Landscape of global urban environmental resistome and its association with local socioeconomic and medical status.

Antimicrobial resistance (AMR) poses a critical threat to global health and development, with environmental factors-particularly in urban areas-contributing significantly to the spread of antibiotic resistance genes (ARGs). However, most research to date has been conducted at a local level, leaving significant gaps in our understanding of the global status of antibiotic resistance in urban environments. To address this issue, we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples, which were collected by the MetaSUB International Consortium involving diverse urban environments in 60 cities of 27 countries, utilizing a deep-learning based methodology. Our findings demonstrated the strong geographical specificity of urban environmental resistome, and their correlation with various local socioeconomic and medical conditions. We also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters (BGCs) across different countries, and discovered that the urban environment represents a rich source of novel antibiotics. Our study provides a comprehensive overview of the global urban environmental resistome, and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis.

Niche differentiation in microbial communities with stable genomic traits over time in engineered systems.

Microbial communities in full-scale engineered systems undergo dynamic compositional changes. However, mechanisms governing assembly of such microbes and succession of their functioning and genomic traits under various environmental conditions are unclear. In this study, we used the activated sludge and anaerobic treatment systems of four full-scale industrial wastewater treatment plants as models to investigate the niches of microbes in communities and the temporal succession patterns of community compositions. High-quality representative metagenome-assembled genomes revealed that taxonomic, functional, and trait-based compositions were strongly shaped by environmental selection, with replacement processes primarily driving variations in taxonomic and functional compositions. Plant-specific indicators were associated with system environmental conditions and exhibited strong determinism and trajectory directionality over time. The partitioning of microbes in a co-abundance network according to groups of plant-specific indicators, together with significant between-group differences in genomic traits, indicated the occurrence of niche differentiation. The indicators of the treatment plant with rich nutrient input and high substrate removal efficiency exhibited a faster predicted growth rate, lower guanine-cytosine content, smaller genome size, and higher codon usage bias than the indicators of the other plants. In individual plants, taxonomic composition displayed a more rapid temporal succession than functional and trait-based compositions. The succession of taxonomic, functional, and trait-based compositions was correlated with the kinetics of treatment processes in the activated sludge systems. This study provides insights into ecological niches of microbes in engineered systems and succession patterns of their functions and traits, which will aid microbial community management to improve treatment performance.

The Association of Metabolic Risk Factors with Advanced Adenomas in Hispanic Patients.

BACKGROUND: Obesity and metabolic syndrome (MetS) have been implicated as rising risk factors for the development of colorectal cancers. A rapid increase in the prevalence of obesity and severe obesity among Hispanic patients in the United States may present substantially increased risk for advanced colorectal neoplasia in this population. Currently, there is very little research in this area. AIMS: We sought to identify metabolic risk factors for advanced adenomas (AA) in Hispanic Americans. METHODS: We retrospectively reviewed data from the Los Angeles General (LAG) Medical Center of asymptomatic Hispanic patients above 45 years of age who underwent their first colonoscopies following a positive screening FBT. Patient demographics, metabolic characteristics, as well as colon polyp size and histology were recorded. Polyps were classified as adenomas or AA (including both high-risk adenomas and high-risk serrated polyps). Relative risk for AA was assessed by multivariate logistical regression analyses. RESULTS: Of the 672 patients in our study, 41.4% were male, 67% had adenomas, and 16% had AA. The mean BMI was 31.2 kg/m2. The mean HDL-C was 49.5 mg/dL (1.28 mmol/L) and the mean triglyceride level was 151 mg/dL. 44.6% had diabetes and 64.1% had hypertension. When comparing patients with AA to patients with no adenoma, male sex, BMI > 34.9 kg/m2, and elevated fasting triglyceride levels were associated with an increased risk of AA. FIB-4 ≥1.45 was also associated with an increased risk of AA in males. There was no significant difference in the risk of AA with diabetes, hypertension, FIB-4 score, LDL-C level, and HDL-C level. CONCLUSIONS: Hispanic patients with a positive FBT were observed to have a high incidence of AA. Class II obesity (BMI ≥ 35 kg/m2), elevated triglyceride levels were identified as risk factors among males in our study. Early interventions to address these modifiable risk factors in at-risk populations, such as multi-disciplinary weight management programs for the treatment of obesity and related co-morbidities, could potentially lead to risk reduction and CRC prevention.

The Effect of Coupling Agents and Graphene on the Mechanical Properties of Film-Based Post-Consumer Recycled Plastic.

This study aims to improve the mechanical properties of post-consumer recycled (PCR) plastic composed primarily of polypropylene (PP) and polyethylene (PE), which generally exhibit poor miscibility, by applying coupling agents and graphene. Here, we compare a commercially available coupling agent with a directly synthesized maleic anhydride (MA) coupling agent. When applied to a 5:5 blend of recycled PP and PE, an optimum tensile strength was achieved at a 3 wt% coupling agent concentration, with the MA coupling agent outperforming the commercial one. Characterization through Fourier transform infrared spectroscopy (FT-IR) and thermogravimetry analysis (TGA) revealed a PP:PE ratio of approximately 3:7 in the PCR plastics, with 4.86% heterogeneous materials present. Applying 3 wt% of the commercial and MA coupling agents to the PCR plastics resulted in a significant 53.9% increase in the tensile strength, reaching 11.25 MPa, and a remarkable 421.54% increase in the melt flow index (MFI), reaching 25.66 g/10 min. Furthermore, incorporating 5 wt% graphene led to a notable 64.84% increase in the tensile strength. In addition, the application of MA coupling agents and graphene improved the thermal stability of the PCR plastics. These findings show significant promise for addressing environmental concerns associated with plastic waste by facilitating the recycling of PCR plastics into new products. The utilization of coupling agents and graphene offers a viable approach to enhance the mechanical properties of PCR plastics, paving the way for sustainable and environmentally friendly solutions.

Surgically Induced Scleritis Associated With Suture Hypersensitivity Following Strabismus Surgery.

A 67-year-old woman with history of mild suture hyper-sensitivity presented with localized scleritis after strabismus surgery. After infection was ruled out, the patient was prescribed topical and systemic non-steroidal anti-inflammatory drugs and systemic steroids, which led to full clinical resolution. [J Pediatr Ophthalmol Strabismus. 2024;61(1):e4-e6.].

Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders.

Glycogen synthase 1 (GYS1), the rate-limiting enzyme in muscle glycogen synthesis, plays a central role in energy homeostasis and has been proposed as a therapeutic target in multiple glycogen storage diseases. Despite decades of investigation, there are no known potent, selective small-molecule inhibitors of this enzyme. Here, we report the preclinical characterization of MZ-101, a small molecule that potently inhibits GYS1 in vitro and in vivo without inhibiting GYS2, a related isoform essential for synthesizing liver glycogen. Chronic treatment with MZ-101 depleted muscle glycogen and was well tolerated in mice. Pompe disease, a glycogen storage disease caused by mutations in acid α glucosidase (GAA), results in pathological accumulation of glycogen and consequent autophagolysosomal abnormalities, metabolic dysregulation, and muscle atrophy. Enzyme replacement therapy (ERT) with recombinant GAA is the only approved treatment for Pompe disease, but it requires frequent infusions, and efficacy is limited by suboptimal skeletal muscle distribution. In a mouse model of Pompe disease, chronic oral administration of MZ-101 alone reduced glycogen buildup in skeletal muscle with comparable efficacy to ERT. In addition, treatment with MZ-101 in combination with ERT had an additive effect and could normalize muscle glycogen concentrations. Biochemical, metabolomic, and transcriptomic analyses of muscle tissue demonstrated that lowering of glycogen concentrations with MZ-101, alone or in combination with ERT, corrected the cellular pathology in this mouse model. These data suggest that substrate reduction therapy with GYS1 inhibition may be a promising therapeutic approach for Pompe disease and other glycogen storage diseases.

Total organic carbon measurements reveal major gaps in petrochemical emissions reporting.

Anthropogenic organic carbon emissions reporting has been largely limited to subsets of chemically speciated volatile organic compounds. However, new aircraft-based measurements revealed total gas-phase organic carbon emissions that exceed oil sands industry-reported values by 1900% to over 6300%, the bulk of which was due to unaccounted-for intermediate-volatility and semivolatile organic compounds. Measured facility-wide emissions represented approximately 1% of extracted petroleum, resulting in total organic carbon emissions equivalent to that from all other sources across Canada combined. These real-world observations demonstrate total organic carbon measurements as a means of detecting unknown or underreported carbon emissions regardless of chemical features. Because reporting gaps may include hazardous, reactive, or secondary air pollutants, fully constraining the impact of anthropogenic emissions necessitates routine, comprehensive total organic carbon monitoring as an inherent check on mass closure.

Safety of the JAK and TNF inhibitors in rheumatoid arthritis: real world data from the Hong Kong Biologics Registry.

OBJECTIVES: To compare the incidence of major adverse cardiovascular events (MACEs), cancer and infective complications in RA patients using Janus kinase (JAKis) and TNF (TNFis) inhibitors. METHOD: A retrospective analysis of data from the Hong Kong Biologics Registry 2008-2021 was performed. RA patients who had ever used JAKis or TNFis were included. The incidence of MACEs, cancer and infections were compared between the two groups, with adjustment for confounding factors. RESULTS: A total of 2471 courses of JAKis (n = 551) and TNFis (n = 1920) were used in 1732 RA patients (83.7% women, age 53.8 [12.5] years; follow-up 6431 patient-years). JAKi users had significantly older age, more atherosclerotic risk factors and higher frequency of past malignancies. A total of 15 and 40 MACEs developed in the JAKi and TNFi users, respectively (incidence 1.34 vs 0.75 per 100 patient-years; P = 0.22). There was no significant difference in the incidence of cancers between the two groups (0.81 [JAKi] vs 0.85 [TNFi] per 100 patient-years; P = 0.25). The adjusted hazard ratios of MACE and cancer in the JAKi users were 1.36 (95% CI: 0.62, 2.96) (P = 0.44) and 0.87 (95% CI: 0.39, 1.95) (P = 0.74), respectively. Rates of infections were significantly higher in the JAKi than TNFi users (16.3 vs 9.9 per 100 patient-years; P = 0.02), particularly herpes zoster (3.49 vs 0.94 per 100 patient-years; P < 0.001). CONCLUSIONS: In a real-life setting, there is no increase in MACEs or cancers in users of JAKis compared with TNFis. However, the incidence of non-serious infections, including herpes zoster, was increased in users of JAKis.

Metagenomics-Based Microbial Ecological Community Threshold and Indicators of Anthropogenic Disturbances in Estuarine Sediments.

Assessing the impacts of cumulative anthropogenic disturbances on estuarine ecosystem health is challenging. Using spatially distributed sediments from the Pearl River Estuary (PRE) in southern China, which are significantly influenced by anthropogenic activities, we demonstrated that metagenomics-based surveillance of benthic microbial communities is a robust approach to assess anthropogenic impacts on estuarine benthic ecosystems. Correlational and threshold analyses between microbial compositions and environmental conditions indicated that anthropogenic disturbances in the PRE sediments drove the taxonomic and functional variations in the benthic microbial communities. An ecological community threshold of anthropogenic disturbances was identified, which delineated the PRE sediments into two groups (H and L) with distinct taxa and functional traits. Group H, located nearshore and subjected to a higher level of anthropogenic disturbances, was enriched with pollutant degraders, putative human pathogens, fecal pollution indicators, and functional traits related to stress tolerance. In contrast, Group L, located offshore and subjected to a lower level of anthropogenic disturbances, was enriched with halotolerant and oligotrophic taxa and functional traits related to growth and resource acquisition. The machine learning random forest model identified a number of taxonomic and functional indicators that could differentiate PRE sediments between Groups H and L. The identified ecological community threshold and microbial indicators highlight the utility of metagenomics-based microbial surveillance in assessing the adverse impacts of anthropogenic disturbances in estuarine sediments, which can assist environmental management to better protect ecosystem health.

Clinical heterogeneity and prognostic factors of anti-synthetase syndrome: a multi-centered retrospective cohort study.

OBJECTIVE: Anti-synthetase syndrome (ASyS) patients have heterogeneous clinical manifestations with different initial presentations, complications, and outcomes. This study aimed to assess the clinical characteristics and complications in patients with ASyS, and to identify factors that were associated with the survival of ASyS patients. METHODS: This was a retrospective multicentre longitudinal study. Patients fulfilling either the Connor's criteria or Solomon's criteria for ASyS were recruited. Electronic health records were reviewed until October 2022. Multivariate Cox-regression analysis was used to determine the independent prognostic factors. Auto-antibodies were checked by commercial immunoassays. RESULTS: A total of 205 patients (anti-Jo-1 49.3%, anti-PL-7 19.0%, anti-EJ 11.2%, anti-PL-12 10.2% and anti-OJ 3.4%) were included. The median follow-up time was 4 years. The time from symptoms onset to diagnosis was significantly longer for non-anti-Jo1 patients (median 5 vs 3 months). Common initial presentations included myositis (56.1%), arthritis (54.6%), and interstitial lung disease (ILD) (54.1%). Patients with anti-Jo-1 had significantly higher muscle enzyme levels and more arthritis. All patients with anti-EJ would develop ILD on follow-up and malignancy was noted in 28.6% of the anti-OJ positive patients. 15.6% of the patients died and pulmonary diseases (ILD or pneumonia) were the major causes. Age at diagnosis, malignancy and rapidly progressive-ILD were independently associated with mortality, while joint manifestation was a protective factor. CONCLUSION: In view of the heterogeneity of clinical presentation of ASyS, high index of suspicion and early checking of specific autoantibodies might help prompt diagnosis of ASyS and detection of related complications.

Recyclability of Post-Consumer Polystyrene at Pilot Scale: Comparison of Mechanical and Solvent-Based Recycling Approaches.

Solvent-based and mechanical recycling technology approaches were compared with respect to each process's decontamination efficiency. Herein, post-consumer polystyrene (PS) feedstock was recycled by both technologies, yielding recycled PS resins (rPS). The process feedstock was subjected to four recycling cycles in succession to assess the technology perennity. The physico-chemical and mechanical properties of the rPS were then evaluated to discern the advantages and drawbacks of each recycling approach. The molecular weight of the mechanically recycled resin was found to decrease by 30% over the reprocessing cycles. In contrast, the solvent-base recycling technology yielded a similar molecular weight regarding the feedstock. This consistency in the rPS product is critical for consumer applications. Further qualitative and quantitative analyses on residual organic compounds and inorganic and particulate contaminants were investigated. It was found that the solvent-based technology is very efficient for purifying deeply contaminated feedstock in comparison to mechanical recycling, which is limited to well-cleaned and niche feedstocks.

Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes.

Pathological placental inflammation increases the risk for several adult disorders, but these mediators are also expressed under homeostatic conditions, where their contribution to adult health outcomes is unknown. Here we define an inflammation-related expression signature, primarily expressed in Hofbauer cells of the term placenta and use expression quantitative trait loci to create a polygenic score (PGS) predictive of its expression. Using this PGS in the UK Biobank we conduct a phenome-wide association study, followed by Mendelian randomization and identify protective, sex-dependent effects of the placental module on cardiovascular and depressive outcomes. Genes differentially regulated by intra-amniotic infection and preterm birth are over-represented within the module. We also identify aspirin as a putative modulator of this inflammation-related signature. Our data support a model where disruption of placental Hofbauer cell function, due to preterm birth or prenatal infection, contributes to the increased risk of depression and cardiovascular disease observed in these individuals.

Acute macular infarctions in pediatric patients with hemoglobin SS disease.

Purpose: To report two cases of symptomatic posterior pole arterial occlusions in patients with hemoglobin SS disease. Observations: Two teenage patients with hemoglobin SS disease presented with visual distortions, and on dilated fundus examination and testing, they were found to have arterial occlusions involving the posterior pole. The patients were evaluated for stroke with head imaging and received exchange transfusion by hematology. Conclusions and Importance: This case series reports the unusual findings of arterial occlusions in the posterior pole resulting in areas of retinal whitening and ischemia in patients with HbSS. While sickle cell retinopathy is typically considered a peripheral retinal disease, these findings underscore the importance of vigilance when examining patients with sickle cell disease.

Signatures of Cooper pair dynamics and quantum-critical superconductivity in tunable carrier bands.

Different superconducting pairing mechanisms are markedly distinct in the underlying Cooper pair kinematics. Quantum-critical soft modes drive pairing interactions in which the pair scattering processes are highly collinear and can be classified into two categories: forward scattering and backscattering. Conversely, in conventional phonon mechanisms, Cooper pair scattering is of a generic noncollinear character. In this study, we present a method to discern the kinematic type by observing the evolution of superconductivity while adjusting the Fermi surface geometry. To demonstrate our approach, we utilize the recently reported phase diagrams of untwisted graphene multilayers. Our analysis connects the emergence of superconductivity at "ghost crossings" of Fermi surfaces in distinct valleys to the pair kinematics of a backscattering type. Together with the observed nonmonotonic behavior of superconductivity near its onset (sharp rise followed by a drop), it lends strong support to a particular quantum-critical superconductivity scenario in which pairing is driven by intervalley coherence fluctuations. These findings offer direct insights into the genesis of pairing in these systems, providing compelling evidence for the electron-electron interactions driving superconductivity. More broadly, our work highlights the potential of tuning bands via ghost crossings as a promising means of boosting superconductivity.

metaSpectraST: an unsupervised and database-independent analysis workflow for metaproteomic MS/MS data using spectrum clustering.

BACKGROUND: The high diversity and complexity of the microbial community make it a formidable challenge to identify and quantify the large number of proteins expressed in the community. Conventional metaproteomics approaches largely rely on accurate identification of the MS/MS spectra to their corresponding short peptides in the digested samples, followed by protein inference and subsequent taxonomic and functional analysis of the detected proteins. These approaches are dependent on the availability of protein sequence databases derived either from sample-specific metagenomic data or from public repositories. Due to the incompleteness and imperfections of these protein sequence databases, and the preponderance of homologous proteins expressed by different bacterial species in the community, this computational process of peptide identification and protein inference is challenging and error-prone, which hinders the comparison of metaproteomes across multiple samples. RESULTS: We developed metaSpectraST, an unsupervised and database-independent metaproteomics workflow, which quantitatively profiles and compares metaproteomics samples by clustering experimentally observed MS/MS spectra based on their spectral similarity. We applied metaSpectraST to fecal samples collected from littermates of two different mother mice right after weaning. Quantitative proteome profiles of the microbial communities of different mice were obtained without any peptide-spectrum identification and used to evaluate the overall similarity between samples and highlight any differentiating markers. Compared to the conventional database-dependent metaproteomics analysis, metaSpectraST is more successful in classifying the samples and detecting the subtle microbiome changes of mouse gut microbiomes post-weaning. metaSpectraST could also be used as a tool to select the suitable biological replicates from samples with wide inter-individual variation. CONCLUSIONS: metaSpectraST enables rapid profiling of metaproteomic samples quantitatively, without the need for constructing the protein sequence database or identification of the MS/MS spectra. It maximally preserves information contained in the experimental MS/MS spectra by clustering all of them first and thus is able to better profile the complex microbial communities and highlight their functional changes, as compared with conventional approaches. tag the videobyte in this section as ESM4 Video Abstract.

Ubiquitous Superconducting Diode Effect in Superconductor Thin Films.

The macroscopic coherence in superconductors supports dissipationless supercurrents that could play a central role in emerging quantum technologies. Accomplishing unequal supercurrents in the forward and backward directions would enable unprecedented functionalities. This nonreciprocity of critical supercurrents is called the superconducting (SC) diode effect. We demonstrate the strong SC diode effect in conventional SC thin films, such as niobium and vanadium, employing external magnetic fields as small as 1 Oe. Interfacing the SC layer with a ferromagnetic semiconductor EuS, we further accomplish the nonvolatile SC diode effect reaching a giant efficiency of 65%. By careful control experiments and theoretical modeling, we demonstrate that the critical supercurrent nonreciprocity in SC thin films could be easily accomplished with asymmetrical vortex edge and surface barriers and the universal Meissner screening current governing the critical currents. Our engineering of the SC diode effect in simple systems opens the door for novel technologies while revealing the ubiquity of the Meissner screening effect induced SC diode effect in superconducting films, and it should be eliminated with great care in the search for exotic superconducting states harboring finite-momentum Cooper pairing.

Updated trends in percutaneous renal arteriography among radiologists and other specialties.

PURPOSE: Prior studies have demonstrated an overall decline in percutaneous renal artery angioplasty with and without stenting from 1988 to 2009. We evaluated the recent utilization trends in percutaneous renal arteriography (PTRA) among radiologists and non-radiologist providers from 2010 to 2018. METHODS: Data from the 2010-2018 nationwide Medicare Part B fee-for-service database were used to tabulate case volumes for PTRA. Annual utilization rates per 10,000 Medicare beneficiaries were calculated and aggregated based on physician specialty: radiologists, cardiologists, vascular surgeons, general surgeons, or others. RESULTS: From 2010 to 2018, the overall utilization rate of PTRA markedly declined (-72% change; from 15.5 to 4.3 cases per 10,000 Medicare beneficiaries). Proportionally, the cardiologist share of PTRA saw the greatest decline, falling from 74% market share in 2010 (11.4/15.5 cases) to only 36% market share in 2018 (1.6/4.3 cases). The market share of PTRA performed by radiologists grew from 12% market share in 2010 (1.9/15.5 cases) to 28% in 2018 (1.2/4.3 cases); despite this, the absolute number of PTRA performed by radiologists saw a smaller decline over this period (-34%; 1.9 to 1.2 cases). CONCLUSION: The total utilization rates of PTRA in the Medicare population has continued to decline from 2010 to 2018, likely due to clinical trials suggesting limited efficacy of angioplasty and stenting in the treatment of renovascular hypertension and other factors such as declining reimbursement. The overall and per-specialty rates continue to decline, reflecting an overarching trend away from procedural management of renovascular hypertension.