Research gaps and priorities for quantitative microbial risk assessment (QMRA).

The coronavirus disease 2019 pandemic highlighted the need for more rapid and routine application of modeling approaches such as quantitative microbial risk assessment (QMRA) for protecting public health. QMRA is a transdisciplinary science dedicated to understanding, predicting, and mitigating infectious disease risks. To better equip QMRA researchers to inform policy and public health management, an Advances in Research for QMRA workshop was held to synthesize a path forward for QMRA research. We summarize insights from 41 QMRA researchers and experts to clarify the role of QMRA in risk analysis by (1) identifying key research needs, (2) highlighting emerging applications of QMRA; and (3) describing data needs and key scientific efforts to improve the science of QMRA. Key identified research priorities included using molecular tools in QMRA, advancing dose-response methodology, addressing needed exposure assessments, harmonizing environmental monitoring for QMRA, unifying a divide between disease transmission and QMRA models, calibrating and/or validating QMRA models, modeling co-exposures and mixtures, and standardizing practices for incorporating variability and uncertainty throughout the source-to-outcome continuum. Cross-cutting needs identified were to: develop a community of research and practice, integrate QMRA with other scientific approaches, increase QMRA translation and impacts, build communication strategies, and encourage sustainable funding mechanisms. Ultimately, a vision for advancing the science of QMRA is outlined for informing national to global health assessments, controls, and policies.

Lack of SARS-CoV-2 in environmental samples collected from September 2020-February 2021 in a university that followed CDC reopening guidance.

This study aimed to provide environmental surveillance data for evaluating the risk of acquiring SARS-CoV-2 in public areas with high foot traffic in a university. Air and surface samples were collected at a university that had the second highest number of COVID-19 cases among public higher education institutions in the U.S. during Fall 2020. A total of 60 samples were collected in 16 sampling events performed during Fall 2020 and Spring 2021. Nearly 9800 students traversed the sites during the study period. SARS-CoV-2 was not detected in any air or surface samples. The university followed CDC guidance, including COVID-19 testing, case investigations, and contact tracing. Students, faculty, and staff were asked to maintain physical distancing and wear face coverings. Although COVID-19 cases were relatively high at the university, the possibility of acquiring SARS-CoV-2 infections at the sites tested was low.

Study on the correlation between B vitamins and breast cancer.

BACKGROUND: Relevant studies suggest that serum vitamin level is related to the risk of breast cancer, and dietary pattern and drug supplementation can significantly affect the level of vitamin in the body. Therefore, intervention of vitamin level in the body is expected to be a potential strategy to reduce the risk of breast cancer. However, the current epidemiological findings of serum vitamin levels and breast cancer risk are inconsistent, and the relationship between serum vitamin and breast cancer is still controversial. In this study, we compared the serum vitamin expression levels of healthy people, benign breast patients, and breast cancer patients, and evaluated the relationship between B vitamin levels and breast cancer risk. METHODS: The study used liquid chromatography-tandem mass spectrometry to determine the serum vitamin levels of 520 people who attended Yunnan Cancer Hospital from September 2020 to December 2020. After screening by exclusion criteria, 38 patients with benign breast diseases, 87 patients with breast cancer and 91 healthy controls were finally included. The kruskal-wallis H test was used to compare the differences in serum vitamin levels of subjects. Χ2 test was used to evaluate the relationship between B vitamin level and age,BMI,TNM staging,Ki-67,Her-2,surgery and chemotherapy, and other baseline characteristics and through binary logistic regression analysis, calculating odds ratio and 95% confidence interval (CI) to evaluate the relationship between B vitamins and breast cancer risk. CONCLUSION: The levels of VitB1 and VitB5 in the serum of breast cancer patients and patients with benign breast diseases were higher than those in the healthy control group, while the expression levels of VitB3 in breast cancer patients were lower than those in the healthy control group and the breast benign disease groups. The level of VitB1 was positively correlated with breast cancer risk. The VitB3 level was negatively correlated with breast cancer risk. The VitB5 level is not significantly related to the risk of breast cancer.

Effects of Return Air Inlets' Location on the Control of Fine Particle Transportation in a Simulated Hospital Ward.

The COVID-19 pandemic has made significant impacts on public health, including human exposure to airborne pathogens. In healthcare facilities, the locations of return air vents in ventilation systems may have important effects on lowering airborne SARS-CoV-2 transmission. This study conducted experiments to examine the influence of different return air vents' heights (0.7 m, 1.2 m, and 1.6 m) on the particle removal effects in a simulated patient ward. Three different ventilation systems were examined: top celling air supply-side wall return (TAS), underfloor air supply-side wall return (UFAS) and side wall air supply-side wall return (SAS). CFD simulation was applied to further study the effects of return air inlets' heights (0.3 m, 0.7 m, 1.2 m, 1.6 m, and 2.0 m) and air exchange rates. The technique for order of preference by similarity to ideal solution (TOPSIS) analysis was used to calculate the comprehensive scores of 60 scenarios using a multi-criterion method to obtain the optimal return air inlets' heights. Results showed that for each additional 0.5 m distance in most working conditions, the inhalation fraction index of medical staff could be reduced by about 5-20%. However, under certain working conditions, even though the distances between the patients and medical personnel were different, the optimal heights of return air vents were constant. For TAS and UFAS, the optimal return air inlets' height was 1.2 m, while for SAS, the best working condition was 1.6 m air supply and 0.7 m air return. At the optimum return air heights, the particle decay rate per hour of SAS was 75% higher than that of TAS, and the rate of particle decay per hour of SAS was 21% higher than that of UFAS. The location of return air inlets could further affect the operating cost-effectiveness of ventilation systems: the highest operating cost-effectiveness was 8 times higher than the lowest one.

Electrochemical removal and recovery of uranium: Effects of operation conditions, mechanisms, and implications.

Removing and recovering uranium (U) from U-mining wastewater would be appealing, which simultaneously reduces the adverse environmental impact of U mining activities and mitigates the depletion of conventional U resources. In this study, we demonstrate the application of a constant-voltage electrochemical (CVE) method for the removal and recovery of U from U-mining wastewater, in an ambient atmosphere. The effects of operation conditions were elucidated in synthetic U-bearing water experiments, and the cell voltage and the ionic strength were found to play important roles in both the U extraction kinetics and the operation cost. The mechanistic studies show that, in synthetic U-bearing water, the CVE U extraction proceeds exclusively via a single-step one-electron reduction mechanism, where pentavalent U is the end product. In real U-mining wastewater, the interference of water matrices led to the disproportionation of the pentavalent U, resulting in the formation of tetravalent and hexavalent U in the extraction products. The U extraction efficacy of the CVE method was evaluated in real U-mining wastewater, and results show that the CVE U extraction method can be efficient with operation costs ranging from $0.55/kgU ~ $64.65/kgU, with varying cell voltages from 1.0 V to 4.0 V, implying its feasibility from the economic perspective.

Robustness of ventilation systems in the control of walking-induced indoor fluctuations: Method development and case study.

Walking-induced fluctuations have a significant influence on indoor airflow and pollutant dispersion. This study developed a method to quantify the robustness of ventilation systems in the control of walking-induced fluctuation control. Experiments were conducted in a full-scale chamber with four different kinds of ventilation systems: ceiling supply and side return (CS), ceiling supply and ceiling return (CC), side supply and ceiling return (SC), and side supply and side return (SS). The measured temperature, flow and pollutant field data was (1) denoised by FFT filtering or wavelet transform; (2) fitted by a Gaussian function; (3) feature-extracted for the range and time scale disturbance; and then (4) used to calculate the range scale and time scale robustness for different ventilation systems with dimensionless equations developed in this study. The selection processes for FFT filtering and wavelet transform, FFT filter cut-off frequency, wavelet function, and decomposition layers are also discussed, as well as the threshold for wavelet denoising, which can be adjusted accordingly if the walking frequency or sampling frequency differs from that in other studies. The results show that for the flow and pollutant fields, the use of a ventilation system can increase the range scale robustness by 19.7%-39.4% and 10.0%-38.8%, respectively; and the SS system was 7.0%-25.7% more robust than the other three ventilation systems. However, all four kinds of ventilation systems had a very limited effect in controlling the time scale disturbance.

Environmental Surveillance for SARS-CoV-2 in Two Restaurants from a Mid-scale City that Followed U.S. CDC Reopening Guidance.

Since mask use and physical distancing are difficult to maintain when people dine indoors, restaurants are perceived as high risk for acquiring COVID-19. The air and environmental surfaces in two restaurants in a mid-scale city located in north central Florida that followed the Centers for Disease Control and Prevention (CDC) reopening guidance were sampled three times from July 2020 to February 2021. Sixteen air samples were collected for 2 hours using air samplers, and 20 surface samples by using moistened swabs. The samples were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for the presence of SARS-CoV-2 genomic RNA. A total of ~550 patrons dined in the restaurants during our samplings. SARS-CoV-2 genomic RNA was not detected in any of the air samples. One of the 20 surface samples (5%) was positive. That sample had been collected from a plastic tablecloth immediately after guests left the restaurant. Virus was not isolated in cell cultures inoculated with aliquots of the RT-PCR-positive sample. The likelihood that patrons and staff acquire SARS-CoV-2 infections may be low in restaurants in a mid-scale city that adopt CDC restaurant reopening guidelines, such as operation at 50% capacity so that tables can be spaced at least 6 feet apart, establishment of adequate mechanical ventilation, use of a face covering except while eating or drinking, and implementation of disinfection measures.

An integrated exposure and pharmacokinetic modeling framework for assessing population-scale risks of phthalates and their substitutes.

To effectively incorporate in vitro-in silico-based methods into the regulation of consumer product safety, a quantitative connection between product phthalate concentrations and in vitro bioactivity data must be established for the general population. We developed, evaluated, and demonstrated a modeling framework that integrates exposure and pharmacokinetic models to convert product phthalate concentrations into population-scale risks for phthalates and their substitutes. A probabilistic exposure model was developed to generate the distribution of multi-route exposures based on product phthalate concentrations, chemical properties, and human activities. Pharmacokinetic models were developed to simulate population toxicokinetics using Bayesian analysis via the Markov chain Monte Carlo method. Both exposure and pharmacokinetic models demonstrated good predictive capability when compared with worldwide studies. The distributions of exposures and pharmacokinetics were integrated to predict the population distributions of internal dosimetry. The predicted distributions showed reasonable agreement with the U.S. biomonitoring surveys of urinary metabolites. The "source-to-outcome" local sensitivity analysis revealed that food contact materials had the greatest impact on body burden for di(2-ethylhexyl) adipate (DEHA), di-2-ethylhexyl phthalate (DEHP), di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), and di(2-propylheptyl) phthalate (DPHP), whereas the body burden of diethyl phthalate (DEP) was most sensitive to the concentration in personal care products. The upper bounds of predicted plasma concentrations showed no overlap with ToxCast in vitro bioactivity values. Compared with the in vitro-to-in vivo extrapolation (IVIVE) approach, the integrated modeling framework has significant advantages in mapping product phthalate concentrations to multi-route risks, and thus is of great significance for regulatory use with a relatively low input requirement. Further integration with new approach methodologies will facilitate these in vitro-in silico-based risk assessments for a broad range of products containing an equally broad range of chemicals.

Overexpression of ING3 is associated with attenuation of migration and invasion in breast cancer.

Inhibitor of growth 3 (ING3) has been identified as a potential cancer drug target, but little is known about its role in breast cancer. Thus, the present study aimed to investigate ING3 expression in breast cancer, its clinical value, and how ING3 influences the migration and invasion of breast cancer cells. The Cancer Genome Atlas and UALCAN databases were used to analyze ING3 expression in cancer tissues and normal tissues. Survival analysis was performed using the UALCAN, UCSC Xena and KM-plot databases. In addition, reverse transcription-quantitative PCR and western blot analyses were performed to detect ING3 mRNA and protein expression levels. ING3 was overexpressed via lentiviral vector transfection, while the Transwell and wound healing assays were performed to assess the cell migratory and invasive abilities. Protein interaction and pathway analyses were performed using the GeneMANIA and Kyoto Encyclopedia of Genes and Genomes databases, respectively. The results demonstrated that ING3 expression was significantly lower in cancer tissues compared with normal tissues (P<0.05). In addition, luminal A and human epidermal growth factor receptor 2 (HER2)-enriched breast cancer tissues expressed lower levels of ING3 compared with normal breast tissues. Notably, statistically significant differences were observed in long-term survival between patients with luminal A (P=0.04) and HER2-enriched (P=0.008) breast cancer, with high and low expression levels of ING3. The results of the Transwell migration and invasion assays demonstrated that overexpression of ING3 significantly inhibited the migratory and invasive abilities of MCF7 (P<0.05) and HCC1937 (P<0.05) cells. The results of the wound healing assay demonstrated that the percentage wound closure significantly decreased in cells transfected with LV5-ING3 compared with the negative control group at 12 h (P<0.05) and 24 h (P<0.01). The PI3K/AKT, JAK/STAT, NF-κB and Wnt/ß-catenin pathways are the potential pathways regulated by ING3. Notably, overexpression of ING3 inhibited migration and invasion in vitro. However, further studies are required to determine whether ING3 regulates the biological behavior of breast cancer via tumor-related pathways.

Evaluation of the body mass index in breast cancer prognosis in a cohort of small-stature overweight patients: multi-center study in China.

BACKGROUND: Overweight and obesity have become a major health issue in the past 30 years. Several studies have already shown that obesity is significantly associated with a higher risk of developing breast cancer. However, few studies have assessed the prognostic value of the body mass index (BMI) in Asian populations. The purpose of this study was to retrospectively analyze the impact of BMI on the prognosis of breast cancer in overweight, under 160 cm tall patients from southern China. METHODS: We retrospectively analyzed data from 525 breast cancer patients diagnosed between 2003 to 2010 in a multi-center of China. After applying the exclusion criteria, 315 patients with complete data were retained. Their clinical and pathological characteristics were compared using the chi-square test. Survival analysis was performed with the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox regression to calculate hormone receptor status, HER-2 status, lymph node status, age, BMI and tumor size hazard ratio (HR), and 95% confidence intervals (95% CI). RESULTS: There was a strong correlation between BMI and age in the baseline feature analysis (P=0.001). After grouping the patients according to the molecular type of cancer, we found that in Luminal A and B, the BMI was related to age (P=0.002, P=0.010). The disease-free survival (DFS) and overall survival (OS) of patients with different BMI were not significantly different. This conclusion was also reached by pairwise comparison of subgroups. There was no significant difference in recurrence in patients from different BMI groups. We did not find a critical weight threshold associated with higher risk of recurrence. There were no statistically significant differences in treatment among the three BMI groups of overweight patients. CONCLUSIONS: We found that the BMI of Chinese breast cancer patients is related to age but not prognosis.

The treatment process of an extremely rare giant borderline phyllodes tumor of breast: case report and literature review.

Giant phyllodes tumors are rare fibroepithelial neoplasms, usually defined as >10 cm. It is often difficult for pathologists to distinguish fibroadenomas from phyllodes tumors and determine the malignant potential level. The current treatment principle is to ensure the extended resection of tumors with a margin of 1 cm or more. For patients with multiple local recurrences or large tumors after surgery, simple mastectomy is recommended. Axillary management should be considered when breast cancer is diagnosed at the same time. We now present a rare case: a female patient found a right breast mass in 2014, and the mass had continued to grow for more than 7 months, and she was ultimately diagnosed with a giant phyllodes tumor with a diameter of 30 cm. Extensive resection is a suitable method to treat smaller phyllodes tumors, but giant phyllodes tumors require mastectomy, so the patient in this case underwent a total mastectomy. We removed the mass completely without destroying the normal tissue and structure. The treatment effect was obvious, and no related adverse events occurred during or after the operation, the postoperative recovery was good, and the patient was discharged once she was verified to be in a stable condition. This case is the first reported case of a patient who had a giant borderline phyllodes tumor with a diameter of 30 cm, underwent total mastectomy, and was followed up for 6 months without recurrence. The long-term effect of the treatment will be further evaluated after 5 years.

Environmental Surveillance and Transmission Risk Assessments for SARS-CoV-2 in a Fitness Center.

Fitness centers are considered high risk for SARS-CoV-2 transmission due to their high human occupancy and the type of activity taking place in them, especially when individuals pre-symptomatic or asymptomatic for COVID-19 exercise in the facilities. In this study, air (N=21) and surface (N=8) samples were collected at a fitness center through five sampling events from August to November 2020 after the reopening restrictions were lifted in Florida. The total attendance was ~2500 patrons during our air and environmental sampling work. Air samples were collected using stationary and personal bioaerosol samplers. Moistened flocked nylon swabs were used to collect samples from high-touch surfaces. We did not detect SARS-CoV-2 by rRT-PCR analyses in any air or surface sample. A simplified infection risk model based on the Wells-Riley equation predicts that the probability of infection in this fitness center was 1.77% following its ventilation system upgrades based on CDC guidelines, and that risk was further reduced to 0.89% when patrons used face masks. Our model also predicts that a combination of high ventilation, minimal air recirculation, air filtration, and UV sterilization of recirculated air reduced the infection risk up to 94% compared to poorly ventilated facilities. Amongst these measures, high ventilation with outdoor air is most critical in reducing the airborne transmission of SARS-CoV-2. For buildings that cannot avoid air recirculation due to energy costs, the use of high filtration and/or air disinfection devices are alternatives to reducing the probability of acquiring SARS-CoV-2 through inhalation exposure. In contrast to the perceived ranking of high risk, the infection risk in fitness centers that follow CDC reopening guidance, including implementation of engineering and administrative controls, and use of personal protective equipment, can be low, and these facilities can offer a relatively safe venue for patrons to exercise.

Direct Transfer of Phthalate and Alternative Plasticizers from Indoor Source Products to Dust: Laboratory Measurements and Predictive Modeling.

Phthalate and alternative plasticizers are semivolatile organic compounds (SVOCs) and among the most abundant indoor pollutants. Although ingestion of dust is one of the major exposure pathways to them, migration knowledge from source products to indoor dust is still limited. Systematic chamber measurements were conducted to investigate the direct transfer of these SVOCs between source products and dust in contact with the source. Substantial direct source-to-dust transfer of SVOCs was observed for all tests. The concentration of bis(2-ethylhexyl)phthalate in dust was 12 times higher than the pre-experimental level after only two days of source-dust contact. A mechanistic model was developed to predict the direct transfer process, and a reasonable agreement between model predictions and measurements was achieved. The octanol/air partition coefficient (Koa) of SVOCs, the emission parameter of the source product (y0), and the characteristics of the dust layer (i.e., porosity and thickness) control the transfer, affecting the SVOC concentration in dust, the kinetics of direct transfer, or both. Dust mass loading has a significant influence on the transfer, while relative humidity only has a limited effect. The findings suggest that minimizing the use of SVOC-containing products and house vacuuming are effective intervention strategies to reduce young children's exposure to SVOCs.

Clinical and pathological response to neoadjuvant chemotherapy with different chemotherapy regimens predicts the outcome of locally advanced breast cancer.

BACKGROUND: This retrospective analysis was designed to research whether clinical response partial response (PR)/complete response (CR) and pathological response (PCR) to neoadjuvant chemotherapy can translate into prognosis benefit pathological response in patients with locally advanced breast cancer and whether different chemotherapy regimens will influence the outcomes. METHODS: One hundred and thirty-five patients with breast cancer patients who received neoadjuvant chemotherapy were included in the retrospective analysis. Patients were followed up strictly. Overall survival (OS) was evaluated by the Kaplan-Meier analysis. The comparison of the clinical and pathological characteristics and recurrence was performed using the carried out by chi-squared and Fisher's exact tests. Univariate and multivariate analyses were performed by the Cox regression analysis. RESULTS: Clinical response was strongly correlated with lymph nodes status (P=0.032). The OS comparison of pathological response between the pCR group and non-pCR groups did not exhibit statistically significant differences (P=0.400). A similar non-significant response result was observed in the comparison of clinical response between the PR/CR and SD/PD groups group (P=0.108). Univariate and multivariate analyses did not support clinical response (P=0.156 P=0.095 respectively) or pathological response (P=0.600 P=0.144 respectively) as the predictors of prognosis. There were no significant differences in either the comparison of the clinical response group it seems no statistically significance (P=0.496) or the comparison of the pathological response group (P=0.460). OS analyses across different neoadjuvant chemotherapy regimens demonstrated no significant differences (P=0.307). In the PR/CR and PD/SD comparison of every single regimen, there were no significant differences. However, for patients with PR/CR patients from the comparison of five regimens, namely, TAC, FAC, AC-T, AT and TCBP demonstrated a significant difference (P=0.022). In the group of patients with luminal A breast cancer, the result of the Fisher's exact test approached significant (P=0.059). CONCLUSIONS: Neither PR/CR nor pCR can translate into long-term outcome benefit. PR/CR and PCR are not independent predictors in patients with advanced breast cancer. Patients who received a taxane + anthracycline regimen exhibited a higher recurrence rate than any other regimens, especially those patients with luminal A breast cancer.

A needle trap device method for sampling and analysis of semi-volatile organic compounds in air.

Semi-volatile organic compounds (SVOCs), such as phthalates, organophosphates, and polybrominated diphenyl ethers, are emerging as an important class of pollutants that are of serious health concerns. Determining concentrations of these pollutants is of great importance for environmental and exposure studies. In this work, a needle trap device (NTD) method was developed to measure the concentration of SVOCs in air samples. Sorbents were packed in the NTD to capture SVOCs with the aid of a sampling pump. NTD operational parameters, such as desorption temperature, desorption time, and sampling flow rate, were optimized for the target SVOCs. The limit of detection for air sampling by the NTD method ranged between 5 pg and 1 ng, depending on the SVOC compound. The variations in terms of NTD repeatability and reproducibility were lower than 14% for all cases. In addition, the influence of other experimental parameters, such as sampling temperature and humidity, breakthrough volume, NTD storage time, as well as carryover effect were examined. Finally, NTDs were used to determine emissions of gas-phase SVOCs from various consumer products in an emission cell and to collect total airborne SVOC samples (gas and particle phases) in an office. The results of NTD method were in an agreement with data obtained by conventional active sampling methods using Tenax® sorbent tubes and polyurethane foam samplers, but with improvements of relative standard deviation, sensitivity, and sampling time. The results demonstrated that the NTD method is a simple, sensitive, effective, reusable, and inexpensive technique for sampling and analyzing SVOCs in the concentration range from 2 ng m-3 to 100 µg m-3 in air.

Phthalates and organophosphates in settled dust and HVAC filter dust of U.S. low-income homes: Association with season, building characteristics, and childhood asthma.

Phthalates and organophosphates are ubiquitous indoor semi-volatile organic contaminants (SVOCs) that have been widely used as plasticizers and flame retardants in consumer products. Although many studies have assessed their levels in house dust, only a few used dust samples captured by filters of building heating, ventilation, and air conditioning (HVAC) systems. HVAC filters collect particles from large volumes of air over a long period of time (potentially known) and thus provide a spatially and temporally integrated concentration. This study measured concentrations of phthalates and organophosphates in HVAC filter dust and settled floor dust collected from low-income homes in Texas, United States, in both the summer and winter seasons. The most frequently detected compounds were benzyl butyl phthalate (BBzP), di-(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DnOP), tris (1-chloro-2-propyl) phosphate (TCIPP), triphenyl phosphate (TPHP), and tris (1,3-dichloroisopropyl) phosphate (TDCIPP). The median level of TCIPP in settled dust was 3- to 180-times higher than levels reported in other studies of residential homes. Significantly higher concentrations were observed in HVAC filter dust as compared to settled dust for most of the frequently detected compounds in both seasons, except for several phthalates in the winter. SVOC concentrations in settled dust in winter were generally higher than in summer, while different seasonality patterns were found for HVAC filter dust. Settled dust samples from homes with vinyl flooring contained significantly higher levels of BBzP and DEHP as compared to homes with other types of floor material. The concentration of DEHP and TDCIPP in settled dust also significantly associated with the presence of carpet in homes. Cleaning activities to remove dust from furniture actually increased the levels of certain compounds in HVAC filter dust, while frequent vacuuming of carpet helped to decrease the concentrations of some compounds in settled dust. Additionally, the size and age of a given house also correlated with the levels of some pollutants in dust. A statistically significant association between DEHP concentration in HVAC filter dust in summer and the severity of asthma in children was observed. These results suggest that HVAC filter dust represents a useful sampling medium to monitor indoor SVOC concentrations with high sensitivity; in contrast, when using settled dust, in addition to consideration of seasonal influences, it is critical to know the sampling location because the type and level of SVOCs may be related to local materials used there.