Assessing the Spatiotemporal Characteristics, Factor Importance, and Health Impacts of Air Pollution in Seoul by Integrating Machine Learning into Land-Use Regression Modeling at High Spatiotemporal Resolutions.

Previous studies have characterized spatial patterns of air pollution with land-use regression (LUR) models. However, the spatiotemporal characteristics of air pollution, the contribution of various factors to them, and the resultant health impacts have yet to be evaluated comprehensively. This study integrates machine learning (random forest) into LUR modeling (LURF) with intensive evaluations to develop high spatiotemporal resolution prediction models to estimate daily and diurnal PM2.5 and NO2 in Seoul, South Korea, at the spatial resolution of 500 m for a year (2019) and to then evaluate the contribution of driving factors and quantify the resultant premature mortality. Our results show that incorporating the random forest algorithm into our LUR model improves the model performance. Meteorological conditions have a great influence on daily models, while land-use factors play important roles in diurnal models. Our health assessment using dynamic population data estimates that PM2.5 and NO2 pollution, when combined, causes a total of 11,183 (95% CI: 5837-16,354) premature mortalities in Seoul in 2019, of which 64.9% are due to PM2.5, while the remaining are attributable to NO2. The air pollution-attributable health impacts in Seoul are largely caused by cardiovascular diseases including stroke. This study pinpoints the significant spatiotemporal variations and health impact of PM2.5 and NO2 in Seoul, providing essential data for epidemiological research and air quality management.

Exploiting evolutionary trade-offs for posttreatment management of drug-resistant populations.

Antibiotic resistance frequently evolves through fitness trade-offs in which the genetic alterations that confer resistance to a drug can also cause growth defects in resistant cells. Here, through experimental evolution in a microfluidics-based turbidostat, we demonstrate that antibiotic-resistant cells can be efficiently inhibited by amplifying the fitness costs associated with drug-resistance evolution. Using tavaborole-resistant Escherichia coli as a model, we show that genetic mutations in leucyl-tRNA synthetase (that underlie tavaborole resistance) make resistant cells intolerant to norvaline, a chemical analog of leucine that is mistakenly used by tavaborole-resistant cells for protein synthesis. We then show that tavaborole-sensitive cells quickly outcompete tavaborole-resistant cells in the presence of norvaline due to the amplified cost of the molecular defect of tavaborole resistance. This finding illustrates that understanding molecular mechanisms of drug resistance allows us to effectively amplify even small evolutionary vulnerabilities of resistant cells to potentially enhance or enable adaptive therapies by accelerating posttreatment competition between resistant and susceptible cells.

Does the low-carbon city pilot policy work in China? A company-level analysis based on the PSM-DID model.

To reduce carbon emissions and pursue sustainable economic development, China's central government formulated the low-carbon city pilot (LCCP) policy. Current studies focus primarily on the impact of the policy at the macro level (provinces and cities). So far, no study has looked at the impact of the LCCP policy on companies' environmental expenditures. Besides, as the LCCP policy is a weak-constraining central policy, it is interesting to see how it works at the company level. We employ company-level empirical data and the Propensity Score Matching - Difference in Differences (PSM-DID) method, which outperforms the traditional DID model in avoiding sample selection bias, to address the above issues. We concentrate on the second phase of the LCCP policy from 2010 to 2016, encompassing 197 listed companies in China's secondary and transportation industries. Our statistical results show that if the listed company's host city has piloted the LCCP policy, the company's environmental expenditures are reduced by 0.91 points at the 1% significance level. The above finding calls attention to the policy-implementation gap between the central and the local governments in China, which may make those weak-constraining central policies like the LCCP policy have purpose-defeating outcomes at the company level.

A novel approach for assessing the spatiotemporal trend of health risk from ambient particulate matter components: Case of Hong Kong.

The spatiotemporal assessment of health risk due to exposure to particulate matter (PM) components should be well studied because of the different toxicity among PM components. However, this research topic has long been overlooked. This study aimed to examine the spatiotemporal variability in ambient respirable PM (PM10) components associated inhalation carcinogenic and non-carcinogenic risk (ICR and INCR) in Hong Kong over 2015-2019. The land-use regression (LUR) approach was adopted to predict the spatial distribution of PM10 component concentrations for the period of 2015-2019, whereas the ICR and INCR values of PM10 components were also estimated using the classic health risk assessment method. Both concentration of PM10 and INCR of PM10 components showed a general decreasing trend, while ICR of PM10 components increased slightly over the study period. LUR-model-based spatial maps at 500 m × 500 m resolution revealed the important spatial variability in PM10 and its eleven components, and their associated ICR and INCR values. High pollution levels and high ICR and INCR of studied PM10 components were generally found in developed urban areas and along the road network. Despite the fact that the PM10 concentrations met the Hong Kong annual PM10 air quality objective of 50 µg/m3, there was still significant potential health risk from the studied PM10 components. This study highlights the importance of taking PM component concentrations and associated inhalation health risk as well as PM mass concentrations into account for the perspective of air quality management and protecting public health.

Prognostic factors for overall survival in malignant ureteral obstruction.

INTRODUCTION: To identify prognostic factors for overall survival (OS) in patients with malignant ureteral obstruction (MUO) from gynecologic malignancy (GM), with the goal of improving patient selection for urinary diversion. MATERIALS AND METHODS: Retrospective review of 126 patients with MUO from GM at two academic centers from 2011-2019. Factors related to OS identified by Cox regression proportional hazard model. In patients with incomplete survival data (n = 30), hospice was used as a surrogate for death. Multivariate models and receivers operating characteristics (ROC) curves were created for hemoglobin and albumin values. RESULTS: Overall median survival was 6.2 months. On univariate analysis, age at diagnosis, Charlson Comorbidity Index (CCI) ≥ 8, advanced clinical stage, ascites, pleural effusion, albumin, and hemoglobin were associated with poor OS. OS was higher for those receiving ureteral stenting as compared with no intervention. There was no survival difference based on hydronephrosis grade, stent failure (SF), or creatinine at the time of intervention. On multivariate analysis, albumin < 2.85 g/dL and hemoglobin < 9.6 g/dL were predictive of poor OS. CONCLUSIONS: OS in patients with MUO due to GM is poor. Several prognostic factors for poor survival including low serum albumin and hemoglobin were identified. Ureteral stenting was associated with improved OS compared to observation, but selection bias likely contributed to this result. Additional studies are needed to clarify this finding. These data can be utilized to counsel patients regarding outcomes after urinary diversion in the setting of MUO and perhaps avoid additional procedures in some of these patients who will not derive meaningful benefit.

Retzius-sparing robot-assisted radical prostatectomy: early learning curve experience in three continents.

OBJECTIVE: To assess the effect of surgical experience on peri-operative, functional and oncological outcomes during the first 50 Retzius-sparing robot-assisted radical prostatectomy (RsRARP) cases performed by surgeons naïve to this novel approach. MATERIALS AND METHODS: We retrospectively evaluated the initial cases operated by 14 surgeons in 12 different international centres. Pre-, peri- and postoperative features of the first 50 patients operated by each surgeon in all the participating centres were collected. The effect of surgical experience on peri-operative, functional and oncological outcomes was firstly evaluated after stratification by level of surgical experience (initial [≤25 cases] and expert [>25 cases]) and after using locally weighted scatterplot smoothing to graphically explore the relationship between surgical experience and the outcomes of interest. RESULTS: We evaluated 626 patients. The median follow-up was 13 months in the initial group and 9 months in the expert group (P = 0.002). Preoperative features overlapped between the two groups. Shorter console time (140 vs 120 min; P = 0.001) and a trend towards lower complications rates (13 vs 5.5%; P = 0.038) were observed in the expert group. The relationship between surgical experience and console time, immediate urinary continence recovery and Clavien-Dindo grade ≥2 complications was linear, without reaching a plateau, after 50 cases. Conversely, a non-linear relationship was observed between surgical experience and positive surgical margins (PSMs). CONCLUSIONS: In this first report of a multicentre experience of RsRARP during the learning curve, we found that console time, immediate urinary continence recovery and postoperative complications are optimal from the beginning and further quickly improve during the learning process, while PSM rates did not clearly improve over the first 50 cases.

Pre-industrial plague transmission is mediated by the synergistic effect of temperature and aridity index.

BACKGROUND: Although the linkage between climate change and plague transmission has been proposed in previous studies, the dominant approach has been to address the linkage with traditional statistical methods, while the possible non-linearity, non-stationarity and low frequency domain of the linkage has not been fully considered. We seek to address the above issue by investigating plague transmission in pre-industrial Europe (AD1347-1760) at both continental and country levels. METHODS: We apply Granger Causality Analysis to identify the casual relationship between climatic variables and plague outbreaks. We then apply Wavelet Analysis to explore the non-linear and non-stationary association between climate change and plague outbreaks. RESULTS: Our results show that 5-year lagged temperature and aridity index are the significant determinants of plague outbreaks in pre-industrial Europe. At the multi-decadal time scale, there are more frequent plague outbreaks in a cold and arid climate. The synergy of temperature and aridity index, rather than their individual effect, is more imperative in driving plague outbreaks, which is valid at both the continental and country levels. CONCLUSIONS: Plague outbreaks come after cold and dry spells. The multi-decadal climate variability is imperative in driving the cycles of plague outbreaks in pre-industrial Europe. The lagged and multi-decadal effect of climate change on plague outbreaks may be attributable to the complexity of ecological, social, or climate systems, through which climate exerts its influence on plague dynamics. These findings may contribute to improve our understanding of the epidemiology of plague and other rodent-borne or flea-borne infectious diseases in human history.

In Utero exposure to low-dose alcohol induces reprogramming of mammary development and tumor risk in MMTV-erbB-2 transgenic mice.

There is increasing evidence that prenatal exposure to environmental factors may modify breast cancer risk later in life. This study aimed to investigate the effects of in utero exposure to low-dose alcohol on mammary development and tumor risk. Pregnant MMTV-erbB-2 mice were exposed to alcohol (6 g/kg/day) between day 13 and day 19 of gestation, and the female offspring were examined for tumor risk. Whole mount analysis indicated that in utero exposure to low-dose alcohol induced significant increases in ductal extension at 10 weeks of age. Molecular analysis showed that in utero alcohol exposure induced upregulation of ERα signaling and activation of Akt and Erk1/2 in pubertal mammary glands. However, enhanced signaling in the EGFR/erbB-2 pathway appeared to be more prominent in 10-week-old glands than did signaling in the other pathways. Interestingly, tumor development in mice with in utero exposure to low-dose alcohol was slightly delayed compared to control mice, but tumor multiplicity was increased. The results indicate that in utero exposure to low-dose alcohol induces the reprogramming of mammary development by mechanisms that include altered signaling in the estrogen receptor (ER) and erbB-2 pathways. The intriguing tumor development pattern might be related to alcohol dose and exposure conditions, and warrants further investigation.

The causality analysis of climate change and large-scale human crisis.

Recent studies have shown strong temporal correlations between past climate changes and societal crises. However, the specific causal mechanisms underlying this relation have not been addressed. We explored quantitative responses of 14 fine-grained agro-ecological, socioeconomic, and demographic variables to climate fluctuations from A.D. 1500-1800 in Europe. Results show that cooling from A.D. 1560-1660 caused successive agro-ecological, socioeconomic, and demographic catastrophes, leading to the General Crisis of the Seventeenth Century. We identified a set of causal linkages between climate change and human crisis. Using temperature data and climate-driven economic variables, we simulated the alternation of defined "golden" and "dark" ages in Europe and the Northern Hemisphere during the past millennium. Our findings indicate that climate change was the ultimate cause, and climate-driven economic downturn was the direct cause, of large-scale human crises in preindustrial Europe and the Northern Hemisphere.

How far can air pollution affect tourism in China? Evidence from panel unconditional quantile regressions.

Previous studies provide empirical evidence for the connection between air pollution and tourism. However, many of them take the nexus as a linear one. It remains unexplored whether any thresholds are required for the nexus to materialize. This study systematically investigates whether PM2.5 concentrations-an essential indicator of air pollution-affect tourism in China at various tourism development levels. We analyze 284 Chinese cities from 2008 to 2018 using the Unconditional Quantile Regression method. Our statistical results reveal that air pollution positively influences tourism (regarding tourist visits and tourism revenue) in areas with low tourism development levels. However, a complex correlation between air pollution and tourism emerges when tourism development has reached a certain level. The correlation is initially negative, then positive, and finally disappears. But, the overall correlation remains negative. The effects of the interaction between air pollution and tourism resources on tourism are inverted U-shaped, implying that tourism resources can mitigate the negative effects of air pollution on tourism only when tourism development has reached a certain level. Based on the above findings, the associated policy implications are discussed.

The Salivary Microbiome and Predicted Metabolite Production Are Associated with Barrett's Esophagus and High-Grade Dysplasia or Adenocarcinoma.

BACKGROUND: Esophageal adenocarcinoma (EAC) is rising in incidence, and established risk factors do not explain this trend. Esophageal microbiome alterations have been associated with Barrett's esophagus (BE) and dysplasia and EAC. The oral microbiome is tightly linked to the esophageal microbiome; this study aimed to identify salivary microbiome-related factors associated with BE, dysplasia, and EAC. METHODS: Clinical data and oral health history were collected from patients with and without BE. The salivary microbiome was characterized, assessing differential relative abundance of taxa by 16S rRNA gene sequencing and associations between microbiome composition and clinical features. Microbiome metabolic modeling was used to predict metabolite production. RESULTS: A total of 244 patients (125 non-BE and 119 BE) were analyzed. Patients with high-grade dysplasia (HGD)/EAC had a significantly higher prevalence of tooth loss (P = 0.001). There were significant shifts with increased dysbiosis associated with HGD/EAC, independent of tooth loss, with the largest shifts within the genus Streptococcus. Modeling predicted significant shifts in the microbiome metabolic capacities, including increases in L-lactic acid and decreases in butyric acid and L-tryptophan production in HGD/EAC. CONCLUSIONS: Marked dysbiosis in the salivary microbiome is associated with HGD and EAC, with notable increases within the genus Streptococcus and accompanying changes in predicted metabolite production. Further work is warranted to identify the biological significance of these alterations and to validate metabolic shifts. IMPACT: There is an association between oral dysbiosis and HGD/EAC. Further work is needed to establish the diagnostic, predictive, and causal potential of this relationship.

Changes in paleo-groundwater levels revealed by water wells and their relationship with climate variations in imperial Southern China.

Based on records of the bottom elevations of 511 ancient water wells from published archaeological reports, we reconstructed the paleo-groundwater levels (PGWL) in urban areas of Chengdu, Changsha, Nanjing, Suzhou, Suqian, Yancheng, Fuzhou, and Guangzhou cities in southern China. Our PGWL reconstruction shows that PGWL varied in two patterns. In the inland monsoon region (Chengdu and Changsha), there was a low PGWL in Jin (AD 266-420) and South Song (AD 1127-1279), and a high PGWL in Tang (AD 618-907) and Ming (AD 1368-1644). In the coastal region (Yancheng, Fuzhou, and Guangzhou), there was a low PGWL in Jin (AD 266-420) and Ming (AD 1368-1644) but a high PGWL in Tang (AD 618-907) and Song (AD 960-1279). Via cross-wavelet transform and wavelet transform coherence analyses, we found that monsoon and temperature significantly drove the PGWL fluctuations at the inter-centennial scale. East Asian Summer Monsoon-induced precipitation has continuously affected cities in the inland monsoon area represented by Chengdu and Changsha over the past 2,500 years. It has also intermittently affected Nanjing and Suzhou when EASM intensified. In parallel, temperature influenced the PGWL in coastal cities such as Yancheng, Fuzhou, and Guangzhou via the changes in the sea level. Also, the temperature affected the PGWL in relatively inland cities during climatic anomalies such as the Medieval Warm Period and Little Ice Age. This study demonstrates the value of archaeological records in learning how climatic factors influence the PGWL variation and its mechanism.

Evaluation of Enterococcal Probiotic Usage and Review of Potential Health Benefits, Safety, and Risk of Antibiotic-Resistant Strain Emergence.

Enterococci are often used in probiotics but can also cause nosocomial infections. As such, enterococcal consumption may have beneficial health effects, but a thorough evaluation of virulence absence and risk of antibiotic resistance spread is needed at the strain level. This article reviewed ten online health product shopping websites in the US. On these websites, 23 probiotic products using enterococci were found across 12 companies. In addition, this article reviewed studies that demonstrated the probiotic potential of enterococcal consumption (e.g., gastrointestinal and respiratory disease, hyperlipidemia alleviation, as well as infection prevention). To investigate the safety aspects of enterococci, the present work examined studies evaluating virulence factors and antibiotic resistance. Furthermore, this article assessed research that explored these virulent factors, specifically in probiotics containing enterococci, as well as the potential transfer mechanism of their antibiotic resistance. Based on reviewed data, enterococcal probiotic consumption has been proven beneficial for conditions or symptoms of multiple diseases without any apparent adverse effects. However, due to the plasmid- or transposon-mediated gene transfer ability of enterococci, surveillance monitoring and further studies regarding enterococcal consumption are warranted. Future studies that identify enterococcal strains safe to use in probiotics without virulence factors and antibiotic resistance are imperative for evidence-based decisions by health organizations and government agencies.

Fossil Carychiidae (Eupulmonata, Ellobioidea) from the Lower Pleistocene Nashua Formation of Florida, with the description of a new species.

Recent fossil shell mining for a new rail line in the Orlando area of Orange County, Florida has uncovered two species of the ellobioid genus Carychium O. F. Müller, 1773 in a bed of freshwater marl from the Lower Pleistocene Nashua Formation. To taxonomically interpret these finds, the well-preserved shells were imaged via high-resolution X-ray tomography (micro-CT) to view significant internal diagnostic characters such as the columellar configuration and the degree of lamellar sinuosity and their relationship in context to the entire shell. The image data are compared to that of type material and extant and fossil Carychium species inhabiting the SE USA, Mexico, Central America, and Jamaica. Based on these results, the species Carychiumfloridanum G. H. Clapp, 1918 and Carychiumnashuaensesp. nov. are identified from fossil shells dating from the Early Pleistocene. This work documents the first fossil members of C.floridanum and the first fossil Carychium from the SE USA.

The Salivary Microbiome and Predicted Metabolite Production are Associated with Progression from Barrett's Esophagus to Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) is rising in incidence and associated with poor survival, and established risk factors do not explain this trend. Microbiome alterations have been associated with progression from the precursor Barrett's esophagus (BE) to EAC, yet the oral microbiome, tightly linked to the esophageal microbiome and easier to sample, has not been extensively studied in this context. We aimed to assess the relationship between the salivary microbiome and neoplastic progression in BE to identify microbiome-related factors that may drive EAC development. We collected clinical data and oral health and hygiene history and characterized the salivary microbiome from 250 patients with and without BE, including 78 with advanced neoplasia (high grade dysplasia or early adenocarcinoma). We assessed differential relative abundance of taxa by 16S rRNA gene sequencing and associations between microbiome composition and clinical features and used microbiome metabolic modeling to predict metabolite production. We found significant shifts and increased dysbiosis associated with progression to advanced neoplasia, with these associations occurring independent of tooth loss, and the largest shifts were with the genus Streptococcus. Microbiome metabolic models predicted significant shifts in the metabolic capacities of the salivary microbiome in patients with advanced neoplasia, including increases in L-lactic acid and decreases in butyric acid and L-tryptophan production. Our results suggest both a mechanistic and predictive role for the oral microbiome in esophageal adenocarcinoma. Further work is warranted to identify the biological significance of these alterations, to validate metabolic shifts, and to determine whether they represent viable therapeutic targets for prevention of progression in BE.

Preterm birth is associated with xenobiotics and predicted by the vaginal metabolome.

Spontaneous preterm birth (sPTB) is a leading cause of maternal and neonatal morbidity and mortality, yet its prevention and early risk stratification are limited. Previous investigations have suggested that vaginal microbes and metabolites may be implicated in sPTB. Here we performed untargeted metabolomics on 232 second-trimester vaginal samples, 80 from pregnancies ending preterm. We find multiple associations between vaginal metabolites and subsequent preterm birth, and propose that several of these metabolites, including diethanolamine and ethyl glucoside, are exogenous. We observe associations between the metabolome and microbiome profiles previously obtained using 16S ribosomal RNA amplicon sequencing, including correlations between bacteria considered suboptimal, such as Gardnerella vaginalis, and metabolites enriched in term pregnancies, such as tyramine. We investigate these associations using metabolic models. We use machine learning models to predict sPTB risk from metabolite levels, weeks to months before birth, with good accuracy (area under receiver operating characteristic curve of 0.78). These models, which we validate using two external cohorts, are more accurate than microbiome-based and maternal covariates-based models (area under receiver operating characteristic curve of 0.55-0.59). Our results demonstrate the potential of vaginal metabolites as early biomarkers of sPTB and highlight exogenous exposures as potential risk factors for prematurity.

Did Hydro-climatic Extremes, Positive Checks, and Economic Fluctuations Modulate the Epidemics Outbreaks in Late Imperial China?

Empirical research has shown that climate-related variables, the decline in economic well-being, and the mutual reinforcement of positive checks are the primary drivers of epidemic outbreaks in recent human history. However, their relative importance in causing the outbreak of epidemics is rarely examined quantitatively in a single study. I sought to address this issue by analyzing the 1402 epidemic incidents in China between 1841 and 1911, which partially overlaps partly with the Third Pandemic period. Fine-grained historical big data, multiple regression, and wavelet coherence analysis were employed. Statistical results show that economic fluctuations drove the country-wide epidemics outbreaks in China in inter-annual and decadal time scales. Economic fluctuations could cause short-term hardship and long-term impoverishment to the underprivileged social groups since a large portion of the Chinese population lived at the subsistence level in the past. The fluctuations might have sustained the repeated waves of epidemic outbreaks during the Third Pandemic period. Supplementary Information: The online version contains supplementary material available at 10.1007/s10745-021-00272-7.

Microsurgical treatment of lower extremity lymphedema: A multidisciplinary approach to improve morbidity in advanced penile cancer patients.

INTRODUCTION: Lower extremity lymphedema is a major source of morbidity in up to 70% of penile cancer patients. Lymphedema is often thought to be incurable, though surgical treatments have started to emerge. This study is the first to apply lymphovenous bypass specifically to penile cancer patients status post lymphadenectomy. METHODS: We performed microsurgical lymphovenous bypass in 3 patients who underwent inguinal lymphadenectomy for advanced penile cancer, and later lymph node transplant in 1 patient. RESULTS: The lymphovenous bypass was performed by a trained microsurgeon: Two patients were treated as outpatients for lymphedema, and 1 patient underwent prophylactic lymphovenous bypass simultaneously with initial lymphadenectomy. We saw significant improvement in patient's clinical lymphedema as well as lymphatic drainage on infared imaging for 2 of 3 patients at 12 months, however 1 of these patients did require later lymph node transfer at 24 months. CONCLUSION: This early proof of concept study shows that these procedures should be considered and studied further in the treatment and prevention of debilitating lymphedema in the penile cancer population.

Do no harm: the role of perioperative heparin in urethroplasty.

OBJECTIVE: To examine the safety of single modality mechanical venous thromboembolism (VTE) prophylaxis in patients undergoing urethroplasty. VTE is a perioperative complication with significant morbidity. Routine use of peri-operative VTE prophylaxis is common guideline-driven practice across multiple surgical specialties. There is a discrepancy between guideline recommendations and clinical practice in the administration of peri-operative low-dose unfractionated heparin (LDUH) for urethroplasty. METHODS: Patients were identified from an IRB-approved database of patients undergoing urethral reconstruction by a single surgeon at MedStar Washington Hospital Center from 2012 to 2020. All patients had sequential compression devices (SCD) prior to anesthesia induction. Select patients received LDUH as dual prophylaxis. Primary endpoint was perioperative VTE within 30 days. RESULTS: We identified 345 patients who met inclusion criteria. Sixty-nine patients received peri-operative LDUH. One patient had a deep vein thrombosis in the SCD only group. CONCLUSION: Routine LDUH administration likely overtreats men undergoing urethroplasty. There may be a subset of men in whom dual prophylaxis with LDUH and SCD is beneficial for prevention of VTE. Current guidelines do not offer adequate criteria to identify these men. We offer clinical considerations to help guide further study to identify these patients.