Miracle-dz/UniFAR-FTUs huggingface dataset:
Moderate sedation by total intravenous remimazolam-alfentanil vs. propofol-alfentanil for third molar extraction: A prospective randomized controlled trial

Background Oral dental treatment cause anxiety, fear, and physical stress. This study aimed to investigate the efficacy and safety of moderate sedation by remimazolam with alfentanil vs. propofol with alfentanil in third molar extraction. Methods This single-center, randomized, single-blind clinical trial included 100 adults who underwent third molar ambulatory extraction. All patients had continuous infusion of Alfentanil 0.2 μg/kg/min. Group remimazolam with alfentanil (group RA) had an induction dose of 80 μg/kg and maintenance dosage of 5 μg/kg/min. In group propofol with alfentanil (PA group), propofol was infused at an initial concentration of 1.8 μg/mL under target controlled infusion (TCI) mode and a maintenance concentration of 1.5 μg/mL. The incidence rates of adverse effects were recorded and compared. Depth of sedation was assessed using the modified observer alertness/sedation assessment (MOAA/S) and entropy index. Recovery characteristics were recorded and complications observed for next 24 h. Results The incident of adverse events 6 (12%) in the group RA was lower than the group PA 25 (50%) [Mean difference 0.136 (95%CI, 0.049–0.377); P < 0.05], with no serious adverse events during the sedation procedure. The incidence of injection pain in group RA was significantly lower than that in group PA [4 vs. 26%, mean difference 0.119 (95%CI, 0.025–0.558); P = 0.004]. Before starting local anesthesia, the mean arterial pressure, heart rate, and respiratory rate of the PA group were lower than those of the RA group. None of the patients required further treatments for a decreased heart rate, blood pressure, or low SpO2. The rate of moderate sedation success was 100% in both groups. The MOAA/S score was similar between the groups indicating that the depth of sedation was effective. Group RA had significantly shorter recovery and discharge times than those of group PA. Conclusions Remimazolam with alfentanil is a safer and more effective alternative for ambulatory sedation and can reduce recovery and discharge time and the incidence of perioperative adverse events compare with propofol. Clinical trial registration http://www.chictr. org.cn/index.aspx, identifier: ChiCTR2200058106.
Identification of novel lactate metabolism signatures and molecular subtypes for prognosis in hepatocellular carcinoma

Background: Evidence has shown that lactate, an immune signaling molecule, is associated with hepatocellular carcinoma (HCC) progression and immune suppression. Therefore, identifying lactate metabolism-related molecules is a promising therapeutic strategy to inhibit the development of HCC and overcome chemotherapy resistance. Long noncoding RNAs (lncRNAs) are related to tumorigenesis and metastasis. Hence, verifying the molecular subtypes of lncRNAs related to lactate metabolism will play a critical role in managing HCC. Methods: Based on HCC data in The Cancer Genome Atlas (TCGA), lactate metabolic pathway-related genes were enriched by gene collection and enrichment analysis (GSEA). Lactate metabolism-related lncRNAs (LM_lncRNAs) were identified by correlation analysis, HCC molecular subtypes were determined using nonnegative matrix factorization (NMF) clustering, and the response of the three subtypes to chemotherapeutics was further evaluated using the Genomic Tumor Sensitive Cell Line (GDSC) dataset. LM_lncRNAs were examined via Lasso-Cox regression analysis to determine prognosis for patients. A Nomagram plot was used to predict patient survival time. Results: Three molecular subtypes of HCC were identified. The survival rate of patients with C1 subtype was higher than that of those with C2 and C3. Additionally, patients with C3 subtype have higher levels of immune cell infiltration and high expression of genes related to immune checkpoints. The GDSC results indicated that patients with C3 subtypes were more sensitive to chemotherapy drugs such as sorafenib and sunitinib. The prognostic risk assessment model consisted of six risk factors (AC034229.4, AC131009.1, MYOSLID, AC008667.1, AC012073.1, AC068025.1) and two protective factors (LINC00402 and AC103858.1). Based on Kaplan-Meier analysis, low-risk HCC patients had a high survival rate, and the receiver operating characteristic curve (ROC), calibration curve, and C-index confirmed good prediction ability. Conclusion: In this study, the molecular subtyping method and prediction model of lactate metabolism-related lncRNAs (LM_lncRNAs) were constructed for the prognosis of HCC patients. This work demonstrated the potential targets of LM_lncRNAs and provided a novel perspective and therapeutic paradigm for future clinical translation.
Case report: Exotropia in waardenburg syndrome with novel variations

Background: Waardenburg syndrome (WS) is a rare genetic disorder characterized by congenital sensorineural hearing loss and pigmentary abnormalities of the hair, skin and eyes. However, exotropia is rarely reported. The purpose of this study is to describe the clinical characteristics of three sporadic patients with WS and congenital exotropia and to investigate the disease-causing genes for them. Methods: Patients underwent detailed physical and ocular examinations. Ocular alignment and binocular status were evaluated. DNA was extracted and whole exome sequencing was performed to detect the pathogenic variations in the disease-causing genes for WS. Cloning sequencing was carried out for those indel variations. Results: Three unrelated patients were diagnosed with Waardenburg syndrome and congenital exotropia. Four novel variants, including c.136delA (p.I46Sfs*64) and c.668G>T (p.R223L) in PAX3, c.709dupC (p.Q237Pfs*119) in COL11A2, c.426G>A (p.W142X) in SOX10 gene, were detected in this study. Conclusion: Simultaneous presence of congenital exotropia and WS in our patients is suggested that WS could be involved in malfunction in the multiple nerve systems. Our genetic study will expand the mutation spectrum of PAX3, COL11A2 and SOX10 genes, and is helpful for further study on the molecular pathogenesis of WS.
Assessing kidney development and disease using kidney organoids and CRISPR engineering

The differentiation of human pluripotent stem cells (hPSCs) towards organoids is one of the biggest scientific advances in regenerative medicine. Kidney organoids have not only laid the groundwork for various organ-like tissue systems but also provided insights into kidney embryonic development. Thus, several protocols for the differentiation of renal progenitors or mature cell types have been established. Insights into the interplay of developmental pathways in nephrogenesis and determination of different cell fates have enabled the in vitro recapitulation of nephrogenesis. Here we first provide an overview of kidney morphogenesis and patterning in the mouse model in order to dissect signalling pathways that are key to define culture conditions sustaining renal differentiation from hPSCs. Secondly, we also highlight how genome editing approaches have provided insights on the specific role of different genes and molecular pathways during renal differentiation from hPSCs. Based on this knowledge we further review how CRISPR/Cas9 technology has enabled the recapitulation and correction of cellular phenotypes associated with human renal disease. Last, we also revise how the field has positively benefited from emerging technologies as single cell RNA sequencing and discuss current limitations on kidney organoid technology that will take advantage from bioengineering solutions to help standardizing the use of this model systems to study kidney development and disease.
A study on sustainable air travel behavior under the possible remedy of risk knowledge: A mediating perspective of risk perception during COVID-19

The aviation industry is the center of gravity for tourism-dependent countries seeking to uplift their economic activities. The COVID-19 pandemic in the early part of 2020 threatened people and the air industry to the maximum extent. This paper investigated the sustainable air travel behavior of passengers under the risk knowledge path. The mediating role of risk perception, i.e., physical risk, psychological risk, and service quality, was also tested for the risk knowledge-air travel behavior association. We surveyed 339 travelers at six airports in Thailand from January to June 2021 to record their responses. We applied covariance–variance-based structural equation modeling (CB-SEM), and the study results revealed a direct effect of risk knowledge with an indirect impact via risk perception paths on air travel behavior. This paper highlights knowledge as a remedial response to the perceptual makeup of air services sustainability. The study has solid managerial implications for aviation management in the design of ideal pathways for retaining air services during the current public emergency of COVID-19.
Identifying key genes of classic papillary thyroid cancer in women aged more than 55 years old using bioinformatics analysis

Background The incidence rate of thyroid carcinoma (THCA) markedly increased in the recent few decades and has been likely over-diagnosed, especially papillary thyroid cancer (PTC) in women. However, the incidence of advanced-stage papillary thyroid cancer is also rising. According to earlier studies, tumors with identical pathology might have different clinical outcomes, which implies some variances in papillary thyroid cancer. Although the mortality of thyroid cancer has remained stable or declined, there is still an important problem in estimating whether it is benign or needs surgery for patients with papillary thyroid cancer. Methods After obtaining data from The Cancer Genome Atlas (TCGA) Project-THCA database by R package TCGA bio links, 18 samples (11 at stage IV as high-risk group and 7 at stage I as low-risk group) were obtained using survival package and edgeR to ensure differential expression; ClusterProfiler package was used to carry on gene set enrichment analysis and searched the possible pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. STRING and Cytoscape were used to construct and modify the protein–protein interaction (PPI) network to get hub genes of differentially expressed genes. Next, the pROC package was used to get the receiver operating characteristic (ROC) curves of hub genes’ disease-free survival (DFS). Then, transcription factors (TFs) and miRNAs of key genes were predicted by ENCORI and AnimalTFDB. In the end, TF–target genes–miRNA regulatory network was also constructed by Cytoscape. Results Our research obtained the top 9 candidate genes from the whole network (IFNA1, MRC1, LGALS3, LOX, POSTN, TIMP1, CD276, SDC4, and TLR2). According to the ROC results, TIMP1, LOX, CD276, IFNA1, TLR2, and POSTN were considered to play a more critical role in malignant papillary thyroid cancer or immature cancer of papillary thyroid cancer. Our analysis concludes that TIMP1, LOX, CD276, IFNA1, TLR2, and POSTN are identified as thyroid cancer biomarkers, which lead to the different clinical courses of a woman older than 55 years old with papillary thyroid cancer. Especially CD276, POSTN, and IFNA1 may be considered as new biomarkers associated with the prognosis of thyroid cancer. Conclusions TIMP1, LOX, CD276, IFNA1, TLR2, and POSTN have different expressions in PTCs, which lead to the various clinical courses of a woman older than 55 years old with papillary thyroid cancer. Especially CD276, POSTN, and IFNA1 may be considered as new potential biomarkers associated with the prognosis of thyroid cancer. In addition, TF–miRNA–target gene regulatory network may help further reach for PTC.
How standardized are “standard protocols”? Variations in protocol and performance evaluation for slow cortical potential neurofeedback: A systematic review

Neurofeedback (NF) aims to alter neural activity by enhancing self-regulation skills. Over the past decade NF has received considerable attention as a potential intervention option for many somatic and mental conditions and ADHD in particular. However, placebo-controlled trials have demonstrated insufficient superiority of NF compared to treatment as usual and sham conditions. It has been argued that the reason for limited NF effects may be attributable to participants' challenges to self-regulate the targeted neural activity. Still, there is support of NF efficacy when only considering so-called “standard protocols,” such as Slow Cortical Potential NF training (SCP-NF). This PROSPERO registered systematic review following PRISMA criteria searched literature databases for studies applying SCP-NF protocols. Our review focus concerned the operationalization of self-regulatory success, and protocol-details that could influence the evaluation of self-regulation. Such details included; electrode placement, number of trials, length per trial, proportions of training modalities, handling of artifacts and skill-transfer into daily-life. We identified a total of 63 eligible reports published in the year 2000 or later. SCP-NF protocol-details varied considerably on most variables, except for electrode placement. However, due to the increased availability of commercial systems, there was a trend to more uniform protocol-details. Although, token-systems are popular in SCP-NF for ADHD, only half reported a performance-based component. Also, transfer exercises have become a staple part of SCP-NF. Furthermore, multiple operationalizations of regulatory success were identified, limiting comparability between studies, and perhaps usefulness of so-called transfer-exercises, which purpose is to facilitate the transfer of the self-regulatory skills into every-day life. While studies utilizing SCP as Brain-Computer-Interface mainly focused on the acquisition of successful self-regulation, clinically oriented studies often neglected this. Congruently, rates of successful regulators in clinical studies were mostly low (<50%). The relation between SCP self-regulation and behavior, and how symptoms in different disorders are affected, is complex and not fully understood. Future studies need to report self-regulation based on standardized measures, in order to facilitate both comparability and understanding of the effects on symptoms. When applied as treatment, future SCP-NF studies also need to put greater emphasis on the acquisition of self-regulation (before evaluating symptom outcomes). Systematic review registration https://www.crd. york.ac. uk/prospero/display_record. php? ID=CRD42021260087, Identifier: CRD42021260087.
The changing view of insulin granule mobility: From conveyor belt to signaling hub

Before the advent of TIRF microscopy the fate of the insulin granule prior to secretion was deduced from biochemical investigations, electron microscopy and electrophysiological measurements. Since Calcium-triggered granule fusion is indisputably necessary to release insulin into the extracellular space, much effort was directed to the measure this event at the single granule level. This has also been the major application of the TIRF microscopy of the pancreatic beta cell when it became available about 20 years ago. To better understand the metabolic modulation of secretion, we were interested to characterize the entirety of the insulin granules which are localized in the vicinity of the plasma membrane to identify the characteristics which predispose to fusion. In this review we concentrate on how the description of granule mobility in the submembrane space has evolved as a result of progress in methodology. The granules are in a state of constant turnover with widely different periods of residence in this space. While granule fusion is associated +with prolonged residence and decreased lateral mobility, these characteristics may not only result from binding to the plasma membrane but also from binding to the cortical actin web, which is present in the immediate submembrane space. While granule age as such affects granule mobility and fusion probability, the preceding functional states of the beta cell leave their mark on these parameters, too. In summary, the submembrane granules form a highly dynamic heterogeneous population and contribute to the metabolic memory of the beta cells.
An Assessment of Quality of Life in Patients With Asthma Through Physical, Emotional, Social, and Occupational Aspects. A Cross-Sectional Study

Background Asthma is a prevalent hyperactive airway disease with physical and emotional impact. Severe asthma is associated with considerable health-related quality of life (HRQoL). The aim of this study is to assess the quality of life through physical, emotional, social and occupational aspects and evaluate the factors affecting HRQoL in patients with asthma. Methods This is a cross-sectional multicenter study conducted on adult asthmatic patients enrolled from community pharmacies across different Lebanese geographic areas. Results Having wheezing sometimes and most of the time (Beta = −0.144 and −0.552), experiencing anxiety sometimes and most of the time (Beta = −0.205 and −0.573), encountering sleep problems sometimes and most of the time (Beta = −0.270 and −0.553), having previous chest discomfort sometimes and most of the time (Beta = −0.421 and −0.713), and having depression most of the times (Beta = −0.415) were associated with higher lower quality of life scores. On the other side, holding a secondary level of education was associated with a higher quality of life score (Beta = 0.192). Conclusion This study highlights that asthma affects adults' quality of life through social, emotional, physical, and occupational impacts. Improved follow-up and patient education may be essential in the future to stop disease progression and achieve ideal therapeutic outcomes.
Positive digital communication among youth: The development and validation of the digital flourishing scale for adolescents

Research has extensively studied the negative effects of digital communication on adolescents’ well-being. However, positive digital experiences and behavior in adolescence are still poorly understood. The recently developed Digital Flourishing Scale addresses this gap and focuses on the positive perceptions of a user’s experiences and behaviors in digital communication among adults. In this paper, we developed an adolescent version of this scale. Study 1 demonstrated the internal consistency of the scale and the same factor structure for adolescence as for adulthood: connectedness, civil participation, positive social comparison, authentic self-presentation, and self-control. Study 2 confirmed the identified factor structure with a second sample of adolescents and established measurement invariance across genders. The construct validity of the scale was confirmed by investigating associations with related constructs, including the basic psychological needs from self-determination theory (competence, autonomy, and relatedness), secure attachment to a close friend, Internet aggression, social media-induced inspiration, authenticity of posted positive content, and social media self-control failure. The results indicated that not all adolescents flourish equally online. Differences occurred depending on the adolescents’ gender and socioeconomic status. The paper concludes that the newly developed scale is a valid and reliable measure for assessing adolescents’ perceptions of digital thriving and digital empowerment.
Metal complexation, FT-IR characterization, and plankton abundance in the marine surface microlayer of coastal areas in the Eastern Mediterranean

Barely any data exist on metal speciation in the marine surface microlayer (SML), a rather complex environment, the study of which contributes to enhancement of knowledge on metal speciation and its effect to the ocean. Metal speciation is significant since life requires a wide variety of trace metals that are essential for the growth of the organisms. Ligand concentrations (L) of copper (Cu), zinc (Zn), and cadmium (Cd) were studied by anodic stripping voltammetry (ASV) in the SML of coastal areas within the Aegean Sea in the Eastern Mediterranean. Complexing capacities in the SML in decreasing order ranged for Cu from 29 to 201 nM (median 101 nM), for Zn 24–149 nM (45 nM), and for Cd 1.0–1.5 nM (1.4 nM). Average enrichment factors (EFs) of SML samples compared to subsurface ones (SSW) were calculated equal to 0.9 ± 0.8, 1.2 ± 0.5, and 1.7 ± 1.6 for L Zn, L Cu, and L Cd, respectively. In five out of the six total paired samples of SML and SSW, lower concentrations of L Zn were measured in the SML, which is not the case for L Cu and L Cd. Due to elevated dissolved Zn concentrations in the SML, its complexation is incomplete, contrary to those of Cu and Cd, which are fully complexed. These trace metals are essential nutrients for biological functions, hence any differences on their concentration and chemical speciation may directly influence the distribution of phytoplankton species in the upper water column and neuston. EFs of SML relatively to subsurface water ranged in average between 1.2 and 2.4 for total organic carbon (TOC), chlorophyll a (Chla), and plankton, being generally >2 for most of the amino acids detected, demonstrating a relative enrichment of the SML in organic matter. A significant correlation was found between Cu ligands and dinoflagellates <20 μm, confirming older findings supporting that marine dinoflagellates of Gymnodinium genera produce Cu ligands. New insights are provided in the study and the importance of investigating bio-essential metal ions (Cu, Zn, Cd) and their organic complexes in the SML is pointed. Data on Zn and Cd complexing capacities in the SML are the first published so far.
Photosynthetic performance, growth, pigment content, and photoprotective compounds of the mangrove macroalgae Bostrychia calliptera and Bostrychia montagnei (Rhodophyta) under light stress

Increased solar radiation on the Earth’s surface is expected due to global change. Mangrove macroalgae can be negatively affected by increased solar radiation, since some species, such as Bostrychia spp. have been characterized as typical “shade” plants. Thus, we investigated the effects of increasing photon flux densities (PFDs: 170, 267, 443, 638, and 1155 µmol photons m–2 s–1) on the physiological performance of Bostrychia calliptera and Bostrychia montagnei from a tropical mangrove. Several photosynthesis–related parameters indicated that both species decreased their photosynthetic performance under increasing PFDs, with photosynthesis of B. montagnei being more affected than that of B. calliptera. Bostrychia calliptera exhibited highest growth under 638 µmol photons m–2 s–1 while at 1155 µmol photons m–2 s–1 it was inhibited. The highest growth of Bostrychia montagnei was observed under 267 µmol photons m–2 s–1. Higher PFDs led to growth inhibition. The phycobiliprotein and chlorophyll a content of B. montagnei was degraded under increased PFDs. In B. calliptera only chlorophyll a degradation was observed. The mycosporine-like amino acid contents (photoprotective metabolites) of both species were degraded under increasing PFDs, which was more pronounced in B. montagnei. Our results demonstrated that increased solar radiation on estuarine tropical ecosystems will be detrimental to the physiological performance of B. calliptera and B. montagnei. Our results also demonstrated that B. montagnei was more negatively affected by increased light stress than B. calliptera. This can explain its preferential occurrence in more shaded microhabitats compared to B. calliptera. Our data document for the first time light acclimation in the studied macroalgae and the deleterious effects of increased light stress on the genus Bostrychia.