Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal Analysis of the Utility of Liver Biochemistry as Prognostic Markers in Hospitalized Patients With Corona Virus Disease 2019

The association of liver biochemistry with clinical outcomes of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is currently unclear, and the utility of longitudinally measured liver biochemistry as prognostic markers for mortality is unknown. We aimed to determine whether abnormal liver biochemistry, assessed at baseline and at repeat measures over time, was associated with death in hospitalized patients with COVID‐19 compared to those without COVID‐19, in a United Kingdom population. We extracted routinely collected clinical data from a large teaching hospital in the United Kingdom, matching 585 hospitalized patients who were SARS‐CoV‐2 real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) positive to 1,165 hospitalized patients who were RT‐PCR negative for age, sex, ethnicity, and preexisting comorbidities. A total of 26.8% (157/585) of patients with COVID‐19 died compared to 11.9% (139/1,165) in the group without COVID‐19 (P < 0.001). At presentation, a significantly higher proportion of the group with COVID‐19 had elevated alanine aminotransferase (20.7% vs. 14.6%, P = 0.004) and hypoalbuminemia (58.7% vs. 35.0%, P < 0.001) compared to the group without COVID‐19. Within the group with COVID‐19, those with hypoalbuminemia at presentation had 1.83‐fold increased hazards of death compared to those with normal albumin (adjusted hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.25‐2.67), while the hazard of death was ~4‐fold higher in those aged ≥75 years (adjusted HR, 3.96; 95% CI, 2.59‐6.04) and ~3‐fold higher in those with preexisting liver disease (adjusted HR, 3.37; 95% CI, 1.58‐7.16). In the group with COVID‐19, alkaline phosphatase (ALP) increased (R = 0.192, P < 0.0001) and albumin declined (R = −0.123, P = 0.0004) over time in patients who died. Conclusion: In this United Kingdom population, liver biochemistry is commonly deranged in patients with COVID‐19. Baseline hypoalbuminemia and rising ALP over time could be prognostic markers for death, but investigation of larger cohorts is required to develop a better understanding of the relationship between liver biochemistry and disease outcome.
Integrative phylogenomics reveals a Permian origin of Adephaga beetles

Beetles are arguably the most diverse group of animals on Earth with over 400 000 described species. Yet the timing of main diversification events among these insects remains debated. The use of phylogenomic data generated using next‐generation sequencing recently resolved most recalcitrant phylogenetic relationships across Coleoptera. However, limited taxon sampling for some major clades still prevents the use of important fossil calibrations that could provide more accurate estimates of the timing of lineage diversification events among beetles. Here, we present a new fossil‐based dated framework with a focus on the suborder Adephaga. We rely on an integrative phylogenomic approach using a combination of genomic, ultraconserved element and RNAseq transcriptomic datasets, further revealing the prevalent exonic nature of ultraconserved elements in Coleoptera. We infer a robust phylogenomic tree under various optimality criteria and analytical conditions. Our preferred phylogenetic reconstruction is consistent with those of previous phylogenomic studies in recovering the paraphyly of ‘Hydradephaga’, Gyrinidae as sister to all other Adephaga, the monophyly of Geadephaga and Haliplidae as sister to a monophyletic Dytiscoidea. We further recover strong support for paraphyly of Aspidytidae and the placement of Hygrobiidae as part of a clade comprising Aspidytes, Ribera, Beutel, Balke & Vogler, Sinaspidytes Balke, Beutel & Ribera and Amphizoidae. Using 23 carefully chosen fossil calibrations across Coleoptera, we infer the origin of modern beetles ca. 317 Ma in the mid‐Carboniferous, the divergence between Archostemata and Adephaga ca. 296 Ma in the early Permian, and the crown of Adephaga in the end‐Permian ca. 255 Ma. Importantly, our analyses provide more precise estimates of divergence times for internal splits within Adephaga, including ground beetles, tiger beetles and aquatic adephagan lineages. These results represent a major step forward in our understanding of beetle diversification and will serve as a fundamental framework to unravel the evolutionary history of many clades within Adephaga.
The mycelial growth and ligninolytic enzyme activity of cauliflower mushroom (Sparassis latifolia)

ABSTRACT We examined the activities of lignin-degrading enzymes of the mycelium of cauliflower mushroom (Sparassis latifolia). Three different strains of S. latifolia collected from several sites in Korea and one crossbred strain were cultured on potato dextrose broth (PDB) and Kirk's medium in order to study the activities of their ligninolytic enzymes. Mycelial growth reached maximum levels between 14 and 21 days after inoculation and pH increased by 0.12 units over 35 days. Laccase activity began increasing after 14 days on both types of media. Manganese peroxidase (MnP) activity followed a trend similar to that of laccase on Kirk's medium, but not on PDB. The activity of lignin peroxidase (LiP) differed from that of other enzymes; its activity decreased by half after 14 days on PDB but remained constant on Kirk's medium over 35 days. The total protein concentration increased considerably after 14 days and peaked at 21 days on PDB. A similar maximum was attained on Kirk's medium. In contrast, the residual glucose increased rapidly at 14 days on Kirk's medium, while increasing gradually up to 28 days on PDB. This study indicates that S. latifolia is more similar to white rot fungi than to other brown rot fungi.
Relationships Among CEO Narcissism, Debt Financing and Firm Innovation Performance: Emotion Recognition Using Advanced Artificial Intelligence

Psychological research shows that as the main component of enterprise decision-making, CEOs are not completely rational, cognitive and psychological biases often influence their decision-making process. CEO narcissism has gradually attracted academic attention. Based on upper echelon theory and subconscious theory, this paper uses advanced artificial intelligence technology to quantify CEO narcissism as a kind of emotional intelligence. Taking A-share listed companies in China from 2010 to 2019 as research objects, this paper empirically tests the impact of CEO narcissism on debt financing and innovation performance. The results show that CEO narcissism has a significant positive impact on firm innovation performance. Debt financing plays a mediating role in the relationship between CEO narcissism and firm innovation performance. CEO narcissism can have a positive impact on firm innovation performance through debt financing. Compared with non-SOEs, SOEs' CEO narcissism has a more significant positive effect on debt financing and enterprise innovation performance. The research in this paper enriches psychology and organizational management and provides a reference for an enterprise's management decisions and for investors' investment decisions.
Nimodipine Improves Function After SCI

Spinal cord injury (SCI) is a devastating condition that results in severe motor, sensory, and autonomic dysfunction. The L-/T-type calcium channel blocker nimodipine (NMD) exerts a protective effect on neuronal injury; however, the protective effects of long-term administration of NMD in subjects with SCI remain unknown. Thus, the aim of this study was to evaluate the role of long-term treatment with NMD on a clinically relevant SCI model. Female rats with SCI induced by 25 mm contusion were subcutaneously injected with vehicle or 10 mg/kg NMD daily for six consecutive weeks. We monitored the motor score, hind limb grip strength, pain-related behaviors, and bladder function in this study to assess the efficacy of NMD in rats with SCI. Rats treated with NMD showed improvements in locomotion, pain-related behaviors, and spasticity-like symptoms, but not in open-field spontaneous activity, hind limb grip strength or bladder function. SCI lesion areas and perilesional neuronal numbers, gliosis and calcitonin gene-related peptide (CGRP+) fiber sprouting in the lumbar spinal cord and the expression of K+–Cl− cotransporter 2 (KCC2) on lumbar motor neurons were also observed to further explore the possible protective mechanisms of NMD. NMD-treated rats showed greater tissue preservation with reduced lesion areas and increased perilesional neuronal sparing. NMD-treated rats also showed improvements in gliosis, CGRP+ fiber sprouting in the lumbar spinal cord, and KCC2 expression in lumbar motor neurons. Together, these results indicate that long-term treatment with NMD improves functional recovery after SCI, which may provide a potential therapeutic strategy for the treatment of SCI.
An Indirect Comparison Between Nivolumab + Ipilimumab + Two Cycles of Chemotherapy vs. Pembrolizumab + Chemotherapy as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer

Background Nivolumab + ipilimumab + two cycles chemotherapy (N-I + chemo, intensive immunotherapy but chemo-light) and pembrolizumab + chemotherapy (Pem + chemo) were both recommended as first-line treatment for metastatic non-small cell lung carcinoma (NSCLC) patients. We conducted this indirect comparison to compare the efficacy of and safety between these two treatments for providing reference for decision making. Methods Relevant databases were searched for eligible trials. A well-accepted adjusted indirect treatment comparison (ITC) approach was selected to pool efficacy results and safety outcomes. Subgroup analyses were stratified according to PD-L1 expression and clinical characteristics. Results Four eligible randomized trials (CheckMate9LA, KEYNOTE-021G, KEYNOTE 189, KEYNOTE 407) involving 2017 patients were available to analyze. The ITC results suggested that N-I + chemo is comparable to Pem + chemo in OS (HR 1.03, 95% CI 0.82-1.30) and ORR (RR 0.81, 95% CI 0.62-1.06), but tended to yield inferior PFS (HR 1.28, 95% CI 1.04-1.59) than did Pem + chemo. As for safety profiles, N-I + chemo showed no significant difference relative to Pem + chemo in any grade adverse events: (RR 1.03, 95% CI 0.99-1.10), but demonstrated reduced toxicity in chemo-related adverse events, such as anemia (RR 0.63, 95% CI 0.49-0.81), neutropenia (RR0.51, 95% CI 0.33-0.79), and thrombocytopenia (RR 0.38, 95% CI 0.21-0.69). Conclusions N-I + chemo is a promising treatment option for providing comparable OS related to Pem + chemo. However, for never smoker female patients, Pem + chemo is preferable to choose for demonstrating favorable OS benefit than N-I + chemo.
Multidisciplinary Evaluation of Pacifier Removal on Oro-Dentofacial Structures: A Controlled Clinical Trial

It is well recognized that pacifier habit leads to occlusal and orofacial functional changes in children. However, the effects of the interruption of prolonged pacifier habit on the development of the dento-facial complex has not yet been fully characterized. Thus, the aim of this study was to investigate the influence of pacifier removal on aspects of oro-dentofacial morphology and function in preschool children. For that, a pacifier group (n = 28) and a control group (n = 32) of 4-year-old children with and without pacifier habit, respectively, were followed up by a group of dentists and speech therapists at baseline, 6 and 12 months after habit removal. Bite force and lip pressure were assessed using digital systems, and the evaluation of breathing and speech functions was performed using validated protocols, together with the measurements of dental casts and facial anthropometry. The Two-way mixed model ANOVA was used in data analysis. After 12 months, a decrease in malocclusion frequency was observed in pacifier group. Additionally, a change over time was observed in facial, intermolar and palate depth measurements, as well in bite and lip forces and speech function scores, increasing in both groups (p < 0.01). The upper and lower intercanine widths and breathing scores differed between groups at baseline and changed over time reducing the differences. The presence of speech distortions was more frequent in the pacifier group at baseline and decreased over time (p < 0.05). The interruption of pacifier habit improved the maxillary and mandibular intercanine widths, as well as the breathing and speech functions, overcoming the oro-dentofacial changes found. Trial Registration: This clinical trial was registered in the Brazilian Clinical Trials Registry (ReBEC; http://www.ensaiosclinicos.gov.br/), protocol no. RBR-728MJ2.
Effects of Adding Eubiotic Lignocellulose on the Growth Performance, Laying Performance, Gut Microbiota, and Short-Chain Fatty Acids of Two Breeds of Hens

Eubiotic lignocellulose is a new and useful dietary fiber source for chickens. However, few studies have been undertaken on the impacts of its use as a supplement in different chicken breeds. In this experiment, 108 Chinese native breed Bian hens (BH) and 108 commercial breed ISA Brown hens (IBH) were chosen. They were randomly divided into three groups, and 0, 2, or 4% eubiotic lignocellulose was added to their feed during the growing periods (9–20 weeks), respectively. We aimed to observe the impacts of adding eubiotic lignocellulose on the growth and laying performance, gut microbiota, and short-chain fatty acid (SCFA) of two breeds of hens. In this study, the addition of eubiotic lignocellulose had no significant effect on the growth performance and gut microbial diversity in the two breeds of chickens (P > 0.05). Compared with the control group, adding 4% eubiotic lignocellulose significantly increased the cecum weight, laying performance (P < 0.05), but had no significant effect on the SCFA of BH (P > 0.05); however, adding 4% significantly inhibited the intestinal development, laying performance, butyrate concentration, and SCFA content of IBH (P < 0.05). Moreover, the relative abundances of the fiber-degrading bacteria Alloprevotella and butyrate-producing bacteria Fusobacterium in the 4% group of BH were significantly higher than those in the 4% group of IBH (P < 0.05), resulting in the concentration of butyrate was significantly higher than those in it (P < 0.05). Combining these results suggests that the tolerance of BH to a high level of eubiotic lignocellulose is greater than that of IBH and adding 2-4% eubiotic lignocellulose is appropriate for BH, while 0–2% eubiotic lignocellulose is appropriate for IBH.
Early Functional and Cognitive Declines Measured by Auditory-Evoked Cortical Potentials in Mice With Alzheimer’s Disease

Alzheimer’s disease (AD) is characterized by a progressive loss of memory and cognitive decline. However, the assessment of AD-associated functional and cognitive changes is still a big challenge. Auditory-evoked cortical potential (AECP) is an event-related potential reflecting not only neural activation in the auditory cortex (AC) but also cognitive activity in the brain. In this study, we used the subdermal needle electrodes with the same electrode setting as the auditory brainstem response (ABR) recording and recorded AECP in normal aging CBA/CaJ mice and APP/PS1 AD mice. AECP in mice usually appeared as three positive peaks, i.e., P1, P2, and P3, and three corresponding negative peaks, i.e., N1, N2, and N3. In normal aging CBA mice, the early sensory peaks P1, N1, and P2 were reduced as age increased, whereas the later cognitive peaks N2, P3, and N3 were increased or had no changes with aging. Moreover, the latency of the P1 peak was increased as age increased, although the latencies of later peaks had a significant reduction with aging. In AD mice, peak P1 was significantly reduced in comparison with wild-type (WT) littermates at young ages, proceeding AD phenotype presentation. In particular, the later cognitive peak P3 was diminished after 3 months old, different from the normal aging effect. However, the latencies of AECP peaks in AD mice generally had no significant delay or changes with aging. Finally, consistent with AECP changes, the accumulation of amyloid precursor protein (APP) at the AC was visible in AD mice as early as 2 months old. These data suggest that AECP could serve as an early, non-invasive, and objective biomarker for detecting AD and AD-related dementia (ADRD).
Clinical Relevance of New World Health Organization Classification System for Pituitary Adenomas: A Validation Study With 2-Year Experience

Background The new World Health Organization (WHO) classification system proposed a cell lineage-based classification scheme for pituitary adenomas in which transcription factors (TFs) play a major role as key classifiers. We aimed to evaluate clinical relevance of the new classification system in a clinical setting. Methods TF staining was retrospectively performed for 153 clinically and histologically well characterized pituitary adenomas. Then, 484 pituitary adenomas were prospectively stained for TFs and then for relevant pituitary hormones. TF and hormone stain-based diagnoses were compared, and differences in clinical manifestations were evaluated. Results The accuracies of antibodies for three TFs were successfully validated and had an overall matching rate was 89.6%. We identified 50 (10.4%) cases with discrepancies between TF and pituitary hormone stains. Gonadotroph adenomas lacking follicle-stimulating hormone and luteinizing hormone stains account for most discrepancies. Null cell adenomas may be more prevalent than reported and may be clinically more aggressive than gonadotroph adenomas. Conclusion The new WHO classification is mostly well matched with the traditional classification. However, until the new classification is further validated and interpreted in the context of long-term clinical outcomes, routine histological examination should include full slate of immunostains for pituitary hormones as well as TFs.
UNC93B1 Is Widely Expressed in the Murine CNS and Is Required for Neuroinflammation and Neuronal Injury Induced by MicroRNA let-7b

The chaperone protein Unc-93 homolog B1 (UNC93B1) regulates internalization, trafficking, and stabilization of nucleic acid-sensing Toll-like receptors (TLR) in peripheral immune cells. We sought to determine UNC93B1 expression and its functional relevance in inflammatory and injurious processes in the central nervous system (CNS). We found that UNC93B1 is expressed in various CNS cells including microglia, astrocytes, oligodendrocytes, and neurons, as assessed by PCR, immunocyto-/histochemistry, and flow cytometry. UNC93B1 expression in the murine brain increased during development. Exposure to the microRNA let-7b, a recently discovered endogenous TLR7 activator, but also to TLR3 and TLR4 agonists, led to increased UNC93B1 expression in microglia and neurons. Microglial activation by extracellular let-7b required functional UNC93B1, as assessed by TNF ELISA. Neuronal injury induced by extracellular let-7b was dependent on UNC93B1, as UNC93B1-deficient neurons were unaffected by the microRNA’s neurotoxicity in vitro. Intrathecal application of let-7b triggered neurodegeneration in wild-type mice, whereas mice deficient for UNC93B1 were protected against injurious effects on neurons and axons. In summary, our data demonstrate broad UNC93B1 expression in the murine brain and establish this chaperone as a modulator of neuroinflammation and neuronal injury triggered by extracellular microRNA and subsequent induction of TLR signaling.
Responses of Epibranchial Placodes to Disruptions of the FGF and BMP Signaling Pathways in Embryonic Mice

Placodes are ectodermal thickenings of the embryonic vertebrate head. Their descendants contribute to sensory organ development, but also give rise to sensory neurons of the cranial nerves. In mammals, the signaling pathways which regulate the morphogenesis and neurogenesis of epibranchial placodes, localized dorsocaudally to the pharyngeal clefts, are poorly understood. Therefore, we performed mouse whole embryo culture experiments to assess the impact of pan-fibroblast growth factor receptor (FGFR) inhibitors, anti-FGFR3 neutralizing antibodies or the pan-bone morphogenetic protein receptor (BMPR) inhibitor LDN193189 on epibranchial development. We demonstrate that each of the three paired epibranchial placodes is regulated by a unique combination of FGF and/or bone morphogenetic protein (BMP) signaling. Thus, neurogenesis depends on fibroblast growth factor (FGF) signals, albeit to different degrees, in all epibranchial placodes (EP), whereas only EP1 and EP3 significantly rely on neurogenic BMP signals. Furthermore, individual epibranchial placodes vary in the extent to which FGF and/or BMP signals (1) have access to certain receptor subtypes, (2) affect the production of Neurogenin (Ngn)2+ and/or Ngn1+ neuroblasts, and (3) regulate either neurogenesis alone or together with structural maintenance. In EP2 and EP3, all FGF-dependent production of Ngn2+ neuroblasts is mediated via FGFR3 whereas, in EP1, it depends on FGFR1 and FGFR3. Differently, production of FGF-dependent Ngn1+ neuroblasts almost completely depends on FGFR3 in EP1 and EP2, but not in EP3. Finally, FGF signals turned out to be responsible for the maintenance of both placodal thickening and neurogenesis in all epibranchial placodes, whereas administration of the pan-BMPR inhibitor, apart from its negative neurogenic effects in EP1 and EP3, causes only decreases in the thickness of EP3. Experimentally applied inhibitors most probably not only blocked receptors in the epibranchial placodes, but also endodermal receptors in the pharyngeal pouches, which act as epibranchial signaling centers. While high doses of pan-FGFR inhibitors impaired the development of all pharyngeal pouches, high doses of the pan-BMPR inhibitor negatively affected only the pharyngeal pouches 3 and 4. In combination with partly concordant, partly divergent findings in other vertebrate classes our observations open up new approaches for research into the complex regulation of neurogenic placode development.
Relationship Between Nutrition Knowledge and Dietary Intake: An Assessment Among a Sample of Italian Adults

Background: Assessing nutrition knowledge provides useful information especially if coupled with the self-perception of nutrition knowledge that could lead to bias and personal conviction. The objective of this study was to assess nutrition knowledge (NK) and its relationship with eating habits in a group of adults. Methods: A cross-sectional study with the administration of self-reported questionnaires was conducted on a sample of 591 parents (43 ± 5.82 years old) of primary school pupils recruited from the municipality of Rome (urban) and province (rural). The fieldwork was carried out in May 2017. An indicator to evaluate adherence to Italian dietary guidelines was developed. ANOVA (Welch's ANOVA in case of unequal variances) test and chi-squared test were used fixing the significance level at 5% (p < 0.05). Results: The percentage of correct answers to nutrition knowledge was 46%, with the expert recommendation section having the highest percentage (59%). The majority of the respondents (66%) were confident that they had a high level of nutrition knowledge. In 37% of the sample, nutrition knowledge and self-perception nutrition knowledge levels were found to be associated. A total of 40% of the sample showed eating habits congruent with nutrition knowledge level. In the investigated sample, living in rural areas, being young, and having low school education level were factors associated with low nutrition literacy or/and unhealthy eating habits. Conclusions: This study provided a demonstration that an assessment based on a multidimensional and multilevel approach is helpful to identify knowledge gaps and to profile critical segments to put in place targeted policy interventions.