Miracle-dz/UniFAR-FTUs huggingface dataset:
Visual Short-term Memory Impairments in Presymptomatic Familial Alzheimer’s Disease: a Longitudinal Observational Study

Background: Cross-sectional studies in presymptomatic familial Alzheimer’s disease (FAD), have associated binding de�cits with preclinical AD. How impairments in visual-short term memory (VSTM) relate to longitudinal change and proximity to expected symptom onset (EYO) is less characterized. Methods: Thirty-two FAD mutation carriers (23 presymptomatic; 9 symptomatic) carrying a mutation in either presenilin 1 or amyloid precursor protein genes and 67 healthy controls were included in an extension VSTM cross-sectional study. Forty-eight participants (23 presymptomatic carriers, 6 symptomatic and 19 healthy controls) who had at least two annual visits (median= 3), were included in the longitudinal study. Participants completed the “What was where? ” relational binding task (which measures memory for object identi�cation, localisation and object-location binding under different conditions of memory load and delay), neuropsychology assessments and genetic testing. Results: While cross-sectionally only symptomatic carriers (N=9) showed signi�cant impairments in VSTM performance, longitudinally, presymptomatic carriers within 8.5 years of estimated symptom onset (mean=5.8 years ±SD [1.8], N=11) showed a faster rate of decline in localisation performance in long-delay conditions (4s) compared to controls: increase/year in localisation error was 6.9% greater in the high-memory load condition (p=0.008) and 7.0% greater for the low-memory load condition (p=0.043). Change in this metric preceded presymptomatic changes in traditional measures of verbal episodic memory. Symptomatic carriers had 15% faster reduction in identi�cation performance per year compared to controls (p=0.036) and some evidence of faster increase in localisation error (6.5% increase/year; p=0.066). The earliest signi�cant difference in VSTM performance between FAD mutation carriers (presymptomatic and symptomatic) and controls was in localisation performance, six years prior to estimated symptom onset (p=0.024).
En länk till Gud i cd-format? : Om qawwalimusiken i rörelse och globaliseringskrafter

Denna text handlar om qawwalimusiken. Qawwali ar en musikform medrotterna i Indien och Pakistan. Den ar ocksa en del av en specifik religios tradition namligen sufismen. Qawwali ar en musikalisk ge .
DIRAC OPERATORS

The spectral propinquity is a distance, up to unitary equivalence, on the class of metric spectral triples. We prove in this paper that if a sequence of metric spectral triples converges for the propinquity, then the spectra of the Dirac operators for these triples do converge to the spectrum of the Dirac oper- ator at the limit. We obtain this result by ﬁrst proving that, in an appropriate sense induced by some natural metric, the bounded, continuous functional cal-culi deﬁned by the Dirac operators also converge. As an application of our work, we see, in particular, that action functionals of a wide class of metric spectral triples are continuous for the spectral propinquity, which clearly connects convergence for the spectral propinquity with the applications of noncommutative geometry to mathematical physics. This fact is a consequence of results on the continuity of the multiplicity of eigenvalues of Dirac operators. In particular, we formalize convergence of adjoinable operators of diﬀerent C*-correspondences, endowed with appropriate quantum metric data.
A Survey on Self-supervised Learning: Algorithms, Applications, and Future Trends

Deep supervised learning algorithms typically require a large volume of labeled data to achieve satisfactory performance. However, the process of collecting and labeling such data can be expensive and time-consuming. Self-supervised learning (SSL), a subset of unsupervised learning, aims to learn discriminative features from unlabeled data without relying on human-annotated labels. SSL has garnered significant attention recently, leading to the development of numerous related algorithms. However, there is a dearth of comprehensive studies that elucidate the connections and evolution of different SSL variants. This paper presents a review of diverse SSL methods, encompassing algorithmic aspects, application domains, three key trends, and open research questions. Firstly, we provide a detailed introduction to the motivations behind most SSL algorithms and compare their commonalities and differences. Secondly, we explore representative applications of SSL in domains such as image processing, computer vision, and natural language processing. Lastly, we discuss the three primary trends observed in SSL research and highlight the open questions that remain. A curated collection of valuable resources can be accessed at https://github.com/guijiejie/SSL.
Design, synthesis, and in vitro biological evaluation of 14-hydroxytylophorine-dichloroacetate co-drugs as antiproliferative agents.

Co-drug, or mutual-prodrug, is a drug design approach consisting of covalently linking two active drugs so as to improve the pharmacokinetics and/or pharmacodynamics properties of one or both drugs. Co-drug strategy has proven good success in overcoming undesirable properties such as absorption, poor bioavailability, nonspecificity, and GIT side effects. In this work, we successfully developed a co-drug of 14-hydroxytylophorine, a phenanthroindolizidine derivative with remarkable antiproliferative activity, and dichloroacetate, a known inhibitor of pyruvate dehydrogenase kinase. Dichloroacetate steers tumour cell metabolism from glycolysis back to glucose oxidation, which in turn reverses the Warburg effect and renders tumour cells with a proliferative disadvantage. The obtained co-drugs retained the cytotoxicity of 14-hydroxytylophorine. However, they showed similar unselectivity towards normal cells.
A cyber-physical system to design 3D models using mixed reality technologies and deep learning for additive manufacturing

I-nteract is a cyber-physical system that enables real-time interaction with both virtual and real artifacts to design 3D models for additive manufacturing by leveraging mixed-reality technologies. This paper presents novel advances in the development of the interaction platform to generate 3D models using both constructive solid geometry and artificial intelligence. In specific, by taking advantage of the generative capabilities of deep neural networks, the system has been automated to generate 3D models inferred from a single 2D image captured by the user. Furthermore, a novel generative neural architecture, SliceGen, has been proposed and integrated with the system to overcome the limitation of single-type genus 3D model generation imposed by differentiable-rendering-based deep neural architectures. The system also enables the user to adjust the dimensions of the 3D models with respect to their physical workspace. The effectiveness of the system is demonstrated by generating 3D models of furniture (e.g., chairs and tables) and fitting them into the physical space in a mixed reality environment. The presented developmental advances provide a novel and immersive form of interaction to facilitate the inclusion of a consumer into the design process for personal fabrication.
Clinical Performance Evaluation of Continuous Glucose Monitoring Systems: A Scoping Review and Recommendations for Reporting

The use of different approaches for design and results presentation of studies for the clinical performance evaluation of continuous glucose monitoring (CGM) systems has long been recognized as a major challenge in comparing their results. However, a comprehensive characterization of the variability in study designs is currently unavailable. This article presents a scoping review of clinical CGM performance evaluations published between 2002 and 2022. Specifically, this review quantifies the prevalence of numerous options associated with various aspects of study design, including subject population, comparator (reference) method selection, testing procedures, and statistical accuracy evaluation. We found that there is a large variability in nearly all of those aspects and, in particular, in the characteristics of the comparator measurements. Furthermore, these characteristics as well as other crucial aspects of study design are often not reported in sufficient detail to allow an informed interpretation of study results. We therefore provide recommendations for reporting the general study design, CGM system use, comparator measurement approach, testing procedures, and data analysis/statistical performance evaluation. Additionally, this review aims to serve as a foundation for the development of a standardized CGM performance evaluation procedure, thereby supporting the goals and objectives of the Working Group on CGM established by the Scientific Division of the International Federation of Clinical Chemistry and Laboratory Medicine.
Performance of Sustainable Self-Compacting Fiber Reinforced Concrete with Substitution of Marble Waste (MW) and Coconut fibers (CFs)

Self compacting concrete (SSC) is also brittle nature, resulting in abrupt failure without giving any warning, which is unacceptable for any construction materials. Therefore, SCC requires tensile reinforcement to increase tensile capacity and avoid the undesirable brittle failure of SCC. However, fiber improved tensile capacity more efficiently than compressive strength. Therefore, it important add pozzolanic material to fiber reinforced concrete to obtain high strength, durable and ductile concrete. This research is carried out to evaluate the qualities of concrete with addition of waste marble and coconut fiber in concrete. Marble waste used as binding (pozzolanic) materials in proportion of 5.0 to 30% by weight of cement in increment of 5.0% and concrete is reinforced with coconut fiber in proportion of 0.5% to 3.0% by weight of cement in increment of 0.5 %. Rheological properties were assessed through its passing ability and flowability by using Slump flow, Slump T50, L-Box, and V-funnel tests while mechanical performance were evaluated through compressive, split tensile, flexure and pull out tests. Tests results indicate that marble waste and coconut fiber decrease the passing ability and filling ability of SCC. Furthermore, tests results indicate that marble waste up to 20% and coconut fiber addition 2.0% by weight of cement have a tendency to enhance the mechanical strength of SCC. Finally, Statistical analysis (RSM) was used to optimize the combined substitution of marble waste and coconut fiber to obtain high strength concrete.
Cooperative effects of SIRT1 and SIRT2 on APP acetylation

Alzheimer's disease (AD) is an age‐related neurodegenerative disorder characterized by amyloid‐β (Aβ) deposition and neurofibrillary tangles. Although the NAD+‐dependent deacetylases SIRT1 and SIRT2 play pivotal roles in age‐related diseases, their cooperative effects in AD have not yet been elucidated. Here, we report that the SIRT2:SIRT1 ratio is elevated in the brains of aging mice and in the AD mouse models. In HT22 mouse hippocampal neuronal cells, Aβ challenge correlates with decreased SIRT1 expression, while SIRT2 expression is increased. Overexpression of SIRT1 prevents Aβ‐induced neurotoxicity. We find that SIRT1 impedes SIRT2‐mediated APP deacetylation by inhibiting the binding of SIRT2 to APP. Deletion of SIRT1 reduces APP recycling back to the cell surface and promotes APP transiting toward the endosome, thus contributing to the amyloidogenic processing of APP. Our findings define a mechanism for neuroprotection by SIRT1 through suppression of SIRT2 deacetylation, and provide a promising avenue for therapeutic intervention of AD.
Shared and organ-specific gene-expression programs during the development of the cochlea and the superior olivary complex

ABSTRACT The peripheral and central auditory subsystems together form a complex sensory network that allows an organism to hear. The genetic programs of the two subsystems must therefore be tightly coordinated during development. Yet, their interactions and common expression pathways have never been systematically explored. MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and are essential for normal development of the auditory system. We performed mRNA and small-RNA sequencing of organs from both auditory subsystems at three critical developmental timepoints (E16, P0, P16) to obtain a comprehensive and unbiased insight of their expression profiles. Our analysis reveals common and organ-specific expression patterns for differentially regulated mRNAs and miRNAs, which could be clustered with a particular selection of functions such as inner ear development, Wnt signalling, K+ transport, and axon guidance, based on gene ontology. Bioinformatics detected enrichment of predicted targets of specific miRNAs in the clusters and predicted regulatory interactions by monitoring opposite trends of expression of miRNAs and their targets. This approach identified six miRNAs as strong regulatory candidates for both subsystems. Among them was miR-96, an established critical factor for proper development in both subsystems, demonstrating the strength of our approach. We suggest that other miRNAs identified by this analysis are also common effectors of proper hearing acquirement. This first combined comprehensive analysis of the developmental program of the peripheral and central auditory systems provides important data and bioinformatics insights into the shared genetic program of the two sensory subsystems and their regulation by miRNAs.
A prospective cohort study identifies two types of HIV+ Kaposi Sarcoma lesions: proliferative and inflammatory

Kaposi sarcoma (KS) is the most common cancer in people living with HIV (PLWH) in many countries where KS‐associated herpesvirus is endemic. Treatment has changed little in 20 years, but the disease presentation has. This prospective cohort study enrolled 122 human immunodeficiency virus (HIV) positive KS patients between 2017 and 2019 in Malawi. Participants were treated with bleomycin, vincristine and combination antiretroviral therapy, the local standard of care. One‐year overall survival was 61%, and progression‐free survival was 58%. The 48‐week complete response rate was 35%. RNAseq (n = 78) differentiated two types of KS lesions, those with marked endothelial characteristics and those enriched in inflammatory transcripts. This suggests that different KS lesions are in different disease states consistent with the known heterogeneous clinical response to treatment. In contrast to earlier cohorts, the plasma HIV viral load of KS patients in our study was highly variable. A total of 25% of participants had no detectable HIV; all had detectable KSHV viral load. Our study affirms that many KS cases today develop in PLWH with well‐controlled HIV infection and that different KS lesions have differing molecular compositions. Further studies are needed to develop predictive biomarkers for this disease.
Citizen science approaches to crowdsourcing food environment data: A scoping review of the literature

Globally, the adoption and implementation of policies to improve the healthiness of food environments and prevent population weight gain have been inadequate. This is partly because of the complexity associated with monitoring dynamic food environments. Crowdsourcing is a citizen science approach that can increase the extent and nature of food environment data collection by engaging citizens as sensors or volunteered computing experts. There has been no literature synthesis to guide the application of crowdsourcing to food environment monitoring. We systematically conducted a scoping review to address this gap. Forty‐two articles met our eligibility criteria. Photovoice techniques were the most employed methodological approaches (n = 25 studies), commonly used to understand overall access to healthy food. A small number of studies made purpose‐built apps to collect price or nutritional composition data and were scaled to receive large amounts of data points. Twenty‐nine studies crowdsourced food environment data by engaging priority populations (e.g., households receiving low incomes). There is growing potential to develop scalable crowdsourcing platforms to understand food environments through the eyes of everyday people. Such crowdsourced data may improve public and policy engagement with equitable food policy actions.
Stomatal pore width and area measurements in Zea mays

Stomatal pores are adjustable microscopic holes on the surface of photosynthetic tissues that help regulate multiple aspects of plant physiology. Stomatal pores facilitate gas exchange necessary for photosynthesis, water transport, and temperature regulation. Pore size is influenced by many intertwined environmental, molecular, cellular, and physiological cues. Accurate and precise measurements of pore size is important for understanding the mechanisms that adjust pores and plant physiology. Here we investigate whether conventional pore measurements of width are appropriate for the economically important crop plant Zea mays . Our studies demonstrate that pore area is a more sensitive measurement than width in this plant.
The evolution of selective autophagy as a mechanism of oxidative stress response

Ageing is associated with a decline in autophagy and elevated reactive oxygen species (ROS), which can breach the capacity of antioxidant systems. Resulting oxidative stress can cause further cellular damage, including DNA breaks and protein misfolding. This poses a challenge for longevous organisms, including humans. In this review, we hypothesise that in the course of human evolution selective autophagy receptors (SARs) acquired the ability to sense and respond to localised oxidative stress. We posit that in the vicinity of protein aggregates and dysfunctional mitochondria oxidation of key cysteine residues in SARs induces their oligomerisation which initiates autophagy. The degradation of damaged cellular components thus could reduce ROS production and restore redox homeostasis. This evolutionarily acquired function of SARs may represent one of the biological adaptations that contributed to longer lifespan. Inversely, loss of this mechanism can lead to age‐related diseases associated with impaired autophagy and oxidative stress.
Kidney urinary biomarkers in patients with branched‐chain amino acid and cobalamin metabolism defects

There is a clinical need for early detection of chronic kidney disease (CKD) in patients with organic acidurias. We measured kidney markers in a longitudinal study over 5 years in 40 patients with methylmalonic aciduria (Mut0), propionic aciduria (PA), cobalamin A (CblA), and cobalamin C (CblC) deficiencies. Neutrophil gelatinase‐associated lipocalin (NGAL), calprotectin (CLP), kidney injury molecule‐1 (KIM‐1), dickkopf‐3 (DKK‐3), albumin and beta‐2‐microglobulin (B2MG) in urine, as well as cystatin C (CysC) in serum were quantified. In Mut0 patients, mean concentrations of B2MG, KIM‐1, and DKK‐3 were elevated compared with healthy controls, all markers indicative of proximal tubule damage. In PA patients, mean B2MG, albumin, and CLP were elevated, indicating signs of proximal tubule and glomerulus damage and inflammation. In CblC patients, mean B2MG, NGAL, and CLP were increased, and considered as markers for proximal and distal tubule damage and inflammation. B2MG, was elevated in all three diseases, and correlated with DKK‐3 in Mut0/CblA and with eGFR(CysC) and KIM‐1 in PA patients, respectively. None of the markers were elevated in CblA patients. Significant deterioration of kidney function, as determined by steady increase in CysC concentrations was noted in seven patients within the observation period. None of the investigated biomarker profiles showed a clear increase or added value for early detection. In conclusion, we identified disease‐specific biomarker profiles for inflammation, tubular, and proximal damage in the urine of Mut0, PA, and CblC patients. Whether these biomarkers can be used for early detection of CKD requires further investigation, as significant kidney function deterioration was observed in only a few patients.
Development of a simplified human embryonic stem cell-based retinal pre-organoid model for toxicity evaluations of common pollutants

Abstract Objective To explore the retinal toxicity of pharmaceuticals and personal care products (PPCPs), flame retardants, bisphenols, phthalates, and polycyclic aromatic hydrocarbons (PAHs) on human retinal progenitor cells (RPCs) and retinal pigment epithelial (RPE) cells, which are the primary cell types at the early stages of retinal development, vital for subsequent functional cell type differentiation, and closely related to retinal diseases. Materials and methods After 23 days of differentiation, human embryonic stem cell (hESC)-based retinal pre-organoids, containing RPCs and RPE cells, were exposed to 10, 100, and 1000 nM pesticides (butachlor, terbutryn, imidacloprid, deltamethrin, pendimethalin, and carbaryl), flame retardants (PFOS, TBBPA, DBDPE, and TDCIPP), PPCPs (climbazole and BHT), and other typical pollutants (phenanthrene, DCHP, and BPA) for seven days. Then, mRNA expression changes were monitored and compared. Results (1) The selected pollutants did not show strong effects at environmental and human-relevant concentrations, although the effects of flame retardants were more potent than those of other categories of chemicals. Surprisingly, some pollutants with distinct structures showed similar adverse effects. (2) Exposure to pollutants induced different degrees of cell detachment, probably due to alterations in extracellular matrix and/or cell adhesion. Conclusions In this study, we established a retinal pre-organoid model suitable for evaluating multiple pollutants’ effects, and pointed out the potential retinal toxicity of flame retardants, among other pollutants. Nevertheless, the potential mechanisms of toxicity and the effects on cell detachment are still unclear and deserve further exploration. Additionally, this model holds promise for screening interventions aimed at mitigating the detrimental effects of these pollutants.
Outcomes of topography-guided PRK/CXL in keratoconus using the NIDEK CXIII system—”Bharat Protocol” (Pilot study)

Purpose: Outcome of topography-guided excimer laser ablation in conjunction with accelerated, high-fluence cross-linking in corneal ecstatic disease using the NIDEK CXIII equipped with CATz algorithm from the FinalFit software—”Bharat Protocol. ” Methods: Retrospective case record review of 30 eyes of 17 patients of stage 1-3 keratoconus who underwent the procedure was performed. Data collected were for visual acuity, distortion-induced eye pain, and keratometry. Pachymetry, lower order and higher order aberrations, spherical aberrations, and topographic cylinder were documented from by Scheimpflug imaging (Pentacam 70700: Oculus, Wetzlar, Germany). Results: At a minimum follow-up of 6 months (range 6.2–13 months), there was significant improvement in UCVA (P < 0.00001), BCVA (P = 0.0061), decrease in Kmax (P = 0.0349), Ksteep (P < 0.0411), Kflat (P = 0.0099), and pachymetry (P = 0.0001). Significant improvement was also seen in distortion-induced eye pain (27/30 to 2/30; P < 0.00001). A more than two-line improvement in UCVA and BCVA was seen in 23/30 and 17/30 cases, respectively. Ectasia was stabilized in all cases at the last follow-up, and no complications were seen. Conclusions: The “Bharat” Protocol to arrest keratectasia progression and improve corneal regularity is a safe and efficacious alternative as a keratoconus management option. This is the first such study on Nidek Platform for the same.