Miracle-dz/UniFAR-FTUs huggingface dataset:
Fossil calibrations for molecular analyses and divergence time estimation for true crabs (Decapoda: Brachyura)

True crabs, or Brachyura, comprise over 7,600 known species and are among the most ecologically dominant, economically significant, and popularly recognized group of extant crustaceans. There are over 3,000 fossil brachyuran species known from mid and upper Jurassic, Cretaceous, and Cenozoic deposits across the globe, many of them preserved in exquisite detail, but the origins and early evolution of true crabs remain unresolved. This uncertainty hinders the identification of the stratigraphically earliest occurrence of major brachyuran groups in the fossil record, obscuring our understanding of their phylogenetic relationships and thus the ability to estimate divergence times to answer large scale macroevolutionary questions. Here, we present 36 vetted fossil node calibration points for molecular phylogenetic analysis of crabs (one Anomura and 35 Brachyura) and reassess the earliest occurrences of several key clades based on recent fossil discoveries or re-examination of previous studies. For each calibrated node, we provide the minimum and tip maximum ages for the stratigraphically oldest fossil that can be reliably assigned to the group. Disentangling the anatomical disparity of fossil forms and their phylogenetic relationships is crucial to recognize the earliest branching members among brachyuran groups. This represents a critical first step understanding the evolution of carcinization and decarcinization in true crabs, the appearance of key adaptations, and the transition from sea to land and freshwater. The identification of reliable fossils for deep time calibrations, both as tips and nodes, is pivotal to ensure not only precise but more accurate divergence time estimations when reconstructing the crab tree of life.
InVitro Biocompatibility Evaluation of Acellular Porcine Dura mater Grafts and Native Dura

Damage to the dura mater may occur during intracranial or spinal surgeries, which can result in cerebrospinal fluid leakage as well as other potentially fatal physiological changes. As a result, biological scaffolds derived from xenogeneic materials are typically used to repair and regenerate dura mater post intracranial or spinal surgeries. The extracellular matrix of xenogeneic dura scaffolds has been shown to exhibit better cell infiltration and regeneration than synthetic material. In this study, we investigated the biocompatibility of native and decellularized porcine dura. Cell proliferation, cell viability, and mechanical properties of dural grafts were evaluated post re-seeding on days 3,7, and 14. Live-dead staining and resazurin salts were used to quantify cell viability and cell proliferation, respectively. Micro indentation was conducted to quantify the mechanical integrity of the native and acellular dura graft. The results show that the acellular porcine dural graft provides a favorable environment for rat fibroblast cell infiltration. Cell viability, proliferation, and micro indentation results on the acellular grafts are comparable with the native control porcine dura tissue. In conclusion, the porcine scaffold material showed increasing viable cells at each time point. The mechanics and biocompatibility results provide promising insight into the potential use of porcine dura in future cranial dura mater graft applications.
Maggot extracts chemo-prevent inflammation and tumorigenesis accompanied by changes in the intestinal microbiome and metabolome in AOM/DSS-induced mice

Inflammatory responses and intestinal microbiome play a crucial role in the progression of colitis-associated carcinoma (CAC). The traditional Chinese medicine maggot has been widely known owing to its clinical application and anti-inflammatory function. In this study, we investigated the preventive effects of maggot extract (ME) by intragastric administration prior to azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CAC in mice. The results showed that ME had superior advantages in ameliorating disease activity index score and inflammatory phenotype, in comparison with the AOM/DSS group. The number and size of polypoid colonic tumors were decreased after pre-administration of ME. In addition, ME was found to reverse the downregulation of tight junction proteins (zonula occluden-1 and occluding) while suppressing the levels of inflammatory factors (IL-1β and IL-6) in models. Moreover, Toll-like receptor 4 (TLR4) mediated intracellular nuclear factor-κB (NF-κB)-containing signaling cascades, including inducible nitric oxide synthase and cyclooxygenase-2, and exhibited decreasing expression in the mice model after ME pre-administration. 16s rRNA analysis and untargeted-metabolomics profiling of fecal samples inferred that ME revealed ideal prevention of intestinal dysbiosis in CAC mice, accompanied by and correlated with alterations in the composition of metabolites. Overall, ME pre-administration might be a chemo-preventive candidate in the initiation and development of CAC.
Whole genome sequence of Lactiplantibacillus plantarum MC5 and comparative analysis of eps gene clusters

Introduction Probiotic Lactiplantibacillus plantarum MC5 produces large amounts of exopolysaccharides (EPS), and its use as a compound fermentor can greatly improve the quality of fermented milk. Methods To gain insight into the genomic characteristics of probiotic MC5 and reveal the relationship between its EPS biosynthetic phenotype and genotype, we analyzed the carbohydrate metabolic capacity, nucleotide sugar formation pathways, and EPS biosynthesis-related gene clusters of strain MC5 based on its whole genome sequence. Finally, we performed validation tests on the monosaccharides and disaccharides that strain MC5 may metabolize. Results Genomic analysis showed that MC5 has seven nucleotide sugar biosynthesis pathways and 11 sugar-specific phosphate transport systems, suggesting that the strain can metabolize mannose, fructose, sucrose, cellobiose, glucose, lactose, and galactose. Validation results showed that strain MC5 can metabolize these seven sugars and produce significant amounts of EPS (> 250 mg/L). In addition, strain MC5 possesses two typical eps biosynthesis gene clusters, which include the conserved genes epsABCDE, wzx, and wzy, six key genes for polysaccharide biosynthesis, and one MC5-specific epsG gene. Discussion These insights into the mechanism of EPS-MC5 biosynthesis can be used to promote the production of EPS through genetic engineering.
Metformin attenuates high-fat diet induced metabolic syndrome related osteoarthritis through inhibition of prostaglandins

High-fat diet induces bone marrow inflammation and osteoarthritis phenotype in knee joint, but the underlying mechanisms is unknown. Here, we report that high-fat diet induces aberrant bone formation and cartilage degeneration in knee joint. Mechanistically, a high-fat diet increases the number of macrophages and the secretion of prostaglandins in subchondral bone, promoting bone formation. Metformin treatment is able to decrease the number of macrophages and also the level of prostaglandins induced by high-fat diet in subchondral bone. Importantly, metformin rescues aberrant bone formation and cartilage lesions by decreasing the number of osteoprogenitors and type-H vessels, which also results in relief of osteoarthritis pain response. Thus, we demonstrate prostaglandins secreted by macrophages may be a key reason for high-fat diet induced aberrant bone formation and metformin is a promising therapy for high-fat diet induced osteoarthritis.
The application of autologous cancer immunotherapies in the age of memory-NK cells

Cellular immunotherapy has revolutionized the oncology field, yielding improved results against hematological and solid malignancies. NK cells have become an attractive alternative due to their capacity to activate upon recognition of “stress” or “danger” signals independently of Major Histocompatibility Complex (MHC) engagement, thus making tumor cells a perfect target for NK cell-mediated cancer immunotherapy even as an allogeneic solution. While this allogeneic use is currently favored, the existence of a characterized memory function for NK cells (“memory-like” NK cells) advocates for an autologous approach, that would benefit from the allogeneic setting discoveries, but with added persistence and specificity. Still, both approaches struggle to exert a sustained and high anticancer effect in-vivo due to the immunosuppressive tumor micro-environment and the logistical challenges of cGMP production or clinical deployment. Novel approaches focused on the quality enhancement and the consistent large-scale production of highly activated therapeutic memory-like NK cells have yielded encouraging but still unconclusive results. This review provides an overview of NK biology as it relates to cancer immunotherapy and the challenge presented by solid tumors for therapeutic NKs. After contrasting the autologous and allogeneic NK approaches for solid cancer immunotherapy, this work will present the current scientific focus for the production of highly persistent and cytotoxic memory-like NK cells as well as the current issues with production methods as they apply to stress-sensitive immune cells. In conclusion, autologous NK cells for cancer immunotherapy appears to be a prime alternative for front line therapeutics but to be successful, it will be critical to establish comprehensives infrastructures allowing the production of extremely potent NK cells while constraining costs of production.
Metal interactions of α-synuclein probed by NMR amide-proton exchange

The aberrant aggregation of α-synuclein (αS), a disordered protein primarily expressed in neuronal cells, is strongly associated with the underlying mechanisms of Parkinson’s disease. It is now established that αS has a weak affinity for metal ions and that these interactions alter its conformational properties by generally promoting self-assembly into amyloids. Here, we characterised the nature of the conformational changes associated with metal binding by αS using nuclear magnetic resonance (NMR) to measure the exchange of the backbone amide protons at a residue specific resolution. We complemented these experiments with 15N relaxation and chemical shift perturbations to obtain a comprehensive map of the interaction between αS and divalent (Ca2+, Cu2+, Mn2+, and Zn2+) and monovalent (Cu+) metal ions. The data identified specific effects that the individual cations exert on the conformational properties of αS. In particular, binding to calcium and zinc generated a reduction of the protection factors in the C-terminal region of the protein, whereas both Cu(II) and Cu(I) did not alter the amide proton exchange along the αS sequence. Changes in the R2/R1 ratios from 15N relaxation experiments were, however, detected as a result of the interaction between αS and Cu+ or Zn2+, indicating that binding to these metals induces conformational perturbations in distinctive regions of the protein. Collectively our data suggest that multiple mechanisms of enhanced αS aggregation are associated with the binding of the analysed metals.
Can change in phase angle predict the risk of morbidity and mortality during an 18-year follow-up period? A cohort study among adults

Introduction Phase angle (PhA, degrees), measured via bioimpedance (BIA, 50 kHz), is an index that has been used as an indicator of nutritional status and mortality in several clinical situations. This study aimed to determine the relationship between 6-year changes in PhA and total mortality as well as the risk of incident morbidity and mortality from cardiovascular disease (CVD) and coronary heart disease (CHD) during 18 years of follow-up among otherwise healthy adults. Methods A random subset (n = 1,987) of 35–65 years old men and women was examined at the baseline in 1987/1988 and 6 years later in 1993/1994. Measures included weight, height, and whole-body BIA, from which PhA was calculated. Information on lifestyle was obtained through a questionnaire. The associations between 6-year PhA changes (ΔPhA) and incident CVD and CHD were assessed by Cox proportional hazard models. The median value of ΔPhA was used as the reference value. The hazard ratio (HR) model and confidence intervals (CIs) of incident CVD and CHD were used according to the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ΔPhA. Results During 18 years of follow-up, 205 women and 289 men died. A higher risk of both total mortality and incident CVD was present below the 50th percentile (Δ = −0.85°). The highest risk was observed below the 5th percentile (ΔPhA = −2.60°) in relation to total mortality (HR: 1.55; 95% CI: 1.10–2.19) and incident CVD (HR: 1.52; 95% CI: 1.16–2.00). Discussion The larger the decrease in PhA, the higher the risk of early mortality and incident CVD over the subsequent 18 years. PhA is a reliable and easy measure that may help identify those apparently healthy individuals who may be at increased risk of future CVD or dying prematurely. More studies are needed to confirm our results before it can be definitively concluded that PhA changes can improve clinical risk prediction.
Application of microbial membrane tetraether lipids in speleothems

Glycerol dialkyl glycerol tetraethers (GDGTs), which are derived from microbial membranes, occur widely in soils, peats, lake sediments, marine sediments, hot springs, and other environments. GDGTs respond sensitively to environmental changes and have become an important tool in paleoenvironmental reconstruction. However, their application in speleothems, one of the most important archives of the study of past climates, has been quite limited. In this paper, we review the recent progress in the study of GDGTs in speleothems, from their sources to their distribution characteristics and paleoenvironmental applications. GDGTs in speleothems have been shown to come from dripping water, and cave systems. The distribution of GDGTs in speleothems shows that archaeal isoprenoid GDGTs (isoGDGTs) dominate over bacterial branched GDGTs (brGDGTs). The proxies based on isoGDGTs (TEX86) and brGDGTs (MBT/CBT) are correlated with temperature, which may offer promising potential methods for reconstructing terrestrial palaeotemperature. Ultimately, we discuss the difficulties and problems to be solved in studying speleothem GDGTs and the possible future directions for this field.
Cellular and molecular insights into incomplete immune recovery in HIV/AIDS patients

Highly active antiretroviral therapy (ART) can effectively inhibit virus replication and restore immune function in most people living with human immunodeficiency virus (HIV). However, an important proportion of patients fail to achieve a satisfactory increase in CD4+ T cell counts. This state is called incomplete immune reconstitution or immunological nonresponse (INR). Patients with INR have an increased risk of clinical progression and higher rates of mortality. Despite widespread attention to INR, the precise mechanisms remain unclear. In this review, we will discuss the alterations in the quantity and quality of CD4+ T as well as multiple immunocytes, changes in soluble molecules and cytokines, and their relationship with INR, aimed to provide cellular and molecular insights into incomplete immune reconstitution.
Growth of late preterm infants fed nutrient-enriched formula to 120 days corrected age—A randomized controlled trial

Objectives We aimed to compare the effects of nutrient-enriched formula with standard term formula on rate of body weight gain of late preterm infants appropriately grown for gestational age. Study design A multi-center, randomized, controlled trial. Late preterm infants (34–37 weeks' gestation), with weight appropriate for gestational age (AGA), were randomized to nutrient enriched formula (NEF) with increased calories (22 kcal/30 ml) from protein, added bovine milk fat globule membrane, vitamin D and butyrate or standard term formula 20 kcal/30 ml (STF). Breastfed term infants were enrolled as an observational reference group (BFR). Primary outcome was rate of body weight gain from enrollment to 120 days corrected age (d/CA). Planned sample size was 100 infants per group. Secondary outcomes included body composition, weight, head circumference and length gain, and medically confirmed adverse events to 365 d/CA. Results The trial was terminated early due to recruitment challenges and sample size was substantially reduced. 40 infants were randomized to NEF (n = 22) and STF (n = 18). 39 infants were enrolled in the BFR group. At 120 d/CA there was no evidence of a difference in weight gain between randomized groups (mean difference 1.77 g/day, 95% CI, −1.63 to 5.18, P = 0.31). Secondary outcomes showed a significant reduction in risk of infectious illness in the NEF group at 120 d/CA [relative risk 0.37 (95% CI, 0.16–0.85), P = 0.02]. Conclusion We saw no difference in rate of body weight gain between AGA late preterm infants fed NEF compared to STF. Results should be interpreted with caution due to small sample size. Clinical Trial Registration The Australia New Zealand Clinical Trials Registry (ACTRN 12618000092291). “mailto:maria.makrides@sahmri.com” maria.makrides@sahmri.com.
Neuroimaging findings in preclinical amyotrophic lateral sclerosis models—How well do they mimic the clinical phenotype? A systematic review

Background and objectives Animal models for motor neuron diseases (MND) such as amyotrophic lateral sclerosis (ALS) are commonly used in preclinical research. However, it is insufficiently understood how much findings from these model systems can be translated to humans. Thus, we aimed at systematically assessing the translational value of MND animal models to probe their external validity with regards to magnetic resonance imaging (MRI) features. Methods In a comprehensive literature search in PubMed and Embase, we retrieved 201 unique publications of which 34 were deemed eligible for qualitative synthesis including risk of bias assessment. Results ALS animal models can indeed present with human ALS neuroimaging features: Similar to the human paradigm, (regional) brain and spinal cord atrophy as well as signal changes in motor systems are commonly observed in ALS animal models. Blood-brain barrier breakdown seems to be more specific to ALS models, at least in the imaging domain. It is noteworthy that the G93A-SOD1 model, mimicking a rare clinical genotype, was the most frequently used ALS proxy. Conclusions Our systematic review provides high-grade evidence that preclinical ALS models indeed show imaging features highly reminiscent of human ALS assigning them a high external validity in this domain. This opposes the high attrition of drugs during bench-to-bedside translation and thus raises concerns that phenotypic reproducibility does not necessarily render an animal model appropriate for drug development. These findings emphasize a careful application of these model systems for ALS therapy development thereby benefiting refinement of animal experiments. Systematic review registration https://www.crd. york.ac. uk/PROSPERO/, identifier: CRD42022373146.
Feasibility, acceptability, and preliminary efficacy of yoga to improve maternal mental health and immune function during the COVID-19 crisis (Yoga-M2 trial): a pilot randomized controlled trial

Introduction Women are vulnerable during pregnancy as they experience multiple physical and psychological problems which can lead to stress and poor quality of life ultimately affecting the development of the fetus and their health during and after pregnancy. Prior evidence suggests that prenatal yoga can improve maternal health and well-being and can have a beneficial effect on immune system functioning. To date, no study has been conducted in a rural, low-resource setting in India to assess the feasibility, acceptability, and preliminary efficacy of a yoga-based intervention on perceived stress, quality of life, pro-inflammatory biomarkers, and symptoms of upper respiratory tract infections. Methods To address this gap and assess whether a yoga-based intervention could improve maternal mental health and immunity during the COVID-19 crisis (Yoga-M2 trial), a single-blind individual randomized parallel group-controlled pilot trial with a 1:1 allocation ratio was implemented. We randomly allocated 51 adult pregnant women, with gestational age between 12-24 weeks in the Yoga-M2 arm (n = 25) or the enhanced usual care arm (EUC) (n = 26). Feasibility and acceptability were assessed using the process data and In-Depth Interviews (IDIs) with the trial participants and yoga instructors. Multiple linear regression was used to compare follow-up scores for quantitative outcomes. Results A three-month follow-up assessment was completed for 48 out of 51 participants (94.12%). We did not find any statistically significant difference between both arms in total Perceived Stress Scale scores, quality of life (Eq-5D-5L index), and serum C Reactive Protein levels at the three-month follow-up assessment. The critical barriers to practicing yoga were lack of knowledge about the benefits of yoga, lack of ‘felt need' to practice yoga, lack of time to practice, lack of space, lack of transport, and lack of peer group to practice yoga. Despite this, women who regularly practiced yoga described the benefits and factors which motivated them to practice regularly. Discussion The learnings from this trial will help design the explanatory trial in the future and the study findings can also be used by the primary health care system to deliver yoga-based interventions in the newly created health and wellness centers. Trial registration This trial was prospectively registered with the Clinical Trials Registry of India on 25 January 2022. https://www.ctri. nic.in/Clinicaltrials/showallp.php? mid1=65173&EncHid=&userName=CTRI/2022/01/039701. Trial registration number: CTRI/2022/01/039701.
Diagnostic value of artificial intelligence-assisted endoscopy for chronic atrophic gastritis: a systematic review and meta-analysis

Background and aims The diagnosis of chronic atrophic gastritis (CAG) under normal white-light endoscopy depends on the endoscopist's experience and is not ideal. Artificial intelligence (AI) is increasingly used to diagnose diseases with good results. This review aimed to evaluate the accuracy of AI-assisted diagnosis of CAG through a meta-analysis. Methods We conducted a comprehensive literature search of four databases: PubMed, Embase, Web of Science, and the Cochrane Library. Studies published by November 21, 2022, on AI diagnosis CAG with endoscopic images or videos were included. We assessed the diagnostic performance of AI using meta-analysis, explored the sources of heterogeneity through subgroup analysis and meta-regression, and compared the accuracy of AI and endoscopists in diagnosing CAG. Results Eight studies that included a total of 25,216 patients of interest, 84,678 image training set images, and 10,937 test set images/videos were included. The results of the meta-analysis showed that the sensitivity of AI in identifying CAG was 94% (95% confidence interval [CI]: 0.88–0.97, I2 = 96.2%), the specificity was 96% (95% CI: 0.88–0.98, I2 = 98.04%), and the area under the summary receiver operating characteristic curve was 0.98 (95% CI: 0.96–0.99). The accuracy of AI in diagnosing CAG was significantly higher than that of endoscopists. Conclusions AI-assisted diagnosis of CAG in endoscopy has high accuracy and clinical diagnostic value. Systematic review registration http://www.crd. york.ac. uk/PROSPERO/, identifier: CRD42023391853.