Diffuse Large B-cell Lymphoma Complicated with Anti-3-hydroxy-3-methylglutaryl-Coenzyme A Reductase Immune-mediated Necrotizing Myopathy: A Case Report.

A 75-year-old woman presented with significant muscle weakness after statin use. A muscle biopsy revealed necrotizing myopathy, and the patient tested positive for serum anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies, leading to a diagnosis of anti-HMGCR immune-mediated necrotizing myopathy (IMNM). Computed tomography revealed intraperitoneal lymphadenopathy, which was diagnosed as a diffuse large B-cell lymphoma. Immunostaining confirmed HMGCR expression in the lymphoma cells. The patient received chemotherapy and achieved complete remission of the lymphoma, along with nearly complete recovery from IMNM. Although the etiologies of IMNM and lymphoma remain unclear, HMGCR expression in lymphoma cells is likely to be associated with the development of IMNM.

Mechanistic study on the reductive elimination of (aryl)(fluoroaryl)palladium complexes: a key step in regiospecific dehydrogenative cross-coupling.

Cross-dehydrogenative coupling (CDC) reactions have attracted attention as short-step synthetic methods for C-C bond formation. Recently, we have developed CDC reactions between naphthalene and fluorobenzene. Rather than exhibiting general regioselectivity, this reaction proceeds selectively at the ß-position of naphthalene. In this study, investigation using model complexes as reaction intermediates revealed that the origin of the unique selectivity is the exclusive occurrence of reductive elimination at the ß-position. Detailed studies on the reductive elimination showed that the steric hindrance of the naphthyl group and the electron-withdrawing properties of fluorobenzene determine the position at which the reductive elimination reaction proceeds. These results show that the selectivity of the C-H functionalisation of polycyclic aromatic hydrocarbons (PAHs) is determined not by the C-H cleavage step, but by the subsequent reductive elimination step. The regioselective CDC reaction was adaptable to various PAHs but was less selective for pyrene with extended π-conjugation. In fluorobenzene substrates, the F atoms at the two ortho positions of the C-H moiety are necessary for high selectivity. The substrate ranges are in good agreement with the proposed mechanism, in which the reductive elimination step determines the regioselectivity.

The prevalence, risk factors, and outcomes of acute pulmonary embolism complicating sepsis and septic shock: a national inpatient sample analysis.

The study aimed to evaluate the prevalence, risk factors, and clinical outcomes of pulmonary embolism in patients diagnosed with sepsis with and without shock. The National Inpatient Sample was used to identify adults with sepsis with and without shock between 2017 and 2019. The prevalence of acute pulmonary embolism and the association of acute pulmonary embolism with in-hospital mortality, hospital length of stay for survivors, and overall costs of hospitalization were evaluated. Multivariable logistic and linear regression analyses, adjusted for various parameters, were used to explore these associations. Of the estimated 5,019,369 sepsis hospitalizations, 1.2% of patients with sepsis without shock and 2.3% of patients with septic shock developed pulmonary embolism. The odds ratio for in-hospital mortality was 1.94 (95% confidence interval (CI) 1.85-2.03, p < 0.001). The coefficient for hospital length of stay was 3.24 (95% CI 3.03-3.45, p < 0.001). The coefficient for total costs was 46,513 (95% CI 43,079-49,947, p < 0.001). The prevalence of pulmonary embolism in patients diagnosed with sepsis with and without shock was 1.2 and 2.3%, respectively. Acute pulmonary embolism was associated with higher in-hospital mortality, longer hospital length of stay for survivors, and higher overall costs of hospitalization.

Reusable Magnetite Nanoparticle (Fe3O4 NP) Catalyst for Selective Oxidation of Alcohols under Microwave Irradiation.

Iron oxide nanoparticles (NPs) are nontoxic and abundant materials which have long been investigated as reusable catalysts in oxidation reactions, but their use so far has been hampered by a low selectivity. Here, unsupported iron oxide NPs have been found to successfully catalyze the microwave-assisted oxidation of primary and secondary alcohols to their respective aldehydes and ketones with a high selectivity when N-methylmorpholine N-oxide was used as the terminal oxidant. The crystalline phase and size of the iron-based catalyst have a drastic effect on its activity, with small magnetite (Fe3O4) NPs being the optimal catalyst for this reaction. The nanocatalyst could be easily recovered by magnetoseparation and successfully recycled four times without any need for special pretreatment or reactivation step and with a minimal loss of activity. The subsequent loss of activity was attributed to the transition from magnetite (Fe3O4) to maghemite (γ-Fe2O3), as confirmed by X-ray diffraction, Fourier transform infrared, and X-ray absorption near-edge spectroscopy. The nanocatalyst could then be reactivated by the high-temperature microwave treatment and used again for the microwave-assisted oxidation reaction.

Comparison of Central and Peripheral Arterial Blood Pressure Gradients in Critically Ill Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Measurement of blood pressure taken from different anatomical sites, are often perceived as interchangeable, despite them representing different parts of the systemic circulation. We aimed to perform a systematic review and meta-analysis on blood pressure differences between central and peripheral arterial cannulation in critically ill patients. DATA SOURCES: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase from inception to December 26, 2023, using Medical Subject Headings (MeSH) terms and keywords. STUDY SELECTION: Observation study of adult patients in ICUs and operating rooms who underwent simultaneous central (femoral, axillary, or subclavian artery) and peripheral (radial, brachial, or dorsalis pedis artery) arterial catheter placement in ICUs and operating rooms. DATA EXTRACTION: We screened and extracted studies independently and in duplicate. We assessed risk of bias using the revised Quality Assessment for Studies of Diagnostic Accuracy tool. DATA SYNTHESIS: Twenty-four studies that enrolled 1598 patients in total were included. Central pressures (mean arterial pressure [MAP] and systolic blood pressure [SBP]) were found to be significantly higher than their peripheral counterparts, with mean gradients of 3.5 and 8.0 mm Hg, respectively. However, there was no statistically significant difference in central or peripheral diastolic blood pressure (DBP). Subgroup analysis further highlighted a higher MAP gradient during the on-cardiopulmonary bypass stage of cardiac surgery, reperfusion stage of liver transplant, and in nonsurgical critically ill patients. SBP or DBP gradient did not demonstrate any subgroup specific changes. CONCLUSIONS: SBP and MAP obtained by central arterial cannulation were higher than peripheral arterial cannulation; however, clinical implication of a difference of 8.0 mm Hg in SBP and 3.5 mm Hg in MAP remains unclear. Our current clinical practices preferring peripheral arterial lines need not change.

Cryo-EM analysis reveals human SID-1 transmembrane family member 1 dynamics underlying lipid hydrolytic activity.

Two mammalian homologs of systemic RNA interference defective protein 1 (SID-1) (SIDT1/2) are suggested to function as double-stranded RNA (dsRNA) transporters for extracellular dsRNA uptake or for release of incorporated dsRNA from lysosome to cytoplasm. SIDT1/2 is also suggested to be involved in cholesterol transport and lipid metabolism. Here, we determine the cryo-electron microscopy structures of human SIDT1, homodimer in a side-by-side arrangement, with two distinct conformations, the cholesterol-bound form and the unbound form. Our structures reveal that the membrane-spanning region of SIDT1 harbors conserved histidine and aspartate residues coordinating to putative zinc ion, in a structurally similar manner to alkaline ceramidases or adiponectin receptors that require zinc for ceramidase activity. We identify that SIDT1 has a ceramidase activity that is attenuated by cholesterol binding. Observations from two structures suggest that cholesterol molecules serve as allosteric regulator that binds the transmembrane region of SIDT1 and induces the conformation change and the reorientation of the catalytic residues. This study represents a contribution to the elucidation of the cholesterol-mediated mechanisms of lipid hydrolytic activity and RNA transport in the SID-1 family proteins.

[Utilization of Peripheral Neuropathology Tests].

Neuropathological findings rarely lead to a definitive diagnosis of autoimmune and inflammatory peripheral nerve diseases, and indications for invasive nerve biopsy with subsequent disability should be carefully determined. In addition to disease-specific pathological findings, identifying findings that facilitate differential diagnosis in clinical practice is necessary. This article reviews the neuropathological findings that are valuable in the differential diagnosis of autoimmune and inflammatory peripheral nerve diseases.

An anatomo-functional study of the interactivity between the paracentral lobule and the primary motor cortex.

OBJECTIVE: The purpose of this study was to understand the anatomical and functional connections between the paracentral lobule (PCL) and the primary motor cortex (M1) of the human brain. METHODS: This retrospective study included 16 patients who underwent resection of lesions located near M1. Nine patients had lesions in the dominant hemisphere. Tractography was performed to visualize the connectivity between two regions of interest (ROIs)-the convexity and the interhemispheric fissure-that were shown by functional MRI to be activated during a finger tapping task. The number, mean length, and fractional anisotropy (FA) of the fibers between the ROIs were estimated. During surgery, subdural electrodes were placed on the brain surface, including the ROIs, using a navigation system. Cortico-cortical evoked potentials (CCEPs) were evoked by applying electrical stimuli to the hand region of M1 using electrodes placed on the convexity and were measured with electrodes placed on the interhemispheric fissure. To verify CCEP bidirectionality, electrical stimuli were applied to electrodes on the interhemispheric fissure that showed CCEP responses. Correlations of CCEP amplitudes and latencies with the number, mean length, and mean FA value obtained from tractography were determined. The correlations between these parameters and perioperative motor functions were also analyzed. RESULTS: Fibers of 14 patients were visualized by diffusion tensor imaging (DTI). Unidirectional CCEPs between the PCL and M1 were measurable in all 16 patients, and bidirectional CCEPs between them were measurable in 14 patients. There was no significant difference between the two directions in the maximum CCEP amplitude or latency (amplitude, p = 0.391; latency, p = 0.583). Neither the amplitude nor latency showed any apparent correlation with the number, mean length, or mean FA value of the fibers obtained from tractography. Pre- and postoperative motor function of the hands was not significantly correlated with CCEP amplitude or latency. The number and mean FA value of fibers obtained by DTI, as well as the maximum CCEP amplitude, varied between patients. CONCLUSIONS: This study demonstrated an anatomical connection and a bidirectional functional connection between the PCL, including the supplementary motor area, and M1 of the human brain. The observed variability between patients suggests possible motor function plasticity. These findings may serve as a foundation for further studies.

Machine learning-based detection of sleep-disordered breathing in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is often concomitant with sleep-disordered breathing (SDB), which can cause adverse cardiovascular events. Although an appropriate approach to SDB prevents cardiac remodelling, detection of concomitant SDB in patients with HCM remains suboptimal. Thus, we aimed to develop a machine learning-based discriminant model for SDB in HCM. METHODS: In the present multicentre study, we consecutively registered patients with HCM and performed nocturnal oximetry. The outcome was a high Oxygen Desaturation Index (ODI), defined as 3% ODI >10, which significantly correlated with the presence of moderate or severe SDB. We randomly divided the whole participants into a training set (80%) and a test set (20%). With data from the training set, we developed a random forest discriminant model for high ODI based on clinical parameters. We tested the ability of the discriminant model on the test set and compared it with a previous logistic regression model for distinguishing SDB in patients with HCM. RESULTS: Among 369 patients with HCM, 228 (61.8%) had high ODI. In the test set, the area under the receiver operating characteristic curve of the discriminant model was 0.86 (95% CI 0.77 to 0.94). The sensitivity was 0.91 (95% CI 0.79 to 0.98) and specificity was 0.68 (95% CI 0.48 to 0.84). When the test set was divided into low-probability and high-probability groups, the high-probability group had a higher prevalence of high ODI than the low-probability group (82.4% vs 17.4%, OR 20.9 (95% CI 5.3 to 105.8), Fisher's exact test p<0.001). The discriminant model significantly outperformed the previous logistic regression model (DeLong test p=0.03). CONCLUSIONS: Our study serves as the first to develop a machine learning-based discriminant model for the concomitance of SDB in patients with HCM. The discriminant model may facilitate cost-effective screening tests and treatments for SDB in the population with HCM.

Endosomal Toll-Like Receptors as Therapeutic Targets for Autoimmune Diseases.

Nucleic acid (NA)-sensing Toll-like receptors (TLRs) reside in the endosomal compartment of innate immune cells, such as macrophages and dendritic cells. NAs transported to the endosomal compartment are degraded by DNases and RNases. Degradation products, including single-stranded DNA, oligoRNA, and nucleosides, are recognized by TLR7, TLR8, and TLR9 to drive the defense responses against pathogens. NA degradation influences endosomal TLR responses by generating and degrading TLR ligands. TLR ligand accumulation because of impaired NA degradation causes constitutive TLR activation, leading to autoinflammatory and autoimmune diseases. Furthermore, some genes associated with these diseases promote endosomal TLR responses. Therefore, endosomal TLRs are promising therapeutic targets for TLR-mediated inflammatory diseases, and novel drugs targeting TLRs are being developed.

Epoxide Ring-Opening Reactions for Abundant Production of Mugineic Acids and Nicotianamine Probes.

A succinct synthetic approach to mugineic acids and 2'-hydroxynicotianamine was established. Unlike all other synthetic methods, this approach utilized epoxide ring-opening reactions to form two C-N bonds and is characterized by the absence of redox reactions. Mugineic acid was synthesized from three readily available fragments on a gram scale in 6 steps. The protected 2'-hydroxynicotianamine was also synthesized in 4 steps, and the dansyl group, serving as a fluorophore, was introduced through a click reaction after propargylation of the 2'-hydroxy group. The dansyl-labeled nicotianamine (NA) iron complexes were internalized by oocytes overexpressing ZmYS1 (from maize) or PAT1 (from human) transporters, indicating successful transport of the synthesized NA-probe through these transporters.

Hemodynamic profile of cirrhotic patients with sepsis and septic shock: A propensity score matched case-control study.

PURPOSE: Our understanding of hemodynamics in cirrhotic patients with sepsis remains limited. Our study aims to investigate differences in hemodynamic profiles using echocardiography between septic patients with and without cirrhosis. MATERIALS AND METHODS: This is a single-center, retrospective study of septic patients with echocardiogram within 3 days of ICU admission. We compared baseline characteristics, echocardiographic markers of LV systolic function arterial load between patients with and without cirrhosis. A propensity score-matched case-control model was developed to describe the differences in those echocardiography derived parameters between the groups. RESULTS: 3151 patients with sepsis were included of which 422 (13%) had cirrhosis. In the propensity score matched group with 828 patients, cirrhotic patients had significantly higher left ventricular ejection fraction (64 vs.56%, p < 0.001) and stroke volume (72 vs.48 ml, p < 0.001) along with lower arterial elastance (Ea) (1.35 1vs.20.3, p < 0.001) and systemic vascular resistance (SVR) (851 vs.1209 dynes/s/m-5, p = 0.001). The left ventricular elastance (Ees) (2.83 vs 2.45, p = 0.002) was higher and ventricular-arterial coupling (Ea/Ees) (0.48 vs. 0.86, p < 0.001) lower in cirrhotic compared to non-cirrhotic. CONCLUSIONS: Septic patients with cirrhosis had higher LVEF with lower Ea and SVR with higher Ees and significantly lower Ea/Ees suggesting vasodilation as the principal driver of the hyperdynamic profile in cirrhosis.

Prevalence and prognosis of hyperdynamic left ventricular systolic function in septic patients: a systematic review and meta-analysis.

PURPOSE: The prevalence of hyperdynamic left ventricular (LV) systolic function in septic patients and its impact on mortality remain controversial. In this systematic review and meta-analysis, we investigated the prevalence and association of hyperdynamic LV systolic function with mortality in patients with sepsis. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. Primary outcomes were the prevalence of hyperdynamic LV systolic function in adult septic patients and the associated short-term mortality as compared to normal LV systolic function. Hyperdynamic LV systolic function was defined using LV ejection fraction (LVEF) of 70% as cutoff. Secondary outcomes were heart rate, LV end-diastolic diameter (LVEDD), and E/e' ratio. RESULTS: Four studies were included, and the pooled prevalence of hyperdynamic LV systolic function was 18.2% ([95% confidence interval (CI) 12.5, 25.8]; I2 = 7.0%, P < 0.0001). Hyperdynamic LV systolic function was associated with higher mortality: odds ratio of 2.37 [95%CI 1.47, 3.80]; I2 = 79%, P < 0.01. No difference was found in E/e' (P = 0.43) between normal and hyperdynamic LV systolic function, while higher values of heart rate (mean difference: 6.14 beats/min [95%CI 3.59, 8.69]; I2 = 51%, P < 0.0001) and LVEDD (mean difference: - 0.21 cm [95%CI - 0.33, - 0.09]; I2 = 73%, P < 0.001) were detected in patients with hyperdynamic LV systolic function. CONCLUSION: The prevalence of hyperdynamic LV systolic function is not negligible in septic patients. Such a finding is associated with significantly higher short-term mortality as compared to normal LV systolic function.

Size Dependence of Trion and Biexciton Binding Energies in Lead Halide Perovskite Nanocrystals.

Lead halide perovskite nanocrystals (NCs) have attracted much attention as light-source materials for light-emitting diodes, lasers, and quantum light emitters. The luminescence properties of perovskite NCs and the performance of NC-based light-source devices depend on trion and biexciton dynamics. Here, we examined the size dependence of trion and biexciton binding energies by conducting low-temperature single-dot spectroscopy on three different perovskite NCs: CsPbBr3, CsPbI3, and FAPbBr3. While the photoluminescence spectral widths of the all-inorganic CsPbBr3 and CsPbI3 NCs were narrow, compared with those of the organic-inorganic hybrid FAPbBr3 NCs, the binding energies of trions and biexcitons of all three samples showed similar size dependences, independent of the A-site cation and halogen. The effective-mass approximation calculations implied the importance of dynamical dielectric screening on the formation of trions and biexcitons.

Pseudomorphic amorphization of three-dimensional superlattices through morphological transformation of nanocrystal building blocks.

Nanocrystal (NC) superlattices (SLs) have been widely studied as a new class of functional mesoscopic materials with collective physical properties. The arrangement of NCs in SLs governs the collective properties of SLs, and thus investigations of phenomena that can change the assembly of NC constituents are important. In this study, we investigated the dynamic evolution of NC arrangements in three-dimensional (3D) SLs, specifically the morphological transformation of NC constituents during the direct liquid-phase synthesis of 3D NC SLs. Electron microscopy and synchrotron-based in situ small angle X-ray scattering experiments revealed that the transformation of spherical Cu2S NCs in face-centred-cubic 3D NC SLs into anisotropic disk-shaped NCs collapsed the original ordered close-packed structure. The random crystallographic orientation of spherical Cu2S NCs in starting SLs also contributed to the complete disordering of the NC array via random-direction anisotropic growth of NCs. This work demonstrates that an understanding of the anisotropic growth kinetics of NCs in the post-synthesis modulation of NC SLs is important for tuning NC array structures.

Safety and feasibility of a novel total percutaneous post-closure technique after bedside Impella decannulation in patients with cardiogenic shock.

OBJECTIVES: The Impella (Abiomed) is a widely used percutaneous mechanical circulatory support device for high-risk percutaneous coronary intervention in patients with cardiogenic shock. This study aimed to determine the safety and feasibility of a non-angio-guided post-closure approach using the Perclose ProGlide (Abbott) to decannulate the Impella in the intensive care unit. METHODS: This retrospective study included consecutive patients who were successfully weaned from mechanical circulatory support using the Impella device between April 2019 and April 2022 at Hamamatsu University School of Medicine. Fifteen patients underwent complete post-closure of the femoral artery access sites at the bedside. Technical success of the post-closure hemostasis technique was defined as no evidence of bleeding or additional medical procedures after manual compression. The safety endpoints comprised the Valve Academic Research Consortium-3 and Bleeding Academic Research Consortium criteria. RESULTS: All patients achieved successful hemostasis with this novel technique without surgical conversion. There was no significant bleeding; however, procedure-related vessel occlusion was observed in 1 patient who was recanalized with balloon angioplasty. CONCLUSIONS: Bedside post-closure using the Perclose ProGlide device is a safe and feasible alternative to manual compression and surgical removal of the Impella device with low bleeding or vascular complications rates.

Intrinsic Visible Plasmonic Properties of Colloidal PtIn2 Intermetallic Nanoparticles.

Materials that intrinsically exhibit localized surface plasmon resonance (LSPR) in the visible region have been predominantly researched on nanoparticles (NPs) composed of coinage metals, namely Au, Ag, and Cu. Here, as a coinage metal-free intermetallic NPs, colloidal PtIn2 NPs with a C1 (CaF2 -type) crystal structure are synthesized by the liquid phase method, which evidently exhibit LSPR at wavelengths similar to face-centered cubic (fcc)-Au NPs. Computational simulations pointed out differences in the electronic structure and photo-excited electron dynamics between C1-PtIn2 and fcc-Au NPs; reduces interband transition and stronger screening with smaller number of bound d-electrons compare with fcc-Au are unique origins of the visible plasmonic nature of C1-PtIn2 NPs. These results strongly indicate that the intermetallic NPs are expected to address the development of alternative plasmonic materials by tuning their crystal structure and composition.

An overlapping case of IgG4-related disease and systemic lupus erythematosus treated with belimumab: a case-based review.

IgG4-related disease (IgG4-RD) is a systemic condition in which IgG4+ plasma cell infiltration and fibrosis cause organ swelling and lead to diverse clinical manifestations. Although IgG4-RD typically responds to glucocorticoids (GCs), relapse during tapering occurs and an early GC-sparing approach might therefore be beneficial. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with multiple symptoms that is also treated with GCs as a first-line therapy. Recently, belimumab, a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor, was approved, but reports of use for IgG4-RD are scarce. Here, we present a rare case of IgG4-RD complicated with SLE which was successfully treated with belimumab. A 67-year-old man was diagnosed with IgG4-RD based on a high serum IgG4 level and histopathological findings. Furthermore, he had pericardial effusion on echocardiography, and laboratory tests revealed thrombocytopenia, autoimmune hemolysis, positive anti-nuclear antibodies, positive anti-DNA antibodies, and hypocomplementemia. These data led to an SLE diagnosis. Treatment was started with prednisolone at 40 mg/day, plus hydroxychloroquine, which initially improved both the SLE and IgG4-RD symptoms. During the GC tapering, belimumab was added and clinical symptoms resolved completely. Our case and the literature review summarize reported rare overlapping cases of IgG4-RD and SLE and suggest that belimumab is a promising candidate for the treatment of IgG4-RD.