Miracle-dz/UniFAR-FTUs huggingface dataset:
Population Attributable Risks of Subtypes of Esophageal and Gastric Cancers in the United States

INTRODUCTION: To help target preventive strategies, we estimated US population attributable risks (PARs) of demographic and potentially modifiable risk factors for esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric noncardia adenocarcinoma (GNCA). METHODS: We prospectively examined the associations for risk factors and these cancers in 490,605 people in the National Institutes of Health-the American Association of Retired Persons Diet and Health cohort Diet and Health Study cohort from 1995 to 2011. Exposures were obtained from the baseline questionnaire. Diagnoses of gastroesophageal reflux disease were extracted for a subset of eligible National Institutes of Health-the American Association of Retired Persons Diet and Health cohort subjects through linkage to Medicare and then multiply imputed for non–Medicare-eligible subjects. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazards regression. Adjusted population attributable risks were calculated for the US population aged 50–71 years by combining the hazard ratios with the estimated joint distribution of risk factor prevalence from the 2015 National Health Interview Survey. RESULTS: Smoking remained the most important risk factor for ESCC and was estimated to cause more than 1/3 of EAC and GCA and 1/10 of GNCA. Obesity and gastroesophageal reflux disease were associated with more than 1/2 of EAC and 1/3 of GCA. Compared with each lowest-risk level category, common risk factors were estimated to be associated with 73.7% of ESCC (95% confidence interval [CI]: 62.1%–85.4%), 70.3% of EAC (95% CI: 64.4%–76.2%), 69.3% of GCA (95% CI: 61.0%–77.7%), and 33.6% of GNCA (95% CI: 21.7%–45.5%). DISCUSSION: These factors accounted for a large proportion of esophageal and gastric cancers in the United States, highlighting opportunities for education and intervention to reduce the burden of these highly fatal cancers.
Higher perceived stress and exacerbated motor symptoms in Parkinson's disease during the COVID-19 lockdown in New Zealand.

AIMS Stress plays a key role in Parkinson's disease (PD) by acting on the dopaminergic system and worsening patients' motor function. The impact of New Zealand's strict lockdown measures to contain COVID-19 on perceived stress and PD motor symptoms remains unknown. Here we examined the relationship between perceived levels of stress, changes in physical activity levels and PD motor symptoms during lockdown. METHODS During lockdown, 134 participants with PD and 49 controls completed a survey assessing perceived stress, self-reported changes in PD motor symptoms and physical activity duration and intensity prior to and during lockdown. RESULTS Perceived stress was higher in PD than controls, and in those reporting a worsening of tremor, balance/gait, dyskinesia and bradykinesia compared to those indicating no change during the COVID-19 lockdown. These effects were not modulated by physical activity. CONCLUSIONS Reducing stressors may be an important adjunct treatment strategy to improve motor function in PD.
Characterization of short‐period and long‐period incremental markings in porcine enamel and dentine—Results of a fluorochrome labelling study in wild boar and domestic pigs

Mammalian dental hard tissues exhibit incremental markings that reflect the periodic variation of appositional growth rates. In order to use these markings to characterize dental growth processes and to infer life‐history traits, an unequivocal identification of their periodicities is required. We performed a fluorochrome labelling study on forming enamel and dentine in molar teeth of wild boar and domestic pigs to establish the periodicity and temporal correspondence of incremental markings in enamel and dentine. The dominant incremental markings in enamel (laminations) and dentine (von Ebner lines) recorded in the pig teeth are of a daily nature. In addition, long‐period incremental markings with a periodicity of 2 days were recorded in enamel (striae of Retzius) and dentine (Andresen lines). The 2‐day growth rhythm was also expressed at the lateral crown surface, as evidenced by the pattern of perikymata. In enamel, also markings with a sub‐daily periodicity, representing an ultradian growth rhythm, were observed. Our study provides experimental evidence for the periodicity of incremental markings in porcine enamel and dentine. The findings correct previous misconceptions on incremental markings in dental hard tissues of pigs and other ungulates that had led to erroneous conclusions regarding crown formation parameters.
Regulation of spatial distribution of BMP ligands for pattern formation

Bone morphogenetic proteins (BMPs), members of the transforming growth factor‐ß (TGF‐ß) family, have been shown to contribute to embryogenesis and organogenesis during animal development. Relevant studies provide support for the following concepts: (a) BMP signals are evolutionarily highly conserved as a genetic toolkit; (b) spatiotemporal distributions of BMP signals are precisely controlled at the post‐translational level; and (c) the BMP signaling network has been co‐opted to adapt to diversified animal development. These concepts originated from the historical findings of the Spemann‐Mangold organizer and the subsequent studies about how this organizer functions at the molecular level. In this Commentary, we focus on two topics. First, we review how the BMP morphogen gradient is formed to sustain larval wing imaginal disc and early embryo growth and patterning in Drosophila. Second, we discuss how BMP signal is tightly controlled in a context‐dependent manner, and how the signal and tissue dynamics are coupled to facilitate complex tissue structure formation. Finally, we argue how these concepts might be developed in the future for further understanding the significance of BMP signaling in animal development.
The SWI/SNF complex regulates the expression of miR-222, a tumor suppressor microRNA in lung adenocarcinoma.

SWI/SNF chromatin remodeling complexes are key epigenetic regulators that are recurrently mutated in cancer. Most studies of these complexes are focused on their role in regulating protein-coding genes. However, here we show that SWI/SNF complexes control the expression of microRNAs. We used a SMARCA4-deficient model of lung adenocarcinoma (LUAD) to track changes in the miRNome upon SMARCA4 restoration. We found that SMARCA4-SWI/SNF complexes induced significant changes in the expression of cancer-related microRNAs. The most significantly dysregulated microRNA was miR-222, whose expression was promoted by SMARCA4-SWI/SNF complexes but not by SMARCA2-SWI/SNF complexes via their direct binding to a miR-222 enhancer region. Importantly, miR-222 expression decreased cell viability, phenocopying the tumor-suppressor role of SMARCA4-SWI/SNF complexes in LUAD. Finally, we showed that the miR-222 enhancer region resides in a topologically associated domain that does not contain any cancer-related protein-coding genes, suggesting that miR-222 may be involved in exerting the tumor suppressor role of SMARCA4. Overall, this study highlights the relevant role of the SWI/SNF complex in regulating the non-coding genome, opening new insights into the pathogenesis of LUAD.
Comparing urinary biomarkers of exposure to polycyclic aromatic hydrocarbons

JON RUSSELL SOBUS: Comparing Urinary Biomarkers of Exposure to Polycyclic Aromatic Hydrocarbons (Under the direction of Stephen M. Rappaport) Polycyclic aromatic hydrocarbons (PAHs), which consist of two or more fused aromatic rings, are ubiquitous products of combustion. These compounds are found in wood and tobacco smoke, engine (particularly diesel) exhausts, and in numerous workplaces, including those producing coke and aluminum and those processing hot asphalt. Because some PAHs are potent carcinogens, it is important to assess the levels of exposure to these compounds that are received by workers and the general public. However, PAHs are difficult to measure in the environment because they exist in both the gas phase and the particulate phase, and the carcinogenic particle-bound compounds are present at very low concentrations. In contrast, the smaller vapor-phase PAHs are more abundant in the environment and produce a host of urinary products that can be used as biomarkers of exposure. Here we consider the hypothesis that urinary biomarkers of naphthalene (a 2-ring compound) and phenanthrene (a 3-ring compound) can be used as measures of exposure to total PAHs. We test this hypothesis in three distinct phases of research. First, we determine the predictive value of airborne naphthalene and phenanthrene as measures of exposure to diesel exhaust in a controlled chamber study. Second, we determine the predictive value of urinary levels of naphthalene and phenanthrene as measures of occupational exposure to diesel exhaust, asphalt emissions, and coke-oven emissions. And finally, we develop statistical models of
Listeria monocytogenes infection rewires host metabolism with regulatory input from type I interferons

Listeria monocytogenes (L. monocytogenes) is a food-borne bacterial pathogen. Innate immunity to L. monocytogenes is profoundly affected by type I interferons (IFN-I). Here we investigated host metabolism in L. monocytogenes-infected mice and its potential control by IFN-I. Accordingly, we used animals lacking either the IFN-I receptor (IFNAR) or IRF9, a subunit of ISGF3, the master regulator of IFN-I-induced genes. Transcriptomes and metabolite profiles showed that L. monocytogenes infection induces metabolic rewiring of the liver. This affects various metabolic pathways including fatty acid (FA) metabolism and oxidative phosphorylation and is partially dependent on IFN-I signaling. Livers and macrophages from Ifnar1-/- mice employ increased glutaminolysis in an IRF9-independent manner, possibly to readjust TCA metabolite levels due to reduced FA oxidation. Moreover, FA oxidation inhibition provides protection from L. monocytogenes infection, explaining part of the protection of Irf9-/- and Ifnar1-/- mice. Our findings define a role of IFN-I in metabolic regulation during L. monocytogenes infection. Metabolic differences between Irf9-/- and Ifnar1-/- mice may underlie the different susceptibility of these mice against lethal infection with L. monocytogenes.
The gravitostat protects diet‐induced obese rats against fat accumulation and weight gain

The gravitostat is a novel homeostatic body weight‐regulating mechanism, mostly studied in mice, and recently confirmed in obese humans. In the present study, we explored the effect of weight loading on metabolic outcomes, meal patterns and parameters linked to energy expenditure in both obese and lean rats. Diet‐induced obese (DIO) and lean rats were implanted with capsules weighing either 15% of biological body weight (load) or empty capsules (1.3% of body weight; controls). Loading protected against fat accumulation more markedly in the DIO group. In line with this, the obesity‐related impairment in insulin sensitivity was notably ameliorated in DIO rats upon loading, as revealed by the reduction in serum insulin levels and homeostatic model assessment for insulin resistance index scores. Although 24‐hour caloric intake was reduced in both groups, this effect was greater in loaded DIO rats than in loaded lean peers. During days 10‐16, after recovery from surgery, loading: (i) decreased meal size in both groups (only during the light phase in DIO rats) but this was compensated in lean rats by an increase in meal frequency; (ii) reduced dark phase locomotor activity only in lean rats; and (iii) reduced mean caloric efficiency in DIO rats. Muscle weight was unaffected by loading in either group. Dietary‐obese rats are therefore more responsive than lean rats to loading.
An AI Approach for Identifying Patients With Cirrhosis

Goal: The goal of this study was to evaluate an artificial intelligence approach, namely deep learning, on clinical text in electronic health records (EHRs) to identify patients with cirrhosis. Background and Aims: Accurate identification of cirrhosis in EHR is important for epidemiological, health services, and outcomes research. Currently, such efforts depend on International Classification of Diseases (ICD) codes, with limited success. Materials and Methods: We trained several machine learning models using discharge summaries from patients with known cirrhosis from a patient registry and random controls without cirrhosis or its complications based on ICD codes. Models were validated on patients for whom discharge summaries were manually reviewed and used as the gold standard test set. We tested Naive Bayes and Random Forest as baseline models and a deep learning model using word embedding and a convolutional neural network (CNN). Results: The training set included 446 cirrhosis patients and 689 controls, while the gold standard test set included 139 cirrhosis patients and 152 controls. Among the machine learning models, the CNN achieved the highest area under the receiver operating characteristic curve (0.993), with a precision of 0.965 and recall of 0.978, compared with 0.879 and 0.981 for the Naive Bayes and Random Forest, respectively (precision 0.787 and 0.958, and recalls 0.878 and 0.827). The precision by ICD codes for cirrhosis was 0.883 and recall was 0.978. Conclusions: A CNN model trained on discharge summaries identified cirrhosis patients with high precision and recall. This approach for phenotyping cirrhosis in the EHR may provide a more accurate assessment of disease burden in a variety of studies.
HapWheel: In-Car Infotainment System Feedback Using Haptic and Hovering Techniques

In-car devices are growing both in complexity and capacity, integrating functionalities that used to be divided among other controls in the vehicles. These systems appear increasingly in the form of touchscreens as a cost-saving measure. Screens lack the physicality of traditional buttons or switches, requiring drivers to look away from the road to operate them. This paper presents the design, implementation, and two studies that evaluated HapWheel, a system that provides the driver with haptic feedback in the steering wheel while interacting with an Infotainment System. Results show that the proposed system reduced both the duration of and the number of times a driver looked away from the road. HapWheel was also successful at reducing the number of mistakes during the interaction.
Negative affect and alcohol craving in trauma-exposed young adult drinkers.

BACKGROUND Clinical research indicates that successful posttraumatic stress disorder (PTSD) treatment does not lead to improvements in alcohol use outcomes in comorbid PTSD and alcohol use disorder (AUD). Emerging theory suggests that treating PTSD may not disrupt an association between negative affect and alcohol craving, which underlies negative reinforcement drinking. The goal of the current study was to determine the respective influences of PTSD symptoms, coping motives, and negative affect on trauma and alcohol cue reactivity to inform theoretical models of co-occurring PTSD and AUD. METHODS The sample consisted of 189 young adults (50.3% women; 49.2% current PTSD; 84.0% current AUD) who endorsed interpersonal trauma (e.g., sexual/physical assault) and current weekly alcohol use. Participants completed a trauma and alcohol cue reactivity assessment, in which subjective (e.g., craving, affect) and physiological (i.e., salivation) measures were recorded in response to 4 narrative (i.e., personalized trauma or standard neutral) and in vivo beverage (i.e., personalized alcohol or water) cue combinations. RESULTS Forward-fitted linear mixed-effects (LME) models confirmed that trauma cue-elicited craving was elevated among those high but not low in PTSD symptoms, consistent with prior research and theory. Trauma cue-elicited craving was fully explained by increases in negative affect, with no evidence of a direct effect of trauma cue on craving. PTSD symptoms moderated an association between trauma cue and negative affect (but not negative affect and craving), and coping motives for alcohol moderated an association between negative affect and craving (but not trauma cue and negative affect). CONCLUSIONS This study provides novel laboratory evidence for the respective contributions of negative affect, PTSD symptoms, and coping motives on alcohol craving in trauma-exposed drinkers. It offers a methodological framework in which to evaluate novel strategies that aim to disrupt negative reinforcement drinking in individuals with co-occurring PTSD and AUD.
Sex‐related differences in reading achievement

Over the last 40 years, ever‐growing interest in sex‐related differences in the human brain has led to a vast amount of literature on the subject, a small part of which relates to studies of differences in the ability to read. The data concerning typically developing children mainly come from school‐based screening projects (Programme for International Student Assessment, INVALSI) and partially from the standardization of reading tests. These have revealed the existence of a gap in favor of females that primarily appears during adolescence and in situations of sociocultural disadvantage, usually explained on the basis of environmental factors such as socioeconomic status and gender‐based education. Dyslexia is a neurodevelopmental disorder that is significantly more prevalent among males, a difference that neuroimaging and genetic studies have attributed to the presence of hormone‐related protective factors in females, although it has been hypothesized that a different neurocognitive substrate may also be involved. However, the literature on the subject is still limited, and further studies of the interactions between genetic risk, environmental factors, and brain phenotypes are needed to clarify why females are better at performing reading tasks and less susceptible to dyslexia, regardless of their language or the educational system in the country in which they live. The aim of this mini‐review was to describe the studies that have investigated sex‐related differences in reading ability in both typically and atypically developing subjects.
Preoperative Neutrophil-Lymphocyte Ratio Can Predict Outcomes for Patients Undergoing Tetralogy of Fallot Repair

Introduction Elevated neutrophil-lymphocyte ratio (NLR) has been associated with poorer outcomes in cyanotic patients undergoing single ventricle palliation. Little is known about this biomarker on patients with tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease. Our objective is to study the impact of preoperative NLR on outcomes of TOF patients undergoing total repair. Methods This retrospective study included 116 consecutive patients between January 2014 and December 2018. Preoperative NLR was measured from the last complete blood count test before the surgery. Using the cutoff value of 0.80, according to the receiver-operating characteristic (ROC) curve, the sample was divided into two groups (NLR < 0.80 and ≥ 0.80). The primary endpoint was hospital length of stay (LOS). Results ROC curves showed that higher preoperative NLR was associated with longer hospital LOS, with an area under the curve of 0.801±0.040 (95% confidence interval 0.722 - 0.879; P<0.001). High preoperative NLR was also associated with long intensive care unit (ICU) LOS (P=0.035). Preoperative NLR predicted longer hospital LOS with a sensitivity of 63% and a specificity of 81.4%. Conclusion Higher preoperative NLR was associated with long ICU and hospital LOS in patients undergoing TOF repair.
Research Review: The most effective parenting program content for disruptive child behavior - a network meta-analysis.

BACKGROUND Programs to support parents are the recommended strategy to reduce disruptive child behavior problems. Efforts have been made to demonstrate which program components (i.e., clusters of techniques taught) increase program effects, but these methods fail to account for the fact that components rarely operate in isolation. We examine how combinations of components cluster together to form program types and use network meta-analysis to estimate the relative effects of these program types. METHODS We updated an existing systematic review of parenting programs for disruptive child behavior and identified 197 randomized trials. We modeled clusters of components in each trial arm and chose the best-fitting model. We subsequently took 20 draws from the probability distribution of the latent class for each arm, entered each draw into a network meta-analysis model and combined findings using Rubin's rules. Combined estimates were bootstrapped to rank the clusters. We estimated main models and separate models for prevention and treatment settings. RESULTS A five-class solution fit the data best: (1) behavior management; (2) behavior management with parental self-management; (3) behavior management with psychoeducation and relationship enhancement; (4) maximal component loading and (5) no/minimal component loading (i.e. control). In the main model and in treatment settings, all four program types were effective compared to no/minimal components. In prevention settings, only behavior management and behavior management with parental self-management were effective compared to no/minimal components. Probabilistic ranking showed that overall and in treatment settings, behavior management had the largest chance, and in prevention settings, behavior management with self-management had the largest chance, of being most effective compared to no/minimal components. CONCLUSIONS Programs with more focused content seem more likely to yield stronger effects, and different foci may be needed in treatment versus prevention settings. Next steps include identifying individual family differences in optimal program content.
Assessment of Apparent Diffusion Coefficients and SUVs as Predicators of Histological Differentiation in Anal Squamous Cell Carcinoma

Aim The study aims to assess minimal apparent diffusion coefficient (ADCmin) and SUVmax as predictors of histological differentiation in patients with anal squamous cell carcinoma (ASCC) and to determine cutoff values for each histopathological tumor grade. Patients and Methods A retrospective study of 41 ASCC patients (14 males, 27 females; mean age, 65 ± 13 years) staged with FDG PET/CT and MRI (mean scan time interval, 21 ± 11 days). SUVmax and ADCmin values were measured and compared with histopathological tumor grading obtained from biopsy. Results The mean size and tumor volume were 3 ± 2 cm and 16.5 ± 27.3 cm3, respectively. The mean ADCmin values for well-, moderately, and poorly differentiated ASCC were 935 ± 179, 896 ± 123, and 637 ± 114, respectively. The mean SUVmax for well-, moderately, and poorly differentiated ASCC were 6.9 ± 1.8, 11.5 ± 4.1, and 13.4 ± 2.6, respectively. The difference in mean ADCmin values between poorly and moderately/well-differentiated tumors was statistically significant, whereas this was not significant between moderately and well-differentiated tumors. Differences in SUVmax values were statistically significant between poorly/moderately and well-differentiated tumors, whereas there was no statistical significance between poorly and moderately differentiated tumors. By combining the 2 modalities using cutoff values of 675 × 10−6 mm2·s−1 for ADCmin and 8.5 for SUVmax, it was possible to differentiate the tumor categories with a sensitivity, specificity, positive predictive value, and negative predictive value, respectively, of 84.6%, 96.4%, 91.7%, and 93.1% for well-differentiated ASCC, 76.5%, 87.5%, 81.3%, and 84% for moderately, and 90.9%, 89.3%, 76.9%, and 96.2% for poorly differentiated ASCC, respectively. Conclusions ADCmin and SUVmax values correlated with the degree of differentiation in ASCC and can be used as predictors of tumor grading and aggressiveness. Combined ADCmin and SUVmax cutoff values can therefore be used for early patient risk stratification and treatment decision making.