Miracle-dz/UniFAR-FTUs huggingface dataset:
Real-world data on the efficacy and safety of tezacaftor-ivacaftor in adults living with cystic fibrosis homozygous for F508del and heterozygous for F508del and a residual function mutation

ABSTRACT Background To examine safety and efficacy of tezacaftor-ivacaftor (TEZ/IVA) in a real-life setting in adults living with cystic fibrosis. Methods A multicentre retrospective observational study, including adults living with cystic fibrosis (pwCF) eligible for TEZ/IVA, with assessments at baseline, 3 months (visit3mo) and 6 months (visit6mo) after start of treatment. Outcomes included change in FEV1, LCI, FeNO, CFQ-R, estimated number of annual acute exacerbations, BMI, dosage of pancreatic enzyme replacement therapy (PERT) and airway microbiology. We also assessed safety. Results Forty-eight adult pwCF (mean (±SD) age 33 (±12) years; mean FEV1 65 (±19) %P) were included. Three subgroups were identified: pwCF F/F CFTR modulator-naive (n = 28; 58%), pwCF F/F previously treated with lumacaftor-ivacaftor (n = 11; 23%) and pwCF F/RF (n = 9; 19%). Adverse events were described in 3 pwCF (6%) during the 6-month observation period (in one leading to treatment interruption). At visit3mo, FEV1 had improved in all subgroups. In the entire group, mean FEV1 had increased from 66 (±2.9) %P to 72 (±2.9) %P (p < 0.0001). Similarly, LCI improved by approximately one unit at visit3mo (p = 0.02). At visit6mo mean annual acute exacerbation rate decreased significantly (p = 0.02). Only in the CFQ-R social functioning domain score, a significant improvement was observed at visit6mo (p < 0.01). Conclusions We showed that TEZ/IVA is safe, well tolerated and effective in terms of improvement of lung function, ventilation inhomogeneity, health-related social functioning, and reduction of estimated annual acute exacerbation rate, in adult pwCF F/F and F/RF. Results in this real-life study reflect those observed in RCTs.
Movement in low gravity environments (MoLo) programme–The MoLo-L.O.O.P. study protocol

Background Exposure to prolonged periods in microgravity is associated with deconditioning of the musculoskeletal system due to chronic changes in mechanical stimulation. Given astronauts will operate on the Lunar surface for extended periods of time, it is critical to quantify both external (e.g., ground reaction forces) and internal (e.g., joint reaction forces) loads of relevant movements performed during Lunar missions. Such knowledge is key to predict musculoskeletal deconditioning and determine appropriate exercise countermeasures associated with extended exposure to hypogravity. Objectives The aim of this paper is to define an experimental protocol and methodology suitable to estimate in high-fidelity hypogravity conditions the lower limb internal joint reaction forces. State-of-the-art movement kinetics, kinematics, muscle activation and muscle-tendon unit behaviour during locomotor and plyometric movements will be collected and used as inputs (Objective 1), with musculoskeletal modelling and an optimisation framework used to estimate lower limb internal joint loading (Objective 2). Methods Twenty-six healthy participants will be recruited for this cross-sectional study. Participants will walk, skip and run, at speeds ranging between 0.56–3.6 m/s, and perform plyometric movement trials at each gravity level (1, 0.7, 0.5, 0.38, 0.27 and 0.16g) in a randomized order. Through the collection of state-of-the-art kinetics, kinematics, muscle activation and muscle-tendon behaviour, a musculoskeletal modelling framework will be used to estimate lower limb joint reaction forces via tracking simulations. Conclusion The results of this study will provide first estimations of internal musculoskeletal loads associated with human movement performed in a range of hypogravity levels. Thus, our unique data will be a key step towards modelling the musculoskeletal deconditioning associated with long term habitation on the Lunar surface, and thereby aiding the design of Lunar exercise countermeasures and mitigation strategies.
Associations of Rap1 with Cell Wall Integrity, Biofilm Formation, and Virulence in Candida albicans

C. albicans is an important fungal pathogen of humans. The cell wall is the outermost layer of C. albicans and is important for commensalism and infection by this pathogen. ABSTRACT Rap1 (repressor activator protein 1) is a multifunctional protein, playing important roles in telomeric and nontelomeric functions in many eukaryotes. Candida albicans Rap1 has been previously shown to be involved in telomeric regulation, but its other functions are still mostly unknown. In this study, we found that the deletion of the RAP1 gene altered cell wall properties, composition, and gene expression. In addition, deletion of RAP1 affected C. albicans biofilm formation and modulated phagocytosis and cytokine release by host immune cells. Finally, the RAP1 gene deletion mutant showed attenuation of C. albicans virulence in a Galleria mellonella infection model. Therefore, these findings provide new insights into Rap1 functions that are particularly relevant to pathogenesis and virulence of C. albicans. IMPORTANCE C. albicans is an important fungal pathogen of humans. The cell wall is the outermost layer of C. albicans and is important for commensalism and infection by this pathogen. Moreover, the cell wall is also an important target for antifungals. Studies of how C. albicans maintains its cell wall integrity are critical for a better understanding of fungal pathogenesis and virulence. This work focuses on exploring unknown functions of C. albicans Rap1 and reveals its contribution to cell wall integrity, biofilm formation, and virulence. Notably, these findings will also improve our general understanding of complex machinery to control pathogenesis and virulence of fungal pathogens.
Spin dynamics in InAs nanowire quantum dots coupled to a transmission line

We study theoretically electron spins in nanowire quantum dots placed inside a transmission line resonator. Because of the spin-orbit interaction, the spins couple to the electric component of the resonator electromagnetic field and enable coherent manipulation, storage, and readout of quantum information in an all-electrical fashion. Coupling between distant quantum-dot spins, in one and the same or different nanowires, can be efficiently performed via the resonator mode either in real time or through virtual processes. For the latter case, we derive an effective spin-entangling interaction and suggest means to turn it on and off. We consider both transverse and longitudinal types of nanowire quantum dots and compare their manipulation time scales against the spin relaxation times. For this, we evaluate the rates for spin relaxation induced by the nanowire vibrations (phonons) and show that, as a result of phonon confinement in the nanowire, this rate is a strongly varying function of the spin operation frequency and thus can be drastically reduced compared to lateral quantum dots in GaAs. Our scheme is a step forward to the formation of hybrid structures where qubits of different nature can be integrated in a single device.
A Retrospective Clinical Study of Endoscopic Treatment of Carpal Tunnel Syndrome using the Modified Soft Tissue Release kit

Carpal tunnel syndrome (CTS) is the most common peripheral entrapment neuropathy, and endoscopic carpal tunnel release (ECTR) is one of the minimally invasive procedures for the treatment of CTS. Based on the shortcomings of ECTR, we designed the “Modified Soft Tissue Release Kit” to assist the endoscopic operation. This study aimed to evaluate the effectiveness and safety of endoscopic treatment of CTS using this kit.
Phylogenomics and the flowering plant tree of life.

The advances accelerated by next-generation sequencing and long-read sequencing technologies continue to provide an impetus for plant phylogenetic study. In the past decade, a large number of phylogenetic studies adopting hundreds to thousands of genes across a wealth of clades have emerged and ushered plant phylogenetics and evolution into a new era. In the meantime, a roadmap for researchers when making decisions across different approaches for their phylogenomic research design is imminent. This review focuses on the utility of genomic data (from organelle genomes, to both reduced representation sequencing and whole-genome sequencing) in phylogenetic and evolutionary investigations, describes the baseline methodology of experimental and analytical procedures, and summarizes recent progress in flowering plant phylogenomics at the ordinal, familial, tribal and lower levels. We also discuss the challenges, such as the adverse impact on orthology inference and phylogenetic reconstruction raised from systematic errors, and underlying biological factors, such as whole-genome duplication (WGD), hybridization/introgression, and incomplete lineage sorting (ILS), together suggesting that a bifurcating tree may not be the best model for the tree of life. Finally, we discuss promising avenues for future plant phylogenomic studies. This article is protected by copyright. All rights reserved.
Promoting a culture of reciprocity to build social capital in advanced practice nursing students

ABSTRACT A virtual activity integrating the evidence-based Reciprocity Ring model was designed to enhance confidence and skills for building social capital for advanced practice registered nursing (APRN) students. The central objective of the activity was to reduce the stigma of asking for help by providing a framework for the balanced exchange of favors, thus supporting new connections and feelings of trust among APRN students. Students from two APRN practice tracks (N = 44) participated in a virtual Reciprocity Ring activity where they could post and respond to requests for help. On average, students posted 2.5 requests and received three offers for assistance; 220 connections were made overall with the major theme requests related to stress management. A retrospective survey was administered at the conclusion of the activity. Questions inquired about student confidence before, and then after, the activity for identifying resources, providing help to others, finding personal support when needed, accessing resources related to academic success, and finding solutions to problems. Student mean confidence scores were significantly higher after the activity compared with mean confidence scores before the activity (p = .01). Additionally, the effect size was large (Cohen d = 0.89). Therefore, we suggest that integrating Reciprocity Ring exercises into nursing curricula and practice can be a useful tool for promoting skills related to productive help-seeking that will support APRN students' academic and professional success.
Malnutrition diagnosed by GLIM criteria better predicts long‐term outcomes for patients with non‐Hodgkin's lymphoma: A prospective multicenter cohort study

Since Global Leadership Initiative on Malnutrition (GLIM) method was proposed, few studies have applied these new criteria to hematological tumors. In this study, we explored the prevalence of malnutrition according to the GLIM criteria and scored Patient‐Generated Subjective Global Assessment (sPG‐SGA) and their association with 1‐year, 3‐year and 5‐year mortality among patients with non‐Hodgkin's lymphoma (NHL). Malnutrition of all patients were assessed by GLIM criteria and sPG‐SGA. Relationship between the malnutrition based on GLIM criteria or sPG‐SGA and mortality was investigated by Cox regression analyses. The performance of GLIM criteria was evaluated by assessing the sensitivity, specificity, k‐value, receiver operating characteristic (ROC) curve and time‐dependent ROC. Of 963 patients with NHL, the prevalence of malnutrition was 38.8% with GLIM criteria, 65.3% with GLIM‐omitted NRS‐2002 and 53.2% with sPG‐SGA. In comparison with sPG‐SGA, the sensitivity of GLIM criteria was 61.7%, the specificity was 84.8%, and the agreement was moderate (k = 0.48, p < 0.001). Malnutrition based on GLIM criteria could also predict 3‐year and 5‐year mortality after adjusting for confounders, except for sPG‐SGA (HR = 1.816, 95%CI = 1.274–2.589, p = 0.001 for 3‐year mortality; HR = 1.707, 95%CI = 1.223–2.382, p = 0.002 for 5‐year mortality). For patients with NHL, GLIM criteria could be applied as an effective replacement to sPG‐SGA for nutrition assessment and mortality prediction, especially for predicting long‐term prognostic outcomes.
Understanding the immunological interactions of engineered nanomaterials: Role of the bio‐corona

Abstract Engineered nanomaterials are a broad class of materials with the potential for breakthrough applications in many sectors of society not least in medicine. Consequently, safety assessment of nanomaterials and nano‐enabled products with respect to human health and the environment is of key importance. To this end, the biological interactions of nanoscale materials must be understood. Here, the dual “identities” of nanomaterials, namely, the material‐intrinsic properties or synthetic identity and the acquired, context‐dependent properties or biological identity, are discussed in relation to nanomaterial interactions with the immune system, our main defense against foreign intrusion. Specifically, we address whether macrophages and other innate immune cells respond to the synthetic identity or the biological identity of nanomaterials, that is, the surface adsorbed proteins and/or other biomolecules known as the bio‐corona, or both? This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Ameliorative Effects of Propolis and Royal Jelly against CCl4‐Induced Hepatotoxicity and Nephrotoxicity in Wistar Rats

Carbon tetrachloride (CCl4) is known to have hepatotoxic and nephrotoxic effects. During the two‐month CCl4 exposure of Wistar rats, propolis extract (PE) and royal jelly (RJ) were added in order to test the potential protective effect against hepato‐renal injury. Ketonuria, proteinuria, high creatinine and urea levels are the result of CCl4‐induced nephrotoxicity. Severe disorders of hematological indicators indicate anemia; high values of leukocytes indicate inflammatory condition. Cytogenetic impairments in hepatocytes, aggregation of platelets, and hypoproteinemia indicate severe liver impairment. Results suggest a more significant protective role of RJ compared to PE. Both extracts regulated proteinuria, ketonuria, hypoproteinemia and reduced platelet aggregation in the hepatic circulation. The increase in the number of erythrocytes (RBC) suggest protective effects against anemia; the decrease in the number of leukocytes can be linked to anti‐inflammatory effects. PE and RJ have a beneficial effect against hepato‐renal injury, anemia and anti‐inflammatory conditions caused by CCl4.
From single- to multi-omics: future research trends in medicinal plants

Abstract Medicinal plants are the main source of natural metabolites with specialised pharmacological activities and have been widely examined by plant researchers. Numerous omics studies of medicinal plants have been performed to identify molecular markers of species and functional genes controlling key biological traits, as well as to understand biosynthetic pathways of bioactive metabolites and the regulatory mechanisms of environmental responses. Omics technologies have been widely applied to medicinal plants, including as taxonomics, transcriptomics, metabolomics, proteomics, genomics, pangenomics, epigenomics and mutagenomics. However, because of the complex biological regulation network, single omics usually fail to explain the specific biological phenomena. In recent years, reports of integrated multi-omics studies of medicinal plants have increased. Until now, there have few assessments of recent developments and upcoming trends in omics studies of medicinal plants. We highlight recent developments in omics research of medicinal plants, summarise the typical bioinformatics resources available for analysing omics datasets, and discuss related future directions and challenges. This information facilitates further studies of medicinal plants, refinement of current approaches and leads to new ideas.
Cross-sectional and Prospective Associations of Rest-Activity Rhythms With Body Mass Index in Older Men: A Novel Analysis Using Harmonic Hidden Markov Models

Growing evidence supports a role for rest-activity rhythms (RARs) in metabolic health. Epidemiological studies in adolescents and young adults showed that RAR characteristics consistent with weakened rhythmicity were associated with obesity. However, studies in older adults are lacking. The objective of this study was to examine the cross-sectional and prospective associations between RAR and obesity in older men using the Harmonic Hidden Markov Model (HHMM), a novel analytical approach with several advantages over conventional methods for characterizing RAR. The analysis included nearly 3,000 participants in the Osteoporotic Fractures in Men study with 5-day 24-h actigraphy data. The strength of RAR was measured by rhythmic index (RI), a scaled value between 0 and 1 with higher values indicating better RAR. Multiple linear and logistic regression adjusting for multiple confounders were performed to examine the RI in relation to body mass index (BMI) and obesity status at baseline and after ~3.5 years of follow-up. We showed that the HHMM can derive both meaningful visual profile and quantifier of RAR. A lower RI was associated with higher BMI and obesity at baseline, and an elevated likelihood for developing obesity over follow-up. Specifically, when compared with men in the highest quartile of RI, those in the lowest quartile on average had a higher BMI (β [95% confidence interval (CI)], 1.76 [1.39, 2.13]) and were more likely to be obese at baseline (odds ratio (OR) [95% CI], 2.63 [2.03, 3.43]). Moreover, among nonobese men at baseline, those in the lowest quartile of RI were 2.06 times (OR [95% CI], 2.06 [1.02, 4.27]) more likely to develop obesity over follow-up when compared with those in the highest quartile. In conclusion, our study demonstrated the utility of HHMM in characterizing RAR and showed that rhythmicity strength was associated with BMI and risk of obesity in older men.
Oligodendrocyte precursor cells ingest axons in the mouse neocortex

Significance Oligodendrocyte precursor cells (OPCs) are a population of glia cells that tile across the brain and retain the ability to proliferate. They can become myelinating oligodendrocytes or remain in the precursor state. An unresolved question has been what other functions OPCs might carry out. Using high-throughput transmission electron microscopy and dense 3D reconstructions, we were able to visualize evidence of ingestion and breakdown of axons by OPCs. Analysis of the abundant tertiary lysosomes or phagolysosomes (PLs) in OPC branches confirmed the presence of 40-nm vesicular structures within their chambers. Furthermore, analysis of PLs in microglia demonstrated that their numbers were significantly lower and rarely contained vesicles. This study provides evidence of engulfment and pruning by OPCs.
Modal-based attention modulates the redundant-signals effect: Role of unimodal target probability

Multisensory integration includes two behavioral manifestations: the modality dominance effect and the redundant-signals effect (RSE). RSE is a multisensory improvement effect in which individuals respond more quickly and accurately to bimodal audiovisual (AV) targets than to unimodal auditory (A) or visual (V) targets. Previous studies have confirmed that RSE is the product of modality interactions between different modalities. The goal of this study was to systematically investigate the effects of the modality dominance manipulated by modal-based attention and unimodal target probability on RSE. The results showed that when paying attention to both the A and V modalities (Exp. 1), RSE was not significantly different between unimodal target probabilities. When selectively paying attention to the A modality (Exp. 2A), RSE was also not significantly different between unimodal target probabilities. However, when selectively paying attention to the V modality (Exp. 2B), the magnitude of RSE showed a significant decreasing trend with the increasing probability of V targets. Our study is the first to reveal that the unimodal target probability significantly modulates RSE in visual selective attention, and this modulatory effect of the unimodal target probability on RSE is opposite to the modulatory effect on the modality dominance effect.
Predicting nanomaterials pulmonary toxicity in animals by cell culture models: Achievements and perspectives

Abstract Animal experiments are highly relevant models for the assessment of toxicological effects of engineered nanomaterials (ENMs), due to lack of biomonitoring and epidemiological studies. However, the expanding number of ENMs with different physico‐chemical properties strains this approach, as there are ethical concerns and economical challenges with the use of animals in toxicology. There is an urgent need for cell culture models that predict the level of toxicological responses in vivo, consequently reducing or replacing the use of animals in nanotoxicology. However, there is still a limited number of studies on in vitro–in vivo correlation of toxicological responses following ENMs exposure. In this review, we collected studies that have compared in vitro and in vivo toxic effects caused by ENMs. We discuss the influence of cell culture models and exposure systems on the predictability of in vitro models to equivalent toxic effects in animal lungs after pulmonary exposure to ENMs. In addition, we discuss approaches to qualitatively or quantitatively compare the effects in vitro and in vivo. The magnitude of toxicological responses in cells that are exposed in submerged condition is not systematically different from the response in cells exposed in air–liquid interface systems, and there appears to be similar ENMs hazard ranking between the two exposure systems. Overall, we show that simple in vitro models with cells exposed to ENMs in submerged condition can be used to predict toxic effects in vivo, and identify future strategies to improve the associations between in vitro and in vivo ENMs‐induced pulmonary toxicity. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
A Noninvasive Method for Monitoring Breathing Patterns in Nonhuman Primates Using a Nasal Thermosensor

Abstract Respiration is strongly linked to internal states such as arousal, emotion, and even cognitive processes and provides objective biological information to estimate these states in humans and animals. However, the measurement of respiration has not been established in macaque monkeys, which have been widely used as model animals for understanding various higher brain functions. In the present study, we developed a method to monitor the respiration of behaving monkeys. We first measured the temperature of their nasal breathing, which changes between inspiration and expiration phases, in an anesthetized condition and estimated the respiration pattern. We compared the estimated pattern with that obtained by a conventional chest band method that has been used in humans and applied to anesthetized, but not behaving, monkeys. These respiration patterns matched well, suggesting that the measurement of nasal air temperature can be used to monitor the respiration of monkeys. Furthermore, we confirmed that the respiration frequency in behaving monkeys monitored by the measurement of nasal air temperature was not affected by the orofacial movement of licking to obtain the liquid reward. We next examined the frequency of respiration when they listened to music or white noise. The respiratory frequency was higher when the monkeys listened to music than the noise. This result is consistent with a phenomenon in humans and indicates the accuracy of our monitoring method. These data suggest that the measurement of nasal air temperature enables us to monitor the respiration of behaving monkeys and thereby estimate their internal states.