Silencing endomucin in bone marrow sinusoids improves hematopoietic stem and progenitor cell homing during transplantation.

Efficient homing of infused hematopoietic stem and progenitor cells (HSPCs) into the bone marrow (BM) is the prerequisite for successful hematopoietic stem cell transplantation. However, only a small part of infused HSPCs find their way to the BM niche. A better understanding of the mechanisms that facilitate HSPC homing will help to develop strategies to improve the initial HSPC engraftment and subsequent hematopoietic regeneration. Here, we show that irradiation upregulates the endomucin expression of endothelial cells in vivo and in vitro. Furthermore, depletion of endomucin in irradiated endothelial cells with short interfering RNA (siRNA) increases the HSPC-endothelial cell adhesion in vitro. To abrogate the endomucin of BM sinusoidal endothelial cells (BM-SECs) in vivo, we develop a siRNA-loaded bovine serum albumin nanoparticle for targeted delivery. Nanoparticle-mediated siRNA delivery successfully silences endomucin expression in BM-SECs and improves HSPC homing during transplantation. These results reveal that endomucin plays a critical role in HSPC homing during transplantation and that gene-based manipulation of BM-SEC endomucin in vivo can be exploited to improve the efficacy of HSPC transplantation.

Vaginal extracellular vesicles impair fertility in endometriosis by favoring Th17/Treg imbalance and inhibiting sperm activity.

Extracellular vesicles (EVs) play a key role in various diseases. However, their effect on endometriosis (EMs)-associated infertility is poorly understood. We co-cultured EVs from the female vaginal secretions with human sperm and also generated a mouse model of EMs by allogenic transplant to explore the effect of EVs on fertility. EVs from individuals with EMs-associated infertility (E-EVs) significantly inhibited the total motility (26.46% vs. 47.1%), progressive motility (18.78% vs. 41.06%), linear velocity (21.98 vs. 41.91 µm/s) and the acrosome reaction (AR) rate (5% vs. 22.3%) of human sperm in contrast to the control group (PBS). Furthermore, E-EVs dose-dependently decreased the intracellular Ca2+ ([Ca2+]i), a pivotal regulator of sperm function. Conversely, healthy women (H-EVs) increased human sperm motion parameters, the AR rate, and sperm [Ca2+]i. Importantly, the mouse model of EMs confirmed that E-EVs further decreased the conception rate and the mean number of embryo implantations (7.6 ± 3.06 vs. 4.5 ± 3.21) compared with the control mice by inducing the production of inflammatory cytokines leading to a Th17/Treg imbalance. H-EVs could restore impaired fertility by restoring the Th17/Treg balance. We determined the impact of EVs derived from the female genital tract on human sperm function and studied the possible mechanisms by which it affects fertility. Our findings provide a novel rationale to ameliorate EMs-associated infertility.

Gd(III)-Catalyzed Regio-, Diastereo-, and Enantioselective [4 + 2] Photocycloaddition of Naphthalene Derivatives.

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

Association between ambient exposure to PM2.5 and upper aerodigestive tract cancer in Los Angeles.

Fine particulate matter (PM2.5 ) contains carcinogens similar to those generated by tobacco smoking, which may increase the risks of developing smoking-related cancers, such as upper aerodigestive track (UADT) cancers, for both smokers and never-smokers. Therefore, it is imperative to understand the relation between ambient PM2.5 exposure and risk of UADT cancers. A population-based case-control study involving 565 incident UADT cancer cases and 983 controls was conducted in Los Angeles County from 1999 to 2004. The average residential PM2.5 concentration 1 year before the diagnosis date for cases and the reference date for controls was assessed using a chemical transport model. The association between ambient PM2.5 and the UADT cancers was estimated by unconditional logistic regression, adjusting for confounders at the individual and block-group level. Stratified analyses were conducted by sex, tobacco smoking status and UADT subsites. We also assessed the interaction between PM2.5 and tobacco smoking on UADT cancers. PM2.5 concentrations were associated with an elevated odds of UADT cancers (adjusted odds ratio = 1.21 per interquartile range [4.5 µg/m3 ] increase; 95% confidence interval: 1.02, 1.44). The association between PM2.5 and UADT cancers was similar across UADT subsites, sex and tobacco smoking status. The interaction between PM2.5 and tobacco smoking on UADT cancers was approximately additive on the odds scale. The effect estimate for PM2.5 and UADT cancers was similar among never smokers. Our findings support the hypothesis that exposure to PM2.5 increases the risk of UADT cancers. Improvements in air quality may reduce the risk of UADT cancers.

The protective effect of dietary folate intake on gastric cancer is modified by alcohol consumption: A pooled analysis of the StoP Consortium.

Dietary folate intake has been identified as a potentially modifiable factor of gastric cancer (GC) risk, although the evidence is still inconsistent. We evaluate the association between dietary folate intake and the risk of GC as well as the potential modification effect of alcohol consumption. We pooled data for 2829 histologically confirmed GC cases and 8141 controls from 11 case-control studies from the international Stomach Cancer Pooling Consortium. Dietary folate intake was estimated using food frequency questionnaires. We used linear mixed models with random intercepts for each study to calculate adjusted odds ratios (OR) and 95% confidence interval (CI). Higher folate intake was associated with a lower risk of GC, although this association was not observed among participants who consumed >2.0 alcoholic drinks/day. The OR for the highest quartile of folate intake, compared with the lowest quartile, was 0.78 (95% CI, 0.67-0.90, P-trend = 0.0002). The OR per each quartile increment was 0.92 (95% CI, 0.87-0.96) and, per every 100 µg/day of folate intake, was 0.89 (95% CI, 0.84-0.95). There was a significant interaction between folate intake and alcohol consumption (P-interaction = 0.02). The lower risk of GC associated with higher folate intake was not observed in participants who consumed >2.0 drinks per day, ORQ4v Q1 = 1.15 (95% CI, 0.85-1.56), and the OR100 µg/day = 1.02 (95% CI, 0.92-1.15). Our study supports a beneficial effect of folate intake on GC risk, although the consumption of >2.0 alcoholic drinks/day counteracts this beneficial effect.

Reproductive factors, hormonal interventions, and gastric cancer risk in the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Gastric cancer incidence is higher in men, and a protective hormone-related effect in women is postulated. We aimed to investigate and quantify the relationship in the Stomach cancer Pooling (StoP) Project consortium. METHODS: A total of 2,084 cases and 7,102 controls from 11 studies in seven countries were included. Summary odds ratios (ORs) and 95% confidence intervals (CIs) assessing associations of key reproductive factors and menopausal hormone therapy (MHT) with gastric cancer were estimated by pooling study-specific ORs using random-effects meta-analysis. RESULTS: A duration of fertility of ≥ 40 years (vs. < 20), was associated with a 25% lower risk of gastric cancer (OR = 0.75; 95% CI: 0.58-0.96). Compared with never use, ever, 5-9 years and ≥ 10 years use of MHT in postmenopausal women, showed ORs of 0.73 (95% CI: 0.58-0.92), 0.53 (95% CI: 0.34-0.84) and 0.71 (95% CI: 0.50-1.00), respectively. The associations were generally similar for anatomical and histologic subtypes. CONCLUSION: Our results support the hypothesis that reproductive factors and MHT use may lower the risk of gastric cancer in women, regardless of anatomical or histologic subtypes. Given the variation in hormones over the lifespan, studies should address their effects in premenopausal and postmenopausal women. Furthermore, mechanistic studies may inform potential biological processes.

Dietary intake of vitamin C and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Previous studies suggest that dietary vitamin C is inversely associated with gastric cancer (GC), but most of them did not consider intake of fruit and vegetables. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project, a consortium of epidemiological studies on GC. METHODS: Fourteen case-control studies were included in the analysis (5362 cases, 11,497 controls). We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the association between dietary intake of vitamin C and GC, adjusted for relevant confounders and for intake of fruit and vegetables. The dose-response relationship was evaluated using mixed-effects logistic models with second-order fractional polynomials. RESULTS: Individuals in the highest quartile of dietary vitamin C intake had reduced odds of GC compared with those in the lowest quartile (OR: 0.64; 95% CI: 0.58, 0.72). Additional adjustment for fruit and vegetables intake led to an OR of 0.85 (95% CI: 0.73, 0.98). A significant inverse association was observed for noncardia GC, as well as for both intestinal and diffuse types of the disease. The results of the dose-response analysis showed decreasing ORs of GC up to 150-200 mg/day of vitamin C (OR: 0.54; 95% CI: 0.41, 0.71), whereas ORs for higher intakes were close to 1.0. CONCLUSIONS: The findings of our pooled study suggest that vitamin C is inversely associated with GC, with a potentially beneficial effect also for intakes above the currently recommended daily intake (90 mg for men and 75 mg for women).

Fruits and vegetables intake and bladder cancer risk: a pooled analysis from 11 case-control studies in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) consortium.

PURPOSE: High consumption of fruits and vegetables decrease the risk of bladder cancer (BC). The evidence of specific fruits and vegetables and the BC risk is still limited. METHODS: Fruit and vegetable consumptions in relation to BC risk was examined by pooling individual participant data from case-control studies. Unconditional logistic regression was used to estimate study-specific odds ratio's (ORs) with 95% confidence intervals (CIs) and combined using a random-effects model for intakes of total fruits, total vegetables, and subgroups of fruits and vegetables. RESULTS: A total of 11 case-control studies were included, comprising 5637 BC cases and 10,504 controls. Overall, participants with the highest intakes versus the lowest intakes of fruits in total (OR 0.79; 95% CI 0.68-0.91), citrus fruits (OR 0.81; 95% CI 0.65-0.98), pome fruits (OR 0.76; 95% CI 0.65-0.87), and tropical fruits (OR 0.84; 95% CI 0.73-0.94) reduced the BC risk. Greater consumption of vegetables in total, and specifically shoot vegetables, was associated with decreased BC risk (OR 0.82; 95% CI 0.68-0.96 and OR 0.87; 95% CI 0.78-0.96, respectively). Substantial heterogeneity was observed for the associations between citrus fruits and total vegetables and BC risk. CONCLUSION: This comprehensive study provides compelling evidence that the consumption of fruits overall, citrus fruits, pome fruits and tropical fruits reduce the BC risk. Besides, evidence was found for an inverse association between total vegetables and shoot vegetables intake.

The association between dietary fiber intake and gastric cancer: a pooled analysis of 11 case-control studies.

PURPOSE: Gastric cancer (GC) is among the leading causes of cancer mortality worldwide. The objective of this study was to investigate the association between dietary fiber intake and GC. METHODS: We pooled data from 11 population or hospital-based case-control studies included in the Stomach Cancer Pooling (StoP) Project, for a total of 4865 histologically confirmed cases and 10,626 controls. Intake of dietary fibers and other dietary factors was collected using food frequency questionnaires. We calculated the odds ratios (OR) and 95% confidence intervals (CI) of the association between dietary fiber intake and GC by using a multivariable logistic regression model adjusted for study site, sex, age, caloric intake, smoking, fruit and vegetable intake, and socioeconomic status. We conducted stratified analyses by these factors, as well as GC anatomical site and histological type. RESULTS: The OR of GC for an increase of one quartile of fiber intake was 0.91 (95% CI: 0.85, 0.97), that for the highest compared to the lowest quartile of dietary fiber intake was 0.72 (95% CI: 0.59, 0.88). Results were similar irrespective of anatomical site and histological type. CONCLUSION: Our analysis supports the hypothesis that dietary fiber intake may exert a protective effect on GC.

VNP20009-Abvec-Igκ-MIIP suppresses ovarian cancer progression by modulating Ras/MEK/ERK signaling pathway.

Ovarian cancer poses a significant threat to women's health, with conventional treatment methods encountering numerous limitations, and the emerging engineered bacterial anti-tumor strategies offer newfound hope for ovarian cancer treatment. In this study, we constructed the VNP20009-Abvec-Igκ-MIIP (VM) engineered strain and conducted initial assessments of its in vitro growth performance and the expression capability of migration/invasion inhibitory protein (MIIP). Subsequently, ID8 ovarian cancer cells and mouse cancer models were conducted to investigate the impact of VM on ovarian cancer. Our results revealed that the VM strain demonstrated superior growth performance, successfully invaded ID8 ovarian cancer cells, and expressed MIIP, consequently suppressing cell proliferation and migration. Moreover, VM specifically targeted tumor sites and expressed MIIP which further reduced the tumor volume of ovarian cancer mice (p < 0.01), via the downregulation of epidermal growth factor receptor (EGFR), Ras, p-MEK, and p-ERK. The downregulation of the PI3K/AKT signaling pathway and the decrease in Bcl-2/Bax levels also indicated VM's apoptotic potency on ovarian cancer cells. In summary, our research demonstrated that VM exhibits promising anti-tumor effects both in vitro and in vivo, underscoring its potential for clinical treatment of ovarian cancer. KEY POINTS: • This study has constructed an engineered strain of Salmonella typhimurium capable of expressing anticancer proteins • The engineered bacteria can target and colonize tumor sites in vivo • VM can inhibit the proliferation, migration, and invasion of ovarian cancer cells.

Quantum gate control of polar molecules with machine learning.

We propose a scheme for achieving basic quantum gates using ultracold polar molecules in pendular states. The qubits are encoded in the YbF molecules trapped in an electric field with a certain gradient and coupled by the dipole-dipole interaction. The time-dependent control sequences consisting of multiple pulses are considered to interact with the pendular qubits. To achieve high-fidelity quantum gates, we map the control problem for the coupled molecular system into a Markov decision process and deal with it using the techniques of deep reinforcement learning (DRL). By training the agents over multiple episodes, the optimal control pulse sequences for the two-qubit gates of NOT, controlled NOT, and Hadamard are discovered with high fidelities. Moreover, the population dynamics of YbF molecules driven by the discovered gate sequences are analyzed in detail. Furthermore, by combining the optimal gate sequences, we successfully simulate the quantum circuit for entanglement. Our findings could offer new insights into efficiently controlling molecular systems for practical molecule-based quantum computing using DRL.

Effects of combined morbid insomnia and sleep apnea on long-term cardiovascular risk and all-cause mortality in elderly patients: a prospective cohort study.

PURPOSE: It is reported that insomnia and obstructive sleep apnea (OSA) increase the incidence of adverse cardiovascular events. The aim of this study was to analyze the risk of cardiovascular disease and mortality in elderly patients with comorbid insomnia and obstructive sleep apnea (COMISA). METHODS: We included 868 elderly patients with OSA who underwent sleep monitoring at a multicenter sleep room from January 2015 to October 2017. We collected demographic data, clinical features, medical history, sleep parameters, and laboratory findings. Cox proportional hazards analysis was used to identify the relationship between COMISA and adverse cardiovascular events and all-cause mortality. RESULTS: There were 181 elderly patients with COMISA. The median follow-up was 43 months, during which we observed major adverse cardiac events (MACE) in 90 patients. The Kaplan-Meier survival curve indicated a significant relationship between COMISA and MACE (Plog Rank < 0.001). Multivariate Cox regression analysis showed that COMISA increased the incidence of MACE (HR = 2.328, 95% CI: 1.349-4.018, P = 0.002), hospitalization for unstable angina (HR = 2.915, 95% CI: 1.397-6.081, P = 0.004), and the combination of all events (HR = 2.301, 95% CI: 1.393-3.803, P = 0.001). However, there were no significant differences in cardiovascular death, all-cause mortality, myocardial infarction, or hospitalized heart failure in patients with COMISA (P > 0.05). Subgroup analyses showed that among COMISA patients, male sex (HR = 2.800, 95% CI: 1.458-5.377, P = 0.002), age < 70 years (HR = 4.050, 95% CI: 2.022-8.115, P < 0.001), and overweight and obesity (HR = 2.482, 95% CI: 1.383-4.453, P = 0.002) were associated with a higher risk of MACE. CONCLUSIONS: Our results showed that COMISA increased the risk of MACE, unstable angina, and the compound occurrence of all events. Male, overweight or obese COMISA patients under 70 years of age have an increased risk of MACE.

Ultrasound characteristics of breast fibromatosis mimicking carcinoma.

PURPOSE: To explore the value of ultrasound (US) characteristics in diagnosing breast fibromatosis (BF) and evaluate their differences from breast carcinoma. METHODS: A total of 121 patients with BF (n = 24, 29 lesions) or invasive ductal carcinoma (IDC) (n = 97, 102 lesions) of the breast were included. Their clinical and US findings were recorded and analyzed. RESULTS: The mean age of BF was younger than that of IDC (28.75 ± 5.55 vs. 50.19 ± 9.87, p < 0.001). The mean size of the BF was smaller than that of IDC (2.09 ± 0.91 vs. 2.71 ± 1.20, p = 0.011). Compared to IDC, BF had more frequency of posterior echo attenuation (p < 0.001), less frequency of peripheral hyperechoic halo (p = 0.002), calcification (p = 0.001), US reported axillary lymph node positive (p = 0.025), and grade 2-3 vascularity (p < 0.001). The Breast Imaging Reporting and Data System categorized BF at a lower level than IDC (p < 0.001). After adjusting for age, the peripheral hyperechoic halo, posterior echo feature, and vascularity could independently identify the differences between these two entities. CONCLUSION: Some differences were observed between BF and IDC in terms of patient age, lesion size, and US characteristics.

An ultrasound-based histogram analysis model for prediction of tumour stroma ratio in pleomorphic adenoma of the salivary gland.

OBJECTIVES: Preoperative identification of different stromal subtypes of pleomorphic adenoma (PA) of the salivary gland is crucial for making treatment decisions. We aimed to develop and validate a model based on histogram analysis (HA) of ultrasound (US) images for predicting tumour stroma ratio (TSR) in salivary gland PA. METHODS: A total of 219 PA patients were divided into low-TSR (stroma-low) and high-TSR (stroma-high) groups and enrolled in a training cohort (n = 151) and a validation cohort (n = 68). The least absolute shrinkage and selection operator regression algorithm was used to screen the most optimal clinical, US, and HA features. The selected features were entered into multivariable logistic regression analyses for further selection of independent predictors. Different models, including the nomogram model, the clinic-US (Clin + US) model, and the HA model, were built based on independent predictors using logistic regression. The performance levels of the models were evaluated and validated on the training and validation cohorts. RESULTS: Lesion size, shape, cystic areas, vascularity, HA_mean, and HA_skewness were identified as independent predictors for constructing the nomogram model. The nomogram model incorporating the clinical, US, and HA features achieved areas under the curve of 0.839 and 0.852 in the training and validation cohorts, respectively, demonstrating good predictive performance and calibration. Decision curve analysis and clinical impact curves further confirmed its clinical usefulness. CONCLUSIONS: The nomogram model we developed offers a practical tool for preoperative TSR prediction in PA, potentially enhancing clinical decision-making.

Function of the GABAergic System in Diabetic Encephalopathy.

Diabetes is a common metabolic disease characterized by loss of blood sugar control and a high rate of complications. γ-Aminobutyric acid (GABA) functions as the primary inhibitory neurotransmitter in the adult mammalian brain. The normal function of the GABAergic system is affected in diabetes. Herein, we summarize the role of the GABAergic system in diabetic cognitive dysfunction, diabetic blood sugar control disorders, diabetes-induced peripheral neuropathy, diabetic central nervous system damage, maintaining diabetic brain energy homeostasis, helping central control of blood sugar and attenuating neuronal oxidative stress damage. We show the key regulatory role of the GABAergic system in multiple comorbidities in patients with diabetes and hope that further studies elucidating the role of the GABAergic system will yield benefits for the treatment and prevention of comorbidities in patients with diabetes.

Simulation of quantum walks on a circle with polar molecules via optimal control.

Quantum walks are the quantum counterpart of classical random walks and have various applications in quantum information science. Polar molecules have rich internal energy structure and long coherence time and thus are considered as a promising candidate for quantum information processing. In this paper, we propose a theoretical scheme for implementing discrete-time quantum walks on a circle with dipole-dipole coupled SrO molecules. The states of the walker and the coin are encoded in the pendular states of polar molecules induced by an external electric field. We design the optimal microwave pulses for implementing quantum walks on a four-node circle and a three-node circle by multi-target optimal control theory. To reduce the accumulation of decoherence and improve the fidelity, we successfully realize a step of quantum walk with only one optimal pulse. Moreover, we also encode the walker into a three-level molecular qutrit and a four-level molecular ququart and design the corresponding optimal pulses for quantum walks, which can reduce the number of molecules used. It is found that all the quantum walks on a circle in our scheme can be achieved via optimal control fields with high fidelities. Our results could shed some light on the implementation of discrete-time quantum walks and high-dimensional quantum information processing with polar molecules.

Alcohol Consumption and Mental Health during the COVID-19 Pandemic.

AIMS: To examine the association between alcohol consumption and mental health during the COVID-19 pandemic. METHODS: An anonymous online survey was distributed among US adults during May-August 2020 through social networks and ResearchMatch. We collected information on demographic, lifestyles and mental health symptoms including anxiety, depression, stress and post-traumatic stress disorder. Logistic regression models were used to examine the cross-sectional association between alcohol consumption and mental health symptoms. We also examined effect modification by race, age, gender, social support, financial insecurity and quarantine status. RESULTS: The analytical sample consists of 3623 adults. Stable drinking habits and regular drinking behaviors were found to co-exist with better mental health status. Participants who increased their alcohol use had higher odds of developing mental health disorders than those who maintained their pre-pandemic drinking habits. Additionally, participants who engaged in binge drinking during the pandemic had higher odds of depression and stress than those who did not. The associations regarding increased drinking and binge drinking in relation to adverse mental health outcomes were stronger among females, racial minorities, and individuals with financial concerns, poor social support and restricted quarantine status than their counterparts. CONCLUSIONS: During the early stage of the COVID-19 pandemic, increased alcohol use and binge drinking are cross-sectionally associated with higher odds of mental health disorders, which highlighted the need for targeted intervention to address the mental health needs of individuals who have engaged in these behaviors, especially among females, minorities, those with insecurities or with restricted quarantine status.

A feasibility study for objective evaluation of visual acuity based on pattern-reversal visual evoked potentials and other related visual parameters with machine learning algorithm.

BACKGROUND: To develop machine learning models for objectively evaluating visual acuity (VA) based on pattern-reversal visual evoked potentials (PRVEPs) and other related visual parameters. METHODS: Twenty-four volunteers were recruited and forty-eight eyes were divided into four groups of 1.0, 0.8, 0.6, and 0.4 (decimal vision). The relationship between VA, peak time, or amplitude of P100 recorded at 5.7°, 2.6°, 1°, 34', 15', and 7' check sizes were analyzed using repeated-measures analysis of variance. Correlations between VA and P100, contrast sensitivity (CS), refractive error, wavefront aberrations, and visual field were analyzed by rank correlation. Based on meaningful P100 peak time, P100 amplitude, and other related visual parameters, four machine learning algorithms and an ensemble classification algorithm were used to construct objective assessment models for VA. Receiver operating characteristic (ROC) curves were used to compare the efficacy of different models by repeated sampling comparisons and ten-fold cross-validation. RESULTS: The main effects of P100 peak time and amplitude between different VA and check sizes were statistically significant (all P < 0.05). Except amplitude at 2.6° and 5.7°, VA was negatively correlated with peak time and positively correlated with amplitude. The peak time initially shortened with increasing check size and gradually lengthened after the minimum value was reached at 1°. At the 1° check size, there were statistically significant differences when comparing the peak times between the vision groups with each other (all P < 0.05), and the amplitudes of the vision reduction groups were significantly lower than that of the 1.0 vision group (all P < 0.01). The correlations between peak time, amplitude, and visual acuity were all highest at 1° (rs = - 0.740, 0.438). VA positively correlated with CS and spherical equivalent (all P < 0.001). There was a negative correlation between VA and coma aberrations (P < 0.05). For different binarization classifications of VA, the classifier models with the best assessment efficacy all had the mean area under the ROC curves (AUC) above 0.95 for 500 replicate samples and above 0.84 for ten-fold cross-validation. CONCLUSIONS: Machine learning models established by meaning visual parameters related to visual acuity can assist in the objective evaluation of VA.

Opium, phencyclidine, and crack cocaine smoking associations with lung and upper aerodigestive tract cancers: exploratory findings from a case-control study in Los Angeles County.

Background: Illicit drug use has become a global epidemic, yet it is unclear if drug smoking increases the risk of tobacco-related cancers.Objectives: We aimed to evaluate hypothesized associations between smoking three drugs - opium, phencyclidine (PCP) and crack cocaine and lung and upper aerodigestive tract (UADT) cancers.Methods: A population-based case-control study with 611 lung cancer cases (50% male), 601 UADT cancers cases (76% male), and 1,040 controls (60% male) was conducted in Los Angeles County (1999-2004). Epidemiologic data including drug smoking histories were collected in face-to-face interviews. Associations were estimated with logistic regressions.Results: Adjusting for potential confounders, ever vs. never crack smoking was positively associated with UADT cancers (aOR = 1.56, 95% CI: 1.05, 2.33), and a dose-response relationship was observed for lifetime smoking frequency (p for trend = .024). Heavy (> median) vs. never crack smoking was associated with UADT cancers (aOR = 1.81, 95% CI: 1.07, 3.08) and lung cancer (aOR = 1.58, 95% CI: 0.88, 2.83). A positive association was also observed between heavy PCP smoking and UADT cancers (aOR = 2.29, 95% CI: 0.91, 5.79). Little or no associations were found between opium smoking and lung cancer or UADT cancers.Conclusion: The positive associations between illicit drug use and lung and/or UADT cancers suggest that smoking these drugs may increase the risk of tobacco-related cancers. Despite the low frequency of drug smoking and possible residual confounding, our findings may provide additional insights on the development of lung and UADT cancers.

Molecular Modelling of Ionic Liquids: Situations When Charge Scaling Seems Insufficient.

Charge scaling as an effective solution to the experiment-computation disagreement in molecular modelling of ionic liquids (ILs) could bring the computational results close to the experimental reference for various thermodynamic properties. According to the large-scale benchmark calculations of mass density, solvation, and water-ILs transfer-free energies in our series of papers, the charge-scaling factor of 0.8 serves as a near-optimal option generally applicable to most ILs, although a system-dependent parameter adjustment could be attempted for further improved performance. However, there are situations in which such a charge-scaling treatment would fail. Namely, charge scaling cannot really affect the simulation outcome, or minimally perturbs the results that are still far from the experimental value. In such situations, the vdW radius as an additional adjustable parameter is commonly tuned to minimize the experiment-calculation deviation. In the current work, considering two ILs from the quinuclidinium family, we investigate the impacts of this vdW-scaling treatment on the mass density and the solvation/partition thermodynamics in a fashion similar to our previous charge-scaling works, i.e., scanning the vdW-scaling factor and computing physical properties under these parameter sets. It is observed that the mass density exhibits a linear response to the vdW-scaling factor with slopes close to -1.8 g/mL. By further investigating a set of physiochemically relevant temperatures between 288 K and 348 K, we confirm the robustness of the vdW-scaling treatment in the estimation of bulk properties. The best vdW-scaling parameter for mass density would worsen the computation of solvation/partition thermodynamics, and a marginal decrease in the vdW-scaling factor is considered as an intermediate option balancing the reproductions of bulk properties and solvation thermodynamics. These observations could be understood in a way similar to the charge-scaling situation. i.e., overfitting some properties (e.g., mass density) would degrade the accuracy of the other properties (e.g., solvation free energies). Following this principle, the general guideline for applying this vdW-tuning protocol is by using values between the density-derived choice and the solvation/partition-derived solution. The charge and current vdW scaling treatments cover commonly encountered ILs, completing the protocol for accurate modelling of ILs with fixed-charge force fields.