Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Dent disease 1 cellular models reveal biological processes underlying ClC-5 loss-of-function

Abstract Dent disease 1 (DD1) is a rare X-linked renal proximal tubulopathy characterized by low molecular weight proteinuria and variable degree of hypercalciuria, nephrocalcinosis and/or nephrolithiasis, progressing to chronic kidney disease. Although mutations in the electrogenic Cl−/H+ antiporter ClC-5, which impair endocytic uptake in proximal tubule cells, cause the disease, there is poor genotype–phenotype correlation and their contribution to proximal tubule dysfunction remains unclear. To further discover the mechanisms linking ClC-5 loss-of-function to proximal tubule dysfunction, we have generated novel DD1 cellular models depleted of ClC-5 and carrying ClC-5 mutants p.(Val523del), p.(Glu527Asp) and p.(Ile524Lys) using the human proximal tubule-derived RPTEC/TERT1 cell line. Our DD1 cellular models exhibit impaired albumin endocytosis, increased substrate adhesion and decreased collective migration, correlating with a less differentiated epithelial phenotype. Despite sharing functional features, these DD1 cell models exhibit different gene expression profiles, being p.(Val523del) ClC-5 the mutation showing the largest differences. Gene set enrichment analysis pointed to kidney development, anion homeostasis, organic acid transport, extracellular matrix organization and cell-migration biological processes as the most likely involved in DD1 pathophysiology. In conclusion, our results revealed the pathways linking ClC-5 mutations with tubular dysfunction and, importantly, provide new cellular models to further study DD1 pathophysiology.
The relationship between worry and attentional bias to threat cues signalling controllable and uncontrollable dangers

People vary in the frequency with which they worry and there is large variation in the degree to which this worry disrupts their everyday functioning. Heightened tendency to experience disruptive worry is characterised by an attentional bias towards threat. While this attentional bias is often considered maladaptive, it can be adaptive when it concerns threat cues signalling dangers that can be mitigated through personal action. In this case, the resulting worry may increase the likelihood of this action being taken, with beneficial rather than disruptive consequences for everyday functioning. Thus, depending on its focus, attentional bias to threat could potentially drive worry that is high or low in disruptiveness. The current study addressed this possibility, by testing the novel hypothesis that the degree to which worry is disruptive is a function of the degree to which this attentional bias concerns all threat cues, rather than being restricted to threat cues signalling controllable dangers. Participants completed a novel probe task assessing their attention to threat cues signalling a future danger that could be controlled on some blocks, but not on others. Thus, the task revealed the degree to which their selective attention to threat cues was ‘aligned’ with danger controllability, by being more evident on blocks that permitted participant control of the danger signalled by the threat cues. The results indicate, contradicting the hypothesis under test, participants who reported high levels of disruptive worry demonstrated alignment of attentional bias to variations in danger controllability, whereas this was not the case for participants who reported high levels of non-disruptive worry. While caution is needed in the interpretation of the results due to methodological limitations, this study provides a new conceptual and methodological framework for future research on the attentional basis of individual differences in the tendency to experience disruptive vs non-disruptive worry.
Cross-linguistic influence of phonological awareness and phonological recoding skills in Chinese reading acquisition among early adolescent students

Abstract This study investigated crosslinguistic phonological awareness and phonological recoding skills in Chinese reading acquisition among early Chinese adolescent students. 76 Chinese children participated in this study and finished a series of reading measurements over 1 year (from Grade 5 to Grade 6). In Grade 5, they were assessed by Chinese phonological awareness (syllable, onset, rhyme, phoneme, and tone awareness), English phonological awareness (syllable, onset, and rime, phoneme awareness) as well as English and Chinese phonological recoding skills. In Grade 6, the students completed the measurement of Chinese lexical inferencing ability. Subsequent hierarchical regression analyses showed that Time 1 (Grade 5) Chinese phonological awareness and recoding skills made a joint intra-lingual contribution to later Chinese lexical inferencing ability. Moreover, English phonological recoding skills had a unique inter-lingual contribution to later Chinese lexical inferencing ability after age, nonverbal intelligence, and English phonological awareness were controlled for. Results expanded the self-teaching hypothesis to account for variations within and across languages over time and underscored the uniqueness of inter-lingual phonological recoding in later orthographic and semantic learning.
Microinvasive glaucoma surgery: a review and classification of implant‐dependent procedures and techniques

The aim of this article is to discuss how physiology and anatomical background affect the effectiveness of implant‐dependent microinvasive glaucoma surgery (MIGS). First, we provide a micro view of aqueous outflow and tissue behaviour. Second, we review studies exploring the mechanisms of the pressure‐lowering effect of MIGS, as well as tissue behaviour during aqueous flow and tissue motion. We also describe and classify microinvasive surgical procedures and the most important types of implants, as well as their mechanisms of action, implantation techniques and efficacy. Further, we summarize the indications and surgical results presented in recent studies, providing an evidence‐based update on novel and emerging MIGS techniques for the treatment of open‐angle glaucoma. These data can help surgeons to personalize the management of glaucoma and to choose the best MIGS option for individual glaucoma patients.
Effect of Neprilysin Inhibition on Left Ventricular Remodeling in Patients With Asymptomatic Left Ventricular Systolic Dysfunction Late After Myocardial Infarction

Supplemental Digital Content is available in the text. Background: Patients with left ventricular (LV) systolic dysfunction after myocardial infarction are at a high risk of developing heart failure. The addition of neprilysin inhibition to renin angiotensin system inhibition may result in greater attenuation of adverse LV remodeling as a result of increased levels of substrates for neprilysin with vasodilatory, antihypertrophic, antifibrotic, and sympatholytic effects. Methods: We performed a prospective, multicenter, randomized, double-blind, active-comparator trial comparing sacubitril/valsartan 97/103 mg twice daily with valsartan 160 mg twice daily in patients ≥3 months after myocardial infarction with a LV ejection fraction ≤40% who were taking a renin angiotensin system inhibitor (equivalent dose of ramipril ≥2.5 mg twice daily) and a β-blocker unless contraindicated or intolerant. Patients in New York Heart Association class ≥II or with signs and symptoms of heart failure were excluded. The primary outcome was change from baseline to 52 weeks in LV end-systolic volume index measured using cardiac magnetic resonance imaging. Secondary outcomes included other magnetic resonance imaging measurements of LV remodeling, change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin I, and a patient global assessment of change questionnaire. Results: From July 2018 to June 2019, we randomized 93 patients with the following characteristics: mean age, 60.7±10.4 years; median time from myocardial infarction, 3.6 years (interquartile range, 1.2–7.2); mean LV ejection fraction, 36.8%±7.1%; and median NT-proBNP, 230 pg/mL (interquartile range, 124–404). Sacubitril/valsartan, compared with valsartan, did not significantly reduce LV end-systolic volume index; adjusted between-group difference, –1.9 mL/m2 (95% CI, –4.8 to 1.0); P=0.19. There were no significant between-group differences in NT-proBNP, high-sensitivity cardiac troponin I, LV end-diastolic volume index, left atrial volume index, LV ejection fraction, LV mass index, or patient global assessment of change. Conclusions: In patients with asymptomatic LV systolic dysfunction late after myocardial infarction, treatment with sacubitril/valsartan did not have a significant reverse remodeling effect compared with valsartan. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT03552575.
Endozoicomonadaceae symbiont in gills of Acesta clam encodes genes for essential nutrients and polysaccharide degradation

ABSTRACT Gammaproteobacteria from the family Endozoicomonadaceae have emerged as widespread associates of dense marine animal communities. Their abundance in coral reefs involves symbiotic relationships and possibly host nutrition. We explored functions encoded in the genome of an uncultured Endozoicomonadaceae ‘Candidatus Acestibacter aggregatus’ that lives inside gill cells of large Acesta excavata clams in deep-water coral reefs off mid-Norway. The dominance and deep branching lineage of this symbiont was confirmed using 16S rRNA gene sequencing and phylogenomic analysis from shotgun sequencing data. The 4.5 Mb genome binned in this study has a low GC content of 35% and is enriched in transposon and chaperone gene annotations indicating ongoing adaptation. Genes encoding functions potentially involved with the symbiosis include ankyrins, repeat in toxins, secretion and nutritional systems. Complete pathways were identified for the synthesis of eleven amino acids and six B-vitamins. A minimal chitinolytic machinery was indicated from a glycosyl hydrolase GH18 and a lytic polysaccharide monooxygenase LPMO10. Expression of the latter was confirmed using proteomics. Signal peptides for secretion were identified for six polysaccharide degrading enzymes, ten proteases and three lipases. Our results suggest a nutritional symbiosis fuelled by enzymatic products from extracellular degradation processes.
Facing an unexpected reality - oscillating between health and suffering 4-6 years after bariatric surgery.

BACKGROUND Obesity is a significant public health problem that is on the increase worldwide, and treatment with bariatric surgery is becoming more and more common. This type of surgery has proved to be good for weight reduction and for preventing complications, but few studies have investigated patients' long-term experiences of health and suffering. AIM To explore people's experiences of health after bariatric surgery. What are their thoughts about their life, body and sexuality? METHODS This study is based on semi-structured interviews with eight women and eight men, 4-6 years after bariatric surgery. The data were analysed using qualitative content analysis and resulted in 5 main themes and 14 subthemes. RESULTS The new body enabled a healthy life due to better treatment in society, enhanced self-esteem, the pleasure of purchasing clothes and the courage to become more sexually active. At the same time, the body could be experienced as so unfamiliar that their life was dominated by despondency, a lack of freedom and a feeling of being lost, which made them wish to return to their old body. CONCLUSION AND IMPLICATIONS The participants received extensive information before as well as follow-up conversations up to one year after surgery. Nevertheless, they all experienced that changing from life as an obese person to a radically reduced body often meant a confrontation with an unexpected reality that oscillated between health and suffering. This indicates that preparedness for the life changes that bariatric surgery may entail is inadequate and that moving towards health and suffering takes its own time. Therefore, more time should be allocated to talking about how life is and can become in the long term, which may facilitate a dialogical, person-centred approach to the setbacks and situations each person needs to manage in order to improve her/his health.
Moderately differentiated esophageal squamous cell carcinoma has a poor prognosis after neoadjuvant chemoradiotherapy

Background Neoadjuvant chemoradiotherapy (NCRT) plus surgery is the standard treatment for esophageal squamous cell carcinoma (ESCC); however, further analysis is needed to detail the histopathological characteristics of ESCC and their clinical significance after NCRT. This study aimed to present the pathological characteristics of ESCC and their association with prognosis after NCRT. Methods All patients with ESCC who underwent NCRT followed by surgical resection at Sichuan Cancer Hospital (China) from January 2018 to December 2019 were included. Resection specimens of both the primary disease and lymph nodes were re-evaluated by an experienced pathologist. After NCRT, the pathological characteristics of the residual tumor were evaluated based on the Japanese residual tumor pattern, Mandard tumor regression grade (Mandard-TRG), local inflammatory infiltration classification, and lymph node status. Results Among the 103 patients with ESCC included in this study, the pathological complete response (pCR) rate was 34% (35/103). The pCR rate of patients with poorly differentiated tumors (31/72) was higher (43.1%) than that of patients with well or moderately differentiated tumors (P<0.05). The residual tumor rate was 66% (68/103). A positive correlation was noted between the Japanese residual tumor pattern and Mandard-TRG (Kendall’s tau-b =0.857, P<0.001). Tumor infiltration depth, lymph node positivity, moderate differentiation, and tumor recurrence were associated with poor oncological outcomes (P<0.05). Conclusions Patients with poorly differentiated tumors can obtain an excellent short-term response; however, they have extremely poor long-term survival. For patients with moderately differentiated tumors, both the short- and long-term outcomes are poor. Lymph node status after NCRT is a prognostic factor for ESCC treated with NCRT.
Emergency Department Visits for Bicycle-Related Traumatic Brain Injuries Among Children and Adults — United States, 2009–2018

Bicycling leads to the highest number of sport and recreation-related emergency department (ED) visits for traumatic brain injuries (TBIs) in the United States (1). Because bicycling continues to grow in popularity,* primarily among U.S. adults, examining the strategies that mitigate the risk for TBI is important. CDC analyzed data from the National Electronic Injury Sursveillance System-All Injury Program (NEISS-AIP) to determine the incidence of EDs for bicycle-related TBIs during 2009-2018. An estimated 596,972 ED visits for bicycle-related TBIs occurred in the United States during the study period. Rates of ED visits were highest among adult males (aged ≥18 years) and among children and adolescents aged 10-14 years during 2009-2018. Overall, the rate of ED visits for bicycle-related TBIs decreased by approximately one half (48.7%) among children and by 5.5% among adults. As the number of persons riding bicycles increases, expansion of comprehensive bicycling safety interventions for bicyclists and drivers by states and local communities, such as interventions to increase driver compliance with traffic laws and helmet use among riders, improvements in bicycling infrastructure, and customized interventions for males and other groups at high risk might help reduce bicycle-related injuries.
Planar Laser Induced Fluorescence Experiments and Modeling Study of Jets in Crossflow at Various Injection Angles

Planar Laser Induced Fluorescence (PLIF) with acetone seeding was applied to measure the scalar fields of an axisymmetric freejet and an inclined jet-in-crossflow as applicable to film cooling. From the scalar fields, jet-mixing and trajectory characteristics were obtained. In order to validate the technique, the canonical example of a nonreacting freejet of Reynolds Numbers 900-9000 was investigated. Desired structural characteristics were observed and showed strong agreement with computational modeling. After validating the technique with the axisymmetric jet, the jet-in-crossflow was tested with various velocity ratios and jet injection angles. Results indicated the degree of wall separation for different injection angles and demonstrate both the time-averaged trajectories as well as select near-wall concentration results for varying jet momentum fluxes. Consistent with literature findings, the orthogonal jet trajectory for varying blowing ratios collapsed when scaled by the jet-to-freestream velocity ratio and hole diameter, rd. Similar collapsing was demonstrated in the cases of a non-orthogonal jets. Computational Fluid Dynamic (CFD) simulations using the OpenFOAM software were used to compare predictions with select experimental cases, and yielded reasonable agreement. Insight into the importance and structure of the counter rotating vortex pair and general flowfield turbulence was highlighted by cross validation between CFD and experimental results.
Proteomic profiling of ovine milk after grading up

Abstract We have previously bred Chinese local dairy sheep through grading up with local Small-Tailed Han (STH) sheep as female parent and DairyMeade (DM) sheep as male parent. In this research communication we characterize the whey protein profile of STH sheep and their offspring (F1, F2) to reveal physiological differences and variation in milk traits. A total of 1032 whey proteins were identified through tandem mass tag labeling (TMT) proteome profiling. Three proteins were significantly differentially abundant between F1 and STH milk, six between F2 and STH milk and five between F1 and F2 milk. In terms of differential changes between generations, WASHC4 and CUTA of F1 and Ig-like domain-containing protein of F2 milk were dominant whey proteins. Overall, the results showed that the whey protein profiles of different generations varied little. The crossbreeds of STH and DM sheep would be suitable for the development of the Chinese local sheep milk industry, and the F2 may be a better population for sheep milk production.
Validation of the European Prospective Investigation into Cancer (EPIC) FFQ for use among adults in Lebanon

Abstract Objective: To validate the European Prospective Investigation into Cancer (EPIC) FFQ in Lebanon. Design: Validation of the EPIC FFQ was done against three 24-h recalls (24-HR). Unadjusted and energy-adjusted correlations, Bland–Altman plots and weighed kappa statistics were used to assess the agreement between the two methods. Setting: Lebanon. Participants: 119 adults (staff and students) at a Lebanese University. Results: Good unadjusted and energy-adjusted correlation coefficients were found between data from the two methods which ranged from –0·002 (vitamin A) to 0·337 (carbohydrates) and were all statistically significant except for vitamin D, vitamin E, vitamin A, Se and niacin. Slight/fair agreement was reported through weighed kappa estimates for unadjusted data ranging from –0·05 (vitamin C) to 0·248 (Mg) and for energy-adjusted data ranging from –0·034 (vitamin A) to 0·203 (P). Individuals were categorised into exact and adjacent quartiles with an average of 78 % for unadjusted data and 70 % for energy-adjusted data, indicating a very good agreement between the EPIC FFQ and the average of the 24-HR data. The visual inspection of the Bland–Altman plots revealed an overestimation of energy, carbohydrates, protein and fat intakes by the FFQ method. Conclusion: Overall, when all tests were taken into consideration, the current study demonstrated an acceptable agreement of the EPIC FFQ with the 24-h dietary recall method and significantly good correlations between dietary intakes. Therefore, the EPIC FFQ can be considered a valid tool for assessing diet in epidemiological studies among Lebanese adults.
Development and external validation of the ‘Flower-FFQ’: a FFQ designed for the Lifelines Cohort Study

Abstract Objective: FFQ assess habitual dietary intake and are relatively inexpensive to process, but may take up to 60 min to complete. This article describes the validation of the Flower-FFQ, which consists of four short FFQ measuring the intake of energy and macronutrients or specific (micro)nutrients/foods that can be merged into one complete daily assessment using predefined algorithms. Design: Participants completed the Flower-FFQ and validated regular-FFQ (n 401). Urinary N (n 242) and K excretions (n 361) were measured. We evaluated: (1) group-level bias, (2) correlations and (3) cross-classification. Setting: Observational study. Participants: Dutch adults, 54 ± 11 (mean ± SD) years. Results: Flower-FFQ1, Flower-FFQ2, Flower-FFQ3 and Flower-FFQ4 were completed in ±24, 9, 8 and 9 min (±50 min total), respectively. The regular-FFQ was completed in ±43 min. Mean energy (flower v. regular: 7953 v. 8718 kJ/d) and macronutrient intakes (carbohydrates: 204 v. 222 g/d; protein: 75 v. 76 g/d; fat: 74 v. 83 g/d; ethanol: 8 v. 12 g/d) were comparatively similar. Spearman correlations between Flower-FFQ and regular-FFQ ranged from 0·60 to 0·80 for macronutrients and from 0·40 to 0·80 for micronutrients and foods. For all micronutrients and foods, ≥ 78 % of the participants classified in the same/adjacent quartile. The Flower-FFQ underestimated urinary N and K excretions by 24 and 18 %; 75 and 73 % of the participants ranked in the same/adjacent quartile. Conclusion: Completing the Flower-FFQ required 50 min with a maximum of 25 min per short FFQ. The Flower-FFQ has a moderate to good ranking ability for most nutrients and foods and performs sufficiently to study diet–disease associations.
DNA Methylation and Resting Brain Function Mediate the Association between Childhood Urbanicity and Better Speed of Processing

Abstract Urbanicity has been suggested to affect cognition, but the underlying mechanism remains unknown. We examined whether epigenetic modification (DNA methylation, DNAm), and brain white matter fiber integrity (fractional anisotropy, FA) or local spontaneous brain function activity (regional homogeneity, ReHo) play roles in the association between childhood urbanicity and cognition based on 497 healthy Chinese adults. We found significant correlation between childhood urbanicity and better cognitive performance. Multiset canonical correlation analysis (mCCA) identified an intercorrelated DNAm-FA-ReHo triplet, which showed significant pairwise correlations (DNAm-FA: Bonferroni-adjusted P, Pbon = 4.99E−03, rho = 0.216; DNAm-ReHo: Pbon = 4.08E−03, rho = 0.239; ReHo-FA: Pbon = 1.68E−06, rho = 0.328). Causal mediation analysis revealed that 1) ReHo mediated 10.86% childhood urbanicity effects on the speed of processing and 2) childhood urbanicity alters ReHo through DNA methylation in the cadherin and Wnt signaling pathways (mediated effect: 48.55%). The mediation effect of increased ReHo in the superior temporal gyrus underlying urbanicity impact on a better speed of processing was further validated in an independent cohort. Our work suggests a mediation role for ReHo, particularly increased brain activity in the superior temporal gyrus, in the urbanicity-associated speed of processing.