Miracle-dz/UniFAR-FTUs huggingface dataset:
The clinical differentiation of blood culture-positive and -negative sepsis in burn patients: a retrospective cohort study

Abstract Background Sepsis is a potentially life-threatening condition that occurs when the body’s response to infection leads to widespread inflammation and tissue damage. Negative cultures can make it difficult for clinicians to make a diagnosis and may raise questions about the validity of the definition of sepsis. In addition, the clinical distinctions between burn patients with blood culture-positive and -negative sepsis are also poorly understood. Therefore, this study aimed to examine the clinical differences between blood culture-positive and -negative sepsis in burn patients in order to improve the understanding of the pathophysiology and epidemiology of sepsis in this population. Methods This study had a retrospective design, and the participants were adults aged ≥18 years. Patients diagnosed with sepsis were divided into two groups based on their blood culture results within 1 week of sepsis diagnosis. Results We enrolled 1643 patients admitted to our institution’s burn intensive care unit between January 2010 and December 2021. pH, platelet count, bicarbonate and haematocrit were significant in both the positive and negative groups. However, lymphocyte, red cell distribution width and blood urea nitrogen were significant only in the positive group, whereas lactate dehydrogenase was significant only in the negative group. Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumonia are common gram-negative bacterial species, and Staphylococcus aureus and Staphylococcus epidermidis are common gram-positive bacterial species seen in burn patients with positive blood cultures. Carbapenem resistance was found to be associated with an unfavourable prognosis in gram-negative bacteria, with the exception of P. aeruginosa. Conclusions pH, platelet count, bicarbonate and haematocrit were routine biomarkers that demonstrated statistical significance in both groups. Lactate dehydrogenase was significant in the blood-negative group, while red cell distribution width, blood urea nitrogen and lymphocyte count were significant in the positive group. Furthermore, the most common causes of sepsis are gram-negative bacteria, including A. baumannii, K. pneumoniae and P. aeruginosa. Additionally, resistance to carbapenems is associated with unfavourable outcomes.
MicroED as a Powerful Tool for Structure Determination of Macrocyclic Drug Compounds Directly from Their Powder Formulations

Macrocycles are important drug leads with many advantages including the ability to target flat and featureless binding sites as well as to act as molecular chameleons and thereby reach intracellular targets. However, due to their complex structures and inherent flexibility, macrocycles are difficult to study structurally, and there are limited structural data available. Herein, we use the cryo-EM method MicroED to determine the novel atomic structures of several macrocycles that have previously resisted structural determination. We show that structures of similar complexity can now be obtained rapidly from nanograms of material and that different conformations of flexible compounds can be derived from the same experiment. These results will have an impact on contemporary drug discovery as well as natural product exploration.
Morbimortality and determinants of reperfusion in ischemic stroke

SUMMARY BACKGROUND: Cerebrovascular accident (or stroke) and ischemic heart disease are the the major causes of death in the world. It is estimated that about 85% of strokes are ischemic in origin. Reperfusion therapy in the acute phase of ischemic stroke with a recombinant human tissue plasminogen activator is effective, but some factors influence the success of this treatment. OBJECTIVE: The aim of this study was to evaluate clinical aspects and possible determinants for reperfusion after venous thrombolysis. METHODS: This is a retrospective, cross-sectional, observational study based on a review of hospital records of inpatients diagnosed with ischemic stroke treated with intravenous thrombolysis, the main outcome being reperfusion or not. RESULTS: Data from this study revealed a predominance of females in the group of reperfused patients and males in the non-reperfused group, both maintaining moderate severity on the National Institutes of Health Stroke Scale and admission without statistical significance (p>0.18). In addition, the mean admission severity score was 13.2 for the group of reperfused patients and 14.2 for those not reperfused, and the mean ejection fraction of both groups was within normal functionality, with a mean of 0.50 for reperfused patients and 0.62 for non-reperfused patients. CONCLUSION: We found an association between successful venous chemical thrombolysis reperfusion and lower mortality in patients with acute stroke.
Explainable artificial intelligence for omics data: a systematic mapping study

Abstract Researchers increasingly turn to explainable artificial intelligence (XAI) to analyze omics data and gain insights into the underlying biological processes. Yet, given the interdisciplinary nature of the field, many findings have only been shared in their respective research community. An overview of XAI for omics data is needed to highlight promising approaches and help detect common issues. Toward this end, we conducted a systematic mapping study. To identify relevant literature, we queried Scopus, PubMed, Web of Science, BioRxiv, MedRxiv and arXiv. Based on keywording, we developed a coding scheme with 10 facets regarding the studies’ AI methods, explainability methods and omics data. Our mapping study resulted in 405 included papers published between 2010 and 2023. The inspected papers analyze DNA-based (mostly genomic), transcriptomic, proteomic or metabolomic data by means of neural networks, tree-based methods, statistical methods and further AI methods. The preferred post-hoc explainability methods are feature relevance (n = 166) and visual explanation (n = 52), while papers using interpretable approaches often resort to the use of transparent models (n = 83) or architecture modifications (n = 72). With many research gaps still apparent for XAI for omics data, we deduced eight research directions and discuss their potential for the field. We also provide exemplary research questions for each direction. Many problems with the adoption of XAI for omics data in clinical practice are yet to be resolved. This systematic mapping study outlines extant research on the topic and provides research directions for researchers and practitioners.
Machine learning algorithm‐based estimation model for the severity of depression assessed using Montgomery‐Asberg depression rating scale

Abstract Aim Depressive disorder is often evaluated using established rating scales. However, consistent data collection with these scales requires trained professionals. In the present study, the “rater & estimation‐system” reliability was assessed between consensus evaluation by trained psychiatrists and the estimation by 2 models of the AI‐MADRS (Montgomery‐Asberg Depression Rating Scale) estimation system, a machine learning algorithm‐based model developed to assess the severity of depression. Methods During interviews with trained psychiatrists and the AI‐MADRS estimation system, patients responded orally to machine‐generated voice prompts from the AI‐MADRS structured interview questions. The severity scores estimated from two models of the AI‐MADRS estimation system, the max estimation model and the average estimation model, were compared with those by trained psychiatrists. Results A total of 51 evaluation interviews conducted on 30 patients were analyzed. Pearson's correlation coefficient with the scores evaluated by trained psychiatrists was 0.76 (95% confidence interval 0.62–0.86) for the max estimation model, and 0.86 (0.76–0.92) for the average estimation model. The ANOVA ICC rater & estimation‐system reliability with the evaluation scores by trained psychiatrists was 0.51 (−0.09 to 0.79) for the max estimation model, and 0.75 (0.55–0.86) for the average estimation model. Conclusion The average estimation model of AI‐MADRS demonstrated substantially acceptable rater & estimation‐system reliability with trained psychiatrists. Accumulating a broader training dataset and the refinement of AI‐MADRS interviews are expected to improve the performance of AI‐MADRS. Our findings suggest that AI technologies can significantly modernize and potentially revolutionize the realm of depression assessments.
Patient’s Perspective on Psychiatric Drugs: A Multicenter Survey-Based Study

Objective We aimed to identify the expectations and preferences for medication and medical decision-making in patients with major psychiatric disorders. Methods A survey was conducted among patients with major psychiatric disorders who visited psychiatric outpatient clinics at 15 hospitals between 2016 and 2018 in Korea. The survey consisted of 12 questions about demographic variables and opinions on their expectations for medication, important medical decision-makers, and preferred drug type. The most preferred value in each category in the total population was identified, and differences in the preference ratio of each item among the disease groups were compared. Results A total of 707 participants were surveyed. In the total population, patients reported high efficacy (44.01%±21.44%) as the main wish for medication, themselves (37.39%±22.57%) and a doctor (35.27%±22.88%) as the main decision makers, and tablet/capsule (36.16%±30.69%) as the preferred type of drug. In the depressive disorders group, the preference ratio of high efficacy was significantly lower, and the preference ratio of a small amount was significantly higher than that of the psychotic disorder and bipolar disorder groups. The preference ratio of a doctor as an important decision maker in the bipolar disorder group was higher compared to the other groups. Conclusion This study revealed the preference for medications and showed differences among patients with psychiatric disorders. Providing personalized medicine that considers a patient’s preference for the drug may contribute to the improvement of drug compliance and outcomes.
Prognostic, immunity, stemness, and anticancer drug sensitivity characterization of pyroptosis related genes in non‐small cell lung cancer

Abstract Background Pyroptosis plays a pivotal role in the tumor immune microenvironment (TME) dynamics, particularly in non‐small cell lung cancer (NSCLC). The aim of our study was to explore its effects on tumor progression, TME patterns, and the efficacy of therapeutic interventions in NSCLC. Methods Our investigation encompassed a thorough analysis of pyroptosis‐related genes (PRGs), integrating immunohistochemistry (IHC) data, TME characteristics, stemness indices, and anticancer drug sensitivities. We aimed to analyze mRNA expression profiles across various cancers, constructing benchmark datasets to assess the clinical significance of PRGs in NSCLC. This included evaluating their association with clinical responses and efficacy. Notably, both our and HPA IHC data demonstrated significantly elevated GSDMD‐N protein levels in lung squamous cell carcinoma (LUSC) tissues. Results The expression of PRGs differed significantly between tumor and normal tissues across various cancers, as validated by IHC data, and was correlated with prognosis (p < 0.05). Moreover, our investigation revealed significant differences (p < 0.05) in the expression of the PRGs among distinct TME subtypes categorized as C1 (wound healing), C3 (inflammatory), C2 (IFN‐gamma dominant), C5 (immunological quiet), C4 (lymphocyte deficient), and C6 (TGF‐beta dominant). Additionally, our research on anticancer drug sensitivity uncovered compelling connections between specific anticancer medications and the expression of PRGs, including GSDMD, ELANE, IL18, and CHMP4A (p < 0.05). Conclusion Our study provided valuable insights into the critical role of PRGs in TME modulation, tumor stemness, and anticancer drug sensitivity across diverse cancers. Our findings illuminate the intricate relationship between pyroptosis and the TME, offering new perspectives for enhancing NSCLC treatment and prognosis.
Exercising sheep as a preclinical model for musculoskeletal research.

OBJECTIVE To establish an orthopedic, preclinical, ovine model of controlled exercise using an equine walker. ANIMALS 20 Dorset-Polypay sheep. PROCEDURES Sheep underwent 11 weeks of exercise, 4 days per week. Exercise duration and intensity increased until sheep performed 25 minutes at 1.3 m/s and 5 min at 2.0 m/s. Physical/lameness examinations were conducted every 14 days. Blood was collected every 28 days for analysis of serum bone biomarkers (SBB): bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), carboxy-telopeptide of type I collagen cross-links (CTX-I), tartrate-resistant acid phosphatase 5b (TRAP5b), and receptor activator of nuclear factor-kβ ligand (RANKL). RESULTS Sheep adapted easily to group exercise. Animals grew taller (P = .006) but had a 4% weight loss (P = .003). RANKL was reduced on days 28 and 84 compared to day 56 (P < .05), CTX-1 was reduced on days 28 and 84 compared to days 0 and 56 (P < .05), and TRAP5b was greater on day 28 compared to day 0 (P = .009). BALP and PINP did not change. CLINICAL RELEVANCE The described preclinical model of exercising sheep has distinct advantages including ease of handling, an established lameness scale, commercially available ovine SBB assays, and the ability to alter footing characteristics and complete circular exercise. Decreasing CTX-I and RANKL with no change in BALP and PINP suggests reduced bone resorption over the study period. Future studies may include a sedentary group or utilize adult animals to alleviate any influence of growth on SBB.
Does enhanced cognitive performance reduce fracture risk? a Mendelian randomization study

Objective: While observational studies have suggested a link between cognitive performance and fracture risk, the causality and site-specific nature are unclear. We applied Mendelian randomization (MR) to elucidate these associations. Methods: 147 single-nucleotide polymorphisms (SNPs) tied strongly to cognitive performance (p< 5e-8) were selected. We performed MR analysis to investigate the causal relationship between cognitive performance and fractures at specific sites, including the wrist, upper arm, shoulder, ribs, sternum, thoracic spine, lumbar spine, pelvis, femur, leg, and ankle. The primary estimate was determined using the inverse variance-weighted method. Additionally, we examined heterogeneity using the MR Pleiotropy RESidual Sum Outlier test and Cochran Q, and employed MR-Egger regression to identify horizontal pleiotropy. Results: MR analysis identified a causal association between cognitive performance and fractures at the lumbar-spine-pelvis (odds ratio [OR] = 0.727, 95% CI = 0.552–0.956, p = 0.023), and ribs-sternum-thoracic spine sites (OR = 0.774, 95% CI = 0.615–0.974, p = 0.029). However, no causal association was found for fractures at other sites. Conclusions: This study provided evidence of a causal connection between cognitive performance and fracture risk at certain locations. These findings underline the potential of cognitive enhancement strategies as innovative and effective methods for fracture prevention.
G-quadruplexes control hepatitis B virus replication by promoting cccDNA transcription and phase separation in hepatocytes

Abstract Phase separation regulates fundamental processes in gene expression and is mediated by the local concentration of proteins and nucleic acids, as well as nucleic acid secondary structures such as G-quadruplexes (G4s). These structures play fundamental roles in both host gene expression and in viral replication due to their peculiar localisation in regulatory sequences. Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is an episomal minichromosome whose persistence is at the basis of chronic infection. Identifying the mechanisms controlling its transcriptional activity is indispensable to develop new therapeutic strategies against chronic hepatitis B. The aim of this study was to determine whether G4s are formed in cccDNA and regulate viral replication. Combining biochemistry and functional studies, we demonstrate that cccDNA indeed contains ten G4s structures. Furthermore, mutations disrupting two G4s located in the enhancer I HBV regulatory region altered cccDNA transcription and viral replication. Finally, we showed for the first time that cccDNA undergoes phase separation in a G4-dependent manner to promote its transcription in infected hepatocytes. Altogether, our data give new insight in the transcriptional regulation of the HBV minichromosome that might pave the way for the identification of novel targets to destabilize or silence cccDNA.
Enlarged Perivascular Spaces in Infancy and Autism Diagnosis, Cerebrospinal Fluid Volume, and Later Sleep Problems

Key Points Question Are enlarged perivascular spaces (PVS) in infancy associated with autism diagnosis, cerebrospinal fluid (CSF) volume, and later sleep problems? Findings In this cohort study of 311 infants at high or low familial likelihood of autism, infants aged 24 months with high familiar risk and a diagnosis of autism had significantly higher prevalence rates of enlarged PVS than infants with no autism with or without familial risk. Enlarged PVS were also associated with increased CSF volume and later sleep problems. Meaning These findings suggest that enlarged PVS could be an early indication of glymphatic dysfunction and that aberrant CSF dynamics may play a role in the development of autism.
Overlap in distribution of forest and meadow insect species in mesoecotones. I. Epigeic beetle assemblages (Coleoptera : Carabidae, Silphidae)

The paper presents results of original observations made in several forest mesoecotones. During the summer periods of 1988-1993 the distribution of epigeic beetles (Coleoptera: Carabidae, Silphidae) in relation to forest borders was studied in different vegetation zones of Central Siberia (Russia). With the use of pitfall traps, the distribution of 16080 individuals of 50 species was noted along transects crossing forest borders. The degree of overlap of neighbouring woodland and grassland beetle assemblages was examined in all experimental plots. The average extension of overlap changed from 6 m in the case of sharp coenotic transition, to over 25 m when the abruptness of transition declined. In the site subjected to secondary succession, the overlap zone was characterized by consecutive broadening from 13 to 22 m during the years of observation. General features of the overlap zones (size, species diversity and evenness, transitional character) are discussed into the limits of ecotone conception.
Cardiac MR modelling of systolic and diastolic blood pressure

Aims Blood pressure (BP) is a crucial factor in cardiovascular health and can affect cardiac imaging assessments. However, standard outpatient cardiovascular MR (CMR) imaging procedures do not typically include BP measurements prior to image acquisition. This study proposes that brachial systolic BP (SBP) and diastolic BP (DBP) can be modelled using patient characteristics and CMR data. Methods In this multicentre study, 57 patients from the PREFER-CMR registry and 163 patients from other registries were used as the derivation cohort. All subjects had their brachial SBP and DBP measured using a sphygmomanometer. Multivariate linear regression analysis was applied to predict brachial BP. The model was subsequently validated in a cohort of 169 healthy individuals. Results Age and left ventricular ejection fraction were associated with SBP. Aortic forward flow, body surface area and left ventricular mass index were associated with DBP. When applied to the validation cohort, the correlation coefficient between CMR-derived SBP and brachial SBP was (r=0.16, 95% CI 0.011 to 0.305, p=0.03), and CMR-derived DBP and brachial DBP was (r=0.27, 95% CI 0.122 to 0.403, p=0.0004). The area under the curve (AUC) for CMR-derived SBP to predict SBP>120 mmHg was 0.59, p=0.038. Moreover, CMR-derived DBP to predict DBP>80 mmHg had an AUC of 0.64, p=0.002. Conclusion CMR-derived SBP and DBP models can estimate brachial SBP and DBP. Such models may allow efficient prospective collection, as well as retrospective estimation of BP, which should be incorporated into assessments due to its critical effect on load-dependent parameters.
Mandating reimbursement for non-FDA-regulated cannabis is bad public policy

Abstract An influential cannabis lobby and its allies are engaged in an aggressive initiative to mandate health and worker’s compensation insurance coverage for non-standardized, non-FDA-regulated cannabis products. If successful, mandated reimbursement would present a severe public health risk and force taxpayers to fund a risky and under-regulated industry. Leaders in psychiatry and other medical specialties have sounded the alarm about the marketing and sale of cannabis products for medical uses without prior review by the FDA. We echo their strong opposition to bills requiring workers’ compensation carriers and health insurance plans to cover the cost of dispensary-purchased “medical” cannabis. Mandated insurance reimbursement of dispensary products is “a recipe for a public health disaster, as lowering or eliminating out-of-pocket costs will encourage more consumers to become certified under a state’s medical cannabis program, and result in more frequent use of higher-potency cannabinoids (e.g., THC and CBD) that are associated with serious adverse events. ” Until there are thorough studies into these products, including adverse events, side effects and long-term concerns, these products should not be considered appropriate alternatives to FDA-approved medications. Their use should not be encouraged nor paid for through mandated reimbursement by public or private third-party payers.
WHAT TO DO ABOUT THE NORTH AMERICAN INVASION BY THE COLLARED DOVE

The attention of American ornithologists is drawn to the North American in- vasion of a renowned European invader, the Collared Dove (Streptopelia decaocto). After the experience obtained in Europe, several aspects can now be studied in North America, (1) how the spread across the continent is progressing, (2) how the local populations build up, (3) whether, by using a recent model, the rate of spatial progression of the invasion wave can be predicted, (4) how much, where and when pheno-genetic differentiation is generated, and (5) how it affects the local fauna. Americans have a unique opportunity to study the invasion of one of the best-known invaders, on their own ground, on the basis of extensive experience from Europe.