Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetics of Renal Function during Induction in Newly Diagnosed Multiple Myeloma: Results of Two Prospective Studies by the German Myeloma Study Group DSMM

Simple Summary Renal insufficiency is frequently seen in newly diagnosed multiple myeloma and can be due to the disease itself but also caused by medical interventions or infections. Patients with severe renal insufficiency are known to have an adverse prognosis, but recently, it was shown that even moderately impaired kidney function can have long-term sequelae. Achieving quick disease control by effective antimyeloma therapy can lead to the recovery of renal function. We investigated the kidney-specific variables in a large cohort of 770 myeloma patients receiving three different three-drug regimens for initial myeloma treatment to learn more about the differential effects on kidney function in an early disease phase. All regimens had a positive impact on kidney function without a difference in the proportion of patients who reached normal renal function after three cycles. Interestingly, patients who received bortezomib, lenalidomide, and dexamethasone tended to have higher risk for a worse renal function following induction when compared to the initial values. Abstract Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD). The minimum required estimated glomerular filtration rate (eGFR) was >30 mL/min. We analyzed the percent change of the renal function using the International Myeloma Working Group (IMWG) criteria and Kidney Disease: Improving Global Outcomes (KDIGO)-defined categories. Results: Seven hundred and seventy-two patients were eligible. Three hundred and fifty-six received VCD, 214 VRd, and 202 RAD. VCD patients had the best baseline eGFR. The proportion of pts with eGFR <45 mL/min decreased from 7.3% at baseline to 1.9% PInd (p < 0.0001). Thirty-seven point one percent of VCD versus 49% of VRd patients had a decrease of GFR (p = 0.0872). IMWG-defined “renal complete response (CRrenal)” was achieved in 17/25 (68%) pts after VCD, 12/19 (63%) after RAD, and 14/27 (52%) after VRd (p = 0.4747). Conclusions: Analyzing a large and representative newly diagnosed myeloma (NDMM) group, we found no difference in CRrenal that occurred independently from the myeloma response across the three regimens. A trend towards deterioration of the renal function with VRd versus VCD may be explained by a better pretreatment “renal fitness” in the latter group.
NUTRITIONAL COMPOSITION AND SENSORY PROPERTIES OF IRON FORTIFIED FUFU FLOUR

Cassava fufu flour was fortified with iron Sulphate, iron fumarate and sodium iron EDTA at three concentrations (25, 35 and 45 mg/kg) in this study. The samples were analyzed for proximate and minerals composition as well as sensory and pasting properties. There were significant differences (p 0.05) in sensory taste, texture and odour of unfortified and fortified samples. In terms of overall acceptability, panelists rated unfortified cassava products higher followed by samples with 25 mg/kg NaFeEDTA and iron sulphate respectively. The rate of return on investment for iron fortified fufu flour was 1.41. The study has shown that the use of iron fortified cassava products has potentials for practical application and economic viability.
Effects of a Home Literacy Environment Program on Psychlinguistic Variables in Children from 6 to 8 Years of Age

(1) Background: the objective of this study was to improve certain psycholinguistic and cognitive skills that are fundamental to the development of the reading process, such as phonological awareness, reading decoding, vocabulary and oral narrative comprehension, through the introduction of an Home Literacy Environment Active (HLE(A)) program that involved 54 participants enrolled in the first and second grades of elementary school (from 6 to 8 years old) in the city of Malaga area. (2) Methods: The central task of the intervention program was for the child to read aloud to an adult in the family for between 10 and 15 min, four days per week. In addition, the school students were evaluated on four occasions, at the beginning and end of each academic year, using the Batería de Evaluación de los Procesos Lectores Revisada, Test para la Detección de la Dislexia en niños and Escala Weschsler de Inteligencia instruments. (3) Results: the results demonstrated the efficacy of the HLE(A) program in the improvement of psycholinguistic and cognitive variables measured and, consequently, to an improvement in reading learning and cognitive development. Ultimately, the scientific literature on the subject and the data from the study led us to suggest that it would not only be beneficial for HLE(A) programs to be instituted in early childhood education stage (up to 6 years of age), but that they should be continued after age 6, in elementary education.
Characterization of Differentially Expressed Circulating miRNAs in Metabolically Healthy versus Unhealthy Obesity

Obese individuals without metabolic comorbidities are categorized as metabolically healthy obese (MHO). MicroRNAs (miRNAs) may be implicated in MHO. This cross-sectional study explores the link between circulating miRNAs and the main components of metabolic syndrome (MetS) in the context of obesity. We also examine oxidative stress biomarkers in MHO vs. metabolically unhealthy obesity (MUO). We analysed 3536 serum miRNAs in 20 middle-aged obese individuals: 10 MHO and 10 MUO. A total of 159 miRNAs were differentially expressed, of which, 72 miRNAs (45.2%) were higher and 87 miRNAs (54.7%) were lower in the MUO group. In addition, miRNAs related to insulin signalling and lipid metabolism pathways were upregulated in the MUO group. Among these miRNAs, hsa-miR-6796-5p and hsa-miR-4697-3p, which regulate oxidative stress, showed significant correlations with glucose, triglycerides, HbA1c and HDLc. Our results provide evidence of a pattern of differentially expressed miRNAs in obesity according to MetS, and identify those related to insulin resistance and lipid metabolism pathways.
A Generative Adversarial Network for Infrared and Visible Image Fusion Based on Semantic Segmentation

This paper proposes a new generative adversarial network for infrared and visible image fusion based on semantic segmentation (SSGAN), which can consider not only the low-level features of infrared and visible images, but also the high-level semantic information. Source images can be divided into foregrounds and backgrounds by semantic masks. The generator with a dual-encoder-single-decoder framework is used to extract the feature of foregrounds and backgrounds by different encoder paths. Moreover, the discriminator’s input image is designed based on semantic segmentation, which is obtained by combining the foregrounds of the infrared images with the backgrounds of the visible images. Consequently, the prominence of thermal targets in the infrared images and texture details in the visible images can be preserved in the fused images simultaneously. Qualitative and quantitative experiments on publicly available datasets demonstrate that the proposed approach can significantly outperform the state-of-the-art methods.
New Cladosporium Species from Normal and Galled Flowers of Lamiaceae

A series of isolates of Cladosporium spp. were recovered in the course of a cooperative study on galls formed by midges of the genus Asphondylia (Diptera, Cecidomyidae) on several species of Lamiaceae. The finding of these fungi in both normal and galled flowers was taken as an indication that they do not have a definite relationship with the midges. Moreover, identification based on DNA sequencing showed that these isolates are taxonomically heterogeneous and belong to several species which are classified in two different species complexes. Two new species, Cladosporium polonicum and Cladosporium neapolitanum, were characterized within the Cladosporium cladosporioides species complex based on strains from Poland and Italy, respectively. Evidence concerning the possible existence of additional taxa within the collective species C. cladosporioides and C. pseudocladosporioides is discussed.
Barley Leaf Insoluble Dietary Fiber Alleviated Dextran Sulfate Sodium-Induced Mice Colitis by Modulating Gut Microbiota

Supplementation of dietary fiber has been proved to be an effective strategy to prevent and relieve inflammatory bowel disease (IBD) through gut microbiota modulation. However, more attention has been paid to the efficacy of soluble dietary fiber than that of insoluble dietary fiber (IDF). In the present study, we investigated whether IDF from barley leaf (BLIDF) can inhibit gut inflammation via modulating the intestinal microbiota in DSS-induced colitis mice. The mice were fed 1.52% BLIDF-supplemented diet for 28 days. Results demonstrated that feeding BLIDF markedly mitigated DSS-induced acute colitis symptoms and down-regulated IL-6, TNF-α, and IL-1β levels in the colon and serum of colitis mice. BLIDF supplementation effectively reduced the abundance of Akkermansia and increased the abundance of Parasutterella, Erysipelatoclostridium, and Alistipes. Importantly, the anti-colitis effects of BLIDF were abolished when the intestinal microbiota was depleted by antibiotics. Furthermore, the targeted microbiota-derived metabolites analysis suggested that BLIDF feeding can reverse the DSS-induced decline of short-chain fatty acids and secondary bile acids in mice feces. Finally, BLIDF supplementation elevated the expression of occludin and mucin2, and decreased the expression of claudin-1 in colons of DSS-treated mice. Overall, our observations suggest that BLIDF exerts anti-inflammatory effects via modulating the intestinal microbiota composition and increasing the production of microbiota-derived metabolites.
Segmented School Physical Activity and Weight Status in Children: Application of Compositional Data Analysis

The purpose of this study was to apply compositional data analysis (CoDA) for the analysis of segmented school step counts and associate the school step count composition to body mass index (BMI) z-scores in a sample of children. Participants were 855 (51.8% female) children recruited from the fourth and fifth grades from four schools following a 7-h school schedule. Using piezoelectric pedometers, step count data were collected during physical education, recess, lunch, and during academic class time. A multi-level mixed effects model associated the step count composition with BMI z-scores. Compositional isotemporal substitution determined changes in BMI z-scores per reallocation of steps between pairs of school segments. A higher percentage of steps accrued during physical education (b = −0.34, 95%CI: −0.65–−0.03, p = 0.036) and recess (b = −0.47, 95%CI: −0.83–−0.11, p = 0.012), relative to other segments, was associated with lower BMI z-scores. Specifically, a 5% to 15% reallocation of steps accrued during lunchtime to either physical education or recess was associated with lower BMI z-scores, ranging from −0.07 to −0.25 standard deviation units. Focusing school-based promotion of physical activity during physical education and recess may have greater relative importance if targeted outcomes are weight-related.
The Association between Blood Pressure Trajectories and Risk of Cardiovascular Diseases among Non-Hypertensive Chinese Population: A Population-Based Cohort Study

Although previous studies have discussed the association between trajectories of blood pressure (BP) and risk of cardiovascular diseases (CVDs), the association among the non-hypertensive general population of youth and middle age has not been elucidated. We used the growth mixture model to explore the trajectories of BP among the non-hypertensive Chinese population and applied Cox regression to evaluate the association between trajectories of BP and the risk of stroke or myocardial infarction (MI). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were categorized into three classes, respectively. Statistically significant associations were observed between SBP trajectories and stroke (range of adjusted hazard ratios (aHR): 1.369–3.837) or MI (rang of aHR = 6.047–13.017). Association between DBP trajectories and stroke (aHR: 3.685) or MI (range of aHR = 1.312–2.821) were also observed, although they did not reach statistical significance. Trajectories of SBP were more important risk factors than that of DBP in stroke and MI in our study population. BP management is important among pre-hypertensive adults to prevent stroke and MI when they age. Well-designed research with a larger sample size is required to confirm our findings and develop efficient methods to prevent CVDs.
Pan-Cancer Analysis of Human Kinome Gene Expression and Promoter DNA Methylation Identifies Dark Kinase Biomarkers in Multiple Cancers

Simple Summary Due to their central role in many biological processes, studies on protein kinases are an area of active research. In the last few decades, several inhibitors that target kinases have been approved by U.S. Food and Drug Administration (FDA). However, a large proportion of kinases remain uncharacterized, with very little information on their functionality. Variations in genome-wide DNA methylation and gene expression pattern have been extensively studied in many cancers. However, an extensive kinome-centered pan-cancer methylation and expression analysis are still lacking. This study aims to identify prognostic and diagnostic biomarkers, focusing on uncharacterized (dark) kinases to further encourage their research as therapeutic targets. Abstract Kinases are a group of intracellular signaling molecules that play critical roles in various biological processes. Even though kinases comprise one of the most well-known therapeutic targets, many have been understudied and therefore warrant further investigation. DNA methylation is one of the key epigenetic regulators that modulate gene expression. In this study, the human kinome’s DNA methylation and gene expression patterns were analyzed using the level-3 TCGA data for 32 cancers. Unsupervised clustering based on kinome data revealed the grouping of cancers based on their organ level and tissue type. We further observed significant differences in overall kinase methylation levels (hyper- and hypomethylation) between the tumor and adjacent normal samples from the same tissue. Methylation expression quantitative trait loci (meQTL) analysis using kinase gene expression with the corresponding methylated probes revealed a highly significant and mostly negative association (~92%) within 1.5 kb from the transcription start site (TSS). Several understudied (dark) kinases (PKMYT1, PNCK, BRSK2, ERN2, STK31, STK32A, and MAPK4) were also identified with a significant role in patient survival. This study leverages results from multi-omics data to identify potential kinase markers of prognostic and diagnostic importance and further our understanding of kinases in cancer.
A Comprehensive Review on Critical Issues and Possible Solutions of Motor Imagery Based Electroencephalography Brain-Computer Interface

Motor imagery (MI) based brain–computer interface (BCI) aims to provide a means of communication through the utilization of neural activity generated due to kinesthetic imagination of limbs. Every year, a significant number of publications that are related to new improvements, challenges, and breakthrough in MI-BCI are made. This paper provides a comprehensive review of the electroencephalogram (EEG) based MI-BCI system. It describes the current state of the art in different stages of the MI-BCI (data acquisition, MI training, preprocessing, feature extraction, channel and feature selection, and classification) pipeline. Although MI-BCI research has been going for many years, this technology is mostly confined to controlled lab environments. We discuss recent developments and critical algorithmic issues in MI-based BCI for commercial deployment.
The Potential of Nail Mini-Organ Stem Cells in Skin, Nail and Digit Tips Regeneration

Nails are highly keratinized skin appendages that exhibit continuous growth under physiological conditions and full regeneration upon removal. These mini-organs are maintained by two autonomous populations of skin stem cells. The fast-cycling, highly proliferative stem cells of the nail matrix (nail stem cells (NSCs)) predominantly replenish the nail plate. Furthermore, the slow-cycling population of the nail proximal fold (nail proximal fold stem cells (NPFSCs)) displays bifunctional properties by contributing to the peri-nail epidermis under the normal homeostasis and the nail structure upon injury. Here, we discuss nail mini-organ stem cells’ location and their role in skin and nail homeostasis and regeneration, emphasizing their importance to orchestrate the whole digit tip regeneration. Such endogenous regeneration capabilities are observed in rodents and primates. However, they are limited to the region adjacent to the nail’s proximal area, indicating the crucial role of nail mini-organ stem cells in digit restoration. Further, we explore the molecular characteristics of nail mini-organ stem cells and the critical role of the bone morphogenetic protein (BMP) and Wnt signaling pathways in homeostatic nail growth and digit restoration. Finally, we investigate the latest accomplishments in stimulating regenerative responses in regeneration-incompetent injuries. These pioneer results might open up new opportunities to overcome amputated mammalian digits and limbs’ regenerative failures in the future.
Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options in the advanced stages. Immunotherapy offers hope for altering the orthodox management of cancer, and its role in advanced ACC has been investigated in different studies. With the aim clarifying the role of immunotherapy in ACC we performed a comprehensive review about this topic focusing on the predictors of response, efficacy, safety, and the mechanisms of resistance. Five clinical trials with four immune checkpoint inhibitors (pembrolizumab, avelumab, nivolumab, and ipilimumab) have investigated the role of immunotherapy in advanced ACC. Despite, the different primary endpoints used in these studies, the reported rates of overall response rate and progression free survival were generally poor. Three main potential markers of response to immunotherapy in ACC have been described: Expression of PD-1 and PD-L1, microsatellite instability and tumor mutational burden. However, none of them has been validated in prospective studies. Several mechanisms of ACC immunoevasion may be responsible of immunotherapy failure, and a greater knowledge of these mechanisms might lead to the development of new strategies to overcome the immunotherapy resistance. In conclusion, although currently the role of immunotherapy is limited, the identification of immunological markers of response and the implementation of strategies to avoid immunotherapy resistance could improve the efficacy of this therapy.
Adaptive Divergence under Gene Flow along an Environmental Gradient in Two Coexisting Stickleback Species

There is a general and solid theoretical framework to explain how the interplay between natural selection and gene flow affects local adaptation. Yet, to what extent coexisting closely related species evolve collectively or show distinctive evolutionary responses remains a fundamental question. To address this, we studied the population genetic structure and morphological differentiation of sympatric three-spined and nine-spined stickleback. We conducted genotyping-by-sequencing and morphological trait characterisation using 24 individuals of each species from four lowland brackish water (LBW), four lowland freshwater (LFW) and three upland freshwater (UFW) sites in Belgium and the Netherlands. This combination of sites allowed us to contrast populations from isolated but environmentally similar locations (LFW vs. UFW), isolated but environmentally heterogeneous locations (LBW vs. UFW), and well-connected but environmentally heterogenous locations (LBW vs. LFW). Overall, both species showed comparable levels of genetic diversity and neutral genetic differentiation. However, for all three spatial scales, signatures of morphological and genomic adaptive divergence were substantially stronger among populations of the three-spined stickleback than among populations of the nine-spined stickleback. Furthermore, most outlier SNPs in the two species were associated with local freshwater sites. The few outlier SNPs that were associated with the split between brackish water and freshwater populations were located on one linkage group in three-spined stickleback and two linkage groups in nine-spined stickleback. We conclude that while both species show congruent evolutionary and genomic patterns of divergent selection, both species differ in the magnitude of their response to selection regardless of the geographical and environmental context.
Liver Transplantation for T2 Hepatocellular Carcinoma during the COVID-19 Pandemic: A Novel Model Balancing Individual Benefit against Healthcare Resources

Simple Summary Using Italian national data from more than 8000 patients, we proposed a novel model calculating the net benefit of liver transplantation (individual benefit minus harm to others on the waiting list) in T2 hepatocellular carcinoma (HCC) patients in different scenarios of transplant activity reduction. Our results show that the transplant net benefit is closely related to the decrease in the number of organs, but it is also higher in T2 HCC patients than in non-HCC patients with the same model for end-stage liver disease (MELD) scores. Our model supports liver transplantation for T2 HCC with the highest net benefit also during crises such as COVID-19. Abstract The COVID-19 pandemic caused temporary drops in the supply of organs for transplantation, leading to renewed debate about whether T2 hepatocellular carcinoma (HCC) patients should receive priority during these times. The aim of this study was to provide a quantitative model to aid decision-making in liver transplantation for T2 HCC. We proposed a novel ethical framework where the individual transplant benefit for a T2 HCC patient should outweigh the harm to others on the waiting list, determining a “net benefit”, to define appropriate organ allocation. This ethical framework was then translated into a quantitative Markov model including Italian averages for waiting list characteristics, donor resources, mortality, and transplant rates obtained from a national prospective database (n = 8567 patients). The net benefit of transplantation in a T2 HCC patient in a usual situation varied from 0 life months with a model for end-stage liver disease (MELD) score of 15, to 34 life months with a MELD score of 40, while it progressively decreased with acute organ shortage during a pandemic (i.e., with a 50% decrease in organs, the net benefit varied from 0 life months with MELD 30, to 12 life months with MELD 40). Our study supports the continuation of transplantation for T2 HCC patients during crises such as COVID-19; however, the focus needs to be on those T2 HCC patients with the highest net survival benefit.