The diversity of healthcare systems across Europe has predictably resulted in significant variations in point-of-care ultrasound (PoCUS) training and practice for emergency medicine (EM). To encourage a more synchronized approach and address these inconsistencies, the European Society of Emergency Medicine (EUSEM) chartered its ultrasound section to develop a comprehensive curriculum compendium that should serve as a foundational guide for European Emergency Medicine PoCUS clinical and educational guidelines and policies. Under the leadership of a dedicated task force, the EUSEM ultrasound section developed this compendium to provide a structured, tiered framework designed to meet the needs of physicians at every skill level, from novice to advanced users. The compendium emphasizes applications that are currently practiced in different and diverse emergency departments in Europe, including a broad range of topics. An important goal was allowing flexibility to accommodate the unique resources and challenges of different healthcare environments, so that EM physicians can achieve PoCUS competencies matching their local circumstances and needs. To achieve this goal, good educational and clinical stewardship throughout this process is a key part to the success of advancing PoCUS in European EM. This compendium is intended as a resource for creating standardized yet adaptable training pathways. It represents a major step toward harmonizing and advancing PoCUS practice in European EM. Die Vielfalt der verschiedenen Gesundheitssysteme in Europa hat dazu geführt, dass grosse Unterschiede in der Ausbildung und Anwendung des Point-of-Care-Ultraschalls (PoCUS) in der Notfallmedizin bestehen. Um einen stärker synchronisierten Ansatz zu fördern und diesen Unterschieden zu begegnen, hat die Europäische Gesellschaft für Notfallmedizin (EUSEM) ihre Ultraschallsektion damit beauftragt, ein umfassendes Curriculum-Kompendium zu entwickeln. Dieses soll als ein Leitfaden für Europäische Richtlinien und Standards für PoCUS in der klinischen Ausbildung in der Notfallmedizin dienen. Unter der Leitung einer Task Force hat die Ultraschallsektion der EUSEM dieses Kompendium erarbeitet, um Rahmenbedingungen zu schaffen, die den Bedürfnissen von Ärztinnen und Ärzten auf jedem Kompetenzniveau - vom Einsteiger bis zum fortgeschrittenen Anwender - gerecht werden. Das Kompendium beinhaltet Ultraschallanwendungen, die in derzeit sehr diversen Notfallstationen in ganz Europa praktiziert werden, und deckt daher ein breites Spektrum PoCUS-Anwendungen in der Notfallmedizin ab. Ein zentrales Ziel dieser Arbeit war es, Flexibilität zu ermöglichen, um die spezifischen Merkmale wie auch Ressourcen der jeweiligen Gesundheitssysteme zu berücksichtigen, sodass Notfallmediziner:innen PoCUS-Kompetenzen erwerben können, die ihren lokalen Gegebenheiten und Anforderungen entsprechen. Um das Ziel der Weiterentwicklung von PoCUS in der europäischen Notfallmedizin zu erreichen, ist ein entscheidender Erfolgsfaktor eine gute Begleitung sowohl in der klinischen Anwendung, wie auch in der Ausbildung. Dieses Kompendium soll als Grundlage zur Entwicklung standardisierter, zugleich aber anpassungsfähiger Ausbildungspfade dienen. Es stellt einen wichtigen Schritt zur Harmonisierung und Weiterentwicklung des PoCUS in der europäischen Notfallmedizin dar.
Sorghum bicolor (Sorghum) is a drought and heat tolerant C4 grass crop used to produce grain, forage, biofuels, and other bioproducts. Genetic improvement of sorghum hybrid crops is aided by a large and diverse germplasm, sorghum's diploid inbreeding genetics, and a relatively small genome that has facilitated genomic research. Over the past 20 years, the sorghum research community characterized the cytogenetic and recombinant landscapes of sorghum's 10 chromosomes, sequenced and annotated the sorghum genome, and used that information to identify genes/alleles that modulate flowering time, plant height, seed shattering, and other important traits. More recently, >1000 RNA-seq transcriptome profiles were collected from 15 sorghum genotypes to help understand the genetic basis of variation in growth and development of sorghum stems, tillers, roots, and leaves, and the regulation of biosynthetic pathways that produce epicuticular wax, dhurrin, and RFOs, compounds that contribute to sorghum's resilience. Transcriptome studies were designed to identify differentially expressed genes that are co-expressed during development or in response to a treatment to enable construction of gene regulatory networks. Co-expression and network analysis identified transcription factors and their cognate binding sites in target gene promoters and signaling pathways that modulate gene regulatory networks providing gene editing targets for further trait optimization. RNA-seq data from >20 experiments targeting sorghum organs, tissues, cell types, developmental stages, and responses to environmental conditions (i.e., diel, day-length, shading, water-deficit, temperature) has been compiled in a sorghum transcriptome compendium. The goal of this resource paper is to describe compendium content, accessibility, and a compendium data analysis pipeline and to illustrate the types of information that can be derived from the compendium with a focus on the elucidation of gene regulatory networks useful for guiding the improvement of sorghum traits through gene editing.
High-quality and transparent reporting is fundamental to the credibility, reproducibility, and impact of health research. While widely endorsed reporting guidelines such as CONSORT and PRISMA have improved reporting across many fields, traditional, complementary, and integrative medicine (TCIM) research presents distinctive conceptual, methodological, and contextual challenges that are not always adequately addressed by general frameworks. In response, a growing number of TCIM-specific reporting guidelines have been developed over the past two decades. This manuscript provides a structured compendium of all 30 reporting guidelines listed on the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network under the clinical area labelled "Complementary and Alternative Medicine" as of March 2026. The compendium summarizes each reporting guideline's scope, study design focus, TCIM modality, relationship to established parent reporting guidelines where applicable, and methodological strengths and weaknesses. The identified reporting guidelines span a wide range of research domains, including randomized trials, protocols, systematic reviews, case reports, case series, clinical practice guidelines, and basic research, and encompass modalities such as acupuncture, herbal medicine, homeopathy, massage, moxibustion, cupping, biofield therapies, and reflexology. By consolidating these resources in a single, accessible overview, this compendium aims to support researchers, journal editors, and peer reviewers in identifying and applying appropriate TCIM-specific reporting guidance, thereby strengthening the transparency, consistency, and overall quality of TCIM research.
Natural variations in cochlear anatomy have substantial implications for both clinical care and research in the fields of otology, neurotology, and audiology. While precise anatomic characterization is essential for a multitude of applications, comprehensive reference dimensions of both osseous and membranous cochlear structure obtained from a large and morphologically heterogeneous sample set do not currently exist. In this study, one hundred healthy human cadaveric temporal bone samples, without historical or visible pathology, underwent high-resolution three-dimensional synchrotron radiation phase-contrast imaging (SR-PCI) to develop a morphometric compendium of the human cochlea. Measurements of both bone and soft tissue in the cochlea were obtained, including basal turn diameter and width, cochlear height, and cochlear length along multiple anatomic paths (lateral wall, basilar membrane, and modiolar wall). The hook region, scalar geometry (diameter, area, tilt, width, and volume), and round window dimensions were also comprehensively characterized. Normative tonotopic frequency distributions of the basilar membrane and spiral ganglion were derived using cochlear length measurements and Greenwood's frequency-position function. These anatomic benchmarks establish invaluable reference data which may be used for anatomically informed, precision medicine approaches, including patient-specific surgical planning, intracochlear pharmaceutical delivery optimization, the development of automated image analysis algorithms, and the investigation of cochlear structure-function relationships in pathological conditions.
Translating universal health coverage (UHC) commitments into explicit, evidence-informed benefits packages remains a challenge for many resource-constrained health systems. This paper describes the methods and findings of a full-system benefits package revision applying the WHO Universal Health Coverage Compendium (UHCC) within an evidence-informed deliberative process (EDP) to redesign the State-Guaranteed Benefits Programme in Kyrgyzstan. The revision was carried out using the UHCC, following an EDP. The UHCC provided standardised service definitions and resource requirements for analysis. An assessment and appraisal process incorporated technical analysis and governance oversight through the Health Policy Council. The costing methodology estimated input costs per service and multiple financing scenarios were developed with decision-makers to explore coverage-cost trade-offs. The revision was conducted over 2023-2025, with the Health Policy Council endorsing key methodological decisions. Technical evidence on cost, impact and equity was generated for all services. Through deliberative appraisal, 182 services were prioritised as essential. With an available fiscal space of US$19 per capita, only 66 essential services could be financed under fully public funding. A mixed public-private financing scenario maintained comprehensive essential service coverage while reducing public costs. Kyrgyzstan's experience demonstrates that comprehensive, evidence-informed revision of benefits package is feasible in resource-constrained settings when supported by political commitment, strong governance, global tools, structured deliberation and integrated costing. Use of the WHO UHCC enabled standardised service definitions. The approach offers practical lessons for countries seeking to institutionalise priority setting and strengthen progress towards UHC.
NTRK gene fusions are oncogenic drivers for a variety of adult and pediatric tumors, making them a target for tumor-agnostic precision medicine. Tropomyosin receptor kinase (TRK) inhibitors are approved by the US Food and Drug Administration for cancers driven by TRK fusions. However, NTRK genes can fuse with many different partner genes, leading to diverse TRK fusion proteins, highlighting the importance of identifying the specific fusion partner with optimal pan-cancer diagnostics. This analysis aims to provide an updated descriptive compendium of NTRK gene fusions. NTRK gene fusions were identified via literature searches (PubMed), a search of a clinical trials database (larotrectinib), and searches of two genomic databases (Memorial Sloan Kettering and Children's Hospital of Philadelphia). In total, 358 distinct NTRK gene fusion-tumor pairings were identified across 25 tumor types. Primary CNS tumors were observed to harbor 86 distinct NTRK gene fusions, followed by sarcomas (n = 73). Overall, 229 different fusion partners were identified across tumor types (regardless of NTRK gene). Twenty-three fusion partners were found to fuse with >1 NTRK gene across tumor types, while 183 fusion partners were associated with only a single NTRK gene in one tumor type. ETV6::NTRK3 was found in the highest number of different tumor types. This analysis illustrates the diversity of NTRK gene fusion partners across various tumor types and highlights the importance of selecting a pan-tumor fusion-partner agnostic test that can identify both known and novel fusion partners to identify patients who may benefit from treatment with TRK inhibitors.
The Asian bush mosquito, Aedes japonicus (Theobald, 1901), is an invasive species and a competent vector for several arboviruses, including chikungunya virus, dengue virus, Japanese encephalitis virus, West Nile virus, and Zika virus. Field studies have also detected La Crosse virus in wild populations, further supporting its potential role in arbovirus transmission. To address the fragmented and incomplete state of knowledge regarding its spread, we have assembled a global dataset of documented presences from 1950 to 2025. This data descriptor presents a curated database of geolocated records, formatted as points, derived primarily from peer-reviewed literature and supplemented with validated national survey data and selectively integrated records from the Global Biodiversity Information Facility (GBIF) following rigorous quality control. We detail the methodology for data acquisition, coordinate assignment, and the rigorous validation steps applied. This first comprehensive repository specifically for Ae. japonicus, containing 4618 validated records, provides a critical resource for spatial mapping and risk assessment of this vector and its associated pathogens.
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The Lyme disease agent Borrelia burgdorferi belongs to a class of metabolically compromised bacteria that cannot survive without host-derived lipids. Survival of the agent in tick and vertebrate hosts requires substantial nutrient acquisition and potential cell envelope remodeling. While prior studies identified cholesterol, cholesterol glycolipids, and phosphatidylcholines as membrane lipids in B. burgdorferi, the identity of many other membrane lipids, their origin, and their physiological relevance remain unknown. Here, we used a suite of untargeted and targeted high-resolution mass spectrometry methods to reveal a complex lipid profile of the pathogen and to identify the origin of its lipids. The analysis detected more than 500 lipids in B. burgdorferi, the majority of which are sourced from the environment. However, the bacterium selectively accumulates certain lipids while excluding others, suggesting discriminatory uptake. These include cholesteryl esters and triglycerides that are organized in foci within the pathogen. Intriguingly, the pathogen also synthesizes predominantly eukaryotic lipids such as the lysosomal bis(monoacylglycerol)phosphate and the plant glycolipid sulfoquinovosyl diacylglycerol (SQDG). The biosynthesis of the latter is carried out by enzymes that exhibit structural homology to plant oxidoreductases and galactosyltransferases, yet their closest orthologs are found in bacteria. This hints that the capability of SQDG synthesis is more widespread in spirochaetes and other bacteria. Together, the comprehensive lipid profiling we report here uncovers novel aspects of the physiology of the metabolically challenged B. burgdorferi and highlights lipid acquisition and synthesis pathways as potentially critical for pathogen survival.
With more eukaryotic genomes available for study researchers have been able to identify a growing number of horizontal gene transfer (HGT) candidates. We compiled 9,495 protein coding genes that were identified as horizontally transferred to metazoan hosts in the published literature. This dataset contains gene transfers from bacteria, fungi, archaea and protists to metazoans. We assigned a confidence score to each gene based on the methods used in the scientific paper reporting HGT. All the coding sequences and protein sequences for the HGT genes are stored in a fig share repository. This dataset can be used to identify trends in genome and protein evolution and provide a foundation for creating a centralized HGT database for eukaryotes.
Heterozygous FOXL2 (non)coding sequence and structural variants (SVs) lead to blepharophimosis, ptosis and epicanthus inversus syndrome (BPES), a rare, autosomal dominant developmental disorder characterized by a completely penetrant eyelid malformation and incompletely penetrant primary ovarian insufficiency (POI). We collected variants from our in-house database, generated via clinical genetic testing and downstream research testing in the Center for Medical Genetics Ghent, Belgium (2001-2024) and via literature and other resources in the same period. All retrieved variants were categorized using ACMG/AMP classifications to increase the knowledge of pathogenicity. We collected 413 unique genetic defects of the FOXL2 region, including 76 novel variants, in 864 index patients. Of these, 87% of patients were identified with a coding FOXL2 sequence variant. The polyalanine tract is a known mutational hotspot of FOXL2, illustrated here by the high percentage of pathogenic polyalanine expansions (24%). Furthermore, the molecular spectrum in typical BPES index patients is characterized by 8% coding deletions and 3% deletions located up- and downstream of FOXL2. The remaining 2% carry translocations along with chromosomal rearrangements of 3q23. This uniform and structured reclassification, incorporating the largest dataset of variants implicated in FOXL2-associated disease so far, will improve both the diagnosis as well as genetic counselling for individuals with BPES.
Traditional, knowledge-driven pathway annotations and bulk transcriptomic analyses often fail to capture the cellular specificity and mechanistic heterogeneity of immune responses. We present scImmuneCo, a comprehensive resource of immune cell-specific co-expression modules derived from single-cell RNA sequencing across 17 immunological conditions and 1.78 million cells. Using a modified graph-based framework, we constructed 873 robust modules spanning 7 major immune cell types, providing stable, cell-type-specific interaction networks for functional inference. scImmuneCo resolves complex biology at cellular resolution. We identify 20 interferon-related modules that reveal both conserved and cell-type-specific regulatory programs, clarifying disease-dependent differences that are invisible to pathway tools treating interferon signaling as a unitary process. We also uncover age-associated CD8+ T cell programs, capturing state transitions from naive to effector/memory cells and exposing a progressive imbalance in translation and cytotoxicity with age. Together, these results demonstrate the power of high-resolution, data-driven functional inference to link gene groups to biological roles and disease processes. To support broad application, we provide an R package (https://github.com/FrankQYW/scImmuneCo_R) for module-based analysis of both single-cell and bulk transcriptomic data, along with an interactive web portal (http://www.scimmuneco.site/) for visualization and gene-module exploration. scImmuneCo offers a scalable and interpretable framework for dissecting immune mechanisms and identifying disease-relevant transcriptional programs with cellular resolution.
Shared decision making (SDM) can be conceptualized as observable communication behaviors that foster collaborative decision making. We aimed to develop a compendium of patient-reported SDM instruments and characterize the communication behaviors assessed by them. We then used the identified behaviors to develop a contemporary integrative model of the SDM process. PubMed, Embase, Cochrane Library, and CINAHL were systematically searched through July 2024. Published reviews of SDM instruments were eligible if they included instruments without context restrictions and were available as full text in English, supplemented by a primary search since the last review for potential instruments not included in reviews. Instruments were eligible if they were patient-reported and included at least one item assessing a SDM communication behavior. All items from the included instruments were extracted verbatim and directed content analysis was used to code for SDM communication behaviors. Of 1049 records, 14 reviews underwent full-text assessment, and 9 were included (2007-2021), collectively identifying 98 unique instruments. Twenty-one patient-reported instruments met inclusion criteria, comprising 283 items. Nineteen instruments measured information exchange communication behaviors, including creating choice awareness (n = 8), sharing information and discussing options (n = 12), eliciting and integrating patient preferences (n = 19), and discussing choice enactment (n = 8). Eighteen instruments measured relationship building communication behaviors separately from information exchange, including partnership building (n = 17) and rapport building (n = 6). Sixteen spanned both informational and relational domains, and none contained at least one item measuring all six domains. This review provides a compendium of patient-reported SDM process instruments to support selection of measures aligned with specific conceptual, practice, and research needs. Drawing from the communication behaviors represented in existing instruments, we propose a contemporary integrative model of the SDM process. To comprehensively conceptualize and measure the SDM process, measurement instruments need to consider both information exchange and relationship building communication behaviors.
Gene set enrichment analysis (GSEA) is widely used to interpret genome-wide expression data, but pathway inference from differentially expressed gene (DEG) signatures remains limited by data scarcity, model incompatibility with tabular data, and limited interpretability. We aimed to develop an efficient and explainable model that predict gene-pathway associations from a large curated DEG signature compendium and supports potential therapeutic target discovery in complex diseases such as osteoarthritis (OA) and other disease contexts. We developed SaintGSE, a supervised prediction framework combining an autoencoder for dimensionality reduction and the SAINT for modeling tabular DEG signatures. The model was trained on a large public DEG compendium with pathway labels derived from EnrichR and interpreted using Integrated Gradients (IG) to prioritize driver genes. Experimental validation was conducted using mouse (n=5) and human (n=3) chondrocyte cultures, and in vivo OA-induced mouse models (n=5 per group). SaintGSE analysis identified key OA-related signaling pathways potentially modulated by natural extract from Senna obtusifolia, including NF-κB and p38. In vitro, the extract reduced OA catabolic factors compared with IL-1β-treated controls, including Mmp3 (mean difference 52.06, 95% CI 32.8-71.3, p<0.0001), Mmp13 (mean difference 5.13, 95% CI 2.9-7.4, p<0.0001), and Cox2 (mean difference 1.39, 95% CI 1.1-1.7, p<0.0001). In vivo, the extract significantly reduced cartilage damage compared with the DMM-operated PBS-treated group (effect estimate [mean rank difference] 13.3, p=0.0009). IG-based driver genes provided compact, condition-specific candidates supporting each pathway prediction. SaintGSE offers scalable, explainable pathway prediction from DEG signatures and enables mechanism- and target-oriented follow-up for disease studies and drug candidate screening.
Heart failure (HF) remains a major cause of morbidity, mortality and costs for the healthcare systems worldwide, despite advances in diagnostic and therapeutic strategies. The enhancement of preventive measures is now a priority, but effective prevention requires a multidisciplinary strategy addressing a broad spectrum of comorbidities and risk factors. It must also consider the changes in the prevailing phenotype of the patients with HF with a lower impact of coronary artery disease and the increasing role of renal and metabolic conditions leading mostly to HF with preserved ejection fraction. Prevention of HF must take into consideration arterial hypertension, chronic kidney disease, diabetes mellitus, sedentary lifestyle, obesity, dyslipidemia, female-specific risk factors, as well as adverse effects of chemotherapy and radiotherapy. Other key factors include infections and the protective role of vaccination, and environmental and socio-economic determinants of health. In 2022, a position paper of the Heart Failure Association and the European Association of Preventive Cardiology of the ESC was published as a complete overview on this topic and as a compendium to the 2021 ESC Guidelines on HF. However, since then, significant evidence has emerged regarding the potential to prevent HF, particularly in the context of metabolic disorders, diabetes and kidney diseases. This scientific statement aims to provide an updated perspective, highlighting the importance of a holistic and tailored approach to managing the multifaceted contributors to this syndrome.
Gastrodia elata Blume (G. elata) is a traditional Chinese medicinal herb documented in the Compendium of Materia Medica and has been widely used for dizziness, convulsive disorders, vertigo, and neurological symptoms. Gastrodin (GAS), the principal bioactive constituent of G. elata, is known to exhibit anti-inflammatory, antioxidant, and neuroprotective properties. Nevertheless, whether GAS is beneficial for vascular cognitive impairment associated with dietary risk factors remains unclear. Clarifying this issue may help explain the pharmacological basis of the traditional neurological use of G. elata. This study investigated whether GAS could alleviate cognitive dysfunction aggravated by a high-salt diet (HSD) in chronic cerebral hypoperfusion (CCH) mice, and explored its possible involvement in cerebral blood flow (CBF) regulation, blood-brain barrier (BBB)-related structural preservation, and amyloidogenic processing. A mouse model of CCH combined with dietary risk was generated using bilateral common carotid artery stenosis (BCAS) and HSD exposure. Cognitive performance was assessed by the novel object recognition test, Y-maze test, and open field test. CBF was monitored using laser speckle imaging. Hippocampal transcriptomic sequencing was conducted to identify GAS-regulated pathways. Nissl staining, immunohistochemistry, Western blotting, and transmission electron microscopy were used to examine neuronal injury, BBB structure, and related protein expression. Serum Aβ and inflammatory cytokines were quantified by ELISA. HSD exposure further worsened BCAS-induced cerebral hypoperfusion and cognitive deficits. GAS administration restored CBF, improved behavioral performance, and showed a tendency toward partial improvement of hippocampal morphology. Transcriptomic analysis indicated that GAS-responsive differentially expressed genes were enriched in pathways associated with extracellular matrix interaction, tight junctions, vascular function, and PI3K-Akt signaling. Further experiments showed that GAS increased ZO-1, Occludin, and eNOS expression, preserved BBB-related ultrastructural features, restored Akt/mTOR pathway-associated phosphorylation, and attenuated BACE1/APP-, sAPPβ-, Aβ-, and serum TNF-α-related changes. GAS ameliorates cognitive impairment induced by HSD exposure combined with BCAS, and this effect is associated with improved CBF, restoration of Akt/mTOR pathway-associated phosphorylation, eNOS-related endothelial regulation, preservation of BBB-related structural integrity, and attenuation of amyloidogenic processing-related and serum inflammatory marker changes. These results provide experimental support for the potential role of GAS in treating vascular cognitive impairment associated with dietary risk factors.
Programa Criança Feliz (PCF) is Brazil's home visitation program aimed at enhancing early childhood development. Evaluations of the program have found significant program challenges and implementation barriers, including the lack of a structured curriculum, insufficient training, and little supervisory support. This study tests the revised content of the home visits and new implementation strategies aimed at addressing these barriers and enhancing the quality of PCF home visits. The implementation strategies were piloted across 8 diverse municipalities in an implementation feasibility trial. The strategy bundle included a 40-hour initial training for home visitors using demonstration and simulation-based methods (based on the Reach Up methodology), an 8-hour supervision-focused training module for supervisors, and standardized home visit guidelines and an activities compendium. The new strategies were assessed using a one group pre-post analysis along with mixed methods to assess the extent to which they were acceptable, feasible, and associated with a change in home visit quality. A paired t-test and an independent t-test analysis were used to assess the change in home visit quality. The implementation outcomes were assessed with qualitative analysis and the Framework Method approach. The proposed home visitation guidelines, material, training, and supervision process were determined to be highly acceptable, feasible, and associated with improved quality of home visits. The home visit quality scores significantly increased by 14.68 points (SD = 14.89, CI 95%: 7.27-22.08, p = 0.0006), according to the paired t-test. The study participants provide insightful suggestions for adaptations that can occur before testing the strategies more broadly. Key suggested adaptations included adjusting activity difficulty to individual developmental levels rather than age alone, shortening training duration to improve staff access, and incorporating guidance for culturally diverse and traditional communities. The findings suggest three transferable design principles for home visitation and paraprofessional-delivered public health programs: reducing excessive discretion through structured, age-appropriate visit guidance; externalizing quality through experiential training methods such as demonstration and role-play; and embedding feedback loops through structured supervision and monitoring. These principles may generalize to programs facing heterogeneous staff preparation, high turnover, and limited supervisory capacity.
As in other mammalian species, the complex and specific interactions between internal biological processes and external factors regulate and impact the male dog reproductive system functions. This comprehensive review integrates physiological and molecular mechanisms underlying the reproductive system maintenance throughout the anatomical and histological structure of reproductive organs and their functions from development to aging. Simultaneously, the presentation of fundamental hormonal regulations and functions of the reproductive system is comprised. Special attention is put on e.g., genetic, developmental, age- and environmental-related disorders. The structural and hormonal status of the reproductive organs in response to single or mixed influences: genetic predispositions (e.g., cryptorchidism, sex chromosome aneuploidy syndrome), developmental courses (e.g., cryptorchidism, uterus masculinus, hypospadias), age-related diseases (e.g., tumors), and environmental stressors: e.g., endocrine-disrupting chemicals, toxins, heat stress (possibly leading to e.g., hypogonadism, cryptorchidism, infertility, tumors, precocious aging) is provided. Such multidirectional and comprehensive associations of grouped, selected, clinically significant pathological processes and diseases are broadly considered and linked here for the first time. Based on both epidemiological and experimental findings, the etiologies, current diagnostic approaches, treatment options, and prognostic assessments of these common male dog disorders are presented. This compendium seems useful for young veterinarians, researchers, breeders, and dog owners, enabling them to integrate knowledge on biological principles and processes with clinical practices and research in recent and future canine andrology.
Cannabinoids comprise a chemically diverse group of meroterpenoids whose extensive isomerism, variable side-chain length, and frequent oxidative or rearranged derivatives lead to strongly overlapping yet characteristic MS/MS fragmentation patterns. In untargeted LC-MS/MS datasets, this combination of structural diversity and spectral similarity complicates annotation, particularly when reference spectra are sparse or unavailable. Library-based approaches, therefore, recover only a limited fraction of the cannabinoid-related chemical space that is routinely observed in experimental data. In this work, we apply MassQL to encode established cannabinoid fragmentation chemistry into rule-based queries. The resulting compendium covers major cannabinoid subclasses, including neutral and acidic cannabinoids, varinic analogs (C3 side-chain cannabinoids), and structurally modified derivatives, using combinations of diagnostic fragment ions, neutral loss patterns, adducts, and fragment co-occurrence logic. Importantly, class-level retrieval does not depend on complete or unambiguous precursor m/z information and can be driven solely by MS/MS evidence. Application of this framework to a publicly available untargeted LC-MS/MS dataset demonstrates that rule-based querying can recover known cannabinoids while highlighting additional features that share consistent cannabinoid-like fragmentation patterns. These features include putative analogs, transformation products, and derivatized forms that are not represented in current spectral libraries. At the same time, certain known features, such as in-source dehydrated ions, may be under-recovered depending on query design, illustrating current methodological limitations. This study demonstrates the feasibility and interpretability of chemically informed, rule-based MS/MS querying for cannabinoid discovery. Rather than replacing spectral library matching, MassQL-based class-level retrieval provides complementary hypothesis-generating evidence capable of expanding detectable cannabinoid chemical space beyond currently available reference spectra. The results also highlight the importance of polarity-aware fragmentation curation for reliable query-driven metabolomics workflows. MassQL class-level matches should be viewed as chemically informed hypotheses that complement, rather than replace, spectral library identification, while providing a basis for future systematic validation and benchmarking.
Immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) share symptomatic and therapeutic similarities with chronic inflammatory diseases (CIDs). However, the molecular distinctions between irAEs and CIDs remain unclear. Herein, we systematically compared irAEs and CIDs across multiple tissues using large-scale multi-omics profiling. We compiled a transcriptomic compendium of over 4.3 million cells from 1137 samples and 24 spatial transcriptomes across diverse inflammatory sites in irAEs and CIDs. In addition, we collected 526 pre-ICI and post-ICI treatment-matched blood transcriptomes coupled with germline exomes, alongside 75 serum proteomes with irAE information. Hallmark gene signatures and cell states that characterize the inflammatory milieu of various irAEs and CIDs were defined. Across tissues, irAEs involve a distinct inflammatory ecosystem enriched with myeloid-derived components, including NLRP3 + mononuclear phagocytes, LAMP3 + dendritic cells, and CXCL8/10 cytokine signaling, alongside TNFRSF18 + regulatory T cell, T/natural killer interferon, and HAVCR2 + exhausted T cell. These cell states exhibit unique interaction patterns, forming spatially localized niches specific to irAEs but absent in CIDs. Severe irAEs are accompanied by elevated CXCL10 cytokine signaling post-ICI treatment, with a higher prevalence among HLA-B*46:01 carriers. Our multimodal analyses highlight key differences between irAEs and CIDs, indicating that irAEs constitute a distinct inflammatory ecosystem that differentiates them from CIDs. Our study provides insights into potential biomarkers and therapeutic targets for improved irAE management.