Miracle-dz/UniFAR-FTUs huggingface dataset:
Progressive Interstitial Lung Disease in Relatives of Patients with Pulmonary Fibrosis

sequencing study. Lancet Respir Med 2018;6:603–614. 12. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al.; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405–424. 13. Kropski JA, Reiss S, Markin C, Brown KK, Schwartz DA, Schwarz MI, et al. rare genetic variants in PARN are associated with pulmonary fibrosis in families. Am J Respir Crit Care Med 2017;196:1481–1484. 14. Bendix L, Thinggaard M, Fenger M, Kolvraa S, Avlund K, Linneberg A, et al. Longitudinal changes in leukocyte telomere length and mortality in humans. J Gerontol A Biol Sci Med Sci 2014;69:231–239. 15. Nettle D, Gadalla SM, Lai TP, Susser E, Bateson M, Aviv A. Measurement of telomere length for longitudinal analysis: implications of assay precision. Am J Epidemiol 2021;190: 1406–1413. 16. Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, et al. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci USA 2004;101:17312–17315. 17. McDonough JE, Martens DS, Tanabe N, Ahangari F, Verleden SE, Maes K, et al. A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis. Respir Res 2018;19:132. 18. van der Vis JJ, van der Smagt JJ, van Batenburg AA, Goldschmeding R, van Es HW, Grutters JC, et al. Pulmonary fibrosis in non-mutation carriers of families with short telomere syndrome gene mutations. Respirology 2021;26:1160–1170.
Progress and challenges in fungal lung disease in cystic fibrosis

Purpose of review This review is an overview of the recent progress made for the diagnosis and understanding of fungal lung disease in people with cystic fibrosis (CF), with a focus on Aspergillus fumigatus, the most common filamentous fungus in the CF airway. Currently, the longstanding question of the clinical significance of Aspergillus fumigatus and other fungi in CF respiratory cultures, in the absence of allergy, remains. Clinical criteria and biomarkers are needed to classify fungal lung disease and determine who may warrant therapy. Recent findings Several retrospective and prospective studies have described the prevalence of A. fumigatus and other fungi in the CF lung and factors contributing to the changes in fungal epidemiology. Selective fungus culture testing for the detection of fungi in CF sputa has been well studied, yet a standardized fungus culture protocol has yet to be defined. Culture-independent molecular studies and other fungal diagnostic testing have been conducted in the CF population, leading to efforts to better understand the clinical role of these tests. Recent works have aimed to determine whether chronic A. fumigatus colonization is associated with lung disease progression measured by FEV1 percentage predicted, structural lung disease, lung clearance index and respiratory quality-of-life. However, the existing knowledge gaps remain: definition of a fungal respiratory infection, the association between fungal infection and clinical outcomes, and indications for antifungal therapy. Summary Significant progress has been made for the detection and diagnosis of fungal lung disease. Yet, the role and impact of A. fumigatus and other fungal infections on respiratory health in people with CF remains to be determined.
More to the story than executive function: Effortful control soon after injury predicts long-term functional and social outcomes following pediatric traumatic brain injury in young children

Abstract Objective: To examine the impact of early traumatic brain injury (TBI) on effortful control (EC) over time and the relationship of EC and executive functioning (EF) to long-term functional and social outcomes. Method: Parents of children (N = 206, ages 3–7) with moderate-to-severe TBI or orthopedic injuries (OIs) rated EC using the Child Behavior Questionnaire at 1 (pre-injury), 6, 12, and 18 months post-injury. Child functioning and social competence were assessed at 7 years post-injury. Mixed models examined the effects of injury, time since injury, and their interaction on EC. General linear models examined the associations of pre-injury EC and EC at 18 months with long-term functional and social outcomes. Models controlled for EF to assess the unique contribution of EC to outcomes. Results: Children with severe TBI had significantly lower EC than both the OI and moderate TBI groups at each post-injury time point. Both pre-injury and 18-month EC were associated with long-term outcomes. Among those with low EC at baseline, children with moderate and severe TBI had more functional impairment than those with OI; however, no group differences were noted at high levels of EC. EC had main effects on parent-reported social competence that did not vary by injury type. Conclusions: Findings suggest that EC is sensitive to TBI effects and is a unique predictor of functional outcomes, independent of EF. High EC could serve as a protective factor, and as such measures of EC could be used to identify children for more intensive intervention.
Supporting Reading Aloud Beginning Prenatally and in Early Infancy: A Randomized Trial in Brazil

This article has supplementary material on the web site: www.jdbp. org. ABSTRACT: Objective: A previous study of a reading aloud intervention in Brazil, called Universidade do Bebê (UBB), demonstrated impacts on parenting and child outcomes for families with toddlers and preschoolers, even for parents with low literacy, and cognitive stimulation mediated effects on child outcomes. In a new study, we sought to determine whether similar results would be found when UBB was provided beginning in pregnancy through early toddlerhood, including (1) impacts on parenting and child development, (2) variation in impact on parenting and child outcomes by parent literacy level, and (3) indirect impacts on child outcomes through cognitive stimulation. Method: Women with low income who were either pregnant or with children aged 0 to 24 months were randomized to UBB or control groups. UBB consisted of monthly workshops focused on reading aloud complemented by a book-lending library. Participants were evaluated at baseline and approximately 11 months later (M = 11.0, SD = 0.4; range 9.9–12.2 months) on parenting (cognitive stimulation, beliefs about early reading, screen time, and discipline) and child development. Results: Four hundred families (n = 200 UBB) were randomized; 286 (71.5%; n = 150 UBB) received 11-month follow-up. UBB families showed increased cognitive stimulation (Cohen's d = 0.92) and awareness about the importance of early reading (d = 0.90) than controls, with no differences by parent literacy level. UBB was associated with reduced screen time and increased vocabulary, but only for families with low parent literacy. UBB effects on child outcomes were mediated by cognitive stimulation. Conclusion: The findings support implementation of reading aloud programs beginning in pregnancy and early childhood.
Time between inhibitor detection and start of immune tolerance induction: Association with outcome in the BrazIT study

Immune tolerance induction (ITI) is the treatment of choice for eradication of anti‐factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and high‐responding inhibitor (PwHA‐HRi). The association between ITI outcome and time elapsed between inhibitor detection and start of ITI (∆tinhi‐ITI) is debatable.
DHA and EPA Prevent Seizure and Depression-Like Behavior by Inhibiting Ferroptosis and Neuroinflammation via Different Mode-of-actions in a Pentylenetetrazole-Induced Kindling Model in Mice.

SCOPE It has been reported that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anticonvulsant effects, yet the respective mechanism of EPA and DHA on epilepsy are still unclarified. This study aimed to investigate the effect of EPA and DHA on pentylenetetrazol (PTZ) induced seizures and depression. METHODS AND RESULTS The administration of EPA and DHA at a dose of 1% (w/w) significantly inhibited PTZ-induced seizures and depressive-like behavior, whereas EPA outcompetes DHA. Further mechanistic studies revealed that the higher effect of EPA can be partly attributed to the promotion of M2 polarization, inhibition of M1 polarization of microglia, and lower iron content in the brain, resulting from the stronger activation of nuclear factor E2-related factor 2 (Nrf2). We found that DHA and EPA comparably inhibited NLRP3 inflammasome activation but with different mode-of-actions: EPA preferred to inhibit the binding of NLRP3 and ASC, while DHA decreased the protein levels of ASC and Caspase-1. CONCLUSIONS These results indicated that DHA and EPA could efficaciously alleviate PTZ-induced seizure and depressive-like behavior but with different efficiency and molecular mechanisms. This article is protected by copyright. All rights reserved.
Semiclassical quantum mechanics, IV : large order asymptotics and more general states in more than one dimension

We solve the n-dimensional time dependent Schrodinger equation i¬h ∂Ψ / ∂ t=-¬h 2 /2m Δ Ψ+V Ψ modulo errors which have L 2 norms on the order of ¬h 1/2 for arbitrary large1. The initial conditions are fairly general states whose position and momentum uncertainties are proportional to ¬h 1/2 On resout l'equation de Schrodinger dependant du temps i¬hd Ψ /dt=-¬h 2 Δ Ψ/2m+V Ψ en dimension n modulo des erreurs dont la norme dans L 2 est d'ordre ¬h 1/2 pour l'arbitrairement grand. Les conditions initiales sont des etats relativement generaux dont les incertitudes de position et d'impulsion sont proportionnelles a ¬h 1/2
Zigzag and spiral configurations for fullerenes in carbon nanotubes

The success or otherwise of nanoscale devices hinges on a correct understanding of the physical effects at this scale. Research in nanotechnology is predominantly through either experimentation using electron and atomic force microscopy or through large-scale computation using molecular dynamics simulation. In this paper, we employ elementary mechanical principles and classical modelling procedures to investigate the packing of C60 fullerene chains inside a single-walled carbon nanotube by utilizing the Lennard–Jones potential function and the continuum approximation. Such assemblies are often referred to as nanopeapods. We examine both zigzag and spiral chain configurations inside (10, 10), (16, 16) and (20, 20) carbon nanotubes and we obtain analytical expressions in terms of hypergeometric functions for the potential energy for such configurations. We find that for a (10, 10) tube, the C60 fullerene chain is formed linearly along the tube axis. In the case of both (16, 16) and (20, 20) tubes, both zigzag and spiral configurations are more clearly evident along the tube. In particular, the resulting pattern obtained for the zigzag chain is entirely consistent with a specific angular spacing for the spiral pattern.
Methylation of the 4q35 D4Z4 repeat defines disease status in facioscapulohumeral muscular dystrophy.

Genetic diagnosis of facioscapulohumeral muscular dystrophy (FSHD) remains a challenge in clinical practice as it cannot be detected by standard sequencing methods despite being the third most common muscular dystrophy. The conventional diagnostic strategy addresses the known genetic parameters of FSHD: the required presence of a permissive haplotype, a size reduction of the D4Z4 repeat of chromosome 4q35 (defining FSHD1), or a pathogenic variant in an epigenetic suppressor gene (consistent with FSHD2). Incomplete penetrance and epistatic effects of the underlying genetic parameters as well as epigenetic parameters (D4Z4 methylation) pose challenges to diagnostic accuracy and hinder prediction of clinical severity. In order to circumvent the known limitations of conventional diagnostics and to complement genetic parameters with epigenetic ones, we developed and validated a multistage diagnostic workflow that consists of a haplotype analysis and a high throughput methylation profile analysis (FSHD-MPA). FSHD-MPA determines the average global methylation level of the D4Z4 repeat array as well as the regional methylation of the most distal repeat unit by combining bisulfite conversion with next-generation sequencing (NGS) and a bioinformatics pipeline and uses these as diagnostic parameters. We applied the diagnostic workflow to a cohort of 148 patients and compared the epigenetic parameters based on FSHD-MPA to genetic parameters of conventional genetic testing. In addition, we studied the correlation of repeat length and methylation level within the most distal repeat unit with age-corrected clinical severity and age at disease onset in FSHD patients. The results of our study show that FSHD-MPA is a powerful tool to accurately determine the epigenetic parameters of FSHD, allowing discrimination between FSHD patients and healthy individuals, while simultaneously distinguishing FSHD1 and FSHD2. The strong correlation between methylation level and clinical severity indicates that the methylation level determined by FSHD-MPA accounts for differences in disease severity among individuals with similar genetic parameters. Thus, our findings further confirm that epigenetic parameters rather than genetic parameters represent FSHD disease status and may serve as a valuable biomarker for disease status.
Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multi-centre randomised clinical trial.

INTRODUCTION Hyperbaric oxygen treatment (HBOT) is sometimes used in the management of open fractures and severe soft tissue crush injury, aiming to reduce complications and improve outcomes. METHODS Patients with open tibial fractures were randomly assigned within 48 hours of injury to receive standard trauma care or standard care plus 12 sessions of HBOT. The primary outcome was the incidence of necrosis or infection or both occurring within 14 days of injury. RESULTS One-hundred and twenty patients were enrolled. Intention to treat primary outcome occurred in 25/58 HBOT assigned patients and 34/59 controls (43% vs 58%, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25 to 1.18, P = 0.12). Tissue necrosis occurred in 29% of HBOT patients and 53% of controls (OR 0.35, 95% CI 0.16 to 0.78, P = 0.01). There were fewer late complications in patients receiving HBOT (6/53 vs 18/52, OR 0.22, 95% CI 0.08 to 0.64, P = 0.007) including delayed fracture union (5/53 vs 13/52, OR 0.31, 95% CI 0.10 to 0.95, P = 0.04). Quality of life measures at one and two years were superior in HBOT patients. The mean score difference in short form 36 was 2.90, 95% CI 1.03 to 4.77, P = 0.002, in the short musculoskeletal function assessment (SMFA) was 2.54, 95% CI 0.62 to 4.46, P = 0.01; and in SMFA daily activities was 19.51, 95% CI 0.06 to 21.08, P = 0.05. CONCLUSIONS In severe lower limb trauma, early HBOT reduces tissue necrosis and the likelihood of long-term complications, and improves functional outcomes. Future research should focus on optimal dosage and whether HBOT has benefits for other injury types.
Habitat-specific responses of soil organic matter decomposition to Spartina alterniflora invasion along China's coast.

Plant invasions cause a fundamental change in soil organic matter (SOM) turnover. Disentangling the biogeographic patterns and key drivers of SOM decomposition and its temperature sensitivity (Q10 ) under plant invasion are prerequisites for the projections of global carbon feedback. We collected soil samples along China's coast across salt marshes to mangrove ecosystems invaded by the smooth cordgrass (Spartina alterniflora Loisel.). Microcosm experiments were carried out to determine the patterns of SOM decomposition and its thermal response. Soil microbial biomass and communities were also characterized accordingly. SOM decomposition constant dramatically decreased along the mean annual temperature (MAT) gradient, whereas the cordgrass invasion retarded this change (significantly reduced slope, P < 0.05). The response of Q10 to invasion and soil microbial quotient peaked at mid-latitude salt marshes, which can be explained by the microbial metabolism strategies. Climatic variables showed strong negative controls on the Q10 , while dissolved carbon fraction exerted a positive influence on its spatial variance. Higher microbial diversity appeared to weaken the temperature-related response of SOM decomposition, with apparent benefits for carbon sequestration. Inconsistent responses to invasion were exhibited among habitat types, with SOM accumulation in salt marshes but the carbon loss in mangroves, which were, at least in part, explained by the SOM decomposition patterns under invasion. This study elucidates the geographic pattern of SOM decomposition and its temperature sensitivity in coastal ecosystems and underlines the importance of interactions between climate, soil, and microbiota for stabilizing SOM under plant invasion.
A comparison of MVP and MSVT performance among a diverse clinical pediatric sample

Abstract The Memory Validity Profile (MVP) and Medical Symptom Validity Test (MSVT) are performance validity tests (PVTs) used to identify potential noncredible test performance during psychological evaluations. This study sought to examine the agreement between MVP and MSVT pass rates, as well as to determine if there are differences in MVP pass rates when using the cutoff score in the MVP professional manual compared with the experimental cutoff score of <31. Via retrospective review of records, 106 clients at a private neuropsychological clinic who had been given the MVP and the MSVT were identified. Results indicated that only one client met the manual cutoff scores, compared to 20 clients who failed the MSVT, raising concerns regarding the sensitivity of the MVP. Utilizing the receiver operator characteristic (ROC), curve analyses indicated fair discriminability of the MVP for the 106 participants (AUC = .717) with acceptable sensitivity (.50) and specificity (.92) for an MVP total score cutoff of <31. These findings support the utility of the experimental cut score in improving the sensitivity while maintaining adequate specificity in a clinically mixed population.
Upfront therapy for diffuse large B-cell lymphoma: looking beyond R-CHOP

ABSTRACT Introduction Diffuse large B-cell lymphoma (DLBCL) is not a single entity but instead represents a collection of interrelated malignancies having distinct molecular features. Recent multiomics studies have independently identified the presence of at least five different subsets of DLBCL, further subcategorizing previously recognized subtypes of this disease. Clinical trials attempting to improve outcomes with the addition of novel therapeutic agents have approached advanced-stage DLBCL as either a single entity or as an overly broad subtype, and have been largely unsuccessful. Areas covered We review, here, in detail the similarities between the novel advanced molecular classification systems. We also review several large phase-3 clinical trials in DLBCL, including those that failed to demonstrate an improvement in outcomes. We explore details of the POLARIX trial data supporting the use of the anti-CD79B antibody drug conjugate (ADC) polatuzumab vedotin. Expert opinion Future efforts to improve the outcomes of frontline treatment of DLBCL patients will require a precision medicine approach in which individual-targeted agents are used to treat patients with specific subgroups of DLBCL, based on molecular features. This will require a validated molecular assay with results available in real-time and coordinated effort by academic clinical investigators and industry partners.
Spatial Attention Tunes Temporal Processing in Early Visual Cortex by Speeding and Slowing Alpha Oscillations

The perception of dynamic visual stimuli relies on two apparently conflicting perceptual mechanisms: rapid visual input must sometimes be integrated into unitary percepts but at other times must be segregated or parsed into separate objects or events. Though they have opposite effects on our perceptual experience, the deployment of spatial attention benefits both operations. Little is known about the neural mechanisms underlying this impact of spatial attention on temporal perception. Here, we record magnetoencephalography (MEG) in male and female humans to demonstrate that the deployment of spatial attention for the purpose of segregating or integrating visual stimuli impacts prestimulus oscillatory activity in retinotopic visual brain areas where the attended location is represented. Alpha band oscillations contralateral to an attended location are therefore faster than ipsilateral oscillations when stimuli appearing at this location will need to be segregated, but slower in expectation of the need for integration, consistent with the idea that α frequency is linked to perceptual sampling rate. These results demonstrate a novel interaction between temporal visual processing and the allocation of attention in space. SIGNIFICANCE STATEMENT Our environment is dynamic and visual input therefore varies over time. To make sense of continuously changing information, our visual system balances two complementary processes: temporal segregation in order to identify changes, and temporal integration to identify consistencies in time. When we know that a circumstance requires use of one or the other of these operations, we are able to prepare for this, and this preparation can be tracked in oscillatory brain activity. Here, we show how this preparation for temporal processing can be focused spatially. When we expect to integrate or segregate visual stimuli that will appear at a specific location, oscillatory brain activity changes in visual areas responsible for the representation of that location. In this way, spatial and temporal mechanisms interact to support adaptive, efficient perception.
Nonadiabatic Vibrational Resonance Raman Spectra from Quantum Dynamics Propagations with LVC Models. Application to Thymine

We present a viable protocol to compute vibrational resonance Raman (vRR) spectra for systems with several close-lying and potentially coupled electronic states. It is based on the parametrization of linear vibronic coupling (LVC) models from time-dependent density functional theory (TD-DFT) calculations and quantum dynamics propagations of vibronic wavepackets with the multilayer version of the multiconfiguration time-dependent Hartree (ML-MCTDH) method. Our approach is applied to thymine considering seven coupled electronic states, comprising the three lowest bright states, and all vibrational coordinates. Computed vRR at different excitation wavelengths are in good agreement with the available experimental data. Up to 250 nm the signal is dominated by the lowest HOMO → LUMO transition, whereas at 233 nm, in the valley between the two lowest energy absorption bands, the contributions of all the three bright states, and their interferences and couplings, are important. Inclusion of solvent (water) effects improves the agreement with experiment, reproducing the coalescence of vibrational bands due to CC and C=O stretchings. With our approach we disentangle and assess the effect of interferences between the contribution of different quasi-resonant states to the transition polarizability and the effect of interstate couplings. Our findings strongly suggest that in cases of close-lying and potentially coupled states a simple inclusion of interference effects is not sufficient, and a fully nonadiabatic computation should instead be performed. We also document that for systems with strong couplings and quasi-degenerate states, the use of HT perturbative approach, not designed for these cases, may lead to large artifacts.