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Abstract Background Among the Citrus species, lemon (Citrus limon Burm f.) is one of the most affected by the two-spotted spider mite (Tetranychus urticae Koch). Moreover, chemical control is hampered by the mite’s ability to develop genetic resistance against acaricides. In this context, the identification of the genetic basis of the host resistance could represent a sustainable strategy for spider mite control. In the present study, a marker-trait association analysis was performed on a lemon population employing an association mapping approach. An inter-specific full-sib population composed of 109 accessions was phenotyped through a detached-leaf assays performed in modified Huffaker cells. Those individuals, complemented with two inter-specific segregating populations, were genotyped using a target-sequencing approach called SPET (Single Primer Enrichment Technology), the resulting SNPs were employed for the generation of an integrated genetic map. Results The percentage of damaged area in the full-sib population showed a quantitative distribution with values ranging from 0.36 to 9.67%. A total of 47,298 SNPs were selected for an association mapping study and a significant marker linked with resistance to spider mite was detected on linkage group 5. In silico gene annotation of the QTL interval enabled the detection of 13 genes involved in immune response to biotic and abiotic stress. Gene expression analysis showed an over expression of the gene encoding for the ethylene-responsive transcription factor ERF098-like, already characterized in Arabidopsis and in rice for its involvement in defense response. Conclusion The identification of a molecular marker linked to the resistance to spider mite attack can pave the way for the development of marker-assisted breeding plan for the development of novel selection coupling favorable agronomical traits (e.g. fruit quality, yield) with a higher resistance toward the mite.

Abstract Breast cancer represents the most common malignancy in women worldwide. In most cases, metastasis is the leading cause of mortality. Early diagnosis is still challenging despite standardised, government‐led screening programs, but is crucial in achieving improved survival rates. Additionally, a deeper understanding of the metastatic potential of breast cancer is critical for developing therapeutic interventions to combat widespread disease. Cutaneous metastasis from underlying breast carcinoma is uncommon as the first manifestation of visceral malignancies and is commonly observed in advanced‐stage malignancies, often associated with poor prognosis, and a prompt, precise tissue diagnosis is mandatory. A high index of suspicion in oncologic patients is required to diagnose these lesions, as they can mimic benign skin manifestations and clinical findings may be subtle and going unnoticed. We report on a case of a 76‐year‐old female patient presenting to our non‐invasive diagnostic outpatient clinic with an unusual cutaneous presentation, as an early sign of locally advanced invasive ductal carcinoma breast cancer recurrence. The aim of our article is to underline the importance of the dermatologist in the multi‐disciplinary oncologic diagnostic process, including non‐invasive imaging evaluation of cutaneous lesions, especially insidious breast carcinomas. Dynamic optical coherence tomography (D‐OCT) is not routinely used due to its cost, therefore lesion's aspect has not been completely described, consequently, the correct evaluation of skin architecture appearance can add important information, especially in cutaneous oncology where it can help in early diagnosis or cancer recurrency. OCT may contribute to the detection of subclinical cutaneous manifestations of cancer or recurrence, in particular, when they are difficult to differentiate clinically from benign lesion. In the case we described, OCT of suspected lesion showed the loss of the DEJ with solid nests and irregular vessels.

Introduction: Cutaneous chondroid syringoma (CS) is a rare benign mixed skin tumor originating from sweat glands. Despite its rarity, accurate diagnosis and management are crucial due to its potential for malignant transformation. Objective: This study aims to provide comprehensive insights into the main features of cutaneous CS, encompassing its epidemiology, clinical presentation, and particularly, dermoscopic findings. Methods: A systematic review was conducted to identify relevant literature on CS up to November 2023. Data extraction included clinical and histopathological characteristics from case reports and small case series. Results: The systematic review identified 347 unique CS cases, predominantly benign. Clinical features included a predilection for the head and neck region, with variations in morphology observed. Dermoscopic patterns, although limited, revealed recurrent features aiding diagnosis. Malignant CS cases constituted a notable subset, exhibiting distinct clinical and histopathological features. Conclusion: Cutaneous chondroid syringoma presents with characteristic clinical and histopathological features, necessitating comprehensive diagnostic approaches. Dermoscopy emerges as a valuable tool, although further research is needed to establish definitive patterns. Treatment primarily involves wide local excision, with collaboration among clinicians essential for optimal management. Future studies are warranted to address existing knowledge gaps and enhance understanding of this rare skin neoplasm.

Abstract Background Triggering final oocyte maturation is a pivotal step in modern patient-tailored IVF/ICSI treatment, securing the optimal number of mature oocytes retrieved without compromising fertilization, embryo development, and live birth. Several factors need to be considered when deciding the time of the trigger: the size of the leading follicles, distribution of the follicular cohort, the duration of stimulation, the protocol used for stimulation, and ovarian response status. Main body The current narrative review aims to appraise all available evidence for determining the proper time for inducing final oocyte maturation following IVF treatment. Moreover, it discusses the impact of the stimulation protocol, follicular size, and magnitude of ovarian response on choosing the proper timing for trigger. Comprehensive literature search of all available articles and relevant articles studying the criteria for timing of final oocyte maturation trigger in IVF/ICSI cycles were included in this review. It was found that leading follicles size of 16–22 mm is associated with the optimum oocyte maturation ratio, size of the remaining cohort of follicles should be ≥ 14 mm, 10–12 days of minimum length of stimulation should be auspicated in normal responders before trigger, and the timing of trigger administration should not depend solely on hormonal levels. Conclusion In conclusion, the timing of triggering of final oocyte maturation in ICSI cycles should be individualized on a case-by-case basis.

The monitoring of stranded marine mammals represents a strategic method to assess their health, conservation status, and ecological role in the marine ecosystem. Networks worldwide track stranding events for the passive monitoring of mortality patterns, emerging and reemerging pathogens, climate change, and environmental degradation from a One Health perspective. This study summarizes pathogen prevalence data from the Italian Stranding Network (ISN) derived from post-mortem investigations on cetaceans found dead stranded along the Italian coastline between 2015 and 2020. The decomposition of the carcasses and logistics limited the post-mortem examination to 585 individuals, out of 1236 single-stranding reports. The most relevant pathogens identified were Cetacean Morbillivirus, Herpesvirus, Brucella spp., and Toxoplasma gondii, whose roles as environmental stressors are well known, despite their real impact still needing to be investigated in depth. Statistical analysis showed that age and sex seem to be positively related to the presence of pathogens. This study represents the first step in harmonizing post-mortem investigations, which is crucial for evidence-based conservation efforts. Implementing diagnostic and forensic frameworks could offer an indirect insight into the systematic monitoring of diseases to improve the identification of regional and temporal hotspots in which to target specific mitigation, management, and conservation strategies.

Self-incompatibility (SI) is a genetic mechanism common in flowering plants to prevent self-fertilization. Among citrus species, several pummelo, mandarin, and mandarin-like accessions show SI behavior. In these species, SI is coupled with a variable degree of parthenocarpy ensuring the production of seedless fruits, a trait that is highly appreciated by consumers. In Citrus, recent evidences have shown the presence of a gametophytic SI system based on S-ribonucleases (S-RNases) ability to impair self-pollen tube growth in the upper/middle part of the style. In the present study, we combined PCR analysis and next-generation sequencing technologies, to define the presence of S7- and S11-Rnases in the S-genotype of the Citrus clementina (Hort. ex Tan.), the self-incompatible ‘Comune’ clementine and its self-compatible natural mutant ‘Monreal’. The reference genome of ‘Monreal’ clementine is presented for the first time, providing more robust results on the genetic sequence of the newly discovered S7-RNase. SNP discovery analysis coupled with the annotation of the variants detected enabled the identification of 7,781 SNPs effecting 5,661 genes in ‘Monreal’ compared to the reference genome of C. clementina. Transcriptome analysis of unpollinated pistils at the mature stage from both clementine genotypes revealed the lack of expression of S7-RNase in ‘Monreal’ suggesting its involvement in the loss of the SI response. RNA-seq analysis followed by gene ontology studies enabled the identification of 2,680 differentially expressed genes (DEGs), a significant number of those is involved in oxidoreductase and transmembrane transport activity. Merging of DNA sequencing and RNA data led to the identification of 164 DEGs characterized by the presence of at least one SNP predicted to induce mutations with a high effect on their amino acid sequence. Among them, four candidate genes referring to two Agamous-like MADS-box proteins, to MYB111 and to MLO-like protein 12 were validated. Moreover, the transcription factor MYB111 appeared to contain a binding site for the 2.0-kb upstream sequences of the S7- and S11-RNase genes. These results provide useful information about the genetic bases of SI indicating that SNPs present in their sequence could be responsible for the differential expression and the regulation of S7-RNase and consequently of the SI mechanism.

Endometriosis is a chronic inflammatory disease defined by the presence of endometrial-like tissue outside theuterine cavity. Several authors have reported on the association between changes in inflammatory marker levelsand the maintenance or progression of endometriosis and associated infertility. Interleukin-6 (IL-6) is the moststudied cytokine in endometriosis and has important functions in reproductive physiology. The aim of this study isto review systematically available evidence about altered IL-6 concentrations in endometriosis-related infertility.This is a systematic review including all studies until December 2022 in which IL-6 in serum, peritoneal fluid,follicular fluid, or endometrial biopsy specimens was measured and that correlated their findings with endometriosis-associated infertility. Fifteen studies were included in the systematic review. There seems to be a correlationbetween elevated serum and peritoneal fluid IL-6 concentrations and the occurrence of endometriosis-associatedinfertility. IL-6 may be a potential diagnostic or biomarker tool for the prediction of endometriosis-related infertility.However, the numerous biases affecting the available studies, and challenges in endometriosis research reproducibilitymust be considered. Future investigations should pay attention to factors that may affect the results, suchas the choice of suitable control groups, and carefully consider other pathological conditions affecting the patients,endometriosis stage, and type of lesion.

This article deals with Central Nervous System (CNS) disorders of marine mammals as putative neuropathology and neuropathogenesis models for their human and, to some extent, their animal “counterparts” in a dual “One Health” and “Translational Medicine” perspective. Within this challenging context, special emphasis is placed upon Alzheimer’s disease (AD), provided that AD-like pathological changes have been reported in the brain tissue of stranded cetacean specimens belonging to different Odontocete species. Further examples of potential comparative pathology interest are represented by viral infections and, in particular, by “Subacute Sclerosing Panencephalitis” (SSPE), a rare neurologic sequela in patients infected with Measles virus (MeV). Indeed, Cetacean morbillivirus (CeMV)-infected striped dolphins (Stenella coeruleoalba) may also develop a “brain-only” form of CeMV infection, sharing neuropathological similarities with SSPE. Within this framework, the global threat of the A(H5N1) avian influenza virus is another major concern issue, with a severe meningoencephalitis occurring in affected pinnipeds and cetaceans, similarly to what is seen in human beings. Finally, the role of Brucella ceti-infected, neurobrucellosis-affected cetaceans as putative neuropathology and neuropathogenesis models for their human disease counterparts is also analyzed and discussed. Notwithstanding the above, much more work is needed before drawing the conclusion marine mammal CNS disorders mirror their human “analogues”.

A recent major study has shown that there is an increased risk of myocardial infarction, stroke and lethal outcomes in patients affected by carotid atheromas that contain micro-nanoplastics (MNPs) compared to subjects that do not have MNPs in their lesions [...]

Abstract Background Endometrial scratching (ES) or injury is intentional damage to the endometrium performed to improve reproductive outcomes for infertile women desiring pregnancy. Moreover, recent systematic reviews with meta-analyses and randomized controlled trials demonstrated that ES is not effective, data on the safety are limited, and it should not be recommended in clinical practice. The aim of the current study was to assess the view and behavior towards ES among fertility specialists throughout infertility centers in Italy, and the relationship between these views and the attitudes towards the use of ES as an add-on in their commercial setting. Methods Online survey among infertility centers, affiliated to Italian Society of Human Reproduction (SIRU), was performed using a detailed questionnaire including 45 questions with the possibility to give “closed” multi-choice answers for 41 items and “open” answers for 4 items. Online data from the websites of the infertility centers resulting in affiliation with the specialists were also recorded and analyzed. The quality of information about ES given on infertility centers websites was assessed using a scoring matrix including 10 specific questions (scored from 0 to 2 points), and the possible scores ranged from 0 to 13 points (‘excellent’ if the score was 9 points or more, ‘moderate’ if the score was between 5 and 8, and ‘poor’ if it was 4 points or less). Results The response rate was of 60.6% (43 questionnaires / 71 infertility SIRU-affiliated centers). All included questionnaires were completed in their entirety. Most physicians (~ 70%) reported to offer ES to less than 10% of their patients. The procedure is mainly performed in the secretory phase (69.2%) using pipelle (61.5%), and usually in medical ambulatory (56.4%) before IVF cycles to improve implantation (71.8%) without drugs administration (e.g., pain drugs, antibiotics, anti-hemorrhagics, or others) before (76.8%) or after (64.1%) the procedure. Only a little proportion of infertility centers included in the analysis proposes formally the ES as an add-on procedure (9.3%), even if, when proposed, the full description of the indications, efficacy, safety, and costs is never addressed. However, the overall information quality of the websites was generally “poor” ranging from 3 to 8 and having a low total score (4.7 ± 1.6; mean ± standard deviation). Conclusions In Italy, ES is a procedure still performed among fertility specialists for improving the implantation rate in IVF patients. Moreover, they have a poor attitude in proposing ES as an add-on in the commercial setting.

Durable remissions are observed in 10%–20% of treated patients with advanced metastatic melanoma but the factors associated with long-term complete clinical responses are largely unknown. Here, we report the molecular characteristics of tumor evolution during disease progression along a 9-year clinical course in a patient with advanced disseminated melanoma who received different treatments, including trametinib, ipilimumab, radiation, vemurafenib, surgical tumor debulking and a second ipilimumab course, ultimately achieving complete long-term disease remission.Longitudinal analyses of therapies-resistant metastatic tumors revealed the effects of different treatments on tumor’s microenvironment and immunogenicity, ultimately creating a milieu favorable to immunotherapy response. Monitoring of the temporal dynamics of T cells by analysis of the T cell receptor (TCR) repertoire in the tumor and peripheral blood during disease evolution indicated that T-cell clones with common TCR rearrangements, present at low levels at baseline, were maintained and expanded after immunotherapy, and that TCR diversity increased. Analysis of genetic, molecular, and cellular components of the tumor depicted a multistep process in which treatment with kinase inhibitors strongly conditioned the immune microenvironment creating an inflamed milieu converting cold into hot tumors, while ipilimumab impacted and increased the TCR repertoire, a requirement for tumor rejection.Since the optimal sequencing of treatment with antibodies targeting immune checkpoints and kinase inhibitors for advanced melanoma is still clinically debated, this case indicates that immunotherapy success is possible even after progression on targeted therapy.

This paper presents the Mechanical Ventilator Milano (MVM), a novel intensive therapy mechanical ventilator designed for rapid, large-scale, low-cost production for the COVID-19 pandemic. Free of moving mechanical parts and requiring only a source of compressed oxygen and medical air to operate, the MVM is designed to support the long-term invasive ventilation often required for COVID-19 patients and operates in pressure-regulated ventilation modes, which minimize the risk of furthering lung trauma. The MVM was extensively tested against ISO standards in the laboratory using a breathing simulator, with good agreement between input and measured breathing parameters and performing correctly in response to fault conditions and stability tests. The MVM has obtained Emergency Use Authorization by U.S. Food and Drug Administration (FDA) for use in healthcare settings during the COVID-19 pandemic and Health Canada Medical Device Authorization for Importation or Sale, under Interim Order for Use in Relation to COVID-19. Following these certifications, mass production is ongoing and distribution is under way in several countries. The MVM was designed, tested, prepared for certification, and mass produced in the space of a few months by a unique collaboration of respiratory healthcare professionals and experimental physicists, working with industrial partners, and is an excellent ventilator candidate for this pandemic anywhere in the world.

Background and Objectives: Cellulite, or edemato-fibro-sclerotic panniculopathy (EFP), is characterized by dermal and hypodermal changes leading to adipose tissue accumulation and compromised venous circulation. This study investigates the efficacy of a hypertonic cream containing concentrated sodium chloride (Jovita Osmocell®) in addressing water retention and structural alterations in adipose tissue, aiming to interrupt the cellulite formation process. Materials and Methods: A 12-week, prospective, monocentric, double-blind, placebo-controlled study enrolled 30 female subjects with grade II or III cellulite. Patients were randomized to receive hypertonic cream or a placebo. Thigh circumference, ultrasound evaluations, and standardized photographs were collected at baseline, intermediate, and endpoint visits. Adverse events were monitored. Results: After 84 days, the hypertonic cream group exhibited a significant reduction in thigh circumference compared to the placebo group (p = 0.0037). B-mode ultrasound examinations revealed significant changes in the parameters studied, such as the thickness of the subcutaneous tissue. No statistically significant changes were noticed in the placebo group. Volunteers reported the investigational product’s pleasantness and good anti-cellulite activity, with no reported adverse events. Conclusions: The hypertonic cream demonstrated efficacy in reducing thigh circumference, addressing water retention and structural alterations in adipose tissue. The proposed mechanism involves osmosis, releasing accumulated fluids between fat cells, supporting drainage, and reducing inflammation. This study supports the efficacy and safety of hypertonic sodium chloride emulsions in cellulite treatment and confirms safety and user satisfaction.

An interesting article recently published in Science Translational Medicine reports a variable risk of persistent COVID-19 among patients affected by different immunodeficiency conditions [...]

Cetacean morbillivirus (CeMV) is an enveloped, non-segmented, negative-stranded RNA virus that infects marine mammals, spreading across species and causing lethal disease outbreaks worldwide. Among the eight proteins encoded by the CeMV genome, the haemagglutinin (H) glycoprotein is responsible for the virus attachment to host cell receptors. CeMV H represents an attractive target for antiviral and diagnostic research, yet the elucidation of the molecular mechanisms underlying its role in infection and inter-species transmission was hampered thus far due to the unavailability of recombinant versions of the protein. Here we present the cloning, expression and purification of a recombinant CeMV H ectodomain (rH-ecto), providing an initial characterization of its biophysical and structural properties. Sodium dodecyl sulphate - polyacrylamide gel electrophoresis (PAGE) combined to Western blot analysis and periodic acid Schiff assay showed that CeMV rH-ecto is purifiable at homogeneity from insect cells as a secreted, soluble and glycosylated protein. Miniaturized differential scanning fluorimetry, Blue Native PAGE and size exclusion chromatography coupled to multiangle light scattering revealed that CeMV rH-ecto is globularly folded, thermally stable and exists in solution in the oligomeric states of dimer and multiple of dimers. Furthermore, negative stain electron microscopy single particle analysis allowed us to delineate a low-resolution molecular architecture of the CeMV rH-ecto dimer, which recapitulates native assemblies from other morbilliviral H proteins, such as those from measles virus and canine distemper virus. This set of experiments by orthogonal techniques validates the CeMV rH-ecto as an experimental model for future biochemical studies on its structure and functions.