Suppression of MCP-1, IFN-γ and IL-6 production of HNSCC by pembrolizumab added to docetaxel and cisplatin (TP) exceeding those of TP alone is linked to improved survival.

Background: Adding pembrolizumab, an anti-PD-1 antibody approved for treatment of head and neck squamous cell carcinoma (HNSCC) to neoadjuvant (induction-) chemotherapy utilizing docetaxel and cisplatin (TP) followed by radiotherapy may improve outcome in larynx organ-preservation (LOP) that is investigated in the European Larynx-Organ preservation Study (ELOS). As biomarkers for response to TP and pembrolizumab +TP are missing but may include cytokines, this work aims on determining cytokines potentially linked to outcome as prognostic markers sufficient to predict and/or monitor response to successful LOP.

Methods: Collagenase IV digests were generated from 47 histopathological confirmed HNSCC tumor samples and seeded in 96-well plates containing pembrolizumab, docetaxel, cisplatin either solely or in binary or ternary combination.

High-Yield Generation of Glucose-Responsive Pseudoislets From Murine Insulinoma Cells for Studies and Longitudinal Monitoring of Graft Survival .

Compared to primary pancreatic islets, insulinoma cell-derived 3D pseudoislets offer a more accessible, consistent, renewable, and widely applicable model system for optimization and mechanistic studies in type 1 diabetes (T1D). Here, we report a simple and efficient method for generating 3D pseudoislets from MIN6 and NIT-1 murine insulinoma cells. These pseudoislets are homogeneous in size and morphology (~150 µm), exhibit functional glucose-stimulated insulin secretion (GSIS) up to 18 days (NIT-1) enabling long-term studies, are produced in high yield [>35,000 Islet Equivalence from 30 ml culture], and are suitable for both and studies, including for encapsulation studies.

Impact of commercial gut health interventions on caecal metagenome and broiler performance.

Background: Maintaining gut health is a persistent and unresolved challenge in the poultry industry. Given the critical role of gut health in chicken performance and welfare, there is a pressing need to identify effective gut health intervention (GHI) strategies to ensure optimal outcomes in poultry farming. In this study, across three broiler production cycles, we compared the metagenomes and performance of broilers provided with ionophores (as the control group) against birds subjected to five different GHI combinations involving vaccination, probiotics, prebiotics, essential oils, and reduction of ionophore use.

Unsupervised detection of novel SARS-CoV-2 mutations and lineages in wastewater samples using long-read sequencing.

The COVID-19 pandemic has underscored the importance of virus surveillance in public health and wastewater-based epidemiology (WBE) has emerged as a non-invasive, cost-effective method for monitoring SARS-CoV-2 and its variants at the community level. Unfortunately, current variant surveillance methods depend heavily on updated genomic databases with data derived from clinical samples, which can become less sensitive and representative as clinical testing and sequencing efforts decline.In this paper, we introduce HERCULES (High-throughput Epidemiological Reconstruction and Clustering for Uncovering Lineages from Environmental SARS-CoV-2), an unsupervised method that uses long-read sequencing of a single 1 Kb fragment of the Spike gene.

Sequential testing with Xpert MTB/RIF assay for diagnosis of tuberculous meningitis in Maharaj Nakorn Chiang Mai University Hospital.

Early diagnosis and appropriate treatment are essential for reducing morbidity and mortality in tuberculous meningitis (TBM). This study aimed to evaluate the diagnostic performance of the Xpert MTB/RIF assay for the diagnosis of TBM in patients with subacute lymphocytic meningitis. This cross-sectional study included 65 cerebrospinal fluid (CSF) specimens from patients at Maharaj Nakorn Chiang Mai University Hospital, Thailand, between January 2015 and March 2016.

Intricacies of human-AI interaction in dynamic decision-making for precision oncology.

AI decision support systems can assist clinicians in planning adaptive treatment strategies that can dynamically react to individuals' cancer progression for effective personalized care. However, AI's imperfections can lead to suboptimal therapeutics if clinicians over or under rely on AI. To investigate such collaborative decision-making process, we conducted a Human-AI interaction study on response-adaptive radiotherapy for non-small cell lung cancer and hepatocellular carcinoma.

Unveiling the epidemiology and community perspectives on bovine brucellosis in North Shewa, Central Highlands of Ethiopia.

Brucellosis is a bacterial disease of many domestic and wild animals with great economic and public health importance. Although it has a major constraint in dairy production, comprehensive information regarding the epidemiology of brucellosis in dairy herds is limited. Besides, evaluating the dairy farmers' knowledge, attitude, and practice (KAP) regarding brucellosis is crucial for generating information that can enhance control programs and public health interventions.

Maxillary MRSA osteomyelitis in a paediatric patient: non-surgical management.

Methicillin-resistant (MRSA) osteomyelitis of the maxilla is a rare condition in paediatric patients, with limited evidence available for optimal treatment protocols. We present the case of a paediatric patient in the early childhood age group with post-traumatic maxillary osteomyelitis caused by MRSA. The child developed facial swelling following trauma, and imaging revealed maxillary sinus wall thickening and bone erosions.

Prevalence and clinical profile of hepatitis C virus infections in multitransfused thalassemic patients in the capital twin cities of Pakistan.

Hepatitis C virus (HCV) presents a significant global health concern, affecting 3.3% of the world's population. The primary mode of HCV transmission is through blood and blood products.

Comparison of observational methods to identify and characterize post-COVID syndrome in the Netherlands using electronic health records and questionnaires.

Background: Some of those infected with SARS-CoV-2 suffer from post-COVID syndrome (PCS). However, an uniform definition of PCS is lacking, causing uncertainty about the prevalence and nature of this syndrome. We aimed to improve understanding of PCS by operationalizing different classifications and to explore clinical subtypes.

2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione protects against MPP-induced neurotoxicity by ameliorating oxidative stress, apoptosis and autophagy in SH-SY5Y cells.

2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) is a cyclohexanedione compound extracted from the roots of Averrhoa carambola L. Several studies have documented its beneficial effects on diabetes, Alzheimer's disease, and cancer. However, its potential neuroprotective effects on Parkinson's disease (PD) have not yet been explored.

Characterization of the host specificity of the SH3 cell wall binding domain of the staphylococcal phage 88 endolysin.

Bacteriophages produce endolysins at the end of the lytic cycle, which are crucial for lysing the host cells and releasing virion progeny. This lytic feature allows endolysins to act as effective antimicrobial alternatives when applied exogenously. Staphylococcal endolysins typically possess a modular structure with one or two enzymatically active N-terminal domains (EADs) and a C-terminal cell wall binding domain (CBD).

Short-term costs of alcohol-associated hepatitis care in different clinical settings.

Background: Alcohol-associated hepatitis (AH) leads to high rates of mortality and health care costs. Understanding the immediate costs after an AH diagnosis and identifying key cost factors is crucial for health care policies and clinical decisions.

Objectives: This study quantifies medical costs within 30 days of an AH diagnosis across outpatient (OP), emergency department (ED), and inpatient (IP) settings.

Cryptic genetic diversity and molecular detection of Trypanosoma theileri complex in the deer fly Chrysops dispar Fabricius from Thailand.

The deer fly (Diptera, Tabanidae), Chrysops dispar Fabricius is a common and widespread pest and vector species transmitting pathogens to animals including economically significant livestock. However, there is only limited information on genetic diversity, which crucial for understanding disease epidemiology. In this study, we examined genetic diversity of C.

Case reports of Strongyloides stercoralis infection in three patients with haematological malignancies.

Strongyloidiasis is a parasitic nematode infection mainly caused by Strongyloides stercoralis. Immunocompromised conditions, particularly cancer patients treated with chemotherapy and corticosteroids, have a significant risk of developing Strongyloides hyperinfection. The lack of a gold standard laboratory method to rule out this infection and the insensitivity of microscopic stool examination due to low and intermittent larvae output in stool contribute to the low detection rate of this infection.

First molecular detection of hemotropic Mycoplasma spp. and molecular screening of other vector-borne pathogens in camels from the greater Cairo metropolitan area, Egypt.

In Egypt, knowledge about vector-borne bacterial pathogens in camels remains limited. To address this gap, 181 blood samples from adult one-humped camels (Camelus dromedarius) in the greater Cairo metropolitan area were collected from October 2021 to March 2022. Through PCR assays, four pathogens were detected, where Anaplasmataceae being the most common (54.

First report of Anaplasma marginale and Anaplasma ovis in goats in Kelantan, Malaysia.

Anaplasma species are obligate rickettsial intraerythrocytic pathogens that cause an important tick-borne disease of economic importance in livestock production in many countries. Anaplasma species have been detected from farm animals worldwide, there is a paucity of information on Anaplasma infections in goats from Malaysia. Thus, this study aimed to assess the infection rate and identify Anaplasma species and some selected risk factors in goats across selected districts in Kelantan, Malaysia.

Molecular screening of Babesia, Hepatozoon, and Theileria (Apicomplexa: Piroplasmida) in ticks (Acari: Ixodidae) infesting farm ruminants in Peninsular Malaysia.

Ticks are obligate hematophagous arachnids that feed on both humans and animals. Despite the extensive research on detection of bacteria in ixodid ticks in Malaysia, there remains limited knowledge about the detection of protozoa in these ectoparasites, especially in those that feed on farm ruminants. In this study, 1,241 ticks belonging to four species (Rhipicephalus microplus, R.

NEAT1 regulates BMSCs aging through disruption of FGF2 nuclear transport.

Background: The aging of bone marrow mesenchymal stem cells (BMSCs) impairs bone tissue regeneration, contributing to skeletal disorders. LncRNA NEAT1 is considered as a proliferative inhibitory role during cellular senescence, but the relevant mechanisms remain insufficient. This study aims to elucidate how NEAT1 regulates mitotic proteins during BMSCs aging.

Changes in incidence and epidemiology of antimicrobial resistant pathogens before and during the COVID-19 pandemic in Germany, 2015-2022.

Background: Carbapenem-resistant Gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA) are among WHO's priority pathogens with antimicrobial resistance (AMR). Studies suggest potential impacts of the COVID-19-pandemic on AMR. We described changes in AMR incidence and epidemiology in Germany during the COVID-19-pandemic.

Intestinal neutrophil extracellular traps promote gut barrier damage exacerbating endotoxaemia, systemic inflammation and progression of diabetic retinopathy in type 2 diabetes.

Aims/hypothesis: Within the small intestine, neutrophils play an integral role in preventing bacterial infection. Upon interaction with bacteria or bacteria-derived antigens, neutrophils initiate a multi-staged response of which the terminal stage is NETosis, formation of protease-decorated nuclear DNA into extracellular traps. NETosis has a great propensity to elicit ocular damage and has been associated with diabetic retinopathy and diabetic macular oedema (DME) progression.

Intraperitoneal chemotherapy is now back for ovarian cancer.

The Intraperitoneal Carboplatin for Ovarian Cancer (iPocc) trial demonstrated that intraperitoneal (IP) administration of carboplatin is more effective than intravenous (IV) administration for advanced ovarian cancer, especially in cases with large residual tumors, challenging previous assumptions that IP chemotherapy is only beneficial for small residual tumors. Additionally, the iPocc trial showed that IP chemotherapy has a comparable safety profile to IV chemotherapy, with the exception of port-related toxicities. This review summarizes the principles, development, and significance of IP chemotherapy and discusses its future potential in light of recent studies.

Digital framework for georeferenced multiplatform surveillance of banana wilt using human in the loop AI and YOLO foundation models.

Bananas (Musa spp.) are a critical global food crop, providing a primary source of nutrition for millions of people. Traditional methods for disease monitoring and detection are often time-consuming, labor-intensive, and prone to inaccuracies.

Neural circuits underlying context-dependent competition between defensive actions in Drosophila larvae.

To ensure their survival, animals must be able to respond adaptively to threats within their environment. However, the precise neural circuit mechanisms that underlie flexible defensive behaviors remain poorly understood. Using neuronal manipulations, machine learning-based behavioral detection, electron microscopy (EM) connectomics and calcium imaging in Drosophila larvae, we map second-order interneurons that are differentially involved in the competition between defensive actions in response to competing aversive cues.

Structural insights into the role of reduced cysteine residues in SOD1 amyloid filament formation.

The formation of superoxide dismutase 1 (SOD1) filaments has been implicated in amyotrophic lateral sclerosis (ALS). Although the disulfide bond formed between Cys57 and Cys146 in the active state has been well studied, the role of the reduced cysteine residues, Cys6 and Cys111, in SOD1 filament formation remains unclear. In this study, we investigated the role of reduced cysteine residues by determining and comparing cryoelectron microscopy (cryo-EM) structures of wild-type (WT) and C6A/C111A SOD1 filaments under thiol-based reducing and metal-depriving conditions, starting with protein samples possessing enzymatic activity.