first 17,401 patients treated for keloids during 1998-2010 with 69,604 controls without keloids at a ratio of 1:4 were evaluated. The association between keloids and risk of cancer was estimated by logistic regression or Cox proportional hazard regression models after adjustment of covariates. In total, 893 first-time cases of cancer were identified in the 17,401 patients with keloids. The overall cancer risk was 1.49-fold higher in the keloids group compared to controls. Regarding specific cancers, the keloids group, had a significantly higher risk of skin cancer compared to controls (Relative risk = 1.73). The relative risk for skin cancer was even higher for males with keloids (Relative risk = 2.16). Further stratified analyses also revealed a significantly higher risk of developing pancreatic cancer in female patients with keloids compared to controls (Relative risk = 2.19) after adjustment for known pancreatic cancer risk factors. This study indicates that patients with keloids have a higher than normal risk for several cancer types, especially skin cancers (both genders) and pancreatic cancer (females). Therefore, patients with keloids should undergo regular skin examinations, and females with keloids should regularly undergo abdominal ultrasonography.

Brazil has one of the fastest-growing COVID-19 epidemics worldwide. Non-pharmaceutical interventions (NPIs) have been adopted at the municipal level with asynchronous actions taken across 5,568 municipalities and the Federal District. This paper systematises the fragmented information on NPIs reporting on a novel dataset with survey responses from 4,027 mayors, covering 72.3% of all municipalities in the country. This dataset responds to the urgency to track and share findings on fragmented policies during the COVID-19 pandemic. Quantifying NPIs can help to assess the role of interventions in reducing transmission. We offer spatial and temporal details for a range of measures aimed at implementing social distancing and the dates when these measures were relaxed by local governments.

The Kuroshio-literally "the Black Stream"-is the most substantial current in the Pacific Ocean. It was called the Black Stream because this oligotrophic current is so nutrient-poor in its euphotic zone that the water appears black without the influence of phytoplankton and the associated, often colored dissolved organic matter. Yet, below the euphotic layer, nutrient concentrations increase with depth while current speed declines. Consequently, a core of maximum nutrient flux, the so-called nutrient stream, develops at a depth of roughly between 200 and 800 m. This poorly studied nutrient stream transports nutrients to and supports high productivity and fisheries on the East China Sea continental shelf; it also transports nutrients to and promotes increased productivity and fisheries in the Kuroshio Extension and the subarctic Pacific Ocean. Three modes of the Kuroshio nutrient stream are detected off SE Taiwan for the first time: one has a single-core; one has two cores that are apparently separated by the ridge at 120.6-122° E, and one has two cores that are separated by a southward flow above the ridge. More importantly, northward nutrient transports seem to have been increasing since 2015 as a result of a 30% increase in subsurface water transport, which began in 2013. Such a nutrient stream supports the Kuroshio's high productivity, such as on the East China Sea continental shelf and in the Kuroshio Extension SE of Japan.

We aimed to compare the (1) clinical outcomes including composite cardiovascular outcomes, cardiovascular death, and all-cause death, and (2) healthcare costs of using liraglutide and basal insulin as an initial treatment for patients with type 2 diabetes mellitus (T2DM) and high cardiovascular diseases (CVD) risk. This is a retrospective cohort study using Taiwan's Health and Welfare Database. A total of 1057 patients treated with liraglutide were identified and matched with 4600 patients treated with basal insulin. The liraglutide group had a lower risk of a composite CVD outcome (hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.50-0.85; p < 0.01), all-cause mortality (HR 0.40; 95% CI 0.28-0.59; p < 0.0001), and nonfatal stroke (HR 0.54; 95% CI 0.34-0.87; p = 0.01). Compared to the basal insulin group, the liraglutide group had lower median per-patient-per-month (PPPM) inpatient, emergency room (ER), and total medical costs, but higher median PPPM outpatient, total pharmacy, and total costs (all p < 0.0001). In conclusion, compared to basal insulin, liraglutide was found to be associated with reduced risk of a composite CVD outcome, nonfatal stroke, and all-cause mortality among high CVD risk patients with T2DM. In addition, liraglutide users had lower inpatient, ER, and total medical costs, but they had higher outpatient and total pharmacy costs.

Massive hepatic necrosis after therapeutic embolization has been reported. We employed a 320-detector CT scanner to compare liver perfusion differences between blunt liver trauma patients treated with embolization and observation. This prospective study with informed consent was approved by institution review board. From January 2013 to December 2016, we enrolled 16 major liver trauma patients (6 women, 10 men; mean age 34.9 ± 12.8 years) who fulfilled inclusion criteria. Liver CT perfusion parameters were calculated by a two-input maximum slope model. Of 16 patients, 9 received embolization and 7 received observation. Among 9 patients of embolization group, their arterial perfusion (78.1 ± 69.3 versus 163.1 ± 134.3 mL/min/100 mL, p = 0.011) and portal venous perfusion (74.4 ± 53.0 versus 160.9 ± 140.8 mL/min/100 mL, p = 0.008) were significantly lower at traumatic parenchyma than at non-traumatic parenchyma. Among 7 patients of observation group, only portal venous perfusion was significantly lower at traumatic parenchyma than non-traumatic parenchyma (132.1 ± 127.1 vs. 231.1 ± 174.4 mL/min/100 mL, p = 0.018). The perfusion index between groups did not differ. None had massive hepatic necrosis. They were not different in age, injury severity score and injury grades. Therefore, reduction of both arterial and portal venous perfusion can occur when therapeutic embolization was performed in preexisting major liver trauma, but hepatic perfusion index may not be compromised.

The Protein Ontology (PRO) provides an ontological representation of protein-related entities, ranging from protein families to proteoforms to complexes. Protein Ontology Linked Open Data (LOD) exposes, shares, and connects knowledge about protein-related entities on the Semantic Web using Resource Description Framework (RDF), thus enabling integration with other Linked Open Data for biological knowledge discovery. For example, proteins (or variants thereof) can be retrieved on the basis of specific disease associations. As a community resource, we strive to follow the Findability, Accessibility, Interoperability, and Reusability (FAIR) principles, disseminate regular updates of our data, support multiple methods for accessing, querying and downloading data in various formats, and provide documentation both for scientists and programmers. PRO Linked Open Data can be browsed via faceted browser interface and queried using SPARQL via YASGUI. RDF data dumps are also available for download. Additionally, we developed RESTful APIs to support programmatic data access. We also provide W3C HCLS specification compliant metadata description for our data. The PRO Linked Open Data is available at https://lod.proconsortium.org/ .

Thin gold (Au) films (10 nm) are deposited on different substrates by using a e-beam deposition system. Compared with sapphire and SiO 2 surfaces, longer migration length of the Au adatoms is observed on MoS 2 surfaces, which helps in the formation of a single-crystal Au film on the MoS 2 surface at 200 °C. The results have demonstrated that with the assistance of van der Waals epitaxy growth mode, single-crystal 3D metals can be grown on 2D material surfaces. With the improved crystalline quality and less significant Au grain coalescence on MoS 2 surfaces, sheet resistance 2.9 Ω/sq is obtained for the thin 10 nm Au film at 100 °C, which is the lowest value reported in literature. The highly conductive thin metal film is advantageous for the application of backend interconnects for the electronic devices with reduced line widths.

Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide and prognosis after potentially curative gastrectomy remains poor. Administration of GC-targeting molecules in combination with adjuvant chemo- or radiotherapy following surgical resection has been proposed as a potentially effective treatment option. Here, we have identified DOCK6, a guanine nucleotide exchange factor (GEF) for Rac1 and CDC42, as an independent biomarker for GC prognosis. Clinical findings indicate the positive correlation of higher DOCK6 expression with tumor size, depth of invasion, lymph node metastasis, vascular invasion, and pathological stage. Furthermore, elevated DOCK6 expression was significantly associated with shorter cumulative survival in both univariate and multivariate analyses. Gene ontology analysis of three independent clinical GC cohorts revealed significant involvement of DOCK6-correlated genes in the WNT/β-catenin signaling pathway. Ectopic expression of DOCK6 promoted GC cancer stem cell (CSC) characteristics and chemo- or radioresistance concomitantly through Rac1 activation. Conversely, depletion of DOCK6 suppressed CSC phenotypes and progression of GC, further demonstrating the pivotal role of DOCK6 in GC progression. Our results demonstrate a novel mechanistic link between DOCK6, Rac1, and β-catenin in GCCSC for the first time, supporting the utility of DOCK6 as an independent marker of GC.

This retrospective cohort study aims to assess the clinical and urodynamic outcomes of single-incision mesh surgery with the Uphold system. The medical records of 140 women with anterior and/or apical compartment prolapse stage 2 or greater who underwent Uphold mesh surgeries were reviewed. The clinical evaluation included a pelvic examination, a urodynamic study (UDS), and a personal interview to evaluate lower urinary tract symptoms (LUTS). After a follow-up time of 12-30 months, the anatomical reduction rates were 100% and 96.4% for the apical and anterior compartments, respectively, and these rates were similar across women with or without hysterectomy. All of the LUTS and several UDS parameters improved significantly. The continence rate in women with stress urinary incontinence (SUI) was improved if they also underwent a mid-urethral sling (MUS) operation. However, the continence rate did not differ between women with and without occult urodynamic stress incontinence who did not undergo a concomitant MUS operation. The rate of vaginal mesh extrusion was 2.8%, and this complication rarely occurred beyond the learning curve. In conclusion, the anatomic correction of the Uphold system was satisfactory with a low rate of mesh extrusion. Women with SUI would benefit from a concomitant MUS operation.

This study aimed to evaluate whether the addition of oxaliplatin to a neoadjuvant chemoradiotherapy (CRT) regimen could improve survival benefit in locally advanced rectal cancer (LARC) patients. We retrospectively analysed 73 LARC patients (cT2-4 and/or cN1-2) who received preoperative CRT with capecitabine followed by surgery (arm A, 43 patients) or capecitabine plus oxaliplatin followed by surgery (arm B, 30 patients). The main endpoints of the study were pathologic complete response (pCR) rate, overall survival (OS) and disease-free survival (DFS). The secondary endpoints included the sphincter preservation rate and safety. The pCR for arms A and B were 28% and 17% (P = 0.267). In arms A and B, the mean OS was 84.287 months (95% CI 68.413-100.160) and 106.333 months (95% CI 99.281-113.386) (P = 0.185); the mean DFS was 72.812 months (95% CI 56.271-89.353) and 95.073 months (95% CI 83.392-106.754) (P = 0.310); and the sphincter preservation rates were 72% and 67%, respectively (P = 0.619). The incidence of grade 3 toxicity was much higher in arm B than in arm A (57% vs. 21%, P = 0.002). Adding oxaliplatin to a preoperative CRT regimen for LARC did not improve the survival benefits of patients or increase toxicity.

Patients with kidney failure rely on life-saving peritoneal dialysis to facilitate waste exchange and maintain homeostasis of physical conditions. However, peritoneal dialysis often results in peritoneal fibrosis and organ adhesion that subsequently compromise the efficiency of peritoneal dialysis and normal functions of visceral organs. Despite rodent models provide clues on the pathogenesis of peritoneal fibrosis, no current large animal model which shares high degree of physiological and anatomical similarities to human is available, limiting their applications on the evaluation of pre-clinical therapeutic efficacy. Here we established for the first time, hypochlorite-induced porcine model of peritoneal fibrosis in 5-week-old piglets. We showed that administration 15-30 mM hypochlorite, a dose- and time-dependent severity of peritoneal fibrosis characterized by mesothelium fragmentation, αSMA + myofibroblasts accumulation, organ surface thickening and type I collagen deposition were observed. We also demonstrated in vitro using human mesothelial cells that hypochlorite-induced fibrosis was likely due to necrosis, but not programmed apoptosis; besides, overexpression of IL1β, CX3CL1 and TGFβ on the peritoneal mesothelium in current model was detected, similar to observations from peritoneal dialysis-induced peritoneal fibrosis in human patients and earlier reported mouse model. Moreover, our novel antemortem evaluation using laparoscopy provided instant feedback on the progression of organ fibrosis/adhesion which allows immediate adjustments on treatment protocols and strategies in alive individuals that can not and never be performed in other animal models.

The efficacy of prior activation of an anti-inflammatory pathway called the cholinergic anti-inflammatory pathway (CAP) through vagus nerve stimulation (VNS) has been reported in renal ischemia-reperfusion injury models. However, there have been no reports that have demonstrated the effectiveness of VNS after injury. We investigated the renoprotective effect of VNS in a cisplatin-induced nephropathy model. C57BL/6 mice were injected with cisplatin, and VNS was conducted 24 hours later. Kidney function, histology, and a kidney injury marker (Kim-1) were evaluated 72 hours after cisplatin administration. To further explore the role of the spleen and splenic macrophages, key players in the CAP, splenectomy, and adoptive transfer of macrophages treated with the selective α7 nicotinic acetylcholine receptor agonist GTS-21 were conducted. VNS treatment significantly suppressed cisplatin-induced kidney injury. This effect was abolished by splenectomy, while adoptive transfer of GTS-21-treated macrophages improved renal outcomes. VNS also reduced the expression of cytokines and chemokines, including CCL2, which is a potent chemokine attracting monocytes/macrophages, accompanied by a decline in the number of infiltrating macrophages. Taken together, stimulation of the CAP protected the kidney even after injury in a cisplatin-induced nephropathy model. Considering the feasibility and anti-inflammatory effects of VNS, the findings suggest that VNS may be a promising therapeutic tool for acute kidney injury.

The overexpression of SOX4 in various kinds of cancer cells was associated with poor prognosis for patients. The role of SOX4 in angiogenesis and tumor microenvironment modulation was recently documented in breast cancer but remains unclear in hepatocellular carcinoma (HCC). In our study, the clinical relevance of SOX4 overexpression in HCC and its role in the tumor microenvironment were investigated. The overexpression of SOX4 (SOX4 high ) in tumor lesions was associated with higher microvessel density (P = 0.012), tumor thrombosis formation (P = 0.012), distant metastasis (P < 0.001), and an independent prognostic factor for disease-free survival in HCC patients (P = 0.048). Endogenous SOX4 knockout in Hep3B cells by the CRISPR/cas9 system reduced the expression of CXCL12, which, in turn, attenuated chemotaxis in human umbilical vein endothelial cells, tube formation in vitro, reduced tumor growth, reticular fiber production, and angiogenesis in vivo in a xenograft mouse model. Treatment with an antagonist targeting CXCR4 (AMD3100), a receptor of CXCL12, inhibited chemotaxis and tube formation in endothelial cells in vitro. The CXCL12 promoter was activated by ectopic expression of a Flag-tagged SOX4 plasmid, endogenous SOX4 knockdown abolished promoter activity of CXCL12 as shown by luciferase assays, and an association with the CXCL12 promoter was identified via chromatin immunoprecipitation in HCC cells. In conclusion, SOX4 modulates the CXCL12 promoter in HCC cells. The secretory CXCL12, in turn, modulates CXCR4 in endothelial cells, reticular fibers to regulate the tumor microenvironment and modulate neovascularization, which might contribute to the distant metastasis of tumors.

Non-invasive far infrared radiation (FIR) has been observed to improve the health of patients with coronary artery disease (CAD). Endothelial colony forming cells (ECFCs) contribute to vascular repair and CAD. The goal of this study was to uncover the role of FIR in ECFCs function and to reveal potential biomarkers for indication of FIR therapy in CAD patients. FIR significantly enhanced in vitro migration (transwell assay) and tube formation (tube length) capacities in a subpopulation of CAD ECFCs. Clinical parameters associated with the responsiveness of ECFCs to FIR include smoking and gender. ECFCs from CAD patients that smoke did not respond to FIR in most cases. In contrast, ECFCs from females showed a higher responsiveness to FIR than ECFCs from males. To decipher the molecular mechanisms by which FIR modulates ECFCs functions, regardless of sex, RNA sequencing analysis was performed in both genders of FIR-responsive and FIR-non/unresponsive ECFCs. Gene Ontology (GO) analysis of FIR up-regulated genes indicated that the pathways enriched in FIR-responsive ECFCs were involved in cell viability, angiogenesis and transcription. Small RNA sequencing illustrated 18 and 14 miRNAs that are up- and down-regulated, respectively, in FIR-responsive CAD ECFCs in both genders. Among the top 5 up- and down-regulated miRNAs, down-regulation of miR-548aq-3p in CAD ECFCs after FIR treatment was observed in FIR-responsive CAD ECFCs by RT-qPCR. Down-regulation of miR-548aq-3p was correlated with the tube formation activity of CAD ECFCs enhanced by FIR. After establishment of the down-regulation of miR-548aq-3p by FIR in CAD ECFCs, we demonstrated through overexpression and knockdown experiments that miR-548aq-3p contributes to the inhibition of the tube formation of ECFCs. This study suggests the down-regulation of miR-548aq-3p by FIR may contribute to the improvement of ECFCs function, and represents a novel biomarker for therapeutic usage of FIR in CAD patients.

We have demonstrated that with e-beam deposition of a thin Al 2 O 3 layer before atomic layer deposition, a uniform Al 2 O 3 film can be obtained on WSe 2 /sapphire samples. Device performances are observed for WSe 2 top-gate transistors by using oxide stacks as the gate dielectric. By using thermal evaporation, epitaxially grown multilayer antimonene can be prepared on both MoS 2 and WSe 2 surfaces. With multilayer antimonene as the contact metal, a significant increase in drain currents and ON/OFF ratios is observed for the device, which indicates that high contact resistance between metal/2D material interfaces is a critical issue for 2D devices. The observation of multilayer antimonene grown on different 2D material surfaces has demonstrated less dependence on the substrate lattice constant of the unique van der Waals epitaxy for 2D materials. The results have also demonstrated that stacking 2D materials with different materials plays an important role in the practical applications of 2D devices.

Cases of a novel coronavirus were first reported in Wuhan, Hubei province, China, in December 2019 and have since spread across the world. Epidemiological studies have indicated human-to-human transmission in China and elsewhere. To aid the analysis and tracking of the COVID-19 epidemic we collected and curated individual-level data from national, provincial, and municipal health reports, as well as additional information from online reports. All data are geo-coded and, where available, include symptoms, key dates (date of onset, admission, and confirmation), and travel history. The generation of detailed, real-time, and robust data for emerging disease outbreaks is important and can help to generate robust evidence that will support and inform public health decision making.

Extracorporeal shockwave therapy (ESWT) is proposed to be effective in reducing pain and improving functional outcome in chronic plantar fasciitis. However, no long-term reports exist on the changes in plantar fascia (PF) elasticity after ESWT. We aimed to evaluate the changes in PF stiffness in patients with plantar fasciitis undergoing ESWT. The visual analogue scale (VAS, 0-100) was used for evaluating heel pain severity. B-mode sonography and strain sonoelastography were used for evaluating the PF thickness and stiffness. The sonoelastogram was analyzed using hue histogram analysis (value: 0-255, from stiffer to softer). All evaluations were recorded before ESWT, and 1 week, 1 month, 3 months, 6 months, and 12 months after ESWT. Repeated measures ANOVA was used to compare pain VAS, PF thickness, and PF hue value at different follow-up time-points. Twenty-two participants (8 men, 14 women) completed all measurements for 12 months. The VAS of heel pain, PF thickness, and PF hue values at pre-ESWT, and 1-week, 1-month, 3-month, 6-month, and 12-month evaluations after ESWT were 62.4 ± 4.2, 49.3 ± 5.8, 38.3 ± 5.7, 27.9 ± 5.3, 18.9 ± 4.7, and 13.2 ± 3.0 (p < 0.01 in all measurements post ESWT versus pre-ESWT); 5.57 ± 0.22 mm, 5.64 ± 0.18 mm, 5.45 ± 0.24 mm, 5.37 ± 0.20 mm, 5.08 ± 0.20 mm, and 4.62 ± 0.15 mm (p < 0.01 at 6-month; otherwise p > 0.05); and 24.5 ± 2.4, 35.2 ± 3.1, 31.0 ± 4.1, 30.5 ± 3.9, 21.4 ± 2.1, and 15.9 ± 1.6 (p < 0.01 at 1-week and 6-month; otherwise p > 0.05), respectively. In conclusion, the heel pain intensity and PF thickness reduced gradually over 12 months after ESWT. The PF stiffness decreased during the first week and increased thereafter; at the 12-month follow-up, stiffness was more than at pre-ESWT.