Miracle-dz/UniFAR-FTUs huggingface dataset:
Home Tobacco Use Policies and Exposure to Secondhand Tobacco Smoke: Findings from Waves 1 through 4 of the Population Assessment of Tobacco and Health (PATH) Study

Background: The 2006 Surgeon General’s Report recommended the elimination of smoking in homes as an effective protective measure against the harmful effects of secondhand tobacco smoke exposure. This study aims to examine trends in the prevalence and levels of the adoption of home tobacco use policies specifically for cigarettes, e-cigarettes, smokeless tobacco, and the relationships between home tobacco use policies and self-reported exposure to secondhand tobacco smoke. Methods: This study utilizes data from Wave 1 (2013–2014) through Wave 4 (2016–2018) of the Population Assessment of Tobacco and Health (PATH) Study, a large prospective cohort study of youths and adults in the United States which collected information about both smoke-free and tobacco-free home policies. We present the weighted, population-based, self-reported prevalence of home tobacco use policies overall and by product, and the average number of self-reported hours of secondhand smoke (SHS) exposure by levels of home tobacco policy and by survey wave. In addition, we examine the characteristics of those who adopted (by yes or no) a home tobacco use ban between survey waves. Results: We found a high prevalence of completely tobacco-free home policies (69.5%). However, 10.6% of adults allow the use of any type of tobacco product inside their homes, and 19.8% have a policy allowing the use of some types of tobacco products and banning the use of others. Adults with a complete tobacco use ban inside their homes were more likely to be nonusers of tobacco (79.9%); living with children in the home (71.8%); at or above the poverty level (70.8%); non-white (76.0%); Hispanic (82.7%); and aged 45 or older (71.9%). The adoption of 100% tobacco-free home policies is associated with a 64% decrease in secondhand smoke exposure among youths and a 69% decrease in exposure among adults. Conclusions: Most US adults have implemented tobacco-free home policies; however, there is still exposure to SHS in the home, for both adults and children, particularly in the homes of tobacco users. Additional research should investigate tobacco-free home policies for different types of products and what effect they have on future tobacco use behaviors.
Gambling-Related Harms for Affected Others: A Finnish Population-Based Survey

Aims This study explores the prevalence of being a past-year affected other (AO) of a problem gambler by gender. The aims were to study the amount and type of gambling-related harms (GRHs) for subgroups of AOs and to distinguish GRH profiles for AO subgroups. Methods A total of 7186 adults aged 18 years and over participated in the Gambling Harms Survey evaluating year 2016. The data were analyzed using descriptive statistics and binary logistic regression. Results Of all respondents, 12.9% were defined as past-year AOs (women 13.7%; men 12.1%). The proportion of affected non-family members (ANFs) was 8.4%, and 5.6% were affected family members (AFMs). AFMs were usually women, and ANFs were usually men. Emotional, relationship, and financial harms were the most common types of harm. The odds of experiencing financial harm were highest for the 18- to 34-year-olds (OR 1.82) and for those whose partner/ex-partner had a gambling problem (OR 3.91). Having a parent/step-parent (OR 1.93) and child/stepchild (OR 3.64) increased the odds of experiencing emotional harm, whereas male gender (OR 0.50) and being an ANF (OR 0.58) decreased emotional harm. Relationship harm was evident for partners/ex-partners (OR 1.97–5.07). Conclusions GRH profiles for AO subgroups varied, which emphasizes the need for effective harm minimization strategies for those in need.
The Oncogenic Signaling Disruptor, NDRG1: Molecular and Cellular Mechanisms of Activity

NDRG1 is an oncogenic signaling disruptor that plays a key role in multiple cancers, including aggressive pancreatic tumors. Recent studies have indicated a role for NDRG1 in the inhibition of multiple tyrosine kinases, including EGFR, c-Met, HER2 and HER3, etc. The mechanism of activity of NDRG1 remains unclear, but to impart some of its functions, NDRG1 binds directly to key effector molecules that play roles in tumor suppression, e.g., MIG6. More recent studies indicate that NDRG1s-inducing drugs, such as novel di-2-pyridylketone thiosemicarbazones, not only inhibit tumor growth and metastasis but also fibrous desmoplasia, which leads to chemotherapeutic resistance. The Casitas B-lineage lymphoma (c-Cbl) protein may be regulated by NDRG1, and is a crucial E3 ligase that regulates various protein tyrosine and receptor tyrosine kinases, primarily via ubiquitination. The c-Cbl protein can act as a tumor suppressor by promoting the degradation of receptor tyrosine kinases. In contrast, c-Cbl can also promote tumor development by acting as a docking protein to mediate the oncogenic c-Met/Crk/JNK and PI3K/AKT pathways. This review hypothesizes that NDRG1 could inhibit the oncogenic function of c-Cbl, which may be another mechanism of its tumor-suppressive effects.
The Manifold Cellular Functions of von Willebrand Factor

The plasma glycoprotein von Willebrand factor (VWF) is exclusively synthesized in endothelial cells (ECs) and megakaryocytes, the precursor cells of platelets. Its primary function lies in hemostasis. However, VWF is much more than just a “fishing hook” for platelets and a transporter for coagulation factor VIII. VWF is a true multitasker when it comes to its many roles in cellular processes. In ECs, VWF coordinates the formation of Weibel–Palade bodies and guides several cargo proteins to these storage organelles, which control the release of hemostatic, inflammatory and angiogenic factors. Leukocytes employ VWF to assist their rolling on, adhesion to and passage through the endothelium. Vascular smooth muscle cell proliferation is supported by VWF, and it regulates angiogenesis. The life cycle of platelets is accompanied by VWF from their budding from megakaryocytes to adhesion, activation and aggregation until the end in apoptosis. Some tumor cells acquire the ability to produce VWF to promote metastasis and hide in a shell of VWF and platelets, and even the maturation of osteoclasts is regulated by VWF. This review summarizes the current knowledge on VWF’s versatile cellular functions and the resulting pathophysiological consequences of their dysregulation.
Periconceptional Maternal Diet Characterized by High Glycemic Loading Is Associated with Offspring Behavior in NEST

Maternal periconceptional diets have known associations with proper offspring neurodevelopment. Mechanisms for such associations include improper energy/nutrient balances between mother and fetus, as well as altered offspring epigenetics during development due to maternal nutrient and inflammatory status. Using a comprehensive food frequency questionnaire and assessing offspring temperament with the Infant-Toddler Social and Emotional Assessment (n = 325, mean age = 13.9 months), we sought to test whether a maternal periconceptional diet characterized by high glycemic loading (MGL) would affect offspring temperament using adjusted ordinal regression. After limiting false discovery to 10%, offspring born to mothers in tertile 3 of glycemic loading (referent = tertile 1) were more likely to be in the next tertile of anxiety [OR (95% CI) = 4.51 (1.88–11.07)] and inhibition-related behaviors [OR (95% CI) = 3.42 (1.49–7.96)]. Male offspring were more likely to exhibit impulsive [OR (95% CI) = 5.55 (1.76–18.33)], anxiety [OR (95% CI) = 4.41 (1.33–15.30)], sleep dysregulation [OR (95% CI) = 4.14 (1.34–13.16)], empathy [6.68 (1.95–24.40)], and maladaptive behaviors [OR (95% CI) = 9.86 (2.81–37.18)], while females were more likely to exhibit increased anxiety-related behaviors [OR (95% CI) = 15.02 (3.14–84.27)]. These associations persisted when concurrently modeled with the maternal–Mediterranean dietary pattern. In a subset (n = 142), we also found MGL associated with increased mean methylation of the imprint control region of SGCE/PEG10. In conclusion, these findings highlight the importance of maternal dietary patterns on offspring neurodevelopment, offering avenues for prevention options for mothers.
8-Amino-6-Methoxyquinoline—Tetrazole Hybrids: Impact of Linkers on Antiplasmodial Activity

A new series of compounds was prepared from 6-methoxyquinolin-8-amine or its N-(2-aminoethyl) analogue via Ugi-azide reaction. Their linkers between the quinoline and the tert-butyltetrazole moieties differ in chain length, basicity and substitution. Compounds were tested for their antiplasmodial activity against Plasmodium falciparum NF54 as well as their cytotoxicity against L-6-cells. The activity and the cytotoxicity were strongly influenced by the linker and its substitution. The most active compounds showed good activity and promising selectivity.
CytokineLink: A Cytokine Communication Map to Analyse Immune Responses—Case Studies in Inflammatory Bowel Disease and COVID-19

Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of infectious and inflammatory diseases. By releasing these small molecular weight peptides, the source cells can influence numerous intracellular processes in the target cells, including the secretion of other cytokines downstream. However, there are no readily available bioinformatic resources that can model cytokine–cytokine interactions. In this effort, we built a communication map between major tissues and blood cells that reveals how cytokine-mediated intercellular networks form during homeostatic conditions. We collated the most prevalent cytokines from the literature and assigned the proteins and their corresponding receptors to source tissue and blood cell types based on enriched consensus RNA-Seq data from the Human Protein Atlas database. To assign more confidence to the interactions, we integrated the literature information on cell–cytokine interactions from two systems of immunology databases, immuneXpresso and ImmunoGlobe. From the collated information, we defined two metanetworks: a cell–cell communication network connected by cytokines; and a cytokine–cytokine interaction network depicting the potential ways in which cytokines can affect the activity of each other. Using expression data from disease states, we then applied this resource to reveal perturbations in cytokine-mediated intercellular signalling in inflammatory and infectious diseases (ulcerative colitis and COVID-19, respectively). For ulcerative colitis, with CytokineLink, we demonstrated a significant rewiring of cytokine-mediated intercellular communication between non-inflamed and inflamed colonic tissues. For COVID-19, we were able to identify cell types and cytokine interactions following SARS-CoV-2 infection, highlighting important cytokine interactions that might contribute to severe illness in a subgroup of patients. Such findings have the potential to inform the development of novel, cytokine-targeted therapeutic strategies. CytokineLink is freely available for the scientific community through the NDEx platform and the project github repository.
Potential of Vasoprotectives to Inhibit Non-Enzymatic Protein Glycation, and Reactive Carbonyl and Oxygen Species Uptake

Reactive carbonyl species (RCS) such as methylglyoxal (MGO) or glyoxal (GO) are the main precursors of the formation of advanced glycation end products (AGEs). AGEs are a major factor in the development of vascular complications in diabetes. Vasoprotectives (VPs) exhibit a wide range of activities beneficial to cardiovascular health. The present study aimed to investigate selected VPs and their structural analogs for their ability to trap MGO/GO, inhibit AGE formation, and evaluate their antioxidant potential. Ultra-high-performance liquid chromatography coupled with an electrospray ionization mass spectrometer (UHPLC-ESI-MS) and diode-array detector (UHPLC-DAD) was used to investigate direct trapping capacity and kinetics of quenching MGO/GO, respectively. Fluorimetric and colorimetric measurements were used to evaluate antiglycation and antioxidant action. All tested substances showed antiglycative effects, but hesperetin was the most effective in RCS scavenging. We demonstrated that rutin, diosmetin, hesperidin, and hesperetin could trap both MGO and GO by forming adducts, whose structures we proposed. MGO-derived AGE formation was inhibited the most by hesperetin, and GO-derived AGEs by diosmetin. High reducing and antiradical activity was confirmed for quercetin, rutin, hesperetin, and calcium dobesilate. Therefore, in addition to other therapeutic applications, some VPs could be potential candidates as antiglycative agents to prevent AGE-related complications of diabetes.
Bioconjugation Strategies for Connecting Proteins to DNA-Linkers for Single-Molecule Force-Based Experiments

The mechanical properties of proteins can be studied with single molecule force spectroscopy (SMFS) using optical tweezers, atomic force microscopy and magnetic tweezers. It is common to utilize a flexible linker between the protein and trapped probe to exclude short-range interactions in SMFS experiments. One of the most prevalent linkers is DNA due to its well-defined properties, although attachment strategies between the DNA linker and protein or probe may vary. We will therefore provide a general overview of the currently existing non-covalent and covalent bioconjugation strategies to site-specifically conjugate DNA-linkers to the protein of interest. In the search for a standardized conjugation strategy, considerations include their mechanical properties in the context of SMFS, feasibility of site-directed labeling, labeling efficiency, and costs.
Unveiling the Metabolic Effects of Glycomacropeptide

For many years, the main nitrogen source for patients with phenylketonuria (PKU) was phenylalanine-free amino acid supplements. Recently, casein glycomacropeptide (GMP) supplements have been prescribed due to its functional and sensorial properties. Nevertheless, many doubts still persist about the metabolic effects of GMP compared to free amino acids (fAA) and intact proteins such as casein (CAS). We endeavour to compare, in rats, the metabolic effects of different nitrogen sources. Twenty-four male Wistar rats were fed equal energy density diets plus CAS (control, n = 8), fAA (n = 8) or GMP (n = 8) for 8 weeks. Food, liquid intake and body weight were measured weekly. Blood biochemical parameters and markers of glycidic metabolism were assessed. Glucagon-like peptide-1 (GLP-1) was analysed by ELISA and immunohistochemistry. Food intake was higher in rats fed CAS compared to fAA or GMP throughout the treatment period. Fluid intake was similar between rats fed fAA and GMP. Body weight was systematically lower in rats fed fAA and GMP compared to those fed CAS, and still, from week 4 onwards, there were differences between fAA and GMP. None of the treatments appeared to induce consistent changes in glycaemia, while insulin levels were significantly higher in GMP. Likewise, the production of GLP-1 was higher in rats fed GMP when compared to fAA. Decreased urea, total protein and triglycerides were seen both in fAA and GMP related to CAS. GMP also reduced albumin and triglycerides in comparison to CAS and fAA, respectively. The chronic consumption of the diets triggers different metabolic responses which may provide clues to further study potential underlying mechanisms.
Studies to Improve Perinatal Health through Diet and Lifestyle among South Asian Women Living in Canada: A Brief History and Future Research Directions

South Asians (i.e., people who originate from India, Pakistan, Sri Lanka, Nepal, and Bangladesh) have higher cardiovascular disease rates than other populations, and these differences persist in their offspring. Nutrition is a critical lifestyle-related factor that influences fetal development, and infant and child health in early life. In high-income countries such as Canada, nutrition-related health risks arise primarily from overnutrition, most strikingly for obesity and associated non-communicable diseases. Evidence for developmental programming during fetal life underscores the critical influence of maternal diet on fetal growth and development, backed by several birth cohort studies including the Pune Maternal Nutrition Study, the South Asian Birth Cohort Study, and the Born in Bradford Study. Gestational diabetes mellitus is a strong risk factor for type 2 diabetes, future atherosclerosis and cardiovascular disease in the mother and increases the risk of type 2 diabetes in her offspring. Non-pharmacological trials to prevent gestational diabetes are few, often not randomized, and are heterogeneous with respect to design, and outcomes have not converged upon a single optimal prevention strategy. The aim of this review is to provide an understanding of the current knowledge around perinatal nutrition and gestational diabetes among the high-risk South Asian population as well as summarize our research activities investigating the role of culturally-tailored nutrition advice to South Asian women living in high-income settings such as Canada. In this paper, we describe these qualitative and quantitative studies, both completed and underway. We conclude with a description of the design of a randomized trial of a culturally tailored personalized nutrition intervention to reduce gestational glycaemia in South Asian women living in Canada and its implications.
Modern Approaches to Lower Lipoprotein(a) Concentrations and Consequences for Cardiovascular Diseases

Lipoprotein(a) (Lp(a)) is a low density lipoprotein particle that is associated with poor cardiovascular prognosis due to pro-atherogenic, pro-thrombotic, pro-inflammatory and pro-oxidative properties. Traditional lipid-lowering therapy does not provide a sufficient Lp(a) reduction. For PCSK9 inhibitors a small reduction of Lp(a) levels could be shown, which was associated with a reduction in cardiovascular events, independently of the effect on LDL cholesterol. Another option is inclisiran, for which no outcome data are available yet. Lipoprotein apheresis acutely and in the long run decreases Lp(a) levels and effectively improves cardiovascular prognosis in high-risk patients who cannot be satisfactorily treated with drugs. New drugs inhibiting the synthesis of apolipoprotein(a) (an antisense oligonucleotide (Pelacarsen) and two siRNA drugs) are studied. Unlike LDL-cholesterol, for Lp(a) no target value has been defined up to now. This overview presents data of modern capabilities of cardiovascular risk reduction by lowering Lp(a) level.
Neurons in Primary Motor Cortex Encode External Perturbations during an Orientation Reaching Task

When confronting an abrupt external perturbation force during movement, subjects continuously adjust their behaviors to adapt to changes. Such adaptation is of great importance for realizing flexible motor control in varied environments, but the potential cortical neuronal mechanisms behind it have not yet been elucidated. Aiming to reveal potential neural control system compensation for external disturbances, we applied an external orientation perturbation while monkeys performed an orientation reaching task and simultaneously recorded the neural activity in the primary motor cortex (M1). We found that a subpopulation of neurons in the primary motor cortex specially created a time-locked activity in response to a “go” signal in the adaptation phase of the impending orientation perturbation and did not react to a “go” signal under the normal task condition without perturbation. Such neuronal activity was amplified as the alteration was processed and retained in the extinction phase; then, the activity gradually faded out. The increases in activity during the adaptation to the orientation perturbation may prepare the system for the impending response. Our work provides important evidence for understanding how the motor cortex responds to external perturbations and should advance research about the neurophysiological mechanisms underlying motor learning and adaptation.
Individuals with Major Depressive Disorder Report High Scores of Insecure-Avoidant and Insecure-Anxious Attachment Styles, Dissociative Identity Symptoms, and Adult Traumatic Events

Objective: Individuals with major depressive disorder (MDD) report more issues in social interaction compared to the general population. Moreover, dimensions of dissociation are considered dysfunctional strategies to cope with adverse life events. In this regard, current symptoms of MDD could be associated with traumatic events that occurred in childhood and in adult life. Given this background, the aim of the present study was to explore the associations between attachment styles as a proxy of quality of social interaction, dimensions of dissociation, and childhood and adult traumatic life events among individuals with MDD. Method: A total of 300 individuals with MDD (mean age: 31.31 years; 58.7% female) took part in this study. They completed a series of questionnaires on sociodemographic information, attachment styles, dimensions of dissociation, and childhood and adult traumatic life events. Results: Prevalence rates for attachment styles were as follows: anxious/ambivalent attachment style—71.7%; avoidant/dependent attachment style—13%; secure/close attachment style—15.3%. Compared to the general population, the participants reported higher prevalence rates of insecure attachment styles. Current symptoms of dissociation were associated with adult but not childhood traumatic life events. An anxious attachment style was associated with higher scores of dissociation. Conclusion: Psychotherapeutic treatment of individuals with MDD should consider the individuals’ challenging attachment styles and their risk of dissociation. While it is important to consider both adult and childhood traumatic events, in this research, more recent trauma occurring in adulthood was associated with current symptoms of dissociation.
Romantic Love and Sleep Variations: Potential Proximate Mechanisms and Evolutionary Functions

Simple Summary Romantic love is a topic of immense interest to scientists and the general public. This article defines and describes romantic love and sleep. It then summarises what research says about sleep in people experiencing romantic love. People in love experience changes in their sleep. We explain why people in love may experience sleep changes and what evolutionary purpose they might serve. We suggest that we are not able to determine whether sleep changes are a result of evolution or a secondary consequence. We finish by suggesting ideas for future research. Abstract This article provides a narrative review of what is known about romantic love and sleep variations and provides possible explanations for the association. Romantic love and sleep are described using a comprehensive, unifying framework advocated by Tinbergen. We summarise the findings of studies investigating the relationship between romantic love and sleep. Sleep variations are associated with romantic love in adolescents and young adults. We then detail some proximate mechanisms that may contribute to sleep variations in people experiencing romantic love before considering potential evolutionary functions of sleep variations in people experiencing romantic love. The relationship between symptoms of psychopathology and sleep variations in people experiencing romantic love is described. With the current state of knowledge, it is not possible to determine whether sleep variations associated with romantic love are adaptations or by-products of romantic love. We conclude by proposing areas for future research.