Miracle-dz/UniFAR-FTUs huggingface dataset:
Apical Sodium-Dependent Bile Acid Cotransporter, A Novel Transporter of Indocyanine Green, and Its Application in Drug Screening

Bile acid plays critical roles in the elimination of inorganic compounds such as bilirubin, heavy metals, and drug metabolites. Apical sodium-dependent bile acid cotransporter (ASBT), a solute carrier membrane transport protein, transports bile acids. Several inhibitors of ASBT have been evaluated in clinical trials. Sodium taurocholate cotransporting polypeptide (NTCP), belonging to the same family as ASBT, has fluorescein 5(6)-isothiocyanate (FITC) and indocyanine green (ICG) transportability. ICG, a Food and Drug Administration-approved fluorophore at near-infrared range, has perfect optical characteristics, so it can be applied in cell tracking and drug screening. In this study, ASBT and NTCP were transduced into the HT-1080 cell line. Nude mice were subcutaneously xenografted with control and ASBT-expressing cells. ICG transportability was observed through flow cytometry, fluorescent microscopy, multi-mode plate readers, and an in vivo imaging system. Several molecules, including taurocholate, sodium deoxycholate, cyclosporine A, nifedipine, and Primovist, were used to evaluate an in vitro drug-screening platform by using the combination of ICG and ASBT through flow cytometry. ICG and FITC were validated and shown to be transported by ASBT. NTCP had a higher ICG intensity compared with ASBT. For cell tracking, the ASBT xenograft had similar ICG signals as the control. For a drug-screening platform, the ICG intensity decreased with 186 μM taurocholate (56.8%), deoxycholate (83.8%), and increased with nifedipine (133.2%). These findings are suggestive of opportunities for the high-throughput drug screening of cholestasis and other diseases that are related to the dynamics of bile acid reabsorption.
Practice Guidelines for Ocular Telehealth-Diabetic Retinopathy, Third Edition

Contributors The following document and appendices represent the third edition of the Practice Guidelines for Ocular Telehealth-Diabetic Retinopathy. These guidelines were developed by the Diabetic Retinopathy Telehealth Practice Guidelines Working Group. This working group consisted of a large number of subject matter experts in clinical applications for telehealth in ophthalmology. The editorial committee consisted of Mark B. Horton, OD, MD, who served as working group chair and Christopher J. Brady, MD, MHS, and Jerry Cavallerano, OD, PhD, who served as cochairs. The writing committees were separated into seven different categories. They are as follows: 1. Clinical/operational: Jerry Cavallerano, OD, PhD (Chair), Gail Barker, PhD, MBA, Christopher J. Brady, MD, MHS, Yao Liu, MD, MS, Siddarth Rathi, MD, MBA, Veeral Sheth, MD, MBA, Paolo Silva, MD, and Ingrid Zimmer-Galler, MD.2. Equipment: Veeral Sheth, MD (Chair), Mark B. Horton, OD, MD, Siddarth Rathi, MD, MBA, Paolo Silva, MD, and Kristen Stebbins, MSPH.3. Quality assurance: Mark B. Horton, OD, MD (Chair), Seema Garg, MD, PhD, Yao Liu, MD, MS, and Ingrid Zimmer-Galler, MD.4. Glaucoma: Yao Liu, MD, MS (Chair) and Siddarth Rathi, MD, MBA.5. Retinopathy of prematurity: Christopher J. Brady, MD, MHS (Chair) and Ingrid Zimmer-Galler, MD.6. Age-related macular degeneration: Christopher J. Brady, MD, MHS (Chair) and Ingrid Zimmer-Galler, MD.7. Autonomous and computer assisted detection, classification and diagnosis of diabetic retinopathy: Michael Abramoff, MD, PhD (Chair), Michael F. Chiang, MD, and Paolo Silva, MD.
Glyceollin Transcription Factor GmMYB29A2 Regulates Soybean Resistance to Phytophthora sojae1[OPEN]

Two homologous transcription factors have opposite roles in regulating accumulation of the soybean phytoalexin glyceollin I to provide resistance to Phytophthora. Glyceollin isomers I, II, and III are the major pathogen-elicited secondary metabolites (i.e. phytoalexins) of soybean (Glycine max) that, collectively with other 5-deoxyisoflavonoids, provide race-specific resistance to Phytophthora sojae. The NAC-family transcription factor (TF) GmNAC42-1 is an essential regulator of some but not all glyceollin biosynthesis genes, indicating other essential TF(s) of the glyceollin gene regulatory network remain to be identified. Here, we conducted comparative transcriptomics on soybean hairy roots of the variety Williams 82 and imbibing seeds of Harosoy 63 upon treatment with wall glucan elicitor from P. sojae and identified two homologous R2R3-type MYB TF genes, GmMYB29A1 and GmMYB29A2, up-regulated during the times of peak glyceollin biosynthesis. Overexpression and RNA interference silencing of GmMYB29A2 increased and decreased expression of GmNAC42-1, GmMYB29A1, and glyceollin biosynthesis genes and metabolites, respectively, in response to wall glucan elicitor. By contrast, overexpressing or silencing GmMYB29A1 decreased glyceollin I accumulation with marginal or no effects on the expressions of glyceollin synthesis genes, suggesting a preferential role in promoting glyceollin turnover and/or competing biosynthetic pathways. GmMYB29A2 interacted with the promoters of two glyceollin I biosynthesis genes in vitro and in vivo. Silencing GmMYB29A2 in Williams 82, a soybean variety that encodes the resistance gene Rps1k, rendered it compatible with race 1 P. sojae, whereas overexpressing GmMYB29A2 rendered the susceptible Williams variety incompatible. Compatibility and incompatibility coincided with reduced and enhanced accumulations of glyceollin I but not other 5-deoxyisoflavonoids. Thus, GmMYB29A2 is essential for accumulation of glyceollin I and expression of Phytophthora resistance.
Multiscale modeling of vertebrate limb development

We review the current state of mathematical modeling of cartilage pattern formation in vertebrate limbs. We place emphasis on several reaction–diffusion type models that have been proposed in the last few years. These models are grounded in more detailed knowledge of the relevant regulatory processes than previous ones but generally refer to different molecular aspects of these processes. Considering these models in light of comparative phylogenomics permits framing of hypotheses on the evolutionary order of appearance of the respective mechanisms and their roles in the fin‐to‐limb transition.
Intra-site differential inhibition of multi-specific enzymes

Abstract The ability to catalyse a reaction acting on different substrates, known as “broad-specificity” or “multi-specificity”, and to catalyse different reactions at the same active site (“promiscuity”) are common features among the enzymes. These properties appear to go against the concept of extreme specificity of the catalytic action of enzymes and have been re-evaluated in terms of evolution and metabolic adaptation. This paper examines the potential usefulness of a differential inhibitory action in the study of the susceptibility to inhibition of multi-specific or promiscuous enzymes acting on different substrates. Aldose reductase is a multi-specific enzyme that catalyses the reduction of both aldoses and hydrophobic cytotoxic aldehydes and is used here as a concrete case to deal with the differential inhibition approach.
Impact of diabetes, obesity and hypertension on preterm birth: Population-based study

Objective To determine the impact of pre-pregnancy diabetes mellitus (D), obesity (O) and chronic hypertension (H) on preterm birth (PTB). Methods Retrospective population-based cohort study in Ontario, Canada between 2012–2016. Women who had a singleton livebirth or stillbirth at > 20 weeks gestation were included in the cohort. Exposures of interest were D, O and H, individually, and in various combinations. The primary outcome was PTB at 241/7 to 366/7 weeks. PTB was further analyzed by spontaneous or provider-initiated, early (< 34 weeks) or late (34–37 weeks), and the co-presence of preeclampsia, large for gestational age (LGA), and small for gestational age (SGA). Multivariable Poisson regression models with robust error variance were used to generate relative risks (RR), further adjusted for maternal age and parity (aRR). Population attributable fractions (PAF) were calculated for each of the outcomes by exposure state. Results 506,483 women were eligible for analysis. 30,139 pregnancies (6.0%) were complicated by PTB < 37 weeks, of which 7375 (24.5%) had D or O or H. Relative to women without D or O or H, the aRR for PTB < 37 weeks was higher for D (3.51; 95% CI 3.26–3.78) and H (3.81; 95% CI 3.55–4.10) than O (1.14; 95% CI 1.10–1.17). The combined state of DH was associated with a significantly higher aRR of PTB < 37 weeks (6.34; 95% CI 5.14–7.80) and < 34 weeks (aRR 10.33, 95% CI 6.96–15.33) than D alone. The risk of provider initiated PTB was generally higher than that for spontaneous PTB. Pre-pregnancy hypertension was associated with the highest risk for PTB with preeclampsia (aRR 45.42, 95% CI 39.69–51.99) and PTB with SGA (aRR 9.78, 95% CI 7.81–12.26) while pre-pregnancy diabetes was associated with increased risk for PTB with LGA (aRR 28.85, 95% CI 24.65–33.76). Conclusion Combinations of DOH significantly magnify the risk of PTB, especially provider initiated PTB, and PTB with altered fetal growth or preeclampsia.
Research on a Pedestrian Crossing Intention Recognition Model Based on Natural Observation Data

Accurate identification of pedestrian crossing intention is of great significance to the safe and efficient driving of future fully automated vehicles in the city. This paper focuses on pedestrian intention recognition on the basis of pedestrian detection and tracking. A large number of natural crossing sequence data of pedestrians and vehicles are first collected by a laser scanner and HD camera, then 1980 effective crossing samples of pedestrians are selected. Influencing parameter sets of pedestrian crossing intention are then obtained through statistical analysis. Finally, long short-term memory network with attention mechanism (AT-LSTM) model is proposed. Compared with the support vector machine (SVM) model, results show that when the pedestrian crossing intention is recognized 0 s prior to crossing, the recognition accuracy of the AT-LSTM model for pedestrian crossing intention is 96.15%, which is 6.07% higher than that of SVM model; when the pedestrian crossing intention is recognized 0.6 s prior, the recognition accuracy of AT-LSTM model is 90.68%, which is 4.85% higher than that of the SVM model. The determination of pedestrian crossing intention parameter set and the more accurate recognition of pedestrian intention provided in this work provide a foundation for future fully automated driving vehicles.
Classification of the Molecular Defects Associated with Pathogenic Variants of the SLC6A8 Creatine Transporter.

Over 80 loss-of-function (LOF) mutations in the SLC6A8 creatine transporter (hCRT1) are responsible for cerebral creatine deficiency syndrome (CCDS), which gives rise to a spectrum of neurological defects including intellectual disability, epilepsy, and autism spectrum disorder. To gain insight into the nature of the molecular defects caused by these mutations, we quantitatively profiled the cellular processing, trafficking, expression, and function of eight pathogenic CCDS variants in relation to wild-type and one neutral isoform. All eight CCDS variants exhibit measurable proteostatic deficiencies that likely contribute to the observed LOF. However, the magnitude of their specific effects on expression and trafficking of hCRT1 vary considerably, and we find that the LOF associated with two of these variants primarily arises from the disruption of the substrate-binding pocket. In conjunction with an analysis of structural models of the transporter, we use these data to suggest mechanistic classifications for these variants. To evaluate potential avenues for therapeutic intervention, we assessed the sensitivity of these variants to temperature and measured their response to the proteostasis regulator 4-phenylbutyrate (4-PBA). Only one of the tested variants (G132V) is temperature-sensitive, though its response to 4-PBA is negligible. Nevertheless, 4-PBA significantly enhances the activity of WT hCRT1 in HEK293T cells, which suggests it may be worth evaluating as a therapeutic for female intellectual disability patients carrying a single CCDS mutation. Together, these findings reveal that pathogenic SLC6A8 mutations cause a spectrum of molecular defects that should be taken into consideration in future efforts to develop CCDS therapeutics.
Orb-weaving spiders are fewer but larger and catch more prey in lit bridge panels from a natural artificial light experiment

Artificial light at night is rapidly changing the sensory world. While evidence is accumulating for how insects are affected, it is not clear how this impacts higher trophic levels that feed on insect communities. Spiders are important insect predators that have recently been shown to have increased abundance in urban areas, but have shown mixed responses to artificial light. On a single bridge with alternating artificially lit and unlit sections, I measured changes in the orb-weaving spider Larinioides sclopetarius (Araneidae) web abundance, web-building behavior, prey-capture, and body condition. In artificially lit conditions, spiders caught more prey with smaller webs, and had higher body conditions. However, there were fewer spiders with active webs in those lit areas. This suggests that either spiders were not taking advantage of an ecological insect trap, perhaps due to an increased risk of becoming prey themselves, or were satiated, and thus not as active within these habitats. The results from this natural experiment may have important consequences for both insects and spiders in urban areas under artificial lighting conditions.
Comparison of periarticular multidrug infiltration and epidural catheter use in total knee arthroplasty: A prospective randomized controlled study

Purpose: The purpose of this study was to assess the effectiveness of periarticular multidrug infiltration (PMDI) and compare it with that of epidural catheter use. Methods: Fifty-eight patients (58 joints) who underwent total knee arthroplasty were included in this single-center, prospective, parallel, randomized, controlled trial. Preoperatively, patients were randomly categorized into the PMDI and epidural catheter groups. We evaluated postoperative pain (visual analog scale (VAS) and narcotic consumption), functional outcomes (range of motion (ROM) of knee flexion, the day patients could perform the straight-leg raising (SLR) test, and day of starting cane use), and laboratory data (white blood cell (WBC) and C-reactive protein (CRP)). Results: There was no significant difference in the VAS score, ROM of knee flexion, the day patients could do SLR, and the day of starting cane use between the PMDI and epidural catheter groups. However, the PMDI group could perform SLR on a postoperative day (POD) 1 (p < 0.05). WBC level on POD 1 was significantly higher in the PMDI group (p < 0.05), whereas the CRP levels on POD 1 (p < 0.01), 3 (p < 0.01), and 5 (p < 0.01) were significantly lower in the PMDI group than in the epidural catheter group. The frequency of side effects was not significantly different between the groups. Conclusion: PMDI was as effective as epidural catheter use for pain control. A higher percentage of patients who underwent PMDI could perform SLR on POD 1; therefore, the functional recovery was earlier in the PMDI group than in the epidural catheter group. PMDI may suppress inflammation in the whole body because of steroids.
Robust Time-Delay Feedback Control of Vehicular CACC Systems with Uncertain Dynamics

This paper proposes a new, robust time-delay cooperative adaptive cruise control (CACC) approach for vehicle platooning systems with uncertain dynamics and varying communication delay. The uncertain CACC models with perturbed parameters are used to describe the uncertain dynamics of the vehicle platooning system. By combining the constant time headway strategy and predecessor-following communication topology, a set of robust delay feedback controllers is designed for the uncertain vehicle platoon with varying communication delay. Then, the set of CACC controllers is computed by solving some linear matrix inequalities, which further establish the robust (string) stability of the uncertain platooning system with the varying communication delay. The co-simulation experiment of CarSim and Simulink with a group of a seven-car platoons and varying velocity is used to demonstrate the effectiveness of the presented method.
Endovascular treatment of wide-necked aneurysms of the visceral and renal arteries using the double microcatheter technique via a single access route.

PURPOSE We aimed to evaluate the utility of and complications associated with the double microcatheter technique for the treatment of wide-necked visceral and renal artery aneurysms (VRAAs). METHODS Nine patients (mean age, 58 years; age range, 42-69 years; 4 men, 5 women) with wide-necked VRAAs who underwent treatment with the double microcatheter technique from January 2016 to July 2018 were included in the study. For all patients, anatomical features were confirmed using cone-beam computed tomography (CT) with rotational angiography. The aneurysmal location, size, volume, neck-to-dome ratio, number of coils used, and coil packing density were investigated. Technical success, complications (coil migration and organ ischemia), changes in the complete blood count or serum creatine level, and recurrence were also evaluated. RESULTS Three renal artery aneurysms and 6 splenic artery aneurysms were treated by the double microcatheter technique. The mean size of the aneurysms was 26.09±4.76 mm, mean volume was 6.19±3.69 cm3, and mean neck-to-dome ratio was 1.53±0.24. The number of coils used ranged from 7 to 16. The mean packing density was 11.32%±3.72%. Technical success was achieved in all 9 patients. Renal ischemia occurred in two patients with renal artery aneurysm, one of whom showed minimal scar formation on follow-up CT after infarction. No coil migrations or disease recurrences were observed. CONCLUSION The double microcatheter technique for the treatment of wide-necked VRAAs appears to be relatively safe and useful. However, complex renal artery aneurysm should be carefully managed in order to prevent infarction.
Integration metal single atoms on hierarchical porous nitrogen-doped carbon for highly-efficient hydrogenation of large-sized molecules in pharmaceutical industry.

Single-atom catalysts (SACs) often exhibit superior activity and selectivity in heterogeneous catalysis due to their maximized atom utilization and unique coordination environments. However, most reported works about SACs in heterogeneous catalysis focus on model reactions with simple molecules. In addition, many reported single atoms are confined in microporous structures, hindering the mass transfer of molecules with large sizes, and thus limiting their applications in practical industry. In this study, we report a molten salt assisted method to synthesize metal sin-gle atoms anchored on hierarchical porous nitrogen-doped carbon support (denoted as M1/h-NC, M includes Co, Fe, Ni, Mn and Cu). Taking Co1/h-NC as an example, comparing to the control sam-ple which has Co single atoms being encapsulated in mi-croporous N-doped carbon support (denoted as Co1/m-NC), Co1/h-NC exhibits significantly higher catalytic activity in the selective hydrogenation of large-sized pharmaceutical molecules, such as nimodipine (calcium channel blocker) and 2-(3',4'-methylenedioxyphenylethyl)quinoline (antispasmodic natural alkaloid intermediate). The superior catalytic performance of Co1/h-NC is directly ascribed to the integration of the advantages of single atom active sites and hierarchical mesoporous structure, which is beneficial for the mass transfer of molecules with large sizes and enables all the Co single atoms to be accessible for catalytic reactions.
RETRACTED ARTICLE: Exosomes-carried microRNA-26b-5p regulates microglia M1 polarization after cerebral ischemia/reperfusion

Statement of Retraction We, the Editors and Publisher of the journal Cell Cycle, have retracted the following article: Guangying Li, Longhai Xiao, Hao Qin, Qiang Zhuang, Weiwei Zhang, Long Liu, Chao Di and Yabo Zhang. Exosomes-carried microRNA-26b-5p regulates microglia M1 polarization after cerebral ischemia/reperfusion. Cell Cycle. 2020;19(9);1022-1035. doi: 10.1080/15384101.2020. 1743912 Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
Damage-Associated Molecular Patterns and Th-Cell-Related Cytokines Released after Progressive Effort

Inflammation-induced processes commence with the activation of signalling pathways at the cellular level, which mobilize inflammatory cells and stimulate the secretion of chemokines, cytokines, and damage-associated molecular pattern molecules (DAMPs). Physical effort stimulates inflammation, contributing to muscle repair and regeneration. We have examined the impact of different protocols of progressive-effort tests on T-cell DAMP levels, extracellular cleavage products (fibronectin and hyaluronan), and Th-cell-related cytokine levels among soccer players. Thirty male soccer players with a median age of 17 (16–22) years performed different defined protocols for progressive exercise until exhaustion: (1) YO-YO intermittent recovery test level 1 (YYRL1, n = 10); (2) maximal multistage 20 m shuttle run (Beep, n = 10); and mechanical treadmill (MT, n = 10); and (3) shuttle-run test (n = 10). Blood samples were taken three times as follows: at baseline, post effort, and in recovery. Significantly higher post-effort concentrations of IL-4, IL-6, IL-10, and IFN-γ were observed in the Beep group, IL-4 in the YYRL1 group, and IL-6 and IFN-γ in the MT group as compared with the baseline values. Recovery values were significantly higher for concentrations of IL-4, IL-10, and IFN-γ in the YYRL1 group, only for IFN-γ in the Beep group, and for IL-6, IL-10, and INF-γ in the MT group as compared with the baseline values. Post-effort concentrations of DEFβ2, Hsp27, Fn, and UA in the Beep group and Hsp27 and HA in the YYRL1 group were significantly higher as compared with the baseline values. It seems the performed efficiency test protocols caused a short-term imbalance in Th1/Th2 cytokine levels without giving common molecular patterns. The rapidity of these changes was apparently related to specific physical movements and the type of running surface.