[Early Structural Valve Deterioration of Trifecta Aortic Bioprosthesis:Report of a Case].

Trifecta, an externally mounted bovine pericardial bioprosthetic aortic valve, provides excellent hemodynamic performance;however, early structural deterioration of this valve has been reported. A 60-year-old man with progressive dyspnea was admitted to the emergency unit of our institution. Seven years prior, he underwent aortic valve replacement with 23-mm Trifecta valve. Severe aortic valve regurgitation and stenosis due to structural valve deterioration was diagnosed and redo aortic valve replacement using an Inspiris valve was performed. Intraoperative findings revealed a large laceration in the left coronary cusp adjacent to the non coronary-left coronary commissure and leaflet calcification. Further, circumferential fibrous pannus ingrowth at the inflow portion was also noted. To avoid anticoagulation therapy and repeat surgery, mitral valve plasty and left atrial appendage clipping were performed simultaneously. Postoperative course was uneventful, and he was transferred to a rehabilitation facility on 36th postoperative day.

Quantitative Assessment of Calf Muscle Volume, Strength, and Quality After Achilles Tendon Rupture Repair: A 1-Year Prospective Follow-up Study.

BACKGROUND: A number of studies have reported that calf muscle atrophy is a common long-term problem after Achilles tendon repair; however, there is still a lack of data concerning early postoperative morphological changes in the calf muscle after surgery. PURPOSE: To investigate changes over time in calf muscle volume and fatty degeneration during 1 year after Achilles tendon repair. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A prospective 1-year serial magnetic resonance imaging study was carried out with 20 patients who underwent tendon repair for unilateral acute Achilles tendon rupture. The magnetic resonance imaging assessment in addition to clinical and functional evaluations was performed at 1, 3, 6, and 12 months after surgery. The muscle volume of the medial and lateral gastrocnemius, soleus, and flexor hallucis longus (FHL) and fatty degeneration of the medial and lateral gastrocnemius and soleus were measured for the calf muscles, and the relative volume and fatty degeneration changes in the affected leg compared with the healthy contralateral leg were calculated as a percentage ([injured/healthy control] × 100) to assess structural changes over time. RESULTS: Muscle volumes of the medial gastrocnemius, lateral gastrocnemius, soleus, and FHL were 92.3%, 92.8%, 84.6%, and 95.9% at 12 months after surgery, respectively. Medial and lateral gastrocnemius and FHL muscle volumes improved over time and recovered to almost equal to that of the healthy side at 12 months after surgery. The soleus muscle volume did not recover significantly over time and was statistically significantly smaller than that of the healthy side at 12 months (P = .029). Fatty degeneration rates of the medial gastrocnemius, lateral gastrocnemius, and soleus were 118.2%, 113.9% and 121.1% at 12 months after surgery, respectively. Fatty degeneration of the medial and lateral gastrocnemius did not change significantly, but there was a statistically significant increase in fatty degeneration of the soleus over time (P < .001). CONCLUSION: Within the triceps surae muscle, the soleus was the most negatively affected by injury and repair for both muscle volume and fatty degeneration. Postoperative management to recover the soleus muscle function before a return to sporting activities should be considered in the future.

Remote C-H Olefination of Heterocyclic Biaryls Enabled by Reversibly Bound Templates.

Remote C-H functionalization of heterocyclic biaryls will be of great importance in synthesis and medicinal chemistry. Through adjusting the geometric relationship of the directing atom and target C-H bonds, two new catalytic templates have been developed to enable the functionalization of the more hindered ortho-C-H bonds of heterobiaryls bearing directing heteroatom at the meta- or para-positions, affording unprecedented site-selectivity. The use of template chaperone also overcomes product inhibition and renders the directing templates catalytic. The utility of this protocol was demonstrated by olefination of heterocyclic biaryls with various substituents, overriding conventional steric and electronic effects. These ortho-C-H olefinated heterobiaryls are sterically hindered and can often be challenging to prepare through aryl-aryl coupling reactions.

Syntheses and structures of ammonium transition-metal dialuminium tris-(phosphate) dihydrates (NH4)MAl4(PO4)3·2H2O (M = Mn and Ni).

The structures of ammonium manganese(II) dialuminium tris-(phosphate) dihydrate, (NH4)MnAl2(PO4)3·2H2O, and ammonium nickel(II) dialuminium tris-(phosphate) dihydrate, (NH4)NiAl2(PO4)3·2H2O, were determined using single-crystal diffraction data. The structures of title compounds are isotypic to cobalt aluminophosphate, (NH4)CoAl2(PO4)3·2H2O (LMU-3) [Panz et al. (1998 ▸). Inorg. Chim. Acta, 269, 73-82], in which a three-dimensional network of vertex-sharing AlO5 and PO4 moieties delineate twelve-membered channels in which ammonium, NH4 +, and transition-metal cations (M = Mn2+ and Ni2+) reside as charge compensators for the anionic [Al2(PO4)3]3- aluminophosphate framework. In both structures, the N atom of the ammonium cation, the transition-metal ion and one of the P atoms lie on crystallographic twofold axes.

Polymorphism at the nestling stage and host-specific mimicry in an Australasian cuckoo-host arms race.

Decades of research have shown that the coevolutionary arms race between avian brood parasites and their hosts can promote phenotypic diversification in hosts and brood parasites. However, relatively little is known about the role of brood parasitism in promoting phenotypic diversification of nestlings. We review field data collected over four decades in Australia, New Caledonia and New Zealand to assess potential for coevolutionary interactions between the shining bronze-cuckoo (Chalcites lucidus) and its hosts, and how diversification at the nestling stage may be generating different subspecies. The shining bronze-cuckoo is a specialist parasite of a few hosts in the family Acanthizidae. It has diversified into subspecies, of which the nestlings closely mimic the respective host nestlings in each region. Additionally, some cuckoo subspecies have polymorphic nestlings. The Acanthizidae hosts have similar breeding and nesting habits and only moderately effective frontline defences against parasitism at cuckoo egg laying or at the egg stages. However, some hosts have developed highly effective defences at the nestling stage by recognising and ejecting cuckoo nestlings from the nest. As with the cuckoo nestlings, some hosts have polymorphic nestlings. The coevolutionary interactions in each region suggest different evolutionary stages of the arms race in which either the parasite or the host is currently in the lead. The presence of moderately effective defences at the egg laying and egg stages might explain why some hosts do not have defences at the nestling stage. The south-Pacific cuckoo - host systems are excellent models to explore the evolutionary mechanisms driving the diversification at the nestling stage in the coevolutionary arms race between avian brood parasites and their hosts.

Photochemical Alkene Hydrophosphination with Bis(trichlorosilyl)phosphine.

Bis(trichlorosilyl)phosphine (HP(SiCl3)2, 1) was prepared from [TBA][P(SiCl3)2] ([TBA]2, TBA = tetra-n-butylammonium) and triflic acid in 36% yield. Phosphine 1 is an efficient reagent for hydrophosphination of unactivated terminal olefins under UV irradiation (15-60 min) and gives rise to bis(trichlorosilyl)alkylphosphines (RP(SiCl3)2, R = (CH2)5CH3, 88%; (CH2)7CH3, 98%; (CH2)2C(CH3)3, 76%; CH2Cy, 93%; (CH2)2Cy, 95%; CH2CH(CH3)(CH2)2CH3, 82%; (CH2)3O(CH2)3CH3, 95%; (CH2)3Cl, 83%; (CH2)2SiMe3, 92%; (CH2)5C(H)CH2, 44%) in excellent yields. The products require no further purification beyond filtration and removal of volatile material under reduced pressure. The P-Si bonds of prototypical products RP(SiCl3)2 (R = -(CH2)5CH3, -(CH2)7CH3) are readily functionalized to give further phosphorus-containing products: H3C(CH2)7PCl2 (56%), [H3C(CH2)5P(CH2Ph)3]Br (84%), H3C(CH2)7PH2 (61%), H3C(CH2)5P(O)(H)(OH) (81%), and H3C(CH2)5P(O)(OH)2 (55%). Experimental mechanistic investigations, accompanied by quantum chemical calculations, point toward a radical-chain mechanism. Phosphine 1 enables the fast, high-yielding, and atom-efficient preparation of compounds that contain phosphorus-carbon bonds in procedures that bypass white phosphorus (P4), a toxic and high-energy intermediate of the phosphorus industry.

Molecular editing of aza-arene C-H bonds by distance, geometry and chirality.

Direct molecular editing of heteroarene carbon-hydrogen (C-H) bonds through consecutive selective C-H functionalization has the potential to grant rapid access into diverse chemical spaces, which is a valuable but often challenging venture to achieve in medicinal chemistry1. In contrast to electronically biased heterocyclic C-H bonds2-9, remote benzocyclic C-H bonds on bicyclic aza-arenes are especially difficult to differentiate because of the lack of intrinsic steric/electronic biases10-12. Here we report two conceptually distinct directing templates that enable the modular differentiation and functionalization of adjacent remote (C6 versus C7) and positionally similar (C3 versus C7) positions on bicyclic aza-arenes through careful modulation of distance, geometry and previously unconsidered chirality in template design. This strategy enables direct C-H olefination, alkynylation and allylation at adjacent C6 and C7 positions of quinolines in the presence of a competing C3 position that is spatially similar to C7. Notably, such site-selective, iterative and late-stage C-H editing of quinoline-containing pharmacophores can be performed in a modular fashion in different orders to suit bespoke synthetic applications. This Article, in combination with previously reported complementary methods, now fully establishes a unified late-stage 'molecular editing' strategy to directly modify bicyclic aza-arenes at any given site in different orders.

Introducing N-Heterocyclic Iminophosphoranes (NHIPs): Synthesis by [3 + 2] Cycloaddition of Azophosphines with Alkynes and Reactivity Studies.

Azophosphines (Ar-N═N-PR2) were prepared from N-aryl-N'-(trimethylsilyl)diazenes (Ar-N═N-SiMe3) and R2PCl by Me3SiCl elimination or oxidation of phosphinohydrazines (Ar-NH-NH-PR2) by 2,5-dialkyl-1,4-benzoquinones. Azophosphines underwent 1,3-dipolar cycloaddition with cyclooctyne and dimethylacetylene dicarboxylate to give N-heterocyclic iminophosphoranes (NHIPs), which are structurally similar to cyclic (alkyl)(amino)carbenes. The cycloaddition reaction is compatible with various phosphorus atom substituents including phenyl (NHIP-1,4,6), isopropyl (NHIP-2), cyclohexyl (NHIP-3), and dimethylamino (NHIP-5) groups. The pKBH+ values of the NHIPs in acetonitrile range from 13.13 to 23.14. On the basis of the Huynh electronic parameter, NHIP-1 and NHIP-2 have σ-donor strengths comparable with that of 1,8-diazabicyclo[5.4.0]undec-7-ene. NHIP-1 underwent facile 1,2-addition with pentafluoropyridine to form a rare fluorophosphorane. The treatment of NHIP-1 with triphenylsilane resulted in P-N bond cleavage, accompanied by the reduction of phosphorus(V) to phosphorus(III). A homoleptic, cationic CuI-NHIP-1 complex was also prepared. The potential utility of π-donating NHIPs was demonstrated by the stabilization of a reactive iminoborane (Cl-B≡N-SiMe3). The facile scalable synthesis, tunability of steric demands, and basicity of NHIPs suggest that this new heterocycle class may find a wide range of applications in synthetic chemistry.

Relationship between perioperative oncological evaluation and recurrence using circulating tumor DNA with KRAS mutation in patients with colorectal cancer.

BACKGROUND: The detection of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) by liquid biopsy may have prognostic information. In this perioperative study, we evaluate if there is a relationship between mutant allele frequency (MAF) of Kirsten rat sarcoma viral oncogene homolog (KRAS) and tumor recurrence and how that could be useful in the early detection of recurrence. METHODS: Among 304 cases of colorectal cancer surgery, ctDNA was sampled from the perioperative blood of 84 patients with CRC with KRAS mutation (exon 4 p.A146T, exon 4 p.A146V, exon 2 p.G12A, exon 2 p.G12C, exon 2 p.G12D, exon 2 p.G12S, exon 2 p.G12V, exon 2 p.G13D, exon 3 p.Q61H) and analyzed using the digital polymerase chain reaction system. The median observation period was 26 months. RESULTS: Although the relationship between the perioperative MAF of KRAS and recurrence was not proved, tumor diameter, tumor depth, and stage were correlated with the preoperative MAF of KRAS (p = 0.034, p = 0.002, p = 0.008). However, tumor diameter, tumor depth, and stage did not correlate with MAF of KRAS at postoperative day 30. CONCLUSIONS: In this study, pathological tumor size, tumor depth, and stage were correlated with preoperative MAF of KRAS, but it was unreliable to predict recurrence by detection of ctDNA with KRAS mutation in the perioperative period of colorectal surgery.

Endoscopic full-thickness resection of an esophageal leiomyoma located in close proximity to the azygos vein.

Third-space endoscopic techniques, such as peroral endoscopic tumor resection (POET) and submucosal tunneling endoscopic resection (STER), enable access to deep organs and tissues that have been previously inaccessible with an endoscope. We present a 29-year-old man with a submucosal tumor (40 × 25 mm) located at 5 o'clock in the upper thoracic esophagus. Histological diagnosis by endoscopic ultrasound-fine needle aspiration was leiomyoma. Computed tomography showed the azygos vein posterior to the tumor. However, because endoscopic ultrasound revealed space between them, POET was performed. Because the tumor originated from the deep layer of the muscularis propria, full-thickness resection was performed to achieve R0 resection. The azygos vein arch was seen through the mediastinal space after tumor enucleation. The final histopathological diagnosis was leiomyoma. POET is a potentially revolutionary endoscopic technique that enables full-thickness resection of nonepithelial lesions. Preoperative computed tomography or endoscopic ultrasound to determine peritumoral anatomy is important to ensure safety. During the procedure, it is important to operate under direct vision, accurately identify the tumor boundary, and dissect along the boundary to avoid damaging the tumor and surrounding structures.

Discrimination and ejection of eggs and nestlings by the fan-tailed gerygone from New Caledonia.

Nestling rejection is a rare type of host defense against brood parasitism compared with egg rejection. Theoretically, host defenses at both egg and nestling stages could be based on similar underlying discrimination mechanisms but, due to the rarity of nestling rejector hosts, few studies have actually tested this hypothesis. We investigated egg and nestling discrimination by the fan-tailed gerygone Gerygone flavolateralis, a host that seemingly accepts nonmimetic eggs of its parasite, the shining bronze-cuckoo Chalcites lucidus, but ejects mimetic parasite nestlings. We introduced artificial eggs or nestlings and foreign gerygone nestlings in gerygone nests and compared begging calls of parasite and host nestlings. We found that the gerygone ejected artificial eggs only if their size was smaller than the parasite or host eggs. Ejection of artificial nestlings did not depend on whether their color matched that of the brood. The frequency of ejection increased during the course of the breeding season mirroring the increase in ejection frequency of parasite nestlings by the host. Cross-fostered gerygone nestlings were frequently ejected when lacking natal down and when introduced in the nest before hatching of the foster brood, but only occasionally when they did not match the color of the foster brood. Begging calls differed significantly between parasite and host nestlings throughout the nestling period. Our results suggest that the fan-tailed gerygone accepts eggs within the size range of gerygone and cuckoo eggs and that nestling discrimination is based on auditory and visual cues other than skin color. This highlights the importance of using a combined approach to study discrimination mechanisms of hosts.

Erratum to: Discrimination and ejection of eggs and nestlings by the fan-tailed gerygone from New Caledonia.

[This corrects the article DOI: 10.1093/cz/zoab066.].

Comparing Methods of Feature Extraction of Brain Activities for Octave Illusion Classification Using Machine Learning.

The aim of this study was to find an efficient method to determine features that characterize octave illusion data. Specifically, this study compared the efficiency of several automatic feature selection methods for automatic feature extraction of the auditory steady-state responses (ASSR) data in brain activities to distinguish auditory octave illusion and nonillusion groups by the difference in ASSR amplitudes using machine learning. We compared univariate selection, recursive feature elimination, principal component analysis, and feature importance by testifying the results of feature selection methods by using several machine learning algorithms: linear regression, random forest, and support vector machine. The univariate selection with the SVM as the classification method showed the highest accuracy result, 75%, compared to 66.6% without using feature selection. The received results will be used for future work on the explanation of the mechanism behind the octave illusion phenomenon and creating an algorithm for automatic octave illusion classification.

Identification of Novel Histone Deacetylase 6-Selective Inhibitors Bearing 3,3,3-Trifluorolactic Amide (TFLAM) Motif as a Zinc Binding Group.

Pharmacological inhibition of histone deacetylase 6 (HDAC6) is an effective therapeutic strategy for cancer and immunological diseases. Most of the previously reported HDAC6 inhibitors have a hydroxamate group as a zinc binding group (ZBG), which coordinates to the catalytic zinc ion of HDAC6. The hydroxamate group is liable to metabolically generate mutagenetic hydroxylamine; therefore, non-hydroxamate HDAC6 inhibitors would be advantageous. In this study, to identify novel non-hydroxamate HDAC6-selective inhibitors, screening of a chemical library and the subsequent structural optimization were performed, which led to the identification of HDAC6-selective inhibitors with 3,3,3-trifluorolactic amide (TFLAM) as a novel ZBG. The identified inhibitor showed potent and selective HDAC6-inhibitory activity in cells and induced regulatory T (Treg) cell differentiation.

Neurophysiological Evaluation of Right-Ear Advantage During Dichotic Listening.

Right-ear advantage refers to the observation that when two different speech stimuli are simultaneously presented to both ears, listeners report stimuli more correctly from the right ear than the left. It is assumed to result from prominent projection along the auditory pathways to the contralateral hemisphere and the dominance of the left auditory cortex for the perception of speech elements. Our study aimed to investigate the role of attention in the right-ear advantage. We recorded magnetoencephalography data while participants listened to pairs of Japanese two-syllable words (namely, "/ta/ /ko/" or "/i/ /ka/"). The amplitudes of the stimuli were modulated at 35 Hz in one ear and 45 Hz in the other. Such frequency-tagging allowed the selective quantification of left and right auditory cortex responses to left and right ear stimuli. Behavioral tests confirmed the right-ear advantage, with higher accuracy for stimuli presented to the right ear than to the left. The amplitude of the auditory steady-state response was larger when attending to the stimuli compared to passive listening. We detected a correlation between the attention-related increase in the amplitude of the auditory steady-state response and the laterality index of behavioral accuracy. The right-ear advantage in the free-response dichotic listening was also found in neural activities in the left auditory cortex, suggesting that it was related to the allocation of attention to both ears.

Oncological evaluation in the perioperative period using cfDNA with BRAF V600E mutation in patients with colorectal cancer.

The detection of circulating cell-free DNA (cfDNA) by liquid biopsy is reported to provide prognostic information in colorectal cancer (CRC). Although the frequency of BRAF V600E mutation in CRC is less than 10%, it is associated with poor responses to conventional chemotherapy. We conducted a prospective study to investigate the relationship between the perioperative mutant allele frequency (MAF) of BRAF V600E and tumor recurrence, and to evaluate the possibility of early detection of recurrence. Among 362 patients who underwent radical resection, cfDNA was extracted from the perioperative blood of 11 CRC patients with BRAF V600E mutation and analyzed using the digital polymerase chain reaction (dPCR) system. The median follow-up time was 22 months, and there were four cases of recurrence. Although there was no correlation between recurrence and the perioperative MAF of BRAF V600E, tumor diameter was correlated with the MAF (p = 0.024), and the MAF increased with time in two patients from whom additional samples were obtained prior to recurrence. In this study, we identified a correlation between the pathological tumor diameter and the MAF, but it was difficult to predict recurrence by measuring cfDNA with BRAF V600E mutation in the perioperative period of radical resection of CRC.

[Hybrid Two-stage Repair of Syphilitic Aortic Aneurysm, Total Arch Replacement and Thoracic Endovascular Aortic Repair;Report of a Case].

Syphilitic aortic aneurysm is seldom seen in the antibiotic era. Statistically the number of patients is increasing today and 10% of them seem to develop syphilitic aortitis. A 59-year-old male visited the emergency room due to chest discomfort and general fatigue. Treponema pallidum latex agglutination (TPLA) and rapid plasma reagin (RPR) were both strongly positive on blood tests. White blood cell counts and C-reactive protein elevation were also found. He couldn't figure out how or when he was suffering from syphilis. He needed to undergo a hybrid 2-stage surgery urgently, Total arch replacement and thoracic endovascular aortic repair (TEVAR), because his thoracic aortic aneurysm was growing more rapidly. No complication has occurred during or after surgery. Computed tomography after surgery showed successful exclusion of the thoracic aneurysm. It is important not to forget that syphilis is one of the causes of aortic aneurysm.

UDP-glucosyltransferase UGT84B1 regulates the levels of indole-3-acetic acid and phenylacetic acid in Arabidopsis.

Auxin is a key plant growth regulator for diverse developmental processes in plants. Indole-3-acetic acid (IAA) is a primary plant auxin that regulates the formation of various organs. Plants also produce phenylacetic acid (PAA), another natural auxin, which occurs more abundantly than IAA in various plant species. Although it has been demonstrated that the two auxins have distinct transport characteristics, the metabolic pathways and physiological roles of PAA in plants remain unsolved. In this study, we investigated the role of Arabidopsis UDP-glucosyltransferase UGT84B1 in IAA and PAA metabolism. We demonstrated that UGT84B1, which converts IAA to IAA-glucoside (IAA-Glc), can also catalyze the conversion of PAA to PAA-glucoside (PAA-Glc), with a higher catalytic activity in vitro. Furthermore, we showed a significant increase in both the IAA and PAA levels in the ugt84b1 null mutants. However, no obvious developmental phenotypes were observed in the ugt84b1 mutants under laboratory growth conditions. Moreover, the overexpression of UGT84B1 resulted in auxin-deficient root phenotypes and changes in the IAA and PAA levels. Our results indicate that UGT84B1 plays an important role in IAA and PAA homeostasis in Arabidopsis.

Architecture of DNA elements mediating ARF transcription factor binding and auxin-responsive gene expression in Arabidopsis.

The hormone auxin controls many aspects of the plant life cycle by regulating the expression of thousands of genes. The transcriptional output of the nuclear auxin signaling pathway is determined by the activity of AUXIN RESPONSE transcription FACTORs (ARFs), through their binding to cis-regulatory elements in auxin-responsive genes. Crystal structures, in vitro, and heterologous studies have fueled a model in which ARF dimers bind with high affinity to distinctly spaced repeats of canonical AuxRE motifs. However, the relevance of this "caliper" model, and the mechanisms underlying the binding affinities in vivo, have remained elusive. Here we biochemically and functionally interrogate modes of ARF-DNA interaction. We show that a single additional hydrogen bond in Arabidopsis ARF1 confers high-affinity binding to individual DNA sites. We demonstrate the importance of AuxRE cooperativity within repeats in the Arabidopsis TMO5 and IAA11 promoters in vivo. Meta-analysis of transcriptomes further reveals strong genome-wide association of auxin response with both inverted (IR) and direct (DR) AuxRE repeats, which we experimentally validated. The association of these elements with auxin-induced up-regulation (DR and IR) or down-regulation (IR) was correlated with differential binding affinities of A-class and B-class ARFs, respectively, suggesting a mechanistic basis for the distinct activity of these repeats. Our results support the relevance of high-affinity binding of ARF transcription factors to uniquely spaced DNA elements in vivo, and suggest that differential binding affinities of ARF subfamilies underlie diversity in cis-element function.

[Bentall Procedure for Annuloaortic Ectasia in a Patient with Systemic Lupus Erythematosus;Report of a Case].

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, rarely complicated with cardiac valvular abnormality or aortic aneurysm. An asymptomatic 40-year-old woman with a 15-year history of SLE developed annuloaortic ectasia and aortic valve regurgitation. She had long been maintained on steroid therapy for the treatment of SLE. Her serum anti-phospholipid antibodies were positive. An enhanced computed tomography revealed a dilated aortic root and ascending aorta (57 mm in diameter). Cardiac ultrasonography demonstrated severe aortic regurgitation. We performed the Bentall procedure using a composite graft with the Carrel patch technique. Histopathological examination of the aortic wall showed cystic medial necrosis without any evidence of vascu-litis. Careful long-term follow-up is mandatory for assessing the risk of later anastomotic dehiscence and pseudoaneurysm formation.