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Dietary restriction (DR) is a potent method to enhance lifespan and healthspan, but individual responses are influenced by genetic variations. Understanding how metabolism-related genetic differences impact longevity and healthspan are unclear. To investigate this, we used metabolites as markers to reveal how different genotypes respond to diet to influence longevity and healthspan traits. We analyzed data from Drosophila Genetic Reference Panel (DGRP) strains raised under AL and DR conditions, combining metabolomic, phenotypic, and genome-wide information. We employed two computational and complementary methods across species-random forest modeling within the DGRP as our primary analysis and Mendelian randomization in human cohorts as a secondary analysis. We pinpointed key traits with cross-species relevance as well as underlying heterogeneity and pleiotropy that influence lifespan and healthspan. Notably, orotate was linked to parental age at death in humans and blocked the DR lifespan extension in flies, while threonine supplementation extended lifespan, in a strain- and sex-specific manner. Thus, utilizing natural genetic variation data from flies and humans, we employed a systems biology approach to elucidate potential therapeutic pathways and metabolomic targets for diet-dependent changes in lifespan and healthspan.

Pineal cysts are benign, nonneoplastic lesions of the pineal gland, often identified incidentally on MRI scans. Although these cysts are usually asymptomatic, they can occasionally enlarge and compress adjacent structures, leading to neurological complications such as obstructive hydrocephalus and Parinaud's syndrome. The underlying mechanisms of pineal cyst development remain largely unclear, although inflammation - common in rheumatological conditions such as fibromyalgia - and mechanical stress have been suggested as contributing factors. In addition, the incomplete blood-brain barrier of the pineal gland raises the possibility that chronic lithium therapy, commonly used for psychiatric disorders and also known for its hyperplastic effects, could facilitate cysts formation through lithium accumulation and epithelial stimulation.We report the case of a 49-year-old woman with bipolar disorder on long-term lithium treatment who presented with a pineal cyst and clinical symptoms consistent with fibromyalgia. A review of the literature highlights possible links between pineal cyst formation, systemic inflammation associated with rheumatological disorders and prolonged lithium exposure.Although the hyperplastic properties of lithium in glandular tissue are well documented, there is no conclusive evidence directly linking lithium use to the development of pineal cysts in humans. The possibility of cystic growth driven by the pro-inflammatory environment of fibromyalgia remains plausible and warrants further investigation of the complex interactions between lithium therapy, systemic inflammation and pineal cystogenesis, particularly in patients with coexisting rheumatological and psychiatric disorders.

Abstract Vitality Forms (VFs) constitute the dynamic essence of human actions, providing insights into how individuals engage in activities. The ability to perceive and express VFs during interpersonal interactions is pivotal for understanding others’ intentions, behaviors, and fostering effective social communication. Despite their ubiquity in all actions, research exploring the role of VFs in neurodivergent conditions related to social and communicative skills, particularly in autism, remains limited. This study aims to investigate the expression of different VFs during the execution of both social and non-social actions in children with an Autism Spectrum Condition (ASC) in comparison to neurotypical children (NT). ASC children and NT children were asked to move a small bottle either towards a target point (non-social context) or moving it towards a receiver (social context) with different VFs specifically neutral, gentle, or rude. Videotaped tasks were subsequently analyzed to study kinematic parameters characterizing VFs. Our results highlighted three main findings: (1) overall, ASC children are able to tune the motor profile of their actions, effectively conveying both gentle and rude VFs; (2) distinct kinematic parameters in the execution of VFs are able to distinguish autistic children from NT children; (3) the social context significantly influences the child’s ability to express positive and negative VFs in autism. Taken together, these findings provide new insights to understand how VFs contribute to the complex dynamics of social communication in neurodivergent autistic children, providing a valuable contribution for future interventions and support strategies.

Linguistic strategies humans use for communication are designed to meet the informational needs of their addressees. Speakers not only adapt their speech but also increase the rate of iconic gestures to enhance the clarity of a message for children. Although sign languages allow signers to take advantage of iconicity far more than what is possible in speech, little is known about whether signers use iconicity as a strategy in child-directed communication. In the present study, we used automatic video pose estimation to analyze descriptions aimed at a child (12yo) vs. an adult produced by 7 deaf adult signers of Italian Sign Language. Overall, signers used iconic constructions more than lexical signs and with comparable frequency in descriptions for both age groups. However, iconic constructions were longer in duration for children. Thus, the present study presents the first evidence that, unlike speakers, signers do not modulate quantitative but only qualitative aspects of iconicity for children.

Aim: Accurately identifying primary lesions in oral medicine, particularly elementary white lesions, is a significant challenge, especially for trainee dentists. This study aimed to develop and evaluate a deep learning (DL) model for the detection and classification of elementary white mucosal lesions (EWMLs) using clinical images. Materials and Methods: A dataset was created by collecting photographs of various oral lesions, including oral leukoplakia, OLP plaque-like and reticular forms, OLL, oral candidiasis, and hyperkeratotic lesions from the Unit of Oral Medicine. The SentiSight.AI (Neurotechnology Co.®, Vilnius, Lithuania) AI platform was used for image labeling and model training. The dataset comprised 221 photos, divided into training (n = 179) and validation (n = 42) sets. Results: The model achieved an overall precision of 77.2%, sensitivity of 76.0%, F1 score of 74.4%, and mAP of 82.3%. Specific classes, such as condyloma and papilloma, demonstrated high performance, while others like leucoplakia showed room for improvement. Conclusions: The DL model showed promising results in detecting and classifying EWMLs, with significant potential for educational tools and clinical applications. Expanding the dataset and incorporating diverse image sources are essential for improving model accuracy and generalizability.

Growing scientific evidence suggests a link between the expression of toll-like receptor 4 (TLR4) and cervical cancer carcinogenesis. Specifically, a close relation between TLR4 expression and FIGO stage, lymph node metastases, and tumor size has been reported in cervical cancer. In the present study, we aimed to evaluate the relationship between TLR4 expression levels and human papillomavirus (HPV) infection and/or high-risk (hr) HPV integration status in patients with a histological diagnosis of high-grade squamous intraepithelial lesion (H-SIL), and squamous cell carcinoma (SCC) of the uterine cervix. Sixty biopsies of cervical neoplasia, comprising H-SIL (n = 20) and SCC (n = 40), were evaluated for TLR4 expression by immunohistochemistry. All samples were positive for high-risk HPV as confirmed by in situ hybridization (ISH) and broad-spectrum PCR followed by Sanger sequencing analysis. The intensity of TLR4 staining was higher in tissues negative for intraepithelial lesion or malignancy (NILM) than in H-SIL, and further reduced in SCC. Moreover, statistically significant differences have been observed in the percentage of TLR4 expression between NILM and H-SIL and between H-SIL and SCC, with higher percentages of expression in H-SIL than in SCC. Our results showed a significant downregulation of TLR4 in HPV-related H-SIL and SCC, compared to NILM. These data support the hypothesis that TLR4 expression is suppressed in HPV-driven oncogenesis.

Abstract Dietary restriction (DR) is a potent method to enhance lifespan and healthspan, but individual responses are influenced by genetic variations. Understanding how metabolism-related genetic differences impact longevity and healthspan are unclear. To investigate this, we used metabolites as markers to reveal how different genotypes respond to diet to influence longevity and healthspan traits. We analyzed data from Drosophila Genetic Reference Panel (DGRP) strains raised under AL and DR conditions, combining metabolomic, phenotypic, and genome-wide information. We employed two computational and complementary methods across species—random forest modeling within the DGRP as our primary analysis and Mendelian randomization in human cohorts as a secondary analysis. We pinpointed key traits with cross-species relevance as well as underlying heterogeneity and pleiotropy that influence lifespan and healthspan. Notably, orotate was linked to parental age at death in humans and blocked the DR lifespan extension in flies, while threonine supplementation extended lifespan, in a strain- and sex-specific manner. Thus, utilizing natural genetic variation data from flies and humans, we employed a systems biology approach to elucidate potential therapeutic pathways and metabolomic targets for diet-dependent changes in lifespan and healthspan.

Introduction: Metastatic breast cancer (MBC) presents an enduring and significant challenge for affected women, requiring sustained commitment over the years. Case Presentation: This paper presents a case of a woman affected by bone and visceral MBC with a very long 20-year survival, excellent quality of life, and high resilience. She is now 51 years old and underwent quadrantectomy for breast cancer in 2005, and in 2013, she developed a recurrence with bone and liver metastases. Despite the widespread stage of the disease with visceral compromise, the patient was treated with a multidisciplinary approach that included surgery, chemotherapy, radiotherapy, hormone therapy, bone target agents, metabolic radiotherapy, and ozone therapy for medication-related osteonecrosis of the jaw. Multidisciplinary management results in a complete clinical and metabolic response to treatment in a visceral metastatic setting. Conclusion: This report supports the possibility of achieving unusual survival outcomes in patients with MBC. This study also highlights the importance of resilience in breast cancer patients who continue to manage their disease and pursue treatment for over 2 decades. Understanding these resilience factors can improve clinical practice and support patients’ long-term care.

Endogenous retroviruses (ERVs) are remnants of ancient parasitic infections and comprise sizable portions of most genomes. Although epigenetic mechanisms silence most ERVs by generating a repressive environment that prevents their expression (heterochromatin), little is known about mechanisms silencing ERVs residing in open regions of the genome (euchromatin). This is particularly important during embryonic development, where induction and repression of distinct classes of ERVs occur in short temporal windows. Here, we demonstrate that transcription-associated RNA degradation by the nuclear RNA exosome and Integrator is a regulatory mechanism that controls the productive transcription of most genes and many ERVs involved in preimplantation development. Disrupting nuclear RNA catabolism promotes dedifferentiation to a totipotent-like state characterized by defects in RNAPII elongation and decreased expression of long genes (gene-length asymmetry). Our results indicate that RNA catabolism is a core regulatory module of gene networks that safeguards RNAPII activity, ERV expression, cell identity, and developmental potency.

Background: Low-doses of bone modifying agents (LD-BMAs) compared to those used to treat bone metastases are used in breast or prostate cancer patients on adjuvant endocrine therapy to prevent Cancer Treatment Induced Bone Loss (CTIBL). Their use is associated with an increased risk of developing Medication-Related Osteonecrosis of the Jaw (MRONJ). However, there is not clarity about strategies aimed to minimize the MRONJ risk in cancer patients at different conditions as low- vs high-doses of BMA. This joint report from the Italian Societies of Oral Pathology and Medicine (SIPMO) and of Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS) aims to define the dental management of breast and prostate cancer patients with CTIBL under LD-BMAs, to reduce their risk to develop MRONJ. Methods: This interdisciplinary SIPMO-SIOMMMS Expert Italian Panel reviewed the available international scientific literature and developed a set of recommendations to implement strategies of MRONJ prevention in breast (BC) and prostate cancer (PC) patients undertaking LD-BMAs to prevent CTIBL. Results: The Expert Panel, after addressing some introductive topics (i.e., CTIBL and its management, pharmacology and pharmacodynamics of BMAs, definition and diagnosis of MRONJ), developed a joint report on the following five issues: a) prevention and dental management in cancer patients candidates to LD-BMAs, or under LD-BMAs; b) prophylactic drug holiday; c) MRONJ treatment; d) LD-BMAs therapeutic drug holiday; and e) restart of LD-BMA treatment after successful healing of MRONJ.Finally, ten key questions with answers were prepared and placed at the end of the document. Conclusions: Despite obvious weaknesses of the available international literature, the Expert Panel recognized the need to tailor separate MRONJ preventive approach for breast and prostate cancer patients on adjuvant endocrine therapy who begin low-dose BMA therapy to prevent CTIBL and provided this practical guidance for bone specialists and oral healthcare providers. In view of a MRONJ risk for BC and PC patients receiving low-dose BMAs, which approximates that of patients with osteoporosis and other non-malignant diseases undergoing similar treatment schedules, the SIPMO-SIOMMMS Expert Panel recognizes the need for less stringent preventive strategies than those already developed for BC or PC patients with bone metastases taking HD-BMAs.

ABSTRACT In early‐stage lung cancer, lung function appears to be less compromised after segmentectomy than lobectomy, though the advantage seems modest. We aimed to re‐assess postoperative lung function in surgical patients, with a particular focus on the diffusion capacity for carbon monoxide (DLCO). We evaluated all patients who underwent either lobectomy or segmentectomy for T1a‐c lung cancer at our center between March 2016 and March 2023. From January to June 2024, patients who had undergone segmentectomy, along with a matched cohort of patients who had undergone lobectomy, were invited for a repeat lung function evaluation. Patients were matched 1:1 based on age, sex, surgical approach, year in which the procedure was performed, and tumor location. Lung function testing data including DLCO were then compared to preoperative measures. During the study period, 480 patients received a lobectomy, and 97 received a segmentectomy. Complete lung function evaluation for the study was available for 52 patients (26 matched pairs). The median time from lung resection to repeat spirometry was 35 months. A modest reduction of lung function measures was observed in the segmentectomy group. Conversely, all lung function measures, including DLCO, were significantly impaired in the lobectomy group. In early‐stage lung cancer, patients who perform segmentectomy demonstrated better long‐term lung function preservation compared to those who underwent lobectomy. Whenever feasible, segmentectomy should be considered the procedure of choice for early‐stage lung cancer patients.

IntroductionExploring modifiable and non-modifiable determinants—like sex of new-borns, maternal characteristics, and lifestyle—of maternal and child health is a priority in Public Health. Understanding these sex-based differences is essential for tailored care and informed public health policies.MethodsThe present study aimed to delineate sex disparities in delivery and neonatal characteristics within the “MAMI MED” cohort, an ongoing prospective study involving mother–child pairs from Catania, Italy. The analysis included 1,090 mother–child pairs.ResultsThe comparison of birth weight and birth length distribution showed some differences between sexes, confirmed by higher birth weight (β = 0.121; 95% CI = 0.071–0.172) and greater birth length (β = 0.659; 95% CI = 0.360–0.958) in males compared to females. However, the comparison of small and adequate for gestational age (SGA vs. AGA) revealed that the likelihood of being SGA was higher in males than in females (OR = 1.592; 95% CI = 1.005–2.563).DiscussionThus, the focus should be on improving the assessment of gender-based differences in diagnostic criteria and incorporating gender-specific aspects into existing preventive guidelines to deeply understand the effect of gender disparities and risk factors on maternal-child health.