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Abstract Multi-modal image analysis using deep learning (DL) lays the foundation for neoadjuvant treatment (NAT) response monitoring. However, existing methods prioritize extracting multi-modal features to enhance predictive performance, with limited consideration on real-world clinical applicability, particularly in longitudinal NAT scenarios with multi-modal data. Here, we propose the Multi-modal Response Prediction (MRP) system, designed to mimic real-world physician assessments of NAT responses in breast cancer. To enhance feasibility, MRP integrates cross-modal knowledge mining and temporal information embedding strategy to handle missing modalities and remain less affected by different NAT settings. We validated MRP through multi-center studies and multinational reader studies. MRP exhibited comparable robustness to breast radiologists, outperforming humans in predicting pathological complete response in the Pre-NAT phase (ΔAUROC 14% and 10% on in-house and external datasets, respectively). Furthermore, we assessed MRP’s clinical utility impact on treatment decision-making. MRP may have profound implications for enrolment into NAT trials and determining surgery extensiveness.

The article aims to provide an analysis based on the practical experience of social intervention in violence prevention with migrant minors arriving alone in Spain. In order to offer keys and recommendations, and based on situated knowledge, we provide insights on how to approach the intervention framework from a methodological point of view using liminal spaces as border and transition places that need to be named and taken into consideration for a transformative work. Different metaphorical borders, characterized by tension and potential change, are analyzed from a gender and intersectional perspective. We discuss the Law-border and the tension between protection they receive as minors and exclusion/politics of suspicion they receive as migrants. The Age-border (children/men) is discussed taking into account the different gender regimes they cross. The Color-border: here issues of racism and colonialism are considered. Finally, we discuss the Masculinity-border and the tension between reception and the reproduction of violence. We use the concept of liminal masculinities as a specific state or form that subordinate or marginalized masculinity adopts in migrant minors, suspended legally, functionally, and biographically, among others borders.

The volatilome profile of some biofluids (blood, urine, and human semen) identified by Solid-Phase Microextraction–Gas Chromatography/Mass Spectrometry (SPME-GC/MS) and collected from young men living in two high-pollution areas in Italy, i.e., Land of Fires and Valley of Sacco River, have been coupled to sperm parameters obtained by spermiogram analysis to build general multiple regression models. Panels of volatile organic compounds (VOCs) have been selected to optimize the models and used as predictive variables to estimate the different sperm quality parameters (sperm cell concentration, total and progressive motility/immotile cells, total/head/neck/tail morphology anomalies, semen round cell concentration). The results of the multiple linear regression models based on the different subgroups of data joining VOCs from one/two or three biofluids have been compared. Surprisingly, the models based on blood and urine VOCs have allowed an excellent estimate of spermiogram values, paving the way towards a new method of indirect evaluation of semen quality and preventive screening. The significance of VOCs in terms of toxicity and dangerousness was discussed with the support of chemical databases available online.

Background: Vaccination is one of the most important measures to contain the COVID-19 pandemic, especially for frail patients. VACCINATE is a multicentre prospective observational study promoted by the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) aimed at assessing the long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases (rcCTDs) in terms of efficacy and safety. Methods: Adult rcCTDs patients were eligible for recruitment. Demographic, clinical and vaccination data were collected at enrolment. Follow-up visits were scheduled 4, 12, 24, 36 and 48 weeks after completion of the first vaccination cycle; data on adverse events, disease exacerbations and the occurrence of new SARS-CoV-2 infections were collected at these time-points. Findings: 365 rcCTDs patients (87 % female, mean age 51.8 ± 14.6 years) were recruited. Overall, 200 patients (54.8 %) experienced at least one adverse event, generally mild and in most cases occurring early after the vaccination. During follow-up, 55 disease exacerbations were recorded in 39 patients (10.7 %), distributed over the entire observation period, although most frequently within 4 weeks after completion of the vaccination cycle. The incidence of new SARS-CoV-2 infections was 8.9 per 1000 person-months, with no cases within 12 weeks from vaccine administration and an increasing trend of infections moving away from the primary vaccination cycle. Only one case of severe COVID-19 was reported during the study period. Interpretation: COVID-19 vaccination seems effective and safe in rcCTDs patients. The rate of new infections was rather low and serious infections were uncommon in our cohort. No increased risk of disease flares was observed compared to previous disease history; however, such exacerbations may be potentially severe, emphasising the need for close monitoring of our patients.

Cardiovascular diseases represent one of the most frequent diseases worldwide; among these, lower limb ischemia is a threatening condition, which can lead to permanent disability if not promptly and correctly diagnosed and treated. A patient’s clinical evaluation and diagnostic imaging (e.g., color-Doppler ultrasound, computed tomography angiography (CTA), and magnetic resonance imaging (MRI)) are mandatory to carefully assess arterial lesion extension and severity. Digital subtraction angiography (DSA) is a minimally invasive technique that represents the gold standard for percutaneous revascularization treatment of symptomatic patients who are refractory to medical management. However, when dealing with patients with lower limb terminal ischemia, the correct interpretation of diagnostic DSA findings is mandatory for treatment re-planning and to effectively evaluate post-treatment results and complications. The purpose of this review is to provide interventional radiologists and endovascular practitioners with an up-to-date practical guide to diagnostic angiography of the lower limbs, which is mandatory to address correct treatment decisions and post-treatment evaluation.

In this retrospective study we share our single-center experience using a magnetic seed for the preoperative localization of non-palpable breast lesions. Patients who underwent a preoperative localization with Magseed® (Endomagnetics, Cambridge, UK) placement between 2020 and 2022 were enrolled. Indications to Magseed placement have been established during multidisciplinary meetings prior to surgery and all patients underwent breast-conserving surgery (BCS). 45 patients were included. Magnetic seeds have been introduced under ultrasound guidance in 40 patients (88.9%) and under stereotactic guidance in 5 patients (11.1%). We registered a highly successful placement rate (97.8%), with only one case of migration (2.2%). After BCS, all the magnetic seeds were recovered (100% retrieval rate). The re-excision rate for positive margins was 0%. Our experience, with a highly successful placement and retrieval rate and a re-excision rate equal to 0%, is consistent with the encouraging literature published on Magseed so far, suggesting this technique to be extremely effective. Moreover, our single case of seed migration supports the existing data stating that Magseed migration is rare. In conclusion, despite acknowledging Magseed limitations, we highly value the advantages linked to this technique, and we, therefore, uphold its use.

Gallbladder percutaneous tissue sampling is a not-so-common technique in cytohistological diagnosis of gallbladder tissue or masses, which can be useful in cases of surgically unresectable disease and unfeasible endoscopic assessment to address the most adequate chemotherapy course. Nonetheless, gallbladder percutaneous tissue sampling can be of great utility in the patient’s diagnostic and therapeutic work-up. This article summarizes the literature evidence on gallbladder biopsy techniques, complications, and technical precautions for a safe and effective sampling.

Although association between hearing impairment and dementia has been widely documented by epidemiological studies, the role of auditory sensory deprivation in cognitive decline remains to be fully understood. To address this issue we investigated the impact of hearing loss on the onset and time-course of cognitive decline in an animal model of Alzheimer’s disease (AD), that is the 3×Tg-AD mice and the underlying mechanisms. We found that hearing loss induced by noise exposure in the 3×Tg-AD mice before the phenotype is manifested caused persistent synaptic and morphological alterations in the auditory cortex. This was associated with earlier hippocampal dysfunction, increased tau phosphorylation, neuroinflammation, and redox imbalance, along with anticipated memory deficits compared to the expected time-course of the neurodegenerative phenotype. Our data suggest that a mouse model of AD is more vulnerable to central damage induced by hearing loss and shows reduced ability to counteract noise-induced detrimental effects, which accelerates the neurodegenerative disease onset.

Background: Although the diffusion of novel synthetic opioids has become a worldwide phenomenon, their prevalence of use in Italy seems to be limited. Existing national data is mainly derived by anamnestic surveyslacking of toxicological validation and not always disclosing the use of these compounds, which might remain under-diagnosed. Methods: an assessment of the metabolites of the main synthetic opioids on hair samples was carried out among patients admitted at the Addiction Treatment Unit of Trento. The analytical approach included: (a) screening by means of immunoenzymatic method for fentanyl, fentanyl analogs and oxicodone; (b) confirmation of the samples resulted positive for fentanyl and oxicodone by means of HPLC-MS/; (c) search and dosage detection of Tramadol by means of HPLC-MS/MS. Results: 3 out of 309 analysed samples were found positive: one was positive to Fentanyl and two to 4-ANPP. In the same cohort, 6 samples were also found positive for Oxycodone . Tramadol was searched in 189 samples and 12 of them resulted positive. Discussion and conclusion: Those found positive were mainly young adults engaging in dangerous patterns of use and lacking awareness of risks. The phenomenon requires further consideration by health professionals. Training and more evidence-based information on synthetic opioids as well as other Novel Psychoactive Substances (NPS) are urgently needed.

Early diagnosis of Alzheimer’s disease (AD) supposedly increases the effectiveness of therapeutic interventions. However, presently available diagnostic procedures are either invasive or require complex and expensive technologies, which cannot be applied at a larger scale to screen populations at risk of AD. We were looking for a biomarker allowing to unveil a dysfunction of molecular mechanisms, which underly synaptic plasticity and memory, before the AD phenotype is manifested and investigated the effects of transcranial direct current stimulation (tDCS) in 3×Tg-AD mice, an experimental model of AD which does not exhibit any long-term potentiation (LTP) and memory deficits at the age of 3 months (3×Tg-AD-3M). Our results demonstrated that tDCS differentially affected 3×Tg-AD-3M and age-matched wild-type (WT) mice. While tDCS increased LTP at CA3-CA1 synapses and memory in WT mice, it failed to elicit these effects in 3×Tg-AD-3M mice. Remarkably, 3×Tg-AD-3M mice did not show the tDCS-dependent increases in pCREBSer133 and pCaMKIIThr286, which were found in WT mice. Of relevance, tDCS induced a significant increase of plasma BDNF levels in WT mice, which was not found in 3×Tg-AD-3M mice. Collectively, our results showed that plasticity mechanisms are resistant to tDCS effects in the pre-AD stage. In particular, the lack of BDNF responsiveness to tDCS in 3×Tg-AD-3M mice suggests that combining tDCS with dosages of plasma BDNF levels may provide an easy-to-detect and low-cost biomarker of covert impairment of synaptic plasticity mechanisms underlying memory, which could be clinically applicable. Testing proposed here might be useful to identify AD in its preclinical stage, allowing timely and, hopefully, more effective disease-modifying interventions.

Abstract In buffalo (Bubalus bubalis) reproductive seasonality, causing cycles of milk production, is one of the major factors affecting farming profitability. Follicular fluid (FF) contains extracellular vesicles (EVs) playing an important role in modulating oocyte developmental competence and carrying microRNAs (miRNAs) essential for in vitro fertilization outcomes. The aim of this work was to characterize the FF-EVs-miRNA cargo of antral (An) and preovulatory (pO) follicles collected in the breeding (BS) and non-breeding (NBS) seasons, to unravel the molecular causes of the reduced oocyte competence recorded in buffalo during the NBS. In total, 1335 miRNAs (538 known Bos taurus miRNAs, 324 homologous to known miRNAs from other species and 473 new candidate miRNAs) were found. We identified 413 differentially expressed miRNAs (DE-miRNAs) (FDR

This work aimed to evaluate the effect of crocin on frozen-thawed sperm quality in buffalo. Spermatozoa were incubated in Tyrode’s Albumin Lactate Pyruvate medium supplemented with 0, 0.5, 1, and 2 mM crocin for 2 h. Sperm motility was evaluated by phase-contrast microscopy, viability and acrosome integrity by Trypan blue Giemsa staining, and membrane functional integrity by the hypoosmotic swelling test. The DNA fragmentation was evaluated by Tunel and ROS levels by spectrofluorometric analysis. The treatment with 2 mM of crocin increased (P

The study evaluated the effects of eCG treatment prior to ovum pick up (OPU) on follicular population, oocyte and embryo yields in summer and autumn in Podolic cattle. The effects of repeated OPU on cattle wellbeing was also documented. Twenty-six animals were used, and split into two groups, treatment (OPU; n = 18) and control (CG; n = 8). The OPU cattle were subsequently split into two subgroups (n = 9) and underwent repeated OPU, without and with eCG priming, for a total of 8 sessions (4 sessions/season). Follicular population, oocyte and embryo yields were recorded in those sub-groups. CG was handled in the same manner of OPU, except for epidural anaesthesia and follicular aspiration. Biochemical profile, serum protein electrophoresis and haptoglobin levels were analysed in OPU and CG. Hormonal priming increased the number of medium follicles (1.7 ± 0.2 vs 0.9 ± 0.2, p

The aim of this study was to determine whether buffalo heifers maintained at a constant live weight (LW) and body condition score (BCS) by a restricted diet show changes in reproductive function in response to changes in day length. Heifers were fed a low energy diet (86% daily intake recommended for the species) throughout the study, which involved an 8-week period of decreasing day length and a 7-week period of increasing day length. Weekly, LW, BCS and ovarian follicular/oocyte population were assessed. Blood and follicular fluid samples were taken at the time of ovum pick-up for hormone analyses and at 30-day intervals to measure metabolic substrates. Buffalo heifers maintained LW and BCS throughout the study and blood concentrations of the main metabolic hormones, such as GH, insulin, IGF-1 and thyroid hormones were not influenced by photoperiod. Likewise, there were no differences in metabolic substrates such as glucose, NEFA, triglycerides and HDL cholesterol, suggesting that the metabolic condition remained essentially the same. During increasing day length periods, the number of total follicles (8.4 ± 0.5 vs. 11.9 ± 0.6; p

Antioxidant supplementation has been proposed as a new strategy to improve the long-term preservation of semen. The aim of this study was to evaluate the effect of Maca supplementation of semen extender on quality-related canine semen parameters during cooling. Ejaculates from nine dogs were cooled for 7 days in the absence (control group) or in the presence of 10, 20 and 50 μL/mL of an aqueous extract of Maca. Sperm were evaluated for sperm viability, motility, DNA fragmentation and lipid peroxidation after 3 h, 24 h, 4 days and 7 days of storage. The addition of 10 μL/mL of Maca preserved sperm DNA and plasma membrane integrity at 3 h and increased sperm curvilinear velocity after 24 h. Treatment with 20 and 50 μL/mL of Maca increased the percentage of hyperactivated sperm after 3 h. Moreover, semen treated with 20 μL/mL of Maca decreased lipid peroxidation at 24 h. A significant reduction of sperm DNA and plasma membrane integrity as well as of kinetics parameters between 3 and 24 h of refrigerated storage with the higher concentration tested was observed. Although Maca was not able to protect canine semen with extended refrigeration storage time, it increased hyperactivation and preserved DNA integrity in short-term storage.

Chromosomal aberrations are relatively frequent pathologies in both humans and animals. Among them, translocations present a specific meiotic segregation pattern able to give a higher percentage of unbalanced gametes that can induce fertility problems. In this study, the meiotic segregation patterns of 1p, 1q and 18 Bubalus bubalis chromosomes were analyzed in both total sperm fraction and motile sperm fraction of a t(1p;18) carrier and a control bulls by triple-color FISH analysis with a pool of specific BAC probes. The frequencies of each total sperm fraction products in the carrier resulting from alternate, adjacent I, adjacent II and 3:1 segregation were 39%, 20%, 1% and 38%, respectively. On the other hand, the frequencies of each motile sperm fraction products in the carrier resulting from alternate, adjacent I, adjacent II and 3:1 segregation were 93%, 5%, 0% and 2%, respectively. The frequencies of normal sperms in the carrier were 27% and 69% in total sperm fraction and motile sperm fraction, respectively. The frequencies detected in motile sperm fraction were also validated by comparison with bull's progeny. To our knowledge, this is the first report on the meiotic segregation patterns in motile sperm fractions of B. bubalis bull carrying a chromosomal translocation. These data suggest that translocation has a very limited effect on aneuploidy in the gametes, and therefore, on the reproductive abilities of the bull.

Isomers of conjugated linoleic acid (CLA) enhances circulating insulin-like growth factor I (IGF-I) levels. Furthermore, fertility rate of breeding bulls is positively correlated to seminal plasma IGF-I concentration. Our objective was to evaluate the effect of dietary CLA supplementation and inclusion to the semen extender on bovine semen quality and freezability. Fourteen bulls, randomly assigned to control (CTL) and CLA (50 g/day) groups, were supplemented for 10 weeks. Samples were collected at Weeks −2 (before supplementation), 0, 4, 6 (during supplementation), 10, and 11 (after supplementation). Blood and seminal plasma were analyzed for IGF-I; the ejaculates were frozen in the following subgroups: CTL (no addition to semen extender), CLA c9, t11 (50 µM), CLA c9, t11 (100 µM), CLA t10, c12 (50 µM), CLA t10, c12 (100 µM), and CLA mix (50 µM each of CLA c9, t11 and CLA t10, c12). Sperm motility, morphology, viability, mitochondrial membrane potential, and reactive oxidative species were assessed. CLA supplementation decreased ejaculates’ total volume, increased sperm concentration, beat cross frequency, and decreased oxidative stress; it also increased plasma and seminal plasma IGF-I levels compared to the CTL. The inclusion of CLA c9, t11 100 µM and CLA mixture in the extender increased live spermatozoa percentage post-thawing compared to other groups. Our results show a beneficial effect of CLA supplementation on semen quality; however, further studies evaluating fertilization rates are necessary to corroborate the results.

The aim of this work was to evaluate whether the residual amount of γ-glutamyl-transferase (GGT) and alkaline phosphatase (ALP) in bovine sperm after freezing/thawing is correlated with fertility parameters, including blastocyst rates after in vitro fertilisation (IVF). The enzyme activities were determined in both spermatozoa and supernatant after centrifugation. While ALP was only correlated with sperm viability, GGT activity was correlated with sperm motility (rs = .4; p

The effect of crocin in the semen extender before cryopreservation was evaluated on sperm parameters of 20 bucks of five different breeds: Garganica (GA), Jonica (JO), Maltese (MA), Mediterranean Red (MR) and Saanen (SA). Semen samples were centrifuged, to remove seminal plasma, divided in two aliquots and diluted with Tris-egg-yolk-based extender, containing 0 (control group) and 1 mM crocin. Crocin concentration was established after a preliminary dose trial. On fresh and frozen-thawed sperm, motility, viability, morphology, membrane integrity, DNA fragmentation and ROS levels were evaluated. The freezing process led to a decrease (p < 0.05) in all the sperm parameters recorded, confirming the deleterious effect of cryopreservation on goat semen. The most interesting result regarding the inclusion of crocin in the extender before cryopreservation was as follows: Crocin significantly improved (p < 0.05) sperm motility in all breeds, except for Mediterranean Red, compared to the control group. Furthermore, 1 mM crocin reduced percentage of spermatozoa with DNA fragmentation with a marked decrement (p < 0.05) in Garganica and Saanen, as compared to the control group. Finally, intracellular ROS decreased (p < 0.01) in the crocin-treated sperm of all breeds, as compared to the control. In conclusion, supplementation of 1 mM crocin in the extender decreased oxidative stress, improving sperm motility and the DNA integrity of frozen-thawed sperm in different breeds.

Semen cryopreservation determines several sperm damages, including the loss of fertility-associated proteins. The purpose of the study was to compare the metabolite contents in bovine sperm and seminal plasma before and after cryopreservation, and between high- and low-fertility bulls in vitro. Forty-eight ejaculates, collected from eight bulls (six per bull), were analyzed by liquid chromatography–mass spectrometry. Cryopreservation resulted in an over-expression of lysophosphatidylcholine (0:0/18:2(9Z,12Z)) in seminal plasma. In addition, higher levels of glycine betaine and pyro-l-glutaminyl-l-glutamine were observed in cryopreserved compared to fresh spermatozoa. The fresh seminal plasma of high-fertility bulls showed an over-expression of l-acetylcarnitine, glycerol tripropanoate, 2,3-diacetoxypropyl stearate and glycerophosphocholine, and an under-expression of lysophosphatidylcholine and butyrylcarnitine, compared to low-fertility bulls. Higher levels of glycerophosphocholine and lysophosphatidylcholine (16:0/0:0) were recorded in fresh spermatozoa from high-fertility bulls. In high-fertility bulls, a greater content of glycerophosphocholine and lower levels of butyrylcarnitine, glycine betaine and l-carnitine were found in cryopreserved seminal plasma, and lower levels of glycine betaine were detected in cryopreserved spermatozoa. In conclusion, cryopreservation affects bovine semen metabolome at both plasmatic and cellular compartments, and metabolic profile differs between high- and low-fertility bulls.

Recent studies advocated the use of active cycling coupled with functional electrical stimulation to induce neuroplasticity and enhance functional improvements in stroke adult patients. The aim of this work was to evaluate whether the benefits induced by such a treatment are superior to standard physiotherapy. A single-blinded randomized controlled trial has been performed on post-acute elderly stroke patients. Patients underwent FES-augmented cycling training combined with voluntary pedaling or standard physiotherapy. The intervention consisted of fifteen 30-minutes sessions carried out within 3 weeks. Patients were evaluated before and after training, through functional scales, gait analysis and a voluntary pedaling test. Results were compared with an age-matched healthy group. Sixteen patients completed the training. After treatment, a general improvement of all clinical scales was obtained for both groups. Only the mechanical efficiency highlighted a group effect in favor of the experimental group. Although a group effect was not found for any other cycling or gait parameters, the experimental group showed a higher percentage of change with respect to the control group (e.g. the gait velocity was improved of 35.4% and 25.4% respectively, and its variation over time was higher than minimal clinical difference for the experimental group only). This trend suggests that differences in terms of motor recovery between the two groups may be achieved increasing the training dose. In conclusion, this study, although preliminary, showed that FES-augmented active cycling training seems to be effective in improving cycling and walking ability in post-acute elderly stroke patients. A higher sample size is required to confirm results.

Myoepithelioma is an extremely rare tumour subtype and diagnosis is based on a wide variation of cellular morphology. FNAC specimens do not always suffice for a definitive differential diagnosis which depends on histology and immunohistochemistry of the lesion. Case Presentation. A 54-year-old female came to our attention with dysphagia and dyslalia of 6-month standing. Ear, Nose, and Throat (ENT) examination revealed a voluminous mass on the right portion of the base of her tongue, where postcontrast T2-weighted Magnetic Resonance Imaging (MRI) evidenced a hyperintense lesion. The fine-needle aspiration specimen taken for cytology was not diagnostic, as a differential diagnosis between myoepithelioma and a malignant neoplasm of the salivary glands necessitates parameters that cytology alone cannot provide. Therefore, the whole lesion was excised by diode laser through a transoral approach. Histology and immunohistochemistry of the completely excised lesion confirmed a myoepithelioma.