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Objective. Patients on hemodialysis are highly susceptible to falls and fractures. Amplified apprehension regarding the fear of falling (FOF) constitutes a risk factor that restricts physical activity and escalates the probability of falls among the elderly population. This study aimed to elucidate the association between falls and FOF and physical activity in patients on hemodialysis. Methods. A prospective cohort study was conducted across 9 centers. FOF was assessed using the Falls Efficacy Scale-International (FES-I). Physical activity was assessed using the Japanese version of the International Physical Activity Questionnaire short form. Subsequently, falls were monitored over a duration of 1 year. Logistic regression analysis was performed to evaluate the relationship between falls and FOF and physical activity. In addition, in the receiver operating characteristic analysis, the cutoff value of FES-I that predicts falls was determined using the Youden Index. A restricted cubic spline curve was utilized to analyze the nonlinear association between falls and the FES-I. Results. A total of 253 patients on hemodialysis (70.0 [59.0-77.0] years old; 105 female [41.5%]) were included in the analysis. During the 1-year observation period, 90 (35.6%) patients experienced accidental falls. The median FES-I score was 36.0 (24.0-47.0) points, and patients with higher FES-I scores had more falls. Following adjusted logistic regression analysis, FES-I exhibited an independent association with falls (OR = 1.04; 95% CI = 1.01 -1.06), but physical activity was not. The area under the receiver operating characteristic curve was 0.70 (95% CI = 0.64-0.77), and the FES-I threshold value for distinguishing fallers from non-fallers was determined as 37.5 points (sensitivity 65.6%, specificity 35.0%). A nonlinear relationship between falls and FES-I was observed. Conclusion. FOF was associated with the incidence of falls in patients on hemodialysis. Impact. The evaluation and implementation of interventions targeting the FOF may mitigate the risk of falls. Keywords: Falls, Fear of Falling, Hemodialysis, Physical Activity, Physical Function, Introduction Patients on hemodialysis exhibit a heightened propensity for both falls and fractures compared with their healthier counterparts. (1) The susceptibility of patients on hemodialysis to frailty and sarcopenia surpasses [...]

In the endovascular aneurysm repair era, open surgical repair (OSR) is performed for ruptured abdominal aorta aneurysm (RAAA) in patients with complex aneurysm neck and technical difficulties. Understanding the risk factors of OSR is essential for the clinical selection of the ideal surgical procedure. We aimed to re-evaluate the outcomes of OSR and treatment options for RAAA.

Like many viruses, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mutates. (1) When mutations occur in key proteins, the virus can become more [...]

Neoadjuvant therapy is the standard treatment for patients with locally advanced oesophageal squamous cell carcinoma (OSCC). However, the prognosis remains poor and more intensive neoadjuvant treatment might be needed to improve patient outcomes. We therefore aimed to compare the efficacy and safety of neoadjuvant doublet chemotherapy, triplet chemotherapy, and doublet chemotherapy plus radiotherapy in patients with previously untreated locally advanced OSCC.

In this paper, we describe our discovery of burnettiene A (1) as an antimalarial compound from the culture broth of Lecanicillium primulinum(current name: Flavocillium primulinum) FKI-6715 strain utilizing our original multidrug-sensitive yeast system. This polyene-decalin polyketide natural product was originally isolated as an antifungal active compound from Aspergillus burnettii. However, the antifungal activity of 1has been revealed in only one fungal species, and the mechanism of action of 1remains unknown. After the validation of mitochondrial function inhibitory of 1, we envisioned a new antimalarial drug discovery platform based on mitochondrial function inhibitory activity. We evaluated antimalarial activity and 1showed antimalarial activity against Plasmodium falciparumFCR3 (chloroquine sensitive) and the K1 strain (chloroquine resistant). Our study revealed the utility of our original screening system based on a multidrug-sensitive yeast and mitochondrial function inhibitory activity for the discovery of new antimalarial drug candidates.Graphical AbstractDiscovery of burnettiene A (1) as an antimalarial compound A.

Widely used genotype imputation methods are based on the Li and Stephens model, which assumes that new haplotypes can be represented by modifying existing haplotypes in a reference panel through mutations and recombinations. These methods use genotypes from SNP arrays as inputs to estimate haplotypes that align with the input genotypes by analyzing recombination patterns within a reference panel, and then infer unobserved variants. While these methods require reference panels in an identifiable form, their public use is limited due to privacy and consent concerns. One strategy to overcome these limitations is to use de-identified haplotype information, such as summary statistics or model parameters. Advances in deep learning (DL) offer the potential to develop imputation methods that use haplotype information in a reference-free manner by handling it as model parameters, while maintaining comparable imputation accuracy to methods based on the Li and Stephens model. Here, we provide a brief introduction to DL-based reference-free genotype imputation methods, including RNN-IMP, developed by our research group. We then evaluate the performance of RNN-IMP against widely-used Li and Stephens model-based imputation methods in terms of accuracy (R2), using the 1000 Genomes Project Phase 3 dataset and corresponding simulated Omni2.5 SNP genotype data. Although RNN-IMP is sensitive to missing values in input genotypes, we propose a two-stage imputation strategy: missing genotypes are first imputed using denoising autoencoders; RNN-IMP then processes these imputed genotypes. This approach restores the imputation accuracy that is degraded by missing values, enhancing the practical use of RNN-IMP.

Guidelines recommend pharmacologic VTE prophylaxis for acutely ill medical patients at acceptable bleeding risk, but only the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) model has been validated for bleeding risk assessment.

Proteorhodopsin (PR) is a major family of microbial rhodopsins that function as light-driven outward proton pumps. PR is now widely recognized for its ecological importance as a molecule responsible for solar energy flow in various ecosystems on the earth. However, few concrete examples of the actual use of light by natural microorganisms via PR have been demonstrated experimentally. This study reveals one example of that in a cryophilic bacterium Hymenobacter nivisP3Tisolated from red snow in Antarctica. The results demonstrate light-dependent biochemical and biological responses in H. niviscells, such as the proton pump activity of H. nivisPR (HnPR), which leads to the production of proton motive force, cellular ATP production, and cell growth. In addition, the results of this study demonstrate the photochemical properties of a PR, namely, HnPR, in the membrane of a natural host bacterium. The photocycle of HnPR was much faster than other PRs even at 5 °C, indicating that the proton pump function of HnPR has adapted to the low-temperature environment of Antarctica. Although it is well-known that PR helps natural host microorganisms to use light energy, this study provides another concrete example for understanding the biological role of PR by demonstrating the link between the molecular functions of PR and the light-dependent biochemical and biological responses of a PR-bearing host.

Highly efficient anti-Stokes (AS) photoluminescence (PL) is observed from halide perovskite quantum dots (QDs) due to their strong electron–phonon interactions. The AS PL is particularly intriguing, as it suggests the potential for semiconductor optical cooling if the external quantum efficiency approaches 100%. However, the PL quantum efficiency in QDs is primarily dominated by multiparticle nonradiative Auger recombination processes under intense photoexcitation, which impose limits on the optical cooling gain. Here, we investigate the Auger recombination of dot-in-crystal perovskites. We quantitatively estimate the maximum optical cooling gain and the corresponding excitation intensity. We further conducted optical cooling experiments and demonstrate a maximum photocooling of approximately 9 K from room temperature. Additionally, we confirmed that increasing the excitation intensity leads to a transition from photocooling to photoheating. These observations are consistent with our time-resolved measurements, offering insights into the potential and limitations of optical cooling in semiconductor QDs.

In this paper, we propose a novel physical-layer secret key generation (SKG) scheme, which is based on reduced random pilot selection at a legitimate transmitter and channel interpolation at a legitimate receiver. As a result, the proposed scheme is capable of reducing pilot overhead and increasing secret key capacity (SKC) while suppressing information leakage to an eavesdropper in a correlated eavesdropping channel. More specifically, a subset of full pilot sequence is activated based on the legitimate channels at the legitimate transmitter, and the full channel coefficients are estimated from the received pilot symbol subset at the legitimate receiver with the aid of our channel interpolation. Additionally, despite the non-reciprocal channel due to the presence of a Doppler shift and an additive noise, our scheme achieves high SKG reliability in comparison to that without our reduced pilot selection or channel interpolation. We also derive the theoretical SKC for the proposed scheme. Our simulation results demonstrate that the proposed SKG scheme exhibits a higher performance in terms of both the SKC and key disagreement ratio.

In this paper, we propose a novel physical-layer secret key generation (SKG), which randomly activates a pilot sequence during the channel probing phase. Each legitimate user interpolates the received signals to recover the full channel state information (CSI). Due to the random reduction of the pilot sequence, the proposed scheme can degrade the eavesdropping performance regardless of the correlation between legitimate users and eavesdroppers, thereby improving the secret key capacity (SKC). Furthermore, low power consumption during the channel probing phase can be achieved. Our simulation results demonstrate that the proposed scheme exhibits superior performance in the presence of eavesdroppers.

Purpose: This study proposes a process for detecting slices with bone marrow edema (BME), a typical finding of axSpA, using MRI scans as the input. This process does not require manual input of ROIs and provides the results of the judgment of the presence or absence of BME on a slice and the location of edema as the rationale for the judgment. Methods: First, the signal intensity of the MRI scans of the sacroiliac joint was normalized to reduce the variation in signal values between scans. Next, slices containing synovial joints were extracted using a slice selection network. Finally, the BME slice detection network determines the presence or absence of the BME in each slice and outputs the location of the BME. Results: The proposed method was applied to 86 MRI scans collected from 15 hospitals in Japan. The results showed that the average absolute error of the slice selection process was 1.49 slices for the misalignment between the upper and lower slices of the synovial joint range. The accuracy, sensitivity, and specificity of the BME slice detection network were 0.905, 0.532, and 0.974, respectively. Conclusion: This paper proposes a process to detect the slice with BME and its location as the rationale of the judgment from an MRI scan and shows its effectiveness using 86 MRI scans. In the future, we plan to develop a process for detecting other findings such as bone erosion from MR scans, followed by the development of a diagnostic support system.

Analysis of forward bias degradation reduction of 4H-Silicon Carbide (4H-SiC) PiN diodes on bonded substrates was performed. In the analysis, cathodoluminescence (CL), photoluminescence imaging (PL imaging), and transmission electron microscope (TEM) were used. Under high forward bias stress, the Shockley-type stacking fault (SSF) does not expand into the transferred layer of the bonded substrate, while in the monocrystalline substrate, the SSF expands below the epilayer/substrate interface. The basal plane dislocation (BPD) within the transferred layer does not expand to the SSF. The transferred layer has the effect of suppressing the expansion of SSFs. This effect can be caused by hydrogen implantation for wafer splitting to produce bonded SiC substrates.

A Schiff base in the retinal chromophore of microbial rhodopsin is crucial to its ion transport mechanism. Here, we discovered an unprecedented isotope effect on the C═N stretching frequency of the Schiff base in sodium ion-pumping rhodopsins, showing an unusual interaction of the Schiff base. No amino acid residue attributable to the unprecedented isotope effect was identified, suggesting that the H–O–H bending vibration of a water molecule near the Schiff base was coupled with the C═N stretching vibration. A twist in the polyene chain in the chromophore for the sodium ion-pumping rhodopsins enabled this unusual interaction of the Schiff base. The present discovery provides new insights into the interaction network of the retinal chromophore in microbial rhodopsins.

The superconducting tokamak fusion test device, JT-60SA, was constructed as the Satellite Tokamak project in the Broader Approach Program between Japan and EU. During the JT-60SA integrated commissioning tests of the Nb-Ti equilibrium magnetic field coil EF1 high voltage (∼5 kV) test, the EF1 power supply current surged suddenly and was stopped by the overcurrent interlock of the power supply. At the same time, the vacuum in the cryostat deteriorated, and the pressure in the magnet cooling loops increased. After the system warmed up, visual inspection revealed that discharges occurred between ground and both positive and negative terminal joints of EF1. Several holes, melted by the electrical short and identified as the source of the helium leak into the cryostat, were found in the cylindrical metal part of the joint. The data recorded at the time of the event were analyzed with a conclusion that the discharge first occurred between the positive terminal joint and its support bracket at ground potential and immediately afterward between the neighboring negative terminal joint and its support bracket. These two arcs created a short-circuited loop through which the coil discharged for about 1.4 s. The energy during the short circuit is estimated to be about 60 kJ.

Background: The optimal approach for the safe implementation and education of robotic pancreaticoduodenectomy (RPD) remains unclear. Prolonged operation time may cause surgeon fatigue and result in perioperative complications. To solve this issue, our department adopted task division by the console surgeon turnover between resection and reconstruction in 2022. Methods: This study retrospectively investigated consecutive patients who underwent RPD from November 2009 (initial introduction of RPD) to December 2023. The analysis excluded patients who underwent concomitant resection of other organs. The cases performed by a single console surgeon (single approach) were compared with those performed by two or more console surgeons (multiple approach). Results: This study analyzed 85 consecutive RPD cases, including 51 with the single approach and 34 with the multiple approach. The operation time was significantly shorter (832 vs. 618 min, p< 0.001), and the postoperative major complication was less frequent (45% vs. 12%, p= 0.003) in the multiple approach group, although less experienced surgeons performed the multiple approach (number of RPD experiences: 19 cases vs. 5 cases, p< 0.001). The console surgeon turnover between the resection and reconstruction resulted in a safe pancreatojejunostomy performed by the less experienced surgeon (number of pancreatic reconstruction experiences: 6.5 vs. 14 cases, p= 0.010). Surgeons who started RPD with a multiple approach observed a reduction in surgical time and a lower incidence of complications earlier than those who started with a single approach. Conclusion: Task division during the early introduction phase of RPD using the multiple approach demonstrated potential contributions to improved surgical outcomes and enhanced educational benefits.

The objective of this study was to investigate the lab-scale manufacturing process of insulation fiberboard (1FB) with cellulose nanofibers (CNFs) and evaluate the effects of CNFs on the mechanical and physical properties of the IFB. Because the fabricated IFBs with CNFs had a homogeneous appearance, it was assumed that CNFs can be easily dispersed within IFB by adding them during the mixing stage of the wet process of wood-based board production. The results for the IFBs with CNFs revealed that the density and bending properties increased, while the thickness decreased with an increase in the CNF addition ratio. Furthermore, after the water absorption test, the weight change rates of the IFBs decreased, and the thickness swelling rates increased. Although the size of the specimens was different from the size in JIS A 5905 (Japan Standards Association 2014), the modulus of rupture (MOR) values of IFBs with a target density more than or equal to 0.20 g/[cm.sup.3] were higher than the value of A-class IFB in the standard for all CNF addition ratios. In addition, lower thermal conductivity may be realized under similar MOR values by adding CNFs to IFB. On the other hand, to produce CNF-reinforced IFBs with target density/thickness, it is necessary to develop a method for decreasing the cohesive force derived from CNF aggregation and the compressive force originating from the water surface tension caused by the high water retention of CNFs., Wood-based materials are used extensively in residential construction, particularly in Japan. These materials are made of virgin wood, recycled wood, unused wood species, or thinning wood. Many of the materials [...]

The practical applications of bifunctional ruthenium-based electrocatalysts with two active sites of Ru nanoparticles covered with RuO2skins are limited. One reason is the presence of multiple equally distributed facets, some of which are inactive. In contrast, ruthenium nanorods with a high aspect ratio have multiple unequally distributed facets containing the dominance of active faces for efficient electrocatalysis. However, the synthesis of ruthenium nanorods has not been achieved due to difficulties in controlling the growth. Additionally, it is known that the adsorption capacity of intermediates can be impacted by the surface of the catalyst. Inspired by these backgrounds, the surface-modified (SM) ruthenium nanorods having a dominant active facet of hcp (100) through chemisorbed oxygen and OH groups (SMRu-NRs@NF) are rationally synthesized through the surfactant coordination method. SMRu-NRs@NF exhibits excellent hydrogen evolution in acid and alkaline solutions with an ultralow overpotential of 215 and 185 mV reaching 1000 mA cm–2, respectively. Moreover, it has also shown brilliant oxygen evolution electrocatalysis in alkaline solution with a low potential of 1.58 V to reach 1000 mA cm–2. It also exhibits high durability over 143 h for the evolution of oxygen and hydrogen at 1000 mA cm–2. Density functional theory studies confirmed that surface modification of a ruthenium nanorod with chemisorbed oxygen and OH groups can optimize the reaction energy barriers of hydrogen and oxygen intermediates. The surface-modified ruthenium nanorod strategy paves a path to develop the practical water splitting electrocatalyst.

Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2+) gastric cancer in the DESTINY-Gastric01 trial. Exploratory results from DESTINY-Gastric01 suggested a potential benefit in patients with HER2-low gastric cancer. Spatial and temporal heterogeneity in HER2 expression or gene alteration, an inherent characteristic of gastric cancer tumors, presents a challenge in identifying patients who may respond to T-DXd. Specific biomarkers related to therapeutic response have not been explored extensively. Exploratory analyses were conducted to assess baseline HER2-associated biomarkers in circulating tumor DNA and tissue samples, and to investigate mechanisms of resistance to T-DXd. Baseline HER2-associated biomarkers were correlated with objective response rate (ORR) in the primary cohort of patients with HER2+gastric cancer. The primary cohort had 64% concordance between HER2 positivity and HER2(ERBB2) plasma gene amplification. Other key driver gene amplifications, specifically MET, EGFRand FGFR2, in circulating tumor DNA were associated with numerically lower ORR. Among 12 patients with HER2gain-of-function mutations, ORR was 58.3% (7 of 12). ORR was consistent regardless of timing of immunohistochemistry sample collection. Further investigations are required in larger studies.

We found that the culture broth of fungi showed anti-fungal activity against multidrug-sensitive budding yeast. However, we could not identify the anti-fungal compound due to the small quantity. Therefore, we attempted to increase the productivity of the target compound by the introduction of a global secondary metabolism regulator, laeAto the strain, which led to the successful isolation of 10-folds greater amount of MS-347a (1) than Aspergillussp. FKI-5362. Compound 1was not effective against Candida albicansand the detailed anti-fungal activity of 1remains unverified. After our anti-fungal activity screening, 1was found to inhibit the growth of broad plant pathogenic fungal species belonging to the Ascomycota. It is noteworthy that 1showed little insecticidal activity against silkworms, suggesting its selective biological activity against plant pathogenic fungi. Our study implies that the combination strategy of multidrug-sensitive yeast and the introduction of laeAis useful for new anti-fungal drug discovery.Graphical AbstractDrug discovery platform with a multidrug-sensitive yeast screening system and the introduction of laeAgene.

Few data are available for surveillance decisions focusing on factors related to mortality, as the primary outcome, in intraductal papillary mucinous neoplasm (IPMN) patients. We aimed to identify imaging features and patient backgrounds associated with mortality risks by comparing pancreatic cancer (PC) and comorbidities. We retrospectively conducted a multicenter long‐term follow‐up of 1864 IPMN patients. Competing risk analysis was performed for PC‐ and comorbidity‐related mortality. During the median follow‐up period of 5.5 years, 14.0% (261/1864) of patients died. Main pancreatic duct ≥5 mm and mural nodules were significantly related to all‐cause and PC‐related mortality, whereas cyst ≥30 mm did not relate. In 1730 patients without high‐risk imaging features, 48 and 180 patients died of PC and comorbidity. In the derivation cohort, a prediction model for comorbidity‐related mortality was created, comprising age, cancer history, diabetes mellitus complications, chronic heart failure, stroke, paralysis, peripheral artery disease, liver cirrhosis, and collagen disease in multivariate analysis. If a patient had a 5 score, 5‐ and 10‐year comorbidity‐related mortality is estimated at 18.9% and 50.2%, respectively, more than 7 times higher than PC‐related mortality. The model score was also significantly associated with comorbidity‐related mortality in a validation cohort. This study demonstrates main pancreatic duct dilation and mural nodules indicate risk of PC‐related mortality, identifying patients who need periodic examination. A comorbidity‐related mortality prediction model based on the patient's age and comorbidities can stratify patients who do not require regular tests, especially beyond 5 years, among IPMN patients without high‐risk features. T2022‐0046.

A proposal to change the conserved type of Ipomoeawas published in December 2020, and recommended by the Nomenclature Committee in 2023. This was done in the light of the possible negative consequences for a name change in the crop sweetpotato, which risk our proposal would significantly minimize. Recently, Muñoz‐Rodríguez & al. have published a rebuttal to this proposal, which we respond to here. The objections raised by these authors focus as much on the expertise and credibility of our group of authors as on the merits of our arguments. In this “rebuttal to the rebuttal”, we respond to the scientific questions raised, highlight demonstrated misinterpretation of the specialised literature relevant to this discussion and counter the assertion that a reclassification of Ipomoeeae is impossible given existing evidence. While the currently recognised genera of Ipomoeeae are not all monophyletic, the proposal to change the conserved type of Ipomoeais a necessary step that will allow exploring an improved classification for the tribe Ipomoeeae, either in the form of a better recircumscription of the genera or an efficient infrageneric classification for Ipomoea. Previously published literature has not advocated for the integration of all genera into a single genus, as Muñoz‐Rodríguez and co‐authors have incorrectly suggested, and instead have recommended a reanalysis of the high morphological diversity of the group in the context of expanded phylogenetic studies, with the possible maintenance of some of the existing genera. We believe that, in a concerted collaborative approach and with the contribution of experts from different regions and scientific backgrounds, an improved classification of Ipomoeeae that integrates the principles of monophyly and diagnosability may soon be achieved, and until when some uncertainty may need to be accommodated, with the added reassurance that, regardless of the direction of future systematic rearrangements, the stability of the scientific name of sweetpotato would be preserved.

Abstract: The temperature and pressure dependences of low-frequency Raman scattering were studied on structural phase transformations of Sr2Ta2O7ceramics. The Raman spectrum was measured over a temperature range from 0 to –185°C. The temperature dependence of the Raman shift of a low-lying mode of the B1gsymmetry shows at T= –110°C. This anomaly of Sr2Ta2O7is related to a ferroelectric phase transition. During cooling, the peak width of the B1gmode shows a change at 150°C, and the temperature dependence of Raman shifts of B3g, and B1gmodes becomes abnormal. Under high pressure, we discovered a phase transition between 4 and 5.5 GPa. Angle-dispersive X-ray diffraction data suggest the phase transition from incommensurate to commensurate states.

This study demonstrates that frailty in geriatric trauma patients increases the odds of failure to rescue, defined as mortality after major complications using the TQIP. The study highlights the importance of considering patient frailty when assessing the quality of trauma care.

Pudexacianinium (ASP5354) chloride is an indocyanine green derivative designed to enable enhanced ureter visualization during surgery. The objective of the present analysis was to determine appropriate doses of pudexacianinium for a phase 2, dose‐ranging study (NCT04238481). Real‐time urine pudexacianinium concentration is considered a good pharmacodynamic surrogate marker, since ureter visualization likely depends on its concentration in the ureter. Using plasma and urine concentrations of pudexacianinium from a phase 1 single‐ascending‐dose (0.1‐24.0 mg) study in healthy participants, a 3‐compartment population pharmacokinetic model with a urine output compartment was developed and effectively described the concentration‐time profiles. The individual estimated glomerular filtration rates had a significant impact on drug clearance. Simulations suggested that a 1.0 mg intravenous injection would achieve target urine concentrations over 1 μg/mL (determined from previous nonclinical studies) for 3 hours postdose, assuming a urine production rate of 1.0 mL/min. Based on this simulation, doses of 0.3, 1.0, and 3.0 mg were proposed for the phase 2 study. The observed plasma concentrations were generally consistent with model predictions. For urine, although only limited data could be obtained due to the difficulties of spot urine collection from surgical patients, intraoperative ureter visualization was successful at 1.0 and 3.0 mg.

The objective of this study was to evaluate the relationship between scoliosis and skeletal jaw asymmetry.

Identifying the mechanisms of action of anticancer drugs is an important step in the development of new drugs. In this study, we established a comprehensive screening platform consisting of 68 oncogenes (MANO panel), encompassing 243 genetic variants, to identify predictive markers for drug efficacy. Validation was performed using drugs that targeted EGFR, BRAF, and MAP2K1, which confirmed the utility of this functional screening panel. Screening of a BRCA2-knockout DLD1 cell line (DLD1-KO) revealed that cells expressing SMOand GLI1were resistant to olaparib. Gene set enrichment analysis identified genes associated with DNA damage repair that were enriched in cells overexpressing SMOand GLI1. The expression of genes associated with homologous recombination repair (HR), such as the FANCfamily and BRCA1/2, was significantly upregulated by GLI1expression, which is indicative of PARP inhibitor resistance. Although not all representative genes of the nucleotide excision repair (NER) pathway were upregulated, NER activity was enhanced by GLI1. The GLI1 inhibitor was effective against DLD1-KO cells overexpressing GLI1both in vitro and in vivo. Furthermore, the combination therapy of olaparib and GLI1 inhibitor exhibited a synergistic effect on DLD1-KO, suggesting the possible clinical application of GLI1 inhibitor targeting cancer with defective DNA damage repair. This platform enables the identification of biomarkers associated with drug sensitivity, and is a useful tool for drug development.

A healthy diet is one of the pillars of familial hypercholesterolemia (FH) treatment. However, the best dietary pattern and indication for specific supplementation have not been established. Our aim is to conduct a pilot study to assess the effect of an adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in participants with a probable or definitive diagnosis of FH, treated with moderate/high potency statins.

This study aimed to assess the current state of brachytherapy (BT) resources, practices and resident education in Japan. A nationwide survey was undertaken encompassing 177 establishments facilitating BT in 2022. Questionnaires were disseminated to each BT center, and feedback through online channels or postal correspondence was obtained. The questionnaire response rate was 90% (159/177), and every prefecture had a response in at least one center. The number of centers in each prefecture ranged from 0.6 to 3.6 (median: 1.3) per million population. The annual number of patients in each center ranged from 0 to 272 (median: 31). While most prefectures provided intracavitary (IC) BT for gynecological cancers and interstitial (IS) BT for prostate cancer, only one-third of the prefectures provided IS BT for cancer sites other than the prostate. The institutional image-guided BT implementation rate was 71%. IC and IS BT was performed for 15.4% of IC BT cases of gynecological cancer. Only 47% of the BT training centers answered that they could provide adequate training in BT for residents. The most common reason for this finding was the insufficient number of patients in each center. The results show that, although BT has achieved uniformity in terms of facility penetration, new technologies are not yet widespread enough. Furthermore, IS BT, which requires advanced skills, is limited to a few BT centers, and considerable number of BT training centers do not have sufficient caseloads to provide the necessary experience for their residents.