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First part duodenal web presenting with Gastric Outlet Obstruction in 8-year-old boy:...
Rajabu Athumani Bakari
Alfred Chibwae

Rajabu Bakari

and 7 more

June 06, 2025
First part duodenal web presenting with Gastric Outlet Obstruction in 8-year-old boy: A case report.Rajabu Athumani Bakari1,2*, Alfred Chibwae1, Nurdin Swago1, Salma J. Ali 2, Gerald Mpemba3, Mwajabu Rashidi Mbaga1,2, Zaitun M. Bokhary2, Victor T. Ngotta2 .1 Department of Surgery, School of Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.2 Department of Surgery, Muhimbili National Hospital, Dar es Salaam, Tanzania.3Department of Radiology, Muhimbili National Hospital, Dar es Salaam, Tanzania.*Correspondence : Rajabu Athumani Bakari, Department of Surgery, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. Tel: +255738297925; E-mail: rogerluhizo@gmail.com
Further Generalizations of the Eisenstein Series and Weierstrass peh-function
Philipp Harland

Philipp Harland

June 06, 2025
In this paper, we will be providing further generalizations for the Eisenstein series and ℘-function, which vastly generalize and enlarge the original notions. We will be focusing on results that pertain to specific kinds of subsets of C.
Observation of a Veraguan mango (Anthracothorax veraguensis) with male-like plumage p...
Dallas Levey
Gretchen Daily

Dallas Levey

and 1 more

June 06, 2025
Male plumage mimicry by adult females of sexually dimorphic hummingbird species provides an intriguing system for understanding social and ecological selection mechanisms. However, our understanding of female male-mimicry is limited by a lack of behavioral observations of wild hummingbirds with male plumage, such as in giving parental care. Using photos and 2.5 min of video taken at close proximity, we documented a Veraguan mango (Anthracothorax veraguensis) with male plumage both incubating eggs and later feeding young in the town of Palmar Norte in southern Costa Rica. Based on plumage characteristics and range, we ruled out the similar green-breasted mango (A. prevostii) that occurs in close geographic proximity. Using Google Earth imagery, we characterized the landscape surrounding the nest as a heterogeneous mix of urban, residential, and agricultural land. We speculated on potential mechanisms that may maintain female-limited polymorphisms in the Veraguan mango and related species, including the interaction of social and ecological selection pressures. This observation provides the first empirical evidence of male-mimicry polymorphism in the Veraguan mango, contributing valuable information to the species’ natural history and to the broader understanding of male-plumaged females in hummingbirds.
Isotopic Incorporation of Carbon and Nitrogen in Invasive Burmese Pythons (Python mol...
K.R. Davis
Andrea Currylow

Katherine Davis

and 4 more

June 06, 2025
Abstract RATIONALE The carbon and nitrogen stable isotope composition of animal tissues provide valuable insights into foraging ecology and trophic interactions. However, dietary isotopic composition varies widely among organisms and tissues. This study established carbon and nitrogen trophic discrimination and tissue-to-tissue conversion factors in Burmese pythons ( Python molurus bivittatus) and explored tissue turnover dynamics. METHODS Trophic discrimination conversion factors ( Δ 13C diet-tissue and Δ 15N diet-tissue) were established by analyzing shed skin from captive pythons and comparing to known diet values. Tissue-to-tissue conversion factors between muscle, dermis, and scale (n=25) and muscle and shed (n=10) were determined from paired tissue samples from the remains of stored snake tail clips. Tissue turnover time was investigated with opportunistically collected samples: red blood cells from wild snakes held in captivity on a known diet. RESULTS The Δ 13C diet-tissue and Δ 15N diet-tissue values between diet and shed were significantly different between adult and subadult snakes. For Δ 13C diet-tissue, adult shed averaged 0.8‰ higher than diet while subadult shed averaged -1.4‰ lower than diet. Both age groups had higher mean δ 15N values than their diet, resulting in positive Δ 15N diet-tissue values (subadults = 2.3 ± 0.4 ‰, adults = 4.3 ± 0.2 ‰). Conversion equations were established between muscle, dermis, scale, and shed skin. Tissue turnover time could not be determined over the duration of available samples. CONCLUSIONS Our results highlight the importance of taking ontogeny into consideration when interpreting Burmese python stable isotope composition. The isotopic metrics measured here can be used in future ecological research on Burmese pythons and expand the limited information on isotopic dynamics of herpetofauna.
Constructing Atomically Dispersed Bimetallic Electrocatalyst by a Topologically Confi...
Yawei Zhang
Xia Li

Yawei Zhang

and 2 more

June 06, 2025
The development of atomically dispersed multi-metallic catalysts is imperative for tailoring catalytic performance and elucidating structure-activity relationships. However, synthesizing such precisely engineered architectures while maintaining atomic dispersion of distinct metal centers remains a formidable challenge due to thermodynamic instability and synthetic complexity. We herein propose a topological confinement pre-anchoring strategy via pre-anchoring spatially resolved Zn/Fe dual-metal sources in a structurally engineered metal-organic framework precursor to synthesize atomically dispersed ZnFe bimetallic single-atom catalysts (ZnFe-BMSAC). Extended X-ray absorption fine structure measurements and X-ray absorption near-edge structure reveal that the atomically dispersed Zn/Fe metal sites and electronic redistribution in ZnFe-BMSAC. The ultrahigh surface area, hierarchical pore and synergistic effect between Zn/Fe can greatly favor the exposure of active site, mass transport, and improvement of intrinsic activity. Consequently, the ZnFe-BMSAC catalyst demonstrates superior oxygen reduction reaction performance, achieving a half-wave potential of 0.86 V and delivering a kinetic current density of 10.1 mA cm⁻² at 0.85 V vs. RHE in 0.1 M KOH electrolyte. These metrics not only surpass those of commercial Pt/C, but also rival the highest-performing catalysts reported to date. The Zn–air battery built with ZnFe-BMSAC exhibits high power density (278.5 mW cm-2) and specific discharging capacities (657 mAh g-1). This work provides a new design pathway for constructing atomically dispersed multi-metal electrocatalysts for high-performance energy-related applications.
    A Propositional Approach for Genome-Guided Supplementation of Environmental Subst...
Maxwel Adriano Abegg

Maxwel Adriano Abegg

June 06, 2025
TitleA Propositional Approach for Genome-Guided Supplementation of Environmental Substrates to Induce Silent Biosynthetic Gene Clusters in ActinomycetesRunning TitlePropositional Activation of Silent BGCs via Genome-Guided ElicitorsAuthorMaxwel A. Abegg Institute of Exact Sciences and Technology (ICET), Graduate Program in Sciences, Technology and Health (PPGCTS), Federal University of Amazonas (UFAM), Itacoatiara, Brazil ORCID: 0000-0002-0328-1122 | maxabegg@gmail.comAbstractThe pervasive transcriptional silence of biosynthetic gene clusters (BGCs) in actinomycetes under standard laboratory conditions limits access to their full metabolic potential. We propose a conceptual, genome-guided protocol that uses comparative mining of both actinomycete genomes and genomes of co-occurring Gram-negative bacteria to identify with higher confidence which small molecules may activate silent BGCs. Mining the producer’s genome locates cluster-situated regulators (e.g., LuxR-like proteins) and identifies key enzymatic domains—such as NRPS adenylation domains—whose sequence features can be analyzed by specialized tools (e.g., NRPSpredictor2, SANDPUMA) to predict which amino acid substrates the cluster may incorporate. Simultaneously, mining competitor genomes uncovers their quorum-sensing and siderophore pathways (e.g., AHL synthases, enterobactin operons), indicating which interspecies signals are likely present in that habitat. By selecting elicitors—such as long-chain N-acyl homoserine lactones (AHLs), enterobactin, sodium bromide, and L-tryptophan—that align with both the producer’s regulatory elements and competitors’ signals, we aim to target silent BGCs more effectively. Deployment of devices in supplemented, sterile substrates for 2–4 weeks is intended to recreate these ecological cues under controlled conditions, potentially facilitating discovery of novel secondary metabolites. This protocol remains untested in the field due to technical and financial constraints, but we present it conservatively to encourage exploration of new approaches for activating silent BGCs.Keywords: Actinomycetes; Biosynthetic Gene Clusters; Genome Mining; Chemical Elicitors; iChip; In Situ CultivationIntroductionActinomycetes harbor dozens of biosynthetic gene clusters (BGCs) in their genomes, yet the majority of these clusters remain transcriptionally silent under conventional laboratory cultivation, leaving a vast reservoir of potentially novel natural products unexplored [1,2]. Genomic surveys indicate that a singleStreptomyces genome may encode 30–50 BGCs, but less than 10% of these are expressed when grown on standard agar or broth media [1,3]. This disconnect arises because laboratory media often lack key environmental signals—nutrient limitations, interspecies cues, or abiotic stresses—necessary to trigger cluster activation. Consequently, many actinomycete-derived metabolites remain undetected, hindering drug discovery efforts.Several approaches have been developed to awaken cryptic BGCs. Manipulating culture conditions via OSMAC (One Strain–Many Compounds) can reveal new metabolites by varying carbon, nitrogen, or trace element sources [3]. Co-cultivation with other microorganisms has been shown to stimulate interspecies signaling that derepresses silent clusters [4]. Genetic methods, including heterologous expression of regulatory genes or deletion of pathway repressors, have successfully refactored silent clusters [5]. Chemical elicitation, using small-molecule inducers such as subinhibitory antibiotics or epigenetic modifiers, has also unlocked cryptic pathways [6]. Despite these advances, identifying which environmental signals specifically activate a given BGC remains challenging, because most methods rely on trial-and-error screening of large elicitor libraries or extensive genetic manipulation. This gap motivates a more targeted, genome-guided strategy.Here, we propose a protocol to activate silent BGCs in actinomycetes by integrating comparative genome mining with rational selection of chemically stable, ecologically relevant elicitors and in situ cultivation. Specifically, we hypothesize that (1) genomic analysis of the producer strain can reveal cluster-situated regulators (e.g., LuxR-like proteins, two-component system sensors) and core enzymatic domains whose predicted substrate specificities guide precursor supplementation; (2) mining genomes of co-occurring Gram-negative bacteria identifies quorum-sensing and siderophore pathways that suggest interspecies signals present in the native habitat; and (3) by supplementing environmental matrices with elicitors aligned to both producer regulators and competitor signals—and incubating in diffusion chambers or iChips within sterile substrates—silent BGCs can be derepressed without extensive genetic manipulation. This targeted approach aims to reduce randomness in BGC activation, leveraging ecological context and bioinformatic predictions to focus on a smaller set of candidate elicitors.To perform the in silico analyses and manage data efficiently, we recommend the following software tools:antiSMASH : Annotates and predicts BGC regions within microbial genomes.DeepBGC : Uses machine-learning classifiers to detect BGCs not captured by traditional homology searches.CoreFinder : Refines functional annotations within BGCs by applying a context-aware protein-language model to recognize enzymatic domains (e.g., halogenases, methyltransferases).CHAMOIS : Translates Pfam domain annotations into predicted chemical scaffolds and precursor dependencies, thereby guiding elicitor selection.NRPSpredictor2 & SANDPUMA : Predict amino acid substrate specificity of NRPS adenylation domains by comparing signature residues against database profiles.BLAST : Identifies homologous genes in competitor genomes, such as quorum-sensing synthases (LuxI homologs) and outer membrane porins (OmpF/OprF).GNPS (Global Natural Products Social Molecular Networking) : Facilitates molecular networking of LC-MS/MS data to group related metabolites and highlight novel compounds.SIRIUS : Performs in silico fragmentation analysis for structural elucidation of unknown metabolites.These tools collectively enable genome mining, substrate-preference prediction, homolog identification, and metabolomic data interpretation, forming the computational backbone of our proposed protocol.Methodology1. Comparative Genome Mining and Elicitor Selection1.1 Producer Genome Analysis antiSMASH & DeepBGCAnnotate all BGC regions in the actinomycete genome, highlighting core enzymatic domains (e.g., ketosynthase, adenylation, precursor peptides) and cluster-situated regulators (e.g., LuxR-like transcription factors).CoreFinder & CHAMOISApply CoreFinder to refine functional annotation within each predicted BGC, confirming domains such as halogenases or methyltransferases.Use CHAMOIS to translate Pfam domain annotations into predicted chemical features (e.g., likely phenazine or siderophore scaffolds), thereby guiding which elicitors or precursors may be most relevant.NRPSpredictor2 / SANDPUMAFor each NRPS adenylation domain detected by antiSMASH/DeepBGC, analyze signature residues to infer the preferred amino acid substrate (e.g., L-tryptophan or L-phenylalanine).Record high-confidence predictions (probability ≥ 0.90) to inform precursor supplementation.1.2 Competitor Genome Analysis antiSMASH & DeepBGCScreen co-occurring Gram-negative genomes for quorum-sensing clusters (LuxI/LuxR homologs) and siderophore biosynthesis clusters (e.g., enterobactin operons).BLAST SearchesIdentify genes encoding outer membrane porins (e.g., OmpF, OprF) whose peptide fragments may mimic cell-envelope stress signals.Inference of Ecological SignalsPresence of a long-chain AHL synthase (e.g., 3-oxo-C12-HSL) indicates that corresponding AHLs are authentic interspecies signals in the producer’s habitat.Detection of an enterobactin operon suggests iron limitation is signaled by enterobactin, potentially activating siderophore BGCs in actinomycetes.Identification of porin genes implies that porin-derived peptides may trigger membrane-stress responsive clusters.Overlay of Producer and Competitor InsightsCross-reference cluster-situated regulators with competitor-derived signals to shortlist candidate elicitors that (a) have affinity for the actinomycete’s regulatory network and (b) emulate genuine environmental cues.2. Selection of Environmentally Relevant ElicitorsExamples of potential elicitors revealed by comparative genome analyses include:Long-Chain AHLs (e.g., 3-oxo-C12-HSL): Selected when competitor genomes encode corresponding AHL synthases; these molecules may cross-activate LuxR-like regulators in actinomycetes.Enterobactin : Emulates iron limitation; chosen if competitor genomes harbor enterobactin operons, potentially inducing siderophore BGCs in actinomycetes.Porin-Derived Peptides (10–15 amino acids from OmpF/OprF): Mimic outer membrane stress, potentially triggering stress-responsive BGCs.Sodium Bromide (NaBr) : Provides halide ions to support halogenase-containing BGCs predicted by CHAMOIS.Amino Acids (e.g., L-tryptophan, L-phenylalanine): Serve as precursors when NRPSpredictor2/SANDPUMA predict these as NRPS substrates.Alternative Carbon Sources (e.g., mannitol, trehalose): Maintain basal microbial growth without repressing secondary metabolism.Stock PreparationDissolve each elicitor in sterile water or buffer to prepare concentrated stocks (e.g., 10 mM AHL, 10 mM enterobactin, 100 mM NaBr, 100 mM amino acids).Matrix Sterilization and EnrichmentObtain an environmental matrix (e.g., leaf litter, humic soil, decomposed wood) and sterilize by autoclaving (121 °C, 20 min) to eliminate native microbial communities.Incorporate elicitor stocks into the sterile matrix at empirically determined final concentrations—e.g.:• 50 µM long-chain AHL • 1 mM enterobactin • 5 mM NaBr • 5 mM L-tryptophan • 1–2% (w/v) mannitol or trehaloseEquilibrate the supplemented matrix at ambient temperature for 12–24 h to ensure uniform distribution of elicitors.3. In Situ Cultivation Using Diffusion Chambers or iChipsDevice DescriptionDiffusion Chambers [14]: Two-part devices sealed with 0.03 µm semipermeable membranes that allow passive diffusion of small molecules from the environment into an agar-based inoculum.iChips [15]: High-throughput, multiwell devices, each well containing an individual cell or colony separated by semipermeable membranes; designed to replicate in situ conditions with minimal disturbance to native cues.Inoculum PreparationHarvest actinomycete spores or cells (10^4–10^6 CFU/mL) and suspend in 0.5–1% (w/v) agar or gellan-gum solution.Pipette ~5 µL of the inoculum into each diffusion chamber or iChip well.Seal wells with semipermeable membranes, ensuring airtight contact.DeploymentEmbed diffusion chambers or iChips within the elicitor-supplemented, sterile matrix, ensuring intimate contact between membrane and substrate.Maintain substrate moisture at ~40–60% water-holding capacity by periodic addition of sterile water; avoid waterlogging.Incubate devices in situ for 2–4 weeks (up to 30 days if needed). Position them in shaded or semi-shaded locations to prevent rapid desiccation and extreme temperatures. Since the substrate is sterile and enriched only with selected elicitors, any detected metabolites can be attributed to the inoculated producer.Downstream Applications4. Gene Expression MonitoringRNA Extraction & RT-qPCRRetrieve devices; aseptically recover agar/gellan-gum carriers containing cells.Disrupt carriers mechanically (e.g., bead beating) and extract total RNA using an RNA purification kit compatible with environmental samples.Treat RNA with DNase I to remove genomic DNA.Synthesize cDNA using random hexamer primers.Design primers targeting:• Core biosynthetic genes (e.g., ketosynthase domains in PKS, adenylation domains in NRPS). • Cluster-situated regulators (e.g., LuxR-like transcription factors).Place primers within –192 to –66 bp upstream of start codons, where transcription-factor binding is often concentrated.Normalize expression against housekeeping genes (e.g., rpoB, gyrA).Use the ΔΔCₜ method to compare expression levels in elicited versus control samples, thereby assessing whether silent BGCs exhibit upregulated transcription. Because the substrate is sterile, background expression from contaminating microbes is minimized, yielding more accurate relative quantification of the producer’s transcripts.5. Metabolite Detection and ProfilingLC-HRMSExtract metabolites from carriers and surrounding matrix using organic solvents (e.g., methanol, ethyl acetate).Concentrate extracts under reduced pressure and reconstitute in an LC-MS–compatible solvent (e.g., 50% acetonitrile with 0.1% formic acid).Analyze extracts on a high-resolution LC-MS system, employing gradients optimized for separation of polyketides, nonribosomal peptides, and small polar compounds.Compare induced versus uninduced chromatograms to identify novel peaks corresponding to elicited metabolites.Utilize GNPS for molecular networking and SIRIUS (or similar tools) for in silico fragmentation, proposing structures guided by CHAMOIS-predicted formulas. Because the substrate began as sterile and only the inoculated actinomycete contributes metabolites, any new mass features likely represent elicitor-driven products.MALDI-TOF MSSpot crude extracts onto a MALDI plate with an appropriate matrix (e.g., α-cyano-4-hydroxycinnamic acid).Acquire mass spectra to rapidly screen for new mass features indicative of elicited compounds. Minimal substrate background facilitates detection of low-abundance producer-derived ions.ConclusionThis technical framework outlines a conceptually grounded approach—based on comparative genome mining—to select ecologically relevant elicitors and deploy diffusion chambers or iChips in sterile, supplemented substrates, thereby recreating native environmental cues under controlled conditions that favor direct comparison of metabolite expression. By identifying cluster-situated regulators and predicted substrate specificities in actinomycete genomes, alongside quorum-sensing and siderophore pathways in competitor bacteria, one can assemble a targeted elicitor suite. Devices such as diffusion chambers and iChips offer minimally invasive, in situ cultivation platforms to test these elicitor combinations. Sterilizing the environmental matrix ensures that observed metabolites arise from the inoculated producer, simplifying downstream analyses. Ultimately, careful validation of this framework could broaden access to cryptic secondary metabolites and inspire new avenues for natural product discovery.ReferencesRui S, Fengrui G, Zhang Y, et al. Biological activity of secondary metabolites of actinomycetes and their potential sources as antineoplastic drugs: a review. Front Microbiol. 2025 May;16:1550516. doi:10.3389/fmicb.2025.1550516.Coelho LP, Alves R, Rodríguez del Río Á, et al. Towards the biogeography of prokaryotic genes. Nature. 2022;601(7892):252–256. doi:10.1038/s41586-022-04271-8.Ribeiro Monteiro S, Kerdel Y, Gathot J, Rigali S. The Transcriptional Architecture of Bacterial Biosynthetic Gene Clusters. bioRxiv. 2025 Mar 19; doi:10.1101/2025.03.18.644061.Covington BC, Xu F, Seyedsayamdost MR. A Natural Product Chemist’s Guide to Unlocking Silent Biosynthetic Gene Clusters. Annu Rev Biochem. 2021;90:763–788.Kang Z, Zhang H, Liang C, Yang R, Ye Y, Bai H, et al. Deciphering Biosynthetic Gene Clusters with a Context-aware Protein Language Model. bioRxiv. 2025 May 03; doi:10.1101/2025.04.29.651206.Kurtböke İ. Actinomycetes: what more can they offer in an era of metabolic engineering and artificial intelligence? Microbiology Australia. 2025;46(2):72–76. doi:10.1071/MA25022.Schniete JK, Fernández-Martínez LT. Natural product discovery in soil actinomycetes: unlocking their potential within an ecological context. Curr Opin Microbiol. 2024;79:102487. doi:10.1016/j.mib.2024.102487.Pinedo-Rivilla C, Aleu J, Durán-Patrón R. Cryptic Metabolites from Marine-Derived Microorganisms Using OSMAC and Epigenetic Approaches. Mar Drugs. 2022;20(2):84. doi:10.3390/md20020084.Yook G, Nam J, Jo Y, Yoon H, Yang D. Metabolic engineering approaches for the biosynthesis of antibiotics. Microbial Cell Factories. 2025;24:35.Libis V, MacIntyre LW, Mehmood R, et al. Multiplexed mobilization and expression of biosynthetic gene clusters. Nat Commun. 2022;13:5256. doi:10.1038/s41467-022-32858-0.Tay DWP, Tan LL, Heng E, et al. Exploring a general multi-pronged activation strategy for natural product discovery in Actinomycetes. Commun Biol. 2024;7:50. doi:10.1038/s42003-023-05648-7.Salamzade R, Kalan LR. Context matters: assessing the impacts of genomic background and ecology on microbial biosynthetic gene cluster evolution. mSystems. 2025;10(3):e01538-24. doi:10.1128/msystems.01538-24.Arivuselvam R, Nagappan K, Raj PV, Rajeshkumar R. Unveiling Nature’s Secrets: Activating Silent Biosynthetic Gene Clusters in Fungi and Bacteria. Int J Nutr Pharmacol Neurol Dis. 2024;14:292–299.Kaeberlein T, Lewis K, Epstein SS. Isolating “uncultivable” microorganisms in pure culture in a simulated natural environment. Science. 2002;296(5570):1127–1129.Nichols D, Cahoon N, Trakhtenberg EM, Pham L, Mehta A, Belanger A, Kanigan T, Lewis K, Epstein SS. Use of iChip for high-throughputin situ cultivation of “uncultivable” microbial species. Environ Microbiol. 2010;12(12):348–355.
Protruding left main coronary stent detected by transoesophageal echocardiography in...
Calum Downes
Anita Szabo-Barnes

Calum Downes

and 2 more

June 05, 2025
We report a rare case of left main coronary artery stent migration in a young patient with Takayasu arteritis, first identified intraoperatively using transoesophageal echocardiography (TOE). The protruding stent was visualised in real time on 2D and 3D TOE. The patient underwent urgent coronary artery bypass grafting with good clinical outcome. This case highlights the diagnostic value of intraoperative TOE in identifying coronary complications in large-vessel vasculitis.
Echocardiographic Features of Cardiomyopathies: A Comprehensive Review
Ghassan Al-Naami

Ghassan Al-Naami

June 05, 2025
Cardiomyopathies represent a heterogeneous group of myocardial diseases characterized by structural and functional abnormalities that can lead to heart failure, arrhythmias, and sudden cardiac death. Echocardiography remains the first-line, non-invasive imaging modality for the evaluation of cardiomyopathies, owing to its broad availability, safety profile, and diagnostic versatility. This review comprehensively outlines the echocardiographic features associated with the major morphofunctional subtypes of cardiomyopathy: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and left ventricular non-compaction cardiomyopathy (LVNC). Emphasis is placed on both adult and pediatric populations, with attention to age-specific diagnostic criteria and measurement standards. The article also includes structured tabular summaries to facilitate clinical interpretation and application across diverse patient settings. Through an integrated and standardized echocardiographic approach, this review aims to support accurate diagnosis, effective monitoring, and informed therapeutic decision-making in the management of cardiomyopathies.
Amiodarone-Induced Pulmonary Toxicity in an Elderly Patient: A Case Report
Bal Subedi
Naveen Gautam

Bal Subedi

and 4 more

June 05, 2025
AbstractAmiodarone, a widely utilized and effective class III antiarrhythmic agent, carries a significant risk of severe organ toxicities, notably including the pulmonary system. This report details a case of an 82-year-old female who developed amiodarone-induced pulmonary toxicity (APT) following two years of standard 200mg daily maintenance therapy for atrial fibrillation. The patient presented with progressive dyspnea, non-productive cough, and new-onset oxygen dependency. Diagnostic evaluation, including chest computed tomography revealing diffuse interstitial opacities, alongside the systematic exclusion of other etiologies, confirmed the diagnosis. Prompt discontinuation of amiodarone and initiation of corticosteroid therapy resulted in clinical stabilization. This case underscores the insidious nature of amiodarone-induced adverse effects, particularly in the elderly population, and reinforces the critical necessity for a high index of clinical suspicion and vigilant, proactive monitoring strategies to facilitate early detection and appropriate management of this potentially life-threatening iatrogenic complication, even with standard therapeutic dosages.
Eccrine Hidrocystoma: A Clinical Image
Fatemeh Mehrabian
Emmanuel Odega

Fatemeh Mehrabian

and 2 more

June 05, 2025
A document by Fatemeh Mehrabian. Click on the document to view its contents.
Pond edge vegetation influences movement and spatial ecology in the Monkey leaf frog...
Guilherme Franco de Lima
Tiago dos Santos

Guilherme Franco de Lima

and 4 more

June 05, 2025
Understanding the spatial ecology of amphibians is essential for assessing the factors that shape population dynamics and habitat selection in heterogeneous, patchy populations. Monkey leaf frog (Phyllomedusa iheringii Boulenger, 1885) is endemic to the Uruguayan Savanna in Pampa of southernmost Brazil and Uruguay, an ecoregion threatened by habitat loss and fragmentation. This study investigated how breeding pond features influence displacement among ponds, breeding pond temporal occupancy, and abundance in P. iheringii. Field surveys were conducted over three reproductive periods (2018–2021) in 12 permanent ponds, using individual photo-identification to track individual movements. Our results indicate that the local abundance of individuals significantly influenced emigration rates, with higher densities associated with increased emigration, likely reflecting trade-offs between habitat availability and population density. The percentage of arboreal/shrubby edge vegetation was the strongest predictor of immigration and individual abundance, which in turn increased emigration rates from the pond. The strong influence of pond edge vegetation suggests that the dispersal of individuals relies on visual or chemical cues rather than acoustic conspecific attraction. Breeding pond temporal occupancy was higher in ponds with more individuals, possibly because of the mitigating effect of the abundance of individuals on deleterious stochastic effects. These findings indicate that movement and pond selection in P. iheringii are driven by a combination of local and social factors. The strong association between edge vegetation, abundance of individuals, and immigration rates highlights the importance of preserving edge vegetation to maintain resilient and connected populations.
Stigmasterol alleviates AML by impeding lipogenesis and cholesterogenesis via promoti...
Ye Zhang

Ye Zhang

June 05, 2025
Acute myeloid leukemia (AML) is one of the most common hematologic malignancies, thus large amounts of patients relapse and succumb to the disease. In this study, we investigated the effects of stigmasterol on leukemia both in vitro and in vivo. We identified a critical dependence of AML blasts on cholesterol for proliferation and morphogenesis. Stigmasterol treatment induced apoptosis and caused G1/S cell cycle arrest in leukemia cells. Furthermore, stigmasterol effectively suppressed AML progression in vivo. Mechanistically, stigmasterol supplementation resulted in reduced intracellular cholesterol levels, along with decreased expression of sterol regulatory element-binding protein 2 (SREBP2) and its downstream effectors. These findings indicate that stigmasterol inhibits leukemia cell proliferation and promotes apoptosis by disrupting SREBP2-dependent cholesterogenesis in leukemia cells. Collectively, our study reveals a crucial role for stigmasterol in suppressing AML progression through apoptosis induction and highlights the potential mechanisms of SREBP2-mediated abnormal cholesterogenesis in regulating AML.
Systematic ileostomy to avoid anastomotic leakage after posterior exenteration for ad...
Navid Mokarram Dorri
Clementine Bernard

Navid Mokarram Dorri

and 8 more

June 05, 2025
Objective: To compare the rate of anastomotic leakage in patients treated with posterior pelvic exenteration for advanced ovarian cancer, regardless of whether or not a systematic ileostomy was performed.. Secondary objectives include surgical and oncologic outcomes. Method: This is an observational retrospective, multicenter study comparing two cohorts of patients managed for advanced stage ovarian cancer in two French cancer centers, from January 2019 to February 2023. All patients underwent cytoreductive surgery with colorectal resection and immediate colorectal anastomosis. Protective ileostomy could be performed in a center (center A) whereas it was never done in the other one (center B). Results: A total of 122 patients were included (54 patients in center A and 68 patients in center B). Protective ileostomy was performed in 64,9% of cases in center A. All seven anastomotic leakage concerned center B (10.3%; p=0.017). Occurrence of complications between center A and center B are similar (p=0.65). Grade 3 complications were more frequent in center B. We observed higher rate of incomplete cytoreduction in center A (p=0.04). Survival analyses do not show significative difference between center A group and center B group, for OS (p=0,32) and DFS (p=0,41). Conclusion: Performing a protective ileostomy is an effective way to prevent anastomotic leakage in cytoreduction surgery of advanced ovarian cancer. However, there is no clear evidence in term of long-term oncologic outcome and a broad policy of this procedure exposes to specific morbidity that can negatively affect the patient’s prognostic.
Theory of C-Universe: revised Theory of Creation, a recursive-creation cipher
Bruno Wayne Salter

Bruno Wayne Salter

November 20, 2025
This paper presents the "Theory of C-Universe," a novel meta-theoretical framework proposing a unified, recursive mechanism for the universe's operation, from its origin to the emergence of life and its evolution. It posits that the universe possesses a fundamental spiral geometry, which is termed the "Universe Code" due to its resemblance to human DNA, dictating its evolution. After a Big Bang, the universe initially restarts with a slightly balanced distribution of matter and antimatter. This spiral geometry acts as the conduit through which dark energy expands, causing the observed curvature and contributing to the perception of higher dimensions. Within this spiraling expansion, black holes absorb more antimatter than matter, thereby creating a crucial imbalance of antimatter exceeding matter within the ultimate black hole. This observed matter-antimatter asymmetry in the universe is a prelude to this inverted, internal imbalance. The ultimate state-an antimatter-heavy, information-dense, spiraling singularity-triggers a recursive detonation. This true Big Bang is induced by intense spiraling momentum, the internal antimatter imbalance (leading to a quantum gravitational instability through highenergy fluctuation/pressure), and interference from pressure and gravity. This process ensures not all matter and antimatter are absorbed, preventing complete annihilation and allowing for a continuous, cyclical rebirth, characteristic of a "meta-asymmetry" where difference recurs in structure through evolution, not reset. Please, review "Hypothesis of the 5th Force of Physics"for updated content.
An estimation of population density of Punjab urial (Ovis vignei punjabiensis) at Kal...
Rizwan Hanif

Rizwan Hanif

June 05, 2025
A study on Punjab urial ( Ovis vignei punjabiensis) was conducted in Kalabagh Game reserve, during November 2024 to April 2025 to find out its population density and population estimation. Eleven potnetial sites namely; Jaba, Saran, Dheranwali, Rodhan, Drai, Sokan, Rodywali, Bandowali, Dargah, Herowali and Harnikalan were selected. The study conducte dwas based ib sample count technique and Line transect method as well as discussion with of the game reserve. The occurance was confirmed on these sites.Using the transect 60% of the total area was sampled and 532 Punjab urial were estimated with a population density of 8.9 animals/km2. The vegetation was analyzed from thr studied areaa and almost 32 plant speices were found: 15 trees and shrubs sepcies, 4 herbs species and 13 grass species. . Observed population and estimated population were compared by using Pearson ’ s correlation represented by r, the value of r was 0.9, that mean they statistical significant. Urial were abundant with god survival of lambs and yearlings rams during recent years and good survival or rams into older age classes.
When lack of cooperation in public health is the problem, is cocreation the solution?
Roar Amdam
Lena Waage

Roar Amdam

and 1 more

June 05, 2025
The article explores the concept of cocreation as a solution to the lack of cooperation in public health. It discusses the transformation of traditional health prevention and coordination of health services to health promotion and capacity building, involving the whole of society. The authors examine this shift from government to governance in Norwegian health system, highlighting the challenges and opportunities of network and partnerships. The article reviews different political governing regimes, including Traditional Public Administration, New Public Management, and New Public Governance, and their impact on health collaboration. The authors argue that cocreation, as part of New Public Governance, can address complex and dynamic problems by mobilizing relevant actors in collaborative processes. The article concludes that cocreation demands active public participation and clear national framing to ensure high capacity and legitimacy in health cooperation based on the New Public Governance regime.
Application of digital health in prenatal care in China: A scoping review
Xue Mei Fan
You Jing Jin

Xue Mei Fan

and 2 more

June 05, 2025
Purpose This study aims to explore the scope of application of digital health in pregnancy care in China, summarize the characteristics of digital health, and examine its effectiveness in improving maternal and infant health and health behaviours. Method The databases PubMed, CINAHL, PsycINFO, Cochrane library, EMBASE, and CNKI were searched using keywords “pregnant woman,” “digital health,” “obstetric care,” “China,” and their synonyms. The updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used as the guideline. The targeted information was narratively described using figures and percentages. Result The review included 49 publications. The targeted health problems included gestational diabetes mellitus, perinatal depression, infant feeding, urinary incontinence. WeChat, health mobile apps, short message services, and phone calls were found to be the most commonly used digital platforms. Digital-based health education, doctor patient interaction, and health monitoring were shown to be the most often used intervention methods. Digital interventions showed positive effects on blood glucose control, decreasing anxiety or depression symptom, and enhance medical care compliance, but most of these examined studies have risk of bias. Conclusion The application of digital health in pregnancy care in China is limited, having only been used to target a few common health problems. Aside from the traditional communication technologies such as mobile apps, and SMS, advanced technologies like artificial intelligence and virtual devices are rarely utilized. Digital interventions have demonstrated positive effects on some maternal health outcomes. Future research should explore the use of more advanced technologies to address more health problems.
Impacts of Fire Regime on Small Mammal Communities in California
Reina Warnert
Jessica Blois

Reina Warnert

and 1 more

June 05, 2025
California is considered a biodiversity hotspot based on its high species richness and endemism, and the considerable threats to the ecosystems that support these species. The Sierra Nevada region of California harbors much of the state's biodiversity, including unique small mammal communities which represent an important component of healthy ecosystems. Recently, the Sierra Nevada has experienced increasing amounts of climate change, drought, vegetation change, and alterations to fire regime. Small mammals are known to be sensitive to changes in climate and habitat. However, the long-term influence of these changes is poorly understood. In this study, we aim to understand the drivers of small mammal communities, with a focus on fire regime. We make use of historical surveys and resurveys from the Sierra Nevada, which provide high-quality species occurrence data from the last century. We compare richness and community turnover to fire regime, climate, and habitat variables using single- and multiple-variable linear regression. Results indicate that historic fire regime plays a key role explaining variation in modern small mammal richness across the Sierra Nevada. In the multivariate models, time since last fire and fire return interval significantly impact richness, and inclusion of these variables improve model fit compared to models with just climate and habitat. Additionally, time since last fire, number of fires and fire return interval have significant effects on small mammal community turnover. Overall, our work contributes knowledge of the factors influencing small mammal communities in an era of global change.
Existential Psychotherapy for Romantic Breakups: Human Universals, Cultural Specifics...
Jerrold Lee Shapiro
Shelly Kousnetz

Jerrold Lee Shapiro

and 1 more

June 05, 2025
As social animals, predictability in our primary relationships is essential. Loss of intimate connection is reliably related to loneliness, distress, anxiety, depression, guilt, shame, reduced self-esteem, and lower life-satisfaction. Romantic breakups may activate or exacerbate these symptoms. To underscore the depth of romantic breakups, musical lyrics are offered. Existential psychotherapy is specifically oriented toward experiences such as isolation, fears of the unknown, questions about lif3e meaning, and a balance between security and freedom needs. Existential psychotherapists primarily offer therapeutic intimacy and process empathy with clients in their here-and-now phenomenological worlds. Two foci of interventions are miscommunication and more complex structural readjustments. A client’s full experiential context is explored through three interlocking perspectives: human universals, cultural specifics, and individual subjective experience. The therapeutic context during romantic breakups includes clients’ culture of origin, and the contextual forces in the moment. A predictable sequence of relationship development and dissolution for individuals and couples in the process of breakups is offered, along with interventions at each escalation along with the somewhat non-linear process of post-breakup patterns of recovery. Considerations of romantic breakups within individualistic cultures are contrasted with those in collectivistic cultures, including those with arranged marriages, in first- and second-generation immigrants living in the United States. Unique, culturally-attuned therapeutic interventions are suggested.
Validation and Psychometric Evaluation of the Turkish Version of the Reward Deficienc...
Oğuz Peker
İrem Peker

Oğuz Peker

and 7 more

June 05, 2025
Objective: This study aimed to assess the validity and reliability of the Turkish version of the Reward Deficiency Syndrome Questionnaire (RDSQ-29), a scale designed to measure characteristics associated with reward deficiency syndrome, including activity, risk-seeking behavior, lack of sexual disfunction and social concerns. Methods: 481 participants completed the Turkish version of the RDSQ-29 along with related psychological scales. Confirmatory Factor Analysis was conducted to evaluate the scale’s factor structure. A bifactor model, comprising one general factor and four specific factors, was tested for suitability. Model fit was assessed using χ 2, RMSEA, CFI, TLI, and SRMR indices. Internal consistency was measured with Cronbach’s alpha, and test-retest reliability was evaluated a two-week interval. Pearson correlation analyses were performed for criterion validity. Results: The bifactor model demonstrated an acceptable fit (χ 2(362) = 1396.31, p < .001, RMSEA = 0.077, CFI = 0.916, TLI = 0.906, SRMR = 0.072). Factor loadings for the general factor ranged between 0.044 and 0.851, while subscale loadings varied. Although some items (RDSQ-1, RDSQ-2, RDSQ-23, and RDSQ-27) showed low loadings, they were retained following consultation with the original developers. The total scale showed strong internal consistency (α = 0.920), with subscale values ranging from 0.671 to 0.813. Test-retest reliability was high for the total score (r = .884) and subscales (r = .717 to .887). Significant correlations with impulsivity and anxiety supported the scale’s criterion validity. Gender differences were found, with women scoring lower on the total scale and the Lack of Sexual Satisfaction subscale, while men scored higher in the Social Concern and Risk-Seeking Behavior subscales. Conclusion: The findings indicate that the Turkish version of the RDSQ-29 is a valid and reliable tool for assessing reward deficiency syndrome and related traits. Study results support the use of the Turkish version of the scale in clinical and research contexts.
Fine-scale spatial genetic structure and leaf shape variation in five Fagaceae specie...
Rongle Wang
Yanjun Luo

Rongle Wang

and 6 more

June 05, 2025
Fine-scale spatial genetic structure (FSGS) refers to the pattern of spatial distribution of genetic variation at the local scale, which can indirectly estimate gene flow among individuals and reveal microevolutionary processes in plant populations. Although FSGS is important in explaining dispersal patterns and adaptive variation in plants, few studies have explored its potential application in species conservation strategies. In addition, phenotypic traits, particularly leaf shape, may also exhibit specific spatial variation patterns at fine scales. In this study, we investigated the genetic and leaf shape variation of two genus Quercus species (Quercus glauca Thunb. and Q. multinervis J. Q. Li) and three genus Castanopsis species (Castanopsis tibetana Hance, C. faberi Hance, and C. fargesii Franch.) in Wuyishan National Park in southeastern China. Using genetic markers, we found that Quercus species exhibited stronger FSGS and more limited gene flow than Castanopsis species, suggesting greater habitat fragmentation affecting local Quercus species. Leaf morphological analysis revealed inter-generic differences and partial overlap in leaf shape between Quercus and Castanopsis species, with the greatest variation observed in leaf area (LA) and leaf mass (LM). In addition, all five Fagaceae species exhibited significant diminishing returns, with C. fargesii showing the most pronounced effect and possessing the smallest leaves, which may enhance its adaptability to the harsh environments. Despite the leaf shape overlaps blurring species boundaries between Quercus and Castanopsis species, their genetic structure is remained clearly distinct. The observed differences in FSGS intensity and leaf shape variation between the two genera reflect their different environmental adaptability, offering new insights into the integration of genetic and phenotypic data for conservation planning.
A REVIEW ON EXPLAINABLE AI IN ProTEIN FUNCTION
Aastha Katiyar

Aastha Katiyar

June 05, 2025
The fast pace of incorporation of artificial intelligence (AI) in bioinformatics, though providing immense advantages, is frequently hindered by the fundamental opaqueness of ”black-box” models. The lack of transparency in predictive models is a significant drawback to the field, preventing the identification of underlying mechanisms that govern predictions, the deficiency of interpretability in these ”black-box” models greatly restricts credibility & applicability for protein design and optimization. This non-transparency prevents trust and slows down the creation of actionable results, especially in key areas like drug discovery, enzyme engineering and precision medicine. In response to this challenge, this review presents an overview on Explainable Artificial Intelligence (XAI) methods and their use in bioinformatics with emphasis on how such methods facilitate the gap between high predictive accuracy and biological interpretability. XAI is not just about understanding, but about accelerating discovery, building trust, and enabling responsible AI in biology. and unlocking a next generation of insight into protein function XAI is transforming protein function prediction from a black-box task into transparent results, bridging the gap between prediction and biological causality. We explored how explainable AI (XAI) is used in bioinformatics, especially for analyzing biological data like proteins and sequence-structure-function relationships. This review synthesizes insights from the growing significance of XAI in improving transparency, interpretability and accountability in protein function determination. Furthermore, will explore evolution around various machine learning and deep learning techniques in protein function prediction, emphasizing transformative role of XAI in enhancing interpretability and guiding future research. Although recognizing current challenges like data sparsity, model generalizability, and domain-specific interpretability gaps. we promote the creation of standardized benchmarks, hybrid knowledge-AI frameworks, and ethical guidelines to guarantee the reproducibility and fairness of predictive models. Finally, this review highlights the revolutionizing promise of XAI in bringing computational predictions closer to biological insight and thus opening the way toward scalable and reliable tools for functional genomics and personalized medicine alongside, it covers the practical application, challenging aspects of XAI that governs the process further. This helps researchers to navigate through the XAI methods and their implications.
Radiographic findings of candidate stallions presented for licensing at all German Wa...
Muriel Sarah Folgmann
Kathrin F. Stock

Muriel Sarah Folgmann

and 3 more

June 05, 2025
Background: Current studies on the health status of young German Warmblood stallions, which will probably shape future equestrian sport and horse-breeding, are lacking. Objectives: To evaluate the prevalences of radiographic findings at licensing examinations of Warmblood candidate stallions and quantify the influences of season of birth, age at licensing, year of licensing, and the evaluator on the distribution of recorded findings. Study design: Retrospective observational study. Methods: The records of 1693 radiographic examinations performed on 1678 German Warmblood stallions presented for licensing in 2018–2020 were reviewed. Data were provided by all German Warmblood horse-breeding associations and their official veterinarians. The collection and storage of the records were performed using the German equine health database. The influences of environmental effects (season of birth, age at licensing, year of licensing, evaluator) on main radiographic findings were determined using generalised linear models with a significance level of p < 0.05. Results: Overall, 71.4 % of the candidate stallions had remarks in their radiographic examinations protocols. However, the majority of the respective stallions had only single (49.8 %) or two (34.4 %) radiological findings. Main regions of the recorded findings were the proximal phalanx including the fetlock joint (25.3 %), the cannon bone (20.3 %), the navicular bone (17.2 %), and the hock (17.2 %). Specifically, radiopaque bodies in the fetlock joint, contour changes of the proximal phalanx and cannon bone, and changes of the navicular synovial invaginations were documented. The distributions of several radiographic findings differed significantly between evaluators. Main limitations: Homogenous study population and retrospective data. Conclusion: The majority of German Warmblood candidate stallions presented for licensing in 2018–2020 had radiographic findings recorded. The clinical relevance of several of these findings in clinically healthy horses remains uncertain. Follow-up evaluations could contribute to better risk assessment and are, therefore, recommended.
Scene-EEGCNN: Visualization of Zen Meditation Experience Based on EEG-Cultural Herita...
Hui Liang
Longfei Yang

Hui Liang

and 1 more

June 05, 2025
In the context of intensifying global cultural exchanges, Zen culture---emblematic of traditional Chinese heritage---has increasingly captured the attention of the modern world. Zazen, the fundamental practice of Zen, yet the emotional transitions experienced during Zazen are not easily discernible or representable. This study introduces a novel approach to portraying the internal experiences of practitioners by leveraging scenes inspired by Zen. Elements of Chinese cultural heritage, such as Buddhist sculptures, poetry, and landscape paintings, serve as a rich repository for crafting these Zen scenes. We propose a methodology that utilizes EEG data to analyze emotional shifts and correlates these findings with traditional Chinese cultural elements, employing virtual scenes to depict the emotional journey of a Zazen practitioner. Specifically, we present the Scene-EEGCNN algorithm, which captures and interprets EEG signals in real time to evaluate the practitioner's emotional state and internal dynamics. Given the challenge of externally recognizing the emotional shifts in a Zazen practitioner, our algorithm correlates the emotional data with specific facets of Zen culture, creating a virtual scene that intuitively portrays the practitioner's inner landscape. This technology enables them to share their Zen meditation experiences visually, thereby enhancing global cultural exchange.
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