Miracle-dz/UniFAR-FTUs huggingface dataset:
Network pharmacology and transcriptomic profiling elucidate the therapeutic effects of Ranunculus ternatus Thunb on liver fibrosis via MK3-NF-κB inhibition

Activation of hepatic stellate cells (HSCs) is critical in the progression of liver fibrosis and is a promising target for anti-hepatic fibrosis drug development. Moreover, effective pharmacological interventions targeting this pathomechanism are scarce. Our study confirms the therapeutic value of β-sitosterol, a major constituent of Ranunculus ternatus Thunb, in hepatic fibrosis and identifies its underlying mechanisms. After treatment with β-sitosterol, CCL4-induced hepatic fibrosis was reversed in mice, while inflammatory and hepatic fibrosis indices were improved. Meanwhile, we explored the molecular mechanism of β-sitosterol treatment for hepatic fibrosis and, based on RNA-seq results, found that the ameliorative effect of β-sitosterol on hepatic fibrosis was associated with the MK3 and NF-κB signalling pathways. MK3, an important kinase in the MAPK pathway, plays a role in transmitting upstream and downstream signals, whereas the NF-κB signalling pathway has been shown to be associated with HSC activation. We verified the interaction between MK3 and IκB in HSC cells using endogenous Co-IP, whereas β-sitosterol reduced the binding of MK3 to IκB and the activation of the NF-κB signalling pathway. Our findings reveal the mechanism of β-sitosterol in the treatment of liver fibrosis, suggesting that β-sitosterol may be a promising drug for the treatment of liver fibrosis and deserves further investigation.
Risk Factors Associated with PTLD Related Mortality in Adult Multivisceral Transplant Recipients - A Single Centre Cohort Study.

Background: PTLD is a heterogeneous group of lymphoproliferative diseases which can add significant mortality following multivisceral transplantation (MVTx). Our study aimed to identify potential risk factors of mortality in adult MVTx recipients who developed PTLD. Methods: All adult recipients of intestinal-containing grafts transplanted in our institution between 2013 and 2022, and who developed PTLD, were included in the study. Results: PTLD-associated mortality was 28.6% (6/21). Increased relative risk of mortality was associated with Stage 3 ECOG performance score (p=0.005; HR 34.77; 95%CI 2.94-410.91), if the recipients had a splenectomy (p=0.036; HR 14.36; 95%CI 1.19-172.89), or required retransplantation (p=0.039; HR 11.23; 95% CI 1.13-112.12). There was a significant trend for increased risk of PTLD mortality with higher peak EBV load (p=0.008), longer time from MVTx to PTLD diagnosis (p=0.008), and higher donor age (p 0.001). Peak LDH before treatment commencement was significantly higher in the mortality group vs the survival group (520.3 +- 422.8 IU/L vs 321.8 +- 154.4 IU/L; HR 1.00, 95%CI 1.00 to 1.01, p=0.019). Peak viral load prior to treatment initiation (Cycle Threshold (CT) cutoff = 32) correlated with the relative risk of death in MVTx patients who developed PTLD [29.4 (3.5) CTs in survivors compared to 23.0 (4.0) CTs in the mortality group]. Conclusions: This is the first study to identify risk factors for PTLD-associated mortality in an adult MVTx recipient cohort. Validation in larger multicentre studies and subsequent risk stratification according to these risk factors may contribute to better survival in this group of patients.
Machine learning models reveal distinct disease subgroups and improve diagnostic and prognostic accuracy for individuals with pathogenic SCN8A gain-of-function variants.

Distinguishing clinical subgroups for patients suffering with diseases characterized by a wide phenotypic spectrum is essential for developing precision therapies. Patients with gain-of-function (GOF) variants in the SCN8A gene exhibit substantial clinical heterogeneity, viewed historically as a linear spectrum ranging from mild to severe. To test for hidden clinical subgroups, we applied two machine learning algorithms to analyze a dataset of patient features collected by the International SCN8A Patient Registry. We utilized two research methodologies: a supervised approach that incorporated feature severity cutoffs based on clinical conventions, and an unsupervised approach employing an entirely data-driven strategy. Both approaches found statistical support for three distinct subgroups and were validated by correlation analyses utilizing external variables. However, distinguishing features of the three subgroups within each approach were not concordant, suggesting a more complex phenotypic landscape. The unsupervised approach yielded strong support for a model involving three partially-ordered subgroups rather than a linear spectrum. Application of these machine-learning approaches may lead to improved prognosis and clinical management of individuals with SCN8A GOF variants and provide insights into the underlying mechanisms of the disease.
Recurrence and Carcinogenetic Rates of Colorectal Polyps.

AIM to determin the recurrence rate of benign recto-colonic polyps in a 5-year interval, and compare the development rate of intrapolypoid carcinomatous lesions in polypectomized versus nonpolypectomized subjects. MATERIAL AND METHOD a group of 77 patients diagnosed with recto-colonic polypoid lesions during the period 2014-2019 underwent colonoscopy at the time of study initiation and then annually during a five-year interval. Results: The recurrence rate of polyps increased annually from 5 to 12.5%; the highest rate was noted in the last two years. The five-year cumulative risk of neoplastic lesions was 73% in patients without polypectomy and 20% among those with endoscopic resection (p 0.05). Comparing the recurrence rate of benign lesions (60%) in patients without neoplastic findings with the recurrence rate of adenomas in patients with benign lesions (40%), a higher risk of recurrence was found in the first category, and seemed to be influenced by the personal history of pre-existing adenomatous lesions. CONCLUSION an increased risk of colorectal polyps recurrence was reported during five year follow up; moreover, during the first three years an increased risk of malignant transformation was observed among cases in which endoscopic resection was not feasible when compared to those in which complete excision was feasible.
EL FACTOR DE IMPACTO: SU USO, ABUSO Y MAL USO

In different times was marked that the scientific papers in journal published in peripheral coubtries, sometimes no have trascendency. If impact factor is the apology by writing papers, there is remember that exist another scientometric indicators in order to evaluate the quality of journals and papers. The qualitative estimation marked by clearness, accuracy and precision, to must be communicating ideas according to international guidelines. As many as greater are the quality and quantity information appearing in national and/or regional publications, greatest the inclusion in the whole scientific world. No own estimation based only in impact factor of journals, whose use and bad using interfere in many times.
Validation of the Openwater wearable optical system: cerebral hemodynamic monitoring during a breath-hold maneuver

Abstract. Significance Bedside cerebral blood flow (CBF) monitoring has the potential to inform and improve care for acute neurologic diseases, but technical challenges limit the use of existing techniques in clinical practice. Aim Here, we validate the Openwater optical system, a novel wearable headset that uses laser speckle contrast to monitor microvascular hemodynamics. Approach We monitored 25 healthy adults with the Openwater system and concurrent transcranial Doppler (TCD) while performing a breath-hold maneuver to increase CBF. Relative blood flow (rBF) was derived from changes in speckle contrast, and relative blood volume (rBV) was derived from changes in speckle average intensity. Results A strong correlation was observed between beat-to-beat optical rBF and TCD-measured cerebral blood flow velocity (CBFv), R=0.79; the slope of the linear fit indicates good agreement, 0.87 (95% CI: 0.83 −0.92). Beat-to-beat rBV and CBFv were also strongly correlated, R=0.72, but as expected the two variables were not proportional; changes in rBV were smaller than CBFv changes, with linear fit slope of 0.18 (95% CI: 0.17 to 0.19). Further, strong agreement was found between rBF and CBFv waveform morphology and related metrics. Conclusions This first in vivo validation of the Openwater optical system highlights its potential as a cerebral hemodynamic monitor, but additional validation is needed in disease states.
Genotype-Phenotype of CRB1-Associated Early-Onset Retinal Dystrophy: Novel Insights on Retinal Architecture and Therapeutic Window for Clinical Trials

Purpose The purpose of this study was to investigate the genotypic and phenotypic characteristics of CRB1-associated early onset retinal dystrophy (CRB1-eoRD) and retinal architecture by swept-source optical coherence tomography (SS-OCT). Methods Eleven probands with CRB1-eoRD were recruited. Clinical information, genetic analysis, and comprehensive ophthalmic examinations including SS-OCT and SS-OCT angiography (SS-OCTA) were conducted. Results A total of 81.8% (9/11) of CRB1-eoRD presented as Leber congenital amaurosis (LCA). Common clinical manifestations included coin-like yellow-white retinal spots (20/22, 90.9%) and para-arteriolar retinal pigment epithelial retention (12/22, 54.5%). Nineteen different CRB1 variants were detected in our case series, including 12 missense, 3 frameshifts, 3 nonsense, and 1 splicing. Of them, 12 variants had been reported, and 7 were novel. SS-OCT showed thinner central macula (the LCA group, P < 0.0001), thicker total retina (P < 0.0001), thinner outer retina (P < 0.05), and thicker inner retina (P < 0.0001) compared with the healthy control. The inner/outer (I/O) retina thickness ratio of CRB1-eoRD was 3.0, higher than the healthy control of 1.2 and other inherited retinal diseases (IRDs) of 2.2 (P < 0.0001 and P = 0.0027, respectively). SS-OCTA revealed an increased vascular density and perfusion area of the superficial vascular complex and deep vascular complex in CRB1-eoRD. Conclusions LCA emerges as a frequently occurring phenotype in CRB1-eoRD. The unique features of SS-OCT and SS-OCTA are illustrated, and the novel biomarker, I/O ratio, may facilitate early diagnosis. The insights gained from this study hold significant value in determining the treatment window for potential forthcoming CRB1 gene therapy.
New data on the herpetofauna of the National Park “Arcipelago di La Maddalena” (NE Sardinia, Italy)

The data available on the herpetofauna of the Archipelago della Maddalena are mainly based on investigations carried out during the 1980’s by the Sezione di Zoologia “La Specola” of the Museo di Storia Naturale dell’Università di Firenze. Such records have not been specifically updated successively. Here field data on the composition and distribution of the herpetofauna of the Archipelago are presented, with particular attention to the micro-insular areas for which no bibliographic data were available. Between 2011 and 2012 a total of 51 islands and islets have been visited: new records have been gained for 15 islands and islets already studied in past while on 4 the herpetofauna has been recorded for the first time. The lack of herpetofauna on 9 islets and rocks seemingly never previously studied has been reported too.
Auto-scoring Student Responses with Images in Mathematics

Teachers often rely on the use of a range of open-ended problems to assess students’ understanding of mathematical concepts. Beyond traditional conceptions of student open-ended work, commonly in the form of textual short-answer or essay responses, the use of figures, tables, number lines, graphs, and pictographs are other examples of open-ended work common in mathematics. While recent developments in areas of natural language processing and machine learning have led to automated methods to score student open-ended work, these methods have largely been limited to textual answers. Several computer-based learning systems allow students to take pictures of hand-written work and include such images within their answers to open-ended questions. With that, however, there are few-to-no existing solutions that support the auto-scoring of student hand-written or drawn answers to questions. In this work, we build upon an existing method for auto-scoring textual student answers and explore the use of OpenAI/CLIP, a deep learning embedding method designed to represent both images and text, as well as Optical Character Recognition (OCR) to improve model performance. We evaluate the performance of our method on a dataset of student open-responses that contains both text-and image-based responses, and find a reduction of model error in the presence of images when controlling for other answer-level features.
Intraspecific variation of thermal tolerance in freshwater insects along elevational gradients: the case of a widespread diving beetle

Species distributed along wide elevational gradients are likely to experience local adaptation and exhibit high plasticity of thermal tolerance traits, as these gradients are characterised by steep environmental changes over short geographic distances (i.e., strong selection differentials). However, the prevalence of adaptive clinal intraspecific variation in thermal tolerance with elevation remains unclear, and this aspect has been poorly studied in freshwater insects. We explored variation in upper (heat coma temperature) and lower (supercooling point) thermal limits and acclimation capacity among Iberian populations of the widespread aquatic beetle Agabus bipustulatus (fam. Dytiscidae) across a 2,000-m elevational gradient, from lowland to alpine areas. As minimum, maximum and mean temperatures decline with elevation, we predicted that higher elevation populations will show lower heat tolerances and higher cold tolerances. We also explored whether acclimation capacity is positively related with climatic variability across different elevations. We found significant variation in upper and lower thermal limits among populations of A. bipustulatus, but no evidence of local adaptation to different thermal conditions along the altitudinal gradient, as relationships between thermal limits and elevation or climatic variables were in general not significant. Plasticity of upper and lower thermal limits was overall and consistently low in all populations. These results suggest conservatism of the thermal niche, which might be the result of gene flow counteracting the effects of divergent selection, or adaptations in other traits that buffer the exposure of populations to climate extremes. The limited adaptive potential and plasticity of thermal tolerance found here for A. bipustulatus imply that even generalist species, distributed along wide environmental gradients, may have little resilience to global warming.
Disparities of Implementation of National Test Based on Computer Between Western and Eastern Indonesia

E Government is an innovation of government in organizing government. This paper will explain about how currently the Government of Indonesia is running a system change of Education, which is the implementation of National test based on Computer (UNBK) through the Indonesian Ministry of Education and Culture. The implementation of National test based on Computer (UNBK) is expected to improve in terms of efficiency, quality, reliability, integrity and thrift of the implementation of the National Examination of the National budget. But the classic dilemma is still adjacent to the innovation made by the Government still there the Disparities that appeared on the implementation of National test based on Computer (UNBK) in 2017. Data show based on the division of Western Indonesia and Eastern Indonesia with three indicators of implementation of National test based on Computer (UNBK), Implementation in Other Schools and Non-National test based on Computer (UNBK) for the whole, National test based on Computer (UNBK) implemented in Western Indonesia 28.24% and in Eastern Indonesia 11.82%. Non National test based on Computer (UNBK) in West Indonesia only 57.83% and in Eastern Indonesia 84.48%. So this paper will give an in-depth analysis of why such a high Disparity occurs in the innovation of the implementation of the National test based on Computer (UNBK), as well as the factors that affect the disparity of the implementation of the National test based on Computer (UNBK). The research method used in this paper is literature study method, utilizing the source library as secondary data to obtain research data.
Adaptive admixture at ACKR1 (the Duffy locus) may have shaped Plasmodium vivax prevalence in Oman

Malaria in humans is largely caused by two divergent species of Plasmodium parasites, P. vivax and P. falciparum, both of which have driven the spread of protective alleles in human populations. Notably, an erythrocyte-specific Duffy null allele (FyES) confers resistance to P. vivax malaria and has been identified as a target of strong, recent positive selection in multiple African admixed populations. Here, we evaluate evidence for selection via adaptive admixture in Oman, where compared to neighboring countries, P. vivax has recently been less common. Genetic ancestry inference using whole genome sequence data from 100 Omanis suggests 9.8% (95% CI: 7.3-12.2%) of their genetic ancestry is shared with east Africa. At the Duffy locus, we find a high frequency of FyES and an increase to 76% African ancestry. Comparing with blood group serology for the same individuals, we identify an additional Duffy-null allele that is rare but present across multiple Arabian Peninsula (AP) populations. Finally, we estimate the selection coefficient at FyES as 0.031 (95% CI: 0.029-0.034) with likely introduction at least 59 generations ago, older than estimates in other African admixed populations. Although we also observe higher frequency of some P. falciparum-protective alleles in Oman than in other AP populations, African ancestry is not enriched indicating a lack of evidence for adaptive admixture driven by P. falciparum selective pressure. Together, our analyses suggest that Oman’s long history with east African populations resulted in early introduction and selection for Duffy null alleles and may have influenced the prevalence of P. vivax in the region.
Nucleotidyltransferase toxin MenT targets and extends the aminoacyl acceptor ends of serine tRNAs in vivo to control Mycobacterium tuberculosis growth

Toxins of toxin-antitoxin systems use diverse mechanisms to control bacterial growth and represent attractive therapeutic targets to fight pathogens. In this study, we characterized the translation inhibitor toxin MenT3 of Mycobacterium tuberculosis, the bacterium responsible for human tuberculosis in humans. We show that MenT3 is a robust cytidine specific tRNA nucleotidyltransferase in vitro, capable of modifying the aminoacyl acceptor ends of most tRNA but with a marked preference for tRNASer, to which long stretches of cytidines were added. Furthermore, transcriptomic-wide analysis of MenT3 targets in M. tuberculosis identified tRNASer as the sole target of MenT3 in vivo and revealed significant detoxification attempts by ribonuclease PH in response to MenT3 overexpression. Finally, under physiological conditions, only in the presence the native menAT3 operon, we found the unexpected presence of an active pool of endogenous MenT3 targeting tRNASer in M. tuberculosis, likely reflecting the importance of MenT3 during infection.
Large contribution of repeats to genetic variation in a transmission cluster of Mycobacterium tuberculosis

Repeats are the most diverse and dynamic, but also the least well understood component of microbial genomes. For all we know, repeat-associated mutations such as duplications, deletions, inversions, and gene conversion might be as common as point mutations, but because of short-read myopia and methodological bias they have received much less attention. Long-read sequencing opens the perspective of resolving repeats and systematically investigating the mutations they induce. For this study, we assembled the genomes of 16 closely related strains of the bacterial pathogen Mycobacterium tuberculosis from PacBio HiFi reads, with the aim of characterizing the full spectrum of DNA polymorphisms. We find that complete and accurate genomes can be assembled from HiFi reads, with read size being the main limitation in the presence of duplications. By combining a reference-free pangenome graph with extensive repeat annotation, we identified 110 variants, 58 of which can be assigned to repeat-associated mutational mechanisms such as strand slippage and homologous recombination. While recombination events are less frequent than point mutations, they can affect large regions and introduce multiple variants at once, as shown by three gene conversion events and a duplication of 7.3 kb that involve ppe18 and ppe57, two genes possibly involved in immune subversion. Our study shows that the contribution of repeat-associated mechanisms of mutation can be similar to that of point mutations at the microevolutionary scale of an outbreak. A large reservoir of unstudied genetic variation in this “monomorphic” bacterial pathogen awaits investigation.
Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling

Activation of the Wnt/β-catenin pathway crucially depends on polymerization of dishevelled 2 (DVL2) into biomolecular condensates. However, given the low affinity of known DVL2 self-interaction sites and its low cellular concentration it is unclear how polymers can form. Here, we detect oligomeric DVL2 complexes at endogenous protein levels, using a biochemical ultracentrifugation assay. We identify a low-complexity region (LCR4) in the C-terminus whose deletion and fusion decreased and increased the complexes, respectively. Notably, LCR4-induced complexes correlated with the formation of microscopically visible multimeric condensates. Adjacent to LCR4, we mapped a conserved domain (CD2) promoting condensates only. Molecularly, LCR4 and CD2 mediated DVL2 self-interaction via aggregating residues and phenylalanine stickers, respectively. Point mutations inactivating these interaction sites impaired Wnt pathway activation by DVL2. Our study discovers DVL2 complexes with functional importance for Wnt/β-catenin signaling. Moreover, we provide evidence that DVL2 condensates form in two steps by pre-oligomerization via high-affinity interaction sites, such as LCR4, and subsequent condensation via low-affinity interaction sites, such as CD2.
An a contrario approach for plant disease detection

Detecting plant diseases or abnormalities is not a trivial task, as they can be caused by multiple factors such as environmental conditions, genetics, pathogens, etc. Because there is a need to help farmers make decisions to maximize crop yields, many studies have emerged in recent years using deep learning on agricultural images to detect plant diseases, which can be considered as an anomaly detection task. However, these approaches are often limited by the availability of annotated data or prior knowledge of the existence of an anomaly. We propose an approach that can detect part of the anomalies without prior knowledge of their existence, thus overcoming some of these limitations. To this end, we train a model on an auxiliary prediction task (plants’ age regression). We then use an explicability model to retrieve heatmaps whose distributions are studied. For each new observation, we propose to study how closely its heatmap follows the desired distribution and we derive a score indicating potential anomalies. Experiments on the GrowliFlower dataset indicate how our proposed method can help potential end-user to automatically find anomalies.