Search Results (22)

ANKRD26-related thrombocytopenia (ANKRD26-RT) is characterized by lifelong mild to moderate thrombocytopenia. Patients suffer from an increased susceptibility to acute or chronic myeloid leukemia, myelodysplastic syndrome, or chronic lymphocytic leukemia. We described here a patient with inherited thrombocytopenia initially misdiagnosed as immune thrombocytopenic purpura. A chromosomal deletion involving the ANKRD26 gene was identified. Gene and protein expression analyses suggest an alternative pathogenic mechanism of altered megakaryopoiesis: the synthesis of a chimeric protein with aberrant expression due to the unregulated action of a promoter from a gene located upstream of ANKRD26. This study highlights the importance of advanced genetic testing and functional analysis of patients’ primary cells in the case of the detection of previously unrecognized structural variants in order to understand pathogenic mechanisms. These investigations provided a definitive diagnosis for the patient and facilitated the development of a tailored clinical management strategy, especially concerning the potential for myeloid transformation. Full article

Adjuvant endocrine therapy for early breast cancer significantly reduces recurrence but increases bone fragility. Given limited data on denosumab (60 mg every 6 months) in premenopausal patients receiving endocrine therapy for early breast cancer, we conducted a retrospective real-world study at the Gemelli Hospital (September 2018–January 2025). A descriptive analysis was performed. The primary endpoint was to assess efficacy, evaluated by changes in bone mineral density via dual-energy X-ray absorptiometry and by monitoring bone turnover markers, particularly serum C-terminal telopeptide of type I collagen. Safety was evaluated based on adverse endocrine therapy events (osteoporotic fractures) and adverse denosumab events (osteonecrosis of the jaw). Sixty-nine patients were eligible for the study. Endocrine therapy included ovarian function suppression with exemestane (89.8%) or tamoxifen (10.1%). Baseline spinal osteoporosis decreased from 20.3% to 5.8%, osteopenia from 39.1% to 34.8%, with normal T-scores rising from 17.4% to 34.8%. Femoral improvements were similar. Serum C-terminal telopeptide of type I collagen levels (evaluated in 35.8%) showed stable reduction in 97%. Denosumab adherence was 89.9%. One osteonecrosis of the jaw case occurred (1.4%); no fractures were reported. Denosumab demonstrated efficacy in improving bone density and reducing bone turnover, with excellent adherence and favorable safety. Longer follow-up is needed to assess post-discontinuation effects. Full article

Background/Objectives: HER2-positive breast cancer (HER2⁺BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2⁺BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting. The secondary objective was to assess the effectiveness. Methods: This was a multicenter, retrospective study across 24 Italian oncology centers, including 410 patients with HER2⁺BC treated with adjuvant T-DM1 following a lack of pCR after NAT. Patient characteristics, NAT regimens, and surgical outcomes were recorded. Tolerability was assessed by documenting adverse events (AEs) according to the CTCAE (v5.0). Preliminary effectiveness was evaluated in terms of relapse-free survival (RFS) and overall survival (OS). Results: Overall, 228 patients (55.6%) experienced at least one AE related to T-DM1, with 4.9% experiencing grade 3 or higher AEs. The most common AEs were hepatotoxicity (18.5%) and thrombocytopenia (17.6%). T-DM1 was discontinued in 10.0% of patients due to toxicity. After a median follow-up of 25 months, 31 relapse events (7.6%) and 22 deaths (5.4%) were reported. The preliminary incidence of RFS and OS events was similar between patients who completed the T-DM1 course and those who discontinued it early. Conclusions: T-DM1 demonstrated a manageable safety profile, and the adverse events were consistent with those reported in randomized trials. The data are not yet sufficient to allow for a formal analysis of RFS and OS, and long-term follow-up is required. Full article

The development of synergies between rural and urban areas is one of the EU’s objectives to contribute to smart and inclusive growth. Effective governance of rural–urban links is essential for balanced development but often lacks policy coherence. This study examines the role of spatial planning and food policy integration in enhancing local food system sustainability and resilience, specifically in peri-urban areas. It investigates challenges and enablers in this integration through a Living Lab experiment in Lucca (Italy) as part of the ROBUST H2020 project. The Living Lab methodology entailed envisioning, experimenting, and experiencing phases to identify key rural–urban connections and assess governance arrangements, focusing on reclaiming abandoned land in peri-urban areas together with local stakeholders. By highlighting the strengths and limitations of a multi-year collaborative research approach, the research highlights a weak recognition of rural–urban linkages and the need for improved dialogue between rural stakeholders and urban planners. Key recommendations comprise formalising public–private partnerships and cross-sectoral projects linking agriculture with education, tourism, and landscape (e.g., agricultural parks). Full article

Q fever is a widespread zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii, primarily transmitted through the inhalation of contaminated aerosols. This study aimed to detect C. burnetii in two Sicilian sheep flocks, with no better defined reproductive disorders reported by the farmers. Blood, individual and bulk milk, ticks, and conjunctival swabs were collected from both flocks (A and B). Real-time and traditional PCRs were carried out to detect C. burnetii DNA and anti-C. burnetii antibodies were searched using an ELISA. In terms of Farm A, C. burnetii DNA was detected in 7.1% of blood samples, 20% of individual milk samples, bulk milk, 66.6% of conjunctival swabs, and in all the examined tick pools. Anti-C. burnetii antibodies were found in 77.0% of sera, 92.5% of individual milk samples, and bulk milk. In terms of Farm B, C. burnetii DNA was detected in 3.8% of blood samples, 39.4% of individual milk samples, bulk milk, 100% of conjunctival swabs, and in all tick pools; anti-C. burnetii antibodies were present in 53.6% of sera, 73.2% of milk samples, and in bulk milk. Our results highlight the high diffusion of C. burnetii in the two outbreaks, with widespread pathogen circulation, significant shedding in dairy products, and high environmental contamination, highlighting the need for enhanced surveillance and control measures in dairy sheep farms. Full article

We assessed the impact of DNA damage response and repair (DDR) biomarker expressions in 222 node-positive early breast cancer (BC) patients from a previous Phase III GOIM 9902 trial of adjuvant taxanes. At a median follow-up of 64 months, the original study showed no disease-free survival (DFS) or overall survival (OS) differences with the addition of docetaxel (D) to epirubicine-cyclophosphamide (EC). Immunohistochemistry was employed to assess the expression of DDR phosphoproteins (pATM, pATR, pCHK1, γH2AX, pRPA32, and pWEE1) in tumor tissue, and their association with clinical outcomes was evaluated through the Cox elastic net model. Over an extended follow-up of 234 months, we confirmed no significant differences in DFS or OS between patients treated with EC and those receiving D → EC. A DDR risk score, inversely driven by ATM and ATR expression, emerged as an independent prognostic factor for both DFS (HR = 0.41, p < 0.0001) and OS (HR = 0.61, p = 0.046). Further validation in a public adjuvant BC cohort was possible only for ATM, confirming its protective role. Overall, our findings confirm the potential role of the DDR pathway in BC prognostication and in shaping treatment strategies advocating for an integrated approach, combining molecular markers with clinical–pathological factors. Full article

Serine/arginine-rich splicing factors (SRSFs) are a family of proteins involved in RNA metabolism, including pre-mRNA constitutive and alternative splicing. The role of SRSF proteins in regulating mitochondrial activity has already been shown for SRSF6, but SRSF4 altered expression has never been reported as a cause of bone marrow failure. An 8-year-old patient admitted to the hematology unit because of leukopenia, lymphopenia, and neutropenia showed a missense variant of unknown significance of the SRSF4 gene (p.R235W) found via whole genome sequencing analysis and inherited from the mother who suffered from mild leuko-neutropenia. Both patients showed lower SRSF4 protein expression and altered mitochondrial function and energetic metabolism in primary lymphocytes and Epstein–Barr-virus (EBV)-immortalized lymphoblasts compared to healthy donor (HD) cells, which appeared associated with low mTOR phosphorylation and an imbalance in the proteins regulating mitochondrial biogenesis (i.e., CLUH) and dynamics (i.e., DRP1 and OPA1). Transfection with the wtSRSF4 gene restored mitochondrial function. In conclusion, this study shows that the described variant of the SRSF4 gene is pathogenetic and causes reduced SRSF4 protein expression, which leads to mitochondrial dysfunction. Since mitochondrial function is crucial for hematopoietic stem cell maintenance and some genetic bone marrow failure syndromes display mitochondrial defects, the SRSF4 mutation could have substantially contributed to the clinical phenotype of our patient. Full article

Although the 6-Minute Walk Test (6MWT) is among the recommended clinical tools to assess gait impairments in individuals with Parkinson’s disease (PD), its standard clinical outcome consists only of the distance walked in 6 min. Integrating a single Inertial Measurement Unit (IMU) could provide additional quantitative and objective information about gait quality complementing standard clinical outcome. This study aims to evaluate the test–retest reliability, validity and discriminant ability of gait parameters obtained by a single IMU during the 6MWT in subjects with mild PD. Twenty-two people with mild PD and ten healthy persons performed the 6MWT wearing an IMU placed on the lower trunk. Features belonging to rhythm and pace, variability, regularity, jerkiness, intensity, dynamic instability and symmetry domains were computed. Test–retest reliability was evaluated through the Intraclass Correlation Coefficient (ICC), while concurrent validity was determined by Spearman’s coefficient. Mann–Whitney U test and the Area Under the receiver operating characteristic Curve (AUC) were then applied to assess the discriminant ability of reliable and valid parameters. Results showed an overall high reliability (ICC ≥ 0.75) and multiple significant correlations with clinical scales in all domains. Several features exhibited significant alterations compared to healthy controls. Our findings suggested that the 6MWT instrumented with a single IMU can provide reliable and valid information about gait features in individuals with PD. This offers objective details about gait quality and the possibility of being integrated into clinical evaluations to better define walking rehabilitation strategies in a quick and easy way. Full article

Introduction: Health professionals and bodyworkers may be pivotal in promoting prevention programs, providing tailored advice and guidance to patients’ adherence to self-care strategies, such as physical activity. Contemporary evidence encourages manual therapists to involve patients in decision-making and treatment procedures integrating passive and active approaches in treatment planning. This manuscript provides a definition and applications of neuromyofascial movement patterns, discusses the significance of functional assessment, and gives an example of clinical applications in the osteopathic field to highlight how this assessment can promote interdisciplinarity. Methods: The reporting framework used in the current manuscript followed guidelines for writing a commentary. Results: The manuscript highlights the crucial role that the neuromyofascial system plays in human movement and overall well-being and the importance of a functional neuromyofascial activity assessment in the context of person-centered participative care. Conclusions: Understanding individual neuromyofascial patterns could help healthcare practitioners, movement specialists, and bodyworkers in tailoring treatment plans, meeting patients’ unique needs, and promoting a more effective personalized approach to care. The current perspective could spark debates within the professional community and provide a research roadmap for developing an evidence-informed interprofessional framework. Full article

Leptospirosis is a worldwide widespread zoonosis caused by Leptospira genus. We report an acute leptospirosis case in a puppy housed at a municipal kennel and the subsequent diagnostic investigations carried out on all dogs housed in the kennel. Laboratory investigation included mainly a microagglutination test, real-time PCR, and multi-locus sequence typing (MLST) for Leptospira genus. Other agents of infection were excluded. The puppy resulted positive for Leptospira interrogans Icterohaemorrhagiae both with serological and molecular assays. All of the other 66 dogs in the kennel underwent clinical and laboratory investigations twice, 15 days apart. No other dog showed leptospirosis clinical signs. At the first sampling, eight dogs (12%) showed antibodies against Leptospira interrogans serogroup Icterohaemorragiae serovar Copenhageni. Real-time PCR on urine samples of seropositive dogs detected Leptospira spp. DNA in one sample, then identified as Leptospira interrogans serogroup Icterohaemorragiae by MLST. Fifteen days after, four of the previous seropositive dogs still showed antibodies against Leptospira spp. All urine samples collected from seropositive dogs were negative at real-time PCR. The study allowed the early confirmation of a Leptospirosis case and the identification of at least one asymptomatic carrier of pathogenic Leptospira spp. The prompt activation of all appropriate management measures allowed limiting and extinguishing the infection. Full article

Complexity analysis of electroencephalogram (EEG) signals has emerged as a valuable tool for characterizing Parkinson’s disease (PD). Fractal dimension (FD) is a widely employed method for measuring the complexity of shapes with many applications in neurodegenerative disorders. Nevertheless, very little is known on the fractal characteristics of EEG in PD measured by FD. In this study we performed a spatio-temporal analysis of EEG in PD using FD in four dimensions (4DFD). We analyzed 42 resting-state EEG recordings comprising two groups: 27 PD patients without dementia and 15 healthy control subjects (HC). From the original resting-state EEG we derived the cortical activations defined by a source reconstruction at each time sample, generating point clouds in three dimensions. Then, a sliding window of one second (the fourth dimension) was used to compute the value of 4DFD by means of the box-counting algorithm. Our results showed a significantly higher value of 4DFD in the PD group (p < 0.001). Moreover, as a diagnostic classifier of PD, 4DFD obtained an area under curve value of 0.97 for a receiver operating characteristic curve analysis. These results suggest that 4DFD could be a promising method for characterizing the specific changes in the brain dynamics associated with PD. Full article

Cardiovascular involvement has a great impact on morbidity and mortality in sickle cell disease (SCD). Currently, few studies are available regarding the paediatric setting and, moreover, current guidelines for the echocardiogram screening program in the asymptomatic paediatric population are controversial. We performed a retrospective observational monocentric study on 64 SCD patients (37 male and 27 female, median age 10) at the Bambino Gesù Childrens’ Hospital, who had undergone a routine transthoracic echocardiogram. In total, 46 (72%) patients had at least one cardiac abnormality. Left atrial dilatation (LAD) was present in 41 (65%) patients and left ventricular hypertrophy (LVH) was found in 29 (45%) patients. Patients with LAD showed lower median haemoglobin levels (p = 0.009), and a higher absolute reticulocyte count (p = 0.04). LVH was negatively correlated with the median haemoglobin value (p = 0.006) and positively with the reticulocyte count (p = 0.03). Moreover, we found that patients with cardiac anomalies had higher transfusion needs and a lower frequency of pain crises. In our setting, cardiac involvement has a high prevalence in the paediatric cohort and seems to be associated with specific laboratory findings, and with a specific clinical phenotype characterized by complications related to high haemodynamic load. Full article

Bioclimatic solar greenhouses are passive solar systems of relevant interest in the building sector, as they allow the reduction of energy needs related to air-conditioning. The aim of this work is to analyze the thermal behavior of a bioclimatic solar greenhouse attached to a residential building. It is equipped with photovoltaic solar blinds (SPBs) to manage solar inputs and produce electricity. Automated control systems are implemented to activate the vents and SPBs. The parametric performance analysis conducted using the dynamic simulation software EnergyPlus allowed the evaluation of the influence of glass type, thermal mass, size, ventilation and location. The results show how the automation of the vents allows the maximization of heat exchange throughout the year, leading to a reduction in consumption even during the summer period. Analyses conducted for some cities in the Mediterranean area show that the maximum energy saving obtained is greater than 13%; in addition, photovoltaic solar shading contributes to the production of more than 1000 kWh/year of electricity. Full article

In recent years, the knowledge about the immune-mediated impairment of bone marrow precursors in immune-dysregulation and autoimmune disorders has increased. In addition, immune-dysregulation, secondary to marrow failure, has been reported as being, in some cases, the most evident and early sign of the disease and making the diagnosis of both groups of disorders challenging. Dyskeratosis congenita is a disorder characterized by premature telomere erosion, typically showing marrow failure, nail dystrophy and leukoplakia, although incomplete genetic penetrance and phenotypes with immune-dysregulation features have been described. We report on a previously healthy 17-year-old girl, with a cousin successfully treated for acute lymphoblastic leukemia, who presented with leukopenia and neutropenia. The diagnostic work-up showed positive anti-neutrophil antibodies, leading to the diagnosis of autoimmune neutropenia, a slightly low NK count and high TCR-αβ+-double-negative T-cells. A next-generation sequencing (NGS) analysis showed the 734C>A variant on exon 6 of the TINF2 gene, leading to the p.Ser245Tyr. The telomere length was short on the lymphocytes and granulocytes, suggesting the diagnosis of an atypical telomeropathy showing with immune-dysregulation. This case underlines the importance of an accurate diagnostic work-up of patients with immune-dysregulation, who should undergo NGS or whole exome sequencing to identify specific disorders that deserve targeted follow-up and treatment. Full article

Breast cancer represents the most common type of cancer and is the leading cause of death due to cancer among women. Thus, the prevention and early diagnosis of breast cancer is of primary urgency, as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor involved in the regulation of neuronal functions through the binding of the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). In addition, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin, or by binding to TrkA receptors with low affinity. Several examples of in vitro and in vivo evidence show that NGF is both synthesized and released by breast cancer cells, and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signaling has been related to breast cancer invasion and metastasis. Other studies suggested that NGF and its receptors could represent a good diagnostic and prognostic tool, as well as promising therapeutic targets for breast cancer. In this paper, we comprehensively summarize and systematically review the current experimental evidence on this topic. INPLASY ID: INPLASY2022100017. Full article