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Within a practical course of cytotaxonomy organized in Pisa (Italy) on February 2024 by the Group for Floristics, Systematics and Evolution of the Italian Botanical Society, we tested whether relevant differences in karyotype asymmetry and structure occur in four tetraploid European taxa from Paeonia sect. Paeonia (P. mascula subsp. russoi, P. officinalis subsp. huthii, P. officinalis subsp. italica, and P. peregrina). Our results point towards a homogeneous karyotype asymmetry and structure among studied tetraploid species, with no statistically significant difference among taxa and high overlap in variation highlighted by PCA.

Abstract Objective Lennox–Gastaut syndrome (LGS) is a severe form of epilepsy characterized by difficult‐to‐control seizures and cognitive dysfunction. Previous studies mainly focused on pediatric populations, and little is known about the long‐term cognitive outcome in adult patients with LGS. The objective of this study was to investigate the long‐term functional and adaptive behavior in adult patients with LGS. Methods This cross‐sectional study enrolled adult patients diagnosed with LGS according to the recently published International League Against Epilepsy (ILAE) diagnostic criteria. The adaptive behavior of participants was assessed using the Vineland Adaptive Behavior Scales, Survey Interview, Second Edition (VABS‐II). Demographic, clinical, electroencephalography (EEG), and antiseizure medication (ASM) data were also collected at different timepoints, to investigate their association with VABS‐II scores. Results The study included 38 adult patients with LGS. A low score on the Adaptive Behavior Composite Scale was found in all patients. When considering single VABS‐II domains, particularly low scores were found in daily living skills and socialization, whereas slightly higher performances were observed in communication. An earlier age at LGS diagnosis was identified as the most significant predictor of worse adaptive outcomes in adult life. At the time of study evaluation, high seizure frequency, higher EEG background slowing, and multifocal EEG epileptiform abnormalities were significantly associated with lower VABS‐II raw scores. Furthermore, in an exploratory correlation analysis with ASM regimen at the study visit, treatment with cannabidiol was associated with higher adaptive behavior scores, whereas benzodiazepine intake correlated with lower scores. Significance This study provides relevant insights into the long‐term challenges faced by adults with Lennox–Gastaut syndrome (LGS), highlighting significant impairments in adaptive behavior as well as the associated clinical and electroencephalography features. Additionally, this study provides a more specific neuropsychological profile in adults with LGS and underscores the importance of comprehensive care approaches that go beyond seizure control in this population. Plain Language Summary This study examined adults with Lennox–Gastaut syndrome (LGS), a severe type of epilepsy, to understand their long‐term abilities to perform daily tasks and adapt socially. We found that these adults have significant difficulties with daily living and social skills, although not all areas were equally affected. They performed somewhat better in communication, particularly in understanding others (receptive communication). Importantly, the younger the age at which LGS was diagnosed, the worse their outcomes were as adults. This study highlights the need for research and treatment approaches that focus not only on controlling seizures but also on improving daily life skills.

Abstract Background Spitz tumors are relatively uncommon melanocytic lesions, typically affecting a relatively younger population but can be encountered at any age. They are characterized by a proliferation of melanocytes with epithelioid and/or spindled cytomorphology features, and interpretation is often challenging. The majority of these tumors are driven by kinase fusions or HRAS mutations. MAP3K8 fusions, although rare, are characteristic genomic events in Spitz tumors, especially in more atypical or malignant lesions. Case presentation Here, we present the case of a 43-year-old woman with a clinically cystic mass in her right groin, histologically characterized as a spindle and epithelioid cell malignant tumor. Immunohistochemistry revealed diffuse expression of S100 protein, tyrosinase and SOX10, patchy weak PRAME, HMB45 and Melan-A reactivity, and negative staining for BRAF V600E. Next-generation sequencing analysis revealed the presence of a MAP3K8::ABLIM1 fusion gene, as well as GRIN2A and TERT promoter mutations. The morphology, immunohistochemistry and molecular analysis confirmed Spitz melanoma with molecular features suggesting a worse prognosis. Conclusion This case introduces a novel fusion partner of MAP3K8 in the context of Spitz melanoma and expands the morphologic and molecular spectrum of Spitz melanoma.

Background: Piperazines, synthetic compounds known for their stimulant and hallucinogenic effects, have gained prominence among novel psychoactive substances (NPS) and are frequently associated with adverse psychiatric outcomes, including psychosis. Methods: A systematic review of the literature available up to 23 May 2024 was conducted, using the PubMed, Scopus, and Web of Science databases, in addition to the related gray literature, utilizing the following search strategy: “piperazines” AND (“psychosis” OR “hallucination” OR “delusion” OR “schizophrenia” OR “delusional” OR “schizoaffective”) NOT review NOT animal. Data collection adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research methods were registered with PROSPERO (CRD42024549204). Results: Out of a total of 4547 articles identified, 4 met the inclusion criteria. We observed an important relationship between piperazine abuse and the onset of acute psychotic episodes, marked by symptoms such as paranoia, auditory, and visual hallucinations. Conclusion: The complex polyreceptor action mechanism of piperazines may explain these psychopathological effects, similar to those observed with other NPS. Although studies confirm a link between piperazine use and psychosis, data on long-term outcomes are limited. Recovery is common following cessation and treatment. Further research into the effects of piperazine abuse and the development of specific treatment protocols for substance-induced psychosis is necessary.

Although the risk of fluoropyrimidine toxicity may be decreased by identifying poor metabolizers with a preemptive dihydropyrimidine dehydrogenase (DPYD) test, following international standards, many patients with wild-type (WT) genotypes for classic variations may still exhibit adverse drug reactions (ADRs). Therefore, the safety of fluoropyrimidine therapy could be improved by identifying new DPYD polymorphisms associated with ADRs. This study was carried out to assess whether testing for the underestimated c.2194G>A (DPYD*6 polymorphism, rs1801160) is useful, in addition to other well-known variants, in reducing the risk of ADRs in patients undergoing chemotherapy treatment. This retrospective study included 132 patients treated with fluoropyrimidine-containing regimens who experienced ADRs such as gastrointestinal, dermatological, hematological, and neurological. All subjects were screened for DPYD variants DPYD2A (IVS14+1G>A, c.1905+1G>A, rs3918290), DPYD13 (c.1679T>G, rs55886062), c.2846A>T (rs67376798), c.1236G>A (rs56038477), and c.2194G>A by real-time polymerase chain reaction (RT-PCR). In this cohort, the heterozygous c.2194G>A variant was present in 26 patients, while 106 individuals were WT; both subgroups were compared for the incidence of ADRs. This assessment revealed a high incidence of gastrointestinal and hematological ADRs in DPYD6 carriers compared to WT. Moreover, we have shown a higher prevalence of ADRs in females compared to males when stratifying c.2194G>A carrier individuals. Considering that c.2194G>A was linked to clinically relevant ADRs, we suggest that this variant should also be assessed preventively to reduce the risk of fluoropyrimidine-related ADRs.

Background: Differentiated thyroid carcinoma (DTC), mainly papillary (PTC), at low risk of recurrence is currently managed with active surveillance strategies or less aggressive surgeries. However, total thyroidectomy with 131I treatment is still performed both if these tumors are diagnosed before or occasionally after surgery. This real-life study aimed to evaluate the rate of biochemical, structural, and functional events in a large series of consecutive DTCs at low risk of recurrence treated by total thyroidectomy, but not with 131I, in a medium–long-term follow-up. Patients and Methods: We evaluated clinical–pathologic data of 383 consecutive patients (2006–2012) with unifocal DTC [T1a/b(s)] at low risk of recurrence, treated with total thyroidectomy but without lymph node dissection and 131I treatment after surgery. We evaluated if structural, biochemical, and functional events were detected during the follow-up. Results: Females accounted for 75.7% of our study group, and the median age was 50 years. The median tumor dimension was 0.4 cm (range 0.1–1.2). Most of the patients had a unifocal T1a tumor (98.9%), and 73.6% had a classic variant of PTC. We divided the patients according to the absence (group A—n = 276) or presence (group B—n = 107) of interfering TgAb at first control after surgery. After a median follow-up of 10 years, no structural events were detected. Sixteen out of three hundred and eighty-three (4.2%) patients developed biochemical events: 12/276 (4.3%) in group A and 4/107 (3.7%) in group B. The median time elapsed from surgery to detecting a biochemical event was 14.5 and 77.5 months in groups A and B, respectively. No patients performed additional treatments and were followed up with an active surveillance strategy. Conclusions: This study confirmed that patients with DTC at low risk of recurrence showed an excellent outcome in a medium long-term follow-up since no structural events were diagnosed. Significant variations in Tg/TgAb were detected in a few cases, all managed with an active surveillance strategy without the need for other treatments. Therefore, a relaxed follow-up with neck ultrasound and Tg/TgAb measurement is enough to early identify those very unusual cases of recurrence.

Within a practical course of cytotaxonomy organized in Pisa (Italy) on February 2024 by the Group for Floristics, Systematics and Evolution of the Italian Botanical Society, we tested whether using image analysis softwares possible biases are still introduced by different observers. We conclude that observer bias selectively applies in possibly overestimating the length of short arms in a karyotype. As a consequence, the parameters most sensitive to these possible errors are CVCI and CVCL, and to a less degree MCA and THL. To achieve more stable results among observers, a still lacking standardized measurement protocol could be helpful.

Abstract We study CFTs at finite temperature and derive explicit sum rules for one-point functions of operators by imposing the KMS condition and we explicitly estimate one-point functions for light operators. Turning to heavy operators we employ Tauberian theorems and compute the asymptotic OPE density for heavy operators, from which we extract the leading terms of the OPE coefficients associated with heavy operators. Furthermore, we approximate and establish bounds for the two-point functions.

Abstract Background Anti-IgLON5 disease is an autoimmune encephalitis overlapping with neurodegenerative disorders due to pathological accumulation of hyperphosphorylated tau. It is characterized by several clinical manifestations determined by involvement of different brain areas, and mild response to first-line immunotherapies. We report a case of anti-IgLON5 disease with a multifaceted semiology and an unusually good response to glucocorticoid monotherapy. Case presentation A 68-year-old man with type 2 diabetes was evaluated for an 8-month history of progressive gait disorder causing frequent falls. He also suffered from obstructive sleep apneas and complained of dysphonia, dysarthria, occasional dysphagia, urinary incontinence, and upper limb action tremor. Neurological examination demonstrated bilateral eyelid ptosis, limitation of ocular horizontal smooth pursuit movements, slow horizontal saccades, and lack of inhibition of the vestibulo-ocular reflex during rapid horizontal head torsions. The patient also displayed involuntary, slow, rhythmic movements of the left periorbital and perioral muscles, spreading to the ipsilateral hemipalate and hemitongue, along with bilateral negative upper limb myoclonus. There were proximal muscle wasting in the upper limbs, proximal weakness of the four limbs, and diffuse fasciculations. Ataxia of stance and gait and of the four limbs was noted. MRI of the brain and spine was unremarkable; nerve conduction studies revealed a chronic, predominantly demyelinating, sensory-motor polyneuropathy, probably due to diabetes. Routine CSF examination was unrevealing and serum GFAP level was 89.6 pg/mL; however, the autoimmunity tests revealed a high-titer positivity for anti-IgLON5 autoantibodies in both CSF and serum, leading to the diagnosis of anti-IgLON5 disease. Symptoms improved significantly after intravenous methylprednisolone. Conclusions Hemifacial and hemiorolingual myorhythmia along with peculiar oculomotor abnormalities characterizes the multifaceted clinical picture of our case. The complex semiology of our patient may reflect multifocal targeting of the autoimmune process or sequential spreading of tau inclusions in different brain areas. Our patient’s optimal response to glucocorticoid monotherapy could be underpinned by a slightly different phenotype in which autoimmunity plays a greater pathogenic role than tauopathy, with a lower burden of tau deposition. In such patients, neurodegeneration and tau accumulation could be merely secondary to immune-mediated neuronal dysfunction, supporting the existence of a group of glucocorticoid-responsive patients.

Abstract Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, accompanied by chemotherapy and radiotherapy. Malignant cells escape surgical resection by migrating into the surrounding healthy brain tissue, where they give rise to the recurrent tumor. Based on gene expression, tumor cores can be subtyped into mesenchymal, proneural, and classical tumors, each being associated with differences in genetic alterations and cellular composition. In contrast, the adjacent brain parenchyma where infiltrating malignant cells escape surgical resection is less characterized in patients. Using spatial transcriptomics (n = 11), we show that malignant cells within proneural or mesenchymal tumor cores display spatially organized differences in gene expression, although such differences decrease within the infiltrated brain tissue. Malignant cells residing in infiltrated brain tissue have increased expression of genes related to neurodevelopmental pathways and glial cell differentiation. Our findings provide an updated view of the spatial landscape of glioblastomas and further our understanding of the malignant cells that infiltrate the healthy brain, providing new avenues for the targeted therapy of these cells after surgical resection.

Abstract With the rising prevalence of shoulder arthroplasty, the incidence of revision shoulder arthroplasty is also increasing. The complexity of these revision procedures poses significant challenges, with bone loss being a critical factor impacting treatment outcomes. Addressing substantial humeral bone defects is crucial for ensuring implant stability and functionality. A comprehensive literature review was conducted using PubMed, Medline, and Google Scholar to identify existing classification systems for proximal humeral bone loss in the context of revision shoulder arthroplasty. The study assessed the advantages and limitations of these classifications, using this information to propose a new diagnostic and therapeutic algorithm. Several classification systems for proximal humeral bone loss were identified. McLendon et al. classify proximal humeral bone loss based on a 5-cm bone loss threshold and suggest an allograft prosthesis composite for losses exceeding this limit. Boileau’s system stratifies bone loss into four types based on the extent of loss, with specific recommendations for each category. The PHAROS classification provides a detailed anatomical assessment but lacks quantitative precision. The proposed PHBL-SCORe system offers a novel algorithm incorporating preoperative radiographic measurements to determine the percentage of bone loss and guide treatment options. Proximal humeral bone loss presents significant challenges in revision shoulder arthroplasty, necessitating precise preoperative planning and classification to guide surgical intervention. Existing classification systems provide valuable frameworks but often rely on average population values, neglecting individual anatomical variations. The proposed PHBL-SCORe system offers a patient-specific approach, improving the accuracy of bone loss assessment and optimizing treatment strategies. Implementing this classification in clinical practice could enhance surgical outcomes and reduce complications associated with rRSA (revision Reverse Shoulder arthroplasty). Further studies are required to validate this algorithm and explore its long-term efficacy in diverse patient populations.

This work presents the first ecosystem accounts for Marine-Based Tourism (MBT) in Italy. We develop a methodological approach to connect biophysical and economic information required to fill ecosystem accounting supply and use tables. Coherent with the System of Environmental Economic Accounting – Ecosystem Accounting (SEEA EA) framework, this approach starts by estimating the extent and the condition of marine ecosystems, showing the urgency in improving the availability, organisation and accessibility of biophysical data. This work provides valuable insights into understanding MBT from an ecosystem accounting perspective. We focus on the Posidonia oceanica and its role in the MBT sector in Italy, providing a physical quantification of such contribution and converting this flow into monetary terms. Our findings show that such habitat significantly contributes to the tourism sector, resulting in exchange values of MBT of €6 million in 2019 and €3.7 million in 2021.

Magnetic resonance imaging is a novel imaging technique for guiding electrophysiology based ablation operations for atrial flutter and typical atrial fibrillation. When compared to standard electrophysiology ablation, this innovative method allows for better outcomes. Intra-procedural imaging is important for following the catheter in real time throughout the ablation operation while also seeing cardiac architecture and determining whether the ablation is being completed appropriately utilizing oedema sequences. At the same time, intra-procedural imaging allows immediate visualization of any complications of the procedure. We describe a case of a 67 year old male underwent an isthmus-cavo-tricuspid magnetic resonance-guided thermoablation procedure for atrial flutter episodes. During the procedure we noted an atypical focal thinning of the right atrial wall at the isthmus cava-tricuspidal zone. The post-procedural Black Blood T2 STIR showed an area of hyperintensity at the hepatic dome and glissonian capsule, which was consistent with intraparenchymal hepatic oedema, in close proximity to the atrial finding. Given the opportunity to direct monitoring of adjacent tissues, we aim to highlight with our case the ability of magnetic resonance-guided cardiac ablation to immediately detect peri-procedural complications in the ablative treatment of atrial fibrillation.

In the dynamic realm of civil engineering, the principles of structural analysis and rehabilitation are pivotal in extending the lifespan and enhancing the performance of existing structures [...]

This suspect case focuses on investigating the presence of halite (NaCl) crystals on the clothing of a deceased individual to determine whether they resulted from immersion in seawater or residual absorption after immersion (i.e., the crystals were left on the clothing after contact with the victim’s wet body). Thirteen clothing samples were collected from various garments worn by the victim and were subjected to optical stereomicroscopy, Scanning Electron Microscopy (SEM), coupled with Energy Dispersive Spectroscopy (EDS), and Simultaneous Thermal Analysis (STA). Optical stereomicroscopy revealed numerous white-colored, vitreous, and greasy luster microcrystals dispersed between fabric fibers, with higher concentrations observed near the hem seams and metal rivets. These microcrystals exhibited predominantly cubic and irregular morphologies. Additionally, sandy particles and organic elements, such as plant fragments and micro seashells, were detected, indicative of coastal environment exposure. SEM-EDS analysis confirmed the presence mainly of sodium and chlorine in stoichiometric ratios consistent with halite, with crystals exhibiting amorphous, needle-shaped, or cubic morphologies. Furthermore, STA analysis identified weight loss events attributed to organic decomposition and halite decomposition at high temperatures, corroborating SEM-EDS findings. The distribution and characteristics of halite crystals, along with other trace elements, support the hypothesis of immersion in seawater while wearing clothing. Specifically, the higher concentrations of halite crystals near thicker fabric portions and metal rivets suggest slower drying rates and longer evaporation times, indicative of immersion rather than residual absorption after swimming. This finding not only helps in determining the victim’s exposure to seawater but also establishes a methodology for distinguishing between different sources of halite residue on clothing. Overall, the comprehensive mineralogical characterization of halite crystals on clothing samples, using best practices of forensic mineralogy, provides valuable forensic insights related to the circumstances that led to the victim’s death. This approach aided investigators in reconstructing the sequence of events, enhancing the accuracy of forensic reconstructions. Moreover, this study contributes to the broader field of forensic geoscience by demonstrating the practical applications of mineralogical analysis in criminal investigations, potentially guiding future research and improving investigative techniques in similar cases.

The aim of these evidence-based guidelines is to present a consensus position from members of the Italian Unitary Society of Colon-Proctology (Società Italiana Unitaria di Colon-Proctologia, SIUCP) on the diagnosis and management of hemorrhoidal disease, with the goal of guiding physicians in the choice of the best treatment option. A panel of experts was charged by the Board of the SIUCP to develop key questions on the main topics related to the management of hemorrhoidal disease and to perform an accurate and comprehensive literature search on each topic, in order to provide evidence-based answers to the questions and to summarize them in statements. All the clinical questions were discussed by the expert panel in multiple rounds through the Delphi approach and, for each statement, a consensus among the experts was reached. The questions were created according to PICO (patients, intervention, comparison, and outcomes) criteria, and the statements were developed adopting the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology. In cases of grade 1 hemorrhoidal prolapse, outpatient procedures including hemorrhoidal laser procedure and sclerotherapy may be considered the preferred surgical options. For grade 2 prolapse, nonexcisional procedures including outpatient treatments, hemorrhoidal artery ligation and mucopexy, laser hemorrhoidoplasty, the Rafaelo procedure, and stapled hemorrhoidopexy may represent the first-line treatment options, whereas excisional surgery may be considered in selected cases. In cases of grades 3 and 4, stapled hemorrhoidopexy and hemorrhoidectomy may represent the most effective procedures, even if, in the expert panel opinion, stapled hemorrhoidopexy represents the gold-standard treatment for grade 3 hemorrhoidal prolapse.

Abstract We revisit and extend Fisher’s argument for a Ginzburg-Landau description of multicritical Yang-Lee models in terms of a single boson Lagrangian with potential φ 2(iφ) n . We explicitly study the cases of n = 1, 2 by a Truncated Hamiltonian Approach based on the free massive boson perturbed by PT symmetric deformations, providing clear evidence of the spontaneous breaking of PT symmetry. For n = 1, the symmetric and the broken phases are separated by the critical point corresponding to the minimal model M 2 5 $$ \mathcal{M}\left(2,5\right) $$ , while for n = 2, they are separated by a critical manifold corresponding to the minimal model M 2 5 $$ \mathcal{M}\left(2,5\right) $$ with M 2 7 $$ \mathcal{M}\left(2,7\right) $$ on its boundary. Our numerical analysis strongly supports our Ginzburg-Landau descriptions for multicritical Yang-Lee models.

Abstract In silico prediction of xenobiotic metabolism is an important strategy to accelerate the drug discovery process, as candidate compounds often fail in clinical phases due to their poor pharmacokinetic profiles. Here we present MetaQM, a dataset of quantum-mechanical (QM) optimized metabolic substrates, including force field parameters, electronic and physicochemical properties. MetaQM comprises 2054 metabolic substrates extracted from the MetaQSAR database. We provide QM-optimized geometries, General Amber Force Field (FF) parameters for all studied molecules, and an extended set of structural and physicochemical descriptors as calculated by DFT and PM7 methods. The generated data can be used in different types of analysis. FF parameters can be applied to perform classical molecular mechanics calculations as exemplified by the validating molecular dynamics simulations reported here. The calculated descriptors can represent input features for developing improved predictive models for metabolism and drug design, as exemplified in this work. Finally, the QM-optimized molecular structures are valuable starting points for both ligand- and structure-based analyses such as pharmacophore mapping and docking simulations.

This study compares the clinical performances of two lithium disilicate (Initial LiSi press vs. Initial LiSi Block, GC Corp.) and a 3D printed resin (Temp Print, GC Corp.) partial crown using modified United States Public Health Service (USPHS) evaluation criteria and survival rates after one year of clinical service. Eighty-nine partial adhesive restorations on posterior teeth were realized using different materials: Group 1 used Initial LiSi press, Group 2 used Initial LiSi Block, and Group 3 used Temp Print. An analog workflow was used to realize the restoration of Group 1, while a fully digital workflow was used for Groups 2 and 3. The modified USPHS parameters, together with periodontal parameters, were collected at baseline and at the one-year recall. Contingency tables to assess for significant differences of success over time in each group were used. All modified USPHS parameters showed Alpha or Bravo; no Charlie was recorded. No statistically significant difference emerged between the three groups in any of the assessed variables (p > 0.05). All modified USPHS scores were compatible with the outcome of clinical success, no restoration was replaced or repaired, and the survival rate was 100% at the one-year recall. No difference was found between the traditional and digital workflows used to fabricate the restorations.

Abstract The dynamics of first-order phase transitions in strongly coupled systems are relevant in a variety of systems, from heavy ion collisions to the early universe. Holographic theories can be used to model these systems, with fluctuations usually suppressed. In this case the system can come close to a spinodal point where theory and experiments indicate that the behaviour should be similar to a critical point of a second-order phase transition. We study this question using a simple holographic model and confirm that there is critical slowing down and scaling behaviour close to the spinodal point, with precise quantitative estimates. In addition, we determine the start of the scaling regime for the breakdown of quasistatic evolution when the temperature of a thermal bath is slowly decreased across the transition. We also extend the analysis to the dynamics of second-order phase transitions and strong crossovers.

Abstract The presence of bacteria from the Dickeya spp. and Pectobacterium spp. in farmlands leads to global crop losses of over $420 million annually. Since 1982, the scientists have started to suspect that the development of disease symptoms in crops might be inhibited by bacteria present in the soil. Here, we characterized in terms of physicochemical properties and the composition of bacterial soil microbiota two fields differing, on the basis of long-term studies, in the occurrence of Dickeya spp.- and Pectobacterium spp.-triggered infections. Majority, i.e. 17 of the investigated physicochemical features of the soils collected from two fields of either low or high potato blackleg and soft rot diseases incidences turned out to be similar, in contrast to the observed 4 deviations in relation to Mg, Mn, organic C and organic substance contents. By performing microbial cultures and molecular diagnostics-based identification, 20 Pectobacterium spp. strains were acquired from the field showing high blackleg and soft rot incidences. In addition, 16S rRNA gene amplicon sequencing followed by bioinformatic analysis revealed differences at various taxonomic levels in the soil bacterial microbiota of the studied fields. We observed that bacteria from the genera Bacillus, Rumeliibacillus, Acidobacterium and Gaiella turned out to be more abundant in the soil samples originating from the field of low comparing to high frequency of pectinolytic bacterial infections. In the herein presented case study, it is shown for the first time that the composition of bacterial soil microbiota varies between two fields differing in the incidences of soft rot and blackleg infections.

Abstract With just the Standard Model Higgs doublet, there are only three types of seesaw models that generate light Majorana neutrino masses at tree level after electroweak spontaneous symmetry breaking. However, if there exist additional TeV scalars acquiring vacuum expectation values, coupled with heavier fermionic multiplets, several new seesaw models become possible. These new seesaws are the primary focus of this study and correspond to the tree-level ultraviolet completions of the effective operators studied in a companion publication. We are interested in the genuine cases, in which the standard seesaw contributions are absent. In addition to the tree-level generation of neutrino masses, we also consider the one-loop contributions. Furthermore, we construct low-energy versions that exhibit a very rich phenomenology. Specifically, we scrutinise the generation of dimension-6 operators and explore their implications, including non-unitarity of the leptonic mixing matrix, non-universal $$Z-$$ Z - boson interactions, and lepton flavor violation. Finally, we provide (Generalised) Scotogenic-like variants that incorporate viable dark matter candidates.

Abstract Epidermal stem cells (EPSCs) are essential for maintaining skin homeostasis and ensuring a proper wound healing. During in vitro cultivations, EPSCs give rise to transient amplifying progenitors and differentiated cells, finally forming a stratified epithelium that can be grafted onto patients. Epithelial grafts have been used in clinics to cure burned patients or patients affected by genetic diseases. The long-term success of these advanced therapies relies on the presence of a correct amount of EPSCs that guarantees long-term epithelial regeneration. For this reason, a deeper understanding of self-renewal and differentiation is fundamental to fostering their clinical applications. The coordination between energetic metabolism (e.g., glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, and amino acid synthesis pathways), molecular signalling pathways (e.g., p63, YAP, FOXM1, AMPK/mTOR), and epigenetic modifications controls fundamental biological processes as proliferation, self-renewal, and differentiation. This review explores how these signalling and metabolic pathways are interconnected in the epithelial cells, highlighting the distinct metabolic demands and regulatory mechanisms involved in skin physiology.

Abstract Background The Pharyngeal Endoderm (PE) is an extremely relevant developmental tissue, serving as the progenitor for the esophagus, parathyroids, thyroids, lungs, and thymus. While several studies have highlighted the importance of PE cells, a detailed transcriptional and epigenetic characterization of this important developmental stage is still missing, especially in humans, due to technical and ethical constraints pertaining to its early formation. Results Here we fill this knowledge gap by developing an in vitro protocol for the derivation of PE-like cells from human Embryonic Stem Cells (hESCs) and by providing an integrated multi-omics characterization. Our PE-like cells robustly express PE markers and are transcriptionally homogenous and similar to in vivo mouse PE cells. In addition, we define their epigenetic landscape and dynamic changes in response to Retinoic Acid by combining ATAC-Seq and ChIP-Seq of histone modifications. The integration of multiple high-throughput datasets leads to the identification of new putative regulatory regions and to the inference of a Retinoic Acid-centered transcription factor network orchestrating the development of PE-like cells. Conclusions By combining hESCs differentiation with computational genomics, our work reveals the epigenetic dynamics that occur during human PE differentiation, providing a solid resource and foundation for research focused on the development of PE derivatives and the modeling of their developmental defects in genetic syndromes.

Abstract Recent years have seen a surge in research on the role of quantum geometry in condensed matter physics. For instance, the Aharonov-Bohm effect is a physical phenomenon where the vector potential induces a phase shift of electron wavepackets in regions with zero magnetic fields due to an obstruction in space associated with a magnetic flux. A similar effect can be observed in solid-state systems, where the topology of the Berry connection can influence electron dynamics. These are paradigmatic examples of how the dynamics can be affected by the system’s geometry. Here, we show that in chiral-symmetric processes the quantum metric has a measurable effect on the mean chiral displacement of delocalized wavefunctions. This finding is supported by a photonic experiment realizing a topological quantum walk and demonstrates an effect that can be attributed directly to the geometry of the state space.

Abstract As major terrestrial carbon sinks, forests play an important role in mitigating climate change. The relationship between the seasonal uptake of carbon and its allocation to woody biomass remains poorly understood, leaving a significant gap in our capacity to predict carbon sequestration by forests. Here, we compare the intra-annual dynamics of carbon fluxes and wood formation across the Northern hemisphere, from carbon assimilation and the formation of non-structural carbon compounds to their incorporation in woody tissues. We show temporally coupled seasonal peaks of carbon assimilation (GPP) and wood cell differentiation, while the two processes are substantially decoupled during off-peak periods. Peaks of cambial activity occur substantially earlier compared to GPP, suggesting the buffer role of non-structural carbohydrates between the processes of carbon assimilation and allocation to wood. Our findings suggest that high-resolution seasonal data of ecosystem carbon fluxes, wood formation and the associated physiological processes may reduce uncertainties in carbon source-sink relationships at different spatial scales, from stand to ecosystem levels.

Abstract Castration-resistant prostate cancer (CRPC) is a frequently occurring disease with adverse clinical outcomes and limited therapeutic options. Here, we identify methionine adenosyltransferase 2a (MAT2A) as a critical driver of the androgen-indifferent state in ERG fusion-positive CRPC. MAT2A is upregulated in CRPC and cooperates with ERG in promoting cell plasticity, stemness and tumorigenesis. RNA, ATAC and ChIP-sequencing coupled with histone post-translational modification analysis by mass spectrometry show that MAT2A broadly impacts the transcriptional and epigenetic landscape. MAT2A enhances H3K4me2 at multiple genomic sites, promoting the expression of pro-tumorigenic non-canonical AR target genes. Genetic and pharmacological inhibition of MAT2A reverses the transcriptional and epigenetic remodeling in CRPC models and improves the response to AR and EZH2 inhibitors. These data reveal a role of MAT2A in epigenetic reprogramming and provide a proof of concept for testing MAT2A inhibitors in CRPC patients to improve clinical responses and prevent treatment resistance.

We report a case of myxofibrosarcoma of the posterior region of the femur, part of the group of soft-tissue sarcomas: a set of rare and heterogeneous tumors with various subtypes and different prognostic. It is characterized by local infiltrative activity and an extremely high rate of local recurrence. A 58-year-old man came to the Radiology Department to examine a voluminous round and expansive formation of the posterior thigh region. The patient stated that the mass had grown suddenly for about 3 months, maybe after a trauma, increasing in volume exponentially and causing him discomfort, embarrassment, and pain. The result of the first diagnostic approach, with the US, was unexpected and suspicious, and the radiologist wanted to do first a CT, and then maybe plan an MRI. The CT revealed an inhomogeneous density formation and in MRI the mass resulted to be compatible, with the radiologic pattern, with the diagnosis of a sarcoma of the soft tissue. The physicians had already alerted the pathological anatomy, as they suspected something malignant. So, some days after the MRI examination, the patient underwent histological sampling, confirming the suspicion: a myxofibrosarcoma (stage III) of the posterior region of the femoral region. The patient started on radio and chemotherapy, which increases survival and in the hope of reducing the size of the mass, and a strict follow-up was posed before doing the surgery.

This case report aims to describe the clinical presentation, imaging findings, histopathological features and therapeutic approach of a patient diagnosed with coexisting breast sarcoma and thymoma. A 64-year-old woman presented with a palpable lump in her left breast, and subsequent imaging studies (ultrasound, mammography, and MRI) revealed breast sarcoma, a rare and aggressive subtype of breast cancer. At the same time, the MRI revealed the presence of a thymoma. A multidisciplinary approach involving surgeon, breast specialist and oncologist is essential for optimal management and favorable outcomes in patients with this rare diagnosis.

Phlegmasia cerulea dolens (PCD) is a devastating presentation of deep venous thrombosis (DVT), that may cause venous gangrene, amputation, and death.A 69-year old male presented with PCD in the lower limbs. Ultrasound (US) and CT-angiogram revealed lower extremities DVT cranially extended to iliac veins and inferior vena cava (IVC) involving an infrarenal IVC filter. In his history, there was 10 years earlier his first occurrence of filter-related PCD, which did require surgical thrombectomy. Currently, we gained access to IVC-filter thrombus from left internal jugular vein and easily placed an EKOS catheter in right femoral vein. Then we started the US-assisted fibrinolysis (EKOS) with low-dose r-TPA. Immediate overnight clinical improvement occurred and a postprocedure venography at 48 hours confirmed complete recanalization.We report the present case upon PCD to remark 2 unique features. First, we used successfully EKOS by transjugular route for PCD. EKOS combines the effectiveness of low dose r-TPA catheter direct thrombolysis (CDT) with the ultrasound's technology. The descending transjugular approach, previously unreported in this clinical setting, can reduce operative time, invasiveness and risk of filter's displacement in comparison with other thrombectomy devices used via popliteal or femoral approach. Second, we verified for the first time to the best of our knowledge the relapse of PCD in a very long time span (a decade) in the same patient underscoring the significance of vena cava filter as a powerful and persistent risk factor for IVC-thrombosis.

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues. Pyrroloquinoline quinone is present in the diet being available in foodstuffs, conferring the potential of this compound to be supplemented by dietary administration. Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction, growth, and immunity resulting from the dietary absence of pyrroloquinoline quinone, and as such, pyrroloquinoline quinone has been considered as a “new vitamin.” Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established, the wide range of benefits for health provided has been reported in many studies. In this respect, pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts, thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life. Through the regulation of different metabolic mechanisms, pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death. Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration, although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated. Here, we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts. In addition, we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

Over recent decades, there was a substantial evolution in the productive management of dairy animals worldwide with a consequent boost in individual milk yield. This evolution positioned the milk production as the central metabolic priority around which all other physiological functions are coordinated and partially minimised. This shift underscores the crucial role of effectively managing stressful phases in intensive dairy farming systems, also highlighting the resilience exhibited by the animals. Indeed, monitoring the nutritional and health status becomes paramount, aiming for an early detection of (sub)clinical health impairments. Given the mammary gland’s centrality in high-yielding dairy breeds, it’s unsurprising that the milk matrix provides insights about udder itself but also systemic metabolic function. The emerging field of milk phenomics explores links between milk components and animal health, holding great promise for studying dairy cow resilience. The use of infrared spectroscopy on milk to predict indicators and complex traits at the herd level is a promising approach. In the dairy sector, the available infrared instruments mainly implement the Fourier transform infrared (FTIR) spectroscopy. This method is widely employed in milk recording schemes worldwide for animal monitoring and breeding purposes. In addition, visible and near-infrared (NIR) spectroscopy is increasingly integrated into milking systems for daily on-farm monitoring of milk quality and animals’ physiological status. This review examines the topic of milk phenomics together with potential and challenges of infrared spectroscopy to predict indicators and complex traits related to health and nutritional disorders exploiting the biological bonds that exist between milk and blood in dairy animals.HIGHLIGHTS Milk is a valuable source of information for assessing nutritional and health proxies in dairy animals. Infrared spectroscopy is used within routine milk recording systems for the determination of major components, but other useful applications exist. This review summarises research on milk phenomics carried out by mean of infrared spectroscopy to predict complex traits related to animals’ health and nutritional disorders.

Cortisol is the primary biomarker associated with the hypothalamic–pituitary–adrenal (HPA) axis. This research aimed at assessing the predictive potential and the relationship of cortisol concentrations in four media (blood, milk, whey and hair) with parity, lactation stage and productive classes. Multiparous (n = 30) and primiparous (n = 38) Italian Mediterranean buffaloes were used and assigned to four productive classes (based on percentiles of mature equivalent milk yield (EMY) and mature equivalent energy corrected milk (eECM)), and cortisol concentrations were measured using a in house radioimmunoassay (RIA) method. Parity did not show a significant effect on cortisol concentrations of the four media. The catabolic stage of lactation (up to 90 d in milk (DIM)) was characterised by higher cortisol concentrations compared to the second anabolic stage (beyond 150 DIM) in milk formulations. The plasmatic concentrations of cortisol were higher at the catabolic and the first anabolic stage (91–150 DIM) compared to the second anabolic (p = 0.022 and p = 0.009, respectively). Buffaloes beyond 150 DIM differed from those below 90 DIM (p

Molecular docking is a widely used technique in drug discovery to predict the binding mode of a given ligand to its target. However, the identification of the near-native binding pose in docking experiments still represents a challenging task as the scoring functions currently employed by docking programs are parametrized to predict the binding affinity, and, therefore, they often fail to correctly identify the ligand native binding conformation. Selecting the correct binding mode is crucial to obtaining meaningful results and to conveniently optimizing new hit compounds. Deep learning (DL) algorithms have been an area of a growing interest in this sense for their capability to extract the relevant information directly from the protein-ligand structure. Our review aims to present the recent advances regarding the development of DL-based pose selection approaches, discussing limitations and possible future directions. Moreover, a comparison between the performances of some classical scoring functions and DL-based methods concerning their ability to select the correct binding mode is reported. In this regard, two novel DL-based pose selectors developed by us are presented.

ABSTRACTBackground The question of whether influenza vaccine effectiveness (VE) wanes over the winter season is still open and some contradictory findings have been reported. This study investigated the possible decline in protection provided by the available influenza vaccines.Research design and methods An individual-level pooled analysis of six test-negative case-control studies conducted in Italy between the 2018/2019 and 2022/2023 seasons was performed. Multivariable logistic regression analyses were performed to estimate weekly change in the odds of testing positive for influenza 14 days after vaccination.Results Of 6490 patients included, 1633 tested positive for influenza. Each week that had elapsed since vaccination was associated with an increase in the odds of testing positive for any influenza (4.9%; 95% CI: 2.0–8.0%) and for A(H3N2) (6.5%; 95% CI: 2.9–10.3%). This decline in VE was, however, significant only in children and older adults. A similar increase in the odds of testing positive was seen when the dataset was restricted to vaccinees only. Conversely, VE waning was less evident for A(H1N1)pdm09 or B strains.Conclusions Significant waning of VE, especially against influenza A(H3N2), may be one of the factors associated with suboptimal end-of-season VE. Next-generation vaccines should provide more durable protection against A(H3N2).

This study aimed at evaluating the environmental impact (EI) of herds representative of the Italian heavy pig production system to investigate the EI variation associated with farm management (FM), diet formulation (DF) and animal response (AR) variables. Data originated from 8 breeding farms, which included the sows and preweaning piglets (Site1) and the post-weaned piglets (7.5–30 kg body weight – BW, Site2) and 10 growing–fattening farms, dealing with 30–170 kg BW pigs (Site3). A cradle-to-farm gate Life Cycle Assessment was used, with 1 kg BW gain (BWG) as functional unit. Impact categories were global warming (GWP), acidification (AP) and eutrophication (EP) potentials and land occupation (LO). Whole-production cycle EI (Site123, 0–170 kg BW) was obtained summing up EIs of 0–30 and 30–170 kg BW animals. Impacts were analysed with one- or two-way PERMANOVA to test the effect of FM, DF and AR variables. The Site123-related EI averaged nearly 3.1 kg CO2-eq (GWP), 50 g SO2-eq (AP), 22 g PO4-eq (EP) and 4.9 m2/y (LO) per kg BWG. Site3 contributed nearly 80% of the whole impact. Regarding Site1, GWP resulted mitigated by increasing sow productivity. Site2 EI resulted mitigated by decreasing feed conversion ratio and increasing average daily gain, whereas Site3 EI by increasing feed self-sufficiency and decreasing dietary crude protein and mortality. In perspective, given the relevance of Site3 on the whole-pig system EI, a deeper integration between the farm agronomical management and the growing–finishing pigs’ diets formulation would support the environmental sustainability of heavy pig operations.

IntroductionEating Disorders (EDs) affect individuals globally and are associated with significant physical and mental health challenges. However, access to adequate treatment is often hindered by societal stigma, limited awareness, and resource constraints.MethodsThe project aims to utilize the power of Artificial Intelligence (AI), particularly Machine Learning (ML) and Deep Learning (DL), to improve EDs diagnosis and treatment. The Master Data Plan (MDP) will collect and analyze data from diverse sources, utilize AI algorithms for risk factor identificat io n, treatment planning, and relapse prediction, and provide a patient-facing chatbot for information and support. This platform will integrate patient data, support healthcare professionals, and empower patients, thereby enhancing care accessibility, personalizing treatment plans, and optimizing care pathways. Robust data governance measures will ensure ethical and secure data management.ResultsAnticipated outcomes include enhanced care accessibility and efficiency, personalized treatment plans leading to improved patient outcomes, reduced waiting lists, heightened patient engagement, and increased awareness of EDs with improved resource allocation.DiscussionThis project signifies a pivotal shift towards data-driven, patient-centered ED care in Italy. By integrat ing AI and promoting collaboration, it seeks to redefine mental healthcare standards and foster better well- being among individuals with EDs.

BackgroundSarcopenia, characterized by muscle mass, strength, and performance decline, significantly impacts outcomes in older adults. This study aims to assess the predictive value of calf circumference (CC), in conjunction with SARC-F and hand grip, concerning in-hospital complications and post-discharge mortality among hospitalized frail older adults.MethodsA cohort of 158 hospitalized patients aged over 65 years underwent Comprehensive Geriatric Assessment and sarcopenia screening, including CC measurement. Multivariable regression analyses, adjusted for confounders, were conducted to assess predictive associations.ResultsThe study cohort, comprising 53% males with a median age of 86 years, exhibited significant sarcopenia prevalence based on SARC-F (85% indicating sarcopenia), hand grip strength (probable sarcopenia in 77% of males and 72% of females), and CC (sarcopenia in 83%). Multivariate analysis, adjusting for age, sex, Clinical Frailty Scale (CFS), and Mini Nutritional Assessment-Short Form (MNA-SF), demonstrated associations of CC and SARC-F with in-hospital complications, while CC also showed a significant association with reduced risks of in-hospital mortality (OR 0.441, 95% CI 0.257 to 0.754, p = 0.003) and 90-day mortality (OR 0.714, 95% CI 0.516 to 0.988, p = 0.043).ConclusionThis study provides insights into the predictive accuracy of sarcopenia screening tools on mortality in real-world hospitalized older adults with frailty. Notably, CC emerges as a robust predictor of mortality outcomes. Further research is warranted to validate and elucidate the respective contributions of CC and frailty to mortality in vulnerable populations.

Rolling stock manufacturers are finding innovative structural solutions to improve the quality and reliability of railway vehicle components. Structural optimization processes represent an effective strategy for reducing manufacturing costs, resulting in geometries that are easier to design and produce combined with innovative materials. In this framework, the present paper proposes the development of a design methodology to innovate a railway bolster beam using topological optimization techniques, assessing the effect of different manufacturing constraints oriented to the casting process. A comprehensive numerical testing campaign was conducted to establish an effective testing procedure. Two different designs were obtained and compared, statically and dynamically, evaluating the difference in terms of mass, mechanical performance and manufacturability. Reductions in stress values up to 70% were observed, along with an 8% increase in the first natural frequency of the component, leading to beneficial effects in terms of stiffness. The methodology shows encouraging results to streamline the design of complex casting components, moving to a new generation of structural railway components.

This paper reports the preliminary experimental studies carried out on an innovative sliding bearing made of polycrystalline diamond, a material with excellent mechanical and chemical characteristics, used mainly in the drilling industry. Bearings crafted from this material do not necessitate lubrication due to their extremely low coefficient of friction and high resistance to wear. For this reason, they are prime candidates for replacing traditional oil bearings, eliminating the need for auxiliary systems and thereby reducing environmental risks. In this regard, an innovative test rig was designed, capable of reaching speeds up to 6000 rpm both in vertical and horizontal configurations thanks to a novel tilting frame. Moreover, with a high modularity it was possible to test three different kinds of radial PCD bearings. Dynamic data were acquired and elaborated to evaluate orbits, acceleration and absorbed torque, to finally compare these different configurations to better understand how dynamic behavior is influenced by bearings’ geometrical characteristics.

(1) Background: Lower gastrointestinal bleeding (LGIB) accounts for 20% of all gastrointestinal bleeds. LGBI originates in the colon, rectum, and anus, mainly in patients who are receiving antiaggregant or anticoagulant treatment. The major causes are diverticular disease, colitis, hemorrhoids, and angiodysplasia. The literature studies underline that Direct Oral Anticoagulants (DOACs) are effective in reducing the risk of thromboembolic events but are associated with a higher risk of lower gastrointestinal bleeding (LGIB), particularly lower hemorrhoid bleeding. (2) Methods: The aim of our review is to revise the risk of hemorrhoid bleeding, pathophysiology, and management in patients taking DOACs in light of the most modern evidence. (3) Conclusions: central to the management of hemorrhoid bleeding in patients receiving DOAC therapy is the consideration of a tailored approach that respects the delicate equilibrium between the need for thromboembolic prophylaxis and the potential for bleeding complications. Cessation of anticoagulation, if clinically feasible, constitutes a fundamental cornerstone in the control of hemorrhage. This pause in therapy aims to mitigate the exacerbation of bleeding risk while offering a window for the implementation of local measures to manage hemorrhoid bleeding.

Abstract Introduction Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics. Methods In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. Results Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01–6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05–72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16–0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively. Conclusions Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.

Abstract Compared to other malignancies, few studies have investigated the role of family history of cancer (FHC) in patients with lung cancer, yielding largely heterogeneous results. We performed a systematic literature review in accordance with PRISMA guidelines, searching the PubMed and Scopus databases from their inception to November 25, 2023, to identify studies reporting on the role of FHC in patients with lung cancer. A total of 53 articles were included, most with a retrospective design and encompassing a variety of geographical areas and ethnicities. Thirty studies (56.6%) assessed patients with non-small cell lung cancer (NSCLC), while 17 studies (32.1%) assessed patients with mixed histologies. Overall, the rates of FHC ranged from 8.3 to 68.9%, and the rates of family history of lung cancer ranged from 2 to 46.8%. Twenty-seven studies investigated FHC as a potential risk factor for lung cancer, with more than half reporting an increased risk for subjects with FHC. Five studies reported on the potential role of FHC in determining clinical outcomes, and twelve studies examined the relationship between FHC and germline mutations. Notably, only one study reported a significantly increased rate of germline mutations, including ATM, BRCA2, and TP53, for patients with a family history of lung cancer compared to those without, but both groups had a low prevalence of mutations (

Abstract Poultry meat-production is increasing worldwide; leading to the selection of chickens for meat-production that show a fast growth. A label-free quantitative proteomic-approach and Western-blot were applied to investigate the dynamics of muscle protein under rapid growth conditions in two common fast-growing broiler genetic-lines (Ross 508 and AZ Extra Heavy Red-chicken). Muscle exudate from chicken Pectoralis major was used as substrate to unveil the proteome of these genetic-lines. Six-hundred forty-five proteins were identified in total from all samples, and after statistical-analysis 172 proteins were found to be differentially-expressed, clearly distinguishing the two chicken genetic-lines. Several of these differentially-expressed proteins were involved with the proteasome and glycolysis/gluconeogenesis-pathways. Changes in meat-quality traits were also observed, which were reflected in the proteomic-profile. Proteins involved in the ubiquitin–proteasome system were associated with the bigger muscle mass of Ross 508, while phosphoglucomutase 1 was associated with a possible higher capability of AZ Extra Heavy Red-chickens to cope with stressors. This pilot proteomic-approach applied on muscle exudate samples provided key evidence about the pathways and processes underlying these two chicken genetic-lines and their meat-quality parameters. We also identified potential biomarkers that could determine the peculiar production potentials (e.g. breast-growth) of these broilers-lines, which arise from differences in their genetic-backgrounds.

Abstract Maintenance of NAD pools is critical for neuronal survival. The capacity to maintain NAD pools declines in neurodegenerative disease. We identify that low NMNAT2, the critical neuronal NAD producing enzyme, drives retinal susceptibility to neurodegenerative insults. As proof of concept, gene therapy over-expressing full length human NMNAT2 is neuroprotective. To pharmacologically target NMNAT2, we identify that epigallocatechin gallate (EGCG) can drive NAD production in neurons through an NMNAT2 and NMN dependent mechanism. We confirm this by pharmacological and genetic inhibition of the NAD-salvage pathway. EGCG is neuroprotective in rodent (mixed sex) and human models of retinal neurodegeneration. As EGCG has poor drug-like qualities, we use it as a tool compound to generate novel small molecules which drive neuronal NAD production and provide neuroprotection. This class of NMNAT2 targeted small molecules could have an important therapeutic impact for neurodegenerative disease following further drug development.

Abstract Background In assisted reproductive technology (ART), the choice between intracytoplasmic sperm injection (ICSI) and conventional in vitro insemination (IVF) remains a pivotal decision for couples with female or unexplained infertility. The hypothesis that ICSI may not confer significant improvements in live birth rates in the absence of a male infertility factor was explored in this study. Methods This was a retrospective collection of data recorded by the Human Fertilisation and Embryology Authority (HFEA) in the UK from 2005 to 2018 and analysed through regression analysis models on both the entire dataset and a matched-pair subset. First fresh ART cycles were analysed according to the insemination technique in order to compare live birth as the main outcome. Cycles were included if complete information regarding infertility cause, female age, number of oocytes retrieved, allocation to ICSI or IVF, and treatment outcome in terms of live birth was available. Matching was performed at a 1:1 ratio between IVF and ICSI cycles according to the cause of infertility, female age, number of oocytes, and year of treatment. Results This study, based on 275,825 first cycles, revealed that, compared with IVF, ICSI was associated with higher fertilization rates and lower cycle cancellations rates. However, ICSI was associated with a lower chance of implantation and live birth than IVF in cycles with female-only infertility: in the entire dataset, the adjusted odds of having a live birth decreased by a factor of 0.95 (95% CI 0.91–0.99, p = 0.011), while in the matched-pair analyses it decreased by a factor of 0.91 (95% CI 0.86–0.96, p = 0.003) using ICSI compared to IVF. For unexplained infertility cycles, the adjusted odds ratios for live birth in ICSI compared to IVF cycles were 0.98 (95% CI 0.95–1.01) in the entire dataset and 0.97 (95% CI 0.93–1.01) in the matched-pair analysis. Conclusions Compared with IVF, ICSI was associated with a reduction in live births when ART was indicated due to female-only factors. Additionally, no significant improvements were associated with the use of ICSI in cycles with unexplained infertility. Our findings impose a critical reevaluation regarding the use of ICSI over IVF for cases with female-only factors and unexplained infertility.

Architectures for health have a crucial role in collectivity: according to international ranking scores (for example, CEOWorld Magazine’s Health Care Index), in Italy, there are very advanced and well-functioning healthcare services, even though many facilities are old and obsolete, unorganized, dilapidated, and sometimes unsafe. It has been estimated that 60% of facilities have been built more than 40 years ago. Recent studies suggest that the service life of hospitals should be set around 60 years; after reaching this age, the structure must be redesigned. The present contribution analyses this “rule of thumb” in relation to its impact on user perception. It adopts a Multi-Criteria Decision Analysis (MCDA) method to assess the importance users attribute to the quality of the structure and the personnel working there. Specifically, 9 criteria have been selected, including extrinsic and intrinsic features not directly associated with the abovementioned issues. With this approach in mind, we analyzed the 10 best Italian hospitals’ structures and the quality of treatments. The contribution highlights a significant methodological gap in identifying the relationship between building characteristics and their effects on the service, which are often treated as separate. Thus, the research proposes an innovative method by placing users at the center of the evaluation of priorities. This is particularly crucial in healthcare facilities where all the individuals (patients and staff) and the systems’ processes affect each other. This research line has several possible results; here, it preliminarily involves questioning the 60-year-old threshold for providing highquality services in hospitals.

Abstract The ongoing international negotiations on a global plastics treaty will have pivotal implications for future efforts to transform the plastic economy. This is essential since the current use of plastic in the economy impacts the environment beyond the planetary carrying capacity. To ensure that the forthcoming Treaty can provide the foundation for this transition, the best available science must be made available in the negotiations, but with no formal scientific mechanism to inform the negotiations process, this is not ensured. The Scientists’ Coalition for an Effective Plastic Treaty serves as an example of how the global scientific community has self-organized and come together to address this task, working with five different categories of science-policy communication. The Scientists’ Coalition’s work is made transparent here with the hope that it can inspire organization of scientific input into other future policy areas.