Local environment and fragmentation by drought and damming shape different components of native and non-native fish beta diversity across pool refuges.

Pool refuges are critical for maintaining stream fish diversity in increasingly intermittent streams. Yet, the patterns and drivers of beta diversity of native and non-native fish in pool refuges remain poorly known. Focusing on Mediterranean streams, we decomposed beta diversity of native and non-native fish into richness difference (RichDiff) and species replacement (Repl), and local (LCBD, LCBDRichDiff and LCBDRepl) and species (SCBD) contributions. We assessed the influence of environmental and spatial factors associated with drought and damming fragmentations on beta diversity components and LCBDs, and of local species richness and occupancy on LCBDs and SCBD, respectively. Overall, non-native species showed a more limited occupancy of pool refuges than native fish. RichDiff dominated beta diversity, though it was influenced by drought and damming fragmentations for native fish and local environment for non-native fish. Repl for native fish was slightly influenced by local environment, but for non-native fish was largely driven by drought and damming, albeit with a contribution of local environment as well. LCBD and LCBDRichDiff increased in pools in low order streams for native fish and at low elevations for non-native fish, and with high or low species richness. SCBD was higher for native species with intermediated pool occupancy, but for non-native species with low occupancy. Our results suggest that stream fragmentation may drive native species loss and non-native species replacement in pool refuges, and that environmental filtering may shape non-native species loss. Pools in lower order streams harbouring unique species-rich or species-poor assemblages should be prioritize for conservation and restoration, respectively, and pools at low elevation with unique non-native assemblages should deserve control efforts. We encourage the partitioning of beta diversity and individual analysis of native and non-native fish in intermittent streams, which may be key in stressing the importance of pool refuges in safeguarding native fish diversity.

Leveraging large-scale biobank EHRs to enhance pharmacogenetics of cardiometabolic disease medications.

Electronic health records (EHRs) coupled with large-scale biobanks offer great promises to unravel the genetic underpinnings of treatment efficacy. However, medication-induced biomarker trajectories stemming from such records remain poorly studied. Here, we extract clinical and medication prescription data from EHRs and conduct GWAS and rare variant burden tests in the UK Biobank (discovery) and the All of Us program (replication) on ten cardiometabolic drug response outcomes including lipid response to statins, HbA1c response to metformin and blood pressure response to antihypertensives (N = 740-26,669). Our findings at genome-wide significance level recover previously reported pharmacogenetic signals and also include novel associations for lipid response to statins (N = 26,669) near LDLR and ZNF800. Importantly, these associations are treatment-specific and not associated with biomarker progression in medication-naive individuals. Furthermore, we demonstrate that individuals with higher genetically determined low-density and total cholesterol baseline levels experience increased absolute, albeit lower relative biomarker reduction following statin treatment. In summary, we systematically investigated the common and rare pharmacogenetic contribution to cardiometabolic drug response phenotypes in over 50,000 UK Biobank and All of Us participants with EHR and identified clinically relevant genetic predictors for improved personalized treatment strategies.

Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients.

Among the many lysosomal storage disorders (LSDs) that would benefit from the establishment of novel cell models, either patient-derived or genetically engineered, is mucopolysaccharidosis type II (MPS II). Here, we present our results on the establishment and characterization of two MPS II patient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population has been isolated from LSD patient samples obtained from the dental pulp. Taking into account our results on the molecular and biochemical characterization of those cells and the fact that they exhibit visible and measurable disease phenotypes, we consider these cells may qualify as a valuable disease model, which may be useful for both pathophysiological assessments and in vitro screenings. Ultimately, we believe that patient-derived dental pulp stem cells (DPSCs), particularly those isolated from human exfoliated deciduous teeth (SHEDs), may represent a feasible alternative to induced pluripotent stem cells (iPSCs) in many labs with standard cell culture conditions and limited (human and economic) resources.

Advances in Condition Monitoring of Railway Infrastructure.

In recent years, there has been a notable surge in investments directed towards developing new railway lines and revitalising existing ones, reflecting a global commitment to enhance transportation infrastructure [...].

Help Comes from Unexpected Places: How a Tiny Fairy and a Tropical Fish may help us Model Mucopolysaccharidoses.

INTRODUCTION: When it comes to disease modeling, countless models are available for Lysosomal Storage Diseases (LSD). Historically, two major approaches are well-established: in vitro assessments are performed in patient fibroblasts, while in vivo pre-clinical studies are performed in mouse models. Still, both platforms have a series of drawbacks. Thus, we implemented two alternative and innovative protocols to mimic a particular sub-group of LSDs, the Mucopolysaccharidoses both in vitro and in vivo. METHODS: The first one relies on a non-invasive approach using dental pulp stem cells from deciduous teeth (SHEDs). SHEDs are multipotent neuronal precursors that can easily be collected. The second uses a state-of-the-art gene editing technology (CRISPR/Cas9) to generate zebrafish disease models. RESULTS: Even though this is an ongoing project, we have already established and characterized two MPS II and one MPS VI SHED cell models. These cells self-maintain through several passages and can give rise to a variety of cells including neurons. Furthermore, all MPS-associated sub-cellular phenotypes we have assessed so far are easily observable in these cells. Regarding our zebrafish models, we have successfully knocked down both naglu and hgsnat and the first results we got from the behavioral analysis are promising ones, as we can observe altered activity and sleep patterns in the genetically modified fish. For this particular approach we chose MPS III forms as our target disorders, since their neurological features (hyperactivity, seizures and motor impairment) and lifespan decrease would be easily recognizable in zebrafish. CONCLUSION: Now that these methods are well-established in our lab, their potential is immense. On one hand, the newly developed models will be of ultimate value to understand the mechanisms underlying MPS sub-cellular pathology, which have to be further elucidated. On the other hand, they will constitute an optimal platform for drug testing in house. Also noteworthy, our models will be published as lab resources and made available for the whole LSD community.

Pilot Study on Newborn Screening for Spinal Muscular Atrophy.

INTRODUCTION: Newborn screening (NBS) in Portugal is a significant public health measure to provide early detection for specific disorders so that early treatment is possible. Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder that causes degeneration of anterior horn cells in the human spinal cord and subsequent loss of motor neurons. Its incidence is estimated in 1.6000-11.800 live births. A pilot study on 100.000 newborns is being carried out at the neonatal screening laboratory with the aim of determining the specificity, sensitivity, and feasibility of the SMA screening at the NBS laboratory in Portugal. METHODS: The study presented here was based on data obtained from neonatal screening, involving the analysis of 25.000 newborns. SMA screening is performed by a qualitative detection of exon 7 of the SMN1 gene. The assay was performed using a commercially available real-time PCR, the Eonis SMN1, TREC, and KREC kit. RESULTS/CASE REPORT: The dried blood spots of a total of 25.000 newborns were tested; among these newborns, two were diagnosed as having SMA with survival motor neuron 1 (SMN1) deletion. These two SMA-positive samples were sent to a specialized clinical centre and a peripheral blood sample was sent to the reference laboratory for confirmation of the exon 7 deletion and determination of the SMN2 copy number. CONCLUSION: Early diagnosis and intervention are important for SMA treatment to be effective; the treatment should be started at the pre-symptomatic stage of SMA. Thus, newborn screening for SMA is strongly recommended. Currently, targeted therapies for SMA are available, and attempts are being made worldwide to include SMA screening in newborns.

Testing phylogenetic signal with categorical traits and tree uncertainty.

SUMMARY: The phylogenetic signal, frequently used to identify signatures of adaptive evolution or important associations between genes and phenotypes, measures the tendency for recently diverged species to resemble each other more than distantly related species. An example of such a measure is the δ statistic, which uses Shannon entropy to measure the degree of phylogenetic signal between a categorical trait and a phylogeny. In this study, we refined this statistic to account for tree uncertainty, resulting in more accurate assessments of phylogenetic associations. In addition, we provided a more accessible and computationally efficient implementation of the δ statistic that will facilitate its use by the evolutionary community. AVAILABILITY AND IMPLEMENTATION: github.com/diogo-s-ribeiro/delta-statistic.

Accurate rare variant phasing of whole-genome and whole-exome sequencing data in the UK Biobank.

Phasing involves distinguishing the two parentally inherited copies of each chromosome into haplotypes. Here, we introduce SHAPEIT5, a new phasing method that quickly and accurately processes large sequencing datasets and applied it to UK Biobank (UKB) whole-genome and whole-exome sequencing data. We demonstrate that SHAPEIT5 phases rare variants with low switch error rates of below 5% for variants present in just 1 sample out of 100,000. Furthermore, we outline a method for phasing singletons, which, although less precise, constitutes an important step towards future developments. We then demonstrate that the use of UKB as a reference panel improves the accuracy of genotype imputation, which is even more pronounced when phased with SHAPEIT5 compared with other methods. Finally, we screen the UKB data for loss-of-function compound heterozygous events and identify 549 genes where both gene copies are knocked out. These genes complement current knowledge of gene essentiality in the human genome.

Diagnostic outcomes of robotic-assisted bronchoscopy for pulmonary lesions in a real-world multicenter community setting.

BACKGROUND: Robot-assisted bronchoscopy (RAB) is among the newest bronchoscopic technologies, allowing improved visualization and access for small and hard-to-reach nodules. RAB studies have primarily been conducted at academic centers, limiting the generalizability of results to the broader real-world setting, while variability in diagnostic yield definitions has impaired the validity of cross-study comparisons. The objective of this study was to determine the diagnostic yield and sensitivity for malignancy of RAB in patients with pulmonary lesions in a community setting and explore the impact of different definitions on diagnostic yield estimates. METHODS: Data were collected retrospectively from medical records of patients ≥ 21 years who underwent bronchoscopy with the Monarch® Platform (Auris Health, Inc., Redwood City, CA) for biopsy of pulmonary lesions at three US community hospitals between January 2019 and March 2020. Diagnostic yield was calculated at the index RAB and using 12-month follow-up data. At index, all malignant and benign (specific and non-specific) diagnoses were considered diagnostic. After 12 months, benign non-specific cases were considered diagnostic only when follow-up data corroborated the benign result. An alternative definition at index classified benign non-specific results as non-diagnostic, while an alternative 12-month definition categorized index non-diagnostic cases as diagnostic if no malignancy was diagnosed during follow-up. RESULTS: The study included 264 patients. Median lesion size was 19.3 mm, 58.9% were peripherally located, and 30.1% had a bronchus sign. Samples were obtained via Monarch in 99.6% of patients. Pathology led to a malignant diagnosis in 115 patients (43.6%), a benign diagnosis in 110 (41.7%), and 39 (14.8%) non-diagnostic cases. Index diagnostic yield was 85.2% (95% CI: [80.9%, 89.5%]) and the 12-month diagnostic yield was 79.4% (95% CI: [74.4%, 84.3%]). Alternative definitions resulted in diagnostic yield estimates of 58.7% (95% CI: [52.8%, 64.7%]) at index and 89.0% (95% CI: [85.1%, 92.8%]) at 12 months. Sensitivity for malignancy was 79.3% (95% CI: [72.7%, 85.9%]) and cancer prevalence was 58.0% after 12 months. CONCLUSIONS: RAB demonstrated a high diagnostic yield in the largest study to date, despite representing a real-world community population with a relatively low prevalence of cancer. Alternative definitions had a considerable impact on diagnostic yield estimates.

Structural and functional brain correlates of suicidal ideation and behaviors in depression: A scoping review of MRI studies.

Identifying and integrating the neural correlates of suicidal ideation and behaviors is crucial to expand the knowledge and develop targeted strategies to prevent suicide. This review aimed to describe the neural correlates of suicidal ideation, behavior and the transition between them, using different magnetic resonance imaging (MRI) modalities, providing an up-to-date overview of the literature. To be included, the observational, experimental, or quasi-experimental studies must include adult patients currently diagnosed with major depressive disorder and investigate the neural correlates of suicidal ideation, behavior and/or the transition using MRI. The searches were conducted on PubMed, ISI Web of Knowledge and Scopus. Fifty articles were included in this review: 22 on suicidal ideation, 26 on suicide behaviors and two on the transition between them. The qualitative analysis of the included studies suggested alterations in the frontal, limbic and temporal lobes in suicidal ideation associated with deficits in emotional processing and regulation, and in the frontal, limbic, parietal lobes, and basal ganglia in suicide behaviors associated with impairments in decision-making. Gaps in the literature and methodological concerns were identified and might be addressed in future studies.

Effects of Semisupervised Exercise Training on Health Outcomes in People With Lung or Head and Neck Cancer: Protocol for a Randomized Controlled Trial.

BACKGROUND: Lung or head and neck cancers are known for their high prevalence and mortality rates. Chemotherapy and radiotherapy are usually recommended as cancer treatment for these malignancies; however, they can negatively impact both the physical and mental status of patients. Hence, it is reasonable to consider resistance and aerobic exercise training to prevent these negative health outcomes. Further, several factors prevent patients from attending outpatient exercise training programs, and, therefore, a semisupervised home-based exercise training program may be seen as a well-accepted alternative. OBJECTIVE: The aim of this study will be to investigate the effects of a semisupervised home-based exercise training program on physical performance, body composition, and self-reported outcomes; changes in the initial cancer treatment dose prescribed; number of hospitalizations at 3, 6, and 9 months; and 12-month survival in people with primary lung or head and neck cancer. METHODS: Participants will be randomly allocated to the training group (TG) or control group (CG). The TG will undergo semisupervised home-based resistance and aerobic exercise training throughout their cancer treatment. The resistance training will be performed using elastic bands (TheraBand) twice a week. The aerobic training (ie, brisk walk) will be performed for at least 20 minutes per day outdoors. The equipment and tools used during the training sessions will be provided. This intervention will start the week before treatment commencement, will be performed throughout the duration of the treatment, and will continue for 2 weeks after treatment completion. The CG will undergo usual care (ie, cancer treatment with no formal exercise prescription). Assessments will take place 2 weeks before the beginning of the usual cancer treatment and 2 weeks after treatment completion. The measures of physical function (peripheral muscle strength, functional exercise capacity, and physical activity), body composition, and self-reported outcomes (symptoms of anxiety and depression, health-related quality of life, and symptoms related to the disease and treatment) will be collected. We will report on any change in the initial cancer treatment dose prescribed; number of hospitalizations at 3, 6, and 9 months; and 12-month survival. RESULTS: In February 2021, the clinical trial registration was approved. Recruitment and data collection for the trial are ongoing (as of April 2023, 20 participants had already been randomized), and findings of this study are likely to be published late in 2024. CONCLUSIONS: This exercise training as a complementary treatment for patients with cancer is likely to promote positive effects on the health outcomes assessed, over and above any change in the CG, and prevent the reduction of initial cancer treatment dose prescribed. If these positive effects are shown, they will likely impact long-term outcomes such as hospitalizations and 12-month survival. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (ReBEC) RBR-5cyvzh9; https://ensaiosclinicos.gov.br/rg/RBR-5cyvzh9. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/43547.

Multimodal single cell analysis infers widespread enhancer co-activity in a lymphoblastoid cell line.

Non-coding regulatory elements such as enhancers are key in controlling the cell-type specificity and spatio-temporal expression of genes. To drive stable and precise gene transcription robust to genetic variation and environmental stress, genes are often targeted by multiple enhancers with redundant action. However, it is unknown whether enhancers targeting the same gene display simultaneous activity or whether some enhancer combinations are more often co-active than others. Here, we take advantage of recent developments in single cell technology that permit assessing chromatin status (scATAC-seq) and gene expression (scRNA-seq) in the same single cells to correlate gene expression to the activity of multiple enhancers. Measuring activity patterns across 24,844 human lymphoblastoid single cells, we find that the majority of enhancers associated with the same gene display significant correlation in their chromatin profiles. For 6944 expressed genes associated with enhancers, we predict 89,885 significant enhancer-enhancer associations between nearby enhancers. We find that associated enhancers share similar transcription factor binding profiles and that gene essentiality is linked with higher enhancer co-activity. We provide a set of predicted enhancer-enhancer associations based on correlation derived from a single cell line, which can be further investigated for functional relevance.

Genetic variation in cis-regulatory domains suggests cell type-specific regulatory mechanisms in immunity.

Studying the interplay between genetic variation, epigenetic changes, and regulation of gene expression is crucial to understand the modification of cellular states in various conditions, including immune diseases. In this study, we characterize the cell-specificity in three key cells of the human immune system by building cis maps of regulatory regions with coordinated activity (CRDs) from ChIP-seq peaks and methylation data. We find that only 33% of CRD-gene associations are shared between cell types, revealing how similarly located regulatory regions provide cell-specific modulation of gene activity. We emphasize important biological mechanisms, as most of our associations are enriched in cell-specific transcription factor binding sites, blood-traits, and immune disease-associated loci. Notably, we show that CRD-QTLs aid in interpreting GWAS findings and help prioritize variants for testing functional hypotheses within human complex diseases. Additionally, we map trans CRD regulatory associations, and among 207 trans-eQTLs discovered, 46 overlap with the QTLGen Consortium meta-analysis in whole blood, showing that mapping functional regulatory units using population genomics allows discovering important mechanisms in the regulation of gene expression in immune cells. Finally, we constitute a comprehensive resource describing multi-omics changes to gain a greater understanding of cell-type specific regulatory mechanisms of immunity.

An Unsupervised Learning Approach for Wayside Train Wheel Flat Detection.

One of the most common types of wheel damage is flats which can cause high maintenance costs and enhance the probability of failure and damage to the track components. This study aims to compare the performance of four feature extraction methods, namely, auto-regressive (AR), auto-regressive exogenous (ARX), principal component analysis (PCA), and continuous wavelet transform (CWT) capable of automatically distinguishing a defective wheel from a healthy one. The rail acceleration for the passage of freight vehicles is used as a reference measurement to perform this study which comprises four steps: (i) feature extraction from acquired responses using the specific feature extraction methods; (ii) feature normalization based on a latent variable method; (iii) data fusion to enhance the sensitivity to recognize defective wheels; and (iv) damage detection by performing an outlier analysis. The results of this research show that AR and ARX extraction methods are more efficient techniques than CWT and PCA for wheel flat damage detection. Furthermore, in almost every feature, a single sensor on the rail is sufficient to identify a defective wheel. Additionally, AR and ARX methods demonstrated the potential to distinguish a defective wheel on the left and right sides. Lastly, the ARX method demonstrated robustness to detect the wheel flat with accelerometers placed only in the sleepers.

Detection of Wheel Polygonization Based on Wayside Monitoring and Artificial Intelligence.

This research presents an approach based on artificial intelligence techniques for wheel polygonization detection. The proposed methodology is tested with dynamic responses induced on the track by passing a Laagrss-type rail vehicle. The dynamic response is attained considering the application of a train-track interaction model that simulates the passage of the train over a set of accelerometers installed on the rail and sleepers. This study, which considers an unsupervised methodology, aims to compare the performance of two feature extraction techniques, namely the Autoregressive Exogenous (ARX) model and Continuous Wavelets Transform (CWT). The extracted features are then submitted to data normalization considering the Principal Component Analysis (PCA) applied to suppress environmental and operational effects. Next to data normalization, data fusion using Mahalanobis distance is performed to enhance the sensitivity to the recognition of defective wheels. Finally, an outlier analysis is employed to distinguish a healthy wheel from a defective one. Moreover, sensitivity analysis is performed to analyze the influence of the number of sensors and their location on the accuracy of the wheel defect detection system.

Parent-of-Origin inference for biobanks.

Identical genetic variations can have different phenotypic effects depending on their parent of origin. Yet, studies focusing on parent-of-origin effects have been limited in terms of sample size due to the lack of parental genomes or known genealogies. We propose a probabilistic approach to infer the parent-of-origin of individual alleles that does not require parental genomes nor prior knowledge of genealogy. Our model uses Identity-By-Descent sharing with second- and third-degree relatives to assign alleles to parental groups and leverages chromosome X data in males to distinguish maternal from paternal groups. We combine this with robust haplotype inference and haploid imputation to infer the parent-of-origin for 26,393 UK Biobank individuals. We screen 99 phenotypes for parent-of-origin effects and replicate the discoveries of 6 GWAS studies, confirming signals on body mass index, type 2 diabetes, standing height and multiple blood biomarkers, including the known maternal effect at the MEG3/DLK1 locus on platelet phenotypes. We also report a novel maternal effect at the TERT gene on telomere length, thereby providing new insights on the heritability of this phenotype. All our summary statistics are publicly available to help the community to better characterize the molecular mechanisms leading to parent-of-origin effects and their implications for human health.

Audiological biomarkers of tinnitus in an older Portuguese population.

Tinnitus is a phantom sound perceived in the absence of external acoustic stimulation. It is described in a variety of ways (e.g., buzzing, ringing, and roaring) and can be a single sound or a combination of different sounds. Our study evaluated associations between audiological parameters and the presence or severity of tinnitus, to improve tinnitus diagnosis, treatment, and prognosis. Our sample included 122 older participants (63 women and 59 men), aged 55-75 years from the Portuguese population, with or without sensory presbycusis and with or without tinnitus. All participants underwent a clinical evaluation through a structured interview, Ear, Nose, and Throat observation, and audiological evaluation (standard and extended audiometry, psychoacoustic tinnitus evaluation, auditory brainstem responses, and distortion product otoacoustic emissions). The Tinnitus Handicap Inventory was used to measure tinnitus symptom severity. Our data confirmed that the odds of developing tinnitus were significantly higher in the presence of noise exposure and hearing loss. Also, participants who had abrupt tinnitus onset and moderate or severe hyperacusis featured higher odds of at least moderate tinnitus. However, it was in the ABR that we obtained the most exciting and promising results, namely, in wave I, which was the common denominator in all findings. The increase in wave I amplitude is a protective factor to the odds of having tinnitus. Concerning the severity of tinnitus, the logistic regression model showed that for each unit of increase in the mean ratio V/I of ABR, the likelihood of having at least moderate tinnitus was 10% higher. Advancing knowledge concerning potential tinnitus audiological biomarkers can be crucial for the adequate diagnosis and treatment of tinnitus.

Shared regulation and functional relevance of local gene co-expression revealed by single cell analysis.

Most human genes are co-expressed with a nearby gene. Previous studies have revealed this local gene co-expression to be widespread across chromosomes and across dozens of tissues. Yet, so far these studies used bulk RNA-seq, averaging gene expression measurements across millions of cells, thus being unclear if this co-expression stems from transcription events in single cells. Here, we leverage single cell datasets in >85 individuals to identify gene co-expression across cells, unbiased by cell-type heterogeneity and benefiting from the co-occurrence of transcription events in single cells. We discover >3800 co-expressed gene pairs in two human cell types, induced pluripotent stem cells (iPSCs) and lymphoblastoid cell lines (LCLs) and (i) compare single cell to bulk RNA-seq in identifying local gene co-expression, (ii) show that many co-expressed genes - but not the majority - are composed of functionally related genes and (iii) using proteomics data, provide evidence that their co-expression is maintained up to the protein level. Finally, using single cell RNA-sequencing (scRNA-seq) and single cell ATAC-sequencing (scATAC-seq) data for the same single cells, we identify gene-enhancer associations and reveal that >95% of co-expressed gene pairs share regulatory elements. These results elucidate the potential reasons for co-expression in single cell gene regulatory networks and warrant a deeper study of shared regulatory elements, in view of explaining disease comorbidity due to affecting several genes. Our in-depth view of local gene co-expression and regulatory element co-activity advances our understanding of the shared regulatory architecture between genes.

Unicortical Bone Necrosis of the Fibula Free Flap Associated to the Fixation with a Nonlocking 2.0-mm Reconstruction Plate and Screws.

The authors present a unique case of osteonecrosis of a cortical half of a fibula free flap that has not been reported in the literature yet. This complication was associated with the impairment of the vascularization of periosteum in the cortical half of fibula that was fixated with a nonlocking reconstructive 2.0-mm plate and screws but other factors could have been involved. The patient was submitted to excision of a cemento-ossifying fibroma that resulted in a left hemimaxilectomy mesoinfrastructure defect classified as the Cordeiro type 2B. The 42-year-old female patient was submitted to reconstruction with an osteomusculocutaneous fibula free flap plus a segment of fibula graft. The two bone segments of the free flap used to reconstruct the anterior and left alveolar crest were fixated with a reconstructive 2.0-mm plate of matrixMANDIBLE system. The only reported complication was an oronasal fistula that healed with conservative treatment and the referred osteonecrosis of the external cortical half of the fibula free flap with plate exposure at 2.5 years postoperatively. Surgical excision of the osteonecrosed cortical half of the fibula with the plate and screws was performed, while the other cortical underwent bone union as corroborated by computed tomography scans.

Correction: MiR-277/4989 regulate transcriptional landscape during juvenile to adult transition in the parasitic helminth Schistosoma mansoni.

[This corrects the article DOI: 10.1371/journal.pntd.0005559.].