Miracle-dz/UniFAR-FTUs huggingface dataset:
An optimized protocol for assessment of sputum macrorheology in health and muco-obstructive lung disease

Background: Airway mucus provides important protective functions in health and abnormal viscoelasticity is a hallmark of muco-obstructive lung diseases such as cystic fibrosis (CF). However, previous studies of sputum macrorheology from healthy individuals and patients with CF using different experimental protocols yielded in part discrepant results and data on a systematic assessment across measurement settings and conditions remain limited. Objectives: The aim of this study was to develop an optimized and reliable protocol for standardized macrorheological measurements of airway mucus model systems and native human sputum from healthy individuals and patients with muco-obstructive lung disease. Methods: Oscillatory rheological shear measurements were performed using bovine submaxillary mucin (BSM) at different concentrations (2% and 10% solids) and sputum samples from healthy controls (n = 10) and patients with CF (n = 10). Viscoelastic properties were determined by amplitude and frequency sweeps at 25°C and 37°C with or without solvent trap using a cone-plate geometry. Results: Under saturated atmosphere, we did not observe any temperature-dependent differences in 2% and 10% BSM macrorheology, whereas in the absence of evaporation control 10% BSM demonstrated a significantly higher viscoelasticity at 37°C. Similarly, during the measurements without evaporation control at 37°C we observed a substantial increase in the storage modulus G′ and the loss modulus G″ of the highly viscoelastic CF sputum but not in the healthy sputum. Conclusion: Our data show systematically higher viscoelasticity of CF compared to healthy sputum at 25°C and 37°C. For measurements at the higher temperature using a solvent trap to prevent evaporation is essential for macrorheological analysis of mucus model systems and native human sputum. Another interesting finding is that the viscoelastic properties are not much sensitive to the applied experimental deformation and yield robust results despite their delicate consistency. The optimized protocol resulting from this work will facilitate standardized quantitative assessment of abnormalities in viscoelastic properties of airway mucus and response to muco-active therapies in patients with CF and other muco-obstructive lung diseases.
The role of motivation factors in exergame interventions for fall prevention in older adults: A systematic review and meta-analysis

Balance disorders and falls are common in the elderly population. Regular balance exercises are an evidence-based physical intervention to prevent falls in older adults, while patient motivation and adherence are important factors for intervention outcome. Exergames are a relatively new, alternative intervention for physical rehabilitation as they improve balance and strength in older adults. The aims of this systematic review and meta-analysis were to assess the (1) effect of motivation factors as per the Capability, Opportunity and Motivation model of Behavior change (COM-B) on the effectiveness of exergame interventions in healthy older adults, (2) effectiveness of exergames to improve balance in older healthy adults and, (3) impact of exergames on cognitive outcomes. Results show that motivation and capability components influence the general outcome of the exergame training. Motivational factors should thus be considered when setting-up an exergame intervention. Furthermore, exergame intervention appears to be a promising training method in comparison to traditional exercise training. However, exergame training in itself might not be sufficient to improve fall risk and cognitive performance.
A randomized single-blind controlled trial of a prototype digital polytherapeutic for tinnitus

Objective This randomized single-blind controlled trial tested the hypothesis that a prototype digital therapeutic developed to provide goal-based counseling with personalized passive and active game-based sound therapy would provide superior tinnitus outcomes, and similar usability, to a popular passive sound therapy app over a 12 week trial period. Methods The digital therapeutic consisted of an app for iPhone or Android smartphone, Bluetooth bone conduction headphones, neck pillow speaker, and a cloud-based clinician dashboard to enable messaging and app personalization. The control app was a popular self-help passive sound therapy app called White Noise Lite (WN). The primary outcome measure was clinically meaningful change in Tinnitus Functional Index (TFI) between baseline and 12 weeks of therapy. Secondary tinnitus measures were the TFI total score and subscales across sessions, rating scales and the Client Oriented Scale of Improvement in Tinnitus (COSIT). Usability of the US and WN interventions were assessed using the System Usability Scale (SUS) and the mHealth App Usability Questionnaire (MAUQ). Ninety-eight participants who were smartphone app users and had chronic moderate-severe tinnitus (>6 months, TFI score > 40) were enrolled and were randomly allocated to one of the intervention groups. Thirty-one participants in the USL group and 30 in the WN group completed 12 weeks of trial. Results Mean changes in TFI for the USL group at 6 (16.36, SD 17.96) and 12 weeks (17.83 points, SD 19.87) were clinically meaningful (>13 points reduction), the mean change in WN scores were not clinically meaningful (6 weeks 10.77, SD 18.53; 12 weeks 10.12 points, SD 21.36). A statistically higher proportion of USL participants achieved meaningful TFI change at 6 weeks (55%) and 12 weeks (65%) than the WN group at 6 weeks (33%) and 12 weeks (43%). Mean TFI, rating and COSIT scores favored the US group but were not statistically different from WN. Usability measures were similar for both groups. Conclusions The USL group demonstrated a higher proportion of responders than the WN group. The usability of the USL therapeutic was similar to the established WN app. The digital polytherapeutic demonstrated significant benefit for tinnitus reduction supporting further development.
Hairy roots: An untapped potential for production of plant products

While plants are an abundant source of valuable natural products, it is often challenging to produce those products for commercial application. Often organic synthesis is too expensive for a viable commercial product and the biosynthetic pathways are often so complex that transferring them to a microorganism is not trivial or feasible. For plants not suited to agricultural production of natural products, hairy root cultures offer an attractive option for a production platform which offers genetic and biochemical stability, fast growth, and a hormone free culture media. Advances in metabolic engineering and synthetic biology tools to engineer hairy roots along with bioreactor technology is to a point where commercial application of the technology will soon be realized. We discuss different applications of hairy roots. We also use a case study of the advancements in understanding of the terpenoid indole alkaloid pathway in Catharanthus roseus hairy roots to illustrate the advancements and challenges in pathway discovery and in pathway engineering.
Upregulation of XIAP promotes lung adenocarcinoma brain metastasis by modulating ceRNA network

Dysregulation of XIAP has been shown to affect the progression of a variety of cancers, including lung adenocarcinoma (LUAD). However, the function and mechanisms of XIAP in lung adenocarcinoma with brain metastasis (LUAD-BM) remains poorly understood. In this study, we analyzed the differential mRNA of 58 lung adenocarcinomas samples and 28 lung adenocarcinomas with brain metastases in GEO database. 191 differentially expressed mRNAs were significantly associated with immune response, the proliferation of the immune cell, cell-cell adhesion. Subsequent analyzed by lasso and SVM found that XIAP was significantly elevated in LUAD-BM and significantly associated with LUAD grade and metastasis. Then we constructed a molecular regulatory network of ncRNA-miRNA-mRNA ceRNA by Cystoscope based on the correlation obtained from Starbase. It was found that SBF2-AS1 or RUNDC3A-AS1, has-miR-338-3p and XIAP may have a regulatory relationship. Furthermore, we also initially found that XIAP was closely correlation with T cells, B cells, Mast cells, macrophages, and dendritic cells. In conclusion, we found that XIAP was significantly higher expressed in LUAD-BM compared with LUAD without brain metastasis, suggesting that XIAP may play an important role in the future prediction and clinical treatment of LUAD-BM.
Association between density of convenience and small grocery stores with diet quality in adults living in Mexico City: A cross sectional study

There is evidence of the association between different retail stores and food consumption, yet research is still limited in low- and medium-income countries, where the context of the food retail environment is different from that observed in high-income countries. Specifically, less is known about how convenience and small grocery stores, which offer products with immediate access, are associated with the diet as a whole. The present study assessed the association between density of convenience and small grocery stores and diet quality in adults from the Mexico City Representative Diabetes Survey 2015. A final sample size of 1,023 adults aged 20–69 years was analyzed. The density of stores was measured using Euclidean buffers within 500 meters of each participant's home. The Mexican Alternate Healthy Eating Index (MxAHEI) was used to assess diet quality. Multivariable Poisson models were used to test the association of convenience and small grocery stores densities with the MxAHEI. Although our results were not statistically significant, we observed a lower diet quality score among adults from Mexico City living in areas with a higher density of small grocery and convenience stores. More research is needed on the influence of environmental food retail on food consumption.
Application of a novel lytic phage vB_EcoM_SQ17 for the biocontrol of Enterohemorrhagic Escherichia coli O157:H7 and Enterotoxigenic E. coli in food matrices

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 and Enterotoxigenic E. coli (ETEC) are important foodborne pathogens, causing serious food poisoning outbreaks worldwide. Bacteriophages, as novel antibacterial agents, have been increasingly exploited to control foodborne pathogens. In this study, a novel broad-host range lytic phage vB_EcoM_SQ17 (SQ17), was isolated, characterized, and evaluated for its potential to control bacterial counts in vitro and in three different food matrices (milk, raw beef, and fresh lettuce). Phage SQ17 was capable of infecting EHEC O157:H7, ETEC, and other E. coli strains. Morphology, one-step growth, and stability assay showed that phage SQ17 belongs to the Caudovirales order, Myoviridae family, and Mosigvirus genus. It has a short latent period of 10 min, a burst size of 71 PFU/infected cell, high stability between pH 4 to 12 as well as thermostability between 30°C and 60°C for 60 min. Genome sequencing analysis revealed that the genome of SQ17 does not contain any genes associated with antibiotic resistance, toxins, lysogeny, or virulence factors, indicating the potential safe application of phage SQ17 in the food industry. In Luria-Bertani (LB) medium, phage SQ17 significantly decreased the viable counts of EHEC O157:H7 by more than 2.40 log CFU/ml (p < 0.05) after 6 h of incubation at 37°C. Phage SQ17 showed great potential to be applied for biocontrol of EHEC O157:H7 in milk and raw beef. In fresh lettuce, treatment with SQ17 also resulted in significant reduction of viable cell counts of EHEC O157:H7 and ETEC at both 4°C and 25°C. Our results demonstrate that SQ17 is a good candidate for application as an EHEC O157:H7 and ETEC biocontrol agent in the processing stages of food production and food preservation.
‘An experience of meaning’: A 20-year prospective analysis of delusional realities in schizophrenia and affective psychoses

Delusions are transdiagnostic and heterogeneous phenomena with varying degrees of intensity, stability, and dimensional attributes where the boundaries between everyday beliefs and delusional beliefs can be experienced as clearly demarcated, fuzzy, or indistinguishable. This highlights the difficulty in defining delusional realities. All individuals in the current study were evaluated at index and at least one of six subsequential follow-ups over 20 years in the Chicago Longitudinal Study. We assessed 16 distinct delusions categorized as thought or thematic delusions. We also examined the probability of recurrence and the relationships between delusions and hallucinations, depression, anxiety, and negative symptoms. The sample consisted of 262 individuals with schizophrenia vs. affective psychosis. Thought delusions were significantly different between groups at all follow-up evaluations except the 20-year timepoint. Thematic delusions were more common than thought delusions and show a significant decreasing pattern. In general, delusional content varied over time. Referential, persecutory, and thought dissemination delusions show the highest probability of recurrence. Hallucinations were the strongest indicator for thought, thematic, and overall delusions. The formation and maintenance of delusions were conceptualized as a multimodal construct consisting of sensory, perceptual, emotional, social, and somatic embodiment of an “experience of meanings”. Given the significant associations between delusions and hallucinations, future work incorporating participatory research is needed to better define and align subjective and objective perspectives. Our research also points to the need for future clinical interventions that specifically evaluate and target the coexistence and entanglement of delusions and hallucinations.
Brain network analysis of interictal epileptiform discharges from ECoG to identify epileptogenic zone in pediatric patients with epilepsy and focal cortical dysplasia type II: A retrospective study

Objective For patients with drug–resistant focal epilepsy, intracranial monitoring remains the gold standard for surgical intervention. Focal cortical dysplasia (FCD) is the most common cause of pharmacoresistant focal epilepsy in pediatric patients who usually develop seizures in early childhood. Timely removal of the epileptogenic zone (EZ) is necessary to achieve lasting seizure freedom and favorable developmental and cognitive outcomes to improve the quality of life. We applied brain network analysis to investigate potential biomarkers for the diagnosis of EZ that will aid in the resection for pediatric focal epilepsy patients with FCD type II. Methods Ten pediatric patients with focal epilepsy diagnosed as FCD type II and that had a follow–up after resection surgery (Engel class I [n = 9] and Engel class II [n = 1]) were retrospectively included. Time–frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation were combined to calculate brain network parameters based on interictal epileptiform discharges from ECoG. Results Clustering coefficient, local efficiency, node out–degree, and node out–strength with higher values are the most reliable biomarkers for the delineation of EZ, and the differences between EZ and margin zone (MZ), and EZ and normal zone (NZ) were significant (p < 0.05; Mann–Whitney U-test, two–tailed). In particular, the difference between MZ and NZ was significant for patients with frontal FCD (MZ > NZ; p < 0.05) but was not significant for patients with extra–frontal FCD. Conclusions Brain network analysis, based on the combination of time–frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation, can aid in the diagnosis of EZ for pediatric focal epilepsy patients with FCD type II.
Superior temporal gyrus functional connectivity predicts transcranial direct current stimulation response in Schizophrenia: A machine learning study

Transcranial direct current stimulation (tDCS) is a promising adjuvant treatment for persistent auditory verbal hallucinations (AVH) in Schizophrenia (SZ). Nonetheless, there is considerable inter-patient variability in the treatment response of AVH to tDCS in SZ. Machine-learned models have the potential to predict clinical response to tDCS in SZ. This study aims to examine the feasibility of identifying SZ patients with persistent AVH (SZ-AVH) who will respond to tDCS based on resting-state functional connectivity (rs-FC). Thirty-four SZ-AVH patients underwent resting-state functional MRI at baseline followed by add-on, twice-daily, 20-min sessions with tDCS (conventional/high-definition) for 5 days. A machine learning model was developed to identify tDCS treatment responders based on the rs-FC pattern, using the left superior temporal gyrus (LSTG) as the seed region. Functional connectivity between LSTG and brain regions involved in auditory and sensorimotor processing emerged as the important predictors of the tDCS treatment response. L1-regularized logistic regression model had an overall accuracy of 72.5% in classifying responders vs. non-responders. This model outperformed the state-of-the-art convolutional neural networks (CNN) model—both without (59.41%) and with pre-training (68.82%). It also outperformed the L1-logistic regression model trained with baseline demographic features and clinical scores of SZ patients. This study reports the first evidence that rs-fMRI-derived brain connectivity pattern can predict the clinical response of persistent AVH to add-on tDCS in SZ patients with 72.5% accuracy.
The impact of cathodal tDCS on the GABAergic system in the epileptogenic zone: A multimodal imaging study

Objectives We aimed to investigate the antiepileptic effects of cathodal transcranial direct current stimulation (c-tDCS) and mechanisms of action based on its effects on the neurotransmitters responsible for the abnormal synchrony patterns seen in pharmacoresistant epilepsy. This is the first study to test the impact of neurostimulation on epileptiform interictal discharges (IEDs) and to measure brain metabolites in the epileptogenic zone (EZ) and control regions simultaneously in patients with pharmacoresistant epilepsy. Methods This is a hypothesis-driven pilot prospective single-blinded repeated measure design study in patients diagnosed with pharmacoresistant epilepsy of temporal lobe onset. We included seven patients who underwent two sessions of c-tDCS (sham followed by real). The real tDCS session was 20 min in duration and had a current intensity of 1.5 mA delivered via two surface electrodes that had dimensions of 3 × 4 cm. The cathode electrode was placed at FT7 in the center whereas the anode at Oz in the center. After each session, we performed electroencephalographic recording to count epileptiform IEDs over 30 min. We also performed magnetic resonance spectroscopy (MRS) to measure brain metabolite concentrations in the two areas of interest (EZ and occipital region), namely, gamma-aminobutyric acid (GABA), glutamate (Glx), and glutathione. We focused on a homogenous sample where the EZ and antiepileptic medications are shared among patients. Results Real tDCS decreased the number of epileptiform IEDs per min (from 9.46 ± 2.68 after sham tDCS to 5.37 ± 3.38 after real tDCS), p = 0.018, as compared to sham tDCS. GABA was decreased in the EZ after real c-tDCS stimulation as compared to sham tDCS (from 0.129 ± 0.019 to 0.096 ± 0.018, p = 0.02). The reduction in EZ GABA correlated with the reduction in the frequency of epileptiform IED per min (rho: 0.9, p = 0.003). Conclusion These results provide a window into the antiepileptic mechanisms of action of tDCS, based on local and remote changes in GABA and neural oscillatory patterning responsible for the generation of interictal epileptiform discharges.
An expanded role for the transcription factor WRINKLED1 in the biosynthesis of triacylglycerols during seed development

The transcription factor WRINKLED1 (WRI1) is known as a master regulator of fatty acid synthesis in developing oilseeds of Arabidopsis thaliana and other species. WRI1 is known to directly stimulate the expression of many fatty acid biosynthetic enzymes and a few targets in the lower part of the glycolytic pathway. However, it remains unclear to what extent and how the conversion of sugars into fatty acid biosynthetic precursors is controlled by WRI1. To shortlist possible gene targets for future in-planta experimental validation, here we present a strategy that combines phylogenetic foot printing of cis-regulatory elements with additional layers of evidence. Upstream regions of protein-encoding genes in A. thaliana were searched for the previously described DNA-binding consensus for WRI1, the ASML1/WRI1 (AW)-box. For about 900 genes, AW-box sites were found to be conserved across orthologous upstream regions in 11 related species of the crucifer family. For 145 select potential target genes identified this way, affinity of upstream AW-box sequences to WRI1 was assayed by Microscale Thermophoresis. This allowed definition of a refined WRI1 DNA-binding consensus. We find that known WRI1 gene targets are predictable with good confidence when upstream AW-sites are phylogenetically conserved, specifically binding WRI1 in the in vitro assay, positioned in proximity to the transcriptional start site, and if the gene is co-expressed with WRI1 during seed development. When targets predicted in this way are mapped to central metabolism, a conserved regulatory blueprint emerges that infers concerted control of contiguous pathway sections in glycolysis and fatty acid biosynthesis by WRI1. Several of the newly predicted targets are in the upper glycolysis pathway and the pentose phosphate pathway. Of these, plastidic isoforms of fructokinase (FRK3) and of phosphoglucose isomerase (PGI1) are particularly corroborated by previously reported seed phenotypes of respective null mutations.
Tandem integration of circular plasmid contributes significantly to the expanded mitochondrial genomes of the green-tide forming alga Ulva meridionalis (Ulvophyceae, Chlorophyta)

Comparative mitogenomics of Ulva species have revealed remarkable variations in genome size due to the integration of exogenous DNA fragments, the proliferation of group I/II introns, and the change of repeat sequences. The genus Ulva is a species-rich taxonomic group, containing a variety of green-tide forming algae. In this study, five complete mitogenomes of the green-tide forming macroalga, Ulva meridionalis R. Horimoto and S. Shimada, were assembled and compared with the available ulvophyceae mtDNAs. The main circular mitogenomes of U. meridionalis ranged from 82.94 to 111.49 kb in size, and its 111.49-kb mitogenome was the largest Ulva mitogenome sequenced so far. The expansion of U. meridionalis mitogenomes is mainly due to the tandem integration of a 5.36-kb mitochondrial circular plasmid (pUme), as well as the proliferation of introns. An intact DNA-directed RNA polymerase gene (rpo) was present in pUme of U. meridionalis and was then detected in two putative plasmids (pUmu1 and pUmu2) found in Ulva mutabilis. The observed integration of the circular plasmid into U. meridionalis mitogenomes seems to occur via homologous recombination, and is a more recent evolutionary event. Many highly homologous sequences of these three putative plasmids can be detected in the other Ulva mtDNAs sequenced thus far, indicating the integration of different mitochondrial plasmid DNA into the mitogenomes is a common phenomenon in the evolution of Ulva mitogenomes. The random incidence of destruction of plasmid-derived rpos and open reading frames (orfs) suggests that their existence is not the original characteristic of Ulva mitogenomes and there is no selective pressure to maintain their integrity. The frequent integration and rapid divergence of plasmid-derived sequences is one of the most important evolutionary forces to shape the diversity of Ulva mitogenomes.