Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel blood derived hemostatic agents for bleeding therapy and prophylaxis

Purpose of review Hemorrhage is a major cause of preventable death in trauma and cancer. Trauma induced coagulopathy and cancer-associated endotheliopathy remain major therapeutic challenges. Early, aggressive administration of blood-derived products with hypothesized increased clotting potency has been proposed. A series of early- and late-phase clinical trials testing the safety and/or efficacy of lyophilized plasma and new forms of platelet products in humans have provided light on the future of alternative blood component therapies. This review intends to contextualize and provide a critical review of the information provided by these trials. Recent findings The beneficial effect of existing freeze-dried plasma products may not be as high as initially anticipated when tested in randomized, multicenter clinical trials. A next-generation freeze dried plasma product has shown safety in an early phase clinical trial and other freeze-dried plasma and spray-dried plasma with promising preclinical profiles are embarking in first-in-human trials. New platelet additive solutions and forms of cryopreservation or lyophilization of platelets with long-term shelf-life have demonstrated feasibility and logistical advantages. Summary: Recent trials have confirmed logistical advantages of modified plasma and platelet products in the treatment or prophylaxis of bleeding. However, their postulated increased potency profile remains unconfirmed.
Impactful scientists have higher tendency to involve collaborators in new topics

Significance Scientific collaboration is an important feature of modern science. The topics involved in scientific collaborations have been associated with creativity and the impact of research. Yet, how scientists involve collaborators in their research topics remains poorly understood. We reveal here the general tendency of collaborators to be involved in a single topic. The tendency is stronger for the collaborators of productive scientists, but weaker for the collaborators of impactful scientists. We further identify the past research productivity and impact of collaborators as key factors affecting their probability to join a new topic of a given scientist. The analysis framework is general and applicable for understanding collaborations in various other systems, such as film-making, patent design, and software development.
Setting up regional diagnostic reference levels for pediatric interventional cardiology in Latin America and the Caribbean countries: preliminary results and identified challenges

The goal of the present study was to propose a set of preliminary regional diagnostic reference levels (DRLs) for pediatric interventional cardiology (IC) procedures in Latin America and the Caribbean countries, classified by age and weight groups. The study was conducted in the framework of the Optimization of Protection in Pediatric Interventional Radiology in Latin America and the Caribbean program coordinated by the World Health Organization and the Pan American Health Organization in cooperation with the International Atomic Energy Agency. The first step of the program was focused on pediatric IC. Dose data from diagnostic and therapeutic procedures were collected between December 2020 and December 2021. Regional DRLs were set as the third quartile of patient dose data (kerma area product) collected in 18 hospitals from 10 countries in an initial sample of 968 procedures. DRLs were set for four age bands and five weight ranges. The values obtained for the four age bands (<1 yr, 1 to <5 yr, 5 to <10 yr and 10 to <16 yr) were 2.9, 6.1, 8.8 and 14.4 Gy cm2 for diagnostic procedures, and 4.0, 5.0, 10.0 and 38.1 Gy cm2 for therapeutic procedures, respectively. The values obtained for the five weight bands (<5 kg, 5 to <15 kg, 15 to <30 kg, 30 to <50 kg and 50 to <80 kg) were 3.0, 4.5, 8.1, 9.2 and 26.8 Gy cm2 for diagnostic procedures and 3.7, 4,3, 7.3, 16.1 and 53.4 Gy cm2 for therapeutic procedures, respectively. While initial data were collected manually as patient dose management systems (DMSs) were not available in most of the hospitals involved in the program, a centralized automatic DMS for the collection and management of patient dose indicators has now been introduced and is envisaged to increase the sample size. The possibility of alerting on high dose values and introducing corrective actions will help in optimization.
Evidence for a theta‐band behavioural oscillation in rapid face detection

Theories of rhythmic perception propose that perceptual sampling operates in a periodic way, with alternating moments of high and low responsiveness to sensory inputs. This rhythmic sampling is linked to neural oscillations and thought to produce fluctuations in behavioural outcomes. Previous studies have revealed theta‐ and alpha‐band behavioural oscillations in low‐level visual tasks and object categorization. However, less is known about fluctuations in face perception, for which the human brain has developed a highly specialized network. To investigate this, we ran an online study (N = 179) incorporating the dense sampling technique with a dual‐target rapid serial visual presentation (RSVP) paradigm. In each trial, a stream of object images was presented at 30 Hz and participants were tasked with detecting whether or not there was a face image in the sequence. On some trials, one or two (identical) face images (the target) were embedded in each stream. On dual‐target trials, the targets were separated by an interstimulus interval (ISI) that varied between 0 to 633 ms. The task was to indicate the presence of the target and its gender if present. Performance varied as a function of ISI, with a significant behavioural oscillation in the face detection task at 7.5 Hz, driven mainly by the male target faces. This finding is consistent with a high theta‐band‐based fluctuation in visual processing. Such fluctuations might reflect rhythmic attentional sampling or, alternatively, feedback loops involved in updating top‐down predictions.
Sphingosine‐1‐phosphate receptor modulators in stroke treatment

Sphingosine‐1‐phosphate (S1P) is a bioactive lysophospholipid that can influence a broad range of biological processes through its binding to five distinct G‐protein‐coupled receptors. S1P receptor modulators are a new group of immunosuppressive agents currently used in the immunotherapy of multiple sclerosis. Inflammation following stroke can exacerbate neuronal injury. Given that S1P signaling is linked to multiple immune processes, therapies targeting the S1P axis may be suitable for treating stroke. In this review, we outline S1P metabolism and S1P receptors, discuss the mechanisms of action of S1P receptor modulators in lymphocyte migration and their direct action on cells of the central nervous system, and provide a concise summary of the efficacy of S1P receptor modulators in animal studies and clinical trials on treatments for stroke.
Reducing patient delay in acute coronary syndrome: Randomized controlled trial testing effect of behaviour change intervention on intentions to seek help

Abstract Objectives The aim of this study was to evaluate the efficacy of a behaviour change intervention to reduce patient delay with symptoms of acute coronary syndrome. Design A 3‐arm web‐based, parallel randomized controlled trial. Methods The intervention comprised 12 behaviour change techniques (BCTs) embedded in a text‐only or text+visual narrative (the techniques were systematically identified through systematic review and a consensus exercise). Between February and November 2017, n = 145 people who had recently experienced acute coronary syndrome were randomly allocated to intervention (‘text+visual’ or ‘text‐only’) or control. Intentions to phone an ambulance immediately for acute coronary syndrome symptoms were assessed before and after the intervention using symptom scenarios, and the change in intention was compared across the three groups. Results Significant increases in intention to phone an ambulance immediately for ACS symptoms were seen following the ‘text+visual’ intervention but not following ‘text‐only’ or control. However, the study was underpowered to detect any significant changes in intention between the 3 groups. There were no unintended effects on intentions for non‐urgent symptoms. Conclusions A ‘text+visual’ BCT‐based intervention may significantly increase intention to phone an ambulance with symptoms of ACS. Further testing of the effect of the intervention on actual behaviour is required.
Measuring subjective clustering of verbal information after moderate-severe traumatic brain injury: a preliminary study

ABSTRACT Background There is no agreed upon measure of subjective clustering for clinical use in patients following moderate-severe traumatic brain injury (TBI). Objective This study investigated whether measures of subjective clustering, subjective organization (SO) and adjusted ratio of clustering (ARC), were appropriate for use in patients following moderate-severe TBI. Methods Twenty participants with moderate-severe TBI in the chronic stage of recovery and 20 control participants recalled a list of unrelated words over six trials. The authors assessed if the SO and ARC measures could discriminate the groups’ ability to subjectively cluster the words. The authors also examined whether the SO and ARC measures correlated with recall and learning rate, and if combining the measures improved the predictive accuracy. Results Participants with moderate-severe TBI performed significantly worse on the SO measure, but there were no group differences regarding the ARC measure. The SO measure positively correlated with recall, but not learning rate. The ARC measure did not positively correlate with recall or learning rate, and combining the measures did not enhance the predictive accuracy. Conclusions The SO measure is likely an appropriate candidate for clinical use. However, there are problems with the ARC measure that limit its use as a clinical tool.
Respirable Clofazimine Particles Produced by Air Jet Milling Technique Are Efficacious in Treatment of BALB/c Mice with Chronic Mycobacterium tuberculosis Infection

Tuberculosis (TB) remains a major cause of morbidity and mortality, particularly in low- and middle-income countries where access to health care workers, cold-chain storage, and sterile water sources may be limited. Inhaled drug delivery is a promising alternative to systemic delivery of antimycobacterial drugs, as it enables rapid achievement of high infection-site drug concentrations. ABSTRACT Tuberculosis (TB) remains a major cause of morbidity and mortality, particularly in low- and middle-income countries where access to health care workers, cold-chain storage, and sterile water sources may be limited. Inhaled drug delivery is a promising alternative to systemic delivery of antimycobacterial drugs, as it enables rapid achievement of high infection-site drug concentrations. The off-patent drug clofazimine (CFZ) may be particularly suitable for this route, given its known systemic toxicities. In this study, micronized CFZ particles produced by air jet milling were assessed for shelf-stability, pharmacokinetics, and anti-TB efficacy by the oral and pulmonary routes in BALB/c mice. Intratracheal instillation of micronized CFZ particles produced several-fold higher lung concentrations after a single 30 mg/kg dose compared to delivery via oral gavage, and faster onset of bactericidal activity was observed in lungs of mice with chronic Mycobacterium tuberculosis infection compared to the oral route. Both infection status and administration route affected the multidose pharmacokinetics (PK) of micronized CFZ. Increased lung and spleen accumulation of the drug after pulmonary administration was noted in infected mice compared to naive mice, while the opposite trend was noted in the oral dosing groups. The infection-dependent PK of inhaled micronized CFZ may point to a role of macrophage trafficking in drug distribution, given the intracellular-targeting nature of the formulation. Lastly, air jet milled CFZ exhibited robustness to storage-induced chemical degradation and changes in aerosol performance, thereby indicating the suitability of the formulation for treatment of TB in regions with limited cold chain supply.
Low-Dose Occupational Exposure to Nickel and Thyroid Hormones

The results suggest that occupational exposure to low doses of Nickel present in urban pollution may influence the thyroid hormones in outdoor workers. Preventive measures should be taken to protect the health of outdoor workers and general population. During medical examination Nickel exposure should be carefully considered. Introduction The aim of this study was to evaluate the effects of a low-dose exposure to nickel, as it is present in urban air, on thyroid hormones and on thyrotropin in outdoor workers exposed to urban pollutants. Materials and Methods A total of 164 outdoor workers were studied and divided by sex and smoking habit. Each worker underwent measurement of urinary nickel and of blood triiodothyronine, L-thyroxine, and thyrotropin levels. The statistical analysis was performed. Results Statistical analysis shows a significant and positive correlation between urinary nickel and L-thyroxine, both in total sample and in males. Discussion and Conclusion The study suggests that occupational exposure to a low dose of nickel may affect thyroid function in municipal police workers. These data may provide information on other categories of outdoor workers with similar exposure.
Approaches to discern if microbiome associations reflect causation in metabolic and immune disorders

ABSTRACT Our understanding of microorganisms residing within our gut and their roles in the host metabolism and immunity advanced greatly over the past 20 years. Currently, microbiome studies are shifting from association and correlation studies to studies demonstrating causality of identified microbiome signatures and identification of molecular mechanisms underlying these interactions. This transformation is crucial for the efficient translation into clinical application and development of targeted strategies to beneficially modulate the intestinal microbiota. As mechanistic studies are still quite challenging to perform in humans, the causal role of microbiota is frequently evaluated in animal models that need to be appropriately selected. Here, we provide a comprehensive overview on approaches that can be applied in addressing causality of host-microbe interactions in five major animal model organisms (Caenorhabditis elegans, Drosophila melanogaster, zebrafish, rodents, and pigs). We particularly focused on discussing methods available for studying the causality ranging from the usage of gut microbiota transfer, diverse models of metabolic and immune perturbations involving nutritional and chemical factors, gene modifications and surgically induced models, metabolite profiling up to culture-based approached. Furthermore, we addressed the impact of the gut morphology, physiology as well as diet on the microbiota composition in various models and resulting species specificities. Finally, we conclude this review with the discussion on models that can be applied to study the causal role of the gut microbiota in the context of metabolic syndrome and host immunity. We hope this review will facilitate important considerations for appropriate animal model selection.
Noradrenaline activation of hippocampal dopamine D1 receptors promotes antidepressant effects

Significance Dopamine receptors in the brain are important targets for the therapeutic treatment of psychiatric disorders. Dopamine receptors are generally thought to be activated by dopamine. In the present study, however, we reveal that noradrenaline can also robustly activate dopamine D1 receptors in the mouse hippocampus. Noradrenaline-activated D1 receptor signaling was highly sensitive to the neuronal activity and experience of mice. Chronic stress and voluntary exercise synergistically augmented noradrenaline–D1 receptor signaling. This augmented noradrenaline–D1 receptor signaling promoted the induction of hippocampal neuronal plasticity by an antidepressant drug acting on the noradrenergic system. Our results suggest that noradrenaline–D1 receptor signaling increases the efficacy of antidepressant treatment and therefore can be a unique therapeutic target for augmenting antidepressant medication.
Emotion-Based Reinforcement Attention Network for Depression Detection on Social Media: Algorithm Development and Validation

Background Depression detection has recently received attention in the field of natural language processing. The task aims to detect users with depression based on their historical posts on social media. However, existing studies in this area use the entire historical posts of the users and select depression indicator posts. Moreover, these methods fail to effectively extract deep emotional semantic features or simply concatenate emotional representation. To solve this problem, we propose a model to extract deep emotional semantic features and select depression indicator posts based on the emotional states. Objective This study aims to develop an emotion-based reinforcement attention network for depression detection of users on social media. Methods The proposed model is composed of 2 components: the emotion extraction network, which is used to capture deep emotional semantic information, and the reinforcement learning (RL) attention network, which is used to select depression indicator posts based on the emotional states. Finally, we concatenated the output of these 2 parts and send them to the classification layer for depression detection. Results Experimental results of our model on the multimodal depression data set outperform the state-of-the-art baselines. Specifically, the proposed model achieved accuracy, precision, recall, and F1-score of 90.6%, 91.2%, 89.7%, and 90.4%, respectively. Conclusions The proposed model utilizes historical posts of users to effectively identify users’ depression tendencies. The experimental results show that the emotion extraction network and the RL selection layer based on emotional states can effectively improve the accuracy of detection. In addition, sentence-level attention layer can capture core posts.
Rewiring Cortico-Muscular Control in the Healthy and Poststroke Human Brain with Proprioceptive β-Band Neurofeedback

In severely affected stroke survivors, cortico-muscular control is disturbed and volitional upper limb movements often absent. Mental rehearsal of the impaired movement in conjunction with sensory feedback provision are suggested as promising rehabilitation exercises. Knowledge about the underlying neural processes, however, remains vague. In male and female chronic stroke patients with hand paralysis, a brain-computer interface controlled a robotic orthosis and turned sensorimotor β-band desynchronization during motor imagery (MI) of finger extension into contingent hand opening. Healthy control subjects performed the same task and received the same proprioceptive feedback with a robotic orthosis or visual feedback only. Only when proprioceptive feedback was provided, cortico-muscular coherence (CMC) increased with a predominant information flow from the sensorimotor cortex to the finger extensors. This effect (1) was specific to the β frequency band, (2) transferred to a motor task (MT), (3) was proportional to subsequent corticospinal excitability (CSE) and correlated with behavioral changes in the (4) healthy and (5) poststroke condition; notably, MI-related enhancement of β-band CMC in the ipsilesional premotor cortex correlated with motor improvements after the intervention. In the healthy and injured human nervous system, synchronized activation of motor-related cortical and spinal neural pools facilitates, in accordance with the communication-through-coherence hypothesis, cortico-spinal communication and may, thereby, be therapeutically relevant for functional restoration after stroke, when voluntary movements are no longer possible. SIGNIFICANCE STATEMENT This study provides insights into the neural processes that transfer effects of brain-computer interface neurofeedback to subsequent motor behavior. Specifically, volitional control of cortical oscillations and proprioceptive feedback enhances both cortical activity and behaviorally relevant connectivity to the periphery in a topographically circumscribed and frequency-specific way. This enhanced cortico-muscular control can be induced in the healthy and poststroke brain. Thereby, activating the motor cortex with mental rehearsal of the impaired movement and closing the loop by robot-assisted feedback synchronizes ipsilesional premotor cortex and spinal neural pools in the β frequency band. This facilitates, in accordance with the communication-through-coherence hypothesis, cortico-spinal communication and may, thereby, be therapeutically relevant for functional restoration after stroke, when voluntary movements are no longer possible.
Impaired renal reserve contributes to preeclampsia via the kynurenine and soluble fms–like tyrosine kinase 1 pathway

To understand how kidney donation leads to an increased risk of preeclampsia, we studied pregnant outbred mice with prior uninephrectomy and compared them with sham-operated littermates carrying both kidneys. During pregnancy, uninephrectomized (UNx) mice failed to achieve a physiological increase in the glomerular filtration rate and during late gestation developed hypertension, albuminuria, glomerular endothelial damage, and excess placental production of soluble fms–like tyrosine kinase 1 (sFLT1), an antiangiogenic protein implicated in the pathogenesis of preeclampsia. Maternal hypertension in UNx mice was associated with low plasma volumes, an increased rate of fetal resorption, impaired spiral artery remodeling, and placental ischemia. To evaluate potential mechanisms, we studied plasma metabolite changes using mass spectrometry and noted that l-kynurenine, a metabolite of l-tryptophan, was upregulated approximately 3-fold during pregnancy when compared with prepregnant concentrations in the same animals, consistent with prior reports suggesting a protective role for l-kynurenine in placental health. However, UNx mice failed to show upregulation of l-kynurenine during pregnancy; furthermore, when UNx mice were fed l-kynurenine in drinking water throughout pregnancy, their preeclampsia-like state was rescued, including a reversal of placental ischemia and normalization of sFLT1 levels. In aggregate, we provide a mechanistic basis for how impaired renal reserve and the resulting failure to upregulate l-kynurenine during pregnancy can lead to impaired placentation, placental hypoperfusion, an antiangiogenic state, and subsequent preeclampsia.
Hand Hygiene Compliance Rates in 9 Pediatric Intensive Care Units Across Europe: Results from the Reducing Antimicrobial use and Nosocomial Infections in Kids Network

A unified surveillance mechanism for hand hygiene and hospital-acquired infections for pediatric wards is lacking in Europe. We managed to setup such a mechanism in 9 pediatric intensive care units in 7 European countries, using World Health Organization’s definitions and common methodology which allows for benchmarking among units and countries. Median hand hygiene compliance was found high 82.3% (interquartile range 71.6–94.5%), but gaps in practices were identified.