Miracle-dz/UniFAR-FTUs huggingface dataset:
Strategy for reliable identification of ischaemic stroke, thrombolytics and thrombectomy in large administrative databases

Background Administrative data are frequently used in stroke research. Ensuring accurate identification of patients who had an ischaemic stroke, and those receiving thrombolysis and endovascular thrombectomy (EVT) is critical to ensure representativeness and generalisability. We examined differences in patient samples based on mode of identification, and propose a strategy for future patient and procedure identification in large administrative databases. Methods We used non-public administrative data from the state of California to identify all patients who had an ischaemic stroke discharged from an emergency department (ED) or inpatient hospitalisation from 2010 to 2017 based on International Classification of Disease (ICD-9) (2010–2015), ICD-10 (2015–2017) and Medicare Severity-Diagnosis-related Group (MS-DRG) discharge codes. We identified patients with interhospital transfers, patients receiving thrombolytics and patients treated with EVT based on ICD, Current Procedural Terminology (CPT) and MS-DRG codes. We determined what proportion of these transfers and procedures would have been identified with ICD versus MS-DRG discharge codes. Results Of 365 099 ischaemic stroke encounters, most (87.70%) had both a stroke-related ICD-9 or ICD-10 code and stroke-related MS-DRG code; 12.28% had only an ICD-9 or ICD-10 code and 0.02% had only an MS-DRG code. Nearly all transfers (99.99%) were identified using ICD codes. We identified 32 433 thrombolytic-treated patients (8.9% of total) using ICD, CPT and MS-DRG codes; the combination of ICD and CPT codes identified nearly all (98%). We identified 7691 patients treated with EVT (2.1% of total) using ICD and MS-DRG codes; both MS-DRG and ICD-9/ICD-10 codes were necessary because ICD codes alone missed 13.2% of EVTs. CPT codes only pertain to outpatient/ED patients and are not useful for EVT identification. Conclusions ICD-9/ICD-10 diagnosis codes capture nearly all ischaemic stroke encounters and transfers, while the combination of ICD-9/ICD-10 and CPT codes are adequate for identifying thrombolytic treatment in administrative datasets. However, MS-DRG codes are necessary in addition to ICD codes for identifying EVT, likely due to favourable reimbursement for EVT-related MS-DRG codes incentivising accurate coding.
Children’s Signaling of Incomprehension: The Diagnosticity of Practice Questions During Interview Instructions

Forensic interviewers are routinely advised to instruct children that they should indicate when they do not understand a question. This study examined whether administering the instruction with a practice question may help interviewers identify the means by which individual children signal incomprehension. We examined 446 interviews with children questioned about abuse, including 252 interviews in which interviewers administered the instruction with a practice question (4- to 13-year-old children; Mage = 7.7). Older children more often explicitly referred to incomprehension when answering the practice question and throughout the interviews, whereas younger children simply requested repetition or gave “don’t know” responses, and individual children’s responses to the practice questions predicted their responses later in the interviews. Similarly, older children were more likely to seek confirmation of their understanding of interviewers’ questions and to request specification. The results highlight the need for interviewers to test and closely monitor younger children’s responses for ambiguous signs of incomprehension.
A Novel Live Attenuated Respiratory Syncytial Virus Vaccine Candidate with Mutations in the L Protein SAM Binding Site and the G Protein Cleavage Site Is Protective in Cotton Rats and a Rhesus Macaque

Globally, respiratory syncytial virus (RSV) is a major cause of death in children under 1 year of age, yet no vaccine is available. We have generated a novel RSV live attenuated vaccine candidate containing mutations in the L and G proteins. ABSTRACT Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in children of <5 years of age worldwide, infecting the majority of infants in their first year of life. Despite the widespread impact of this virus, no vaccine is currently available. For more than 50 years, live attenuated vaccines (LAVs) have been shown to protect against other childhood viral infections, offering the advantage of presenting all viral proteins to the immune system for stimulation of both B and T cell responses and memory. The RSV LAV candidate described here, rgRSV-L(G1857A)-G(L208A), contains two modifications: an attenuating mutation in the S-adenosylmethionine (SAM) binding site of the viral mRNA cap methyltransferase (MTase) within the large (L) polymerase protein and a mutation in the attachment (G) glycoprotein that inhibits its cleavage during production in Vero cells, resulting in virus with a “noncleaved G” (ncG). RSV virions containing the ncG have an increased ability to infect primary well-differentiated human bronchial epithelial (HBE) cultures which model the in vivo site of immunization, the ciliated airway epithelium. This RSV LAV candidate is produced efficiently in Vero cells, is highly attenuated in HBE cultures, efficiently induces neutralizing antibodies that are long lasting, and provides protection against an RSV challenge in the cotton rat, without causing enhanced disease. Similar results were obtained in a rhesus macaque. IMPORTANCE Globally, respiratory syncytial virus (RSV) is a major cause of death in children under 1 year of age, yet no vaccine is available. We have generated a novel RSV live attenuated vaccine candidate containing mutations in the L and G proteins. The L polymerase mutation does not inhibit virus yield in Vero cells, the cell type required for vaccine production, but greatly reduces virus spread in human bronchial epithelial (HBE) cultures, a logical in vitro predictor of in vivo attenuation. The G attachment protein mutation reduces its cleavage in Vero cells, thereby increasing vaccine virus yield, making vaccine production more economical. In cotton rats, this RSV vaccine candidate is highly attenuated at a dose of 105 PFU and completely protective following immunization with 500 PFU, 200-fold less than the dose usually used in such studies. It also induced long-lasting antibodies in cotton rats and protected a rhesus macaque from RSV challenge. This mutant virus is an excellent RSV live attenuated vaccine candidate.
Prospective Study of Disease-Specific Quality-of-Life in Sporadic Vestibular Schwannoma Comparing Observation, Radiosurgery, and Microsurgery

Background: Previous cross-sectional studies analyzing quality of life (QOL) outcomes in patients with sporadic vestibular schwannoma (VS) have shown surprisingly little difference among treatment modalities. To date, there is limited prospective QOL outcome data available comparing baseline to posttreatment scores. Study Design: Prospective longitudinal study using the disease-specific Penn Acoustic Neuroma Quality of Life (PANQOL) scale. Setting: Large academic skull base center. Patients: Patients diagnosed with unilateral VS who completed a baseline survey before treatment and at least one posttreatment survey. Main Outcome Measures: Change in PANQOL scores from baseline to most recent survey. Results: A total of 244 patients were studied, including 78 (32%) who elected observation, 118 (48%) microsurgery, and 48 (20%) stereotactic radiosurgery. Patients who underwent microsurgery were younger (p < 0.001) and had larger tumors (p < 0.001) than those who underwent observation or radiosurgery; there was no significant difference in duration of follow-up among management groups (mean 2.1 yrs; p = 0.28). When comparing the total PANQOL score at baseline to the most recent survey, the net change was only –1.1, –0.1, and 0.3 points on a 100-point scale for observation, microsurgery, and radiosurgery, respectively (p = 0.89). After multivariable adjustment for baseline features, there were no statistically significant changes when comparing baseline to most recent scores within each management group for facial function, general health, balance, hearing loss, energy, and pain domains or total score. However, the microsurgical group experienced a 10.8-point improvement (p = 0.002) in anxiety following treatment, compared with 1.5 (p = 0.73) and 5.3 (p = 0.31) for observation and radiosurgery, respectively. Conclusions: In this prospective longitudinal study investigating differences in QOL outcomes among VS treatment groups using the disease-specific PANQOL instrument, treatment did not modify QOL in most domains. Microsurgery may confer an advantage with regard to patient anxiety, presumably relating to the psychological benefit of “cure” from having the tumor removed.
Genome-wide admixture is common across the Heliconius radiation

How frequent is gene flow between species? The pattern of evolution is typically portrayed as a phylogenetic tree, implying that speciation is a series of splits between lineages. Yet gene flow between good species is increasingly recognized as an important mechanism in the diversification of radiations, often spreading adaptive traits and leading to a complex pattern of phylogenetic incongruence. This process has thus far been studied in cases involving few species, or geographically restricted to spaces like islands, but not on the scale of a continental radiation. Previous studies have documented gene flow, adaptive introgression and hybrid speciation in a small subsection of the charismatic Neotropical butterflies Heliconius. Using genome-wide resequencing of 40 out of 45 species in the genus we demonstrate for the first time that admixture has played a role throughout the evolution of Heliconius and the sister genus Eueides. Modelling of phylogenetic networks based on 6848 orthologous autosomal genes (Maximum Pseudo-Likelihood Networks) or 5,483,419 high quality SNPs (Ancestral Recombination Graph) uncovers nine new cases of interspecific gene flow at up to half of the genome. However, f4 statistics of admixture show that the extent of the process has varied between subgenera. Evidence for introgression is found at all five loci controlling the colour and shape of the mimetic wing patterns, including in the putative hybrid species H. hecalesia, characterised by an unusual hindwing. Due to hybridization and incomplete coalescence during rapid speciation, individual gene trees show rampant discordance. Although reduced gene flow and faster coalescence are expected at the Z chromosome, we discover high levels of conflict between the 416 sex-linked loci. Despite this discordant pattern, both concatenation and multispecies coalescent approaches yield surprisingly consistent and fully supported genome-wide phylogenies. We conclude that the imposition of the bifurcating tree model without testing for interspecific gene flow may distort our perception of adaptive radiations and thus the ability to study trait evolution in a comparative framework.
The emergence of Q1 genotype of avian infectious bronchitis virus in Iran, 2019: the first report.

Background Avian infectious bronchitis (IB) is an infectious viral disease of chickens. The effective protection of chickens against many different infectious bronchitis virus (IBV) variants is not achieved unless the circulating genotypes in the region are identified and the cross-protection of the potential of vaccines in use is assessed. Aims In a monitoring program of IBVs, a new genotype was identified in the north of Iran, 2019. This work was conducted to isolate and characterize this new IBV genotype. Methods Tracheal tissues were collected from chickens showing signs of respiratory involvement. Specimens were homogenized and inoculated to the allantoic fluid of embryonated specific pathogen-free (SPF) eggs. Infectious bronchitis virus was detected using real time-polymerase chain reaction (RT-PCR). The hypervariable region of the IBV S1 gene was amplified for sequencing. Results Positive samples were phylogenetically analyzed, and both positive isolates were clustered with Q1 IBV strains. Conclusion This is the first report of the Q1 outbreak in Iran. More investigations are needed to find the role of Q1 IBV in the respiratory disease complex of chickens.
Gene regulation in psoriatic keratinocytes: microRNAs and cytokine responses

Psoriasis is the most common chronic skin inflammation in adults which affects 2-4% of the world population. Keratinocytes are the key structural cells in epidermis which hyperproliferate and undergo aberrant differentiation in psoriasis. Keratinocyte-derived cytokines and chemokines are essential in maintaining the vicious auto-inflammatory loop in psoriasis. MicroRNAs (miRNAs) are small RNAs (22-25 nucleotides) which regulates gene expression at the post-transcriptional level. In this thesis, we explored the functional role of miRNAs/ cytokine networks in psoriasis. Paper I: A strong protective association of SNP (rs2910164-CC) of miR-146a to early onset of psoriasis was observed in HLA-C*06-negative patients. In addition, miR-146a deletion in mice led to earlier onset, more severe inflammation and impaired healing of imiquimod-induced psoriasis-like skin inflammation. Therapeutically, miR-146a mimic injection prevented psoriasiform skin-inflammation in WT mice, suggesting an anti-inflammatory role of miR146a. Paper II: Here we explored the landscape of miRNAs in psoriatic keratinocytes. We identified several miRNAs, which were not identified in psoriasis before and their expression was altered in keratinocyte. In addition, upregulation of miR-1307-3p and human-specific miR-941 was validated with qRT-PCR. Paper III: MiR-149 was found to be downregulated in psoriatic keratinocytes compared to keratinocytes from non-lesional or healthy skin. In vitro studies revealed that the downregulation of miR-149 is mediated by IFN-γ/JAK/STAT axis. Functionally, miR-149 targeted the inflammatory and JAK/STAT pathway genes in resting as well as in IFN-γ treated keratinocytes. Moreover, miR-149 inhibition potentiated IFN-γ responses in keratinocytes. Paper IV: Here we outlined a new mode of action of tofactinib, a JAK inhibitor with effects on psoriasis in clinical trials. We showed that JAK proteins that are targets of tofacitinib are expressed by keratinocytes and tofacitinib had a robust impact on IL-22regulated transcriptome in keratinocytes. Our results imply that effects of tofacitinib are not just limited to T-cells as previously thought but can also be observed in keratinocytes.
Balance, Lateropulsion, and Gait Disorders in Subacute Stroke

Objective To test the hypothesis that impaired body orientation with respect to gravity (lateropulsion) would play a key role in poststroke balance and gait disorders. Methods Cohort study of 220 individuals consecutively admitted to a neurorehabilitation ward after a first hemisphere stroke (DOBRAS cohort [Determinants of Balance Recovery After Stroke] 2012–2018, ClinicalTrials.gov: NCT03203109), with clinical data systematically collected at 1 month, then at discharge. Primary outcomes were balance and gait disorders, quantified by the Postural Assessment Scale for Stroke and the modified Fugl-Meyer Gait Assessment, to be explained by all deficits on day 30, including lateropulsion assessed with the Scale for Contraversive Pushing. Statistics comprised linear regression analysis, univariate and multivariate analyses, and receiver operating characteristic curves. Results Lateropulsion was frequent, especially after right hemisphere stroke (RHS, D30, 48%; discharge 24%), almost always in right-handers. Among all deficits, impaired body orientation (lateropulsion) had the most detrimental effect on balance and gait. After RHS, balance disorders were proportional to lateropulsion severity, which alone explained almost all balance disorders at initial assessment (90%; 95% confidence interval [CI] [86–94], p < 0.001) and at discharge (92%; 95% CI 89–95, p < 0.001) and also the greatest part of gait disorders at initial assessment (66%; 95% CI 56–77, p < 0.001) and at discharge (68%; 95% CI 57–78, p < 0.001). Conclusion Lateropulsion is the primary factor altering poststroke balance and gait at the subacute stage and therefore should be systematically assessed. Poststroke balance and gait rehabilitation should incorporate techniques devoted to misorientation with respect to gravity.
Impact of a volume challenge on haemodynamics and prognosis in patients with severe aortic stenosis

A volume challenge can unmask pulmonary hypertension (PH) and its mechanism. We evaluated the impact of a volume challenge on mean pulmonary artery pressure (mPAP) and mean pulmonary artery wedge pressure (mPAWP) and its prognostic implications in patients with severe aortic stenosis (AS) undergoing aortic valve replacement (AVR).
Flow in the time of COVID-19: Findings from China

In February 2020, the Novel Coronavirus (COVID-19) was raging in Wuhan, China and quickly spreading to the rest of the world. This period was fraught with uncertainty for those in the affected areas. The present investigation examined the role of two potential coping resources during this stressful period of uncertainty: flow and mindfulness. Participants in Wuhan and other major cities affected by COVID-19 (N = 5115) completed an online survey assessing subjective experiences of flow, mindfulness, and well-being. Longer quarantine was associated with poorer well-being; flow and mindfulness were associated with better well-being on some measures. However, flow—but not mindfulness—moderated the link between quarantine length and well-being, such that people who experienced high levels flow showed little or no association between quarantine length and poorer well-being. These findings suggest that experiencing flow (typically by engaging in flow-inducing activities) may be a particularly effective way to protect against potentially deleterious effects of a period of quarantine.
Mapping bilayer thickness in the ER membrane

Ceramide locally thickens the ER-bilayer to compartmentalize diffusion in the ER-membrane and structure ER-TGN-contact sites. In the plasma membrane and in synthetic membranes, resident lipids may laterally unmix to form domains of distinct biophysical properties. Whether lipids also drive the lateral organization of intracellular membranes is largely unknown. Here, we describe genetically encoded fluorescent reporters visualizing local variations in bilayer thickness. Using them, we demonstrate that long-chained ceramides promote the formation of discrete domains of increased bilayer thickness in the yeast ER, particularly in the future plane of cleavage and at ER–trans-Golgi contact sites. Thickening of the ER membrane in the cleavage plane contributed to the formation of lateral diffusion barriers, which restricted the passage of short, but not long, protein transmembrane domains between the mother and bud ER compartments. Together, our data establish that the ER membrane is laterally organized and that ceramides drive this process, and provide insights into the physical nature and biophysical mechanisms of the lateral diffusion barriers that compartmentalize the ER.
From Fable to Reality at Parkland Hospital: The Impact of Evidence-Based Design Strategies on Patient Safety, Healing, and Satisfaction in an Adult Inpatient Environment

Objective: This research aimed to evaluate the quantitative effects of new hospital design on adult inpatient outcomes. Background: Tenets of evidence-based healthcare design, notably single-patient acuity-adaptable and same-handed rooms, decentralized nursing stations, onstage offstage layout, and access to nature were expected to promote patient healing and increase patient satisfaction, while decreasing adverse events. Methods: Patient healing was operationalized through length of stay (LOS) and patient safety through three adverse events: falls, hospital-acquired infections (HAI), and medication-related events. Standard patient surveys captured patient satisfaction. Patient records from 2013 through 2017 allowed for equivalent time periods surrounding the move to the new hospital in August 2015. Stratified by hospital division where significant, pre/post comparisons utilized proportional hazards or logistic regression models as appropriate; interrupted time series analyses afforded longitudinal interpretations. Results: Observed higher postmove LOS was due to previously increasing trends, not increases after the move. In surgical and trauma units, a constant increase in falls was unaffected by the move. Medication events decreased consistently over time; medication events with harm dropped significantly after the move. No change in HAI was found. Significant improvement on most relevant patient satisfaction items occurred after the move. Call button response decreased immediately after the move but subsequently improved. Conclusion: Results did not clearly indicate a net change in adult inpatient outcomes of healing and safety due to the hospital design. There was evidence that the new hospital improved patient satisfaction outcomes related to the environment, including comfort, noise, temperature, and aesthetics.
Peptide-Mediated Synthesis of Zeolitic Imidazolate Framework-8 with Controllable Morphology and Size.

Peptides with a sequence of Nap-Ix-GPLGLAG-R4-NH2 (x = 2, 4, and 6, shorted as I2R4, I4R4, and I6R4) were used as capping agents for the synthesis of zeolitic imidazolate framework-8 (ZIF-8) in water. Peptide addition can significantly inhibit the growth of ZIF-8 crystals. The shape and size of ZIF-8 crystals was related closely to the number of isoleucine (Ile, I) residues as well as concentration of the peptide. The shape of ZIF-8 crystals changes from rhomboid dodecahedron to truncated rhombic dodecahedron to cube with the decreasing number of isoleucine residues from six to two. At a peptide concentration of 1.0 mM, the morphology of ZIF-8 crystals was cubic, truncated rhombic dodecahedron, and typical rhombic dodecahedron in the cases of I2R4, I4R4, and I6R4, respectively. Also, the particle size can be regulated from ca. 1.7 μm to <100 nm by controlling the peptide concentration from 0 to 2.0 mM. This work develops a simple and green method for the synthesis of ZIF-8 crystals with controllable shape and size in water, which shows high potential for biomedical and biological applications.