Miracle-dz/UniFAR-FTUs huggingface dataset:
The gate to metastasis: key players in cancer cell intravasation

Metastasis is a leading cause of cancer‐related death and consists of a sequence of events including tumor expansion, intravasation of cancer cells into the circulation, survival in the bloodstream, extravasation at distant sites, and subsequent organ colonization. Particularly, intravasation is a process whereby cancer cells transverse the endothelium and leave the primary tumor site, pioneering the metastatic cascade. The identification of those mechanisms that trigger the entry of cancer cells into the bloodstream may reveal fundamentally novel ways to block metastasis at its start. Multiple factors have been implicated in cancer progression, yet, signals that unequivocally provoke the detachment of cancer cells from the primary tumor are still under investigation. Here, we discuss the role of intrinsic properties of cancer cells, tumor microenvironment, and mechanical cues in the intravasation process, outlining studies that suggest the involvement of various factors and highlighting current understanding and open questions in the field.
Association with Longevity of Phosphatidylinositol 3-Kinase Regulatory Subunit 1 Gene Variants Stems from Protection against Mortality Risk in Men with Cardiovascular Disease

Introduction: Genetic variation in the phosphatidylinositol 3-kinase reregulatory subunit 1 gene (PIK3R1) is associated with longevity. Objective: The aim of the study was to determine whether cardiovascular disease (CVD) affects this association. Methods: We performed a longitudinal study of longevity-associated PIK3R1 single-nucleotide polymorphism rs7709243 genotype by CVD status in 3,584 elderly American men of Japanese ancestry. Results: At baseline (1991–1993), 2,254 subjects had CVD and 1,314 did not. The follow-up until Dec 31, 2019 found that overall, men with a CVD had higher mortality than men without a CVD (p = 1.7 × 10−5). However, survival curves of CVD subjects differed according to PIK3R1 genotype. Those with longevity-associated PIK3R1 TT/CC had survival curves similar to those of subjects without a CVD (p = 0.11 for TT/CC, and p = 0.054 for TC), whereas survival curves for CVD subjects with the CT genotype were significantly attenuated compared with survival curves of subjects without a CVD (p = 0.0000012 compared with TT/CC, and p = 0.0000028 compared with TC). Men without CVD showed no association of longevity-associated genotype with life span (p = 0.58). Compared to subjects without any CVD, hazard ratios for mortality risk were 1.26 (95% CI, 1.14–1.39; p = 0.0000043) for CT subject with CVD and 1.07 (95% CI 0.99–1.17; p = 0.097) for CC/TT subjects with CVD. There was no genotypic effect on life span for 1,007 subjects with diabetes and 486 with cancer. Conclusion: Our study provides novel insights into the basis for PIK3R1 as a longevity gene. We suggest that the PIK3R1 longevity genotype attenuates mortality risk in at-risk individuals by protection against cellular stress caused by CVD.
Self-reported functional impairment in college students: relationship to noncredible reporting, ADHD, psychological disorders, and other psychological factors

ABSTRACT Introduction Both symptoms and functional impairment should be assessed in college students seeking evaluations for Attention Deficit Hyperactivity Disorder (ADHD). However, impairment is not specific to ADHD. Although it is well documented that self-reported symptoms can be reported noncredibly, there is less research examining credibility of self-reported impairment, and few clinicians rule out alternative causes for impairment. Method Participants (N = 428) completed self-report measures of functional impairment, sleep, perceived stress, and in an ADHD symptom measure with embedded validity indicators. Results Noncredible reporters endorsed greater functional impairment than credible reporters in several domains, but impairment was reported at a high rate even in credible responders (N = 323) in several domains. Participants who reported prior ADHD and participants who reported prior psychiatric diagnoses reported greater impairment and higher rates of clinically significant impairment than those who reported no prior diagnoses. Few differences in reported impairment emerged between those who reported ADHD and psychiatric diagnoses. Sleep and stress accounted for significant variance in impairment, and the ADHD group reported greater impairment than the psychiatric diagnosis and no diagnosis groups after controlling for these variables. Conclusions Results reinforce the importance of considering the validity of, and alternative sources for, self-reported impairment in college students with ADHD concerns.
Implementation of START (STrAtegies for RelaTives) for dementia carers in the third sector: Widening access to evidence-based interventions

Family members remain the main care providers for the increasing numbers of people with dementia, and often become depressed or anxious. In an implementation research project, we aimed to widen access to Strategies for RelaTives (START), a clinically and cost-effective intervention for the mental health of family carers, by laying the foundations for its implementation in the third sector. We used the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to guide implementation of START, a manual-based, individually-delivered, multicomponent eight-session coping strategy intervention. We interviewed a maximum variation sample of twenty-seven stakeholders from the English Alzheimer’s Society (AS), about possible difficulties in management, training, and delivery of START. We trained and supervised three AS dementia support workers in different locations, to each deliver START to three family carers. Two researchers independently coded pre-intervention interviews for themes. We assessed intervention feasibility through monitoring delivery fidelity, rating audio-recordings from 1–5 (5 being high) and interviewing facilitators, family carers and AS managers about their experiences. We assessed effectiveness on family carers’ mental health using the Hospital Anxiety and Depression Scale (HADS) before and after receiving START (scores 0–42). We changed START’s format by reflecting carer diversity more and increasing carer stories prominence, but core content or delivery processes were unchanged. All carers received START and attended every session. The mean fidelity score was 4.2. Mean HADS-total score reduced from baseline 18.4 (standard deviation 7.4) to follow-up 15.8 (9.7). Six (67%) carers scored as clinically depressed on baseline HADS and 2 (22%) at follow-up. Facilitators and carers rated START positively. Appropriately experienced third sector workers can be trained and supervised to deliver START and it remains effective. This has the potential for widened access at scale.
Association of VEGFA polymorphisms with chronic obstructive pulmonary disease in Chinese Han and Mongolian populations

What is the central question of this study? Vascular endothelial growth factor A (VEGFA) is an important growth factor involved in changes in the bronchial microvascular and airway inflammation in chronic obstructive pulmonary disease (COPD) progression. What is the association of single nucleotide polymorphisms (SNPs) in VEGFA with the risk of COPD in the Chinese Han and Mongolian populations? What is the main finding and its importance? The effect of five SNPs in the VEGFA gene was analysed and compared between the Chinese Han and Mongolian populations. A contribution of risk alleles rs833068, rs833070 and rs3024997 to COPD was detected in the Chinese Mongolian population only. The study provided data from different populations to validate the role of VEGFA polymorphisms in COPD and provided reliable SNPs to predict the risk of COPD.
Endogenous erythropoietin concentrations and association with retinopathy of prematurity and brain injury in preterm infants

Background Endogenous erythropoietin (EPO) concentrations vary widely in preterm infants and may be associated with perinatal risk factors and neurological outcomes. Erythropoietin is elevated in fetal hypoxia but is also a potential neuroprotectant. Methods In a prospective study of 27 infants ≤ 30 weeks gestation, serum erythropoietin concentrations were measured during the first month of life, on day 1 and weeks 1, 2, and 4, and related to perinatal risk factors and outcomes including retinopathy of prematurity and cerebral injury evaluated near term-equivalent post menstrual age using magnetic resonance imaging with quantitative scoring. Results Lower birth weight was associated with higher EPO concentrations throughout the first 2 weeks of life (r = -0.6, p < 0.01). Higher day 1 and week 1 EPO concentrations were associated with lower Apgar score at 1 minute (r = - 0.5) and 5 minutes (r = -0.7), respectively (p < 0.01). Higher day 1 EPO concentrations and 2-week area under the curve were associated with increased risk (p = 0.01) and severity (r = 0.5, p < 0.02) of retinopathy of prematurity. Higher EPO concentrations at 2 weeks were associated with increased total brain injury score (r = 0.5, p < 0.05). Conclusion Elevated endogenous erythropoietin concentrations in the first two weeks of life are associated with lower birth weight and increased risk of adverse outcomes.
The menopausal transition does not influence skeletal muscle capillary growth in response to cycle training in women.

The influence of the menopausal transition, with a consequent loss of oestrogen, on capillary growth in response to exercise training remains unknown. In the present study, we evaluated the effect of a period of intense endurance training on skeletal muscle angiogenesis in late pre-menopausal and recently post-menopausal women with an age difference of <4 years. Skeletal muscle biopsies were obtained from the thigh muscle prior to and after 12 weeks of intense aerobic cycle training, and analyzed for capillarization, fiber type distribution and content of vascular endothelial growth factor (VEGF). At baseline, there was no difference in capillary per fiber ratio (C:F; 1.41 ± 0.22 vs 1.40 ± 0.30), capillary density (CD; 305±61 vs 336±52 mm2), muscle fiber area (MFA) or percentage distribution of muscle fiber type I (47.3±10.1 vs 49.3±15.1 %) and type II (52.7±10.1 vs 50.7±15.1%) between the pre- and post-menopausal women. The training period resulted in a similar increase in C:F in pre- and post-menopausal women (by 9.2 vs 12.1 %, respectively) and CD (by 6.9 vs 8.9 %, respectively), whereas MFA and fiber type distribution remained unaltered. Skeletal muscle VEGF protein content was similar between groups at baseline and increased to a similar extent with training (by 21.1 vs 27.2 %, respectively) in the pre- and post-menopausal women. In conclusion, the loss of oestrogen per se at menopause does not influence the capillary growth response to intense aerobic exercise training.
A story to tell: the role of narratives in reducing delay discounting for people who strongly discount the future

ABSTRACT Delay Discounting (DD) or devaluing a future, larger reward in favour of a smaller, more immediate reward, has been linked to negative health behaviours. One intervention that reduces DD is Episodic Future Thinking (EFT). EFT has participants generate cues representing positive future events that correspond to temporal windows during the DD task. The current study examined if incorporating EFT cues into narratives would strengthen effects on DD. One hundred and sixty adults were recruited from Amazon Mechanical Turk and were randomised to traditional or narrative EFT. Results showed that participants in narrative EFT discounted the future less (p = 0.034) than participants who engaged in traditional EFT. This novel approach to EFT is well grounded in research and theory on the power of narratives to influence behaviour and can open a new window into ways to reduce DD to strengthen engagement in positive choices.
Fibrosis: Sirtuins at the checkpoints of myofibroblast differentiation and profibrotic activity

Fibrotic diseases are still a serious concern for public health, due to their high prevalence, complex etiology and lack of successful treatments. Fibrosis consists of excessive accumulation of extracellular matrix components. As a result, the structure and function of tissues are impaired, thus potentially leading to organ failure and death in several chronic diseases. Myofibroblasts represent the principal cellular mediators of fibrosis, due to their extracellular matrix producing activity, and originate from different types of precursor cells, such as mesenchymal cells, epithelial cells and fibroblasts. Profibrotic activation of myofibroblasts can be triggered by a variety of mechanisms, including the transforming growth factor‐β signalling pathway, which is a major factor driving fibrosis. Interestingly, preclinical and clinical studies showed that fibrotic degeneration can stop and even reverse by using specific antifibrotic treatments. Increasing scientific evidence is being accumulated about the role of sirtuins in modulating the molecular pathways responsible for the onset and development of fibrotic diseases. Sirtuins are NAD+‐dependent protein deacetylases that play a crucial role in several molecular pathways within the cells, many of which at the crossroad between health and disease. In this context, we will report the current knowledge supporting the role of sirtuins in the balance between healthy and diseased myofibroblast activity. In particular, we will address the signalling pathways and the molecular targets that trigger the differentiation and profibrotic activation of myofibroblasts and can be modulated by sirtuins.
Dose–Response Relationships Between Polypharmacy and All-Cause and Cause-Specific Mortality Among Older People

Abstract Background Although medicines are prescribed based on clinical guidelines and expected to benefit patients, both positive and negative health outcomes have been reported associated with polypharmacy. Mortality is the main outcome, and information on cause-specific mortality is scarce. Hence, we investigated the association between different levels of polypharmacy and all-cause and cause-specific mortality among older adults. Method The English Longitudinal Study of Ageing is a nationally representative study of people aged 50+. From 2012/2013, 6 295 individuals were followed up to April 2018 for all-cause and cause-specific mortality. Polypharmacy was defined as taking 5–9 long-term medications daily and heightened polypharmacy as 10+ medications. Cox proportional hazards regression and competing-risks regression were used to examine associations between polypharmacy and all-cause and cause-specific mortality, respectively. Results Over a 6-year follow-up period, both polypharmacy (19.3%) and heightened polypharmacy (2.4%) were related to all-cause mortality, with hazard ratios of 1.51 (95% CI: 1.05–2.16) and 2.29 (95% CI: 1.40–3.75) respectively, compared with no medications, independently of demographic factors, serious illnesses and long-term conditions, cognitive function, and depression. Polypharmacy and heightened polypharmacy also showed 2.45 (95% CI: 1.13–5.29) and 3.67 (95% CI: 1.43–9.46) times higher risk of cardiovascular disease deaths, respectively. Cancer mortality was only related to heightened polypharmacy. Conclusion Structured medication reviews are currently advised for heightened polypharmacy, but our results suggest that greater attention to polypharmacy in general for older people may reduce adverse effects and improve older adults’ health.
Message Interactivity and Source Credibility in Online Dental Practice Reviews: Responding to Reviews Triggers Positive Consumer Reactions Regardless of Review Valence

ABSTRACT Online health reviews are powerful since people use them to glean information about medical professionals. Nonetheless, less is known about what strategies can cultivate positive relationships with consumers when the latter are exposed to patient reviews. A 2 (review valence: negative vs. positive) x 3 (message interactivity: low vs medium vs high) x 2 (review responding source: customer service representative vs. dentist) between-subjects (N = 410) online experiment was conducted. The results showed that positive reviews (vs. negative reviews) and increased organizational responsiveness led to more favorable prospective patient reactions toward the reviewed dental practice. Most importantly, this study detected a significant two-way interaction between review valence and message interactivity. As found, even in the presence of negative reviews higher levels of message interactivity on online review sites can significantly improve the health organization-public relationship (e.g., trust, commitment, satisfaction, control mutuality) as well as enhance organizational reputation and patient behavioral intentions. Mediation tests revealed that source credibility mediated the effects of the review responding source on the relational outcomes, organizational reputation, and consumer behavioral intentions. More specifically, when a dentist replied to the reviews prospective patients perceived favorably the dental clinic and were more likely to visit it in the future than when a customer service representative responded. Theoretical and practical implications for effective online relationship management in the healthcare industry are discussed.
“The Master’s Tools Will Never Dismantle the Master’s House”: Ten Critical Lessons for Black and Other Health Equity Researchers of Color

Audre Lorde’s provocative admonishment, “The master’s tools will never dismantle the master’s house,” is a fitting caution for Black and other scholars of color who seek to use traditional social and behavioral sciences research as a tool to achieve social justice and health equity in Black communities. Invoking Lorde, I use the “master’s tools” as a metaphor for conventional theoretical and methodological approaches and “dismantle the master’s house” as a metaphor for intersectional structures and systems of oppression that created and sustain health inequity in U.S. Black communities. Using a blend of personal narrative and insights from a 23-year career as a Black critical health equity researcher, I share 10 critical lessons for Black and other health equity researchers of color. And because the personal typically reflects the structural, I recommend system and structural-level mitigation strategies for departments, universities, extramural institutions (e.g., journals), and the government, for each critical lesson.
Human click-based echolocation: Effects of blindness and age, and real-life implications in a 10-week training program

Understanding the factors that determine if a person can successfully learn a novel sensory skill is essential for understanding how the brain adapts to change, and for providing rehabilitative support for people with sensory loss. We report a training study investigating the effects of blindness and age on the learning of a complex auditory skill: click-based echolocation. Blind and sighted participants of various ages (21–79 yrs; median blind: 45 yrs; median sighted: 26 yrs) trained in 20 sessions over the course of 10 weeks in various practical and virtual navigation tasks. Blind participants also took part in a 3-month follow up survey assessing the effects of the training on their daily life. We found that both sighted and blind people improved considerably on all measures, and in some cases performed comparatively to expert echolocators at the end of training. Somewhat surprisingly, sighted people performed better than those who were blind in some cases, although our analyses suggest that this might be better explained by the younger age (or superior binaural hearing) of the sighted group. Importantly, however, neither age nor blindness was a limiting factor in participants’ rate of learning (i.e. their difference in performance from the first to the final session) or in their ability to apply their echolocation skills to novel, untrained tasks. Furthermore, in the follow up survey, all participants who were blind reported improved mobility, and 83% reported better independence and wellbeing. Overall, our results suggest that the ability to learn click-based echolocation is not strongly limited by age or level of vision. This has positive implications for the rehabilitation of people with vision loss or in the early stages of progressive vision loss.
Bacterial cell wall-degrading enzymes induce basidiomycete natural product biosynthesis.

Natural products play a vital role for intermicrobial interactions. In the basidiomycete arena an important representative is variegatic acid, a lactone natural product pigment whose ecological relevance stems from both inhibiting bacterial swarming and from indirect participation in breakdown of organic matter by brown-rotting fungi. Previous work showed that the presence of bacteria stimulates variegatic acid production. However, the actual external molecular trigger that prompts its biosynthesis in the mushroom hyphae remained unknown. Here, we report on the identification of Bacillus subtilis subtilisin E (AprE) and chitosanase (Csn) as primary inducers of pulvinic acid pigment formation. Using the established co-culture system of B. subtilis and Serpula lacrymans, we used activity-guided FPLC-based fractionation of B. subtilis culture supernatants and subsequent peptide fingerprinting to identify candidates, and their role was corroborated by means of a pigment production assay using heterologously produced chitosanase and subtilisin. B. subtilis mutants defective in either the aprE or the csn gene still triggered pigmentation, yet to a lower degree, which points to a multicausal scenario and suggests the combined activity of these cell wall polymer-attacking enzymes as true stimulus. This article is protected by copyright. All rights reserved.
The inference of HIV-1 transmission direction between a man who has sex with men and his heterosexual wife based on the sequences of HIV-1 quasi-species

ABSTRACT Currently, homosexual transmission has become one of the main routes of HIV-1 spread in China. Furthermore, about 80% Chinese men, who have sex with men (MSM), feel forced to enter eventually into heterosexual marriages due to the Chinese traditional marriage culture, which may cause HIV-1 infection in families. In this study, we identified HIV-1 transmission in a family and the direction of HIV-1 transmission from a MSM to his wife and infant, which indicated Chinese MSM may have become a potential bridge of HIV-1 transmission to their wives and children. Therefore, we need to develop more effective defence measures to prevent the spread of HIV-1 in MSM families in China.