Background and Purpose: Human mesenchymal stem cells (MSCs) show promise for treating ischaemic and inflammatory conditions, yet their clinical utility is limited by a failure to replicate preclinical efficacy. We hypothesized that dual priming of human bone marrow-derived MSCs (hBMSCs) with interleukin-1alpha (IL-1α) and cobalt chloride, CoCl 2 (a hypoxia mimetic) would potentiate their therapeutic efficacy for hypoxic-ischaemic conditions. Experimental Approach: hBMSCs were primed individually or in combination. Their conditioned media (CM) was analysed for relevant secreted biomolecules. To test the anti-inflammatory and cytoprotective properties, primed-hBMSCs-derived CM was applied to LPS-treated BV2 microglial cells ( in vitro inflammation model) and BV2 cells exposed to oxygen glucose deprivation (OGD) ( in vitro hypoxic injury model). The neuroprotective effect was evaluated by assessing neuronal death (using NLCs) following exposure to OGD/reoxygenation (OGD/R) in the presence of various CMs. Key Finding: Priming significantly altered hBMSCs’ secretion profiles. IL-1α triggered significant ( p<0.05) release of inflammatory mediators/cytokines, notably TNF-α, ICAM-1, and G-CSF. Except for G-SCF, dual-priming did not potentiate the release of these inflammatory molecules. However, while single priming with either IL-1α or hypoxia did not induce remarkable secretion of the neurotrophins β-NGF and BDNF, the dual-priming resulted in significant ( p<0.05) and additive secretion of these neurotrophins. In the LPS model, CM from dual-primed hBMSCs significantly reduced the secretion of pro-inflammatory cytokines, TNF-α and IL-6. In the hypoxia model, priming did not significantly influence the marked reduction ( p<0.05) of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Lastly, CMs from primed hBMSCs significantly (p<0.05) reduced neuronal cytotoxicity, yet only CM from dual-primed hBMSCs significantly (p<0.05) preserved the viability of NLCs following 24 h reperfusion after OGD. Conclusion: Dual priming of hBMSCs with both hypoxia and IL-1α significantly enhanced their therapeutic potential for managing hypoxic-ischemic conditions and offers a promising strategy for developing more effective cell-based therapies for ischaemic stroke.

Early detection of severe patient deterioration through continuous home monitoring: Insights from two WARD-HOME cases

Rhizosphere-associated microbiota can contribute to functioning of agroecosystems. The insect-pathogenic fungus Metarhizium is an important component of this microbiota and can contribute to the suppression of insect pests, potentially reducing the need for agricultural inputs. We examine the species composition of Metarhizium in a coffee agroecosystem, sampling isolates from rhizosphere and associated soils of five groups of plants. Coffee, trees and spontaneous monocotyledons harboured the greatest density of Metarhizium and species. Five Metarhizium species were revealed by 5'TEF DNA sequences, being M. robertsii isolated in all the groups of plants and soil. Considering its high prevalence, it may be important in strengthening interactions between soilborne fungi and natural enemies of pests within agroforests. Metarhizium pemphigi was the second most abundant species and was isolated mostly from coffee roots, indicating a potential ecological specialization of this fungus colonising coffee plants. We observed a great abundance and diversity of Metarhizium in plant roots, suggesting that a diversified agroecological system may foster this diversity and benefit from these fungi playing varied roles in the rhizosphere and soil. In particular, native M. pemphigi could be investigated as an inoculant in coffee as it appears to be capable of establishing persistent associations with the plant.

Visualizing Groundwater Dynamics in VR: From Animated Rendering to Interactive and Immersive Experiences of the Landscape Evolution Observatory, Biosphere 2Seongyoon Woo1, Ji Eun Yang1, Aaron Bugaj2, Ash Black3, Richard Gin4, Siyoon Kwon5,Hannes H. Bauser6, Peter A. Troch7, Minseok Kim1*1 Department of Civil Engineering, Pusan National University, Busan, ROK2Biosphere 2, The University of Arizona, Tucson, AZ, USA3College of Information Science, The University of Arizona, Tucson, AZ, USA4Department of Electrical and Computer Engineering, The University of Arizona, Tucson, AZ, USA5Department of Civil and Infrastructure Engineering, Gyeongsang National University, Jinju, Gyeongsangnam-do, ROK6Department of Geoscience, University of Nevada, Las Vegas, NV, USA7Department of Hydrology and Atmospheric Sciences, The University of Arizona, Tucson, AZ, USA*Corresponding Author: Minseok Kim (minseok.kim@pusan.ac.kr)

Abstract Despite its widespread application in public financial management reforms across low- and middle-income countries, programme-based budgeting (PBB) implementation often remains relative superficial. The technical weaknesses of the reform have been widely documented; however, the political economy dynamics around the introduction and implementation of PBB in the health sector have not been studied. This comparative case study analysis of seven low and middle-income countries (Burkina Faso, Cameroon, Ghana, Kenya, Peru, Philippines, and South Africa) aims to unpack the political economy drivers of PBB reform in the health sector. The study draws from a global literature review, as well as documentary reviews and expert interviews in each of the seven study settings. Findings describe the policy processes relating to PBB introduction and implementation in the health sector, and provide a detailed, comparative stakeholder mapping and political economy analysis. This describes the position of the key actors in relation to PBB reform in health, which is explained by their interests and how PBB reform would impact them, and how they used their power to affect the PBB reform processes in health. Our analysis identifies political dynamics, processes and narratives that can be strategically leveraged to better inform PBB implementation in the health sector. It also underscores how the insights from PEA can help to advance budgeting reforms in the health sector as part of overall health financing reforms in support of UHC agenda in low and middle-income settings, which experience has shown do not lend themselves to technical solutions alone.

Adaptations of coexisting species to climate-driven environmental changes might not necessarily lead to extinctions, but rather to trait variations that generate new competitive hierarchies in ecosystems. Top predators have a pivotal role as indicators or even generators of high biodiversity in ecosystems, but effects of climate change on top predators have not been sufficiently explored. We used long-term data on the territory and breeding dynamics of two coexisting, ecologically similar and closely related forest raptors, the temperate zone Tawny Owl (Strix aluco) and the boreal zone Ural Owl (S. uralensis), in an area that has experienced significant climate change (>1°C mean temperature increase) but not habitat change in the last 20 years. We analysed long-term population dynamics of both species along an altitudinal gradient by measuring changes in territory overlap and nest displacement rate as well as effects on species breeding productivity and body size. As a result of concurrent population growth and range expansion, we observed a gradual intensification of competition for space and nest sites, including direct nest displacement of the smaller Tawny Owl by the larger Ural Owl. We observed that breeding Ural Owl females became significantly larger in shared territories with Tawny Owls compared to those in unshared territories. From an evolutionary-ecological perspective, this size disparity could bolster the Ural Owl’s dominance over the Tawny Owl. However, it could also pose long-term risks for the Ural Owl, as the advantages of larger size come with increased energy demands and reduced hunting agility. This study highlights that, beyond theoretical model predictions, robust long-term monitoring data are urgently needed to capture the actual changes taking place due to the effects of global warming and to reveal the hidden and trait-based adaptations of coexisting species and unforeseen drivers of extinction.

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A document by Linh Ton. Click on the document to view its contents.

A document by Emmanuel Siddig. Click on the document to view its contents.

TitleFetal growth restriction and left ventricular cardiomyopathy associated with a derivative chromosome 15: 46,XX,der(15)t(7;15)(q33;q26.2)

Studying the stability, steady-state behavior, and transient responses of stochastic delay differential equations presents significant numerical challenges. The Monte Carlo method, commonly used to estimate statistical properties, relies on averaging over numerous simulated trajectories. While straightforward, this approach is computationally intensive and often slow to converge, especially when estimating higher-order moments. We propose a more efficient and accurate alternative: a direct integration framework for the mean square dynamics of the system. The presented Mean Square Direct Integration (MSDI) method is based on the Euler-Maruyama scheme and directly captures the evolution of second-order moments, such as variance and standard deviation. This enables the assessment of fluctuations around the mean trajectory without computing an ensemble of sample paths. Numerical experiments demonstrate that MSDI achieves higher accuracy at significantly lower computational cost than traditional Monte Carlo simulations.

Trypanosoma equiperdum is a protozoan parasite recognized as the etiological agent of dourine, a debilitating and often fatal venereal disease that affects only equids. Dourine has historically exerted a substantial impact on equine populations globally, influencing both animal health and the socio-economic stability of communities reliant on equids for transportation, agriculture, and cultural activities. Unlike most pathogenic trypanosomes, which require invertebrate vectors for transmission, T. equiperdum is transmitted directly through coitus between infected and susceptible animals. This unique transmission mode has shaped the epidemiology and control strategies for dourine, distinguishing it from other trypanosomoses. This review consolidates current knowledge on Trypanosoma equiperdum, integrating recent research to provide an updated understanding of its taxonomy, biology, pathogenesis, diagnosis, treatment, control, epidemiology, and socio-economic impact.

Title pageA Novel Missense Mutation of COL7A1 Gene in Dominant Dystrophic Epidermolysis Bullosa, PruriginosaZhixin Zheng1,2, Jiaojiao Zhong1,2, Wen Dong1,2, Huifei Yang3, Ming Zeng1,2, IDDepartment of Dermatology, The Sixth Affiliated Hospital, Sun Yat-sen University, No.26, Road yuancun-er-heng, Guangzhou 510655, ChinaBiomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, No.7, Road Xingdao-huan-bei, Guangzhou 510000, ChinaDepartment of Pathology, Fuda Cancer Hospital，No. 2, Road tangde-xi, Guangzhou, 510000, ChinaCorresponding Author: Ming Zeng, Department of Dermatology, The Sixth Affiliated Hospital, Sun Yat-sen University, No.26, Road yuancun-er-heng, Guangzhou, 510655.Email: zengm55@mail.sysu.edu.cnTel: 86-20-38254127

IntroductionLynch syndrome (LS), which was known as hereditary non‑polyposis colorectal cancer (HNPCC), is present in 1 in 279 people around the world. It is the most common hereditary cause of colorectal cancer (CRC) and cause about 2–4% of all CRC cases (1). It results from a germline pathogenic (P) or likely pathogenic (LP) variant in one of the DNA mismatch repair (MMR) genes, MLH1, MSH2, MSH6, or PMS2, or in the EPCAM gene. these deletions cause MSH2 inactivation (2, 3). Data from hereditary cancer registries show that specific MMR gene variants are associated with different cancer risks. The most malignancies that are associated to LS are cancers of the colon, rectum, endometrium, ovary, stomach, renal pelvis, ureter, bladder, small intestine, pancreas, skin (particularly sebaceous neoplasms), biliary tract, and brain (4). Besides, multiple reports from hereditary cancer registries and institutional series describe rare or atypical tumor types that occurre in the context of LS (5).LS‑associated malignancies are characterized by deficient DNA mismatch repair (dMMR), which results in a high level of microsatellite instability (MSI‑H) and an elevated tumor mutational burden (TMB). Molecular assays assessing MSI status and MMR protein expression are routinely used to detect MSI‑H/dMMR phenotypes (6). MSI‑H tumors, in the context of LS or sporadically, show distinct biological and clinical behavior compared with microsatellite‑stable (MSS) tumors. it makes them appropriate candidates for immunotherapy and other emerging targeted strategies (7). In contrast to LS‑related colorectal cancers, sporadic MSI‑H CRCs are typically associated with somatic BRAF V600E mutations or MLH1 promoter hypermethylation (8). These molecular features are clinically useful for distinguishing germline‑associated dMMR from sporadic dMMR colorectal cancers (8).Pancreatic neuroendocrine tumors (P‑NETs) are a subtype of gastroenteropancreatic neuroendocrine neoplasms (GEP‑NENs) that arise from the hormone‑secreting cells of the pancreatic neuroendocrine system and represent the second most common form of pancreatic neoplasm (9). Although most P‑NETs occur sporadically, a subset develops in association with hereditary cancer predisposition syndromes such as multiple endocrine neoplasia type 1 (MEN1), von Hippel–Lindau (VHL) syndrome, tuberous sclerosis complex (TSC), and neurofibromatosis type 1 (NF1) (10). Neuroendocrine tumors are uncommon in Lynch syndrome, and the combination of Lynch syndrome with a pancreatic neuroendocrine tumor (P-NET) has been only sporadically reported (9, 11); however, a definitive causal association is still vague. We report a case of a young woman with MLH1‑related LS who presented with primary colon adenocarcinoma and a non‑functional metastatic P‑NET involving the liver.

A document by Setareh Tavakkolijebelli. Click on the document to view its contents.

A document by Zhiyu Liu. Click on the document to view its contents.

INTRODUCTIONFemale genital Tuberculosis (FG-TB) is an important but often overlooked cause of infertility.(1) However, there is paucity of epidemiological and clinical data on FG-TB.(2) Thus, FG-TB prevalence remains difficult to estimate because patients remain asymptomatic and undiagnosed.(3) Reports in developed countries like USA, Australia and Western European countries suggested an incidence of less than 1% in developed countries but up to 15 – 19% in developing countries, specifically 17% and 6 - 21% in Nigeria and South Africa respectively.(4) FG-TB is usually spread hematogenously from the lungs or through lymphatic circulation or directly through contiguous organs like the bowels to the genital regions of females.(5) Diagnosis remains challenging due to the paucibacillary nature of genital specimens and the limited sensitivity of microscopy and culture.(6) As a result, hysteroscopy and histopathology are crucial instruments for recognizing necrotizing granulomatous inflammation and detecting distinctive intrauterine alterations.(7) In Ghana, reports of FG-TB remain scarce, and documentation of hysteroscopic diagnosis is virtually absent. This case report highlights the need for increased clinical suspicion in TB-endemic areas by providing what appears to be the first Ghanaian instance of hysteroscopically suspected and histologically confirmed FG-TB in a woman presenting with infertility and amenorrhoea.

A document by Nadia Bhuyain. Click on the document to view its contents.