Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and validation of a prognostic immune-related lncRNA signature in bladder cancer

Background Recently, researches have implied that immune-related lncRNAs (IR-lncRNAs) have a vital role in tumor occurrence and development. However, the study in bladder cancer (Bca) is still unclear. New biomarkers and reliable prognostic models for Bca are still limited. Here, we investigated the potential application value of immune-related lncRNAs in the prognostic evaluation of Bca patients. Methods We obtained clinical information and corresponding sequencing data from the The Cancer Genome Atlas (TCGA) database, and the cohort of Bca patients was divided into training and validation cohorts (ratio 7:3) randomly. An immune-related lncRNA co-expression network was constructed to identify immune-related lncRNAs. The candidate module intimately associated with overall survival (OS) was identified by using weighted gene co-expression network analysis (WGCNA). Univariate, multivariate Cox regression and LASSO analysis were performed to build the immune-related lncRNA signature. A prognostic model was further developed and its prognostic value was evaluated by Kaplan-Meier (KM) analysis. GSEA, KEGG analysis and GO annotation were used for functional annotation in this study. Results Totally, we identified 1,249 differentially expressed IR-lncRNAs were and six of which (AC005674.2, AC090948.1, TFAP2A-AS1, AL354919.2, AC011468.1 and AC018809.2) were finally selected in the gene signature. According to survival analysis, patients with high-risk scores were significantly related to poor survival outcomes. Furthermore, we established a novel gene signature demonstrated high prognostic value, and can be utilized as an independent risk factor (validation cohort: P<0.001, HR =3.832; training cohort: P<0.001, HR =2.843). Additionally, we built a nomogram on account of the clinicopathologic characteristics and gene signature to predict the survival probability of 1-, 3- and 5-year in Bca patients. The value of AUC curve of 1-, 3- and 5-year survival probability was 0.724, 0.777 and 0.77, severally. Furthermore, some enrichment pathways were identified by KEGG and GO analysis, and might be useful to display the potential mechanism for Bca. Conclusions Our results indicated that the signature of six immune-related lncRNAs had an underlying value in the prognosis of Bca patients and might be helpful for the immunotherapy of Bca.
Er81 Transcription Factor Fine-Tunes Striatal Cholinergic Interneuron Activity and Drives Habit Formation

The molecular mechanisms tuning cholinergic interneuron (CIN) activity, although crucial for striatal function and behavior, remain largely unexplored. Previous studies report that the Etv1/Er81 transcription factor is vital for regulating neuronal maturation and activity. While Er81 is known to be expressed in the striatum during development, its specific role in defining CIN properties and the resulting consequences on striatal function is unknown. We report here that Er81 is expressed in CINs and its specific ablation leads to prominent changes in their molecular, morphologic, and electrophysiological features. In particular, the lack of Er81 amplifies intrinsic delayed-rectifier and hyperpolarization-activated currents, which subsequently alters the tonic and phasic activity of CINs. We further reveal that Er81 expression is required for normal CIN pause and time-locked responses to sensorimotor inputs in awake mice. Overall, this study uncovers a new cell type-specific control of CIN function in the striatum which drives habit formation in adult male mice. SIGNIFICANCE STATEMENT Although previous studies have shown that cholinergic interneurons drive striatal activity and habit formation, the underlying molecular mechanisms controlling their function are unknown. Here we reveal that key cholinergic interneuron physiological properties are controlled by Er81, a transcription factor regulating neuronal activity and development in a cell-specific manner. Moreover, our findings uncover a link between the Er81-dependent molecular control of cholinergic interneuron function and habit formation in mice. These insights will contribute to the future enhancement of our understanding of disorders that involve behavioral inflexibility, such as autism and addiction.
Comparative study of the digastric and the stylohyoid muscles between wild boars (Sus scrofa scrofa) and domestic swine (Sus scrofa domesticus): revisiting the gross anatomy

Considering Suidae Familie as a perfect and viable experimental biomedical model for research applied to human medicine, it has been sought to describe the comparative anatomy of the digastric and the stylohyoid muscles between boars and domestic swine. Heads of Sus scrofa scrofa and Sus scrofa domesticus were dissected. The digastric muscle presented only one muscle belly as anatomical component of a tendinous origin in the jugular process of the occipital bone, and muscle insertion in the midventral edge of the caudal two thirds of the body of the mandible. Thus, its function is fundamentally associated with the lowering and the retracting of the mandible which, by the way, can deliver greater muscle power at lesser energy expense. For the stylohyoid muscle, the tendinous origin was in the laterocaudal edge of the dorsal third of the stylohyoid bone. The muscle insertion - primarily, was in the lateral and caudal edges from the mid third portion up to the ventral extremity of the thyrohyoid bone, and secondarily as a laterolateral aponeurotic blade which would unite, in a bilateral manner, an insertion that was common to the sternohyoid, the geniohyoid, and the mylohyoid muscles in a median ventral region. This morphology were similar to the two specimens studied expanding the information available, which were completely unknown for the suidae until the moment.
Rare Case of Gastric Xanthoma in a 15-Year-Old Patient

We present a rare case of gastric xanthoma (GX) in a 15-year-old male with a history of prematurity (born at 29 weeks gestation), cerebral palsy and epilepsy. He presented with episodes of distress related to feeding, bloating, flatulence and intermittent constipation. He weighed 40kg (<3rd percentile) despite normal intake of food. A trial of proton pump inhibitor (PPI) therapy was ineffective. Faecal calprotectin was normal. No organisms were isolated on stool microscopy and culture. Ferritin was low (17 ug/L), with a normal haemoglobin and
Auditory discrimination and frequency modulation learning in schizophrenia patients: amphetamine within-subject dose response and time course

Abstract Background Auditory frequency modulation learning (‘auditory learning’) is a key component of targeted cognitive training (TCT) for schizophrenia. TCT can be effective in enhancing neurocognition and function in schizophrenia, but such gains require significant time and effort and elude many patients. Methods As a strategy to increase and/or accelerate TCT-induced clinical gains, we tested the dose- and time-course effects of the pro-attentional drug, amphetamine (AMPH; placebo, 2.5, 5 or 10 mg po; within-subject double-blind, order balanced) on auditory learning in schizophrenia patients [n = 32; M:F = 19:13; age 42.0 years (24–55)]. To understand predictors and/or mechanisms of AMPH-enhanced TCT, we also measured auditory fidelity (words-in-noise (WIN), quick speech-in-noise (QuickSIN)) and neurocognition (MATRICS comprehensive cognitive battery (MCCB)). Some measures were also acquired from age-matched healthy subjects (drug free; n = 10; M:F = 5:5). Results Patients exhibited expected deficits in neurocognition. WIN and QuickSIN performance at low signal intensities was impaired in patients with low v. high MCCB attention/vigilance (A/V) scores; these deficits were corrected by AMPH, maximally at 2.5–5 mg (d's = 0.79–1.29). AMPH also enhanced auditory learning, with maximal effects at 5 mg (d = 0.93), and comparable effects 60 and 210 min post pill. ‘Pro-learning’ effects of AMPH and AMPH-induced gains in auditory fidelity were most evident in patients with low MCCB A/V scores. Conclusions These findings advance our understanding of the impact of pro-attentional interventions on auditory information processing and suggest dose- and time-course parameters for studies that assess the ability of AMPH to enhance the clinical benefits of TCT in schizophrenia patients.
Autonomic and cholinergic mechanisms mediating cardiovascular and temperature effects of donepezil in conscious mice.

Donepezil is a centrally-acting acetylcholinesterase (AChE) inhibitor with therapeutic potential in inflammatory diseases; however, the underlying autonomic and cholinergic mechanisms remain unclear. Here, we assessed effects of donepezil on mean arterial pressure (MAP), heart rate (HR), HR variability, and body temperature in conscious adult male C57BL/6 mice to investigate the autonomic pathways involved. Central vs. peripheral cholinergic effects of donepezil were assessed using pharmacological approaches including comparison with the peripherally-acting AChE inhibitor, neostigmine. Drug treatments included donepezil (2.5 or 5 mg/kg s.c.), neostigmine methyl sulfate (80 or 240 μg/kg i.p.), atropine sulfate (5 mg/kg i.p.), atropine methyl bromide (5 mg/kg i.p.), or saline. Donepezil, at 2.5 and 5 mg/kg, decreased HR by 36±4 and 44±3% compared to saline (n=10, P<0.001). Donepezil, at 2.5 and 5 mg/kg, decreased temperature by 13±2 and 22±2% compared to saline (n=6, P<0.001). Modest (P<0.001) increases in MAP were observed with donepezil after peak bradycardia occurred. Atropine sulfate and atropine methyl bromide blocked bradycardic responses to donepezil, but only atropine sulfate attenuated hypothermia. The pressor response to donepezil was similar in mice co-administered atropine sulfate; however, co-administration of atropine methyl bromide potentiated the increase in MAP. Neostigmine did not alter HR or temperature but did result in early increases in MAP. Despite the marked bradycardia, donepezil did not increase normalized high frequency HR variability. We conclude that donepezil causes marked bradycardia and hypothermia in conscious mice via activation of muscarinic receptors while concurrently increasing MAP via autonomic and cholinergic pathways that remain to be elucidated.
Modulating Carrier Density and Transport Properties of MoS2 by Organic Molecular Doping and Defect Engineering

Using first-principles calculations, we investigate the effect of molecular doping and sulfur vacancy on the electronic properties and charge modulation of monolayer MoS2. It is found that tetrathiafulvalene and dimethyl-p-phenylenediamine molecules are effective donors, whereas tetracyanoethylene (TCNE) and tetracyanoquinodimethane (TCNQ) are effective acceptors, and all these molecules are able to shift the work function of MoS2. For MoS2 containing sulfur vacancies, these molecules are able to change the position of the defect levels within the band gap and modulate the carrier density around the defect center. Charge transfer analysis shows that TCNE and TCNQ induce a free-carrier depletion of the defect states, which is beneficial for the suppression of the nonradiative trionic decay and a higher excitonic efficiency due to a decrease in the screening of excitons. Furthermore, the effects of molecular adsorption on Seebeck coefficient of MoS2 are also explored. Our work suggests that an enhanced exci.
Perceived helpfulness of depression treatments among young adults with autism

Currently available treatments for depression show limited effectiveness in adults with autism spectrum disorders (ASD) based on measures of symptom changes and clinician impressions. Perceived helpfulness is another metric that has been found to be useful for understanding treatment outcomes in the general population, but it has not yet been explored in adults with ASD. Thus, the current study collected online survey data to examine patient‐perceived treatment helpfulness in a sample of 144 adults with ASD who reported that they were currently receiving community‐based treatment for depression. Findings indicate that while there was variability in the levels of perceived helpfulness for both medication and individual therapy, most adults with ASD perceived treatment to be at least moderately helpful. Notably, adults with ASD reported having been in treatment for a prolonged duration (5 to 6 years). Ordinal logistic regression models showed that adults with more depressive symptoms perceived treatments to be less helpful (i.e., medications: odds ratio [OR] = 0.92, 95% confidence interval[CI] = 0.89–0.95; individual therapy: OR = 0.95, 95% CI = 0.92–0.99). Moreover, women perceived medication as more helpful than men (OR = 2.33, 95% CI = 1.13–4.82). Other individual (i.e., age, race, education level) and treatment (i.e., treatment length, concurrent treatment) characteristics were not significantly associated with perceived helpfulness. These findings suggest that future studies may want to use perceived helpfulness, in addition to traditionally used objective outcomes, to understand patients' treatment experience and evaluate depression treatments for adults with ASD.
[Mechanism of blunt spleen injury: a finite element analysis].

OBJECTIVE To explore the biomechanical mechanism of blunt spleen injury based on finite element analysis. OBJECTIVE A fist finite element model was used to simulate the impact at 4-8 m/s in the spleen area of THUMS4.0 human body model from the front of the left costal area, the left anterior axillary line and the rear scapular line. The strain distribution and damage of the spleen under different conditions were observed. The simulation results were compared with the clinical cases of spleen rupture to analyze the mechanism of spleen injury. OBJECTIVE The damage location and strain distribution of the spleen could vary under different conditions. Due to the special anatomical location of the spleen, a blunt impact at the speed of 4-8 m/s on the front side did not easily cause spleen injury, and the strain was distributed mainly in the front of the spleen and the spleen hilum; a similar blunt impact on the left side was likely to cause spleen diaphragmatic surface injury, the splenic visceral surface could be injured by the compression of the medial tissue and organs and the traction of the splenic pedicle, and the strain was distributed in the spleen diaphragmatic and visceral surfaces; an impact on the back side was likely to cause injuries in the posterior portion and hilum of the spleen, and the strain was mainly concentrated in the injured area. OBJECTIVE Blunt spleen injuries caused by punches on the abdomen are mostly caused by direct impact on the ribs, the compression by the surrounding tissues and organs and the traction by the spleen pedicle.
NMDA receptor‐dependent and ‐independent effects of natural compounds and crude drugs on synaptic states as revealed by drebrin imaging analysis

Effective drugs that can cure cognitive impairments remain elusive. Because synaptic dysfunction has been correlated with cognitive impairments, drug development to target synaptic dysfunction is important. Recently, natural compounds and crude drugs have emerged as potential therapeutic agents for cognitive disorders. However, their effects on synaptic function remain unclear, because of lack of evaluation system with high reproducibility. We have recently developed highly reproducible in vitro high‐content imaging analysis system for evaluation of synaptic function using drebrin as a marker for synaptic states. Therefore, we aimed to examine the direct effects of well‐known natural compounds and crude drugs on synaptic states using this system. Rat hippocampal neurons were treated using natural compounds (nobiletin, diosgenin and tenuifolin) and crude drugs (Uncaria Hook [UH], Bezoar Bovis [BB], Coptis Rhizome [CR], Phellodendron Bark [PB] and Polygala Root [PR]). Immunocytochemical analysis was performed, and dendrite lengths and drebrin cluster densities were automatically quantified. We found that diosgenin, tenuifolin, CR, PB and PR decreased drebrin cluster densities, and the effects of PB and PR were partially dependent on N‐methyl‐D‐aspartic acid‐type glutamate receptors (NMDARs). Nobiletin and UH did not show any effects, whereas low‐dose BB treatment increased drebrin cluster densities. Our results showed that diosgenin, tenuifolin, BB, CR, PB and PR appeared to directly change synaptic states. Particularly, the NMDAR dependency of PB and PR appears to affect synaptic plasticity.
Characteristic chemical probing patterns of loop motifs improve prediction accuracy of RNA secondary structures

Abstract RNA structures play a fundamental role in nearly every aspect of cellular physiology and pathology. Gaining insights into the functions of RNA molecules requires accurate predictions of RNA secondary structures. However, the existing thermodynamic folding models remain less accurate than desired, even when chemical probing data, such as selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) reactivities, are used as restraints. Unlike most SHAPE-directed algorithms that only consider SHAPE restraints for base pairing, we extract two-dimensional structural features encoded in SHAPE data and establish robust relationships between characteristic SHAPE patterns and loop motifs of various types (hairpin, internal, and bulge) and lengths (2–11 nucleotides). Such characteristic SHAPE patterns are closely related to the sugar pucker conformations of loop residues. Based on these patterns, we propose a computational method, SHAPELoop, which refines the predicted results of the existing methods, thereby further improving their prediction accuracy. In addition, SHAPELoop can provide information about local or global structural rearrangements (including pseudoknots) and help researchers to easily test their hypothesized secondary structures.
Flexibility of equine bioenergetics and muscle plasticity in response to different types of training: An integrative approach, questioning existing paradigms

Equine bioenergetics have predominantly been studied focusing on glycogen and fatty acids. Combining omics with conventional techniques allows for an integrative approach to broadly explore and identify important biomolecules. Friesian horses were aquatrained (n = 5) or dry treadmill trained (n = 7) (8 weeks) and monitored for: evolution of muscle diameter in response to aquatraining and dry treadmill training, fiber type composition and fiber cross-sectional area of the M. pectoralis, M. vastus lateralis and M. semitendinosus and untargeted metabolomics of the M. pectoralis and M. vastus lateralis in response to dry treadmill training. Aquatraining was superior to dry treadmill training to increase muscle diameter in the hindquarters, with maximum effect after 4 weeks. After dry treadmill training, the M. pectoralis showed increased muscle diameter, more type I fibers, decreased fiber mean cross sectional area, and an upregulated oxidative metabolic profile: increased β-oxidation (key metabolites: decreased long chain fatty acids and increased long chain acylcarnitines), TCA activity (intermediates including succinyl-carnitine and 2-methylcitrate), amino acid metabolism (glutamine, aromatic amino acids, serine, urea cycle metabolites such as proline, arginine and ornithine) and xenobiotic metabolism (especially p-cresol glucuronide). The M. vastus lateralis expanded its fast twitch profile, with decreased muscle diameter, type I fibers and an upregulation of glycolytic and pentose phosphate pathway activity, and increased branched-chain and aromatic amino acid metabolism (cis-urocanate, carnosine, homocarnosine, tyrosine, tryptophan, p-cresol-glucuronide, serine, methionine, cysteine, proline and ornithine). Trained Friesians showed increased collagen and elastin turn-over. Results show that branched-chain amino acids, aromatic amino acids and microbiome-derived xenobiotics need further study in horses. They feed the TCA cycle at steps further downstream from acetyl CoA and most likely, they are oxidized in type IIA fibers, the predominant fiber type of the horse. These study results underline the importance of reviewing existing paradigms on equine bioenergetics.
[Diagnostic value of serum amyloid A, procalcitonin and hypersensitive C-reactive protein for pulmonary tuberculosis complicated by pneumonia].

OBJECTIVE To assess the value of serum amyloid A (SAA), procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in the diagnosis of pulmonary tuberculosis (PTB) complicated by pneumonia. OBJECTIVE We collected serum samples from patients with pneumonia, patients with PTB, patients with PTB complicated by pneumonia and patients with PTB complicated by sepsis hospitalized in our hospital between April, 2019 and April, 2020. Serum levels of SAA, PCT and hs-CRP were tested, and receiver- operating characteristic (ROC) curves were used to evaluate their efficacy for predicting PTB with concurrent pneumonia and the possibility of differentiating PTB cases with pneumonia from those with sepsis using these 3 parameters. We also tested serum levels of SAA, PCT and hs-CRP in patients with PTB and those with PTB complicated by pneumonia admitted from May to July in 2020 to verify the accuracy of these 3 parameters combined for predicting the complication of PTB by pneumonia. OBJECTIVE Compared with the patients with PTB, the patients with pneumonia had significantly higher SAA and hs-CRP levels; serum SAA, PCT and hs-CRP levels were all significantly elevated in patients with PTB complicated by pneumonia (all P < 0.05). The levels of hs-CRP, white blood cell, D-dimer, FIB, APTT and neutrophil ratio were positively correlated with serum SAA level (all P < 0.05). The areas under the ROC curve (AUC) for serum SAA, PCT, and hs-CRP were 0.762, 0.781, and 0.800, respectively, and their combined AUC was 0.849 (all P < 0.001). For predicting PTB complicated by pneumonia, SAA combined with PCT had the same sensitivity (53.85%) and specificity (90.48%) as SAA, PCT and hs-CRP all combined. Serum SAA and PCT levels were similar between PTB patients with pneumonia and those with sepsis. OBJECTIVE Combined detection of serum SAA and PCT levels can be helpful in the diagnosis of PTB complicated by pneumonia, but neither of them is capable of differentiating the complication of pneumonia from sepsis possibly due to influence by abnormal blood coagulation.
Stapedial Reflex: A Possible Novel Biomarker of Early Bulbar Involvement in Amyotrophic Lateral Sclerosis Patients

Background and Aim: Amyotrophic lateral sclerosis (ALS) is a neuromuscular progressive disorder, characterized by limb and bulbar muscle wasting and weakness. 30% of patients present a bulbar onset, while 70% a spinal outbreak, although most of them develop bulbar impairment later on. Due to the lack of an early biomarker of bulbar involvement, we chose to evaluate the role of stapedial reflex (SR) in order to predict preclinical bulbar impairment in ALS. Materials and Methods: We enrolled 36 ALS patients. We assessed revised-ALS functional-rating-scale and SR for a total of 4 visits. We established the presence of SR, acoustic reflex latency test (ARLT), and SRs Decay. Patients who had not develop bulbar signs at fourth visit continued follow-up up to 15 months. Data were analyzed by using Mann-Whitney U test, Friedman test, and Cox regression analysis. Results: We observed that SRs Decay at 500 and 1,000 Hz is the first parameter of SR to get altered in all ALS patients before the development of bulbar impairment. Twenty-eight patients developed bulbar impairment during the study. We highlighted a correlation between the progression rate of disease and both time of SRs Decay alteration and time of bulbar impairment from disease onset. Four patients who did not develop bulbar impairment had a progression rate lower than the other ones (p < 0.05). Discussion and Conclusions: This study shows that SR Decay test could be a sensitive measure for detecting pre-symptomatic bulbar involvement in ALS and could represent a simple, noninvasive, and useful biomarker of disease progression.