Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimal Weighting of Preclinical Alzheimer’s Cognitive Composite (PACC) Scales to Improve their Performance as Outcome Measures for Alzheimer’s Disease Clinical Trials

Introduction: Cognitive composite scales constructed by combining existing neuropsychometric tests are seeing wide application as endpoints for clinical trials and cohort studies of Alzheimer’s disease (AD) predementia conditions. Preclinical Alzheimer’s Cognitive Composite (PACC) scales are composite scores calculated as the sum of the component test scores weighted by the reciprocal of their standard deviations at the baseline visit. Reciprocal standard deviation is an arbitrary weighting in this context, and may be an inefficient utilization of the data contained in the component measures. Mathematically derived optimal composite weighting is a promising alternative. Methods: Sample size projections using standard power calculation formulas were used to describe the relative performance of component measures and their composites when used as endpoints for clinical trials. Power calculations were informed by (n=1,333) amnestic mild cognitive impaired participants in the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set. Results: A composite constructed using PACC reciprocal standard deviation weighting was both less sensitive to change than one of its component measures and less sensitive to change than its optimally weighted counterpart. In standard sample size calculations informed by NACC data, a clinical trial using the PACC weighting would require 38% more subjects than a composite calculated using optimal weighting. Discussion: These findings illustrate how reciprocal standard deviation weighting can result in inefficient cognitive composites, and underscore the importance of component weights to the performance of composite scales. In the future, optimal weighting parameters informed by accumulating clinical trial data may improve the efficiency of clinical trials in AD.
Substantiation of creation of transdermal forms of drug delivery with antihypertensive action

The article presents the theoretical justification for the choice of active pharmaceutical ingredients of antihypertensive action for the creation of new forms of delivery - transdermal therapeutic systems. Purpose: monitoring of studies on the use of angiotensin-converting enzyme (ACE) inhibitors in the development of transdermal drugs for the treatment of hypertension. Materials: open access electronic resources of scientific periodicals from around the world: Google Scholar (https://scholar.google.com/); PubMed (https://pubmed.ncbi.nlm.nih.gov/); Sciencedirect (https://www.sciencedirect.com/); Pubchem (https://pubchem.ncbi.nlm.nih.gov/); National Library of Ukraine named after V. I. Vernadskyi (http://www.nbuv.gov.ua/); Ukrainian Institute of Intellectual Property (Ukrpatent) (https://sis.ukrpatent.org/uk/); Industrial Property (https://base.uipv.org/searchBul/); USPTO. The United States Patent and Trademark Office (https://www.uspto.gov/patents/search); European Patent Office (EPO) (https://www.epo.org/). Methods of the research: information search, theoretical analysis and systematization of data from scientific sources, logical analysis. Results: a review of scientific sources was carried out, and an analysis of ACE inhibitors as candidates for the creation of transdermal forms for the treatment of arterial hypertension was carried out. The pharmacological and physicochemical aspects of the possibility of their use for introduction through the skin are defined. It has been established that the search and development of the latest means of treatment of arterial hypertension, which would significantly increase the duration and quality of life of patients, are extremely relevant. Transdermal drug delivery systems are one of the pharmaceutical products being developed on the world market, and their use allows overcoming the associated disadvantages of other delivery routes. Conclusions: the review of domestic and foreign literature confirmed the relevance of biopharmaceutical research in the field of development of innovative dosage forms - transdermal therapeutic systems for the treatment of hypertension. The choice of promising antihypertensive active pharmaceutical ingredients of the ACE group (enalapril maleate, lisinopril dihydrate, and captopril) is substantiated, taking into account their specific physicochemical properties that are suitable for penetration through the skin. The market for transdermal drug delivery is increasing, and there is a prospect of higher growth rates in this market in the coming years
The Properties of Linezolid, Rifampicin, and Vancomycin, as Well as the Mechanism of Action of Pentamidine, Determine Their Synergy against Gram-Negative Bacteria

Combining pentamidine with Gram-positive-targeting antibiotics has been proven to be a promising strategy for treating infections from Gram-negative bacteria (GNB). However, which antibiotics pentamidine can and cannot synergize with and the reasons for the differences are unclear. This study aimed to identify the possible mechanisms for the differences in the synergy of pentamidine with rifampicin, linezolid, tetracycline, erythromycin, and vancomycin against GNB. Checkerboard assays were used to detect the synergy of pentamidine and the different antibiotics. To determine the mechanism of pentamidine, fluorescent labeling assays were used to measure membrane permeability, membrane potential, efflux pump activity, and reactive oxygen species (ROS); the LPS neutralization assay was used to evaluate the target site; and quantitative PCR was used to measure changes in efflux pump gene expression. Our results revealed that pentamidine strongly synergized with rifampicin, linezolid, and tetracycline and moderately synergized with erythromycin, but did not synergize with vancomycin against E. coli, K. pneumoniae, E. cloacae, and A. baumannii. Pentamidine increased the outer membrane permeability but did not demolish the outer and inner membranes, which exclusively permits the passage of hydrophobic, small-molecule antibiotics while hindering the entry of hydrophilic, large-molecule vancomycin. It dissipated the membrane proton motive force and inactivated the efflux pump, allowing the intracellular accumulation of antimicrobials that function as substrates of the efflux pump, such as linezolid. These processes resulted in metabolic perturbation and ROS production which ultimately was able to destroy the bacteria. These mechanisms of action of pentamidine on GNB indicate that it is prone to potentiating hydrophobic, small-molecule antibiotics, such as rifampicin, linezolid, and tetracycline, but not hydrophilic, large-molecule antibiotics like vancomycin against GNB. Collectively, our results highlight the importance of the physicochemical properties of antibiotics and the specific mechanisms of action of pentamidine for the synergy of pentamidine–antibiotic combinations. Pentamidine engages in various pathways in its interactions with GNB, but these mechanisms determine its specific synergistic effects with certain antibiotics against GNB. Pentamidine is a promising adjuvant, and we can optimize drug compatibility by considering its functional mechanisms.
Evaluation of the Knowledge of the Most Common Cancers Among Health Students at Jazan University, Saudi Arabia: A Cross-Sectional Study

Background: Cancer is a major public health problem worldwide, and medical students are expected to have adequate knowledge and awareness of the most common types of cancer. This study aimed to assess the cancer knowledge of medical students at Jazan University, Saudi Arabia, focusing on breast cancer (BC), prostate cancer (PC), cervical cancer (CC), and colorectal cancer (CRC). Methods: This study employed a self-administered survey to evaluate both general and specialized knowledge of cancer types. A total of 321 medical students from different academic years participated in the study. The questionnaire used a scoring system where each correct answer was given one point, and each incorrect answer or “I don’t know” response was given zero points. Results: The overall knowledge scores were 18.75 ± 4.43 out of 28 (67%). The students had a good level of general knowledge about cancer (5.26 ± 1.44 out of 7, 75%) and breast cancer (5.47 ± 1.44 out of 7, 78%) and a moderate knowledge level of prostate cancer (2.83 ± 1.07 out of 4, 71%), cervical cancer (2.74 ± 1.53 out of 5, 55%), and colorectal cancer (2.55 ± 1.61 out of 5, 50%). There were significant differences in cancer knowledge by gender, academic year, and having a relative or friend with cancer. All types of cancer knowledge were positively and significantly correlated with each other. Conclusion: This study revealed the strengths and weaknesses of cancer knowledge among medical students at Jazan University, Saudi Arabia. The overall score for knowledge indicated a moderate level. The students had some knowledge about cancer prevention, detection, and treatment, but some gaps and misconceptions need to be addressed. More education and awareness programs are necessary to improve cancer literacy among students and promote healthy behaviors that can reduce cancer risk.
The effect of dialogic-practical work on secondary school students mechanics achievement

This study aimed to examine the effects of dialogic-practical work on secondary school students‘ mechanics' achievement. It also examined whether the students‘ mechanics achievement would vary with achievement levels. A quasi-experimental pre- and post-test research design was used. The study participants were 91 students from two secondary schools in Bahir Dar town, Ethiopia. The treatment group conducted dialogic-practical work and the comparison group carried out recipe-based practical work. A 25-item Mechanics Achievement Test was used for data collection. A paired- and independent sample t-tests were performed to analyze the data. It was found that there was a statisitcally significant difference in mechanics achievement between the dialogic-and recipe-based practical work groups, t (76) = 7.80, p < . 001, d= 1.76. It also indicated that the dialogic-practical work resulted more improvements in mechanics achievement of the different achievement levels as compared to the recipe-based practical work. This suggests that students who engaged in dialogic practical work enhanced their mechanics achievement more than students who simply follow prescribed recipes. It is important to raise physics teachers’ awareness about the benefits of dialogic-practical work to enhance students’ mechanics' achievement.
Game values and equilibria for undetermined sentences of Dependence Logic

Logics of imperfect information, such as IF-Logic or Dependence Logic, admit a game-theoretic semantics: every formula φ corresponds to a gameH(φ) between a Verifier and a Falsifier, and the formula is true [false] if and only if the Verifier [Falsifier] has a winning strategy. Since the rule of the excluded middle does not hold in these logics, it is possible for a game H(φ) to be undetermined; this thesis attempts to examine the values of such games, that is, the maximum expected payoffs that the Verifier is able to guarantee. For finite models, the resulting “Probabilistic Dependence Logic” can be shown, by means of the Minimax Theorem, to admit a compositional semantics similar to Hodges’ one for Slash Logic.
Site-Directed Mutations at Phosphorylation Sites in Zea mays PHO1 Reveal Modulation of Enzymatic Activity by Phosphorylation at S566 in the L80 Region

Starch phosphorylase (PHO) is a pivotal enzyme within the GT35-glycogen–phosphorylase (GT; glycosyltransferases) superfamily. Despite the ongoing debate surrounding the precise role of PHO1, evidence points to its substantial influence on starch biosynthesis, supported by its gene expression profile and subcellular localization. Key to PHO1 function is the enzymatic regulation via phosphorylation; a myriad of such modification sites has been unveiled in model crops. However, the functional implications of these sites remain to be elucidated. In this study, we utilized site-directed mutagenesis on the phosphorylation sites of Zea mays PHO1, replacing serine residues with alanine, glutamic acid, and aspartic acid, to discern the effects of phosphorylation. Our findings indicate that phosphorylation exerts no impact on the stability or localization of PHO1. Nonetheless, our enzymatic assays unveiled a crucial role for phosphorylation at the S566 residue within the L80 region of the PHO1 structure, suggesting a potential modulation or enhancement of PHO1 activity. These data advance our understanding of starch biosynthesis regulation and present potential targets for crop yield optimization.
Cervical muscle morphometry and composition demonstrate prognostic value in degenerative cervical myelopathy outcomes

Objectives This study aimed to examine whether preoperative cervical muscle size, composition, and asymmetry from magnetic resonance imaging (MRI) can predict post-operative outcomes in patients with degenerative cervical myelopathy (DCM). Methods A total of 171 patients with DCM were included. Relative total cross-sectional area (RCSA), functional CSA (fat-free area, FCSA), ratio of FCSA/CSA (fatty infiltration) and asymmetry of the multifidus (MF) and semispinalis cervicis (SCer) together (MF + SCer), and cervical muscle as a group (MF, SCer, semispinalis capitis, and splenius capitis) were obtained from T2-weighted axial MR images at the mid-disk, at the level of maximum cord compression and the level below. Univariate and multivariate linear regression analyses were used to assess the relationship between baseline cervical muscle measurements of interest with the modified Japanese Orthopedic Association (mJOA), Nurick Classification, Neck Disability Index (NDI), and SF-36 health survey at 6-month and 12-month post-surgery. Results Lower RCSA of MF + SCer, less CSA MF + SCer asymmetry and greater FCSA/CSA for the cervical muscle group (e.g., less fatty infiltration), and younger age were significant predictors of higher mJOA scores (e.g., less disability) at 6-month and 12-month post-surgery (all p < 0.05). Greater CSA asymmetry in MF + SCer and lower FCSA/CSA (e.g., more fatty infiltration) for the cervical muscle group were significant predictors of higher Nurick scores (e.g., more disability) at 6-month and 12-month post-surgery (all p < 0.05). Lower FCSA MF + Scer asymmetry, lower FCSA/CSA asymmetry of the muscle group, and greater RCSA MF + SCer were significant predictors of higher NDI scores at 6-month and 12-month post-surgery. Finally, greater FCSA/CSA asymmetry of the MF + SCer, greater FCSA asymmetry of the muscle group, greater RCSA of the muscle group, and greater CSA asymmetry of MF + SCer were significant predictors of lower post-operative SF-36 scores at 6- and 12-month post-surgery. Conclusion Our result suggested that cervical paraspinal muscle morphology, specifically greater asymmetry, and fatty infiltration may be important predictors of functional recovery and post-surgical outcomes in patients with DCM.
Characterizing the Variability of a Physical Driver of North Atlantic Right Whale Foraging Habitat Using Altimetric Indices

Physical ocean circulation features, especially the Gaspé Current (GC) intrusion, influence the transport and aggregation of whale prey, thereby influencing the whale foraging habitat in the Gulf of St. Lawrence (GSL), Canada. We employ satellite altimetry-derived sea level anomaly (SLA) indices to monitor interannual variations in the intensity of the GC in the North Atlantic Right Whale (Eubalaena glacialis; NARW) habitat in the GSL. Measurements of surface slope and volume transport are taken from the SLA profiles along a repeating ground track of the Jason-2/3 satellites. These are employed as complementary proxies in characterizations of physical processes in the GSL. The relationship between altimetric indices and indices of zooplankton abundance are explored in the southern GSL. Results demonstrate that an altimetric index estimated from surface slope (Indexslope−half) is correlated with river discharge of the St. Lawrence River and can be utilized to infer variations in GC intensities. Time series of the altimetric indices during 2009–2021 are found to exhibit interannual and seasonal environmental variability, which influence transport into the southern GSL. As captured by the altimetric indices, these features of the surface ocean circulation can be linked to zooplankton variations in the Shediac Valley, where NARWs are frequently observed. Therefore, in linking physical drivers of ocean dynamics to the NARW foraging habitat, variations in these indices can also potentially help describe some features of the distribution patterns of NARW sightings in this area.
A Study of Cockroach (Dictyoptera: Blattidae) Infestation in Different Types of Residential Buildings in Makurdi. Nigeria.

Environmental assessment of 234 residential apartments in Makurdi was undertaken after which cockroaches were collected from kitchens and toilets from 2400 -0200 h between Mar. and Jul. 2006 using the killing and counting technique. One hundred and forty three (61.6%) of the residential apartments visited had occupant ratio of>4 persons per room. A total of 4,037 cockroaches were collected in 88.5% of residential apartments visited; the toilet and kitchen accounted for 54.6% and 45.4% of the collection, respectively. The American cockroach, Periplaneta americana, and the German cockroach, Blattela germanica, were the predominant species encountered; the least was Supella longipalpi. There was no significant difference in species preference for kitchen or toilet (X2 = 0.11, df= 1, P>0.05). The number of cockroaches collected from multi-unit apartments with several tenants was significantly higher than the numbers collected from duplex or detached buildings (X2 = l3.8, df = 2, P<0.05). Overcrowding and poor maintenance of buildings were common to all the study locations and these enhanced cockroach infestation. There is an urgent need to put in place a comprehensive cockroach prevention and control intervention strategy that will emphasize community participation in planning and implementation in order to protect and safeguard human health.
The Heterogeneity of Social Network and Institutional Covariance in the American Southeast

Abstract Social, political, and economic institutions covary with one another in heterogenous ways across space and time. Social Network Analysis (SNA) offers a set of analytical tools and conceptual frameworks that have allowed for formal comparisons of interactions, affiliations, and relationships in reconstructing historical trajectories of institutional change. Although archaeologists have made full use of a range of metrics that describe the structural variation of social networks, formal approaches to analyzing the covariance of networks, and the institutions that structured networks in the past, remain undertheorized. In most cases, descriptive metrics are compared between networks built from different datasets or networks separated in time. Using quadratic assignment procedure (QAP) correlations to compare matrices of archaeological data, I draw on a ceramic dataset of approximately 350,000 sherds from the Southern Appalachian region to investigate how decisions related to manufacture choice and to stylistic design covaried with one another between roughly AD 800 and 1650. I explore how material attributes may or may not vary independently of one another and what that means for our analyses of the institutions they reflect. The results contribute to broader comparative analyses of institutional change and perennial discussions of social evolution.
Living with the European Union: The Northern Ireland Experience

List of Tables Notes on the Contributors Preface Introduction: Portrait of a Region A Region Among Regions: The Wider View T.Christiansen Europe and the Northern Ireland Economy G.Gudgin Changing Scene: EU Impact on the Rural Economy J.Davis Trading Partners: Northern Ireland's External Economic Links E.Birnie For Richer or Poorer: The Social Impact Q.Oliver European Rules and a Changing Environment J.S. Furphy Europe and the Northern Ireland Problem D.Kennedy The European Connection and Public Opinion M.L. Smith Index
An Overview of CD133 as a Functional Unit of Prognosis and Treatment Resistance in Glioblastoma

Biomarkers for resistance in Glioblastoma multiforme (GBM) are lacking, and progress in the clinic has been slow to arrive. CD133 (prominin-1) is a membrane-bound glycoprotein on the surface of cancer stem cells (CSCs) that has been associated with poor prognosis, therapy resistance, and tumor recurrence in GBM. Due to its connection to CSCs, to which tumor resistance and recurrence have been partially attributed in GBM, there is a growing field of research revolving around the potential role of CD133 in each of these processes. However, despite encouraging results in vitro and in vivo, the biological interplay of CD133 with these components is still unclear, causing a lack of clinical application. In parallel, omic data from biospecimens that include CD133 are beginning to emerge, increasing the importance of understanding CD133 for the effective use of these highly dimensional data sets. Given the significant mechanistic overlap, prioritization of the most robust findings is necessary to optimize the transition of CD133 to clinical applications using patient-derived biospecimens. As a result, this review aims to compile and analyze the current research regarding CD133 as a functional unit in GBM, exploring its connections to prognosis, the tumor microenvironment, tumor resistance, and tumor recurrence.
The effect of Surround sound on embodiment and sense of presence in cinematic experience: a behavioral and HD-EEG study

Although many studies have investigated spectators' cinematic experience, only a few of them explored the neurophysiological correlates of the sense of presence evoked by the spatial characteristics of audio delivery devices. Nevertheless, nowadays both the industrial and the consumer markets have been saturated by some forms of spatial audio format that enrich the audio-visual cinematic experience, reducing the gap between the real and the digitally mediated world. The increase in the immersive capabilities corresponds to the instauration of both the sense of presence and the psychological sense of being in the virtual environment and also embodied simulation mechanisms. While it is well-known that these mechanisms can be activated in the real world, it is hypothesized that they may be elicited even in a virtual acoustic spatial environment and could be modulated by the acoustic spatialization cues reproduced by sound systems. Hence, the present study aims to investigate the neural basis of the sense of presence evoked by different forms of mediation by testing different acoustic space sound delivery (Presentation modes: Monophonic, Stereo, and Surround). To these aims, a behavioral investigation and a high-density electroencephalographic (HD-EEG) study have been developed. A large set of ecological and heterogeneous stimuli extracted from feature films were used. Furthermore, participants were selected following the generalized listener selection procedure. We found a significantly higher event-related desynchronization (ERD) in the Surround Presentation mode when compared to the Monophonic Presentation mode both in Alpha and Low-Beta centro-parietal clusters. We discuss this result as an index of embodied simulation mechanisms that could be considered as a possible neurophysiological correlation of the instauration of the sense of presence.