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Abstract Purpose To evaluate the relationship between delivered radiation (RT) and post-RT inversion-recovery ultrashort-echo-time (IR-UTE) MRI signal-intensity (SI) in gynecologic cancer patients treated with high-dose-rate (HDR) brachytherapy (BT). Methods Seven patients underwent whole-pelvis RT (WPRT) followed by BT to the high-risk clinical target volume (HR-CTV). MR images were acquired at three time-points; pre-RT, post-WPRT/pre-BT, and 3–6 months post-BT. Diffuse-fibrosis (FDiffuse) was imaged with a non-contrast dual-echo IR (inversion time [TI] = 60 ms) UTE research application, with image-subtraction of the later echo, only retaining the ultrashort-echo SI. Dense-fibrosis (FDense) imaging utilized single-echo Late-Gadolinium-Enhanced IR-UTE, acquired ∼ 15 min post-Gadavist injection. Resulting FDiffuse and FDense SI were normalized to the corresponding gluteal-muscle SI. Images were deformably registered between time-points based on normal tissue anatomy. The remnant tumor at both time-points was segmented using multi-parametric MRI. Contours corresponding to the 50%, 100%, 150%, and 200% isodose lines (IDLs) of the prescription BT-dose were created. Mean FDiffuse and FDense SI within (i) each IDL contour and (ii) the remnant tumor were calculated. Post-BT FDiffuse and FDense SI were correlated with prescribed BT-dose. To determine the relationship between BT-dose and IR-UTE SI, the differences in the post-BT FDense across IDLs was determined using paired t-tests with Bonferroni correction. Results FDense was higher in regions of higher dose for 6/7 patients, with mean ± SD values of 357 ± 103% and 331 ± 97% (p = .03) in the 100% and 50% IDL, respectively. FDense was higher in regions of higher dose in the responsive regions with mean ± SD values of 380 ± 122% and 356 ± 135% (p = .03) in the 150% and 50% IDL, respectively. Within the segmented remnant tumor, an increase in prescribed dose correlated with an increase in FDense post-BT (n = 5, r = .89, p = .04). Post-BT FDiffuse inversely correlated (n = 7, r = -.83, p = .02) with prescribed BT-dose within the 100% IDL. Conclusions Results suggest that FDense SI 3–6 months post-BT is a sensitive measure of tissue response to heterogeneous BT radiation-dose. Future studies will validate whether FDiffuse and FDense are accurate biomarkers of fibrotic radiation response.

Abstract Miniaturized silicon thermal probes for plant’s sap flow measurement, or micro sap flow sensors, have advantages in minimum invasiveness, low power consumption, and fast responses. Practical applications in sap flow measurement has been demonstrated with the single-probe silicon micro sensors. However, the sensors could not detect flow directions and require estimating zero sap flow output that leads to significant source of uncertainty. Furthermore, silicon-needles would break easily during the insertion into plants. We present the first three-element micro thermal sap flow sensor packaged on a durable printed circuit board needle that can measure bidirectional flows with improved dynamics and precision. The performance of the newly designed calorimetric flow sensor was confirmed through precision calibration and field test on tomato stems. A calibration curve for a tomato stem was obtained with a sensitivity of 0.299 K/(µL mm−2 s−1) under the maximum temperature increase of 4.61 K. Results from the field test for one month revealed a correlation between the measured sap flux density and related conditions such as solar radiation, vapor pressure deficit, sunshade and irrigation. The developed sensor will contribute to practical long-term sap flow monitoring for small and delicate plants with minimal physical invasion.

PURPOSE Laminar blood flow is known to play a critical role in maintaining endothelial homeostasis in blood vessels. It exerts a shear stress on the endothelial cells (ECs), which is essential for the regulation of various vascular functions. In this study, the effects of laminar blood flow-induced enhanced endothelial homeostasis on the maintenance of vascular function were investigated. METHODS Human umbilical vein endothelial cells (HUVECs) were employed to study gene expression associated with vessel dilation and angiogenesis in response to varying shear stress levels. To assess angiogenesis, experimental mice participated in voluntary wheel running for 16 weeks. To evaluate the vascular autophagic function, the six weeks old C57BL/6 mice underwent an hour of forced treadmill running for 10 weeks. The resulting gene expression was evaluated through western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS Disturbed flow resulting from partial ligation surgery in the mice's carotid artery led to a decrease in angiogenic capacity compared to the laminar flow observed in ex vivo sprouting assays. Cultured HUVECs exhibited a significant increase in VEGF expression when exposed to increased durations of 20 dyne/cm² laminar shear stress (LSS). Following a 10-week treadmill exercise regimen, ECs in the carotid arteries of mice showed a significant increase in the expression of autophagic genes, such as LC3II, Atg3, and Atg7, which was not observed in smooth muscle cells (SMCs). LSS was found to boost the expression of both total and phosphorylated eNOS, genes involved in vascular dilation regulation, specifically in ECs. CONCLUSIONS These findings suggest that laminar blood flow sustains vascular function, such as angiogenic capacity, through the enhancement of endothelial homeostasis.

Abstract Despite its great scientific and technological importance, wall-bounded turbulence is an unresolved problem in classical physics that requires new perspectives to be tackled. One of the key strategies has been to study interactions among the energy-containing coherent structures in the flow. Such interactions are explored in this study using an explainable deep-learning method. The instantaneous velocity field obtained from a turbulent channel flow simulation is used to predict the velocity field in time through a U-net architecture. Based on the predicted flow, we assess the importance of each structure for this prediction using the game-theoretic algorithm of SHapley Additive exPlanations (SHAP). This work provides results in agreement with previous observations in the literature and extends them by revealing that the most important structures in the flow are not necessarily the ones with the highest contribution to the Reynolds shear stress. We also apply the method to an experimental database, where we can identify structures based on their importance score. This framework has the potential to shed light on numerous fundamental phenomena of wall-bounded turbulence, including novel strategies for flow control.

We present a turbulence-sustaining mechanism in a spinor Bose-Einstein condensate, which is based on the chaotic nature of internal spin dynamics. Magnetic driving induces a complete chaotic evolution of the local spin state, thereby continuously randomizing the spin texture of the condensate to maintain the turbulent state. We experimentally demonstrate the onset of turbulence in the driven condensate as the driving frequency changes and show that it is consistent with the regular-to-chaotic transition of the local spin dynamics. This chaos-assisted turbulence establishes the spin-driven spinor condensate as an intriguing platform for exploring quantum chaos and related superfluid turbulence phenomena.

Abstract Background Sarcopenic obesity, defined as the coexistence of low muscle mass and high adiposity, is associated with cardiovascular disease (CVD) and mortality. However, to what extent sarcopenia contributes to these risks independently or in conjunction with other cardiovascular risk factors remains unclear. This study aimed to investigate the association of low muscle mass, central obesity (COB), metabolic abnormalities, and their combinations with CVD and mortality risk. Methods This cross‐sectional analysis used data from the National Health and Nutrition Examination Survey 1999–2006 and 2011–2018. Participants aged >20 years and with reported whole‐body dual X‐ray absorptiometry data were included. Participants were divided into eight groups based on low muscle mass, metabolic abnormalities, and COB status. Results The mean age of participants was 55 years, and 50.4% of participants were male. Low muscle mass was observed in 2472 (14.6%) out of 16 839 participants. Among the eight groups, the metabolically unhealthy COB group with low muscle mass had the highest hazard ratio (HR) for all‐cause mortality (HR, 2.00; 95% CI, 1.56–2.56; P

A new two-phase mass transfer Computational Fluid Dynamics (CFD) method is developed using a meshfree collocation approach, or Generalized Finite Difference Method (GFDM), to resolve the evaporation phenomenon at the waterair interface since it is essential to estimate the water dry-out-time for corrosion protection schemes on automotive components. Thereby, the volume-volume-coupling to couple the phases – air and water – is used in order to keep a stable phase interface. At the interface, it is assumed that the main driving force of the liquid mass transfer into vapor is diffusion driven by the vapor concentration gradient. The automatized adaptive refinement based on the humidity- and velocity-gradient enabling the automation of the whole process is also developed. The newly developed method is validated with one simple and actual vehicle geometries. In vehicle geometry case, the total-dry-out times of an accumulated water source at the corner of a sunroof are measured. In order to extend the time scale of the simulation to real, the water reduction rate at the free surface is artificially accelerated once the evaporation rates are quasi stabilized. The validation results are promising, and the method could be extended into further complex vehicle applications.

In Wire Arc Additive Manufacturing (WAAM), solidification grain morphology in titanium alloy tends to be columnar rather than equiaxed due to heat dissipation and repeated thermal cycles. This study demonstrates improved microstructure and anisotropic properties in Ti-6Al-4V specimens fabricated by WAAM and treated with hammer peening, resulting in a transition from columnar grains to fine equiaxed grains (~300 μm) in both single-pass and four-bead WAAM walls. The anisotropic elongation decreased by approximately 7%, and tensile strength along the building direction decreased by ~50 MPa for a single-pass wall. Additionally, small and large equiaxed prior-β grains appeared alternately due to the combined effect of hammer peening and welding deposition. The region can be categorized into three parts (MAX, MED, MIN) based on the degree of plastic strain characterized by KAM mapping of EBSD data. In current WAAM parameters, the ratio of strong (~1.5 mm) deformation field (MAX) is about 50% within one deposition layer (MAX+MIN), suggesting a new approach for producing equiaxed prior-β grains. We expect that this method will be applicable for transforming the prior-β grains from columnar to equiaxed. Furthermore, the distribution of plastic strain and phase transformation mechanisms offers innovative approaches to optimize the hammer peening process, with potential applications to optimize the process for more complex components in the aerospace and power plant industries.

This paper presents insights about schemes required to provide ultra-precise positioning services for multifarious environments. It describes positioning services and their requirements, and divides the services into “living convenience” and “productivity improvement”, and the requirements into “positioning quality” and “system efficiency”. It also presents the current accuracy levels, technical challenges, and research directions of positioning schemes that are based on satellite/communication system, image, ray-tracing, and fingerprint. Ultimately, this paper presents scenarios and solutions that provide 10cm-level positioning accuracy for both outdoor and indoor environments.

Abstract Vigorous training increases the production of reactive oxygen species (ROS) from skeletal muscle, which can contribute to impairing athletic performance and health. Mitochondrial antioxidant such as MitoQ may contribute to protecting against training-induced oxidative stress such as mitochondrial ROS, but the effects on athletic performance are unknown. The purpose of this study was to determine the effects of MitoQ to exercise training (EX) on VO2max, miRNA expression involved in inflammation and oxidative stress. In this double-blind clinical trial, 32 professional cyclists (25.6±3.8yr) were randomly divided into 4 groups (n=8); 1) Placebo, 2) EX (cycle ergometer, 75% of VO2max, 90 minutes, 3 sessions/week, and 4 weeks), 3) MitoQ (20 mg.day-1 for 4 weeks), and 4) EX+MitoQ (combined EX with MitoQ for 4 weeks). V˙O2max and gene expression of MicroRNAs (miRNAs)-19b, -181b, -155, and -146a and Serum levels of ROS (peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha oxygen), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were measured by the gas analyzer, real-time polymerase chain reaction (2-ΔΔCt) and ELISA, respectively. Both EX+MitoQ and MitoQ reduced serum levels of ROS (P < 0.05), but there was no change in EX group. Serum GPx levels were increased in EX, MitoQ, and EX+MitoQ (P < 0.05), but there was no difference between groups. Serum SOD remained unchanged in all groups. miRNA-155 and miRNA-19b expressions were decreased in EX+MitoQ compared to EX, whereas miRNA-146a was increased in EX+MitoQ compared to EX (P < 0.05). Placebo-controlled intervention (tapioca powder) had no effects on all outcomes (P < 0.05). MitoQ supplementation and EX reduced ROS levels and altered expression of key miRNAs mediating ROS generation and vascular endothelial inflammation could contribute to improving vascular function.

Abstract Cigarette smoking is one of the leading causes of preventable and premature death worldwide. Even worse, many people are generally exposed to passive smoking, which leads to several respiratory diseases and related mortalities. Considering, more than 7000 compounds are included in cigarettes, their combustion results intoxicants that have deleterious effects on health. However, there is a lack of research analyzing the effects of smoking and passive smoking on all-cause and disease-specific mortality through its chemical compounds including heavy metals. Thus, this study aimed to evaluate the effect of smoking and passive smoking on all-cause and disease-specific mortality mediated by cadmium, one of the representative smoking-related heavy metals using data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 in the United States. We found that current smoking and passive smoking was related to increased risk of all-cause, CVD-related, and cancer-related mortality. Notably, passive smoking showed a synergistic effect with smoking status on the risk of mortality. In particular, current smokers with passive smoking had the highest risk of all-cause and disease-specific deaths. In addition, the accumulation of cadmium in the blood due to smoking and passive smoking mediates the increased risk of all-cause mortality. Further studies are needed to monitor and treat cadmium toxicity to improve smoking-related mortality rates.

Abstract Despite the emerging scientific interest in polymer‐based stretchable electronics, the trade‐off between the crystallinity and stretchability of intrinsically stretchable polymer semiconductors—charge‐carrier mobility increases as crystallinity increases while stretchability decreases—hinders the development of high‐performance stretchable electronics. Herein, a highly stretchable polymer semiconductor is reported that shows concurrently improved thin film crystallinity and stretchability upon thermal annealing. The polymer thin films annealed at temperatures higher than their crystallization temperatures exhibit substantially improved thin film stretchability (> 200%) and hole mobility (≥ 0.2 cm2 V−1 s−1). The simultaneous enhancement of the crystallinity and stretchability is attributed to the thermally‐assisted structural phase transition that allows the formation of edge‐on crystallites and reinforces interchain noncovalent interactions. These results provide new insights into how the current crystallinity–stretchability limitation can be overcome. Furthermore, the results will facilitate the design of high‐mobility stretchable polymer semiconductors for high‐performance stretchable electronics.

Background: Accelerated skeletal muscle wasting is a shared trait among many pathologies and aging. Acupuncture has been used as a therapeutic intervention to control pain; however, little is known about its effects on skeletal muscle atrophy and function. The study's purpose was to compare the effects of acupuncture, electro-acupuncture, and electrical stimulation on cast-induced skeletal muscle atrophy. Methods: Forty female Sprague Dawley rats were randomly divided into groups: Control, casted (CAST), CAST+Acupuncture (CAST-A), 4) CAST+Electro-acupuncture (CAST-EA), and CAST+Electrical stimulation (CAST-ES) (n = 8). Plaster casting material was wrapped around the left hind limb. Acupuncture and electro-acupuncture (10 Hz, 6.4 mA) treatments were applied by needling acupoints (stomach-36 and gallbladder-34). Electrical stimulation (10 Hz, 6.4 mA) was conducted by needling the lateral and medial gastrocnemius muscles. Treatments were conducted for 15 min, three times/week for 14 days. Muscle atrophy F-box (MAFbx), muscle RING finger 1 (MuRF1), and contractile properties were assessed. Results: Fourteen days of cast-immobilization decreased muscle fiber CSA by 56% in the CAST group (p = 0.00); whereas, all treatment groups demonstrated greater muscle fiber CSA than the CAST group (p = 0.00). Cast-immobilization increased MAFbx and MuRF1 protein expression in the CAST group (p

We investigated the prognosis of BCG induction-only treatment and non-complete response (CR) at the first 3-month evaluation and examined factors associated with CR. In total, 209 patients with moderate- and high-risk NMIBC who received BCG induction-only treatment between 2008 and 2020 were retrospectively analyzed. Recurrence-free survival (RFS) and progression-free survival (PFS) were assessed based on the initial NMIBC stage. PFS and associated factors of non-CR compared to CR were also assessed. Initial T1 high-grade (HG) (n = 93) had poorer RFS and PFS after BCG induction-only treatment than Ta low-grade (LG) (p = 0.029, p = 0.002). Non-CR (n = 37) had a different neutrophil-to-lymphocyte ratio (NLR) (2.81 ± 1.02 vs. 1.97 ± 0.92) and T staging from CR (p < 0.001, p = 0.008). T1HG recurrence was associated with a worse PFS compared to non-T1HG (13.7 months vs. 101.7 months, p < 0.001). There was no difference in PFS between T1HG and T1LG. T1 and NLR were predictors of response at 3 months in multivariable analysis (p = 0.004, p = 0.029). NLR was also found to be an associated factor with RFS and PFS of bladder cancer (p < 0.001, p < 0.001). BCG induction-only treatment was effective for high-risk TaLG but not for T1HG. T1HG recurrence at 3 months after BCG induction has a poor prognosis for bladder cancer. Preoperative NLR and T1 were predictors of non-CR, and NLR was also associated with the long-term prognosis of bladder cancer.

Abstract To compare the postoperative estimated-glomerular-filtration-rate (eGFR) and parenchymal changes between cold ischemia and zero/selective ischemia for a T1a mass. We analyzed 104 patients who underwent open partial nephrectomy with cold ischemia (53) or zero/selective ischemia (51) for T1a between 2008 and 2018 to determine postoperative renal function changes and associated factors. Postoperative renal function was expressed as (postoperative-eGFR − preoperative-eGFR)/preoperative-eGFR × 100%. Parenchymal enhancement and thicknesses of the ipsilateral kidney as tissue changes were measured on postoperative CT to identify the correlation with the renal function change. Patients with 10% or 25% decrease in eGFR were significantly more in the cold ischemia group (p = 0.032, p = 0.006). On multivariable analysis, preoperative eGFR, ischemic type, and percent change of parenchymal thickness were identified to be significantly associated with postoperative 12 months renal function (B = − 0.367, p = 0.020; B = 6.788, p = 0.042; B = 0.797, p = 0.029). Change in parenchymal thickness was negatively correlated with changes in postoperative renal function (r = − 0.277, p = 0.012). Changes in eGFR were associated with a decrease in parenchymal thickness and the type of ischemic technique. Zero/selective ischemia during partial nephrectomy may have an advantage in preserving postoperative renal function compared to cold ischemia.

Background: One of the most life-threatening comorbidities in elderly cancer patients is cancer cachexia, which is characterized by the ongoing loss of skeletal muscular strength and mass and is also associated with aging. There is a lack of recommendations for optimal resistance training (RT) for those patients. The purpose of this study was to systematically review and quantify the effects of RT on muscular strength and hypertrophy in elderly cancer patients. Methods: Five electronic databases were searched (until January 2020) for studies that met the following criteria: (i) cancer patients aged ≥60 years; (ii) structured and supervised RT intervention for ≥6 weeks; and (iii) measured muscular strength and/or hypertrophy. Results: Thirteen studies (717 participants, average age = 66 years) met the inclusion criteria. RT significantly increased muscular strength (mean effect size = 0.87, 95% confidence interval (95%CI): 0.43–1.32, p < 0.001) and did not significantly induce muscle hypertrophy (mean effect size = 0.09, 95%CI: –0.14 to 0.31, p = 0.45). In subgroup analyses for muscle strength, higher weekly frequency was significantly associated with larger effect size. Egger's test showed no significant publication bias for the 2 outcomes. Conclusion: The results suggest that RT improves muscular strength but does not significantly induce muscle hypertrophy in elderly cancer patients.

Abstract To investigate the significance of detrusor muscle thickness (DMT) to bladder wall thickness (BWT) ratio as a detrusor-sarcopenia and a consistently applicable factor for noninvasive diagnosis of detrusor underactivity (DU). We prospectively performed a urodynamic study of 100 male with medical refractory lower-urinary-tract-symptoms during 2017–2019. The DMT, BWT and DMT/BWT ratio were measured by ultrasonography every 50 mL during bladder filling, and were analyzed for non-invasive diagnosis of DU and prediction of prostate surgery outcome with questionnaire and the maximum-flow-rate. Of the 94 patients, DU was urodynamically diagnosed in 24 (25.5%). The DMT/BWT ratio was maintained in all patients until the 50% of the maximum cystometric capacity (MCC), and then rapidly decreased. At 20% of the MCC, the DMT/BWT ratio was significantly lower in the DU group (44.0 ± 4.9% vs. 49.4 ± 6.7%, p = 0.008). The DMT/BWT ratio of less than 47.5% at 20% of the MCC showed the ideal accuracy for diagnosing DU (AUC = 0.763), and was a predictor of failure at 12 months after prostate surgery (OR 8.78, p = 0.024). A DMT/BWT ratio of less than 47.5% at 20% of the MCC is a consistently applicable factor for non-invasive diagnosis of DU and could also be considered detrusor-sarcopenia.

The obligate intracellular Chlamydiaceae do not need to resist osmotic challenges and thus lost their cell wall in the course of evolution. Nevertheless, these pathogens maintain a rudimentary peptidoglycan machinery for cell division. They build a transient peptidoglycan ring, which is remodeled during the process of cell division and degraded afterwards. Uncontrolled degradation of peptidoglycan poses risks to the chlamydial cell, as essential building blocks might get lost or trigger host immune response upon release into the host cell. Here, we provide evidence that a primordial enzyme class prevents energy intensive de novo synthesis and uncontrolled release of immunogenic peptidoglycan subunits in Chlamydia trachomatis. Our data indicate that the homolog of a Bacillus NlpC/P60 protein is widely conserved among Chlamydiales. We show that the enzyme is tailored to hydrolyze peptidoglycan-derived peptides, does not interfere with peptidoglycan precursor biosynthesis, and is targeted by cysteine protease inhibitors in vitro and in cell culture. The peptidase plays a key role in the underexplored process of chlamydial peptidoglycan recycling. Our study suggests that chlamydiae orchestrate a closed-loop system of peptidoglycan ring biosynthesis, remodeling, and recycling to support cell division and maintain long-term residence inside the host. Operating at the intersection of energy recovery, cell division and immune evasion, the peptidoglycan recycling NlpC/P60 peptidase could be a promising target for the development of drugs that combine features of classical antibiotics and anti-virulence drugs.

Cholesterol serves as an essential lipid molecule in various membrane organelles of mammalian cells. The metabolites of cholesterol also play important functions. Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1), also named as sterol O-acyltransferase 1, is a membrane-bound enzyme residing at the endoplasmic reticulum (ER). It converts cholesterol to cholesteryl esters (CEs) for storage, and is expressed in all cells. CEs cannot partition in membranes; they can only coalesce as cytosolic lipid droplets. Excess CEs are found in the vulnerable region of the brains of patients with late-onset Alzheimer’s disease (AD), and in cell and mouse models for AD. Reducing CE contents by genetic inactivation of ACAT1, or by pharmacological inhibition of ACAT is shown to reduce amyloidopathy and other hallmarks for AD. To account for the various beneficial actions of the ACAT1 blockade (A1B), a working hypothesis is proposed here: the increase in CE contents observed in the AD brain is caused by damages of cholesterol-rich lipid rafts that are known to occur in neurons affected by AD. These damages cause cholesterol to release from lipid rafts and move to the ER where it will be converted to CEs by ACAT1. In addition, the increase in CE contents may also be caused by overloading with cholesterol-rich substances, or through activation of ACAT1 gene expression by various pro-inflammatory agents. Both scenarios may occur in microglia of the chronically inflamed brain. A1B ameliorates AD by diverting the cholesterol pool destined for CE biosynthesis such that it can be utilized more efficiently to repair membrane damage in various organelles, and to exert regulatory actions more effectively to defend against AD. To test the validity of the A1B hypothesis in cell culture and in vivo, the current status of various anti-ACAT1 agents that could be further developed is briefly discussed.

Lubricant (or oil)-impregnated porous surface has been considered as a promising surface treatment to realize multifunctionality. In this study, silicone oil was impregnated into a hard porous oxide layer created by the plasma electrolytic oxidation (PEO) of aluminum (Al) alloys. The monolayer of polydimethylsiloxane (PDMS) from silicone oil is formed on a porous oxide layer; thus, a water-repellent slippery oil-impregnated surface is realized on Al alloy, showing a low contact angle hysteresis of less than 5°. This water repellency significantly enhanced the corrosion resistance by more than four orders of magnitude compared to that of the PEO-treated Al alloy without silicone oil impregnation. The silicone oil within the porous oxide layer also provides a lubricating effect to improve wear resistance by reducing friction coefficients from ~0.6 to ~0.1. In addition, because the PDMS monolayer can be restored by frictional heat, the water-repellent surface is tolerant to physical damage to the oxide surface. Hence, the results of this fundamental study provide a new approach for the post-treatment of PEO for Al alloys.

Background: Diabetes mellitus (DM) is a well-known risk factor for adverse cardiovascular events in patients receiving percutaneous coronary intervention (PCI). Limited data are available on the relative performance of different types of contemporary drug-eluting stents (DES) for diabetic patients. Objectives: The authors investigated the effectiveness and safety profiles of several contemporary DES in patients with DM in a “real-world” clinical setting. Methods: Among 24,516 patients enrolled in a multicenter, prospective registry, 7,823 patients with DM were treated with 4 contemporary DES: 2,877 with a cobalt chromium everolimus-eluting stent (EES), 789 with a biodegradable polymer biolimus-eluting stent, 2,286 with a platinum chromium-EES, and 1,871 with a Resolute zotarolimus-eluting stent. The primary outcome was target vessel failure (TVF) (a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization). Results: The median follow-up duration was 2.9 years. Observed 3-year rates of TVF were not significantly different according to different DES types. On multigroup propensity-score analysis, the adjusted HRs for TVF were similar in between-group comparisons: biodegradable polymer biolimus-eluting stent (HR: 0.94; 95% CI: 0.76-1.16; P = 0.57), platinum chromium-EES (HR: 0.94; 95% CI: 0.81-1.09; P = 0.41), and Resolute zotarolimus-eluting stent (HR: 1.01; 95% CI: 0.86-1.18; P = 0.93) compared with the cobalt chromium-EES (reference). This trend was maintained in patients with non–insulin- and insulin-treated DM. Conclusions: In this multicenter clinical-practice PCI registry, no significant between-group differences were found for a 3-year risk of TVF in patients with DM undergoing PCI with various types of contemporary DES. (Evaluation of the First, Second, and New Drug-Eluting Stents in Routine Clinical Practice [IRIS-DES]; NCT01186133)

Purpose: To determine if chronic administration of Jun-amino terminal kinase (JNK)-inhibitors and LIM-kinase 2 (LIMK2)-inhibitors from the immediate post-injury period in a rat model of cavernous-nerve-crush-injury could normalize cavernous-veno-occlusive-function, and to compare it with phosphodiesterase type 5 (PDE5)-inhibitors. Materials Materials and and Methods:Methods: A total of 75 12-week-old male Sprague–Dawley-rats were randomized into five groups: sham-sur-gery (S), cavernous-nerve-crush-injury (I), cavernous-nerve-crush-injury treated with 10.0 mg/kg LIMK2-inhibitor (L) or 10.0 mg/kg JNK-inhibitor and 10.0 mg/kg LIMK2-inhibitor (J+L) or 20.0 mg/kg udenafil (P) for five-weeks. Five-weeks after surgery, dynamic-infusion-cavernosometry, histological-studies, caspase-3-activity-assay, and Western-blot were investigated. Results:Results: Group-I had lower papaverine-response, higher maintenance-rate and higher drop-rate, compared to Group-S. Group-L, Group-J+L and Group-P showed improvement in the three dynamic-infusion-cavernosometry parameters. The papaverine-response and drop-rate in Group-J+L and Group-P recovered to sham-control level, but those in Group-L did not. Regarding apoptosis, Group-I had decreased content of α-smooth-muscle-actin, increased caspase-3 activity and increased cJun-phosphorylation. The cJun-phosphorylation improved only in Group-J+L. The α-smooth-muscle-actin content and caspase-3-activity in Group-J+L and Group-P improved, but those in Group-L were not. Regarding fibrosis, Group-I had de-creased smooth muscle (SM)/collagen-ratio, increased protein-expression of fibronectin, and increased Cofilin-phosphoryla-tion. Cofilin-phosphorylation was normalized in Group-L and Group-J+L, but not in Group-P. SM/collagen-ratio and protein-expression of fibronectin in Group-L, Group-J+L and Group-P improved. Conclusions:Conclusions: Our data indicate that chronic inhibition of JNK and LIMK2 can restore cavernous-veno-occlusive-function by suppressing cavernous-apoptosis and cavernous-fibrosis, comparable to the results by PDE5-inhibitors. Chronic inhibition of JNK and LIMK2 might be a potential mechanism-specific targeted therapy for cavernous-veno-occlusive-dysfunction induced by cavernous nerve-injury.

PurposeIn this study, we aim to further evaluate the accuracy of ultrasound tracking for intra-fraction pancreatic tumor motion during radiotherapy by a phantom-based study.MethodsTwelve patients with pancreatic cancer who were treated with stereotactic body radiation therapy were enrolled in this study. The displacement points of the respiratory cycle were acquired from 4DCT and transferred to a motion platform to mimic realistic breathing movements in our phantom study. An ultrasound abdominal phantom was placed and fixed in the motion platform. The ground truth of phantom movement was recorded by tracking an optical tracker attached to this phantom. One tumor inside the phantom was the tracking target. In the evaluation of the results, the monitoring results from the ultrasound system were compared with the phantom motion results from the infrared camera. Differences between infrared monitoring motion and ultrasound tracking motion were analyzed by calculating the root-mean-square error.ResultsThe 82.2% ultrasound tracking motion was within a 0.5 mm difference value between ultrasound tracking displacement and infrared monitoring motion. 0.7% ultrasound tracking failed to track accurately (a difference value > 2.5 mm). These differences between ultrasound tracking motion and infrared monitored motion do not correlate with respiratory displacements, respiratory velocity, or respiratory acceleration by linear regression analysis.ConclusionsThe highly accurate monitoring results of this phantom study prove that the ultrasound tracking system may be a potential method for real-time monitoring targets, allowing more accurate delivery of radiation doses.

Pathogenic Chlamydia species are coccoid bacteria that use the rod-shape determining protein MreB to direct septal peptidoglycan synthesis during their polarized cell division process. How the site of polarized budding is determined in this bacterium, where contextual features like membrane curvature are seemingly identical, is unclear. We hypothesized that the accumulation of the phospholipid, cardiolipin (CL), in specific regions of the cell membrane induces localized membrane changes that trigger the recruitment of MreB to the site where the bud will arise. To test this, we ectopically expressed cardiolipin synthase (Cls) and observed a polar distribution for this enzyme in Chlamydia trachomatis. In early division intermediates, Cls was restricted to the bud site where MreB is localized and peptidoglycan synthesis is initiated. The localization profile of 6xHis tagged Cls (Cls_6xH) throughout division mimicked the distribution of lipids that stain with NAO, a dye that labels CL. Treatment of Chlamydia with 3',6-dinonylneamine (diNN), an antibiotic targeting CL-containing membrane domains, resulted in redistribution of Cls_6xH and NAO-staining phospholipids. In addition, 6xHis tagged MreB localization was altered by diNN treatment, suggesting an upstream regulatory role for CL-containing membranes in directing the assembly of MreB. This hypothesis is consistent with the observation that the clustered localization of Cls_6xH is not dependent upon MreB function or peptidoglycan synthesis. Furthermore, expression of a CL-binding protein at the inner membrane of C. trachomatis dramatically inhibited bacterial growth supporting the importance of CL in the division process. Our findings implicate a critical role for localized CL synthesis in driving MreB assembly at the bud site during the polarized cell division of Chlamydia.

Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), the cardinal feature of congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD). KATNAL2, a member of Katanin family microtubule-severing ATPases, is a known ASD risk gene, but its roles in human brain development remain unclear. Here, we show that nonsense truncation of Katnal2 (Katnal2Δ17) in mice results in classic ciliopathy phenotypes, including impaired spermatogenesis and cerebral ventriculomegaly. In both humans and mice, KATNAL2 is highly expressed in ciliated radial glia of the fetal ventricular-subventricular zone as well as in their postnatal ependymal and neuronal progeny. The ventriculomegaly observed in Katnal2Δ17 mice is associated with disrupted primary cilia and ependymal planar cell polarity that results in impaired cilia-generated CSF flow. Further, prefrontal pyramidal neurons in ventriculomegalic Katnal2Δ17 mice exhibit decreased excitatory drive and reduced high-frequency firing. Consistent with these findings in mice, we identified rare, damaging heterozygous germline variants in KATNAL2 in five unrelated patients with neurosurgically treated CH and comorbid ASD or other neurodevelopmental disorders. Mice engineered with the orthologous ASD-associated KATNAL2 F244L missense variant recapitulated the ventriculomegaly found in human patients. Together, these data suggest KATNAL2 pathogenic variants alter intraventricular CSF homeostasis and parenchymal neuronal connectivity by disrupting microtubule dynamics in fetal radial glia and their postnatal ependymal and neuronal descendants. The results identify a molecular mechanism underlying the development of ventriculomegaly in a genetic subset of patients with ASD and may explain persistence of neurodevelopmental phenotypes in some patients with CH despite neurosurgical CSF shunting. [ABSTRACT FROM AUTHOR]

Abstract Background This study, by using a variable-controlled survey model, sought to compare clinical decisions made by dentists with different clinical backgrounds in South Korea regarding teeth with apical periodontitis and to identify factors that influenced decision-making. Methods A questionnaire with 36 questions about identical patient information, clinical signs, and symptoms was filled out by participants. Each question referred to a radiograph that had been manipulated using computer software in order to control tooth-related factors. Participants were instructed to record their demographic information and choose the ideal treatment option related to each radiograph. Simple and multivariable logistic regression analyses (p

Background There are still limited data about the differential effect of sex on long‐term outcomes after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for left main coronary artery disease. This extended follow‐up study of the MAIN‐COMPARE (Ten‐Year Outcomes of Stents Versus Coronary‐Artery Bypass Grafting for Left Main Coronary Artery Disease) registry evaluated clinical outcomes beyond 10 years. Methods and Results Of 2240 patients with unprotected left main coronary artery disease (PCI=1102 and CABG=1138), all‐cause mortality, the composite of death, Q‐wave myocardial infarction, or stroke, and target vessel revascularization were separately evaluated in both sexes. Of 2240 patients, 631 (28.2%) were women and 1609 (71.8%) were men. Women had lower 10‐year incidences of death and serious composite outcomes than men. The adjusted 10‐year risks of adverse outcomes were similar in men. However, the adjusted 10‐year risks were different according to a prespecified period in women. In the short‐term (0–1 year) period, PCI had a significantly lower risk for serious composite outcomes (adjusted hazard ratio [HR], 0.41; 95% CI, 0.19–0.91; P=0.03) compared with CABG. The adjusted risks for death and serious composite outcomes were significantly higher after PCI than after CABG, during the midterm (1–5 years) period (death; adjusted HR, 3.99; 95% CI, 2.01–7.92; P