Title pageTitle: Reply to Jasinski M et al.: ´Indeed, there is still room for improvement in long‐term durability of BAV repair´Authors: Tomas Holubec, MD, PhD, Mojyan Safari, MD, Arnaud Van Linden, MD, Anton Moritz, MDInstitutions and Affiliations: Department of Cardiovascular Surgery, University Hospital Frankfurt and Goethe University Frankfurt, Frankfurt, GermanyCorresponding author: Assoc. Prof. Tomas Holubec, MD, PhD, Theodor-Stern-Kai 7, 60596 Frankfurt/Main, Germany, Tel.: +49 69 6301 80094, Email: [email protected]

- The Gerbode type of ventricular septal defect is rare and can be congenital or acquired. - The defect can be closed retrograde or through the transvenous approach. - Short term follow-up suggests that transcatheter closure of the Gerbode type defect is feasible, safe, and effective and should be considered an alternative to surgical repair

Significant dilemma exists regarding management of the aortic root pathology in acute aortic dissections. Several strategies for both repair and replacement exist and there is a lack of clarity on the superiority of one over the other. Important factors that influence management strategies include involvement of the sinuses, competence of the aortic valve, presence of Marfan's syndrome and connective tissue disorders, as well as availability of surgical expertise. The wide variability in these factors makes it unlikely for any one technique to be suitable for management of all aortic roots and the root pathology has to be tailored to an individual patient.

Ventricular septal rupture (VSR) is a rare complication of myocardial infarction that requires surgical repair. Herein we describe a case of intraoperative VSR requiring a second bypass run and patch repair. This case highlights the importance of early reperfusion and poses concern for delayed patient presentation during the COVID-19 pandemic.

Magnesium-based hydrogen storage material (MgH2) has attracted much attention due to its high hydrogen storage density (7.6 wt%). However, the high hydrogen dissociation enthalpy and slow hydrogen dissociation rate in bulk Mg hinder its wide application in the efficient hydrogen storage. In the present work, we study the hydrogen adsorption and desorption reactions of MgmHn (m = 1-6) nanoclusters using density functional theory (DFT). From the global search for the configurations of MgmHn nanoclusters, we found not only stable saturated MgmHn (n = 2m) nanoclusters, but four hydrogen-enriched MgmHn (n:m>2:1) nanoclusters, Mg3H7, Mg4H9, Mg5H11, Mg6H13, with the hydrogen storage density higher than 8.3 wt%. The electronic-structure calculations indicate that the stability of the hydrogen-enriched cluster gets relatively higher for larger nanocluster. The ab initio dynamics simulations shows that all hydrogen-enriched clusters have very fast hydrogen dissociation rates, which is promising for the hydrogen dissociation at ambient temperature and pressure. This work provides insights into the hydrogen storage mechanism of nano-magnesium materials.

Inferior vena cava thrombosis (IVCT) is a rare occurrence and is a result of leg deep vein thrombosis (DVT). The etiology of IVC thrombosis can be divided into congenital versus acquired etiological factors found in Virchow’s triad of stasis, injury, and hypercoagulability. Hyperhomocysteinemia is a rare risk factor for thromboembolism.

In arid area, the liquid water and water vapor states in soil profiles and fluxes at the upper and bottom interfaces are extremely complex due to heterogeneity of soil textures and the driving forces of heat and matrix potential. In this study, we used Hydrus-1D to simultaneously simulate liquid water, water vapor, and heat transports based on the observed data of atmosphere, soil and groundwater at three soil profiles in an arid area of northwest China. Comparison and contrast of the observed and simulated results at the three soil profiles show that there are diurnal vapor entry and outlet fluxes at the dry surface layer (DSL) of 30 cm in the summer season. The vapor entry and re-evaporation account for about 14% of annual precipitation for the heterogeneity soil profile with a mean groundwater depth of 210 cm. Because of limited soil moisture in this arid area, vapor induced re-evaporation occurs shortly in the early daytime. Moreover, the extent of vapor entry, condensation and re-evaporation strong depends on soil properties and water table depths. The lower water table produces the drier soil surface, allowing more vapor entry, condensation and re-evaporation. Whereas the finer grained soil layers benefits the vapor fixation to produce zero fluxes that substantially inhibit the upward liquid water and vapor fluxes, and thereby reduces soil evaporation. The reduced soil evaporation correspondingly decreases the capillary effect on phreatic evaporation, proven by that soil evaporation decreases slowly with decline of water table and the large extinct depth of phreatic evaporation for the finer grained soil profiles. The estimated extinct depth is 180 cm and 200 cm for the soil profiles consisting of silt loam and loamy sand, respectively, much larger than 100 cm of the sandy soil profile. Additionally, as water table is higher and lower than the extinct depth, the models neglecting the vapor - heat function could respectively overestimate and underestimate soil evaporation.

Floods claim a high toll in fatalities and economic impacts. Despite their societal relevance, there is much more to learn about the projected changes in discharge and flooding. Here we force an operational hydrologic model over the state of Iowa with high-resolution convection-permitting climate-model precipitation to evaluate the response of 140 watersheds to climate change. At the end of the century, under the most aggressive scenario in terms of fossil fuel use, we show that the transition from snow to rainfall and a ~30% increase in extreme precipitation rates lead to a doubling of maximum discharge during the spring and extended the flood season into the fall. Total discharge volumes are also expected to increase. Our results suggest that flood projections based on extreme precipitation increases alone substantially underestimate future risk due to the nonlinearity of the hydrologic response explained by long-term soil moisture memory and its feedbacks with precipitation.

Editorial to the special issue “Environmental influences on childhood asthma”Back in 1892, Sir William Osler gave an accurate description of asthma as a disease that is associated with “spasm of the bronchial muscles, inflammation of the smaller bronchioles, bizarre and extraordinary variety of circumstances and cold infections, often running in families (1,2). This is basically a true reflection of our modern understanding of asthma which states that asthma is a complex genetic disorder that involves interactions between genetic and environmental factors.Since the human genetic makeup has not changed significantly in the last couple of decades, there is reason to believe that the overall increase in asthma prevalence (3) can be attributed to the changing environmental conditions of modern life. The role of environment in asthma is not limited to its role in the pathogenesis of the disease. Since it is currently not possible to change the genetic make-up of an individual underlying a complex genetic disorder such as asthma, modification of environmental conditions emerges as a significant tool for its treatment. Therefore, understanding the environmental factors that play an important role in asthma is crucial in understanding the disease pathogenesis as well as modification of factors that modulate the inception and progress of the disease as well as its treatment.Various studies published in the last years in the journal and included in this virtual issue have addressed these questions. Garcia-Serna et al. have found out that gestational exposure to traffic-related air pollutants (TRAP) may increase the pro-inflammatory and Th2-related cytokines in newborns which might influence immune system responses later in life (4). Similarly, Pesce et al. (5) have investigated the association between prenatal exposures to heavy metals and atopic diseases. The serum concentrations of lead, cadmium and manganese were assessed in maternal blood samples collected during pregnancy and in cord blood of 651 mother-children pairs. The authors have concluded that the levels of cadmium in cord blood were associated with greater risk of asthma at the age of 8. Baek et al. have documented that exposure to phthalates are associated with airway dysfunction in childhood and this effect was partially attributable to increased serum periostin levels (6). Regarding the association between the genes and environment, Theodorou et al. (7) have investigated the role of mitogen-activated protein kinase (MAPK) pathway in 232 children who were selected from two cross-sectional cohorts and one birth cohort study. They have isolated peripheral blood mononuclear cells (PBMC) from children with asthma along with healthy controls and stimulated them with farm-dust extracts or lipopolysaccharide. The results have shown that the children with asthma have expressed significantly less dual-specificity phosphatase-1 (DUSP1) which is the negative regulator of MAPK pathway. They have conclusively indicated the possible role of DUSP1 for future therapeutical interventions regarding the anti-inflammatory features of farming environments.In an effort to further elucidate the environmental factors that are central to our understanding of asthma, the journal has started a review series to provide a comprehensive picture on the role of environment on various aspect of asthma. Major subheadings includedBiodiversityUrban exposuresGene-environment interactionsFarm effectAir pollutionClimate changeAllergensDiet microbiome and obesityIn the virtual issue of the journal Tari Haahtela (8) has focused on the effect of biodiversity. Evidence supports that the immunomodulating roles of different micro-organisms may be protective for asthma and allergic diseases. The studies from the neighboring Finnish and Russian Karelia regions, which the author named as “the living laboratory”, have shown strong evidence for the central role of environment and lifestyle which modify the human microbiome, immune balance, and thus allergy and asthma risk. Diversity of the human microbiome as well as the diversity of the natural environment that we live in and more contact with the nature are important determinants of physical health.Grant et al. (9) have focused on the influence of urban exposures on childhood asthma. The authors have meticulously summarized and analyzed the results of previous studies which aimed to investigate the interaction between indoor allergens, microbes, indoor and outdoor pollutants, social determinants and childhood asthma along with the opportunities for intervention. Multiple environmental exposures and influences contribute to the increased incidence of asthma and excess asthma morbidity among children with asthma living in urban communities. Indoor pest allergen and mold exposures have been repeatedly linked to increased asthma diagnosis, symptoms, and exacerbations in urban children. However, studies in high-risk urban populations also found that early life pest allergen exposure, along with microbial and endotoxin exposure may be associated with a decreased risk of wheezing and asthma suggesting that the association is more complex than previously thought.Since asthma prevalence varies widely depending on the socio-economical level, changes to help reduce inequities and inequalities in social determinants of health such as poverty, housing disrepair, higher rates of obesity, and chronic stress may produce positive effects at the population-level.Hernandez-Pacheco et al (10) have reviewed the latest gene-environment interaction (GxE) studies in childhood asthma. They have summarized the role of various environmental exposures and the current state of knowledge on asthma genetics. The field of GxE in asthma has drastically evolved together with technological advances over the last years. However, despite reports on the effect of numerous environmental factors on childhood asthma, the availability of detailed and diverse exposure data is limited. Tobacco smoke remains to be the most accessible and extensively explored factor followed by traffic-related air pollution in GxE studies.Airway epithelium seems to be central in gene-environment interactions. The effect of the exposure to certain environmental factors early in life on the modification of the risk and severity of asthma later in childhood is partially dependent on the functionality and integrity of the airway epithelium. It is known that the environmental exposures can trigger an inflammatory response and the disruption of the barrier and mucociliary function.Although there are several methodological and conceptual challenges with GxE interaction studies, recent data have led to new insights into childhood asthma pathophysiology which is best exemplified by the 17q12-21 asthma locus. Some of the SNPs at this locus seem to be associated with the onset of childhood asthma, thereby highlighting the importance of age related factors in gene environment interactions.The need for longitudinal and functional studies which provide insights into the biological mechanisms underlying the observed associations between environmental exposures and epigenetic changes that modify the asthma risk is highlighted.Another extensively studied environmental factor that is associated with childhood as is the so called “farm effect”. Frei et al. (11) have summarized the current knowledge on how “farm effect” influences the immune homeostasis during the intrauterine period and in childhood with a focus on immune mechanisms induced by environmental microbial diversity and microbial components. Farming lifestyle factors including nutrition influence the immune homeostasis either by regulating the innate immune system or by induction of regulatory T cells or TH1. We see diversity as a significant factor also in the farm effect. Diversity of environmental microbes, the diversity of the gut microbiome, or the diversity of the nutrition emerge as significant factors.Paciencia et al. (12) investigated the association and mechanisms between air pollution and asthma in children along with the precautions that should be taken to reduce the burden of air pollution on asthma. Environmental conditions are not shared equally across the populations, regions, and settings where people live, work, and spend their time. Urban conditions and air quality are not only important features for national and local authorities to shape healthy cities and protect their citizens from environmental and health risks, but they also provide opportunities to mitigate inequalities in the most deprived areas where the environmental burden is highest. Actions to avoid exposure to indoor and outdoor air pollutants should be complementary at different levels –individual, local, and national levels – to take strong measures to protect children.Taken together, these reviews provide a very comprehensive coverage on the role of environmental factors on childhood asthma and suggest that efforts to modify these factors may have beneficial effects not only on the individual level but also at the population level.S. Tolga Yavuz1Ömer Kalayci2Philippe A. Eigenmann3

Large eddy simulation (LES) is used to simulate flame acceleration (FA) and deflagration to detonation transition (DDT) of methane–air mixtures in a small-scale 3D channel. The simulation results show that, in the early stages, the flame velocity increases exponentially because of the expansion of combustion products and the wrinkle of flame surface. In the next stage, the interaction between flame and pressure wave makes flame accelerate continuously, and the acceleration rate of the flame velocity decreases first and then increases. As the pressure of the leading shock increases, the boundary layer is heated by the preheating area in front of the flame surface which causes the ultrafast flame propagates in the boundary layer. The ultrafast flame generates oblique shock waves continuously moving to the center of the channel and colliding with each other, which promote the occurrence of local explosion and the coupling of flame surface and leading shock wave.

Mucormycosis affects most commonly immunocompromised patients. We report two cases: a 61-year old female with diabetes whose the upper gastrointestinal endoscopy showed a budding greyish process which corresponded with an invasive mycormucosis in histology and a 59-year old man who presented with worsening of general state. No patients survived.

Cone-beam computed tomography and clinical examinations including pulp vital testing and pocket probing depth showed a cemental tear with a severe labial alveolar bony defect, but no endodontic lesions in #25, which had a sinus tract at the labial site, in a 75-year-old woman.

We present a 15-year-old female with syndromic intellectual disability whose exome reanalysis identified paternal pathogenic BRCA1 and BRCA2 variants. We highlight the significant challenges posed by this finding in genetic counseling and cancer risk management of an adolescent with nonverbal intellectual disability.

Conducting large-scale phylogeographic studies to understand processes affecting population structure and genetic diversity across multiple species is difficult because the key genetic (NCBI) and spatial (GBIF) repositories are disconnected. In this issue of Molecular Ecology Resources, Pelletier et al. (2022) demonstrate the power of connecting these in the program phylogatR. This program assembled 87,852 species and 102,268 sequence alignments in a taxonomic hierarchy, yielding multiple sequence alignments per species, mainly for animals (88%), composed mostly of mtDNA data. The authors discuss several caveats with these alignments and provide flags identifying particular problems associating locality and genetic data with certain taxa (e.g., multiple localities per individuals). They provide a test that nucleotide diversity should increase with area, but find a significant relationship in only 32% of taxa with no clear taxonomic or ecological factors accounting for this. To examine the potential of this program, I tested the idea that the degree of population expansion should increase with latitude given potential environmental stability in the tropics and instability in temperate regions. In under two hours, I downloaded all squamates (lizards and snakes) and regressed Tajima’s D on latitude and found a weak but significant negative relationship, indicating a potential association between latitude and population expansion. The phylogatR database is a powerful resource for researchers wanting to test the relationship between genetic diversity and some aspect of space or environment.

Vegetation restoration in ecologically fragile areas has a significant carbon sequestration effect, and the driving factors affecting it are complex. In particular, it is usually difficult to achieve quantitative assessment at the regional scale for this part of human activity intervention in the ecological environment. The Chinese government’s ex-situ poverty alleviation and relocation project has relocated approximately 10 million people from areas with a fragile ecological environment to urban centralized resettlement, which is a typical case of weakened environmental intervention by human activities. Guizhou Province, an ecologically fragile region in southwest China, was selected as the study area, with a relocated population of 1.92 million, accounting for approximately 20% of the total relocated population in China. The carbon sequestration (CS) model of vegetation photosynthesis and spatial analysis of geographic information were used to quantify the contribution of human activities to the natural restoration of vegetation carbon sequestration at the regional scale caused by the weakening of environmental interventions, based on the data of net primary productivity (NPP) of vegetation from 2000 to 2020. The results show that the implementation of the ex-situ poverty alleviation and relocation project acts as an external force to drive vegetation restoration and carbon sequestration, which increases the slope of the carbon density change trend (from k=30.9 to k=57.41), resulting in an overall carbon density increase of 26.51 tCkm -2. The results of the regional spatial analysis showed that the correlation coefficients between carbon density and relocation intensity in the 5-year and 10-year change intervals before and after relocation were r=0.976 (p<0.01) and r=0.949 (p<0.05), respectively, indicating a significant positive correlation between vegetation carbon sequestration and relocation intensity. Based on this, the carbon sequestration contribution of vegetation in 84 counties (districts) in Guizhou Province that implemented ex-situ poverty alleviation and relocation projects was calculated, showing that 79 counties (districts) contributed positively, accounting for 94%. The average contribution of carbon sequestration by vegetation restoration in each county (district) was 0.0556 Tg, and the CO 2 emissions during the emission reduction period were 0.2059 Tg. The other five counties (districts) with a negative contribution to carbon sequestration were distributed in regions with relatively stable ecosystems and mature forests. This shows that human intervention in the environment changes significantly in fragile ecological areas.

Tracer-aided studies to understand source water partitioning in tropical ecosystems are limited. Here we report dry season source water partitioning in five unique ecosystems distributed across Costa Rica in altitudinal (<150-3,400 m asl) and latitudinal (Caribbean and Pacific slopes) gradients: evergreen and seasonal rainforests, cloud forest, Páramo, and dry forest. Soil and plant samples were collected during the dry season (2021). Plant and soil water extractions (triplicates) were conducted using controlled centrifugation. Stem water extraction efficiency and stem water content were calculated via gravimetric measurements. Water source contributions were estimated using a Bayesian mixing model. Isotope ratios in soil and stems exhibited a strong meteoric origin. Enrichment trends were detected mainly in stems and cactus samples within the dry forest ecosystem. Soil profiles revealed nearly uniform isotopic profiles; however, a depletion trend was observed in the Páramo ecosystem below 25 cm depth. More enriched compositions were reported in cactus samples for extracted water volumes above ~20% ( Adj. r2=0.34, p<0.01). The most prominent dry season water source in the evergreen rainforest (74.0%), seasonal rainforest (86.4%), and cloud forest (66.0%) corresponded with soil water. In the Páramo ecosystem, recent rainfall produced by trade wind incursions resulted in the most significant water source (61.9%), whereas in the dry forest, mean annual precipitation (38.6%) and baseflow (33.1%) were the dominant sources. The latter highlights the prevalence of distinct water uptake sources between recent cold front’s rainfall to more well-mixed soil moisture during the dry season.

Background A core outcome set could address inconsistent outcome reporting and improve evidence for stillbirth care research, which has been identified as an important research priority. Objectives To identify outcomes and outcome measurement instruments reported by studies evaluating interventions after the diagnosis of a stillbirth. Search strategy Amed, BNI, CINAHL, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, MEDLINE, PsycINFO, and WHO ICTRP from 1998 to August 2021. Selection criteria Randomised and non-randomised comparative or non-comparative studies reporting a stillbirth care intervention. Data collection and analysis Interventions, outcomes reported, definitions and outcome measurement tools were extracted. Main results 40 randomised and 200 non-randomised studies were included. 58 different interventions were reported, labour and birth care (52 studies), hospital bereavement care (28 studies), clinical investigations (116 studies), care in a multiple pregnancy (2 studies), psychosocial support (28 studies) and care in a subsequent pregnancy (14 studies). 391 unique outcomes were reported and organised into 14 outcome domains: labour and birth; postpartum; delivery of care; investigations; multiple pregnancy; mental health; emotional functioning; grief and bereavement; social functioning; relationship; whole person; subsequent pregnancy; subsequent children and siblings and economic. 242 outcome measurement instruments were used, with 0-22 tools per outcome. Conclusions Heterogeneity in outcome reporting, outcome definition and measurement tools in care after stillbirth exists. Considerable research gaps on specific intervention types in stillbirth care were identified. A core outcome set is needed to standardise outcome collection and reporting for stillbirth care research.

The Darboux theorem, one of the fundamental results in analysis, states that the derivative of a real (not necessarily continuously) differentiable function defined on a compact interval has the intermediate value property, i.e. attains each value between the derivatives at the endpoints. The Bolzano intermediate value theorem, which implies Darboux’s theorem when the derivative is continuous, states that a continuous real-valued function $f$ defined on $[-1,1]$ satisfying $f(-1)<0$ and $f(1)>0$ 0, has a zero, i.e. $f(x) = 0$ for at least one number $-1