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We present ∼0.″10 resolution Atacama Large Millimeter/submillimeter Array (ALMA) CO(2-1) imaging of the arcsecond-scale (r ≈ 150 pc) dusty molecular disk in the giant elliptical galaxy NGC 3258. The data provide unprecedented resolution of the cold gas disk kinematics within the dynamical sphere of influence of a supermassive black hole (BH), revealing a quasi-Keplerian central increase in projected rotation speed rising from 280 km s-1 at the disk's outer edge to >400 km s-1 near the disk center. We construct dynamical models for the rotating disk and fit beam-smeared model CO line profiles directly to the ALMA data cube. Our models incorporate both flat and tilted-ring disks that provide a better fit of the mildly warped structure in NGC 3258. We show that the exceptional angular resolution of the ALMA data makes it possible to infer the host galaxy's mass profile within r = 150 pc solely from the ALMA CO kinematics, without relying on optical or near-infrared imaging data to determine the stellar mass profile. Our model therefore circumvents any uncertainty in the BH mass that would result from the substantial dust extinction in the galaxy's central region. The best model fit yields , with a statistical model-fitting uncertainty of just 0.18% and systematic uncertainties of 0.62% from various aspects of the model construction and 12% from uncertainty in the distance to NGC 3258. This observation demonstrates the full potential of ALMA for carrying out highly precise measurements of in early-type galaxies containing circumnuclear gas disks.

We present results from an Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 2 program to map CO(2-1) emission in nearby early-type galaxies (ETGs) that host circumnuclear gas disks. We obtained ∼0.″3 resolution Band 6 observations of seven ETGs selected on the basis of dust disks in Hubble Space Telescope images. We detect CO emission in five at high signal-to-noise ratio with the remaining two only faintly detected. All CO emission is coincident with the dust and is in dynamically cold rotation. Four ETGs show evidence of rapid central rotation; these are prime candidates for higher-resolution ALMA observations to measure the black hole masses. In this paper, we focus on the molecular gas and continuum properties. Total gas masses and H2 column densities for our five CO-bright galaxies are on average ∼108 M and cm-2 over the ∼kpc-scale disks, and analysis suggests that these disks are stabilized against gravitational fragmentation. The continuum emission of all seven galaxies is dominated by a central unresolved source, and in five we also detect a spatially extended component. The ∼230 GHz nuclear continua are modeled as power laws ranging from Sv ∼ V-0.4 to V1.6 within the observed frequency band. The extended continuum profiles of the two radio-bright (and CO-faint) galaxies are roughly aligned with their radio jet and suggest resolved synchrotron jets. The extended continua of the CO-bright disks are coincident with optically thick dust absorption and have spectral slopes that are consistent with thermal dust emission.

We present first results from a program of Atacama Large Millimeter/submillimeter Array (ALMA) CO(2-1) observations of circumnuclear gas disks in early-type galaxies. The program was designed with the goal of detecting gas within the gravitational sphere of influence of the central black holes (BHs). In NGC 1332, the 0.″3-resolution ALMA data reveal CO emission from the highly inclined () circumnuclear disk, spatially coincident with the dust disk seen in Hubble Space Telescope images. The disk exhibits a central upturn in maximum line-of-sight velocity, reaching ±500 km s-1 relative to the systemic velocity, consistent with the expected signature of rapid rotation around a supermassive BH. Rotational broadening and beam smearing produce complex and asymmetric line profiles near the disk center. We constructed dynamical models for the rotating disk and fitted the modeled CO line profiles directly to the ALMA data cube. Degeneracy between rotation and turbulent velocity dispersion in the inner disk precludes the derivation of strong constraints on the BH mass, but model fits allowing for a plausible range in the magnitude of the turbulent dispersion imply a central mass in the range of ∼(4-8) × 108 . We argue that gas-kinematic observations resolving the BH's projected radius of influence along the disk's minor axis will have the capability to yield BH mass measurements that are largely insensitive to systematic uncertainties in turbulence or in the stellar mass profile. For highly inclined disks, this is a much more stringent requirement than the usual sphere-of-influence criterion.

We present Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 3 observations of CO(2-1) emission from the circumnuclear disk in the E/S0 galaxy NGC 1332 at 0.″044 resolution. The disk exhibits regular rotational kinematics and central high-velocity emission (±500 km s-1) consistent with the presence of a compact central mass. We construct models for a thin, dynamically cold disk in the gravitational potential of the host galaxy and black hole and fit the beam-smeared model line profiles directly to the ALMA data cube. Model fits successfully reproduce the disk kinematics out to r = 200 pc. Fitting models just to spatial pixels within projected r = 50 pc of the nucleus (two times larger than the black hole's gravitational radius of influence), we find MBH =(6.64+0.65-0.63) × 108 Mo. This observation demonstrates ALMA's powerful capability to determine the masses of supermassive black holes by resolving gas kinematics on small angular scales in galaxy nuclei.

Many recent observations and numerical simulations suggest that nearby massive, early-type galaxies (ETGs) were formed through a "two-phase" process. In the proposed second phase, the extended stellar envelope was accumulated through many dry mergers. However, details of the past merger history of present-day ellipticals, such as the typical merger mass ratio, are difficult to constrain observationally. Within the context and assumptions of the two-phase formation scenario, we propose a straightforward method, using photometric data alone, to estimate the average mass ratio of mergers that contributed to the build-up of massive elliptical galaxies. We study a sample of nearby massive elliptical galaxies selected from the Carnegie-Irvine Galaxy Survey, using two-dimensional analysis to decompose their light distribution into an inner, denser component plus an extended, outer envelope, each having a different optical color. The combination of these two substructures accurately recovers the negative color gradient exhibited by the galaxy as whole. The color difference between the two components (〈Δ(B-V)〉 ≃ 0.10 mag; 〈Δ(B-R) 〉 ≃ 0.14 mag), based on the slope of the M∗-color relation for nearby ETGs, can be translated into an estimate of the average mass ratio of the mergers. The rough estimate, 1:5 to 1:10, is consistent with the expectation of the two-phase formation scenario, suggesting that minor mergers were largely responsible for building up the outer stellar envelopes of present-day massive ellipticals. With the help of accurate photometry, large sample sizes and more choices of colors promised by ongoing and future surveys, the approach proposed here can provide more insights into the growth of massive galaxies during the last few Gyr.

We obtained Hubble Space Telescope/Wide Field Camera 3 imaging of a sample of ten of the nearest and brightest nuclear clusters (NCs) residing in late-type spiral galaxies, in seven bands that span the near-UV to the near-IR. Structural properties of the clusters were measured by fitting two-dimensional surface brightness profiles to the images using GALFIT. The clusters exhibit a wide range of structural properties, with F814W absolute magnitudes that range from -11.2 to -15.1 mag and F814W effective radii that range from 1.4 to 8.3 pc. For 6 of the 10 clusters in our sample, we find changes in the effective radius with wavelength, suggesting radially varying stellar populations. In four of the objects, the effective radius increases with wavelength, indicating the presence of a younger population that is more concentrated than the bulk of the stars in the cluster. However, we find a general decrease in effective radius with wavelength in two of the objects in our sample, which may indicate extended, circumnuclear star formation. We also find a general trend of increasing roundness of the clusters at longer wavelengths, as well as a correlation between the axis ratios of the NCs and their host galaxies. These observations indicate that blue disks aligned with the host galaxy plane are a common feature of NCs in late-type galaxies, but are difficult to detect in galaxies that are close to face-on. In color-color diagrams spanning the near-UV through the near-IR, most of the clusters lie far from single-burst evolutionary tracks, showing evidence for multi-age populations. Most of the clusters have integrated colors consistent with a mix of an old population (>1 Gyr) and a young population (∼100-300 Myr). The wide wavelength coverage of our data provides a sensitivity to populations with a mix of ages that would not be possible to achieve with imaging in optical bands only. The surface brightness profiles presented in this work will be used for future stellar population modeling and dynamical studies of the clusters.

SN 1999aw was discovered during the first campaign of the Nearby Galaxies Supernova Search project. This luminous, slow-declining [Δm 15(B) = 0.81 ± 0.03] Type Ia supernova was noteworthy in at least two respects. First, it occurred in an extremely low luminosity host galaxy that was not visible in the template images nor in initial subsequent deep imaging. Second, the photometric and spectral properties of this supernova indicate that it very likely was similar to the subclass of Type Ia supernovae whose prototype is SN 1999aa. This paper presents the BVRI and J SHKS light curves of SN 1999aw (through ∼100 days past maximum light), as well as several epochs of optical spectra. From these data, we calculate the bolometric light curve and give estimates of the luminosity at maximum light and the initial 56Ni mass. In addition, we present deep BVI images obtained recently with the Baade 6.5 m telescope at Las Campanas Observatory that reveal the remarkably low-luminosity host galaxy.

OBJECTIVE: To evaluate the effectiveness of intrauterine lignocaine as an anaesthetic during endometrial sampling. DESIGN: Prospective, randomised, double-blind, placebo-controlled trial. SETTING: Outpatient gynaecological minor operation unit in a public hospital. POPULATION: Two hundred premenopausal women scheduled for endometrial sampling because of abnormal uterine bleeding. METHODS: Transcervical intrauterine instillation of 5 mL of 2% lignocaine or 5 mL of normal saline before performing endometrial sampling with vacuum aspirator. MAIN OUTCOME MEASURES: Evaluation of pain associated with the procedure using a visual analogue scale. RESULTS: The use of intrauterine lignocaine reduced pain during suction curettage in endometrial sampling. CONCLUSIONS: Transcervical instillation of lignocaine reduced pain during endometrial sampling. [ABSTRACT FROM AUTHOR]

We report an unusual case of ependymoma with pigmentation, a phenomenon that has only been described in a few cases, to our knowledge. This tumor occurred in the fourth ventricle of a 45-year-old man. It showed the typical histologic appearance of ependymoma with perivascular pseudorosettes and rare ependymal rosettes. Some tumor cells contained brown cytoplasmic pigment, which was shown histochemically to represent a mixture of lipofuscin and neuromelanin. The pigment was positive for acid-fast and periodic acid--Schiff stains and was also focally positive for Masson-Fontana and Schmorl stains (bleached by pretreatment with potassium permanganate). In addition, some other tumor cells showed a signet ring morphology as a result of prominent intracytoplasmic vacuolation. Immunohistochemically, all the tumor cells expressed glial fibrillary acidic protein, and rare pigmented tumor cells also expressed HMB-45. Ultrastructural examination showed irregularly shaped heterogeneous electron-dense bodies corresponding to the pigment, and the cytoplasmic vacuoles were formed by dilatation of intracytoplasmic lumens lined by microvilli. Since lipofuscin production can occur in normal ependymal cells and neuromelanin has been suggested to be a melanized form of lipofuscin, it is not surprising that these 2 pigments can be found in ependymoma. In all the previously reported cases, the pigment was shown to represent melanin only. In our case, the HMB-45 positivity in rare tumor cells indicated that there might also be a minor melanin component in the pigment in addition to lipofuscin and neuromelanin. (Arch Pathol Lab Med. 2003;127:872-875). [ABSTRACT FROM AUTHOR]

Examines blossom-end rot (BER) in relation to growth rate and calcium content in fruits of sweet pepper. Calcium concentration of the pericarp in mature fruits; BER in relation to pollination; BER in relation to cultivar susceptibility and fruit load; Correlation between growth rate and calcium concentration.

Self-administered pre-participation screening for physical activity (PA) requires an instrument that should be easily used and identify individuals at high risk. The Physical Activity Readiness Questionnaire (PAR-Q+) has been used for many years. Its ease of use and ability to identify those not fit to undergo PA has not been assessed. This study was to determine the rates of the PAR-Q+ in identifying adults who may not be fit for moderate or intense PA and obtain feedback on the use of this tool. A randomized, cross-sectional study involving a wide spectrum of members of the public was carried out. Participants were asked to provide their bio-characteristics, complete the PARQ+, and provide feedback on the questionnaire. With 1019 participants, about 33.1% of the participants using the PARQ+ would have required further medical evaluation. Except for those patients with respiratory illness, there was no difference in levels of PA in those who answered yes or no to the seven PARQ+ questions. Only 4 of the 7 main PAR-Q+ questions were perceived by the public as easily understood. Difficulties were encountered with 21 of the 45 follow-up questions, especially amongst those with co-morbidities. The wordiness of the questions and the large number of technical terms were also sources of concern. Suggestions were provided by participants on areas where improvements may be made to the wording of the questions. The study suggests that the PAR-Q+ probably over-identified those who require further medical evaluation. In addition, the wordiness of the questions and frequent use of medical jargon made the PARQ+ challenging to understand and use. The suggestions provide opportunities to review areas for possible improvements.

The nucleus of almost all massive galaxies contains a supermassive black hole (BH) 1 . The feedback from the accretion of these BHs is often considered to have crucial roles in establishing the quiescence of massive galaxies 2-14 , although some recent studies show that even galaxies hosting the most active BHs do not exhibit a reduction in their molecular gas reservoirs or star formation rates 15-17 . Therefore, the influence of BHs on galaxy star formation remains highly debated and lacks direct evidence. Here, based on a large sample of nearby galaxies with measurements of masses of both BHs and atomic hydrogen (HI), the main component of the interstellar medium 18 , we show that the HI gas mass to stellar masses ratio (μ HI  = M HI /M ⋆ ) is more strongly correlated with BH masses (M BH ) than with any other galaxy parameters, including stellar mass, stellar mass surface density and bulge masses. Moreover, once the μ HI -M BH correlation is considered, μ HI loses dependence on other galactic parameters, demonstrating that M BH serves as the primary driver of μ HI . These findings provide important evidence for how the accumulated energy from BH accretion regulates the cool gas content in galaxies, by ejecting interstellar medium gas and/or suppressing gas cooling from the circumgalactic medium., (© 2024. The Author(s).)

Background: Inhibiting the development and progression of diabetic kidney disease (DKD) is an important issue, but the renoprotective effect of metformin is still controversial., Aims: To assess the renoprotective effect of metformin in patients with type 2 diabetes., Methods: This retrospective observational multicenter cohort study included 316,693 patients with type 2 diabetes from seven hospital. After age, gender, medical year, baseline estimated glomerular filtration rate (eGFR), urine protein (dipstick), glycated hemoglobin (HbA1C) and propensity score matching; a total of 13,096 metformin and 13,096 non-metformin patients were included. The main results were doubling of serum creatinine, eGFR ≤ 15 mL/min/1.73 m2 and end stage kidney disease (ESKD)., Results: After conducting a multivariable logistic regression analysis on the variables, the metformin group was revealed to have better renal outcomes than non-metformin group, including a lower incidence of doubling of serum creatinine (hazard ratio [HR], 0.71; 95% CI, 0.65-0.77), eGFR ≤ 15 mL/min/1.73 m2 (HR 0.61; 95% CI 0.53-0.71), and ESKD (HR 0.55; 95% CI 0.47-0.66). The subgroup analyses revealed a consistent renoprotective effect across patients with various renal functions. Furthermore, when considering factors such as age, sex, comorbidities, and medications in subgroup analyses, it consistently showed that the metformin group experienced a slower deterioration in renal function across nearly all patient subgroups., Conclusions: Metformin decreased the risk of renal function deterioration., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Objectives: This study aimed to investigate the clinical impact of the Intelligent Antimicrobial System (iAMS) on patients with bacteraemia due to methicillin-resistant (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA)., Methods: A total of 1008 patients with suspected SA infection were enrolled before and after the implementation of iAMS. Among them, 252 with bacteraemia caused by SA, including 118 in the iAMS and 134 in the non-iAMS groups, were evaluated., Results: The iAMS group exhibited a 5.2% (from 55.2% to 50.0%; P = 0.96) increase in the 1-year survival rate. For patients with MRSA and MSSA compared to the non-iAMS group, the 1-year survival rate increased by 17.6% (from 70.9% to 53.3%; P = 0.41) and 7.0% (from 52.3% to 45.3%; P = 0.57), respectively, both surpassing the rate of the non-iAMS group. The iAMS intervention resulted in a higher long-term survival rate (from 70.9% to 52.3%; P = 0.984) for MRSA patients than for MSSA patients. MRSA patients experienced a reduced length of hospital stay (from 23.3% to 35.6%; P = 0.038), and the 45-day discharge rate increased by 20.4% (P = 0.064). Furthermore, the intervention resulted in a significant 97.3% relative decrease in near miss medication incidents reported by pharmacists (P = 0.013)., Conclusions: Implementation of iAMS platform improved long-term survival rates, discharge rates, hospitalization days, and medical cost (although no significant differences were observed) among patients with MRSA bacteraemia. Additionally, it demonstrated significant benefits in ensuring drug safety., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

The formation of jets in black hole accretion systems is a long-standing problem. It has been proposed that a jet can be formed by extracting the rotation energy of the black hole ("BZ-jet") or the accretion flow ("disk-jet"). While both models can produce collimated relativistic outflows, neither has successfully explained the observed jet morphology. By using general relativistic magnetohydrodynamic simulations and considering nonthermal electrons accelerated by magnetic reconnection that is likely driven by magnetic eruption in the underlying accretion flow, we obtain images by radiative transfer calculations and compared them to millimeter observations of the jet in M87. We find that the BZ-jet originating from a magnetically arrested disk around a high-spin black hole can well reproduce the jet morphology, including its width and limb-brightening feature.

Background: Narrative medicine demonstrated positive impact on empathy in medicine and nursing students. However, this pedagogical approach had not been evaluated in pharmacy education. This study sought to apply and evaluate the narrative medicine approach in extending empathy in Asian undergraduate pharmacy students., Methods: Narrative medicine was applied through workshops which used narratives of people with different experiences and perspectives. First-year undergraduate pharmacy students who volunteered and attended these workshops formed the intervention group (N = 31) and the remaining first-year cohort formed the control group (N = 112). A sequential explanatory mixed methods approach was adopted in which quantitative methods were first used to measure impact on pharmacy students' empathy using the Jefferson Scale of Empathy- Health Professions Student (JSE-HPS), and qualitative methods (i.e. group interviews) were then used to assess pharmacy students' emotional responses to narratives, and the perspectives of pharmacy students and faculty of this pedagogical approach., Results: There was no difference in JSE-HPS scores between intervention and control groups across baseline (i.e. upon matriculation), pre-intervention, and post-intervention timepoints. Pharmacy students in the intervention group had lower scores in Factor 3 ("Standing in People's Shoes") following the intervention. Five themes, guided by internal and external factors in cognition, emerged from the Group Interviews: (1) incongruence between students' motivation and faculty's perception, (2) learning context, (3) academic context, (4) cognitive system, and (5) affective system. Themes 1, 4 and 5 referred to internal factors such as students' motivation, perceived learnings, and feelings. Themes 2 and 3 referred to external factors including workshop materials, activities, content, and facilitation., Conclusion: This study is the first to demonstrate that pharmacy students engaged with the narrative medicine approach as narratives elicited emotional responses, exposed them to diverse perspectives, and deepened their appreciation of the importance of empathy and complexities of understanding patients' perspectives. Scaffolded educational interventions using narratives and real-life patient encounters, alongside longitudinal measurements of empathy, are necessary to bring about meaningful and sustained improvements in empathy., (© 2024. The Author(s).)

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. Sprague-Dawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. The results showed that a single dose of MOC at 2.0 g/kg significantly increased the AUC 0-t and MRT of MTX by 352% and 308%, and a single dose at 4.0 g/kg significantly enhanced the AUC 0-t and MRT by 362% and 291%, respectively. Likewise, repeated seven doses of MOC at 2.0 g/kg significantly increased the AUC 0-t and MRT of MTX by 461% and 334%, respectively. Mechanism studies indicated that the function of MRP2 was significantly inhibited by MN, HK and the serum metabolites of MOC (MOCM), whereas BCRP was not inhibited by MOCM. In conclusion, coadministration of MOC markedly enhanced the systemic exposure and mean residence time of MTX through inhibiting the MRP2-mediated excretion of MTX.

Background: The use of synthetic computed tomography (CT) for radiotherapy treatment planning has received considerable attention because of the absence of ionizing radiation and close spatial correspondence to source magnetic resonance (MR) images, which have excellent tissue contrast. However, in an MR-only environment, little effort has been made to examine the quality of synthetic CT images without using the original CT images., Purpose: To estimate synthetic CT quality without referring to original CT images, this study established the relationship between synthetic CT uncertainty and Bayesian uncertainty, and proposed a new Bayesian deep network for generating synthetic CT images and estimating synthetic CT uncertainty for MR-only radiotherapy treatment planning., Methods and Materials: A novel deep Bayesian network was formulated using probabilistic network weights. Two mathematical expressions were proposed to quantify the Bayesian uncertainty of the network and synthetic CT uncertainty, which was closely related to the mean absolute error (MAE) in Hounsfield Unit (HU) of synthetic CT. These uncertainties were examined to demonstrate the accuracy of representing the synthetic CT uncertainty using a Bayesian counterpart. We developed a hybrid Bayesian architecture and a new data normalization scheme, enabling the Bayesian network to generate both accurate synthetic CT and reliable uncertainty information when probabilistic weights were applied. The proposed method was evaluated in 59 patients (13/12/32/2 for training/validation/testing/uncertainty visualization) diagnosed with prostate cancer, who underwent same-day pelvic CT- and MR-acquisitions. To assess the relationship between Bayesian and synthetic CT uncertainties, linear and non-linear correlation coefficients were calculated on per-voxel, per-tissue, and per-patient bases. For accessing the accuracy of the CT number and dosimetric accuracy, the proposed method was compared with a commercially available atlas-based method (MRCAT) and a U-Net conditional-generative adversarial network (UcGAN)., Results: The proposed model exhibited 44.33 MAE, outperforming UcGAN 52.51 and MRCAT 54.87. The gamma rate (2%/2 mm dose difference/distance to agreement) of the proposed model was 98.68%, comparable to that of UcGAN (98.60%) and MRCAT (98.56%). The per-patient and per-tissue linear correlation coefficients between the Bayesian and synthetic CT uncertainties ranged from 0.53 to 0.83, implying a moderate to strong linear correlation. Per-voxel correlation coefficients varied from -0.13 to 0.67 depending on the regions-of-interest evaluated, indicating tissue-dependent correlation. The R 2 value for estimating MAE solely using Bayesian uncertainty was 0.98, suggesting that the uncertainty of the proposed model was an ideal candidate for predicting synthetic CT error, without referring to the original CT., Conclusion: This study established a relationship between the Bayesian model uncertainty and synthetic CT uncertainty. A novel Bayesian deep network was proposed to generate a synthetic CT and estimate its uncertainty. Various metrics were used to thoroughly examine the relationship between the uncertainties of the proposed Bayesian model and the generated synthetic CT. Compared with existing approaches, the proposed model showed comparable CT number and dosimetric accuracies. The experiments showed that the proposed Bayesian model was capable of producing accurate synthetic CT, and was an effective indicator of the uncertainty and error associated with synthetic CT in MR-only workflows., (© 2023 American Association of Physicists in Medicine.)

This study investigated combination of the Rapid Sepsityper Kit and a machine learning (ML)-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) approach for rapid prediction of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Klebsiella pneumoniae (CRKP) from positive blood culture bottles. The study involved 461 patients with monomicrobial bloodstream infections. Species identification was performed using the conventional MALDI-TOF MS Biotyper system and the Rapid Sepsityper protocol. The data underwent preprocessing steps, and ML models were trained using preprocessed MALDI-TOF data and corresponding labels. The interpretability of the model was enhanced using SHapely Additive exPlanations values to identify significant features. In total, 44 S. aureus isolates comprising 406 MALDI-TOF MS files and 126 K. pneumoniae isolates comprising 1249 MALDI-TOF MS files were evaluated. This study demonstrated the feasibility of predicting MRSA among S. aureus and CRKP among K. pneumoniae isolates using MALDI-TOF MS and Sepsityper. Accuracy, area under the receiver operating characteristic curve, and F1 score for MRSA/methicillin-susceptible S. aureus were 0.875, 0.898 and 0.904, respectively; for CRKP/carbapenem-susceptible K. pneumoniae, these values were 0.766, 0.828 and 0.795, respectively. In conclusion, the novel ML-based MALDI-TOF MS approach enables rapid identification of MRSA and CRKP from flagged blood cultures within 1 h. This enables earlier initiation of targeted antimicrobial therapy, reducing deaths due to sepsis. The favourable performance and reduced turnaround time of this method suggest its potential as a rapid detection strategy in clinical microbiology laboratories, ultimately improving patient outcomes., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Aims: The aim of this study is to clarify the role of NLRP3 inflammasome in phosphate burden-induced vascular smooth muscle cell (VSMC) calcification., Main Methods: VSMC calcification was induced using a high concentration of inorganic phosphate. After pharmacological inhibition or genetic silencing of the NLRP3 inflammasome, pyroptosis, or potassium efflux, the cells were examined by RT-qPCR, immunofluorescence, and western blotting to identify the NLRP3-mediated pathway for VSMC calcification., Key Findings: Calcified VSMCs with α-smooth muscle actin (α-SMA) disarray presented features of pyroptosis, including caspase-1 maturation, cleaved gasdermin D (GSDMD), and a high supernatant level of lactate dehydrogenase A. Pharmacological inhibitions of caspase-1 and pyroptosis attenuated VSMC calcification, whereas interleukin-1β receptor antagonism did not. Unlike canonical NLRP3 activation, osteogenic VSMCs did not upregulate NLRP3 expression. However, NLRP3 genetic silencing or inhibitions, which targets different domains of the NLRP3 protein, could ameliorate VSMC calcification by aborting caspase-1 and GSDMD activation. Furthermore, potassium efflux through the inward-rectifier potassium channel, and not through the P2X7 receptor, triggered NLRP3 inflammasome activation and VSMC calcification., Significance: In the present study, we identified a potassium efflux-triggered NLRP3-caspase-1-mediated pyroptotic pathway for VSMC calcification that is unique and different from the canonical NLRP3 inflammasome activation. Therefore, targeting this pathway may serve as a novel therapeutic strategy for vascular calcification., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to develop a rapid prediction method for carbapenem-resistant Klebsiella pneumoniae (CRKP) and colistin-resistant K. pneumoniae (ColRKP) based on routine MALDI-TOF mass spectrometry (MS) results in order to formulate a suitable and rapid treatment strategy. A total of 830 CRKP and 1462 carbapenem-susceptible K. pneumoniae (CSKP) isolates were collected; 54 ColRKP isolates and 1592 colistin-intermediate K. pneumoniae (ColIKP) isolates were also included. Routine MALDI-TOF MS, antimicrobial susceptibility testing, NG-Test CARBA 5, and resistance gene detection were followed by machine learning (ML). Using the ML model, the accuracy and area under the curve for differentiating CRKP and CSKP were 0.8869 and 0.9551, respectively, and those for ColRKP and ColIKP were 0.8361 and 0.8447, respectively. The most important MS features of CRKP and ColRKP were m/z 4520-4529 and m/z 4170-4179, respectively. Of the CRKP isolates, MS m/z 4520-4529 was a potential biomarker for distinguishing KPC from OXA, NDM, IMP, and VIM. Of the 34 patients who received preliminary CRKP ML prediction results (by texting), 24 (70.6%) were confirmed to have CRKP infection. The mortality rate was lower in patients who received antibiotic regimen adjustment based on the preliminary ML prediction (4/14, 28.6%). In conclusion, the proposed model can provide rapid results for differentiating CRKP and CSKP, as well as ColRKP and ColIKP. The combination of ML-based CRKP with preliminary reporting of results can help physicians alter the regimen approximately 24 h earlier, resulting in improved survival of patients with timely antibiotic intervention., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

BACKGROUND This study from a single center in Taiwan aimed to evaluate the impact of remote patient monitoring (RPM) using the Sharesource connectivity platform on adherence to automated peritoneal dialysis (APD) in 51 patients. MATERIAL AND METHODS We analyzed data on 51 patients with end-stage renal disease (ESRD) under APD. They were treated with a traditional APD machine HomeChoice (phase 1), changed to new APD machine HomeChoice Claria for 12 weeks (phase 2), then connected to the Sharesource platform for another 12 weeks (phase 3), and were followed up for 1 year. The non-adherence rate was compared between the 3 phases. The secondary outcomes included peritonitis rate, hospitalization rate, and hospitalization days, 1 year before and after receiving a new APD machine. Patients were subdivided into good and poor adherence (>1 episode of non-adherence in phase 1) groups for further analysis. RESULTS The average non-adherence rates were 10.5%, 5.1%, and 4.9% in phases 1, 2, and 3, respectively, although differences were not significant. Serum potassium (P<0.0001) and C-reactive protein (CRP) (P=0.026) levels significantly decreased in phase 3. The 1-year peritonitis rate, hospitalization rate, and number of days of hospitalization showed no significant changes. Subgroup analysis revealed that the non-adherence rate in the poor adherence group decreased from 48.4% in phase 1 to 14.2% and 12.4% in phases 2 and 3, respectively (P=0.007). CONCLUSIONS Remoting monitoring using the Sharesource connectivity platform increased dialysis adherence in APD treatment, especially in patients with poor adherence. Serum potassium level and inflammation status were also improved by this system.

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an oligomeric complex that assembles in response to exogenous signals of pathogen infection and endogenous danger signals of non-microbial origin. When NLRP3 inflammasome assembly activates caspase-1, it promotes the maturation and release of the inflammatory cytokines interleukin-1B and IL-18. Aberrant activation of the NLRP3 inflammasome has been implicated in various diseases, including chronic inflammatory, metabolic, and cardiovascular diseases. The NLRP3 inflammasome can be activated through several principal mechanisms, including K+ efflux, lysosomal damage, and the production of mitochondrial reactive oxygen species. Interestingly, metabolic danger signals activate the NLRP3 inflammasome to induce metabolic diseases. NLRP3 contains three crucial domains: an N-terminal pyrin domain, a central nucleotide-binding domain, and a C-terminal leucine-rich repeat domain. Protein-protein interactions act as a 'pedal or brake' to control the activation of the NLRP3 inflammasome. In this review, we present the mechanisms underlying NLRP3 inflammasome activation after induction by metabolic danger signals or via protein-protein interactions with NLRP3 that likely occur in metabolic diseases. Understanding these mechanisms will enable the development of specific inhibitors to treat NLRP3-related metabolic diseases.

Peroxisome proliferator-activated receptor γ (PPARγ) gene mutations in humans and mice lead to whole-body insulin resistance and partial lipodystrophy. It is unclear whether preserved fat depots in partial lipodystrophy are beneficial for whole-body metabolic homeostasis. We analyzed the insulin response and expression of metabolic genes in the preserved fat depots of Pparg C/- mice, a familial partial lipodystrophy type 3 (FPLD3) mouse model resulting from a 75% decrease in Pparg transcripts. Perigonadal fat of Pparg C/- mice in the basal state showed dramatic decreases in adipose tissue mass and insulin sensitivity, whereas inguinal fat showed compensatory increases. Preservation of inguinal fat metabolic ability and flexibility was reflected by the normal expression of metabolic genes in the basal or fasting/refeeding states. The high nutrient load further increased insulin sensitivity in inguinal fat, but the expression of metabolic genes became dysregulated. Inguinal fat removal resulted in further impairment of whole-body insulin sensitivity in Pparg C/- mice. Conversely, the compensatory increase in insulin sensitivity of the inguinal fat in Pparg C/- mice diminished as activation of PPARγ by its agonists restored insulin sensitivity and metabolic ability of perigonadal fat. Together, we demonstrated that inguinal fat of Pparg C/- mice plays a compensatory role in combating perigonadal fat abnormalities.

Patients with end-stage renal disease (ESRD) are at a higher mortality risk compared with the general population. Previous studies have described a relationship between mortality and patients with ESRD, but the data on standardized mortality ratio (SMR) corresponding to different causes of death in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD) are limited. This study was designed as a nationwide population-based retrospective cohort study. Incident dialysis patients between January 2000 and December 2015 in Taiwan were included. Using data acquired from the Taiwan Death Registry, SMR values were calculated and compared with the overall survival. The results showed there were a total of 128,966 patients enrolled, including 117,376 incident HD patients and 11,590 incident PD patients. It was found that 75,297 patients (58.4%) died during the period of 2000-2017. The overall SMR was 5.21. The neoplasms SMR was 2.11; the endocrine, nutritional, metabolic, and immunity disorders SMR was 13.53; the circulatory system SMR was 4.31; the respiratory system SMR was 2.59; the digestive system SMR was 6.1; and the genitourinary system SMR was 27.22. Therefore, more attention should be paid to these diseases in clinical care.