Miracle-dz/UniFAR-FTUs huggingface dataset:
The Progression of Behavior in Dementia: An In-Office Guide for Clinicians

This article examines the progression of behavioral changes in 200 community living and long term care patients using the Kingston Standardized Behavioral Assessment, a measure of traditional neuropsychiatric behaviors (behavioral and psychological symptoms of dementia) and neuropsychological behaviors. A group of patients diagnosed with probable Alzheimer's disease or mixed dementia (Alzheimer's disease and vascular dementia), was assessed using the Kingston Standardized Behavioral Assessment, ranked by total Kingston Standardized Behavioral Assessment score and were divided into quartile-based groups. The scores revealed changes in behavior patterns across quartiles. Significant behavior change appeared even in quartile one. Lower scores were predominantly associated with neuropsychological behaviors; as scores increased, neuropsychiatric behaviors became equally common. An at-a-glance guide characterizing the patterns of increasing behavioral change is provided for clinicians. Behavioral changes appear both early and throughout dementia; the type and pattern of these emerging behaviors change as the disease progresses. Clinicians can use the typical patterns of behavioral change to identify behavioral impairment in individual patients and anticipate future changes and related care needs.
cis- and trans-Acting Localization Determinants of pH Response Regulator Rim13 in Saccharomyces cerevisiae

ABSTRACT The Rim101/PacC pathway governs adaptation to alkaline pH in many fungi. Output of the pathway is mediated by transcription factors of the Rim101/PacC family, which are activated by proteolytic cleavage. The proteolytic complex includes scaffold protein Rim20 and endosome-associated subunits of the endosomal sorting complex required for transport (ESCRT). We provide here evidence that Saccharomyces cerevisiae Rim13, the protease that is implicated in Rim101 cleavage, is associated with the Rim20-ESCRT complex, and we investigate its regulation. Rim13-GFP is dispersed in cells grown in acidic medium but forms punctate foci when cells encounter alkaline conditions. A vps4Δ mutant, which accumulates elevated levels of endosomal ESCRT, also accumulates elevated levels of Rim13-GFP foci, independently of external pH. In the vps4Δ background, mutation of ESCRT subunit Snf7 or of Rim20 blocks the formation of Rim13 foci, and we found that Rim13 and Rim20 are colocalized. The Rim13 ortholog PalB of Aspergillus nidulans has been shown to undergo ESCRT and membrane association through an N-terminal MIT domain, but Rim13 orthologs in the Saccharomyces clade lack homology to this N-terminal region. Instead, there is a clade-limited C-terminal region, and we show that point mutations in this region prevent punctate localization and impair Rim13 function. We suggest that RIM13 arose from its ancestral gene through two genome rearrangements. The ancestor lost the coding region for its MIT domain through a 5′ rearrangement and acquired the coding region for the Saccharomyces-specific functional equivalent through a 3′ rearrangement.
The Effects of a Multimodal Intervention on Outcomes of Persons With Early-Stage Dementia

Theories supporting the existence of a use-dependent neuroplasticity in the older brain were used to guide this pilot study. A repeated-measures randomized design was used to test the effectiveness of a multimodal (Taiji exercises, cognitive-behavioral therapies, support group) intervention on cognitive functioning, physical functioning, and behavioral outcomes in persons with dementia. The treatment group (n = 24 persons with dementia) participated in a 40-week intervention, with outcomes assessed at 20 and 40 weeks to assess optimal treatment length. Control group subjects (n = 19 persons with dementia) received attention-control educational programs. At 20 weeks, differences between groups were found for mental ability and self-esteem, with gains in balance being evident. Also, stability in depression and physical health were evident at 20 and 40 weeks for treatment group subjects. Continued improvement in outcomes was not observed at 40 weeks. However, findings support further testing of the intervention along with potential for achieving positive outcomes in early-stage dementia.
Functional Differentiation of tbf1 Orthologues in Fission and Budding Yeasts

ABSTRACT In Saccharomyces cerevisiae, TBF1, an essential gene, influences telomere function but also has other roles in the global regulation of transcription. We have identified a new member of the tbf1 gene family in the mammalian pathogen Pneumocystis carinii. We demonstrate by transspecies complementation that its ectopic expression can provide the essential functions of Schizosaccharomyces pombe tbf1 but that there is no rescue between fission and budding yeast orthologues. Our findings indicate that an essential function of this family of proteins has diverged in the budding and fission yeasts and suggest that effects on telomere length or structure are not the primary cause of inviability in S. pombe tbf1 null strains.
Monitoring ``De Novo'' APP Synthesis by Taking Advantage of the Reversible Effect of Cycloheximide

By blocking ``de novo'' protein synthesis using cycloheximide, we previously described a dynamic model system to monitor turnover of a specific population of the Alzheimer's amyloid precursor protein. Here we show that cycloheximide is nontoxic and its effect is reversible, allowing protein synthesis to reinitiate. Upon cycloheximide removal protein synthesis restarted and by 1 hour the amyloid precursor protein— green fluorescent protein could be clearly detected, permitting the monitoring of amyloid precursor protein anterograde transport, particularly the secretory pathway. The consensus NPTY motif in amyloid precursor protein, typically associated with endocytosis, was mutated to NPTF or NPTE to mimic a constitutively dephosphorylated or phosphorylated residue, respectively. Our data reveal that disruption of this motif affects amyloid precursor protein endocytosis, as shown previously, but also its incorporation into trans-Golgi network budding vesicles. Thus, cycloheximide can be a useful tool to study both anterograde and retrograde ``in vivo'' protein transport.
Our Paths Might Cross: the Role of the Fungal Cell Wall Integrity Pathway in Stress Response and Cross Talk with Other Stress Response Pathways

ABSTRACT Fungi occupy diverse environments and are subjected to many extreme conditions. Among the stressful conditions faced by fungi are pH changes, osmotic changes, thermal changes, oxide radicals, nutrient deprivation, and exposure to chemicals. These adversities can be found either in the environment or in animal and human hosts. The cell wall integrity (CWI) pathway provides a means to fortify and repair damages to the cell wall in order to withstand stressful environments. The CWI pathway in comprised of cell wall stress sensors that lead to activation of a mitogen-activated protein kinase (MAPK) cascade. Signaling through the MAPK cascade leads to expression of transcription factors that facilitate biosynthesis of cell wall components and actin organization. Given the relatively limited number of components of the CWI pathway and the very diverse stimuli, there must be a means of expanding the pathway. To manage the diverse stress conditions, the CWI pathway cross talks with other pathways or proteins, and these cross talk events enhance the signaling capabilities of the CWI pathway. Lateral influences that facilitate maintaining the cell wall under stress conditions are TOR signaling, calcineurin signaling, the high-osmolarity glycerol pathway, the cyclic AMP-protein kinase A pathway, and additional proteins. In this article, we highlight several of the cross talk events that have been described for Saccharomyces cerevisiae and several other fungi.
100 Years After Alzheimer: Contemporary Neurology Practice Assessment of Referrals for Dementia

Background: The prevalence of dementia is placing an increased burden on specialists. Methods: Canadian neurologists responded to a structured questionnaire to assess reasons for referral and services provided as well as to compare the neurologists' perceptions of their practice characteristics against cases seen over a 3-month period. Results: The audit confirmed the participants' perception that family practitioners are the main referral source (358/453, 79%). Sixty-two percent of patients had undergone clinical investigation for dementia prior to being seen by the neurologist; 39% (177/453) were on pharmacotherapy at the time of referral, 68% were initiated on pharmacotherapy by the neurologist. A fifth of the referrals did not meet clinical criteria for dementia, which may be directly related to the prevalence of prior workup that did not include mental status testing. Conclusions: Neurologists currently treat patients referred for dementia who may already have been adequately evaluated and treated by primary care providers.
Evolutionary Dynamics of Mating-Type Loci of Mycosphaerella spp. Occurring on Banana

ABSTRACT The devastating Sigatoka disease complex of banana is primarily caused by three closely related heterothallic fungi belonging to the genus Mycosphaerella: M. fijiensis, M. musicola, and M. eumusae. Previous phylogenetic work showing common ancestry led us to analyze the mating-type loci of these Mycosphaerella species occurring on banana. We reasoned that this might provide better insight into the evolutionary history of these species. PCR and chromosome-walking approaches were used to clone the mating-type loci of M. musicola and M. eumusae. Sequences were compared to the published mating-type loci of M. fijiensis and other Mycosphaerella spp. , and a novel organization of the MAT loci was found. The mating-type loci of the examined Mycosphaerella species are expanded, containing two additional Mycosphaerella-specific genes in a unique genomic organization. The proteins encoded by these novel genes show a higher interspecies than intraspecies homology. Moreover, M. fijiensis, M. musicola, and M. eumusae contain two additional mating-type-like loci, containing parts of both MAT1-1-1 and MAT1-2-1. The data indicate that M. fijiensis, M. musicola, and M. eumusae share an ancestor in which a fusion event occurred between MAT1-1-1 and MAT1-2-1 sequences and in which additional genes became incorporated into the idiomorph. The new genes incorporated have since then evolved independently in the MAT1-1 and MAT1-2 loci. Thus, these data are an example of the evolutionary dynamics of fungal MAT loci in general and show the great flexibility of the MAT loci of Mycosphaerella species in particular.
EEG Markers Discriminate Among Different Subgroup of Patients With Mild Cognitive Impairment

Aim of the study is to discriminate among participants with mild cognitive impairment through electroencephalography brain rhythms. A total of 79 participants with MCI were classified into 4 subgroups based on the beginning of memory complaints up to the time of first visit. All participants underwent electroencephalography recording, magnetic resonance imaging, apolipoprotein E characterization, and volumetric morphometry estimation of hippocampal region. Electroencephalography markers show 2 distinct patterns: (1) increase of theta/ delta power ratio and highest value of alpha2 band power in the group with shorter duration of disease, the greater right-left hippocampal volume difference and worst memory performance; (2) the highest value of alpha3 band power and the highest alpha3/alpha2 power ratio in the group with the lesser total hippocampal volume but preserved memory performance. Apolipoprotein E4 is linked to a major risk of early beginning of disease. Electroencephalography markers allow a mean correct percentage of correct classification up to 89%.
Multiple Mobile Data Offloading Through Disruption Tolerant Networks

To cope with explosive traffic demands on current cellular networks of limited capacity, Disruption Tolerant Networking (DTN) is used to offload traffic from cellular networks to high capacity and free device-to-device networks. Current DTN-based mobile data offloading models are based on simple and unrealistic network assumptions which do not take into account the heterogeneity of mobile data and mobile users. We establish a mathematical framework to study the problem of multiple-type mobile data offloading under realistic assumptions, where (i) mobile data are heterogeneous in terms of size and lifetime; (ii) mobile users have different data subscribing interests; and (iii) the storages of offloading helpers are limited. We formulate the objective of achieving maximum mobile data offloading as a submodular function maximization problem with multiple linear constraints of limited storage, and propose three algorithms, suitable for the generic and more specific offloading scenarios, respectively, to solve this challenging optimization problem. We show that the designed algorithms effectively offload data to the DTN by using both the theoretical analysis and simulation investigations which employ both real human and vehicular mobility traces.
Contactless Respiration Monitoring Via Off-the-Shelf WiFi Devices

Non-invasive human sensing based on radio signals has attracted numerous research interests in recent years. Previous work mainly focused on detecting the presence of a person or identifying human gestures and activities. In this paper, we show that with off-the-shelf WiFi devices, fine-grained respiration information of a person under different sleeping positions can be extracted successfully. We do this by introducing a breath monitoring system based on WiFi signals. This system adopts off-the-shelf WiFi devices to continuously collect the fine-grained wireless channel state information (CSI) around a person. From the CSI, the rhythmic patterns associated with respiration and abrupt changes due to the body movement are identified. Compared to existing respiration monitoring systems that usually require special devices attached to human body, this system is completely contactless. In addition, different from many vision-based sleep monitoring systems, it is robust to low-light environments and does not raise privacy concerns. Preliminary testing results show that our system can reliably track a person's respiration reliably in different sleeping postures.
Role of Tec1 in the Development, Architecture, and Integrity of Sexual Biofilms of Candida albicans

ABSTRACT MTL-homozygous (a/a or α/α) white cells form a complex sexual biofilm that exhibits the same architecture as that of MTL-heterozygous (a/α) pathogenic biofilms. However, the former is regulated by the mitogen-activated protein (MAP) kinase pathway, while the latter is regulated by the Ras1/cyclic AMP (cAMP) pathway. We previously demonstrated that in the formation of an MTL-homozygous, mature (48 h) sexual biofilm in RPMI 1640 medium, the MAP kinase pathway targets Tec1 rather than Cph1, the latter of which is the target of the same pathway, but for the opaque cell mating response. Here we continued our analysis of the role of Tec1 by comparing the effects of deleting TEC1 on initial adhesion to silicone elastomer, high-resolution confocal microscopy assessments of the stages and cellular phenotypes during the 48 h of biofilm development, human white cell penetration, and biofilm fragility. We show that although Tec1 plays only a minor role in initial adhesion to the silicone elastomer, it does play a major role in the growth of the basal yeast cell polylayer, vertical extension of hyphae and matrix deposition in the upper portion of the biofilm, final biofilm thickness, penetrability of human white blood cells, and final biofilm integrity (i.e., resistance to fluid flow). These results provide a more detailed description of normal biofilm development and architecture and confirm the central role played by the transcription factor Tec1 in the biofilm model employed here.
Internet-Based Program for Dementia Caregivers

The overall goal of the Internet-Based Savvy Caregiver (IBSC) program was to develop and bring to market an Internet-based psycho-educational program designed to provide dementia caregivers the knowledge, skills, and outlook they need to undertake and succeed in the caregiving role they have assumed. The IBSC program’s concept is based on a face-to-face caregiver-training program and curriculum, the previously validated Savvy Caregiver Program (SCP). The project used an iterative design with expert and consumer input to develop the initial prototype. Forty-seven participants completed the IBSC program and follow-up questionnaire. Results of the formative evaluation showed that participants found the program educational, convenient, useful, and interesting. Participants endorsed feeling more confident in caregiving skills and communication with their family members. The evidence points to the feasibility of an Internet-based program to strengthen family caregivers’ confidence in caring for persons with dementia.
Quantifying Interdependent Privacy Risks with Location Data

Co-location information about users is increasingly available online. For instance, mobile users more and more frequently report their co-locations with other users in the messages and in the pictures they post on social networking websites by tagging the names of the friends they are with. The users’ IP addresses also constitute a source of co-location information. Combined with (possibly obfuscated) location information, such co-locations can be used to improve the inference of the users’ locations, thus further threatening their location privacy: As co-location information is taken into account, not only a user's reported locations and mobility patterns can be used to localize her, but also those of her friends (and the friends of their friends and so on). In this paper, we study this problem by quantifying the effect of co-location information on location privacy, considering an adversary such as a social network operator that has access to such information. We formalize the problem and derive an optimal inference algorithm that incorporates such co-location information, yet at the cost of high complexity. We propose some approximate inference algorithms, including a solution that relies on the belief propagation algorithm executed on a general Bayesian network model, and we extensively evaluate their performance. Our experimental results show that, even in the case where the adversary considers co-locations of the targeted user with a single friend, the median location privacy of the user is decreased by up to 62 percent in a typical setting. We also study the effect of the different parameters (e.g., the settings of the location-privacy protection mechanisms) in different scenarios.
tRNA Gene Sequences Are Required for Transcriptional Silencing in Entamoeba histolytica

ABSTRACT Transcriptional silencing by trans inactivation can contribute to the regulation of gene expression in eukaryotic cells. In the human intestinal protozoan parasite Entamoeba histolytica, trans inactivation of the amoebapore-A gene (AP-A) was recently achieved by episomal transfection of E. histolytica trophozoites with the plasmid psAP1. The mechanism of AP-A trans inactivation is largely unknown, though it was suggested that a partial short interspersed transposable element (SINE) is required. By systematic assessment of various E. histolytica isolates transfected with psAP1 derivates, trans inactivation of AP-A was restricted to the strain HM-1:IMSS (2411) but could not be achieved in other standard laboratory strains. Importantly, sequences of an E. histolytica tRNA array that were located on psAP1 in close proximity to the AP-A upstream region and comprising the glutamic acid (TTC) (E) and tyrosine (GTA) (Y) tRNA genes were indispensable for AP-A silencing. In contrast to the case described in previous reports, SINE was not required for AP-A trans inactivation. AP-A expression could be regained in silenced cells by episomal transfection under the control of a heterologous E. histolytica promoter, opening a way toward future silencing of individual genes of interest in E. histolytica. Our results indicate that tRNA gene-mediated silencing is not restricted to Saccharomyces cerevisiae.
Changes in the N-Glycome, Glycoproteins with Asn-Linked Glycans, of Giardia lamblia with Differentiation from Trophozoites to Cysts

ABSTRACT Giardia lamblia is present in the intestinal lumen as a binucleate, flagellated trophozoite or a quadranucleate, immotile cyst. Here we used the plant lectin wheat germ agglutinin (WGA), which binds to the disaccharide di-N-acetyl-chitobiose (GlcNAc2), which is the truncated Asn-linked glycan (N-glycan) of Giardia, to affinity purify the N-glycomes (glycoproteins with N-glycans) of trophozoites and cysts. Fluorescent WGA bound to the perinuclear membranes, peripheral acidified vesicles, and plasma membranes of trophozoites. In contrast, WGA bound strongly to membranes adjacent to the wall of Giardia cysts and less strongly to the endoplasmic reticulum and acidified vesicles. WGA lectin-affinity chromatography dramatically enriched secreted and membrane proteins of Giardia, including proteases and acid phosphatases that retain their activities. With mass spectroscopy, we identified 91 glycopeptides with N-glycans and 194 trophozoite-secreted and membrane proteins, including 42 unique proteins. The Giardia oligosaccharyltransferase, which contains a single catalytic subunit, preferred N glycosylation sites with Thr to those with Ser in vivo but had no preference for flanking amino acids. The most-abundant glycoproteins in the N-glycome of trophozoites were lysosomal enzymes, folding-associated proteins, and unique transmembrane proteins with Cys-, Leu-, or Gly-rich repeats. We identified 157 secreted and membrane proteins in the Giardia cysts, including 20 unique proteins. Compared to trophozoites, cysts were enriched in Gly-rich repeat transmembrane proteins, cyst wall proteins, and unique membrane proteins but had relatively fewer Leu-rich repeat proteins, folding-associated proteins, and unique secreted proteins. In summary, there are major changes in the Giardia N-glycome with the differentiation from trophozoites to cysts.
Agitation and Psychosis Associated With Dementia With Lewy Bodies Exacerbated by Modafinil Use

Dementia with Lewy bodies (DLB) is commonly associated with excessive daytime somnolence (EDS). Modafinil is a wakefulness-promoting agent that is considered to have limited interaction with the dopaminergic system. As individuals with DLB are predisposed to psychotic symptoms that might be exacerbated by dopaminergic stimulation, modafinil is considered to be an attractive option for the treatment of EDS in DLB. We describe 2 cases in which administration of modafinil exacerbated agitation and hallucinations in DLB, and we also review data that may explain the mechanisms underlying this effect. In both cases, psychotic symptoms emerged concomitantly with modafinil administration and remitted following its discontinuation. Although definitive data regarding the benefits and adverse effects of modafinil for the treatment of EDS in DLB await controlled prospective randomized studies, our observations warrant caution regarding its use in this context.