Background and Purpose: Toll-like receptor 4 (TLR4) polymorphisms, dysregulated enteric neuro-glia network, and dysmotility have been observed in patients with Crohn’s Disease (CD) and related experimental animal models. However, the poorly understood pathological role of TLR4, combined with the absence of effective therapies for CD-associated gastrointestinal motor disorders, highlights the need for a deeper morpho-functional characterization of the underlying neuropathy. Experimental Approach: Male C57BL/6J (WT) and TLR4 -/- mice (10±2 weeks old) received intrarectally a single dose of 2.5% DNBS. After eight days, pro-inflammatory cytokines’ mRNA levels and histological anomalies were measured in ileal samples. Gut motility and ileal contractility were evaluated by changes in fluorescent-labelled dextran transit and by neuromuscular responses of ileal full-thickness to receptor/non-receptor-mediated stimuli, respectively. Enteric nervous system (ENS) neuroglial network was determined by confocal immunofluorescence microscopy in longitudinal muscle-myenteric plexus whole-mount preparations. Key Results: DNBS-induced ileitis led to prolonged gastrointestinal transit, reduced excitatory neuromuscular responses, accompanied by reactive gliosis, neurodegeneration and increased infiltration of IBA1 + macrophages in the ENS of WT mice. TLR4 deficiency elicits a protective effect towards DNBS-mediated damage on the morpho-functional integrity of ENS by modulating excitatory cholinergic and tachykinergic neurotransmissions as well as counteracting neuroglial alterations. An altered 5-HT-mediated neuromuscular response and 5-HT 4R transcripts were identified during ileitis which was reversed by TLR4 deficiency. Conclusion and Implications: These outcomes reveal TLR4 signaling as a potential therapeutic target for addressing ENS-immunity axis anomalies, implicated in CD onset/progression.

Abstract

Title PageDr Joseph McGeary6 St Johns,Sandymount,Dublin 4D04 K6R9

A document by Fazeela Bibi. Click on the document to view its contents.

A case report of HIV-associated pituitary lymphoma and review of the literatureKey Clinical Message: Acute hypopituitarism with abnormal enhancing lesions of the hypothalamic pituitary on imaging requires consideration of the possibility of pituitary lymphoma. A definitive diagnosis requires histopathology.Abstract: Primary saddle region tumours are most commonly pituitary adenomas: they account for more than 90% of all saddle region tumours. Primary central nervous system lymphoma (PCNSL) lesions are relatively rare and are usually found around the ventricles. Reports of PCNSL lesions located in the saddle region are even rarer. This article reports on a 33-year-old man with a PCNSL. The primary lesion was in the pituitary-pituitary stalk-papillary body and was detected by magnetic resonance imaging after an acute endocrine abnormality associated with cavernous sinus syndrome. Initially, he presented with malaise, nausea and vomiting with double vision. Endocrinological tests suggest anterior pituitary hypopituitarism and secondary hypothyroidism, gonadal and adrenocortical hypopituitarism. Combined head MRI showed a pituitary stalk-pituitary enhancement lesion with invasion of the right cavernous sinus and loss of high signal in the MRI T1WI sequence in the posterior pituitary lobe. Initial hospital visit was considered non-bacterial inflammatory pituitary lesions and methylprednisolone was sequenced. After treatment, the patient’s malaise and malignant vomiting improved, and there was no significant change in visual double vision. Repeat MRI suggested a slightly reduced pituitary enhancement lesion. The above symptoms worsened again after 2 weeks of hormone withdrawal. Repeat MRI examination showed recovery of high signal in the T1WI sequence of the posterior pituitary lobe and enlargement of the pituitary space-occupying lesion with large necrosis and stroke. The pituitary stalk and papillary body enhancement were not significantly altered. After correction of cortisol, thyroid hormone and other abnormalities, endoscopic pituitary occupancy resection was performed and postoperative pathology showed B-cell-derived lymphoma.Keywords: pituitary gland; lymphoma; hypopituitarism; HIV

Rare Acinetobacter soli infection presenting as a BEHCET disease relapse: a case reportRadinasoa RP1*, Rakotonirainy OH2, Solofoniaina MH1, Rakotonirina LN2, Vololontiana HMD1, Rapelanoro Rabenja F31 Departement of Internal Medecine, University of Antananarivo Faculty of Medecine, Antananarivo, Madagascar2 Departement of Rheumatology, University of Antananarivo Faculty of Medecine, Antananarivo, Madagascar3 Departement of Dermatology, University of Antananarivo Faculty of Medecine, Antananarivo, MadagascarCorresponding author: Rajo Païdia Radinasoa, Departement of Internal Medecine, University Hospital of Antananarivo, Antananarivo, Madagascar. paidiaradinasoa@gmail.com

Correspondence : Leisheng Wang（wlsh1005@163.com）

IntroductionLeishmaniasis is a diverse group of infectious diseases, caused by Leishmania parasites1,2, intracellular protozoan parasites3, transmitted by female phlebotomine sand flies.3–5 Leishmaniasis is endemic in the Middle East and Mediterranean countries, although more than ninety percent of cases occur in Bangladesh, India, Nepal, and other countries.6 It has various clinical forms (mainly cutaneous, mucosal, or visceral), the most severe form is visceral leishmaniasis (VL).6 VL is also known as kala-azar or Black disease. It is a tropical and subtropical parasitic disease, also prevalent in poor communities where care is lacking.5VL is reported in over 70 countries, and it has become an endemic disease in more than 60 countries.4 There are two species of leishmania that cause VL: L. donovani in the Old World, including Asia, Africa, and Europe, and L. infantum (L. chagasi) in Latin America, Iran, Pakistan, and the Mediterranean countries (Syria).2,5–7 The infection may be asymptomatic or an oligosymptomatic illness that either resolves spontaneously or evolves into active kala-azar.3 Common Clinical symptoms of the disease include: prolonged fever, weakness, loss of appetite, and hepatosplenomegaly.4 Laboratory results, including pancytopenia and hyperglobulinemia.3,4 The gold standard for diagnosis of VL is bone marrow aspiration, lymph node aspiration, or spleen biopsy.4 All patients with VL should receive therapy with anti-leishmanial drugs, the pentavalent antimony compounds or amphotericin B.4 The importance of our clinical case comes from the similarity of the disease to other diseases, the difficulty of diagnosing it, and its sometimes being overlooked, and the fact that early diagnosis and treatment are the two main measures to control leishmaniasis.

To address the uncertainty in determining the optimal spherical base curvature radius ( SR) for tapered roller bearings, this study develops dynamic and friction torque models under combined loading conditions to evaluate three SR configurations (0.85 ρ p, 0.90 ρ p, and 0.95 ρ p, where ρ p denotes the inner rib’s curvature radius) in terms of load capacity, friction losses, and operational precision. The results demonstrate that: (1) the 0.85 ρ p configuration minimizes friction by optimizing the contact zone’s fV parameter under combined loads, making it ideal for low-friction applications; (2) the 0.95 ρ p design achieves superior operational accuracy; while (3) the intermediate 0.90 ρ p value provides an optimal compromise between friction torque reduction and operational precision. These findings establish quantitative guidelines for SR selection based on specific bearing performance requirements.

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Abstract: Background: Table tennis (TT) is an increasingly investigated intervention for supporting cognitive, motor, and psychosocial functions in older adults with neurodegenerative diseases, including Alz-heimer’s disease (AD), Parkinson’s disease (PD), and dementia. However, evidence remains fragmented, and the effect sizes and reliability of TT-based programs remain unclear. Materials and Methods: Following PRISMA 2020 guidelines, a systematic search of four databases (PubMed, Scopus, Web of Science, SPORTDiscus) was conducted through March 2025. Ten studies met inclusion criteria, with five eligible for quantitative synthesis. Random-effects meta-analyses (DerSimonian–Laird) were performed on cognitive and motor outcomes. Risk of bias was assessed using the JBI checklist, and certainty of evidence was graded using the GRADE framework. Results: Meta-analysis revealed large effects for cognitive outcomes (MMSE: d = 1.44; MoCA: d = 1.31), motor function (UPDRS-III: d = 1.27), and dual-task gait (TUG: d = 0.93), with low-to-moderate heterogeneity (I² = 18–42%). Sensitivity analyses confirmed the robustness of pooled effects. GRADE evaluations indicated moderate certainty. No serious adverse events were reported. Conclusions: Table tennis appears to be a safe, feasible, and effective non-pharmacological intervention for enhancing cognitive and motor outcomes in individuals with AD, PD, and dementia. Further high-quality trials with standardized protocols and mechanistic endpoints are needed to confirm these findings and expand clinical applicability.

Abstract Objective: This study investigates the effectiveness of an 8-week structured cognitive and social skills training program in improving cognitive function, communication, and functional independence among individuals with traumatic brain injury (TBI) in Qatar. The goal is to assess the program’s impact on real-world reintegration and quality of life, contributing to evidence-based rehabilitation strategies in this population. Method: A retrospective analysis was conducted on clinical data from TBI patients aged 15–65 who were admitted to the Adult Day Rehabilitation Unit at Qatar Rehabilitation Institute between January 2022 and December 2024. All participants demonstrated cognitive and communication impairments and completed a multidisciplinary rehabilitation program that included individualized speech-language and occupational therapy. Outcome measures included the Montreal Cognitive Assessment (MoCA) for cognitive function, Functional Communication Measures (FCMs) for communication and social interaction, and the Functional Independence Measure (FIM) for overall functional status and return-to-work or school outcomes. Data were collected at baseline, mid-intervention, post-intervention, and follow-up. Results: Post-rehabilitation assessments showed significant improvements across all outcome domains. Participants demonstrated measurable cognitive gains (MoCA), enhanced communication and social function (FCMs), and greater independence (FIM), with many successfully reintegrating into work or academic environments. Conclusions: The findings support the efficacy of integrated cognitive-social rehabilitation for TBI patients, highlighting the benefits of collaborative sessions between speech-language pathologists and occupational therapists. The program demonstrated real-life functional gains, reinforcing the value of multidisciplinary interventions in promoting recovery and social reintegration post-TBI.

The breakout of African swine fever virus have severely impacted food safety and public health . Here, a point-of-care testing method based on solvent-responsive magnetic beads suitable for large-area diagnosis and mutation screening in remote areas was developed to detect it by combining bioluminescenct pyrophosphate in real-time technology and recombinase-aid amplification technology. The combined testing method included selection of different dATP modification structures and DNA polymerases. The method was conducted on plasmids of African swine fever virus at various concentrations. Based on above, the detection device was developed and achieved detection in real-time. The detection limit was around 10 copies, with no cross-reaction of nucleic acid samples from other viruses. Then it was applied on clinical samples and showed good specificity and detection efficiency. Moreover, this method was also compatible with a digital testing method and digital point-of-care testing devices based on bioluminescent pyrophosphate in real-time and recombinase-aid amplification including a digital detection RAA-BART device and a mobile phone shell (based on bionic hydrogel) were developed here. Finally, the sensitive of them were tested and showed a comparable detection limit of single copy.

The digital domain has become a core battleground where nation-state cyber actors increasingly deploy sophisticated Advanced Persistent Threats (APTs). This paper explores their Tactics, Techniques, and Procedures (TTPs), evaluating the efficacy of existing cyber defense frameworks. Drawing from well-documented campaigns-APT28's DNC breach, APT10's Operation Cloud Hopper, and Lazarus Group's WannaCry ransomware this study applies the MITRE ATT&CK and Cyber Kill Chain frameworks to map and analyze adversarial operations. Findings underscore widespread use of stealthy, persistent TTPs leveraging phishing, living-off-the-land techniques, and supply chain compromise. The analysis identifies critical defense gaps in detection, response, and attribution. The paper proposes strategic recommendations including AI-driven behavioral detection, Zero Trust Architecture, and enhanced intelligence-sharing frameworks to improve cyber resilience against evolving state-sponsored threats. The digital landscape has profoundly transformed into a critical domain of conflict, with nation-state cyberattacks posing an escalating and sophisticated threat to global stability and national security. This paper comprehensively investigates the Tactics, Techniques, and Procedures (TTPs) employed by state-sponsored Advanced Persistent Threat (APT) groups and critically evaluates existing defense mechanisms. Utilizing a qualitative, analytical, and interpretivist research design, the study dissects prominent campaigns, including APT28's DNC Hack, APT10's Operation Cloud Hopper, and the Lazarus Group's WannaCry ransomware attack, through the structured lenses of the MITRE ATT&CK framework and the Cyber Kill Chain. Findings reveal the pervasive use of stealth-oriented and persistent TTPs, such as sophisticated spearphishing, credential theft, and exploitation of unpatched vulnerabilities, often leveraging legitimate system functionality and supply chain dependencies. The analysis highlights critical defense gaps, including detection delays, patching failures, and persistent attribution challenges. Importantly, this study reinforces the hypothesis that the consistent use of structured cybersecurity frameworks contributes significantly to effective threat management, particularly MITRE ATT&CK for threat behavior mapping and Zero Trust Architecture for defense implementation, demonstrably enhances detection, attribution, and mitigation capabilities against these evolving threats. Based on these insights, actionable strategic recommendations are proposed, advocating for AI-driven behavior-based detection, robust threat intelligence sharing, and advancement of international cyber norms, thereby contributing to a more proactive and resilient global digital ecosystem.

The mating-type locus of the miso and soy sauce yeast Zygosaccharomyces sp. contains a gene encoding the transcription factor Mat a2 (hereafter ZygoMat a2), which has a DNA-binding domain containing a high mobility group (HMG)-box not found in the baker’s yeast Saccharomyces cerevisiae. To investigate the role of ZygoMat a2 in mating-type a expression, we constructed mutant strains of ZygoMAT a2 using CRISPR-Cas9. The resulting mutants showed reduced expression of ZygoSTE6, which is specific to mating-type a, and did not mate, suggesting that ZygoMat a2 regulates the expression of mating-type a in Zygosaccharomyces sp. Expression of ZygoSTE6 was observed when the HMG-box of ZygoMat a2 was exchanged with that of Mat1-Mc, which regulates mating-type expression in Schizosaccharomyces pombe, indicating that ZygoMat a2 recognizes its target DNA sequence via the HMG-box. Substitution of the predicted upstream activation sequence (UAS) in ZygoSTE6 with the UAS of a mating-type a-specific gene from another yeast species led to mating-type a-specific gene expression in transformed Zygosaccharomyces sp. yeast, indicating that ZygoMat a2 can recognize the UAS of mating-type a-specific genes of other species. We speculated that the flexibility in the binding sequences of ZygoMat a2 is due to synergistic or cooperative binding with the DNA-binding protein ZygoMcm1. This hypothesis was supported by replacement of the UAS of ZygoSTE6 with the complete palindrome sequence, P(PAL), and by the results of protein and DNA structure prediction using AlphaFold. Collectively, our study indicates that ZygoMat a2 regulates mating-type a-specific gene expression via its HMG-box, which shows flexible recognition of the binding sequence of other HMG-box transcription factors.

What a state: why the U.S. is still bad for your health (policy)Calum Paton, Emeritus Professor of Public Policy, School of Social, Political and Global Studies, Keele University, U.K.AbstractThe second Trump administration’s centrepiece legislation, the modestly-named Big Beautiful Bill, passed by the House of Representatives and going through the Senate at time of writing, offers an opportunity to reflect upon how the U.S. state affects health policy and the prospects for equitable access to affordable healthcare. Is the U.S. still an outlier (by comparison with Europe and much of the world), in that its many of its citizens are either uncovered, poorly covered or tenuously and only temporarily covered by health insurance? The answer is yes. And the chipping away at Obamacare and Medicaid by Trump 2.0 (learning from his failure to repeal Obamacare in 2017) as part of the Big Beautiful Bill, shows us that it is easier for the Right to dismantle progressive social legislation than it is for the Liberal-Left to assemble it.To understand why, and to revisit why the U.S. polity struggles to enact progressive healthcare reform, we have to understand the effect of the U.S. state (i.e. political structure) upon public policy. This article revisits the nature of that state, to depict the underlying causes of ‘American exceptionalism’ which are partly ideological but also more significantly institutional than often realised.Key Words : Trump; Obamacare, the U.S. state; conservative bias; political institutions v ideology

High-performance lithium-sulfur batteries capable of stable operation under extreme environmental conditions have garnered significant scientific interest, though critical challenges persist regarding insufficient polysulfide conversion kinetics at subzero temperatures and persistent shuttle effects at elevated temperatures. While crystalline materials dominate current high-capacity electrode design, their intrinsic structural anisotropy typically induces lattice strain and structural degradation during electrochemical cycling. This study presents an engineered two-dimensional heterostructure combining amorphous molybdenum sulfide (MoS3) with reduced graphene oxide (MoS3-rGO), demonstrating dual functionality through robust polysulfide chemisorption and enhanced catalytic activity. When implemented as a sulfur host, the composite enables lithium-sulfur batteries with high specific capacity (1263 mAh g-1 at 0.2 C), exceptional rate performance (645 mAh g-1 at 5 C) and cycling stability (remaining 642 mAh g-1 after 800 cycles at 2 C) under room temperature conditions. The configuration achieves remarkable areal capacity of 9.7 mAh cm-2 even under high sulfur loading of 8.8 mg cm-2 and lean electrolyte conditions of 5.5 μL mg-1. Notably, the as-constructed two-dimensional architecture demonstrates unprecedented temperature adaptability, maintaining stable operation across a wide thermal spectrum (-25°C to 70°C), thereby addressing critical barriers to real-world implementation in extreme environments.

This note shows why geodesic domes are the most efficient buildable way to enclose space. They approximate the sphere—the shape with the least surface for a given volume—using rigid triangular panels you can actually fabricate. As subdivision increases, material use approaches the theoretical minimum and member strength scales favorably.

Software architectural design is one of the most important elements impacting software systems. Successfully running systems at scale has become a primary focus in the field of software engineering and computer science, given the unprecedented levels of data and users demanded by IoT, machine learning, user generated content, and increasing software complexity. All of these changes require specific attention and particular tools and approaches, however, certain elements can be identified as common and considered state of the art in regards to architecture. This paper presents a systematic review of both academic literature and widely referenced industry publications to identify and evaluate architectural patterns and practices for scalable and resilient systems. The objective of this review is to extract key architectural components, methods, and patterns that are extensible, repeatable, and problem-agnostic while addressing challenges posed by modern demands such as IoT, machine learning, and big data. By employing a systematic review methodology, we address the following research questions: (1) What are the architectural properties essential for data-intensive systems? (2) What patterns and practices are most effective for achieving scalability and resilience? (3) How do industry guidelines and real-world implementations align with academic insights? The review results combined with the other knowledge we present provide support for recommendations for designing data-intensive systems.

Software agents and multi-agent systems are critical components in the development of distributed autonomous systems, as they exhibit a wide range of “intelligence”, from reactive behaviours to advanced reasoning and planning. Integrating these capabilities into multi-agent systems enables distributed artificial intelligence, a programming paradigm in which autonomous entities work together efficiently across a network to achieve shared goals. Another important aspect we consider in this work is represented by the disruptive impact of 5G technology, which is moving computation to the edge of the network. As a result of this shift, embedded devices with microcontrollers – which are renowned for their low power consumption and limited computing power – have proliferated. This paradigm fits in well with the small cooperating entities scattered across the network in this situation but, at the same time, it is difficult to provide agent platforms for embedded devices, though. Indeed, the most recent state-of-the-art MAS platforms, which are primarily Java-based, raise issues with microcontroller speed and memory overhead. To achieve this goal, we designed and implemented an ecosystem, entirely written in C++, to create multi-agent systems in an actual Internet of Things setting. Our ecosystem is compounded by Democle, a logic/declarative agent programming framework, and Hermes, a unified wireless network interface, both specifically created for embedded systems. In this paper, we describe our ecosystem’s functionality, architecture, and benefits of use. In addition, we provide a case study and a few experiments to prove how our platform works and its efficiency in terms of overhead.

Large carnivores are considered necessary for the maintenance of biodiversity and ecosystem services, i.e. benefits provided to humans. However, bears do not always fit the definition of carnivores in their habitat, having divers foraging strategies. The results of this literature review supported the crucial role played by all bear species in providing a diverse array of ecosystem services. While bears from North America and Europe have been extensively studied, species from South America and Southeast Asia have received relatively less attention. The main benefits derived from bears encompass recreation and cultural value, while also contributing to biodiversity maintenance through seed dispersal and forest shaping as ecosystem engineers. However, knowledge gaps persist regarding the ecosystem services provided by bears with tropical distributions. The economic impact of the Ecosystem services provided by bears is reported in a minority of works, with limited transferability, but globally recreation revenues largely exceed those related to hunting. Limitations such as resource constraints, social dynamics, and restricted access to remote areas call for future more interdisciplinary research in general and especially on tropical bear species.

Author:Rupesh NandiIndependent ResearcherORCID: https://orcid.org/0009-0003-0511-5296Email:  rupeshnandi330@gmail.comDate of Completion: June 10, 2025

Where human-wildlife conflicts lead to illegal persecution, wide ranging impacts for recovering predator populations can ensue. They may include reducing vital rates such as reproduction as well as survival. Illegal activities and their impacts are difficult to quantify. Nonetheless, often linked to gamebird shooting management, illegal persecution of raptors notoriously occurs in the UK, in detriment to several species’ distributions and abundance. How its impact varies with population density deserves more study. We examined the impact of persecution proxies on reproductive traits of northern goshawks Accipiter gentilis in northern UK. We found no evidence of an effect of the persecution proxies or of rainfall on goshawk reproduction. However, there was a strong negative density-dependence effect on productivity. Despite the impact of persecution on reproduction being certainly underestimated in our data, the overall growth of the goshawk population indicates that it at least partially compensated for prevailing persecution levels. The observation that goshawks produced more chicks in low density neighbourhoods must have contributed to this compensation. Our study extends previous work by elucidating the spatial scale of density-dependence. This suggested that density effects extended beyond typical nearest neighbour distances, implying that individuals may be interacting and interfering with a wider section of the population than previously thought. Should the population continue to increase in size, density-dependence will probably play an increasing role in population regulation.

Giant Frontal Sinus Mucocele with Headache and Vision Changes: Case ReportSujan Ghimire1, Ritika Bhatta2, Yagya Raj Sharma1, Vitasta Muskan3, Alok Dahal31 Maharajgunj Medical Campus, Institute of Medicine, Maharajgunj, Kathmandu, Nepal2 Nepal Medical College and Teaching Hospital, Jorpati, Kathmandu, Nepal3 BP Koirala Institute of Health Science, Dharan, Sunsari, Nepal