Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiotoxicity of immune checkpoint inhibitors: A frequency network meta-analysis

Immune checkpoint inhibitors (ICIs) in combination withother anti-cancer treatments have been approved for a variety of cancers. While the difference in the incidence of cardiovascular adverse events has not been fully investigated. We aimed to assess the the differences in cardiotoxicity among cancer patients receiving different ICI therapies. PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. websites were searched for all randomized controlled trials (RCTs) of ICI. The primary outcomes were any grade cardiotoxicity and Grade 3-5 cardiotoxicity, the secondary outcomes were any grade myocarditis and Grade 3-5 myocarditis, with sub-analyses based on cancer type and does of ICI. A systematic review and frequency network meta-analysis were then performed for cardiotoxicity events. 91 RCTs (n=52247) involving 12 treatment arms were finally included. We observed that PD-L1 + CTLA-4 had the highest risk among all therapies inducing any grade cardiotoxicity, and the differences were significant except PD-1 + CTLA-4, PD-1 + TTD and PD-L1 + TTD. In addition, CTLA-4 had a higher risk of Grade 3-5 cardiotoxicity than PD-1 and anit-PD-L1. For Grade 1-5 myocarditis and Grade 3-5 myocarditis, no significant difference was found among differences therapies. No differences were observed in subgroup analyses according to does and cancer type. There were differences in the incidence of cardiotoxicity among different ICI therapies. For ICI monotherapy, CTLA-4 may be linked to Grade 3-5 cardiotoxicity than PD-1 or PD-L1. For dual therapy, the cardiotoxicity of dual ICI therapy seems to be higher than that of chemotherapy or targeted therapy.
Selenium biofortification of soybean genotypes in a tropical soil via Se-enriched phosphate fertilizers

Soybean is a major crop in Brazil and is usually grown in oxidic soils that need high rates of phosphate (P) fertilizers. Soybean is also very suitable for biofortification with Se, since its grains have high protein contents and are widely consumed worldwide (directly or indirectly). Few studies have addressed Se application under field conditions for soybean biofortification, especially in tropical soils. Here, we evaluated agronomic and physiological responses resulting from different strategies for biofortifying soybean grains with Se by applying this element via soil, using both conventional and enhanced-efficiency P fertilizers as Se carriers. The experiment was carried out at the Uva Farm, in Capão Bonito (São Paulo), Brazil. The experimental design was a randomized block split-plot design, with four fertilizer sources—conventional monoammonium phosphate (C-MAP), conventional monoammonium phosphate + Se (C-MAP + Se), enhanced-efficiency monoammonium phosphate (E-MAP), and enhanced-efficiency monoammonium phosphate + Se (E-MAP + Se), and four soybean genotypes (M5917, 58I60 LANÇA, TMG7061, and NA5909). The selenium rate applied via C-MAP + Se and E-MAP + Se was 80 g ha−1. The application of the tested fertilizers was carried out at the sowing of the 2018/2019 cropping season, with their residual effect being also assessed in the 2019/2020 cropping season. Selenium application increased grain yield for the TMG7061 genotype. For all evaluated genotypes, Se content in grains increased in the 2018/2019 harvest with the application of Se via C-MAP + Se and E-MAP + Se. In general, the application of Se via C-MAP favored an increase in amino acid contents in grains and decreased lipid peroxidation. In summary, the application of Se-enriched P fertilizers via soil increased soybean grain yield, leading to better grain quality. No residual effects for biofortifying soybean grains were detected in a subsequent soybean cropping season.
Early predictors of language outcomes in Down syndrome: A mini-review

As children with Down syndrome (DS) typically manifest significant delays in language development, the research has pointed out the predictors of later language skills for this clinical population. The purpose of this study was to systematically explore the evidence for early predictors of language outcomes in infants and toddlers with DS from studies published between 2012 and 2022. After the search, nine studies met the inclusion criteria. The results indicated that maternal educational level, adaptive level of functioning, cognitive function, attention skills, communicative intent of the child, early vocalizations, gestures, baby signs, parents’ translation of their children’s gestures into words, and vocabulary level are significant predictors of language outcomes in children with DS. These findings provide a timely and warranted summary of published work that contributes to current understanding of the development of language and communication in DS. They are therefore useful to researchers, clinicians, and families.
Comparing Biorefinery Processes at the Early Design Stage Using Large Block Analysis

The transformation of pulp and paper mills through the integration of biorefineries is increasingly considered essential to the future of many existing sites. However, evaluating the risk and return of different biorefinery process alternatives at the early design stage is challenging. There are many strategies and technologies that must be considered, each of which is typically accompanied by its unique risks, including high levels of uncertainty in capital and operating cost estimates often obtained from technology providers. The novel methodology presented in this study, called Large Block Analysis (LBA), comprises a systematic approach for addressing these important challenges at the early design stage. LBA is used to obtain relative cost estimates for six process/product combinations incorporating different Technology Readiness Levels (TRLs), for adding value to a hemicellulose stream extracted from hardwood chips. In this case study, it was found that the fixed capital costs obtained using the LBA method differed from the original costs by between 121 and −19%, and operating cost estimates differed by between 117 and −17% from the original. The results show that the most economically-viable options for the hemicellulose stream having reasonable technology risk included the production of (1) animal feed additives, (2) xylitol using a variant of the classical chemical process, and (3) furfural.
Preoperative excessive lateral anterior tibial subluxation is related to posterior tibial tunnel insertion with worse sagittal alignment after anterior cruciate ligament reconstructions

Objective To investigate whether preoperative lateral anterior tibial subluxation (LATS) measured from magnetic resonance imaging (MRI) can influence tibial insertion and postoperative sagittal alignment after anterior cruciate ligament reconstructions (ACLRs). Methods 84 patients who underwent single-bundle ACLRs were retrospectively investigated. Among them, 39 patients (LATS of <6 mm) 23 patients (LATS of ≥6 mm and <10 mm) and 22 patients (excessive LATS of ≥10 mm) were defined as group 1, 2 and 3, respectively. LATS, the position of graft insertion into tibia as ratio of anterior-posterior width (AP ratio) and the sagittal graft angle (SGA) were postoperatively assessed from MRI at 2-year follow-up. Following linear regression analyses were employed. Results The group 3 exhibited the largest preoperative LATS and remained the most postoperative LATS. Moreover, the group 3 possessed the most posteriorly located tunnel insertion with the largest AP ratio and the most vertical graft orientation. Of all included patients, a moderate correlation was demonstrated between pre- and postoperative LATS (r = 0.635). A low correlation was observed between preoperative LATS and AP ratio (r = 0.300) and a moderate correlation was displayed between AP ratio and SGA (r = 0.656). Conclusion For ACL injuries with excessive LATS (≥10 mm), most posteriorly located tibial insertion was found out, and worse sagittal alignment containing high residual LATS was associated with more vertical graft orientation following ACLRs.
Volumetric optoacoustic neurobehavioral tracking of epileptic seizures in freely-swimming zebrafish larvae

Fast three-dimensional imaging of freely-swimming zebrafish is essential to understand the link between neuronal activity and behavioral changes during epileptic seizures. Studying the complex spatiotemporal patterns of neuronal activity at the whole-brain or -body level typically requires physical restraint, thus hindering the observation of unperturbed behavior. Here we report on real-time volumetric optoacoustic imaging of aberrant circular swimming activity and calcium transients in freely behaving zebrafish larvae, continuously covering their motion across an entire three-dimensional region. The high spatiotemporal resolution of the technique enables capturing ictal-like epileptic seizure events and quantifying their propagation speed, independently validated with simultaneous widefield fluorescence recordings. The work sets the stage for discerning functional interconnections between zebrafish behavior and neuronal activity for studying fundamental mechanisms of epilepsy and in vivo validation of treatment strategies.
Fecal microbiota in patients with a stoma decreases anaerobic bacteria and alters taxonomic and functional diversities

Colorectal cancer (CRC) is one of the most common malignant diseases. Generally, stoma construction is performed following surgery for the resection of the primary tumor in patients with CRC. The association of CRC with the gut microbiota has been widely reported, and the gut microbiota is known to play an important role in the carcinogenesis, progression, and treatment of CRC. In this study, we compared the microbiota of patients with CRC between with and without a stoma using fecal metagenomic sequencing data from SCRUM-Japan MONSTAR-SCREEN, a joint industry-academia cancer research project in Japan. We found that the composition of anaerobes was reduced in patients with a stoma. In particular, the abundance of Alistipes, Akkermansia, Intestinimonas, and methane-producing archaea decreased. We also compared gene function (e.g., KEGG Orthology and KEGG pathway) and found that gene function for methane and short-chain fatty acids (SCFAs) production was underrepresented in patients with a stoma. Furthermore, a stoma decreased Shannon diversity based on taxonomic composition but increased that of the KEGG pathway. These results suggest that the feces of patients with a stoma have a reduced abundance of favorable microbes for cancer immunotherapy. In conclusion, we showed that a stoma alters the taxonomic and functional profiles in feces and may be a confounding factor in fecal microbiota analysis.
Expression profiling suggests the involvement of hormone-related, metabolic, and Wnt signaling pathways in pterygium progression

Background Pterygium is an ocular surface disease that can cause visual impairment if it progressively invades the cornea. Although many pieces of research showed ultraviolet radiation is a trigger of pterygium pathological progress, the underlying mechanism in pterygium remains indistinct. Methods In this study, we used microarray to evaluate the changes of transcripts between primary pterygium and adjacent normal conjunctiva samples in China. Then, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Moreover, we constructed protein-protein interaction (PPI) and miRNA-mRNA regulatory networks to predict possible regulatory relationships. We next performed gene set enrichment analysis (GSEA) to explore the similarities and differences of transcripts between Asian studies from the Gene Expression Omnibus database. Furthermore, we took the intersection of differentially expressed genes (DEGs) with other data and identified hub genes of the development of pterygium. Finally, we utilized real-time quantitative PCR to verify the expression levels of candidate genes. Results A total of 49 DEGs were identified. The enrichment analyses of DEGs showed that pathways such as the Wnt-signaling pathway and metabolism-related pathways were upregulated, while pathways such as hormone-related and transcription factor-associated pathways were downregulated. The PPI and miRNA-mRNA regulatory networks provide ideas for future research directions. The GSEA of selecting Asian data revealed that epithelial-mesenchymal transition and myogenesis existed in the pathology of pterygium in the Asian group. Furthermore, five gene sets (interferon-gamma response, Wnt beta-catenin signaling, oxidative phosphorylation, DNA repair, and MYC targets v2) were found only in our Chinese datasets. After taking an intersection between selecting datasets, we identified two upregulated (SPP1 and MYH11) and five downregulated (ATF3, FOS, EGR1, FOSB, and NR4A2) hub genes. We finally chose night genes to verify their expression levels, including the other two genes (SFRP2 and SFRP4) involved in Wnt signaling; Their expression levels were significantly different between pterygium and conjunctiva. Conclusions We consider hormone-related, metabolic, and Wnt signaling pathways may be important in the pathology of pterygium development. Nine candidate genes we identified deserve further study and can be potential therapeutic targets.
Molecular characterization of PI*Shangzhou, a SERPINA1 allele from continental China encoding a defective alpha-1-antitrypsin

Alpha-1-antitrypsin deficiency (AATD) is a heritable condition that predisposes to respiratory and hepatic complications. Screenings in East Asia human populations for the AATD alleles most commonly found among Caucasians have yielded poor outcomes. Serum alpha-1-antitrypsin (AAT) levels, AAT phenotypes, and sequences of SERPINA1 gene were examined in a Chinese child with a moderate deficit of serum AAT, who had suffered several episodes of liver disease, as well as in his first-order relatives. Results allowed the identification of PI*Shangzhou, a novel SERPINA1 defective allele, which has been characterized by a L276R substitution, found in a SERPINA1-M3 genetic background. Moreover, potential effects of PI*Shangzhou mutation over the AAT structure were studied by 3D homology modeling. The presence of an arginine residue at position 276 could destabilize the tertiary structure of AAT, since it occurs at a highly conserved hydrophobic cavity in the protein surface, and very close to two positively-charged lysine residues. Attending to the frequency of R276 variant reported in databases for individuals of East Asian ancestry, the PI*Shangzhou allele may explain the global prevalence of the PiS phenotype observed in China.
Prognostic relevance of left atrial function and stiffness in heart failure with preserved ejection fraction patients with and without diabetes mellitus

Background Although the left atrium (LA) plays a key role in the pathophysiology and disease progression of heart failure with preserved ejection fraction (HFpEF), the impact of type 2 diabetes mellitus (T2DM) on LA function and stiffness in HFpEF patients remains unclear. Furthermore, the prognostic value of different phases of LA function and stiffness is less well-established in HFpEF patients. Methods This study prospectively enrolled 164 HFpEF patients who were in sinus rhythm at the time of echocardiography, including 61 (37%) HFpEF patients with T2DM. LA reservoir, conduit, and pump function were assessed using two-dimensional volume indices and speckle tracking echocardiography. The LA stiffness was calculated as the ratio of early mitral inflow velocity-to-early annular tissue velocity (E/e’) and LA reservoir function. The primary end point was a combined outcome of heart failure hospitalization or death. Results Left atrium reservoir function [measured by peak LA strain (LAS-peak)] and LA pump function (measured by LAS-active) remained significantly lower in the HFpEF patients with T2DM compared with those without T2DM, even after adjustment for potential confounders. In addition, the LA stiffness of HFpEF patients with T2DM was higher than those without T2DM. After a median follow-up of 13.7 months, 46 patients (28.1%) reached the composite end point. LAS-peak (hazard ratios: 0.88; 95% confidence interval: 0.81–0.95; P = 0.001) was significantly associated with the risk of heart failure hospitalization or death after adjusting for demographic and clinical characteristics, LV global longitudinal strain, E/e’, and LA volume index. In contrast, other LA function and stiffness parameters did not independently predict the risk of adverse events. Kaplan-Meier analysis showed that HFpEF patients with T2DM and low LAS-peak (<27.2%) had a significantly increased risk of heart failure-related hospitalization or death (log-rank P < 0.001). Conclusion Left atrium reservoir and pump function are impaired, whereas LA stiffness is increased in HFpEF patients with T2DM compared with those without T2DM. LAS-peak is a powerful predictor of adverse clinical outcomes and may be crucial for risk stratification in HFpEF patients with and without T2DM.
The FLOTAC basic technique as a new extraction method for root-knot nematodes (Meloidogyne spp.) from soil and roots

FLOTAC Techniques have been widely acknowledged as an effective method for the extraction of human and animal parasites. The present study is the first application of FLOTAC basic technique (FBT) for the extraction of phytoparasitic nematodes from soil and infested plant roots. Eggs and second stage juveniles (J2) of the root-knot nematode Meloidogyne incognita were extracted from infested soil and tomato roots either by FBT and conventional nematode extraction methods, such as centrifugal flotation and root maceration techniques, respectively. The number of M. incognita J2 and eggs extracted from soil by FBT was always significantly higher compared to the extraction with the centrifugal flotation method, averaging 277 vs 35 eggs and J2 mL-1 soil. Conversely, no significant differences were observed between FBT and the root maceration technique in the extraction of eggs and J2 from tomato roots. Results demonstrated that FBT can be highly effective also for the extraction of phytoparasitic nematodes. Due to its accuracy and sensitivity, FBT seems particularly suitable for nematode surveys in wide geographical areas, where an accurate and rapid detection of present phytoparasitic nematofauna is required.
The association between global cognitive function and walking capacity in individuals with broad ranges of cognitive and physical function: Are there sex differences?

Introduction Cognitive function is known to be associated with physical function, where greater walking capacity has been shown to have moderate to strong correlations with global cognitive function and other various domains of cognition in older adults with and without chronic conditions. Biological sex may moderate the relationship between cognitive and physical function, but whether sex differences exist in this association has not been examined in an aging population. The purpose of this study was to examine the associations between global cognitive function (Montreal Cognitive Assessment; MoCA), walking capacity (6-Minute Walk Test distance; 6 MWT) and sex in an aging population with broad ranges of cognitive and physical function. Methods Participants were assessed for global cognitive function (MoCA) and walking capacity (6 MWT). Multivariable regression analyses were performed to examine the interaction of sex in the association between MoCA and 6 MWT. First, we presented the unadjusted model (Model 1), then the model adjusted for age, history of stroke, and height (Model 2). To determine if there were sex-based differences in the association between global cognitive function and walking capacity, we included sex and an interaction term between sex*6 MWT distance in Models 3 and 4. Results Twenty-three females and 36 males were included in the multivariable regression analyses, respectively. Our sample represented broad ranges of cognitive and physical function levels, where MoCA scores ranged from 13 to 30, and 6 MWT distances from 203 to 750 m. 6 MWT distance was associated with MoCA in models unadjusted (R2 = 0.17; F(1,56) = 11.4; p < 0.01) and adjusted for age, stroke history, and height (R2 = 0.20; F(4,53) = 3.2; p = 0.02). No interaction with sex was found, but a main effect of sex was observed (R2 = 0.26; F(5,21) = 3.72; p = 0.03). When adjusting for age, height and history of stroke, males MoCA scores were 2.9 ± 1.3 less than the mean MoCA scores for females. Discussion Our findings confirm the positive relationship between cognitive and physical function in older adults. Notably, we also observed superior performance in global cognition among females that was consistent across a broad spectrum of walking capacity.
Anti-proliferative and pro-apoptotic effects of curcumin on skin cutaneous melanoma: Bioinformatics analysis and in vitro experimental studies

Objective: To reveal the potential mechanisms of curcumin for the treatment of skin cutaneous melanoma (SKCM) and its identify novel prognostic biomarkers. Methods: We searched the Cancer Genome Atlas and Traditional Chinese Medicine Systems Pharmacology database for the data on SKCM and curcumin. We conducted data analysis using R and online tools. The propagation and migration of SKCM cells were assessed with CCK-8 and scratch wound assays, respectively. We assessed apoptosis by TUNEL assay and western blot. Results: The survival analysis revealed that the mRNA expressions of DPYD, DPYS, LYN, PRKCQ, and TLR1 were significantly related to a favorable overall survival in SKCM patients. Additionally, the mRNA expression level of DPYD was associated with GPI, LYN, PCSK9, PRKCQ, and TLR1 mRNAs. GSEA results showed that the prognostic hub genes were augmented with ultraviolet, apoptosis, and metastasis. Curcumin expressed proliferation and migration of SK-MEL-1 cells (p < 0.05), and induced apoptosis (p < 0.05) significantly. Conclusion: Curcumin may have potential therapeutic effects in SKCM by inhibiting cell proliferation and migration and inducing apoptosis by regulating oxygen-related signaling pathways. The hub genes might be identified as novel biomarkers for SKCM.
Comparación de Métodos de Reducción de Dimensión Basados en Análisis por Localidades

In this paper, a comparison of methods for nonlinear dimensionality reduction is proposed in order to determine which technique preserves better the local properties, without losing the overall structure of the original data. We seek to establish which of these methods is the most appropriate for visualization tasks. The embeddings obtained with each technique are evaluated by two criteria Preservation Neighborhood Error and Preserved Neighbors Average. The methodologies were tested on artificial and real-world data sets which allow us to visually confirm the quality of the embedding. The results obtained show that Maximum variance unfolding computes high quality embeddings, because the optimization problem pretends to preserve exactly the local pair-wise distance between neighbors and conserve the global manifold structure.
A New Class of Complex Ejecta Resulting From the Interaction of Two Coronal Mass Ejections With Diﬀerent Orientations and Its Expected Geo-Eﬀectiveness

A signiﬁcant portion of transients measured by spacecraft at 1 AU does not show the well-deﬁned properties of magnetic clouds (MCs). Here, we propose a new class of complex, non-MC ejecta resulting from the interaction of two CMEs with diﬀerent orientation, which diﬀer from the previously studied multiple-MC event. At 1 AU, they are associated with a smooth rotation of the magnetic ﬁeld vector over an extended duration and do not show clear signs of interaction. We determine the characteristics of such events based on a numerical simulation and identify and analyze a potential case in the long-duration CME measured in situ in 2001 March 19–22. Such events may result in intense, long-duration geo-magnetic storms, with sawtooth events, and may sometimes be misidentiﬁed as isolated CMEs.