Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimized Vivid-derived Magnets photodimerizers for subcellular optogenetics in mammalian cells

Light-inducible dimerization protein modules enable precise temporal and spatial control of biological processes in non-invasive fashion. Among them, Magnets are small modules engineered from the Neurospora crassa photoreceptor Vivid by orthogonalizing the homodimerization interface into complementary heterodimers. Both Magnets components, which are well-tolerated as protein fusion partners, are photoreceptors requiring simultaneous photoactivation to interact, enabling high spatiotemporal confinement of dimerization with a single excitation wavelength. However, Magnets require concatemerization for efficient responses and cell preincubation at 28°C to be functional. Here we overcome these limitations by engineering an optimized Magnets pair requiring neither concatemerization nor low temperature preincubation. We validated these ‘enhanced’ Magnets (eMags) by using them to rapidly and reversibly recruit proteins to subcellular organelles, to induce organelle contacts, and to reconstitute OSBP-VAP ER-Golgi tethering implicated in phosphatidylinositol-4-phosphate transport and metabolism. eMags represent a very effective tool to optogenetically manipulate physiological processes over whole cells or in small subcellular volumes.
Cognitive Practice Effects Delay Diagnosis; Implications for Clinical Trials

Objective: Practice effects on cognitive tests obscure decline, thereby delaying detection of mild cognitive impairment (MCI). This reduces opportunities for slowing Alzheimer's disease progression and can hinder clinical trials. Using a novel method, we assessed the ability of practice-effect-adjusted diagnoses to detect MCI earlier, and tested the validity of these diagnoses based on AD biomarkers. Methods: Of 889 Alzheimer's Disease Neuroimaging Initiative participants who were cognitively normal (CN) at baseline, 722 returned at 1-year-follow-up (mean age=74.9; SD=6.8). Practice effects were calculated by comparing returnee scores at follow-up to demographically-matched individuals who had only taken the tests once, with an additional adjustment for attrition effects. Practice effects for each test were subtracted from follow-up scores. The lower scores put additional individuals below the impairment threshold for MCI. CSF amyloid-beta, phosphorylated tau, and total tau were measured at baseline and used for criterion validation. Results: Practice-effect-adjusted scores increased MCI incidence by 26% (p<.001). Adjustment increased proportions of amyloid-positive MCI cases (+20%) and reduced proportions of amyloid-positive CNs (-6%) (ps<.007). With the increased MCI base rate, adjustment for practice effects would reduce the sample size needed for detecting significant drug treatment effects by an average of 21%, which we demonstrate would result in multi-million-dollar savings in a clinical trial. Interpretation: Adjusting for practice effects on cognitive testing leads to earlier detection of MCI. When MCI is an outcome, this reduces recruitment needed for clinical trials, study duration, staff and participant burden, and can dramatically lower costs. Importantly, biomarker evidence also indicates improved diagnostic accuracy.
Acceptability of self- collection for human papillomavirus detection in the Eastern Cape, South Africa

Human papillomavirus (HPV) testing on vaginal self-collected and cervical clinician-collected specimens shows comparable performance. Self-sampling on FTA cards is suitable for women residing in rural settings or not attending regular screening and increases participation rate in the cervical cancer screening programme. We aimed to investigate and compare high-risk (HR)-HPV prevalence in clinician-collected and self-collected genital specimens as well as two different HPV tests on the clinician collected samples. A total of 737 women were recruited from two sites, a community health clinic (n = 413) and a referral clinic (n = 324) in the Eastern Cape Province. Cervical clinician-collected (FTA cards and Digene transport medium) and vaginal self-collected specimens were tested for HR-HPV using the hpVIR assay (FTA cards) and Hybrid Capture-2 (Digene transport medium). There was no significant difference in HR-HPV positivity between clinician-collected and self-collected specimens among women from the community-based clinic (26.4% vs 27.9%, p = 0.601) or the referral clinic (83.6% vs 79.9%, p = 0.222). HPV16, HPV35, and HPV33/52/58 group were the most frequently detected genotypes at both study sites. Self-sampling for HPV testing received a high positive response of acceptance (77.2% in the community-based clinic and 83.0% in referral clinic). The overall agreement between hpVIR assay and HC-2 was 87.7% (k = 0.754). The study found good agreement between clinician-collected and self-collected genital specimens. Self-collection can have a positive impact on a cervical screening program in South Africa by increasing coverage of women in rural areas, in particular those unable to visit the clinics and women attending clinics where cytology-based programs are not functioning effectively.
Identification of curcumin as a novel natural inhibitor of rDNA transcription

ABSTRACT Ribosomal DNA (rDNA) transcription drives cell growth and cell proliferation via the product ribosomal RNA (rRNA), the essential component of ribosome. Given the fundamental role of rRNA in ribosome biogenesis, rDNA transcription has emerged as one of the effective targets for a number of human diseases including various types of cancers. In this study, we identify curcumin, an ancient drug, as a novel natural inhibitor of rDNA transcription. Curcumin treatment impairs the assembly of the RNA polymerase I preinitiation complex at rDNA promoters and represses rDNA promoter activity, which leads to the decrease of rRNA synthesis. In addition, curcumin treatment stimulates autophagosome formation and promotes autophagic degradation in cells. Mechanistically, curcumin inactivates the mechanistic target of rapamycin complex 1 (mTORC1), the upstream regulator of rDNA transcription and autophagy induction, by inhibiting mTOR lysosomal localization. Functionally, curcumin treatment inhibits protein synthesis, cell growth and cell proliferation. Taken together, these findings identify curcumin as an effective inhibitor of rDNA transcription and provide novel mechanisms for the anticancer properties of curcumin. Abbreviations: Atg: autophagy-related; GFP: green fluorescent protein; LAMP2: lysosomal associated membrane protein 2; LC3: microtubule-associated protein 1 light chain 3; MEF: mouse embryonic fibroblast; mTORC1: mechanistic target of rapamycin complex 1; rDNA: ribosomal DNA; rRNA: ribosomal RNA; TP53INP2: tumor protein p53 inducible nuclear protein 2.
JAK-STAT Inhibitors in Atopic Dermatitis from Pathogenesis to Clinical Trials Results

A common disease worldwide is known as atopic dermatitis (AD), named also as atopic eczema, which is a chronic recurrent complex inflammatory skin disorder. It affects 2–10% of the adult population and up to 20% of the pediatric population. The clinical AD picture appears in typically localized eczema and dry skin, and is dominated by a persistent pruritus followed by sleep disturbances. AD strongly impacts on the quality of life of AD patients and their families as well as on social and economic aspects. The pathogenesis of the disease is complex and consists of multiple interactions between immunological disturbances, skin barrier defect, and microbial dysbiosis with environmental influences. The treatment of AD reflects the pathogenetic disorders, starting from basic emollient therapy, and goes to topical anti-inflammatory regimens followed by phototherapy, systemic immunosuppressive drugs, and new biologic immunomodulators. This paper will thus summarize the novel collection of biological treatment JAK-STAT inhibitors dedicated to AD.
Biological variation of total thyroxine (T4), free T4 and thyroid-stimulating hormone in 11 clinically healthy cats

Objectives The aim of this study was to investigate the biological variation of total thyroxine (T4), free T4 (fT4) and thyroid-stimulating hormone (TSH) in 11 clinically healthy cats aged between 3 and 15 years old, in Sydney, Australia. Methods Blood was collected weekly for up to 6 weeks and serum T4, fT4 and TSH concentrations were analysed using canine-specific reagents. Restricted maximum likelihood was used to estimate within-subject, between-subject and analytical variance components, which were recorded in terms of the related coefficients of variation. The index of individuality and reference change values were then calculated for each analyte. Results T4 and TSH had intermediate individuality, indicating both subject-based and population-based reference intervals (RIs) could be used, with the knowledge that population-based RIs are suboptimally sensitive. fT4 had high individuality, indicating subject-based RIs are more appropriate than population-based RIs. Conclusions and relevance This study has demonstrated that subject-based RIs could be more sensitive than population-based RIs for the diagnosis of thyroid dysfunction in cats.
How Many Messenger RNAs Can Be Translated by the START Mechanism?

Translation initiation is a key step in the protein synthesis stage of the gene expression pathway of all living cells. In this important process, ribosomes have to accurately find the AUG start codon in order to ensure the integrity of the proteome. “Structure Assisted RNA Translation”, or “START”, has been proposed to use stable secondary structures located in the coding sequence to augment start site selection by steric hindrance of the progression of pre-initiation complex on messenger RNA. This implies that such structures have to be located downstream and at on optimal distance from the AUG start codon (i.e., downstream nucleotide +16). In order to assess the importance of the START mechanism in the overall mRNA translation process, we developed a bioinformatic tool to screen coding sequences for such stable structures in a 50 nucleotide-long window spanning the nucleotides from +16 to +65. We screened eight bacterial genomes and six eukaryotic genomes. We found stable structures in 0.6–2.5% of eukaryotic coding sequences. Among these, approximately half of them were structures predicted to form G-quadruplex structures. In humans, we selected 747 structures. In bacteria, the coding sequences from Gram-positive bacteria contained 2.6–4.2% stable structures, whereas the structures were less abundant in Gram-negative bacteria (0.2–2.7%). In contrast to eukaryotes, putative G-quadruplex structures are very rare in the coding sequence of bacteria. Altogether, our study reveals that the START mechanism seems to be an ancient strategy to facilitate the start codon recognition that is used in different kingdoms of life.
The Role of Early Programming and Early Nutrition on the Development and Progression of Celiac Disease: A Review

Experimental and epidemiological evidence has shown that modifications of the intrauterine environment can have deleterious consequences for individuals, expressed as an increased risk of suffering non-communicable pathologies in adult life, which is known as the hypothesis of the early origin of diseases or fetal programming. On the other hand, changes in gene expression patterns through epigenetic modifications can be the basis for long-term maintenance of the effects of fetal programming. In this sense, epigenetics comprises the study of intrauterine disturbances, which develop diseases in the adult, including celiac disease (CD). In addition, early feeding practices could influence the risk of CD development, such as breastfeeding timing and duration and age of gluten introduction in the diet. Gluten acts as a trigger for CD in genetically predisposed subjects, although approximately 30% of the world population has HLA DQ2 or DQ8, the prevalence of the disease is only 1–3%. It is not known what factors act to modify the risk of disease in genetically at-risk subjects. Taking into account all these considerations, the aim of the current review is to elucidate the role of early programming and the effect of early nutrition on the development and progression of CD. It is logical that attention has been paid to gluten as a key element in preventing the disease. However, there is no strong evidence in favor of the protective factor of breastfeeding, timing of introduction of gluten during lactation, and the development of CD. Diet, genetic risk, microbiota, and environmental interaction are possible triggers of the change in tolerance to an immune response to gluten, but large-scale cohort studies are needed. Emerging scientific concepts, such as epigenetics, may help us establish the role of these factors.
Disability among adults with diagnosed HIV in the United States, 2017

ABSTRACT In the United States, one in four adults is living with a disability. Age-related changes, disease-related pathology and treatments can place a person with HIV at risk for a disability. We analyzed nationally representative data to describe disability status among adults ≥18 years with diagnosed HIV in the United States and Puerto Rico by demographic characteristics, health behaviors, quality of care, clinical outcomes and mental health status. We reported weighted percentages and prevalence ratios with predicted marginal means to evaluate significant differences between groups (P < .05). Overall, 44.5% reported any disability; the most frequently reported disabilities were related to mobility (24.8%) and cognition (23.9%). Persons who lived in households at or below the poverty level or who experienced homelessness in the last 12 months reported a higher prevalence of any disability than persons who were not poor or not homeless (60.2% vs. 33.4% and 61.8% vs. 42.8%, respectively). Prevalence of depression and anxiety was higher among persons with any disability compared with those with no disability (32.8% and 26.6% versus 10.1% and 7.0%, respectively). Enhancing support from clinicians and ancillary providers may help optimize long-term health outcomes among HIV-positive persons with disabilities.
Adding Rigor to Biomarker Evaluations—EDRN Experience

The cancer early-detection biomarker field was, compared with the therapeutic arena, in its infancy when the Early Detection Research Network (EDRN) was initiated in 2000. The EDRN has played a crucial role in changing the culture and the ways people conduct biomarker studies. The EDRN proposed biomarker developmental guidelines and biomarker pivotal trial study design standards, created biomarker reference sets and functioned as an unbiased broker for the field, implemented the most rigorous blinding policy in the biomarker field, developed an array of statistical and computational tools for early-detection biomarker evaluations, and developed a multidisciplinary team-science approach. We reviewed these contributions made by the EDRN and their impacts on maturing the field. Future challenges and opportunities in cancer early-detection biomarker translational research are discussed, particularly in strengthening biomarker discovery pipeline and conducting more efficient biomarker validation studies. See all articles in this CEBP Focus section, “NCI Early Detection Research Network: Making Cancer Detection Possible. ”
Single-water-dipole-layer-driven Reversible Charge Order Transition in 1T-TaS2.

Water-solid interactions are crucial for many fundamental phenomena and technological processes. Here, we report a scanning tunneling microscopy study about the charge density wave (CDW) transition in 1T-TaS2 driven by a single water dipole layer. At low temperature, pristine 1T-TaS2 is a prototypical CDW compound with 13 × 13 charge order. After growing a highly ordered water adlayer, a new charge order with 3 × 3 periodicity emerges on water-covered 1T-TaS2. After water desorption, the entire 1T-TaS2 surface appears as localized 13 × 13 CDW domains that are separated by residual-water-cluster-pinned CDW domain walls. First-principles calculations show that the electric dipole moments in the water adlayer attract electrons to the top layer of 1T-TaS2, which shifts the phonon softening mode and induces the 13 × 13 to 3 × 3 charge order transition. Our results pave the way for creating new collective quantum states of matter with a molecular dipole layer.
Internet Addiction among Young Adult University Students: The Complex Interplay between Family Functioning, Impulsivity, Depression, and Anxiety

International research has underlined that both interpersonal, self-regulation, and comorbid variables can lead to a higher risk of developing internet addiction (IA) among young adults. To date, no studies have explored the interplay between young adults’ family functioning, impulsivity, and psychopathological difficulties. In a community sample of 244 young adult university students, this study aims to assess the relationship between young adults’ IA and young adults’ gender, the perception of their family functioning, impulsivity level, and depressive and anxiety symptoms, considering the possible interplay between these variables. The presence and the severity of IA were addressed through the Internet Addiction Test (IAT). Moreover, young adults filled out self-reporting questionnaires, assessing their perception of family functioning and their impulsivity levels and psychopathological symptoms. Results showed no significant association between the youth’s gender and IA. However, moderately addicted young adults were more likely to report poorer quality of family affective involvement and higher attentional impulsivity and depressive problems than other groups. Moreover, young adults’ attentional impulsivity mediated the relationship between family affective involvement and IA. This study provides new evidence on the complex interaction between individuals and interpersonal risk factors involved in IA among young adults, with important implications for the planning of intervention treatments.
Systemic Disease and Ocular Comorbidity Analysis of Geographically Isolated Federally Recognized American Indian Tribes of the Intermountain West

Background: The American Indian Navajo and Goshute peoples are underserved patient populations residing in the Four Corners area of the United States and Ibupah, Utah, respectively. Methods: We conducted a cross-sectional study of epidemiological factors and lipid biomarkers that may be associated with type II diabetes, hypertension and retinal manifestations in tribal and non-tribal members in the study areas (n = 146 participants). We performed multivariate analyses to determine which, if any, risk factors were unique at the tribal level. Fundus photos and epidemiological data through standardized questionnaires were collected. Blood samples were collected to analyze lipid biomarkers. Univariate analyses were conducted and statistically significant factors at p < 0.10 were entered into a multivariate regression. Results: Of 51 participants for whom phenotyping was available, from the Four Corners region, 31 had type II diabetes (DM), 26 had hypertension and 6 had diabetic retinopathy (DR). Of the 64 participants from Ibupah with phenotyping available, 20 had diabetes, 19 had hypertension and 6 had DR. Navajo participants were less likely to have any type of retinopathy as compared to Goshute participants (odds ratio (OR) = 0.059; 95% confidence interval (CI) = 0.016–0.223; p < 0.001). Associations were found between diabetes and hypertension in both populations. Older age was associated with hypertension in the Four Corners, and the Navajo that reside there on the reservation, but not within the Goshute and Ibupah populations. Combining both the Ibupah, Utah and Four Corners study populations, being American Indian (p = 0.022), residing in the Four Corners (p = 0.027) and having hypertension (p < 0.001) increased the risk of DM. DM (p < 0.001) and age (p = 0.002) were significantly associated with hypertension in both populations examined. When retinopathy was evaluated for both populations combined, hypertension (p = 0.037) and living in Ibupah (p < 0.001) were associated with greater risk of retinopathy. When combining both American Indian populations from the Four Corners and Ibupah, those with hypertension were more likely to have DM (p < 0.001). No lipid biomarkers were found to be significantly associated with any disease state. Conclusions: We found different comorbid factors with retinal disease outcome between the two tribes that reside within the Intermountain West. This is indicated by the association of tribe and with the type of retinopathy outcome when we combined the populations of American Indians. Overall, the Navajo peoples and the Four Corners had a higher prevalence of chronic disease that included diabetes and hypertension than the Goshutes and Ibupah. To the best of our knowledge, this is the first study to conduct an analysis for disease outcomes exclusively including the Navajo and Goshute tribe of the Intermountain West.
Infant Facial Expression Analysis: Towards a Real-Time Video Monitoring System Using R-CNN and HMM

The manual monitoring of young infants suffering from diseases like reflux is significant, since infants can hardly articulate their feelings. In this work, we propose a video-based infant monitoring system for the analysis of infant expressions and states, approaching real-time performance. The expressions of interest consist of discomfort, unhappy, joy and neutral, whereas states include sleep, pacifier and open mouth. Benefiting from the expression analysis, the discomfort moments can also be used and correlated with a symptom-related disease, such as a reflux measurement for the diagnosis of gastroesophageal reflux. The system consists of three components: infant expressions and states detection, object tracking and detection compensation. The proposed system is based on combining expression detection using Fast R-CNN with a compensated detection using analyzing information from the previous frame and utilizing a Hidden Markov Model. The experimental results show a mean average precision of 81.9% and 84.8% for 4 infant expressions and 3 states evaluated with both clinical and daily datasets. Meanwhile, the average precision for discomfort detection achieves up to 90%.
Effects of a 12-Week Change-of-Direction Sprints Training Program on Selected Physical and Physiological Parameters in Professional Basketball Male Players

Multidirectional repeated sprints with quick changes-of-direction (CoD) are considered a key performance determinant in basketball. The objective of this study was to investigate the effects of a 12-week CoD sprint training program compared to regular basketball training on selected measures of physical fitness and physiological adaptations in male basketball players. Sixteen professional basketball players were randomly assigned to an intervention group (INT = 8) or an active control group (CON = 8). INT completed a 12-week CoD sprint training program with two sessions per week while CON continued their regular training. Training volume was similar between groups. Before and after the intervention, the two groups were evaluated for the repeated sprint ability test with CoD (IRSA5COD), the squat jump (SJ) and countermovement jump (CMJ) test, the five time-jump test (FJT) and change of direction t-test. Blood samples were taken before the beginning of the experimental protocol, after 4, 8 and 12 weeks to monitor the testosterone/cortisol ratio (T/C). For t-test, post-hoc tests revealed significant pre-to-post improvements for INT (3.4%; p = 0.001, ES = 0.91). For CMJ, post-hoc tests revealed a significant pre-to-post decrease for INT (−11.6%; p = 0.001, ES = 0.94), and a significant improvement for CON (4.96%; p = 0.014, ES = 0.60). For T/C ratio, post-hoc tests revealed a significant decrease after 12 weeks of training for INT (52.3%; p < 0.001; ES = 0.63). In conclusion, twelve weeks of CoD sprint training enhanced CoD performance but negatively affected vertical jump capacity in male basketball players. T/C ratio indicated that the physiological demands associated with INT were well-balanced.