Miracle-dz/UniFAR-FTUs huggingface dataset:
Deregulated MTOR (mechanistic target of rapamycin kinase) is responsible for autophagy defects exacerbating kidney stone development

ABSTRACT Kidney stone disease is a lifestyle-related disease prevalent in developed countries; however, effective medical treatment for the disease is not yet well established. As cellular damage in renal tubular cells (RTCs) is responsible for the disease, here, we focused on the role of macroautophagy/autophagy in RTCs. We found that autophagic activity was significantly decreased in mouse RTCs exposed to calcium oxalate (CaOx) monohydrate crystals and in the kidneys of ﻿GFP-conjugated MAP1LC3B (microtubule- associated protein 1 light chain 3 beta) transgenic mice with CaOx nephrocalcinosis induced by glyoxylate. This caused accumulation of damaged intracellular organelles, such as mitochondria and lysosomes, the normal functioning of which is mediated by functional autophagy. An impairment of autophagy was also observed in the mucosa with plaques of CaOx kidney stone formers. We determined that the decrease in autophagy was caused by an upregulation of MTOR (mechanistic target of rapamycin kinase), which consequently resulted in the suppression of the upstream autophagy regulator TFEB (transcription factor EB). Furthermore, we showed that an MTOR inhibitor could recover a decrease in autophagy and alleviate crystal-cell interactions and the formation of crystals associated with increased inflammatory responses. Taken together, we conclude that autophagy compromised by MTOR deregulation is a fundamental feature in the pathology of kidney stone formation, and propose that chemical inhibition of MTOR could be a prospective strategy for disease suppression. Abbreviations: ACTB: actin, beta; CaOx: calcium oxalate; CKD: chronic kidney disease; COM: calcium oxalate monohydrate; LGALS3/galectin-3: lectin, galactose binding, soluble 3; GFP: ﻿green fluorescent protein; GOX: glyoxylate; HE: hematoxylin and eosin; MAPLC3B: microtubule- associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; NAC: N-acetyl-L-cysteine; ROS: ﻿reactive oxygen species; RTC: renal tubular cell; ﻿SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TEM: transmission electron microscopy; tfLC3: tandem fluorescent-tagged LC3; 3-MA: 3-methyladenine.
Six Weeks of Calorie Restriction Improves Body Composition and Lipid Profile in Obese and Overweight Former Athletes

Objective: The aim of the study was to compare the impact of 6 weeks of reducing daily caloric intake by 20% of total daily energy expenditure (TDEE)-CRI vs. reducing daily caloric intake by 30% of TDEE-CRII on body mass reduction and insulin metabolism in former athletes. Methods: 94 males aged 35.7 ± 5.3 years, height 180.5 ± 4.1 cm, and body mass 96.82 ± 6.2 kg were randomly assigned to the CRI (n = 49) or CRII (n = 45) group. Thirty-one participants (18 subjects from CRI and 13 from CRII) resigned from the study. The effects of both diets on the body composition variables (body mass—BM; body fat—BF; fat free mass—FFM; muscle mass—MM; total body water—TBW), lipid profile (total lipids—TL; total cholesterol—TCh; HDL cholesterol—HDL; LDL cholesterol—LDL; triglycerides—TG), and glucose control variables (glucose—GL, insulin—I, HOMA-IR, insulin-like growth factor-1—IGF-1, leptin and adiponectin) were measured. Results: After adhering to the CR I diet, significant differences were observed in FFM, MM and TG. After adhering to the CR II diet, significant differences were registered in tCh, TL and LDL. Both diets had a significant influence on leptin and adiponectin concentrations. Significant differences in FFM, MM, and tCh were observed between the CR I and CR II groups. At the end of the dietary intervention, significant differences in BF, FFM, MM and TBW were observed between the CR I and CR II groups. Conclusion: The 6 weeks of CR II diet appeared to be more effective in reducing BF and lipid profile and proved to be especially suitable for subjects with high body fat content and an elevated level of lipoproteins and cholesterol. Both reductive diets were effective in improving the levels of leptin and adiponectin in obese former athletes.
Biomonitoring Study of Deoxynivalenol Exposure in Chinese Inhabitants

Objective: To investigate the levels of a deoxynivalenol (DON) biomarker in the urine of subjects living in two China provinces with different geographic locations and dietary patterns, and estimate their dietary DON exposures and health risks. Methods: First morning urine samples were collected on three consecutive days from 599 healthy subjects—301 from Henan province and 298 from Sichuan province—to analyze the total DON concentrations (tDON) after β-glucuronidase hydrolysis using a high-performance liquid chromatography tandem mass spectrometry-based method. The consumption of cereal foods in the previous 24 h before each urine collection was recorded using a duplicate diet method. DON exposure levels were estimated based on the urinary tDON concentrations. Results: Total DON were detected in 100% and 92% of the urine samples from Henan and Sichuan, respectively. Mean urinary tDON concentrations were 52.83 ng/mL in Henan subjects and 12.99 ng/mL in Sichuan subjects, respectively. The tDON levels were significantly higher in the urine of Henan subjects than that of the Sichuan subjects (p < 0.001). Urinary tDON levels were significantly different among age groups in both areas (Henan: p < 0.001; Sichuan: p = 0.026) and were highest in adolescents aged 13–17 years, followed by children aged 7–12 years. Based on the DON biomarker and exposure conversion reported by the European Food Safety Authority (EFSA), the mean estimated dietary intakes of DON were 1.82 μg/kg bw/day in Henan subjects and 0.45 μg/kg bw/day in Sichuan subjects. A total of 56% of Henan subjects and 12% of Sichuan subjects were estimated to exceed the PMTDI of 1 μg/kg bw/day. Consistent with urinary tDON levels, the highest estimated dietary DON intakes were also in children and adolescents aged 7–17 years. For all kinds of wheat-based foods except dumplings, the consumptions were significantly higher in Henan than those in Sichuan. The mean consumption of steamed buns was 8.4-fold higher in Henan (70.67 g/d) than that in Sichuan (8.45 g/d). The mean consumption of noodles in Henan (273.91 g/d) was 3.6-fold higher than that in Sichuan (75.87 g/d). Conclusions: The levels of urinary DON biomarker and the estimated dietary DON intakes in Henan province were high and concerning, especially for children and adolescents. The overall exposure level of Sichuan inhabitants was low.
A Visual Data Mining Tool To SupportCooperative Learning

A cooperative data mining team consists of two or more diverse data mining tools that cooperate to learn. The data mining tools learn from one another by accessing the other team member's knowledge, generating new data and thus adapting its own perspective of the problem at hand. By combining the complementary learning approaches followed by diverse tools, new insights into the problem domain are obtained. This paper describes the ViziMine cooperative data mining tool that acts as a personal assistant, assisting domain experts to explore and increase their expertise regarding a problem domain. The tool provides a uniform interface that incorporates a number of data mining tools that express their knowledge as rules. Results indicate that the approach successfully facilitates the cooperative learning process and eases the transfer of knowledge between learners. This is especially evident in an environment where the human expert actively participates in cooperative learning.
Conserved motifs in the CRISPR leader sequence control spacer acquisition levels in Type I-D CRISPR-Cas systems

ABSTRACT Integrating short DNA fragments at the correct leader-repeat junction is key to successful CRISPR-Cas memory formation. The Cas1–2 proteins are responsible to carry out this process. However, the CRISPR adaptation process additionally requires a DNA element adjacent to the CRISPR array, called leader, to facilitate efficient localization of the correct integration site. In this work, we introduced the core CRISPR adaptation genes cas1 and cas2 from the Type I-D CRISPR-Cas system of Synechocystis sp. 6803 into Escherichia coli and assessed spacer integration efficiency. Truncation of the leader resulted in a significant reduction of spacer acquisition levels and revealed the importance of different conserved regions for CRISPR adaptation rates. We found three conserved sequence motifs in the leader of I-D CRISPR arrays that each affected spacer acquisition rates, including an integrase anchoring site. Our findings support the model in which the leader sequence is an integral part of type I-D adaptation in Synechocystis sp. acting as a localization signal for the adaptation complex to drive CRISPR adaptation at the first repeat of the CRISPR array.
EUS versus percutaneous management of postoperative pancreatic fluid collection: A systematic review and meta-analysis

Postoperative pancreatic fluid collection (POPFC) is an important complication following abdominal surgery. POPFC causes significant morbidity and mortality. Management options are time-consuming and severely affect patient's quality of life. Surgical and/or percutaneous drainage (PCD) is the traditional mainstay of treatment. Studies have shown that EUS could have a role to play in the management of POPFC. Data are limited in the comparison of clinical outcomes with EUS as compared to PCD to this end. We conducted a comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, Google Scholar, LILACS, and Web of Science databases (earliest inception through September 2018) to identify studies that reported on the clinical outcomes of EUS and PCD in the management of POPFC. The goals were to estimate and compare the pooled rates of technical success, clinical success, adverse events, and POPFC recurrence with EUS and PCD. A total of 13 studies were included in the analysis. Ten studies (239 patients) used EUS and 6 studies (267 patients) used PCD in the management of POPFC. The pooled rate of clinical success with EUS was 93.2% (95% confidence interval [CI] 88.2–96.2, I2 = 0) and with PCD was 79.8% (95% CI 70–87, I2 = 74). The difference was statistically significant, P = 0.002. Recurrence rate was significantly lower with EUS as compared to PCD (9.4%: 95% CI 5.2–16.5 vs. 25.7%: 95% CI 24.3–41.7; P = 0.02). Pooled rates of technical success and adverse events were similar with EUS and PCD. Our meta-analysis shows that EUS has significantly better clinical outcomes, in terms of clinical success and disease recurrence, in the management of POPFC as compared to PCD.
Deciphering isomers with a multiple reaction monitoring method for the complete detectable O-glycan repertoire of the candidate therapeutic, lubricin.

Glycosylation is a fundamental post translational modification, occurring on half of all proteins. Despite its significance, our understanding is limited, in part due to the inherent difficulty in studying these branched, multi-isomer structures. Accessible, detailed and quantifiable methods for studying glycans, particularly O-glycans, are needed. Here we take a multiple reaction monitoring (MRM) approach to differentiate and relatively quantify all detectable glycans, including isomers, on the heavily O-glycosylated protein lubricin. Lubricin (proteoglycan 4) is essential for lubrication of the joint and eye. Given the therapeutic potential of lubricin it is essential to understand its O-glycan repertoire in biological and recombinantly produced samples. O-glycans were released by reductive β-elimination and defined showing a range of twenty six neutral, sulfated, sialylated, and both sulfated and sialylated core 1 (Galβ1-3GalNAcα1-) and core 2 (Galβ1-3(GlcNAcβ1-6)GalNAcα1-) structures. Isomer-specific MRM transitions allowed effective differentiation of neutral glycan isomers as well as sulfated isomeric structures, where the sulfate was retained on the fragment ions. This strategy was not as effective with labile sialylated structures, instead it was observed that the optimal collision energy for the m/z 290.1 sialic acid B-fragment differed consistently between sialic acid isomers, allowing differentiation between isomers when fragmentation spectra was insufficient. This approach was also effective for purchased Neu5Acα2-3Galβ1-4Glc and Neu5Acα2-6Galβ1-4Glc, and Neu5Acα2-3Galβ1-4GlcNAc and Neu5Acα2-6Galβ1-4GlcNAc linkage isomers with the Neu5Acα2-6 consistently requiring more energy for optimal generation of the m/z 290.1 fragment. Overall, this method provides an effective and easily accessible approach for the quantification and annotation of complex released O-glycan samples.
Nutrient and Mineral Profile of Chosen Fresh and Smoked Fish

In the present study, were determined the basic nutrients (dry matter, crude ash, crude protein, ether extract, and energy) and mineral elements content in chosen species of raw and smoked freshwater and sea fish. The content of dry matter, and basic nutrients and Na+, K+, Ca+2, Mg+2, P+2, Zn+2, and Cu+2 in the fish samples was determined. The dietary intake of several macro- and microconstituents per one serving (150 g fresh or smoked fish) was calculated. The fresh fish contained on average 220.2 to 283.7 g·kg−1 of dry matter, 12.4 to 10.7 g·kg−1 of crude ash, 176.2 to 173.5 g·kg−1 of crude protein, 32.6 to 78.6 g·kg−1 of ether extract, and 104.6 to 119.1 kcal (freshwater and sea fish, respectively). Thermal treatment reduces the water and fat content in fish meat. Reduction of the K, Ca, Mg, P, Zn, and Cu levels was observed most frequently. The one serving of fish covers approximately 23% and 12% of the recommended dietary amount of K, 7.5–5.0% of Ca, ~12% of Mg, 6.8 to 12.5% of Zn, and about covered 6.7% of Cu. The smoking process increased the concentration of some basic nutrients and reduced the fat and mineral content. Whitefish, trout, halibut, mackerel, and herring had the highest levels of the analyzed minerals.
The Psoriasis Therapeutic Potential of a Novel Short Laminin Peptide C16

Psoriasis is a chronic inflammatory skin disease characterized by excessive growth of keratinocytes and hyperkeratosis in the epidermis. An abnormality of the non-lesional epidermis at an early stage of psoriasis is involved in triggering inflammatory cell infiltration into the dermis. Integrin α5β1 acts as a receptor for fibronectin and has been found to be overexpressed in non-lesional psoriatic epidermis. To investigate whether α5β1 integrin has a potential as a drug target for psoriasis treatment, the α5β1 integrin-binding peptide, C16, was used to obstruct the HaCat keratinocyte cellular responses induced by fibronectin (Fn) in culture and psoriasis-like skin inflammation induced in mice by imiquimod (IMQ). The C16 exhibited antagonistic activity against α5β1 integrin in HaCat cells, with evidence of suppression of the Fn-mediated proliferative, cytoskeletal, and inflammatory responses. Topical treatment with C16 greatly reduced the IMQ-induced epidermal hyperplasia, infiltration of neutrophils/macrophages, and expression of pro-inflammatory mediators in mouse skin. The C16SP (C16-derived short peptide; DITYVRLKF) also exhibited antagonistic activity, suppressing α5β1 integrin activity in culture, and reducing IMQ-induced skin inflammation. Taken together, this study provides the first evidence that α5β1 integrin may be a potential drug target for psoriasis. The synthetic C16 peptide may serve as an agent for psoriasis therapy.
Mechanisms of Social Media Effects on Attitudes Toward E-Cigarette Use: Motivations, Mediators, and Moderators in a National Survey of Adolescents

Background Exposure to risk behavior on social media is associated with risk behavior tendencies among adolescents, but research on the mechanisms underlying the effects of social media exposure is sparse. Objective This study aimed to investigate the motivations of social media use and the mediating and moderating mechanisms of their effects on attitude toward electronic cigarette (e-cigarette) use among adolescents. Methods Using data from a national sample survey of adolescents (age=14-17 years, N=594), we developed and validated a social media use motivation scale. We examined the roles of motivations in the effect of social media use on risk exposure and risk attitude. Results Motivations for social media use included agency, self-expression, realism, social learning, social comparison, and filter. These motivations were associated differentially with the frequency of use of Facebook, Instagram, Snapchat, and YouTube. Frequency of social media use was positively associated with exposure to e-cigarette messages across the four platforms (Ps<.001). Exposure to e-cigarette messages on Instagram (P=.005) and Snapchat (P=.03) was positively associated with attitude toward e-cigarette use. Perceived social media realism moderated the effects of e-cigarette message exposure such that when realism was high, the exposure effect was amplified, but when realism was low, the effect was mitigated (P<.001). A three-way interaction effect (P=.02) among exposure, social learning motivation, and social norm on attitude toward e-cigarette use was found. When perceived social norm was high, the moderating effect of social learning motivation on e-cigarette use attitude was amplified, but when social norm was low, the social learning motivation effect was attenuated. Conclusions Because perceived social media realism moderates the effect of exposure to e-cigarette messages on attitude toward e-cigarette use, future intervention efforts should address the realism perceptions. The three-way interaction among exposure, social learning motivation, and social norm indicates the importance of addressing both the online and offline social environments of adolescents. The social media use motivation scale, reflecting perceived affordances, is broadly applicable. Understanding social media use motivations is important, as they indirectly influence attitude toward e-cigarette use via frequency of social media use and/or frequency of exposure to e-cigarette messages on social media.
ALS and TLS data fusion in cultural heritage documentation and modeling

Abstract. One of the most important aspects of documenting cultural heritage sites is acquiring detailed and accurate data. A popular method of storing 3D information about historical structures is using 3D models. These models are built based on terrestrial or aerial laser scanning data. These methods are seldom used together. Historical buildings usually have a very complex design, therefore the input data, on the basis of which their 3D models are being built, must provide a high enough accuracy to model these complexities. The data processing methods used, as well as the modeling algorithms implemented, should be highly automated and universal. The main of the presented research was to analyze and compare various methods for extracting matching points. The article presents the results of combining data from ALS and TLS using reference points extracted both manually and automatically. Finally, the publication also includes an analysis of the accuracy of the data merging process.
Human Frequency Following Responses to Vocoded Speech: Amplitude Modulation Versus Amplitude Plus Frequency Modulation

Objectives: The most commonly employed speech processing strategies in cochlear implants (CIs) only extract and encode amplitude modulation (AM) in a limited number of frequency channels. Zeng et al. (2005) proposed a novel speech processing strategy that encodes both frequency modulation (FM) and AM to improve CI performance. Using behavioral tests, they reported better speech, speaker, and tone recognition with this novel strategy than with the AM-alone strategy. Here, we used the scalp-recorded human frequency following responses (FFRs) to examine the differences in the neural representation of vocoded speech sounds with AM alone and AM + FM as the spectral and temporal cues were varied. Specifically, we were interested in determining whether the addition of FM to AM improved the neural representation of envelope periodicity (FFRENV) and temporal fine structure (FFRTFS), as reflected in the temporal pattern of the phase-locked neural activity generating the FFR. Design: FFRs were recorded from 13 normal-hearing, adult listeners in response to the original unprocessed stimulus (a synthetic diphthong /au/ with a 110-Hz fundamental frequency or F0 and a 250-msec duration) and the 2-, 4-, 8- and 16-channel sine vocoded versions of /au/ with AM alone and AM + FM. Temporal waveforms, autocorrelation analyses, fast Fourier Transform, and stimulus-response spectral correlations were used to analyze both the strength and fidelity of the neural representation of envelope periodicity (F0) and TFS (formant structure). Results: The periodicity strength in the FFRENV decreased more for the AM stimuli than for the relatively resilient AM + FM stimuli as the number of channels was increased. Regardless of the number of channels, a clear spectral peak of FFRENV was consistently observed at the stimulus F0 for all the AM + FM stimuli but not for the AM stimuli. Neural representation as revealed by the spectral correlation of FFRTFS was better for the AM + FM stimuli when compared to the AM stimuli. Neural representation of the time-varying formant-related harmonics as revealed by the spectral correlation was also better for the AM + FM stimuli as compared to the AM stimuli. Conclusions: These results are consistent with previously reported behavioral results and suggest that the AM + FM processing strategy elicited brainstem neural activity that better preserved periodicity, temporal fine structure, and time-varying spectral information than the AM processing strategy. The relatively more robust neural representation of AM + FM stimuli observed here likely contributes to the superior performance on speech, speaker, and tone recognition with the AM + FM processing strategy. Taken together, these results suggest that neural information preserved in the FFR may be used to evaluate signal processing strategies considered for CIs.
A vertical flow method for sensitive Raman protein measurement in aqueous solutions.

Raman scattering is intrinsically faint. Raman spectroscopy is more valuable with improvements in the signal detection efficiency. To im-prove the signal detection efficiency, we propose a vertical flow method, which is a derivative of the liquid core optical fiber technique employed for sensitive Raman signal detection. In the vertical flow method, the sample solution flows from a pinhole to prepare a liquid column wrapped with air and uses total reflection at the sample-air interface to confine the excitation beam and Raman signal. The Ra-man signal emerges from the pinhole for efficient collection. This method enhanced Raman signal intensity by up to 90 times. When measuring a bovine serum albumin aqueous solution, the limit of detection (LOD) was 0.029 ± 0.003 mg mL-1 (0.44 ± 0.05 µM). We discuss the signal enhancement factor dependence on several parameters in the vertical flow method. Our method provides a simple technique to improve Raman spectroscopy sensitivity using universal materials.