Miracle-dz/UniFAR-FTUs huggingface dataset:
Effectiveness of a Simulation Curriculum on Clinical Application

Introduction The use of simulation to develop clinical reasoning and medical decision-making skills for common events is poorly established. Validated head trauma rules help identify children at low risk for clinically important traumatic brain injury and guide the need for neuroimaging. We predicted that interns trained using a high-fidelity, immersive simulation would understand and apply these rules better than those trained using a case-based discussion. Our primary outcomes were to determine the effectiveness of a single targeted intervention on an intern's ability to learn and apply the rules. Methods This was a prospective randomized controlled trial. Interns were randomized to participate in either a manikin-based simulation or a case discussion. Knowledge and application of the Pediatric Emergency Care Applied Research Network Head Trauma tool were assessed both under testing conditions using standardized vignettes and in clinical encounters. In both settings, interns completed a validated assessment tool to test their knowledge and application of the Pediatric Emergency Care Applied Research Network Head Trauma tool when assessing patients with head injury. Results Under testing conditions, both being in the simulation group and shorter time from training were independently associated with higher score under testing conditions using standardized vignettes (P = 0.038 and P < 0.001), but not with clinical encounters. Conclusions Interns exposed to manikin-based simulation training demonstrated performance competencies that are better than those in the case discussion group under testing conditions using standardized vignettes, but not in real clinical encounters. This study suggests that information delivery and comprehension may be improved through a single targeted simulation-based education.
The Knockdown of Mitochondrial Uncoupling Proteins 1 and 2 (AtUCP1 and 2) in Arabidopsis thaliana Impacts Vegetative Development and Fertility.

Mitochondrial Uncoupling Proteins (UCPs) are mitochondrial inner membrane proteins that dissipate the proton electrochemical gradient generated by the respiratory chain complexes. In plants, these proteins are crucial for maintaining mitochondrial reactive oxygen species (ROS) homeostasis. In this study, single T-DNA insertion mutants for two (AtUCP1and AtUCP2) out of the three UCP genes present in Arabidopsis thaliana were employed to elucidate their potential roles in planta. Our data revealed a significant increase in the ATP/ADP ratios of both mutants, indicating clear alterations in energy metabolism, and a reduced respiratory rate in atucp2. Phenotypic characterization revealed that atucp1 and atucp2 plants displayed reduced primary root growth under normal and stressed conditions. Moreover, a reduced fertility phenotype was observed in both mutants, which exhibited increased number of sterile siliques and lower seed yield compared with wild-type plants. Reciprocal crosses demonstrated that both male and female fertility were compromised in atucp1, while such effect was exclusively observed in the male counterpart in atucp2. Most strikingly, a pronounced accumulation of hydrogen peroxide in the reproductive organs was observed in all mutant lines, indicating a disturbance in ROS homeostasis of mutant flowers. In line, the atucp1 and atucp2 mutants exhibited higher levels of ROS in pollen grains. Also in support, alternative oxidase 1a was highly induced in mutant flowers, while the expression profiles of transcription factors implicated in gene regulation during female and male reproductive organ/tissue development were perturbed. Overall, these data give support for an important role for AtUCP1 and AtUCP2 in flower oxidative homeostasis and overall plant fertility.
Superior Fitting of Arterial Resistance and Compliance Parameters With Genetic Algorithms in Models of Dynamic Cerebral Autoregulation

Objective: The capacity of discriminating between normal and impaired dynamic cerebral autoregulation (dCA), based on spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CBF), has considerable clinical relevance. This study aimed to quantify the separate contributions of vascular resistance and compliance as parameters that could reflect myogenic and metabolic mechanisms to dCA. Methods: Forty-five subjects were studied under normo and hypercapnic conditions induced by breathing a mixture of 5% carbon dioxide in air. Dynamic cerebrovascular resistance and compliance models with ABP as input and CBFV as output were fitted using Genetic Algorithms to identify parameter values for each subject, and respiratory condition. Results: The efficiency of dCA was assessed from the model's generated CBFV response to an ABP step change, corresponding to an autoregulation index of 5.56 ± 1.57 in normocapnia and 2.38 ± 1.73 in hypercapnia, with an area under the ROC curve (AUC) of 0.9 between both conditions. Vascular compliance increased from 0.75 ± 0.7 ml/mmHg in normocapnia to 5.82 ± 12.0 ml/mmHg during hypercapnia, with an AUC of 0.88. Conclusion: Further work is needed to validate this approach in clinical applications where individualised model parameters could provide relevant diagnostic and prognostic information about dCA impairment.
Comparative transcriptomic analysis of ovaries from high and low egg‐laying Lingyun black‐bone chickens

Abstract Egg‐laying rate is mainly determined by ovarian function and regulated by the hypothalamic‐pituitary‐gonadal axis; however, the mechanism by which the ovary regulates the egg‐laying rate is still poorly understood. The purpose of this study was to compare the differences in the transcriptomes of the ovary of Lingyun black‐bone chickens with relatively high and low egg‐laying rates and screen candidate genes related to the egg‐laying rate. RNA‐sequencing (RNA‐Seq) was conducted to explore the chicken transcriptome from the ovarian tissue of six Lingyun black‐bone chickens with high (group G, n = 3) and low (group D, n = 3) egg‐laying rates. The results showed that 235 differentially expressed genes (DEGs) were identified between the chickens with high and low egg‐laying rates; among them, 209 DEGs were up‐regulated and 26 DEGs were down‐regulated. Gene Ontology analysis showed that the up‐regulated 209 DEGs were enriched in 50 GO terms and the down‐regulated 26 DEGs were enriched in 40 GO terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that up‐regulated DEGs were significantly enriched in 25 pathways and down‐regulated DEGs were significantly enriched in three pathways. Among the pathways, we found the longevity regulating pathway‐multiple species pathway, Estrogen signalling pathway and PPAR signalling pathway may have an essential function in regulating the egg‐laying rate. The results highlighted DEGs in the ovarian tissues of relatively high and low laying Lingyun black‐bone chicken and identified essential candidate genes related to the egg‐laying rate, thereby providing a theoretical basis for improving the egg‐laying rate of Lingyun black‐bone chicken.
Determination of Cilnidipine and its Tablets by RP-HPLC

AIM To establish a RP-HPLC method for determination of content of cilnidipine tablets and its related substances. METHOD The chromatographic procedure was carried out on a ODS column,using a mixture of 81% volumes of menthol and 19% volumes of 0.03 mol/L potassium dihydrogen orthophosphate(the pH adjusted to 3.5 with phosphase) as the mobile phase with a flow rate of 1.0 ml/min and ultraviolet detection wavelength at 240 nm. RESULTS Cilnidipine and the other components were separated completely under the selected chromatographic condition. The relationship between response and the concentration over the range of 1.6～300 μg/ml was linear with the correlation coefficient of 0.9999 and the average recovery was 99.78%( n =9,RSD=0.5%). CONCLUSION This method could be used in quality control of cilnidipine.
Regional variation of corneal stromal deformation measured by high-frequency ultrasound elastography

The cornea’s mechanical response to intraocular pressure elevations may alter in ectatic diseases such as keratoconus. Regional variations of mechanical deformation in normal and keratoconus eyes during intraocular pressure elevation have not been well-characterized. We applied a high-frequency ultrasound elastography technique to characterize the regional deformation of normal and keratoconus human corneas through the full thickness of corneal stroma. A cross-section centered at the corneal apex in 11 normal and 2 keratoconus human donor eyes was imaged with high-frequency ultrasound during whole globe inflation from 5 to 30 mmHg. An ultrasound speckle tracking algorithm was used to compute local tissue displacements. Radial, tangential, and shear strains were mapped across the imaged cross-section. Strains in the central (1 mm surrounding apex) and paracentral (1 to 4 mm from apex) regions were analyzed in both normal and keratoconus eyes. Additional regional analysis was performed in the eye with severe keratoconus presenting significant thinning and scarring. Our results showed that in normal corneas, the central region had significantly smaller tangential stretch than the paracentral region, and that within the central region, the magnitudes of radial and shear strains were significantly larger than that of tangential strain. The eye with mild keratoconus had similar shear strain but substantially larger radial strains than normal corneas, while the eye with severe keratoconus had similar overall strains as in normal eyes but marked regional heterogeneity and large strains in the cone region. These findings suggested regional variation of mechanical responses to intraocular pressure elevation in both normal and keratoconus corneas, and keratoconus appeared to be associated with mechanical weakening in the cone region, especially in resisting radial compression. Comprehensive characterization of radial, tangential, and shear strains through corneal stroma may provide new insights to understand the biomechanical alterations in keratoconus.
SARS‐CoV‐2 spike glycoprotein‐reactive T cells can be readily expanded from COVID‐19 vaccinated donors

The COVID‐19 vaccine was designed to provide protection against infection by the severe respiratory coronavirus 2 (SARS‐CoV‐2) and coronavirus disease 2019 (COVID‐19). However, the vaccine's efficacy can be compromised in patients with immunodeficiencies or the vaccine‐induced immunoprotection suppressed by other comorbidity treatments, such as chemotherapy or immunotherapy. To enhance the protective role of the COVID‐19 vaccine, we have investigated a combination of the COVID‐19 vaccination with ex vivo enrichment and large‐scale expansion of SARS‐CoV‐2 spike glycoprotein‐reactive CD4+ and CD8+ T cells.
Automatic segmentation of brain metastases using T1 magnetic resonance and computed tomography images

An increasing number of patients with multiple brain metastases are being treated with stereotactic radiosurgery (SRS). Manually identifying and contouring all metastatic lesions is difficult and time-consuming, and a potential source of variability. Hence, we developed a 3D deep learning approach for segmenting brain metastases on MR and CT images. Five-hundred eleven patients treated with SRS were retrospectively identified for this study. Prior to radiotherapy, the patients were imaged with 3D T1 spoiled-gradient MR post-Gd (T1 + C) and contrast-enhanced CT (CECT), which were co-registered by a treatment planner. The gross tumor volume contours, authored by the attending radiation oncologist, were taken as the ground truth. There were 3 ± 4 metastases per patient, with volume up to 57 ml. We produced a multi-stage model that automatically performs brain extraction, followed by detection and segmentation of brain metastases using co-registered T1 + C and CECT. Augmented data from 80% of these patients were used to train modified 3D V-Net convolutional neural networks for this task. We combined a normalized boundary loss function with soft Dice loss to improve the model optimization, and employed gradient accumulation to stabilize the training. The average Dice similarity coefficient (DSC) for brain extraction was 0.975 ± 0.002 (95% CI). The detection sensitivity per metastasis was 90% (329/367), with moderate dependence on metastasis size. Averaged across 102 test patients, our approach had metastasis detection sensitivity 95 ± 3%, 2.4 ± 0.5 false positives, DSC of 0.76 ± 0.03, and 95th-percentile Hausdorff distance of 2.5 ± 0.3 mm (95% CIs). The volumes of automatic and manual segmentations were strongly correlated for metastases of volume up to 20 ml ( r=0.97, p<0.001 ). This work expounds a fully 3D deep learning approach capable of automatically detecting and segmenting brain metastases using co-registered T1 + C and CECT.
Integrated respiratory chemoreflex‐mediated regulation of cerebral blood flow in hypoxia: Implications for oxygen delivery and acute mountain sickness

What is the central question of this study? To what extent do hypoxia‐induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral oxygen delivery, with corresponding implications for susceptibility to acute mountain sickness? What is the main finding and its importance? We provide evidence for site‐specific regulation of cerebral blood flow in hypoxia that preserves oxygen delivery in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. External carotid artery vasodilatation might prove to be an alternative haemodynamic risk factor that predisposes to acute mountain sickness.
Evidence and theory for lower rates of depression in larger US urban areas

Significance Depression is the global leading cause of disability and related economic losses. Cities are associated with increased risk for depression, but how do depression risks change between cities? Here, we develop a mathematical theory for how the built urban environment influences depression risk and predict lower depression rates in larger cities. We demonstrate that this model fits empirical data across four large-scale datasets in US cities. If our model captures some of the underlying causal mechanisms, then these results suggest that depression within cities can be understood, in part, as a collective ecological phenomenon mediated by human social networks and their relationship to the urban built environment. It is commonly assumed that cities are detrimental to mental health. However, the evidence remains inconsistent and at most, makes the case for differences between rural and urban environments as a whole. Here, we propose a model of depression driven by an individual’s accumulated experience mediated by social networks. The connection between observed systematic variations in socioeconomic networks and built environments with city size provides a link between urbanization and mental health. Surprisingly, this model predicts lower depression rates in larger cities. We confirm this prediction for US cities using four independent datasets. These results are consistent with other behaviors associated with denser socioeconomic networks and suggest that larger cities provide a buffer against depression. This approach introduces a systematic framework for conceptualizing and modeling mental health in complex physical and social networks, producing testable predictions for environmental and social determinants of mental health also applicable to other psychopathologies.
Bacteriophage ICP1: A Persistent Predator of Vibrio cholerae

Bacteriophages or phages—viruses of bacteria—are abundant and considered to be highly diverse. Interestingly, a particular group of lytic Vibrio cholerae–specific phages (vibriophages) of the International Centre for Diarrheal Disease Research, Bangladesh cholera phage 1 (ICP1) lineage show high levels of genome conservation over large spans of time and geography, despite a constant coevolutionary arms race with their host. From a collection of 67 sequenced ICP1 isolates, mostly from clinical samples, we find these phages have mosaic genomes consisting of large, conserved modules disrupted by variable sequences that likely evolve mostly through mobile endonuclease-mediated recombination during coinfection. Several variable regions have been associated with adaptations against antiphage elements in V. cholerae; notably, this includes ICP1’s CRISPR-Cas system. The ongoing association of ICP1 and V. cholerae in cholera-endemic regions makes this system a rich source for discovery of novel defense and counterdefense strategies in bacteria-phage conflicts in nature.
Knee function 30 years after ACL reconstruction: a case series of 60 patients

Background and purpose — Until now, there have been no studies beyond 30 years after anterior cruciate ligament (ACL) reconstruction. We report knee function a mean 31 years after ACL reconstruction. Patients and methods — This cohort comprised a case series of 60 patients with a mean follow-up of 31 years (28–33) after ACL reconstruction. Patients were evaluated with the International Knee Documentation Committee (IKDC) objective assessment, Knee injury Osteoarthritis Outcome Score (KOOS), Tegner Activity Scale, radiography, and MRI. Results — 30 patients showed an intact ACL graft and 30 a ruptured or missing ACL graft. 40 patients had osteoarthritis in the tibiofemoral compartment and 24 patients in the patellofemoral compartment. Patients with intact ACL grafts scored higher than those with ruptured or missing ACL grafts when it comes to KOOS Sport/Rec. The Hodges Lehmann estimated median difference between groups was 15 (95% CI 0–35). The KOOS scores were lower in the group with ruptured or missing ACL grafts when compared with a healthy-knee reference group of males in terms of Pain, mean difference –8 (CI –15 to –1), Symptoms, mean difference –18 (CI –27 to –9), and Sport/Rec, mean difference –21 (CI –34 to –8). In the group with intact ACL grafts, the KOOS score was lower than a healthy-knee reference group of males in terms of Symptoms, mean difference –12 (CI –21 to –3). Scores for all subgroups of KOOS were higher in patients without osteoarthritis. The IKDC overall clinical assessment outcome was worse in patients with a ruptured or missing ACL graft. The Hodges Lehmann estimated median difference between groups was 1 (CI 0–1). Interpretation — Patients with an intact ACL graft reported higher sports activity and recreation, as measured with KOOS, than patients with a ruptured or missing ACL graft. Patients with severe osteoarthritis reported lower sports activity and recreation, as measured with KOOS.
Entrapment of the Non-wetting Phase during Co-current Spontaneous Imbibition

Oil displacement from water-wet fractured reservoirs by spontaneous imbibition leads to the entrapment of a considerable fraction of oil. Understanding the entrapment phenomenon and mechanism is significant for designing recovery processes. In this study, experiments of pure co-current spontaneous imbibition are conducted with packed columns. The packed columns are filled with either glass beads or quartz sands and saturated completely with oil or gas. The geometry of the glass bead is regular with a narrow size distribution. In contrast, the geometry of the quartz sand is irregular with a wide size distribution. In experiments, one end of the packed column is in contact with brine and the other end is in contact with oil or gas. Both the oil/gas production and the advancing distance of the imbibition front versus imbibition time are measured. The relative permeability to brine behind the imbibition front and the capillary pressure at the imbibition front are estimated as well. For glass-bead-packed colum.
Transient astrocyte‐like NG2 glia subpopulation emerges solely following permanent brain ischemia

NG2 glia display wide proliferation and differentiation potential under physiological and pathological conditions. Here, we examined these two features following different types of brain disorders such as focal cerebral ischemia (FCI), cortical stab wound (SW), and demyelination (DEMY) in 3‐month‐old mice, in which NG2 glia are labeled by tdTomato under the Cspg4 promoter. To compare NG2 glia expression profiles following different CNS injuries, we employed single‐cell RT‐qPCR and self‐organizing Kohonen map analysis of tdTomato‐positive cells isolated from the uninjured cortex/corpus callosum and those after specific injury. Such approach enabled us to distinguish two main cell populations (NG2 glia, oligodendrocytes), each of them comprising four distinct subpopulations. The gene expression profiling revealed that a subpopulation of NG2 glia expressing GFAP, a marker of reactive astrocytes, is only present transiently after FCI. However, following less severe injuries, namely the SW and DEMY, subpopulations mirroring different stages of oligodendrocyte maturation markedly prevail. Such injury‐dependent incidence of distinct subpopulations was also confirmed by immunohistochemistry. To characterize this unique subpopulation of transient astrocyte‐like NG2 glia, we used single‐cell RNA‐sequencing analysis and to disclose their basic membrane properties, the patch‐clamp technique was employed. Overall, we have proved that astrocyte‐like NG2 glia are a specific subpopulation of NG2 glia emerging transiently only following FCI. These cells, located in the postischemic glial scar, are active in the cell cycle and display a current pattern similar to that identified in cortical astrocytes. Astrocyte‐like NG2 glia may represent important players in glial scar formation and repair processes, following ischemia.
Normal-sized basal ganglia perivascular space related to motor phenotype in Parkinson freezers

Changes in basal ganglia (BG) perivascular spaces (PVSs) are related to motor and cognitive behaviors in Parkinson’s disease (PD). However, the correlation between the initial motor phenotype and PVSs distribution/burden in PD freezing of gait (FOG) remains unclear. In addition, the normal-sized PVSs (nPVSs) have not been well-studied. With high-resolution 7T-MRI, we studied nPVSs burden in BG, thalamus, midbrain and centrum semiovale. The numbers and volume of nPVSs were assessed in 10 healthy controls, 10 PD patients without FOG, 20 with FOG [10 tremor dominant (TD), 10 non-TD subtype]. Correlation analyses were further performed in relation to clinical parameters. In this proof of concept study, we found that the nPVS burden of bilateral and right BG were significantly higher in freezers. A negative correlation existed between the tremor score and BG-nPVSs count. A positive correlation existed between the levodopa equivalent daily dose and BG-nPVSs count. The nPVS burden correlated with the progression to FOG in PD, but the distribution and burden of nPVS differ in TD vs. non-TD subtypes. High resolution 7T-MRI is a sensitive and reliable tool to evaluate BG-nPVS, and may be a useful imaging marker for predicting gait impairment that may evolve into FOG in PD.