Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment Response of Add-On Esketamine Nasal Spray in Resistant Major Depression in Relation to Add-On Second-Generation Antipsychotic Treatment

Abstract In this meta-analysis, we aimed to estimate and compare the efficacy of add-on treatment of antidepressants with esketamine nasal spray and second-generation antipsychotics in patients with nonpsychotic major depressive disorder and inadequate response to antidepressants. Searching for acute-phase, double-blind, placebo-controlled, randomized trials, we found 22 second-generation antipsychotic (n = 8363) and 3 intranasal esketamine (n = 641) studies. Mean change in the Montgomery Åsberg Depression Rating Scale total score served as outcome. We determined a higher mean difference (vs placebo) for the pooled esketamine nasal spray trials (mean difference = 4.09, 95% confidence interval: 2.01 to 6.17) than for the pooled second-generation antipsychotic augmentation trials (mean difference = 2.05, 95% confidence interval: 1.51 to 2.59). Thus, the effect size for intranasal esketamine was nearly twice as high as those for the second-generation antipsychotics. This indicates high efficacy of add-on esketamine nasal spray in treatment-resistant major depressive disorder compared with other well-established, evidence-based pharmacological options such as augmentation with second-generation antipsychotics.
Effectiveness and safety of thymectomy plus prednisone compares with prednisone monotherapy for the treatment of non-thymomatous Myasthenia Gravis

Abstract Background: The pathogenesis of myasthenia gravis (MG) has strong connection with thymic abnormalities. Thymic hyperplasia or thymoma can be found with most patients. Thymectomy is currently one of the regular treatment in clinic, which is, however, still controversial for non-thymomatous MG. This research will assess the effectiveness and safety of thymectomy plus prednisone compared to prednisone monotherapy for the treatment of non-thymomatous MG systematically. Methods: According to eligibility and ineligibility criteria, 8 databases, including PubMed, EMBASE, the Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan-fang Database, Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (CSTJ), will be searched to gather the up-to-standard articles from September 2000 to September 2025. Inclusion criteria are as follows: randomized controlled trials of thymectomy plus prednisone for the treatment of non-thymomatous MG. The quantitative myasthenia gravis score (QMG) and the dose of prednisone required will be accepted as the main outcomes. Data synthesis, subgroup analysis, sensitivity analysis, and meta-regression analysis will be conducted using RevMan 5.3 software. We will use Egger or Begg test to evaluate symmetry on a funnel plot which is made to assess reporting bias, and use trial sequential analysis (TSA) to exclude the probability of false positives. Results: This systematic review will measure the QMG and the dose of prednisone required, the myasthenia gravis activities of daily living scale scores (MG-ADL), treatment-associated complications, incidence of myasthenic crisis and other aspects to comprehensively assess the clinical benefits of thymectomy plus prednisone for MG patients without thymoma. Conclusion: The conclusion of this study will achieve convincing evidence to evaluate the effectiveness and safety of thymectomy plus prednisone for the treatment of non-thymomatous MG. PROSPERO registration number: CRD 42020167735.
Some Physiological Aspects of Organogenesis in the Insect Embryo

Abstract In the embryo, as in the postembryonic insect, morphological development is accompanied by an increase or change in enzyme activity. The appearance of certain enzymatically active proteins in a particular tissue or organ may indicate when that tissue or organ has become functional. The time and place of appearance of several types of esterase has been determined in the tissues and organs of the developing embryo of the large milkweed bug, Oncopeltus fasciatus (Dall.). The appearance of acetylcholinesterase in the neuropile of the nervous system reflects the morphological development of this system; it may also determine the onset of functional activity. Similarly, the appearance of non-specific esterase in many tissues and organs at a definite time during their morphological development suggests a relationship between their functional differentiation and the appearance of the enzyme. Evidence for such a relationship will remain circumstantial until the physiological significance of these esterases is understood.
Risk assessment via genotoxicity, metabolism, apoptosis, and cell growth effects in a HepG2/C3A cell line upon treatment with Rubus rosifolius (Rosaceae) leaves extract

ABSTRACT Rubus rosifolius Sm. (Rosaceae) is a plant traditionally used in Brazil and some other countries to treat diarrhea, stomach diseases, and as an analgesic, antimicrobial, antihypertensive, and as well as other pharmacological properties. The aim of this study was to examine cytotoxic and genotoxic effects of R. rosifolius leaves extract on HepG2/C3A cells and correlate these findings with the expression of mRNA to underlying mechanisms of action. At concentrations between 0.01 and 100 µg/ml, cytotoxic effects were not detected by the MTT assay. This was confirmed by mRNA induction of the CYP3A4 gene (by RT-qPCR assay). However, genotoxic effects occurred at treatments from 1 µg/ml extract (comet and micronucleus test). An increase in the number of cells in S phase was observed at 100 µg/ml, and an elevation in apoptotic cell number was found for all tested concentrations (10, 20, or 100 µg/ml) (cell cycle and apoptosis analysis by flow cytometry). The genotoxicity induced by the extract was the main cause of the rise in the number of cells undergoing apoptosis, as indicated by rise in mRNA of CASP7 gene, and elevation of cells in the S phase of the cell cycle at the higher tested concentrations, as an attempt to repair genetic damage that occurred. These observations suggest that, despite its pharmacological potential, the use of R. rosifolius leaves extract may pose a risk to the integrity of the genetic material of human cells.
Assessing Opioid Use Patient Representations and Subtypes

Precision medicine, diagnosis, treatment, and prevention that accounts for natural human variability, can be beneficial for complex populations. The opioid user population is heterogeneous, characterized by many disorders, medications, and procedures. Using Electronic Health Record data, we create a patient representation, finding similarities between structured data, and then cluster the patients into patient subtypes. These subtypes can then be used for subsequent analysis.
Microwave assisted extraction and evaluation of in vitro antioxidant activity of Cinnamomum aromaticum

Cinnamomum aromaticum or Chinese cinnamon, belonging to the laurel family (Lauraceae) is an evergreen tree native to southern China, Bangladesh, India, and Vietnam. The dried bark ofC. aromaticum is used as a spice. In this study, extraction and evaluation of in vitro antioxidant activity of C. aromaticum bark with ethanol using microwave - assisted extraction and soxhlet extraction were carried out. Antioxidant properties of two extracts were investigated employing various established systems in vitro including 2,2’-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, ABTS assay, total antioxidant activity, hydroxyl radical assay and total reducing power. Total phenolic content of microwave - assisted extract (MCA) and conventional extract of C. aromaticum (CCA) reached 546.2±0.45 and 543.9±0.86 mg/g dry weight, respectively, expressed as gallic acid equivalents, which were quantified using Folin-Ciocalteau reagent. Subsequently, total flavonoids content of MCA and CCA extracts were found to be 126±0.18 and 121±0.34 mg/g dry weight, respectively, expressed as rutin equivalents (P < 0.05). MCA and CCA showed excellent antioxidant in all test systems compared to standard ascorbic acid and the antioxidant activities of MCA were all superior to those of CCA. The results obtained in this study clearly indicate that C. aromaticum has a significant potential to use as a natural anti-oxidant agent. Key words: Cinnamomum aromaticum, microwave assisted extract, antioxidant activity, total flavonoids content, total phenolic content.
Appendicular Skeleton in Amphisbaenians (Reptilia: Squamata)

Abstract The appendicular skeletal elements in 32 species from all 23 extant genera of amphisbaenians were surveyed via the preparation and study of radiographs, dry skeletons, and cleared-and-stained specimens. Here I report on the presence or absence of those elements, describe their morphology, and make comparisons to several other limbless or limb-reduced squamate taxa that have previously been suggested as close relatives to amphisbaenians. Variability found here in the appendicular skeleton provides a new source of character data for ongoing phylogenetic studies of the group. Comparisons of these elements to those found in potential squamate sister groups indicate that some amphisbaenians share plesiomorphic similarities with limbed squamates such as gymnophthalmid lizards, whereas others share only absence or reduction features with other limbless or limb-reduced squamates, such as dibamid lizards and snakes. This pattern is considered potentially inconsistent with previously proposed hypotheses of amphisbaenian sister groups within squamates. For the pectoral girdle, every stage of reduction—including complete loss—occurs among lizards, amphisbaenians, and snakes. However, the pelvic girdle is never completely lost in lizards or amphisbaenians regardless of the degree of limb reduction or loss; all these taxa retain at least the ilium, and this is also true of most basal snakes. These pelvic girdle elements are variously modified among these taxa, a fact that, together with their widespread persistence, suggests both different patterns of reduction among higher taxa and possible new functional roles beyond the primitive one of supporting the hind limb.
A lineage-tracing tool to map the fate of hypoxic tumour cells

ABSTRACT Intratumoural hypoxia is a common characteristic of malignant treatment-resistant cancers. However, hypoxia-modification strategies for the clinic remain elusive. To date, little is known on the behaviour of individual hypoxic tumour cells in their microenvironment. To explore this issue in a spatial and temporally controlled manner, we developed a genetically encoded sensor by fusing the O2-labile hypoxia-inducible factor 1α (HIF-1α) protein to eGFP and a tamoxifen-regulated Cre recombinase. Under normoxic conditions, HIF-1α is degraded but, under hypoxia, the HIF-1α-GFP-Cre-ERT2 fusion protein is stabilised and in the presence of tamoxifen activates a tdTomato reporter gene that is constitutively expressed in hypoxic progeny. We visualise the random distribution of hypoxic tumour cells from hypoxic or necrotic regions and vascularised areas using immunofluorescence and intravital microscopy. Once tdTomato expression is induced, it is stable for at least 4 weeks. Using this system, we could show in vivo that the post-hypoxic cells were more proliferative than non-labelled cells. Our results demonstrate that single-cell lineage tracing of hypoxic tumour cells can allow visualisation of their behaviour in living tumours using intravital microscopy. This tool should prove valuable for the study of dissemination and treatment response of post-hypoxic tumour cells in vivo at single-cell resolution. This article has an associated First Person interview with the joint first authors of the paper. Summary: Here, we developed and characterised a novel HIF-1α-Cre fusion protein to trace the progeny of hypoxic tumour cells in a temporal and spatially resolved manner using intravital microscopy.
MtcB, a member of the MttB superfamily from the human gut acetogen Eubacterium limosum, is a cobalamin-dependent carnitine demethylase

The trimethylamine methyltransferase MttB is the first described member of a superfamily comprising thousands of microbial proteins. Most members of the MttB superfamily are encoded by genes that lack the codon for pyrrolysine characteristic of trimethylamine methyltransferases, raising questions about the activities of these proteins. The superfamily member MtcB is found in the human intestinal isolate Eubacterium limosum ATCC 8486, an acetogen that can grow by demethylation of l-carnitine. Here, we demonstrate that MtcB catalyzes l-carnitine demethylation. When growing on l-carnitine, E. limosum excreted the unusual biological product norcarnitine as well as acetate, butyrate, and caproate. Cellular extracts of E. limosum grown on l-carnitine, but not lactate, methylated cob-(I)alamin or tetrahydrofolate using l-carnitine as methyl donor. MtcB, along with the corrinoid protein MtqC and the methylcorrinoid:tetrahydrofolate methyltransferase MtqA, were much more abundant in E. limosum cells grown on l-carnitine than on lactate. Recombinant MtcB methylates either cob(I)alamin or Co(I)-MtqC in the presence of l-carnitine and, to a much lesser extent, γ-butyrobetaine. Other quaternary amines were not substrates. Recombinant MtcB, MtqC, and MtqA methylated tetrahydrofolate via l-carnitine, forming a key intermediate in the acetogenic Wood–Ljungdahl pathway. To our knowledge, MtcB methylation of cobalamin or Co(I)-MtqC represents the first described mechanism of biological l-carnitine demethylation. The conversion of l-carnitine and its derivative γ-butyrobetaine to trimethylamine by the gut microbiome has been linked to cardiovascular disease. The activities of MtcB and related proteins in E. limosum might demethylate proatherogenic quaternary amines and contribute to the perceived health benefits of this human gut symbiont.
Combinative effect of Salvia sclarea L., Artemisia annua and Dracocephalum heterophyllum B. essential oils against Salmonella enterica in raw chicken

Antibacterial properties of essential oils (EOs) extracted from Salvia sclarea, Artemisia annua and Dracocephalum heterophyllum against 17 food borne pathogens was studied. EOs of the three plants showed a broad spectrum of antimicrobial activity with different degrees of inhibition against the tested Gram-positive and Gram-negative bacteria. EOs of Salvia and Dracocephalum depicted bactericidal mode of action while that of Artemisia inhibited the bacteria with bacteriostatic mode. Salmonella enterica MTCC 733 was the most sensitive strain to Salvia, Artemisia and Dracocephalum EOs with minimum inhibitory concentration (MIC) values of 2000, 2000 and 8000 µg/ml, respectively. The antimicrobial activity of EOs individually and in combinations based on their respective MIC values against S. enterica was tested in raw chicken. Treatment of food sample with 20 times MIC value of S. sclarea, A. annua and D. heterophyllum EOs individually caused reduction of bacterial load to 3.36, 3.64 and 4.22 log cfu/g after 180 min. In contrast the bacterial cell loads reduced to an undetectable level by the combinative effect ( Salvia + Dracocephalum and Salvia + Artemisia ) of EOs at MIC value after 120 and 180 min, respectively. This study suggests that combinations of EOs could minimize application concentrations in real food system.
Models to Study Colonisation and Colonisation Resistance

This review describes various in vivo animal models (humans; conventional animals administered antimicrobial agents and animals species used; gnotobiotic and germ-free animals), in vitro models (luminal and mucosal), and in silico and mathematical models which have been developed to study colonisation and colonisation resistance and effects of gut flora on hosts. Where applicable, the advantages and disadvantages of each model are discussed.
The Role of Animal-derived Remedies as Complementary Medicine in Brazil

ABSTRACT Although animal-derived remedies constitute an integral part of folk medicine in many parts of the world, particularly for people with limited or no access to mainstream medical services, their role in health care has generally been overlooked in discussions about public health, conservation and management of faunistic resources, and ecosystem protection. In this article, we report on the use of 283 medicinal animal species in Brazil, 96% of which are wild caught and 27% of which are on one or more lists of endangered species. Further population declines may limit users' access to these bioresources and diminish the knowledge base upon which traditional medicine is built.
p38 mitogen-activated protein kinase regulates chamber specific perinatal growth in heart.

In mammalian heart, left ventricle (LV) rapidly becomes more dominant in size and function over right ventricle (RV) after birth. The molecular regulators responsible for this chamber specific differential growth are largely unknown. We found the cardiomyocytes in neonatal mouse RV had lower proliferation, more apoptosis and smaller sizes comparing to the LV. Such chamber specific growth pattern was associated with a selective activation of p38 MAPK activity in the RV and simultaneous inactivation in the LV. Cardiomyocyte-specific deletion of both mapk14 and mapk11 genes in mice results in loss of p38 MAP kinase expression and activity in the neonatal heart. Inactivation of p38 activity led to marked increase in myocytes proliferation and hypertrophy but diminished myocyte apoptosis, specifically in the RV. Consequently, the p38 inactivated hearts showed RV specific enlargement postnatally, progressing to pulmonary hypertension and right heart failure at adult stage. Chamber-specific p38 activity was associated with differential expression of dual-specific phosphatases (DUSPs) in neonatal hearts, including Dusp26. Unbiased transcriptome analysis revealed IRE1/XBP mediated gene regulation contributed to p38 MAPK dependent regulation of neonatal myocyte proliferation and binucleation. These findings establish an obligatory role of DUSP-p38-IRE1 signaling in myocytes for chamber specific growth in postnatal heart.
IL10RA Modulates Crizotinib Sensitivity in NPM1-ALK-positive Anaplastic Large Cell Lymphoma.

Anaplastic Large Cell Lymphoma (ALCL) is a T-cell malignancy predominantly driven by a hyperactive Anaplastic Lymphoma Kinase (ALK) fusion protein. ALK inhibitors such as crizotinib provide alternatives to standard chemotherapy with reduced toxicity and side effects. Children with lymphomas driven by NPM1-ALK fusion proteins achieved an objective response rate to ALK inhibition therapy of 54-90% in clinical trials. However, a subset of patients progress within the first 3 months of treatment. The mechanism for the development of ALK inhibitor resistance is unknown. Through genome-wide CRISPR activation and knockout screens in ALCL cell lines combined with RNA-seq data derived from ALK inhibitor relapsed patient tumors, we show that resistance to ALK inhibition by crizotinib in ALCL can be driven by aberrant upregulation of IL10RA. Elevated IL10RA expression rewires the STAT3 signaling pathway bypassing otherwise critical phosphorylation by NPM1-ALK. IL10RA expression does not correlate with response to standard chemotherapy in pediatric patients suggesting that combination of crizotinib with chemotherapy could prevent ALK-inhibitor resistance-specific relapse. Trials registered as NCT01979536/NCT02034981/UMIN000028075.
Microstructural Changes in Motor Functional Conversion Disorder: Multimodal Imaging Approach on a Case

Background: Functional motor conversion disorders are characterized by neurological symptoms unrelated to brain structural lesions. The present study was conducted on a woman presenting motor symptoms causing motor dysfunction, using advanced multimodal neuroimaging techniques, electrophysiological and neuropsychological assessment. Methods. The patient underwent fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) and functional magnetic resonance imaging (fMRI) with both task and resting-state paradigms and was compared with 11 healthy matched controls. To test differences in structural parameters, Bayesian comparison was performed. To test differences in functional parameters, a first- and second-level analysis was performed in task fMRI, while a seed-to-seed analysis to evaluate the connections between brain regions and identify intersubject variations was performed in resting-state fMRI. Results. FDG-PET showed two patterns of brain metabolism, involving the cortical and subcortical structures. Regarding the diffusion data, microstructural parameters were altered for U-shape fibers for the hand and feet regions. Resting-state analysis showed hypoconnectivity between the parahippocampal and superior temporal gyrus. Neurophysiological assessment showed no alterations. Finally, an initial cognitive impairment was observed, paralleled by an anxiety and mild depressive state. Conclusions. While we confirmed no structural alterations sustaining this functional motor disorder, we report microstructural changes in sensory–motor integration for both the hand and feet regions that could functionally support clinical manifestations.
Clues of production for the Neolithic Çatalhöyük (central Anatolia) pottery

Adiyaman University, Department of Ceramics, 02040, Adiyaman Turkey. Cukurova University, Department of Archaeometry, 01330, Adana, Turkey University of Ege, Vocational School of Ce me, zmir, Turkey. University of Stanford, Department of Social and Cultural Anthropology, CA, USA. Katholieke University Leuven, Department of Archaeology, Leuven, Belgium. University of Northern British Columbia, College of Science and Management, Canada University of Keele, School of Physical Sciences and Geography, Keele, UK Ca University, Depatment of Economics, Mersin, Turkey.