DNA methylation biomarkers for predicting lymph node metastasis in colorectal cancer.

Colorectal cancer is one of the most common cancers worldwide. Lymph node metastasis is an important marker of colorectal cancer progression and plays a key role in the evaluation of patient prognosis. Accurate preoperative assessment of lymph node metastasis is crucial for devising appropriate treatment plans. However, current clinical imaging methods have limitations in many aspects. Therefore, the discovery of a method for accurately predicting lymph node metastasis is crucial clinical decision-making. DNA methylation is a common epigenetic modification that can regulate gene expression, which also has an important impact on the development of colorectal cancer. It is considered to be a promising biomarker with good specificity and stability and has promising application in predicting lymph node metastasis in patients with colorectal cancer. This article reviews the characteristics and limitations of currently available methods for predicting lymph node metastasis in patients with colorectal cancer and discusses the role of DNA methylation as a biomarker.

Bone and joint infection complicated with sepsis in neonates and infants under three months of age

Abstract Objective: Studies focusing on bone and joint infections (BJIs) in young infants are rare. Some cases of BJI are accompanied by sepsis. This study aimed to identify the clinical and bacteriological features of sepsis in neonates and young infants with BJIs. Methods: Neonates and infants younger than 3 months diagnosed with BJI in the present institution from 2014 to 2021 were retrospectively reviewed. Patient characteristics, clinical data, and outcomes were documented and compared between those with and without sepsis. Results: Twenty-five patients with a mean age of 34.8 days were included. Nine BJI cases had concomitant sepsis (group A), and 16 had BJI without sepsis (group B). Within group A, staphylococcus aureus was the major pathogenic germ (5 cases, of which 4 were of the methicillin-resistant staphylococcus aureus (MRSA) type). There was no statistical difference in male-to-female ratio, age, history of hospitalization, anemia, birth asphyxia, peripheral leukocyte counts, C-reactive protein on admission, and sequelae between groups. Univariate analyses indicated a significant difference in the incidence of septic arthritis (SA) combined with osteomyelitis (OM) (88.9% vs 37.5%), congenital deformities (44.4% vs 0%), and mean duration of symptoms (2.83 days vs 9.21 days) in comparisons between groups A and B. Conclusion: Staphylococcus aureus is the main pathogenic bacteria in BJI cases complicated with sepsis in neonates and young infants. Among infants younger than 3 months diagnosed with BJI, those with concurrent SA and OM, MRSA infection, or congenital deformities are more likely to develop sepsis.

The relationship between brain metastasis and HER2 expression status in gastric cancer.

BACKGROUND: Brain metastasis (BM) in gastric cancer (GC) is underestimated, and human epidermal growth factor receptor 2 (HER2) overexpression is a durable poor prognostic factor. We explored the relationship between the two and made a survival analysis. METHODS: HER2 expression and BM status were collected from GC patients who were diagnosed between December 2009 and May 2021. We collected GC patients diagnosed between 2010 and 2016 from the SEER database. The primary endpoint was survival from the diagnosis of BM. Multivariable logistic regression was used to determine potential risk factors of BM at diagnosis in SEER database. Survival analysis was performed using the Kaplan-Meier method. RESULT: There were 513 HER2-positive GC patients, including 16 (3.1%) with BM. Among 38 brain metastasis GC patients we collected, 16 (42.1%) patients were HER2 positive. We collected 34,199 GC patients from the SEER database and there were 260 (0.76%) patients with BM at diagnosis. GC patients that are male, white, of younger age, with primary lesions located in the proximal stomach or with distant lymph nodes, liver, bone, or lung metastasis are more likely to develop BM. The median overall survival time from diagnosis of BM was 12.73 months, and the survival time from brain metastasis of HER2-positive patients was numerically shorter, though the difference was not significant (5.30 months vs.16.13 months, P = 0.28.) CONCLUSION: The incidence of BM in patients with HER2-positive gastric cancer is 4.08 times higher than that in general patients. The median overall survival time from BM is shorter for HER2-positive patients.

Bone and joint infection complicated with sepsis in neonates and infants under three months of age.

OBJECTIVE: Studies focusing on bone and joint infections (BJIs) in young infants are rare. Some cases of BJI are accompanied by sepsis. This study aimed to identify the clinical and bacteriological features of sepsis in neonates and young infants with BJIs. METHODS: Neonates and infants younger than 3 months diagnosed with BJI in the present institution from 2014 to 2021 were retrospectively reviewed. Patient characteristics, clinical data, and outcomes were documented and compared between those with and without sepsis. RESULTS: Twenty-five patients with a mean age of 34.8 days were included. Nine BJI cases had concomitant sepsis (group A), and 16 had BJI without sepsis (group B). Within group A, staphylococcus aureus was the major pathogenic germ (5 cases, of which 4 were of the methicillin-resistant staphylococcus aureus (MRSA) type). There was no statistical difference in male-to-female ratio, age, history of hospitalization, anemia, birth asphyxia, peripheral leukocyte counts, C-reactive protein on admission, and sequelae between groups. Univariate analyses indicated a significant difference in the incidence of septic arthritis (SA) combined with osteomyelitis (OM) (88.9% vs 37.5%), congenital deformities (44.4% vs 0%), and mean duration of symptoms (2.83 days vs 9.21 days) in comparisons between groups A and B. CONCLUSION: Staphylococcus aureus is the main pathogenic bacteria in BJI cases complicated with sepsis in neonates and young infants. Among infants younger than 3 months diagnosed with BJI, those with concurrent SA and OM, MRSA infection, or congenital deformities are more likely to develop sepsis.

Neobaicalein prevents isoflurane anesthesia-induced cognitive impairment in neonatal mice via regulating CREB1.

OBJECTIVES: Isoflurane (ISO) is widely used in the clinic and research. The authors aimed to explore whether Neobaicalein (Neob) could protect neonatal mice from ISO-induced cognitive damage. METHOD: The open field test, Morris water maze test, and tail suspension test was performed to assess the cognitive function in mice. Enzyme-linked immunosorbent assay was used to evaluate inflammatory-related protein concentrations. Immunohistochemistry was used to assess Ionized calcium-Binding Adapter molecule-1 (IBA-1) expression. Hippocampal neuron viability was detected using the Cell Counting Kit-8 assay. Double immunofluorescence staining was employed to confirm the interaction between proteins. Western blotting was used to assess protein expression levels. RESULTS: Neob notably improved cognitive function and exhibited anti-inflammatory effects; moreover, under iso-treatment, it exhibited neuroprotective effects. Furthermore, Neob suppressed interleukin-1ß, tumor necrosis factor-α, and interleukin-6 levels and upregulated interleukin-10 levels in ISO-treated mice. Neob significantly mitigated iso-induced increases in IBA-1-positive cell numbers of the hippocampus in neonatal mice. Furthermore, it inhibited ISO-induced neuronal apoptosis. Mechanistically, Neob was observed to upregulate cAMP Response Element Binding protein (CREB1) phosphorylation and protected hippocampal neurons from ISO-mediated apoptosis. Moreover, it rescued ISO-induced abnormalities of synaptic protein. CONCLUSIONS: Neob prevented ISO anesthesia-induced cognitive impairment by suppressing apoptosis and inflammation through upregulating CREB1.

Neobaicalein prevents isoflurane anesthesia-induced cognitive impairment in neonatal mice via regulating CREB1

Abstract Objectives: Isoflurane (ISO) is widely used in the clinic and research. The authors aimed to explore whether Neobaicalein (Neob) could protect neonatal mice from ISO-induced cognitive damage. Method: The open field test, Morris water maze test, and tail suspension test was performed to assess the cognitive function in mice. Enzyme-linked immunosorbent assay was used to evaluate inflammatory-related protein concentrations. Immunohistochemistry was used to assess Ionized calcium-Binding Adapter molecule-1 (IBA-1) expression. Hippocampal neuron viability was detected using the Cell Counting Kit-8 assay. Double immunofluorescence staining was employed to confirm the interaction between proteins. Western blotting was used to assess protein expression levels. Results: Neob notably improved cognitive function and exhibited anti-inflammatory effects; moreover, under isotreatment, it exhibited neuroprotective effects. Furthermore, Neob suppressed interleukin-1β, tumor necrosis factor-α, and interleukin-6 levels and upregulated interleukin-10 levels in ISO-treated mice. Neob significantly mitigated iso-induced increases in IBA-1 - positive cell numbers of the hippocampus in neonatal mice. Furthermore, it inhibited ISO-induced neuronal apoptosis. Mechanistically, Neob was observed to upregulate cAMP Response Element Binding protein (CREB1) phosphorylation and protected hippocampal neurons from ISO-mediated apoptosis. Moreover, it rescued ISO-induced abnormalities of synaptic protein. Conclusions: Neob prevented ISO anesthesia-induced cognitive impairment by suppressing apoptosis and inflammation through upregulating CREB1.

A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus.

Atrial fibrillation (AF) represents the most common type of sustained cardiac arrhythmia in humans and confers a significantly increased risk for thromboembolic stroke, congestive heart failure and premature death. Aggregating evidence emphasizes the predominant genetic defects underpinning AF and an increasing number of deleterious variations in more than 50 genes have been involved in the pathogenesis of AF. Nevertheless, the genetic basis underlying AF remains incompletely understood. In the current research, by whole-exome sequencing and Sanger sequencing analysis in a family with autosomal-dominant AF and congenital patent ductus arteriosus (PDA), a novel heterozygous variation in the PRRX1 gene encoding a homeobox transcription factor critical for cardiovascular development, NM_022716.4:c.373G>T;p.(Glu125*), was identified to be in co-segregation with AF and PDA in the whole family. The truncating variation was not detected in 306 unrelated healthy individuals employed as controls. Quantitative biological measurements with a reporter gene analysis system revealed that the Glu125*-mutant PRRX1 protein failed to transactivate its downstream target genes SHOX2 and ISL1, two genes that have been causally linked to AF. Conclusively, the present study firstly links PRRX1 loss-of-function variation to AF and PDA, suggesting that AF and PDA share a common abnormal developmental basis in a proportion of cases.

Vascular Endothelial Cells and Innate Immunity.

In addition to the roles of endothelial cells (ECs) in physiological processes, ECs actively participate in both innate and adaptive immune responses. We previously reported that, in comparison to macrophages, a prototypic innate immune cell type, ECs have many innate immune functions that macrophages carry out, including cytokine secretion, phagocytic function, antigen presentation, pathogen-associated molecular patterns-, and danger-associated molecular patterns-sensing, proinflammatory, immune-enhancing, anti-inflammatory, immunosuppression, migration, heterogeneity, and plasticity. In this highlight, we introduce recent advances published in both ATVB and many other journals: (1) several significant characters classify ECs as novel immune cells not only in infections and allograft transplantation but also in metabolic diseases; (2) several new receptor systems including conditional danger-associated molecular pattern receptors, nonpattern receptors, and homeostasis associated molecular patterns receptors contribute to innate immune functions of ECs; (3) immunometabolism and innate immune memory determine the innate immune functions of ECs; (4) a great induction of the immune checkpoint receptors in ECs during inflammations suggests the immune tolerogenic functions of ECs; and (5) association of immune checkpoint inhibitors with cardiovascular adverse events and cardio-oncology indicates the potential contributions of ECs as innate immune cells.

Correlación entre los microorganismos oxidantes del amonio y los factores ambientales durante el compostaje de estiércol de ganado / Correlation between ammonia-oxidizing microorganisms and environmental factors during cattle manure composting

Abstract Cattle manure composting was performed in an aerated vessel. Community structure and diversity of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) were investigated using polymerase chain reaction and denaturing gradient gel electrophoresis (PCR-DGGE) techniques targeting the ammonia monooxygenase alpha subunit (amoA) gene and the correlation between AOB and AOA communities and environmental factors was explored. Thirteen (13) AOB sequences were obtained, which were closely related to Nitrosomonas spp., Nitrosomonas eutropha, and Nitrosospira spp. and uncultured bacteria, among which Nitrosomonas spp. were predominant. Excessively high temperature and high ammonium concentration were not favorable for AOB growth. Five AOA sequences, belonging to Candidatus Nitrososphaera gargensis and to an uncultured archaeon, were obtained. During composting, community diversity of AOB and AOA fluctuated, with AOA showing a higher Shannon-Wiener index. The AOB community changed more dramatically in the mesophilic stage and the early thermophilic stage, whereas the most obvious AOA community succession occurred in the late thermophilic stage, the cooling stage and the maturity stage. Water content, total nitrogen (TN) and ammonium concentration were more relevant to the AOB community structure, while higher correlations were observed between ammonia, nitrate and TN and the AOA community. AOB community diversity was negatively correlated with pH (r = -0.938, p < 0.01) and water content (r = -0.765, p < 0.05), while positively correlated with TN (r = 0.894, p < 0.01). AOA community diversity was negatively correlated with ammonium concentration (r = -0.901, p < 0.01). Ammonium concentration played an important role in the succession of AOB and AOA communities during composting.

Resumen Se llevó a cabo un compostaje de estiércol de ganado en un recipiente aireado. Se investigó la estructura de la comunidad y la diversidad de bacterias oxidantes del amoníaco (AOB) y las arqueas oxidantes del amoníaco (AOA) mediante el uso de las técnicas de reacción en cadena de la polimerasa y la electroforesis en gel con gradiente de desnaturalización (PCR-DGGE) dirigidas al gen de la subunidad alfa de la amonio monooxigenasa (amoA), y se exploró la correlación entre las comunidades AOB, AOA y los factores ambientales. Se obtuvieron 13 secuencias de AOB, las cuales se relacionaron estrechamente con Nitrosomonas spp., Nitrosomonas eutropha y Nitrosospira spp., y bacterias no cultivadas, entre las cuales fueron predominantes las Nitrosomonas spp. La temperatura excesivamente alta y la concentración de amonio elevada no fueron favorables para el crecimiento de las AOB. Se obtuvieron 5 secuencias de AOA, pertenecientes a Candidatus Nitrososphaera gargensis y un Archaeon no cultivado. Durante el compostaje, la diversidad de AOB y AOA fluctuó y las AOA mostraron un índice de Shannon-Wiener más alto. La comunidad de AOB cambió significativamente en la etapa mesofílica y la etapa termofílica temprana, mientras que la sucesión más obvia de la comunidad AOA ocurrió en la etapa termofílica tardía y las etapas de enfriamiento y de maduración. El contenido de agua, el nitrógeno total (TN) y la concentración de amonio fueron más relevantes para la estructura de la comunidad AOB, mientras que se observaron correlaciones mayores entre amoníaco, nitrato y TN, y la comunidad AOA. La diversidad de la comunidad AOB se correlacionó negativamente con el pH (r= -0,938; p < 0,01) y el contenido de agua (r = -0,765; p < 0,05), mientras que se relacionó positivamente con TN (r = 0,894; p < 0,01). La diversidad de la comunidad AOA se correlacionó negativamente con la concentración de amonio (r = -0,901; p < 0,01). La concentración de amonio desempenó un papel importante en la sucesión de las comunidades AOB y AOA durante el compostaje.

Semi-volatile organic compounds in infant homes: Levels, influence factors, partitioning, and implications for human exposure.

While infants are developing, they are easily affected by toxic chemicals existing in their environments, such as semi-volatile organic compounds (SVOCs): phthalates, polycyclic aromatic hydrocarbons (PAHs), polybrominated diphenyl ethers (PBDEs), and organophosphate esters (OPEs). However, the specific living environment of infants, including increased plastic products and foam floor mats, may increase the presence of these chemicals. In this study, 68 air, dust, and window film samples were collected from homes, with 3- to 6-month-old infant occupants, to analyze phthalates, PAHs, PBDEs, and OPEs. High detection rates and concentrations suggest that these SVOCs are widespread in infant environments and are associated with cooking methods, smoking habits, the period of time after decoration, and room floors. The partitioning behavior of SVOCs indicates that the logarithms of the dust/gas-phase air partition coefficient (logKD) and the window film/gas-phase air partition coefficient (logKF) in homes are not at an equilibrium state when the logarithm of the octanol/air partition coefficient (logKOA) is less than 8 or greater than 11. Considering the 3 exposure routes, ingestion and dermal absorption have become the main routes of infant exposure to phthalates and OPEs, and ingestion and inhalation have become the dominant routes of exposure to PAHs and PBDEs. The total carcinogenic risk of SVOCs, which have carcinogenic toxicities, via ingestion and dermal absorption for infants in homes exceeds the acceptable value, suggesting that the current levels of these SVOCs in homes might pose a risk to infant health.

Correlation between ammonia-oxidizing microorganisms and environmental factors during cattle manure composting.

Cattle manure composting was performed in an aerated vessel. Community structure and diversity of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) were investigated using polymerase chain reaction and denaturing gradient gel electrophoresis (PCR-DGGE) techniques targeting the ammonia monooxygenase alpha subunit (amoA) gene and the correlation between AOB and AOA communities and environmental factors was explored. Thirteen (13) AOB sequences were obtained, which were closely related to Nitrosomonas spp., Nitrosomonas eutropha, and Nitrosospira spp. and uncultured bacteria, among which Nitrosomonas spp. were predominant. Excessively high temperature and high ammonium concentration were not favorable for AOB growth. Five AOA sequences, belonging to CandidatusNitrososphaera gargensis and to an uncultured archaeon, were obtained. During composting, community diversity of AOB and AOA fluctuated, with AOA showing a higher Shannon-Wiener index. The AOB community changed more dramatically in the mesophilic stage and the early thermophilic stage, whereas the most obvious AOA community succession occurred in the late thermophilic stage, the cooling stage and the maturity stage. Water content, total nitrogen (TN) and ammonium concentration were more relevant to the AOB community structure, while higher correlations were observed between ammonia, nitrate and TN and the AOA community. AOB community diversity was negatively correlated with pH (r = -0.938, p < 0.01) and water content (r = -0.765, p < 0.05), while positively correlated with TN (r = 0.894, p < 0.01). AOA community diversity was negatively correlated with ammonium concentration (r = -0.901, p < 0.01). Ammonium concentration played an important role in the succession of AOB and AOA communities during composting.

Transantarctic disjunctions in Schistochilaceae (Marchantiophyta) explained by early extinction events, post-Gondwanan radiations and palaeoclimatic changes.

The liverworts are the first diverging land plant group with origins in the Ordovician. The family Schistochilaceae exhibits diverse morphology and widely disjunct geographic ranges within the Southern Hemisphere. The family has been presented as a classic example of Gondwanan biogeographic distribution, with extant species ranges resulting from vicariance events. In this study, we present results that elucidate the origin and diversification of Schistochilaceae. We conducted a comprehensive time-calibrated, molecular-based phylogenetic analysis and different approaches for ancestral range inference of the family. Schistochilaceae is inferred to have originated in the Late Cretaceous, in an ancestral area including southern South America, West Antarctica and New Zealand. Despite a family origin at c. 100Ma, most of the diversification of Schistochilaceae occurred in New Zealand after the 80Ma opening of the Tasman Sea that isolated New Zealand from the rest of Gondwana. Most dispersals were transoceanic. The northward migration of the Schistochilaceae is probably linked with the spread of temperate vascular plant forest ecosystems that have Late Cretaceous southern origins and have maintained suitable environments for the family throughout the Cenozoic. The distribution and biogeographic history of the family is very similar to that of Nothofagaceae.

Serum uric acid levels and non-alcoholic fatty liver disease in Uyghur and Han ethnic groups in northwestern China.

OBJECTIVE: The aim of this study was to compare serum uric acid values in two ethnically distinct Chinese populations: Uyghur, with a high prevalence of nonalcoholic fatty liver disease, and Han, with a lower prevalence. SUBJECTS AND METHODS: Serum uric acid and several clinical features and laboratory tests relevant to the metabolic syndrome were measured in 4,157 Uyghur and 6,448 Han subjects in a health examination program. The diagnosis of hepatic steatosis was established by abdominal ultrasound examination. RESULTS: The prevalence of nonalcoholic fatty liver disease was 42.3% and 33.3% among Uyghur and Han subjects, respectively. The corresponding prevalence of hyperuricemia was 8.8% and 14.7%. The mean concentration of serum uric acid in Uyghurs also was lower than in Hans (282.75 vs. 310.79 µmol/L; p < 0.01). However, in both populations, the prevalence of nonalcoholic fatty liver disease was increased in association with increasing serum uric acid concentrations, a trend that was more pronounced in Uyghur than in Han subjects (OR 3.279 and 3.230, respectively). Several components of the metabolic syndrome were more pronounced in Uyghurs than in Hans. CONCLUSIONS: Serum uric acid is an independent risk factor in nonalcoholic fatty liver disease in both Uyghurs and Hans, but other risk factors may be more important in the differences in prevalence of the disease between the two ethnic groups.

Serum uric acid levels and non-alcoholic fatty liver disease in Uyghur and Han ethnic groups in northwestern China / Concentração sérica de ácido úrico e doença hepática gordurosa não alcoólica em grupos étnicos Uyghur e Han no nordeste da China

OBJECTIVE: The aim of this study was to compare serum uric acid values in two ethnically distinct Chinese populations: Uyghur, with a high prevalence of nonalcoholic fatty liver disease, and Han, with a lower prevalence. SUBJECTS AND METHODS: Serum uric acid and several clinical features and laboratory tests relevant to the metabolic syndrome were measured in 4,157 Uyghur and 6,448 Han subjects in a health examination program. The diagnosis of hepatic steatosis was established by abdominal ultrasound examination. RESULTS: The prevalence of nonalcoholic fatty liver disease was 42.3% and 33.3% among Uyghur and Han subjects, respectively. The corresponding prevalence of hyperuricemia was 8.8% and 14.7%. The mean concentration of serum uric acid in Uyghurs also was lower than in Hans (282.75 vs. 310.79 µmol/L; p < 0.01). However, in both populations, the prevalence of nonalcoholic fatty liver disease was increased in association with increasing serum uric acid concentrations, a trend that was more pronounced in Uyghur than in Han subjects (OR 3.279 and 3.230, respectively). Several components of the metabolic syndrome were more pronounced in Uyghurs than in Hans. CONCLUSIONS: Serum uric acid is an independent risk factor in nonalcoholic fatty liver disease in both Uyghurs and Hans, but other risk factors may be more important in the differences in prevalence of the disease between the two ethnic groups.

OBJETIVO: O objetivo deste estudo foi comparar os valores de ácido úrico em duas populações chinesas etnicamente diferentes: Uyghur, com alta prevalência de doença hepática gordurosa não alcoólica, e Han, com prevalência mais baixa. SUJEITOS E MÉTODOS: A concentração sérica de ácido úrico e várias características clínicas e testes laboratoriais relevantes para a síndrome metabólica foram determinados em 4.157 indivíduos Uyghur e 6.448 indivíduos Han submetidos a um programa de checkups. O diagnóstico de esteatose hepática foi estabelecido por ultrassom abdominal. RESULTADOS: A prevalência de doença hepática gordurosa não alcoólica foi de 42,3% e 33,3% entre os indivíduos Uyghur e Han, respectivamente. A prevalência correspondente de hiperuricemia foi de 8,8% e 14,7%. A concentração sérica média de ácido úrico em Uyghurs também foi mais baixa do que em Hans (282,75 contra 310,79 µmol/L; p < 0,01). Entretanto, em ambas as populações, a prevalência de doença hepática gordurosa não alcoólica aumentou com a elevação da concentração sérica de ácido úrico, uma tendência mais pronunciada em Uyghurs do que em Hans (OR 3,279 e 3,230, respectivamente). Vários componentes da síndrome metabólica são mais pronunciados em Uyghurs do que em Hans. CONCLUSÕES: A concentração sérica de ácido úrico é um fator de risco independente para a doença hepática gordurosa não alcoólica tanto em Uyghurs quando em Hans, mas outros fatores de risco podem ser mais importantes nas diferenças na prevalência da doença entre esses dois grupos étnicos.

Demographic characteristics and prevalence of serologic markers among blood donors who use confidential unit exclusion (CUE) in São Paulo, Brazil: implications for modification of CUE policies in Brazil.

BACKGROUND: This study evaluated demographic profiles and prevalence of serologic markers among donors who used confidential unit exclusion (CUE) to assess the effectiveness of CUE and guide public policies regarding the use of CUE for enhancing safety versus jeopardizing the blood supply by dropping CUE. STUDY DESIGN AND METHODS: We conducted a cross-sectional analysis of whole blood donations at a large public blood center in São Paulo from July 2007 through June 2009, compared demographic data, and confirmed serologic results among donors who used and who have never used CUE (CUE never). RESULTS: There were 265,550 whole blood units collected from 181,418 donors from July 2007 through June 2009. A total of 9658 (3.6%) units were discarded, 2973 (1.1%) because CUE was used at the current donation (CUE now) and 6685 (2.5%) because CUE was used in the past (CUE past). The CUE rate was highest among donors with less than 8 years of education (odds ratio [OR], 2.78; 95% confidence interval [CI], 2.51-3.08). CUE now donations were associated with higher positive infectious disease marker rates than CUE never donations (OR, 1.41; CI, 1.13-1.77), whereas CUE past donations were not (OR, 1.04; CI, 0.75-1.45). CONCLUSION: The CUE process results in a high rate of unit discard. CUE use on an individual donation appears predictive of a high-risk marker-positive donation and, thus, appears to contribute modestly to blood safety. The policy of discarding units from donors who have previously CUE-positive donations does not improve safety and should be discontinued.