Highly migratory sharks such as the shortfin mako ( Isurus oxyrinchus) undertake extensive oceanic movements that cross ecological and political boundaries. This wide-ranging behaviour increases their exposure to human impacts, primarily from fishing activities, as the species is frequently caught as bycatch in longline fisheries. Consequently, the shortfin mako is listed as Endangered globally and Critically Endangered in the Mediterranean Sea. Despite growing conservation concerns, knowledge of its population structure within the Mediterranean, and its genetic and ecological connectivity with the Atlantic Ocean, remains limited, hindering the development of effective management measures. We investigated the population structure and demographic history of shortfin mako across the Eastern Atlantic Ocean and Mediterranean Sea using double-digest restriction-site associated DNA (ddRADseq) sequencing on 66 individuals collected from six regions in the two areas. After sequence filtering, we retained 4349 neutral SNPs to assess population structure and demography. Our results indicated a single, genetically mixed population across the Eastern Atlantic-Mediterranean range, suggesting high connectivity and gene flow. Demographic analyses revealed a historically stable population size, although recent declines may not be detectable given the resolution of our genetic markers. While such connectivity may enhance resilience to localized pressures, it also implies that intense Mediterranean fishing could have population-wide consequences. These findings challenge the assumption of strong genetic isolation between basins but do not preclude demographic differentiation. Given that ICCAT currently treats the Mediterranean as a separate, data-poor stock, our results highlight the need for coordinated, basin-wide monitoring and management to safeguard this endangered species.

Severe postpartum inguinal neuralgia relieved by ultrasound‑guided nerve blocks: a case report

Key Clinical Message Arthroscopic synovectomy for severe hemophilic knee arthropathy revealed unrecognized microbleeding. Although a second surgery was required for catching symptoms, cartilage repair was confirmed, hemorrhage did not recur, and clinical symptoms improved.

The selection and optimization of drug leads is largely driven by equilibrium parameters such as IC50 values. However, this approach does not account for the time-dependence of drug-target interactions which is important given that drug and target concentrations fluctuate in the human body. A fundamental understanding of drug-target binding kinetics is particularly important when the formation and breakdown of the drug-target complex is slow compared to the rate of drug elimination and becomes critical when dealing with covalent drugs where the drug is irreversibly bound to the target. The parameters that define covalent inhibition, specifically kinact and KI, can be determined by quantifying target binding as a function of drug concentration and time. However, such assays are difficult to implement in early stages of drug discovery. Here, we review practical approaches to quantify irreversible inhibition including progress-curve kinetics, multi-timepoint IC50 fitting (EPIC) for scalable library triage, intact- and peptide-level mass spectrometry to confirm adducts and sites, label-free biophysics (SPR, NMR) for orthogonal validation, and washout/jump-dilution experiments to diagnose reversibility and measure residence time (τ). We then describe the translation of these microscopic rates to pharmacology through three system determinants: protein turnover, target vulnerability, and pharmacokinetics using case studies from BTK, JAK3, KRASG12C, and EGFR to illustrate how aligning chemistry with context yields durable efficacy. Finally, we propose reporting standards (IC50 with incubation time; kinact/KI; τ; turnover-driven occupancy) and a kinetics-first design paradigm to replace static potency with mechanism-anchored optimization of covalent inhibitors.

One of the most effective strategies for avian hosts to defend against brood parasitism is to reject the parasitic egg from the focal nest. However, much of the variation in egg-rejection frequency between individuals remains unexplained. A precondition for egg ejection is recognizing the parasitic egg. Hosts may potentially improve recognition accuracy by augmenting inspection frequency and time to facilitate comparative assessment between foreign and conspecific eggs. In this study, we investigated the relationship between egg inspection and egg-rejection propensity in the Daurian redstarts Phoenicurus auroreus, a common host of the common cuckoo Cuculus canorus. After adding a foreign cuckoo egg model, redstarts spent longer time inspecting and inspected it more often. Moreover, females more frequently and spent more time inspected it when inspecting the parasitic egg were more likely to recognize the foreign egg. Our results thus demonstrate that the inspect eggs facilitates the host’s ability to recognize the foreign egg. Keywords: Cuckoo parasitism, Daurian redstart, egg inspection, egg recognition, egg rejection

A document by Mohammd Rahimi. Click on the document to view its contents.

Anion exchange membrane (AEM)-based CO2 electrolyzers powered by renewable energy provide a promising pathway for a sustainable CO2-to-CO conversion. However, they suffer from CO2 crossover via the formation of (bi)carbonates, limiting carbon utilization to 50%, and electrolyte-driven salt precipitation, which shortens device lifetime. A forward-biased bipolar membrane (BPM) addresses these issues by operating with pure-water and regenerating CO2 at the bipolar junction. Nevertheless, instability of the bipolar interface, lower faradaic efficiency, and high cell potential remain open challenges. Here, we present a BPM incorporating a porous anion exchange layer (AEL) to facilitate CO2 release out of the bipolar junction. Two BPM configurations are compared with porous or dense AEL deposited either onto a silverbased gas diffusion electrode (GDE) or onto the CEM. Porous AEL-coated GDEs achieved enhanced stability, lower cell potentials, and partial current densities for CO up to 214 mA cm-2 at 3.25 V. Implementation of this BPM architecture reduces CO2 crossover by at least 80% compared with an AEM-based electrolyzer, although CO2 losses to the anode persist, highlighting the need for further optimization. These findings establish porous AEL-coated GDEs as a promising strategy for advancing BPM CO2 electrolysis.

A document by Nishchal Regmi. Click on the document to view its contents.

A giant cervical decidual polyp in pregnancy managed with lactoferrin, probiotics, and ligation: A case reportSatoshi Yoneda1, Noriko Yoneda1, Masami Ito1, Kanto Shozu1, Tatsuhiro Tsuda1, Kazushige Sugie2, Akitoshi Nakashima11Department of Obstetrics and Gynecology, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan2Clinical Laboratory and Transfusion Medicine & Cell Therapy Center, Toyama University HospitalAddress correspondence to: Satoshi Yoneda, M.D., Associate Professor, the University of Toyama, 2630 Sugitani, Toyama, 930-0194, JapanTel.: +81-076-434-7357Fax: +81-076-434-5036E-mail: s812yone@med.u-toyama.ac.jp

Ancestry-associated immune signalling differences in atopic dermatitis and dupilumab treatmentDuan Ni1,2,3,4, Ralph Nanan1,2,3*1 Sydney Medical School Nepean, The University of Sydney, Sydney, NSW, Australia2 Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia3 Nepean Hospital, Nepean Blue Mountains Local Health District, Sydney, NSW, Australia4 Sydney Infectious Disease Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia*Correspondence:Ralph Nananralph.nanan@sydney.edu.auSydney Medical School Nepean, The University of Sydney.Nepean Hospital, Level 5, South Block, Penrith NSW, 2751, AustraliaTelephone: +61 2 4734 1614Fax: +61 2 4734 1144

AI-based solutions offer the potential for rapid taxonomic identification of species of biosecurity concern, enhanced global accessibility, and time-saving in contrast to traditional taxonomic identification by humans. 2. This study provides a systematic approach to the application of deep learning for biosecurity surveillance, using the Asian House Gecko (AHG), Hemidactylus frenatus, Schlegel, 1836, as a case study. An effective triage tool was developed using machine learning for rapid initial identification of this invasive species, with the tool achieving a high degree of accuracy. This demonstrates the efficacy of deep learning for identifying complex morphological characteristics. 3. The AI model used the AHG’s head as a key identifying feature, highlighting the importance of specific morphological features for effective identification of target species. 4. A structured approach for the use of machine learning was developed, which included the collation of source images, cataloguing, tagging, naming, and storing images, validating and uploading images, labelling images, creating, training, and deploying the model, testing model accuracy, and retraining the model. 5. This procedure allows for more rapid application of the methodology in biosecurity surveillance. The structured methodology developed can be applied to similar AI-based projects. Synthesis and applications 6. Outcomes of this research have the potential to reduce the time delays associated with taxonomic identification of invasive species, allowing follow-up action to occur sooner. Reducing time delays is critical for the implementation of effective biosecurity measures.

Against conventional wisdom we have recently shown that sucrose a “non-volatile” compound can reach the retro nasal olfactory region and effect perception, when aerosolized. This suggests other “non-volatile” sweet tastes might also be processed via retro nasal pathways challenging the “non-Volatile” taste assumption that pure tastes are only processed via oral pathways. Stevia is a sweet taste commonly used to replace sugar in food products. Knowing if stevia also activate retro nasal pathways could help us understand how to modulate sweet tastes to improve low calorie food acceptability. We examined the neural activity to stevia with a nose clip on (blocking retro nasal pathways) and nose clip off, in robust sample of healthy adults (N=34, mean 25 yrs.). Neural activity to stevia was reduced with the nose clip on in the olfactory cortex, hypothalamus, the subgenual and pregenual anterior cingulate, and the nucleus accumbens. Stevia pleasantness was tracked by the posterior insula, bitterness by the amygdala and mouth fullness by the olfactory cortex but these were either not apparent with the nose clip on or much weaker. In conclusion, our findings are the first to demonstrate that blocking retro nasal pathways significantly reduces neural responses to stevia taste supporting the proposal that retro nasal pathways play a role in the perception of “non-volatile” tastes like stevia, and that stevia sweetened products could be made more palatable via retro nasal pathways.

Bone defect repair remains a significant challenge in clinical orthopedics, primarily due to the limitations of traditional techniques, such as insufficient osteogenic efficiency and non-functional bone regeneration. Recently, the regulation of energy metabolism has emerged as a promising avenue for bone regeneration. This review systematically examines the critical yet underexplored role of energy metabolism in bone regeneration, focusing on the dynamic regulatory mechanisms in osteoblasts and bone marrow mesenchymal stem cells across various metabolic pathways, and clarifies the influence of glucose metabolism and mitochondrial function on cellular proliferation and differentiation. Besides, three complementary strategies are proposed: leveraging cell derivatives (e.g., mitochondria, exosomes) to provide metabolic support; employing active factors (e.g., ions, enzymes) to target key metabolic pathways; and designing biomimetic scaffolds to reconstruct a favorable metabolic microenvironment. Furthermore, deficiencies in current research—such as the lack of systematic analysis of metabolic networks, clinical validation, and multidisciplinary collaborative innovation—are noted. Future directions should explore the interplay between metabolism and epigenetics, the development of responsive metabolic regulatory materials, and advancements in clinical translation, ultimately advocating for a new paradigm in precise bone defect repair to significantly enhance patient outcomes.

A document by Jean Michel Hovsepian. Click on the document to view its contents.

Case reportProsthetic rehabilitation of atrophic maxilla by extrasinus zygomatic implants: An illustrative case reportNabina Miya a, Bikal Ghimire a,*, Bidhan Shrestha baKantipur Dental College Teaching Hospital & Research Center, Kathmandu University, Basundhara, Kathmandu, Bagmati, NepalbDepartment of Prosthodontics, Kantipur Dental College Teaching Hospital & Research Center, Kathmandu University, Basundhara, Kathmandu, Bagmati, Nepal

Article type : Case Images, Clinical Case ReportsTitle : Linear supravenous hypopigmentation four months after intralesional triamcinolone for tendinitisAuthors : Emily Ames, B.B.A.,1 Victor Huang, M.D., F.A.A.D.1,2Institutional Affiliations :1. Kirk Kerkorian School of Medicine at UNLV, Las Vegas, Nevada2. University of California, Davis, Department of Dermatology, Sacramento, CACorresponding Author : Victor Huang, MDUniversity of California, Davis, Department of Dermatology3301 C Street, Suite 1400Sacramento, CA 95816Office Phone : 916-551-2600Fax : 916-442-5702Email address : vtrhuang@ucdavis.eduReprint Requests : Victor Huang, MDWord count : 489Reference count : 3Figure count : 2Key words : linear hypopigmentation, perilymphatic hypopigmentation, injection site adverse effectsAcknowledgements : Authors would like to acknowledge their respective departments for their support and guidance.Statement of Data Availability: No datasets were generated for this case image.Statement of Funding Sources : This article has no funding source.Statement of Conflicts of Interest : The authors have no conflict of interest to declare.Statement on any Prior Presentation : This case has not been published previously.Statement on Patient Consent : The patient in this manuscript has given written informed consent to publication of their case details.Statement on Permission to Reproduce Material : No previously published material has been reproduced in this manuscript.

Title: “Formulation Breakthroughs Driving Broader Tyrosine Kinase Use”Dear editor, Huntjens et al. reported an AI-based model developed to predict the risk of reduced gastrointestinal (GI) absorption and bioavailability (F) for tyrosine kinase inhibitors (TKIs) in patients with altered GI conditions. Various strategies to enhance absorption, reduce first-pass extraction, and improve bioavailability was proposed¹. While their work provides valuable predictive tools for identifying pH-dependent absorption challenges with conventional TKI formulations, it underscores the urgent need for modern and improved oral dosage forms that eliminate rather than manage, these GI absorption challenges through patient behavioral modifications.The strategies they presented include dissolving tablets in cola (acid), implementing precise timing protocols with acid reducing agents (ARAs), split-dosing regimens, and/or pharmacokinetic (PK) boosting with enzyme inhibitors (CYP 3A4)¹. While these approaches may improve F, they impose significant behavioral burdens that compromise long-term adherence. Studies indicate that >90% adherence significantly improves the probability of achieving major molecular response2⁻4, yet real-world adherence is already suboptimal5. Requiring patients to source specific beverages, implement complex dose timing intervals, or manage additional medications adds complexity that may affect other treatments, particularly in patients with several comorbidities and in the elderly population.A more rational and sustainable approach to improve several therapies with TKIs is based on innovative oral dosage forms and overall product performance that ensure predictable and consistent plasma exposure regardless of many GI conditions, which is key to optimize long-term efficacy and safety6. Drugs from BCS classes II and IV are very sensitive to highly dynamic changes of GI luminal conditions during fasted and fed states, GI comorbidities that causes hypo- and achlorhydria, and drug-drug interactions (DDIs) with ARAs7-12. By eliminating pH-dependent variability at the formulation level, it is expected to maintain simple dosing regimens and support high adherence rates. Improving GI absorption of lipophilic basic BCS class II and IV drugs with low and pH-dependent solubility typically requires an enabling formulation strategy13, 14. One such strategy is the use of amorphous solid dispersions (ASDs), which improve the luminal solubility and subsequent intestinal absorption of lipophilic and basic TKIs15-17The highly variable plasma exposure may compromise therapeutic efficacy or increase the risk for adverse effects due to subtherapeutic or excessive drug levels, respectively, depending on how the dosing schedule is set6.Formulating TKIs as ASDs can mitigate inter- and intraindividual variability in plasma exposure, reduce the risk of DDIs with current and future ARAs, and limit food-drug interactions15, 18, 19. Other examples include the maleate salt of acalabrutinib in an oral formulation to overcome the limitations of the free base, and an oral dosage form with palbociclib, which incorporates succinic acid as a pH-modifying excipient to enhance absorption during elevated gastric pH20, 21. These examples clearly demonstrate that it is the dissolution properties of the finished dosage form that determines the GI absorption and plasma exposure-time profile for most BCS class II TKIs.A successful formulation can also enable lower doses. Higher oral doses and high plasma exposure may increase adverse events, contributing to dose discontinuation and suboptimal adherence6, 22. Therefore, a consistent drug plasma exposure with lower doses is crucial in TKI therapy. Non-adherence, often caused by tolerability issues and regimen complexity, remains key factors for treatment success. Studies indicate that >90% adherence significantly improves the probability of achieving major molecular response2-4. This high adherence is even more crucial in real-world patients, as they are more likely to discontinue TKIs due to adverse events than patients in clinical trials5.While Huntjens et al. provide valuable predictive tools and describe intervention strategies for managing pH-dependent GI absorption with conventional formulations¹, the future of achieving optimal TKI therapy lies in pharmaceutical innovation that eliminates the need for complex patient behavioral modifications. Formulation advances such as ASD technology offer a more accessible, scalable, and patient-centered solution than strategies requiring special beverages, precise timing protocols, or pharmacokinetic boosting. These formulation innovations should be prioritized as first-line approaches, while behavioral interventions should be reserved to rescue and critical circumstances, where pH-independent formulations are not yet available.Looking forward, the future of TKI therapy lies not only in better molecules but also in smarter oral drug delivery systems. As the CML treatment paradigm shifts toward optimizing long-term disease control and patient quality of life, novel formulations will play a pivotal role in driving improved outcomes across broader patient populations, also those with other cancer diagnoses.

Pressure sensors are essential for acquiring real-time information that directly influences the performance and safety of modern engine control systems. However, developing pressure sensors that can operate reliably at high temperatures remains a formidable challenge due to the lack of stable sensing materials. Here, we report a novel polymer-derived SiHfBCN ceramic coating exhibiting outstanding pressure-sensing behavior and remarkable thermal stability at elevated temperatures. The SiHfBCN coating was fabricated on sapphire substrates through a preceramic polymer route and subsequently pyrolyzed at various temperatures up to 1500 °C. The amorphous ceramic film features a nanodomain structure composed of amorphous SiHfBCN and crystalline HfC(N) nanoparticles together with in-situ forms carbon ribbons, which provides excellent electrical and mechanical stability. The optimized coating demonstrates a high gauge factor K of up to 42.000, excellent repeatability, and stable signal response under cyclic compression, maintaining its performance up to 1300 °C. These results highlight the potential of SiHfBCN ceramics as next-generation materials for high-temperature pressure-sensing applications.