Miracle-dz/UniFAR-FTUs huggingface dataset:
miRNAs and Multiple Myeloma: Focus on the Pathogenesis, Prognosis, and Drug Resistance

Multiple myeloma (MM) produces clonal plasma cells and aberrant monoclonal antibody accumulation in patients’ bone marrow (BM). Around 1% of all cancers and 13% of hematological malignancies are caused by MM, making it one of the most common types of cancer. Diagnostic and therapeutic methods for managing MM are currently undergoing extensive research. MicroRNAs (miRNAs) are short noncoding RNAs that reduce or inhibit the translation of their target mRNA after transcription. Because miRNAs play an influential role in how myeloma develops, resources, and becomes resistant to drugs, miRNA signatures may be used to diagnose, do prognosis, and treat the myeloma response. Consequently, researchers have investigated the levels of miRNA in plasma cells from MM patients and developed tools to test whether they directly impacted tumor growth. This review discusses the latest discoveries in miRNA science and their role in the development of MM. We also emphasize the potential applications of miRNAs to diagnose, prognosticate, and treat MM in the future.
Malaria species positivity rates among symptomatic individuals across regions of differing transmission intensities in Mainland Tanzania

Recent data indicate that non-Plasmodium falciparum species may be more prevalent than previously realized in sub-Saharan Africa, the region where 95% of the world's malaria cases occur. Although Plasmodium malariae, Plasmodium ovale spp. , and Plasmodium vivax are generally less severe than P. falciparum, treatment and control are more challenging, and their geographic distributions are not well characterized. In order to characterize the distribution of malaria species in Mainland Tanzania (which has a high burden and geographically heterogeneous transmission levels), we randomly selected 3,284 samples from 12,845 samples to determine presence and parasitemia of different malaria species. The samples were collected from cross-sectional surveys in 100 health facilities across ten regions and analyzed via quantitative real-time PCR to characterize regional positivity rates for each species. P. falciparum was most prevalent, but P. malariae and P. ovale were found in all regions except Dar es Salaam, with high levels (>5%) of P. ovale in seven regions (70%). The highest positivity rate of P. malariae was 4.5% in Mara region and eight regions (80%) had positivity rates [≥]1%. We also detected three P. vivax infections in the very low-transmission Kilimanjaro region. While most samples that tested positive for non-falciparum malaria were co-infected with P. falciparum, 23.6% (n = 13/55) of P. malariae and 14.7% (n = 24/163) of P. ovale spp. samples were mono-infections. P. falciparum remains by far the largest threat, but our data indicate that malaria elimination efforts in Tanzania will require increased surveillance and improved understanding of the biology of non-falciparum species.
Structural dynamics at the active site of the cancer‐associated flavoenzyme NQO1 probed by chemical modification with PMSF

A large conformational heterogeneity of human NAD(P)H:quinone oxidoreductase 1 (NQO1), a flavoprotein associated with various human diseases, has been observed to occur in the catalytic site of the enzyme. Here, we report the X‐ray structure of NQO1 with phenylmethylsulfonyl fluoride (PMSF) at 1.6 Å resolution. Activity assays confirmed that, despite being covalently bound to the Tyr128 residue at the catalytic site, PMSF did not abolish NQO1 activity. This may indicate that the PMSF molecule does not reduce the high flexibility of Tyr128, thus allowing NADH and DCPIP substrates to bind to the enzyme. Our results show that targeting Tyr128, a key residue in NQO1 function, with small covalently bound molecules could possibly not be a good drug discovery strategy to inhibit this enzyme.
Development, Validation, and Usability of the Chatbot ESTOMABOT to Promote Self-care of People With Intestinal Ostomy

This study aimed to describe the process of construction, validation, and usability of the chatbot ESTOMABOT to assist in the self-care of patients with intestinal ostomies. Methodological research was conducted in three phases: construction, validation, and usability. The first stage corresponded to the elaboration of a script through a literature review, and the second stage corresponded to face and content validation through a panel of enterostomal therapy nurses. In the third phase, the usability of ESTOMABOT was assessed with the participation of surgical clinic nurses, patients with intestinal elimination ostomies, and information technology professionals, using the System Usability Scale. The ESTOMABOT content reached excellent criteria of adequacy, with percentages of agreement equal to or greater than 90%, which were considered adequate, relevant, and representative. The evaluation of the content validity of the script using the scale content validity index/average proportion method reached a result above 0.90, and the Fleiss κ was excellent (P < .05). The overall usability score of the chatbot was 81.5, demonstrating excellent usability. The script, developed and incorporated into the ESTOMABOT prototype, achieved satisfactory content validity. The usability of the chatbot was considered to be good, thereby increasing the credibility of the instrument.
Temporal trends of post-contrast acute kidney injury in patients with intravenous administration of iodinated contrast medium

Abstract Little is known about whether preventative practices for post-contrast acute kidney injury (PC-AKI) recommended in guidelines have been adopted in clinical practice and translated into a lower incidence of PC-AKI. The aim of this study was to examine the yearly trends in the incidence of PC-AKI, and comorbidities and care practices associated with PC-AKI in hospitalized patients who received intravenous administration of iodinated contrast medium (ICM). Adult patients receiving intravenous ICM at the Second Xiangya Hospital of Central South University in China between 2015 and 2021 were included. Temporal trends in the incidence and risk factors for PC-AKI were evaluated using logistic regression analyses with adjustments for relevant variables. The incidence of PC-AKI has declined significantly from 5.3% in 2015 to 4.1% in 2021 (p < 0.001). This decreasing trend persisted after extensive multivariable adjustments. Of the comorbidities associated with PC-AKI, the proportion of patients with congestive heart failure or hypertension increased, while the proportion of patients older than 75 years, or with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, diabetic nephropathy, or renal stone disease decreased. Among the care practices associated with PC-AKI, the proportion of patients using nephrotoxic drugs decreased, whereas the proportion of patients receiving intravenous fluids > 1000 mL on the day of ICM administration or using iso-osmolar ICM increased. In conclusion, a declining trend in PC-AKI incidence was observed in patients receiving intravenous ICM between 2015 and 2021, which may be related to increased awareness and efforts to prevent PC-AKI.
A Novel Aberrantly Spliced Gain-of-Function NT5C2 Isoform Contributes to Thiopurine Resistance in Acute Lymphoblastic Leukemia

Relapse-specific mutations do not account for all chemotherapy failures in patients with B-cell acute lymphoblastic leukemia (B-ALL). By mining RNA-seq datasets of paired diagnostic/relapse pediatric B-ALL samples, we discovered pervasive aberrant splicing (AS) patterns linked with relapse. They affected drivers of resistance to glucocorticoids, anti-folates, and thiopurines. Most splicing variations represent exon skipping, “poison” exon inclusion, and intron retention, phenocopying well-documented loss-of-function mutations. In addition, relapse-associated AS of NT5C2 mRNA yields an isoform with a cryptic 24-nt in-frame exon 6a. Inclusion of the extra 8 amino acids into this enzyme results in elevated nucleosidase activity, a known consequence of gain-of-function mutations in NT5C2 and a common determinant of 6-mercaptopurine resistance. Furthermore, in B-ALL cells NT5C2ex6a and the R238W hotspot variant confers comparable levels of resistance to 6-mercaptopurine in vitro and in vivo. These results support a role for alternative splicing as a prevalent mechanism driving chemotherapy resistance in relapsed B-ALL. Statement of significance Mutations in chemoresistance genes are found in relapsed/refractory acute lymphoblastic leukemia. However, in this low-mutational-burden disease, up to 30% of cases have no known relapse-specific genetic alterations. Our identification of aberrant splicing as an alternative mechanism of acquired drug resistance fills this gap and suggests new opportunities for therapeutic interventions.
Paleoseismological investigations on a slow-moving active fault in central Anatolia, Tecer Fault, Sivas

Tecer Fault is a N60˚-70˚E-trending, left-lateral, strike-slip fault to the south of the town of Sivas, Turkey. This fault is considered as the eastward continuation of Deliler Fault, which was classified as a probably active, left-lateral fault on the Active Fault Map of Turkey. We investigated the field characteristics and paleoseismic history of Tecer Fault in detail. After analyzing aerial photographs and satellite images, we mapped the exact fault trace on a 1/25,000 scale topographic map, between the towns of Deliilyas in southwest and Bogazdere in northeast. Tecer Fault is characterized by morphological features such as offset streams and gullies, linear depressions and scarps, and elongated hills. Four paleoseismological trenches were excavated on the northeastern extent of the fault. Two past earthquakes were identified in these trenches, and the dates of the collected charcoal samples suggested that the first of these earthquakes occurred about 8000 B.C. while the more recent event took place around 3500 B.C. Field observations and paleoseismic data indicate that Tecer Fault is an active, pure sinistral, strike-slip fault, and that there is about a 4500 years time span between the two earthquakes. It is also clear that there has not been any surface-ruptured faulting over the last 800 years. Compared with the earthquake characteristics of other strike-slip fault zones in Turkey in terms of time-slip relations, the slip rate can be estimated as about 1 mm/yr on Tecer Fault.
Calculation and study for the growth process and electrical characteristics of the conductive filament in nanoscale resistance memory under current-driven mode

After investigating the behavior of ions during the growth of conductive filaments, we suggested a model for the growth process and electrical characteristics of the conductive filament under current-driven mode. In this model, the ionic displacement equation is derived by Arrhenius law, and a differential equation for the conductive filament growth has been established. We have also proved that the dielectric layer with the leakage current under current-driven mode can be equivalent to a parallel plate capacitor, which has a the equivalent dielectric constant. Consequently, the forming/set time of the device is gotten. At the same time, the kinetics process of ion motion is analyzed in detail, so that many microscopic parameters of the ion motion, such as the height of the potential barrier, the jump step, mobility and diffusion coefficient, can be obtained. Due to divalent and monovalent copper ions all participate in conduction, an equivalent copper ion Cuz+ is used for replacing both Cu+ and Cu2+, solving the computational complexity problem caused by multivalent metal ions. Finally, an equivalent circuit is proposed to calculate output voltage versus time characteristic. The calculation results of the model are consistent with experimental data.
A new laser technology for LISA

Within the European Space Agency (ESA) activity “Gravitational Wave Observatory Metrology Laser” we designed a laser head to fulfill the LISA laser requirements using a non-NPRO seed laser technology: an external cavity diode laser (ECDL) with resonant optical feedback from an external cavity as master oscillator for further linewidth narrowing. Furthermore, our design features a single-stage fiber amplifier with an amplification factor of about 20 dB. This paper covers the requirements on the laser source for LISA, the design and first results of performance characterization of the laser head breadboard.
ddtlcm: An R package for overcoming weak separation in Bayesian latent class analysis via tree-regularization

Traditional applications of latent class models (LCMs) often focus on scenarios where a set of unobserved classes are well-defined and easily distinguishable. However, in numerous real-world applications, these classes are weakly separated and difficult to distinguish, creating significant numerical challenges. To address these issues, we have developed an R package ddtlcm that provides comprehensive analysis and visualization tools designed to enhance the robustness and interpretability of LCMs in the presence of weak class separation, particularly useful for small sample sizes. This package implements a tree-regularized Bayesian LCM that leverages statistical strength between latent classes to make better estimates using limited data. A Shiny app has also been developed to improve user interactivity. In this paper, we showcase a typical analysis pipeline with simulated data using ddtlcm. All software has been made publicly available on CRAN and GitHub.
Efficacy and safety of cannabidiol for the treatment of canine osteoarthritis: a systematic review and meta-analysis of animal intervention studies

Introduction Canine osteoarthritis (OA) is a degenerative disease with chronic inflammation of internal and external joint structures in dogs. Cannabis spp. contains cannabidiol (CBD), a substance known for various potential indications, such as pain relief and anti-inflammatory in various types of animals, including dogs with OA. As CBD is increasingly in the spotlight for medical use, we aimed to perform a systematic review and meta-analysis to evaluate the efficacy and safety of CBD in treating canine OA. Methods We searched PubMed, Embase, Scopus, and CAB Direct for animal intervention studies investigating the effects of CBD for canine OA from database inception until February 28, 2023. Study characteristics and findings were summarized. A risk of bias in the included studies was assessed. Meta-analyses were performed using a random-effects model to estimate the effects of CBD on pain scores (0–10), expressed as mean difference (MD) and 95% confidence interval (95% CI). Certainty of evidence was assessed using GRADE. Results Five articles were included, which investigated the effects of CBD in 117 dogs with OA. All studies were rated as having a high risk of bias. CBD products varied substantially, i.e., oral full-spectrum CBD oil in four studies, and isolated CBD oil and liposomal CBD oil in another study. Treatment duration varied from 4–12 weeks. Meta-analyses of three studies found that, in dogs with OA, treatment with oral full-spectrum CBD oil may reduce pain severity scores (MD; −0.60, 95% CI; −1.51 to 0.31, I2 = 45.64%, p = 0.19) and pain interference scores (MD; −1.52, 95% CI; −3.84 to 0.80, I2 = 89.59%, p = 0.20) but the certainty of evidence was very low. CBD is generally considered safe and well-tolerated in the short-run, with few mild adverse events observed, such as vomiting and asymptomatic increase in alkaline phosphatase level. Conclusion CBD is considered safe for treating canine OA. CBD may reduce pain scores, but the evidence is very uncertain to conclude its clinical efficacy. High-quality clinical trials are needed to further evaluate the roles of CBD in canine OA.
Artificial neural network modeling of solar photovoltaic panel energy output

Solar panel energy output is an essential parameter for the design and operation of renewable energy systems. Previously, little was known about the precise relationship between the energy outputs of solar panels with various meteorological, radiometric, and weather conditions in the southern California region. Without precise modeling or prediction systems, solar energy can potentially be wasted due to grid energy fluctuation. Thus, it is intended to use an artificial neural network (ANN) to develop solar panel energy output prediction model with a high degree of accuracy. A self-developed feedforward ANN model utilizing the Rectified linear unit (ReLu) activation function was used in the present study. Meteorological, weather, and sun irradiation data collected throughout the last year from a residential location have been used to train the models. The model’s performance was identified based on the minimum mean absolute error (MAE) and root mean square error (RMSE) and maximum linear correlation coefficient (R2). Further, the present self-developed ANN model was consistent with other solar energy experimental results and theoretical analysis. The developed ANN model using the Python programming language achieved a high R2 of more than 85% which ascertains the accuracy and suitability of the model to predict the daily solar energy output in local southern California area. This ANN modeling approach can be extended to many other applications such as SCORE, commercial, and residential building design.
A latent cardiomyocyte regeneration potential in human heart disease

Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate around 0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial. Using retrospective 14C birth dating we analyzed cardiomyocyte renewal in patients with end-stage heart failure. We show that cardiomyocyte generation is minimal in end-stage heart failure patients at rates 18-50 times lower compared to the healthy heart. However, patients receiving left ventricle support device therapy, who showed significant functional and structural cardiac improvement, had a >6-fold increase in cardiomyocyte renewal relative to the healthy heart. Our findings reveal a substantial cardiomyocyte regeneration potential in human heart disease, which could be exploited therapeutically.
The Intricacies of Sprott-B System with Fractional-Order Derivatives: Dynamical Analysis, Synchronization, and Circuit Implementation

Studying simple chaotic systems with fractional-order derivatives improves modeling accuracy, increases complexity, and enhances control capabilities and robustness against noise. This paper investigates the dynamics of the simple Sprott-B chaotic system using fractional-order derivatives. This study involves a comprehensive dynamical analysis conducted through bifurcation diagrams, revealing the presence of coexisting attractors. Additionally, the synchronization behavior of the system is examined for various derivative orders. Finally, the integer-order and fractional-order electronic circuits are implemented to validate the theoretical findings. This research contributes to a deeper understanding of the Sprott-B system and its fractional-order dynamics, with potential applications in diverse fields such as chaos-based secure communications and nonlinear control systems.
Gallation and B-Ring Dihydroxylation Increase Green Tea Catechin Residence Time in Plasma by Differentially Affecting Tissue-Specific Trafficking: Compartmental Model of Catechin Kinetics in Healthy Adults

Catechins in green tea extract (GTE) (epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), epicatechin gallate (ECG)) vary in bioactivity. We developed a physiologically relevant mathematical model of catechin metabolism to test the hypothesis that fractional catabolic rates of catechins would be differentially affected by their structural attributes. Pharmacokinetic data of plasma and urine catechin concentrations were used from healthy adults (n = 19) who ingested confections containing 0.5 g GTE (290 mg EGCG, 87 mg EGC, 39 mg EC, 28 mg ECG). A 7-compartmental model of catechin metabolism comprised of the gastrointestinal tract (stomach, small and large intestine), liver, plasma, extravascular tissues, and kidneys was developed using a mean fraction dose of EGCG, ECG, EGC, and EC. Fitting was by iterative least squares regression analysis, and goodness of fit was ascertained by the estimated variability of parameters (FSD < 0.5). The interaction of gallation and B-ring dihydroxylation most greatly extended plasma residence time such that EGC > EC = EGCG > EGC. The interaction between gallation and B-ring dihydroxylation accelerated the transfer from the upper gastrointestinal tract to the small intestine but delayed subsequent transfers from the small intestine through the liver to plasma and from kidneys to urine. Gallation and B-ring dihydroxylation independently delayed the transfer from plasma to extravascular tissues, except the uptake to kidneys, which was slowed by gallation only. This multi-compartment model, to be validated in a future study, suggests that gallation and B-ring dihydroxylation affect catechin catabolism in a tissue-specific manner and thus their potential bioactivity.
Therapies and Challenges in the Post-Stroke Aphasia Rehabilitation Arena: Current and Future Prospects

Aphasia is a serious consequence of stroke that results in a breakdown in communication. The course of aphasia recovery differs between afflicted individuals, and responsiveness to treatment cannot be predicted. Aphasiologists continue to investigate numerous behavioral treatment protocols that have shifted their focus to complimentary rehabilitation strategies. The aim of this study is threefold. First, to summarize the different categories of aphasia interventions post-stroke, considering their respective protocols, and present available evidence on the effectiveness of those protocols. Second, to document the challenges regarding the prediction of aphasia treatment response post-stroke in individual patients. Third, to report the challenges faced by researchers in recruiting people with aphasia (PWA) for treatment studies, and provide recommendations on how to increase participant recruitment and retention. This study provides up-to-date information on (i) effective therapies and aphasia recovery processes, and (ii) research recruitment hurdles together with potential strategies for overcoming them.