An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms.

Vector-borne diseases are a leading cause of death worldwide and pose a substantial unmet medical need. Pathogens binding to host extracellular proteins (the "exoproteome") represents a crucial interface in the etiology of vector-borne disease. Here, we used bacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT)-a technique enabling interrogation of microbial interactions with 3,324 human exoproteins-to profile the interactomes of 82 human-pathogen samples, including 30 strains of arthropod-borne pathogens and 8 strains of related non-vector-borne pathogens. The resulting atlas revealed 1,303 putative interactions, including hundreds of pairings with potential roles in pathogenesis, including cell invasion, tissue colonization, immune evasion, and host sensing. Subsequent functional investigations uncovered that Lyme disease spirochetes recognize epidermal growth factor as an environmental cue of transcriptional regulation and that conserved interactions between intracellular pathogens and thioredoxins facilitate cell invasion. In summary, this interactome atlas provides molecular-level insights into microbial pathogenesis and reveals potential host-directed targets for next-generation therapeutics.

Structural evolution of an immune evasion determinant shapes pathogen host tropism.

Modern infectious disease outbreaks often involve changes in host tropism, the preferential adaptation of pathogens to specific hosts. The Lyme disease-causing bacterium Borrelia burgdorferi (Bb) is an ideal model to investigate the molecular mechanisms of host tropism, because different variants of these tick-transmitted bacteria are distinctly maintained in rodents or bird reservoir hosts. To survive in hosts and escape complement-mediated immune clearance, Bb produces the outer surface protein CspZ that binds the complement inhibitor factor H (FH) to facilitate bacterial dissemination in vertebrates. Despite high sequence conservation, CspZ variants differ in human FH-binding ability. Together with the FH polymorphisms between vertebrate hosts, these findings suggest that minor sequence variation in this bacterial outer surface protein may confer dramatic differences in host-specific, FH-binding-mediated infectivity. We tested this hypothesis by determining the crystal structure of the CspZ-human FH complex, and identifying minor variation localized in the FH-binding interface yielding bird and rodent FH-specific binding activity that impacts infectivity. Swapping the divergent region in the FH-binding interface between rodent- and bird-associated CspZ variants alters the ability to promote rodent- and bird-specific early-onset dissemination. We further linked these loops and respective host-specific, complement-dependent phenotypes with distinct CspZ phylogenetic lineages, elucidating evolutionary mechanisms driving host tropism emergence. Our multidisciplinary work provides a novel molecular basis for how a single, short protein motif could greatly modulate pathogen host tropism.

Lizards and the enzootic cycle of Borrelia burgdorferi sensu lato.

Emerging and re-emerging pathogens often stem from zoonotic origins, cycling between humans and animals, and are frequently vectored and maintained by hematophagous arthropod vectors. The efficiency by which these disease agents are successfully transmitted between vertebrate hosts is influenced by many factors, including the host on which a vector feeds. The Lyme disease bacterium Borrelia burgdorferi sensu lato has adapted to survive in complex host environments, vectored by Ixodes ticks, and maintained in multiple vertebrate hosts. The versatility of Lyme borreliae in disparate host milieus is a compelling platform to investigate mechanisms dictating pathogen transmission through complex networks of vertebrates and ticks. Squamata, one of the most diverse clade of extant reptiles, is comprised primarily of lizards, many of which are readily fed upon by Ixodes ticks. Yet, lizards are one of the least studied taxa at risk of contributing to the transmission and life cycle maintenance of Lyme borreliae. In this review, we summarize the current evidence, spanning from field surveillance to laboratory infection studies, supporting their contributions to Lyme borreliae circulation. We also summarize the current understanding of divergent lizard immune responses that may explain the underlying molecular mechanisms to confer Lyme spirochete survival in vertebrate hosts. This review offers a critical perspective on potential enzootic cycles existing between lizard-tick-Borrelia interactions and highlights the importance of an eco-immunology lens for zoonotic pathogen transmission studies.

Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that can result in hospitalization or death. We used exome sequence data to investigate associations between rare genetic variants and seven COVID-19 outcomes in 586,157 individuals, including 20,952 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome wide or when specifically focusing on (1) 13 interferon pathway genes in which rare deleterious variants have been reported in individuals with severe COVID-19, (2) 281 genes located in susceptibility loci identified by the COVID-19 Host Genetics Initiative, or (3) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, and results are publicly available through the Regeneron Genetics Center COVID-19 Results Browser.

VlsE, the nexus for antigenic variation of the Lyme disease spirochete, also mediates early bacterial attachment to the host microvasculature under shear force.

Hematogenous dissemination is a critical step in the evolution of local infection to systemic disease. The Lyme disease (LD) spirochete, which efficiently disseminates to multiple tissues, has provided a model for this process, in particular for the key early event of pathogen adhesion to the host vasculature. This occurs under shear force mediated by interactions between bacterial adhesins and mammalian cell-surface proteins or extracellular matrix (ECM). Using real-time intravital imaging of the Lyme spirochete in living mice, we previously identified BBK32 as the first LD spirochetal adhesin demonstrated to mediate early vascular adhesion in a living mouse; however, deletion of bbk32 resulted in loss of only about half of the early interactions, suggesting the existence of at least one other adhesin (adhesin-X) that promotes early vascular interactions. VlsE, a surface lipoprotein, was identified long ago by its capacity to undergo rapid antigenic variation, is upregulated in the mammalian host and required for persistent infection in immunocompetent mice. In immunodeficient mice, VlsE shares functional overlap with OspC, a multi-functional protein that displays dermatan sulfate-binding activity and is required for joint invasion and colonization. In this research, using biochemical and genetic approaches as well as intravital imaging, we have identified VlsE as adhesin-X; it is a dermatan sulfate (DS) adhesin that efficiently promotes transient adhesion to the microvasculature under shear force via its DS binding pocket. Intravenous inoculation of mice with a low-passage infectious B. burgdorferi strain lacking both bbk32 and vlsE almost completely eliminated transient microvascular interactions. Comparative analysis of binding parameters of VlsE, BBK32 and OspC provides a possible explanation why these three DS adhesins display different functionality in terms of their ability to promote early microvascular interactions.

Characterization of Fe-Containing and Pb-Containing Nanoparticles Resulting from Corrosion of Plumbing Materials in Tap Water Using a Hyphenated ATM-DMA-spICP-MS System.

Single-particle inductively coupled plasma mass spectrometry (spICP-MS) has been used to characterize metallic nanoparticles (NPs) assuming that all NPs are spherical and composed of pure element. However, environmental NPs generally do not meet these criteria, suggesting that spICP-MS may underestimate their true sizes. This study employed a system hyphenating the atomizer (ATM), differential mobility analyzer (DMA), and spICP-MS to characterize metallic NPs in tap water. Its performance was validated by using reference Au nanoparticles (AuNPs) and Ag-shelled AuNPs. The hyphenated system can determine the actual size and metal composition of both NPs with additional heating after ATM, while stand-alone spICP-MS misidentified the Ag-shelled AuNPs as smaller individual AgNPs and AuNPs. Dissolved metal ions could introduce artifact NPs after heating but could be eliminated by centrifugation. The hyphenated system was applied to characterize Fe-containing and Pb-containing NPs resulting from the corrosion of plumbing materials in tap water. The mode sizes of Fe-containing and Pb-containing NPs were determined to be 110 and 100 nm and the particle number concentrations were determined to be 4.99 × 107 and 1.40 × 106 #/mL, respectively. Cautions should be paid to potential changes in particle size induced by heating for metallic NPs with a low melting point or a high organic content.

The Relationship between the Bevel of the Radial Head Epiphysis and the Posterior Synovial Fringe During Rotation of the Elbow: An Ultrasonography Study with Possible Implications Regarding the Pathophysiology of Nursemaid's Elbow.

BACKGROUND: Nursemaid's elbow is the most common upper extremity injury in children under 5 years of age. However, the exact pathomechanism underlying the nursemaid's elbow remains elusive, and approximate one-third of patients present with a nonclassical history. Using a high-frequency ultrasound probe, we attempted to determine the relationship between the anterior edge of the posterior synovial fringe and the peripheral rim of the radial head epiphysis during rotation. It is possible that the primary reason for the nursemaid's elbow is due to the pronator position. METHODS: Twenty-one patients had a history of nursemaid's elbow and had a successful reduction before enrollment in this study. A high-frequency linear array 6 to 24 MHz hockey stick transducer was used to detect small morphologic changes in the peripheral rim of the radial head epiphysis and the posterior synovial fringe during rotation of the capitellum-radial joint. RESULTS: In complete pronation, the anterior edge of the posterior synovial fringe contacts the beveled articular surface of the radial head peripheral rim in all 21 patients. In neutral and complete supination, the anterior edge of the posterior synovial fringe contacts the convexly nonarticular surface of the radial head peripheral rim and extends deep into the foveal radius. The posterior synovial fringe and the capsule-aponeurotic membrane were tightened in passive pronation in all 21 cases. The posterior synovial fringe and the capsule-aponeurosis membrane were all loose in the neutral and supination positions. CONCLUSION: The anterior edge of the posterior synovial fringe touches the beveled peripheral rim of the radial head epiphysis during complete pronation, and the tension of the lateral collateral ligament complex during pronation may further cause unstable conditions of the anterior edge of the posterior synovial fringe. We hypothesized that the beveled peripheral rim of the radial epiphysis and its relationship with the anterior edge of the posterior synovial fringe could be the reason why nursemaid's elbow only occurs while the elbow is in the pronator position.

Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system.

Pathogens possess the ability to adapt and survive in some host species but not in others-an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement, a defense in vertebrate blood, and a polymorphic bacterial protein, CspA, which inactivates complement by binding to a host complement inhibitor, Factor H (FH). CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. CspA is the only member of the Pfam54 gene family to exhibit host-specific FH-binding. Phylogenetic analyses revealed convergent evolution as the driver of such uniqueness, and that FH-binding likely emerged during the last glacial maximum. Our results identify a determinant of host tropism in Lyme disease infection, thus defining an evolutionary mechanism that shapes host-pathogen associations.

A Rare Heterozygote with a Novel IVS-â ¡-786 (T>A) Mutation on ß-Globin Gene in a Patient with Thalassemia.

BACKGROUND: Thalassemia is an inherited hemolytic blood disease, whose pathogenesis is an imbalance in the expression of hemoglobin. We report a case of a rare ß-globin gene intron mutation for thalassemia patient. METHODS: The blood routine test was performed with an automatic blood cell analyzer. Hb analysis was conducted by hemoglobin (Hb) analyzer. The common ß-thalassemia and α-thalassemia gene mutations were detected by Gap-PCR and fluorescence PCR melting curve, and the rare ß-thalassemia gene mutations were detected by DNA sequencing. RESULTS: A rare heterozygous mutation of ß-globin gene IVS-II-786 (T>A) was found in this case. Blood routine analysis showed the following values: Hb 92 g/L, RBC 4.1 x 1012/L, MCV 74.10 fL, MCH 22.4 pg, MCHC 303 g/L, HCT 0.304 L/L, and RET-He 22.7 pg. Hemoglobin analysis showed values of HbA2 2.2% and HbF < 2% by automatic capillary electrophoresis. The results of gene analysis and DNA sequencing showed that the ß-globin gene IVS-II-786 (T>A) mutation was heterozygous. CONCLUSIONS: The heterozygote of ß-globin gene IVS-II-786 (T>A) mutation was detected for the first time, and the clinical manifestation was moderate anemia. Hemoglobin analysis indicated that the level of HbA2 was decreased. This mutation is relatively rare and easy to misdiagnose in clinical practice. It will provide a new type of evidence and guidance for genetic counseling and clinical treatment of beta thalassemia.

A Novel RHCE*cE (c.827C>A) Allele, Containing the Single-Nucleotide Change, Encodes Altered c/E Antigens.

The RH blood group system is the most complex with over 50 antigens. So far over hundreds of RhCE variant alleles have been described resulting in weakened and/or partial expression of RhCE antigens [1], some variant Rh phenotypes are caused by exchange of genetic material between the RHD and RHCE genes, resulting in many hybrid genes, other phenotypes result from missense mutations. Variant alleles encode altered phenotypes with either weakened antigens, lacked antigens, or unexpected antigens. Besides, the mutation of RH blood group genes may lead to the changes of Rh antigen epitopes. RHCE gene mutations or polymorphisms may bring about altered RH antigens in quality and quantity [2]. Serologic weaknesses or discrepancies are regularly faced by blood transfusion laboratories, and molecular background explaining this feature can be precisely characterized only by the molecular biological methods.

The Usefulness of Dynamic Ultrasonography in Nursemaid's Elbow: A Prospective Case Series of 13 Patients Reconsideration of the Pathophysiology of Nursemaid's Elbow.

BACKGROUND: Nursemaid's elbow is a common musculoskeletal disorder among children under 5 years of age. However, diagnostic imaging to confirm a nursemaid's elbow diagnosis is still unavailable. Through the use of a high-frequency ultrasound probe, we determined the etiology and possible pathophysiology of nursemaid's elbow. METHODS: Thirteen consecutive patients with the clinical suspicion of nursemaid's elbows were examined. A high-frequency linear array 6 to 24 MHz hockey stick transducer was used to detect small changes (partial eclipse signs) of the radial head in the axial view before and after manipulation. RESULTS: All patients in this study had a successful reduction. A partial eclipse sign was found in all patients before reduction and disappeared after successful reduction. CONCLUSION: These pathologic features detected through high-frequency ultrasonography suggest the role of the escaped posterior synovial fringe in the pathogenesis of the nursemaid's elbow. The specific finding of a "partial eclipse sign" could be a useful additional clue leading to the correct diagnosis of the nursemaid's elbow and may help avoid the unnecessary reduction in patients who do not have a "partial eclipse sign". LEVEL OF EVIDENCE: Level II, diagnostic studies.

CspZ FH-Binding Sites as Epitopes Promote Antibody-Mediated Lyme Borreliae Clearance.

Transmitted by ticks, the bacterium Borrelia burgdorferi sensu lato is the causative agent of Lyme disease (LD), the most common vector-borne disease in the Northern hemisphere. No effective vaccines are currently available. B. burgdorferi sensu lato produces the CspZ protein that binds to the complement inhibitor, factor H (FH), promoting evasion of the host complement system. We previously showed that while vaccination with CspZ did not protect mice from B. burgdorferi infection, mice can be protected after immunization with CspZ-Y207A/Y211A (CspZ-YA), a CspZ mutant protein without FH-binding activity. To further study the mechanism of this protection, herein we evaluated both poly- and monoclonal antibodies recognizing CspZ FH-binding or non-FH-binding sites. We found that the anti-CspZ antibodies that recognize the FH-binding sites (i.e., block FH-binding activity) eliminate B. burgdorferi sensu lato in vitro more efficiently than those that bind to the non-FH-binding sites, and passive inoculation with anti-FH-binding site antibodies eradicated B. burgdorferi sensu lato in vivo. Antibodies against non-FH-binding sites did not have the same effect. These results emphasize the importance of CspZ FH-binding sites in triggering a protective antibody response against B. burgdorferi sensu lato in future LD vaccines.

Robust Virus-Specific Adaptive Immunity in COVID-19 Patients with SARS-CoV-2 Δ382 Variant Infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have become dominant as the pandemic progresses bear the ORF8 mutation together with multiple spike mutations. A 382-nucleotide deletion (Δ382) in the ORF7b and ORF8 regions has been associated with milder disease phenotype and less systemic inflammation in COVID-19 patients. However, its impact on host immunity against SARS-CoV-2 remains undefined. Here, RNA-sequencing was performed to elucidate whole blood transcriptomic profiles and identify contrasting immune signatures between patients infected with either wildtype or Δ382 SARS-CoV-2 variant. Interestingly, the immune landscape of Δ382 SARS-CoV-2 infected patients featured an increased adaptive immune response, evidenced by enrichment of genes related to T cell functionality, a more robust SARS-CoV-2-specific T cell immunity, as well as a more rapid antibody response. At the molecular level, eukaryotic initiation factor 2 signaling was found to be upregulated in patients bearing Δ382, and its associated genes were correlated with systemic levels of T cell-associated and pro-inflammatory cytokines. This study provides more in-depth insight into the host-pathogen interactions of ORF8 with great promise as a therapeutic target to combat SARS-CoV-2 infection.

Cellular and immunological mechanisms influence host-adapted phenotypes in a vector-borne microparasite.

Predicting pathogen emergence and spillover risk requires understanding the determinants of a pathogens' host range and the traits involved in host competence. While host competence is often considered a fixed species-specific trait, it may be variable if pathogens diversify across hosts. Balancing selection can lead to maintenance of pathogen polymorphisms (multiple-niche-polymorphism; MNP). The causative agent of Lyme disease, Borrelia burgdorferi (Bb), provides a model to study the evolution of host adaptation, as some Bb strains defined by their outer surface protein C (ospC) genotype, are widespread in white-footed mice and others are associated with non-rodent vertebrates (e.g. birds). To identify the mechanisms underlying potential strain × host adaptation, we infected American robins and white-footed mice, with three Bb strains of different ospC genotypes. Bb burdens varied by strain in a host-dependent fashion, and strain persistence in hosts largely corresponded to Bb survival at early infection stages and with transmission to larvae (i.e. fitness). Early survival phenotypes are associated with cell adhesion, complement evasion and/or inflammatory and antibody-mediated removal of Bb, suggesting directional selective pressure for host adaptation and the potential role of MNP in maintaining OspC diversity. Our findings will guide future investigations to inform eco-evolutionary models of host adaptation for microparasites.

Strain-specific joint invasion and colonization by Lyme disease spirochetes is promoted by outer surface protein C.

Lyme disease, caused by Borrelia burgdorferi, B. afzelii and B. garinii, is a chronic, multi-systemic infection and the spectrum of tissues affected can vary with the Lyme disease strain. For example, whereas B. garinii infection is associated with neurologic manifestations, B. burgdorferi infection is associated with arthritis. The basis for tissue tropism is poorly understood, but has been long hypothesized to involve strain-specific interactions with host components in the target tissue. OspC (outer surface protein C) is a highly variable outer surface protein required for infectivity, and sequence differences in OspC are associated with variation in tissue invasiveness, but whether OspC directly influences tropism is unknown. We found that OspC binds to the extracellular matrix (ECM) components fibronectin and/or dermatan sulfate in an OspC variant-dependent manner. Murine infection by isogenic B. burgdorferi strains differing only in their ospC coding region revealed that two OspC variants capable of binding dermatan sulfate promoted colonization of all tissues tested, including joints. However, an isogenic strain producing OspC from B. garinii strain PBr, which binds fibronectin but not dermatan sulfate, colonized the skin, heart and bladder, but not joints. Moreover, a strain producing an OspC altered to recognize neither fibronectin nor dermatan sulfate displayed dramatically reduced levels of tissue colonization that were indistinguishable from a strain entirely deficient in OspC. Finally, intravital microscopy revealed that this OspC mutant, in contrast to a strain producing wild type OspC, was defective in promoting joint invasion by B. burgdorferi in living mice. We conclude that OspC functions as an ECM-binding adhesin that is required for joint invasion, and that variation in OspC sequence contributes to strain-specific differences in tissue tropism displayed among Lyme disease spirochetes.

Utilizing Two Borrelia bavariensis Isolates Naturally Lacking the PFam54 Gene Array To Elucidate the Roles of PFam54-Encoded Proteins.

Lyme borreliosis is the most common vector-borne disease in the Northern Hemisphere, caused by spirochetes belonging to the Borrelia burgdorferi sensu lato species complex, which are transmitted by ixodid ticks. B. burgdorferi sensu lato species produce a family of proteins on the linear plasmid 54 (PFam54), some of which confer the functions of cell adhesion and inactivation of complement, the first line of host defense. However, the impact of PFam54 in promoting B. burgdorferi sensu lato pathogenesis remains unclear because of the hurdles to simultaneously knock out all PFam54 proteins in a spirochete. Here, we describe two Borrelia bavariensis strains, PBN and PNi, isolated from patients naturally lacking PFam54 but maintaining the rest of the genome with greater than 95% identity to the reference B. bavariensis strain, PBi. We found that PBN and PNi less efficiently survive in human serum than PBi. Such defects were restored by introducing two B. bavariensis PFam54 recombinant proteins, BGA66 and BGA71, confirming the role of these proteins in providing complement evasion of B. bavariensis. Further, we found that all three strains remain detectable in various murine tissues 21 days post-subcutaneous infection, supporting the nonessential role of B. bavariensis PFam54 in promoting spirochete persistence. This study identified and utilized isolates deficient in PFam54 to associate the defects with the absence of these proteins, building the foundation to further study the role of each PFam54 protein in contributing to B. burgdorferi sensu lato pathogenesis. IMPORTANCE To establish infections, Lyme borreliae utilize various means to overcome the host's immune system. Proteins encoded by the PFam54 gene array play a role in spirochete survival in vitro and in vivo. Moreover, this gene array has been described in all currently available Lyme borreliae genomes. By investigating the first two Borrelia bavariensis isolates naturally lacking the entire PFam54 gene array, we showed that both patient isolates display an increased susceptibility to human serum, which can be rescued in the presence of two PFam54 recombinant proteins. However, both isolates remain infectious to mice after intradermal inoculation, suggesting the nonessential role of PFam54 during the long-term, but may differ slightly in the colonization of specific tissues. Furthermore, these isolates show high genomic similarity to type strain PBi (>95%) and could be used in future studies investigating the role of each PFam54 protein in Lyme borreliosis pathogenesis.

DeepLensNet: Deep Learning Automated Diagnosis and Quantitative Classification of Cataract Type and Severity.

PURPOSE: To develop deep learning models to perform automated diagnosis and quantitative classification of age-related cataract from anterior segment photographs. DESIGN: DeepLensNet was trained by applying deep learning models to the Age-Related Eye Disease Study (AREDS) dataset. PARTICIPANTS: A total of 18 999 photographs (6333 triplets) from longitudinal follow-up of 1137 eyes (576 AREDS participants). METHODS: Deep learning models were trained to detect and quantify nuclear sclerosis (NS; scale 0.9-7.1) from 45-degree slit-lamp photographs and cortical lens opacity (CLO; scale 0%-100%) and posterior subcapsular cataract (PSC; scale 0%-100%) from retroillumination photographs. DeepLensNet performance was compared with that of 14 ophthalmologists and 24 medical students. MAIN OUTCOME MEASURES: Mean squared error (MSE). RESULTS: On the full test set, mean MSE for DeepLensNet was 0.23 (standard deviation [SD], 0.01) for NS, 13.1 (SD, 1.6) for CLO, and 16.6 (SD, 2.4) for PSC. On a subset of the test set (substantially enriched for positive cases of CLO and PSC), for NS, mean MSE for DeepLensNet was 0.23 (SD, 0.02), compared with 0.98 (SD, 0.24; P = 0.000001) for the ophthalmologists and 1.24 (SD, 0.34; P = 0.000005) for the medical students. For CLO, mean MSE was 53.5 (SD, 14.8), compared with 134.9 (SD, 89.9; P = 0.003) for the ophthalmologists and 433.6 (SD, 962.1; P = 0.0007) for the medical students. For PSC, mean MSE was 171.9 (SD, 38.9), compared with 176.8 (SD, 98.0; P = 0.67) for the ophthalmologists and 398.2 (SD, 645.4; P = 0.18) for the medical students. In external validation on the Singapore Malay Eye Study (sampled to reflect the cataract severity distribution in AREDS), the MSE for DeepSeeNet was 1.27 for NS and 25.5 for PSC. CONCLUSIONS: DeepLensNet performed automated and quantitative classification of cataract severity for all 3 types of age-related cataract. For the 2 most common types (NS and CLO), the accuracy was significantly superior to that of ophthalmologists; for the least common type (PSC), it was similar. DeepLensNet may have wide potential applications in both clinical and research domains. In the future, such approaches may increase the accessibility of cataract assessment globally. The code and models are available at https://github.com/ncbi/deeplensnet.

Release of Particulate Lead from Four Lead Corrosion Products in Drinking Water: A Laboratory Study Coupled with Microscopic Observations and Computational Fluid Dynamics.

Particulate lead resulting from the detachment of lead corrosion products (LCPs) contributes significantly to lead contamination in drinking water. Since LCPs formed under different water chemistry possesses different crystal structures, their hydrodynamic behaviors could be significantly different in flowing water. In this study, flushing experiments and microscopic observations were employed to investigate the release of cerussite (PbCO3), hydrocerussite (Pb3(CO3)2(OH)2), chloropyromorphite (Pb5(PO4)3Cl), and lead dioxide (scrutinyite α-PbO2/plattnerite ß-PbO2), the four LCPs commonly found in the drinking water distribution system. Under the same flow rate, particulate lead release showed the following trend: lead dioxide > cerussite ∼ chloropyromorphite > hydrocerussite. In the range of 1-10 L/min, a higher flow rate enhanced the release of cerussite, chloropyromorphite, and lead dioxide, while the release of hydrocerussite was not significantly affected, likely due to its platelike crystal structure that reduced the shear force exerted by the flowing water. The detachments of visible cerussite and chloropyromorphite particles were captured using a digital microscope at flow rates of 8.0 and 8.2 L/min, and the shear forces causing their detachments were determined to be 5.8 × 10-11 and 3.1 × 10-10 N, respectively, using computational fluid dynamics (CFD). Our study demonstrated that crystal structure could be an important factor affecting the detachment of LCPs and CFD could be a useful tool to characterize their hydrodynamic behaviors.

Immunochemical and urodynamic outcomes after polypropylene mesh explant from the pelvic wall of rats.

INTRODUCTION AND HYPOTHESIS: To analyze the immunochemical and urodynamic outcomes after partial versus complete excision of transvaginal polypropylene mesh (PPM) from pelvic walls of rats. METHODS: Forty-eight female Sprague-Dawley (SD) rats were randomly distributed into seven groups: control, mesh total removal 60 days (M-T 60D), mesh total removal 180 days (M-T 180D), mesh partial removal 60 days (M-H 60D), mesh partial removal 180 days (M-H 180D), sham 60 days (Sham 60D), and sham 180 days (Sham 180D). In the mesh groups, PPM was inserted and partially (0.3 × 0.3 cm) or completely removed 30 days later. In the Sham group, the space between the vagina and bladder was dissected without placing or removing the synthetic mesh at day 1 and day 30 later. Urodynamic studies, immunochemical analysis, and Western blot were done at days 60 and 180. RESULTS: The M-T 60D voiding pressure was significantly decreased compared to the Sham 60D and M-H 60D. The voiding interval of M-T 60D was significantly shorter than that of M-H 60D. In the M-T 60D and M-T 180D groups, the leak point pressure was significantly less than in their corresponding sham groups. IL-1 and TNF-α were significantly more intense in M-T 60D compared to M-H 60D and Sham 60D. NGF was significantly greater in M-T 60D compared to Sham 60D. There were no significant differences in MMP-2 and CD-31s throughout the group. CONCLUSION: Total mesh excision incites a host inflammatory response and transitory lower urinary tract dysfunction. Despite the good outcomes after total excision, the invasiveness and surgical risk associated with repeated procedures should not be underestimateded.

Recovery of phosphate and ammonia from wastewater via struvite precipitation using spent refractory brick gravel from steel industry.

Spent refractory brick (SRB) generated from the steel industry has a high magnesium content. In this study, a procedure was developed to utilize SRB gravels for efficient recovery of phosphate and ammonia from high strength wastewater via struvite (MgNH4PO4∙6H2O(s)) precipitation. Mg2+ and Ca2+ were first leached from SRB gravels using nitric acid solution. Ca2+ in the solution could inhibit struvite precipitation and was sequestered by dosing SO32- to form calcium sulfite (CaSO3(s)). The resulting Mg2+-rich solution was then employed to initiate struvite precipitation for phosphate and ammonia recovery. The optimal precipitation was achieved with a molar ratio of [Mg2+]:[NH3-N]:[PO43-P] = 2:1:2 at pH 9.5. The residual phosphate in the solution can be further removed via the precipitation of calcium phosphate minerals. Overall, 99.6% phosphate and 98.2% ammonia could be recovered and the treated wastewater could meet the discharging standards of ammonia and phosphate. The resulting solids, including calcium sulfite, struvite and calcium phosphate can be potentially used in the cement industry and agriculture sector to achieve sustainable recycle of spent materials.