Miracle-dz/UniFAR-FTUs huggingface dataset:
Midlife socioeconomic position and old-age dementia mortality: a large prospective register-based study from Finland

Objectives To assess the association between multiple indicators of socioeconomic position and dementia-related death, and to estimate the contribution of dementia to socioeconomic differences in overall mortality at older ages. Design Prospective population-based register study. Setting Finland. Participants 11% random sample of the population aged 70–87 years resident in Finland at the end of year 2000 (n=54 964). Main outcome measure Incidence rates, Kaplan-Meier survival probabilities and Cox regression HRs of dementia mortality in 2001–2016 by midlife education, occupational social class and household income measured at ages 53–57 years. Results During the 528 387 person-years at risk, 11 395 individuals died from dementia (215.7 per 10 000 person-years). Lower midlife education, occupational social class and household income were associated with higher dementia mortality, and the differences persisted to the oldest old ages. Compared with mortality from all other causes, however, the socioeconomic differences emerged later. Dementia accounted for 28% of the difference between low and high education groups in overall mortality at age 70+ years, and for 21% of the difference between lowest and highest household income quintiles. All indicators of socioeconomic position were independently associated with dementia mortality, low household income being the strongest independent predictor (HR=1.24, 95% CI 1.16 to 1.32), followed by basic education (HR=1.14, 1.06 to 1.23). Manual occupational social class was related to a 6% higher hazard (HR=1.06, 1.01 to 1.11) compared with non-manual social class. Adjustment for midlife economic activity, baseline marital status and chronic health conditions attenuated the excess hazard of low midlife household income, although significant effects remained. Conclusion Several indicators of socioeconomic position predict dementia mortality independently and socioeconomic inequalities persist into the oldest old ages. The results demonstrate that dementia is among the most important contributors to socioeconomic inequalities in overall mortality at older ages.
Association of energy drink consumption with substance-use initiation among adolescents: A 12-month longitudinal study

Background: Aggressive marketing has resulted in exponential growth of energy drink sales in recent years. Despite growing concerns about the negative health effects of energy drinks, they are increasingly popular among young people. Little is known about temporal associations between energy drink consumption and other drug use, though some researchers have suggested that energy drink consumption reflects an entry into a drug-using lifestyle. Aims: The purpose of this study was to evaluate whether energy drink use among adolescents who have never tried substances is associated with a risk of initiating tobacco (i.e. cigarettes, e-cigarettes, and hookah) and alcohol use. Methods: A school-based longitudinal study of 3071 adolescents ages 9–17 years was conducted in six federal states of Germany. Data analyses involved two assessment waves that took place approximately 12 months apart: baseline (fall-winter of school year 2016–2017), and 12-month follow-up (fall-winter of school year 2017–2018). Results: Multilevel models revealed that energy drink use at baseline was associated with cigarette (odds ratio for energy drink ever use, 3.15 (95% confidence interval, 2.07–4.78 )), e-cigarette (odds ratio, 4.32 (95% confidence interval, 2.87–6.51)), hookah smoking (odds ratio, 3.15 (95% confidence interval, 2.06–4.82)), and alcohol use (odds ratio, 2.26 (95% confidence interval, 1.75–2.93)) initiation within 12 months. Conclusions: These results raise the possibility that energy drinks may potentially act as a gateway drug to other substances. However, inferences regarding whether this association is or is not causal cannot yet be made.
Effects of intervention on self-efficacy and text quality in elementary school students’ narrative writing

Abstract Aim Self-efficacy for writing is an important motivational factor and considered to predict writing performance. Self-efficacy for narrative writing has been sparsely studied, and few studies focus on the effects of writing intervention on self-efficacy. Additionally, there is a lack of validated measures of self-efficacy for elementary school students. In a previous study, we found that a trained panel rated personal narrative text quality higher for girls than for boys, which led to our aim: to investigate boys’ and girls’ self-efficacy for narrative writing before and after an intervention, and to explore associations between self-efficacy and text quality. Methods An 18-item self-efficacy scale was developed. Fifty-five fifth-grade students (M 11:2 years, SD 3.7 months) filled out the scale before and after a five-lesson observational learning intervention. Self-efficacy was then related to writing performance as measured by holistic text quality ratings. Results The students demonstrated strong self-efficacy, which increased significantly post-intervention. Girls and boys demonstrated similar self-efficacy, despite girls’ higher text quality. There were moderate correlations between self-efficacy and writing performance pre- and post-intervention. Conclusions The results support previous findings of strong self-efficacy at this age. The interaction between writing self-efficacy and performance is complex. Young students may not be able to differentiate between self-efficacy, general writing skills, task performance, and self-regulation. Self-efficacy scales should thus be carefully constructed with respect to age, genre, instruction, and to students’ general educational context.
Optimal therapeutic strategies for mixed phenotype acute leukemia.

PURPOSE OF REVIEW Mixed phenotype acute leukemia (MPAL) encompasses a rare group of clinically, immunophenotypically, and genetically diverse leukemias. Diagnosing and treating these patients remains challenging. In recent years, systematic efforts have been made to better define the genetic landscape of MPAL. These insights allow better understanding of the pathophysiology of MPAL, have the potential for a more biologically meaningful classification and may promote targeted, novel approaches to treat these leukemias. RECENT FINDINGS Recent studies suggest that MPALs originate in a multipotent primitive cell, demonstrate large genetic diversity and include subgroups that may benefit from targeted therapy. Recent data support the use of ALL-type induction followed by allogeneic stem cell transplantation in first remission for most adults. Novel targeted approaches hold promise for treatment of MPAL; however, some may unpredictably select for clonal expansion of cells from a different lineage than observed at presentation. SUMMARY A biologically and genetically driven classification of MPAL may yield more accurate prognosis and potentially direct therapy in patients with MPAL. Prospective efforts that incorporate targeted approaches based on genetics and immunophenotype are warranted.
Impact of healthcare access and HIV testing on utilisation of cervical cancer screening among US women at high risk of HIV infection: cross-sectional analysis of 2016 BRFSS data

Objective Previous studies identified several factors associated with cervical cancer screening. However, many of them used samples from the general population and limited studies focused on women with high-risk health behaviours. We aimed to disentangle the association of cervical cancer screening with healthcare access and HIV testing among women at a high risk of HIV infection. Design Nationwide cross-sectional survey in the USA. Setting 2016 Behavioral Risk Factor Surveillance System. Participants 3448 women with a history of high-risk behaviours associated with HIV infection Exposure and outcome Clinical check-up, having personal healthcare provider, health coverage and HIV testing history were treated as exposures. Appropriate cervical cancer screening, which was defined according to 2016 US Preventive Services Task Force guideline, was treated as the outcome of interest. Data analysis Multivariable logistic regression model was performed to evaluate associations of healthcare access and HIV testing with the uptake of cervical cancer screening; adjusted odds ratio (aOR) and 95% CI were reported. We further investigated if educational attainment modified associations identified in the primary multivariable model. Results A total of 2911 (84.4%) high-risk women in our sample underwent cervical cancer screening. In the multivariable model, delayed clinical check-up (≥5 years ago vs within the past year: aOR: 0.19, 95% CI: 0.14 to 0.26), having no health insurance (aOR: 0.60, 95% CI: 0.46 to 0.79) and no history of HIV testing (no testing vs testing within the past year: aOR: 0.46, 95% CI: 0.35 to 0.61) were inversely associated with cervical cancer screening utilisation. Conclusion Factors reflecting healthcare access, specifically clinical check-up and health coverage, as well as history of HIV testing were associated with cervical cancer screening in this population-based study of high-risk women. Targeted interventions are warranted to further increase cervical cancer screening among women at high risk of HIV infection.
Twin enzymes, divergent control: The cholesterogenic enzymes DHCR14 and LBR are differentially regulated transcriptionally and post-translationally

Cholesterol synthesis is a tightly regulated process, both transcriptionally and post-translationally. Transcriptional control of cholesterol synthesis is relatively well-understood. However, of the ∼20 enzymes in cholesterol biosynthesis, post-translational regulation has only been examined for a small number. Three of the four sterol reductases in cholesterol production, 7-dehydrocholesterol reductase (DHCR7), 14-dehydrocholesterol reductase (DHCR14), and lamin-B receptor (LBR), share evolutionary ties with a high level of sequence homology and predicted structural homology. DHCR14 and LBR uniquely share the same Δ-14 reductase activity in cholesterol biosynthesis, yet little is known about their post-translational regulation. We have previously identified specific modes of post-translational control of DHCR7, but it is unknown whether these regulatory mechanisms are shared by DHCR14 and LBR. Using CHO-7 cells stably expressing epitope-tagged DHCR14 or LBR, we investigated the post-translational regulation of these enzymes. We found that DHCR14 and LBR undergo differential post-translational regulation, with DHCR14 being rapidly turned over, triggered by cholesterol and other sterol intermediates, whereas LBR remained stable. DHCR14 is degraded via the ubiquitin-proteasome system, and we identified several DHCR14 and DHCR7 putative interaction partners, including a number of E3 ligases that modulate DHCR14 levels. Interestingly, we found that gene expression across an array of human tissues showed a negative relationship between the C14-sterol reductases; one enzyme or the other tends to be predominantly expressed in each tissue. Overall, our findings indicate that whereas LBR tends to be the constitutively active C14-sterol reductase, DHCR14 levels are tunable, responding to the local cellular demands for cholesterol.
Scientists’ incentives and attitudes toward public communication

In an era of large-scale science-related challenges and rapid advancements in groundbreaking science with major societal implications, communicating about science is critical. The profile of science communication has increased over the last few decades, with multiple sectors calling for such activities. As scientists respond to calls for public-facing communication, we need to evaluate where the scientific community stands. We conducted a unique census of science faculty at land-grant universities across the United States intended to spur the next generation of science communicators and research. Despite scientists’ strong approval of science communication efforts, potential areas of tension, attributable to lack of institutional support and confidence in communication skills, constrain these efforts.
Large-scale screening and identification of novel pathogenic Staphylococcus aureus genes using a silkworm infection model.

The regulatory network of virulence factors produced by the opportunistic pathogen Staphylococcus aureus is unclear, and the functions of many uncharacterized genes in its genome remain to be elucidated. In this study, we screened 380 genes whose function was unassigned utilizing gene-disrupted transposon mutants of the community-acquired methicillin-resistant S. aureus USA300 for pathogenicity using silkworms. We identified 10 strains with reduced silkworm killing ability. Among them, 8 displayed reduced virulence in a mouse model as evidenced by reduced colony-forming units in organs of infected mice. The role of each gene in pathogenicity was further confirmed by complementation and pathogenicity tests in silkworms, where we found that the phenotype was not restored in one strain. Additionally, some of the mutants displayed reduced hemolysis, proteolysis, pigment production, and survival in murine RAW 264.7 monocyte-macrophage cells. These newly identified genes involved in virulence will enhance our understanding of the pathogenicity of S. aureus.
Photorespiration in the context of Rubisco biochemistry, CO2 diffusion, and metabolism.

Photorespiratory metabolism is essential for plants to maintain functional photosynthesis in an oxygen-containing environment. Because the oxygenation reaction of Rubisco is followed by the loss of previously fixed carbon, photorespiration is often considered a wasteful process and considerable efforts are aimed at minimizing the negative impact of photorespiration on the plant's carbon uptake. However, the photorespiratory pathway has also many positive aspects, as it is well integrated within other metabolic processes, such as nitrogen assimilation and C1 metabolism, and it is important for maintaining the redox balance of the plant. The overall effect of photorespiratory carbon loss on the net CO2 fixation of the plant is also strongly influenced by the physiology of the leaf related to CO2 diffusion. This review outlines the distinction between Rubisco oxygenation and photorespiratory CO2 release as a basis to evaluate the costs and benefits of photorespiration.
A mouse model of gestation-specific transient hyperglycemia for translational studies.

The prevalence of gestational diabetes mellitus (GDM) is estimated at 14% globally, and in some countries, such as Singapore, exceed 20%. Both women and children exposed to GDM have an increased risk of late onset of metabolic diseases, cardiovascular disease and other health issues. Beyond lifestyle changes and pharmaceutical intervention using existing type 2 diabetic medications for expecting women, there is almost no prevention or therapeutic options for affected offspring. Numerous animal models have been generated for understanding of pathological processes of GDM development and for development of treatment strategies. These models, however, suffer from limited window of opportunity to examine potential intervention options. By combining short term high fat diet (HFD) feeding and low-dose streptozotocin (STZ) treatments before pregnancy, we have established a consistent mouse model with transient gestation-specific hyperglycemia, which allows testing of nutritional and pharmacological interventions during and beyond a pregnancy.
Remote ischemic preconditioning reduces the incidence of contrast‐induced nephropathy in patients undergoing coronary angiography/intervention: Systematic review and meta‐analysis of randomized controlled trials

Contrast‐induced nephropathy (CIN) is associated with increased mortality and morbidity in patients undergoing coronary angiography (CAG) and percutaneous coronary intervention (PCI). We aimed to assess the latest evidence on the effect of remote ischemic preconditioning (RIPC) on the incidence of CIN in patients undergoing CAG/PCI.
Myeloid-derived Growth Factor Promotes Intestinal Glucagon-like Peptide-1 Production in Male Mice with Type 2 Diabetes.

Myeloid-derived growth factor (MYDGF), which is produced by bone marrow-derived cells, mediates cardiac repair following myocardial infarction by inhibiting cardiac myocyte apoptosis to subsequently reduce the infarct size. However, the functions of MYDGF in the incretin system of diabetes is still unknown. Here, loss- and gain-of-functions experiments in mice revealed that MYDGF maintains glucose homeostasis by inducing glucagon-like peptide-1 (GLP-1) production and secretion and improves glucose tolerance and lipid metabolism. A treatment with recombinant MYDGF increased the secretion and production of GLP-1 in STC-1 cells in vitro. Mechanistically, the positive effects of MYDGF are potentially attributed to the activation of protein kinase A/glycogen synthase kinase 3β/β-catenin (PKA/GSK-3β/β-catenin) and mitogen-activated protein kinase (MAPK) kinases/extracellular regulated protein kinase (MEK/ERK) pathways. Based on these findings, MYDGF promotes the secretion and production of GLP-1 in intestinal L-cells and potentially represents a potential therapeutic medication for type 2 diabetes.
NMR signal processing, prediction, and structure verification with machine learning techniques

Machine learning (ML) methods have been present in the field of NMR since decades, but it has experienced a tremendous growth in the last few years, especially thanks to the emergence of deep learning (DL) techniques taking advantage of the increased amounts of data and available computer power. These algorithms are successfully employed for classification, regression, clustering, or dimensionality reduction tasks of large data sets and have been intensively applied in different areas of NMR including metabonomics, clinical diagnosis, or relaxometry. In this article, we concentrate on the various applications of ML/DL in the areas of NMR signal processing and analysis of small molecules, including automatic structure verification and prediction of NMR observables in solution.
HIV persists throughout deep tissues with repopulation from multiple anatomical sources.

BACKGROUND Understanding HIV dynamics across the human body is important for cure efforts. This goal has been hampered by technical difficulties and the challenge to obtain fresh tissues. METHODS This observational study evaluated 6 persons with HIV (4 virally suppressed with antiretroviral therapy and 2 with rebound viremia after stopping therapy) who provided blood serially before death and their bodies for rapid autopsy. HIV reservoirs were characterized by digital droplet PCR and single genome amplification and sequencing of full-length (FL) envelope HIV. Phylogeographic methods reconstructed HIV spread and generalized linear models tested for viral factors associated with dispersal. RESULTS Across participants, HIV DNA levels varied from ~0 to 659 copies/106 cells (IQR:22.9-126.5). A total of 605 intact FL env sequences were recovered in antemortem blood cells and across 28 tissues (IQR:5-9). Sequence analysis showed: 1) emergence of large, identical, intact HIV RNA populations in blood after stopping therapy, which repopulated tissues throughout the body, 2) multiple sites acted as hubs for HIV dissemination but blood and lymphoid tissues were the main source, and 3) viral exchanges occurred within brain areas and across the blood brain barrier, and 4) migration was associated with low HIV divergence between sites and higher diversity at the recipient site. CONCLUSION HIV reservoirs persist in all deep tissues, and blood is the main source of dispersal. This may explain why eliminating HIV susceptibility in circulating T cells via bone marrow transplants allowed some people with HIV to have therapy free remission, even though deeper tissue reservoirs were not targeted. TRIAL REGISTRATION Not applicable. FUNDING National Institute of Health Grants (P01 AI31385, P30 AI036214, AI131971-01, AI120009AI036214,HD094646, AI027763, AI134295, AI68636).
Prognostic significance of lymphovascular space invasion in patients with endometrioid endometrial cancer: a retrospective study from a single center

Objective This study aims to analyze factors associated with lymphovascular space invasion (LVSI) and evaluate the prognostic significance of LVSI in Chinese endometrioid endometrial cancer (EEC) patients. Methods Five-hundred eighty-four EEC patients undergoing surgery in our center from 2006 to 2016 were selected for analysis. Univariate analysis and multivariate logistic regression were used to examine relevant factors of LVSI. To evaluate the prognostic role of LVSI, survival analyses were conducted. In survival analyses, both multivariate Cox regression and propensity score matching were used to control the confounders. Results The incidence of LVSI was 12.16% (71/584). Diabetes history (p=0.021), lymph node metastasis (p=0.005), deep myometrial invasion (p<0.001) and negative PR expression (p=0.007) were independently associated with LVSI. Both Kaplan-Meier method and univariate Cox regressions showed LVSI negative and positive cases had similar tumor-specific survival (TSS) and disease-free survival (DFS). After adjusting for the influence of adjuvant therapy and other clinicopathological factors with multivariate Cox regressions, LVSI still could not bring additional survival risk to the patients (p=0.280 and p=0.650 for TSS and DFS, respectively). This result was verified by Kaplan-Meier survival analyses after propensity score matching (p=0.234 and p=0.765 for TSS and DFS, respectively). Conclusion LVSI does not significantly compromise the survival outcome of Chinese EEC patients.
Integrative network analysis identifies cell-specific trans regulators of m6A

Abstract N6-methyladenosine (m6A) is a reversible and dynamic RNA modification in eukaryotes. However, how cells establish cell-specific m6A methylomes is still poorly understood. Here, we developed a computational framework to systematically identify cell-specific trans regulators of m6A through integrating gene expressions, binding targets and binding motifs of large number of RNA binding proteins (RBPs) with a co-methylation network constructed using large-scale m6A methylomes across diverse cell states. We applied the framework and successfully identified 32 high-confidence m6A regulators that modulated the variable m6A sites away from stop codons in a cell-specific manner. To validate them, we knocked down three regulators respectively and found two of them (TRA2A and CAPRIN1) selectively promoted the methylations of the m6A sites co-localized with their binding targets on RNAs through physical interactions with the m6A writers. Knockdown of TRA2A increased the stabilities of the RNAs with TRA2A bound near the m6A sites and decreased the viability of cells. The successful identification of m6A regulators demonstrates a powerful and widely applicable strategy to elucidate the cell-specific m6A regulators. Additionally, our discovery of pervasive trans-acting regulating of m6A provides novel insights into the mechanisms by which spatial and temporal dynamics of m6A methylomes are established.