Search

Uncovering the mystery of efficient and directional energy transfer in photosynthetic organisms remains a critical challenge in quantum biology. Recent experimental evidence and quantum theory developments indicate the significance of quantum features of molecular vibrations in assisting photosynthetic energy transfer, which provides the possibility of manipulating the process by controlling molecular vibrations. Here, we propose and theoretically demonstrate efficient manipulation of photosynthetic energy transfer by using vibrational strong coupling between the vibrational state of a Fenna–Matthews–Olson (FMO) complex and the vacuum state of an optical cavity. Specifically, based on a full-quantum analytical model to describe the strong coupling effect between the optical cavity and molecular vibration, we realize efficient manipulation of energy transfer efficiency (from 58% to 92%) and energy transfer time (from 20 to 500 ps) in one branch of FMO complex by actively controlling the coupling strength and the quality factor of the optical cavity under both near-resonant and off-resonant conditions, respectively. Our work provides a practical scenario to manipulate photosynthetic energy transfer by externally interfering molecular vibrations via an optical cavity and a comprehensible conceptual framework for researching other similar systems. [ABSTRACT FROM AUTHOR]

Sampling reference data is crucial in machine learning potential (MLP) construction. Inadequate coverage of local configurations in reference data may lead to unphysical behaviors in MLP‐based molecular dynamics (MLP‐MD) simulations. To address this problem, this study proposes a new on‐the‐fly reference data sampling method called radial distribution function (RDF)‐based data sampling for MLP construction. This method detects and extracts anomalous structures from the trajectories of MLP‐MD simulations by focusing on the shapes of RDFs. The detected structures are added to the reference data to improve the accuracy of the MLP. This method allows us to realize a reasonable MLP construction for liquid water with minimal additional data. We prepare data from an H2O molecular cluster system and verify whether the constructed MLPs are practical for bulk water systems. MLP‐MD simulations without RDF‐based data sampling show unphysical behaviors, such as atomic collisions. In contrast, after applying this method, we obtain MLP‐MD trajectories with features, such as RDF shapes and angle distributions, that are comparable to those of ab initio MD simulations. Our simulation results demonstrate that the RDF‐based data sampling approach is useful for constructing MLPs that are robust to extrapolations from molecular cluster systems to bulk systems without any specialized know‐how. [ABSTRACT FROM AUTHOR]

The sympathetic nervous system is crucial for responding to environmental changes. This regulation is coordinated by the spinal sympathetic preganglionic neurons (SPNs), innervating both postganglionic neurons and the adrenal gland. Despite decades of research supporting the concept of selective control within this system, the neural circuit organization responsible for the output specificity remains poorly understood. Here, by combining recent single-cell transcriptome data with viral-genetic toolkits in mice, we identify two subtypes of SPNs in the lower thoracic spinal cord, defined at the molecular level, exhibiting nonoverlapping patterns of innervation: one specifically projecting to the celiac/superior mesenteric ganglia, and the other targeting the adrenal grand. Chemogenetic manipulations on these distinct SPN subtypes revealed selective impacts on the motility of the gastrointestinal tracts or glucose metabolism mediated by the adrenal gland, respectively. This molecularly delineated parallel labeled-line organization in sympathetic outflows presents a potential avenue for selectively manipulating organ functions. How individual organs are specifically regulated by the sympathetic neurons at the cellular level remains not fully understood. Here, authors identify two molecularly distinct sympathetic pathways that independently control the adrenal medulla and intestine. [ABSTRACT FROM AUTHOR]

Simple Summary: We evaluated the efficacy of bevacizumab (BEV) in first-line chemotherapy for clear cell carcinoma (CCC). We categorized patients with advanced clear cell carcinoma (CCC) who received platinum-based first-line chemotherapy into a non-BEV group and a BEV group, and compared the progression-free survival (PFS), overall survival (OS), response rates, adverse events, and platinum agent-resistant recurrence rates. The PFS was improved and response rates were higher in the BEV group. One patient in the BEV group had grade 4 gastrointestinal perforation, although no treatment-related death was reported. First-line chemotherapy with BEV in advanced CCC showed the potential for high response rates and an improved PFS. Objective: The usefulness of bevacizumab (BEV) as first-line chemotherapy for advanced ovarian clear cell carcinoma (CCC) was retrospectively evaluated at Tohoku Gynecologic Cancer Unit institutions. Patients and Methods: A total of 81 patients (52 patients without BEV and 29 with BEV) with advanced ovarian CCC who received initial platinum-based chemotherapy were enrolled. We selected 26 patients each without and with BEV according to propensity score matching methods, and compared the platinum-resistant recurrence rate, response rate, progression-free survival (PFS), overall survival (OS), and adverse events between the two groups. Results: The objective response rates for the patients with measurable disease in the non-BEV and BEV groups were 60.0% and 95.5%, respectively (p = 0.007). The recurrence of platinum-resistant patients was observed in 50.0% of the non-BEV group and 23.1% of the BEV group (p = 0.117). The median PFS was 12 and 22 months, respectively (p = 0.034), and the median OS was 32 and 47 months, respectively (p = 0.223). In the BEV group, grade 3 hypertension and proteinuria occurred in two patients, and thrombosis and carboplatin hypersensitivity occurred in one patient. Grade 4 gastrointestinal perforation occurred in one patient. Conclusions: First-line chemotherapy with BEV in advanced CCC showed the potential for high response rates and improved PFS. [ABSTRACT FROM AUTHOR]

The α-oxyalkylation of aryl chlorides with ethers and alcohols using a small amount of a peroxide was found to be induced by photoirradiation. The reaction proceeds through a homolytic aromatic substitution (HAS) mechanism consisting of addition of an α-oxyalkyl radical to an aryl chloride and elimination of the chlorine atom to give the α-oxyalkylation product, where photoirradiation is considered to effect not only the initiation step to facilitate homolysis of a peroxide, but also the propagating radical chain. [ABSTRACT FROM AUTHOR]

Gamma oscillation regularity (GOR) indicates the synchronization of inhibitory interneurons, while the reactivity of cortico-cortical evoked potentials (CCEPs) is supposed to reflect local cortical excitability. Under the assumption that the early response of CCEP near the stimulation site also indicates excitatory activity primarily mediated by pyramidal cells, we aimed to visualize the cortical inhibitory and excitatory activities using GOR and CCEP in combination and to use them to predict the epileptogenic zone (EZ) in mesial temporal lobe epilepsy (MTLE). In five patients who underwent intracranial electrode implantation, GOR and CCEP reactivity in the vicinity of the stimulation site was quantified. The interictal GOR was calculated using multiscale entropy (MSE), the decrease of which was related to the enhanced GOR. These parameters were compared on an electrode-and-electrode basis, and spatially visualized on the brain surface. As a result, elevated GOR and CCEP reactivities, indicative of enhanced inhibitory and excitatory activities, were observed in the epileptogenic regions. Elevated CCEP reactivity was found to be localized to a restricted area centered on the seizure onset region, whereas GOR elevation was observed in a broader region surrounding it. Although these parameters independently predicted the EZ with high specificity, we combined the two to introduce a novel parameter, the excitatory and inhibitory (EI) index. The EI index predicted EZ with increased specificity compared with GOR or CCEP reactivity alone. Our results demonstrate that GOR and CCEP reactivity provided a quantitative visualization of the distribution of cortical inhibitory and excitatory activities and highlighted the relationship between the two parameters. The combination of GOR and CCEP reactivities are expected to serve as biomarkers for localizing the epileptogenic zone in MTLE from interictal intracranial electroencephalograms. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the nonlinear dynamics of convection flow using the thermodynamic variational principle, focusing on scenarios where multiple external forces, such as a thermal gradient and rotational field, are applied to a shallow annular pool. We observed that with the increase in the thermal gradient, the flow changed from an axial flow to a rotational oscillatory flow with the wave amplitudes aligned. Further increasing the temperature difference led to a rotational oscillatory flow characterized by alternating wave generation and annihilation. Our analysis of the flow, considering heat fluxes orthogonal to the thermal gradient, allowed us to describe the flow state as a phase at equilibrium. The state transition of the flow was accompanied by a discontinuous jump in the heat flux, which occurred at the intersection of the entropy production curves. The first transition occurred at a temperature difference Δ T = 12.4   K   M a r a n g o n i   n u m b e r , M a = 1716 and the second at ΔT = 16.3 K M a = 2255 . Analysis based on entropy production could accurately predict the observed transition points. [ABSTRACT FROM AUTHOR]

Rationale: Thromboembolism is a serious complication of endovascular treatment for ruptured cerebral aneurysms. The administration of antiplatelet agents before endovascular treatment for ruptured cerebral aneurysms may reduce the risk of thromboembolic complications. Aim: This study aimed to assess the safety and efficacy of preoperative aspirin administration in endovascular treatment for ruptured cerebral aneurysms. Sample size estimates: Assuming a 15% incidence rate of both intraoperative thromboembolic morbidity and symptomatic ischemic lesions on magnetic resonance imaging diffusion-weighted imaging scans assessed by an Independent Review Committee, a sample size of 484 will be required to detect a 10% improvement with aspirin administration with 90% power using the Pearson's chi-square test at a two-sided significance level of 2.5% for each primary outcome, after accounting for a 5% dropout rate. Methods and design: ASTOP is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 484 patients with ruptured cerebral aneurysms receiving coil embolization within 72 h of onset will be randomly assigned 1:1 to receive 200 mg of aspirin or placebo before the procedure. Study outcomes: The primary outcomes will be the incidence rates of intraoperative thromboembolic complications and symptomatic ischemic lesions on magnetic resonance imaging diffusion-weighted imaging scans evaluated by the Independent Review Committee. The secondary outcomes will be the incidence rate of cerebral ischemic events and all bleeding events within 14 days of enrollment and functional outcomes defined by the modified Rankin Scale score at 90 days. Discussion: This trial will provide valuable data on the role of antiplatelet agents during endovascular treatment for ruptured cerebral aneurysms. Trial registration: Registration: Japan Registry of Clinical Trials, Identifier: jRCTs031210421. [ABSTRACT FROM AUTHOR]

Purpose: Radiofrequency (RF) ablation with half-normal saline (HNS) irrigation is reported to potentially enlarge local lesion compared to normal saline (NS) in power-controlled ablation (PC-Abl). However, the effect of HNS-irrigation in temperature-flow-controlled ablation (TFC-Abl) on lesion characteristics is unknown. We compared this between TFC-Abl with QDOT-Micro™ catheter and PC-Abl with Thermocool SmartTouch SF™ catheter (STSF). Methods: RF-application with NS (n = 480) and HNS (n = 480) irrigation were performed on swine myocardium placed in a circulating saline bath. Lesion characteristics without steam-pops under various conditions (target AI, 400/550; ablation power, 30/50 W; contact force, 10/20/30 g; catheter orientation, perpendicular/parallel) were assessed and compared between two irrigants. Results: After matching, 343 lesions without steam-pops in each group were evaluated. In PC-Abl, lesion size did not differ between two groups (NS, 188 ± 97 vs. HNS, 200 ± 95 mm3, p = 0.28 in volume; 33.9 ± 7.3 vs. 34.8 ± 9.5 mm2, p = 0.34 in surface area; and 4.0 ± 1.0 vs. 4.0 ± 1.0 mm, p = 0.81 in depth), but steam-pops were more frequently observed with HNS-irrigation (23.8% vs. 37.9%, p = 0.001). Contrary, in TFC-Abl, HNS-irrigation produced significantly larger (214 ± 106 vs. 243 ± 128 mm3, p = 0.017) and deeper (4.0 ± 1.0 vs. 4.3 ± 1.1 mm, p = 0.002) lesions without increasing the risk of steam-pops (15.0% vs 15.0%, p = 0.99). Automatic temperature-guided titration was more frequently observed in HNS-irrigation (54.8% vs. 78.5%, p < 0.001). Conclusions: TFC-Abl with QDOT-Micro™ catheter utilizing HNS-irrigation might increase volume and depth of local lesion without increasing the risk of stem-pops compared to NS-irrigation. Power-controlled ablation with HNS-irrigation showed similar focal lesion with higher incidence of steam-pops (SPs) compared to normal saline (NS) irrigation. Contrary, temperature-flow-controlled ablation with HNS-irrigation provided larger and deeper lesion than NS-irrigation with similar incidence of SPs. ns, p > 0.05; *, 0.01 < p ≤ 0.05; **, 0.005 < p ≤ 0.01. HNS, half-normal saline; NS, normal saline. [ABSTRACT FROM AUTHOR]

Patients with pancreatic neuroendocrine tumors (pNETs) have limited access to effective targeted agents and invariably succumb to progressive disease. MUC1-C is a druggable oncogenic protein linked to driving pan-cancers. There is no known involvement of MUC1-C in pNET progression. The present work was performed to determine if MUC1-C represents a potential target for advancing pNET treatment. We demonstrate that the MUC1 gene is upregulated in primary pNETs that progress with metastatic disease. In pNET cells, MUC1-C drives E2F- and MYC-signaling pathways necessary for survival. Targeting MUC1-C genetically and pharmacologically also inhibits self-renewal capacity and tumorigenicity. Studies of primary pNET tissues further demonstrate that MUC1-C expression is associated with (i) an advanced NET grade and pathological stage, (ii) metastatic disease, and (iii) decreased disease-free survival. These findings demonstrate that MUC1-C is necessary for pNET progression and is a novel target for treating these rare cancers with anti-MUC1-C agents under clinical development. [ABSTRACT FROM AUTHOR]

Introduction: Posterior cerebral artery (PCA) aneurysms represent up to 1% of all cerebral aneurysms. P1-P2 perforator aneurysms are thought to be even less prevalent and often require complex treatment strategies due to their anatomical and morphological characteristics, with risk of a perforator infarct. We studied the treatment of P1-P2 perforator aneurysms in a single-center cohort from a high-volume tertiary center, reporting clinical and anatomical characteristics, treatment strategies, and outcomes. Methods: A retrospective analysis of adult patients with a P1-P2 perforator aneurysm who presented at our institution between January 2000 and January 2023 was performed. The patients were analyzed for demographics, clinical presentation, imaging findings, treatment techniques, outcomes, and complications. Subgroup analyses between ruptured versus non-ruptured cases were included. Results: Out of 2733 patients with a cerebral aneurysm, 14 patients (0.5%) presented with a P1-P2 perforator aneurysm. All six patients with a ruptured aneurysm were treated by endovascular coiling, of whom one patient (16.7%) required surgical clipping of a recurrence. One out of eight (12.5%) patients with unruptured aneurysms was treated by surgical clipping. P1-P2 perforator aneurysms predominantly affected middle-aged individuals (median 59.5 years), with 10/14 (71.4%) being female. Endovascular coiling was the primary treatment modality overall, yielding favorable technical outcomes, however, it was complicated by a perforator infarct in two patients (33.3%) without new permanent morbidity or mortality secondary to treatment. Conclusions: P1-P2 perforator aneurysms are a rare subtype of intracranial aneurysm. Endovascular coiling could present an effective treatment modality; however, care should be taken for ischemic complications in the dependent perforator territory. Larger studies are required to provide more insights. [ABSTRACT FROM AUTHOR]

This qualitative study proposes a grounded theory of Christian identity transformation based on the experiences of 100 undergraduate college students (in-group), reported in reflection papers, who attended a free community dinner with their neighbors who were experiencing housing insecurity or homelessness (out-group). The grounded theory that emerged from student reflection papers is that the experience of eating with an out-group in a setting that disrupts in-group/out-group social dynamics, within the context of Christian community and utilizing an action-reflection model of learning, leads to humanizing theological insights that disrupt previously held stereotypes of the out-group. Jack Mezirow's theory of disorienting dilemmas as provoking adult learning is used to explain the transformative impact of the dinner. Extended attention is given to the theological significance of in-group/out-group boundary crossing as it relates to Karl Barth's theological anthropology of mutuality as well as Delores Williams' understanding of sin as invisibilization. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC), predominantly comprising urothelial carcinomas (UCs), ranks as the tenth most common cancer worldwide. UCs with variant histology (variant UC), including squamous differentiation, glandular differentiation, plasmacytoid variant, micropapillary variant, sarcomatoid variant, and nested variant, accounting for 5–10% of cases, exhibit more aggressive and advanced tumor characteristics compared to pure UC. The Vesical Imaging-Reporting and Data System (VI-RADS), established in 2018, provides guidelines for the preoperative evaluation of muscle-invasive bladder cancer (MIBC) using multiparametric magnetic resonance imaging (mpMRI). This technique integrates T2-weighted imaging (T2WI), dynamic contrast-enhanced (DCE)-MRI, and diffusion-weighted imaging (DWI) to distinguish MIBC from non-muscle-invasive bladder cancer (NMIBC). VI-RADS has demonstrated high diagnostic performance in differentiating these two categories for pure UC. However, its accuracy in detecting muscle invasion in variant UCs is currently under investigation. These variant UCs are associated with a higher likelihood of disease recurrence and require precise preoperative assessment and immediate surgical intervention. This review highlights the potential value of mpMRI for different variant UCs and explores the clinical implications and prospects of VI-RADS in managing these patients, emphasizing the need for careful interpretation of mpMRI examinations including DCE-MRI, particularly given the heterogeneity and aggressive nature of variant UCs. Additionally, the review addresses the fundamental MRI reading procedures, discusses potential causes of diagnostic errors, and considers future directions in the use of artificial intelligence and radiomics to further optimize the bladder MRI protocol. [ABSTRACT FROM AUTHOR]

Background and Aim: Tip‐in endoscopic mucosal resection (EMR) has a high en bloc resection rate for large colorectal neoplasms. However, non‐experts' performance in Tip‐in EMR has not been investigated. We investigated whether Tip‐in EMR can be achieved effectively and safely even by non‐experts. Methods: This retrospective study included consecutive patients who underwent Tip‐in EMR for 15–25 mm colorectal nonpedunculated neoplasms at a Japanese tertiary cancer center between January 2014 and December 2020. Baseline characteristics, treatment outcomes, learning curve of non‐experts, and risk factors of failing self‐achieved en bloc resection were analyzed. Results: A total of 597 lesions were analyzed (438 by experts and 159 by non‐experts). The self‐achieved en bloc resection (69.8% vs 88.6%, P < 0.001) and self‐achieved R0 resection (58.3% vs 76.5%, P < 0.001) rates were significantly lower in non‐experts with <10 cases of experience than in experts, but not in non‐experts with >10 cases. Adverse event (P = 0.165) and local recurrence (P = 0.892) rates were not significantly different between experts and non‐experts. Risk factors of failing self‐achieved en bloc resection were non‐polypoid morphology (OR 3.4, 95% CI 1.6–7.3, P = 0.001), lesions with an underlying semilunar fold (OR 3.6, 95% CI 1.6–7.3, P < 0.001), positive non‐lifting sign (OR 3.1, 95% CI 1.2–8.0, P = 0.023), and non‐experts with an experience of ≤10 cases (OR 3.6, 95% CI 2.1–6.3, P < 0.001). Conclusion: The clinical outcomes of Tip‐in EMR for 15–25 mm lesions performed by non‐experts were favorable. [ABSTRACT FROM AUTHOR]

Various autoimmune diseases have been reported to develop as a result of a coronavirus disease 19 (COVID-19) infection. There have been some reports of COVID-19-triggered autoimmune hepatitis and autoimmune hemolytic anemia infection, but none have reported simultaneous onset of these diseases. A 15-year-old girl was admitted to our hospital with severe liver injury and anemia. Three weeks before admission, her father was diagnosed with COVID-19, after which she became aware of a sore throat. Two weeks later, she visited her doctor for malaise. She was referred to our hospital due to severe anemia, elevated hepatobiliary enzymes, and jaundice. A COVID-19 polymerase chain reaction test was positive at the time of referral. She was diagnosed with autoimmune hemolytic anemia based on decreased hemoglobin and haptoglobin, positive direct Coombs test, and increased urinary urobilinogen. Blood tests were positive for antinuclear antibodies, and a liver biopsy revealed interface hepatitis and plasma cell infiltration, consistent with autoimmune hepatitis. Based on these findings, a diagnosis of autoimmune hepatitis and autoimmune hemolytic anemia triggered by COVID-19 infection was made. Steroid therapy was initiated, which resulted in rapid improvement of blood markers and symptoms. [ABSTRACT FROM AUTHOR]

Von Hippel–Lindau (VHL) disease, an autosomal dominant genetic disorder caused by a germline mutation, is associated with non-functional and slow-growing pancreatic neuroendocrine tumor (PNET) and kidney cancer. We describe the case of a 46 year-old man with a 35 mm mass in the pancreatic head causing stricture of the bile duct and main pancreatic duct, a 55 mm mass in the pancreatic tail causing obstruction of the splenic vein (SV), and multiple masses of > 36 mm on both kidneys. We performed a two-stage resection. First, a total pancreatectomy with superior mesenteric vein (SMV) resection and reconstruction and retroperitoneoscopic right partial nephrectomy (NP) for five lesions was performed, followed by retroperitoneoscopic left partial NP of the five lesions 6 months later. Postoperative histopathological examination revealed NET G2 in the pancreatic head with SMV invasion and somatostatin receptor type 2A (SSTR2A) positivity, NET G2 in the pancreatic tail showed SV invasion and negative SSTR2A, and multiple clear cell renal cell carcinomas (RCC) were also noted. Multiple liver recurrences occurred 22 months after primary surgery. The patient remains alive 41 months after primary surgery. Kidney cancer generally determines VHL prognosis; however, we experienced dual-advanced PNETs with a more defined prognosis than multiple RCC associated with VHL. [ABSTRACT FROM AUTHOR]

Background: Chordoma, a rare malignant tumor arising from notochordal tissue, usually occurs along the spinal axis. Only a few published reports of primary lung chordomas exist. Herein, we present a case of primary lung chordoma and discuss important considerations for diagnosing rare chordomas. Case presentation: We report a case of primary lung chordoma in a 39-year-old male with a history of testicular mixed germ-cell tumor of yolk sac and teratoma. Computed tomography revealed slow-growing solid lesions in the left lower lobe. We performed wedge resection for suspected germ-cell tumor lung metastasis. Histologically, large round or oval cells with eosinophilic cytoplasm were surrounded by large cells with granular, lightly eosinophilic cytoplasm. Tumor cells were physaliphorous. Immunohistochemistry was positive for brachyury, S-100 protein, epithelial membrane antigen, vimentin, and cytokeratin AE1/AE3, suggesting pulmonary chordoma. Re-examination of the testicular mixed germ-cell tumor revealed no notochordal elements. Although some areas were positive for brachyury staining, hematoxylin and eosin (HE) staining did not show morphological features typical of chordoma. Complementary fluorescence in situ hybridization (FISH) of the lung tumor confirmed the absence of isochromosome 12p and 12p amplification. Thus, a final diagnosis of primary lung chordoma was established. Conclusions: In patients with a history of testicular mixed germ cell tumors, comparison of histomorphology using HE and Brachyury staining of lung and testicular tumors, and analyzing isochromosome 12p and 12p amplification in lung tumors using FISH is pivotal for the diagnosis of rare lung chordomas. [ABSTRACT FROM AUTHOR]

Patients with pancreatic neuroendocrine tumors (pNETs) have limited access to effective targeted agents and invariably succumb to progressive disease. MUC1-C is a druggable oncogenic protein linked to driving pan-cancers. There is no known involvement of MUC1-C in pNET progression. The present work was performed to determine if MUC1-C represents a potential target for advancing pNET treatment. We demonstrate that the MUC1 gene is upregulated in primary pNETs that progress with metastatic disease. In pNET cells, MUC1-C drives E2F- and MYC-signaling pathways necessary for survival. Targeting MUC1-C genetically and pharmacologically also inhibits self-renewal capacity and tumorigenicity. Studies of primary pNET tissues further demonstrate that MUC1-C expression is associated with (i) an advanced NET grade and pathological stage, (ii) metastatic disease, and (iii) decreased disease-free survival. These findings demonstrate that MUC1-C is necessary for pNET progression and is a novel target for treating these rare cancers with anti-MUC1-C agents under clinical development. [ABSTRACT FROM AUTHOR]

Aim: Serum cholinesterase (ChE) levels are considered to reflect nutritional status. Although ChE has been well documented as a prognostic factor for some cancers, no clear consensus on its use for colorectal cancer (CRC) has been reached. The aim of this study was to investigate the relationship between preoperative serum ChE and postoperative long‐term prognosis in CRC patients. Methods: A total of 1053 CRC patients who underwent curative surgery were included in this study. The correlations between the preoperative ChE value and overall survival (OS) or cancer‐specific survival (CSS) were assessed. By dividing patients into two groups according to their ChE value, OS and CSS were compared between the groups. Results: Multivariate analysis revealed that the continuous ChE value was a significant predictor of OS (hazard ratio, 0.996; 95% CI, 0.993–0.998; p = 0.002) and CSS (hazard ratio, 0.994; 95% CI, 0.991–0.998; p = 0.001), independent of other variables. The low‐ChE (≤234 U/L) group had a significantly poorer prognosis than the high‐ChE (>234 U/L) group for both OS (5‐year OS for low ChE and high ChE: 79.8% and 93.3%, respectively; p < 0.001) and CSS (5‐year CSS for low ChE and high ChE: 84.8% and 95.6%, respectively; p < 0.001). Conclusions: Lower preoperative serum ChE levels are a predictive factor of poor prognosis for CRC patients. As serum ChE levels can be measured quickly and evaluated easily, ChE could become a useful marker for predicting the postoperative long‐term outcomes of CRC patients. [ABSTRACT FROM AUTHOR]

Strigolactones (SLs) are plant apocarotenoids with diverse roles and structures. Canonical SLs, widespread and characterized by structural variations in their tricyclic lactone (ABC-ring), are classified into two types based on C-ring configurations. The steric C-ring configuration emerges during the BC-ring closure, downstream of the biosyn-thetic intermediate, carlactonoic acid (CLA). Most plants produce either type of canonical SLs stereoselectively, e.g., tomato (Solanum lycopersicum) yields orobanchol with an α-oriented C-ring. The mechanisms driving SL structural diversification are partially understood, with limited insight into functional implications. Furthermore, the exact molecular mechanism for the stereoselective BC-ring closure reaction is yet to be known. We identified an enzyme, the stereoselective BC-ring-forming factor (SRF), from the dirigent protein (DIR) family, specifically the DIR-f subfamily, whose biochemical function had not been characterized, making it a key enzyme in stereoselective canonical SL biosynthesis with the α-oriented C-ring. We first confirm the precise catalytic function of the tomato cytochrome P450 SlCYP722C, previously shown to be involved in orobanchol biosynthesis [T. Wakabayashi et al., Sci. Adv. 5, eaax9067 (2019)], to convert CLA to 18-oxocarlactonoic acid. We then show that SRF catalyzes the stereoselective BC-ring closure reaction of 18-oxocarlactonoic acid, forming orobanchol. Our methodology combines experimental and computational techniques, including SRF structure prediction and conducting molecular dynamics simulations, suggesting a catalytic mechanism based on the conrotatory 4π-electrocyclic reaction for the stereoselective BC-ring formation in orobanchol. This study sheds light on the molecular basis of how plants produce SLs with specific stereochemistry in a controlled manner. [ABSTRACT FROM AUTHOR]

In this study, we investigated reversible intermolecular proton shifting (IPS) coupled with spin transition (ST) in a novel FeII complex. The host FeII complex and the guest carboxylic acid anion were connected by intermolecular hydrogen bonds (IHBs). We extended the intramolecular proton transfer coupled ST phenomenon to the intermolecular system. The dynamic phenomenon was confirmed by variable‐temperature single‐crystal X‐ray diffraction, neutron crystallography, and infrared spectroscopy. The mechanism of IPS was further validated using density functional theory calculations. The discovery of IPS‐coupled ST in crystalline molecular materials provides good insights into fundamental processes and promotes the design of novel multifunctional materials with tunable properties for various applications, such as optoelectronics, information storage, and molecular devices. [ABSTRACT FROM AUTHOR]

In this study, we investigated reversible intermolecular proton shifting (IPS) coupled with spin transition (ST) in a novel FeII complex. The host FeII complex and the guest carboxylic acid anion were connected by intermolecular hydrogen bonds (IHBs). We extended the intramolecular proton transfer coupled ST phenomenon to the intermolecular system. The dynamic phenomenon was confirmed by variable‐temperature single‐crystal X‐ray diffraction, neutron crystallography, and infrared spectroscopy. The mechanism of IPS was further validated using density functional theory calculations. The discovery of IPS‐coupled ST in crystalline molecular materials provides good insights into fundamental processes and promotes the design of novel multifunctional materials with tunable properties for various applications, such as optoelectronics, information storage, and molecular devices. [ABSTRACT FROM AUTHOR]

Background: Atezolizumab, one of the immune checkpoint inhibitors, has been approved as an adjuvant treatment following resection and platinum‐based chemotherapy in patients with stage II–IIIA non‐small cell lung cancer with 1% or more programmed death ligand‐1 (PD‐L1) expression. The Food and Drug Administration (FDA) has approved SP263 as a companion diagnostic assay for adjuvant treatment with atezolizumab; however, in clinical practice, the 22C3 assay is most commonly used for advanced non‐small cell lung cancer. Therefore, our study aimed to compare two PD‐L1 assays, SP263 and 22C3, to evaluate whether 22C3 could replace SP263 when deciding whether to administer adjuvant atezolizumab. Methods: We retrospectively and prospectively analyzed 98 patients who underwent surgical resection at Kanagawa Cancer Center (Japan). An immunohistochemistry assay was performed for all the cases with both SP263 and 22C3. We statistically analyzed the concordance of PD‐L1 expression between SP263 and 22C3 assays. Results: The concordance between the two assays using Cohen's kappa was κ = 0.670 (95% CI: 0.522–0.818) at the 1% cutoff and κ = 0.796 (95% CI: 0.639–0.954) at the 50% cutoff. The Spearman correlation coefficient of 0.874 (p < 0.01) indicated high concordance. PD‐L1 expression with 22C3 resulted slightly higher than that with SP263. Conclusions: This study showed a high concordance of PD‐L1 expression with the SP263 and 22C3 assays. Further studies examining the therapeutic effects of adjuvant atezolizumab are required. [ABSTRACT FROM AUTHOR]

Purpose: Testicular volume (TV) is known to be one of the main parameters for testicular function (TF). This study was conducted to re‐evaluate the indications of a varicocelectomy based on a survey of preoperative TV results in left‐side varicocele patients considered to reflect the detrimental effects of a varicocele on TF. Methods: TV results of infertile patients determined using ultrasonography by a single expert physician were retrospectively evaluated. Results: Of 590 examined patients, 424 had no varicocele findings (Group A), while 148 had a left‐side varicocele (Group B). Group B was subdivided based on varicocele grade into Group B0 (subclinical), B1 (grade 1), B2 (grade 2), and B3 (grade 3). Comparisons of left‐side TV showed no significant differences for grade among Group A, B0, and B1, whereas that for Group B2 and B3 was significantly lower as compared with Group A (p < 0.01, 0.02, respectively). The median TV of Group B I (composed of Groups B0 and B1) was 9.8 cm3, while that of Group B II (Groups B2 and B3) was significantly lower at 8.4 cm3 (p < 0.05). In contrast, a comparison of right TV values identified no significant differences among the groups (p = 0.918). Conclusion: A varicocelectomy should be performed for patients with a grade 2 and 3 varicocele for ameliorating testicular function. [ABSTRACT FROM AUTHOR]

Characteristic dynamics in lava flows, such as the formation processes of lava levees, toe-like tips, and overlapped structures, were reproduced successfully through numerical simulation using the smoothed particle hydrodynamics (SPH) method. Since these specific phenomena have a great influence on the flow direction of lava flows, it is indispensable to elucidate them for accurate predictions of areas where lava strikes. At the first step of this study, lava was expressed using a molten metal with known physical properties. The computational results showed that levees and toe-like tips formed at the fringe of the molten metal flowing down on a slope, which appeared for actual lava flows as well. The dynamics of an overlapped structure formation were also simulated successfully; therein, molten metal flowed down, solidified, and changed the surface shape of the slope, and the second molten metal flowed over the changed surface shape. It was concluded that the computational model developed in this study using the SPH method is applicable for simulating and clarifying lava flow phenomena. [ABSTRACT FROM AUTHOR]

Aim: Numerous recent reports have highlighted the association between mental disorders and electrocardiographic findings. The early repolarization pattern (ERP) on electrocardiogram has been linked with a history of suicide attempts and attention deficit hyperactivity disorder, and associations with impulsivity have also been reported. It is known that suicidal intent is more common at night. Patients who have a mental disorder and ERP may have a higher likelihood of impulsivity, potentially increasing the risk of suicide at night. Methods: The subjects were 43 patients with a history of suicide attempts who had undergone electrocardiographic examination at Jikei University School of Medicine Kashiwa Hospital and received intervention from our department. Due to the diurnal variation in electrocardiographic findings, only patients who underwent the examination during the daytime were included. Patients' clinical backgrounds were compared according to the presence or absence of ERP, and the association between nocturnal suicide attempts and ERP was examined using multivariate analysis. Results: The frequency of nocturnal suicidal behavior was 76.2% in patients with ERP and 31.8% in those without ERP, but the difference was not significant after Bonferroni correction. In the multivariate analysis, there was a significant association of ERP with nocturnal suicide attempts (p = 0.018). Conclusion: The finding of an association between ERP and nocturnal suicide attempts indicates that ERP is a biological indicator that can predict nocturnal suicide attempts. [ABSTRACT FROM AUTHOR]

When a mixture containing 1‐halo‐1‐alkyne, a dinucleophilic agent, and a base (Cs2CO3 or K3PO4) was heated in DMF, regio‐ and stereo‐selective nucleophilic addition of the dinucleophilic agent to the acetylenes occurred. This reaction yielded (Z,Z)‐bis(haloalkene), which subsequently underwent Pd‐catalyzed cyclization through C−H bond activation, resulting in the formation of two‐oxygen‐ or ‐nitrogen‐containing hetero‐π‐conjugated compounds. N‐(5‐Hydroxynaphthalen‐1‐yl)methanesulfonamide was treated with 2‐phenyl‐1‐chloroethyne followed by 1‐chloro‐1‐hexadecyne. After these reactions, Pd‐catalyzed double C−H cyclization was employed to produce 1H‐2‐phenyl‐7‐tetradecylbenzofuro[7,6‐g]indole. Notably, this compound transformed into a fan‐shaped structure at 86 °C and transitioned into a smectic A phase characterized by a layered structure. [ABSTRACT FROM AUTHOR]

Background: Cognitive behavioral therapy for insomnia (CBT-I) is among the recommended non-pharmacological treatments for patients with insomnia. While there are multiple reports on the effects of CBT-I treatment, few studies evaluating the factors associated with the treatment response to CBT-I have been reported. The present study aimed to confirm the effects of CBT-I in patients with insomnia and to examine the clinico-demographic factors that can predict the outcomes of CBT-I in these patients. Methods: Overall, 62 patients were included in the present study. To confirm the effectiveness of CBT-I, we compared the pre- and post-CBT-I therapy values of several sleep parameters. Furthermore, to identify the clinico-demographic factors that could be predictive of the treatment response to CBT-I, we performed generalized linear model (GLM) analysis. Results: The values of several sleep parameters were significantly lower after treatment than at baseline. The results of the GLM analysis revealed that sex and occupation were significantly associated with the treatment response to CBT-I. Conclusions: The present results suggest that several clinico-demographic factors should be considered in the treatment of patients with insomnia. [ABSTRACT FROM AUTHOR]

In the pursuit of novel antiretroviral therapies for human immunodeficiency virus type‐1 (HIV‐1) proteases (PRs), recent improvements in drug discovery have embraced machine learning (ML) techniques to guide the design process. This study employs ensemble learning models to identify crucial substructures as significant features for drug development. Using molecular docking techniques, a collection of 160 darunavir (DRV) analogs was designed based on these key substructures and subsequently screened using molecular docking techniques. Chemical structures with high fitness scores were selected, combined, and one‐dimensional (1D) screening based on beyond Lipinski's rule of five (bRo5) and ADME (absorption, distribution, metabolism, and excretion) prediction implemented in the Combined Analog generator Tool (CAT) program. A total of 473 screened analogs were subjected to docking analysis through convolutional neural networks scoring function against both the wild‐type (WT) and 12 major mutated PRs. DRV analogs with negative changes in binding free energy (ΔΔGbind) compared to DRV could be categorized into four attractive groups based on their interactions with the majority of vital PRs. The analysis of interaction profiles revealed that potent designed analogs, targeting both WT and mutant PRs, exhibited interactions with common key amino acid residues. This observation further confirms that the ML model‐guided approach effectively identified the substructures that play a crucial role in potent analogs. It is expected to function as a powerful computational tool, offering valuable guidance in the identification of chemical substructures for synthesis and subsequent experimental testing. [ABSTRACT FROM AUTHOR]

Granulocyte colony-stimulating factor (G-CSF) decreases the incidence, duration, and severity of febrile neutropenia (FN); however, dose reduction or withdrawal is often preferred in the management of adverse events in the treatment of urothelial cancer. It is also important to maintain therapeutic intensity in order to control disease progression and thereby relieve symptoms, such as hematuria, infection, bleeding, and pain, as well as to prolong the survival. In this clinical question, we compared treatment with primary prophylactic administration of G-CSF to maintain therapeutic intensity with conventional standard therapy without G-CSF and examined the benefits and risks as major outcomes. A detailed literature search for relevant studies was performed using PubMed, Ichu-shi Web, and Cochrane Library. Data were extracted and evaluated independently by two reviewers. A qualitative analysis of the pooled data was performed, and the risk ratios with corresponding confidence intervals were calculated and summarized in a meta-analysis. Seven studies were included in the qualitative analysis, two of which were reviewed in the meta-analysis of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) therapy, and one randomized controlled study showed a reduction in the incidence of FN. Primary prophylactic administration of G-CSF may be beneficial, as shown in a randomized controlled study of dose-dense MVAC therapy. However, there are no studies on other regimens, and we made a "weak recommendation to perform" with an annotation of the relevant regimen (dose-dense MVAC). [ABSTRACT FROM AUTHOR]

Background: Docetaxel (DTX) is commonly used as a primary chemotherapy, and cabazitaxel (CBZ) has shown efficacy in patients who are DTX resistant. Primary prophylactic granulocyte colony stimulating factor (G-CSF) therapy is currently used with CBZ treatment in routine clinical care in Japan. Methods: In this study, we performed a systematic review following the Minds guidelines to investigate the effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for prostate cancer and to construct G-CSF guidelines for primary prophylaxis use during chemotherapy. A comprehensive literature search of various electronic databases (PubMed, Cochrane Library, and Ichushi) was performed on January 10, 2020, to identify studies published between January 1990 and December 31, 2019 that investigate the impact of primary prophylaxis with G-CSF during CBZ administration on clinical outcomes. Results: Ultimately, nine articles were included in the qualitative systematic review. Primary G-CSF prophylaxis during CBZ administration for metastatic castration-resistant prostate cancer was difficult to assess in terms of correlation with overall survival, mortality from infection, and patients' quality of life. These difficulties were owing to the lack of randomized controlled trials comparing patients with and without primary prophylaxis of G-CSF during CBZ administration. However, some retrospective studies have suggested that it may reduce the incidence of febrile neutropenia. Conclusion: G-CSF may be beneficial as primary prophylaxis during CBZ administration for metastatic castration resistant prostate cancer, and we made a "weak recommendation to perform" with an annotation of the relevant regimen. [ABSTRACT FROM AUTHOR]

A spatial-frequency-resolved Schlieren photography was developed for the temporally-sequential visualization of the size-selected, multi-directional turbulent structures induced by the arc discharge in a model type gas circuit breaker. The Schlieren-based method was applied to the atmospheric-pressure DC 55-A arc discharge under gas blasting of 100%CO2, 90%CO210%C2F6 or 80%CO220%C2F6, where C2F6 was used as a substitute additive of commercially available polyatomic molecules. The visualization results clearly demonstrated that strong non-reproducible turbulence existed only for the C2F6-blended CO2 gases. The turbulence size was smaller with increasing the radial distance from the arc. The arc-discharge-induced turbulence showed circular structures in 1–5 mm diameters, which was peculiar to the C2F6-blended CO2 gases. The turbulence existence realizes high interruption performance of gas circuit breakers, which provided a new aspect for the search on the SF6-alternative gases. [ABSTRACT FROM AUTHOR]

Introduction: The clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) in Japan has not been adequately investigated. Furthermore, the relationship between stimulation-site pain and the antidepressant effects of rTMS has not been thoroughly examined. Therefore, this study aimed to clarify (1) the real-world efficacy and safety of rTMS for TRD in Japan and (2) the relationship between stimulation-site pain and clinical improvement of depressive symptoms. Methods: We conducted a retrospective observational study involving 50 right-handed patients with TRD. All patients received high-frequency rTMS for up to 6 weeks. Depressive symptoms were assessed using the Montgomery-Åsberg depression rating scale (MADRS). Pain at the stimulation site was reported by the patients using a visual analog scale (VAS) after each session. Remission and response rates at 3 and 6 weeks were calculated based on the MADRS scores. The correlation between changes in the MADRS and VAS scores was examined. Results: Remission and response rates were 36% and 46%, respectively, at the end of 3 weeks, and 60% and 70%, respectively, at 6 weeks. At the end of the treatment, there was significant correlation between the reduction of MADRS and VAS scores (r = 0.42, p = 0.003). Conclusion: This study demonstrates the clinical efficacy of rTMS in Japan and the correlation between its antidepressant effects and stimulation-site pain. [ABSTRACT FROM AUTHOR]

Advances in fluorescence microscopy and tissue-clearing have revolutionised 3D imaging of fluorescently labelled tissues, organs and embryos. However, the complexity and high cost of existing software and computing solutions limit their widespread adoption, especially by researchers with limited resources. Here, we present Acto3D, an open-source software, designed to streamline the generation and analysis of high-resolution 3D images of targets labelled with multiple fluorescent probes. Acto3D provides an intuitive interface for easy 3D data import and visualisation. Although Acto3D offers straightforward 3D viewing, it performs all computations explicitly, giving users detailed control over the displayed images. Leveraging an integrated graphics processing unit, Acto3D deploys all pixel data to system memory, reducing visualisation latency. This approach facilitates accurate image reconstruction and efficient data processing in 3D, eliminating the need for expensive highperformance computers and dedicated graphics processing units. We have also introduced a method for efficiently extracting lumen structures in 3D. We have validated Acto3D by imaging mouse embryonic structures and by performing 3D reconstruction of pharyngeal arch arteries while preserving fluorescence information. Acto3D is a cost-effective and efficient platform for biological research. [ABSTRACT FROM AUTHOR]

Objectives: The superiority and usefulness of liquid material over particles for embolization have been a topic of debate due to differences in materials and techniques. This study aimed to identify the complications and outcomes associated with both embolization materials. Methods: This retrospective multicenter cohort study included 93 patients from an endovascular treatment registry, treated from January 1, 2018 to May 31, 2022. It included patients who underwent preoperative embolization for meningioma, solitary fibrous tumor/hemangiopericytoma, and hemangioblastoma. Data for patient characteristics, procedural factors, complications, and outcomes were collected from medical records. Results: A tortuous access route was the only factor independently associated with complications (p = 0.020). Although liquid material was more frequently used for embolization in relatively high-risk conditions, complication rates did not differ significantly between the groups (p = 0.999). In the liquid material group, the tip of the microcatheter could be guided closer to the tumor (p <0.001) using a distal access catheter and flow-guide microcatheters. The subgroup middle meningeal artery embolization had less operative bleeding in the liquid material group (p <0.001), whereas the particles group exhibited less intraoperative blood loss than the liquid material group (p = 0.006). Conclusion: The vascular tortuosity of the access route was only associated with complications in preoperative tumor embolization. Liquid material and particles showed no difference in complication rates. The use of particles in embolization may reduce intraoperative bleeding, but not in all cases can it be used safely. Therefore, a thorough understanding of the characteristics of both approaches and their relative advantages in clinical practice is essential to opt for the appropriate material according to the case. [ABSTRACT FROM AUTHOR]

Partial anomalous pulmonary venous return (PAPVR) is a rare congenital malformation where the pulmonary vein partially refluxes into the venous system. Here, we present the first robotic-assisted right S3 segmentectomy in a 70-year-old male with early-stage lung cancer and PAPVR in the right upper pulmonary vein. The patient, with suspected primary lung cancer (11 mm diameter, pure solid appearance in right S3 segment), exhibited clinical stage T1bN0M0 stage IA2. Preoperative computed tomography revealed severe lung emphysema, and right V1-3 returned directly to the superior vena cava. However, no signs of right-sided heart failure were observed, and echocardiogram was normal with a pulmonary-to-systemic blood flow ratio of 1.4. Successful robot-assisted right S3 segmentectomy with hilar nodal dissection was performed, and the patient was discharged on the sixth postoperative day without complications. One year postoperatively, there has been no recurrence of lung cancer or respiratory/right-sided heart failure symptoms. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) in patients with dementia lead to caregiver burdens and worsen the patient's prognosis. Although many neuroimaging studies have been conducted, the etiology of NPS remains complex. We hypothesize that brain structural asymmetry could play a role in the appearance of NPS. Objective: This study explores the relationship between NPS and brain asymmetry in patients with Alzheimer's disease (AD). Methods: Demographic and MRI data for 121 mild AD cases were extracted from a multicenter Japanese database. Brain asymmetry was assessed by comparing the volumes of gray matter in the left and right brain regions. NPS was evaluated using the Neuropsychiatric Inventory (NPI). Subsequently, a comprehensive assessment of the correlation between brain asymmetry and NPS was conducted. Results: Among each NPS, aggressive NPS showed a significant correlation with asymmetry in the frontal lobe, indicative of right-side atrophy (r = 0.235, p = 0.009). This correlation remained statistically significant even after adjustments for multiple comparisons (p < 0.01). Post-hoc analysis further confirmed this association (p < 0.05). In contrast, no significant correlations were found for other NPS subtypes, including affective and apathetic symptoms. Conclusions: The study suggests frontal lobe asymmetry, particularly relative atrophy in the right hemisphere, may be linked to aggressive behaviors in early AD. These findings shed light on the neurobiological underpinnings of NPS, contributing to the development of potential interventions. [ABSTRACT FROM AUTHOR]

Background/Objectives: We aimed to determine the trends over time and current status of early Helicobacter pylori-uninfected gastric cancer (HpUIGC) treatment in a region with an aging population. Methods: This retrospective, multi-center observational study was conducted at seven major general hospitals in Kagoshima Prefecture. From January 2009 to July 2022, 2091 patients who received endoscopic resection (ER) for early gastric cancer (EGC) were retrospectively enrolled, of which 35 were identified as early HpUIGC cases. Results: The number of ERs for EGC demonstrated a significant increasing trend from 2010 to 2021 (p = 0.01 for trend). Furthermore, the 12-year period from 2010 to 2021 was divided into an early and late phase every 6 years. In the early phase, there were 5 cases (0.7%) of early HpUIGC, while in the late phase, there were 25 cases (2.1%), indicating a significant increase in the proportion of ERs for early HpUIGC cases in the late phase (p = 0.02). Conclusions: The proportion of ERs for early HpUIGC, which are more common in relatively young patients, may be increasing as a proportion of all ERs for GC, even in areas of Japan with an aging population. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is common and involves α‐glucosidase inhibition to regulate glucose. We synthesized twenty E‐arylidene steroids with hydroxy and methoxy groups on the aromatic ring. Compounds 3 a, 5 a, 5 b, and 5 d showed notable inhibition, with IC50 values ranging from 1.84±0.28 to 9.25±2.53 μM. Key features for bioactivity include ortho methoxy and α‐hydroxy. Various inhibition mechanisms were observed. In silico studies elucidate the possible binding modes of E‐arylidene steroids, confirming their enzymatic mechanisms of non/un‐competitive inhibitors. Allosteric site 2 emerges as a potential binding site for compounds 3 a, 5 a, and 5 b. Compound 5 d holds promise as a potent α‐glucosidase inhibitor compared to acarbose at the orthosteric receptor binding site. [ABSTRACT FROM AUTHOR]