Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicting conversion from mild cognitive impairment to Alzheimer’s disease with multimodal latent factors

ABSTRACT Introduction We studied the ability of latent factor scores to predict conversion from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) and investigated whether multimodal factor scores improve predictive power, relative to single-modal factor scores. Method We conducted exploratory factor analyses (EFAs) and confirmatory factor analyses (CFAs) of the baseline data of MCI subjects in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to generate factor scores for three data modalities: neuropsychological (NP), magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF). Factor scores from single or multiple modalities were entered in logistic regression models to predict MCI to AD conversion for 160 ADNI subjects over a 2-year interval. Results NP factors attained an area under the curve (AUC) of . 80, with a sensitivity of . 66 and a specificity of . 77. MRI factors reached a comparable level of performance (AUC = .80, sensitivity = .66, specificity = .78), whereas CSF factors produced weaker prediction (AUC = .70, sensitivity = .56, specificity = .79). Combining NP factors with MRI or CSF factors produced better prediction than either MRI or CSF factors alone. Similarly, adding MRI factors to NP or CSF factors produced improvements in prediction relative to NP or CSF factors alone. However, adding CSF factors to either NP or MRI factors produced no improvement in prediction. Conclusions Latent factor scores provided good accuracy for predicting MCI to AD conversion. Adding NP or MRI factors to factors from other modalities enhanced predictive power but adding CSF factors did not.
Negative Feedback Loop Mechanism between EAF1/2 and DBC1 in Regulating ELL Stability and Functions

Although ELL-associated factors 1 and 2 (EAF1/2) have been shown to enhance RNA polymerase II-mediated transcription in vitro, their functional roles in vivo are poorly known. In this report, we show functions of these proteins in regulating ELL stability through their competitive binding with HDAC3 at the N terminus of ELL. ABSTRACT Although ELL-associated factors 1 and 2 (EAF1/2) have been shown to enhance RNA polymerase II-mediated transcription in vitro, their functional roles in vivo are poorly known. In this report, we show functions of these proteins in regulating ELL stability through their competitive binding with HDAC3 at the N terminus of ELL. Reduced HDAC3 binding to ELL causes increased acetylation leading to reduced ubiquitylation-mediated degradation. Similar functional roles played by DBC1 in regulating ELL stability further prompted in-depth analyses that demonstrated presence of negative feedback loop mechanisms between DBC1 and EAF1/2 in maintaining overall ELL level. Mechanistically, increased DBC1 reduces EAF1/2 level through increased ubiquitylation involving E3 ubiquitin ligase TRIM28, whereas increased EAF1/2 reduces DBC1 level through reduced transcription. Physiologically, after a few passages, ELL levels in either DBC1 or EAF1 knockdown cells are restored through enhanced expression of EAF1 and DBC1, respectively. Interestingly, for maintenance of ELL level, mammalian cells prefer the EAF1-dependent pathway during exposure to genotoxic stress, and the DBC1-dependent pathway during exposure to growth factors. Thus, we describe coordinated functions of multiple factors, including EAF1/2, HDAC3, DBC1, and TRIM28 in regulating ELL protein level for optimal target gene expression in a context-dependent manner within mammalian cells.
Validity and reliability of the Glittre-ADL test in adults with asthma

ABSTRACT Introduction Adults with asthma may have limitations in their activities of daily living (ADL) and among the most used tests to assess ADL, performance-based instruments such as the Glittre-Activities of Daily Living (Glittre-ADL) test are available. However, metric properties of this instrument have not yet been investigated in this population. Objective To verify the construct validity and reliability of the Glittre-ADL test in adults with asthma. Methods Fifty-eight adults with asthma had their ADL objectively assessed by Glittre-ADL test, which was performed twice by the same rater. Lung function (spirometry), functional exercise capacity (6-minute walk test, 6MWT), and quality of life (St George’s Respiratory Questionnaire, SGRQ) were also assessed. Results Participants were 31% men; 43 ± 14 years; FEV1 74 ± 18% predicted. Performance in the Glittre-ADL test correlated with the 6MWT (r = −0.61; P < .0001) and had excellent intraclass correlation coefficient ICC3,1 = 0.95. Standard error of measurement was 23%, and the minimal detectable change was 29 seconds. Furthermore, the learning effect was 11 seconds (5.03%). Conclusion The Glittre-ADL test is valid and reliable for assessing ADL in adults with asthma. However, considerable learning effect was observed and therefore the best of two measures can avoid underestimation.
Peripheral Blood Telomere Attrition in Persons at Risk for Familial Pulmonary Fibrosis

Shorter than expected telomeres are common among persons with pulmonary fibrosis (PF), even in the absence of a genetic variant impacting telomere maintenance (1–4). Telomere shortening is pathologically implicated in PF through cellular aging and/or senescence mechanisms in lung epithelium and other cell types (1, 5, 6). Most research on telomere length in PF has been crosssectional. A key unanswered question is whether short telomeres observed later in life are primarily inherited or result from accelerated attrition. Some of the results of these studies have been previously reported in the form of an abstract (7).
Outbreak of acute respiratory disease caused by human adenovirus type 7 and human coronavirus‐229E in Zhejiang Province, China

In 2019, an outbreak of pharyngoconjunctival fever (PCF) occurred at a swimming center in Zhejiang Province, China. A total of 97 (13.55%) of the 716 amateur swimmers had illnesses, with 24 patients (24.74%) hospitalized in the pediatric ward. Human adenovirus serotype 7 (HAdV‐7) was isolated from one concentrated water from the swimming pool, and 20 of 97 positive cases without liver damage. This outbreak led to a nosocomial outbreak in the pediatric ward, in which 1 nurse had a fever and was confirmed to be adenovirus positive. The hexon, fiber, and penton genes from 20 outbreak cases, 1 water sample, and 1 nurse had 100% homology. Furthermore, 2 cases admitted to the pediatric ward, 2 parents, and 1 doctor were confirmed to be human coronaviruses (HCoV‐229E) positive. Finally, all outbreak cases had fully recovered, regardless of a single infection (adenovirus or HCoV‐229E) or coinfection of these two viruses simultaneously. Thus, PCF and acute respiratory disease outbreaks in Zhejiang were caused by the completely homologous type 7 adenovirus and HCoV‐229E, respectively. The swimming pool water contaminated with HAdV‐7 was most likely the source of the PCF outbreak, whereas nosocomial transmission might be the source of HCoV‐229E outbreak.
Modulation of Fluorouracil Cytotoxicity by Interferon- a and - g

Because interferons (IFN)- a and - g individually have increased fluorouracil (FUra) cytotoxicity in several in vitro models, we studied the effects of FUra combined with IFN- a 1 g in HT29 colon cancer cells. A 96-hr exposure to IFN- a (500 units/ml) plus IFN- g (10 units/ml) and a 72-hr exposure to 0.25–1 m M FUra (hr 24–96) inhibited cell growth and colony formation in an additive or more-than-additive fashion. When cells were exposed to IFN- a 1 g and FUra, free FdUMP levels became detectable, whereas [ 3 H]FUra-RNA incorporation decreased. dTTP pools to 58%, 43%, and 17% of control, respectively. A marked in the dATP to dTTP without a g . synthase catalytic activity reduced to 28% and 24% of FUra or without a g , must be due to another mechanism. FUra-mediated thy- midylate synthase inhibition was accompanied by a 124-fold increase in total deoxyuridylate immunoreactivity and a 31-fold increase in dUTP pools, but the addition of IFN- a 1 g attenuated the accumulation. Treatment with IFN- a 1 g and FUra individually interfered with nascent DNA chain elongation, whereas the three-drug combination produced the most strik-ing effects. IFN- a 1 g plus FUra produced the greatest amount of single-strand breaks in nascent DNA and dramatically de- creased net DNA synthesis. IFN- a 1 g with or without FUra produced double-strand breaks in parental DNA. These results suggest that dTTP depletion, dATP/dTTP imbalance, pronounced inhibition of DNA synthesis, and damage to nascent and parental DNA contribute to the enhanced cytotoxicity with the triple combination.
Reduced Equol Production and Gut Microbiota Features in Men With Lean Nonalcoholic Fatty Liver Disease

Patients with lean nonalcoholic fatty liver disease (NAFLD) may have different metabolic profiles than those with NAFLD. Estrogenic activity is associated with NAFLD pathogenesis. We evaluated the production ability of equol, which has estrogenic activity, in lean NAFLD and assessed their gut microbiota in relation to their equol-producing ability. Among 684 adult participants, 276 (40%) had NAFLD and 293 (43%) were equol producers. The rates of equol producers in the normal and NAFLD groups were 43% and 42%, respectively. Among the patients with NAFLD, 55 (20%) had lean NAFLD of which 18 (33%) were equol producers. The rate of equol production in men with lean NAFLD was 8%, which was the lowest, while the corresponding rate in the other participants was approximately 40%. The gut microbiota composition of equol producers and nonproducers showed many significant differences. The gut microbiota of men with lean NAFLD showed increased abundance of Caulobacter and decreased abundances of Slackia and Terrisporobacter. Thus, almost all men with lean NAFLD lacked equol-producing ability, and their gut microbiota showed a reduced abundance of Slackia, which is related to equol production. The pathology of lean NAFLD in men may be strongly associated with equol-producing ability and gut microbiota.
Identification of biomarkers for disease severity in nasopharyngeal secretions of infants with upper or lower respiratory tract viral infections

Abstract Lower respiratory tract infections (LRTIs) produced by viruses are the most frequent cause of morbidity and mortality in children younger than 5 years of age. The immune response triggered by viral infection can induce a strong inflammation in the airways and cytokines could be considered as biomarkers for disease severity as these molecules modulate the inflammatory response that defines the outcome of patients. Aiming to predict the severity of disease during respiratory tract infections, we conducted a 1-year follow-up observational study in infants who presented upper or lower respiratory tract infections caused by seasonal respiratory viruses. At the time of enrollment, nasopharyngeal swabs (NPS) were obtained from infants to measure mRNA expression and protein levels of IL-3, IL-8, IL-33, and thymic stromal lymphopoietin. While all cytokines significantly increased their protein levels in infants with upper and lower respiratory tract infections as compared to control infants, IL-33 and IL-8 showed a significant increase in respiratory syncytial virus (RSV)-infected patients with LRTI as compared to patients with upper respiratory tract infection. We also found higher viral loads of RSV-positive samples with a greater IL-8 response at the beginning of the symptoms. Data obtained in this study suggest that both IL-8 and IL-33 could be used as biomarkers for clinical severity for infants suffering from LRTIs caused by the RSV.
Genomic characterization of Staphylococcus aureus isolates causing osteoarticular infections in otherwise healthy children

Background Pediatric osteoarticular infections are commonly caused by Staphylococcus aureus. The contribution of S. aureus genomic variability to pathogenesis of these infections is poorly described. Methods We prospectively enrolled 47 children over 3 1/2 years from whom S. aureus was isolated on culture—12 uninfected with skin colonization, 16 with skin abscesses, 19 with osteoarticular infections (four with septic arthritis, three with acute osteomyelitis, six with acute osteomyelitis and septic arthritis and six with chronic osteomyelitis). Isolates underwent whole genome sequencing, with assessment for 254 virulence genes and any mutations as well as creation of a phylogenetic tree. Finally, isolates were compared for their ability to form static biofilms and compared to the genetic analysis. Results No sequence types predominated amongst osteoarticular infections. Only genes involved in evasion of host immune defenses were more frequently carried by isolates from osteoarticular infections than from skin colonization (p = .02). Virulence gene mutations were only noted in 14 genes (three regulating biofilm formation) when comparing isolates from subjects with osteoarticular infections and those with skin colonization. Biofilm results demonstrated large heterogeneity in the isolates’ capacity to form static biofilms, with healthy control isolates producing more robust biofilm formation. Conclusions S. aureus causing osteoarticular infections are genetically heterogeneous, and more frequently harbor genes involved in immune evasion than less invasive isolates. However, virulence gene carriage overall is similar with infrequent mutations, suggesting that pathogenesis of S. aureus osteoarticular infections may be primarily regulated at transcriptional and/or translational levels.
Elucidating the Effect of Endophytic Entomopathogenic Fungi on Bread Wheat Growth through Signaling of Immune Response-Related Hormones

Microbial control of insect and mite pests is a key tool to develop integrated pest management (IPM) and sustainable agriculture. Entomopathogenic fungi (EF) may have associations with the plants, playing additional ecological roles in the rhizosphere, in the phylloplane, and as plant endophytes. Beauveria bassiana 04/01TIP and Metarhizium brunneum 01/58Su are two strains that showed very good results either in pest control or plant growth promotion and would be good candidates to develop mycoinsecticides as an alternative to pesticides. ABSTRACT Entomopathogenic fungi (EF) provide a potent biocontrol tool; also, their endophytic behavior has broadened their contribution to integrated pest management (IPM) and crop production. In this work, Beauveria bassiana and Metarhizium brunneum were applied to bread wheat (Triticum aestivum) seedlings to elucidate how fungal colonization influences plant growth and the relative expression of 24 genes involved in hormonal syntheses and plant immune mechanisms. A preliminary assay was used to determine the time needed for fungal colonization and assess its effect on wheat growth. Then, plant material collected at various times after inoculation (viz., 2, 8, 20, and 36 h and 9 and 15 days) was used to investigate gene expression by quantitative reverse transcription PCR (RT-qPCR). During the colonization time, B. bassiana and M. brunneum caused strong downregulation of most genes associated with plant immunity and the synthesis of hormones like auxin, cytokinin, and gibberellin. This effect was concomitant with a slowdown of endophytic-colonization-related plant growth until 19 days postinoculation (dpi). However, the wheat started to recover at 15 dpi, simultaneously with upregulation of auxin- and gibberellin-related genes. The results suggest that the EF trigger induced systemic resistance rather than acquired systemic resistance during early plant-microbe cross talk in wheat. Also, they confirm that the hormone and immune responses of wheat triggered by EF inoculation influenced plant growth, which can be useful with a view to optimizing management of these microorganisms for sustainable agriculture. IMPORTANCE Microbial control of insect and mite pests is a key tool to develop integrated pest management (IPM) and sustainable agriculture. Entomopathogenic fungi (EF) may have associations with the plants, playing additional ecological roles in the rhizosphere, in the phylloplane, and as plant endophytes. Beauveria bassiana 04/01TIP and Metarhizium brunneum 01/58Su are two strains that showed very good results either in pest control or plant growth promotion and would be good candidates to develop mycoinsecticides as an alternative to pesticides. However, deep knowledge about their interaction with the plant would let farmers optimize their use and understand the plant response, enhancing and promoting their broader contribution to IPM and crop production.
Neurospora – a model system

The alternative splicing of gene transcripts permits translation of different protein variants from the same gene. In heterothallic Neurospora crassa , strains of different mating type use a pheromone receptor system to find a compatible mating partner. Previously, only a single splice variant was reported from a single tissue (Karlsson et al., 2008; Kim and Borkovich, 2004; Pöggeler and Kuck, 2001). In this study, we show that two splice variants of the pheromone receptor gene ( pre-1 ) co-exist in both vegetative and reproductive tissues of N. crassa . The two splice variants are spliced by intron retention of intron i3, which is predicted to result in a premature stop codon and loss of 322 amino acids from the C-terminal cytosolic region of PRE-1. In addition, we use quantitative PCR and showed that expression of the retained intron splice variant is on average 10-fold lower than the expression of the spliced intron variant. Both splice variants are induced by mycelial age, with higher transcript numbers after 14 days in culture compared with both one or seven days. Our data indicate that sexual reproduction and growth media composition did not influence the expression of either splice variant. , authors exon
The Relationship between Circulating Irisin and Oxidative Stress in Gastric and Colorectal Cancer Patients

Objective: Gastric and colorectal cancers are two obesity-related cancers. Irisin is a dipo-myokine with an important role in the body’s energy homeostasis. Oxidative Stress has a crucial role in tumorigenesis. Therefore, this study aims to investigate the association of circulating irisin with oxidative stress in gastric and colorectal cancer patients. Methods: A case-control study involving 62 gastric and colorectal cancers and 22 healthy individuals was carried out. Serum irisin and Total Antioxidant Capacity were measured by sandwich enzyme-linked immunosorbed assay (ELIZA) kits. Total Oxidative Stress (TOS) was measured using colorimetric methods and oxidative stress index (OSI) was also calculated. Results: Serum irisin decreased significantly (p<0.0001) in gastric and colorectal cancer cases compared to healthy individuals. The TOS and OSI levels increased significantly (p<0.0001) in gastric and colorectal cancer cases compared to healthy individuals. No significant correlation was found in terms of irisin, TOS, TAC, and OSI in gastric and colorectal cancer cases and control groups. Conclusion: Circulating irisin decreases and oxidative stress increases in gastric and colorectal cancers. There is no correlation between irisin and oxidative stress. The mechanism by which irisin is associated with oxidative stress is still not clear.
A simple model of the attentional blink and its modulation by mental training

The attentional blink (AB) effect is the reduced probability of reporting a second target (T2) that appears shortly after a first one (T1) within a rapidly presented sequence of distractors. The AB effect has been shown to be reduced following intensive mental training in the form of mindfulness meditation, with a corresponding reduction in T1-evoked P3b brain potentials. However, the mechanisms underlying these effects remain unknown. We propose a dynamical-systems model of the AB, in which attentional load is described as the response of a dynamical system to incoming impulse signals. Non-task related mental activity is represented by additive noise modulated by meditation. The model provides a parsimonious computational framework relating behavioral performance, evoked brain potentials and training through the concept of reduced mental noise.
Pharmacodynamic evaluation of intermittent versus extended and continuous infusions of piperacillin/tazobactam in a hollow-fibre infection model against Escherichia coli clinical isolates.

OBJECTIVES To compare the bacterial killing and emergence of resistance of intermittent versus prolonged (extended and continuous infusions) infusion dosing regimens of piperacillin/tazobactam against two Escherichia coli clinical isolates in a dynamic hollow-fibre infection model (HFIM). METHODS Three piperacillin/tazobactam dosing regimens (4/0.5 g 8 hourly as 0.5 and 4 h infusions and 12/1.5 g/24 h continuous infusion) against a ceftriaxone-susceptible, non-ESBL-producing E. coli 44 (Ec44, MIC 2 mg/L) and six piperacillin/tazobactam dosing regimens (4/0.5 g 8 hourly as 0.5 and 4 h infusions and 12/1.5 g/24 h continuous infusion; 4/0.5 g 6 hourly as 0.5 and 3 h infusions and 16/2 g/24 h continuous infusion) were simulated against a ceftriaxone-resistant, AmpC- and ESBL-producing E. coli 50 (Ec50, MIC 8 mg/L) in a HFIM over 7 days (initial inoculum ∼107 cfu/mL). Total and less-susceptible subpopulations and MICs were determined. RESULTS All simulated dosing regimens against Ec44 exhibited 4 log10 of bacterial killing over 8 h without regrowth and resistance emergence throughout the experiment. For Ec50, there was the initial bacterial killing of 4 log10 followed by regrowth to 1011 cfu/mL within 24 h against all simulated dosing regimens, and the MICs for resistant subpopulations exceeded 256 mg/L at 72 h. CONCLUSIONS Our study suggests that, for critically ill patients, conventional intermittent infusion, or prolonged infusions of piperacillin/tazobactam may suppress resistant subpopulations of non-ESBL-producing E. coli clinical isolates. However, intermittent, or prolonged infusions may not suppress the resistant subpopulations of AmpC- and ESBL-producing E. coli clinical isolates. More studies are required to confirm these findings.
DBP reduction using mixed oxidants generated on site

This paper describes how mixed oxidants generated on site have a demonstrated track record of reducing both total trihalomethanes (TTHMS) and haloacetic acids (HAAS) without the attendant problems associated with bromates and chlorites or issues regarding safe handling. Mixed‐oxidant chemistry is discussed along with theories for behavioral differences that include: preferential‐acting nonchlorine oxidants; biofilm elimination; improved residual at a reduced dosage; and, microflocculation.