Respiratory syncytial virus (RSV) infection is the leading cause of bronchiolitis among infants <12 months old. It is widely known that coinfections between RSV and other viruses can worsen the clinical picture of affected patients. To evaluate the severity of clinical pictures of bronchiolitis in the 2019-2020 winter season, we performed a retrospective study of our third-level Pediatric Emergency Department (ED) admission charts. From February 2 to March 9, 2020 (start date of the Italian lockdown), we observed a peak of patients with a clinical picture of bronchiolitis requiring oxygen therapy of 55.1%, compared with 18% and 14.5% during the same period in 2017-2018 and 2018-2019, respectively (p<0.0001), without other clinically significant differences between the groups. Several authors hypothesized that SARS-CoV2 was present in northern Italy some weeks be-fore the first confirmed case. We suggest that one of the causes of this unexpected severe bronchiolitis peak may be a SARS-CoV2 - RSV coinfection in a period when SARS-CoV2 was already circulating in north-ern Italy. Given the lack of real-time polymerase chain reaction (RT-PCR) tests for SARS-CoV2 at that time, our suggestion remains a hypothesis.

Objective: To study the profile of patients with obstructive sleep apnea syndrome (OSAS) and laryngopharyngeal reflux (LPR) at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH) and to compare their reflux findings with LPR patients without OSAS. Design: Prospective controlled study. Methods: Patients with LPR and OSAS were prospectively recruited from Augustus 2019 to June 2020. The profile of hypopharyngeal reflux events (HRE) of patients was studied through a breakdown of the HEMII-pH findings over the 24-hour of testing. Reflux symptom score (RSS), gastrointestinal and HEMII-pH outcomes were compared between LPR patients and patients with LPR and OSAS. Multivariate analysis was used to study the relationship between reflux data and the following sleep outcomes: Apnea-Hypopnea Index, Epworth Slippiness Scale (ESS) and paradoxical sleep data. Results: A total of 89 patients completed the study. There were 45 patients with LPR and 44 subjects with both OSAS and LPR. The numbers of upright and daytime HREs and the otolaryngological RSS were significantly higher in patients with LPR compared with those with OSAS and LPR. There was a significant positive association between RSS quality of life score and ESS (p=0.001). The occurrence of HREs in the evening was associated with higher ESS (p=0.015). Patients with OSAS, LPR and GERD had higher number of nocturnal HREs compared with those without GERD (p=0.001). Conclusion: The presence of OSAS in LPR patients is associated with less severe HEMII-pH and ear, nose and throat symptoms. There may have different OSAS patient profiles according to the occurrence of GERD.

In spring of 2012, we studied the feeding habits of snow leopard using a comprehensive approach that combines fecal genetic sampling, macro and microscopic analysis of snow leopard diets and direct observation of Naur and livestock in Kangchenjunga Conservation Area of east Nepal. Out of collected 88 putative snow leopard scat samples from 140 transects (290 km) in 27 (4*4 km2) sampling grid cells, 83% were confirmed to be from snow leopard. The genetic analysis accounted for 19 individual snow leopards (10 male and 9 female) with a mean population size estimate of 24 (95% CI: 19- 29), and an average density of 3.9 snow leopards/100 km2 within 609 km2. Total available prey biomass of Naur and Yak was estimated at 355,236 kg (505 kg yak/km2 and 78 kg Naur/km2). From the available prey biomass, we estimated snow leopards consumed 7% annually which was comprised of wild prey (49%), domestic livestock (45%), and 6% unidentified items. The estimated 47,736 kg Naur biomass gives a snow leopard-Naur ratio of 1: 59 on a weight basis. The proportion of young Naur was estimated at 17%, with an almost double predation rate at 28%. Predators such as common leopard and wolf share the same habitat and might compete with snow leopard for prey which will likely influence future predator-prey associations in KCA. Along with livestock insurance scheme improvement, there needs to be a focus on improved livestock guarding as well as engaging and educating local people to be citizen scientists on the importance of snow leopard conservation, involving them in long-term monitoring programs and promotion of ecotourism.

The mycorrhizal symbiosis is ubiquitous in boreal forests. Trees and plants provide their fungal partners with photosynthetic carbon in exchange for soil nutrients like nitrogen, which is critical to the growth and survival of the plants. But plant carbon allocation to mycorrhizal symbionts can also fuel nitrogen immobilization, hampering tree growth. Here we present results from field and greenhouse experiments combined with mathematical modelling, showing that mycorrhizal fungi can be simultaneously mutualistic to an individual tree and parasitic to the networked community of trees. Mycorrhizal networks connect multiple plants and fungi, and we show that each tree gains additional nitrogen at the expense of its neighbors by supplying more carbon to the fungi. But this additional carbon supply eventually aggravates nitrogen immobilization in the shared fungal biomass. Individual trees may thus independently benefit from increasing their carbon investment to mycorrhiza, while causing a decline in nitrogen availability for the whole plant community. We illustrate the evolutionary underpinnings of this situation by drawing on the analogous the tragedy of the commons, and explain how rising atmospheric CO2 may lead to greater nitrogen immobilization in the future.

While 1992 marked the first major dam – Manwan – on the main stem of the Mekong River, the post-2010 era has seen the construction and operationalisation of mega dams such as Xiaowan (started operations in 2010) and Nuozhadu (started operations in 2014) that were much larger than any dams built before. The scale of these projects implies that their operations will likely have significant ecological and hydrological impacts from the Upper Mekong Basin to the Vietnamese Delta and beyond. Historical water level and water discharge data from 1960 to 2020 were analysed to examine the changes to streamflow conditions across three time periods: 1960-1991 (pre-dam), 1992-2009 (growth) and 2010-2020 (mega-dam). At Chiang Saen, the nearest station to the China border, monthly water discharge in the mega-dam period has increased by up to 98% during the dry season and decreased up as much as -35% during the wet season when compared to pre-dam records. Similarly, monthly water levels also rose by up to +1.16m during the dry season and dropped by up to -1.55m during the wet season. This pattern of hydrological alterations is observed further downstream to at least Stung Treng (Cambodia) in our study, showing that Mekong streamflow characteristics have shifted substantially in the post-2010 era. In light of such changes, the 2019-2020 drought – the most severe one in the recent history in the Lower Mekong Basin – was a consequent of constructed dams reducing the amount of water during the wet season. This reduction of water was exacerbated by the decreased monsoon precipitation in 2019. Concurrently, the untimely operationalisation of the newly opened Xayaburi dam in Laos coincided with the peak of the 2019-2020 drought and could have aggravated the dry conditions downstream. Thus, the mega-dam era (post-2010) may signal the start of a new normal of wet-season droughts.

1. Phyllostomid bats exhibit great diversity in skull size and morphology that reflects the degree of resource division and ecological overlap in the group. In particular, Stenodermatinae has high morphological diversification associated with cranial and mandibular traits that is associated with the ability to consume the full range of available fruits (soft and hard). In terms of morphology, performance (bite force) appears to play an important role in niche partitioning among bat species, however, very few studies have confirmed these relationships using functional cranial traits. 2. Here, we analyzed craniodental traits and their relationship to the bite force in 308 specimens distributed in seven species of stenodermatine bats with two foraging types: nomadic and sedentary frugivorous bats. We evaluated 19 functional traits of the skull and jaw related to feeding and bite force in live animals by correcting bite force with body size. We used a GLM model and post hoc tests to determine possible relationships and differences between cranial traits, species, and sex. 3. The results showed that there is significant interspecific variation between stenodermatines that are nomadic and sedentary. The greatest variation in bite force within species was explained by the mandibular toothrow length (MANDL) between sexes, which was greater in females. The larger species of Artibeus, together with Platyrrhinus helleri, Uroderma convexum and Sturnira giannae, which have a greater length of the skull, condylo-incisor, condylo-canine, mandibular toothrow and height of the coronoid, exhibit greater bite force. By contrast, the smaller species A. anderseni and A. phaeotis have short skulls and the lowest values of bite force, which suggests that the size of the skull confers a biomechanical advantage. 4. Our results highlight the usefulness of analyzing functional traits related to feeding to establish the performance of bats in terms of the bite force.

Stretchable gas barrier films achieved by hydrogen-bond self-assembly of nano-brick multilayers

Product formulations for industrial processes are typically developed at lab-scale. However, the mixing conditions are not easily mimicked in the lab. A rotational device is proposed in this work as a fast lab-scale formulation development, which enables mimicking the mixing conditions in the industrial process. The geometrical configurations of the rotational device are from rheometry devices (plate-plate and cone-plate). The main advantages of this method are the small amounts of raw materials, and shorter testing times. This methodology is applied to an industrial case study, the Reaction Injection Moulding (RIM) process. The mixing length scales evolution in the rotational rheometer were matched to those in RIM machines. The main novelty of this work is the introduction of a protocol that bridges the processing conditions at lab using small amounts of raw materials to high throughput continuous flow reactors.

A rare case of mixed total anomalous pulmonary venous connection (TAPVC) associated to right extra-lobar bronchopulmonary sequestration (BPS) was diagnosed at birth in a full-term newborn. At one month of age, the patient underwent embolization of the BPS, complicated by coil entrapment in the right common iliac artery requiring urgent laparotomy. Few days later, the congenital cardiac repair was accomplished uneventfully. At 12-months follow-up, the patient did not have pulmonary hypertension, but presented a moderate stenosis of the right femoral artery, which was effectively treated with anticoagulation therapy.

Odd chain fatty acids (C15:0 and C17:0) from dairy fat as well as odd chain phenolic lipids (alkylresorcinols) from whole grain are commonly reviewed as candidate biomarkers for dietary analysis and their ingestion are inversely related to chronic disease risks. Therefore, low levels of dietary intake of these odd chain molecules may be related to higher risk of physiological states that cause chronic diseases or mortality. It is a prerequisite to examine and understand their main role in beneficial health effects in disease prevention. We propose odd chain fatty acids (OC-FA) and most importantly odd chain phenolic lipids (OC-PL) as potential essential dietary compounds since they play key roles in physiological mechanisms. This review evaluates potential roles of OC-FA and OC-PL in mitigating chronic diseases in vitro and in vivo studies to support our hypothesis for odd chain molecules as essential dietary lipids. Further studies are needed to investigate the relationship between reduced intake of OC-FA and OC-PL containing foods and susceptibilities to chronic diseases.

White-nose syndrome (WNS) has decimated hibernating bat populations across eastern and central North America for over a decade. Disease severity is driven by the interaction between bat characteristics, the cold-loving fungal agent, and the hibernation environment. While we further improve hibernation energetics models, we have yet to examine how spatial heterogeneity in host traits is linked to survival in this disease system. Here we develop predictive spatial models of body mass for the little brown myotis (Myotis lucifugus) and reassess previous definitions of the duration of hibernation of this species. Using data from published literature, public databases, local experts, and our own fieldwork, we fit a series of generalized linear models with hypothesized abiotic drivers to create distribution-wide predictions of pre-hibernation body fat and hibernation duration. Our results provide improved estimations of hibernation duration and identify a scaling relationship between body mass and body fat; this relationship allows for the first continuous estimates of pre-hibernation body mass and fat across the species’ distribution. We used these results to inform a hibernation energetic model to create spatially-varying fat use estimates for M. lucifugus. These results predict that WNS mortality of newly and soon-to-be infected M. lucifugus populations in western North America may be comparable to the substantial die-off observed in eastern and central populations.

Title PageManuscript TitleComment on: “A newborn with a large NTRK fusion positive infantile fibrosarcoma successfully treated with larotrectinib”Authors:Alana Slomovic, M.D., Pediatric Resident, Department of Pediatrics, Cohen Children’s Medical CenterTerry Amaral, M.D., Associate Chief - Division of Orthopedic Surgery, Long Island Jewish Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellIgor Lobko, M.D., Chief – Division of Vascular/ Interventional Radiology, Long Island Jewish Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellDavid Siegel, M.D., Executive Vice Chairman – Department of Radiology, Long Island Jewish Medical Center, Associate Professor, Zucker School of Medicine at Hofstra/ NorthwellRachelle Goldfisher, M.D., Division of Pediatric Radiology, Department of Pediatrics, Cohen Children’s Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellRachel Kessel, M.D., Division of Pediatric Hematology/Oncology, Department of Pediatrics, Cohen Children’s Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellCarolyn Fein Levy, M.D., Division of Pediatric Hematology/Oncology, Department of Pediatrics, Cohen Children’s Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellCorresponding Author: Carolyn Fein Levy, M.D.269-01 76th Avenue, Suite 255New Hyde Park, NY 11040Phone: (718) 470 3460Fax: (718) 343 4642  email: [email protected] text word count: 564 wordsNumber of figures: 1Short running title: Infantile fibrosarcoma treated with larotrectinibKey Words: Infantile fibrosarcoma, Larotrectinib, NTRK fusionAbbreviations Key:

Catalytic efficiency and thermostability are the two most important characteristics of enzymes. However, it is always tough to improve both catalytic efficiency and thermostability of enzymes simultaneously. In the present study, a computational strategy with double-screening steps was proposed to simultaneously improve both catalysis efficiency and thermostability of enzymes; and a fungal α-L-rhamnosidase was used to validate the strategy. As the result, by molecular docking and sequence alignment analysis within the binding pocket, seven mutant candidates were predicted with better catalytic efficiency. By energy variety analysis, three among the seven mutant candidates were predict with better thermostability. The expression and characterization results showed the mutant D525N had significant improvements in both enzyme activity and thermostability. Molecular dynamics simulations indicated that the mutations located within the 5 Å range of the catalytic domain, which could improve RMSD, electrostatic, Van der Waal interaction and polar salvation values, and formed water bridge between the substrate and the enzyme. The study indicated that the computational strategy based on the binding energy, conservation degree and mutation energy analyses was effective to develop enzymes with better catalysis and thermostability, providing practical approach for developing industrial enzymes.

Beneficial mutations can become costly following an environmental change. Compensatory mutations can relieve these costs, while not affecting the selected function, so that the benefits are retained if the environment shifts back to be similar to the one in which the beneficial mutation was originally selected. Compensatory mutations have been extensively studied in the context of antibiotic resistance, responses to specific genetic perturbations and in the determination of interacting gene network components. Few studies have focused on the role of compensatory mutations during more general adaptation, especially as the result of selection in fluctuating environments where adaptations to different environment components may often involve tradeoffs. We examine if costs of a mutation in lacI, which deregulated expression of the lac operon in evolving populations of Escherichia coli bacteria, was compensated. This mutation occurred in multiple replicate populations selected in environments that fluctuated between growth on lactose, where the mutation was beneficial, and on glucose, where it was deleterious. We found that compensation for the cost of the lacI mutation was rare, but, when it did occur, it did not negatively affect the selected benefit. Compensation was not more likely to occur in a particular evolution environment. Compensation has the potential to remove pleiotropic costs of adaptation, but its rarity indicates that the circumstances to bring about the phenomenon may be peculiar to each individual or impeded by other selected mutations.

Snake bite is a common and very important issue threatening health worldwide. Patients who develop hemorrhagic or non-hemorrhagic blisters following snakebite, in addition to anti-venom, need broad-spectrum antibiotics and sometimes emergency surgical procedures and hospitalization to prevent serious complications such as necrotizing fasciitis, compartment syndrome.

Mini Commentary: BJOG-20-1978.R1Title: Complement Receptors in Preeclampsia: Cleaning up Placental DebrisAuthor: Richard M. Burwick, MD, MPHAffiliation: Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA

Known knowns, unknown unknowns and everything in-between

Scale insects are hemimetabolous, showing “incomplete” metamorphosis and no true pupal stage. Ericerus pela, commonly known as the white wax scale insect (hereafter, WWS), is a wax-producing insect found in Asia and Europe. WWS displays dramatic sexual dimorphism, with notably different metamorphic fates in males and females. Males develop into winged adults, while females are neotenic and maintain a nymph-like appearance, which are flightless and remain stationary. Here we report the de novo assembly of the WWS genome with its size of 638.30 Mb (69.68Mb for scaffold N50) by PacBio sequencing and Hi-C. From these data, we constructed a robust phylogenetic analysis of 24,923 gene families from 16 representative insect genomes, which indicates that holometabola evolved from incomplete metamorphosis insects in the Late Carboniferous, about 50 million years earlier than previously thought. To study the distinct development of males and females, we analyzed the methylome landscape in either sex. Surprisingly, WWS displayed high levels of methylation (4.42% for males) when compared to other insects. We observed differential methylation patterns for genes involved in steroid and sesquiterpenoids production as well as related fatty acid metabolism pathways. We show here that both males and females exhibit distinct titer profiles for ecdysone, the principal insect steroid hormone, and juvenile hormone (a sesquiterpenoid), suggesting that these hormones are the primary drivers of sexually dimorphic features. Our results provide a comprehensive genomic and epigenomic resource of scale insects that provide new insights into the evolution of metamorphosis and sexual dimorphism in insects.