Allergic diseases such as asthma, atopic dermatitis and food allergies are a burgeoning health challenge in the Asia-Pacific region. Compounding this, the region has become increasingly susceptible to the impacts of climate change. The region has weathered extreme precipitation, intense heat waves, and dust storms over the recent decades. While the effects of environmental and genetic factors on allergic diseases are well understood, prevailing gaps in understanding the complex interactions between climate change and these factors remain. We aim to provide insights into the various pathways by which climate change influences allergic diseases in the Asia-Pacific population. We outline practical steps that allergists can take to reduce the carbon footprint of their practice on both a systemic and patient-specific level. We recommend that allergists optimise disease control to reduce the resources required for each patient's care, which contributes to reducing greenhouse gas emissions. We encourage the responsible prescription of metered dose inhalers by promoting the switch to dry powder inhalers for certain patients, at each clinician's discretion. We also recommend the utilisation of virtual consultations to reduce patient travel while ensuring that evidence-based guidelines for rational allergy management are closely adhered to. Finally, eliminating unnecessary testing and medications will also reduce greenhouse gas emissions in many areas of medical care.

Staphylococcus aureus, one of the most notorious pathogens, develops antibiotic resistance by formation of a thick layer of exopolysaccharides known as biofilms. Sortase A, a transpeptidase responsible for biofilm formation and attachment to the host surface, has emerged as an important drug target for development of anti-virulence agent. A number of sortase A inhibitors, both peptide and non-peptides are reported which involved the use of several experiments which may provide insights regarding binding affinity, specificity, safety and efficacy of ligands. In this review, we focus on the principles, pros and cons, and the type of information obtained from biophysical (FRET assay, Microscale Thermophoresis, Surface Plasmon resonance, CD spectroscopy etc.) and biological (Cell viability assay, biofilm formation assay, CLSM, Western blot analysis, in vivo characterization on mice etc.) methods for estimation of probable sortase A inhibitors, which might be helpful to the researchers who might be interested to delve into the development of sortase A inhibitors as a drug, to address the burning question of Anti-microbial Resistance (AMR).

Warming climate impacts aquatic ectotherms both directly, by altering individual vital rates, and indirectly through environmental feedbacks and declines in body size, a phenomenon known as the temperature-size rule (TSR). However, understanding the relative importance of these effects in shaping community responses to environmental change remains limited. We employ a tri-trophic food chain model with size- and temperature-dependent vital rates and species interaction strengths to explore the role of direct kinetic effects of temperature and TSR on community structure along resource productivity and temperature gradients. We find that community structure, including the propensity of sudden shifts, is primarily driven by the direct kinetic effects of temperature on vital rates and thermal mismatches between the consumer and predator species, overshadowing the indirect effects through the TSR. Overall, our study enhances the understanding of the complex interplay between temperature, species traits and community dynamics in aquatic ecosystems.

CHRONIC VIRAL INFECTIONS AND AL AMYLOIDOSIS: AN UNCOMMON ASSOCIATION

Biosensors are valuable tools in accelerating the test phase of the design-build-test-learn cycle of cell factory development, as well as in bioprocess monitoring and control. G protein-coupled receptor (GPCR)-based biosensors enable cells to sense a wide array of molecules and environmental conditions in a specific manner. Due to the extracellular nature of their sensing, GPCR-based biosensors require compartmentalization of distinct genotypes when screening production levels of a strain library to ensure that detected levels originate exclusively from the strain under assessment. Here, we explore the integration of production and sensing modalities into a single Saccharomyces cerevisiae strain and compartmentalization using three different methods: (1) cultivation in microtiter plates, (2) spatial separation on agar plates, and (3) encapsulation in water-in-oil-in-water double emulsion droplets, combined with analysis and sorting via a fluorescence-activated cell sorting (FACS) machine. Employing tryptamine and serotonin as proof-of-concept target molecules, we optimize biosensing conditions and demonstrate the ability of the autocrine screening method to enrich for high producers, showing the enrichment of a serotonin-producing strain over a non-producing strain. These findings illustrate a workflow that can be adapted to screening for a wide range of complex chemistry at high throughput using commercially available microfluidic systems.

1. Introduction Ongoing climate change poses an increasing threat to biodiversity. To avoid decline or extinction, species need to either adjust or adapt to new environmental conditions or track their climatic niches across space. In sessile organisms such as plants, phenotypic plasticity can help maintain fitness in variable and even novel environmental conditions and is therefore likely to play an important role in allowing them to survive climate change, particularly in the short term. Understanding a species’ response to rising temperature is crucial for planning well-targeted and cost-effective conservation measures. 2. Methods We sampled seeds of three Hypericum species (H. maculatum, H. montanum, and H. perforatum), from a total of 23 populations originating from different parts of their native distribution areas in Europe. We grew them under four different temperature regimes in a greenhouse to simulate current and predicted future climatic conditions in the distribution areas. We measured flowering start, flower count, and subsequent seed weight, allowing us to study variations in the thermal plasticity of flowering phenology and its relation to fitness. 3. Results Our results show that individuals flowered earlier with increasing temperature, while the degree of phenological plasticity varied among species. More specifically, the plasticity of H. maculatum varied depending on population origin, with individuals from the leading range edge being less plastic. Importantly, we show a positive relationship between higher plasticity and increased flower production, indicating adaptive phenological plasticity. 4. Synthesis The observed connection between plasticity and fitness supports the idea that plasticity itself may be adaptive. This study underlines the need for information on plasticity for predicting species’ potential to thrive under global change and the need for studies on whether higher phenotypic plasticity is currently being selected for as natural populations experience a rapidly changing climate.

Objective It is often recommended that, in children with bilateral epistaxis, only one side of the nasal septum should be cauterised at a time in order to reduce the risk of septal perforation. This advice may have been reasonable when hot wire electrocautery was in common use. The risk of septal perforation after silver nitrate cautery is unknown but probably low. Methods Retrospective casenote review of children attending the nurse-led epistaxis clinic between 2019 and 2022. Results Nine hundred and twenty children were seen in the nurse-led clinic between January 2019 and December 2022. Six hundred and one children (79%) underwent nasal cautery. Simultaneous bilateral nasal cautery was carried out in 176 (29%) children. Our follow up period ranged between 303 days and 1,744 days, with a median of 809.5 days. No child presented to emergency or ENT services with septal perforation or any other complication of simultaneous bilateral nasal cautery. Conclusion To the author’s knowledge, this is the largest study assessing the safety of simultaneous bilateral nasal cautery with silver nitrate in children. No adverse results have been found after cauterising both sides of the septum at the same sitting, and doing so potentially saves time and money for patients and the health service.

This work explores technical challenges and potential methodologies for understanding electrochemical Reactive CO2 Capture (RCC) mechanisms. RCC offers potential energy cost advantages by directly converting captured CO 2 into fuels and chemicals, unlike traditional carbon capture and utilization (CCU) processes that require sequential capture, concentration, and compression. However, direct conversion of captured CO 2 introduces complexity due to additional equilibrium buffer reactions, making it challenging to identify active species for reduction in electrochemical studies. This work discusses methods to integrate transport, thermodynamics, and kinetics concepts to identify active carbon sources in RCC. Vapor-Liquid Equilibrium (VLE) and transport models are validated against experimental results obtained in a gastight rotating cylinder electrode reactor and are shown as useful tools for studying RCC in heterogeneous electrocatalysts across different capture agents, solvents, and temperatures. This work establishes an experimental framework for advancing research in electrochemical RCC.

This research involved designing and building an interactive generative AI application to conduct a comparative analysis of two advanced Large Language Models (LLMs), GPT-4 and Claude 2, using Langsmith evaluation tools. The project was developed to explore the potential of LLMs in facilitating postgraduate course recommendations within a simulated environment at Munster Technological University (MTU). Designed for comparative analysis, the application enables testing of GPT-4 and Claude 2 and can be hosted flexibly on either AWS (Amazon Web Services) or Azure. It utilizes advanced natural language processing and retrieval-augmented generation (RAG) techniques to process proprietary data tailored to postgraduate needs. A key component of this research was the rigorous assessment of the LLMs using the Langsmith evaluation tool against both customized and standard benchmarks. The evaluation focused on metrics such as bias, safety, accuracy, cost, robustness, and latency. Additionally, adaptability covering critical features like language translation and internet access, was independently researched since the Langsmith tool does not evaluate this metric. This ensures a holistic assessment of the LLM’s capabilities.

Background: Thrombocytopenia is a common hematologic finding in children and adolescents. Immune thrombocytopenia (ITP) is the most common cause of this finding, but the differential diagnosis includes a growing list of genetic disorders. We aimed to report differences in phenotypes of patients with ITP, inherited platelet disorder (IPD)/primary immunodeficiency disorder (PID), and other causes, with a focus on differentiating ITP from inherited thrombocytopenia. Procedure: This retrospective, population-based observational cohort from 2006 to 2020 involved 506 Finnish children under 16 years of age presenting with isolated thrombocytopenia. Results: Of the 506 participants, 79.7% had ITP, 6.7% had IPD/PID, and 13.6% had other causes of thrombocytopenia. A platelet count of ≤12 × 10 9/l best distinguished between ITP and other reasons with a sensitivity of 60% and a specificity of 80%. Among patients with the lowest platelet count of <10 × 10 9/l, 95.9% had ITP, 3.3% had IPD/PID, and 0.8% had other causes. Severe bleeding events were reported in 20 patients (4.0%), but there were no cases of intracranial or fatal bleeding due to thrombocytopenia. Up to 50% of patients with a high suspicion of inherited thrombocytopenia remained without a specific diagnosis despite genetic testing. Conclusions: ITP remains the most common cause of thrombocytopenia. A platelet count of ≤12 × 10 9/l often leads to an ITP diagnosis. Genetic disorders are rare but should be suspected in patients with persisting thrombocytopenia, especially with platelet counts constantly above 12 × 10 9/l, a positive family history, or atypical clinical features.

Crystallographic fragment screening (CFS) has recently matured into an important method for the early stages of drug discovery projects. It is based on high-throughput structure determination and thus requires a high degree of automation as well as specialized workflows and robust analysis tools. Consequently, large-scale research facilities such as synchrotrons have embraced the method, and developed platforms to perform CFS campaigns with the help of crystallography experts and specific tools. The BESSY II synchrotron, operated by the Helmholtz-Zentrum Berlin (HZB), is one of these synchrotron facilities that offer a CFS platform, named the F2X-facility. Here, the specialized F2X workflow is described along with the relevant differences to other existing CFS platforms, and the ongoing developments aimed at supporting users of the facility. The different stages of a CFS campaign including requirements, beamline capabilities, and the software environment are detailed and explained. A unique F2X-GO kit is featured, which allows users the possibility of performing all sample preparation in their home laboratories. Furthermore, at the HZB a computational workflow has been built to support users beyond the hit identification stage. The advantages of the F2X-facility at HZB are described and references are provided to successfully conduct CFS.

Photobiomodulation (PBM) has emerged as a potentially effective therapeutic approach to modulate cellular functions. This study aimed to examine the impact of PBM on reactive oxygen species (ROS) and lipid peroxidation, and glutathione-related antioxidant defense systems in rabbit eye tissues. A polychromatic light source with an intensity of 2.6 J/cm 2/min was used for PBM treatment in New Zealand White rabbits for 12 minutes. The PBM group (n=8) received treatments every two days for a total of twelve sessions, while the control group (n=8) did not undergo any PBM light exposure during the same period. The application of PBM significantly elevated ROS-mediated glutathione levels, along with increased activities of glutathione peroxidase and reductase, particularly in corneal tissue ( p ≤ 0.05). In conclusion, these findings could enhance understanding of PBM’s therapeutic potential for eye health and lead to new strategies for preventing or treating ocular diseases caused by oxidative stress.

Objective: Exploring the evolving geographical distribution pattern of Tetracentron sinense and its main influencing factors since the last interglacial can provide a scientific foundation for the efficient conservation and administration of the species. Methods: The MaxEnt model was used to construct the potential distribution areas of T. sinense in different periods such as the last interglacial, the last glacial maximum, the Mid-Holocene, the current and future. On the premise of discussing the influence of dominant environmental factors on its distribution model, the suitable area changes of T. sinense under different ecological climate situations were quantitatively analyzed. Results: The AUC value predicted by the optimized model was 0.959, indicating a good predictive effect by the MaxEnt model; the potential suitable areas for T. sinense in the current are mainly located in southwest China, which are wider compared to the actual habitats. Jackknife testing showed that the lowest temperature in the coldest month, elevation, seasonal variation coefficient of temperature and surface calcium carbonate content are the dominant environmental factors affecting the distribution of T. sinense. From the last interglacial to the current, the total suitable area of T. sinense showed a decreasing trend; the distribution points of T. sinense populations in Mid-Holocene may be the origin of the postglacial population, and Southwest China may be its glacial biological refuge. Compared with the current, the total suitable area ranges of T. sinense in China in the future decreased, and the centroid location of its total fitness area all migrated to the northwest, with the largest migration distance in 2070s under the SSPs 7.0 climate scenario. Conclusion: Temperature was the most important factor affecting the distribution of T. sinense. With the global warming, its suitable area ranges will show a shrinking trend. Ex-situ conservation measures could be taken to preserve its germplasm resources.

OBESITY AS A MISLEADING FACTOR IN THE DIAGNOSIS OF TYPE 1 DIABETES MELLITUS: A CASE REPORTOlgierd Dróżdż1, Wiktoria Bińczyk1, Bartosz Siudek2, Katarzyna Błaszczyszyn1, Filip Jan Grajnert3, Michalina Zofia Grzelka3, Maciej Rabczyński11Department and Clinic of Diabetology and Internal Medicine, University Teaching Hospital, Wrocław, Poland2T. Marciniak Specialist Hospital, Wrocław, Poland34th Military Clinical Hospital, Wrocław, PolandCorresponding author: Wiktoria Bińczyk, [email protected]:Olgierd Dróżdż, Medical [email protected] and Clinic of Diabetology and Internal Medicine, University Teaching Hospital, 50-556 Wrocław, PolandWiktoria Bińczyk, Medical [email protected] and Clinic of Diabetology and Internal Medicine, University Teaching Hospital, 50-556 Wrocław, PolandBartosz Siudek, Medical [email protected]. Marciniak Specialist Hospital, 54-049 Wrocław, PolandKatarzyna Błaszczyszyn, Medical [email protected] and Clinic of Diabetology and Internal Medicine, University Teaching Hospital, 50-556 Wrocław, PolandFilip Jan Grajnert, Medical [email protected] Military Clinical Hospital, 53-114 Wrocław, PolandMichalina Zofia Grzelka, Medical [email protected] Military Clinical Hospital, 53-114 Wrocław, PolandMaciej Rabczyński, Medical [email protected] and Clinic of Diabetology and Internal Medicine, University Teaching Hospital, 50-556 Wrocław, Poland

5-methylcytosine (m 5C) is a widely known epigenetic moderation in RNA types. Methyltransferases catalyze the genesis of m5C. This site of RNA plays a crucial role in many biological activities. For many years in DNA, the synthetic process and biological role of m 5C sites have remained the concentrating domain for researchers. Recently, many characters of RNA m 5C sites have been discovered, but it is still considered in their infancy. The accurate and systematic detection and classification of m 5C remains a challenging task. The existence of m 5C sites shows a thriving role in numerous organic activities. Machine learning techniques are alternatives to laboratory experiments, which will ease the m 5C site’s identification in Homo sapiens. This article presents a novel computational model named m 5C-TNkmer to extract RNA sequences. The model is enriched with the k-mer feature extraction technique. Four subdatasets of the primary data set are created: DNC, TNC, tetra-NC, and penta-NC. The results highlighted that m 5C-TNKmers achieved 96.15% accuracy. The suggested technique is a talented one that will help scientists correctly identify RNA m 5C sites and their modification. It provides a clue to better understanding genetic function and controlling roles.

Mechanopharmacology is an emerging interdisciplinary field that investigates drug action using biomechanically appropriate in vitro systems to the relevant (patho)physiology. This review outlines emerging technologies and techniques which aim to bridge the gap between mechanical cues influencing cellular biology and conventional pharmacology. We delve into the impact of mechanopharmacology on drug development in cancers and fibrotic diseases. Mechanical cues such as stretch, stiffness, circadian rhythms, fluid flow, intercellular signalling cascades and cytoskeletal structures can modulate drug interactions with molecular targets with implications for drug discovery and development. Models incorporating mechanopharmacological cues to investigate pharmacokinetics, pharmacodynamics and therapeutic outcomes are outlined. Furthermore, this review discusses innovations in the use of biomaterials and microfluidics, to enable further the emulation of the mechanical microenvironment. We advocate for the application of mechanopharmacological considerations to improve the physiological relevance of methods used in the drug discovery pipeline.

A Case Report of Metformin-Associated Lactic Acidosis (MALA)

Title PageSurgical repair of a giant unruptured left sinus of Valsalva aneurysm in an older patientShinichi Oki1, Hirotaka Sato21,2Department of Cardiovascular Surgery, Shin-Oyama City Hospital, 2251-1 Hitotonoya Oyama City, Tochigi, 323-0827, Japan