Resection of a retroperitoneal lumbar vein aneurysm: A case report.

We present a rare case involving a 54-year-old man with a history of pancreatitis who developed a retroperitoneal lumbar vein aneurysm that was initially misidentified as a pancreatic pseudocyst. Subsequent imaging revealed an enlarged mass and retroperitoneal perforation. Despite initial hesitation, the patient eventually underwent radical surgery that enabled the successful removal of the mass, which was near the inferior vena cava. Pathological examination confirmed varicose veins, and the final diagnosis was lumbar vein aneurysm in the retroperitoneum. The patient's postoperative recovery was uneventful, with no symptoms or recurrence observed on 6-month follow-up imaging. We investigated a potential link between pancreatitis and recurrent bleeding due to weakened venous walls. The findings from this case underscore the rarity of venous aneurysms and the diagnostic and treatment challenges due to the limited number of cases; furthermore, they emphasize that surgery should be carefully considered based on the lesion location and associated risks.

Optimal ablation settings of TactiFlex SE laser-cut irrigated-tip catheter: comparison with ThermoCool SmartTouch SurroundFlow porous irrigated-tip catheter.

BACKGROUND: The TactiFlex SE catheter (TFSE, Abbott) with a contact force (CF) sensor and a laser-cut irrigated-tip has recently become available but lacks a lesion quality marker. This study aimed to explore distinctions in lesion characteristics between the TFSE and the ThermoCool SmartTouch SurroundFlow catheter (STSF, Biosense Webster), which utilizes a porous irrigated tip, and to assess the most effective application settings for the TFSE. METHODS: Lesions were generated using varying settings of radiofrequency power (30-50 W), CF (10-20 g), application duration (10-40 s), and catheter orientation (perpendicular or parallel) in an ex vivo porcine model. Comparative analysis between the TFSE and STSF was conducted for lesion characteristics and incidence of steam pops using predictive models in regression analyses. RESULTS: Among 720 applications, the TFSE exhibited a significantly lower incidence of steam pops compared to the STSF (0.6% vs. 36.8%, P < 0.001). Moreover, coefficients of determination (R2) for the TFSE were higher than those for the STSF concerning lesion depth (0.710 vs. 0.541) and volume (0.723 vs. 0.618). The lesion size generated with the TFSE was notably smaller than that with the STSF under identical application settings. Additionally, to achieve a lesion depth ≥ 4.0 mm, the TFSE required an application duration 8-12 s longer than the STSF under similar settings. CONCLUSIONS: The TFSE demonstrated a lower incidence of steam pops and superior predictability in lesion size compared to the STSF. However, the TFSE necessitated a longer application duration than the STSF to achieve an adequate lesion size.

Relationship between the amount of black carbon particles deposited on the leaf surface and leaf surface traits in nine urban greening tree species.

To select urban greening tree species suitable for the purification of the atmosphere polluted by black carbon (BC) particles, it is necessary to clarify the determinants of the amount of BC particles deposited on the tree leaves. In the present study, we investigated the relationship between the amount of BC particles that were deposited from the atmosphere and firmly adhered to the leaf epicuticular wax, and leaf surface traits in seedlings of nine tree species grown for two years under natural conditions (Fuchu, Tokyo, Japan). There was a significant interspecific difference in the maximum amount of BC particles deposited on the leaf surface, and the order was as follows: Ilex rotunda > Cornus florida > Osmanthus fragrans > Cornus kousa > Quercus glauca ≒ Quercus myrsinifolia > Magnolia kobus ≒ Zelkova serrata ≒ Styrax japonicus. In the nine tree species, significant highly positive correlations were observed between the amount of BC particles deposited on the leaf surface, and the hydrophobicity of leaf epicuticular wax determined by its chemical composition. Therefore, we concluded that the hydrophobicity of leaf epicuticular wax is an important determinant of the amount of BC particles deposited on the leaf surface of urban greening tree species.

This is the first paper that shows that the hydrophobicity of leaf epicuticular wax is an important determinant of the amount of BC particles deposited on the leaf surface of urban greening tree species. This study will provide the basic and novel information for the selection of urban greening tree species suitable for the purification of the air polluted by BC particles.

Combined therapeutic effect of YHO-1701 with PD-1 blockade is dependent on natural killer cell activity in syngeneic mouse models.

The signal transducer and activator of transcription 3 (STAT3) signaling pathway is a key mediator of cancer cell proliferation, survival, and invasion. We discovered YHO-1701 as a small molecule inhibitor of STAT3 dimerization and demonstrated its potent anti-tumor activity using xenograft mouse models as monotherapy and combination therapy with molecular targeted drugs. STAT3 is also associated with cancer immune tolerance; therefore, we used the female CT26 syngeneic mouse model to examine the effect of combining YHO-1701 administration with PD-1/PD-L1 blockade. Pretreatment of the mice with YHO-1701 before starting anti-PD-1 antibody administration resulted in a significant therapeutic effect. In addition, the effect of monotherapy and combination treatment with YHO-1701 was significantly abolished by depleting natural killer (NK) cell activity. YHO-1701 was also found to restore the activity of mouse NK cells under inhibitory conditions in vitro. Furthermore, this combination therapy significantly inhibited tumor growth in an immunotherapy-resistant model of murine CMS5a fibrosarcoma. These results suggest that the combination of YHO-1701 with PD-1/PD-L1 blockade might be a new candidate for cancer immunotherapy involving the enhancement of NK cell activity in the tumor microenvironment.

Functional duality in group criticality via ambiguous interactions.

Critical phenomena are wildly observed in living systems. If the system is at criticality, it can quickly transfer information and achieve optimal response to external stimuli. Especially, animal collective behavior has numerous critical properties, which are related to other research regions, such as the brain system. Although the critical phenomena influencing collective behavior have been extensively studied, two important aspects require clarification. First, these critical phenomena never occur on a single scale but are instead nested from the micro- to macro-levels (e.g., from a Lévy walk to scale-free correlation). Second, the functional role of group criticality is unclear. To elucidate these aspects, the ambiguous interaction model is constructed in this study; this model has a common framework and is a natural extension of previous representative models (such as the Boids and Vicsek models). We demonstrate that our model can explain the nested criticality of collective behavior across several scales (considering scale-free correlation, super diffusion, Lévy walks, and 1/f fluctuation for relative velocities). Our model can also explain the relationship between scale-free correlation and group turns. To examine this relation, we propose a new method, applying partial information decomposition (PID) to two scale-free induced subgroups. Using PID, we construct information flows between two scale-free induced subgroups and find that coupling of the group morphology (i.e., the velocity distributions) and its fluctuation power (i.e., the fluctuation distributions) likely enable rapid group turning. Thus, the flock morphology may help its internal fluctuation convert to dynamic behavior. Our result sheds new light on the role of group morphology, which is relatively unheeded, retaining the importance of fluctuation dynamics in group criticality.

Gallbladder cancer concomitant with autosomal dominant polycystic kidney disease: A case report.

The case is a 67-year-old female with autosomal dominant polycystic kidney disease who was followed up regularly. CT scan showed a mural nodule growing over the past 4 years inside the hypodense region surrounded by hepatic cysts. Surgery was performed and the pathological diagnosis was StageI gallbladder cancer.

Identification and Characterization of a Novel Dual Inhibitor of Indoleamine 2,3-dioxygenase 1 and Tryptophan 2,3-dioxygenase.

Kynurenine (Kyn), a metabolite of tryptophan (Trp), is a key regulator of mammal immune responses such as cancer immune tolerance. Indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) are main enzymes regulating the first and rate-limiting step of the Kyn pathway. To identify new small molecule inhibitors of TDO, we selected A172 glioblastoma cell line constitutively expressed TDO. Characterization of this cell line using kinase inhibitor library resulted in identification of MEK/ERK pathway-dependent TDO expression. After knowing the properties for TDO expression, we further proceeded to screen chemical library for TDO inhibitors. We previously determined that S-benzylisothiourea derivatives are enzymatic inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) and suggested that the isothiourea moiety could be an important pharmacophore for binding to heme. Based on this premise, we screened an in-house library composed of various isothiourea derivatives and identified a bisisothiourea derivative, PVZB3001, as an inhibitor of TDO. Interestingly, PVZB3001 also inhibited the enzymatic activity of IDO1 in both cell-based and cell-free assays but did not inhibit other heme enzymes. Molecular docking studies suggested the importance of isothiourea moieties at the ortho position of the phenyl ring for the inhibition of catalytic activity. PVZB3001 showed competitive inhibition against TDO, and this was supported by the docking simulation. PVZB3001 recovered natural killer (NK) cell viability and functions by inhibiting Kyn accumulation in conditioned medium of both IDO1- and TDO-expressing cells. Furthermore, oral administration of IDO1-overexpressing tumor-bearing mice with PVZB3001 significantly inhibited tumor growth. Thus, we identified a novel selective dual inhibitor of IDO1 and TDO using the Kyn production assay with a glioblastoma cell line. This inhibitor could be a useful pharmacological tool for modulating the Kyn pathway in a variety of experimental systems.

Spontaneous behavioral coordination between avoiding pedestrians requires mutual anticipation rather than mutual gaze.

Pedestrians threading through a crowd is a striking example of coordinated actions. Mutual anticipation between pedestrians is a candidate mechanism underlying such coordination. To examine this possibility, we experimentally intervened pairs of pedestrians performing simple avoidance tasks. Pedestrians in the baseline condition spontaneously coordinated their walking speed and angle until passing one another. Visually distracting one of the pedestrians decreased the level of behavioral coordination. Importantly, blocking the pedestrians' gaze information alone did not alter their walking. These results indicate that spontaneous coordination requires mutual anticipation. Eye movement analysis showed that the direction of a pedestrian's gaze changed depending on the uncertainty of the oncoming pedestrian's motion, and that pedestrians tended to look ahead toward the ultimate passing direction before they actually walked in that direction. We propose that body motion cues may be sufficient and available for implicit negotiation of potential future motions.

Septal coronary artery fistula after left bundle branch area pacing assessed by multi-imaging modalities and shunt volume quantification.

Septal coronary artery fistula is a rare but concerning complication of left bundle branch area pacing (LBBAP). We report the case of an 82-year-old man who was indicated for cardiac resynchronization therapy and underwent LBBAP. The patient had no chest symptoms during or after implantation. Postoperative echocardiography demonstrated a new abnormal tunnel inside the interventricular septum (IVS) and shunt flow from the IVS toward the right ventricle. Coronary angiography confirmed a septal coronary artery fistula, which might have been formed by failed deep screw attempts. Since the shunt volume assessed by the Qp /Qs was small, the patient was treated conservatively.

Identification of serum and glucocorticoid-regulated kinase 1 as a regulator of signal transducer and activator of transcription 3 signaling.

Signal transducer and activator of transcription 3 (STAT3) plays key roles in cancer cell proliferation, invasion, and immunosuppression. In many human cancer cells, STAT3 is hyperactivated, which leads to tumor progression and drug resistance, and therefore STAT3 and its modulators are considered effective drug targets. However, the complex regulatory mechanisms of STAT3 have made it difficult to develop potent anticancer drugs that suppress its activity. Here, we report serum and glucocorticoid-regulated kinase 1 (SGK1) as a novel regulator of STAT3 signaling and an effective target for combination therapy with Janus kinase (JAK) inhibitors. We screened small molecules using a gain-of-function mutant of STAT3 resistant to JAK inhibition and found that an SGK1 inhibitor suppressed the constitutive activation of STAT3. Importantly, our results revealed that SGK1 also mediated the activation of wild-type STAT3. Further examination suggested that the tuberous sclerosis complex 2 and mammalian target of rapamycin signaling pathway were involved in STAT3 activation by SGK1. Finally, we demonstrated that SGK1 inhibition enhanced the inhibitory effect of a JAK inhibitor on STAT3 phosphorylation and cancer cell proliferation. Our findings provide new insights into the molecular mechanisms of STAT3 activation and suggest SGK1 as a potential target for STAT3-targeted combination cancer therapy.

Efficacy of His Bundle Pacing on LV Relaxation and Clinical Improvement in HF and LBBB.

OBJECTIVES: This study aimed to compare acute hemodynamic improvements and responses to His bundle pacing (HBP) and conventional biventricular pacing (BVP). BACKGROUND: HBP can correct left bundle branch block (LBBB) and may be an alternative cardiac resynchronization therapy (CRT) to BVP. METHODS: Fourteen consecutive patients with heart failure (HF) and typical LBBB who required CRT were enrolled. The acute hemodynamic responses during HBP and BVP were compared using a micromanometer-tipped catheter inserted into the left ventricle (LV) before CRT. Each configuration was compared with AAI mode. A permanent HBP device was implanted when LBBB correction threshold was ≤1.5 V at 1.0 ms, and remaining patients were treated with BVP. Clinical and echocardiographic improvements were assessed during a 12-month follow-up period. RESULTS: The LV contractile index (positive maximal rate of LV pressure rise [dP/dtmax]) increased similarly during HBP and BVP (18.8% ± 6.4% vs 18.0% ± 10.2%; P = 0.810). LV relaxation indices (negative dP/dtmax and tau) were significantly improved during HBP compared with BVP (negative dP/dtmax: 14.3% ± 5.5% vs 3.1% ± 8.1%; P < 0.001; tau: 7.2% ± 4.3% vs -0.8% ± 8.1%; P = 0.001). Nine (64%) patients received permanent HBP devices, while 5 patients were treated with BVP. The New York Heart Association functional class, LV ejection fraction, LV end-systolic volume, and B-type natriuretic peptide level improved in patients treated with HBP and BVP (all P < 0.05 vs baseline). Patients treated with HBP exhibited earlier and greater improvements of the LV ejection fraction and LV end-systolic volume than did those with BVP. CONCLUSIONS: HBP improves systolic function and LV relaxation in patients with HF and LBBB. CRT via HBP produced earlier and greater clinical responses than BVP.

Permanent His-bundle pacing using distal His-bundle electrogram-guided approach in patients with atrioventricular block.

BACKGROUND: Permanent His-bundle pacing (HBP) is effective and safe; however, the success rate of HBP is low, especially in patients with infranodal block. This study aimed to assess the efficacy and feasibility of HBP implantation using an electrophysiological guided approach targeting a distal His-bundle electrogram (HBE) in patients with atrioventricular block (AVB). METHODS: Thirty-four consecutive patients with AVB (infranodal block in 28 patients) who underwent HBP were enrolled. During implantation, we attempted to target the distal part of the HBE (distal HBE) beyond the block site based on unipolar mapping. The His-capture threshold was evaluated for 1 year after implantation. RESULTS: HBP was achieved in 26 patients and in 21 patients (75%) with infranodal block. Detection of distal HBE was significantly higher in the successful HBP group than in the HBP failure group (65.4% vs. 0%, p = .001). Among 15 patients with intra-Hisian block, 14 patients (93%) successfully achieved HBP with distal HBE detection. During the 1-year follow-up period, an increase in His-capture threshold by ≥1.0 V at 1.0 ms occurred in five (19.2%) of 26 patients. The increased His-capture threshold group exhibited significantly less detection of distal HBE (20% vs. 76.2%; odds ratio 0.078, 95% confidence interval 0.07-0.87, p = .038) and a higher His-capture threshold at implantation (2.0 ± 1.1 V vs. 1.1 ± 0.9 V; odds ratio 1.702, 95% confidence interval 1.025-2.825, p = 0.04) than the non-increased His-capture threshold group. CONCLUSION: HBP implantation guided by distal HBE approach may be feasible with subsequent stable pacing in patients with intra-Hisian and atrioventricular nodal block.

Mutual anticipation can contribute to self-organization in human crowds.

Human crowds provide paradigmatic examples of collective behavior emerging through self-organization. Understanding their dynamics is crucial to help manage mass events and daily pedestrian transportation. Although recent findings emphasized that pedestrians' interactions are fundamentally anticipatory in nature, whether and how individual anticipation functionally benefits the group is not well understood. Here, we show the link between individual anticipation and emergent pattern formation through our experiments of lane formation, where unidirectional lanes are spontaneously formed in bidirectional pedestrian flows. Manipulating the anticipatory abilities of some of the pedestrians by distracting them visually delayed the collective pattern formation. Moreover, both the distracted pedestrians and the nondistracted ones had difficulties avoiding collisions while navigating. These results imply that avoidance maneuvers are normally a cooperative process and that mutual anticipation between pedestrians facilitates efficient pattern formation. Our findings may influence various fields, including traffic management, decision-making research, and swarm dynamics.

Design, synthesis, and evaluation of a novel prodrug, a S-trityl-l-cysteine derivative targeting kinesin spindle protein.

Kinesin spindle protein (KSP) is expressed only in cells undergoing cell division, and hence represents an attractive target for the treatment of cancer. Several KSP inhibitors have been developed and undergone clinical trial, but their clinical use is limited by their toxicity to rapidly proliferating non-cancerous cells. To create new KSP inhibitors that are highly selective for cancer cells, we optimized the amino acid moiety of S-trityl-l-cysteine (STLC) derivative 1 using in silico modeling. Molecular docking and molecular dynamics simulation were performed to investigate the binding mode of 1 with KSP. Consistent with the structure activity relationship studies, we found that a cysteine amino moiety plays an important role in stabilizing the interaction. Based on these findings and the structure of GSH, a substrate of γ-glutamyltransferase (GGT), we designed and synthesized the prodrug N-γ-glutamylated STLC derivative 9, which could be hydrolyzed by GGT to produce 1. The KSP ATPase inhibitory activity of 9 was lower than that of 1, and LC-MS analysis indicated that 9 was converted to 1 only in the presence of GGT in vitro. In addition, the cytotoxic activity of 9 was significantly attenuated in GGT-knockdown A549 cells. Since GGT is overexpressed on the cell membrane of various cancer cells, these results suggest that compound 9 could be a promising prodrug that selectively inhibits the proliferation of GGT-expressing cancer cells.

Lévy Walk in Swarm Models Based on Bayesian and Inverse Bayesian Inference.

While swarming behavior is regarded as a critical phenomenon in phase transition and frequently shows the properties of a critical state such as Lévy walk, a general mechanism to explain the critical property in swarming behavior has not yet been found. Here, we address this problem with a simple swarm model, the Self-Propelled Particle (SPP) model, and propose a way to explain this critical behavior by introducing agents making decisions via the data-hypothesis interaction in Bayesian inference, namely, Bayesian and inverse Bayesian inference (BIB). We compare three SPP models, namely, the simple SPP, the SPP with Bayesian-only inference (BO) and the SPP with BIB models. We show that only the BIB model entails coexisting tornado, splash and translation behaviors, and the Lévy walk pattern.

Pheochromocytoma crisis in a patient with newly diagnosed neurofibromatosis type 1.

Pheochromocytoma occasionally engenders catecholamine-induced hypertension crisis. Pheochromocytoma is clinically identified in 0.1%-5.7% of patients with neurofibromatosis type 1 (NF1), which is 10 times more frequently than in healthy individuals. This report describes a case of newly diagnosed NF1 presenting with pheochromocytoma crisis, with severe electrolyte depletion and deteriorating recurrent ventricular tachycardia storm. Characteristic skin lesions such as café-au-lait macules and neurofibromas contributed to the diagnosis of NF1 and pheochromocytoma. No recurrence of electrolyte depletion was found after the adrenalectomy. Primary care physicians must distinguish the characteristic skin lesions of NF1, such as café-au-lait macules and neurofibromas and recognise the risk for pheochromocytoma.

Four-Types of IIT-Induced Group Integrity of Plecoglossus altivelis.

Integrated information theory (IIT) was initially proposed to describe human consciousness in terms of intrinsic-causal brain network structures. Particularly, IIT 3.0 targets the system's cause-effect structure from spatio-temporal grain and reveals the system's irreducibility. In a previous study, we tried to apply IIT 3.0 to an actual collective behaviour in Plecoglossus altivelis. We found that IIT 3.0 exhibits qualitative discontinuity between three and four schools of fish in terms of Φ value distributions. Other measures did not show similar characteristics. In this study, we followed up on our previous findings and introduced two new factors. First, we defined the global parameter settings to determine a different kind of group integrity. Second, we set several timescales (from Δ t = 5 / 120 to Δ t = 120 / 120 s). The results showed that we succeeded in classifying fish schools according to their group sizes and the degree of group integrity around the reaction time scale of the fish, despite the small group sizes. Compared with the short time scale, the interaction heterogeneity observed in the long time scale seems to diminish. Finally, we discuss one of the longstanding paradoxes in collective behaviour, known as the heap paradox, for which two tentative answers could be provided through our IIT 3.0 analysis.

Development of an automatic turntable-type multiple T-maze device and observation of pill bug behavior.

In recent years, various animal observation instruments have been developed to support long-term measurement and analysis of animal behaviors. This study proposes an automatic observation instrument that specializes for turning behaviors of pill bugs and aims to obtain new knowledge in the field of ethology. Pill bugs strongly tend to turn in the opposite direction of a preceding turn. This alternation of turning is called turn alternation reaction. However, a repetition of turns in the same direction is called turn repetition reaction and has been considered a malfunction of turn alternation. In this research, the authors developed an automatic turntable-type multiple T-maze device and observed the turning behavior of 34 pill bugs for 6 h to investigate whether turn repetition is a malfunction. As a result, most of the pill bug movements were categorized into three groups: sub-diffusion, Brownian motion, and Lévy walk. This result suggests that pill bugs do not continue turn alternation mechanically but elicit turn repetition moderately, which results in various movement patterns. In organisms with relatively simple nervous systems such as pill bugs, stereotypical behaviors such as turn alternation have been considered mechanical reactions and variant behaviors such as turn repetition have been considered malfunctions. However, our results suggest that a moderate generation of turn repetition is involved in the generation of various movement patterns. This study is expected to provide a new perspective on the conventional view of the behaviors of simple organisms.

Diagnostic Value of Serum Procalcitonin in Patients with Convulsion in Emergency Department, an Observational Study.

Procalcitonin (PCT), a widely used biomarker for bacterial infections, is sometimes measured in convulsion patients to distinguish bacterial infections including bacterial meningitis. However, serum PCT elevation is reported in several other conditions. This study assessed the diagnostic value of serum PCT concentrations in convulsion patients. This study examined a convulsion group: patients admitted to our critical care center during April 2018 through September 2019 via the emergency department presenting with convulsions. Randomly sampled patients admitted without convulsions were categorized as a non-convulsion group. Serum PCT analysis was performed with consideration of whether or not the patient had an infection. Diagnostic values of serum PCT for bacterial infection were evaluated for convulsion and non-convulsion patients using the positive likelihood ratio of PCT. This study found 84 patients as eligible for the convulsion group; 1:2 matched 168 control patients were selected as non-convulsion group members. The positive likelihood ratio for bacterial infection was found to be significantly lower in the convulsion group than in the control group (1.94 vs. 2.65) when setting the positive cut-off for PCT as 0.5 ng/mL. Convulsion patients had a higher PCT value. The positive likelihood ratio for patients without bacterial infection was lower.