Ceinge Biotecnologie Avanzate (Italy)

Genomic improvement and sustainable breeding of Mediterranean buffalo are hampered by the lack of breed-specific genomic resources compared with bovine. To address this gap, we aimed to identify a comprehensive set of high-confidence single-nucleotide polymorphisms (SNPs) in Mediterranean buffalo and evaluate their informativeness across other buffalo populations. A total of 58 whole-genome sequencing samples, from three different sets, were merged through the integration of short- and long-read sequencing technologies. Variants, both unique and shared among datasets, were identified using a combination of bioinformatic tools to increase the reliability of the dataset. From these, over 11 million high-confidence biallelic SNPs were identified in the Mediterranean breed. The same SNPs were also tested in additional populations (other rivers and swamps) to evaluate their polymorphism and missingness. These results provide a robust genomic resource for Mediterranean buffalo, overcoming the limitations of bovine-derived genotyping tools available today. The identified SNPs dataset lays the basis for the development of a breed-specific SNP array, providing a dense and informative set of markers that could support cost-effective SNP chip development compared with existing arrays and sequencing technologies. This resource will facilitate more accurate genomic selection, precision breeding, and the conservation of genetic diversity in the Mediterranean buffalo population.

Systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD) comprises a heterogeneous group of fibrosing lung disorders frequently complicated by progressive pulmonary fibrosis, a phenotype associated with accelerated lung function decline and increased mortality. Although antifibrotic therapies have improved clinical outcomes, significant unmet needs remain, particularly regarding treatment tolerability and integration with background immunosuppressive strategies. Preferential phosphodiesterase-4B (PDE4B) inhibition has emerged as a novel therapeutic approach targeting both inflammatory and fibrotic pathways through modulation of intracellular cyclic adenosine monophosphate signaling. This narrative review summarizes the biological rationale and emerging clinical evidence supporting nerandomilast, an oral preferential PDE4B inhibitor, in autoimmune-associated interstitial lung diseases. Preclinical data indicate that PDE4B inhibition may attenuate fibroblast activation, inflammatory signaling, and extracellular matrix deposition. Clinical trials conducted in progressive pulmonary fibrosis populations have demonstrated a reduction in lung function decline, with subgroup analyses suggesting potential benefit in autoimmune-related diseases, although evidence remains limited. The safety profile appears mainly characterized by gastrointestinal adverse events, with ongoing evaluation of neuropsychiatric safety and drug interactions in complex autoimmune populations. Overall, nerandomilast represents a promising investigational strategy bridging antifibrotic and immunomodulatory mechanisms, warranting further dedicated studies in SARD-ILD.

In the original publication [...].

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by reduced expression of the survival motor neuron (SMN) protein. In addition to affecting motor neuron survival, SMN deficiency impacts multisystem physiology and neurotransmission. Dopaminergic dysfunction has been reported in mouse models of SMA, leading to postural and locomotor impairments that improve upon treatment with L-DOPA and benserazide. However, whether altered dopamine metabolism contributes to clinical symptoms in SMA patients remains unclear. To investigate this issue, we conducted a real-world study involving patients with SMA1, SMA2, and SMA3. We measured the main dopamine-related catabolites - 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) - in cerebrospinal fluid (CSF) samples collected at baseline and after five intrathecal doses of Nusinersen, an SMN-enhancing therapy. No significant differences were observed in CSF DOPAC and HVA levels across SMA types or following treatment, and no association emerged with SMN2 copy number. In contrast, lower baseline DOPAC levels were detected in SMA1 patients requiring gastrostomy and tracheostomy, and were associated with reduced improvement on the CHOP-INTEND scale. These findings suggest that reduced central dopaminergic turnover reflects disease progression in SMA1 and is associated with more severe clinical impairment and limited functional recovery.

Identifying chronic myeloid leukaemia (CML) patients at risk of therapeutic switch remains debated. We analysed the cumulative risk of treatment change in the CML Italian network prospective cohort based on first-line tyrosine kinase inhibitors and patient characteristics. Sub-hazard ratios (sHRs) were estimated using Fine and Gray multivariable models. Among 1662 patients, initial treatment consisted of imatinib for 840 (50.5%), nilotinib for 490 (29.5%) and dasatinib for 332 (20.0%). Subsequently, 492 patients (29.6%) required second-line therapy, with 232 (47.1%) switching due to resistance and 176 (35.8%) due to intolerance. At 2 years, the risk of resistance was 18.3% for imatinib, 8.4% for dasatinib (sHR = 0.32; 95% confidence interval 0.21-0.49) and 6.8% for nilotinib (0.29; 0.19-0.42). The risk of switching increased in intermediate (1.95; 1.40-2.72) and high Eutos long term survival (ELTS) risk (3.19; 2.10-4.83) but was reduced with older age (0.97 per year; p < 0.0001). Intolerance at 2 years was 8.5% for imatinib, 12.4% for dasatinib (2.55; 1.73-3.75) and 5.2% for nilotinib (1.04; 0.65-1.65). Switching to a third-line therapy at 3 years was 8% for imatinib, 5% for dasatinib and 4% for nilotinib. The results showed that the time to first treatment switch for resistance is shorter for younger patients, for imatinib and for intermediate/high ELTS risks. The risk of switching for intolerance is higher for patients initially treated with dasatinib.

Schizophrenia is a severe psychiatric disorder that affects approximately 1% of the population. Despite the availability of antipsychotic therapies, about 30% of patients develop treatment-resistant schizophrenia (TRS), defined by a lack of response to at least two different antipsychotic trials. Although several genetic and environmental factors have been proposed to explain treatment resistance, metabolomic studies investigating circulating metabolites in TRS remain limited. In this pilot cross-sectional study, we conducted untargeted 1H NMR-based metabolomics to profile serum metabolites in TRS versus non-TRS patients. Notably, multivariate analysis revealed distinct serum metabolome profiles between the two groups. Additionally, Variable Importance in Projection (VIP) analysis and robust volcano plots showed significant differences between TRS versus non-TRS patients in metabolites involved in lipid and amino acid metabolism. Specifically, serine and glycine emerged as key discriminating molecules, prompting a complementary targeted HPLC analysis in the same serum samples. Although no significant group differences were observed in L-serine, D-serine, the D-serine/total serine ratio, or glycine levels, we found a positive correlation between D-serine levels and cognitive performance, particularly in the area of executive function, across the entire patient cohort. Additionally, a significant correlation between glycine and disorganization symptoms was found selectively in TRS patients. In conclusion, our study offers new insights into potential biomarkers for TRS, highlighting serine-glycine pathway as a possible crossroad between systemic dysmetabolism, NMDA receptor dysfunction, and cognitive impairment in TRS.

In recent years, growing attention has been paid to the lifestyle factors that influence young adults' well-being. University students represent young adults at risk of Sedentary Behavior (SB) and mental distress. Sport Science students represent a health-conscious population, less prone to mental distress. This study aims to investigate the associations between physical activity (PA) levels, different determinants of quality of life (QoL), orthorexia nervosa (ON) symptoms, and internet use among Sport Science students living in Naples. An online survey comprising General Data (GD) and eight validated questionnaires was used to assess PA levels, mood, sleep quality, eating habits, and digital behavior in a population of university students enrolled in Sport Science courses at Parthenope University, Naples. The statistical analyses included descriptive statistics, Student's t-test, a Mann-Whitney U Test, frequencies, chi-square tests, and a Spearman's rank correlation. All the analyses were performed using JASP and Jamovi software. We surveyed 775 students (472 M; 303 F; 22.85 ± 3.85 y; BMI 23.74 ± 3.63 kg/m2). Regarding the MET-min/week, 65% of participants reported being highly active, 28% moderately active, and 7% inactive. Poor sleep quality was reported by 20% of those surveyed. Additionally, 84% of participants declared average internet use, which positively correlated with their emotional profile and sleep quality. High PA levels were directly associated with the presence of ON symptoms in 27% of the participants, most of whom exercised in gyms. To our knowledge, this is the first study conducted on a study population of Sport Science University students addressing the complex and interconnected relationships between PA levels, QoL, ON symptoms, and internet use.

Quality assessment and assembly comparison are essential steps while assembling new genomes. Many tools for evaluating assemblies typically provide synthetic parameters representing assembly quality or overall features, while others provide long detailed files where it is not always easy to identify and visualize the regions of correspondence and difference among different chromosome assemblies. Here we present ChromoMapper, a new tool which scans the output from QUAST, as well as other similar alignment description files, to quickly identify and display similarities and differences between the compared assemblies. It uses the information provided about aligned blocks, combined with additional annotations, to represent the main alignment regions at chromosomal or sub-chromosomal scale, highlighting similarities and collinearity between compared sequences, points of inconsistency, discontinuities, repeated regions and interruptions in the assembled sequences. ChromoMapper is available at https://chromomapper.ceinge.unina.it/ and via Zenodo (https://doi.org/10.5281/zenodo.16778863).

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases originating from hematopoietic stem cell transformation, characterized by the clonal proliferation of hematopoietic progenitors. A specific subset includes myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions, particularly involving PDGFR A or B, which are sensitive to TK inhibitor treatment. We report a case of a 21-year-old patient with a myeloproliferative/myelodysplastic neoplasm, presenting with hyperleukocytosis, anemia, thrombocytopenia, and elevated LDH. The peripheral blood smear showed hypogranular neutrophils, eosinophils, basophils, and myeloid precursors. The absence of BCR::ABL1 and mutations in JAK2, CALR, and MPL excluded common MPNs. Cytogenetic analysis revealed a rearrangement between chromosomes 5 and 14. FISH analysis confirmed an inverted insertion from chromosome 5 to chromosome 14, involving the PDGFRB gene. WGS and RNAseq identified a fusion between PDGFRB and CCDC88C, causing the constitutive activation of PDGFRB. The fusion gene was confirmed by sequencing. This allowed for targeted therapy with a tyrosine kinase inhibitor (TKI), leading to molecular remission monitored by RT-qPCR. This case highlights how a multidisciplinary approach can identify atypical transcripts in MPN, guiding targeted therapy with TK inhibitors, thus resulting in effective treatment and molecular remission.

Odoribacter splanchnicus, a prominent member of the human gut microbiota, has emerged as a promising next-generation probiotic due to its anti-inflammatory properties and association with intestinal health. While previous studies have demonstrated its ability to attenuate inflammation and protect epithelial integrity, the molecular basis underlying these effects remained elusive. In this study, we provide the first comprehensive structural and functional characterization of the O. splanchnicus lipooligosaccharide (LOS), a major immunomodulatory surface component. NMR spectroscopy and mass spectrometry revealed a heterogeneous LOS structure composed of a mono-phosphorylated tetra- and penta-acylated lipid A backbone and a highly branched, short core oligosaccharide featuring unique residues such as 4-lactylmannose and galactosaminuronic acid. Small-angle X-ray scattering demonstrated that the LOS self-assembles into core-shell spherical micelles, with a large oligosaccharide corona shielding the lipid A, thereby limiting its accessibility to the innate immunity TLR4/MD-2 receptor complex. Accordingly, the O. splanchnicus LOS exhibited minimal TLR4 activation and failed to induce IL-8 secretion in enterocyte cell lines, in stark contrast to proinflammatory Escherichia coli LPS; in addition, it potently antagonized E. coli LPS-induced inflammation. These findings identify the LOS as a key effector of the O. splanchnicus anti-inflammatory phenotype and support its further development as a live biotherapeutic agent.