Enantioselective synthesis of 3-(N-indolyl)quinolines containing axial and central chiralities.

Quinoline and indole are important core structures in biologically active compounds and materials. Atropisomeric biaryls consisting of quinoline and indole are a unique class of axially chiral molecules. We report herein enantioselective synthesis of 3-(N-indolyl)quinolines having both C-N axial chirality and carbon central chirality by a photoredox Minisci-type addition reaction catalyzed by a chiral lithium phosphate/Ir-photoredox complex. The catalytic system enabled access to a unique class of 3-(N-indolyl)quinolines with high chemo-, regio-, and stereoselectivities in good yields through the appropriate choice of an acid catalyst and a photocatalyst. This is the first example of the synthesis of 3-(N-indolyl)quinoline atropisomers in a highly enantioselective manner.

Extracting proficiency differences and individual characteristics in golfers' swing using single-video markerless motion analysis.

In this study, we analyzed golfers' swing movement to extract differences in proficiency and individual characteristics using two-dimensional video data from a single camera. We conducted an experiment with 27 golfers who had a wide range of skill levels, using a 7-iron; we acquired video data with a camera on the sagittal plane. For data extraction, we used pose estimation (using HRNet) and object detection (using DeepLabCut) methods to extract human-joint and club-head data. We examined the relationship between proficiency and individual characteristics vis-à-vis forward tilt angle and club trajectory. The results showed that the stability and reproducibility of the forward tilt angle are characteristics of proficiency. Highly skilled golfers showed low variability and high reproducibility between trials in forward tilt angle. However, we found that club trajectory may not be a characteristic of proficiency but rather an individual characteristic. Club trajectory was divided roughly into clockwise rotation and counterclockwise rotation. Thus, the analysis based on video data from a single markerless camera enabled the extraction of the differences in proficiency and individual characteristics of golf swing. This suggests the usefulness of our system for simply evaluating golf swings and applying it to motor learning and coaching situations.

Structural equation modeling of female gait attractiveness using gait kinematics.

In our social lives, movement's attractiveness greatly affects interpersonal cognition, and gait kinematics mediates walkers' attractiveness. However, no model using gait kinematics has so far predicted gait attractiveness. Thus, this study constructed models of female gait attractiveness with gait kinematics and physique factors as explanatory variables for both barefoot and high-heel walking. First, using motion capture data from 17 women walking, including seven professional runway models, we created gait animations. We also calculated the following gait kinematics as candidate variables to explain walking's attractiveness: four body-silhouette-related variables and six health-related variables. Then, 60 observers evaluated each gait animation's attractiveness and femininity. We performed correlation analysis between these variables and evaluation scores to obtain explanatory variables. Structural equation modeling suggested two models for gait attractiveness, one composed of trunk and head silhouette factors and the other of physique, trunk silhouette, and health-related gait factors. The study's results deepened our understanding of mechanisms behind nonverbal interpersonal cognition through physical movement and brought us closer to realization of artificial generation of attractive gait motions.

Preoperative prognostic predictors and treatment strategies for surgical procedure focused on the sequential organ failure assessment score in nonocclusive mesenteric ischemia: a multicenter retrospective cohort study.

BACKGROUND: Several large-scale studies have assessed endovascular and surgical treatment methods for nonocclusive mesenteric ischemia (NOMI); however, the prognostic factors for NOMI remain unclear. Therefore, this study aimed to evaluate risk factors for in-hospital mortality among patients with NOMI who underwent laparotomy and to examine therapeutic strategies that may improve the prognosis. MATERIALS AND METHODS: In this multicenter retrospective study, the authors reviewed the electronic medical records retrieved from the inpatient database of patients with NOMI at eight district general hospitals between January 2011 and January 2021. A total of 88 patients who underwent laparotomies were divided into survivor and nonsurvivor groups, and statistical analysis was performed to determine clinical and physiological factors. RESULTS: Exploratory laparotomy based on second-look surgery was the first treatment choice. The overall mortality rate was 48.8%, with a male-to-female ratio of 1.1:1. The median Sequential Organ Failure Assessment (SOFA) score was 8 [interquartile range: 3.75-14.2], and the median SOFA scores were 5 [3-7] in the survivor group and 13 [9-17.5] in the nonsurvivor group. Univariate analysis revealed a significant difference in BMI ( P <0.001), hypoglycemia ( P =0.0012), previous cardiovascular surgery ( P =0.0019), catecholamine use ( P <0.001), SOFA score ( P <0.001), platelet count ( P =0.0023), and lactate level ( P <0.001). Logistic regression analysis using the factors with significant differences revealed that SOFA score ≥10 (odds ratio 23.3; 95% CI: 1.94-280.00; P =0.013) was an independent prognostic factor. In addition, catecholamine use was suggested as a factor with a SOFA score greater than or equal to 10. CONCLUSION: This study confirmed that a SOFA score of greater than or equal to 10 may be associated with increased mortality. While closely monitoring low blood pressure and renal dysfunction, survival rates may be improved if surgical intervention is performed before the SOFA score reaches greater than or equal to 10.

Cloning of two gene clusters involved in the catabolism of 2,4-dinitrophenol by Paraburkholderia sp. strain KU-46 and characterization of the initial DnpAB enzymes and a two-component monooxygenases DnpC1C2.

Little is currently known about the metabolism of the industrial pollutant 2,4-dinitrophenol (DNP), particularly among gram-negative bacteria. In this study, we identified two non-contiguous genetic loci spanning 22 kb of Paraburkholderia (formerly Burkholderia) sp. strain KU-46. Additionally, we characterized four key initial genes (dnpA, dnpB, and dnpC1C2) responsible for DNP degradation, providing molecular and biochemical evidence for the degradation of DNP via the formation of 4-nitrophenol (NP), a pathway that is unique among DNP utilizing bacteria. Reverse transcription polymerase chain reaction (PCR) analysis indicated that dnpA, which encodes the initial hydride transferase, and dnpB which encodes a nitrite-eliminating enzyme, were induced by DNP and organized in an operon. Moreover, we purified DnpA and DnpB from recombinant Escherichia coli to demonstrate their effect on the transformation of DNP to NP through the formation of a hydride-Meisenheimer complex of DNP, designated as H--DNP. The function of DnpB appears new since all homologs of the DnpB sequences in the protein database are annotated as putative nitrate ABC transporter substrate-binding proteins. The gene cluster responsible for the degradation of DNP after NP formation was designated dnpC1C2DXFER, and DnpC1 and DnpC2 were functionally characterized as the FAD reductase and oxygenase components of the two-component DNP monooxygenase, respectively. By elucidating the hqdA1A2BCD gene cluster, we are now able to delineate the final degradation pathway of hydroquinone to ß-ketoadipate before it enters the tricarboxylic acid cycle.

[Two Cases of Transfusion-Free Hepatectomy Following Chemotherapy for H3 Grade of Simultaneous Liver Metastases].

We report 2 cases of transfusion-free treatment for H3 grade of simultaneous liver metastases of the colon which were treated with the chemotherapy followed by R0 liver resection. Case 1 was a 67-year-old woman bearing ascending colon cancer and a metastatic mass occupying the left lobe of the liver with 160 mm in diameter. Laparoscopic ileocecal resection and 30-day left hepatectomy were performed after the 7 courses of FOLFOX plus bevacizumab(BEV). Case 2 was a 72- year-old woman bearing transverse colon cancer with more than 10 foci of liver metastases ranging from 21 mm to 100 mm in diameter. After the transverse colon resection and 12 months of chemotherapy from FOLFOX plus BEV to FOLFIRI plus panitumumab, partial liver resection was performed for each of size-reduced foci. In both patients who declined blood transfusion, optimization of red cells and autologous transfusion with hemodilution contributed to the safe liver resection with no postoperative complications.

[A Case of Ascending Colon Cancer Metastasis to Right External Iliac Lymph Nodes].

We report a rare case of postoperative ascending colon cancer metastasis to the right external iliac lymph nodes. A 57- year-old woman underwent a laparoscopic right colectomy and D3 lymph node dissection. Pathological findings indicated a Stage Ⅲb, pT4aN1bM0 cancer. Because side effects were observed on adjuvant chemotherapy with FOLFOX, she was switched to S-1 administration every other week. Sixteen months postoperatively, right inguinal pain and elevated CEA values were noted. CT revealed two swollen right external iliac nodes with high FDG uptake on PET-CT. With the diagnosis of lymph node metastasis, an open celiotomy was performed to remove the lymph nodes. Pathological findings confirmed lymph node recurrence of ascending colon cancer. Postoperatively, her CEA values were normal and no recurrence was noted. This rare occurrence highlights the importance of examining adjacent lymph nodes for possible tumor recurrence. We report this case with the necessary literature review.

Experimental determination of the effective point of measurement for cylindrical ionization chambers in megavoltage photon beams.

Current dosimetry protocols specify an effective point of measurement (EPOM) shift of 0.6r for a cylindrical ionization chamber in photon beams. However, prior studies have reported that this shift was excessively large. The objective of this study was to experimentally evaluate the EPOM shifts in photon beams for cylindrical ionization chambers, which are widely used in clinical practice, and thus determine the appropriate EPOM shift. A microdiamond detector, which is a semiconductor detector with a small sensitive volume, was used as a reference detector, and the EPOM shifts of 11 types of cylindrical ionization chambers were evaluated at 6 MV and 10 MV. The depth shift from the percent depth dose (PDD) of the reference detector to that of the evaluated chamber was calculated using the least-squares method and was defined as the EPOM shift. The EPOM shift of the 10 MV condition was slightly larger than that of the 6 MV condition. However, because this trend was not observed for all chambers, the results of the two energies were averaged, and the EPOM shifts were determined to be 0.33r-0.43r (± 0.05) for 10 types of ionization chambers, and 0.03r (± 0.03) for the A1SL chamber. The shifts for all ionization chambers were smaller than 0.6r, indicating that the recommended EPOM shifts were overestimated and the absorbed dose was underestimated at the calibration depth. Hence, the appropriate EPOM shift of the 10 types of ionization chambers was 0.4r (the geometric center of the A1SL chamber), with a dose uncertainty of 0.05%.

Reactivity of Stabilized Vinyldiazo Compounds toward Alkenyl- and Alkynylsilanes under Gold Catalysis: Regio- and Stereoselective Synthesis of Skipped Dienes and Enynes.

We report the gold-catalyzed reaction of vinyldiazo compounds and alkenylsilanes to produce skipped dienes, which are common structural motifs in an array of bioactive compounds. This carbon-carbon bond-forming transformation proceeds with complete regio- and stereoselectivity with the silyl group serving as a regio- and stereocontrolling element. Likewise, the use of alkynylsilanes as reaction partners yielded skipped enynes resulting from a C(sp)-C(sp3) coupling. Mechanistic experiments and DFT studies have provided support for a stepwise mechanism.

Differences in anchoring strategy underlie differences in coordination in novice jugglers.

The learning process of ball juggling is characterized by considerable individual differences in acquired coordination patterns. Previous research has shown that the coordination patterns observed in novice jugglers can be roughly divided into two classes: the high ratio pattern, in which the ball is held for a relatively long time, and the low ratio pattern, in which the ball is held for a relatively short time. To account for these differences in coordination patterns, we examined the anchoring strategies employed by novice jugglers for controlling the juggling movements. Analyses of the correlation between coordination patterns and selected spatiotemporal variabilities revealed that the coordination patterns with a high dwell ratio had lower temporal variability than patterns with a low dwell ratio, which in turn had lower variability of spatial variables than patterns with a high dwell ratio. These findings indicate that individual differences in the coordination patterns adopted by novice jugglers, and hence their learning paths, result from differences in the control strategies employed.

[Laparoscopic Total Gastrectomy for Jehovah's Witness Gastric Cancer Patient after Preoperative Blood Augmentation].

An 80-year-old female of Jehovah's Witness with anemia was diagnosed with advanced gastric cancer(cT4aN2M0, stage ⅢA). The first value of Hb at the clinic was 7.5 g/dL that made it difficult to perform total gastrectomy in safe. The treatment of blood augmentation included the administration of intravenous iron and oral intake of vitamins in the earlier period. The number of hemoglobin was not optimized sufficiently in the first 10 days, that necessitated administration of erythropoietin( ESPO® INJECTION: 24,000 unit×2 times). Hb value increased in 11.6 g/dL 34 days after the treatment, that enabled laparoscopic total gastrectomy to be performed. The tumor infiltrated left crus of diaphragm. The patient was discharged in 16th postoperative day with Hb value of 10.1 g/dL without any complications. Pathological findings showed pT4b(crus) N2M0, stage ⅢB. Preoperative blood augmentation benefited the patients with anemia who decline allogenic blood transfusion. Anemia with malignant tumors is associated with not only iron deficiency due to the chronic bleeding but also functional deficiency or iron sequestration due to malignant itself, inflammation and infection. Erythropoiesis along with infusion of iron contributed to the optimization of Hb value that ensure performing total gastrectomy in safe.

Deep eutectic solvent-catalyzed Meyer-Schuster rearrangement of propargylic alcohols under mild and bench reaction conditions.

The Meyer-Schuster rearrangement of propargylic alcohols into α,ß-unsaturated carbonyl compounds has been revisited by setting up an atom-economic process catalyzed by a deep eutectic solvent FeCl3·6H2O/glycerol. Isomerizations take place smoothly, at room temperature, under air and with short reaction times. The unique solubilizing properties of the eutectic mixture enabled the use of a substrate concentration up to 1.0 M with the medium being recycled up to ten runs without any loss of catalytic activity.

Development of a Web Application That Evaluates Suture Performance in Off-the-Job Training.

Objective: To create a web application that can evaluate suture performance and assess its quality. Material and Methods: We developed the web application using a few cloud computing systems, servers, database, and computing languages. We used 20 anastomosed graft samples for optimizing the application. The images of the anastomosed grafts were captured two-dimensionally. Five vascular surgeons utilized the application to compute the objective score and rank the score of the anastomoses subjectively. Results: Steps for using the application include uploading a two-dimensional image of sutures, tracing the stitch line manually, and pushing the button to have the score displayed. After using this system for more than 1,000 times without server issues or failures, we confirmed its stability and easy accessibility. The system calculated the score within several seconds. The score of the three factors (bite, pitch, and skewness of angle) ranged from 0.25 to 0.76. The error range of the application was acceptable. The interclass correlation coefficient (ICC (2,1)) of the three factors was 0.92. Conclusion: The quality of the application was acceptable considering the low range of interoperator variations in the scores.

Gold-Catalyzed [3+2] Carbocycloaddition Reaction of Pinacol Alkenylboronates: Stereospecific Synthesis of Boryl-Functionalized Cyclopentene Derivatives.

Gold-catalysis has enabled new synthetic opportunities in the chemistry of vinyldiazo compounds. Herein, we report the gold-catalyzed reaction of stabilized vinyldiazo compounds with pinacol alkenylboronates to provide boryl-functionalized cyclopentene derivatives through a formal [3+2] carbocycloaddition reaction, a very unusual pathway in alkenylboronate chemistry. This reaction proceeds with high regio- and stereoselectivity. The synthetic usefulness of the resulting borylated cyclopentene derivatives toward the synthesis of densely functionalized cyclopentanoids is also demonstrated.

The influence of attractor stability of intrinsic coordination patterns on the adaptation to new constraints.

In most human movement tasks, the same goal can be achieved by a diversity of coordination patterns. For instance, when learning to juggle, individuals adopt their own unique coordination patterns in the early stages of acquiring the fundamental skills of juggling. These individual differences in the learning paths lead to differences in adaptability to new constraints. However, the reason for these differences in adaptability is still unknown. To address this problem, we quantified these differences in terms of attractor stability of the coordination patterns of expert jugglers using Recurrence Quantification Analysis. Furthermore, we quantified the attractor stability of intermediate jugglers and examined adaptability in a sensorimotor synchronization task. We found differences in attractor stability among coordination patterns of expert jugglers, as well as a difference in attractor stability between intrinsic coordination patterns of intermediate jugglers. Whereas, almost no significant direct correlation between attractor stability and adaptability of intermediate jugglers was found, suggesting a difference in both attractor stability and adaptability between intrinsic coordination patterns such that the difference in attractor stability might affect adaptability to new constraints. We submit that the learning path selected by each learner in the early stages of learning plays an important role in the subsequent development of expertise.

Egg-shell like Calcification as a Protective Factor for Splenic Artery Aneurysm Dilatation.

BACKGROUND: The purpose of this study was to evaluate the factors associated with asymptomatic splenic artery aneurysm (SAA) dilatation. METHODS: Among patients with SAA admitted to our department from 2001 to 2018, 70 lesions in 59 patients were selected and analyzed retrospectively. There were no cases of rupture or pregnancy in the follow-up period. We defined egg-shell appearance as SAA with >75% calcification of the outer shell. We measured the dilatation rate (mm/year) and evaluated the comorbidity and anatomical factors using univariate and multiple linear regression models. Post-hoc multiple linear regression models were fitted to evaluate the possible interactions. RESULTS: The mean age was 61.4 years (range 35-85 years), and the initial aneurysm diameter was 15.1 mm (range 3-47 mm). The mean dilatation rate was 0.26 mm/year (range 0-3.2 mm/year) during the follow-up period (average 4.6 years). Univariate analysis revealed that, portal hypertension (PHT) (P = 0.0003), egg-shell appearance (P = 0.007), and aneurysm diameter > 20 mm (P = 0.05) were significantly associated with the dilatation rate. Multivariate analysis revealed that egg-shell appearance was found to be an independent inverse risk factor of dilatation rate (P = 0.006). The multivariate analysis, including interaction terms, revealed a stronger effect of PHT and diameter >20 mm in cases with no egg-shell appearance (P = 0.08 and P = 0.05 for interactions, respectively). CONCLUSIONS: The egg-shell appearance of SAA was an independent inverse risk factor affecting the SAA dilatation rate. The dilatation rates in the case of PHT and diameter >20 mm were restricted in the presence of the egg-shell appearance.

Effect of drug-coated balloons in treatment of stenosis of the femoral artery and vein bypass graft not responding to plain old balloon angioplasty: a case report.

BACKGROUND: The use of drug-coated balloons (DCBs) with anti-proliferative agents in treating femoropopliteal lesions was approved in Japan in 2017. A better limb salvage rate or amputation-free rate of DCBs relative to plain old balloon angioplasty (POBA) has been reported; however, there is little evidence of the direct effect on intimal hyperplasia (IH). CASE PRESENTATION: A 70-year-old man with chronic limb-threatening ischemia and foot gangrene had undergone bypass surgery from the left common femoral artery to the dorsalis pedis artery 2 years earlier. We evaluated the bypass graft using ultrasonography and found stenosis around the proximal anastomotic site, presumably due to IH. POBA was performed every 3 months due to the repeated re-stenosis of the lesion. Since using the DCB, no restenosis has been detected to date (10 months). CONCLUSION: DCB might be an effective tool for treating re-stenosis due to IH or vein grafts that do not respond to POBA.

Murine Model of Central Venous Stenosis using Aortocaval Fistula with an Outflow Stenosis.

Central venous stenosis is an important entity contributing to arteriovenous fistula (AVF) failure. A murine AVF model was modified to create a partial ligation of the inferior vena cava (IVC) in the outflow of the fistula, mimicking central venous stenosis. Technical aspects of this model are introduced. The aorta and IVC are exposed, following an abdominal incision. The infra-renal aorta and IVC are dissected for proximal clamping, and the distal aorta is exposed for puncture. The IVC at the midpoint between the left renal vein and the aortic bifurcation is carefully dissected to place an 8-0 suture beneath the IVC. After clamping the aorta and IVC, an AVF is created by puncturing the infra-renal aorta through both walls into the IVC with a 25 G needle, followed by ligating a 22 G intra-venous (IV) catheter and IVC together. The catheter is then removed, creating a reproducible venous stenosis without occlusion. The aorta and IVC are unclamped after confirming primary hemostasis. This novel model of central vein stenosis is easy to perform, reproducible, and will facilitate studies on AVF failure.

Wound healing after revascularization for critical limb ischemia.

BACKGROUND: Wound healing is one of the most important endpoints after revascularization for critical limb ischemia. The purpose of this study was to evaluate the risk factors for wound healing after revascularization for critical limb ischemia (CLI). METHODS: A retrospective study was conducted at a single university hospital, and data were collected retrospectively between January 2005 and September 2016. All admitted patients who were diagnosed with CLI and underwent revascularization for the first time were enrolled. The risk factors for wound healing were analyzed. RESULTS: The risk factors for wound healing were analyzed in 153 patients. The cumulative rate of wound healing at 12 months after revascularization was 79%. The independent risk factors for wound healing were non-ambulatory status (hazard ratio, 1.95; 95% CI [1.22-3.21], P=0.004), and wound, ischemia and foot infection (WIfI) stage 4 (hazard ratio, 1.89; 95% CI [1.25-2.91], P=0.002). CONCLUSIONS: In our study, non-ambulatory status and WIfI stage 4 were independent risk factors for wound healing after revascularization. WIfI criteria well reflected the prognosis of patients with CLI in wound healing, as well as limb salvage.

Stimulation of Caveolin-1 Signaling Improves Arteriovenous Fistula Patency.

Objective- Arteriovenous fistulae (AVF) are the most common access created for hemodialysis; however, many AVF fail to mature and require repeated intervention, suggesting a need to improve AVF maturation. Eph-B4 (ephrin type-B receptor 4) is the embryonic venous determinant that is functional in adult veins and can regulate AVF maturation. Cav-1 (caveolin-1) is the major scaffolding protein of caveolae-a distinct microdomain that serves as a mechanosensor at the endothelial cell membrane. We hypothesized that Cav-1 function is critical for Eph-B4-mediated AVF maturation. Approach and Results- In a mouse aortocaval fistula model, both Cav-1 mRNA and protein were increased in the AVF compared with control veins. Cav-1 KO (knockout) mice showed increased fistula wall thickening ( P=0.0005) and outward remodeling ( P<0.0001), with increased eNOS (endothelial NO synthase) activity compared with WT (wild type) mice. Ephrin-B2/Fc inhibited AVF outward remodeling in WT mice but not in Cav-1 KO mice and was maintained in Cav-1 RC (Cav-1 endothelial reconstituted) mice (WT, P=0.0001; Cav-1 KO, P=0.7552; Cav-1 RC, P=0.0002). Cavtratin-a Cav-1 scaffolding domain peptide-decreased AVF wall thickness in WT mice and in Eph-B4 het mice compared with vehicle alone (WT, P=0.0235; Eph-B4 het, P=0.0431); cavtratin also increased AVF patency (day 42) in WT mice ( P=0.0275). Conclusions- Endothelial Cav-1 mediates Eph-B4-mediated AVF maturation. The Eph-B4-Cav-1 axis regulates adaptive remodeling during venous adaptation to the fistula environment. Manipulation of Cav-1 function may be a translational strategy to enhance AVF patency.