Miracle-dz/UniFAR-FTUs huggingface dataset:
Spontaneous Activity of CB2 Receptors Attenuates Stress-Induced Behavioral and Neuroplastic Deficits in Male Mice

The monoaminergic theory of depression/anxiety disorders cannot fully explain the behavioral and neuroplastic changes observed after ADs chronic treatment. Endocannabinoid system, which comprises CB2 receptors, has been associated with the chronic effects of these drugs, especially in stressed mice. CB2-KO mice display more vulnerability to stressful stimuli. In the present study, we hypothesized that the behavioral and neuroplastic effects observed after repeated treatment with the AD escitalopram (Esc) in chronically stressed mice depend on CB2 receptor signaling. Male mice submitted to chronic unpredictable stress (CUS) paradigm (21 days) were treated daily with AM630 (0.01; 0.03 or 0.3 mg/kg, i.p) a CB2 receptor antagonist/inverse agonist. At e 19th day of the CUS protocol, mice were submitted to Open field test and Tail-suspension test to evaluate antidepressant-like behavior. At the end of the stress protocol, mice were submitted to Novel Suppressed Feeding test (day 22nd) to evaluate anxiety-like behavior. In a second series of experiments, male mice treated with Esc (10 mg/kg, daily, 21 days) in the presence or not of AM630 (0.30 mg/kg) were submitted to the same round of behavioral tests in the same conditions as performed in the dose-response curve protocol. Animals were then euthanized under deep anesthesia, and their brains/hippocampi removed for immunohistochemistry (Doublecortin-DCX) or Western Blot assay. Our results demonstrated that chronic treatment with AM630, a CB2 antagonist/inverse agonist, induces anxiolytic-like effects in stressed mice. Moreover, chronic reduction of CB2 receptor endogenous activity by AM630 attenuated the neuroplastic (potentiating stress-induced decreased expression of pro-BDNF, but enhanced pmTOR and DAGL expression in the hippocampus reduced in stressed mice), the antidepressant- but not the anxiolytic-like effects of Esc. AM630 alone or in combination with Esc decreased the expression of DCX + cell in both the subgranular and granular layers of the dentate gyrus (DG), indicating a general reduction of DCX + neuroblasts and a decrease in their migration through the DG layers. We suggest that the antidepressant-like behavior and the pro-neurogenic effect, but not the anxiolytic like behavior, promoted by Esc in stressed mice are, at least in part, mediated by CB2 receptors.
Relative Deprivation, Income Inequality, and Cardiovascular Health: Observational and Mendelian Randomization Studies in Hong Kong Chinese

The associations between absolute vs. relative income at the household or neighborhood level and cardiovascular disease (CVD) risk remain understudied in the Chinese context. Further, it is unclear whether stress biomarkers, such as cortisol, are on the pathway from income to CVD risk. We examined the associations of absolute and relative income with CVD risk observationally, as well as the mediating role of cortisol, and validated the role of cortisol using Mendelian Randomization (MR) in Hong Kong Chinese. Within Hong Kong's FAMILY Cohort, associations of absolute and relative income at both the individual and neighborhood levels with CVD risk [body mass index (BMI), body fat percentage, systolic blood pressure, diastolic blood pressure, self-reported CVD and self-reported diabetes] were examined using multilevel logistic or linear models (n = 17,607), the mediating role of cortisol using the mediation analysis (n = 1,562), and associations of genetically predicted cortisol with CVD risk using the multiplicative generalized method of moments (MGMMs) or two-stage least squares regression (n = 1,562). In our cross-sectional observational analysis, relative household income deprivation (per 1 SD, equivalent to USD 128 difference in Yitzhaki index) was associated with higher systolic blood pressure (0.47 mmHg, 95% CI 0.30–0.64), but lower BMI (−0.07 kg/m2, 95% CI −0.11 to −0.04), independent of absolute income. Neighborhood income inequality was generally unrelated to CVD and its risk factors, nor was absolute income at the household or neighborhood level. Cortisol did not clearly mediate the association of relative household income deprivation with systolic blood pressure. Using MR, cortisol was unrelated to CVD risk. Based on our findings, relative household income deprivation was not consistently associated with cardiovascular health in Hong Kong Chinese, nor were neighborhood income inequality and absolute income, highlighting the context-specific ways in which relative and absolute income are linked to CVD risk.
Self-Construction, Self-Protection, and Self-Enhancement: A Homeostatic Model of Identity Protection

Abstract Self-protection and self-enhancement, once depicted as biases that impede accurate self-knowledge and hinder effective environmental control, have more recently been viewed as misbeliefs that can have fortuitous, adaptive consequences. I take the next step forward by construing identity protection and enhancement mechanisms as part of a routine, adaptive system. Whereas biological homeostasis regulates physiological processes, psychological homeostasis regulates the emotional states that threaten a desired identity. Ι elaborate on the nature of psychological homeostasis, the identity system that it modulates, and the immune system that safeguards it from harm. Ι discuss the construction of self-views and narratives in the ordinary stream of mental activity, as well as reparative responses to contemporaneous threats, similar to the immune system’s response to microbes that breach the body’s initial defenses. Using basic immunological principles, Ι distinguish between innate and adaptive psychological immunity, compare the spread of disease to that of threatening information among related self-views and narratives, and consider the “memories” of the biological and psychological immune systems to redress future threats. In addition, Ι offer a set of propositions that include predictions about various aspects of immunity, and end by considering the roles of awareness and self-deception in the immunity process.
Topographic and Climatic Control on Chemical Weathering of Mountainous Riverine Sediments of Hainan Island, South China Sea

Hainan Island, the largest island in the northwestern South China Sea (SCS), is characterized by many tropical mountainous rivers that flow into the SCS. The geochemistry of these riverine sediments and the factors controlling the weathering intensity are still not well understood. In this study, sedimentary geochemistry has been investigated by using 45 riverine sediments collected from 18 major rivers on Hainan Island. The Hainan riverine sediments are only first-cycle rather than polycyclic sediments, and they faithfully reflect the present weathering intensity. The high and steady values of the Chemical Index of Alteration (CIA) indicate that the riverine sediments at different parts of the Hainan Island have overall undergone intensive chemical weathering. The low values of Weathering Index of Parker (WIP) and high α C a , α K , α S r , and α B a values of north Hainan indicate the highest weathering degree, which is mainly influenced by the flat topography. The values of α N a , α K , α S r , and α B a of southwest Hainan which are higher than those of east Hainan suggest that the leaching of elements such as Na, K, Sr, and Ba is more extreme (i.e., more intensive weathering). These are mainly caused by the different physical denudation due to different summer precipitation. Overall, the Hainan Island is featured by intensive chemical weathering and is classified as a typical transport-limited weathering regime. Therefore, the geochemistry of the riverine sediments of the Hainan Island is different from that of sediments in tectonically active regions (e.g., Taiwan Island).
Applicability and benefits of the ecosystem concept in the construction industry

Inter-firm collaboration has increased significantly in the last decades. The concept of ecosystem has emerged to explain the nature and implications of businesses’ increasing reliance on networks. The ecosystem concept is intended to be generalizable across sectors, but research on ecosystems has focused on high-tech industries. Moreover, the construction industry has special features that differentiate it from other industries. In this paper, the concept of the ecosystem is introduced and developed in the context of the construction industry and the relationship between ecosystem characteristics and value creation in construction networks is examined. Based on a multiple-case study of six networks in the Finnish and Swedish construction industry, it is suggested that the ecosystem concept is applicable and offers a useful analytical lens for understanding value creation in the construction industry. The results suggest that operating according to ecosystem principles is positively connected to value creation in construction networks. Based on a cross-case analysis, a conceptual framework is presented on the main connections between ecosystem characteristics and value creation. The relevance of the ecosystem concept for the construction industry is predicted to grow in the future, as previous studies suggest that ecosystem-like features are being increasingly employed in construction networks.
Paradox of Success-Mediated Conflicts: Analysing Attitudes of Local Communities Towards Successfully Reintroduced Tigers in India

Conservation programs such as reintroductions are pivotal for the survival and proliferation of endangered species like tigers. However, restoring a carnivore population may create unforeseen problems for communities by fuelling human-wildlife conflict. The long-term persistence of tigers can only be ensured when the support of these local communities is garnered for conservation efforts, especially in release sites from where they were initially eliminated due to anthropogenic causes. The first step to gaining support for tigers and their reintroduction programs is to understand how local communities perceive these large carnivores. This study thus assessed the attitudes of local communities towards the reintroduced tigers of India, in the Panna and Sariska Tiger Reserves, and examined the socio-economic factors that potentially shape their attitudes. Questionnaire surveys were conducted in 330 households across 25 villages in Panna, and 361 households across 32 villages in Sariska. Decision tree and multinomial logistic regression analyses were employed to identify the explanatory variables associated with attitudes. In Panna, more respondents (52.12%) expressed negative opinions about tigers, as compared to positive (24.55%). Whereas in Sariska, more respondents had positive opinions (47.92%) than negative (34.90%). In both the sites, the most frequent reason given by the respondents for their negative attitude towards tigers was “fear. ” Regression modelling suggests that gender and education are key factors associated with the attitude of local communities towards reintroduced tigers. Other factors, specific to the reserves, were the age of the respondent, age of lost livestock, compensation received, and value of fodder obtained from the reserve. Community engagement must be integrated into conservation projects with a focus on educating women and the elderly about carnivores, protecting the traditional rights of local communities, and compensating for their losses.
Commentary: Genomic Analysis Reveals Heterogeneity Between Lesions in Synchronous Primary Right-Sided and Left-Sided Colon Cancer

Surgery Department, Fundación Jiménez Díaz University Hospital, Madrid, Spain, Fundación Jiménez Díaz Research Institute, Madrid, Spain, Hematology Department, Institute of Biomedical Research of Salamanca (IBSAL), Cancer Research Center (CiCIBMCC, CSIC/USAL), Center for Biomedical Research in Network of Cancer (CIBERONC), University Hospital of Salamanca, Salamanca, Spain, Familial Cancer Clinical Unit, Human Cancer Genetics Program, Spanish National Cancer Research Center (CNIO), Madrid, Spain, Molecular Medicine Unit, Biomedical Research Institute of Salamanca (IBSAL), Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-USAL-CSIC, Salamanca, Spain
Quantitative Dissection of the Proximal Ciona brachyury Enhancer

A major goal in biology is to understand the rules by which cis-regulatory sequences control spatially and temporally precise expression patterns. Here we present a systematic dissection of the proximal enhancer for the notochord-specific transcription factor brachyury in the ascidian chordate Ciona. The study uses a quantitative image-based reporter assay that incorporates a dual-reporter strategy to control for variable electroporation efficiency. We identified and mutated multiple predicted transcription factor binding sites of interest based on statistical matches to the JASPAR binding motif database. Most sites (Zic, Ets, FoxA, RBPJ) were selected based on prior knowledge of cell fate specification in both the primary and secondary notochord. We also mutated predicted Brachyury sites to investigate potential autoregulation as well as Fos/Jun (AP1) sites that had very strong matches to JASPAR. Our goal was to quantitatively define the relative importance of these different sites, to explore the importance of predicted high-affinity versus low-affinity motifs, and to attempt to design mutant enhancers that were specifically expressed in only the primary or secondary notochord lineages. We found that the mutation of all predicted high-affinity sites for Zic, FoxA or Ets led to quantifiably distinct effects. The FoxA construct caused a severe loss of reporter expression whereas the Ets construct had little effect. A strong Ets phenotype was only seen when much lower-scoring binding sites were also mutated. This supports the enhancer suboptimization hypothesis proposed by Farley and Levine but suggests that it may only apply to some but not all transcription factor families. We quantified reporter expression separately in the two notochord lineages with the expectation that Ets mutations and RBPJ mutations would have distinct effects given that primary notochord is induced by Ets-mediated FGF signaling whereas secondary notochord is induced by RBPJ/Su(H)-mediated Notch/Delta signaling. We found, however, that ETS mutations affected primary and secondary notochord expression relatively equally and that RBPJ mutations were only moderately more severe in their effect on secondary versus primary notochord. Our results point to the promise of quantitative reporter assays for understanding cis-regulatory logic but also highlight the challenge of arbitrary statistical thresholds for predicting potentially important sites.
How Useful Is Endoscopic Ultrasound in Differentiating T3/T4a T Stage of Colorectal Cancer: A Prospective Study

Objective Endoscopic ultrasound (EUS) is an established method for staging of colorectal cancer. Nevertheless, prior assessments of its T stage accuracy have been limited, particularly ambiguity in assessed T3 and T4a stage. This study was to characterize the EUS image features and pay attention to distinguish T3 from T4a T stage. Methods A total of 638 patients who prospectively underwent colorectal EUS were recorded. The final diagnoses were compared with the concurrent or follow-up histopathology. Univariate and multivariate logistic regressions were used to assess variation in diagnostic performance with case attributes. Results The accuracies of EUS in classifying colorectal cancer for overall, T1, T2, T3, and T4a stages are 73.04, 62.32, 67.46, 71.26, and 83.52%, respectively. With attention to EUS image features, the lesion penetrates the entire wall and locates below the seminal vesicles or cervix is T3 stage. If the lesion locates above clearly-defined space between the anterior rectal wall and the posterior surface of the seminal vesicles or cervix, we identify as T4a stage; However, when located above seminal vesicles or cervix but on the posterior wall of the rectum, the lesion still considers as T3 stage. The tumor location and histological type are associated with inaccuracy T stage. Conclusions EUS provides reliable diagnostic accuracy in the colorectal cancer stage. The seminal vesicles and cervix are the important markers to predict infiltration depth for T3/T4a stage. Furthermore, the tumor location, histological type, and EUS image features for each tumor T stage should warrant attention.
Active Tectonics of the Nantinghe Fault in Southeastern Tibetan Plateau and its Implications for Continental Collision

Quantifying the structure and kinematics of active faults is the key to understanding the India-Eurasia continental collision. While the boundary faults of blocks in the southeastern Tibetan Plateau region have been under scrutiny for decades, relatively less attention has been paid to the active faults within the blocks. Here, we use structural, sedimentary, and geomorphic characteristics to constrain the late Quaternary kinematics and slip rates of the Nantinghe fault, a major fault within the southeastern Tibetan Plateau region. The Nantinghe fault is an active, dominantly left-lateral strike-slip fault that can be traced continuously for 500 km. We analyze the late Quaternary slip rates at five sites along the fault trace. The latest Quaternary apparent throw rates are typically less than 1 mm/a. The rate of strike-slip displacement is estimated to be an order of magnitude higher, 4.0 ± 0.6 (2σ) mm/a. Trenching suggests that active fault behavior is dominated by strike-slip faulting and reveals five earthquake events with refined information of timing in the last 5,000 years, suggesting an averaged recurrence interval of ∼1,000 a. These observations agree with GPS-derived estimates and show that late Quaternary slip rates on the Nantinghe fault are comparable to those on other major active strike-slip faults in the southeastern Tibetan Plateau. The newly-obtained slip rates on the Nantinghe fault, integrated with previous estimates on other faults in this region, provide direct evidence that favors the continuum models over the rigid block ones, on the Quaternary deformation mechanism in the India-Asia continental collision.
Positive Rate of Human Papillomavirus and Its Trend in Head and Neck Cancer in South Korea

Introduction This study aimed to investigate the positive rate of human papillomavirus (HPV) and its trend in head and neck squamous cell carcinoma (HNSCC) in South Korea and to evaluate the clinical differences between HPV-positive and -negative tumors. Methods We studied 300 patients with HNSCC arising in the oropharynx (n = 77), oral cavity (n = 65), larynx (n = 106), hypopharynx (n = 40), and sinonasal cavity (n = 12), treated in a tertiary university hospital in South Korea from January 2008 to July 2020. HPV status was determined using p16 immunohistochemical staining of formalin-fixed paraffin-embedded tissues. Results Of the 300 patients with HNSCC, the positive rate of p16 was 30.3% (91/300). The p16 positive rate was 70.1, 13.9, 20.8, 15, and 0% in the oropharynx, oral cavity, larynx, hypopharynx, and sinonasal cavity, respectively. HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) patients were significantly younger than HPV-negative OPSCC patients. The positive rate of HPV in OPSCC has increased over time from 2008 to 2020, but has not changed significantly in the other primary sites. The disease-free survival curve of HPV-positive OPSCC was significantly better than that of HPV-negative tumors. Conclusion The positive rate of HPV in Korean patients with OPSCC is significantly high (70.1%), similar to that in North America and Europe, and has increased abruptly in the past 12 years.
Health Literacy Among University Students: A Systematic Review of Cross-Sectional Studies

Objective The aim of this systematic review was to provide an overview of cross-sectional studies that examined health literacy among university students and to identify possible determinants related to health literacy. Method The current review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Three databases (PubMed, Scopus, and Web of Science) were systematically searched for cross-sectional studies that examined health literacy among university students. Results of included studies were narratively summarized. Results The systematic review includes twenty-one research studies. The majority of studies report health literacy scores among university students that are lower compared to reference samples. The health literacy of students is influenced by different variables (age, gender, number of semesters, course of studies/curriculum, parental education, and socioeconomic background). Discussion Health literacy activities should target all students. Universities should make use of their resources and offer health literacy courses for students in which content is used from disciplines available at the university (e.g., medicine, health, or psychology). To increase effectiveness, health literacy courses should be adapted according to the different needs and characteristics of the student subgroups.
Metabolic competition between lipid metabolism and histone methylation regulates sexual differentiation in human malaria parasites

For Plasmodium falciparum, the most widespread and virulent malaria parasite that infects humans, persistence depends on continuous asexual replication in red blood cells, while transmission to their mosquito vector requires asexual blood-stage parasites to differentiate into non-replicating gametocytes. This decision is controlled by stochastic de-repression of a heterochromatin-silenced locus encoding PfAP2-G, the master transcription factor of sexual differentiation. The frequency of pfap2-g de-repression was shown to be responsive to extracellular phospholipid precursors but the mechanism linking these metabolites to epigenetic regulation of pfap2-g was unknown. Here we show that this response is mediated by metabolic competition for the methyl donor S-adenosylmethionine between histone methyltransferases and phosphoethanolamine methyltransferase, a critical enzyme in the parasite’s pathway for de novo phosphatidylcholine synthesis. When phosphatidylcholine precursors are scarce, increased consumption of SAM for de novo phosphatidylcholine synthesis impairs maintenance of the histone methylation responsible for silencing pfap2-g, increasing the frequency of derepression and sexual differentiation.