Miracle-dz/UniFAR-FTUs huggingface dataset:
Directed evolution of orthogonal RNA–RBP pairs through library-vs-library in vitro selection

Abstract RNA-binding proteins (RBPs) and their RNA ligands play many critical roles in gene regulation and RNA processing in cells. They are also useful for various applications in cell biology and synthetic biology. However, re-engineering novel and orthogonal RNA–RBP pairs from natural components remains challenging while such synthetic RNA–RBP pairs could significantly expand the RNA–RBP toolbox for various applications. Here, we report a novel library-vs-library in vitro selection strategy based on Phage Display coupled with Systematic Evolution of Ligands by EXponential enrichment (PD-SELEX). Starting with pools of 1.1 × 1012 unique RNA sequences and 4.0 × 108 unique phage-displayed L7Ae-scaffold (LS) proteins, we selected RNA–RBP complexes through a two-step affinity purification process. After six rounds of library-vs-library selection, the selected RNAs and LS proteins were analyzed by next-generation sequencing (NGS). Further deconvolution of the enriched RNA and LS protein sequences revealed two synthetic and orthogonal RNA–RBP pairs that exhibit picomolar affinity and >4000-fold selectivity.
The Starting Big approach to language learning

Abstract The study of language acquisition has a long and contentious history: researchers disagree on what drives this process, the relevant data, and the interesting questions. Here, I outline the Starting Big approach to language learning, which emphasizes the role of multiword units in language, and of coarse-to-fine processes in learning. I outline core predictions and supporting evidence. In short, the approach argues that multiword units are integral building blocks in language; that such units can facilitate mastery of semantically opaque relations between words; and that adults rely on them less than children, which can explain (some of) their difficulty in learning a second language. The Starting Big approach is a theory of how children learn language, how language is represented, and how to explain differences between first and second language learning. I discuss the learning and processing models at the heart of the approach and their cross-linguistic implications.
Accessory right hepatic artery and aberrant bile duct in the hepatocystic triangle: a rare case with clinical implications.

Awareness of variations in the hepatic vasculature and biliary system is extremely important for avoiding iatrogenic injury in upper-abdominal surgery. The objective of this study is to describe a rare case of abnormal vascular and biliary structures in the hepatocystic triangle (HCT) (the modern Calot's triangle). During anatomical dissection of the celiac trunk (CT) in an old man, the authors observed the presence of a hepatosplenic trunk arising from the CT and bifurcating into common hepatic and splenic arteries. The common hepatic artery divided into hepatic artery proper and gastroduodenal artery. The presence of accessory right hepatic artery (ARHA) arising from the superior mesenteric artery was also notable. The aberrant artery ascended retropancreatically ventral to the splenic vein, then posterolaterally to the portal vein before termination into the right hepatic lobe in the HCT. Within this triangle, there was an aberrant bile duct originating in the right hepatic lobe and ending in the common hepatic duct. This accessory duct crossed the ARHA and an associated branch (the cystic artery). There is no known previous report on the co-existence of an AHAR and an aberrant bile duct within the HCT, in addition to the hepatosplenic trunk. The clinical implications of the current case are addressed in discussion.
Impact of age, hypercholesterolemia, and the vitamin D receptor on brain endogenous β‐amyloid peptide accumulation in mice

Age, hypercholesterolemia, and vitamin D deficiency are risk factors that increase the brain accumulation of pathogenic β‐amyloid peptides (40 and 42), precursors leading to Alzheimer's disease (AD) in humans. The relative changes accompanying aging, high cholesterol, and/or treatment of calcitriol, active vitamin D receptor (VDR) ligand, under normal physiology are unknown. We examined these relative changes in C57BL/6 mice of ages 2, 4–8, and more than 10 months old, which were fed a normal or high fat / high cholesterol diet and treated with calcitriol, active ligand of the vitamin D receptor (0 or 2.5 μg/kg ×4, intraperitoneally, every other day to elicit cholesterol lowering in liver). Aβ40 but not Aβ42 accumulation in brain and lower P‐glycoprotein (P‐gp) and neprilysin protein expressions for Aβ efflux and degradation, respectively, were found to be associated with aging. But there was no trend for BACE1 (β‐secretase 1, a cholesterol‐sensitive enzyme) toward Aβ synthesis with age. In response to calcitriol treatment, P‐gp was elevated, mitigating partially the age‐related changes. Although age‐dependent decreasing trends in mRNA expression levels existed for Cyp46a1, the brain cholesterol processing enzyme, whose inhibition increases BACE1 and ApoE to facilitate microglia Aβ degradation, mRNA changes for other cholesterol transporters: Acat1 and Abca1, and brain cholesterol levels remained unchanged. There was no observable change in the mRNA expression of amyloid precursor protein (APP) and the influx (RAGE) and efflux (LRP1) transporters with respect to age, diet, or calcitriol treatment. Overall, aging poses as a risk factor contributing to Aβ accumulation in brain, and VDR‐mediated P‐gp activation partially alleviates the outcome.
Nutritional Factors Associated With Maternal Depression Among Pregnant Women in Urban Low-Income Settlements in Nairobi, Kenya

Background: Nutritional deficiencies are common during pregnancy and a year after childbirth. At the same time, maternal depression affects many women during pregnancy up to 1 year after childbirth. The objectives of this study were to determine the associations between nutrition status, dietary intake, and maternal depression among pregnant women. Methods: This was a cross-sectional study that included 262 pregnant women aged 15 to 49 years attending the antenatal clinic in 2 public health facilities in urban low-income settlements in Nairobi, Kenya. Maternal depression was assessed using Edinburgh Postnatal Depression Scale (EPDS). Mid-upper arm circumference (MUAC) was used to determine nutritional status. Dietary intake was assessed using the 24-hour recall, and brain essential nutrients were assessed through a questionnaire. Odds ratio was used to test the associations. All maternal characteristics with P < . 001 in the univariable analysis were considered in the multivariable logistic regression, variables with P < . 05 were considered significant. Results: Of the 262 pregnant women, 33.6% (95% CI: 27.9-40.7) had depressive illness as indicated by EPDS >13. About 9.9% of pregnant women had MUAC < 23 cm. The study established statistically significant association between poor nutrition by MUAC and maternal depression (P < .001). Maternal depression was statistically significantly associated with inadequate intake of brain food essential (P = .002). Maternal depression was statistically significantly associated with lower income (P < .001). In multivariable regression analysis, the main predictor of maternal depression was poor nutrition (P < .004). Conclusion: These findings reveal an association between poor nutrition and maternal depression. These results suggest that nutritional deficiencies could be a contributing factor for maternal depression. Study recommends dietary interventions as cost-effective way to reduce deficiencies and improve mental health problems for pregnant women. Assessment of maternal depression and dietary intake be integrated as fundamental components of antenatal care.
Earwig mothers consume the feces of their juveniles during family life

Many animals consume the feces of their conspecifics. This allo‐coprophagy can have benefits, such as access to nutrients and symbionts, but also risks for consumers, mainly due to direct contact with pathogens that develop on feces. In the European earwig Forficula auricularia, mothers and juveniles live in nests lined with their feces. This surprising habit allows juveniles to consume the feces of their siblings during family life and provides them with nutritional benefits when mothers provide low care. However, it was unclear whether earwig mothers also practice allo‐coprophagy, and whether this behavior is motivated by their nutritional needs. Here, we set up four types of experimental families in which we manipulated the nutritional needs of mothers and/or juveniles and measured the effects on the production of feces by the juveniles, and the consumption of these feces by the mothers. Our results first show that fed juveniles produced more feces pellet in presence of fed compared to food‐deprived mothers. We also found that, overall, about 50% of the mothers consumed juveniles feces. This consumption was both more likely and larger when the feces were produced by fed compared to food‐deprived juveniles, while the proportion of feces pellets eaten was larger in food‐deprived compared to fed mothers. Overall, our results reveal that allo‐coprophagy involves every family member and suggest that it can have both nutritional and non‐nutritional benefits for earwig mothers. Allo‐coprophagy could thus favor the maintenance of mothers in the nest and, more generally, promote the early evolution of family life.
ER‐anchored CRTH2 antagonizes collagen biosynthesis and organ fibrosis via binding LARP6

Excessive deposition of extracellular matrix, mainly collagen protein, is the hallmark of organ fibrosis. The molecular mechanisms regulating fibrotic protein biosynthesis are unclear. Here, we find that chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a plasma membrane receptor for prostaglandin D2, is trafficked to the endoplasmic reticulum (ER) membrane in fibroblasts in a caveolin‐1‐dependent manner. ER‐anchored CRTH2 binds the collagen mRNA recognition motif of La ribonucleoprotein domain family member 6 (LARP6) and promotes the degradation of collagen mRNA in these cells. In line, CRTH2 deficiency increases collagen biosynthesis in fibroblasts and exacerbates injury‐induced organ fibrosis in mice, which can be rescued by LARP6 depletion. Administration of CRTH2 N‐terminal peptide reduces collagen production by binding to LARP6. Similar to CRTH2, bumetanide binds the LARP6 mRNA recognition motif, suppresses collagen biosynthesis, and alleviates bleomycin‐triggered pulmonary fibrosis in vivo. These findings reveal a novel anti‐fibrotic function of CRTH2 in the ER membrane via the interaction with LARP6, which may represent a therapeutic target for fibrotic diseases.
Trends in dentate status and preventive dental visits of the adult population in Denmark over 30 years (1987-2017).

This study analyzed the trend in self-reported dentate status over 30 years (1987-2017) among Danish adults, the self-reported frequencies of preventive dental visits undertaken annually during the period 1987-2013, and the self-reported use of the 2016 recall scheme for preventive dental check-ups. The impact of social determinants (education, employment, civil status, and ethnic background) on these dental outcome variables in 2017 was explored. Questionnaire data were obtained from the Danish Health and Morbidity Surveys conducted from 1987-2017, and they were analyzed by tri-variate frequency distributions and multivariate analyses. The prevalence of complete tooth loss was 17.7% in 1987 but 3.4% in 2017. The frequency of adults having 20 or more teeth grew markedly from 1987 (65.9%) to 2017 (85.1%). Educational inequality in dentate status persisted over the period. The frequency of preventive dental visits at least annually increased from 1987 to 2013, although visits were less frequent for young people. In 2017, preventive dental check-ups were reported in intervals: less than 12 months (56.4%), 12-18 months (18.9%), 19-24 months (4.8%), and more than 24 months (5.2%). In 2017, dentate status and preventive dental check-ups varied profoundly by social determinants. In conclusion, social policies should be implemented to tackle the persistent inequities in dentate status and public health policies should target Universal Health Coverage.
Electroreduction of Carbon Monoxide Over a Copper Nanocube Catalyst: Surface Structure and pH Dependence on Selectivity

The activity and selectivity for CO2/CO reduction over Cu electrodes is strongly dependent on the local surface structure of the catalyst and the pH of the electrolyte. Here we investigate a unique, Cu nanocube surface (CuCube) as a CO reduction electrode under neutral and basic pH by using online electrochemical mass spectroscopy (OLEMS) to determine the onset potentials and relative intensities of methane and ethylene production. To relate the unique selectivity to the surface structure, the CuCube surface reactivity is compared to polycrystalline Cu and three single crystals under the same reaction conditions. We find that the high selectivity for ethylene over the CuCube surface is most comparable to the Cu(1 0 0) surface, which has a cubic unit cell. However, the suppression of methane production over CuCube is unique to that particular surface. A basic pH is shown to enhance ethylene selectivity on all surfaces, and again the CuCube surface is unique.
Partner and Relationship Predictors of Longitudinal Physical Activity Trajectories Among Individuals with Osteoarthritis Using Latent Class Growth Analysis.

BACKGROUND Physical activity reduces osteoarthritis symptoms, yet many individuals with the disease are insufficiently active. PURPOSE We identified physical activity trajectories over 12 months of individuals with osteoarthritis and examined how their cohabiting spouses'/partners' baseline physical activity and relationship factors affected trajectory membership. METHODS In this longitudinal observational study, we collected data from 168 adults with knee/hip osteoarthritis. We used latent class growth curve analysis to identify physical activity trajectories and logistic regression to predict trajectory membership using partners' physical activity, relationship satisfaction, and communal coping (belief that both partners are responsible for osteoarthritis management). Measures, including objectively assessed physical activity, were collected at baseline from the couple, who then received an educational class on physical activity and social support. Objectively assessed physical activity was also collected from individuals with osteoarthritis at 1 week, 3 months, 6 months, and 12 months post-baseline. RESULTS Three trajectories were identified: stable active, increaser, and stable sedentary (24%, 40%, 37% of participants, respectively). Individuals with osteoarthritis with partners who were more active and who believed they alone were responsible for their osteoarthritis were more likely to follow the stable active (versus stable sedentary) trajectory. Those with partners who were less active and had higher relationship satisfaction were more likely to follow the increaser (vs. stable active) trajectory. CONCLUSIONS Findings demonstrate the importance of considering partner and relationship factors in physical activity interventions for couples.
Will Artificial Intelligence Replace the Movement Disorders Specialist for Diagnosing and Managing Parkinson’s Disease?

The use of artificial intelligence (AI) to help diagnose and manage disease is of increasing interest to researchers and clinicians. Volumes of health data are generated from smartphones and ubiquitous inexpensive sensors. By using these data, AI can offer otherwise unobtainable insights about disease burden and patient status in a free-living environment. Moreover, from clinical datasets AI can improve patient symptom monitoring and global epidemiologic efforts. While these applications are exciting, it is necessary to examine both the utility and limitations of these novel analytic methods. The most promising uses of AI remain aspirational. For example, defining the molecular subtypes of Parkinson’s disease will be assisted by future applications of AI to relevant datasets. This will allow clinicians to match patients to molecular therapies and will thus help launch precision medicine. Until AI proves its potential in pushing the frontier of precision medicine, its utility will primarily remain in individualized monitoring, complementing but not replacing movement disorders specialists.
Neutrophil-to-lymphocyte ratio predicts delirium after stroke.

BACKGROUND Delirium is an underdiagnosed and possibly preventable complication in acute stroke and is linked to poor outcome. Neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, is also associated with poor outcome after acute ischemic stroke. AIM To determine whether NLR is a predictor of post-stroke delirium (PSD). METHODS We reviewed the UZ Brussel stroke database and included 514 patients with acute ischemic stroke within 24 hours from stroke onset between February 2009 and December 2014. The presence of delirium was evaluated by two raters based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, using a retrospective chart review method. When no consensus was reached, a third evaluator was consulted. Patients were divided into two groups: those who developed delirium within the first week after stroke onset (n = 201; 39%) and those who did not (n = 313; 61%). Receiver operating characteristics (ROC) and multiple logistic regression analysis (MLRA) were used to identify predictors of PSD. RESULTS MLRA showed that NLR (odds ratio (OR) 1.14; 95% confidence interval (CI) 1.04-1.26), age (OR 1.05; 95% CI 1.03-1.07), National Institutes of Health Stroke Scale (NIHSS; OR 1.14; 95% CI 1.10-1.18), premorbid modified Rankin Scale (mRS) (OR 1.35; 95% CI 1.05-1.74) and premorbid cognitive dysfunction (OR 3.16; 95% CI 1.26-7.92) predicted PSD. ROC curve of a prediction model including NLR, age, NIHSS and premorbid cognitive dysfunction showed an area under the curve of 0.84 (95% CI = 0.81-0.88). CONCLUSIONS Besides age, stroke severity, premorbid mRS and cognitive impairment, NLR is a predictor of PSD, even independent of the development of pneumonia or urinary tract infection.
Classifying Non-Dementia and Alzheimer's Disease/Vascular Dementia Patients Using Kinematic, Time-Based, and Visuospatial Parameters: The Digital Clock Drawing Test.

BACKGROUND Advantages of digital clock drawing metrics for dementia subtype classification needs examination. OBJECTIVE To assess how well kinematic, time-based, and visuospatial features extracted from the digital Clock Drawing Test (dCDT) can classify a combined group of Alzheimer's disease/Vascular Dementia patients versus healthy controls (HC), and classify dementia patients with Alzheimer's disease (AD) versus vascular dementia (VaD). METHODS Healthy, community-dwelling control participants (n = 175), patients diagnosed clinically with Alzheimer's disease (n = 29), and vascular dementia (n = 27) completed the dCDT to command and copy clock drawing conditions. Thirty-seven dCDT command and 37 copy dCDT features were extracted and used with Random Forest classification models. RESULTS When HC participants were compared to participants with dementia, optimal area under the curve was achieved using models that combined both command and copy dCDT features (AUC = 91.52%). Similarly, when AD versus VaD participants were compared, optimal area under the curve was, achieved with models that combined both command and copy features (AUC = 76.94%). Subsequent follow-up analyses of a corpus of 10 variables of interest determined using a Gini Index found that groups could be dissociated based on kinematic, time-based, and visuospatial features. CONCLUSION The dCDT is able to operationally define graphomotor output that cannot be measured using traditional paper and pencil test administration in older health controls and participants with dementia. These data suggest that kinematic, time-based, and visuospatial behavior obtained using the dCDT may provide additional neurocognitive biomarkers that may be able to identify and tract dementia syndromes.
Associations of objectively measured movement behavior and cardiorespiratory fitness with mental health and quality of life in older adults with hypertension: an exploratory analysis during the COVID-19 pandemic

Abstract Objectives: Herein, we explored the associations of pre-pandemic COVID-19 physical activity (PA), sedentary behavior (SB) and cardiorespiratory fitness (CRF) with mental health and quality of life in older adults with hypertension. Method: Objectively measured PA and SB, perceived stress, depression symptoms, and quality of life were assessed before and during the pandemic in seventeen older adults with hypertension. CRF was assessed before the pandemic by cardiopulmonary exercise testing. Longitudinal and cross-sectional associations were analyzed using the mixed linear model. Results: Pre-pandemic light PA (positive association) and SB (negative association) were associated with quality of life during the pandemic. Higher pre-pandemic CRF was associated with less negative changes in perceived stress, depression symptoms, and quality of life during the pandemic. Conclusion: Our preliminary findings suggest that a healthier pre-pandemic movement behavior (more PA, less SB) and better CRF can mitigate the negative impact of the COVID-19 pandemic on mental health and quality of life in older adults with hypertension.
Concentration of Gallbladder Phosphatidylcholine in Cholangiopathies: A Phosphorus‐31 Magnetic Resonance Spectroscopy Pilot Study

Biliary phosphatidylcholine (PtdC) concentration plays a role in the pathogenesis of bile duct diseases. In vivo phosphorus‐31 magnetic resonance spectroscopy (31P‐MRS) at 7 T offers the possibility to assess this concentration noninvasively with high spectral resolution and signal intensity.
Prevalence and Infection Intensity of Zoonotic Trematode Metacercariae in Fish from Soyang-cheon (Stream), in Wanju-gun, Jeollabuk-do, Korea

We surveyed on the infection status of zoonotic trematode metacercariae (ZTM) in freshwater fishes from Soyang-cheon (a branch stream of Mangyeong-gang) in Wanju-gun, Jeollabuk-do, the Republic of Korea. A total of 927 fishes were individually examined with the artificial digestion method during 2013–2015 (462 fish in 15 spp.) and 2018–2019 (465 fish in 25 spp.). Clonorchis sinensis metacercariae were detected in 207 (31.4%) out of 659 fishes in 14 positive fish species (PFS), and their mean intensity was 114 per fish infected (PFI). Metagonimus spp. metacercariae were found in 302 (37.4%) out of 808 fishes in 21 PFS, and their mean intensity was 12 PFI. Centrocestus armatus metacercariae were detected in 222 (59.0%) out of 376 fishes in 12 PFS, and their mean intensity was 383 PFI. Echinostoma spp. metacercariae were found in 139 (22.1%) out of 628 fishes in 10 PFS, and their mean intensity was 7 PFI. Clinostomum complanatum metacercariae were detected in 14 (6.5%) out of 214 fishes in 4 PFS, and their mean intensity was 2.4 PFI. Metorchis orientalis metacercariae were detected in 36 (13.5%) out of 267 fishes in 5 PFS, and their mean intensity was 4.3 PFI. Conclusively, the prevalence and infection intensity of ZTM is generally not so high in fishes from Soyang-cheon. However, those of C. sinensis metacercariae are more or less higher in 2 fish species, Pungtungia herzi and Sarcocheilichthys variegatus wakiyae.