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Background: Multiple endocrine neoplasia type 2 syndrome (MEN2) is a hereditary disease resulting from mutations of the rearranged during transfection (RET) protooncogene subclassified into MEN2A [medullary thyroid carcinoma (MTC), pheochromocytoma, and primary hyperparathyroidism] and MEN2B (MTC, pheochromocytoma, Marfanoid habitus, mucous neuromas, and intestinal ganglioneuromatosis). Prophylactic thyroidectomy is recommended in RET-mutated patients. The age at which it should be performed depends on the type and aggressiveness of the mutation. Aim of the study: This study aimed to evaluate the genotype/phenotype correlation and outcome in pediatric/adolescent carriers of MEN2 RET mutation. Patients and methods: In a retrospective series of 23 carriers of RET MEN2 mutation who were ≤19 years old at diagnosis and had undergone total thyroidectomy ± lymphadenectomy, the following were analyzed: 1) specific RET mutation, 2) clinical and histopathological characteristics, 3) genotype/phenotype correlation, and 4) outcome at last follow-up. Results: In our series, the female gender was more prevalent (F/M ratio 2.8/1), and the median age was 14.9 years [interquartile range (IQR) 12.6–17.2]. RET mutations were at very high risk in 4.3% of patients (M918T), high risk in 43.5% (C634), and moderate risk in 52.2% (47.8% C618 and 4.3% C620). All patients underwent surgery: at histology, MTC was found in 19/23 (82.6%) patients, C-cell hyperplasia in 2/23 (8.7%), and benign histology in 2/23 (8.7%). Ten patients (52.6%) had a disease event during the follow-up: 2/19 (10.5%) showed biochemical disease, 6/19 (31.6%) lymph node recurrences, and 2/19 (10.5%) distant metastases (50% liver, 50% bone). At the last follow-up, nine MTCs were not cured. One patient died after 9 years of follow-up at 21 years old (M918T RET+). Conclusions: From these data, it is clear to see the importance of genetic counseling and RET screening in all first-degree relatives of patients with proven MEN2. The goal should be to subject patients to surgery for prophylactic and not curative purposes, i.e., before the onset of MTC, given the high risk of persistent or recurrent disease also in pediatric/adolescent patients. [ABSTRACT FROM AUTHOR]

Background: Rigid bronchoscopy (RB) is the gold standard for managing central airway obstruction (CAO), a life-threatening condition caused by both malignant and benign etiologies. Anesthetic management is challenging as it requires balancing deep sedation with maintaining spontaneous breathing to avoid airway collapse. There is no consensus on the optimal anesthetic approach, with options including general anesthesia with neuromuscular blockers or spontaneous assisted ventilation (SAV). Methods: This case series presents our anesthetic protocol using remifentanil–propofol–ketamine total intravenous anesthesia (TIVA) with SAV in four patients with airway obstructions. Muscle relaxants were avoided in all cases. Results: Ketamine's ability to preserve respiratory drive and airway reflexes, along with its bronchodilating properties, made it ideal for managing CAO. All procedures successfully restored airway patency without complications or drug-related side effects. Conclusions: Our findings suggest that remifentanil–propofol–ketamine TIVA combined with SAV is a viable anesthetic approach for therapeutic RB, offering effective sedation, maintaining airway patency, and minimizing perioperative complications. [ABSTRACT FROM AUTHOR]

Background: The Mediterranean diet (MedD) exerts anti-inflammatory and anti-oxidant effects that are beneficial in autoimmune thyroid diseases (ATD). Recently, a gluten-free diet (GFD) has been proposed for non-celiac patients with Hashimoto's thyroiditis (HT), but its usefulness is under debate. The present pilot study evaluates the effects of these two dietary regimes, with a focus on redox homeostasis, in HT. Patients and Methods: 45 euthyroid HT patients (30 F; median age 42 years) were randomly assigned to different dietary regimes: MedD (n = 15), GFD (n = 15) and free diet (FD, n = 15). Thyroid function tests, autoantibodies, and oxidative stress markers (Advanced glycation end products, AGEs; glutathione peroxidase (GPx), thioredoxin reductase (TRxR), and total plasma antioxidant activity (TEAA) were measured at baseline and after 12 weeks. Results: In the MedD group, significantly lower values of AGEs and higher values of GPX, TRX and TEAA with anti-oxidant action were detected (p < 0.05) at 12 weeks compared to baseline, and compared to the GFD and FD groups, in which the oxidative stress parameters did not change significantly (p > 0.05). No significant differences in serum levels of TSH, FT4, Ab-Tg, Ab-TPO compared to baseline were found in any group. Conclusions: This pilot study confirms the protective effect of the MedD against oxidative stress, while a GFD does not significantly influence markers of oxidative stress and/or thyroid autoimmunity/function parameters. [ABSTRACT FROM AUTHOR]

Recent studies have shown that novel collective behaviors emerge in complex systems due to the presence of higher-order interactions. However, how the collective behavior of a system is influenced by the microscopic organization of its higher-order interactions is not fully understood. In this work, we introduce a way to quantify the overlap among the hyperedges of a higher-order network, and we show that real-world systems exhibit different levels of intra-order hyperedge overlap. We then study two types of dynamical processes on higher-order networks, namely complex contagion and synchronization, finding that intra-order hyperedge overlap plays a universal role in determining the collective behavior in a variety of systems. Our results demonstrate that the presence of higher-order interactions alone does not guarantee abrupt transitions. Rather, explosivity and bistability require a microscopic organization of the structure with a low value of intra-order hyperedge overlap. Group interactions can lead to explosive onsets of collective behaviors in biological and sociotechnological systems. Here, the authors show that it is the overlap between these kind of higher-order interactions that drives whether emergence of synchrony and epidemics shows up smoothly or abruptly. [ABSTRACT FROM AUTHOR]

Posidonia oceanica retains a large amount of carbon within its belowground recalcitrant structure, the 'matte,' which is characterized by low oxygen availability and biodegradation. Fungi may play a pivotal role in carbon sequestration within the matte, even if little/no information is available. To fill this gap, we profiled fungal communities from the upper and lower layers of alive and dead matte, by using an ITS2-5.8S rDNA metabarcoding approach. The study was conducted in a shallow coastal stretch of the Aegean Sea (Crete). Then, 184 operational taxonomic units were identified, predominantly belonging to Ascomycota, in alive and dead matte. Nevertheless, their composition significantly differed: the host-specific Posidoniomyces atricolor was dominant in alive but not in dead matte, while fast-growing saprotrophs, potentially accelerating the decomposition rate, increased in dead matte. These findings lay the groundwork for future investigations on the possible increase of biodegradation under the changing environmental conditions. [ABSTRACT FROM AUTHOR]

Purpose: Levothyroxine (L-T4) is the drug of choice for treating primary hypothyroidism. L-T4 tablets should be taken at least 30 min before breakfast. Several studies have suggested that serum thyroid profile is not affected by concomitant intake of liquid/softgel L-T4 with meals. Our aim is to review the evidence on therapeutic efficacy and patient compliance with the liquid and softgel formulation of L-T4 taken with meals, also compared with the standard tablet therapy regimen, in hypothyroid patients. Methods: We performed a systematic review of literature by searching PubMed, Embase, and Cochrane Library databases. PRISMA guidelines were applied, and the risk of bias of the included studies was assessed using the RoB 2 and ROBINS tools. The methodological quality was assessed following the GRADE criteria. Results: We included 13 studies, accounting for a total of 1697 patients. The timing of liquid L-T4 intake from breakfast did not affect the therapeutic efficacy of the treatment. No significant differences in the absorption of liquid L-T4 were found when administered together with different foods, beverages, drugs, or other supplements. TSH levels are not influenced by taking softgel L-T4 at breakfast; the efficacy of softgel and liquid formulation is similar when they are taken with a meal, but superior to that of tablet formulation. Shifting from L-T4 tablets taken 30 min before breakfast to liquid/softgel formulation taken with the meal improved medication adherence and perceived quality of life of patients. Conclusion: Liquid and softgel formulation of L-T4 can be taken at breakfast or close to meals, without losing therapeutic efficacy. These formulations could also improve patient compliance and quality of life compared to L-T4 tablet therapy taken 30 min before breakfast. [ABSTRACT FROM AUTHOR]

Research depicts job crafting as a desirable, ongoing employee behavior rather than a one-off event. However, insights are lacking into how employees' active engagement in job crafting may be sustained across time. In this study, we advance a dynamic framework of how changes that follow employees' periods of job crafting may, in turn, motivate versus impede continued crafting of one's job role over time. Drawing from self-concordance theorizing, we propose and test a framework on how job crafting and employees' attainment of self-concordant and organizational work goals are reciprocally related over time. Longitudinal data from a large, three-wave study collected over four years among church ministers support a positive reciprocal relationship between job crafting and self-concordant goal attainment, as well as an indirect positive relationship between job crafting and organizational goal attainment via self-concordant goal attainment. However, in line with our theorizing, organizational goal attainment did not predict subsequent job crafting. Instead, high organizational goal attainment weakened the extent to which job crafting at one time point positively related to job crafting at the next time point. We discuss the theoretical and practical implications of our findings for employees' continued engagement in job crafting in organizations. [ABSTRACT FROM AUTHOR]

The CDKL5 deficiency disorder (CDD) is a severe neurodevelopmental disorder characterized by early-onset epilepsy, intellectual disability, motor and visual dysfunctions. The causative gene is CDKL5, which codes for a kinase required for brain development. There is no cure for CDD patients; treatments are symptomatic and focus mainly on seizure control. Several pathogenic variants are loss-of-function, but recent studies suggest that the CDD phenotype is sensitive to the CDKL5 gene dosage. Therefore, mRNA-targeted correction strategies that respect the physiological regulation of CDKL5 could be a valid alternative to augmentative gene therapy. Nonsense mutations cause ~ 11% of CDD cases, and these patients might benefit from readthrough therapies. We proved that drug-mediated readthrough efficiently suppresses premature CDKL5 nonsense codons, but the recoded kinase remained highly hypomorphic, curtailing the translational value of this pharmacological approach. In this study we explored if the recently developed Anticodon-edited tRNAs (ACE-tRNAs) offer an alternative readthrough strategy for CDD. Transfecting cells expressing different CDKL5 nonsense variants, we demonstrated that ACE-tRNAs efficiently restore full-length kinase synthesis. The recoded CDKL5 is correctly localized and catalytically active, thereby bringing tRNA-based therapy back into the spotlight for future investigations to assess the efficacy of this approach in correcting the pathological phenotype of CDD. [ABSTRACT FROM AUTHOR]

The beneficial effects of Neural Precursor Cell (NPC) transplantation in several neurological disorders are well established and they are generally mediated by the secretion of immunomodulatory and neurotrophic molecules. We therefore investigated whether Rett syndrome (RTT), that represents the first cause of severe intellectual disability in girls, might benefit from NPC-based therapy. Using in vitro co-cultures, we demonstrate that, by sensing the pathological context, NPC-secreted factors induce the recovery of morphological and synaptic defects typical of Mecp2 deficient neurons. In vivo, we prove that intracerebral transplantation of NPCs in RTT mice significantly ameliorates neurological functions. To uncover the molecular mechanisms underpinning the mediated benefic effects, we analyzed the transcriptional profile of the cerebellum of transplanted animals, disclosing the possible involvement of the Interferon γ (IFNγ) pathway. Accordingly, we report the capacity of IFNγ to rescue synaptic defects, as well as motor and cognitive alterations in Mecp2 deficient models, thereby suggesting this molecular pathway as a potential therapeutic target for RTT. Synopsis: To address the unmet need for a cure for RTT, the therapeutic potential of adult Neural Precursor Cells (NPCs) was investigated in vitro on Mecp2 deficient neurons and in vivo in transplanted Mecp2 deficient mice. NPC-secreted molecules rescue typical phenotypes of Mecp2 deficient neurons in culture. NPCs do not require Mecp2 to exert their beneficial effects. Intracerebral transplantation of NPCs prolongs the lifespan of Mecp2 null mice and restores their memory and motor functions. RNA-sequencing studies on transplanted brains have indicated the activation of the IFNγ pathway as a possible mechanism of action. IFNγ treatment of Mecp2 deficient animals and neurons confirms the therapeutic efficacy of the cytokine for RTT. To address the unmet need for a cure for RTT, the therapeutic potential of adult Neural Precursor Cells (NPCs) was investigated in vitro on Mecp2 deficient neurons and in vivo in transplanted Mecp2 deficient mice. [ABSTRACT FROM AUTHOR]

Background: Infections caused by S. aureus strains encoding Panton–Valentine leukocidin (PVL-SA) have become increasingly relevant in community settings and can cause severe conditions in pediatric populations. We present the pediatric case of an invasive disease caused by PVL-SA and provide a literature review of severe manifestations caused by these strains in children. Methods: A PubMed search (February 2024) found studies that included relevant clinical outcomes, diagnostics, and treatments, excluding cases of asymptomatic infection or in adult populations. A logistical multivariate analysis was used to find predictors of the need for intensive care. Results: A 10-year-old boy came to the attention of our Pediatric Infectious Diseases Unit with fever, chest pain, and tachypnea. A rapid worsening of his clinical conditions was observed, with the development of necrotizing pneumonia, osteomyelitis, deep vein thrombosis (DVT), and multiple abscesses. Blood cultures confirmed the presence of PVL-producing methicillin-resistant S. aureus (MRSA). The initial treatment included linezolid and ceftaroline and was later adjusted to clindamycin, daptomycin, and fosfomycin, with clinical improvement. Discussion: Our review collected 36 articles, including 156 pediatric cases of severe PVL-SA infection. Bacteremia was present in 49% of cases, lung infection in 47%, and osteomyelitis in 37%. The presence of pulmonary localization was predictive of the need for intensive care, O.R. 25.35 (7.46–86.09; p < 0.001). Anti-toxin molecules were used in about half the cases where information on treatment was reported. Our report highlights the capacity of PVL-SA to cause life-threatening complications in children, while also discussing the full range of its clinical spectrum and the most effective therapeutic approaches. [ABSTRACT FROM AUTHOR]

Count Neipperg (1775–1829), the morganatic husband of Maria Luigia of Habsburg, Napoleon's former wife, presented with typical heart failure symptoms and died of bilateral bronchopneumonia. Neipperg's case is an example of the conflict in the medical field, which led to the birth of modern evidence‐based medicine (EBM), and although Neipperg died almost 200 years ago, his case presents the same critical issues that more complex geriatric patients face today. First, the attending physicians provided divergent opinions without reaching an agreement. For example, Francesco Rossi correctly diagnosed heart disease by evaluating the patient's signs and symptoms, a clinical approach that is an early example of modern EBM. By contrast, Giacomo Tommasini made a misdiagnosis based on the philosophical principles of John Brown's vitalist theory, as reworded by Giovanni Rasori. Second, Tommasini's medical report also includes evidence of the Geriatric 5Ms for older patient care, such as multi‐complexity, multimorbidity, medication, mobility, and the mind. Moreover, both physicians considered "what matters most" for the patient and his family. Third, the Count's status and political role were identified as the social and structural determinants of health (SSDoH) and used to justify the exceptional intensity of the health care provided. Subsequently, the ante litteram application of EBM and a clinical evaluation based on Geriatrics 5Ms principles anticipate current multidisciplinary management focused on the patient rather than a single disease. The systematic revision of past clinical cases not examined before could open new windows in the dissemination of the geriatric methodology and discipline. [ABSTRACT FROM AUTHOR]

Background: Hematologic malignancies are a group of heterogeneous neoplasms which originate from hematopoietic cells. The most common among them are leukemia, lymphoma, and multiple myeloma. Machine learning (ML) is a subfield of artificial intelligence that enables the analysis of large amounts of data, possibly finding hidden patterns. Methods: We performed a narrative review about recent applications of ML in the most common hematological malignancies. We focused on the most recent scientific literature about this topic. Results: ML tools have proved useful in the most common hematological malignancies, in particular to enhance diagnostic work-up and guide treatment. Conclusions: Although ML has multiple possible applications in this field, there are some issue that have to be fixed before they can be used in daily clinical practice. [ABSTRACT FROM AUTHOR]

Parathyroid carcinoma (PC) is a rare endocrine malignancy that poses significant diagnostic challenges due to its resemblance to benign conditions. This case series describes the clinical presentation, diagnosis, management, and short-term outcomes of four male patients (aged 54, 65, 73, and 74 years) with primary hyperparathyroidism and hypercalcemia. The preoperative diagnosis of PC remains challenging; suspicion should arise in cases of severe hypercalcemia, elevated parathyroid hormone levels, and the presence of a mass on imaging or during surgery. All patients underwent an initial localized parathyroidectomy, with PC confirmed postoperatively. Subsequently, they received ipsilateral hemithyroidectomy and prophylactic central lymph node dissection. Over a two-year follow-up period, all patients maintained normocalcemia without evidence of disease recurrence or metastasis. In conclusion, whether to perform a complete en bloc resection or a two-step surgical strategy remains a difficult decision in PC patients with intricate preoperative evaluations. [ABSTRACT FROM AUTHOR]

Simple Summary: Advances in instrumentation technology have led to the development of new optical platforms for digital pathology imaging directly from fresh, unfixed specimens, without the need for conventional histological slide preparation. The objective of this study was to evaluate the performance of the new Vivascope 2500 digital microscope in providing real-time adequacy assessment and diagnostic information for echo-endoscopic lung and mediastinal nodes biopsy specimens. Thirty-two patients undergoing an EUS/EBUS procedure for the diagnosis of lung masses or lymph node staging were enrolled in this study: in 87.5% of patients, the specimens were adequate, and the immediate diagnostic hypothesis was a malignant lesion in 71.4%. When compared with paired permanent paraffin sections, there was excellent concordance between immediate digital assessment and final conventional diagnosis. Moreover, all digital real-time negative cases were confirmed as negative on permanent paraffin sections. The use of this approach provides rapid information on both the adequacy and malignancy of the sample obtained in real time during EBUS tissue acquisition, with minimal preparation and without destroying or losing the tissue. Real-time diagnosis with tissue preservation is expected to reduce turnaround time for diagnostic report and ensure adequacy for molecular profiling of the tumor. Background: Ex vivo fluorescence laser scanning microscopes (FCMs) allow digital tissue imaging directly from fresh, unfixed specimens without the need for conventional histological slide preparation. To date, no data have been reported on the use of FCMs in the endoscopy suite for immediate evaluation of endoscopic ultrasound (EUS)/endobronchial ultrasound (EBUS) fine needle aspiration/biopsy (FNA-B) specimens of lung lesions and/or mediastinal lymph nodes. Objectives: The aim of this study was to evaluate the performance of the FCM Vivascope 2500 (Vivascope, Munich, Germany) in providing real-time adequacy assessment and diagnostic information on the digital images of fresh unprocessed EUS/EBUS FNA-B specimens and to compare it with the corresponding final histological sections of formalin-fixed and paraffin-embedded cell blocks. Methods and Results: Thirty-two patients (50% male; 71 ± 8 years old) were enrolled between May 2023 and June 2024. In 28/32 (87.5%) patients, samples were defined as adequate at Vivascope evaluation, and in 20/28 (71.4%) patients, samples were classified as malignant. At final cytohistological evaluation, 87.5% of specimens were defined as adequate and 20/28 (71.4%) were diagnosed as malignant. There was perfect agreement between the Vivascope assessment of adequacy and the final cytohistological assessment on the same specimen (k Cohen 1). From a diagnostic point of view, perfect agreement was found between the two techniques in the identification of malignant neoplasms (k Cohen 1). Conclusions: The use of FCM could provide rapid information on both the adequacy and malignancy of the sample obtained during EBUS tissue acquisition (EBUS-TA), with minimal or no preparation and without destroying or losing the tissue. This technique allows for obtaining representative material in EBUS/EUS for lung cancer staging and is expected to change the turnaround time from biopsy sampling to diagnostic characterization of the tumor, ultimately improving patient management both at diagnosis and at restaging in follow up. [ABSTRACT FROM AUTHOR]

The recent outbreak of monkeypox virus (MPXV) has caused global concern. How the virus evades the interferon (IFN) response is still poorly understood. We analyzed type I/II IFN (IFN-I/II) expression in clinical samples from MPXV-infected patients and measured IFN-I kinetics in MPXV-infected cells. We also evaluated the anti-MPXV activity of IFN-I/II in A549, HeLa and Vero-E6 cell lines. IFN-I/II mRNA expression was detected in skin lesions, anal swabs, nasopharyngeal samples and peripheral blood mononuclear cells (PBMC), with the highest levels in skin lesions (p < 0.05). High MPXV DNA levels in clinical samples were associated with increased IFN-I levels. In vitro, MPXV infection induced a peak of IFN-I between 48 and 72 h post-infection (p < 0.01). Pre-treatment of the A549, HeLa and Vero-E6 cells with high concentrations (≥ 100,000 International Unit, IU/ml) of IFN-α and IFN-ω did not inhibit or had little effect on MPXV replication, while IFN-β moderately reduced MPXV replication by 2.7–1.5 log10 at 100,000 IU/ml. In clinical samples there was a trend for elevated levels of IFN-γ in association with lower MPXV load and in vitro IFN-γ (3,600 IU/ml) strongly reduced viral titers by 3.4–1.6 log10. There were no significant differences in expression of select IFN-stimulated genes (ISGs) in MPXV infection in vitro. This study shows that MPXV delays IFN-I induction and inhibits expression of selected ISGs in vitro and is associated with an IFN-I resistance phenotype in vivo. However, MPXV is less resistant to IFN-γ in vivo and is sensitive to IFN-γ treatment in vitro, suggesting a potential therapeutic role for IFN-γ. [ABSTRACT FROM AUTHOR]

Context: The use of methadone for cancer pain management is gaining wider acceptance. However, switching to methadone treatment can still pose challenges. Consequently, there is ongoing development of its use in low doses in combination with other opioids, despite a lack of clinical evidence regarding its efficacy and safety. Objectives: This study aimed to evaluate the efficacy and tolerability of low-dose methadone in combination with another opioid in patients with moderate-to-severe cancer-related pain in a clinical setting. Patients and methods: This was a prospective, open-label study conducted in 19 pain and/or palliative care centres treating patients with cancer-related pain. Pain intensity, patients' global impression of change, and adverse effects were assessed on day 7 and day 14. The main outcome measure was the proportion of responders. Results: The study included 92 patients. The daily dose of methadone was 3 [3–6] mg at baseline, 9 [4–10] mg on day 7 and 10 [6–15] mg on day 14. The NRS pain ratings significantly decreased from 7 [6–8] at baseline to 5 [3–6] on visit 2 (p <.0001) and 4 [3–6] on visit 3 (p <.0001). Similarly, the VRS pain ratings decreased from 3 [3–3] at baseline to 2 [2–3] on visit 2 (p = 0.026) and 2 [1–3] (p < 0.001) on visit 3. At Visits 1 and 2, half of the patients were considered Responders. Of those responders, 73.5% were High-Responders at Visit 1 and 58.7% were High-Responders at Visit 2. No adverse events related to the risk of QT prolongation, overdose, or drug interactions were reported. Conclusion: For patients experiencing moderate to severe cancer-related pain despite initial opioid treatment, our study found that low-dose methadone, when used in combination with another opioid, was both safe and effective. This supports the use of methadone as an adjunct to opioid-based treatment for cancer pain. [ABSTRACT FROM AUTHOR]

We consider some non-linear non-homogeneous partial differential equations (PDEs) and derive their exact Green function solution as a functional Taylor expansion in powers of the source. The kind of PDEs we consider are dispersive ones where the exact solution of the corresponding homogeneous equations can have some known shape. The technique has a formal similarity with the Dyson–Schwinger set of equations to solve quantum field theories. However, there are no physical constraints. Indeed, we show that a complete coincidence with the statistical field model of a quartic scalar theory can be achieved in the Gaussian expansion of the cumulants of the partition function. [ABSTRACT FROM AUTHOR]

Immunization is a preventive measure of crucial importance. As with any other medication, side effects are a possibility and include the rare occurrence of severe infections, such as osteomyelitis. We report an unusual case of pediatric osteomyelitis following vaccination and provide a review of similar reports submitted to the Vaccine Adverse Event Report System (VAERS), aiming to explore the association between the vaccination procedure and the occurrence of osteomyelitis in childhood. A previously healthy infant, with no history of trauma or infection, presented with hyperpyrexia, swelling, and functional impairment in the left leg and was eventually diagnosed with osteomyelitis of the left femur. An edema was noted at the site of the injection that he received days before for immunization purposes. The infection required surgical drainage and a four-week-long intravenous antibiotic treatment, and the patient was discharged upon showing improved clinical conditions. Forty-seven reports of similar cases submitted to VAERS between 1994 and 2023 were collected, and several cases from the literature, including a case of femoral osteomyelitis in a newborn vaccinated against Hepatitis B, attributed to improper injection technique. Another case was reported in a 15-year-old girl, which aligned with six similar cases of osteomyelitis in adolescents following HPV vaccines collected from VAERS. Despite the small sample number, the findings that in 77% of cases the infection was localized in the vaccinated limb and that symptoms appeared on average 4.3 days (IQR 1.0–5.7 days) post-vaccination suggest a possible link to the injection procedure and highlight the need to adhere to recommendations regarding skin preparation and the selection of the appropriate needle length and injection site. [ABSTRACT FROM AUTHOR]

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. Despite advancements in research, no cure exists due to an incomplete understanding of the molecular effects of MeCP2 deficiency. Previous studies have identified impaired tropomyosin receptor kinase (Trk) neurotrophin (NTP) signaling and mitochondrial redox imbalances as key drivers of the pathology. Moreover, altered glycosphingolipid metabolism has been reported in RTT. GM1 ganglioside is a known regulator of the nervous system, and growing evidence indicates its importance in maintaining neuronal homeostasis via its oligosaccharide chain, coded as GM1-OS. GM1-OS directly interacts with the Trk receptors on the cell surface, triggering neurotrophic and neuroprotective pathways in neurons. In this study, we demonstrate that GM1-OS ameliorates RTT deficits in the Mecp2-null model. GM1-OS restored synaptogenesis and reduced mitochondrial oxidative stress of Mecp2-knock-out (ko) cortical neurons. When administered in vivo, GM1-OS mitigated RTT-like symptoms. Our findings indicate that GM1-OS effects were mediated by Trk receptor activation on the neuron's plasma membrane. Overall, our results highlight GM1-OS as a promising candidate for RTT treatment. [ABSTRACT FROM AUTHOR]

Background/Objectives: Out of 39.9 million adults living with HIV in 2022, 20 million were women. Despite bearing a significant burden, women remain underrepresented in clinical trials, including those for antiretroviral treatments (ART). This study evaluates the safety and efficacy of the bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) regimen in a real-life cohort of 99 women with HIV (females with HIV, FWH) over 48 and 96 weeks. Methods: A retrospective cohort study utilized data from the Sardinian HIV Network and Sicilian HIV Cohort (SHiNe-SHiC) research group. The study included FWH, who started B/F/TAF as a treatment switch. The primary objectives were achieving and maintaining an HIV RNA level of <50 copies/mL at 48 and 96 weeks. Secondary objectives included treatment safety, durability, and reasons for discontinuation. Data on demographics, viro-immunological markers, lipid profiles, and treatment interruptions were extracted for analysis. Results: Among the 99 FWH, the median age was 51.9 years, and the median duration of HIV was 15.1 years. At baseline, 80.8% had undetectable HIV-RNA, which increased to 93.8% at 96 weeks. There was a statistically significant increase in CD4 cells/mL (48w p < 0.001, 96w p < 0.001) and CD4/CD8 ratio (48w p < 0.009, 96w p < 0.048), and reductions in total cholesterol (48w p < 0.003, 96w p < 0.006) and LDL (48w p < 0.004, 96w p < 0.009) levels at 48 and 96 weeks. Nine treatment interruptions were noted, with one due to adverse events. The regimen was well-tolerated overall. Conclusions: B/F/TAF demonstrated high efficacy and safety in this real-world cohort of FWH, highlighting the critical need for gender-focused research in HIV treatment. Ensuring equitable access to effective treatment options for women is imperative for the global health community's efforts to eliminate HIV. [ABSTRACT FROM AUTHOR]

The anchoring and mooring of boats mechanically damage Posidonia oceanica plants; however, no information is available on the effect of this kind of damage on the plant holobiont, i.e., on the associated bacterial and fungal communities. Indeed, bacterial communities are known to change under different plant stress conditions but the dynamics of seagrass-associated fungi remain largely unexplored. We used DNA metabarcoding to profile the bacterial and fungal colonizers of two nearby P. oceanica patches in the Villefranche-sur-Mer bay (France) differing by the amount of exposure to mechanical stress due to boat transit and anchoring. Bacterial communities showed a significant reduction in diversity with an increase in Vibrio sp. in the rhizome and root samples from the impacted site, where the accumulation of dead organic material favors opportunistic heterotrophs. Conversely, fungal communities showed increased diversity in the leaf samples from the impacted site, where a reduction in the dominant P. oceanica host-specific mutualistic endosymbiont, Posidoniomyces atricolor, was found. This change was probably due to the opening up of new colonizable niches for several fungal species. Although this study represents a preliminary assessment of the effect of mechanical stresses on P. oceanica-associated microbial communities, it further supports their putative use as a seagrass descriptor. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MS), a cluster of cardiometabolic disorders, and sexual dysfunction are two conditions that impact a large proportion of the general population. Although they can occur independently, they are frequently linked and significantly affect people's quality of life. In recent years, research has increasingly focused on the importance of diet, particularly the Mediterranean diet (MD), in modulating sexual function due to its anti-inflammatory, antioxidant, and vasodilatory properties. In this narrative review, we examined the relationship between MS and sexual function in both men and women, with a special emphasis on the MD's therapeutic efficacy in improving sexual dysfunction. In men, MD has been shown to ameliorate erectile dysfunction, as well as several sperm parameters, perhaps leading to improved fertility. On the other hand, adherence to MD has been demonstrated to partially recover several sexual dysfunctions in women, such as those related to their menstrual cycle, menopause, endometriosis, and polycystic ovary syndrome. These favorable effects of MD have been demonstrated in both sexes also among people affected by MS. However, more targeted studies are needed to validate these data for different dietary approaches as well. [ABSTRACT FROM AUTHOR]

Background: Brain metastases (BM) are the most common intracranial neoplasms in adults and are a significant cause of morbidity and mortality. The brain is an unusual site for distant metastases of thyroid cancer; indeed, the most common sites are lungs and bones. In this narrative review, we discuss about the clinical characteristics, diagnosis, and treatment options for patients with BM from differentiated thyroid cancer (DTC). Summary: BM can be discovered before initial therapy due to symptoms, but in most patients, BM is diagnosed during follow-up because of imaging performed before starting tyrosine kinase inhibitors (TKI) or due to the onset of neurological symptoms. Older male patients with follicular thyroid cancer (FTC), poorly differentiated thyroid cancer (PDTC), and distant metastases may have an increased risk of developing BM. The gold standard for detection of BM is magnetic resonance imaging with contrast agent administration, which is superior to contrast-enhanced computed tomography. The treatment strategies for patients with BM from DTC remain controversial. Patients with poor performance status are candidates for palliative and supportive care. Neurosurgery is usually reserved for cases where symptoms persist despite medical treatment, especially in patients with favorable prognostic factors and larger lesions. It should also be considered for patients with a single BM in a surgically accessible location, particularly if the primary disease is controlled without other systemic metastases. Additionally, stereotactic radiosurgery (SRS) may be the preferred option for treating small lesions, especially those in inaccessible areas of the brain or when surgery is not advisable. Whole brain radiotherapy is less frequently used in treating these patients due to its potential side effects and the debated effectiveness. Therefore, it is typically reserved for cases involving multiple BM that are too large for SRS. TKIs are effective in patients with progressive radioiodine-refractory thyroid cancer and multiple metastases. Conclusions: Although routine screening for BM is not recommended, older male patients with FTC or PDTC and distant metastases may be at higher risk and should be carefully evaluated for BM. According to current data, patients who are suitable for neurosurgery seem to have the highest survival benefit, while SRS may be appropriate for selected patient. [ABSTRACT FROM AUTHOR]

Context. It is well established that classical T Tauri stars accrete material from a circumstellar disk through magnetic fields. However, the physics regulating the processes in the inner (0.1 AU) disk is still not well understood. Aims. Our aim is to characterize the accretion process of the classical T Tauri Star RU Lup. Methods. Optical high-resolution spectroscopic observations with CHIRON and ESPRESSO were obtained simultaneously with photometric data from AAVSO and TESS. Results. We detected a periodic modulation in the narrow component of the He I 5876 line with a period that is compatible with the stellar rotation period, indicating the presence of a compact region on the stellar surface that we identified as the footprint of the accretion shock. We show that this region is responsible for the veiling spectrum, which is made up of a continuum component plus narrow line emission that fills in the photospheric lines. An analysis of the high-cadence TESS light curve reveals quasi-periodic oscillations on timescales shorter than the stellar rotation period, suggesting that the accretion disk in RU Lup extends inward of the corotation radius, with a truncation radius at ~2 R*. This is compatible with predictions from three-dimensional magnetohydrodynamic models of accretion through a magnetic boundary layer (MBL). In this scenario, the photometric variability of RU Lup is produced by a nonsta-tionary hot spot on the stellar surface that rotates with the Keplerian period at the truncation radius. We also qualitatively discuss how more complex hot spot shapes may generate the same variability pattern. The analysis of the broad components of selected emission lines reveals the existence of a non-axisymmetric, temperature-stratified flow around the star, in which the gas leaves the accretion disk at the truncation radius and accretes onto the star channeled by the magnetic field lines. The unusually rich metallic emission line spectrum of RU Lup might be characteristic of the MBL regime of accretion. Conclusions. Our extensive multiwavelength database of RU Lup reveals many similarities to predictions from the scenario of accretion through a magnetic boundary layer. Alternative explanations would require the existence of a hot spot with a complex shape, perhaps made of two brighter knots, or a warped structure in the inner disk. [ABSTRACT FROM AUTHOR]

Context. Studies of the stellar and accretion properties of classical T Tauri stars (CTTS) require photospheric spectral templates to be compared with. The use of low-activity, slowly rotating field dwarfs or model spectra can be advantageous for the determination of stellar parameters, but it can lead to an overestimate of the mass accretion rate, since both classes of templates do not include the emission of the active chromosphere present in young stars. Observed spectra of non-accreting young stars are best suited to this purpose. Using such templates comes with the downside of a limited number of available templates and observational uncertainties on the properties of the templates. Aims. For this work, we aimed to expand the currently available grid of wide-wavelength coverage observed spectra of non-accreting stars with additional new spectra and an interpolation method that allowed us to obtain a continuous grid of low resolution spectra ranging from spectral type G8 to M9.5, while also mitigating observational uncertainties. This interpolated grid was then implemented in the self-consistent method to derive stellar and accretion properties of CTTS. With the new templates, we aimed to estimate a lower limit on the accretion luminosities that can be obtained through a study of the UV excess emission using observed templates. Methods. We analyzed the molecular photospheric features present in the VLT/X-shooter spectra of the targets to perform a spectral classification, including estimates of their extinction. We applied a non-parametric fitting method to the full grid of observed templates to obtain an interpolated grid of templates. Both the individual templates and interpolated grid are provided to the community. We implemented this grid to improve the method to self-consistently derive stellar and accretion properties of accreting stars. We used the uncertainties on our interpolated grid to estimate a lower limit on the accretion luminosity that we can measure with this method. Results. Our new method, which uses a continuous grid of templates, provides results that are consistent with using individual templates but it significantly improves the reliability of the results in the case of degeneracies associated with the peculiarities of individual observed templates. We find that the measurable accretion luminosities range from ∼2.7 dex lower than the stellar luminosity in M5.5 stars to ∼1.3 dex lower for G8 stars. For young stars with masses of ∼1 M⊙ and ages of 3–6 Myr this limit translates into an observational limit of the mass accretion rate on the order of 10−10 M⊙/yr. This limit is higher than the lower limit on the measurable mass accretion rate when using the various emission lines present in the spectra of young stars to estimate the accretion rate. An analysis of these emission lines allows us to probe lower accretion rates, pending a revised calibration of the relationships between line and accretion luminosities at low accretion rates. Conclusions. The implementation of an interpolated grid of observed templates allows us to better disentangle degenerate solutions, leading to a more reliable estimate of accretion rates in young accreting stars. [ABSTRACT FROM AUTHOR]

Antimicrobials, such as antibiotics or antivirals are medications employed to prevent and treat infectious diseases in humans, animals, and plants. Antimicrobial Resistance occurs when bacteria, viruses, and parasites no longer respond to these medicines. This resistance renders antibiotics and other antimicrobial drugs ineffective, making infections challenging or impossible to treat. This escalation in drug resistance heightens the risk of disease spread, severe illness, disability, and mortality. With datasets now containing hundreds or even thousands of pathogen genomes, machine learning techniques are on the rise for predicting antibiotic resistance in pathogens, prediction based on gene content and genome composition. Aim of this work is to combine and incorporate machine learning methods on bacterial genomic data to predict antimicrobial resistance, we will focus on the case of Klebsiella pneumoniae in order to support clinicians in selecting appropriate therapy. [ABSTRACT FROM AUTHOR]

In this paper, we measured B cell function in elderly healthy individuals (EH) and in elderly patients with Type-2 Diabetes Mellitus (T2DM, ET2DM), which are treatment-naive, as compared to healthy young (YH) individuals. Results show a higher serum inflammatory status of elderly versus young individuals, and especially of ET2DM versus EH. This status is associated with a reduced response to the seasonal influenza vaccine and with increased frequencies of the circulating pro-inflammatory B cell subset called Double Negative (DN) B cells. B cells from ET2DM patients are not only more inflammatory but also hyper-metabolic as compared to those from EH controls. The results herein are to our knowledge the first to show that T2DM superimposed on aging further increases systemic and B cell intrinsic inflammation, as well as dysfunctional humoral immunity. Our findings confirm and extend our previously published findings showing that inflammatory B cells are metabolically supported. [ABSTRACT FROM AUTHOR]

The quality of microalgae-bacteria biomass as an organic soil fertilizer may depend on the biomass's microbial composition, morphology, and growth history. This study aims to characterize the molecular complexity and bioaccessibility of organic matter, nitrogen, and phosphorus from microalgae-bacteria aggregates with different morphologies (flocs and granules) grown under nutrient-abundant and starvation conditions. A biochemical fractionation method was used based on sequential chemical extraction and fluorescence spectroscopy. Microalgae-bacteria aggregates were cultured and collected from photobioreactors using contrasting growth conditions to generate (i) loose flocs, (ii) consolidated flocs, (iii) smooth granules, and (iv) filamentous granules. The organic matter, nitrogen, and phosphorus from consolidated flocs were mostly extractable, accounting for up to 94% of their total content. In contrast, the organic matter from loose flocs was up to 50% non-extractable. The extractability of loose flocs was improved under starvation conditions. All microalgae-bacteria aggregates showed a low structural complexity, corresponding to an abundance of simple microbial-related constituents like tyrosine and tryptophane. Differences between the gradients of bioaccessibility for each microalgae-bacteria structure were related to the abundance of microorganisms and their metabolic products. The findings of this study have implications for the development of sustainable and environment-friendly organic fertilizers. [ABSTRACT FROM AUTHOR]

Immune cells undergo metabolic reprogramming to meet the demands associated with immune responses. The effects of aging on these pathways and on the metabolic phenotype of the immune cells participating in antibody responses to vaccines are still largely unknown. Here we used a vaccine for SARS-CoV-2 that utilizes the cellular heat shock chaperone glycoprotein 96 (gp96), engineered to co-express SARS-CoV-2 Spike (spike) protein (gp96-Ig-S). Results show that this vaccine induces comparable B cell primary responses in young and old mice at later time points, but a significantly lesser secondary response in old as compared to young mice, with the antibodies generated in the secondary response being also of lower avidity. This occurs because aging changes the B cell metabolic phenotype and induces hyper-metabolic B cells that are associated with higher intrinsic inflammation and decreased protective antibody responses. However, the gp96-Ig-S vaccine was found to be effective in significantly reducing the metabolic/inflammatory status of B cells from old mice, suggesting the possibility that targeting metabolic pathways may improve immune function in old mice that do not respond adequately to the vaccine. [ABSTRACT FROM AUTHOR]

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular and immunity alterations and skin/internal organ fibrosis. Aberrant levels of plasma CXCL4, CXCL4–RNA/DNA complexes, type I IFN (IFN-I) and anti-CXCL4 antibodies characterize SSc. These parameters influence each other: CXCL4–self-DNA/RNA complexes are triggers of IFN-I in plasmacytoid dendritic cells (pDCs), and anti-CXCL4 autoantibodies amplify this effect. Here, we assess the modulation over time of plasma CXCL4 and the related parameters of CXCL4–DNA/RNA complexes, anti-CXCL4 antibodies, IFN-α and TNF-α in an SSc cohort under the synthetic analogue of prostacyclin PGI2 (iloprost) treatment to address contribution of these parameters to pathogenesis and their role as biomarkers. Methods: We analyzed immunological parameters at baseline (T0) and after 3 (T3) and 6 (T6) months in 30 SSc patients. Responders were the patients that lowered their disease activity parameters after six months of treatment. Results: Anti-CXCL4 autoantibodies correlated with both IFN-α and TNF-α levels in SSc plasma. Responders significantly down-regulated serum IFN-α. In seven patients with a shorter disease duration, improvement coincides with a decrease in plasma IFN-α, CXCL4 and TNF-α. Iloprost efficiently blocks pDCs IFN-α production induced by CXCL4–DNA/RNA complexes in vitro. Conclusions: The data suggest a possible role of iloprost as a disease-modifying drug, mainly accompanied by down-regulation of plasma IFN-I levels. Since CXCL4, IFN-I and TNF-α down-modulation was evident and significant in improving SSc patients with a shorter disease duration, these results warrant future investigations on the early use of iloprost to slow SSc progression. [ABSTRACT FROM AUTHOR]

Thyroid nodules (TNs) are a common entity, with the majority being benign. Therefore, employing an accurate rule-out strategy in clinical practice is essential. In the thyroid field, the current era is significantly marked by the worldwide diffusion of ultrasound (US)-based malignancy risk stratification systems of TN, usually reported as Thyroid Imaging Reporting And Data System (TIRADS). With the advent of US (and later TIRADS), the role of thyroid scintigraphy (TS) in clinical practice has gradually diminished. The authors of the present paper believe that the role of TS should be reappraised, also considering its essential role in detecting autonomously functioning thyroid nodules and its limited contribution to detecting thyroid cancers. Thus, this document aims to furnish endocrinologists, radiologists, surgeons, and nuclear medicine physicians with practical information to appropriately use TS. [ABSTRACT FROM AUTHOR]

Simple Summary: Total thyroidectomy and dissection of cervical lymph node compartments, depending on serum calcitonin levels and ultrasound findings, is standard treatment for patients with medullary thyroid cancer. The aim of this study was to evaluate whether pre-operative calcitonin and CEA levels can be useful as biomarkers of the extent of lymph node metastases at diagnosis. Results indicate that pre-operative serum calcitonin and CEA levels can predict presence, number, and site of lymph node metastases and, more specifically, values of 90 pg/mL for calcitonin and 17 ng/mL for CEA accurately indicate the N1b status. Since surgery is the only curative treatment for medullary thyroid cancer and there is not a strong indication regarding the extent of lymphadenectomy, these findings may help in the choice of the extent of neck dissection. Background: In medullary thyroid cancer (MTC), lymph node metastases are often present at diagnosis and the extent of surgery is usually based upon pre-operative calcitonin and CEA levels as well as ultrasound findings. The aim of this study was to evaluate the role of pre-operative calcitonin and CEA levels as predictive markers of the burden of lymph node metastases at diagnosis. Methods: we conducted a retrospective study analyzing 87 MTC patients. Results: The median levels of calcitonin and CEA were 88.4 pg/mL and 7.0 ng/mL, respectively, in patients with no lymph nodes metastases; 108.0 pg/mL and 9.6 ng/mL, respectively, in patients with metastases to 1–5 lymph nodes; 520.5 pg/mL and 43.2 ng/mL, respectively, in patients with metastases to >5 lymph nodes. There were no significant differences in pre-operative calcitonin and CEA values between N0 and N1a patients, whereas they were significantly higher in N1b patients. Pre-operative cut-off levels distinguishing N0/N1a from N1b patients were 90 pg/mL for calcitonin (sensitivity 100%, specificity 59.3%, AUC = 0.82) and 17 ng/mL for CEA (sensitivity 100%, specificity 75%, AUC = 0.89). Conclusions: in patients with MTC, pre-operative serum calcitonin and CEA levels may drive the decision-making process to better define the extent of surgery. [ABSTRACT FROM AUTHOR]

This work aimed to assess the potential efficacy of a novel polysaccharides-based extract as a green consolidant for the pictorial layer on marble substrates. Understanding its properties could lead to determining whether it can ensure the correct conservation and transmission of the cultural heritage. Four different types of marble specimens were prepared with paint based on malachite (egg, tempera grassa, rabbit glue, and linseed oil as binders). Colorimetric analyses, peeling tests, SEM-EDS, and FTIR spectroscopy were used to test the properties of the consolidant. Results reveal that no aesthetic changes occur when using the extract on painted surfaces and that the cohesive properties of most pictorial films increase after its application, confirming the consolidating effect. In conclusion, the use of an innovative green product for the restoration of marble-painted surfaces can be considered a possible good solution for consolidating treatment. Through this initial explorative research, we suggest an innovative approach to the protection of cultural heritage that doesn't cause harm to both the restorer's health and the environment. [ABSTRACT FROM AUTHOR]

This research addresses the issue of the heritage preventive conservation in the perspective of energy sustainability, for contributing to the achievement of the Sustainable Development Goals (SDGs) and towards the EU Green Deal. The study analyses and compares four cases associated with different microclimate thresholds as suggested by the standard EN 16893:2018 (Cases 1–3) and as derived from the outputs of three degradation models for preserving paper, wood, and canvas paintings (Case 4). Weather-based indices (degree and gram days) were calculated to estimate trends in the potential energy demand of collection facilities in three European cities belonging to different Köppen-Geiger climate zones (Cfb, Csa, and Dfb), under recent past (1981–2010) and near/far future climate scenarios (2021–2050 and 2071–2100) from two Shared Socioeconomic Pathways (SSP2-4.5 and SSP5-8.5). The findings suggest that adapting facilities' management strategies to focus on collections preservation can facilitate the achievement of 5 out of 17 SDGs, offering a viable alternative to costly energy retrofits and encouraging the development of shared solutions for similar facilities in the same climate zone. The results can contribute to inform the revision of EN 16893 and to face major challenges such as the preservation of paper collections in southern latitudes. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to demonstrate that an adipocyte tissue‐derived conditioned medium (ACM) contains inflammatory molecules that induce senescence in B cells. Methods: We incubated blood‐derived B cells from lean donors with ACM obtained from the adipose tissue of adult female donors with obesity undergoing weight reduction surgery or with medium as control. After 24 h, cells were harvested, and the expression of transcripts for proinflammatory cytokines (TNF/IL‐6), chemokines (IL‐8), and for markers of the senescence‐associated secretory phenotype (SASP) was measured by quantitative polymerase chain reaction. B cells were also stained with the marker of immunosenescence β‐galactosidase, and their metabolic status was evaluated in Seahorse using a Mito Stress Test. Results: We show that the incubation of B cells from lean donors with ACM induces the expression of transcripts for inflammatory and SASP transcripts, increases the amount of β‐galactosidase staining, and induces a metabolic phenotype characterized by higher basal and maximal oxygen consumption, spare respiratory capacity (difference between maximal and basal respiration), nonmitochondrial oxygen consumption, ATP production, and proton leak. Conclusions: These results demonstrate that B cells from lean individuals, after incubation with ACM, become inflammatory and senescent, and this occurs through metabolic pathways needed to support their secretory phenotype. [ABSTRACT FROM AUTHOR]

Background: Hypoalbuminemia is common in heart failure (HF) patients; however, there are no data regarding the possible long-term prognostic role of serum albumin (SA) in the younger population with chronic HF without malnutrition. The aim of this study was to examine the long-term prognostic role of SA levels in predicting major adverse cardiac events (MACE) in middle-aged outpatients with chronic HF. Methods: In the present retrospective analysis, 378 subjects with HF were enrolled. MACE (non-fatal ischemic stroke, non-fatal myocardial infarction, cardiac revascularization or coronary bypass surgery, and cardiovascular death), total mortality, and HF hospitalizations (hHF) occurrence were evaluated during a median follow-up of 6.1 years. Results: In all population, 152 patients had a SA value < 3.5 g/dL and 226 had a SA value ≥ 3.5 g/dL. In patients with SA ≥ 3.5 g/dL, the observed MACE were 2.1 events/100 patient-year; while in the group with a worse SA levels, there were 7.0 events/100 patient-year (p < 0.001). The multivariate analysis model confirmed that low levels of SA increase the risk of MACE by a factor of 3.1. In addition, the presence of ischemic heart disease, serum uric acid levels > 6.0 mg/dL, chronic kidney disease, and a 10-year age rise, increased the risk of MACE in study participants. Finally, patients with SA < 3.5 g/dl had a higher incidence of hHF (p < 0.001) and total mortality (p < 0.001) than patients with SA ≥ 3.5 g/dl. Conclusions: Patients with chronic HF that exhibits low SA levels show a higher risk of MACE, hHF and total mortality. [ABSTRACT FROM AUTHOR]

Background: Medullary Thyroid Carcinoma (MTC) is a neuroendocrine tumor that arises from the thyroid C-cells. Most cases are sporadic (sMTC) while, approximately 25%, are hereditary (hMTC) due to germline mutations of REarranged during Transfection (RET) gene mutations and manifest in the framework of multiple endocrine neoplasia (MEN) 2A or 2B, or as pure familial MTC syndrome (FMTC). Objective: The aim of this study is to evaluate the clinical, histopathological, biochemical and outcome differences between sMTC and hMTC. Methods: Retrospective analysis of a consecutive series of 102 patients with histologically proven MTC diagnosed in the period between 2000 and 2022. For the analysis patients with MTC diagnosed during screening through genetic test were excluded. Results: Patients with hMTC had higher incidence of multifocal and bilateral MTC and younger age at diagnosis. We did not found differences on tumor stage at diagnosis between sMTC and hMTC, such as time to progression and rate of persistent and recurrent disease. At univariate analysis, factors associated with persistent and recurrent disease during follow-up in patients with sMTC were tumor size, extrathyroidal extension, presence of lymph node metastases at diagnosis, pre- and post-operative calcitonin, post-operative CEA; in patients with hMTC, features associated with persistent and recurrent disease were lymph node metastases, post-operative calcitonin and pre- and post-operative CEA values. Conclusion: Patients with hMTC and sMTC had similar histopathological characteristics and clinical outcome. [ABSTRACT FROM AUTHOR]

Introduction: Expeditious initiation of biologic therapy is important in patients with inflammatory bowel disease (IBD). However, initiation of biologics in the outpatient setting may be delayed by various clinical, social, and financial variables. Aim: To evaluate the delay in initiation of an advanced therapy in IBD and to identify factors that contributed to this delay. Methods: This was a multi-center retrospective study. Outpatients who were initiated on a biologic therapy from 3/1/2019 to 9/30/20 were eligible for the study. Univariate and multivariate linear regression analyses were performed to identify variables associated with a delay in biologic treatment initiation. Delay was defined as the days from decision date (prescription placement) to first infusion or delivery of medication. Results: In total 411 patients (Crohn's disease, n = 276; ulcerative colitis, n = 129) were included in the analysis. The median [interquartile range-(IQR)] delay for all drugs was 20 [12–37] days (infliximab, 19 [13–33] days; adalimumab, 10 [5–26] days; vedolizumab, 21 [14–42] days; and ustekinumab, 21 [14–42] days). Multivariate linear regression analysis identified that the most important variables associated with delays in biologic treatment initiation was self-identification as Black, longer distance from treatment site, and lack of initial insurance coverage approval. Conclusion: There may be a significant delay in biologic treatment initiation in patients with IBD. The most important variables associated with this delay included self-identification as Black, longer distance from site, and lack of initial insurance coverage approval. [ABSTRACT FROM AUTHOR]

We present the overview and first results from the North-PHASE Legacy Survey, which follows six young clusters for five years, using the 2 deg |$^2$| FoV of the JAST80 telescope from the Javalambre Observatory (Spain). North-PHASE investigates stellar variability on time-scales from days to years for thousands of young stars distributed over entire clusters. This allows us to find new YSO, characterize accretion, and study inner disc evolution within the cluster context. Each region (Tr 37, Cep OB3, IC 5070, IC 348, NGC 2264, and NGC 1333) is observed in six filters (SDSS griz, u band, and J0660, which covers H |$\alpha$|⁠), detecting cluster members as well as field variable stars. Tr 37 is used to prove feasibility and optimize the variability analysis techniques. In Tr 37, variability reveals 50 new YSO, most of them proper motion outliers. North-PHASE independently confirms the youth of astrometric members, efficiently distinguishes accreting and non-accreting stars, reveals the extent of the cluster populations along Tr37/IC 1396 bright rims, and detects variability resulting from rotation, dips, and irregular bursts. The proper motion outliers unveil a more complex star formation history than inferred from Gaia alone, and variability highlights previously hidden proper motion deviations in the surrounding clouds. We also find that non-YSO variables identified by North-PHASE cover a different variability parameter space and include long-period variables, eclipsing binaries, RR Lyr, and |$\delta$| Scuti stars. These early results also emphasize the power of variability to complete the picture of star formation where it is missed by astrometry. [ABSTRACT FROM AUTHOR]

Salmonella infections have been associated with cardiovascular complications, including myocarditis and myopericarditis. This presentation of Salmonella myopericarditis highlights key clinical features to aid in diagnosis and the importance of prompt treatment with antibiotics, colchicine and non-steroidal antiinflammatory drugs (NSAIDs). [ABSTRACT FROM AUTHOR]

This review focuses on the intersection of artificial intelligence and genomic data in cancer research. It explores the types of genomic data used in the literature, the methodologies of machine learning and deep learning, recent applications, and the challenges associated with this field. Through an analysis of 47,586 articles and addressing seven research questions, the study reveals significant growth in this area over the past years. While there has been remarkable progress, ongoing attention is needed to address ethical considerations, interpretability of algorithms, and potential data biases, to ensure the reliable and responsible use of these advanced technologies. Overall, this paper provides a comprehensive overview of the current research landscape, offering insights into both the potential and challenges of AI in genomic data research. [ABSTRACT FROM AUTHOR]

Introduction: To analyse the perspectives of healthcare professionals (HCPs) regarding the acceptance of digital health solutions for growth hormone (GH) deficiency care. This study identified factors impacting HCPs' intent to use and recommend digital solutions supporting recombinant-human growth hormone (r-hGH) therapy in Italy and Korea with a use case of connected drug delivery system (Aluetta® with Smartdot™) integrated in a platform for GH treatment support (the Growzen™ digital health ecosystem). Methods: Participatory workshops were conducted in Rome, Italy, and Seoul, Korea, to collect the perspectives of 22 HCPs on various predefined topics. HCPs were divided into two teams, each moderated by a facilitator. The workshops progressed in five phases: introduction of the project and experts, capturing views on the current context of digitalisation, perceived usefulness and ease of use of Aluetta® with Smartdot™, exploration of the perception of health technology evolution, and combined team recommendations. Data shared by HCPs on technology acceptance were independently analysed using thematic analysis, and relevant findings were shared and validated with experts. Results: HCPs from both Italy and Korea perceived Aluetta® with Smartdot™ and the Growzen™ based digital health ecosystem as user-friendly, intuitive, and easy-to-use solutions. These solutions can result in increased adherence, a costeffective healthcare system, and medication self-management. Although technology adoption and readiness may vary across countries, it was agreed that using digital solutions tailored to the needs of users may help in data-driven clinical decisions and strengthen HCP--patient relationships. Conclusion: HCPs' perspectives on the digitalisation in paediatric GH therapies suggested that digital solutions enable automatic, real-time injection data transmission to support adherence monitoring and evidence-based therapy, strengthen HCP--patient relationships, and empower patients throughout the GH treatment process. [ABSTRACT FROM AUTHOR]

Background: Graves' orbitopathy (GO) occurs in approximately 25-40% of patients with Graves' disease (GD). High levels of anti-thyrotropin receptor antibodies (TRAbs), smoking habit, sex, older age, longer duration and amount of hyperthyroidism or hypothyroidism are well-recognized risk factors for the occurrence, severity and clinical course of GO. Oxidative stress (OX) has recently been shown to play a role in the pathogenesis of GO, and several clinical conditions related to OX have been investigated regarding the presentation and severity of GO. Aim: We aimed to evaluate the impact of clinical conditions related to oxidative stress on the outcome of intravenous glucocorticoid (ivGCs) therapy in a cohort of patients with active moderate to severe GO (AMS-GOs) treated at a single institution. Methods: We retrospectively studied a series of patients with AMS-GOs who were treated with ivGCs from January 2013 to May 2022. GO clinical evaluation was performed at baseline and at 6 (W6), 12 (W12) and 24 (W24) weeks after starting ivGCs by the seven-point clinical activity score (CAS) alone and by overall clinical criteria (CI) according to the European Group of Graves' Ophthalmopathy (EUGOGO). Total cholesterol and calculated LDL cholesterol (LDLc), triglyceride, body mass index (BMI), diabetes status, history of hypertension (HoH), smoking status, age and sex were used as covariates for the clinical outcome of GO to ivGCs. Results and conclusions: LDLc and HoH negatively and independently modulated the response of AMS-GOs to ivGCs. Notably, slightly elevated LDLc levels (> 130 mg/dl) reduced the response of orbital soft tissue to ivGCs, whereas more elevated LDLc levels (from 175 mg/dl to 190 mg/dl) and HoH were associated with poorer clinical response of eye motility and proptosis. [ABSTRACT FROM AUTHOR]

Context. Young stars accrete matter from their surrounding protoplanetary disk and drive powerful outflows. These two processes shape the final system architecture, and studying how these processes interact is the goal of the ESO Large programme PENELLOPE. PENELLOPE complements the ULLYSES legacy programme on the Hubble Space Telescope (HST) by providing ground-based – Very Large Telescope (VLT) – optical and near-infrared spectroscopy of more than 80 low-mass young stars. Aims. The main goal of this study is to screen the PENELLOPE/UVES targets for outflow activity and find microjets. A spectro-astrometric analysis in the [OI]λ6300 line in the velocity components of the microjet can give insights into the origin of the line emission, that is, if they originate from a magneto-hydrodynamical (MHD) wind or a photoevaporative wind. Methods. In total, 34 T Tauri stars of the PENELLOPE survey have been observed with the high-resolution optical slit spectrograph UVES (R ~ 65 000, λ = 3300–6800 Å). We formulated four criteria to rank the targets according to their outflow activity. Most of the targets have been observed in three different slit positions rotated by 120° with UVES. Using spectro-astrometric techniques in the [OI]λ6300 and Hα emission lines in each slit position of each target, we searched for outflow signatures, that is, an offset emission with respect to the continuum contribution of the associated T Tauri star. We checked all spectra for the presence of other wind line emission of [SII]λ4068, [SII]λ4076, [OI]λ5577, [OI]λ6300, [OI]λ6363, [SII]λ6716, [SII]λ6731, [NII]λ6548, and [NII]λ6583. Line profiles of Hα were inspected for a P Cygni signature. All [OI]λ6300 line profiles were decomposed into their constituent high-velocity component (HVC) and low-velocity component (LVC). Results. Our spectro-astrometric analysis in the [OI]λ6300 wind line reveals two newly discovered microjets associated with Sz 103 and XX Cha. Both microjets have an extent of about 0″.04, that is, <10 au, and we confined their orientation by the three slit observations. We identified two other interesting targets for which all four outflow criteria are fulfilled: Sz 98 and Sz 99. These targets display peculiar wind lines in their spectra with multiple velocity components, however, with the lack of a spectro-astrometric outflow signature. Furthermore, we confirm the binary nature of VWCha and CVSO 109. We present (further) evidence that DK Tau B and CVSO 104 A are spectroscopic binaries. Sz 115 is tentatively a spectroscopic binary. We find that the P Cygni line profile in the Hα line is not a robust indicator for the presence of outflows. Conclusions. The utilised observing strategy (rotating the UVES slit in three different positions) is very powerful in detecting micro-jets in T Tauri stars. The three slit positions can confine the spatial extend of the forbidden emission line regions. The introduced metric to rank targets according to their outflow activity is useful for follow-up observations. The origin of the LVC, that is, MHD winds versus photoevaporative winds, of the Sz 103 and XX Cha microjets remains unclear. [ABSTRACT FROM AUTHOR]