Genomic profiling of Mycosis Fungoides identifies patients at high risk of disease progression.

Mycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well-established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute's Terra bioinformatics platform. We found that gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), or mutations in JUNB and TET2 are associated with high-risk disease stages. Furthermore, gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), and del6q16.3 (TNFAIP3) are coupled with shorter survival. Del6q16.3 (TNFAIP3) was a risk factor for progression in low-risk patients. By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage.

Does the built environment influence location- and trip-based sedentary behaviors? Evidence from a GPS-based activity space approach of neighborhood effects on older adults.

OBJECTIVE: Evidence on the influence of built environments on sedentary behaviors remains unclear and is often contradictory. The main limitations encompass the use of self-reported proxies of sedentary time (ST), the scarce consideration of the plurality of sedentary behaviors, and environmental exposures limited to the residential neighborhood. We investigated the relationships between GPS-based activity space measures of environmental exposures and accelerometer-based ST measured in total, at the place of residence, at all locations, and during trips. METHODS: This study is part of the CURHA project, based on 471 older adults residing in Luxembourg, who wore a GPS receiver and a tri-axial accelerometer during 7 days. Daily ST was computed in total, at the residence, at all locations and during trips. Environmental exposures included exposure to green spaces, walking, biking, and motorized transportation infrastructures. Associations between environments and ST were examined using linear and negative binomial mixed models, adjusted for demographics, self-rated health, residential self-selection, weather conditions and wear time. RESULTS: Participants accumulated, on average, 8 h and 14 min of ST per day excluding sleep time. ST spent at locations accounted for 83 % of the total ST. ST spent at the residence accounted for 87 % of the location-based ST and 71 % of the total ST. Trip-based ST represents 13 % of total ST, and 4 % remained unclassified. Higher street connectivity was negatively associated with total ST, while the density of parking areas correlated positively with total and location-based ST. Stronger associations were observed for sedentary bouts (uninterrupted ST over 20 and 30 min). CONCLUSION: Improving street connectivity and controlling the construction of new parking, while avoiding the spatial segregation of populations with limited access to public transport, may contribute to limit ST. Such urban planning interventions may be especially efficient in limiting the harmful uninterrupted bouts of ST among older adults.

Does work-related and commuting physical activity predict changes in physical activity and sedentary behavior during the transition to retirement? GPS and accelerometer study.

We examined how GPS and accelerometer measured work-related and commuting physical activity contribute to changes in physical activity and sedentary behavior during the retirement transition in the Finnish Retirement and Aging study (n = 118). Lower work-related activity was associated with a decrease in sedentary time and an increase in light physical activity during retirement. Conversely, higher work-related activity was associated with an increase in sedentary time and a decrease in light physical activity, except among those active workers who also were active commuters. Thus, both work-related and commuting physical activity predict changes in physical activity and sedentary behavior when retiring.

DNA methylation episignature and comparative epigenomic profiling of HNRNPU-related neurodevelopmental disorder.

PURPOSE: HNRNPU haploinsufficiency is associated with developmental and epileptic encephalopathy 54. This neurodevelopmental disorder is characterized by developmental delay, intellectual disability, speech impairment, and early-onset epilepsy. We performed genome-wide DNA methylation (DNAm) analysis in a cohort of individuals to develop a diagnostic biomarker and gain functional insights into the molecular pathophysiology of HNRNPU-related disorder. METHODS: DNAm profiles of individuals carrying pathogenic HNRNPU variants, identified through an international multicenter collaboration, were assessed using Infinium Methylation EPIC arrays. Statistical and functional correlation analyses were performed comparing the HNRNPU cohort with 56 previously reported DNAm episignatures. RESULTS: A robust and reproducible DNAm episignature and global DNAm profile were identified. Correlation analysis identified partial overlap and similarity of the global HNRNPU DNAm profile to several other rare disorders. CONCLUSION: This study demonstrates new evidence of a specific and sensitive DNAm episignature associated with pathogenic heterozygous HNRNPU variants, establishing its utility as a clinical biomarker for the expansion of the EpiSign diagnostic test.

Changes in physical activity by context and residential greenness among recent retirees: Longitudinal GPS and accelerometer study.

This study examined the changes in accelerometer-measured physical activity by GPS-measured contexts among Finnish retirees (n = 45 (537 measurement days)) participating in a physical activity intervention. We also assessed whether residential greenness, measured with Normalized Difference Vegetation Index, moderated the changes. Moderate-to-vigorous physical activity (MVPA) increased at home by 7 min/day, (P < 0.001) and during active travel by 5 min/day (P = 0.03). The participants with the highest vs. lowest greenness had 25 min/day greater increase in MVPA over the follow-up (P for Time*Greenness interaction = 0.04). In conclusion, retirees participating in the intervention increased their MVPA both at home and in active travel, and more so if they lived in a greener area.

Utility of DNA barcoding in native Oreochromis species.

The importance of Oreochromis in worldwide aquaculture and regional fisheries motivates the study of their genetic diversity in their native range. In this article, all mitochondrial cytochrome c oxidase subunit I gene (COI) sequences of Oreochromis species are retrieved from Barcode of Life Data system to quantify the available DNA barcoding information from wild individuals collected within the native ranges of the respective species. It is found that 70% of the known species in the genus still lack a COI barcode, and only 15% of the available sequences are from within the respective native ranges. Many of the available sequences have been produced from specimens acquired from aquaculture and introduced, naturalized populations, making the assessment of variation within the original native range challenging. Analyses of the wild-collected fraction of available sequences indicated the presence of cryptic lineages within Nile tilapia Oreochromis niloticus and O. schwebischi, the occurrence of potential introgressive hybridization between O. niloticus and blue tilapia O. aureus, and potential ancestral polymorphism between Karonga tilapia O. karongae and black tilapia O. placidus. This article also reports a case of misidentification of O. mweruensis as longfin tilapia O. macrochir. These results stress the importance of improving the knowledge of genetic variation within the native ranges of Oreochromis species for better-informed conservation of these natural resources.

How and why use the EasyBreath® surface snorkeling mask as a personal protective equipment during the COVID-19 pandemic?

During the COVID-19 outbreak, personal protective equipment is widely used to limit infection of caregivers. Innovative solutions have been described to overcome supply shortage. The adaptation of the EasyBreath® surface snorkeling mask by the Prakash team has benefited from outstanding media coverage. We present four 3D-printed devices that we have modified from the initial innovative design in order to adapt to local constraints. We tested the mask during surgery. The modifications that we made provide better ergonomics, visibility and communication capacities, but that have no official approval for use and can therefore only be recommended in the absence of a validated alternative solution. 3D printing is a tool of prime importance in the production of devices for medical use in health crisis situations.

COVID-19 and ENT Pediatric otolaryngology during the COVID-19 pandemic. Guidelines of the French Association of Pediatric Otorhinolaryngology (AFOP) and French Society of Otorhinolaryngology (SFORL).

OBJECTIVE: Joint guidelines of the French Pediatric Otolaryngology Society (AFOP) and of the French Society of otorhinolaryngology-head and neck surgery (SFORL) on the management of paediatric otolaryngology patients in the context of the COVID-19 pandemic. METHODS: A nation-wide workgroup drew guidelines based on clinical experience, national and local recommendations and scientific literature. Proposals may have to be updated on a day-to-day basis. RESULTS: In children, incidence of symptomatic COVID-19 (1-5%) is low and of good prognosis. The indications for nasal flexible endoscopy should be drastically limited. If undertaken, full Personal Protective Equipment (PPE) including FFP2 masks are required, as well as use of a sheath. Saline nose wash done by caregivers other than parents at home should require PPE. Unless foreign body tracheobronchial aspiration is clinically obvious, CT-scan should be performed to confirm indication of endoscopy. Surgical indications should be limited to emergencies and to cases that cannot be delayed beyond 2 months (especially endonasal, endopharyngeal laryngo-tracheobronchial procedures). Postponement should ideally be a group decision and recorded as such in the medical file. Surgical techniques should be adapted to limit the risk of viral dissemination in the air, avoiding the use of drills, microdebriders, monopolar cautery or lasers. Continuous suction should be placed near the operating field. In case of confirmed Covid-19 cases, or suspected cases (or in some centres systematically), PPE with FFP2 mask should be worn by all staff members present in the operating room.

Disposable microfluidic micromixers for effective capture of Cryptosporidium parvum oocysts from water samples.

BACKGROUND: Protecting drinking water supplies from pathogens such as Cryptosporidium parvum is a major concern for water utilities worldwide. The sensitivity and specificity of current detection methods are largely determined by the effectiveness of the concentration and separation methods used. The purpose of this study is to develop micromixers able to specifically isolate and concentrate Cryptosporidium, while allowing in situ analysis. RESULTS: In this study, disposable microfluidic micromixers were fabricated to effectively isolate Cryptosporidium parvum oocysts from water samples, while allowing direct observation and enabling quantification of oocysts captured in the device using high quality immunofluorescence microscopy. In parallel, quantitative analysis of the capture yield was carried out by analyzing the waste from the microfluidics outlet with an Imaging Flow Cytometer. At the optimal flow rate, capture efficiencies up to 96% were achieved in spiked samples. CONCLUSIONS: Scaled microfluidic isolation and detection of Cryptosporidium parvum will provide a faster and more efficient detection method for Cryptosporidium compared to other available laboratory-scale technologies.

Severe macroglossia after posterior fossa and craniofacial surgery in children.

Massive swelling of the tongue can occur after posterior fossa and craniofacial surgery. Several hypotheses have been proposed to explain the occurrence of such severe postoperative macroglossia, but this phenomenon is still poorly understood. Severe postoperative macroglossia can be a life-threatening condition due to upper airway obstruction. Three cases of severe postoperative macroglossia that occurred after cervical spine, craniofacial, and posterior fossa surgical procedures are reported here. These cases required specialized maxillofacial management and a prolonged stay in the intensive care unit. Causal factors involved in this condition are reported, in order to highlight appropriate prevention and treatment options adapted to the management of paediatric patients. An overview of the current literature on severe postoperative macroglossia in paediatric populations is also provided.

Putative origins of the fungus Leptographium procerum.

Appropriate management of invasive fungi requires adequate understanding of their global diversities and movement histories. The fungus Leptographium procerum is associated with root-colonizing forest insects in pine forests throughout the world, and may have contributed to the aggressive behaviour of the red turpentine beetle (Dendroctonus valens) in the beetle's invasive range in China. We used microsatellites and mating type loci to investigate the global diversity of L. procerum and the source population of L. procerum associated with D. valens in China. Clustering analyses supported the separation of the fungal data set into three genetically and geographically-distinct clusters: Europe, North America, and China. The fungus had the highest genetic diversity in Europe, followed by North America and China. Analyses using Approximate Bayesian Computation supported Europe as the most likely source of the North American and Chinese populations. Overall, the results suggested that Europe is the global centre of diversity of L. procerum. Furthermore, they suggested that L. procerum most likely arrived in China independently of D. valens and adopted this beetle as a vector after its introduction.

Multiple cryptic species in the blue-spotted maskray (Myliobatoidei: Dasyatidae: Neotrygon spp.): An update.

Previous investigations have uncovered divergent mitochondrial clades within the blue-spotted maskray, previously Neotrygon kuhlii (Müller and Henle). The hypothesis that the blue-spotted maskray may consist of a complex of multiple cryptic species has been proposed, and four species have been recently described or resurrected. To test the multiple cryptic species hypothesis, we investigated the phylogenetic relationships and coalescence patterns of mitochondrial sequences in a sample of 127 new individuals from the Indian Ocean and the Coral Triangle region, sequenced at both the CO1 and cytochrome b loci. The maximum-likelihood (ML) tree of concatenated CO1+cytochrome b gene sequences, rooted by the New Caledonian maskray N. trigonoides, yielded 9 strongly supported, main clades. Puillandre's ABGD algorithm detected gaps in nucleotide distance consistent with the ML phylogeny. The general mixed Yule-coalescent algorithm partitioned the dataset into putative species generally consistent with the ML phylogeny. Nuclear markers generally confirmed that distinct mitochondrial clades correspond to genetically isolated lineages. The nine main lineages identified by ML analysis were geographically distributed in a parapatric fashion, indicating reproductive isolation. The hypothesis of multiple cryptic species is thus validated.

Investigating the origin of vagrant dusky groupers, Epinephelus marginatus (Lowe, 1834), in coastal waters of Réunion Island.

Due to their geographic isolation, biotas of oceanic islands are likely influenced by episodic long distance dispersal events, but such observations are scarce. In June 2012, fishermen from Réunion Island caught an unknown specimen of grouper, identified as dusky grouper Epinephelus marginatus (Lowe, 1834). This was highly unexpected considering the large distance of its closest verified occurrence (South Africa, ∼2500km). To identify the origin of this specimen and the mechanisms driving this potential long distance colonization, we combined genetic analyses and hydrodynamic connectivity modeling approaches. Molecular markers and samples from various locations across the distribution range resulted in the identification of three putative source populations. The Réunion specimen clustered genetically with South Africa. The estimated spawning period in relation to the connectivity modeling of larvae showed no possible direct connection between South Africa and Réunion. However, connectivity was predicted through intermediate stepping stone populations likely located around the southern tip of Madagascar, where the occurrence of the species has yet to be verified. The results further highlight the potential role of the cyclone Bingiza (February 2011) in the connection between Madagascar and Réunion. This shows that cyclones may be an important driver in long distance colonization of oceanic islands.

Shallow-water reef ophiuroids (Echinodermata: Ophiuroidea) of Réunion (Mascarene Islands), with biogeographic considerations.

Despite their importance in marine biodiversity, invertebrates are far less studied than vertebrates. Given the current global biodiversity crisis and insufficient taxonomic resources, sustained efforts need to be undertaken to assess species diversity, especially in the highly threatened 'biodiversity hotspots'. Réunion is a young volcanic island lying in the Mascarene Islands (south-western Indian Ocean, SWIO), a marine biodiversity hotspot. A substantial sampling effort was conducted around Réunion Island to document shallow water reef-associated ophiuroid (brittle-stars) diversity, a class recognised as the most diverse among echinoderms. A total of 33 species were documented, increasing the known species richness of the island by 56%. Findings include 15 new records for Réunion, 11 for the Mascarene Islands and 8 for the Indian Ocean. The most diverse family was Ophiocomidae, a family of large, abundant and conspicuous tropical species. Even in this well studied family, a new species was revealed by this survey. Morphological variants together with DNA sequence variations within several species revealed cryptic species. We compared our results with the known fauna of other Mascarene Islands and discuss biogeographic implications for the region.

How to perform endoscopy in paediatric otorhinolaryngology?

Upper airway endoscopy in children is a high-risk procedure, which should only be performed by a well trained and fully equipped team. The sequence of procedures, at least at the beginning of the procedure, is always the same and must be performed very rigorously. Communication between the various operators, especially the surgeon, the anaesthetist and the operating room nurse, is essential before starting the procedure, as anticipation of sudden difficulties is the key to effective management. The authors report their experience and endoscopy practices.

Late Glacial Demographic Expansion Motivates a Clock Overhaul for Population Genetics.

The molecular clock hypothesis is fundamental in evolutionary biology as by assuming constancy of the molecular rate it provides a timeframe for evolution. However, increasing evidence shows time dependence of inferred molecular rates with inflated values obtained using recent calibrations. As recent demographic calibrations are virtually non-existent in most species, older phylogenetic calibration points (>1 Ma) are commonly used, which overestimate demographic parameters. To obtain more reliable rates of molecular evolution for population studies, I propose the calibration of demographic transition (CDT) method, which uses the timing of climatic changes over the late glacial warming period to calibrate expansions in various species. Simulation approaches and empirical data sets from a diversity of species (from mollusk to humans) confirm that, when compared with other genealogy-based calibration methods, the CDT provides a robust and broadly applicable clock for population genetics. The resulting CDT rates of molecular evolution also confirm rate heterogeneity over time and among taxa. Comparisons of expansion dates with ecological evidence confirm the inaccuracy of phylogenetically derived divergence rates when dating population-level events. The CDT method opens opportunities for addressing issues such as demographic responses to past climate change and the origin of rate heterogeneity related to taxa, genes, time, and genetic information content.