mobileOG-db: a Manually Curated Database of Protein Families Mediating the Life Cycle of Bacterial Mobile Genetic Elements.

Bacterial mobile genetic elements (MGEs) encode functional modules that perform both core and accessory functions for the element, the latter of which are often only transiently associated with the element. The presence of these accessory genes, which are often close homologs to primarily immobile genes, incur high rates of false positives and, therefore, limits the usability of these databases for MGE annotation. To overcome this limitation, we analyzed 10,776,849 protein sequences derived from eight MGE databases to compile a comprehensive set of 6,140 manually curated protein families that are linked to the "life cycle" (integration/excision, replication/recombination/repair, transfer, stability/transfer/defense, and phage-specific processes) of plasmids, phages, integrative, transposable, and conjugative elements. We overlay experimental information where available to create a tiered annotation scheme of high-quality annotations and annotations inferred exclusively through bioinformatic evidence. We additionally provide an MGE-class label for each entry (e.g., plasmid or integrative element), and assign to each entry a major and minor category. The resulting database, mobileOG-db (for mobile orthologous groups), comprises over 700,000 deduplicated sequences encompassing five major mobileOG categories and more than 50 minor categories, providing a structured language and interpretable basis for an array of MGE-centered analyses. mobileOG-db can be accessed at mobileogdb.flsi.cloud.vt.edu/, where users can select, refine, and analyze custom subsets of the dynamic mobilome. IMPORTANCE The analysis of bacterial mobile genetic elements (MGEs) in genomic data is a critical step toward profiling the root causes of antibiotic resistance, phenotypic or metabolic diversity, and the evolution of bacterial genera. Existing methods for MGE annotation pose high barriers of biological and computational expertise to properly harness. To bridge this gap, we systematically analyzed 10,776,849 proteins derived from eight databases of MGEs to identify 6,140 MGE protein families that can serve as candidate hallmarks, i.e., proteins that can be used as "signatures" of MGEs to aid annotation. The resulting resource, mobileOG-db, provides a multilevel classification scheme that encompasses plasmid, phage, integrative, and transposable element protein families categorized into five major mobileOG categories and more than 50 minor categories. mobileOG-db thus provides a rich resource for simple and intuitive element annotation that can be integrated seamlessly into existing MGE detection pipelines and colocalization analyses.

Demonstrating a Comprehensive Wastewater-Based Surveillance Approach That Differentiates Globally Sourced Resistomes.

Wastewater-based surveillance (WBS) for disease monitoring is highly promising but requires consistent methodologies that incorporate predetermined objectives, targets, and metrics. Herein, we describe a comprehensive metagenomics-based approach for global surveillance of antibiotic resistance in sewage that enables assessment of 1) which antibiotic resistance genes (ARGs) are shared across regions/communities; 2) which ARGs are discriminatory; and 3) factors associated with overall trends in ARGs, such as antibiotic concentrations. Across an internationally sourced transect of sewage samples collected using a centralized, standardized protocol, ARG relative abundances (16S rRNA gene-normalized) were highest in Hong Kong and India and lowest in Sweden and Switzerland, reflecting national policy, measured antibiotic concentrations, and metal resistance genes. Asian versus European/US resistomes were distinct, with macrolide-lincosamide-streptogramin, phenicol, quinolone, and tetracycline versus multidrug resistance ARGs being discriminatory, respectively. Regional trends in measured antibiotic concentrations differed from trends expected from public sales data. This could reflect unaccounted uses, captured only by the WBS approach. If properly benchmarked, antibiotic WBS might complement public sales and consumption statistics in the future. The WBS approach defined herein demonstrates multisite comparability and sensitivity to local/regional factors.

AgroSeek: a system for computational analysis of environmental metagenomic data and associated metadata.

BACKGROUND: Metagenomics is gaining attention as a powerful tool for identifying how agricultural management practices influence human and animal health, especially in terms of potential to contribute to the spread of antibiotic resistance. However, the ability to compare the distribution and prevalence of antibiotic resistance genes (ARGs) across multiple studies and environments is currently impossible without a complete re-analysis of published datasets. This challenge must be addressed for metagenomics to realize its potential for helping guide effective policy and practice measures relevant to agricultural ecosystems, for example, identifying critical control points for mitigating the spread of antibiotic resistance. RESULTS: Here we introduce AgroSeek, a centralized web-based system that provides computational tools for analysis and comparison of metagenomic data sets tailored specifically to researchers and other users in the agricultural sector interested in tracking and mitigating the spread of ARGs. AgroSeek draws from rich, user-provided metagenomic data and metadata to facilitate analysis, comparison, and prediction in a user-friendly fashion. Further, AgroSeek draws from publicly-contributed data sets to provide a point of comparison and context for data analysis. To incorporate metadata into our analysis and comparison procedures, we provide flexible metadata templates, including user-customized metadata attributes to facilitate data sharing, while maintaining the metadata in a comparable fashion for the broader user community and to support large-scale comparative and predictive analysis. CONCLUSION: AgroSeek provides an easy-to-use tool for environmental metagenomic analysis and comparison, based on both gene annotations and associated metadata, with this initial demonstration focusing on control of antibiotic resistance in agricultural ecosystems. Agroseek creates a space for metagenomic data sharing and collaboration to assist policy makers, stakeholders, and the public in decision-making. AgroSeek is publicly-available at https://agroseek.cs.vt.edu/ .

Data Analytics for Environmental Science and Engineering Research.

The advent of new data acquisition and handling techniques has opened the door to alternative and more comprehensive approaches to environmental monitoring that will improve our capacity to understand and manage environmental systems. Researchers have recently begun using machine learning (ML) techniques to analyze complex environmental systems and their associated data. Herein, we provide an overview of data analytics frameworks suitable for various Environmental Science and Engineering (ESE) research applications. We present current applications of ML algorithms within the ESE domain using three representative case studies: (1) Metagenomic data analysis for characterizing and tracking antimicrobial resistance in the environment; (2) Nontarget analysis for environmental pollutant profiling; and (3) Detection of anomalies in continuous data generated by engineered water systems. We conclude by proposing a path to advance incorporation of data analytics approaches in ESE research and application.

Differential Drivers of Antimicrobial Resistance across the World.

Antimicrobial resistance (AMR) is one of the greatest threats faced by humankind. The development of resistance in clinical and hospital settings has been well documented ever since the initial discovery of penicillin and the subsequent introduction of sulfonamides as clinical antibiotics. In contrast, the environmental (i.e., community-acquired) dimensions of resistance dissemination have been only more recently delineated. The global spread of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) between air, water, soil, and food is now well documented, while the factors that affect ARB and ARG dissemination (e.g., water and air quality, antibiotic fluxes, urbanization, sanitation practices) in these and other environmental matrices are just now beginning to be more fully appreciated. In this Account, we discuss how the global perpetuation of resistance is dictated by highly interconnected socioeconomic risk factors and illustrate that development status should be more fully considered when developing global strategies to address AMR. We first differentiate low to middle income countries (LMICs) and high-income countries (HICs), then we summarize the modes of action of commercially available antibiotics, and then discuss the four primary mechanisms by which bacteria develop resistance to those antibiotics. Resistance is disseminated via both vertical gene transfer (VGT; parent to offspring) as well as by horizontal gene transfer (HGT; cell to cell transference of genetic material). A key challenge hindering attempts to control resistance dissemination is the presence of native, environmental bacteria that can harbor ARGs. Such environmental "resistomes" have potential to transfer resistance to pathogens via HGT. Of particular concern is the development of resistance to antibiotics of last-resort such as the cephalosporins, carbapenems, and polymyxins. We then illustrate how antibiotic use differs in LMICs relative to HICs in terms of the volumes of antibiotics used and their fate within local environments. Antibiotic use in HICs has remained flat over the past 15 years, while in LMICs use over the same period has increased substantially as a result of economic improvements and changes in diet. These use and fate differences impact local citizens and thus the local dissemination of AMR. Various physical, social, and economic circumstances within LMICs potentially favor AMR dissemination. We focus on three physical factors: changing population density, sanitation infrastructure, and solid-waste disposal. We show that high population densities in cities within LMICs that suffer from poor sanitation and solid-waste disposal can potentially impact the dissemination of resistance. In the final section, we discuss potential monitoring approaches to quantify the spread of resistance both within LMICs as well as in HICs. We posit that culture-based approaches, molecular approaches, and cutting-edge nanotechnology-based methods for monitoring ARB and ARGs should be considered both within HICs and, as appropriate, within LMICs.

Predictors of Disease Recurrence after Venoplasty and Stent Placement for May-Thurner Syndrome.

PURPOSE: To identify factors independently associated with disease recurrence after venoplasty and stent placement for May-Thurner syndrome (MTS). MATERIALS AND METHODS: Fifty-nine consecutive patients (age, 47 y ± 15; 93% female) were identified who had undergone endovascular stent placement for MTS. Patient charts were reviewed for demographic data, risk factors for venous thrombosis, comorbidities, and venous inflow or outflow at first follow-up (3 wk to 6 mo after treatment). Logistic regression was used to identify independent predictors of symptom recurrence or repeat intervention, and multivariate analysis of variance and receiver operator characteristic curve analysis were used to assess relationships between degrees of in-stent stenosis and other variables in the 73% of patients with available cross-sectional imaging. Median follow up was 20.7 months (interquartile range, 4.7-49.5 mo). RESULTS: All procedures were technically successful. Disease recurrence, defined as symptom recurrence following initial postprocedural resolution, was observed in 38% of patients. No preprocedural variable was found to be independently predictive of disease recurrence; however, poor venous inflow or outflow were both strongly associated with recurrent disease, with adjusted odds ratios and 95% confidence intervals of 38.02 (3.76-384.20; P = .002) and 7.00 (1.15-42.71; P = .04), respectively. Higher degrees of in-stent stenosis were also associated with symptom recurrence, with an area under the curve of 0.93 (P = .000002) and 39%-41% stenosis being 78%-83% sensitive and 88%-92% specific for symptom recurrence. CONCLUSIONS: These results suggest that cross-sectional imaging can help differentiate patients in whom closer follow-up may be warranted after venoplasty and stent placement for MTS and also guide counseling regarding prognosis.

Ag loaded B-doped-g C3N4 nanosheet with efficient properties for photocatalysis.

Three material engineering strategies in the form of doping (Boron-doping), nanostructuring (nanosheet (NS) formation) and decorating with plasmonic nanoparticles (loading with Ag metal), were integrated to improve the photocatalytic activity of graphitic carbon nitride (gC3N4). Concentrations of B-doping and Ag-loading were optimized to maximize the catalytic performance in the final nanocomposite of Ag-loaded B-doped gC3N4 NS. Combined effect of all three strategies successfully produced over 5 times higher rate towards degradation of organic dye pollutant, when compared to unmodified bulk gC3N4. Detailed characterization results revealed that incorporation of B in gC3N4 matrix reduces the band gap to increase the visible light absorption, while specific surface area is significantly enhanced upon formation of NS. Decoration of Ag nanoparticles (NPs) on B-doped gC3N4 NS assists in fast transfer of photogenerated electrons from gC3N4 to Ag NPs owing to the interfacial electric field across the junctions and thus reduces the recombination process. Investigations on individual strategies revealed that decoration of Ag NPs to induce better charge separation, is the most effective route for enhancing the photocatalytic activity.

Single-Center Retrospective Review of Radiofrequency Wire Recanalization of Refractory Central Venous Occlusions.

PURPOSE: To retrospectively review the effectiveness and safety of radiofrequency (RF) wire recanalization of refractory central venous occlusions (CVOs) and compare recurrent and nonrecurrent CVOs in terms of patient and occlusion characteristics. MATERIALS AND METHODS: Twenty CVOs were treated in 18 patients (age 40 y ± 13; 9 women) with 11 superior vena cava (SVC) or brachiocephalic vein occlusions (ie, supradiaphragmatic) and 9 inferior vena cava or iliac vein occlusions (ie, infradiaphragmatic). Indications included pain, edema, ulceration, and/or dialysis arteriovenous fistula dysfunction peripheral to the CVO(s). All patients had multiple venous thrombotic risk factors, including mechanical venous compression, endothelial injury, and/or coagulopathies. CVO traversal was first attempted with standard and advanced techniques before RF wire recanalization and followed up with computed tomographic venography and clinic visits approximately 1, 3, 6, and 12 months after treatment. RESULTS: Sixteen CVOs (80%) were successfully transversed and associated with symptom relief. One major complication occurred involving SVC perforation into the pericardial space. Primary CVO patency rate was 56% at a median follow-up of 14.1 months (interquartile range [IQR], 9.2-20.0 mo). Recurrent CVOs tended to be infradiaphragmatic (71% vs 12% for supradiaphragmatic; P = .02), longer (12.9 cm ± 10.0 vs 2.3 cm ± 1.3; P < .01), and associated with implanted venous stents, filters, or cardiac pacer/defibrillator leads (86% vs 22%; P = .01). Median time to restenosis/occlusion was 1.5 months (IQR, 1.1-6.1 mo). CONCLUSIONS: RF wire recanalization is a relatively effective and safe option for refractory CVOs. Patients with longer, infradiaphragmatic CVOs associated with indwelling devices may require closer follow-up for CVO recurrence.

Remote Terpyridine Integrated NHC-IrIII Luminophores as Potential Dual-Emissive Ratiometric O2 Probes.

A new class of bi-luminophoric dyad has been designed, consisting of an oxygen-sensitive phosphorescent NHC-IrIII center with a remotely integrated oxygen-insensitive fluorescent terpyridine unit. The new terpyridine flurophore-integrated NHC-IrIII molecule was demonstrated as a potential ratiometric O2 probe with built-in internal reference, exhibiting tunable dual-emissive features, as well as highly linear and reversible O2 -response behavior.

A combined paging alert and web-based instrument alters clinician behavior and shortens hospital length of stay in acute pancreatitis.

OBJECTIVES: There are many published clinical guidelines for acute pancreatitis (AP). Implementation of these recommendations is variable. We hypothesized that a clinical decision support (CDS) tool would change clinician behavior and shorten hospital length of stay (LOS). DESIGN/SETTING: Observational study, entitled, The AP Early Response (TAPER) Project. Tertiary center emergency department (ED) and hospital. PARTICIPANTS: Two consecutive samplings of patients having ICD-9 code (577.0) for AP were generated from the emergency department (ED) or hospital admissions. Diagnosis of AP was based on conventional Atlanta criteria. The Pre-TAPER-CDS-Tool group (5/30/06-6/22/07) had 110 patients presenting to the ED with AP per 976 ICD-9 (577.0) codes and the Post-TAPER-CDS-Tool group (5/30/06-6/22/07) had 113 per 907 ICD-9 codes (7/14/10-5/5/11). INTERVENTION: The TAPER-CDS-Tool, developed 12/2008-7/14/2010, is a combined early, automated paging-alert system, which text pages ED clinicians about a patient with AP and an intuitive web-based point-of-care instrument, consisting of seven early management recommendations. RESULTS: The pre- vs. post-TAPER-CDS-Tool groups had similar baseline characteristics. The post-TAPER-CDS-Tool group met two management goals more frequently than the pre-TAPER-CDS-Tool group: risk stratification (P<0.0001) and intravenous fluids >6L/1st 0-24 h (P=0.0003). Mean (s.d.) hospital LOS was significantly shorter in the post-TAPER-CDS-Tool group (4.6 (3.1) vs. 6.7 (7.0) days, P=0.0126). Multivariate analysis identified four independent variables for hospital LOS: the TAPER-CDS-Tool associated with shorter LOS (P=0.0049) and three variables associated with longer LOS: Japanese severity score (P=0.0361), persistent organ failure (P=0.0088), and local pancreatic complications (<0.0001). CONCLUSIONS: The TAPER-CDS-Tool is associated with changed clinician behavior and shortened hospital LOS, which has significant financial implications.

Asymmetric spermatic cord vessel enhancement on CT: a sign of epididymitis or testicular neoplasm.

PURPOSE: To determine whether asymmetric spermatic cord vessel enhancement (ASE) on contrast-enhanced computed tomography (CECT) indicates scrotal pathology. METHODS: Sixty-one male patients with scrotal symptoms who underwent both scrotal ultrasound (US) and CECT within 24 h were identified through a radiology information system. Twenty-eight emergency department patients who underwent CECT only for unrelated symptoms were included for comparison. Two blinded radiologists independently reviewed each CECT scan for qualitative ASE. These data were compared with US diagnoses, when present. A third blinded radiologist reviewed each CECT scan for quantitative ASE by measuring Hounsfield unit (HU) density ratios. McNemar, Kappa, Student's t test, and ANOVA were used for analysis. RESULTS: Eighty-nine total patients included 28 with CECT only and 61 with CECT and US, of which 41 had abnormal US: 15 acute epididymitis and/or orchitis, 7 testicular neoplasms, 11 varicoceles, and 8 with other pathologies. Twenty patients with normal US and 28 patients with CECT only served as control groups. Identification of ASE agreed with US diagnosis of epididymitis (and/or orchitis) or testicular neoplasm (reader 1: κ = 0.79, reader 2: κ = 0.75) with average 95.5% sensitivity and 88.8% specificity, and no significant difference between readers (p = 0.58). For epididymitis (and/or orchitis) or testicular neoplasm patients, the average ratio of spermatic cord HU density (ipsilateral:contralateral) was significantly different from other patients (4.01 vs. 1.26, p = 0.0025). CONCLUSION: ASE on CECT shows stronger correlation with epididymitis (and/or orchitis) and testicular neoplasm compared with other scrotal pathologies. If discovered on CECT, this should prompt further clinical and/or imaging workup.

EUS-Guided Cholecystoduodenostomy for a Poor Surgical Candidate With Chronic Octreotide-Associated Gallstones From Metastatic Neuroendocrine Tumor.

Chronic octreotide use has been associated with gallstone formation. Historically, cholecystectomy has been the defining treatment for those who have gallstone-related disease. For those who are poor surgical candidates, percutaneous and endoscopic approaches have been used. We describe the endoscopic management of a 74-year-old man with significant gallstone burden and associated sequelae because of chronic octreotide for metastatic neuroendocrine tumor through endoscopic ultrasound-guided cholecystoduodenostomy with gallstone extraction using lumen-apposing metal stents.

Computational analysis followed by in vitro studies to explore cytokines (TNF-α, IL-6 and IL-1ß) inhibition potential of the new natural molecule polonilignan.

Targeting pro-inflammatory cytokines and their production is found to be of therapeutic benefit for the regulation of inflammation in various chronic autoimmune diseases. Our continued efforts to discover small molecular-weight pro-inflammatory cytokine inhibitors resulted in identifying a novel natural lignan molecule named polonilignan, isolated from the culture broth extract of an endophytic fungus Penicillium polonicum. An in silico study (molecular docking, ADME predictions, binding free energy calculation and molecular dynamics simulation) of the polonilignan over the pro-inflammatory cytokines proteins TNF-α, IL-6 and IL-1ß was performed using Schrodinger LLC software to understand the binding interactions, drug-like properties, and stability of the ligand-protein complex. Further, in-vitro testing of inhibition of TNF-α, IL-6 and IL-1ß by polonilignan was carried out using ELISA and RT-PCR on LPS-induced RAW 264.7 cell lines along with the testing of nitrite production effect (Griess assay) and cytotoxicity (MTT) analysis. Under the computational study, polonilignan revealed good docking scores, binding interactions, and stability under MDS and desirable in silico ADME results over the proteins TNF-α, IL-1ß and IL-6. Poloniligan showed significant inhibition of IL-1ß, IL-6 and TNF-α with IC50 values of 2.01 µM, 6.59 µM and 42.10 µM, respectively. Also, it reduced the translocation of the NF-κB subunit p65 to the nucleus (confocal microscopy). The mRNA expression levels of pro-inflammatory markers IL-1ß, TNF-α and IL-6 levels were lowered significantly (p < .001) by the compound, and the diminution was higher with IL-1ß. Further, the lignan was non-cytotoxic and effective in attenuating nitrite release (IC50 48.56 µM). Thus, polonilignan has been identified as a new pan-cytokine and NO inhibitor, it is recommended to optimise a method for the synthesis of this small molecular weight lignan and explore its pharmacokinetic characteristics, toxicity and therapeutic effect under various chronic inflammatory disease models.

Designing Bifunctional Electrocatalysts Based on Complex Cobalt-Sulfo-Boride Compound for High-Current-Density Alkaline Water Electrolysis.

In the quest to harness renewable energy sources for green hydrogen production, alkaline water electrolysis has emerged as a pivotal technology. Enhancing the reaction rates of overall water electrolysis and streamlining electrode manufacturing necessitate the development of bifunctional and cost-effective electrocatalysts. With this aim, a complex compound electrocatalyst in the form of cobalt-sulfo-boride (Co-S-B) was fabricated using a simple chemical reduction method and tested for overall alkaline water electrolysis. A nanocrystalline form of Co-S-B displayed a combination of porous and nanoflake-like morphology with a high surface area. In comparison to Co-B and Co-S, the Co-S-B electrocatalyst exhibits better bifunctional characteristics requiring lower overpotentials of 144 mV for hydrogen evolution reaction and 280 mV for oxygen evolution reaction to achieve 10 mA/cm2 in an alkaline electrolyte. The improved Co-S-B performance is attributed to the synergistic effect of sulfur and boron on cobalt, which was experimentally confirmed through various material characterization tools. Tafel slope, electrochemical surface area, turnover frequency, and charge transfer resistance further endorse the active nature of the Co-S-B electrocatalyst. The robustness of the developed electrocatalyst was validated through a 50 h chronoamperometric stability test, along with a recyclability test involving 10,000 cycles of linear sweep voltammetry. Furthermore, Co-S-B was tested in an alkaline zero-gap water electrolyzer, reaching 1 A/cm2 at 2.06 V and 60 °C. The significant activity and stability demonstrated by the cobalt-sulfo-boride compound render it as a promising and cost-effective electrode material for commercial alkaline water electrolyzers.

Bifunctional Amorphous Transition-Metal Phospho-Boride Electrocatalysts for Selective Alkaline Seawater Splitting at a Current Density of 2A cm-2.

Hydrogen production by direct seawater electrolysis is an alternative technology to conventional freshwater electrolysis, mainly owing to the vast abundance of seawater reserves on earth. However, the lack of robust, active, and selective electrocatalysts that can withstand the harsh and corrosive saline conditions of seawater greatly hinders its industrial viability. Herein, a series of amorphous transition-metal phospho-borides, namely Co-P-B, Ni-P-B, and Fe-P-B are prepared by simple chemical reduction method and screened for overall alkaline seawater electrolysis. Co-P-B is found to be the best of the lot, requiring low overpotentials of ≈270 mV for hydrogen evolution reaction (HER), ≈410 mV for oxygen evolution reaction (OER), and an overall voltage of 2.50 V to reach a current density of 2 A cm-2 in highly alkaline natural seawater. Furthermore, the optimized electrocatalyst shows formidable stability after 10,000 cycles and 30 h of chronoamperometric measurements in alkaline natural seawater without any chlorine evolution, even at higher current densities. A detailed understanding of not only HER and OER but also chlorine evolution reaction (ClER) on the Co-P-B surface is obtained by computational analysis, which also sheds light on the selectivity and stability of the catalyst at high current densities.

Molecular assessment of intratumoral immune cell subsets and potential mechanisms of resistance to odronextamab, a CD20×CD3 bispecific antibody, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

BACKGROUND: Patients with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) have a significant need for effective treatment options. Odronextamab is an Fc-silenced, human, CD20×CD3 bispecific antibody that targets CD20-expressing cells via T-cell-mediated cytotoxicity independent of T-cell/major histocompatibility complex interaction. Phase I results in patients with R/R B-NHL demonstrated that odronextamab monotherapy could achieve deep and durable responses with a generally manageable safety profile (ELM-1; NCT02290951). As part of a biomarker analysis of the same study, we investigated potential biomarkers and mechanisms of resistance to odronextamab. METHODS: Patients with R/R B-NHL enrolled in ELM-1 received one time per week doses of intravenous odronextamab for 4×21 day cycles, then doses every 2 weeks thereafter. Patient tumor biopsies were obtained at baseline, on-treatment, and at progression. Immune cell markers were analyzed by immunohistochemistry, flow cytometry, single-cell RNA sequencing, and whole genome sequencing. RESULTS: Baseline tumor biopsies showed that almost all patients had high proportions of B cells that expressed the CD20 target antigen, whereas expression of other B-cell surface antigens (CD19, CD22, CD79b) was more variable. Responses to odronextamab in patients with diffuse large B-cell lymphoma were not related to the relative level of baseline CD20 expression, cell of origin, or high-risk molecular subtype. A potential link was observed between greater tumor programmed cell death-ligand 1 expression and increased likelihood of response to odronextamab. Similarly, a trend was observed between clinical response and increased levels of CD8 T cells and regulatory T cells at baseline. We also identified an on-treatment pharmacodynamic shift in intratumoral immune cell subsets. Finally, loss of CD20 expression through inactivating gene mutations was identified as a potential mechanism of resistance in patients who were treated with odronextamab until progression, as highlighted in two detailed patient cases reported here. CONCLUSIONS: This biomarker analysis expands on clinical findings of odronextamab in patients with R/R B-NHL, providing verification of the suitability of CD20 as a therapeutic target, as well as evidence for potential mechanisms of action and resistance.

Hydrothermal topotactic epitaxy of SrTiO3 on Bi4Ti3O12 nanoplatelets: understanding the interplay of lattice mismatch and supersaturation.

The engineering of epitaxial, two-dimensional (2D) nano-heterostructures has stimulated great interest owing to an expectation of better functional properties (e.g., photocatalytic, piezoelectric). Hydrothermal topotactic epitaxy is one of the promising synthetic approaches for their preparation, particularly the formation of a highly ordered, epitaxial interface and possibilities for the preparation of anisotropic nanostructures of symmetrical materials. The present study highlights the key parameters when steering the alkaline, hydrothermal, topochemical conversion process from Bi4Ti3O12 nanoplatelets to the intermediate, epitaxial, SrTiO3/Bi4Ti3O12 nano-heterostructures and the final SrTiO3 nanoplatelets by balancing the lattice mismatch and the supersaturation. An atomic-scale examination revealed the formation of an ordered epitaxial SrTiO3/Bi4Ti3O12 interface with the presence of dislocations. The SrTiO3 grows in islands for a stoichiometric amount of Sr (Sr/Ti = 1) and the growth resembles a layer-by-layer mode for surplus Sr content (Sr/Ti ≥ 12). The latter enables SrTiO3 overgrowth of the Bi4Ti3O12 basal surface planes, protecting them against dissolution from the top and consequently ensuring the preservation of the platelet morphology during the entire transformation process, the kinetics of which is controlled by the base concentration. A developed understanding of this particular transformation provides the guiding principles and ideas for designing other defined or complex epitaxial heterostructures and structures under low-temperature hydrothermal conditions.

ARGem: a new metagenomics pipeline for antibiotic resistance genes: metadata, analysis, and visualization.

Antibiotic resistance is of crucial interest to both human and animal medicine. It has been recognized that increased environmental monitoring of antibiotic resistance is needed. Metagenomic DNA sequencing is becoming an attractive method to profile antibiotic resistance genes (ARGs), including a special focus on pathogens. A number of computational pipelines are available and under development to support environmental ARG monitoring; the pipeline we present here is promising for general adoption for the purpose of harmonized global monitoring. Specifically, ARGem is a user-friendly pipeline that provides full-service analysis, from the initial DNA short reads to the final visualization of results. The capture of extensive metadata is also facilitated to support comparability across projects and broader monitoring goals. The ARGem pipeline offers efficient analysis of a modest number of samples along with affordable computational components, though the throughput could be increased through cloud resources, based on the user's configuration. The pipeline components were carefully assessed and selected to satisfy tradeoffs, balancing efficiency and flexibility. It was essential to provide a step to perform short read assembly in a reasonable time frame to ensure accurate annotation of identified ARGs. Comprehensive ARG and mobile genetic element databases are included in ARGem for annotation support. ARGem further includes an expandable set of analysis tools that include statistical and network analysis and supports various useful visualization techniques, including Cytoscape visualization of co-occurrence and correlation networks. The performance and flexibility of the ARGem pipeline is demonstrated with analysis of aquatic metagenomes. The pipeline is freely available at https://github.com/xlxlxlx/ARGem.