The Utility of a Novel Stacked Microvascular Imaging for Enhanced Detection of Fibrosis in Chronic Liver Diseases.

OBJECTIVE: Ultrasonographic imaging plays a primary role to detect fibrotic changes in patients with chronic liver disease (CLD). To enhance detectability of fibrosis in its early stage, we developed a novel stacked microvascular imaging (SMVI) that enables continuous visualization of fibrotic changes in intrahepatic vessels. METHODS: SMVI was produced by accumulating 3-5 seconds of high-definition color images in tilted-scan mode. An SMVI score was devised by quantitating three hallmark vascular changes in liver fibrosis in 0-2 grades (total 0-6): narrowing, caliber irregularity, and tortuosity. To evaluate the clinical utility of the SMVI score, 469 well-defined CLD patients were enrolled and subgrouped by the stage of liver fibrosis defined based on elastography: F0-1Low, F0-1High, F2, F3, and F4. The diagnostic performance of the SMVI score was compared to conventional B-mode liver morphology score and various laboratory test markers of fibrosis. RESULTS: Unlike conventional microvascular imaging that relies on a single image, SMVI enabled an undisrupted view of intrahepatic vessels for easy detection of fibrotic changes. SMVI detected microvascular narrowing in 92% at stage F0-1High. While detection rates for caliber irregularity and tortuosity were low at early stages but increased proportionately in advanced stages. Multiple logistic regression analysis revealed that SMVI score was most accurate in distinguishing F0-1Low from F0-1High cases compared to B-mode or laboratory test scores. CONCLUSION: SMVI provides enhanced vascular images of liver fibrosis in CLD, especially in its early stage. The SMVI score can be used as a primary tool for determining fibrotic stages in CLD.

Pathway crosstalk between the central metabolic and heme biosynthetic pathways in Phanerochaete chrysosporium.

A comprehensive analysis to survey heme-binding proteins produced by the white-rot fungus Phanerochaete chrysosporium was achieved using a biotinylated heme-streptavidin beads system. Mitochondrial citrate synthase (PcCS), glyceraldehyde 3-phosphate dehydrogenase (PcGAPDH), and 2-Cys thioredoxin peroxidase (mammalian HBP23 homolog) were identified as putative heme-binding proteins. Among these, PcCS and PcGAPDH were further characterized using heterologously expressed recombinant proteins. Difference spectra of PcCS titrated with hemin exhibited an increase in the Soret absorbance at 414 nm, suggesting that the axial ligand of the heme is a His residue. The activity of PcCS was strongly inhibited by hemin with Ki oxaloacetate of 8.7 µM and Ki acetyl-CoA of 5.8 µM. Since the final step of heme biosynthesis occurred at the mitochondrial inner membrane, the inhibition of PcCS by heme is thought to be a physiological event. The inhibitory mode of the heme was similar to that of CoA analogues, suggesting that heme binds to PcCS at His347 at the AcCoA-CoA binding site, which was supported by the homology model of PcCS. PcGAPDH was also inhibited by heme, with a lower concentration than that for PcCS. This might be caused by the different location of these enzymes. From the integration of these phenomena, it was concluded that metabolic regulations by heme in the central metabolic and heme synthetic pathways occurred in the mitochondria and cytosol. This novel pathway crosstalk between the central metabolic and heme biosynthetic pathways, via a heme molecule, is important in regulating the metabolic balance (heme synthesis, ATP synthesis, flux balance of the tricarboxylic acid (TCA) cycle and cellular redox balance (NADPH production) during fungal aromatic degradation. KEY POINTS: • A comprehensive survey of heme-binding proteins in P. chrysosporium was achieved. • Several heme-binding proteins including CS and GAPDH were identified. • A novel metabolic regulation by heme in the central metabolic pathways was found.

A large-scale genomically predicted protein mass database enables rapid and broad-spectrum identification of bacterial and archaeal isolates by mass spectrometry.

MALDI-TOF MS-based microbial identification relies on reference spectral libraries, which limits the screening of diverse isolates, including uncultured lineages. We present a new strategy for broad-spectrum identification of bacterial and archaeal isolates by MALDI-TOF MS using a large-scale database of protein masses predicted from nearly 200,000 publicly available genomes. We verify the ability of the database to identify microorganisms at the species level and below, achieving correct identification for > 90% of measured spectra. We further demonstrate its utility by identifying uncultured strains from mouse feces with metagenomics, allowing the identification of new strains by customizing the database with metagenome-assembled genomes.

Use of the Second Revision of the International Staging System for prognostic stratification of multiple myeloma patients in real-world clinical practice and the importance of sub-groups, including age.

Not available.

Polarized Neutrons Observed Nanometer-Thick Crystalline Ice Plates in Frozen Glucose Solution.

Spin-contrast-variation (SCV) small-angle neutron scattering (SANS) is a technique to determine the nanostructure of composite materials from the scattering of polarized neutrons that changes with proton polarization of samples. The SCV-SANS enabled us to determine structure of nanoice crystals that were generated in rapidly frozen sugar solutions by separating the overlapped signals from the nanoice crystals and frozen amorphous solutions. In the frozen glucose solution, we found that the nanoice crystals formed a planar structure with a radius larger than several tens of nanometers and a thickness of 2.5 ± 0.5 nm, which was close to the critical nucleation size of ice crystals in supercooled water. This result suggests that the glucose molecules were preferentially bound to a specific face of nanoice crystals and then blocked the crystal growth perpendicular to that face.

Concordance between HokUS-10 Scoring and Transjugular Liver Biopsy for the Diagnosis of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Allogeneic Stem Cell Transplantation.

The aim of this study was to evaluate the concordance between clinical diagnosis and pathologic findings of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) in post-hematopoietic stem cell transplantation recipients and to investigate the accuracy of the HOKUS-10 score in diagnosing VOD/SOS. We included 13 patients who underwent transjugular liver biopsy for clinical suspicion of VOD/SOS and collected their clinical, laboratory, imaging, and pathologic data. Eleven patients were confirmed to have VOD/SOS by pathologic examination. The median HokUS-10 score and hepatic venous pressure gradient were 6 points (range, 0 to 10 points) and 13 mmHg (range, 7 to 24 mmHg), respectively. There was no significant difference between these scores in VOD/SOS and non-VOD/SOS cases; however, patients with lower HokUS-10 scores tended to have milder histologic features of VOD/SOS compared with severe cases. This study highlights the potential discordance between clinical diagnosis and pathologic diagnosis of VOD/SOS and emphasizes the importance of liver biopsy to optimize treatment.

Safety and efficacy of venetoclax for acute myeloid leukaemia in real-world clinical practice.

Venetoclax combined with low-intensity chemotherapy has led to longer survival and higher remission rates in patients with untreated acute myeloid leukaemia who are ineligible for intensive chemotherapy. We reviewed 41 newly diagnosed and relapse/refractory acute myeloid leukaemia patients who received venetoclax at our institute. Complete remission or complete remission with incomplete recovery was achieved in 73.1% of patients. A total of 95.1% of patients discontinued venetoclax, mainly because of severe cytopenia, disease progression and haematopoietic stem cell transplantation. The median number of courses of venetoclax was 2. In all, 92.6% of the patients experienced grade ≥ 3 neutropenia. The median overall survival was 287 days. Venetoclax dose reduction resulted in better continuity of treatment with fewer complications. In conclusion, venetoclax and low-intensity chemotherapy led to high remission rates, but survival was restrained because of the large number of venetoclax discontinuations. Dose reduction of venetoclax may mitigate cytopenia while maintaining efficacy.

Heterogeneous Aggregation of Humic Acids Studied by Small-Angle Neutron and X-ray Scattering.

Aggregation of humic acids (HAs) was studied by small-angle neutron and X-ray scattering techniques. The combination of these techniques enables us to examine the aggregation structures of HA particles. Two HAs with distinctive compositions were examined: a commercial HA (PAHA) and a HA extracted from deep sedimentary groundwater (HHA). While macroscopic coagulation tests showed that these HAs were stable in solutions except for HHA at pH < 6, small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) revealed that they formed aggregates with sizes exceeding the sub-micrometer length scale. The SAXS curves of PAHA remarkably varied with pD = log aD+, where aD+ stands for the activity of deuterium ions, whereas the SANS curves did not. With the help of theoretical fittings, it was revealed that PAHA aggregates consisted of two domains: poorly hydrated cores and well-hydrated proton-rich shells. The cores were (dis)aggregated with pD inside the aggregates of the shells. The SANS and SAXS curves of HHA resembled each other, and their intensities at low q, where q stands for the scattering vector, increased with a decrease of pD, indicating the formation of homogeneous aggregates within the spatial resolutions of SANS and SAXS. This study revealed that distinctive aggregation behaviors exist in humic substances with nm-scale heterogeneous structures like PAHA, which is important for their roles in the fate of contaminants or nutrients in aqueous environments.

The Effects of Different Molding Orientations, Highly Accelerated Aging, and Water Absorption on the Flexural Strength of Polyether Ether Ketone (PEEK) Fabricated by Fused Deposition Modeling.

Rising prices are currently a problem in the world. In particular, the abnormal increases in the price of metals, which are often used in dental prosthetics, have increased the burden of dental costs on the public. There is therefore an urgent need to develop prosthetic devices made from materials that are not affected by the global situation and that have excellent biocompatibility and mechanical properties comparable to those of metals. Polyether ether ketone (PEEK) is a promising alternative to metal in dentistry. This study compared the effects of different molding orientations, highly accelerated aging, and water absorption on the flexural strength of PEEK fabricated by fused deposition modeling (FDM) and examined its potential for dental applications. The flexural strength of PEEK stacked at 0° to the molding stage (0° PF), with and without highly accelerated aging, was significantly greater than for the other molding orientations. As with PD, the maximum test load for 0° PF was measured without fracture. PEEK stacked at 45° (45° PF) and 90° (90° PF) to the molding stage easily fractured, as the applied load pulled the stacked layers. No statistically significant difference was found between the flexural strength of 45° PF and 90° PF. The flexural strength decreased under all conditions due to defects in the crystal structure of PEEK caused by highly accelerated aging.

Clinical Characteristics and Outcomes of Cyclin D1-Positive AL Amyloidosis.

OBJECTIVES: To demonstrate the clinical features and prognostic impact of cyclin D1 positivity in patients with amyloid light chain amyloidosis (AL). METHODS: We consecutively included 71 patients diagnosed with AL with cyclin D1 positivity between February 2008 and January 2022. t(11;14) was examined through interphase fluorescence in situ hybridization using bone marrow cells. RESULTS: The median age of the patients was 73 years, and 53.5% were male. The underlying diseases included symptomatic multiple myeloma, smoldering multiple myeloma, Waldenström macroglobulinemia, and monoclonal gammopathy of undetermined significance, representing 33.8%, 26.8%, 2.8%, and 36.6%, respectively. The prevalence of cyclin D1 and t(11;14) was 38.0% and 34.7%, respectively. Higher frequency of light chain paraprotein type was seen in cyclin D1-positive patients with AL than in cyclin D1-negative patients (70.4% vs 18.2%). The median overall survival (OS) of patients with AL with and without cyclin D1 expression was 18.9 months and 73.1 months, respectively (P = .019). Early death occurred in 44.4% of cyclin D1-positive patients and 31.8% of cyclin D1-negative patients. Moreover, 83.3% of cyclin D1-positive patients and 21.4% of cyclin D1-negative patients died of cardiac causes. CONCLUSIONS: Cyclin D1 immunohistochemistry accurately identified patients with t(11;14). Cyclin D1-positive patients had significantly inferior OS compared with cyclin D1-negative patients.

Effect of resin composite shade on digital fiber-optic transillumination imaging in vitro.

Digital imaging fiber-optic transillumination (DIFOTI) devices have been used to detect caries, a technique without using X-rays. However, the effects of resin composites (RCs) shades on the images acquired with DIFOTI devices have not been investigated. Thus, this study aimed to elucidate the influence of RC shade on the images obtained with DIFOTI technique. Three shades (A1, A3, and Opaque) for each of four flowable RCs were filled on a cavity prepared in a left mandibular first premolar obtained from a donated body. Then, transmission images with a DIFOTI device (DIAGNOcam; KaVo, Biberach, Germany) were acquired, and the average lightness values of the images in the RC and enamel were used to calculate differences between those areas. To clarify the influence of the optical translucency and color on DIFOTI images, the color parameters (L*, a* and b*) of each RC were obtained with black and white backgrounds. The color differences between the backgrounds were calculated as transparency parameter (TP) values. The number of repetitions was set to 10. Differences in the lightness value of the shades varied in each RC. The difference in lightness was significantly associated with the TP value and color parameters of L* (p < 0.01), with negative (R = - 0.81) and positive (R = 0.84) correlations, respectively. In conclusion, DIFOTI images of RCs with high optical translucency resembled those of the natural tooth structure.

Influence of toothbrush abrasion on the surface characteristics of CAD/CAM composite resin blocks with shade gradations.

Crown restorations in anterior region are recommended highly color-reproductivity because of aesthetic reason. Composite resin block with several shade gradations is especially produced for anterior restorations. To clarify the durability of an aesthetic, the effect of toothbrush abrasion on surface properties was performed. Composite-resin blocks without shade gradation and a ceramic block were used as controls. All specimens were prepared using #2000 SiC paper and polished using an aluminum oxide polishing paste. Toothbrush abrasion tests were carried out for 20,000 cycles at a frequency of 2 Hz with 2.0 N load. Gloss and surface roughness were measured before and after toothbrush abrasion. The number of repetitions was set to five. It was clarified that tooth brushing caused to decrease in the gloss and to increase in the surface roughness with significant negative correlations between these results not only in composite-resin blocks without shade gradation but also in those with gradation.

Antibody status following booster vaccination against SARS-CoV-2 virus in patients with haematologic malignancies.

Antibody titres in 462 patients with haematological malignancies after the second (D2) and third (D3) SARS-CoV-2 vaccine were compared with those of healthy controls (HCs). Significant decay of antibody titre was observed pre D3, but titre surged post D3. The number of seronegative patients decreased from 79 (17.1%) to 44 (9.5%) from post D2 to post D3, and patients with adequate antibody titre increased from 204 (44.2%) to 358 (77.5%). Of the patients who received B-cell-targeted therapy, 80% were seronegative and 71% remained seronegative after D3. CD19+, CD4+, CD8+ cell counts, and immunoglobulin G (IgG) levels were identified as independent predictors for adequate serologic response.

Incidence and Predictors of Cardiac Implantable Electronic Devices Malfunction with Radiotherapy Treatment.

AIMS: To investigate the incidence of cardiac implantable electronic devices (CIED) malfunction with radiotherapy (RT) treatment and assess predictors of CIED malfunction. METHODS: A 6-year retrospective analysis of patients who underwent RT with CIED identified through the radiation oncology electronic database. Clinical, RT (cumulative dose, dose per fraction, beam energy, beam energy dose, and anatomical area of RT) and CIED details (type, manufacturer, and device malfunction) were collected from electronic medical records. RESULTS: We identified 441 patients with CIED who underwent RT. CIED encountered a permanent pacemaker (PPM) (78%), cardiac resynchronization therapy-pacing (CRT-P) (2%), an implantable cardioverter defibrillator (ICD) (10%), and a CRT-defibrillator (CRT-D) (10%). The mean cumulative dose of RT was 36 gray (Gy) (IQR 1.8-80 Gy) and the most common beam energy used was photon ≥10 megavolt (MV) with a median dose of 7 MV (IQR 5-18 MV). We further identified 17 patients who had CIED malfunction with RT. This group had a higher cumulative RT dose of 42.5 Gy (20-77 Gy) and a photon dose of 14 MV (12-18 MV). None of the malfunctions resulted in clinical symptoms. Using logistic regression, the predictors of CIED malfunction were photon beam energy use ≥10 MV (OR 5.73; 95% CI, 1.58-10.76), anatomical location of RT above the diaphragm (OR 5.2, 95% CI, 1.82-15.2), and having a CIED from the ICD group (OR 4.6, 95% CI, 0.75-10.2). CONCLUSION: Clinicians should be aware of predictors of CIED malfunction with RT to ensure the safety of patients.

Hepatic falciform ligament appendagitis evaluated by ultrasound: A report of 2 cases.

Falciform ligament appendagitis is an extremely rare disorder, which is characterized by hematogenous or nonhematogenous inflammatory changes in the fat appendage that is contiguous with the falciform ligament. The imaging and clinical features of this condition are similar to those of epiploic appendagitis, especially when caused by torsion of the fatty appendage (ie, falciform ligament appendage torsion). We report 2 cases of falciform ligament appendagitis with localized epigastric pain. The ultrasound imaging features of the 2 cases presented here were an oval hyperechoic mass contiguous with the falciform ligament and increased echogenicity of the surrounding inflammatory fat. Both patients were managed conservatively with symptomatic treatment alone. Understanding the imaging features of this falciform ligament appendagitis is important, because ultrasound is often the first choice for noninvasive imaging of acute abdomen. As there is limited detailed literature on falciform ligament appendagitis comparing high-frequency linear probes with CT and MRI, we consider this case report to add valuable information on this poorly reported condition.

Inflammatory markers S100A8/A9 and metabolic alteration for evaluating signs of early phase toxicity of anticancer agent treatment.

Anticancer agents can cause various side effects, including tissue damages/inflammatory reactions. Drug-responsive biomarkers are essential for evaluating drug toxicity in disease processes. S100 calcium-binding proteins A8/A9 (S100A8/A9) are highly expressed in neutrophils and monocytes/macrophages accumulated at inflammatory sites and are known to be related to tissue damage/inflammation; however, their response to drug toxicity has not been reported. Herein, we investigated the effects of anticancer agents (doxorubicin, cisplatin, and docetaxel) on S100A8/A9 gene expression profiles in four representative tissues (heart, kidney, liver, and lung) in normal C57BL/6J mice. Both S100A8/A9 expression was transiently or time-dependently elevated in four tissues within 48 h after dosing of the three anticancer agents under toxicity-inducing conditions. S100A8/A9 patterns differed among agents and tissues. This result suggests that S100A8/A9 is useful for evaluating anticancer agent-induced tissue damage. Metabolomic analysis revealed that some metabolites showed temporal patterns similar to that of S100A8/A9 expression. The amounts of fumarate (doxorubicin-treated heart), tyrosine (cisplatin-treated kidney), acetylcarnosine (doxorubicin-treated liver), and 2-phosphoglycerate (docetaxel-treated lung) showed similar patterns to that of S100A8/A9 expression. Although these metabolites showed different behaviors between tissues and serum, they may be useful marker candidates for evaluating anticancer agent-induced tissue damage at an earlier stage after dosing.

Limited efficacy of high-dose methotrexate to prevent the central nervous system relapse in patients with IVLBCL.

To evaluate the efficacy of high-dose methotrexate (HD-MTX, ≥1 g/m2) for the prevention of central nervous system (CNS) recurrence in patients with intravascular large B-cell lymphoma (IVLBCL), we reviewed 51 patients with pathologically diagnosed untreated IVLBCL. In total, there were five cases of CNS relapse (9.8%), and the 12-month CNS relapse rate was 9.2%. No statistical difference in CNS relapse rate (p = 0.86) was observed between patients with and without HD-MTX (n = 20 and 31, respectively). Furthermore, the composite endpoint defined as either CNS and/or neurolymphomatosis relapse was not significant in terms of the administration of HD-MTX (p = 0.25). No significant predictor of CNS relapse was found. In conclusion, patients with IVLBCL are at high risk of CNS recurrence; however, HD-MTX administration may not be effective for CNS recurrence prophylaxis. Key pointsThe administration of HD-MTX for patients with untreated IVLBCL may not be effective for preventing CNS relapse.