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Figure legends of supplementary figure S1-S5

Supplementary Fig. S1: A, CTNNB1 siRNAs suppress the target gene and B, the target protein. C, CTNNB1 siRNAs inhibit reporter activity and D, change the expression of Wnt/β-catenin downstream genes.; Supplementary Fig. S2: A, K-756 does not inhibit cell growth of DLD-1/TCF-Luc cells. B, CTNNB1 siRNAs suppress the target gene in COLO 320DM and SW403 cells. C, K-050, and inactive analogue of K-756, does not inhibit COLO 320DM cells.; Supplementary Fig. S3: A, XAV939 and B, IWR-1 stabilize Axins and suppress active β-catenin in COLO 320DM and SW403 cells. C, The Axin stabilization and active β-catenin levels are higher in K-756-treated cells than XAV939-treated cells.; Supplementary Fig. S4: A, PK data of K-756. B, LGR5 inhibition by K-756 in in vitro. Time course PD experiments of C, FGF20, D, LGR5 and E, reporter activity in tumors of K-756-administered mice.; Supplementary Fig. S5: A, Axin and active β-catenin expression in K-756-treated PC-9 and NCI-H322 cells. B, The expression change of Wnt/β-catenin downstream gene in K-756-treated NCI-H322 cells.

Supplementary Table S1: The correlation coefficients of the gene expression profiles between CTNNB1 siRNAs and XAV939- or K-756-treated cells. Supplementary Table S2: The reporter inhibitory activity and cell growth inhibitory activity of K-756, XAV939 and IWR-1.

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been used as a method of controlling intra-abdominal bleeding in case of hemorrhagic shock and an adjunct to improve traditional advanced cardiac life support in nontraumatic cardiac arrest. Partial REBOA is proposed as an alternative method that regulates low volume continuous blood flow across the area of occlusion with the aim of minimizing ischemia-reperfusion injury. Case Presentation: An 82-year-old male suffered an out-of-hospital cardiac arrest due to massive gastric bleeding. He was initially resuscitated with partial REBOA but died of non-occlusive mesenteric ischemia (NOMI). The possible causes of NOMI were the patient’s age, the low flow state with prolonged cardiopulmonary resuscitation, the lower proximal-to-distal gradient of partial REBOA, and the longer time of total occlusion. Conclusion: Further studies may be required to determine the optimal distal pressure during partial REBOA to limit the burden of mesenteric ischemia.

A pelvic belt decreases patient-reported perception of difficulty during the active straight leg raising (ASLR) test in individuals with pelvic girdle pain. However, the influence of a pelvic belt on the perception of difficulty during ASLR was not investigated in pain-free subjects. Therefore, this influence excluding the impact of pain is not clear. This paper aimed to clarify the effect of a pelvic belt on the perception of difficulty and muscle activity during ASLR performance in the subjective heavier side leg in pain-free subjects. Twenty pain-free female subjects participated. ASLR using the subjective heavier side leg was performed under two conditions: without and with a pelvic belt. Muscle activation of the external oblique, internal oblique, rectus abdominis, rectus femoris, and biceps femoris was measured during ASLR using a surface electromyograph. Difference in perceived difficulty in performing ASLR with and without a belt was assessed. In total, 80% of subjects had decreased perception of difficulty using a pelvic belt during ASLR. For ASLR performed with a pelvic belt, muscle activity significantly decreased in the contralateral rectus abdominis, ipsilateral external oblique, and bilateral internal oblique (P0.05). In conclusion, using a pelvic belt can decrease the perception of difficulty during ASLR, and the pelvic belt may improve impairment of load transfer between the trunk and pelvis.

Using multiple scattering theory, we show that the generally accepted expression of transverse resistivity in magnetic systems that host skyrmions, given by the linear superposition of the ordinary (OHE), the anomalous (AHE) and the topological Hall effect (THE), is incomplete and must be amended by an additional term, the "non-collinear" Hall effect (NHE). Its angular form is determined by the magnetic texture, the spin-orbit field of the electrons, and the underlying crystal structure, allowing to disentangle the NHE from the various other Hall contributions. Its magnitude is proportional to the spin-orbit interaction strength. The NHE is an essential term required for decoding two- and three-dimensional spin textures from transport experiments., Comment: 7 pages, 2 figures

Aim Tracheostomy is a common procedure for intubated patients with traumatic brain injury (TBI) in the intensive care unit (ICU) but optimal timing and the predictors of tracheostomy are still unclear. The aim of our study was to explore whether the traumatic variables of head injury predict the need for tracheostomy in intubated TBI patients. Methods A single‐center, retrospective observational study including a series of TBI patients admitted to Fukui Prefectural Hospital from April 1, 2004 to March 31, 2020 was carried out. Our primary outcome was tracheostomy. Patients with TBI who were intubated and admitted into the ICU within 24 h after injury were enrolled. Exclusion criteria were age less than 18 years, pregnancy, mortality within 24 h, post‐cardiac arrest syndrome, and patients for whom life‐sustaining interventions were withheld. Radiologic images were also reviewed and the morphology of the head injury was categorized. Results Seventy‐six patients were included. Forty‐six patients (60.5%) underwent tracheostomy and 30 patients (39.5%) were successfully extubated. Calvarial fracture (odds ratio [OR] 0.34; 95% confidence interval [CI], 0.13–0.88; P = 0.03), Injury Severity Score (OR 1.07; 95% CI, 1.00–1.15; P = 0.04), and Glasgow Comas Scale score (OR 0.84; 95% CI, 0.73–0.96) were statistically significant in the univariable analysis. Multivariate logistic regression identified calvarial fracture as an independent predictor for tracheostomy. The model involving calvarial fracture, Injury Severity Score ≥16, and Glasgow Coma Scale score ≤8 showed the area under the receiver operating characteristic curve for the model was 0.737 (95% CI, 0.629–0.846). Conclusions The absence of calvarial fracture could predict the necessity for tracheostomy in intubated TBI patients when combined with other factors. Further prospective randomized trials are necessary to confirm the findings., Calvarial fracture (odds ratio [OR] 0.34; 95% confidence interval [CI], 0.13–0.88; P = 0.03), Injury Severity Score (ISS) (OR 1.07; 95% CI, 1.00–1.15; P = 0.04), and Glasgow Coma Scale score (GCS) (OR 0.84; 95% CI, 0.73–0.96) were statistically significant in the univariable analysis. Multivariate logistic regression identified calvarial fracture as an independent predictor for tracheostomy and the area under the receiver operating characteristic curve for the model involving calvarial fracture, ISS ≥16, and GCS ≤8 was 0.737 (95% CI, 0.629–0.846). The absence of calvarial fracture could predict the necessity for tracheostomy in intubated patients with traumatic brain injury, when combined with other factors.

We study the energy dispersion relation of the $\ensuremath{\pi}$ and ${\ensuremath{\pi}}^{*}$ bands in epitaxial monolayer graphene on a semi-infinite Ir(111) substrate by a first-principles density-functional calculation. For this purpose, we employ a realistic surface structure in which the $(10\ifmmode\times\else\texttimes\fi{}10)$ unit cell of graphene matches a $(9\ifmmode\times\else\texttimes\fi{}9)$ cell of Ir(111). We determine the surface geometry by using a slab model containing four Ir layers, and the optimized structure is used as input for the subsequent surface embedded Green's function calculation. By taking advantage of semi-infinite calculations, we discuss mini energy gaps at the crossing of the $\ensuremath{\pi}$ band and its replicas, the Rashba-type spin splitting of the $\ensuremath{\pi}$ and ${\ensuremath{\pi}}^{*}$ bands, and also the energy width of both bands arising from interactions with the energy continuum of bulk Ir bands.

We elucidate how the free-electron-like energy dispersion of the L-gap surface state on a Au(111)-(1 × 1) surface is modified by the experimentally observed uniaxial reconstruction of the topmost atomic layer. For this purpose, we perform a first-principles embedded Green’s function calculation for the ( 22 × 3 ) reconstructed semi-infinite Au(111) surface. The obtained band structure unfolded into the surface Brillouin zone of the (1 × 1) surface can be understood in terms of two spin-split parabolic bands centered at the Γ ¯ point, their umklapp-induced replicas centered at reciprocal lattice vectors of the superlattice (SL) with much weaker intensities, and mini band gaps at the crossing of two of them. More importantly, it is revealed that the band-gap size depends not only on the amplitude of the SL potential but also on mutual spin orientations of two crossing bands. Furthermore, we demonstrate that the band-gap size and the charge density distribution of the surface states are closely correlated with spatial profile of the SL potential.

The Wnt/β-catenin pathway, which is associated with disease progression, is activated in many cancers. Tankyrase (TNKS) has received attention as a target molecule for Wnt/β-catenin pathway inhibition. We identified K-476, a novel TNKS inhibitor, a dual pocket binder that binds to both the nicotinamide and ADP-ribose pockets. In a human colon cancer cell line, K-476 specifically and potently inhibited TNKS and led to stabilization of the Axin protein, resulting in Wnt/β-catenin pathway suppression. Aberrant Wnt/β-catenin pathway activation was recently reported as a possible mechanism of ineffectiveness in immune checkpoint inhibitor (ICI) treatment. Because the Wnt/β-catenin pathway activation causes dendritic cell inactivation and suppresses chemokine production, resulting in a paucity of CD8(+) T cells in tumor tissue, which is an important effector of ICIs. Thus, TNKS inhibitors may enhance the efficacy of ICIs. To examine whether K-476 enhances the antitumor effect of anti-PD-L1 antibodies, K-476 was administered orally with an anti-PD-L1 antibody to melanoma-bearing C57BL/6J mice. Although K-476 was ineffective as a monotherapy, it significantly enhanced the antitumor effect in combination with anti-PD-L1 antibody. In mice, intra-tumor infiltration of CD8(+) T cells was increased by combination treatment. K-476 upregulated the chemokine expression (e.g., Ccl3 and Ccl4), which attracted CD8(+) T cells. This was considered to contribute to the increased CD8(+) T cells in the tumor microenvironment. Furthermore, while the potential gastrointestinal toxicity of TNKS inhibitors has been reported, it was not observed at effective doses. Thus, K-476 could be an attractive therapeutic option to enhance the efficacy of ICIs.

This paper studies the edge state current through two-dimensional topological insulator nanoribbons weakly coupled at their interfaces. The authors demonstrate that it is possible to create current-on and current-off states by changing chemical potentials of the leads or by applying a gate voltage in the central island region.

Here, we report on computational fluid dynamics (CFD) simulations conducted to develop a chemical sample collection device inspired by crayfish. The sensitivity of chemical sensors can be improved when used with a sniffing device. By collecting fluid samples from the surroundings, all solute species are also collected for the sensor. Crayfish generate jet-like water currents for this purpose. Compared to simply sucking water, food smells dissolved in the surrounding water can be more efficiently collected using the inflow induced by the jet discharge because of the smaller decay of the inflow velocity with the distance. Moreover, the angular range of water sample collection can be adjusted by changing the directions of the jet discharge. In our previous work, a chemical sample collection device that mimics the jet discharge of crayfish has been proposed. Here, we report CFD simulations of the flow fields generated by the device. By carefully configuring the simulation setups, we have obtained simulation results in which the angular ranges of the chemical sample collection in real experiments is well reproduced. Although there are still some discrepancies between the simulation and experimental results, such simulations will facilitate the process of designing such devices.

[Purpose] Although the abdominal draw-in maneuver improves delayed onset of transverse abdomen in patients with low back pain, it is difficult to perform. We investigated whether the maneuver with tape measure-based feedback was more effective in facilitating isolated transverse abdominal muscle contractions than that without feedback in healthy participants. [Participants and Methods] Twenty healthy males performed the maneuver without feedback (control condition) and then with feedback using a tape measure (tape measure condition) in the crook lying, sitting, and standing positions. A B-mode ultrasonography imaging system was used to determine lateral abdominal muscle thicknesses, the percent changes from before the maneuver were calculated for each condition, and the main effects and interactions for each tested muscle were determined. [Results] The percent change in the thickness of the transverse abdominal muscle was significantly greater under the tape measure condition than under the control condition. The percent change in internal oblique thickness during the maneuver was significantly greater in the standing position than in the crook lying or sitting positions. Significant condition-by-position interactions were not observed for any of the examined muscles. [Conclusion] The abdominal draw-in maneuver with tape measure-based feedback may be more effective at facilitating isolated transverse abdominal contractions in all the positions than that without feedback.

[Purpose] This study aimed to assess the influence of ultrasound (US) transducer tilt on muscle thickness and echo intensity of the rectus femoris muscle (RF) in healthy subjects. [Subjects and Methods] Fourteen healthy male subjects (20.8 ± 0.8 years) participated in this study. Transducer tilt was measured during US, with a digital angle gauge. Muscle thickness and echo intensity were measured in 4 transducer tilt conditions: reference angle; +3°; +6°; and +9° cranial from the reference angle. [Results] All differences in transducer tilt relative to the reference condition were larger than the minimal detectable change (MDC) of the reference condition. All differences in muscle thickness relative to the reference condition were not larger than the MDC of the reference condition. All differences in the echo intensity relative to the reference condition, except between the reference and the +3° condition, were larger than the MDC of the reference condition. [Conclusion] Our results indicated that an examiner should maintain a precise transducer tilt during repeated US measurements to quantify the minimal change in the echo intensity of the RF.

[Purpose] The purpose of this investigation was to compare the activities of the abdominal muscles and peak expiratory flow between forced vital capacity and fast expiration exercise. [Subjects and Methods] Fifteen healthy male participated in this study. Peak expiratory flow and electromyographic activities of the rectus abdominis, external oblique, and internal oblique/transversus abdominis muscles were measured during forced vital capacity and fast expiration exercise and then peak amplitude and its appearance time were obtained. [Results] Peak expiratory flow values were significantly higher during fast expiration exercise than during forced vital capacity. The internal oblique/transversus abdominis muscles showed significantly higher peak amplitude during fast expiration exercise than during forced vital capacity. However, there were no significant differences between forced vital capacity and fast expiration exercise in the rectus abdominis and external oblique muscles. There was no difference in the appearance time of the peak amplitude between forced vital capacity and fast expiration exercise in any muscle. [Conclusion] Fast expiration exercise might be beneficial for increasing expiratory speed and neuromuscular activation of the internal oblique/transversus abdominis muscles compared to forced vital capacity. These findings could be considered when recommending a variation of expiratory muscle strength training as part of pulmonary rehabilitation programs.

This paper reports on the development of compact surface plasmon resonance (SPR) sensors for mobile robot olfaction. Underwater robots benefit from olfactory sensing capabilities in various tasks including the search for unexploded ordnance and undersea wreckage. Although the SPR-based chemical sensor is a promising sensing platform, the cumbersome optical setup has been limiting its use on mobile robots. The proposed sensor employs a periodic metal structure formed on a self-assembled layer of polystyrene particles of 200 nm in diameter. With the grating of this size, SPR can be excited even with a simple LED light source. The change in the absorbance is simply measured using a photodiode. Demonstration of the proposed SPR sensor is provided by mounting the sensors on an underwater crayfish robot that autonomously searches for a chemical source. The fabricated sensor shows linear response to ascorbic acid for a concentration range from 20 to 80 mM. Responses of the bare and thiol-coated gold nanostructure to different chemical substances are presented to show the change in the selectivity of the sensor by the coating. Discussions are made on the importance of sample collection for the sensor to attain sensitive chemical detection on a mobile robot.

Background Neck pain is one of the most prevalent musculoskeletal conditions. Manual mobilization plus exercise are recommended for treating people with acute neck pain with movement coordination impairments. Therefore, it is important to consider a safe and effective coordination exercise for the cervical muscles. Using an oscillating device by holding it in the mouth might be a type of coordination exercise for the cervical muscles. Objectives This study aimed to compare the activities of the cervical muscles while using an oscillating blade held in the mouth with different swings. Methods Ten healthy male university students participated in this study (20.8 ± 0.9 years). The activities of the sternocleidomastoid and cervical extensor muscles were measured using electromyography while using an oscillating blade held in the mouth in horizontal orientation (up-down oscillation). Participants were asked to oscillate the device in one of the following swings: Cervical flexion-extension and knee flexion-extension. Both exercises were performed in a standing position. All EMG activities were normalized by EMG activities during maximum voluntary contractions of those muscles. Results The activities of the sternocleidomastoid with knee flexion-extension (5.7 ± 4.8 %) present significantly lower muscle activities (P = 0.011) than those with cervical flexion-extension (12.2 ± 8.6%). The activities of the cervical extensor muscles with knee flexion-extension (10.7 ± 6.5%) present significantly lower muscle activities (P < 0.001) than those with cervical flexion-extension (17.5 ± 10.3%). Conclusions The results of this study indicated that the exercise with knee flexion-extension had lower load for the cervical muscles than that with cervical flexionextension. The findings of this study could be basic information for grading intensity of cervical coordination exercise using an oscillating blade held in the mouth.

Convolutional Long Short-Term Memory Neural Networks (CNN-LSTM) are a variant of recurrent neural networks (RNN) that can extract spatial features in addition to classifying or making predictions from sequential data. In this paper, we analyzed the use of CNN-LSTM for gas source localization (GSL) in outdoor environments using time series data from a gas sensor network and anemometer. CNN-LSTM is used to estimate the location of a gas source despite the challenges created from inconsistent airflow and gas distribution in outdoor environments. To train CNN-LSTM for GSL, we used temporal data taken from a 5 &times, 6 metal oxide semiconductor (MOX) gas sensor array, spaced 1.5 m apart, and an anemometer placed in the center of the sensor array in an open area outdoors. The output of the CNN-LSTM is one of thirty cells approximating the location of a gas source. We show that by using CNN-LSTM, we were able to determine the location of a gas source from sequential data. In addition, we compared several artificial neural network (ANN) architectures as well as trained them without wind vector data to estimate the complexity of the task. We found that ANN is a promising prospect for GSL tasks.

Shockley surface states of a bulk crystal with both time reversal and space inversion symmetries exhibit the Rashba spin splitting due to the broken space inversion symmetry at the surface. Since the evanescent states in the bulk region are doubly degenerate with respect to spin degrees of freedom even in the presence of spin-orbit interaction (SOI), one might think that the entire spin splitting occurs via the SOI in the surface region where the potential energy deviates from the bulk one. In the present work, we elucidate why this is not the case. Namely, in the presence of SOI, the complex energy bands are modified such that a pair of evanescent states having the same energy and the same complex wave number become two distinct solutions of the Schr\"odinger equation that do not satisfy the same boundary condition. Since the tail of the surface-state wave function is expressed as a superposition of these evanescent waves, the bulk region also contributes to the Rashba spin splitting. We illustrate this effect by a first-principles calculation for Au(111) and by a simplified $sp$-band model Hamiltonian on a square lattice.

This study examines long-term ocean pH data to evaluate ocean acidification (OA) trends at two coastal research institutions located on the Sea of Japan and the Pacific Ocean. These laboratories are located away from the influences of large rivers and major industrial activity. Measurements were performed daily for the past 30 years (1980s–2010s). The average annual ocean pH for both sites showed generally negative trends. These trends were – 0.0032 and – 0.0068 year–1(p

[Purpose] The aim of this investigation was to determine the effects of 4 weeks of fast expiration exercises performed without pressure on respiratory muscle strength. [Subjects and Methods] Respiratory muscle strength of the training group that performed fast expiration exercises (n=12) was compared with that of a control group that performed no exercises (n=12). The fast expiration exercises were performed using a peak expiratory flow meter device and consisted of 20 fast expiration exercises performed 3 times per week for 4 weeks. Maximal expiratory and inspiratory pressures were evaluated as respiratory muscle strength using a spirometer pre- and post- intervention. [Results] There were significant increases in maximal expiratory pressure from 76.9 ± 29.1 to 96.1 ± 37.5 cmH2O and maximal inspiratory pressure from 80.8 ± 36.6 to 95.3 ± 37.6 cmH2O in the training group, but there was no significant difference in respiratory muscle strength between pre- and post-intervention in the control group. [Conclusion] Fast expiration exercises may be beneficial for increasing respiratory muscle strength. The findings of this study should be considered when prescribing a variation of the expiratory muscle strength training, as part of a pulmonary rehabilitation program.