Oracle (United Kingdom)

Previous research has identified treatment attributes and outcomes for endometriosis patients, highlighting the need for tailored interventions to improve patient care. These studies emphasize the need to understand patient experiences, focusing on pain symptoms and factors that impact quality of life. This study aimed to provide an in-depth description of patient experiences with endometriosis related to treatment attributes and outcomes, including three key types of pain symptoms: Non-menstrual pelvic pain, dyspareunia, and dysmenorrhea, and non-pain factors such as out-of-pocket costs. In this retrospective qualitative study, 47,745 public social media posts from the United States from December 2021 to December 2022 were analyzed. Boolean queries were created incorporating criteria to identify public posts referencing endometriosis and language indicative of patients expressed in the first-person point of view. Data were summarized via descriptive statistics. Findings confirmed the relevance of non-menstrual pain, dyspareunia, and dysmenorrhea for treatment decision-making. Dysmenorrhea, described as excruciating and debilitating, was the most discussed symptom (10% of posts) followed by dyspareunia (3% of posts), with emotional and physical impacts detailed. Non-menstrual pain was specified in 1% of posts, including the follicular, ovulatory, and luteal phases of the menstrual cycle. Key themes that emerged organically included the impact of endometriosis on daily functioning, mental health, intimacy, fertility, and the role of online misinformation. Discussions detailed the struggle to balance symptom relief with long-term solutions, and frustration with diagnosis. The current study highlights the difficulties patients experience with dysmenorrhea, dyspareunia, and non-menstrual pain and the challenges to treatment decisions. The relevance of social media for patient expression of their disease experience, the importance of recognizing the individualized needs of patients necessitating their active involvement in treatment decision-making, and the need for education about treatment options beyond surgery also emerged in the findings.

Volumetric studies in relation to CM/SM have not been reported in Pomeranians. In this study, we aim to (1) report the intermodality agreement between CT- and MRI-based volumetric measurements of the skull and cervical spinal canal, and (2) assess for differences and associations between the volumetric measurements and CM/SM status. Pomeranians were included that underwent CT and MRI studies during the period of February 2022-June 2024. Frontal sinus volume (FSV), caudal cranial fossa volume (CCFV), rostral and middle cranial fossa volume (RMCFV), caudal cranial fossa parenchymal volume (CCFPV), rostral and middle cranial fossa parenchymal volume (RMCFPV), cerebellar parenchymal volume (CPV), brain stem parenchymal volume (BSPV), ventricular system volume (VSV), and spinal canal volume between C1-C7 (CSCV) were measured. CCFV to RMCFV volume index (VI) and CCFPV to CCFV (CCFPV%) were calculated. Agreement between MRI- and CT-based quantitative measurements was assessed with intraclass correlation coefficients. Inferential statistical tests including logistic regression modeling were performed to assess for associations between variables and CM/SM status. For all volumetric assessments that were performed on both CT and MRI, agreement was good or excellent. There were significant differences between SM normal and abnormal dogs for body weight as well as all volumetric parameters except for CCFPV% and RMCFV. Multiple logistic regression showed that a smaller CCFV and larger VSV were associated with SM. Smaller CCFV and larger VSV are associated with the development of SM in Pomeranians and have increased odds of SM.

Metabolic/neurodegenerative encephalopathies encompass a wide list of conditions that share similar clinical and magnetic resonance imaging (MRI) characteristics, challenging the diagnostic process and resulting in numerous tests performed in order to reach a definitive diagnosis. The aims of this multicentric, retrospective and descriptive study are: (I) to describe the MRI features of dogs and cats with metabolic/neurodegenerative encephalopathies; (II) to attempt an MRI recognition pattern classifying these conditions according to the involvement of grey matter, white matter or both; and (III) to correlate the MRI findings with previous literature. A total of 100 cases were recruited, comprising 81 dogs and 19 cats. These included hepatic encephalopathy (20 dogs and three cats), myelinolysis (five dogs), intoxications (seven dogs and one cat), thiamine deficiency (two dogs and seven cats), hypertensive encephalopathy (three dogs and two cats), neuronal ceroid lipofuscinosis (11 dogs and one cat), gangliosidosis (three dogs and two cats), fucosidosis (one dog), L-2-hydroxyglutaric aciduria (13 dogs and one cat), Lafora disease (11 dogs), spongiform leukoencephalomyelopathy (one dog) and cerebellar cortical degeneration (four dogs and two cats). None of the hepatic encephalopathies showed the previously described T1-weighted hyperintensity of the lentiform nuclei. Instead, there was involvement of the cerebellar nuclei (8/23), which is a feature not previously described. Dogs with myelinolysis showed novel involvement of a specific grey matter structure, the claustrum (5/5). Thiamine deficiency affected numerous deep grey nuclei with novel involvement of the oculomotor nuclei (3/9), thalamic nuclei, subthalamus and cerebellar nuclei (1/9). Cats with hypertensive encephalopathy had a more extensive distribution of the white matter changes when compared to dogs, extending from the parietal and occipital lobes into the frontal lobes with associated mass effect and increased brain volume. Lysosomal storage disease showed white matter involvement only, with neuronal ceroid lipofuscinosis characterised by severe brain atrophy when compared to gangliosidosis and fucosidosis. All patients with L-2-hydroxyglutaric aciduria had a characteristic T2-weighted hyperintense swelling of the cerebral and cerebellar cortical grey matter, resulting in increased brain volume. Lafora disease cases showed either normal brain morphology (5/11) or mild brain atrophy (6/11). Dogs with cerebellar cortical degeneration had more marked cerebellar atrophy when compared to cats. This study shows the important role of MRI in distinguishing different metabolic/neurodegenerative encephalopathies according to specific imaging characteristics.

Chiari-like malformation (CM) and syringomyelia (SM) are frequently diagnosed conditions in small and toy dog breeds, such as the Cavalier King Charles Spaniel and Griffon Bruxellois. CM/SM is only rarely reported in Pomeranians in literature to date. The aims of this study are to 1/describe the phenotype of Pomeranians with or without CM/SM and 2/evaluate for differences and associations between CM/SM and owner-reported clinical signs (ORCS) or signalment factors. From February 2015 to June 2023, historical data and signalment (including country of origin, pedigree, sex and neuter status, age, and body weight) and ORCS of Pomeranians were recorded at multiple institutions. MRI studies of all dogs were evaluated for classification of CM/SM. Additionally, quantitative measurements were performed for SM. A total of 796 dogs from 22 different countries were included. Total prevalence of CM was 54.9% (437/796) and the prevalence of SM was 23.9% (190/796). The top 5 ORCS included 1/scratching with skin contact, rubbing head or ears, or both (57.6% of dogs with ORCS), 2/air licking (30.7% of dogs with ORCS), 3/spontaneous signs of pain (26.0% of dogs with ORCS), 4/persistent licking front and/or hind paws (22.6% of dogs with ORCS), 5/phantom scratching (22.6% of dogs with ORCS). Phantom scratching, vocalization, head shaking, spontaneous signs of pain, and air licking were associated with having SM. There were no statistically significant associations between quantitative syrinx measurements and ORCS. There were statistically significant associations between CM classification and 1/country of origin, 2/having a pedigree, and 3/age. There were statistically significant associations between SM classification and 1/age and 2/body weight. This is the first large study evaluating CM/SM in the Pomeranian dog breed. Veterinary clinicians can use these findings to increase the likelihood of correctly determining the presence or absence of CM/SM in Pomeranians. Breeders may consider using the information regarding signalment factors as well as ORCS associated with CM/SM classifications to select dogs for screening procedures. But an MRI-based diagnosis is needed to properly ascertain the exact CM/SM status of their breeding stock until a fool-proof characteristic or genetic marker is found.

A 1.5-year-old female entire French bulldog was referred for neurological evaluation, further diagnostic tests, and treatment 24 h after a road traffic accident. Initial emergency treatment, diagnostic tests, and stabilization had been performed by the referring veterinarian. Neurological examination revealed severe spastic non-ambulatory tetraparesis and was consistent with a C1-5 myelopathy. A magnetic resonance imaging (MRI) study revealed an irregular to elongated ovoid intramedullary lesion centered over the body of C2. The lesion showed marked signal heterogeneity with a central T2W and T2* hyperintense region, surrounded by a hypointense rim on both sequences. The lesion appeared heterogeneously T1W hypointense. The lesion was asymmetric (right-sided), affecting both white and gray matter. The C2-3 intervertebral disk appeared moderately degenerate with a Pfirrmann grade of 3. No evidence of vertebral fracture or luxation was found on radiographs or MRI of the vertebral column. Additional soft tissue abnormalities in the area of the right brachial plexus were suggestive of brachial plexus and muscle injury. A diagnosis of traumatic hemorrhagic myelopathy at the level of C2 and concurrent brachial plexus injury was formed. Conservative treatment was elected and consisted of physiotherapy, bladder care with an indwelling urinary catheter, repeated IV methadone based on pain scoring (0.2 mg/kg), oral meloxicam 0.1 mg/kg q24h, and oral gabapentin 10 mg/kg q8h. The dog was discharged after 4 days, with an indwelling urinary catheter and oral medication as described. The catheter was replaced two times by the referring veterinarian and finally removed after 10 days. Thereafter, voluntary urination was seen. During the 2 months after the road traffic accident, slow recovery of motor function was seen. The right thoracic limb recovery progressed more slowly than the left limb, also showing some lower motor neuron signs during follow-up. This was judged to be consistent with a right-sided brachial plexus injury. The dog was reported ambulatory with mild residual ataxia and residual monoparesis of the right thoracic limb at the last follow-up 3 months post-injury. This case report highlights the MRI-based diagnosis of traumatic hemorrhagic myelopathy in a dog. A fair short-term outcome was achieved with conservative treatment in this case.

2620 Background: Programmed death ligand-1 (PD-L1) contributes to immune suppression in the tumor microenvironment (TME) by interacting with programmed cell death-1 (PD-1) on infiltrating T lymphocytes leading to tumor immune escape. Application of omics technologies has shed light on the relevance of the TME for response to immunotherapies and development of novel treatment options. Here we have applied a multi-plex immunofluorescence/multi-tumor tissue microarray (TMA) approach to examine the immunobiology of different TMEs with respect to the contribution by tumor cells and macrophages to overall PD-L1 expression. Methods: A TMA comprising 11 tumor types and a total of 144 different donors, each represented by two cores [1mm; 1 from invasive margin (IM) and 1 from tumor center (TC)], was stained using Ultivue’s Immuno8 FixVUE panel (CD3, CD4, CD8, FOXP3, CD68, PD-1, PD-L1, pan-CK/SOX10). Whole slide images from two rounds of imaging (x20 magnification; four markers in each round) were aligned using Ultivue's UltiStacker software based on the nuclear counterstains from the two imaging rounds, to provide precise marker colocalization data. Cell phenotype data for each core was generated using Visiopharm software. Results: Overall PD-L1 positivity was greatest for NSCLC, SCLC, TNBC and gastric cancer ranging from approximately 600-1000 PD-L1+ cells/mm2/core, compared with CRC, breast, pancreatic, liver, and gastric esophageal junction (GOJ) cancers (approx. 50-300 PD-L1+ cells/mm2/core). Contribution by macrophages to overall PD-L1 expression (dual CD68+/PD-L1+) varied by tumor type representing 25-35% for NSCLC (SCC and ADC) and gastric cancer, whereas a converse pattern was apparent for SCLC, TNBC, breast (ER+ and Her2+) and pancreatic cancers where PD-L1+ macrophages accounted for a large proportion (approx. 60-85%) of overall tumor PD-L1 expression. Interestingly, as a proportion of total macrophage infiltration, approximately 65% of CD68+ macrophages were PD-L1+ for SCLC and TNBC, compared with less than 10% for pancreatic and liver cancer. Spatial analysis revealed PD-L1+ macrophage infiltration to be generally higher for IM versus TC, and the distribution between tumor (CK+) and stroma (CK-) remained similar despite exclusion of CD3+/CD8+ cytotoxic T cells from CK+ tumor regions for pancreatic and liver cancer. Conclusions: Taken together, these data illustrate the benefits of combining multiplexed immunofluorescence staining, with digital analysis of cell phenotypes within well characterized tumor samples to better understand the relative immunobiology of different TMEs. Here we demonstrate that the relative contribution of macrophages to the overall PD-L1 microenvironment varies between tumor types, which may help guide options for successful immunotherapy strategies.

The differentiation of solitary intra-axial hematomas from hemorrhagic neoplasms based on their magnetic resonance imaging (MRI) features is challenging. The treatment and prognosis for these two disease entities are vastly different and distinction between them is often based on MRI findings alone. The aim of this study was to describe the 1.5 tesla MRI features of canine intra-axial hematomas and correlate these findings with the evolution of hemorrhages described in human brains. Retrospective evaluation of patient details, clinical signs, and MRI findings of dogs with intra-axial hematomas that were histopathologically confirmed or determined via repeat MRI study and/or resolution of neurological signs. Ten dogs met the inclusion criteria. All 10 hematoma lesions were determined to be 2–7 days in age. On MRI, all 10 hemorrhagic lesions were comprised of two distinct regions; a relatively thin T1-weighted (T1W), T2-weighted (T2W) and gradient echo (GRE) hypointense (9/10) peripheral border region and a large central region that was heterogenous but predominantly T1W, T2W and GRE hyperintense (8/10). The peripheral border region was complete in its integrity in all 10 cases on T2W and GRE sequences. Contrast enhancement was present in (6/10) hematoma lesions and was always peripheral in nature with no evidence of central enhancement associated with any of the lesions. An intra-axial hematoma should be suspected in solitary hemorrhagic space occupying lesions that have a complete hypointense peripheral rim, elicit a peripheral contrast enhancement pattern, and display the expected temporal pattern of hematoma evolution.

In large-scale software applications, programmers often combine different programming languages because this allows them to use the most suitable language for a given problem, to gradually migrate existing projects from one language to another, or to reuse existing source code. However, different programming languages have fundamentally different implementations, which are hard to combine. The composition of language implementations often results in complex interfaces between languages, insufficient flexibility, or poor performance. We propose TruffleVM, a virtual machine (VM) that can execute different programming languages and is able to compose them in a seamless way. TruffleVM supports dynamically-typed languages (e.g., JavaScript and Ruby) as well as statically typed low-level languages (e.g., C). It consists of individual language implementations, which translate source code to an intermediate representation that is executed by a shared VM. TruffleVM composes these different language implementations via generic access . Generic access is a language-agnostic mechanism that language implementations use to access foreign data or call foreign functions. It features language-agnostic messages that the TruffleVM resolves to efficient foreign-language-specific operations at runtime. Generic access supports multiple languages, enables an efficient multi-language development, and ensures high performance. We evaluate generic access with two case studies. The first one explains the transparent composition of JavaScript, Ruby, and C. The second one shows an implementation of the C extensions application programming interface (API) for Ruby. We show that generic access guarantees good runtime performance. It avoids conversion or marshalling of foreign objects at the language boundary and allows the dynamic compiler to perform its optimizations across language boundaries.

Context: Software development tools that interact with running programs such as debuggers, profilers, and dynamic analysis frameworks are presumed to demand difficult tradeoffs among implementation complexity (cost), functionality, usability, and performance. Among the many consequences, tools are often delivered late (if ever), have limited functionality, require non-standard configurations, and impose serious performance costs on running programs. Inquiry: Can flexible tool support become a practical, first class, intrinsic requirement for a modern highperformance programming language implementation framework? Approach: We extended the Truffle Language Implementation Framework, which together with the GraalVM execution environment makes possible very high performance language implementations. Truffle's new Instrumentation Framework is language-agnostic and designed to derive high performance from the same technologies as do language implementations. Truffle Instrumentation includes: (1) low overhead capture of execution events by dynamically adding "wrapper" nodes to executing ASTs; (2) extensions to the Language Implementation Framework that allow per-language specialization, primarily for visual display of values and names, among others; and (3) versatile APIs and support services for implementing many kinds of tools without VM modification. Knowledge: It is now possible for a client in a production environment to insert (dynamically, with thread safety) an instrumentation probe that captures and reports abstractly specified execution events. A probe in fully optimized code imposes very low overhead until actually used to access (or modify) execution state. Event capture has enabled construction of numerous GraalVM services and tools that work for all implemented languages, either singly or in combination. Instrumentation has also proved valuable for implementing some traditionally tricky language features, as well as some GraalVM services such as placing bounds on resources consumed by running programs. Grounding: Tools for debugging (via multiple clients), profiling, statement counting, dynamic analysis, and others are now part of GraalVM or are in active development. Third parties have also used Truffle Instrumentation for innovative tool implementations. Importance: Experience with Truffle Instrumentation validates the notion that addressing developer tools support as a forethought can change expectations about the availability of practical, efficient tools for high-performance languages. Tool development becomes a natural part of language implementation, requiring little additional effort and offering the advantage of early and continuous availability.