Previous studies on horseshoe bats (Rhinolophus spp.) have described many coronaviruses related to SARS-CoV (SARSCoVr) in China and only a few coronaviruses related to SARS-CoV-2 (SARSCoV2r) in Yunnan (southern China), Cambodia, Laos and Thailand. Here, we report the results of several field missions carried out in 2017, 2021 and 2022 across Vietnam during which 1,218 horseshoe bats were sampled from 19 locations. Sarbecoviruses were detected in 11% of faecal RNA extracts, with much more positives for Rhinolophus thomasi (46%). We assembled 38 Sarbecovirus genomes, including 32 SARSCoVr, four SARSCoV2r; and two recombinants of SARSCoVr and SARSCoV2r (RecSar), one showing a Spike protein very similar to SARS-CoV-2. We detected a bat co-infected with four coronaviruses, including two sarbecoviruses. Our analyses revealed that Sarbecovirus genomes evolve in Vietnam under strong geographic and host constraints. First, we found evidence for a deep separation between viruses from northern Vietnam and those from central and southern Vietnam. Second, we detected only SARSCoVr in Rhinolophus thomasi, both SARSCoVr and SARSCoV2r in Rhinolophus affinis, and only RecSar in Rhinolophus pusillus captured close to the border with China. Third, the bias in favour of Uracil in synonymous third codon-positions of SARSCoVr viruses showed a negative correlation with latitudes. Our results also provided support for an emergence of SARS-CoV in horseshoe bats from northern Yunnan and emergence of SARS-CoV-2 in horseshoe bats from northern Indochina subtropical forests (southern Yunnan, northern Laos and north-western Vietnam).

Title: Triple Therapy Approach for Treating Chromoblastomycosis in a Lebanese Patient

Key Clinical MessagePatients with hemophilia A can safely undergo cardiac surgery. Combining continuous infusion and boluses of factor VIII is both safe and cost-effective. Interdisciplinary approach and meticulous planning are crucial in the prevention of bleeding complications.

The adaptation of marine fish to freshwater environments is a prodigious example of rapid evolution, and yet the underlying ecological causes of genomic and phenotypic differentiation are poorly understood for traits associated with lipid content and composition. Threespine stickleback (Gasterosteus aculeatus) have repeatedly colonized, and adapted to, freshwater habitats across the northern hemisphere. These freshwater populations often show elevated copy number of the fatty acid desaturase 2 gene (FADS2), which increases the biosynthetic capacity of ω-3 long-chain polyunsaturated fatty acids (LC-PUFA). The starkly lower content of LC-PUFA in freshwater compared to marine prey, especially docosahexaenoic acid (DHA), likely imposes strong positive selection on freshwater fish for either increased biosynthesis or greater dietary acquisition of LC-PUFA. The threespine stickleback populations in postglacial coastal lakes of Southern Greenland offer an exceptional opportunity to study how variation in the copy number of FADS2 is related to abiotic and biotic conditions of lakes and their morphometry. As expected, we found strong sexual dimorphism in FADS2 copy number in all populations (19 freshwater, 1 marine, and 1 brackish), and an increased dimorphism in some freshwater populations. We also found that FADS2 copy number was negatively correlated, for both males and females, with the abundance of copepods, which are a DHA-rich food source in the zooplankton community. Overall, our results suggest that the prey community context of lakes might influence the process of metabolic adaptation of marine fish colonizing freshwater ecosystems.

Refractory CRPS pain treated with psilocybin: a case report David Jevotovsky MD MBA,1 Harman Chopra MD,2 Court Wing,3 CJ Spotswood,3 Joel Castellanos MD41New York University Grossman School of Medicine2Johns Hopkins University School of Medicine3REMAP Therapeutics4University of California San Diego Health

Pterostilbene (PST), a 3,5- O-methylated derivative of resveratrol (RSV), is a natural potent antioxidant produced by some plants in trace amounts as defense compounds. It exhibits various health-promoting activities, such as anticancer, antiviral, and antimicrobial effects. Large-scale biosynthesis of PST is crucial due to the challenges associated with extracting it from plants. This study aims to develop an efficient method for PST production using an engineered E. coli strain by feeding RSV as an intermediate compound. We introduced a two-step substrate addition strategy combined with immobilized RSV (IMRSV) on macroporous adsorption resin (MAR) to enhance PST production. Five MARs were selected for RSV immobilization, and the substrate additions strategy and fermentation parameters for PST synthesis were optimized. A maximum PST concentration of 402.78 ± 9.20 mg/L was achieved, representing a 239% increase over the control. The PST titer reached 395.20 ± 23.89 mg/L in a 3-L bioreactor. In conclusion, the combination of a two-step substrate adding system and IMRSV is a promising approach for the economical and industrial-scale production of PST.

Paradoxical infarction? Inferior STEMI with Unexpected Discovery of ASD in an Oncology Patient:

Background and Purpose Emerging evidence has suggested that somatic stimulation, including electroacupuncture (EA), could produce autonomic reflexes to modulate visceral functions. However, the efficacy and underlying mechanisms for EA on allergic pulmonary inflammation (API) remain elusive. Experimental Approach Papain-induced API mice were treated with distinct current-intensity EA at the back BL13, hindlimb ST36, and forelimb LU5 acupoints. The change in API was determined by whole-body plethysmograph (WBP), immunohistochemistry, flow cytometry, and HE staining. We employed lung functional testing combined with pharmacological inhibition and optogenetic activation approaches to examine the underlying mechanisms for EA effects on API. Key Results EA at the back BL13 region, but not limb regions, via a current-intensity-dependent manner, exacerbated the API. Pharmacological blocking of the local thoracic sensory or the lung-innervated autonomic nerve eliminates the EA-produced detrimental effects. Chemical pulmonary sympathectomy was further enhanced, but inhibition of the upregulated muscarinic M3 acetylcholine receptor within the pulmonary was sufficient to protect from the inflammation-exacerbation effect of EA. Conclusions and Implications Our findings suggest that BL13 EA evokes a somatic-autonomic-pulmonary M3 pathway to enhance API. The revelation of somatotopic organization and intensity-dependency in driving the pulmonary autonomic pathways could help optimize stimulation parameters to improve both efficacy and safety in various forms of physical therapy, including bioelectronic medicine and traditional as well as modern forms of moxibustion and EA, to modulate API.

Urbanisation has reduced the abundance and diversity of many taxonomic groups, and the effects may be more pronounced on islands, which have a smaller regional species pool to compensate. Green spaces within urban environments may help to safeguard wildlife assemblages, and the associated habitat heterogeneity can even increase species diversity. Here, total abundance and species diversity of butterflies, birds, and vegetation at nine rural and nine urban locations were quantified on Lipsi Island, Greece. Sites were assessed using Pollard walks for butterflies, point-count surveys for birds, and quadrats for vegetation. There was no significant difference in the abundance or species diversity of butterflies or vegetation among rural and urban locations, which could pertain to the low building density within urbanised areas and the minimal extent of urbanisation on the island. However, urban areas hosted a significantly greater abundance and richness of birds compared to rural sites. The community composition of butterflies, birds, and vegetation also differed significantly between urban and rural locations, highlighting the impact of urbanisation on species across a broad range of trophic groups. This study contributes to ecological knowledge on the impacts of urbanisation across multiple trophic levels in island ecosystems, with comparisons across a gradient of island size and urbanisation intensity needed in future research.

Background: Valproic acid (VPA) is a widely used anti-epileptic and mood-stabilizing drug, primarily metabolized by glucuronosyltransferases (UGT) and cytochrome P450 (CYP) enzymes. Few drug interactions are known to affect VPA levels, including carbamazepine, phenytoin, and carbapenems. We report a new drug that interacts with VPA: flucloxacillin. Case Presentation: A 79-year-old male with bipolar disorder, treated with VPA, presented with low VPA serum levels during treatment for S. aureus bacteraemia with flucloxacillin. His VPA levels decreased rapidly, despite no apparent explanation. Serial assessments ruled out nonadherence and absorption issues. Flucloxacillin was identified as the probable cause, as VPA levels normalized upon its cessation and dropped again with reintroduction. Discussion: This case illustrates a significant drug-drug interaction between flucloxacillin and VPA, likely mediated by induction of UGT enzymes rather than CYP enzymes. The rapid onset and resolution of the interaction suggest UGT induction as the primary mechanism. Probably, patients with a low albumin are more susceptible to this interaction, like our patient, due to increased metabolism. Conclusion: Flucloxacillin treatment substantially decreases total VPA serum levels while free fraction levels can be still within reference values. Clinicians should consider monitoring free fraction and adjusting dosages accordingly in bipolar disorder. If VPA is used for epilepsy, alternative antibiotics to flucloxacillin should be preferred.

Labile traits, such as behavioural, physiological traits or body mass, exhibit variation within an individual either over time or across environments. Such changes within an individual can be linked across traits, forming within-individual trait correlations. These correlations are particularly expected when ageing causes changes in the expression of multiple traits. The direction of these correlations also depends on mechanisms explaining age-related changes in each traits, such as physiological deterioration or changes in future fitness expectations. Therefore, assessing within-individual trait correlations offers insights into the trait-specific ageing patterns, their integration and age-related reproductive strategies. Here, we tracked individual male cicadas (Tettigetta isshikii) in their natural habitat, repeatedly assessing their plant use (narrow vs. wide-leafed), calling activity, and body mass. Results revealed that male cicadas lost mass, increased calling activity and a preference for narrow-leafed plants as they aged. This integration of age-related plasticity led to negative within-individual correlations between body mass and behaviours. The asset protection principle could explain the age-related increase in calling activity and the preference for narrow-leafed plants. Such an age-related increase in energetically demanding calling activity may also cause an age-related decrease in body mass. Considering that adult cicadas consume nutritionally poor xylem sap, the negative within-individual correlations between body mass and risk-taking behaviour suggest that T. isshikii males follow a capital breeding strategy rather than an income breeding strategy. Therefore, we emphasise the importance of individual-level tracking study in the wild to achieve a comprehensive understanding of the life-history strategies and behavioural ecology of a study animal.

This study investigates the biogeography of the Australian Camphorosmeae (Amaranthaceae s.l.) and how it relates to shifts in climatic niche and habitat types of the lineage. Building on previous research and data resources, we integrate molecular phylogenetics, bioclimatic data and biogeographic models to deepen our understanding of the diversification and adaptation of this group across Australia’s diverse landscapes in relation to palaeoclimatic changes. For 159 species representing 12 genera, georeferenced distribution points were used to define the most informative bioclimatic variables using principal component analyses. Evolutionary shifts in climatic niches and habitat types were analysed, revealing clade-specific shifts and adaptations to different habitats and climatic conditions. Biogeographic analyses allowed us to infer ancestral areas of Camphorosmeae in Australia and relate their expansion over evolutionary time to habitat shifts. Key periods of aridification in Australia, particularly during the Late Miocene to Pliocene, and the already existing adaptation of this group to warm and dry habitats, were critical in driving its diversification through migration and local adaptation to varied habitats of arid Australia. Our analyses suggest that the “Riverine Desert” habitat that existed already in the Late Miocene and “migrated” eastwards offered suitable conditions for ancestral Australian Camphorosmeae and facilitated their early widespread occurrence in the Western and Eastern Desert. We hypothesise that early diverging lineages such as Roycea adapted to the later emerging “Desert Lake” habitat when it spread in Western Australia during the Early Pliocene. Further habitat type shifts occurred from “Riverine Desert” to “Shield Plain”, “Karst Plain” and to “Sand Desert” also during the Pliocene and Pleistocene once these habitat types emerged. This research shows the complex interplay between ecological flexibility and niche conservatism in shaping the biodiversity of Australian Camphorosmeae.

The small mammalian fauna plays pivotal roles in ecosystem dynamics and as crucial biodiversity indicators. However, recent research has raised concerns about the decline of mammalian species due to climate change. Consequently, significant attention is directed towards studying various flagship mammalian species families for conservation. The hog badger (Mustelidae: Arctonyx) remains understudied regarding the impacts of climate change in Asia. The present study offers a comprehensive analysis of climate change effects on two mainland hog badger species, utilizing ensemble species distribution modeling. Findings reveal concerning outcomes, as only 52% of the IUCN extent is deemed suitable for the Great Hog Badger (Arctonyx collaris) and a mere 17% is ideal for the Northern Hog Badger (Arctonyx albogularis). Notably, projections suggest a potential reduction of over 26% in suitable areas for both species under future climate scenarios, with the most severe decline anticipated in the SSP585 scenario. These declines translate into evident habitat fragmentation, particularly impacting A. collaris, whose patches shrink substantially, contrasting with the relatively stable patches of A. albogularis. However, despite their differences, niche overlap analysis reveals an intriguing increase in overlap between the two species, indicating potential ecological shifts. The study underscores the importance of integrating climate change and habitat fragmentation considerations into conservation strategies, urging a reassessment of the IUCN status of A. albogularis. The insights garnered from this research are pivotal for enhancing protection measures for hog badgers across Mainland Asia, emphasizing the urgency of proactive conservation efforts, especially in countries with highly suitable areas, as found in this study. By incorporating these findings into conservation policies, we can strive to safeguard these invaluable mammalian species and the ecosystems they inhabit from the detrimental impacts of climate change.

Main Document

Compared to batch operation, continuous bioprocessing can offer numerous advantages, including increased productivity, improved process control, reduced footprint, and increased flexibility. However, integration of traditional batch operations into a connected process can be challenging. In contrast to batch operations run at constant pressure or high flux, virus filtration in continuous processes may be operated at very low flux. This change in operating conditions may reduce the viral retention performance of the filter which has inhibited adoption of truly continuous virus filtration. To overcome this limitation, a novel approach is described that utilizes serial virus filtration, with a high area ratio between first to second stage filters, to achieve virus retention targets. In this study, virus filters were operated continuously (except for planned process interruptions) for 200 hours in a serial configuration at a first to second stage filter area ratio of 13:1 and at a first stage flux of 5 L/m 2/hr. While the minute virus of mice (MVM) retention performance of the first stage filter was about 4 log reduction value (LRV), there was no virus detected in the second stage filtrate, translating to an MVM LRV across the filtration train of ≥6.7. The second stage filter was the dominant flow resistance at the start of the run but, as it was protected from foulants by the first stage filter, it suffered minimal fouling and the life of the filter train was controlled by the first stage. A theoretical case study projected that continuous virus filtration using serial configuration at high area ratio would have about 30% longer filter changeout time, 14% higher productivity, and virus retention nearly 6 LRV greater than single stage operation. The findings of this research are expected to provide valuable insights into optimizing virus filtration in continuous bioprocessing.

TITLE: A rare case of primary vulvar diffuse large B-cell lymphoma: A case report

Introduction: Uncontrolled or severe asthma results in symptomatic usage of short-acting ß2-agonist usage (SABA). MicroRNAs (miRNAs) are post-translational regulators that can influence asthma biology. This study aims to identify miRNAs that are associated with increased SABA usage. Methods: Small RNA sequenced from blood serum of 1,132 asthmatic children aged 6 to 14 years in the Genetics of Asthma in Costa Rica Study (GACRS) was used for this analysis. Logistic regression identified miRNAs in patients who required increased SABA usage. These miRNA were validated for association with SABA induced BDR. Gene target pathway analysis was performed on validated miRNAs. Results: 21 miRNAs were significantly associated with increased SABA usage with OR ranging from 0.87 to 1.23. Two miRNAs, miR-378a-3p and miR-144-3p, had odds ratio 1.14 (1 - 1.29, p=0.05) and 1.11 (1.01-1.22, p = 0.035), respectively for increased SABA usage and were also significantly associated with bronchodilator response. Furthermore, a linear regression analysis involving these miRNA and bronchodilator response revealed that increased miR-378a-3p correlated with decreased BDR and increased expression of miR-144-3p correlated with improving pulmonary function with bronchodilators. In gene target KEGG pathway analysis, the erythroblastosis viral oncogene (ErbB) signaling pathway had among one of the highest fold enrichment and p-value. Conclusion: Increased expression miR-378a-3p and miR-144-3p was seen in this patient population who required increased SABA usage. There were different bronchodilatory effects seen in these two miRNAs, suggesting different potential mechanisms underlying increased SABA usage.

Introduction: During NICU hospitalization, children born preterm with bronchopulmonary dysplasia (BPD) are frequently prescribed diuretics for treatment of respiratory symptoms. However, less is known about diuretic use and weaning in the outpatient setting. This study sought to characterize clinical features associated with outpatient diuretic use, and timing of diuretic weaning in children with BPD. Methods: Data was obtained by chart review from registry 1224 participants born < 32 weeks gestation, discharged between 2008-2023 and recruited from outpatient BPD clinics at Johns Hopkins Children’s Center and the Children’s Hospital of Philadelphia (97.4% diagnosed with BPD). Data was analyzed using Chi-square tests, t-tests, and ANOVA tests. Results: Children with BPD prescribed diuretics as outpatients (n=737), were more likely to have lower birth weights, earlier gestational age, and severe BPD compared to those not on diuretics (n=487). Of those prescribed diuretics, most children were on a thiazide alone (46.4%) or a thiazide and a potassium sparing agent (44.8%) with a minority on loop diuretics alone (3.3%) or loop diuretic combinations (4.7%). Most children weaned off diuretics by two years of age. Public insurance, earlier gestational age, technology dependence and loop diuretics were associated with slower diuretic weaning. Conclusion: Outpatient diuretic use is common in BPD with > 75% of children being weaned by two years of age. No difference was found in weaning of home oxygen between children on one versus no diuretic. Thiazides were most commonly prescribed with slower outpatient diuretic weaning associated with public insurance, technology dependence and loop diuretic use.