Search

Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is well-established therapy in patients with reduced left ventricular ejection fraction (LVEF) and bundle branch block or indication for pacing. Conduction system pacing (CSP) using His-bundle pacing (HBP) or left bundle branch area pacing (LBBAP) has been shown to be a safe and more physiological alternative to BVP.The purpose of this study was to compare the clinical outcomes between CSP and BVP among patients undergoing CRT.This observational study included consecutive patients with LVEF ≤35% and class I or II indications for CRT who underwent successful BVP or CSP at 2 major health care systems. The primary outcome was the composite endpoint of time to death or heart failure hospitalization (HFH). Secondary outcomes included subgroup analysis in left bundle branch block as well as individual endpoints of death and HFH.A total of 477 patients (32% female) met inclusion criteria (BVP 219; CSP 258 [HBP 87, LBBAP 171]). Mean age was 72 ± 12 years, and mean LVEF was 26% ± 6%. Comorbidities included hypertension 70%, diabetes mellitus 45%, and coronary artery disease 52%. Paced QRS duration in CSP was significantly narrower than BVP (133 ± 21 ms vs 153 ± 24 ms; P.001). LVEF improved in both groups during mean follow-up of 27 ± 12 months and was greater after CSP compared to BVP (39.7% ± 13% vs 33.1% ± 12%; P.001). Primary outcome of death or HFH was significantly lower with CSP vs BVP (28.3% vs 38.4%; hazard ratio 1.52; 95% confidence interval 1.082-2.087; P = .013).CSP improved clinical outcomes compared to BVP in this large cohort of patients with indications for CRT.

IMPORTANCESeveral pharmacotherapies have been authorized to treat non-hospitalized persons with symptomatic COVID-19. Longitudinal information on their use is needed.OBJECTIVETo analyze trends and factors related to prescription of outpatient COVID-19 pharmacotherapies within the Veterans Health Administration (VHA).DESIGN, SETTINGS, AND PARTICIPANTSThis cohort study evaluated non-hospitalized veterans in VHA care who tested positive for SARS-CoV-2 from January 2022 through January 2023, using VHA and linked Community Care and Medicare databases.EXPOSURESDemographic characteristics, regional and local systems of care including Veterans Integrated Services Networks (VISNs), underlying medical conditions, COVID-19 vaccination.MAIN OUTCOMES AND MEASURESMonthly receipt of any COVID-19 pharmacotherapy (nirmatrelvir-ritonavir, molnupiravir, sotrovimab, or bebtelovimab) was described. Multivariable logistic regression was used to identify factors independently associated with receipt of any versus no COVID-19 pharmacotherapy.RESULTSAmong 285,710 veterans (median [IQR] age, 63.1 [49.9-73.7] years; 247,358 (86.6%) male; 28,444 (10%) Hispanic; 198,863 (72.7%) White; 61,269 (22.4%) Black) who tested positive for SARS-CoV-2 between January 2022 and January 2023, the proportion receiving any pharmacotherapy increased from 3.2% (3,285/102,343) in January 2022 to 23.9% (5,180/21,688) in August 2022, and declined slightly to 20.8% (2,194/10,551) by January 2023. Across VISNs, the range in proportion of test-positive patients who received nirmatrelvir-ritonavir or molnupiravir during January 2023 was 5.9 to 21.4% and 2.1 to 11.1%, respectively. Veterans receiving any treatment were more likely to be older (adjusted odds ratio [aOR], 1.18, 95% CI 1.14-1.22 for 65 to 74 versus 50 to 64 years; aOR 1.19, 95% CI 1.15-1.23 for 75 versus 50 to 64 years), have a higher Charlson Comorbidity Index (CCI) (aOR 1.52, 95% CI 1.44-1.59 for CCI ≥6 versus 0), and be vaccinated against COVID-19 (aOR 1.25, 95% CI 1.19-1.30 for primary versus no vaccination; aOR 1.47, 95% CI 1.42-1.53 for booster versus no vaccination). Compared with White veterans, Black veterans (aOR 1.06, 95% CI 1.02 to 1.09) were more likely to receive treatment, and compared with non-Hispanic veterans, Hispanic veterans (aOR 1.06, 95% CI 1.01-1.11) were more likely to receive treatment.CONCLUSIONS AND RELEVANCEAmong veterans who tested positive for SARS-CoV-2 between January 2022 and January 2023, prescription of outpatient COVID-19 pharmacotherapies peaked in August 2022 and declined thereafter. There remain large regional differences in patterns of nirmatrelvir-ritonavir and molnupiravir use.

As its common name implies, tuberculostearic acid is an abundant and genus-specific branched-chain fatty acid in mycobacterial membranes. This fatty acid, 10-methyl octadecanoic acid, has been an intense focus of research, particularly as a diagnostic marker for tuberculosis.

Collective transport properties of a one-dimensional asymmetric periodic substrate (1DAPS) modulated two-dimensional dusty plasma (2DDP) driven by an unbiased sinusoidal excitation force are investigated using Langevin dynamical simulations. It is discovered that, by changing the amplitude and frequency of the unbiased sinusoidal external excitations, as well as the depth of 1DPAS, both the direction and speed of the persistent particle flow can be adjusted, i.e., both the flow rectification and its reversal of the ratchet effect of the steady drift motion for particles are achieved using various excitations. For the studied 2DDP under the 1DAPS, when the amplitude of the excitation increases from zero, the magnitude of the overall drift velocity increases from zero to its first maximum in the easy direction of the 1DAPS, next decreases gradually back to zero, and then increases from zero to its second maximum in the hard direction of 1DAPS before finally gradually decaying. It is found that, as the frequency of the excitation and the depth of 1DAPS change, the maximum overall drift velocity also varies, and the corresponding magnitude of the excitation varies simultaneously. The observed ratchet effect in both the easy and hard directions of 1DAPS for 2DDP is attributed to the combination of the spatial symmetry breaking of 1DAPS and the inertial effects of particles, which is further confirmed by the three different presented diagnostics.

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, once thought to be benign as long as the ventricular rate was controlled, is associated with significant cardiac morbidity and mortality. Increasing life expectancy driven by improved health care and decreased fertility rates has, in most of the world, resulted in the population aged ≥65 years growing more rapidly than the overall population. As the population ages, projections suggest that the burden of AF may increase more than 60% by 2050. Although considerable progress has been made in the treatment and management of AF, primary prevention, secondary prevention, and prevention of thromboembolic complications remain a work in progress. This narrative review was facilitated by a search of MEDLINE to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other clinically relevant studies. The search was limited to English-language reports published between 1950 and 2021. Atrial fibrillation was searched using the terms primary prevention, hyperthyroidism, Wolff-Parkinson-White syndrome, catheter ablation, surgical ablation, hybrid ablation, stroke prevention, anticoagulation, left atrial occlusion and atrial excision. Google and Google scholar as well as bibliographies of identified articles were reviewed for additional references. In these two manuscripts, we discuss the current strategies available to prevent AF, then compare non-invasive and invasive treatment strategies to diminish AF recurrence. In addition, we examine the pharmacological, percutaneous device and surgical approaches to prevent stroke as well as other types of thromboembolic events.

In recent decades, our understanding of periodontitis has evolved from that based on a gross/histologic level to one on a cellular/molecular level. Previous landscape studies have explored molecular subtyping, diagnosis, and gingival tissue cell decomposition in periodontitis, and meaningful results have been obtained at a transcriptomic level. However, current periodontitis transcriptomic studies lack a finer dissection of the intercommunication between immune cells and the biological processes of specific immune cell subtypes. In this study, we classified 15 immune cell types in periodontitis at a single-cell level and conducted a cell communication analysis based on a multicenter integrated single-cell transcriptome profile, in which plasma cell–generated macrophage migration inhibitory factor can communicate with most other immune cells in periodontitis. A pseudotime analysis focusing on B/plasma cell infiltration in periodontitis revealed 2 distinct cell fates (CFs) for B/plasma cells. In addition, at a bulk tissue level, a single-sample gene set enrichment analysis showed a similar immune cell infiltration trend, and a weighted gene coexpression network analysis identified an immune-related gene module. Combined with the above findings, we used machine learning methods to further narrow down potential gene candidates for developing and validating molecular diagnostic models of periodontitis. Multivariable logistic regression of a large public cohort (68 healthy vs. 235 periodontitis) and an independent validation cohort (12 healthy vs. 7 periodontitis) showed the CF1 signature provides a good discrimination and calibration performance with clinical benefits at a proper threshold probability. Furthermore, quantitative real-time polymerase chain reaction validation of the gene candidates was performed in both snap-frozen gingival tissues and gingival crevicular fluids. Our transcriptomic landscape analysis at both single-cell and bulk tissue resolutions thereby illustrates the B/plasma cell infiltration process in periodontitis and reveals a gene signature that may assist in molecular diagnosis of the disease.

Cardiovascular diseases in people living with HIV (PLWH) are becoming increasingly relevant as HIV/AIDS has become more treatable with the advent of highly efficacious antiretroviral therapy. Previous studies suggested that HIV infection is an independent risk factor for atrial arrhythmia. This study aims to collectively analyze these studies to elucidate the incidence and risk factors of atrial arrhythmia in PLWH.Full-text assessments and data extraction were performed from available literature. Atrial arrhythmia was defined as atrial fibrillation or atrial flutter. Incidence rate, risk, and potential risk factors of atrial arrhythmia in PLWH were catalogued, after which random-effects models were used to estimate pooled summary statistics. PRISMA standardized meta-analysis guidelines were followed.Analysis of 94,928 PLWH had an averaged incidence rate of 6.4 cases of atrial arrhythmia per 1000 person-years. Risk of atrial arrhythmia was significantly higher in PLWH than in the general population (RR 1.35; 95% CI 1.19-1.53). Sex had no association with the risk of incidental atrial arrhythmia in PLWH (RR 1.47; 95% CI 0.95-2.28). Black race (RR 0.68; 95% CI 0.47-0.97) was associated with decreased risk, whereas lower CD4 counts (RR 1.80; 95% CI 1.18-2.77) and increased viral load (RR 1.57; 95% CI 1.19-2.09) suggested increased risk of atrial arrhythmia in PLWH.HIV infection is a risk factor of atrial arrhythmia. Providers should be aware of the increased burden of atrial arrhythmia in PLWH and continue to encourage treatment of HIV infection while managing cardiovascular risk factors and screening for arrhythmias in symptomatic patients.

To retrospectively analyse the clinical and MRI data of primary squamous cell carcinoma (SCC), particularly pure squamous cell carcinoma (PSCC) and mixed squamous cell carcinoma (MSCC).The MRI data and clinicopathological characteristics of 20 patients with histopathologically confirmed SCC of the breast, including eight PSCC patients and 12 MSCC patients, from multiple centres between January 2013 and December 2020 were analysed retrospectively.Nine of 12 patients in the MSCC group showed hyperintensity on T1-weighted imaging (WI), while this feature was not observed in the PSCC group (p=0.001). Most of the PSCC group showed rim enhancement, whereas most of the MSCC group showed heterogeneous enhancement (p=0.007). In addition, there was no significant difference in the thickness of the rim enhancement and the percentage of necrotic components in the tumours between the two types of SCCs of the breast (p=0.545 and p=0.662, respectively). Four patients (4/12) in the MSCC group had sentinel lymph node metastasis, while only one patient (1/8) in the PSCC group showed lymph node metastasis (p=0.603). Metastatic disease occurred in 25% of patients with PSCC and in approximately 41.7% of patients with MSCC.The signal on T1WI and internal enhancement characteristics were the key features for differentiating PSCC and MSCC. Therefore, MRI phenotypes may provide additional information for the pathological classification of breast SCC.

Statistically and clinically significant cognitive declines are observed in a small subset of individuals with Parkinson's Disease (PD) following treatment with Deep Brain Stimulation (DBS).We examine the association between multi-domain cognitive decline (MCD) and demographic and baseline clinical variables and the incidence of serious adverse events (SAE) arising within a six-month interval following DBS for PD.Study participants with PD who displayed MCD at 6-month follow-up evaluation after DBS (n = 18) were contrasted with individuals with PD from the same study who did not show cognitive decline after DBS (n = 146). Logistic regression analyses were employed to assess relationship between predictors, including age (70 years old), pre-DBS cognitive screening test performance, SAE, and MCD. MCD+ and MCD-groups were also compared on other baseline clinical and demographic variables.MCD showed modest association with older age and lower baseline neurocognitive screening performance, whereas the groups did not differ on most other baseline clinical and demographic variables. SAEs during the study interval were the most robust predictor of MCD in the DBS group. A variety of SAEs were documented in study participants experiencing MCD after DBS surgery, including, but not limited to, infections and small intracranial hemorrhages.Older age and lower baseline cognition measured prior to treatment are associated with MCD measured at six-months after DBS. SAE occurring following DBS surgery are also predictive of MCD. These predictors may reflect aspects of "frailty" in advanced PD. Risk factors for SAE warrant careful consideration in clinical trials.

Vanillin (VL), a phenolic aromatic carbonyl abundant in biomass burning emissions, forms triplet excited states (3VL∗) under simulated sunlight leading to aqueous secondary organic aerosol (aqSOA) formation. Nitrate and ammonium are among the main components of biomass burning aerosols and cloud or fog water. Under atmospherically relevant cloud and fog conditions, solutions composed of either VL only or VL with ammonium nitrate were subjected to simulated sunlight irradiation to compare aqSOA formation via the direct photosensitized oxidation of VL in the absence and presence of ammonium nitrate. The reactions were characterized by examining the VL decay kinetics, product compositions, and light absorbance changes. Both conditions generated oligomers, functionalized monomers, and oxygenated ring-opening products, and ammonium nitrate promoted functionalization and nitration, likely due to its photolysis products (⚫OH, ⚫NO2, and NO2- or HONO). Moreover, a potential imidazole derivative observed in the presence of ammonium nitrate suggested that ammonium participated in the reactions. The majority of the most abundant products from both conditions were potential brown carbon (BrC) chromophores. The effects of oxygen (O2), pH, and reactants concentration and molar ratios on the reactions were also explored. Our findings show that O2 plays an essential role in the reactions, and oligomer formation was enhanced at pH <4. Also, functionalization was dominant at low VL concentrations, whereas oligomerization was favored at high VL concentrations. Furthermore, oligomers and hydroxylated products were detected from the oxidation of guaiacol (a non-carbonyl phenol) via VL photosensitized reactions. Last, potential aqSOA formation pathways via the direct photosensitized oxidation of VL in the absence and presence of ammonium nitrate were proposed. This study indicates that the direct photosensitized oxidation of VL may be an important aqSOA source in areas influenced by biomass burning and underscores the importance of nitrate in the aqueous-phase processing of aromatic carbonyls.

We report TeV gamma-ray observations of the ultra-high-energy source MGRO J1908+06 using data from the High Altitude Water Cherenkov (HAWC) Observatory. This source is one of the highest-energy known gamma-ray sources, with emission extending past 200 TeV. Modeling suggests that the bulk of the TeV gamma-ray emission is leptonic in nature, driven by the energetic radio-faint pulsar PSR J1907+0602. Depending on what assumptions are included in the model, a hadronic component may also be allowed. Using the results of the modeling, we discuss implications for detection prospects by multi-messenger campaigns., Comment: accepted by ApJ, in press

The rise of antimicrobial resistance (AMR) toward the conventional antibiotics and Ag compounds has made the search for metallodrugs to combat AMR imperative. Bi compounds such as the one reported in this article may emerge as the next silver bullet of metal antimicrobials.

We have performed and analyzed the first combined 151Eu and 57Fe nuclear resonant vibrational spectroscopy (NRVS) for naturally abundant KEu(iii)[Fe(ii)(CN)6] or Eu(iii)[Fe(iii)(CN)6] complex.

In this paper, Ti6Al4V+3 wt.% TiB2 composite powder was used as a raw material to synthesize TiB whiskers in situ and prepare composites reinforced with TiB/Ti6Al4V whiskers by selective laser melting (SLM). The effects of process parameters on the properties of TiB/Ti6Al4V samples were systematically studied. The evolution of the microstructure, including the formation and regulation of whiskers, and the effects on mechanical properties were discussed. The results showed that during the SLM process, adjusting the energy density effectively inhibited cracking in the TiB/Ti6Al4V samples. The TiB2 particles acted as nucleation centers to significantly refine the grains during processing and reacted with elemental Ti to form a needle-like TiB network at the grain boundaries, which strengthened the whiskers. Additionally, TiB played a role in dispersion strengthening. Compared with Ti6Al4V, the microhardness of TiB/Ti6Al4V was 430.6?11.45 HV, an increase of 27.9%, and the wear volume of the sample was 0.85?10-3 mm3, a decrease of 62.64%.

Iron is essential for all forms of life including pathogenic bacteria. However, iron is also a double-edged sword in biology, as increase of iron uptake can result in reactive oxygen species (ROS)-triggered cell death from the iron-catalyzed Fenton reaction. In this study, we demonstrate that iron-hinokitiol, Fe(hinok)(3), a neutral Fe(III) complex formed with the naturally occurring metal chelator hinokitiol; (2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one) can harness the clear ability, due to its high lipophilicity and the nonpolar nature, to penetrate the cell membrane of Staphylococcus aureus (SA) and exhibit potent antimicrobial activity that is enhanced by approximately 10,000 times as compared with hinokitiol itself. Additionally, this Fe(III) complex shows a strong ability to inhibit biofilm formation. More importantly, the development of resistance in SA toward this complex is considerably hampered in comparison with that toward ciprofloxacin. The in vivo evaluation of antimicrobial efficacy in the murine model of skin wound infection by SA confirms that the treatment with a single dose of this complex can reduce the bacterial burden by 83%, demonstrating the therapeutic potential of Fe(hinok)(3) in treating skin and soft tissue infections.

Ventricular tachycardia (VT) is a significant cause of morbidity and mortality in patients with ischaemic and non-ischaemic cardiomyopathies. In most patients, the primary strategy of VT catheter ablation is based on the identification of critical components of reentry circuits and modification of abnormal substrate which can initiate reentry. Despite technological advancements in catheter design and improved ability to localise abnormal substrates, putative circuits and site of origins of ventricular arrhythmias (VAs), current technologies remain inadequate and durable success may be elusive when the critical substrate is deep or near to critical structures that are at risk of collateral damage. In this article, we review the available and potential future non-surgical investigational approaches for treatment of VAs and discuss the viability of these modalities.

We present the results of dark matter (DM) searches in a sample of 31 dwarf irregular (dIrr) galaxies within the field of view of the HAWC Observatory. dIrr galaxies are DM dominated objects, which astrophysical gamma-ray emission is estimated to be negligible with respect to the secondary gamma-ray flux expected by annihilation or decay of Weakly Interacting Massive Particles (WIMPs). While we do not see any statistically significant DM signal in dIrr galaxies, we present the exclusion limits ($95\%~\text{C.L.}$) for annihilation cross-section and decay lifetime for WIMP candidates with masses between $1$ and $100~\text{TeV}$. Exclusion limits from dIrr galaxies are relevant and complementary to benchmark dwarf Spheroidal (dSph) galaxies. In fact, dIrr galaxies are targets kinematically different from benchmark dSph, preserving the footprints of different evolution histories. We compare the limits from dIrr galaxies to those from ultrafaint and classical dSph galaxies previously observed with HAWC. We find that the contraints are comparable to the limits from classical dSph galaxies and $\thicksim2$ orders of magnitude weaker than the ultrafaint dSph limits., Comment: 22 pages, 11 figures, 3 tables

The High-Altitude Water Cherenkov (HAWC) observatory is a second-generation continuously operated, wide field-of-view, TeV gamma-ray observatory. The HAWC observatory and its analysis techniques build on experience of the Milagro experiment in using ground-based water Cherenkov detectors for gamma-ray astronomy. HAWC is located on the Sierra Negra volcano in M\'exico at an elevation of 4100 meters above sea level. The completed HAWC observatory principal detector (HAWC) consists of 300 closely spaced water Cherenkov detectors, each equipped with four photomultiplier tubes to provide timing and charge information to reconstruct the extensive air shower energy and arrival direction. The HAWC observatory has been optimized to observe transient and steady emission from sources of gamma rays within an energy range from several hundred GeV to several hundred TeV. However, most of the air showers detected are initiated by cosmic rays, allowing studies of cosmic rays also to be performed. This paper describes the characteristics of the HAWC main array and its hardware., Comment: Accepted for publications in Nuclear Inst. and Methods in Physics Research, A (2023) 168253 ( https://www.sciencedirect.com/science/article/abs/pii/S0168900223002437 ); 39 pages, 14 Figures

LiV$_2$O$_4$ is a mixed-valent spinel oxide and one of a few transition-metal compounds to host a heavy fermion phase at low temperatures. While numerous experimental studies have attempted to elucidate how its 3$d$ electrons undergo giant mass renormalization, spectroscopic probes that may provide crucial hints, such as scanning tunneling microscopy (STM), remain to be applied. A prerequisite is atomically flat and pristine surfaces, which, in the case of LiV$_2$O$_4$, are difficult to obtain by cleavage of small, three-dimensional crystals. We report the epitaxial growth of LiV$_2$O$_4$ thin films with bulklike properties on SrTiO$_3$(111) via pulsed laser deposition and stable STM imaging of the LiV$_2$O$_4$(111) surface. The as-grown films were transferred $ex$ $situ$ to a room-temperature STM, where subsequent annealing with optional sputtering in ultrahigh vacuum enabled compact islands with smooth surfaces and a hexagonal 1$\times$1 atomic lattice to be resolved. Our STM measurements provide insights into growth mechanisms of LiV$_2$O$_4$ on SrTiO$_3$(111), as well as demonstrate the feasibility of performing surface-sensitive measurements of this heavy fermion compound., Comment: 6 pages, 4 figures + SM

In the quest for high-energy neutrino sources, the Astrophysical Multimessenger Observatory Network has implemented a new search by combining data from the High Altitude Water Cherenkov (HAWC) Observatory and the Astronomy with a Neutrino Telescope and Abyss environmental RESearch (ANTARES) neutrino telescope. Using the same analysis strategy as in a previous detector combination of HAWC and IceCube data, we perform a search for coincidences in HAWC and ANTARES events that are below the threshold for sending public alerts in each individual detector. Data were collected between 2015 July and 2020 February with a live time of 4.39 yr. Over this time period, three coincident events with an estimated false-alarm rate of, The National Science Foundation under grants PHY-1708146, PHY-1806854, The Institute for Gravitation and the Cosmos of the Pennsylvania State University, Centre National de la Recherche Scientifique (CNRS), Commissariat à l’énergie atomique et aux énergies alternatives (CEA), Commission Européenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Région Île-de-France (DIM-ACAV), Région Alsace (contrat CPER), Région Provence-Alpes-Côte d’Azur, Département du Var and Ville de La Seyne-sur-Mer, Bundesministerium für Bildung und Forschung (BMBF), Istituto Nazionale di Fisica Nucleare (INFN), Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), Executive Unit for Financing Higher Education, Research, Development and Innovation (UEFISCDI), Romania; Ministerio de Ciencia, Innovación, Investigación y Universidades (MCIU), Programa Estatal de Generación de Conocimiento (refs. PGC2018- 096663-B-C41, -A-C42, B-C43, B-C44, PID2021- 124591NB-C41, C42, C43, (MCIU/FEDER), Generalitat Valenciana, Prometeo (PROMETEO/2020/019), Grisolía (refs. GRISOLIA/2018/119, /2021/192), GenT (refs. /2019/043, /2020/049, /2021/023) programs, Junta de Andalucía (ref. A-FQM-053-UGR18), La Caixa Foundation (ref. LCF/BQ/IN17/11620019), MSC program (ref. 101025085), Spain; Ministry of Higher Education, Scientific Research and Innovation, The Arab Fund for Economic and Social Development, Kuwait, US National Science Foundation (NSF), The US Department of Energy Office of High-Energy Physics, Laboratory Directed Research and Development (LDRD) program of Los Alamos National Laboratory, Consejo Nacional de Ciencia y Tecnología (CONACyT), México, grants 271051, 232656, 260378, 179588, 254964, 258865, 243290, 132197, A1-S-46288, A1- S-22784, Cátedras 873, 1563, 341, 323, Red HAWC, México, DGAPA-UNAM grants IG101320, IN111716-3, IN111419, IA102019, IN110621, IN110521, VIEP-BUAP, PIFI 2012, PROFOCIE 2014, 2015, the University of Wisconsin Alumni Research Foundation, The Institute of Geophysics, Planetary Physics, Signatures at Los Alamos National Laboratory, Polish Science Centre grant, DEC-2017/27/B/ ST9/02272, Coordinación de la Investigación Científica de la Universidad Michoacana; Royal Society—Newton Advanced Fellowship 180385, Generalitat Valenciana, grant CIDEGENT/ 2018/034, The Program Management Unit for Human Resources & Institutional Development, Research and Innovation, NXPO (grant No. B16F630069), Coordinación General Académica e Innovación (CGAI-UdeG), PRODEP-SEP UDGCA- 499; Institute of Cosmic Ray Research (ICRR), University of Tokyo, NASA under award number 80GSFC21M0002

Metagenomic assembly enables new organism discovery from microbial communities, but it can only capture few abundant organisms from most metagenomes. Here we present MetaPhlAn 4, which integrates information from metagenome assemblies and microbial isolate genomes for more comprehensive metagenomic taxonomic profiling. From a curated collection of 1.01 M prokaryotic reference and metagenome-assembled genomes, we define unique marker genes for 26,970 species-level genome bins, 4,992 of them taxonomically unidentified at the species level. MetaPhlAn 4 explains ~20% more reads in most international human gut microbiomes and >40% in less-characterized environments such as the rumen microbiome and proves more accurate than available alternatives on synthetic evaluations while also reliably quantifying organisms with no cultured isolates. Application of the method to >24,500 metagenomes highlights previously undetected species to be strong biomarkers for host conditions and lifestyles in human and mouse microbiomes and shows that even previously uncharacterized species can be genetically profiled at the resolution of single microbial strains.

Catheter ablation for atrial fibrillation (AF) in comparison to medical therapy alone is known to improve freedom from arrhythmia and quality of life, but the benefit regarding mortality is unclear. The publication of several recent large randomized controlled trials (RCT) comparing ablation with medical therapy has warranted an updated meta-analysis.We sought to compare the effectiveness of catheter ablation versus medical therapy only in patients with AF. MEDLINE, Cochrane, and ClinicalTrials.gov databases were searched from inception until 04/30/2021. Relevant RCTs comparing catheter ablation versus medical therapy in patients with AF were selected.A total of 24 RCTs involving 5730 adult patients were included (2992 in catheter ablation and 2738 in medical therapy). There was a reduction in all-cause mortality with catheter ablation compared with medical therapy only (risk ratio (RR) 0.70 [95% confidence interval (CI) 0.55-0.89]; p = .003). Catheter ablation also demonstrated a reduction in hospitalizations (RR 0.50 [95% CI 0.36-0.70]; p .001), improvement in left ventricular ejection fraction (LVEF) (mean difference [MD] + 5.94% [95% CI 0.40-11.48] p = .04), greater freedom from atrial arrhythmia (RR 2.23 [95% CI 1.79-2.76]; p .001), and AF (RR 1.95 [95% CI 1.44-2.66]; p .001). In subgroup analysis, catheter ablation demonstrated a significant reduction in mortality and hospitalizations among patients with reduced LVEF, and when ablation was compared with antiarrhythmic drug use.In comparison to medical therapy only, catheter ablation for atrial fibrillation reduces mortality, hospitalizations, and increases freedom from arrhythmia.

The dense uniformed joints between molybdenum disilicides (MoSi2) and stainless steel powders were prepared using the spark plasma sintering (SPS) technique with nine graded materials and their welding behavior was investigated. The results showed that such joints can be achieved using graded interlayers because the coefficient of thermal expansion (CTE) of each interlayer closely matched over a wide temperature range. Furthermore, the compatibility between the graded interlayers prevented MoSi2 with low toughness from the occurrence of microcracks resulted from the residual stresses formed during cooling of the joint. Moreover, the 9-layer joint with a thickness of 1.0 mm for each layer exhibited the minimum residual stress if the compositional exponent was 0.8.

Whether chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension is unclear.In a pragmatic trial, we randomly assigned adults 65 years of age or older who were patients in the Department of Veterans Affairs health system and had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 or 25 mg. The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death. Safety was also assessed.A total of 13,523 patients underwent randomization. The mean age was 72 years. At baseline, hydrochlorothiazide at a dose of 25 mg per day had been prescribed in 12,781 patients (94.5%). The mean baseline systolic blood pressure in each group was 139 mm Hg. At a median follow-up of 2.4 years, there was little difference in the occurrence of primary-outcome events between the chlorthalidone group (702 patients [10.4%]) and the hydrochlorothiazide group (675 patients [10.0%]) (hazard ratio, 1.04; 95% confidence interval, 0.94 to 1.16; P = 0.45). There were no between-group differences in the occurrence of any of the components of the primary outcome. The incidence of hypokalemia was higher in the chlorthalidone group than in the hydrochlorothiazide group (6.0% vs. 4.4%, P0.001).In this large pragmatic trial of thiazide diuretics at doses commonly used in clinical practice, patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or non-cancer-related deaths than patients who received hydrochlorothiazide. (Funded by the Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT02185417.).

BackgroundInformation about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes during the Omicron surge is limited. We sought to determine the effectiveness of nirmatrelvir-ritonavir and molnupiravir for the outpatient treatment of COVID-19.MethodsWe conducted three retrospective target trial emulation studies comparing matched patient cohorts who received nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir-ritonavir versus molnupiravir in the Veterans Health Administration (VHA). Participants were Veterans in VHA care at risk for severe COVID-19 who tested positive for SARS-CoV-2 in the outpatient setting during January and February 2022. Primary outcomes included all-cause 30-day hospitalization or death and 31-180-day incidence of acute or long-term care admission, death, or post-COVID-19 conditions. For 30-day outcomes, we calculated unadjusted risk rates, risk differences, and risk ratios. For 31-180-day outcomes, we used unadjusted time-to-event analyses.ResultsParticipants were 90% male with median age 67 years and 26% unvaccinated. Compared to matched untreated controls, nirmatrelvir-ritonavir-treated participants (N=1,587) had a lower 30-day risk of hospitalization (27.10/1000 versus 41.06/1000, risk difference [RD] - 13.97, 95% CI -23.85 to -4.09) and death (3.15/1000 versus 14.86/1000, RD -11.71, 95% CI - 16.07 to -7.35). Among persons who were alive at day 31, further significant reductions in 31-180-day incidence of hospitalization (sub-hazard ratio 1.07, 95% CI 0.83 to 1.37) or death (hazard ratio 0.61, 95% CI 0.35 to 1.08) were not observed. Molnupiravir-treated participants aged ≥65 years (n=543) had a lower combined 30-day risk of hospitalization or death (55.25/1000 versus 82.35/1000, RD -27.10, 95% CI -50.63 to -3.58). A statistically significant difference in 30-day or 31-180-day risk of hospitalization or death was not observed between matched nirmatrelvir- or molnupiravir-treated participants. Incidence of most post-COVID conditions was similar across comparison groups.ConclusionsNirmatrelvir-ritonavir was highly effective in preventing 30-day hospitalization and death. Short-term benefit from molnupiravir was observed in older groups. Significant reductions in adverse outcomes from 31-180 days were not observed with either antiviral.

All-metal 3D printing fabrication technologies provide an attractive alternative for direct manufacturing of waveguide components due to fast and cost-effective prototyping and the possibility to fabricate geometries which cannot be fabricated with traditional machining techniques. In radio astronomy, waveguide components in radio receivers are operated at cryogenic temperatures and inside a cryostat under vacuum conditions. In this paper, we report on the design, fabrication by 3D printing and testing at room and cryogenic temperatures of a corrugated horn to be used in astronomical receivers operating in the 35–50-GHz band.

在欧美国家左心室辅助装置（LVAD）已成为终末期心力衰竭非药物治疗的主要手段，国内亦有数十家医院正在临床开展应用。但LVAD术后患者面临的主要问题仍然是右心室功能衰竭，亦是引起LVAD术后死亡的主要原因。该文围绕LVAD植入术后右心功能障碍的发生机制、右心功能衰竭预测模型以及超声心动图在LVAD植入前后对右心功能的评估要点进行综述。.

ImportanceOlder adults and individuals with medical comorbidities are at increased risk for severe COVID-19. Several pharmacotherapies demonstrated to reduce the risk of COVID-19–related hospitalization and death have been authorized for use.ObjectiveTo describe factors associated with receipt of outpatient COVID-19 pharmacotherapies in the Veterans Affairs (VA) health care system.Design, Settings, and ParticipantsThis cohort study assessed outpatient veterans with risk factors for severe COVID-19 who tested positive for SARS-CoV-2 during January and February 2022. The setting was the VA health care system, the largest integrated health care system in the US.ExposuresDemographic characteristics, place of residence, underlying medical conditions, and COVID-19 vaccination.Main Outcomes and MeasuresThe odds of receipt of any COVID-19 pharmacotherapy, including sotrovimab, nirmatrelvir boosted with ritonavir, molnupiravir, or remdesivir were estimated using multivariable logistic regression.ResultsAmong 111 717 veterans included in this study (median [IQR] age, 60 [46-72] years; 96 482 [86.4%] male, 23 362 [20.9%] Black, 10 740 [9.6%] Hispanic, 75 973 [68.0%] White) who tested positive for SARS-CoV-2 during January to February 2022, 4233 (3.8%) received any COVID-19 pharmacotherapy, including 2870 of 92 396 (3.1%) in January and 1363 of 19 321 (7.1%) in February. Among a subset of 56 285 veterans with documented COVID-19–related symptoms in the 30 days preceding a positive SARS-CoV-2 test, 3079 (5.5%) received any COVID-19 pharmacotherapy. Untreated veterans had a median (IQR) age of 60 (46-71) years and a median (IQR) of 3 (2-5) underlying medical conditions. Veterans receiving any treatment were more likely to be older (aged 65 to 74 years vs 50 to 64 years: adjusted odds ratio [aOR], 1.66 [95% CI, 1.52-1.80]; aged at least 75 years vs 50 to 64 years: aOR, 1.67 [95% CI, 1.53-1.84]) and have a higher number of underlying conditions (at least 5 conditions vs 1 to 2 conditions: aOR, 2.17 [95% CI, 1.98-2.39]). Compared with White veterans, Black veterans (aOR, 0.65 [95% CI, 0.60-0.72]) were less likely to receive treatment; and compared with non-Hispanic veterans, Hispanic veterans (aOR, 0.88 [95% CI, 0.77-0.99]) were less likely to receive treatment. There were 16 546 courses of sotrovimab, nirmatrelvir, and molnupiravir allocated across the VA during this period.Conclusions and RelevanceIn this cohort study of veterans who tested positive for SARS-CoV-2 during January and February when supply of outpatient COVID-19 pharmacotherapies was limited, prescription of these pharmacotherapies was underused, and many veterans with risk factors for severe COVID-19 did not receive treatment. Veterans from minority racial and ethnic groups were less likely to receive any pharmacotherapy.

We have performed and analyzed the first combined

OBJECTIVE: To analyze the feasibility of using vascular plaque quantification (VPQ) to evaluate carotid atherosclerotic plaques and to observe the effect of statins on carotid atherosclerotic plaques. METHODS: Patients with carotid plaques from January 2016 to September 2018 in Peking University First Hospital Neurology Department were recruited and underwent three-dimonsional ultrasound (3DUS). Their gray scale median (GSM) and other parameters of carotid plaques were measured with VPQ. The patients were divided into low GSM group (GSM < 40) and high GSM group (GSM≥40). The clinical characteristics and plaque characteristics of the patients in the two groups were compared to analyze the stability of plaques. According to whether taking statins or not, the patients were further divided into statin group and non-statin group, plaque GSM and other parameters of their carotid plaques were measured and the changes of carotid plaques at the end of 3 months and 2 years were observed. RESULTS: A total of 120 patients were enrolled, including 79 males and 41 females, with an average age of (65.39±9.11) years. The patients were divided into low GSM group (31 cases) (GSM < 40) and high GSM group (89 cases) (GSM≥40). The stenosis of the lumen in the low GSM group was more severe (the area stenosis rate was 41.32%±21.37% vs. 29.79%±17.16%, P < 0.05). The nor-malized wall index (NWI) of plaque in low GSM group was significantly higher than that in high GSM group (0.61 ±0.14 vs. 0.52±0.12, P < 0.01). A total of 77 patients, including 51 males and 26 females, aged (64.96±9.58) years, were enrolled to observe the statin effects on carotid plaque. They were divided into statin group (n=56) and non-statin group (n=21) according to whether taking statins or not. At the baseline and 3-month follow-up, there were no significant differences in carotid plaque volume, area, degree of luminal stenosis and GSM between the two groups (P>0.05). At the end of the 2-year follow-up, GSM increased in the statin group [median 10.00 (2.00, 28.00)] but decreased in the non-statin group [median －7.00 (－11.00, 5.50)], with a statistically significant difference between the two groups (P < 0.01). There was no significant increase in carotid plaque volume in the statin group, while there was a slight increase in the non-statin group, but there was no significant difference between the two groups [median increase in plaque volume was 0.00 (－30.00, 40.00) mm(3) in the statin group and 30.00 (10.00, 70.00) mm(3) in the non-statin group, P>0.05]. CONCLUSION: The VPQ technology of 3DUS can be used to evaluate carotid atherosclerotic plaques. Patients with low GSM (GSM < 40) have more severe vascular stenosis and higher normalized wall index. VPQ technology can also be used to observe the effect of statins on carotid plaque, the GSM of plaques increase in patients who are taking moderate-intensity statin treatment for two years.

Background Nearly 30% of ischemic strokes are attributed to atrial fibrillation (AF) related cardiac thromboembolism. This subset of strokes are associated with higher recurrence rate, morbidity and mortality. As a result, current recommendation suggests a cardiac monitoring of variable intensity and duration to search for unknown AF after a stroke so that optimal secondary prevention could be administered. Unfortunately, it is reported that 24h Holter ECG monitoring for underlying AF is completed routinely in only a minority of stroke centers, making a huge gap between AF detection rate in clinical practice and estimated actual data (2–3% vs 23–30%). So, it is obvious that paroxysmal AF remains undetected in a significant proportion of patients after a stroke and an early and effective identification approach of cardiac disturbances is needed. Purpose We aim to develop an innovative end-to-end artificial intelligence model to rapidly search for atrial fibrillation in post ischemic stroke patients using MRI imaging data. Methods 489 patients diagnosed with ischemic stroke, 174 of which had a prior known history of AF or new AF detected by intensive ECG monitoring poststroke, from January 2018 to October 2021 were enrolled in this study. The MRI images obtained after their admission in the stroke unit were meticulously evaluated and acute ischemic stroke lesions on DWI sequences were segmented and confirmed by two senior neuroradiologists independently. These processed images were randomly split into training (n=315) and testing set (n=174) for the implementation and validation of our AI screening model. And the algorithm was based on the combination of radiomic features and semantic features extracted from convolutional neural network (CNN). The model performance was evaluated by accuracy, recall, precision, F-Measure and AUC. Also, heatmaps which indicate the attention mechanism of the model were generated for interpreting underlying patterns. Results The AUC of our model (COM) reached 0.8 (Figure 1A). Also, the algorithm yielded values for the accuracy, recall, precision and F-Measure of 70%, 92.5%, 63.8% and 75.5%, respectively, which showed satisfactory classification results. As to the interpretability of the AI model, we found that more “attention” was paid to the main lesions (Figure 1B) and radiomic features which indicated the minimum gray level intensity and the sphericity of the lesions (Figure 1C, D) were crucial to the classifier. Conclusions Our work revealed a potential correlation between brain ischemic lesion pattern on DWI images and underlying etiology of AF. Moreover, the AI model we developed may serve as a rapid screening tool for AF in clinical practice of stroke units. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China