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The KMT2A ( MLL ) gene rearrangements ( KMT2A -r) are associated with a diverse spectrum of acute leukemias. Although most KMT2A -r are restricted to nine partner genes, we have recently revealed that KMT2A - USP2 fusions are often missed during FISH screening of these genetic alterations. Therefore, complementary methods are important for appropriate detection of any KMT2A -r. Here we use a machine learning model to unravel the most appropriate markers for prediction of KMT2A -r in various types of acute leukemia. A Random Forest and LightGBM classifier was trained to predict KMT2A -r in patients with acute leukemia. Our results revealed a set of 20 genes capable of accurately estimating KMT2A -r. The SKIDA1 (AUC: 0.839; CI: 0.799–0.879) and LAMP5 (AUC: 0.746; CI: 0.685–0.806) overexpression were the better markers associated with KMT2A -r compared to CSPG4 (also named NG2 ; AUC: 0.722; CI: 0.659–0.784), regardless of the type of acute leukemia. Of importance, high expression levels of LAMP5 estimated the occurrence of all KMT2A-USP2 fusions. Also, we performed drug sensitivity analysis using IC50 data from 345 drugs available in the GDSC database to identify which ones could be used to treat KMT2A -r leukemia. We observed that KMT2A -r cell lines were more sensitive to 5-Fluorouracil (5FU), Gemcitabine (both antimetabolite chemotherapy drugs), WHI-P97 (JAK-3 inhibitor), Foretinib (MET/VEGFR inhibitor), SNX-2112 (Hsp90 inhibitor), AZD6482 (PI3Kβ inhibitor), KU-60019 (ATM kinase inhibitor), and Pevonedistat (NEDD8-activating enzyme (NAE) inhibitor). Moreover, IC50 data from analyses of ex-vivo drug sensitivity to small-molecule inhibitors reveals that Foretinib is a promising drug option for AML patients carrying FLT3 activating mutations. Thus, we provide novel and accurate options for the diagnostic screening and therapy of KMT2A -r leukemia, regardless of leukemia subtype.

Hobert et al.in their case report titled “One-stage craniectomy and cranioplasty digital workflow for three-dimensional printed polyetheretherketone implant for an extensive skull multilobular osteochondosarcoma in a dog”, showcased the application of 3D printing technology in creating custom implants for cranial reconstruction, advancing surgical techniques in veterinary oncology and neurosurgery. Last but not least, in light of a well-known risk in human MRI studies, the report titled “Radiofrequency-induced thermal burn injury in a dog after magnetic resonance imaging” notified the veterinary profession of the possibility of this complication of veterinary MRI procedures, underscoring the need for caution and monitoring during and after imaging (Lichtenauer et al.). Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Veterinary neurology, like its counterpart in human medicine, often deals with rare, unexpected, complex, or poorly understood conditions. [...]the clinical presentations can be daunting for general practitioners and students, possibly leading to a fear of having to manage neurological patients (a phenomenon referred to as neurophobia in human and veterinary medical literature) (1–7). Publications describe newly recognized disorders, superior imaging modalities, advances in neurosurgical procedures and improved therapeutic options, but case numbers are often small. [...]while progress moves more slowly in the veterinary profession, case reports remain useful tools for documentation, education, and innovation. First-in-man (or first-in-dog/cat/...) clinical case reports introduce a novel treatment in patients for which safety and efficacy was first tested in in vitro studies and/or experimental small animals (e.g., rodents). Another impactful case report led to the identification of Neospora caninum which hitherto had been masquerading as Toxoplasma gondii; nowadays, there is extensive literature about this protozoan and its impact in several species (12,13).

A considerable body of published research on meningoencephalitis of unknown origin (MUO) exists; however, certain fundamental aspects relating to the epidemiology remain poorly characterized. These include the frequency of MUO diagnosis at referral level, reliable demographic risk factors, and the extent to which proposed diagnostic criteria are applied in referral clinical settings. Based on 1,121 MUO cases (from 01 January 2017 to 31 December 2021) treated at 13 referral centers in England and 750,000 control dogs from the VetCompass Programme, this study investigated a range of demographic risk factors using multivariable logistic regression analysis. Additionally, we report on clinical methods used for diagnosis. Meningoencephalitis of unknown origin represented 2.21% (95% CI: 2.08-2.34) of new neurological referrals (1,121/50721). Clinical diagnosis included both magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis in 1026 (91.5%) cases. Of these, 961 (89.3%) showed results indicative of MUO in both MRI and CSF. Abnormal MRI but normal CSF were found in 55 cases (5.4%), while normal MRI and abnormal CSF were found in 36 cases (3.5%). Both normal MRI and normal CSF were reported in 19 cases (1.5%). Screening for infectious disease was carried out in 1037 (92.5%) of cases. The diagnosis of MUO peaked at 4 years (median 4.33, IQR 2.50-6.92, range 0.30-15.00) and declined after age 10. Welsh Springer Spaniel (OR 23.76, 95% CI 10.37-54.43), Maltese (OR 20.53, 95% CI 14.53-29.01), Papillon (OR 17.48, 95% CI 7.66-39.91), Boston Terrier (OR 17.31, 95% CI 11.17-26.82), and French Bulldog (OR 9.14, 95% CI 7.14-11.71) had the highest MUO odds compared to crossbreed dogs. Brachycephalic breeds had 2.56 times higher odds (95% CI 2.23-2.95) than mesocephalic breeds. Dogs ≥15 kg had lower odds than those <10 kg. This study provides the largest referral-based analysis of MUO cases to date, offering updated insights into breed predispositions and clinical diagnosis. This more precise characterization of the demographic factors adds valuable context for future research design, particularly in breed-focused investigations and risk stratification. By documenting current diagnostic practices used by referral specialists, this work lays the foundation for greater consistency in case recognition and offers practical guidance for structuring future MUO clinical trials.

The aim of the study was to describe the signalment, clinical presentation and presumptive or final diagnoses of dogs with cranial thoracic spinal cord lesions identified on advanced imaging. Retrospective evaluation of the databases of three veterinary specialty centres, between 2009 and 2021, was performed to identify dogs with a lesion affecting the cranial thoracic vertebral column (T1-T6 vertebrae) as the primary cause for presenting signs of myelopathy and/or spinal pain. Eighty-four dogs were included in the study, with the majority ( n = 76) presenting with a progressive history of over 4-weeks' duration. On neurologic examination, most dogs were ambulatory ( n = 64), and the most common neuroanatomic localisation was the T3-L3 spinal cord segments ( n = 63). Twelve dogs (14%) showed a short-strided thoracic limb gait on clinical examination. The most common diagnosis was neoplasia ( n = 33), followed by anomalies ( n = 22, including vertebral body malformations in 14 dogs) and degenerative disorders ( n = 16, with intervertebral disc protrusion diagnosed in 9 dogs). The most common vertebrae affected were T3 and T5. Most dogs with degenerative conditions showed asymmetric clinical signs, and the majority of dogs with neoplasia showed signs of spinal hyperaesthesia on examination. The findings of this study describe the clinical signs and presumptive or final diagnoses associated with lesions affecting the cranial thoracic spinal cord. When combined with the signalment and clinical history, this information can assist in both the recognition of and problem-based approach to these cases.

Background Acute leukemia in early age (EAL) is characterized by acquired genetic alterations such as MLL rearrangements ( MLL -r). The aim of this case-controlled study was to investigate whether single nucleotide polymorphisms (SNPs) of IKZF1 , ARID5B , and CEBPE could be related to the onset of EAL cases (<24 months-old at diagnosis). Methods The SNPs ( IKZF1 rs11978267, ARID5B rs10821936 and rs10994982, CEBPE rs2239633) were genotyped in 265 cases [169 acute lymphoblastic leukemia (ALL) and 96 acute myeloid leukaemia (AML)] and 505 controls by Taqman allelic discrimination assay. Logistic regression was used to evaluate the association between SNPs of cases and controls, adjusted on skin color and/or age. The risk was determined by calculating odds ratios (ORs) with 95% confidence interval (CI). Results Children with the IKZF1 SNP had an increased risk of developing MLL -germline ALL in white children. The heterozygous/mutant genotype in ARID5B rs10994982 significantly increased the risk for MLL -germline leukemia in white and non-white children (OR 2.60, 95% CI: 1.09-6.18 and OR 3.55, 95% CI: 1.57-8.68, respectively). The heterozygous genotype in ARID5B rs10821936 increased the risk for MLL -r leukemia in both white and non-white (OR 2.06, 95% CI: 1.12-3.79 and OR 2.36, 95% CI: 1.09-5.10, respectively). Furthermore, ARID5B rs10821936 conferred increased risk for MLL - MLLT3 positive cases (OR 7.10, 95% CI:1.54-32.68). Our data do not show evidence that CEBPE rs2239633 confers increased genetic susceptibility to EAL. Conclusions IKZF1 and CEBPE variants seem to play a minor role in genetic susceptibility to EAL, while ARID5B rs10821936 increased the risk of MLL-MLLT3 . This result shows that genetic susceptibility could be associated with the differences regarding MLL breakpoints and partner genes.

γδ T cells are a unique T cell subpopulation that are rare in secondary lymphoid organs but enriched in many peripheral tissues, such as the skin, intestines and lungs. By rapidly producing large amounts of cytokines, γδ T cells make key contributions to immune responses in these tissues. In addition to their immune surveillance activities, recent reports have unravelled exciting new roles for γδ T cells in steady-state tissue physiology, with functions ranging from the regulation of thermogenesis in adipose tissue to the control of neuronal synaptic plasticity in the central nervous system. Here, we review the roles of γδ T cells in tissue homeostasis and in surveillance of infection, aiming to illustrate their major impact on tissue integrity, tissue repair and immune protection.This Review focuses on the roles of γδ T cells in tissue homeostasis and immune surveillance. The authors discuss exciting new studies showing how γδ T cells can regulate diverse physiological responses in tissues, ranging from thermogenesis in adipose tissue to remodelling at neuronal synapses.

Background Although there is consistent evidence of unhealthy changes in the 24-h movement behaviours when comparing pre-COVID-19 periods to the early stages of the pandemic, there is limited research on long-term changes among adolescents. This study aimed to analyze both between- and within-participant differences in accelerometer-assessed 24-h movement behaviours by comparing cross-sectional and prospective data from the pre-COVID-19 period (August to December 2019) to the period following the reopening of schools for in-person classes in southern Brazil (August to December 2022). Methods This is a repeated cross-sectional design with a nested cohort. The 24-h movement behaviours (i.e., light physical activity [LIPA] and moderate-to-vigorous physical activity [MVPA], sedentary behaviour [SB], and sleep time [SPT]) were assessed by processing raw accelerometer data derived from a 24-h/7-day wrist-worn protocol. Compositional multilevel models were applied to compare the 24-h movement behaviour composition between time points for both cross-sectional and prospective data. Self-reported sociodemographic characteristics were examined as potential moderators. Results The cross-sectional and prospective samples comprised, respectively, 1276 (53% female, average age of 16.4 ± 1.1) and 249 (53% female, average age of 15.6 ± 0.8) participants. The 24-h movement behaviour composition differed between time-points in the cross-sectional ( p  < 0.001) and prospective samples ( p  < 0.001). Differences from 2019 to 2022 were explained by lower MVPA (-3.3 and -5.4 min/day in cross-sectional and prospective analysis, respectively) and a higher SB (4.7 and 34 min/day in cross-sectional and prospective analysis, respectively). No significant differences were observed for LIPA and SPT. Conclusions Differences in the 24-h movement behaviour composition comparing the cross-sectional samples, although statistically significant, were considered trivial and unlikely to have a substantial practical impact. However, considerable differences were observed in the prospective analysis. The results suggest that most of the observed changes over time were expected as a natural consequence of aging during high school, with only a small portion attributable to the residual impact of the pandemic.