Miracle-dz/UniFAR-FTUs huggingface dataset:
Autonomy and isolation experienced by patients and primary caregivers during COVID‐19 hospitalization in Barcelona (Spain)

Abstract This study aims to describe patients' and family caregivers' hospitalization experiences during the COVID‐19 pandemic. Using qualitative exploratory descriptive methods, thirteen patients admitted to the largest hospital in Barcelona (Spain) due to COVID‐19 were interviewed by telephone once discharged, as were eight primary caregivers. Data were analyzed using the content analysis method proposed by Krippendorff. Two main themes were identified: a) Acceptance of mandatory isolation for patients and family caregivers, which refers to the verbalization of a feeling that justifies the imposed isolation and the need for the use of personal protective equipment by the health team for everyone’s safety, and b) Limited autonomy during hospitalization for patients and family caregivers, which describes participants' perceptions of autonomy during hospitalization. Patients and caregivers experienced feelings of loneliness, which negatively affected their emotional health. In addition, they experienced reduced autonomy due to new habits and routines intended to control the pandemic for public and global health.
An AI based digital-twin for prioritising pneumonia patient treatment

A digital-twin based three-tiered system is proposed to prioritise patients for urgent intensive care and ventilator support. The deep learning methods are used to build patient-specific digital-twins to identify and prioritise critical cases amongst severe pneumonia patients. The three-tiered strategy is proposed to generate severity indices to: (1) identify urgent cases, (2) assign critical care and mechanical ventilation, and (3) discontinue mechanical ventilation and critical care at the optimal time. The severity indices calculated in the present study are the probability of death and the probability of requiring mechanical ventilation. These enable the generation of patient prioritisation lists and facilitates the smooth flow of patients in and out of Intensive Therapy Units (ITUs). The proposed digital-twin is built on pre-trained deep learning models using data from more than 1895 pneumonia patients. The severity indices calculated in the present study are assessed using the standard benchmark of Area Under Receiving Operating Characteristic Curve (AUROC). The results indicate that the ITU and mechanical ventilation can be prioritised correctly to an AUROC value as high as 0.89. This model may be employed in its current form to COVID-19 patients, but transfer learning with COVID-19 patient data will improve the predictions. The digital-twin model developed and tested is available via accompanying Supplemental material.
Serum levels of copeptin predict adverse outcomes and improve risk prediction of TRISS and MGAP scores in patients with multiple trauma: A single-center prospective cohort study

As demonstrated in this prospective study, copeptin contributes to improved risk prediction when combined with TRISS or MGAP scores for polytrauma. BACKGROUND Multiple trauma deserves early prognostication and stratification. Copeptin, a precursor of vasopressin, is produced in response to stress. We examined the association between serum levels of copeptin and mortality risk in patients with multiple trauma. We aimed to also enhance the previously established Trauma-Related Injury Severity Score (TRISS) and Mechanism, GCS, Age, and Arterial Pressure (MGAP) score with the additional consideration of copeptin levels. METHODS This single-center prospective cohort study enrolled patients who presented to the emergency department with potential major injuries. The serum levels of copeptin were measured, and the correlation to clinical severity in terms of 30-day mortality and requirement of intensive care management was analyzed. By combining copeptin levels with TRISS or MGAP, comparison between performance of the original models with the copeptin-enhanced models was performed via discrimination, calibration, and reclassification analyses. RESULTS There was a significant increase in copeptin levels in patients who died within 30 days (median 644.4 pg/L, interquartile range [472.5, 785.9]) or were admitted to intensive care units (233.8 pg/L, [105.7, 366.4]), compared with those who survived (37.49 pg/L, [17.88, 77.68]). Adding the natural log of copeptin levels to the established TRISS and MGAP models improved the AUC of TRISS from 0.89 to 0.96, and that of MGAP from 0.82 to 0.95. Both calibrations as measured by Brier’s scores and reclassification as measured by net reclassification improvement or integrated discrimination improvement demonstrated significant improvements. A Web-based calculator was built to generate predicted mortality rates of various models for convenient clinical use. CONCLUSION Admission serum copeptin levels were correlated with clinical severity in multiple trauma. Coupling copeptin with preexisting trauma severity scores improved prediction accuracy. Copeptin shows promise as a novel biomarker for the prediction of trauma outcome. LEVEL OF EVIDENCE Prognostic and Epidemiologic; Level III.
Recognizing life-threatening bleeding in pediatric trauma: A standard for when to activate massive transfusion protocol

Pediatric critical administration threshold (CAT) can be defined as >20 mL/kg of blood products within 1 hour. Exceeding this volume is associated with increased in-hospital mortality and need for urgent surgery, and should prompt activation of massive transfusion protocols. BACKGROUND Traumatic hemorrhage is the most common cause of preventable death in civilian and military trauma. Early identification of pediatric life-threatening hemorrhage is challenging. There is no accepted clinical critical administration threshold (CAT) in children for activating massive transfusion protocols. METHODS Children 0 to 17 years old who received any transfusion in the first 24 hours after injury between 2010 and 2019 were included. The type, volume, and time of administration for each product were recorded. The greatest volume of weight-adjusted products transfused within 1 hour was calculated. The cut point for the number of products that maximized sensitivity and specificity to predict in-hospital mortality, need for urgent surgery, and second life-threatening bleeding episode was determined using Youden's index. A binary variable (CAT+) was generated using this threshold for inclusion in a multivariable logistic regression model. RESULTS In total, 287 patients were included. The median (interquartile range) age was 6 (2–14) years, 60% were males, 83% sustained blunt trauma, and the median (interquartile range) Injury Severity Score was 26 (17–35). The optimal cutoff to define CAT+ was >20 mL/kg of product; this optimized test characteristics for mortality (sensitivity, 70%; specificity, 77%), need for urgent hemorrhage control procedure (sensitivity, 65%; specificity, 74%). and second bleeding episode (sensitivity, 77%; specificity, 74%). There were 93 children (32%) who were CAT+. On multivariate regression, being CAT+ was associated with 3.4 increased odds of mortality (95% confidence interval, 1.67–6.89; p = 0.001) after controlling for age, hypotension, Injury Severity Score, and Glasgow Coma Scale. For every unit of product administered, there was a 10% increased risk of mortality (odds ratio, 1.1; p < 0.001). CONCLUSION Transfusion of more than 20 mL/kg of any blood product within an hour should be used as a threshold for activating massive transfusion protocols in children. Children who meet this CAT are at high risk of mortality and need for interventions; this population may benefit from targeted, timely, and aggressive hemostatic resuscitation. LEVEL OF EVIDENCE Therapeutic/Care Management; Level III.
SOX9 maintains human foetal lung tip progenitor state by enhancing WNT and RTK signalling

The balance between self‐renewal and differentiation in human foetal lung epithelial progenitors controls the size and function of the adult organ. Moreover, progenitor cell gene regulation networks are employed by both regenerating and malignant lung cells, where modulators of their effects could potentially be of therapeutic value. Details of the molecular networks controlling human lung progenitor self‐renewal remain unknown. We performed the first CRISPRi screen in primary human lung organoids to identify transcription factors controlling progenitor self‐renewal. We show that SOX9 promotes proliferation of lung progenitors and inhibits precocious airway differentiation. Moreover, by identifying direct transcriptional targets using Targeted DamID, we place SOX9 at the centre of a transcriptional network, which amplifies WNT and RTK signalling to stabilise the progenitor cell state. In addition, the proof‐of‐principle CRISPRi screen and Targeted DamID tools establish a new workflow for using primary human organoids to elucidate detailed functional mechanisms underlying normal development and disease.
Why maternal continuum of care remains low in Northwest Ethiopia? A multilevel logistic regression analysis

Background Non-adherence to the maternal continuum of care remains a significant challenge. Though early initiation and continuum of care are recommended for mothers’ and newborns’ well-being, there is a paucity of evidence that clarify this condition in resource-limited settings. This study aimed to assess the level of women’s completion of the maternal continuum of care and factors affecting it in Northwest Ethiopia. Methods A community-based cross-sectional study was conducted from October to November, 2020. Data were collected from 811 women who had a recent history of birth within the past one year. The random and fixed effects were reported using an adjusted odds ratio with a 95% confidence interval. The p-value of 0.05 was used to declare significantly associated factors with women’s completion of the maternal continuum of care. Results The study revealed that 6.9% (95%CI: 5.3–8.9%) of women were retained fully on the continuum of maternal care, while 7.89% of women did not receive any care from the existing healthcare system. Attending secondary and above education (AOR = 3.15; 95%CI: 1.25,7.89), membership in the women’s development army (AOR = 2.91; 95%CI: 1.56,5.44); being insured (AOR = 2.59; 95%CI: 1.33,5.01); getting health education (AOR = 2.44; 95%CI: 1.33,4.45); short distance to health facility (AOR = 4.81; 95%CI: 1.55,14.95); and mass-media exposure (AOR = 2.39; 95%CI: 1.11,5.15) were significantly associated with maternal continuum of care. Conclusions The maternal continuum of care is low in rural northwest Ethiopia compared to findings from most resource-limited settings. Therefore, the existing health system should consider multilevel intervention strategies that focus on providing maternal health education, facilitating insurance mechanisms, encouraging women’s participation in health clubs, and ensuring physical accessibility to healthcare facilities to be more effective in improving maternal health services.
Use of selective substrates and inhibitors to rapidly characterise batches of cryopreserved primary human hepatocytes for assessment of active uptake liability in drug discovery and development

Abstract The use of hepatocytes to predict human hepatic metabolic clearance is the gold standard approach. However whilst enzymes are well characterised, knowledge gaps remain for transporters. Furthermore, methods to study specific transporter involvement are often complicated by overlapping substrate specificity. Selective substrates and inhibitors would aid investigations into clinically relevant pharmacokinetic effects. However, to date no consensus has been reached. This work defines selective hepatic uptake transporter substrates and inhibitors for the six main human hepatocyte transporters (OATP1B1, OATP1B3, OATP2B1, NTCP, OAT2 & OCT1), and demonstrates their use to rapidly characterise batches of human hepatocytes for uptake transporter activity. Hepatic uptake was determined across a range of substrate concentrations, allowing the definition of kinetic parameters and hence active and passive components. Systematic investigations identified a specific substrate and inhibitor for each transporter, with no overlap between the specificity of substrate and inhibitor for any given transporter. Early characterisation of compound interactions with uptake transporters will aid in early risk assessment and chemistry design. Hence, this work further highlights the feasibility of a refined methodology for rapid compound characterisation for the application of static and dynamic models, for early clinical risk assessment and guidance for the clinical development plan.
The effect of footwear on mechanical behaviour of the human ankle plantar-flexors in forefoot runners

Purpose To compare the ankle plantar-flexor muscle-tendon mechanical behaviour during barefoot and shod forefoot running. Methods Thirteen highly trained forefoot runners performed five overground steady-state running trials (4.5 ± 0.5 m.s-1) while barefoot and shod. Three-dimensional kinematic and ground reaction force data were collected and used as inputs for musculoskeletal modelling. Muscle-tendon behaviour of the ankle plantar-flexors (soleus; medial gastrocnemius; and lateral gastrocnemius) were estimated across the stance phase and compared between barefoot and shod running using a two-way multivariate analysis of variance. Results During barefoot running peak muscle-tendon unit (MTU) power generation was 16.5% (p = 0.01) higher compared to shod running. Total positive MTU work was 18.5% (p = 0.002) higher during barefoot running compared to shod running. The total sum of tendon elastic strain energy was 8% (p = 0.036) greater during barefoot compared to shod running, however the relative contribution of tendon and muscle fibres to muscle-tendon unit positive work was not different between conditions. Conclusion Barefoot forefoot running demands greater muscle and tendon work than shod forefoot running, but the relative contribution of tendon strain energy to overall muscle-tendon unit work was not greater.
Optimized ultrahigh field parallel transmission workflow using rapid presaturated TurboFLASH transmit field mapping with a three‐dimensional centric single‐shot readout

To evaluate the usage of three‐dimensional (3D) presaturated TurboFLASH (satTFL) for B1+$$ {\mathrm{B}}_1^{+} $$ and B0$$ {\mathrm{B}}_0 $$ mapping on single channel and parallel transmission (pTx) systems.
Quality of care in home health agencies with and without accreditation: a cohort study

ABSTRACT While home health agencies (HHAs) can seek accreditation to recognize their quality of service, it is unknown whether agencies with accreditation perform better in providing care than those without accreditation. Using 5-year data from national data sources, the aims of this study were: 1) to depict characteristics of HHAs with and without accreditation; and 2) to examine the relationship between accreditation status and HHA performance on quality-of-care metrics. This study analyzed 7,697 agencies in the US and found that 1) agencies that were for-profit, urban, not-hospital-affiliated, single-branch, Medicare enrolled only, and without hospice program were more likely to have accreditation; and 2) overall, accredited agencies performed better on the three commonly used quality indicators, timely initiation of care, hospitalization, and emergency department visit, though not all the observed differences were substantial in absolute value. Our results provide unique empirical information to agencies considering seeking accreditation.
Transfer effects from language processing to visual attention dynamics: The impact of orthographic transparency

Abstract The consistency between letters and sounds varies across languages. These differences have been proposed to be associated with different reading mechanisms (lexical vs. phonological), processing grain sizes (coarse vs. fine) and attentional windows (whole words vs. individual letters). This study aimed to extend this idea to writing to dictation. For that purpose, we evaluated whether the use of different types of processing has a differential impact on local windowing attention: phonological (local) processing in a transparent language (Spanish) and lexical (global) processing of an opaque language (English). Spanish and English monolinguals (Experiment 1) and Spanish–English bilinguals (Experiment 2) performed a writing to dictation task followed by a global–local task. The first key performance showed a critical dissociation between languages: the response times (RTs) from the Spanish writing to dictation task was modulated by word length, whereas the RTs from the English writing to dictation task was modulated by word frequency and age of acquisition, as evidence that language transparency biases processing towards phonological or lexical strategies. In addition, after a Spanish task, participants more efficiently processed local information, which resulted in both the benefit of global congruent information and the reduced cost of incongruent global information. Additionally, the results showed that bilinguals adapt their attentional processing depending on the orthographic transparency.
SARS-CoV-2-specific immunoglobulin Y antibodies are protective in infected mice

Safe, passive immunization methods are required against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants. Immunization of chickens with antigen is known to induce specific IgY antibodies concentrated in the egg yolk and has a good safety profile, high yield of IgY per egg, can be topically applied, not requiring parenteral delivery. Our data provide the first evidence of the prophylactic efficacy of Immunoglobulin Y antibodies against SARS-CoV-2 in mice. Lohmann hens were injected with recombinant SARS-CoV-2 RBD protein; IgY-Abs were extracted from the eggs and characterized using SDS-PAGE. Antiviral activity was evaluated using plaque reduction neutralization tests. In additional experiments, IgY-RBD efficacy was examined in mice sensitized to SARS-CoV-2 infection by transduction with Ad5-hACE2 (mild disease) or by using mouse-adapted virus (severe disease). In both cases, prophylactic intranasal administration of IgY-Abs reduced SARS-CoV-2 replication, and reduced morbidity, inflammatory cell infiltration, hemorrhage, and edema in the lungs and increased survival compared to control groups that received non-specific IgY-Abs. These results indicate that further evaluation of IgY-RBD antibodies in humans is warranted.
Activation of GPR183 by 7α,25-Dihydroxycholesterol Induces Behavioral Hypersensitivity through Mitogen-Activated Protein Kinase and Nuclear Factor-κB

Emerging evidence implicates the G-protein coupled receptor (GPCR) GPR183 in the development of neuropathic pain. Further investigation of the signaling pathways downstream of GPR183 is needed to support the development of GPR183 antagonists as analgesics. In rodents, intrathecal injection of its ligand, 7α,25-dihydroxycholesterol (7α,25-OHC), causes time-dependent development of mechano-and cold- allodynia (behavioral hypersensitivity). These effects are blocked by the selective small molecule GPR183 antagonist, SAE-14. However, the molecular mechanisms engaged downstream of GPR183 in the spinal cord are not known. Here, we show that 7α,25-OHC-induced behavioral hypersensitivity is Gαi dependent, but not β-arrestin 2-dependent. Non-biased transcriptomic analyses of dorsal-horn spinal cord (DH-SC) tissues harvested at the time of peak hypersensitivity implicate potential contributions of mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB). In support, we found that the development of 7α,25-OHC/GPR183-induced mechano-allodynia was associated with significant activation of MAPKs (extracellular signal-regulated kinase [ERK], p38) and redox-sensitive transcription factors (NF-κB) and increased formation of inflammatory and neuroexcitatory cytokines. SAE-14 blocked these effects and behavioral hypersensitivity. Our findings provide novel mechanistic insight into how GPR183 signaling in the spinal cord produces hypersensitivity through MAPK and NF-κB activation. SIGNIFICANCE STATEMENT Using a multi-disciplinary approach, we have characterized the molecular mechanisms underpinning 7α,25-OHC/GPR183-induced hypersensitivity in mice. Intrathecal injections of the GPR183 agonist 7α,25-OHC induce behavioral hypersensitivity, and these effects are blocked by the selective GPR183 antagonist SAE-14. We found that 7α,25-OHC-induced allodynia is dependent on MAPK and NF-κB signaling pathways and results in an increase in pro-inflammatory cytokine expression. This study provides a first insight into how GPR183 signaling in the spinal cord is pronociceptive.
Early‐life social stress induces permanent alterations in plasticity and perineuronal nets in the mouse anterior cingulate cortex

Child maltreatment disrupts trajectories of brain development, but the underlying pathways are unclear. Stressful stimuli in early life interfere with maturation of local inhibitory circuitry and deposition of perineuronal nets (PNNs), specialized extracellular matrix structures involved in the closure of critical periods of development. Alterations in cortical PNN and parvalbumin (PV) following early‐life stress (ELS) have been detected in human and animal studies. Aberrations in the anterior cingulate cortex (ACC) are the most consistent neuroimaging findings in maltreated people, but the molecular mechanisms linking ELS with ACC dysfunctions are unknown. Here, we employed a mouse model of early social threat to test whether ELS experienced in a sensitive period for ACC maturation could induce long‐term aberrations of PNN and PV development in the ACC, with consequences on plasticity and ACC‐dependent behavior. We found that ELS increased PNN but not PV expression in the ACC of young adult mice. This was associated with reduced frequency of inhibitory postsynaptic currents and long‐term potentiation impairments and expression of intense object phobia. Our findings provide information on the long‐term effects of ELS on ACC functionality and PNN formation and present evidence for a novel neurobiological pathway underlying the impact of early adversity on the brain.
Analytical Theory of the Geodesic Acoustic Mode in the Small and Large Orbit Drift Width Limits and its Application in a Study of Plasma Shaping Effect

Analytical theories of the geodesic acoustic mode (GAM) are reviewed in the small-and large-orbit drift width limits, respectively. Different physics pictures in these two limits are displayed. As an example, these two analytical methods are employed to investigate the plasma shaping effect on the frequency and collisionless damping rate of the GAM.