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The capacitive deionization technology uses the electrochemical adsorption of ions in porous electrodes to desalinate seawater or brackish water. Recently, capacitive deionization has gained significant attention as a technology for selective adsorption of ionic species from multicomponent aqueous electrolytes. To investigate the mechanism of selective adsorption at the molecular level, we performed molecular dynamics simulations of aqueous electrolytes and porous electrodes with different divalent or trivalent ions, electrode pore sizes, and applied voltages. We calculated the free energy barriers preventing ions from entering the pores of the electrode and the structure of the water molecules near the ions and the electrode surface under various conditions. Our results suggest that, when the pore and ion sizes are comparable, the steric and electrostatic interactions between the hydrated ions and electrode pores are comparable in magnitude. Moreover, the relative importance of the two interactions can be reversed by slight changes in the external conditions, such as the ion size, valence of the ions, electrode pore size, and applied voltage. Thus, by finely tuning the electrode pore size and the applied voltage, it may be possible to selectively adsorb a particular ionic species from a multicomponent electrolyte through capacitive deionization using a porous electrode. [ABSTRACT FROM AUTHOR]

The effect of the presence of Ar on the isomerization reaction HCN ⇄ CNH is investigated via machine learning. After the potential energy surface function is developed based on the CCSD(T)/aug-cc-pVQZ level ab initio calculations, classical trajectory simulations are performed. Subsequently, with the aim of extracting insights into the reaction dynamics, the obtained reactivity, that is, whether the reaction occurs or not under a given initial condition, is learned as a function of the initial positions and momenta of all the atoms in the system. The prediction accuracy of the trained model is greater than 95%, indicating that machine learning captures the features of the phase space that affect reactivity. Machine learning models are shown to successfully reproduce reactivity boundaries without any prior knowledge of classical reaction dynamics theory. Subsequent analyses reveal that the Ar atom affects the reaction by displacing the effective saddle point. When the Ar atom is positioned close to the N atom (resp. the C atom), the saddle point shifts to the CNH (HCN) region, which disfavors the forward (backward) reaction. The results imply that analyses aided by machine learning are promising tools for enhancing the understanding of reaction dynamics. [ABSTRACT FROM AUTHOR]

Background: Clear cell sarcoma (CCS) and alveolar soft part sarcoma (ASPS) are rare, and standard systemic therapy is not established except for sunitinib in ASPS. It is known that CCS and ASPS have a common biological feature of melanoma and Xp11.2/TFE3 translocation renal cell carcinoma, and immune‐checkpoint inhibitors (ICIs) are effective in these tumors. The authors conducted a phase 2 trial to evaluate the efficacy and safety of nivolumab for CCS and ASPS. Methods: The number of patients expected to be enrolled was 15–25 and was determined based on the Bayesian design. The primary end point was the confirmed objective response rate (ORR) according to the central review and the secondary end points included ORR, progression‐free survival (PFS), overall survival (OS), and safety. Results: A total of 26 patients (CCS, 12; ASPS, 14) were enrolled. Efficacy and safety were analyzed on 25 and 26 patients, respectively. The minimum number of responses required for a positive conclusion regarding the efficacy was four. However, only one patient (4.0%) with ASPS had a partial response. Complete response, stable disease, progression disease, and not evaluable were 0%, 60%, 32%, and 4.0%, respectively. Adverse events of grade 3 or 4 occurred in 57.7% (15 of 26). The median PFS was 4.9 months (95% confidence interval [CI], 3.7–8.6 months) and the median OS was 15.8 months (95% CI, 8.2–not reached). Conclusions: The primary end point of the ORR was not met for CCS and ASPS on the central review. Further studies are needed to evaluate ICIs in patients with ASPS. This study evaluated the efficacy and safety of nivolumab monotherapy for patients with clear cell sarcoma and alveolar soft part sarcoma in a single‐arm phase 2 trial. The results showed no clinical efficacy among patients with clear cell sarcoma, whereas further investigation was considered necessary among patients with alveolar soft part sarcoma. [ABSTRACT FROM AUTHOR]

Triangulenes as neutral radicals are becoming promising candidates for future applications such as spintronics and quantum technologies. To extend the potential of the advanced materials, it is of importance to control their electronic and magnetic properties by multiple graphitic nitrogen doping. Here, we synthesize triaza[5]triangulene on Au(111) by cyclodehydrogenation, and its derivatives by cleaving C−N bonds. Bond‐resolved scanning tunneling microscopy and scanning tunneling spectroscopy provided detailed structural information and evidence for open‐shell singlet ground state. The antiferromagnetic arrangement of the spins in positively doped triaza[5]triangulene was further confirmed by density function theory calculations. The key aspect of triangulenes with multiple graphitic nitrogen is the extra pz electrons composing the π orbitals, favoring charge transfer to the substrate and changing their low‐energy excitations. Our findings pave the way for the exploration of exotic low‐dimensional quantum phases of matter in heteroatom doped organic systems. [ABSTRACT FROM AUTHOR]

Triangulenes as neutral radicals are becoming promising candidates for future applications such as spintronics and quantum technologies. To extend the potential of the advanced materials, it is of importance to control their electronic and magnetic properties by multiple graphitic nitrogen doping. Here, we synthesize triaza[5]triangulene on Au(111) by cyclodehydrogenation, and its derivatives by cleaving C−N bonds. Bond‐resolved scanning tunneling microscopy and scanning tunneling spectroscopy provided detailed structural information and evidence for open‐shell singlet ground state. The antiferromagnetic arrangement of the spins in positively doped triaza[5]triangulene was further confirmed by density function theory calculations. The key aspect of triangulenes with multiple graphitic nitrogen is the extra pz electrons composing the π orbitals, favoring charge transfer to the substrate and changing their low‐energy excitations. Our findings pave the way for the exploration of exotic low‐dimensional quantum phases of matter in heteroatom doped organic systems. [ABSTRACT FROM AUTHOR]

Objectives: Inguinal hernia (IH) is a common postoperative complication after robot‐assisted radical prostatectomy (RARP). We developed a novel clipping technique for the prevention of IH developing after RARP. Methods: This cohort included 759 consecutive patients who underwent RARP for prostate cancer at the University of Tokyo Hospital between January 2011 and December 2018. We reviewed clinical parameters and identified the risk factors of postoperative IH. The prophylactic preventive procedure of IH development was performed by clipping the peritoneum and underlying tissue around the internal inguinal ring using Hem‐o‐Lok clip to prevent the prolapse of the intestine through the internal inguinal ring. Results: In total, 236 patients received the clipping procedure. The median follow‐up time was 50 months. The incidence rate of IH was 10.8% (78/720). The median time to the diagnosis of IH was 10 months. Univariate analysis revealed that patients with higher age (age ≥ 63), low BMI (BMI < 25 kg/m2), and lower number of surgical experiences (Surgical experience < 40) showed a significantly higher odds ratio of developing IH. Multivariate analysis showed that "BMI < 25 kg/m2" and "Surgical experience < 40" were independent predictive factors of IH. Among the patients with a high risk of IH due to receiving surgery from inexperienced surgeons, there was a statistically significant preventive effect for the patients with "BMI ≥ 25 kg/m2" by the novel clipping procedure. Conclusions: The novel clipping procedure reduced the risk of post‐operative IH in obese patients when the RARP was performed by inexperienced surgeons. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) is common among men and has become a significant societal issue. Localized PC has a good prognosis with appropriate treatment. Prostatectomy, particularly robot-assisted radical prostatectomy (RARP), has become a common treatment since the da Vinci prostatectomy was approved by the FDA in 2001. The current study aimed to assess the learning curve for RARP, focusing on anastomosis time, using the cumulative sum (CUSUM) method. Data were collected from Nagoya City University Hospital between May 2011 and December 2018 and included 469 surgeries performed by experienced surgeons. Our findings indicated that, on average, 11 patients were required to complete the initial phase and 24 patients were required to complete the consolidation phase of anastomosis. Additionally, for complete resection of pT2c cases, 16 cases were required for the initial phase and 27 cases were required for the consolidation phase. The CUSUM method proved useful for visualizing trends in surgical proficiency, although the study noted potential confounding biases and limitations in evaluating surgical proficiency based solely on surgical time or positive surgical margins. [ABSTRACT FROM AUTHOR]

Ice nucleating particles (INPs) affect the cloud radiative budget in the rapidly warming Arctic by changing the cloud liquid/ice phase balance. Dust emitted in the Arctic (Arctic dust) has been suggested to be a major contributor to INPs in the Arctic lower troposphere. However, how Arctic dust and its impacts on ice nucleation change with Arctic warming has not been explored. Here we find that the simulated dust emission flux in the Arctic (>60°N) in global model simulations increases by 20% from 1981–1990 to 2011–2020. This increase weakens the sensitivity of ice nucleation in Arctic lower tropospheric clouds to warming by 40% compared to the case without considering Arctic dust emission increases. Our results demonstrate a better understanding of the counterbalancing feedbacks of Arctic dust (i.e., increasing emissions and decreasing ice nucleation efficiency) is needed for more accurate estimates of changes in ice nucleation in the rapidly changing Arctic climate. [ABSTRACT FROM AUTHOR]

Aim: Central liver resections are considered to be high‐risk procedures due to postoperative biliary complications. However, anatomical aspect‐related causes are underreported. Focusing upon right anterior sectionectomy (H58) and central bisectionectomy (H458), we assessed risk factors for postoperative biliary complications. Methods: We retrospectively reviewed patients who underwent H58 or H458 in our hospital between April 2008 and June 2023 (n = 58). We conducted univariate and multivariate analysis of risk factors of postoperative biliary complications among perioperative factors and anatomical factors including the branching type of the right posterior hepatic duct (RPHD) and the length of the right hepatic duct (RHD). Results: Twenty‐six patients (44.8%) had postoperative biliary complications. Potent risk factors in univariate analysis were the tumor proximity to the right anterior Glissonean branch and longer RHD (both P < 0.01). In multivariate analysis, longer RHD was the only independent risk factor and its hazard (95% confidence interval [CI] was 1.19 (1.05–1.35). Receiver operating characteristics curve (ROC) analysis and the area under the ROC showed that 10 mm was the optimal cutoff value with high discriminatory power (0.72). Considering intraoperative procedures of the right anterior segment Glissonean branch dissection, mass ligation at the second‐order branch had marginal risk, especially in patients with RHD >10 mm; its hazard (95% CI) was 5.83 (0.95–35.7). Conclusion: Anatomical factors of RPHD and RHD influenced postoperative biliary complications in this cohort. The supraportal with RHD type was most common anatomy but considered to be hazardous if the RHD was >10 mm. [ABSTRACT FROM AUTHOR]

Background: Lipolysis-stimulated lipoprotein receptor (LSR), a lipid receptor, is associated with cancer progression. However, detailed effects on intracellular metabolism are unclear. We aimed to elucidate the mechanism of LSR-mediated lipid metabolism in gastric cancer. Methods: We investigated lipid metabolic changes induced by lipoprotein administration in gastric cancer cells and evaluated the significance of LSR expression and lipid droplets formation in gastric cancer patients. The efficacy of inhibiting β-oxidation in gastric cancer cells was also examined in vitro and vivo. Results: In gastric cancer cells, LSR promoted cellular uptake of lipoprotein and cell proliferation. Furthermore, the inhibition of LSR in gastric cancer cells expressing high levels of LSR counteracted both effects. Immunohistochemical analysis of human gastric cancer tissues showed that the increase in lipid droplets via LSR is a factor that influences prognosis. Lipidomics analysis of LSR-high-expressing gastric cancer cells revealed an increase in β-oxidation. Based on these results, we used etomoxir, a β-oxidation inhibitor, and found that it inhibited cell proliferation as well as the suppression of LSR. Similarly, in a mouse xenograft model of LSR-highly expressing gastric cancer cells, the tumor growth effect of high-fat diet feeding was counteracted by etomoxir, consistent with the Ki-67 labeling index. Conclusions: We demonstrated that lipids are taken up into gastric cancer cells via LSR and cause an increase in β-oxidation, resulting in the promotion of cancer progression. Controlling LSR-mediated lipid metabolism may be a novel therapeutic strategy for gastric cancer. [ABSTRACT FROM AUTHOR]

The mechanism of X-ray outbursts in Be X-ray binaries remains a mystery, and understanding their circumstellar discs is crucial for a solution of the mass-transfer problem. In particular, it is important to identify the Be star activities (e.g. pulsations) that cause mass ejection and, hence, disc formation. Therefore, we investigated the relationship between optical flux oscillations and the infrared (IR) excess in a sample of five Be X-ray binaries. Applying the Lomb–Scargle technique to high-cadence optical light curves from the Transiting Exoplanet Survey Satellite (⁠|${\it TESS}$|⁠), we detected several significant oscillation modes in the 3–24 h period range for each source. We also measured the IR excess (a proxy for disc growth) of those five sources, using J -band light curves from Palomar Gattini-IR. In four of the five sources, we found anticorrelations between the IR excess and the amplitude of the main flux oscillation modes. This result is inconsistent with the conventional idea that non-radial pulsations drive mass ejections. We propose an alternative scenario where internal temperature variations in the Be star cause transitions between pulsation-active and mass-ejection-active states. [ABSTRACT FROM AUTHOR]

It is established that neurogenesis of dentate gyrus is increased after ischemic insult, although the regulatory mechanisms have not yet been elucidated. In this study, we focused on Ezh2 which suppresses gene expression through catalyzing trimethylation of lysine 27 of histone 3. Male gerbils were injected with adeno-associated virus (AAV) carrying shRNA targeting to Ezh2 into right dentate gyrus 2 weeks prior to forebrain ischemia. One week after ischemia, animals were injected with thymidine analogue to label proliferating cells. Three weeks after ischemia, animals were killed for histological analysis. AAV-mediated knockdown of Ezh2 significantly decreased the ischemia-induced increment of proliferating cells, and the proliferated cells after ischemia showed significantly longer migration from subgranular zone (SGZ), compared to the control group. Furthermore, the number of neural stem cells in SGZ significantly decreased after ischemia with Ezh2 knockdown group. Of note, Ezh2 knockdown did not affect the number of proliferating cells or the migration from SGZ in the non-ischemic condition. Our data showed that, specifically after ischemia, Ezh2 knockdown shifted the balance between self-renewal and differentiation toward differentiation in adult dentate gyrus. [ABSTRACT FROM AUTHOR]

High clouds play an important role in climate variations by shading the sun and contributing to the greenhouse effect. It has been suggested that these variations are strongly controlled by atmospheric circulations; however, the relationship between high clouds and circulations in global simulations has been confirmed only for a limited number of general circulation models (GCMs). Increasing our understanding of this relationship requires a more complete dataset of state-of-the-art GCMs. This study quantifies the relationship between high clouds and circulations by spatial and temporal correlation using data from 28 atmospheric GCMs along with a global nonhydrostatic model, a new-type of GCM, and reveals a robust and strong relationship in most models. This study also finds that the sensitivity, which is defined as the slope of the relationship between high clouds and mass fluxes of circulations, is highly model-dependent. This suggests that a similar change of circulations does not guarantee that of high clouds, which could be one reason for the complexity in projecting high-cloud changes due to warming. Moreover, this study confirms in both observation and models that the relationship with circulations is stronger for medium-thickness and thick high clouds than for thin clouds. Furthermore, the relationship between high clouds and circulations is more convincing in near-equatorial regions between 15°S–15°N, the ascending branch of the Hadley circulation, where deep convection is especially active. [ABSTRACT FROM AUTHOR]

Myxofibrosarcoma (MFS), an aggressive soft tissue sarcoma, presents a significant challenge because of its high recurrence rate, distal metastasis, and complex genetic background. Although surgical resection is the standard treatment for MFS, the outcomes are unsatisfactory and effective non-surgical treatment strategies, including drug therapy, are urgently warranted. MFS is a rare tumor that requires comprehensive preclinical research to develop promising drug therapies; however, only two MFS cell lines are publicly available worldwide. The present study reports two novel patient-derived MFS cell lines, NCC-MFS7-C1 and NCC-MFS8-C1. These cell lines have been extensively characterized for their genetic profile, proliferation, spheroid-forming capacity, and invasive behavior, confirming that they retain MFS hallmarks. Furthermore, we conducted comprehensive drug screening against these cell lines and six others previously established in our laboratory to identify potential therapeutic candidates for MFS. Among the screened agents, actinomycin D, bortezomib, and romidepsin demonstrated considerable antiproliferative effects that were superior to those of doxorubicin, a standard drug, highlighting their potential as novel drugs. In conclusion, NCC-MFS7-C1 and NCC-MFS8-C1 are valuable research resources that contribute to the understanding of the pathogenesis and development of novel therapies for MFS. [ABSTRACT FROM AUTHOR]

Synovial sarcoma (SS) is identified as a sarcoma with monomorphic blue spindle cells that display variable epithelial differentiation and is characterized by the SS18::SSX fusion gene. SS accounts for approximately 5–10% of all soft tissue sarcomas, making it a relatively common type within this group of tumors. Since SS is generally sensitive to chemotherapy, the standard treatment for SS includes extensive surgical resection, complemented by neoadjuvant chemotherapy with several approved anticancer drugs. However, in advanced and metastatic cases, the efficacy of these drugs is limited, resulting in poor prognoses. This underscores the need for innovative therapeutic strategies. Patient-derived cancer cell lines are essential tools for basic and preclinical research, yet only four SS cell lines are publicly available. To facilitate the studies of SS, we have developed a novel SS cell line, named NCC-SS6-C1, derived from surgically excised tumor tissue of an SS patient. NCC-SS6-C1 cells preserve the SS18::SSX1 fusion gene, consistent with the genetic characteristics of the original tumor. The cells exhibit continuous proliferation, invasiveness, and the ability to form spheroids. Additionally, we confirmed that this cell line was useful for evaluating the efficacy of anticancer drugs. Our results suggest that NCC-SS6-C1 is a useful tool for basic and pre-clinical studies of SS. [ABSTRACT FROM AUTHOR]

Cloud feedback is the largest source of uncertainty in climate sensitivity. This feedback is generally discussed in terms of radiative flux at the top of the atmosphere, but the vertical distribution of the contribution of cloud changes to the top‐of‐atmosphere cloud feedback should be discussed to understand the feedback in greater detail. We have developed a simple analysis method called "vertical profile analysis of cloud feedback," which simply uses radiative flux data from each level of the model. The analysis is applied for typical cloud regimes and the results are discussed together with cloud fraction change profiles. The advantages and disadvantages of the vertical profile analysis, compared with the commonly used International Satellite Cloud Climatology Project (ISCCP) histogram kernel method, are discussed. Our analysis has the advantage of resolving the detailed vertical profiles of the contribution to the top‐of‐atmosphere cloud feedback from the changes in cloud regimes associated with warming, such as reduced cloud cover and upward shifts of the cloud layer in subtropical low‐cloud regions as well as the increased height of the melting layer in tropical deep convection. The main disadvantage is that the vertical profile analysis cannot represent the feedback components sorted by cloud optical thickness as in the ISCCP histogram kernel method. Plain Language Summary: Rising temperature caused by global warming will depend to a large extent on how clouds will change in the future climate. It is therefore important to know in detail how clouds and radiation will change in the future, not only horizontally but also vertically, in order to understand the mechanism. We have developed a simple but useful method for analyzing the vertical profile of changes in radiation and clouds. This detailed information is useful for understanding the mechanism of changes in clouds and radiation. We have compared this analysis method with the conventional method and discussed the advantages and disadvantages of the two methods in detail, based on simulation results. Although our vertical profile analysis provides more detailed vertical profile information, both methods can be used effectively, depending on the purpose of the analysis. Key Points: A simple analysis method is proposed to obtain a detailed vertical profile of cloud feedbackApplications are shown for typical regimes including stratocumulus, shallow convection, mid‐latitude clouds, and tropical deep convectionThe advantages and disadvantages of this analysis method relative to the conventional method are presented [ABSTRACT FROM AUTHOR]

Amyloidosis is a disease in which amyloid protein is deposited in organs and tissues, resulting in functional impairment. Amyloidosis occurs in 12%–30% of patients with multiple myeloma, but in rare cases, amyloidosis may precede the diagnosis of multiple myeloma. Our patient was a 76‐year‐old Japanese male on dialysis. Multiple nodules accompanied by ulcers were observed on his tongue. He had no subjective symptoms or clinical findings associated with multiple myeloma. The histopathological findings suggested amyloidosis. We suspected both systemic and localized amyloidosis and performed a comprehensive systemic examination. Since the patient had been on dialysis for only a short period of time (~3 months), dialysis‐related amyloidosis was ruled out. After blood and urine tests, a diagnosis of multiple myeloma was made. Chemotherapy treatment was started, but the patient's multiple myeloma could not be suppressed and the tongue amyloidosis worsened, leading to his death 2 years and 2 months after the initial diagnosis. [ABSTRACT FROM AUTHOR]

Background: Capicua transcriptional repressor-double homeobox 4 sarcoma (CDS) is a rare and aggressive malignant soft tissue tumor that typically arises within the soft tissues. We report an exceptionally rare case of a gastric CDS successfully resected despite its extensive invasion into surrounding organs. Case presentation: A 48-year-old male presented with a progressively enlarging abdominal mass. Upper gastrointestinal endoscopy revealed a large ulcerative tumor on the posterior gastric wall. Biopsy results initially suggested a neuroendocrine cell carcinoma. Contrast-enhanced computed tomography showed a 20 cm tumor protruding from the posterior stomach wall, directly invading the pancreas and colon. We performed a multivisceral resection (stomach, pancreatic tail, spleen, and transverse colon) achieving an R0 resection. Pathological examination of the permanent specimen revealed small round cells with high nuclear-to-cytoplasmic ratios. Immunohistochemical staining confirmed the diagnosis of CDS. The patient recovered well and was discharged on postoperative day 33. Conclusions: This case report describes the first detailed account of a surgically resected aggressive CDS originating from the stomach. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is often diagnosed at advanced stages, and early-stage diagnosis of pancreatic cancer is difficult because of nonspecific symptoms and lack of available biomarkers. Methods: We performed comprehensive serum miRNA sequencing of 212 pancreatic cancer patient samples from 14 hospitals and 213 non-cancerous healthy control samples. We randomly classified the pancreatic cancer and control samples into two cohorts: a training cohort (N = 185) and a validation cohort (N = 240). We created ensemble models that combined automated machine learning with 100 highly expressed miRNAs and their combination with CA19-9 and validated the performance of the models in the independent validation cohort. Results: The diagnostic model with the combination of the 100 highly expressed miRNAs and CA19-9 could discriminate pancreatic cancer from non-cancer healthy control with high accuracy (area under the curve (AUC), 0.99; sensitivity, 90%; specificity, 98%). We validated high diagnostic accuracy in an independent asymptomatic early-stage (stage 0-I) pancreatic cancer cohort (AUC:0.97; sensitivity, 67%; specificity, 98%). Conclusions: We demonstrate that the 100 highly expressed miRNAs and their combination with CA19-9 could be biomarkers for the specific and early detection of pancreatic cancer. [ABSTRACT FROM AUTHOR]

We herein report photochromic 1,2-bis(2-methoxy-corannulenyl)perfluorocyclopentene (1) possessing two corannulene moieties as the side aryl units of diarylethene. One enantiomer and the other enantiomer of one chiral atropisomer of 1 respectively forming columnar structures in the crystal were revealed via single-crystal X-ray analysis. Compound 1 exhibited an efficient photochromic behaviour with a large molar absorption coefficient of 5.0 × 104 M−1 cm−1, and significantly high photochemical quantum yields of 0.64 and 0.49 were demonstrated for photocyclization and photocycloreversion reactions, respectively. This high efficiency was rationalized by the changed abundance ratios of atropisomers between the open- and closed-isomers and the shortened distance between reactive carbons with the help of the curved structure. In addition, the application possibility of 1 as a photochromic material was demonstrated in a poly(methyl methacrylate) film. [ABSTRACT FROM AUTHOR]

Allogeneic bone grafts are used to treat bone defects in orthopedic surgery, but the osteogenic potential of artificial bones remains a challenge. In this study, we developed a β-tricalcium phosphate (β-TCP) formulation containing MgO, ZnO, SrO, and SiO2 and compared its bone-forming ability with that of β-TCP without biological elements. We prepared β-TCP discs with 60% porosity containing 1.0 wt% of these biological elements. β-TCP scaffolds were loaded with bone marrow-derived mesenchymal stem cells (BMSC) from 7-week-old male rats and cultured for 2 weeks. ALP activity and mRNA expression of osteogenic markers were evaluated. In addition, scaffolds were implanted subcutaneously in rats and analyzed after 7 weeks. In vitro, the MgO group showed lower Ca concentrations and higher osteogenic marker expression compared to controls. In vivo, the MgO group showed higher ALP activity compared to controls, and RT-qPCR analysis showed significant expression of BMP2 and VEGF. Histopathology, fluorescent immunostaining, and micro-CT also showed relatively better bone formation in the MgO group. β-TCP with MgO may enhance bone morphology in vitro and in vivo and improve the prognosis of patients with substantial and refractory bone defects. [ABSTRACT FROM AUTHOR]

Background: Anal fistula cancer is rare and definitive treatment has not yet been established. Laparoscopic abdominoperineal resection is generally the first choice of treatment if the cancer is determined to be resectable. However, complicated anal fistula cancer often requires extensive resection. Using a myocutaneous flap for reconstruction after resection in such cases, radical resection can be performed regardless of the size of the anal fistula cancer. Case presentation: We report two cases in which we performed laparoscopic abdominoperineal resection with extensive buttock resection and myocutaneous flap reconstruction for widespread anal fistula cancer. One of the cases was reconstruction with a posterior thigh flap, the other was with a bilateral expanded gluteus maximus flap. Both cases were anal fistula cancers that developed from complicated anal fistulas. Conclusions: If the size of anal fistula cancer is large and extended buttock resection is necessary, radical resection of anal fistula cancer is possible using myocutaneous flap for reconstruction after extended abdominoperineal resection. [ABSTRACT FROM AUTHOR]

Epoxy resin has been extensively used in the field of advanced electronic materials as an adhesive and encapsulant owing to its excellent material properties. However, recently, there has been a demand for further improvement in heat resistance, high transparency, environmental resistance, and enhanced handling properties for high-brightness light-emitting diodes. Conventional aromatic epoxy resins lack light resistance; therefore, a colorless and transparent epoxy resin without aromatic rings is desirable. In this study, tris(2,3-epoxypropyl) isocyanurate (TEPIC) was used as a nonaromatic epoxy resin, and three types of TEPIC with different side-chain lengths were prepared. The ultraviolet (UV)-visible absorption properties of TEPIC were evaluated using time-dependent density functional theory, and the practicality of the numerical prediction of light resistance was verified. TEPIC yields a UV absorbance spectrum with a lower intensity than those of conventional aromatic epoxy resins, suggesting that TEPIC is expected to have high light resistance. In addition, their thermomechanical properties and the influence of molecular structure were evaluated using both molecular dynamics (MD) simulations and experiments. The MD simulation and experimental results were in good agreement, indicating that the long side chains of TEPIC suppress triaxial deformation-induced failure and improve ductility instead of decreasing strength and stiffness. In addition, the longer side chains form a dense molecular structure with less free volume. These results indicate that numerical approaches can be used to predict various properties of epoxy resins and interpret them from the molecular structure. Accordingly, these approaches can be used to aid the material development process. [ABSTRACT FROM AUTHOR]

Background: Pancreaticoduodenectomy is a highly difficult and invasive type of gastrointestinal surgery. Prevention of postoperative pancreatic fistula is important, and this may be possible by the stapler method. Methods: STRAP-PD is a single center randomized controlled trial. We compare a method of transecting the pancreatic parenchyma in pancreaticoduodenectomy using a surgical stapler device with a conventional transecting method using energy devices (e.g., scalpel, ultrasonic coagulator and incision devices). Patients with soft pancreas who are scheduled to undergo pancreaticoduodenectomy are randomized to arm A (conventional method) or arm B (stapler method). We aim to examine the safety and usefulness of dissection by the automatic suture device, with attention to the rate of pancreatic fistula ISGPF grade B or C and to postoperative complications. This is a single-center randomized study, which began in September 2023 at Wakayama Medical University Hospital. Discussion: Pancreatic parenchymal transection is typically performed either by direct incision using a scalpel or by employing energy devices such as ultrasonic coagulating cutting devices during pancreaticoduodenectomy. In a prospective pilot study, we conducted pancreatic parenchymal transection in 20 consecutive normal pancreatic cases during pancreaticoduodenectomy, observing postoperative pancreatic fistula grade B in one case (5%). Traditional methods involving scalpel incision or the use of ultrasonic coagulating cutting devices have been historically favored but perceived as technically challenging, and they have been reliant upon the surgeon's skill. Notably, relatively high incidences of postoperative pancreatic fistula among patients with soft pancreas have also been observed. Our proposed stapler method may therefore be a useful method responsible for reducing the development of pancreatic fistula. This method would be as part of minimally-invasive surgery for pancreaticoduodenectomy. It uses an endoscopic linear stapler to cut the pancreatic parenchyma, so it is likely to be more convenient than conventional methods and can be used universally. Trial registration: University Hospital Medical Information Network Clinical Trials Registry, UMIN000052089. the Registration Date on 1st September 2023. [ABSTRACT FROM AUTHOR]

Noise from unmanned aerial vehicles, commonly referred to as "drones," will likely shape our acoustic environment in the near future. Yet, reactions of the population to this new noise source are still little explored. The objective of this study was to investigate short-term noise annoyance reactions to drones in a controlled laboratory experiment. Annoyance to (i) two quadcopters of different sizes in relation to common contemporary transportation noise sources (jet aircraft, propeller aircraft, helicopters, single car passbys), and (ii) different drone maneuvers (takeoff; landing; high, medium, and low flybys) flown at different speeds and elevations was systematically assessed. The results revealed that, at the same sound exposure level, drones are perceived as substantially more annoying than other airborne vehicles and passenger cars. Furthermore, for drone maneuvers, landings, and takeoffs are more annoying than flybys, as are maneuvers flown at low speed. Different loudness metrics (LAE, LDE, effective perceived noise level, psychoacoustic loudness level) accounted for drone noise annoyance ratings to an equal degree. An analysis of psychoacoustic parameters highlighted the significant link between drone noise annoyance and tonality, sharpness, and loudness level. The results suggest a different perception and an increased annoyance potential of drones, which will likely require specifically tailored legislation. [ABSTRACT FROM AUTHOR]

Background: Depression is frequently associated with unsuccessful smoking cessation. Objective: In this study, we investigated the impact of depression history on smoking cessation success in a clinical setting. Methods: This retrospective study included 726 patients who visited our smoking cessation clinic between January 1, 2001, and December 31, 2018. Kaplan–Meier analyses and Cox proportional hazards regression models were used to perform univariate and multivariate analyses of smoking cessation success factors. Results: Among the 726 patients, 76 had a history of depression and demonstrated significantly lower 12-week quit rate compared to those without (33.6% vs. 69.6%, p <.001). Multivariate Cox analysis revealed a significant association between abstinence rate and history of depression (hazard ratio 2.251, 95% CI 1.505–3.315, p <.001), history of schizophrenia (hazard ratio 2.716, 95% CI 1.427–4.840, p =.003), and Fagerström Nicotine Dependence Test scores (hazard ratio 1.519, 95% CI 1.053–2.197, p =.025). Conclusions: Our findings suggested that a history of depression is a significant prognostic factor for smoking cessation, underscoring the need for targeted interventions for patients with a history of depression. The findings of this study are subject to potential selection bias due to recruitment from a single hospital, which may limit the generalizability of our results. This study highlights the necessity for novel, specialized smoking cessation therapies to support patients with a history of depression in their cessation journey. [ABSTRACT FROM AUTHOR]

Introduction: In the post-Helicobacter pylori era, autoimmune gastritis (AIG) is attracting increasing attention as an origin of gastric cancer. Here, we performed clinicopathological examination of gastric cancer complicating AIG treated in our hospital. Methods: Eighty-six early gastric cancer lesions complicating AIG in 50 patients were treated by endoscopic submucosal dissection (ESD) at our hospital in 2008–2022. Their clinicopathological characteristics were compared with those of a control group comprising 2,978 early gastric cancer lesions (excluding lesions in the remnant stomach after surgery) in 2,278 patients treated by ESD during the same period. Results: Mean age was significantly higher in the AIG group than in the control group (74.7 years vs. 70.9 years; p < 0.01). In the respective groups, the occurrence rate of synchronous/metachronous lesions was 38.0% and 20.4% (p < 0.01), the ratio of longitudinal cancer locations (upper/middle/lower third [U/M/L]) was 27/32/27 and 518/993/1,467 (p < 0.01), the ratio of circumferential cancer locations (lesser curvature/greater curvature/anterior wall/posterior wall) was 25/31/12/18 and 1,259/587/475/657 (p < 0.01), the ratio of major macroscopic types (I/IIa/IIb/IIc) was 13/38/5/30 and 65/881/220/1,812 (p < 0.01). The rates of multiple gastric cancer and cancers in the U region, at the greater curvature, and of protruding types were significantly higher in the AIG group. Conclusion: The occurrence rate of multiple gastric cancer was significantly higher in gastric cancer complicating AIG (approximately 40%), and compared with the control group, the proportions of cancers at the U region, at the greater curvature, and of protruding types were significantly higher. [ABSTRACT FROM AUTHOR]

The large and growing amount of digital data creates a pressing need for approaches capable of indexing and retrieving multimedia content. A traditional and fundamental challenge consists of effectively and efficiently performing nearest-neighbor searches. After decades of research, several different methods are available, including trees, hashing, and graph-based approaches. Most of the current methods exploit learning to hash approaches based on deep learning. In spite of effective results and compact codes obtained, such methods often require a significant amount of labeled data for training. Unsupervised approaches also rely on expensive training procedures usually based on a huge amount of data. In this work, we propose an unsupervised data-independent approach for nearest neighbor searches, which can be used with different features, including deep features trained by transfer learning. The method uses a rank-based formulation and exploits a hashing approach for efficient ranked list computation at query time. A comprehensive experimental evaluation was conducted on seven public datasets, considering deep features based on CNNs and Transformers. Both effectiveness and efficiency aspects were evaluated. The proposed approach achieves remarkable results in comparison to traditional and state-of-the-art methods. Hence, it is an attractive and innovative solution, especially when costly training procedures need to be avoided. [ABSTRACT FROM AUTHOR]

In this study, we aim to conduct real-time sensing of indoor dust concentration distribution to mitigate the airborne transmission of coronaviruses. Airborne infection, facilitated by viruses present in particulate matter, emphasizes the importance of monitoring dust concentration as an indicator of virus spread. Our approach involves the implementation of a time-synchronized wireless sensor network for real-time sensing of dust concentration distribution. The time-synchronized wireless sensor network relies on a proposed time-synchronization algorithm, ensuring a time error of less than ± 1.27 ms. This precision enables the measurement of even fast-moving dust particles. To validate the feasibility of the wireless time-synchronized sensor network, we utilized a dust ejector (air cannon) and positioned time-synchronized sensors in a row. Dust particles released from the ejector passed through each time-synchronized sensor terminal. Simultaneously, a video recording (60 frames) was conducted, and the measured times of the time-synchronized sensor terminals were compared with the lap times of the video. The results of this comparison revealed identical lap times between the time-synchronized sensor data and the video, affirming the successful operation of the time-synchronized wireless distributed sensor node as designed. [ABSTRACT FROM AUTHOR]

Summary: Palpebral conjunctival hue alteration is used in non‐invasive screening for anaemia, whereas it is a qualitative measure. This study constructed machine/deep learning models for predicting haemoglobin values using 150 palpebral conjunctival images taken by a smartphone. The median haemoglobin value was 13.1 g/dL, including 10 patients with <11 g/dL. A segmentation model using U‐net was successfully constructed. The segmented images were subjected to non‐convolutional neural network (CNN)‐based and CNN‐based regression models for predicting haemoglobin values. The correlation coefficients between the actual and predicted haemoglobin values were 0.38 and 0.44 in the non‐CNN‐based and CNN‐based models, respectively. The sensitivity and specificity for anaemia detection were 13% and 98% for the non‐CNN‐based model and 20% and 99% for the CNN‐based model. The performance of the CNN‐based model did not improve with a mask layer guiding the model's attention towards the conjunctival regions, however, slightly improved with correction by the aspect ratio and exposure time of input images. The gradient‐weighted class activation mapping heatmap indicated that the lower half area of the conjunctiva was crucial for haemoglobin value prediction. In conclusion, the CNN‐based model had better results than the non‐CNN‐based model. The prediction accuracy would improve by using more input data with anaemia. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, characterized by muscle mass decline due to aging or other causes, is exacerbated by decreased estrogen levels after menopause in women. Isoflavones, a class of flavonoids acting on estrogen receptors, may have beneficial effects on metabolic disorders. We examined these effects in ovariectomized mice fed a high-fat, high-sucrose diet (HFHSD). Methods: At 7 weeks old, female C57BL6/J mice (18–20 g, n = 12) underwent bilateral ovariectomy (OVX), and were then fed a high-fat, high-sucrose diet starting at 8 weeks of age. Half of the mice received isoflavone water (0.1%). Metabolic analyses, including glucose and insulin tolerance tests, were conducted. Muscle analysis involved grip strength assays, next-generation sequencing, quantitative RT–PCR, and western blotting of skeletal muscle after euthanizing the mice at 14 weeks old. Additionally, 16S rRNA gene sequence analysis of the gut microbiota was performed. Results: The results demonstrated that isoflavone administration did not affect body weight, glucose tolerance, or lipid metabolism. In contrast, isoflavone-treated mice had higher grip strength. Gene expression analysis of the soleus muscle revealed decreased Trim63 expression, and western blotting showed inactivation of muscle-specific RING finger protein 1 in isoflavone-treated mice. Gut microbiota analysis indicated higher Bacteroidetes and lower Firmicutes abundance in the isoflavone group, along with increased microbiota diversity. Gene sets related to TNF-α signaling via NF-κB and unfolded protein response were negatively associated with isoflavones. Conclusions: Isoflavone intake alters gut microbiota and increases muscle strength, suggesting a potential role in improving sarcopenia in menopausal women. [ABSTRACT FROM AUTHOR]

This study examined teachers' concerns about including students with disabilities (SWDs) in regular classrooms and identified the background variables that were significantly associated with their concerns. A total of 1008 primary school teachers from 236 schools across all 25 provinces and cities in Cambodia participated in the study. The Concern about Inclusive Education Scale (CIES) was used as a research instrument. Descriptive statistics, a principal component analysis, reliability tests, Pearson correlation coefficients and a multiple regression analysis were used for data analysis. The result of the principal component analysis confirmed a four‐factor model for the CIES. The study found that Cambodian teachers had high levels of concern about including SWDs in regular classrooms. They expressed the deepest concerns about the inadequate availability of special education instructional materials and teaching aids, the lack of knowledge and skills required to teach SWDs, the increased workloads and the challenges of providing equal attention to all students. The experience of inclusive education training, years of teaching in regular classrooms, and experience of teaching SWDs were significantly associated with their concerns about inclusion. The findings were discussed with practical implications for improved policy and practice to address Cambodian teachers' concerns and promote their inclusive practices. [ABSTRACT FROM AUTHOR]

Background: Ureteral injury occurs in 0.3–1.5% of colorectal cancer surgeries. Devices to visualize the ureteral course and avoid ureteral injury are required for minimally invasive surgery (MIS). The NIRC™ fluorescent ureteral catheter (FUC) is a versatile ureteral visualization device currently available in Japan that can be used in combination with a variety of laparoscopic and robotic systems. In this study, we examined the outcomes of high-risk patients who underwent colorectal cancer surgery with FUC insertion. Methods: One hundred forty-one patients who underwent MIS for colorectal cancer and colorectal cancer recurrence at our institute between January 2021 and May 2024 underwent preoperative FUC insertion because of the high risk of ureteral injury and surgical difficulty. For these patients, patient background data and short-term outcomes were examined. The results are expressed as the median and interquartile range. Results: Age, 70 [60–78]; M:F(n), 84:57; BMI, 22.1 [19.7–24.7]; T4 (TNM classification), 52 cases (36.9%); preoperative intestinal obstruction, 45 cases (31.9%); abscess formation, 30 cases (21%); surgical history, 70 cases (50%); recurrent cancer, 14 cases (9.9%); preoperative chemo-radiotherapy, 28 cases (19.9%); time required for FUC insertion, 12 [9–19] minutes; operation time, 412 [309–552] minutes; blood loss, 10 [5–30] ml; open conversion, 0 cases; postoperative hospitalization, 12 [9–17.5]; circumferential resection margins < 1 mm (rectal surgery), 4/87 cases (4.6%); comorbidities, 0 ureteral injury, 1 urethral injury during FUC insertion (0.7%) and 16 CD Grade 3 or higher cases (11%). Conclusions: FUC may improve the safety of MIS and reduce blood loss in addition to preventing ureteral injury and is expected to have oncological advantages for ensuring the margin of the tumor without fear of ureteral injury. However, the time required for and complications associated with FUC are challenging. New methods for less invasive and easier ureteral visualization may be needed. [ABSTRACT FROM AUTHOR]

Guanosine 5′‐monophosphate (GMP) synthetase (GuaA) catalyzes the last step of GMP synthesis in the purine nucleotide biosynthetic pathway. This enzyme catalyzes a reaction in which xanthine 5′‐monophosphate (XMP) is converted to GMP in the presence of Gln and ATP through an adenyl‐XMP intermediate. A structure of an XMP‐bound form of GuaA from the domain Bacteria has not yet been determined. In this study, the crystal structure of an XMP‐bound form of GuaA from the thermophilic bacterium Thermus thermophilus HB8 (TtGuaA) was determined at a resolution of 2.20 Å and that of an apo form of TtGuaA was determined at 2.10 Å resolution. TtGuaA forms a homodimer, and the monomer is composed of three domains, which is a typical structure for GuaA. Disordered regions in the crystal structure were obtained from the AlphaFold2‐predicted model structure, and a model with substrates (Gln, XMP and ATP) was constructed for molecular‐dynamics (MD) simulations. The structural fluctuations of the TtGuaA dimer as well as the interactions between the active‐site residues were analyzed by MD simulations. [ABSTRACT FROM AUTHOR]

Background: Transcriptome-based prediction of complex phenotypes is a relatively new statistical method that links genetic variation to phenotypic variation. The selection of large-effect genes based on a priori biological knowledge is beneficial for predicting oligogenic traits; however, such a simple gene selection method is not applicable to polygenic traits because causal genes or large-effect loci are often unknown. Here, we used several gene-level features and tested whether it was possible to select a gene subset that resulted in better predictive ability than using all genes for predicting a polygenic trait. Results: Using the phenotypic values of shoot and root traits and transcript abundances in leaves and roots of 57 rice accessions, we evaluated the predictive abilities of the transcriptome-based prediction models. Leaf transcripts predicted shoot phenotypes, such as plant height, more accurately than root transcripts, whereas root transcripts predicted root phenotypes, such as crown root length, more accurately than leaf transcripts. Furthermore, we used the following three features to train the prediction model: (1) tissue specificity of the transcripts, (2) ontology annotations, and (3) co-expression modules for selecting gene subsets. Although models trained by a gene subset often resulted in lower predictive abilities than the model trained by all genes, some gene subsets showed improved predictive ability. For example, using genes expressed in roots but not in leaves, the predictive ability for crown root diameter was improved by more than 10% (R2 = 0.59 when using all genes; R2 = 0.66, using 1,554 root-specifically expressed genes). Similarly, genes annotated as "gibberellic acid sensitivity" showed higher predictive ability than using all genes for root dry weight. Conclusions: Our results highlight both the possibility and difficulty of selecting an appropriate gene subset to predict polygenic traits from transcript abundance, given the current biological knowledge and information. Further integration of multiple sources of information, as well as improvements in gene characterization, may enable the selection of an optimal gene set for the prediction of polygenic phenotypes. [ABSTRACT FROM AUTHOR]

Utilizing recycled concrete aggregate (RCA) is a countermeasure to address the scarcity of landfills and the depletion of natural aggregates. Surface modification techniques have been proposed and implemented to improve the properties of RCA; however, to our best knowledge, few investigations on improving RCA under various pozzolanic slurry concentrations and extended soaking durations have been done. This study comprehensively assessed the properties and microstructure of low-strength RCA treated with cement–fly ash slurry with different concentrations and soaking durations. The purposes of this study were not only to provide the optimal slurry concentration and treatment duration but also to explore the enhancement mechanism of RCA under various treatment conditions. The RCA from concrete with a low-strength grade of 20 MPa was soaked in cement–fly ash slurry at low and high concentrations (i.e., 30% and 70% by mass of RCA, respectively) for 24 and 72 h. The physical and mechanical properties of RCA before and after treatment were evaluated through water absorption and crushing value measurements, respectively. Additionally, the pore structure, Ca(OH)2 contents, surface morphology, and phase compositions of RCAs were evaluated through a mercury intrusion porosimetry test, thermal gravimetric differential thermal analysis (TG-DTA), scanning electron microscopy, and X-ray diffraction (XRD) analyses, respectively. The water absorption of treated RCA reduced by 9.2%–37.9%, whereas the crushing value decreased by 8.6%–26.9% compared with the untreated RCA. The TG-DTA results indicated a 22.3%–43.8% increase in the Ca(OH)2 content of treated RCA. The XRD analysis depicted a higher ettringite (AFt) peak in all treated RCA samples compared with the untreated sample. For both concentrations, with a 24 h treatment, the slurry infiltration effect was clearly observable, whereas the 72 h treatment resulted in the formation of a pozzolanic coating layer on the RCA surface. In conclusion, the optimal slurry concentration and soaking duration were 70% and 72 h, respectively. [ABSTRACT FROM AUTHOR]

Background: Comprehensive genomic profiling (CGP) can aid the discovery of clinically useful, candidate antitumor agents; however, the variant annotations sometimes differ among the various types of CGP tests as well as the public database. The aim of this study is to clarify the genomic landscape of evaluating detected variants in patients with a malignant solid tumor. Methods: The present, cross-sectional study used data from 57,084 patients with a malignant solid tumor who underwent CGP at the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) between June 1, 2019 and August 18, 2023. The pathogenicity of the variants was annotated using public databases. Results: As a result of re-annotation of the detected variants, 20.1% were pathogenic and 1.4% were benign. The mean number of pathogenic variants was 4.30 (95% confidence interval: 4.27–4.32) per patient. Of the entire cohort, 5.7% had no pathogenic variant. The co-occurrence of the genes depended on the tumor type. Germline findings were detected in 6.2%, 8.8%, and 15.8% of the patients using a tumor/normal panel, tumor-only panel, and liquid panel, respectively, with the most common gene being BRCA2 followed by TP53 and BRCA1. Conclusions: The detected variants should be re-annotated because several benign variants or variants of unknown significance were included in the CGP, and the genomic landscape derived from these results will help researchers and physicians interpret the results of CGP tests. The method of extracting presumptive, germline, pathogenic variants from patients using a tumor-only panel or circulating tumor DNA panel requires improvement. [ABSTRACT FROM AUTHOR]

Aims: In recent years, there has been remarkable development in machine learning (ML) models, showing a trend towards high prediction performance. ML models with high prediction performance often become structurally complex and are frequently perceived as black boxes, hindering intuitive interpretation of the prediction results. We aimed to develop ML models with high prediction performance, interpretability, and superior risk stratification to predict in‐hospital mortality and worsening heart failure (WHF) in patients with acute heart failure (AHF). Methods and results: Based on the Kyoto Congestive Heart Failure registry, which enrolled 4056 patients with AHF, we developed prediction models for in‐hospital mortality and WHF using information obtained on the first day of admission (demographics, physical examination, blood test results, etc.). After excluding 16 patients who died on the first or second day of admission, the original dataset (n = 4040) was split 4:1 into training (n = 3232) and test datasets (n = 808). Based on the training dataset, we developed three types of prediction models: (i) the classification and regression trees (CART) model; (ii) the random forest (RF) model; and (iii) the extreme gradient boosting (XGBoost) model. The performance of each model was evaluated using the test dataset, based on metrics including sensitivity, specificity, area under the receiver operating characteristic curve (AUC), Brier score, and calibration slope. For the complex structure of the XGBoost model, we performed SHapley Additive exPlanations (SHAP) analysis, classifying patients into interpretable clusters. In the original dataset, the proportion of females was 44.8% (1809/4040), and the average age was 77.9 ± 12.0. The in‐hospital mortality rate was 6.3% (255/4040) and the WHF rate was 22.3% (900/4040) in the total study population. In the in‐hospital mortality prediction, the AUC for the XGBoost model was 0.816 [95% confidence interval (CI): 0.815–0.818], surpassing the AUC values for the CART model (0.683, 95% CI: 0.680–0.685) and the RF model (0.755, 95% CI: 0.753–0.757). Similarly, in the WHF prediction, the AUC for the XGBoost model was 0.766 (95% CI: 0.765–0.768), outperforming the AUC values for the CART model (0.688, 95% CI: 0.686–0.689) and the RF model (0.713, 95% CI: 0.711–0.714). In the XGBoost model, interpretable clusters were formed, and the rates of in‐hospital mortality and WHF were similar among each cluster in both the training and test datasets. Conclusions: The XGBoost models with SHAP analysis provide high prediction performance, interpretability, and reproducible risk stratification for in‐hospital mortality and WHF for patients with AHF. [ABSTRACT FROM AUTHOR]

Crimean-Congo Hemorrhagic Fever virus (CCHFV) is a tick-borne pathogen that causes severe acute fever disease in humans and requires a biosafety level 4 laboratory for handling. Hazara virus (HAZV), belonging to the same virus genus as CCHFV, does not exhibit pathogenesis in humans. To investigate host RNA-binding proteins (RBPs) that regulate CCHFV replication, we generated a series of mutant RAW264.7 cells by CRISPR/Cas9 system and these cells were infected with HAZV. The viral titers in the supernatant of these cells was investigated, and HuR (ELAVL1) was identified. HuR KO RAW264.7 cells reduced HAZV replication. HuR is an RBP that enhances mRNA stability by binding to adenyl-uridine (AU)-rich regions in their 3′ non-coding region (NCR). HuR regulates innate immune response by binding to host mRNAs of signaling molecules. The expression of cytokine genes such as Ifnb, Il6, and Tnf was reduced in HuR KO cells after HAZV infection. Although HuR supports the innate immune response during HAZV infection, we found that innate immune activation by HAZV infection did not affect its replication. We then investigated whether HuR regulates HAZV genome RNA stability. HAZV RNA genome was precipitated with an anti-HuR antibody, and HAZV genome RNA stability was lowered in HuR KO cells. We found that HuR associated with HAZV RNA and stabilized it to enhance HAZV replication. Furthermore, HuR-deficiency reduced CCHFV minigenome replication. CCHFV is a negative-strand RNA virus and positive-strand RNA is produced during replication. HuR was associated with positive-strand RNA rather than negative-strand RNA, and AU-rich region in 3'-NCR of S segment was responsible for immunoprecipitation with anti-HuR antibody and minigenome replication. Additionally, HuR inhibitor treatment reduced CCHFV minigenome replication. Our results indicate that HuR aids replication of the CCHFV minigenome by associating with the AU-rich region in the 3′-NCR. Author summary: Crimean-Congo Hemorrhagic Fever virus (CCHFV) is a tick-borne pathogen that causes severe acute fever disease in humans and requires a biosafety level 4 laboratory for handling. Hazara virus (HAZV), the same genus of CCHFV, has been used as a model virus to reveal the molecular mechanism of CCHFV infection. To investigate host factors for CCHFV replication, we generated a series of mutant RAW264.7 cells and conducted screening for host genes that regulate the replication of HAZV, identifying HuR (ELAVL1). HuR is an RNA-binding protein (RBP) that enhances mRNA stability by binding to its 3′ non-coding region (NCR). We found that HuR is associated with the CCHFV RNA stability by binding to its 3'-NCR, and the minigenome assay showed that CCHFV replication is supported by HuR. HuR inhibitor treatment also reduced CCHFV minigenome replication. These findings present a possible starting point for the future development of antiviral drug targeting host RBPs. Combination treatment with RdRp and RBP inhibitors may be a potential therapeutic strategy in the future. [ABSTRACT FROM AUTHOR]

Background: Thymomas complicated with myasthenia gravis are conventionally treated during thoracic surgery. Particularly, invasive thymomas are resected alongside the surrounding organs. Here, we present a case where surgical and perioperative management was performed under the presumption of thymoma with myasthenia gravis. However, definitive pathology revealed the co-occurrence of B3 thymoma and thymic squamous cell carcinoma. This case highlights the unique presentation and exceptional rarity of thymomas that are complicated by myasthenia gravis and thymic carcinoma. Case presentation: A 65-year-old female presented with eyelid ptosis at our hospital. Following a comprehensive examination, the patient was diagnosed with myasthenia gravis. Her computed tomography (CT) scan revealed an anterior mediastinal tumor suggestive of a thymoma, prompting a referral to the Department of Thoracic Surgery. Moreover, preoperative assessment could not definitively exclude pericardial invasion. She subsequently underwent an extended thymectomy via a longitudinal sternal incision. The tumor exhibited partial invasion of the pericardium, necessitating resection and reconstruction. Definitive pathological examination confirmed the co-occurrence of B3 thymoma and thymic squamous cell carcinoma. Positive lymph node metastasis classified the patient as stage IVa according to the Union for International Cancer Control (UICC) TNM Classification of Malignant Tumors, 8th Edition, and she was started on adjuvant radiotherapy postoperatively. Currently, the patient remains under observation, with follow-up CT scans showing no signs of recurrence. Conclusions: This report describes an extremely rare case of thymoma complicated with myasthenia gravis and thymic squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Absolute lymphocyte count (ALC) is a predictive and prognostic factor for various tumor types, including breast cancer. Palbociclib is a CDK4/6 inhibitor widely used for the treatment of metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer. However, predictive biomarkers of the efficacy of palbociclib remain unelucidated. We conducted a retrospective study to examine the predictive value of the baseline ALC in patients treated with palbociclib. Methods: The medical records of patients with ER-positive, HER2-negative breast cancer treated with palbociclib plus hormonal therapy between December 2017 and December 2021 were analyzed retrospectively. The cutoff value of ALC was set at 1800 cells/μL at the initiation of palbociclib treatment. The clinical benefit rate (CBR) was defined as the rate of complete or partial response or stable disease for at least 6 months. Progression-free survival (PFS) rates were estimated using the Kaplan–Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards regression. Results: All of the 202 patients were women, with a median age of 59 years and a performance status (PS) of ≤ 2. The median numbers of lines of chemotherapy and endocrine therapy before palbociclib treatment were 0 (range, 0–9) and 1 (range, 0–7), respectively. Fifty-one patients had liver metastases. Forty-six patients tested negative for progesterone receptor (PgR) expression. The median follow-up time was 9.1 months. The CBR was significantly higher in the ALC-high group than in the ALC-low group (79% vs. 60%; P = 0.018). The median PFS was significantly longer in the ALC-high group than in the ALC-low group (26.8 months vs. 8.4 moths, respectively; P = 0.000013). ALC, age, PS, PgR status, prior chemotherapy, prior endocrine therapy, and liver metastasis were entered into the multivariate analysis. ALC was identified as an independent factor for PFS (P = 0.00085), along with liver metastasis (P = 0.0020), PS (P = 0.026), and prior endocrine therapy (P = 0.019). Conclusion: ALC can serve as a predictor of palbociclib efficacy in patients with metastatic ER-positive, HER2-negative breast cancer. [ABSTRACT FROM AUTHOR]