A centroid- and covariance-invariant deterministic mapping of sets of discrete data points to nonlinear models is introduced. Conditions for bijectivity of this mapping are developed. Since the mapping can be accomplished by look-up tables for the special case of equally-spaced data, the resulting mapping algorithm is considered computationally fast. This could be attractive for real-time operations.

Non-steroidal anti-inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti-inflammatory, antipyretic and analgesic effects are applied against symptoms of respiratory infections, including SARS-CoV-2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID-19 also revealed the gaps in our understanding of their mechanism of action, selectivity and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs-exacerbated respiratory disease (NERD). In this context, the consensus report summarises currently available knowledge, novel discoveries and controversies regarding the use of NSAIDs in COVID-19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID-19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarise the major knowledge gaps and unmet needs in current eicosanoid research.

Concern about potential deleterious effects of pharmaceuticals in the environment is growing fast. From wiping out vulture populations in Asia, to feminization of fish, pharmaceuticals have shown to provoke important consequences albeit at very low concentrations. A recent article addresses the environmental impact of metered-dose inhalers for asthma in the United Kingdom due to the greenhouse effects hydrofluorocarbons they contain. Since 2005, it is mandatory for all new drugs in Europe to be assessed for their environmental impact. Crucially, this regulation solely refers to the active pharmaceutical ingredient, not the “whole medicine” or finished medical product. This can sometimes lead to incongruences. For instance, it does not consider the environmental impact of the hydrofluorocarbons contained in MDIs. Another example is Adasuve®, an antipsychotic (loxapine) aimed at the rapid control of agitation in patients suffering from psychotic disorders. The device was developed as a rapid systemic delivery of loxapine by inhalation of a thermally generated aerosol for single use. Apart from the active substance it holds a medical-grade plastic housing and a lithium battery. Therefore, after every single use, a lithium battery waste is produced. We envision that we are on a brink of a new era in pharmacotherapy, in which environmental aspects of drugs are taken into account. In definitive, we agree with Wilkinson & Woodcock. When considering the environmental impact of pharmaceuticals, we need to take into account the whole package.

Chronic liver diseases comprises a broad spectrum of burdensome diseases that still lack effective pharmacological therapies. Our research group focuses on Fibrosis which is a major precursor of liver cirrhosis. Fibrosis consists in a progressive disturbance of liver sinusoidal architecture characterised by connective tissue deposition as a reparative response to tissue injury. Multifactorial events and several types of cells, participate in fibrosis initiation and progression and the process still needs to be completely understood. The development of experimental models of liver fibrosis alongside the identification of critical factors progressing fibrosis to cirrhosis will facilitate the development of more effective therapeutic approaches for such condition. This review provides an overlook of the main process leading to hepatic fibrosis and therapeutic approaches that have emerged from a deep knowledge of the molecular regulation of fibrogenesis in the liver.

Comprehensive clinical and imaging-based surveillance represents a fundamental aspect in the management of thoracic aortic aneurysms (TAAs), affording the opportunity to identify intermediate-sized TAAs before the onset of worrying symptoms or devastating acute aortic dissection/rupture. Currently, size-based indices are favoured as the major determinants driving patient selection for surgery, as supported by aortic guidelines, although it is recognised that smaller sub-threshold TAAs may still confer substantial risks. Prophylactic aortic surgery can be offered within set timeframes at dedicated aortic centres with excellent outcomes, to mitigate the threat of acute aortic complications associated with repeatedly deferred intervention. In this commentary, we discuss a recent article from the Journal of Cardiac Surgery which highlights important socio-economic disparities in TAA surveillance and follow-up.

Although the process of species formation is notoriously idiosyncratic, the observation of pervasive patterns of reproductive isolation across species pairs suggests that generalities, or “rules”, underlie species formation in all animals. Haldane’s rule states that whenever a sex is absent, rare or sterile in a cross between two taxa, that sex is usually the heterogametic sex. Yet, understanding how Haldane’s rule first evolves and whether it is associated to genome wide barriers to gene flow remains a challenging task because this rule is usually studied in highly divergent taxa that no longer hybridize in nature. Here, we address these questions using the meadow grasshopper Pseudochorthippus parallelus where populations that readily hybridize in two natural hybrid zones show hybrid male sterility in laboratorial crosses. Using mitochondrial data, we infer that such populations have diverged some 100,000 years ago, surviving multiple glacial periods in isolated Pleistocenic refugia. Nuclear data shows that secondary contact has led to extensive introgression throughout the species range, including between populations showing hybrid male sterility. We find repeatable patterns of genomic differentiation across the two hybrid zones, yet such patterns are consistent with shared genomic constraints across taxa rather than their role in reproductive isolation. Together, our results suggest that Haldane’s rule can evolve relatively quickly within species, particularly when associated to strong demographic changes. At such early stages of species formation, hybrid male sterility still permits extensive gene flow, allowing future studies to identify genomic regions associated with reproductive barriers.

Cerebrovascular accident (CVA) is one of the commonest neurological deficits. There is a well-known association between COVID-19 and stroke. We present a case series of Sudanese patients who developed CVA after receiving the AstraZeneca COVID-19 vaccine suggesting a relationship between the vaccine and CVA.

Endoscopic features of gastrointestinal amyloidosis can be nonspecific. In our case, it presented as cat scratch colon, which led to a misdiagnosis as collagen colitis.

Anomalies of the appendix are rare, and one of the rarest is the double appendixes. Most anomalies of the appendix are observed in adults and are discovered incidentally during surgery that does not primarily involve the appendix. It is usually missed, often with life-threatening consequences.

Hordeum murinum induced pustular irritant contact dermatitisKey clinical message: Plant induced contact dermatitis is very rare. We describe the case oftwo siblings with Hordeum murinum induced pustular irritant contact dermatitis.Key words: allergology, Hordeum murinum, contact dermatitis, patch test.We describe the cases of two siblings, aged 8 and 10 years, who consulted with multiple yellowish pustules and well-demarcated erythema on the face (Figure 1). The eruption started a few hours after accidental exposure to a plant, named Hordeum murinum , while they were playing in the garden (Figure 2). The mother mentioned that this had been their first exposure to this plant. There were no other lesions either on the skin or on mucosae. Laboratory findings were without abnormalities. There was no bacterial growth in a culture of a pustular specimen. The patients were treated with a short course of topical corticosteroids. A resolution of the skin lesions was achieved within a few days. Five weeks after the resolution of dermatitis, the patients were patch tested with wetted and pounded leaves and petals of H.murinum.1 Readings were performed on the day (D)2, D4, and D7 and showed negative results.1 So, we diagnosed the patients with H. murinum -induced pustular irritant contact dermatitis.

We introduce a new approach—acoustic restoration—focusing on the applied utility of soundscapes for restoration, recognizing the rich ecological and social values they encapsulate. Broadcasting soundscapes in disturbed areas can accelerate recolonization of animals and the microbes and propagules they carry; long duration recordings are also ideal sources of data for benchmarking restoration initiatives and evocative engagement tools.

Negative density dependence (NDD) has been accepted as a key mechanism for biodiversity maintenance in natural forests and different lineages of natural enemies (fungus, bacterium, insect and virus) may be involved. Previous NDD related studies usually correlated seedling survival to the density of host-specific pests or pathogens along the distance to conspecific neighbors, and molecular defense responses of focal seedlings to natural enemies were seldomly concerned. By employing community functional genomics strategy, we extracted copy numbers of homologous genes in defense responses from transcriptomic data of 99 tree species and their inherent impacts on seedling survival were evaluated using partial linear regression analysis and general linear mixed-effects models. The community-level transcriptomic gene copy number of defense responses to fungus, insect and virus showed significant negative correlations with survival rates of the seedling community and the species-level gene copy number of defense response to insect significantly correlated with survival rates of top-twenty common seedling species. Moreover, presence of adult neighbors with distinct defense response to bacterial and viral pathogens survival of focal seedlings as predicted by NDD, while presence of seedling neighbors with similar defense response to insect tended to promote survival of focal seedlings which may be driven by insect-mediated biotic filtering or competitive exclusion. We conclude that both gene copy number and dissimilarities to adult and seedling neighbors in defense response to natural enemies determined seedling survival, indicating the critical contributions of molecular defense responses of plants to species coexistence and diversity maintenance in subtropical forests.

The arboreal marsupial Monito del Monte (genus Dromiciops, with two recognized species) is a paradigmatic mammal. It is the sole living representative of the order Microbiotheria, the ancestor lineage of Australian marsupials. Also, this marsupial is the unique frugivorous mammal in the temperate rainforest, being the main seed disperser of several endemic plants of this ecosystem, thus acting as keystone species. Dromiciops is also one of the few hibernating mammals in South America, spending half of the year in a physiological dormancy where metabolism is reduced to 10% of normal levels. This capacity to reduce energy expenditure in winter contrasts with the enormous energy turnover rate they experience in spring and summer. The unique life-history strategies of this living Microbiotheria, characterized by an alternation of life in the slow and fast lanes, putatively represent ancestral traits that permitted these cold-adapted mammals to survive in this environment. Here we describe the ecological role of this emblematic marsupial, summarizing the ecophysiology of hibernation and sociality, actualized phylogeographic relationships, reproductive cycle, trophic relationships, mutualisms, conservation and threats. This marsupial shows high densities, despite presenting slow reproductive rates, a paradox that is explained by the unique characteristics of its three-dimensional habitat. We finally suggest immediate actions to protect these locally abundant but globally threatened species.

The structuration processes of mixed oleogels produced with candelilla wax (CW, 0 or 3%), fully hydrogenated soybean oil (FH, 5-15%), and microcrystalline cellulose (MC, 0-9%) were studied to define their rheological effects. During the cooling CW crystals performed as nucleation sites for FH. The elastic modulus (G’) of oleogels with FH and 3% CW were more than two orders of magnitude higher than those produced with 0% CW. Adding MC to the oleogels increased slightly the G’. Independently of the amount of MC, oleogels structured with increasing amounts of FH and 0% CW showed the elastic properties scaling of colloidal gels. This behavior was lost by adding 3% CW, implying that in mixed FH-CW oleogels, the CW crystal network dominated the oleogel rheology. The flow point and the mechanical reversibility of oleogels and commercial butter (CB) was also determined. CB showed flow points at 44 and 59% strain and mechanical reversibility values of 29 and 35% of G’ measured in a pre-shear step. Adding MC to oleogels structured with FH and 0% CW increased their flow point (37.2%) near those of CB. This effect was not produced in mixed FH-3% CW oleogels. The mechanical recovery of oleogels produced with FH, MC, and 0% CW tend to decrease as the FH content increased. CW and MC did not show a simple concentration–effect relationship for the mechanical recovery. Nonetheless, oleogels structured with 3% CW and 10% FH and 6-9% MC showed mechanical recovery (~60%) close to that of CB.

Extramedullary multiple myeloma is seen in advanced and aggressive disease and occurs due to plasma cell infiltration of sites other than the bone marrow. Myelomatous ascites or pleural effusion is seen in less than 1 % of cases and can be differentiated from infectious etiologies based on fluid cytology.

Bangladesh recently faced large outbreaks of both COVID-19 and Dengue fever. A 28-year-old woman suffered from symptoms including hemoptysis as first presentation followed by high-grade fever, sore throat, and fatigue. SARS-CoV-2 was confirmed by RT-PCR and also diagnosed dengue later on.COVID-19 and dengue fever could be a harmful combination.

Unusual tumor of the toeKey clinical message: Giant Cell Tumor is a soft-tissue tumor that has a very low potential for malignant change. Involvement of the phalanges of foot is very rare and only a few cases have been reported.Key words: Dermatology, oncology, Giant cell tumor, bone tumors.A 39-year-old woman presented with complaints of pain and swelling of the left second toe for four months. The mass had been slowly increasing in size over the previous 3 years. On examination, there was diffuse swelling of the left second toe with erythematous and shiny overlying skin (Figure 1). The X-ray showed an osteolytic expansive lesion with cortical destruction in the region of the distal phalanx of the second toe. No calcification or periosteal reaction was observed. Magnetic resonance (MR) images showed a mass measuring 1×1.5 cm that was heterogeneously hypo intense on both T1- and T2-weighted MR images. This mass showed a marked, diffuse and heterogeneous enhancement on the contrast T1- weighted image. Surgical excision of the tumor was performed. Histopathological examination confirmed the diagnosis of Giant Cell Tumor (GCT) (Figure 2). The patient’s postoperative course was uneventful, and no recurrence or metastasis was observed. GCTs are soft-tissue tumors that have a very low potential for malignant change. It account for approximately 6% of all bone tumors.1,2 It typically involves the long bones in young adults. 1,2 Involvement of the phalanges of foot is very rare and only a few cases have been reported.1,2

Hybrid zones can provide clear documentation of range shifts in response to climate change and identify loci important to reproductive isolation. Using a deep temporal (36-38 years) comparison of the black-capped (Poecile atricapillus) and Carolina (P. carolinensis) chickadee hybrid zone, we investigated movement of the under-sampled western portion of the zone (western Missouri) as well as investigating whether loci and pathways underpinning reproductive isolation were similar to those from the eastern portion of the hybrid zone. Using 92 birds sampled along the hybrid zone transect in 2016, 68 birds sampled between 1978 and 1980, and 5 additional reference birds sampled from outside the hybrid zone, we generated 11,669 SNPs via ddRADseq. We used these SNPs to interpolate spatially and assess the movement of the hybrid zone interface through time, and to assess variation in introgression among loci. We demonstrate that the interface has moved approximately 5-8 km to the northwest over the last 36-38 years, i.e., at only one-fifth the rate at which the eastern portion of the hybrid zone (e.g. Pennsylvania, Ohio) has moved. Temperature trends across the last 38 years reveal that eastern areas have warmed 50% more than western areas in terms of annual mean temperature, possibly providing an explanation for the slower movement of the hybrid zone in Missouri. Using genomic cline analyses, we detected four genes that showed restricted introgression in both Missouri and Pennsylvania, including Pnoc, a gene involved in metabolism, learning and memory, concordant with previous physiological and behavioral findings on hybrids and the parental species.

Interspecific interactions within biofilms determine relative species abundance, growth dynamics, community resilience, and success or failure of invasion by an extraneous organism. However, deciphering interspecific interactions and assessing their contribution to biofilm properties and function remain a challenge. Here, we describe the constitution of a model biofilm composed of four bacterial species belonging to four different genera (Rhodocyclus sp., Pseudomonas fluorescens, Kocuria varians, and Bacillus cereus), derived from a biofilm isolated from an industrial milk pasteurization unit. We demonstrate that the growth dynamics and equilibrium composition of this biofilm are highly reproducible. Based on its equilibrium composition, we show that the establishment of this 4-species biofilm is highly robust against initial, transient perturbations but less so towards continuous perturbations. By comparing biofilms formed from different numbers and combinations of the constituent species and by fitting a growth model to the experimental data, we reveal a network of dynamic, positive, and negative interactions that determine the final composition of the biofilm. Furthermore, we reveal that the molecular determinant of one negative interaction is the thiocillin I synthesized by the B. cereus strain, and demonstrate its importance for species distribution and its impact on robustness by mutational analysis of the biofilm ecosystem.

Amazonia is characterized by very heterogeneous riverscapes dominated by two drastically divergent water types: black (ion-poor, dissolved organic carbonate rich and acidic) and white (nutrient rich and turbid) waters. Recent phylogeographic and genomic studies have associated the ecotone formed by these environments to ecologically driven speciation in fishes. With the objective of better understanding the evolutionary forces behind the Amazonian Teleostean diversification, we sampled 240 Mesonauta festivus from 12 sites on a wide area of the Amazonian basin. These sites included three confluences of black and white water environments to seek for repeated evidences of ecological speciation at these ecotones. Results obtained through our genetic assessment based on 41,268 SNPs contrast with previous findings and supports a low structuring power of water types. Conversely, we detected a strong pattern of isolation by unidirectional downstream water current and evidence of past events of vicariance potentially linked to the Amazon River formation. Using a combination of population genetic, phylogeographic analysis and environmental association models, we decomposed the spatial variance from the environmental genetic variance specifically to assess which evolutive forces have shaped inter-population differences in M. festivus’ genome. Our sampling design comprising four major Amazonian rivers and three confluences of black and white water rivers supports the possibility that past studies potentially confounded ecological speciation with a site effect unrepresentative of the full Amazonian watershed. While ecological speciation admittedly played a role in Amazonian fish species diversification, we argue that neutral evolutionary processes explain most of the divergence between M. festivus populations.

Functional regulation via conformational dynamics is well known in structured proteins, but less well characterized in intrinsically disordered proteins and their complexes. Using NMR spectroscopy we have identified a dynamic regulatory mechanism in the human insulin-like growth factor (IGF) system involving the central, intrinsically disordered linker domain of human IGF-binding protein-2 ( hIGFBP2). The bioavailability of IGFs is regulated by the proteolysis of IGF-binding proteins. In the case of hIGFBP2, the linker domain (L- hIGFBP2) retains its intrinsic disorder upon binding IGF-1 but its dynamics are significantly altered, both in the IGF binding region and distantly located protease cleavage sites. The increase in flexibility of the linker domain upon IGF-1 binding may explain the IGF-dependent modulation of proteolysis of IGFBP2 in this domain. As IGF homeostasis is important for cell growth and function, and its dysregulation is a key contributor to several cancers, our findings open up new avenues for the design of IGFBP analogs inhibiting IGF-dependent tumors.

Increased surface temperatures (0.7℃ per decade) in the Arctic affects polar ecosystems by reducing the extent and duration of annual snow cover. Monitoring of these important ecosystems needs detailed information on snow cover properties (depth and density) at resolutions (< 100 m) that influence ecological habitats and permafrost thaw. As arctic snow is strongly influenced by vegetation, an ecotype map at 10 m resolution was added to a method with the Random Forest (RF) algorithm previously developed for alpine environments and applied here over an arctic landscape for the first time. The topographic parameters used in the RF algorithm were Topographic Position Index (TPI) and up-wind slope index (Sx), which were estimated from the freely available Arctic DEM at 2 m resolution. Ecotypes with taller vegetation with moister soils were found to have deeper snow because of the trapping effect. Using feature importance with RF, snow depth distributions were predicted from topographic and ecosystem parameters with a root mean square error = 8 cm (23%) (R² = 0.79) at 10 m resolution for an arctic watershed (1 500 km²) in western Nunavut, Canada.

The mRNA COVID-19 vaccine and COVID-19 infection caused by the SARS-CoV-2 virus may be immunologic triggers for the development of thrombotic thrombocytopenic purpura (TTP). There is not yet literature that discusses TTP induced by COVID-19 vaccination or infection in pediatric or adolescent patients. We describe 4 adolescents presenting with TTP (both de novo and relapsed disease) following administration of the Pfizer COVID-19 vaccine or after COVID-19 infection. Our observations demonstrate that the Pfizer-BioNTech mRNA vaccine and COVID-19 infection can act as triggers for the development/relapse of both congenital and acquired TTP.

Bladder exstrophy is a rare and complex malformation. Often associated with diverse deformations, an accurate diagnosis is a must for adequate management. In the African setting, especially in a remote area, delivery rarely occurs within a healthcare structure thus reducing the chance of an early diagnosis.