High-resolution Screening Research Articles

Identification of Novel Iodinated Polyfluoroalkyl Ether Acids and Other Emerging PFAS in Soils Using a Nontargeted Molecular Network Approach.

Despite advancements in high-resolution screening techniques, the identification of novel perfluoroalkyl and polyfluoroalkyl substances (PFAS) remains challenging without prior structural information. In view of this, we proposed and implemented a new data-driven algorithm to calculate spectral similarity among PFAS, facilitating the generation of molecular networks to screen for unknown compounds. Using this approach, 81 PFAS across 12 distinct classes were identified in soil samples collected near an industrial park in Shandong Province, China, including the first reported occurrence of 12 iodine-substituted PFAS. Among them, the standards of four iodine-substituted polyfluorinated ether sulfonates (I-PFESA) were successfully synthesized, enabling structural confirmation and subsequent quantitative analysis. Although the median concentration of ∑I-PFESA (0.74 ng/g dw) in soil samples was lower than that of ∑H-PFESA (hydrogen-substituted, 61.96 ng/g dw) and ∑Cl-PFESA (chlorine-substituted, 2.98 ng/g dw), embryotoxicity assays in zebrafish revealed that 6:2 I-PFESA exhibited greater toxicity compared to 6:2 Cl-PFESA of the same chain length. This highlights the need for a closer examination of the toxic effects of I-PFESA. Notably, the proposed algorithm, based on novel PFAS spectral similarity, provides new perspectives on the environmental behavior and transformation of I-PFESA, although further investigation is required to elucidate the underlying mechanisms of their toxicity.

CRISPR-StAR enables high-resolution genetic screening in complex in vivo models.

Pooled genetic screening with CRISPR-Cas9 has enabled genome-wide, high-resolution mapping of genes to phenotypes, but assessing the effect of a given genetic perturbation requires evaluation of each single guide RNA (sgRNA) in hundreds of cells to counter stochastic genetic drift and obtain robust results. However, resolution is limited in complex, heterogeneous models, such as organoids or tumors transplanted into mice, because achieving sufficient representation requires impractical scaling. This is due to bottleneck effects and biological heterogeneity of cell populations. Here we introduce CRISPR-StAR, a screening method that uses internal controls generated by activating sgRNAs in only half the progeny of each cell subsequent to re-expansion of the cell clone. Our method overcomes both intrinsic and extrinsic heterogeneity as well as genetic drift in bottlenecks by generating clonal, single-cell-derived intrinsic controls. We use CRISPR-StAR to identify in-vivo-specific genetic dependencies in a genome-wide screen in mouse melanoma. Benchmarking against conventional screening demonstrates the improved data quality provided by this technology.

Evaluating the effectiveness of high-resolution anoscopy screening for anal cancer in HPV- and HIV-positive patients

Evaluating the effectiveness of high-resolution anoscopy screening for anal cancer in HPV- and HIV-positive patients

Structural characterization of degradation products of phenol red used as zero permeability marker in in-situ rat intestinal permeability studies by LCMS-IT-TOF

In this study, the quantitative determination of phenol red with using HPLC, the permeability marker widely used in gastrointestinal studies, and its stability in various apolar phase solvents were investigated. In addition, the mechanisms of degradation products obtained were tried to be elucidated by using the LCMS-IT-TOF device. The proposed HPLC method utilizes a Perkin Elmer C18, 5 μm, 250 mm × 4.6 mm i.d. column, a mobile phase consisting of phosphate buffer and methanol in the proportion of 50:50 (v/v) with apparent pH adjusted to 3.2 and detected at 430 nm using a photodiode array detector. The method exhibits linearity within the concentration range of 5–200 µg/mL, with a calculated R2 of 0.9981. In situ conditions, the recovery is in the range of 89.8–103.6 %. Furthermore, high-resolution mass studies were identified three degradation products that occur when phenol red was dissolved either ethanol or methanol medium. The method has a low cost of consumables and is very easy to apply to the procedure and analyze degradation products while easily applied to phenol red analysis in various mediums. High-resolution mass screening analysis confirmed the proposed structure of the degradation product. The validation and robustness studies were fulfilled to display the performance of the method in various analytical environments. The greenness and blueness evaluations of the developed method were also made in detail. The AGREE score of the method was calculated as 0.64, AGREEprep 0.68, MoGAPI 0.78, and BAGI scale score as 65.0. In short, the method is perfectly green, applicable, and practical. Finally, phenol red concentrations analyzed in samples obtained in in-situ animal studies were conducted to demonstrate the applicability of the developed method.

Identification of organic contaminants in water and related matrices using untargeted liquid chromatography high-resolution mass spectrometry screening with MS/MS libraries

Nontargeted and suspect screening with liquid chromatography-high resolution mass spectrometry (LC-HRMS) has become an indispensable tool for quality assessment in the aquatic environment – complementary to targeted analysis of organic (micro)contaminants. An LC-HRMS method is presented, suitable for the analysis of a wide variety of water related matrices: surface water, groundwater, wastewater, sediment and sludge, including extracts from passive samplers and on-site solid phase enrichment, while focusing on the data processing aspect of the method. A field study is included to demonstrate the practical application and versatility of the whole process. HRMS/MS data were recorded following LC separation in both (ESI) positive and negative ionization modes using data dependent as well as data independent acquisition. Two vendor (Agilent's Personal Compound Database and Library and from National Institute of Standards and Technology) and one open (MassBank/EU) tandem mass spectral libraries were utilized for the identification of compounds via mass spectral match. The development of a novel software tool for parsing, grouping and reduction of MS/MS features in data files converted to mascot generic format (MGF) helped to substantially decrease the amount of time and effort needed for MS library search. While applying the method, in the course of the entire field study, 18771 detections (from 870 individual compounds) in total were recorded in 275 samples, resulting in 68.3 identified compounds per sample, on average. Among the top ten most frequently detected contaminants across all samples and sample types were pharmaceutical compounds carbamazepine, 4-acetamidoantipyrine, 4-formylaminoantipyrine, tramadol, lamotrigine and phenazone and industrial contaminants toluene-2-sulfonamide, tolytriazole, tris(2-butoxyethyl) phosphate and benzotriazole. Exploratory data analysis methods and tools enabled us to discover organic pollutant occurrence patterns within the comprehensive sets of qualitative data collected from various projects between the years 2018–2023. The results may be used as valuable inputs for future water quality monitoring programs.

Multiplexed Microfluidic Platform for Parallel Bacterial Chemotaxis Assays.

The sensing of and response to ambient chemical gradients by microorganisms via chemotaxis regulates many microbial processes fundamental to ecosystem function, human health, and disease. Microfluidics has emerged as an indispensable tool for the study of microbial chemotaxis, enabling precise, robust, and reproducible control of spatiotemporal chemical conditions. Previous techniques include combining laminar flow patterning and stop-flow diffusion to produce quasi-steady chemical gradients to directly probe single-cell responses or loading micro-wells to entice and ensnare chemotactic bacteria in quasi-steady chemical conditions. Such microfluidic approaches exemplify a trade-off between high spatiotemporal resolution of cell behavior and high-throughput screening of concentration-specific chemotactic responses. However, both aspects are necessary to disentangle how a diverse range of chemical compounds and concentrations mediate microbial processes such as nutrient uptake, reproduction, and chemorepulsion from toxins. Here, we present a protocol for the multiplexed chemotaxis device (MCD), a parallelized microfluidic platform for efficient, high-throughput, and high-resolution chemotaxis screening of swimming microbes across a range of chemical concentrations. The first layer of the two-layer polydimethylsiloxane (PDMS) device comprises a serial dilution network designed to produce five logarithmically diluted chemostimulus concentrations plus a control from a single chemical solution input. Laminar flow in the second device layer brings a cell suspension and buffer solution into contact with the chemostimuli solutions in each of six separate chemotaxis assays, in which microbial responses are imaged simultaneously over time. The MCD is produced via standard photography and soft lithography techniques and provides robust,repeatable chemostimulus concentrations across each assay in the device. This microfluidic platform provides a chemotaxis assay that blends high-throughput screening approaches with single-cell resolution to achieve a more comprehensive understanding of chemotaxis-mediated microbial processes. Key features • Microchannel master molds are fabricated using photolithography techniques in a clean room with a mask aligner to fabricate multilevel feature heights. • The microfluidic device is fabricated from PDMS using standard soft lithography replica molding from the master molds. • The resulting microchannel requires a one-time calibration of the driving inlet pressures, after which devices from the same master molds have robust performance. • The microfluidic platform is optimized and tested for measuring chemotaxis of swimming prokaryotes.

Free radical mechanisms of ammonium sulfate as intensively used industrial materials on suppressing organic pollutants

Organic free radicals are critical intermediates for the generation and inhibition of organic pollutants during industrial processes. Clarifying the free radical mechanism of pollutant inhibition is significant for their efficient control. Ammonium sulfate is intensively used in industrial materials to suppress organic pollutants. In this study, organic free radical intermediate species in metal-catalyzed reactions inhibited by ammonium sulfate were identified using continuous-wave electron paramagnetic resonance (EPR) spectroscopy, providing direct evidence for the free radical mechanisms of organic pollutants inhibition. The transverse (T2) and longitudinal (T1) relaxation time variations catalyzed by different metal catalysts in the presence of ammonium sulfate were compared using pulsed-wave EPR. Consequently, after the addition of ammonium sulfate, the observed increase in T2 suggests that ammonium sulfate leads to radical concentration reduction. A decrease in the T1 relaxation time suggests the enhanced interaction between organic radicals and metals, which is an obstacle to subsequent radical reactions. Therefore, ammonium sulfate dominantly changed the free radical intermediates species, concentrations, and their reactivity, and then inhibited the organic pollutants formations. The inhibition mechanisms of ammonium sulfate on metal-catalyzed pollutants were then proposed combining EPR analysis, X-ray characterization, and high-resolution mass spectrometry screening. As a result, (1) occupying the active sites of metal catalysis and (2) inhibiting free radical intermediates are the two main intrinsic inhibition mechanisms of ammonium sulfate. The findings provide new perspectives on the efficient inhibition of organic pollutants in industrial processes involving various metal catalysts.

Cyclin F-EXO1 axis controls cell cycle-dependent execution of double-strand break repair.

Ubiquitination is a crucial posttranslational modification required for the proper repair of DNA double-strand breaks (DSBs) induced by ionizing radiation (IR). DSBs are mainly repaired through homologous recombination (HR) when template DNA is present and nonhomologous end joining (NHEJ) in its absence. In addition, microhomology-mediated end joining (MMEJ) and single-strand annealing (SSA) provide backup DSBs repair pathways. However, the mechanisms controlling their use remain poorly understood. By using a high-resolution CRISPR screen of the ubiquitin system after IR, we systematically uncover genes required for cell survival and elucidate a critical role of the E3 ubiquitin ligase SCFcyclin F in cell cycle-dependent DSB repair. We show that SCFcyclin F-mediated EXO1 degradation prevents DNA end resection in mitosis, allowing MMEJ to take place. Moreover, we identify a conserved cyclin F recognition motif, distinct from the one used by other cyclins, with broad implications in cyclin specificity for cell cycle control.

Clinical and radiographic characteristics of osteosarcomas of the jaws: A retrospective study.

Osteosarcomas in the maxillofacial region are rare and present different clinical and epidemiological aspects than those diagnosed in the long bones. This retrospective cross-sectional observational study aimed to report the characteristics of osteosarcomas of the jaws diagnosed in an oral pathology reference laboratory. Information (gender, location of origin, age, symptoms, lesion evolution time, and clinical appearance) regarding the cases diagnosed as osteosarcomas between 2001 and 2023 were obtained from histopathology reports, exam request forms, and clinical photographs. All radiographs were evaluated on a high-resolution screen by a previously trained radiologist. A 20-year experienced pathologist reviewed the histopathological slides and determined the predominant matrix of the lesions: osteoblastic, chondroblastic, or fibroblastic. Seventeen out of 33,692 cases diagnosed by the oral pathology laboratory over 22 years were osteosarcomas and 10 were included for analysis. The majority were diagnosed in males (60%) and the overall mean age was 37.8±21.6 years. A swollen, reddish, and ulcerated area was the most common clinical appearance. The mean evolution time of the lesions was 5.2±6.6 months. The majority of osteosarcomas were histologically classified as osteoblastic (80%). The radiographic appearance of the lesions was predominantly mixed (60%), presenting tooth resorption (44.4%) or displacement (33.3%), pericementum thickening (55.5%), mandibular canal erosion (71.4%) and sunray periosteal reaction (80%). The osteosarcomas of the jaws are predominantly osteoblastic with a swollen, reddish, and ulcerated clinical appearance. Imaging exams reveal mixed lesions with sunray periosteal reaction. Key words:Oral Pathology, Radiology, Osteosarcoma, Imaging diagnosis.

Non-target liquid chromatography high-resolution mass spectrometry screening to prioritize unregulated micropollutants that persist through domestic wastewater treatment

Efforts to regulate and monitor emerging contaminants are insufficient because new chemicals are continually brought to market, and many are unregulated and potentially harmful. Domestic wastewater treatment plants are not designed to remove micropollutants and are important sources of emerging contaminants in the aquatic environment. In this study, non-target screening, an unbiased method for analyzing compounds without prior information, was used to identify compounds that may be emitted in wastewater treatment plant effluent and should be monitored. Nine wastewater treatment plants using different treatment methods were studied, and a non-target screening data-processing method was used. The frequencies at which the contaminants were detected and contaminant persistence through the treatment processes were considered, and then the contaminants were prioritized. The predicted no-effect concentration of each prioritized contaminant was used to determine whether further analysis and monitoring of the contaminant was necessary. Quantitative analyses of five compounds (amantadine, atenolol, benzotriazole, diphenhydramine, and sulpiride) were performed using reference standards. Probable molecular formulae and structures were proposed for 17 contaminants, and the risks posed by the contaminants were estimated using predicted no-effect concentrations. The results provide valuable insights into how unregulated micropollutants can be identified and prioritized for monitoring in future studies.

Exploring Head-Mounted Virtual Visual Fields for Glaucoma: How do They Stack Up Against Humphrey Tests?

Abstract The integration of virtual reality (VR) technology into visual field (VF) testing has introduced innovative head-mounted perimetry devices, which offer numerous advantages over traditional methods. This review examines the features, accuracy, and reliability of commercially available head-mounted VR perimeters and compares them with the gold standard, the Humphrey Visual Field Analyzer (HFA). While traditional devices like the HFA and Goldmann Perimeter have been reliable for glaucoma management, they are limited by fixed testing environments, long testing durations, and high costs. VR-based perimetry addresses these limitations by providing portable, cost-effective, and engaging testing environments that can be conducted in various settings, including patients’ homes. Head-mounted displays (HMDs) equipped with high-resolution screens, motion sensors, and eye-tracking technology create an immersive testing experience that minimizes distractions and external light interference, potentially enhancing test accuracy. These devices also offer customizable testing protocols, improving patient comfort and compliance, especially among children and elderly patients. However, concerns remain about the reproducibility and accuracy of VR perimetry compared to established standards. Variability among VR platforms and the lack of large normative databases for visual fields pose challenges to their widespread adoption. This review highlights the need for further validation studies and the development of standardized testing protocols to ensure the reliability and accuracy of VR perimetry. Despite these challenges, the flexibility, reduced testing times, and potential for telemedicine applications make VR head-mounted perimetry a promising tool for improving glaucoma management and expanding access to VF testing in diverse clinical environments.

Removal and Recovery of Europium with a New Functionalized Mesoporous Silica-Based Adsorbent

The discharge of acid mine drainage (AMD), characterized by a high concentration of rare earth elements (REEs), poses a significant threat to the health of ecosystems surrounding water sources. The global market demand for REEs has experienced a notable surge in the past decade. Consequently, recovering REEs from waste streams like AMD not only benefits the environment but also offers financial advantages. Europium (Eu), the rarest among REEs, constitutes only 0.1% w/w in monazite and bastnaesite ores. Eu is extensively used in the production of phosphors, alloys, and additives, and is a critical raw material for developing smart devices, ranging from high-resolution color screens to circuitry. Traditional adsorbents typically exhibit limited selectivity towards REE recovery. Mesoporous silica materials, such as SBA15 (Santa Barbara Amorphous-15), provide excellent tunability and modification capabilities, making them an attractive and cost-effective alternative. This research focused on two key aspects: (i) evaluating the dynamic adsorption column performance of granulated SBA15–NH–PMIDA to preferentially recover Eu, and (ii) employing mathematical modeling to optimize the dynamic adsorption column’s operating conditions for real-world applications with a minimal number of experimental runs. Granulated SBA15–NH–PMIDA was chosen as the adsorbent due to its high adsorptive capacity and selectivity in capturing Eu. The study revealed that granulated SBA15–NH–PMIDA exhibited 57.47 mg/g adsorption capacity and an 81% selectivity towards Eu. Furthermore, SBA15–NH–PMIDA demonstrated preferential adsorption toward Eu in complex multi-component solutions, such as AMD. The linear driven force approximation model (LDFAM) provided an acceptable simulation (R2 > 0.91) under varying operational conditions. This validates the use of the model as a tool to effectively simulate and optimize column experiments that used granulated SBA15–NH–PMIDA to recover Eu.

N-glucuronidation and Excretion of Perfluoroalkyl Sulfonamides in Mice Following Ingestion of Aqueous Film-Forming Foam.

Perfluoroalkyl sulfonamides (FASAs) and other FASA-based per- and polyfluoroalkyl substances (PFASs) can transform into recalcitrant perfluoroalkyl sulfonates in vivo. We conducted high-resolution mass spectrometry suspect screening of urine and tissues (kidney and liver) from mice dosed with an electrochemically fluorinated aqueous film-forming foam (AFFF) to better understand the biological fate of AFFF-associated precursors. The B6C3F1 mice were dosed at five levels (0, 0.05, 0.5, 1, and 5 mg kg-1 day-1) based on perfluorooctane sulfonate and perfluorooctanoate content of the AFFF mixture. Dosing continued for 10 days followed by a 6-day depuration. Total oxidizable precursor assay of the AFFF suggested significant contributions from precursors with three to six perfluorinated carbons. We identified C4 to C6 FASAs and N-glucuronidated FASAs (FASA-N-glus) excreted in urine collected throughout dosing and depuration. Based on normalized relative abundance, FASA-N-glus accounted for up to 33% of the total excreted FASAs in mouse urine, highlighting the importance of phase II metabolic conjugation as a route of excretion. High-resolution mass spectrometry screening of liver and kidney tissue revealed accumulation of longer-chain (C7 and C8) FASAs not detected in urine. Chain-length-dependent conjugation of FASAs was also observed by incubating FASAs with mouse liver S9 fractions. Shorter-chain (C4) FASAs conjugated to a much greater extent over a 120-min incubation than longer-chain (C8) FASAs. Overall, this study highlights the significance of N-glucuronidation as an excretion mechanism for short-chain FASAs and suggests that monitoring urine for FASA-N-glus could contribute to a better understanding of PFAS exposure, as FASAs and their conjugates are often overlooked by traditional biomonitoring studies. Environ Toxicol Chem 2024;43:2274-2284. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Sub-surface geospatial intelligence in carbon capture, utilization and storage: A machine learning approach for offshore storage site selection

This study introduces an innovative data-driven and machine-learning framework designed to accurately predict site scores in the site screening study for specific offshore CO2 storage sites. The framework seamlessly integrates diverse sub-surface geospatial data sources with human aided expert-weighted criteria, thereby providing a high-resolution screening tool. Tailored to accommodate varying data accessibility and the significance of criteria, this approach considers both technical and non-technical factors. Its purpose is to facilitate the identification of priority locations for projects associated with Carbon Capture, Utilization, and Storage (CCUS). Through aggregating and analyzing geospatial datasets, the study employs machine learning algorithms and an expert-weighted model to identify suitable geologic CCUS regions. This process adheres to stringent safety, risk control, and environmental guidelines, addressing situations where human analysis may fail to recognize patterns and provide detailed insights in suitable site screening techniques. The primary emphasis of this research is to bridge the gap between scientific inquiry and practical application, facilitating informed decision-making in the implementation of CCUS projects. Rigorous assessments encompassing geological, oceanographic, and eco-sensitivity metrics contribute valuable insights for policymakers and industry leaders. To ensure the accuracy, efficiency, and scalability of the established offshore CO2 storage facilities, the proposed machine learning approach undergoes benchmarking. This comprehensive evaluation includes the utilization of machine learning algorithms such as Extreme Gradient Boosting (XGBoost), Random Forest (RF), Multilayer Extreme Learning Machine (MLELM), and Deep Neural Network (DNN) for predicting more suitable site scores. Among these algorithms, the DNN algorithm emerges as the most effective in site score prediction. The strengths of the DNN algorithm encompass nonlinear modeling, feature learning, scale invariance, handling high-dimensional data, end-to-end learning, transfer learning, representation learning, and parallel processing. The evaluation results of the DNN algorithm demonstrate high accuracy in the testing subset, with values of AAPD (Average Absolute Percentage Difference) = 1.486 %, WAAPD (Weighted Average Absolute Percentage Difference) = 0.0149 %, VAF (Variance Accounted For) = 0.9937, RMSE (Root Mean Square Error) = 0.9279, RSR (Root Sum of Squares Residuals) = 0.0068, and R2 (Coefficient of Determination) = 0.9937.

A virally encoded high-resolution screen of cytomegalovirus dependencies.

Genetic screens have transformed our ability to interrogate cellular factor requirements for viral infections1,2, but most current approaches are limited in their sensitivity, biased towards early stages of infection and provide only simplistic phenotypic information that is often based on survival of infected cells2-4. Here, by engineering human cytomegalovirus to express single guide RNA libraries directly from the viral genome, we developed virus-encoded CRISPR-based direct readout screening (VECOS), a sensitive, versatile, viral-centric approach that enables profiling of different stages of viral infection in a pooled format. Using this approach, we identified hundreds of host dependency and restriction factors and quantified their direct effects on viral genome replication, viral particle secretion and infectiousness of secreted particles, providing a multi-dimensional perspective on virus-host interactions. These high-resolution measurements reveal that perturbations altering late stages in the life cycle of human cytomegalovirus (HCMV) mostly regulate viral particle quality rather than quantity, establishing correct virion assembly as a critical stage that is heavily reliant on virus-host interactions. Overall, VECOS facilitates systematic high-resolution dissection of the role of human proteins during the infection cycle, providing a roadmap for in-depth study of host-herpesvirus interactions.

Scaled-laboratory demonstrations of deep-turbulence conditions

This paper uses five spatially distributed reflective liquid-crystal phase modulators (LcPMs) to accurately simulate deep-turbulence conditions in a scaled-laboratory environment. In practice, we match the Fresnel numbers for long-range, horizontal-path scenarios using optical trombones and relays placed between the reflective LcPMs. Similar to computational wave-optic simulations, we also command repeatable high-resolution phase screens to the reflective LcPMs with the proper path-integrated spatial and temporal Kolmogorov statistics.

Enhancing diagnosis of benign lesions and lung cancer through ensemble text and breath analysis: a retrospective cohort study

Early diagnosis of lung cancer (LC) can significantly reduce its mortality rate. Considering the limitations of the high false positive rate and reliance on radiologists’ experience in computed tomography (CT)–based diagnosis, a multi-modal early LC screening model that combines radiology with other non-invasive, rapid detection methods is warranted. A high-resolution, multi-modal, and low-differentiation LC screening strategy named ensemble text and breath analysis (ETBA) is proposed that ensembles radiology report text analysis and breath analysis. In total, 231 samples (140 LC patients and 91 benign lesions [BL] patients) were screened using proton transfer reaction–time of flight–mass spectrometry and CT screening. Participants were randomly assigned to a training set and a validation set (4:1) with stratification. The report section of the radiology reports was used to train a text analysis (TA) model with a natural language processing algorithm. Twenty-two volatile organic compounds (VOCs) in the exhaled breath and the prediction results of the TA model were used as predictors to develop the ETBA model using an extreme gradient boosting algorithm. A breath analysis model was developed based on the 22 VOCs. The BA and TA models were compared with the ETBA model. The ETBA model achieved a sensitivity of 94.3%, a specificity of 77.3%, and an accuracy of 87.7% with the validation set. The radiologist diagnosis performance with the validation set had a sensitivity of 74.3%, a specificity of 59.1%, and an accuracy of 68.1%. High sensitivity and specificity were obtained by the ETBA model compared with radiologist diagnosis. The ETBA model has the potential to provide sensitivity and specificity in CT screening of LC. This approach is rapid, non-invasive, multi-dimensional, and accurate for LC and BL diagnosis.

Clinical Predictors and Outcomes of Invasive Anal Cancer for People With HIV in an Inception Cohort.

Due to the heterogeneity of risk for invasive anal cancer (IAC) among people with human immunodeficiency virus (PWH), we investigated predictors of IAC and described outcomes among those with a cancer diagnosis. Using a longitudinal inception cohort of anal cancer screening, we evaluated risk factors and outcome probabilities for incident IAC in Cox models. Screening included anal cytology and digital anorectal examination, and, if results of either were abnormal, high-resolution anoscopy. Between 30 November 2006 and 3 March 2021, a total of 8139 PWH received care at the University of California, San Diego, with 4105 individuals undergoing screening and subsequently followed up over a median of 5.5 years. Anal cancer developed in 33 of them. IAC was more likely to develop in patients with anal high-grade squamous intraepithelial lesions (aHSILs) on initial or subsequent follow-up cytology (hazard ratio, 4.54) and a nadir CD4 cell count ≤200/µL (2.99). The joint effect of aHSILs and nadir CD4 cell count ≤200/µL amplified the hazard of IAC by 9-fold compared with the absence of both. PWH with time-updated cytology aHSIL and CD4 cell counts ≤200/µL had 5- and 10-year probabilities of IAC of 3.40% and 4.27%, respectively. Twelve individuals with cancer died, 7 (21% of the total 33) due to cancer progression, and they had clinical stage IIIA or higher cancer at initial diagnosis. PWH with both aHSIL and a nadir CD4 cell count ≤200/µL have the highest risk of IAC. PWH who died due to IAC progression had clinical stage IIIA cancer or higher at diagnosis, highlighting the importance of early diagnosis through high-resolution anoscopic screening.

Establishment of compound database of emerging antioxidants and high-resolution mass spectrometry screening in lake sediment from Taihu Lake Basin, China.

Antioxidants are ubiquitous in various environmental samples, leading to increasing concern regarding their potential risk to environments or humans. However, there is dearth of information regarding the environmental fate of antioxidants and unknown/unexpected antioxidants in the environment. Here, we established a compound database (CDB) containing 320 current-used antioxidants by collecting the chemicals from EPA's functional use database and published documents. Physical-chemical characteristics of these antioxidants were estimated, and 19 ones were considered as persistent and bioaccumulative (P&B) substances. This CDB was further coupled with high resolution mass spectrometry (HRMS) technique, which was employed for suspect screening of antioxidants in extracts of sediments (n = 88) collected from Taihu Lake basin. We screened 119 HRMS features that can match 135 chemical formulas in the CDB, and 20 out of them exhibited the detection frequencies ≥ 90%. The total concentrations of suspect antioxidants in sediments ranged from 6.41 to 830ng/g dw. Statistical analysis demonstrated that concentrations of suspect antioxidants in Taihu Lake were statistically significantly lower than those in Shihu and Jiulihu Lake, but greater than those from other small lakes. Collectively, this study provided a CDB that could be helpful for further monitoring studies of antioxidant in the environments, and also provided the first evidence regarding the ubiquity of antioxidants in aquatic environment of Taihu Lake basin.

High-resolution display screen as programmable illumination for Fourier ptychography

We introduce a new programmable illumination strategy for Fourier ptychographic microscopy (FPM), utilizing a high-resolution organic light-emitting diode (OLED) display screen at the vicinity of the sample to achieve super-resolution and quantitative phase imaging of biological samples. High-density pixels in the OLED screen allow for the angle-scanning illumination required for FP by placing the sample slide directly on the screen, where multiple images of the sample are captured while scanning the pixels on the screen. We discuss the design of the OLED-FP illumination and the corresponding image reconstruction strategies and experimentally validate the super-resolution and phase imaging capabilities of FP using a smartphone screen as illumination. Further, we extend our method to patterned illumination strategies, which multiplexes multiple illumination pixels to achieve full-field FP imaging with a reduced number of measurements, where we identify an optimal illumination pattern and density to maximize the imaging speed without sacrificing the image quality. Our approach offers a simple and compact programmable illuminator that can effectively transform any microscope into a compact FPM with resolution improvement and phase imaging capabilities.