Ovarian high-grade serous carcinoma cells with low SMARCA4 expression and high SMARCA2 expression contribute to platinum resistance.

Platinum resistance is a major obstacle to the treatment of ovarian cancer and is correlated with poor clinical outcomes. Intratumor heterogeneity plays a key role in chemoresistance. Recent studies have emphasized the contributions of genetic and epigenetic factors to the development of intratumor heterogeneity. Although the clinical significance of multi-subunit chromatin remodeler, switch/sucrose nonfermenting (SWI/SNF) complexes in cancers has been reported, the impacts of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4/subfamily A, member 2 (SMARCA4/A2) expression patterns in human cancer tissues have not been fully elucidated. Here, we show that low expression of SMARCA4 and high expression of SMARCA2 are associated with platinum resistance in ovarian high-grade serous carcinoma (HGSC) cells. We used fluorescence multiplex immunohistochemistry (fmIHC) to study resected specimens; we examined heterogeneity in human HGSC tissues at the single-cell level, which revealed that the proportion of cells with the SMARCA4low /SMARCA2high phenotype was positively correlated with clinical platinum-resistant recurrence. We used stable transfection of SMARCA2 and siRNA knockdown of SMARCA4 to generate HGSC cells with the SMARCA4low /SMARCA2high phenotype; these cells had the greatest resistance to carboplatin. Bioinformatics analyses revealed that the underlying mechanism involved in substantial alterations to chromatin accessibility and resultant fibroblast growth factor (FGF) signaling activation, MAPK pathway activation, BCL2 overexpression, and reduced carboplatin-induced apoptosis; these were confirmed by in vitro functional experiments. Furthermore, in vivo experiments in an animal model demonstrated that combination therapy with carboplatin and a fibroblast growth factor receptor (FGFR) inhibitor promoted cell death in HGSC xenografts. Taken together, these observations reveal a specific subpopulation of HGSC cells that is associated with clinical chemoresistance, which may lead to the establishment of a histopathological prediction system for carboplatin response. Our findings may facilitate the development of novel therapeutic strategies for platinum-resistant HGSC cells. © 2023 The Pathological Society of Great Britain and Ireland.

A case of hypervirulent K1-ST23 Klebsiella pneumoniae endocarditis and papillary muscle rupture secondary to multiple site abscesses.

Hypervirulent Klebsiella pneumoniae (hvKP) causes multisite infections and abscesses. However, endocarditis is a rare presentation of hvKP infection. Herein, we report a case of K. pneumoniae native valve infective endocarditis secondary to community-acquired liver and prostate abscesses. The patient developed papillary muscle rupture, leading to mitral regurgitation, and underwent emergent mitral valve replacement. The diagnosis of endocarditis was confirmed microbiologically and histologically. The causative strain belonged to the hypermucoid K1 capsular genotype and possessed the rmpA gene. The genome sequence was deposited in GenBank under the accession number JAQZBZ000000000.

[A case of biliary panperitonitis due to intrahepatic bile duct rupture with intrahepatic bile duct tumor].

An 87-year-old man visited his previous doctor because of jaundice, abdominal pain, and disturbance of consciousness. He was diagnosed with cholangitis and panperitonitis and was referred to our hospital. Emergency laparotomy revealed biliary peritonitis. However, the bile leak point was unclear. Two days after surgery, endoscopic retrograde cholangiopancreatography was performed and revealed hilar bile duct stenosis, slight dilation of the intrahepatic bile duct, and bile leakage from the peripheral left intrahepatic bile duct to the abdominal free space. Endoscopic nasobiliary drainage was performed, and bile leakage decreased. He was discharged from our hospital with improvement from jaundice and peritonitis. Intrahepatic bile duct rupture with neoplastic obstruction of the bile duct is extremely rare. To date, only two cases of intrahepatic bile duct rupture with intrahepatic cholangiocarcinoma have been published.

Superconductivity in infinite-layer nickelates.

The recent discovery of the superconductivity in the doped infinite layer nickelatesRNiO2(R= La, Pr, Nd) is of great interest since the nickelates are isostructural to doped (Ca, Sr)CuO2having superconducting transition temperature (Tc) of about 110 K. Verifying the commonalities and differences between these oxides will certainly give a new insight into the mechanism of highTcsuperconductivity in correlated electron systems. In this paper, we review experimental and theoretical works on this new superconductor and discuss the future perspectives for the 'nickel age' of superconductivity.

Doping Asymmetry and Layer-Selective Metal-Insulator Transition in Trilayer K_{3+x}C_{60}.

Thin films provide a versatile platform to tune electron correlations and explore new physics in strongly correlated materials. Epitaxially grown thin films of the alkali-doped fulleride K_{3+x}C_{60}, for example, exhibit intriguing phenomena, including Mott transitions and superconductivity, depending on dimensionality and doping. Surprisingly, in the trilayer case, a strong electron-hole doping asymmetry has been observed in the superconducting phase, which is absent in the three-dimensional bulk limit. Using density-functional theory plus dynamical mean-field theory, we show that this doping asymmetry results from a substantial charge reshuffling from the top layer to the middle layer. While the nominal filling per fullerene is close to n=3, the top layer rapidly switches to an n=2 insulating state upon hole doping, which implies a doping asymmetry of the superconducting gap. The interlayer charge transfer and layer-selective metal-insulator transition result from the interplay between crystal field splittings, strong Coulomb interactions, and an effectively negative Hund coupling. This peculiar charge reshuffling is absent in the monolayer system, which is an n=3 Mott insulator, as expected from the nominal filling.

Fermi Surface Expansion above Critical Temperature in a Hund Ferromagnet.

Using a cluster extension of the dynamical mean-field theory, we show that strongly correlated metals subject to Hund's physics exhibit significant electronic structure modulations above magnetic transition temperatures. In particular, in a ferromagnet having a large local moment due to Hund's coupling (Hund's ferromagnet), the Fermi surface expands even above the Curie temperature (T_{C}) as if a spin polarization occurred. Behind this phenomenon, effective "Hund's physics" works in momentum space, originating from ferromagnetic fluctuations in the strong-coupling regime. The resulting significantly momentum-dependent (spatially nonlocal) electron correlations induce an electronic structure reconstruction involving a Fermi surface volume change and a redistribution of the momentum-space occupation. Our finding will give a deeper insight into the physics of Hund's ferromagnets above T_{C}.

Purifying Deep Boltzmann Machines for Thermal Quantum States.

We develop two cutting-edge approaches to construct deep neural networks representing the purified finite-temperature states of quantum many-body systems. Both methods commonly aim to represent the Gibbs state by a highly expressive neural-network wave function, exemplifying the idea of purification. The first method is an entirely deterministic approach to generate deep Boltzmann machines representing the purified Gibbs state exactly. This strongly assures the remarkable flexibility of the ansatz which can fully exploit the quantum-to-classical mapping. The second method employs stochastic sampling to optimize the network parameters such that the imaginary time evolution is well approximated within the expressibility of neural networks. Numerical demonstrations for transverse-field Ising models and Heisenberg models show that our methods are powerful enough to investigate the finite-temperature properties of strongly correlated quantum many-body systems, even when the problematic effect of frustration is present.

Orbital Isotropy of Magnetic Fluctuations in Correlated Electron Materials Induced by Hund's Exchange Coupling.

Characterizing nonlocal magnetic fluctuations in materials with strong electronic Coulomb interactions remains one of the major outstanding challenges of modern condensed matter theory. In this Letter, we address the spatial symmetry and orbital structure of magnetic fluctuations in perovskite materials. To this aim, we develop a consistent multiorbital diagrammatic extension of dynamical mean-field theory, which we apply to an anisotropic three-orbital model of cubic t_{2g} symmetry. We find that the form of spatial spin fluctuations is governed by the local Hund's coupling. For small values of the coupling, magnetic fluctuations are anisotropic in orbital space, which reflects the symmetry of the considered t_{2g} model. Large Hund's coupling enhances collective spin excitations, which mixes orbital and spatial degrees of freedom, and magnetic fluctuations become orbitally isotropic. Remarkably, this effect can be seen only in two-particle quantities; single-particle observables remain anisotropic for any value of the Hund's coupling. Importantly, we find that the orbital isotropy can be induced both at half filling and for the case of four electrons per lattice site, where the magnetic instability is associated with different, antiferromagnetic and ferromagnetic, modes, respectively.

Tenosynovitis caused by Mycobacterium marseillense, initially identified as Mycobacterium avium complex using AccuProbe and COBAS TaqMan.

BACKGROUND: Mycobacterium marseillense is a new species of the Mycobacterium avium complex. There has been only a few human infections caused by M. marseillense worldwide. CASE PRESENTATION: We report a case of tenosynovitis caused by M. marseillense in an immunocompetent adult in Japan. The isolate was initially identified as M. intracellulare using commercial real time polymerase chain reaction assays and later identified as M. marseillense with sequencing of the the rpoB and hsp65 regions, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). CONCLUSIONS: This is the first case reporting on M. marseillense generating a positive result with commercial real time PCR assays targeting MAC. Human infections associated by M. marseillense might be underreported due to similarities with Mycobacterium intracellulare. To accurately identify M. marseillese, MALDI-TOF MS might provide a rapid and reliable method.

Detection of MEAF6-PHF1 translocation in an endometrial stromal nodule.

Endometrial stromal nodule (ESN) and low-grade endometrial stromal sarcoma (LG-ESS) are rare uterine tumors known as endometrial stromal tumors (ESTs). In addition to their similarity in morphological features, recent studies have shown that these two tumors share common genetic alterations. In particular, JAZF1-SUZ12 fusion is found with high frequency in both ESN and LG-ESS. In LG-ESS, some minor fusions have also been described, which include rearrangements involving PHF1 and its partner genes, such as JAZF1, EPC1, MEAF6, BRD8, EPC2, and MBTD1. Because of the rarity of ESN, genetic alterations other than JAZF1 fusion have not been investigated in detail. In this study, we performed a next-generation sequencing-based analysis in a case of ESN with peripheral metaplastic bone formation and detected MEAF6-PHF1 fusion, which has been reported in a small subset of uterine LG-ESSs and soft tissue ossifying fibromyxoid tumors. The finding that MEAF6-PHF1 fusion is a background genetic abnormality detected both in ESN and LG-ESS, along with JAZF1-SUZ12, provides further support for the similarity and continuum between these two types of ESTs. Furthermore, the association between metaplastic bone formation and MEAF6-PHF1 fusion may not be limited to soft tissue tumors.

[Diagnostic value of a simple scoring system for the diagnosis and treatment of non-emergency small bowel obstruction].

In order to improve the diagnostic accuracy and treatment strategy for small bowel obstruction, we developed a non-emergency small bowel obstruction scoring system (0-4). We performed a retrospective analysis on 94 patients diagnosed with mechanical small bowel obstruction at our hospital. Anterior adhesion, small bowel feces sign, scoring system, and the usefulness of small bowel feces subtypes were examined. When the non-emergency small bowel obstruction scores 3-4, 99% were non-emergency obstructions, with the exclusion of strangulated small bowel obstruction. On the contrary, when the non-emergency small bowel obstruction scores 0-1, 47.5% were strangulated small bowel obstruction. As the effectiveness of withholding food and fluids (NPO) or short tube is high (about 70%) when small bowel feces are dry, placing a long tube may not be needed.

Evaluation of Pigment Distribution and Depth Analysis Methods for Decorative Soft Contact Lenses.

OBJECTIVES: This study evaluates pigment component distribution and depth in decorative soft contact lenses (DSCLs) using a variety of analytical methods. METHODS: We sampled 18 DSCLs using optical microscopy, optical coherence tomography analysis, Z-stack analysis, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDX), and time-of-flight secondary ion mass spectrometry (TOF-SIMS) to evaluate the distribution and depth of pigment components. RESULTS: Pigment distribution in DSCLs was easily observed with optical methods including Z-stack analysis. X-ray photoelectron spectroscopy, SEM/EDX, and TOF-SIMS were used to evaluate the level of pigment exposure on the lens surface and the results showed significant differences between the methods. Pigment components were detected in 16 samples by SEM/EDX, but not by XPS. Pigment components were only detected in eight samples using TOF-SIMS. CONCLUSIONS: It may be necessary to show that a nanometer-thick monomolecular film does not exist on the surface of DSCLs, to demonstrate the exposure of a pigment particle. Taking into account the principle behind each of the measurement methods and the resolution and sensitivity of each of the analytical methods compared, TOF-SIMS may be the most appropriate method to accurately judge pigment exposure on DSCLs. The Z-stack method may be useful for estimating the depth of pigment components in DSCLs.

[A retrospective study of the clinical characteristics and treatment of 93 adult patients with eosinophilic gastroenteritis].

We performed a retrospective analysis on three patients diagnosed with EGE (eosinophilic gastroenteritis) at our hospital and 90 cases obtained from a case database. The cases' genders, ages, peripheral eosinophils, ascites, endoscopic findings, biopsy findings, diagnostic scores, and rates of glucocorticoid use were evaluated. The gender ratio was 40 males to 53 females, and the median age was 50. 78.5% of cases had peripheral eosinophilia. The prevalence of allergic diseases was 31.2%, and the incidence of ascites was 34.4%. 83.9% of endoscopic findings were positive, and 92.5% of biopsies were positive. The total rate of glucocorticoid use was 77.4%. When both score <5 and age <33 conditions were met, the rate of glucocorticoid use was approximately 30%, meaning it was possible to avoid glucocorticoid use.

A case report of duodenal obstruction due to retroperitoneal bleeding after the rupture of a lower pancreaticoduodenal artery aneurysm.

We report a case of a patient with duodenal obstruction due to retroperitoneal bleeding after the rupture of a lower pancreaticoduodenal artery aneurysm. An 80-year-old female was admitted to our hospital because of nausea and vomiting. During hospitalization, she developed hemorrhagic shock. Enhanced computed tomography revealed retroperitoneal bleeding. Abdominal angiography revealed an 8-mm aneurysm of the lower pancreaticoduodenal artery, stenosis at the trunk of the celiac artery, and increased blood flow through the pancreaticoduodenal arcades from the superior mesenteric artery. Embolization using coils was successful. On day 24, the patient presented with vomiting. Imaging modalities revealed dilatation of the stomach and duodenum. Thus, duodenal obstruction due to the retroperitoneal hematoma was suspected. After percutaneous drainage of the retroperitoneal hematoma, the patient's symptoms improved. In the present case, the formation of the lower pancreaticoduodenal artery aneurysm was related to median arcuate ligament syndrome. After transcatheter embolization of a ruptured visceral aneurysm, obstruction of the gastrointestinal tract by hematoma should be meticulously evaluated.

The Runt domain of AML1 (RUNX1) binds a sequence-conserved RNA motif that mimics a DNA element.

AML1 (RUNX1) is a key transcription factor for hematopoiesis that binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. Aberrations in the AML1 gene are frequently found in human leukemia. To better understand AML1 and its potential utility for diagnosis and therapy, we obtained RNA aptamers that bind specifically to the AML1 Runt domain. Enzymatic probing and NMR analyses revealed that Apt1-S, which is a truncated variant of one of the aptamers, has a CACG tetraloop and two stem regions separated by an internal loop. All the isolated aptamers were found to contain the conserved sequence motif 5'-NNCCAC-3' and 5'-GCGMGN'N'-3' (M:A or C; N and N' form Watson-Crick base pairs). The motif contains one AC mismatch and one base bulged out. Mutational analysis of Apt1-S showed that three guanines of the motif are important for Runt binding as are the three guanines of RDE, which are directly recognized by three arginine residues of the Runt domain. Mutational analyses of the Runt domain revealed that the amino acid residues used for Apt1-S binding were similar to those used for RDE binding. Furthermore, the aptamer competed with RDE for binding to the Runt domain in vitro. These results demonstrated that the Runt domain of the AML1 protein binds to the motif of the aptamer that mimics DNA. Our findings should provide new insights into RNA function and utility in both basic and applied sciences.

Effect of electron-phonon interactions on orbital fluctuations in iron-based superconductors.

To investigate the possibility of whether electron-phonon coupling can enhance orbital fluctuations in iron-based superconductors, we develop an ab initio method to construct the effective low-energy models including the phonon-related terms. With the derived effective electron-phonon interactions and phonon frequencies, we estimate the static part (ω=0) of the phonon-mediated effective on site intra- or interorbital electron-electron attractions as ∼-0.4 eV and exchange or pair-hopping terms as ∼-0.02 eV. We analyze the model with the derived interactions together with the Coulomb repulsions within the random phase approximation. We find that the enhancement of the orbital fluctuations due to the electron-phonon interactions is small, and that the spin fluctuations enhanced by the Coulomb repulsions dominate. It leads to the superconducting state with the sign reversal in the gap functions (s± wave).

First-principles study of the honeycomb-lattice iridates Na2IrO3 in the presence of strong spin-orbit interaction and electron correlations.

An effective low-energy Hamiltonian of itinerant electrons for iridium oxide Na2IrO3 is derived by an ab initio downfolding scheme. The model is then reduced to an effective spin model on a honeycomb lattice by the strong coupling expansion. Here we show that the ab initio model contains spin-spin anisotropic exchange terms in addition to the extensively studied Kitaev and Heisenberg exchange interactions, and allows us to describe the experimentally observed zigzag magnetic order, interpreted as the state stabilized by the antiferromagnetic coupling of the ferromagnetic chains. We clarify possible routes to realize quantum spin liquids from existing Na2IrO3.

Kluyvera georgiana Bacteremia Due to Acute Cholangitis: A Report of the First Known Case and a Literature Review.

We herein present the first known case of bacteremia caused by Kluyvera georgiana in a 67-year-old female undergoing chemotherapy for recurrent pancreatic cancer. The patient underwent choledochojejunotomy and thereafter developed ascending cholangitis. The diagnosis of K. georgiana was confirmed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A literature review of Kluyvera spp. infections indicated potential risk factors including an underlying malignancy and immunosuppression. Although Kluyvera spp. infections are typically sensitive to antibiotics, multidrug resistance is possible. This case highlights the importance of the early diagnosis and treatment of K. georgiana and its associated risk factors.

Effect of Partial Substitution of Zr for Ti Solvent on Young's Modulus, Strength, and Biocompatibility in Beta Ti Alloy.

In orthopedics and dentistry, there is an urgent need to obtain low-stiffness implants that suppress the stress shielding caused by the use of metallic implants. In this study, we aimed to fabricate alloys that can reduce the stiffness by increasing the strength while maintaining a low Young's modulus based on the metastable ß-Ti alloy. We designed alloys in which Ti was partially replaced by Zr based on the ISO-approved metastable ß-Ti alloy Ti-15Mo-5Zr-3Al. All alloys prepared by arc melting and subsequent solution treatment showed a single ß-phase solid solution, with no formation of the ω-phase. The alloys exhibited a low Young's modulus equivalent to that of Ti-15Mo-5Zr-3Al and a high strength superior to that of Ti-15Mo-5Zr-3Al and Ti-6Al-4V. This strengthening was presumed to be due to solid-solution strengthening. The biocompatibility of the alloys was as good as or better than that of Ti-6Al-4V. These alloys have potential as metallic materials suitable for biomedical applications.