Miracle-dz/UniFAR-FTUs huggingface dataset:
The Diagnostic Pathway From Cognitive Impairment to Dementia in Japan

Supplemental Digital Content is available in the text. Objective: This study aimed to quantify the diagnostic pathway from cognitive impairment (CI) to dementia in Japan. Methods: This was a real-world, cross-sectional survey of patients with CI and their physicians. Results: Data for 1107 patients were provided by 106 physicians. Mean time from initial symptoms to the first consultation was 7.4±6.9 months; 42% of patients had moderate/severe CI at first consultation. Mean time from the first consultation to formal diagnosis was 2.9±11.0 months (1.9±8.8 mo if not referred to a secondary physician, and 5.1±14.6 mo if referred). Time from the first consultation to diagnosis was shorter with more severe CI at first consultation (P=0.0072). The highest proportion of patients were diagnosed by neurologists (45.8%). Tests or scales were used to aid diagnosis in 81.2% of patients. There was no association of disease severity and referral to a secondary physician; 30.9% of patients were referred, the majority (57.7%) to a neurologist. Conclusions: A substantial proportion of patients with dementia in Japan experience CI for some time before consulting a physician. Government policy to increase public understanding and awareness of dementia, and a proposed dementia screening system, should increase the proportion of individuals consulting physicians before disease progression.
Mechanisms of resistance against experimental Trypanosoma cruzi infection: the importance of antibodies and antibody-forming capacity in the Biozzi high and low responder mice.

The role of antibodies and the host's antibody-forming capacity in resistance to Trypanosoma cruzi infection has been investigated in the Biozzi high and low responder lines of mice. Ab/L animals with low antibody-forming capacity were found to be more susceptible to i.p. infection with trypomastigotes than high responders (Ab/H), whereas non-selected Swiss albino mice showed an intermediate level of susceptibility. The correlation between antibody-forming potentiality and susceptibility was consistently observed with both the Y and Tulahuén strains of the parasite, which differ in their preferential tissue tropism as well as virulence. A similar divergence in susceptibility was observed after subcutaneous infection with the Y strain which produced a more fulminating disease. Although Ab/L mice neither produced a significant antibody response to the parasite nor responded to prophylactic immunization with killed T. cruzi epimastigotes, they could be effectively protected by passive transfer of immune plasma.
Regulation of tRNA‐dependent translational quality control

Translation is the most error‐prone process in protein synthesis; however, it is important that accuracy is maintained because erroneous translation has been shown to affect all domains of life. Translational quality control is maintained by both proteins and RNA through intricate processes. The aminoacyl‐tRNA synthetases help maintain high levels of translational accuracy through the esterification of tRNA and proofreading mechanisms. tRNA is often recognized by an aminoacyl‐tRNA synthetase in a sequence and structurally dependent manner, sometimes involving modified nucleotides. Additionally, some proofreading mechanisms of aminoacyl‐tRNA synthetases require tRNA elements for hydrolysis of a noncognate aminoacyl‐tRNA. Finally, tRNA is also important for proper decoding of the mRNA message by codon and anticodon pairing. Here, recent developments regarding the importance of tRNA in maintenance of translational accuracy are reviewed. © 2019 IUBMB Life, 2019 © 2019 IUBMB Life, 71(8):1150–1157, 2019
Human Herpesvirus 6 Chromosomal Integration in Immunocompetent Patients Results in High Levels of Viral DNA in Blood, Sera, and Hair Follicles

ABSTRACT Six immunocompetent patients with human herpesvirus 6 (HHV-6) chromosomal integration had HHV-6 and β-globin DNA quantified in various samples by PCR. The mean HHV-6 DNA concentration (log10 copies/milliliter) in blood was 7.0 (≥1 HHV-6 DNA copies/leukocyte), and in serum it was 5.3 (≥1 HHV-6 DNA copies/lysed cell). The mean HHV-6 DNA load (log10 copies)/hair follicle was 4.2 (≥1 copies/hair follicle cell), demonstrating that viral integration is not confined to blood cells. The characteristically high HHV-6 DNA levels in chromosomal integration may confound laboratory diagnosis of HHV-6 infection and should be given due consideration.
Transcriptome maps of general eukaryotic RNA degradation factors

RNA degradation pathways enable RNA processing, the regulation of RNA levels, and the surveillance of aberrant or poorly functional RNAs in cells. Here we provide transcriptome-wide RNA-binding profiles of 30 general RNA degradation factors in the yeast Saccharomyces cerevisiae. The profiles reveal the distribution of degradation factors between different RNA classes. They are consistent with the canonical degradation pathway for closed-loop forming mRNAs after deadenylation. Modeling based on mRNA half-lives suggests that most degradation factors bind intact mRNAs, whereas decapping factors are recruited only for mRNA degradation, consistent with decapping being a rate-limiting step. Decapping factors preferentially bind mRNAs with non-optimal codons, consistent with rapid degradation of inefficiently translated mRNAs. Global analysis suggests that the nuclear surveillance machinery, including the complexes Nrd1/Nab3 and TRAMP4, targets aberrant nuclear RNAs and processes snoRNAs.
Protective Effect of Hyperbaric Oxygen Therapy on Cognitive Function in Patients with Vascular Dementia

Recent studies have shown that hyperbaric oxygen (HBO) has a therapeutic effect on vascular dementia (VD); however, the exact mechanism remains unclear. This article aims to reveal the protective effects and underlying mechanisms of HBO on VD. A total of 158 patients with VD were prospectively included in the study and were randomly divided into control group and HBO group. The control group was given conventional treatment and the HBO group was treated with HBO in addition to conventional treatment. The following HBO protocol was practiced: 5 days per week, 60 min each, 100% oxygen at 2 standard atmospheric pressures for 12 weeks. The Mini-Mental State Examination (MMSE) scores and serum Humanin levels were detected before and after treatments in both groups. The baseline characteristics were not different dramatically between groups (p > 0.05). There was no significant difference in MMSE scores and serum Humanin levels between the two groups before treatment (p > 0.05). After treatment, compared with the control group, the MMSE scores and serum Humanin levels in the HBO group were significantly increased (p < 0.05). Spearman correlation analysis showed that the serum Humanin levels were positively correlated with MMSE scores (r = 0.409, p < 0.05) and this correlation was independent of baseline characteristics (β = 0.312, p < 0.05). HBO therapy can improve cognitive function in patients with VD, and its mechanism may be related to elevated serum Humanin levels.
Discordant occurrence of primary biliary cirrhosis in monozygotic twins.

To the Editor: The cause of primary biliary cirrhosis is unknown but may be associated with an inherited abnormality of immune regulation1,2. It is not known whether abnormal genes alone will cause the disease or whether an additional triggering event is needed. Both a genetic abnormality and a triggering event are needed to cause another chronic liver disease, autoimmune chronic active hepatitis3. We report on a pair of monozygotic twins; one was healthy, and the other had advanced primary biliary cirrhosis. The first twin, a 58-year-old woman, had had primary biliary cirrhosis for eight years (Figure 1).
Finite-Size-Corrected Rotational Diffusion Coefficients of Membrane Proteins and Carbon Nanotubes from Molecular Dynamics Simulations

We investigate system-size effects on the rotational diffusion of membrane proteins and other membrane-embedded molecules in molecular dynamics simulations. We find that the rotational diffusion coefficient slows down relative to the infinite-system value by a factor of one minus the ratio of protein and box areas. This correction factor follows from the hydrodynamics of rotational flows under periodic boundary conditions and is rationalized in terms of Taylor–Couette flow. For membrane proteins like transporters, channels, or receptors in typical simulation setups, the protein-covered area tends to be relatively large, requiring a significant finite-size correction. Molecular dynamics simulations of the protein adenine nucleotide translocase (ANT1) and of a carbon nanotube porin in lipid membranes show that the hydrodynamic finite-size correction for rotational diffusion is accurate in standard-use cases. The dependence of the rotational diffusion on box size can be used to determine the membrane viscosity.
Calcium, iron and zinc uptakes by Caco-2 cells from white beans and effect of cooking

White beans (Phaseolus vulgaris L.) have an interesting content of essential elements, calcium, iron and zinc, but they content also phytates, oxalates, proteins, polyyphenols and complex polysaccharides that are known to interact with minerals and to affect their bioavailability. The bioavailability of calcium, iron and zinc from raw and cooked white beans was estimated using their uptake by Caco-2 cells as the criteria. Previously, the mineral fraction (soluble or dialysable) to be added to the Caco-2 cell monolayer was selected. The results obtained show that cooking increases the Caco-2 cells’ uptake percentages (calcium, 18.8 versus 3.6; iron, 33.7 versus 1.7; and zinc, 17.2 versus 2.1) and improved the value of beans as a dietetic source of minerals.
Joint Uplink and Downlink User Association for Energy-Efficient HetNets Using Nash Bargaining Solution

In heterogeneous networks (HetNets), due to transmit power disparity between macro and pico base stations (BSs), the conventional strongest downlink (DL) reference signal received power (RSRP) based user association results in high uplink (UL) interference. Such interference degrades the UL performance especially in terms of energy efficiency. In this paper, we propose Joint Uplink and Downlink User Association (JUDUA) that takes both the UL and DL energy efficiencies into consideration when deciding the serving BS for user equipments (UEs). JUDUA formulates user association optimization problem as a Nash bargaining problem aiming to maximize the sum of log-scale UL and DL energy efficiencies among all UEs. Simulation results demonstrate that JUDUA improves UL and DL energy efficiencies of UEs, which in turn boosts UL and DL system capacity, reduces UL transmit power compared with the conventional user association schemes.
B7-H1 Up-Regulation on Myeloid Dendritic Cells Significantly Suppresses T Cell Immune Function in Patients with Chronic Hepatitis B1

Although dysfunctional dendritic cells contribute to inadequate adaptive immunity in chronic hepatitis B (CHB), underlying molecular mechanisms remain largely undefined. In this study, we examined B7-H1 expression on circulating myeloid dendritic cells (mDCs) in 46 CHB patients, 10 autoimmune hepatitis patients, and 10 healthy subjects as control. We found that B7-H1 expression is significantly up-regulated on circulating mDCs of CHB and autoimmune hepatitis patients compared with healthy individuals. The B7-H1 up-regulation was significantly correlated with an elevation of serum alanine aminotransaminase levels and plasma viral load. In addition, in vitro, both IFN-α and IFN-γ could strongly stimulate mDCs to express B7-H1. More importantly, elevated B7-H1 expression is also closely associated with the suppression of T cell immune function. In vitro blockade of B7-H1 signaling could not only down-regulate IL-10 and up-regulate IL-12 production by mDCs, but also enhance mDC-mediated allostimulatory capacity and cytokine production of T cells. Blockade of B7-H1 signaling could improve hepatitis B c Ag-pulsed monocyte-derived DC-induced IFN-γ production by autologous hepatitis B virus-specific T cells. These new findings suggested that chronic inflammation may contribute to B7-H1 up-regulation on mDCs in CHB patients, which potentially cause defective hepatitis B virus-specific T cell function and viral persistence. Our findings further support the notion that the blockade of B7-H1 may represent a novel therapeutic approach for this disease.
The Ulip family phosphoproteins--common and specific properties.

The search for intracellular phosphoproteins implicated in the regulation of neuronal differentiation led to the identification of Ulip1, a mammalian protein related to the Caenorhabditis elegans unc-33 gene product [Byk, T. , Dobransky, T. , Cifuentes-Diaz, C. & Sobel, A. (1996) J. Neurosc. 16, 688-701]. The expression level and phosphorylation pattern of Ulip1 were shown to be strongly regulated during development and neuronal differentiation. We have isolated three additional complete coding sequences for members of the Ulip family in the mouse, Ulips 2-4, all preferentially expressed in the nervous system. Furthermore, two Ulip sequences, Ulips A and Ulips B, could be identified in C. elegans. The Ulip family is highly conserved throughout evolution (more than 96 % for Ulips 1-3 and 92.5 % for Ulip4 between mouse and human) and the various members of the family within a single species display about 75% similarity. Sequence comparisons further reveal several highly similar domains and subdomains, including a 32-amino-acid region highly conserved from a bacterial hydantoinase to human Ulips. Two-dimensional immunoblot analysis of in vitro translated Ulips 1-4 demonstrates the existence, for each Ulip protein, of several, most probably differentially phosphorylated forms, in agreement with the presence of conserved phosphorylation consensus sites within their sequences. The expression of Ulips 1-4 mRNAs is differentially regulated during development and nerve-growth-factor-induced neuronal differentiation of PC12 cells. Our results indicate a differential, possibly complementary role of phosphoproteins of the highly conserved Ulip family in the control of neuronal differentiation, in relation with the development and plasticity of the nervous system.
WIC Peer Counselors’ Perceptions of Breastfeeding in African American Women with Lower Incomes

Background: African American women have the lowest breastfeeding rates among all racial/ethnic groups in the United States. Peer counseling is an effective intervention in improving breastfeeding in this population. However, little is known on peer counselors’ perceptions of breastfeeding in African American women. Objective: As part of a larger qualitative study, the goal of this study was to understand the contextual factors influencing breastfeeding decisions of low-income African American women from the perspective of breastfeeding peer counselors (PCs). Methods: Three focus groups were conducted with 23 PCs from the Women, Infants, and Children program in a southeastern state. All focus group discussions were audio-recorded, professionally transcribed, and analyzed using thematic analysis. Bronfenbrenner’s socioecological model was used to group categories into themes. Results: Of the sample, 47.8% were African American, 78.2% were married, and 56.5% had some college education. Five main themes emerged to describe factors at multiple levels influencing breastfeeding in PCs’ low-income African American clients: individual, microsystem, exosystem, macrosystem, and chronosystem. Novel findings included (1) having breast pumps may give African American women a “sense of security,” (2) cultural pressures to be a “strong black woman” can impede breastfeeding support, and (3) breastfeeding “generational gaps” have resulted from American “slavery” and when formula was “a sign of wealth. ” Conclusion: As PCs described, low-income African American women’s breastfeeding decisions are affected by numerous contextual factors. Findings from this study suggest a need to broaden the public health approach to breastfeeding promotion in this population by moving beyond individual characteristics to examining historical and sociocultural factors underlying breastfeeding practices in African American women.
A cross-sectional examination of choice and behavior of veterans with access to free medicinal cannabis

ABSTRACT Background: With a rise in public pressure to increase veteran access to medicinal cannabis, free cannabis collectives for military veterans are proliferating across the US. Objectives: The aim of the current study was to document which cannabis formulations and routes of administration are chosen by veterans with increased access to cannabis, and to determine whether cannabis is being used as a substitute for other licit and illicit drugs. Method: The current study collected cross-sectional self-report data on cannabis use, cannabinoid constituent composition, primary indication of use, and substitution practices among a sample of 93 US military veterans (84.9% male) with access to free cannabis. Result: Most of the sample reported using cannabinoids as a substitute for either alcohol, tobacco, prescription medications, or illicit substances, reported that they use cannabis frequently (Modal frequency >4x/day, Modal quantity = 5 to 8 grams/week), and primarily select higher-risk cannabis formulations (i.e., high THC/low CBD, smoked). The majority of the sample reported that they use cannabis to self-treat multiple physical and mental health conditions/symptoms. Conclusions: Results of the current study suggest that military Veterans with reduced barriers to access cannabis could be making both helpful and harmful choices regarding their cannabis use. These findings suggest that more guidance on the selection of cannabis-based products in this population is warranted, particularly as barriers to medicinal cannabis access are reduced.
Electron Trap Profiling Near $\hbox{Al}_{2} \hbox{O}_{3}$/Gate Interface in TANOS Stack Using Gate-Side Trap Spectroscopy by Charge Injection and Sensing

The goal of this letter is to investigate and characterize the defects at the Al2O3/gate interface in TANOS memory stacks. To this purpose, gate-side trap spectroscopy by charge injection and sensing is applied on devices featuring different metal gates and different postdeposition anneals. The results show that a high concentration of defect is present in crystalline samples with a TaN or TiN gate.
Dietary “Fibre” and Pregnancy Toxaemia*†

The clinical course of nine patients suffering from temporal arteritis is described. The following points emerge: the patients are without exception elderly, often of arthritic disposition, and arteriosclerotic; the disease runs a protracted though benign course but may leave permanent damage to vision; temporal arteritis is a not uncommon cause of sudden visual failure in the elderly, and the underlying disease may be overlooked if the symptoms have not been severe or if they have occurred some weeks or months before ; salicylates are of value, at least in the relief of symptoms. The ischaemia of the scalp may be sufficient to result in necrosis.
Serological evidence and experimental infection of cynomolgus macaques with pteropine orthoreovirus reveal monkeys as potential hosts for transmission to humans

ABSTRACT Pteropine orthoreoviruses (PRV) are emerging bat-borne viruses with proven zoonotic transmission. We recently demonstrated human exposure to PRV in Singapore, which together with previous reports from Malaysia and Vietnam suggest that human infection of PRV may occur periodically in the region. This raises the question whether bats are the only sources of human infection. In this study, we screened 517 cynomolgus macaques caught in Singapore for evidence of exposure to PRV3M (also known as Melaka virus), which was first isolated from human patients in Melaka, Malaysia. We found that 67 serum samples were PRV3M positive by ELISA and 34 were also positive by virus neutralization assay. To investigate whether monkeys could act as hosts for PRV transmission, we experimentally infected cynomolgus macaques with PRV3M and housed these animals with uninfected monkeys. Although no clinical signs of infection were observed in infected animals, viral RNA was detected in nasal and rectal swabs and all infected macaques seroconverted. Additionally, one of the uninfected animals seroconverted, implying active shedding and transmission of PRV3M. We provide evidence that PRV exposure in the macaque population in Singapore occurs at a relatively high prevalence and this study suggests that cynomolgus macaques may be an intermediate or reservoir host for PRVs.
Complete Genome Sequence of the Human Herpesvirus 6A Strain AJ from Africa Resembles Strain GS from North America

ABSTRACT The genome sequence of human herpesvirus 6A (HHV-6A) strain AJ was determined in a comparison of target enrichment and long-range PCR using next-generation sequencing methodologies. The analyses show 85 predicted open reading frames (ORFs), conservation with sequenced HHV-6A reference strain U1102, and closest identity to the recently determined GS strain, despite different geographic origins (United States and Gambia).
Identification of a Combined RNA Prognostic Signature in Adenocarcinoma of the Lung

Background Adenocarcinoma of the lung is a type of non-small cell lung cancer (NSCLC). Clinical outcome is associated with tumor grade, stage, and subtype. This study aimed to identify RNA expression profiles, including long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA, associated with clinical outcome in adenocarcinoma of the lung using bioinformatics data. Material/Methods The miRNA and mRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database, and lncRNA expression profiles were downloaded from The Atlas of Noncoding RNAs in Cancer (TANRIC) database. The independent dataset, the Gene Expression Omnibus (GEO) accession dataset, GSE81089, was used. RNA expression profiles were used to identify comprehensive prognostic RNA signatures based on patient survival time. Results From 7,704 lncRNAs, 787 miRNAs, and 28,937 mRNAs of 449 patients, four joint RNA molecular signatures were identified, including RP11-909N17.2, RP11-14N7.2 (lncRNAs), MIR139 (miRNA), KLHDC8B (mRNA). The random forest (RF) classifier was used to test the prediction ability of patient survival risk and showed a good predictive accuracy of 71% and also showed a significant difference in overall survival (log-rank P=0.0002; HR, 3.54; 95% CI, 1.74–7.19). The combined RNA signature also showed good performance in the identification of patient survival in the validation and independent datasets. Conclusions This study identified four RNA sequences as a prognostic molecular signature in adenocarcinoma of the lung, which may also provide an increased understanding of the molecular mechanisms underlying the pathogenesis of this malignancy.