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Abstract Background Twin pregnancies present unique challenges in maternal healthcare. However, current guidelines primarily address singleton pregnancies, resulting in a knowledge gap regarding their specific metabolic and dietary needs. This study aimed to follow women with twin pregnancies through all three trimesters, assessing basal metabolic rate (BMR), dietary intake, and diet quality. Methods A two-year prospective observational study was conducted at AOU Careggi Hospital, Florence, Italy, involving 35 twin-pregnant women, with 32 completing the study. Participants underwent calorimetric, anthropometric, and dietary assessments during the first (8–13 weeks), second (14–27 weeks), and third trimesters (28–34 weeks). BMR was measured using indirect calorimetry and compared with predictive equations. Dietary intake was evaluated using 7-day food diaries and the Medi-Lite adherence score. Results Indirect calorimetry revealed an increase in BMR by 16%, rising from 1479 ± 196 kcal in the first trimester to 1733 ± 224 kcal in the third trimester. Hronek’s equation, previously validated for singleton pregnancies, was identified as the most accurate predictive tool for estimating BMR. Dietary analysis revealed that mean daily energy intake increased from 1660 ± 244 kcal in the first trimester to 1889 ± 262 kcal in the third trimester, consistently below recommendations, with insufficient macro- and micronutrient consumption. Poor diet quality was characterized by low intake of fruits, vegetables, legumes, and fresh fish, and high consumption of processed meats, cheese, and sugar-sweetened beverages. Adherence to the Mediterranean diet was moderate across all three trimesters. Conclusions This study highlights the increased energy demands and nutritional inadequacies in twin pregnancies, underscoring the need for tailored dietary guidelines and interventions.

Abstract Advances in X-ray crystallography and cryogenic electron microscopy (cryo-EM) offer the promise of elucidating functionally relevant conformational changes that are not easily studied by other biophysical methods. Here we show that 3D variability analysis (3DVA) of the cryo-EM map for wild-type (WT) human asparagine synthetase (ASNS) identifies a functional role for the Arg-142 side chain and test this hypothesis experimentally by characterizing the R142I variant in which Arg-142 is replaced by isoleucine. Support for Arg-142 playing a role in the intramolecular translocation of ammonia between the active site of the enzyme is provided by the glutamine-dependent synthetase activity of the R142 variant relative to WT ASNS, and MD simulations provide a possible molecular mechanism for these findings. Combining 3DVA with MD simulations is a generally applicable approach to generate testable hypotheses of how conformational changes in buried side chains might regulate function in enzymes.

Background We aimed to estimate XBB.1.5 vaccine effectiveness (VE) against COVID-19-related hospitalizations and deaths during BA.2.86/JN.1 predominance, among EU/EEA individuals with ≥65-years.Research design and methods We linked electronic health records to create historical cohorts in Belgium, Denmark, Italy, Navarre (Spain), Norway, Portugal and Sweden. We included individuals aged ≥65-years eligible for the autumnal 2023 COVID-19 vaccine. Follow-up started when ≥80% of country-specific sequenced viruses were BA.2.86/JN.1 (4/dec/23 to 08/jan/24) and ended 25 February 2024. At study site level, we estimated the vaccine confounder-adjusted hazard ratio (aHR) of COVID-19 hospitalizations and deaths between individuals with ≥14 days after vaccination versus unvaccinated in autumn 2023, overall, by time since vaccination and age groups. VE was estimated as (1-pooled aHR)x100 with a random-effects model.Results XBB.1.5 VE against COVID-19 hospitalizations was 50% (95%CI: 45 to 55) and 41% (95%CI: 35 to 46) in 65–79-year-olds and in ≥80-year-olds, respectively. VE against COVID19-related-death was 58% (95%CI: 42 to 69) and 48% (95%CI: 38 to 57), respectively, in both age groups. VE estimates against each outcome declined in all age groups over time.Conclusion Monovalent XBB.1.5 vaccine had a moderate protective effect against severe and fatal COVID-19 likely caused by BA.2.86/JN.1 during the 2023/2024 winter, among persons aged ≥65.

We present a case of a 70-year-old male who presented with left-sided weakness and dysarthria. Cranial imaging was suggestive of a cerebellar infarct and the patient was treated with aspirin and clopidogrel. Two months later a fall prompted further cranial imaging, which was concerning for an intracranial mass with vasogenic edema. Computed tomography angiogram (CTA) was negative for vascular lesion. Ultimately, a DSA revealed a Borden III dAVF between the right occipital artery and the posterior cerebellar vein that was treated with endovascular embolization.

Background: Sarcopenia, a syndrome characterized by age-related loss of muscle mass and function, lacks universally accepted diagnostic criteria, particularly for its role as a prognostic factor in elderly patients with non-small-cell lung cancer (NSCLC). This study aimed to evaluate the prognostic significance of sarcopenia, assessed by psoas muscle size on baseline CT scans, in patients over 70 years of age with metastatic NSCLC. Methods: We retrospectively analyzed 85 elderly patients undergoing palliative radiation therapy between August 2022 and July 2024. Using morphometric analysis of psoas size, we investigated its correlation with overall survival (OS) and progression-free survival (PFS). Results: Our results showed that decreased psoas size was significantly associated with shorter OS and PFS, with median OS of 10 months and PFS of 4 months in sarcopenic patients compared to longer survival times in non-sarcopenic patients. Median survival of non-sarcopenic vs. sarcopenic patients was 21 ± 7 months (muscle area > median) versus 5 ± 2.3 months (muscle area < median). Multivariate analysis confirmed that psoas size, along with ECOG performance status and treatment of primary NSCLC, was a significant predictor of survival. Discussion: These findings suggest that psoas muscle size is a valuable prognostic marker for elderly NSCLC patients, potentially guiding treatment decisions and patient management. Further research is needed to validate these results and refine prognostic models for this population.

Abstract Background X-linked acrogigantism (X-LAG; MIM: 300942) is a severe form of pituitary gigantism caused by chromosome Xq26.3 duplications involving GPR101. X-LAG-associated duplications disrupt the integrity of the topologically associating domain (TAD) containing GPR101 and lead to the formation of a neo-TAD that drives pituitary GPR101 misexpression and gigantism. As X-LAG is fully penetrant and heritable, duplications involving GPR101 identified on prenatal screening studies, like amniocentesis, can pose an interpretation challenge for medical geneticists and raise important concerns for patients and families. Therefore, providing robust information on the functional genomic impact of such duplications has important research and clinical value with respect to gene regulation and triplosensitivity traits. Methods We employed 4C/HiC-seq as a clinical tool to determine the functional impact of incidentally discovered GPR101 duplications on TAD integrity in three families. After defining duplications and breakpoints around GPR101 by clinical-grade and high-density aCGH, we constructed 4C/HiC chromatin contact maps for our study population and compared them with normal and active (X-LAG) controls. Results We showed that duplications involving GPR101 that preserved the centromeric invariant TAD boundary did not generate a pathogenic neo-TAD and that ectopic enhancers were not adopted. This allowed us to discount presumptive/suspected X-LAG diagnoses and GPR101 misexpression, obviating the need for intensive clinical follow-up. Conclusions This study highlights the importance of TAD boundaries and chromatin interactions in determining the functional impact of copy number variants and provides proof-of-concept for using 4C/HiC-seq as a clinical tool to acquire crucial information for genetic counseling and to support clinical decision-making in cases of suspected TADopathies.

Treatment of rectal cancer has improved over the years thanks to a multidisciplinary approach. A correct staging has a fundamental role for risk stratification and to define the best treatment for each patient. Unfortunately, approximately 30% of patients with locally advanced rectal cancers will experience tumor recurrence. Thus, the identification of novel clinical-pathological and radiological prognostic factors represents an urgent unmet clinical need. Here we report the case of a patient with radically resected localized rectal cancer who developed an impressive early pelvic recurrence. To better understand the clinical scenario, we have studied the possible factors related to the aggressiveness of the disease. The only poor prognosticfactor that was evidenced at histological report was perineural invasion. Therefore, we questioned whether we could evaluate perineural invasion with imaging, similar to head and neck tumors. Learning from this clinical case, we believe that improving the risk stratification and radiology reporting is necessary to provide the best care for the patient and allow for a better prognosis prediction. Of course, our data should be considered as hypothesis generating and should be further investigated and validated in larger and prospective studies.

The integration of multidisciplinary tumor boards (MTBs) is fundamental in delivering state-of-the-art cancer treatment, facilitating collaborative diagnosis and management by a diverse team of specialists. Despite the clear benefits in personalized patient care and improved outcomes, the increasing burden on MTBs due to rising cancer incidence and financial constraints necessitates innovative solutions. The advent of artificial intelligence (AI) in the medical field offers a promising avenue to support clinical decision-making. This review explores the perspectives of clinicians dedicated to the care of cancer patients—surgeons, medical oncologists, and radiation oncologists—on the application of AI within MTBs. Additionally, it examines the role of AI across various clinical specialties involved in cancer diagnosis and treatment. By analyzing both the potential and the challenges, this study underscores how AI can enhance multidisciplinary discussions and optimize treatment plans. The findings highlight the transformative role that AI may play in refining oncology care and sustaining the efficacy of MTBs amidst growing clinical demands.

Abstract In the Summer 2021 a seismic passive survey was carried out at Mefite d’Ansanto (Italy), well-known for the cold non-volcanic and lethal CO2 emissions. Mefite is located close to that part of Irpinia region hosting the large historical earthquakes’ faults, that generated the destructive magnitude 6.8 earthquake of 1980 and have been related to the CO2 leakage by the scientific community. The survey was conducted by installing a small short-period seismic array with the purpose of determining the wavefield features and detecting the possible signature of the regional stress variations. By analyzing the acquired data, we have determined the properties of the seismic wavefield associated with the emission vents, in the intermediate frequency band, 1–15 Hz, which was found to be composed of a stationary background component and an intermittent higher energy one. Basing on our results, considerations on the medium properties and the deep source available information, we have depicted a schematic model of the shallow seismic source: the background components are linked to the shallower activity of the hydrothermal system, e.g. the bubbling, while the intermittent ones are likely generated by the passage of the overpressured gas, trapped in the first-tens-meters’ layers, after overcoming the internal cohesion charge. The characteristics of the wavefield that we have defined, refer to a condition in which no regional earthquakes occurred and could be considered as a basis to identify possible significant variations linked to CO2 emissions and to the regional stress changes.

Abstract Adhesive Capsulitis of the shoulder is a painful pathology limiting shoulder movements, commonly known as “Frozen Shoulder”. Since this pathology limits movement, it is important to make an early diagnosis. Diagnosing capsulitis relies on clinical assessment, although diagnostic imaging, such as Magnetic Resonance Imaging, can provide predictive or supportive information for specific characteristic signs. However, its diagnosis is not so simple nor so immediate, indeed it remains a difficult topic for many general radiologists and expert musculoskeletal radiologists. This study aims to investigate whether it is possible to use disease signs within a medical image to automatically diagnose Adhesive Capsulitis. To this purpose, we propose an automatic Model Checking-based approach to quickly diagnose the Adhesive Capsulitis taking as input the radiomic feature values from the medical images. Furthermore, we compare the performance achieved by our method with diagnostic results obtained by professional radiologists with different levels of experience. To the best of our knowledge, this is the first method for the automatic diagnosis of Adhesive Capsulitis of the Shoulder.

IntroductionThis study examined user behavior, e-cigarette dependence, and device characteristics on nicotine intake among users of pod-mod e-cigarettes.Aims and methodsIn 2019-2020, people who use pod-mods in the San Francisco Bay Area completed questionnaires and provided a urine sample for analysis of total nicotine equivalents (TNE). The relationship between TNE and e-cigarette use, e-cigarette brands, e-liquid nicotine strength, e-cigarette dependence, and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), as a measure of combustible cigarette exposure, were examined.ResultsOf 100 participants (64% male, 71% in the 18-34 age group, 45% white), 53 used JUUL primarily, 12 used Puff Bar primarily, and 35 used other brands, including Suorin; 48 participants reported current cigarette smoking. Participants most often reported use of e-liquid with 4.5%-6.0% nicotine (68%), fruit (35%), tobacco (28%), and menthol or mint flavors (26%), used e-cigarettes on 25.5 (SD = 6.3) days a month, 10.2 (SD = 14.2) times a day, and 40% used 1-2 pods/cartridges per week. In bivariate analysis, urinary TNE was higher with greater frequency (days used) and intensity (number of pods used) of e-cigarette use, e-cigarette dependence, and combustible cigarette use. In multivariable analysis, days of e-cigarette use in the last 30 days, number of pods used per week, and NNAL levels were significantly associated with TNE. There was no significant impact of e-liquid nicotine strength on TNE.ConclusionsNicotine intake among people who used pod-mod e-cigarettes increased with e-cigarette consumption and e-cigarette dependence, but not with e-liquid nicotine strength. Our findings may inform whether FDA adopts a nicotine standard for e-cigarettes.ImplicationsThe study examined how device and user characteristics influence nicotine intake among pod-mod e-cigarette users. Nicotine intake increased with frequency (days of e-cigarette use in past 30 days) intensity of use (number of pods used per day) and e-cigarette dependence but not with the flavor or nicotine concentration of the e-liquids. Regulation of nicotine concentration of e-liquids is unlikely to influence nicotine exposure among adult experienced pod-mod users.

Cemiplimab has demonstrated relevant clinical activity in cutaneous squamous cell carcinoma (cSCC) but mechanisms of primary and acquired resistance to immunotherapy are still unknown. We collected clinical data from locally advanced and/or metastatic cSSC patients treated with cemiplimab in two Italian University centers. In addition, gene expression analysis by using Nanostring Technologies platform to evaluate 770 cancer- and immune-related genes on 20 tumor tissue samples (9 responders and 11 non-responders to cemiplimab) was performed. We enrolled 81 patients with a median age of 82 years. After 16.4 months of median follow-up, 12- and 24-months PFS were 53% and 42%, respectively; while 12- and 24-months OS were 71% and 61%, respectively. Treatment was well tolerated. Overall response rate (ORR) was 58%, with a disease control rate (DCR) of 77.8%. The difference between genes expressed in responder versus non-responder patient samples was substantial, particularly for genes involved in immune system regulation. Cemiplimab-resistant tumors were associated with over-expression of CCL-20 and CXCL-8. Cemiplimab confirmed efficacy and safety data in real-life cSCC patients. Overexpression of CCL-20 and CXCL-8 could represent biomarkers of lack of response to immunotherapy.

Background and Aims: the study aimed to investigate the circulation of influenza viruses and SARS-CoV-2 in the 2022-23 and 2023-24 influenza seasons in the provinces of Lucca and Massa Carrara in the northwest of the Tuscany region. Materials and Methods: a retrospective observational study was conducted on adult and pediatric patients who accessed hospital facilities in the considered area during the influenza periods (from September to April) of 2022-23 and 2023-24. Results: the 2022-23 influenza season was characterized by the circulation of the A/H3N2 influenza virus (84% of the total), with a peak of positive samples from weeks 42 to 52 in 2022. Instead, the influenza A/(H1N1)pdm09 virus was responsible for 94% of influenza infections in the 2023-24 season, with a peak of positive samples between weeks 52 of 2023 and 3 of 2024. Conclusions: effective virological diagnostics and constant monitoring of circulating viruses are mandatory to correctly address therapy and contain the viral circulation in the different influenza seasons.

Biomedical graduate research trainees are increasingly pursuing careers beyond academia in response to limited academic positions relative to the trainee population. Biomedical research training must therefore evolve alongside the shifting career landscape by circumventing a “hidden curriculum” to help trainees develop skills complementary to existing graduate training. Here, we describe an approach to implement “soft skills” training for a diverse population of biomedical graduate research trainees from the Duke University BioCoRE program. Qualitative data from the BioCoRE annual program survey revealed that trainees felt they were not meeting crucial benchmarks in areas often absent from graduate training. Responses to open-ended survey questions overwhelmingly focused on “soft skills,” including communication, conflict resolution, and time management. Using these themes as a guide, the BioCoRE Program Director and graduate student-led Professional Development Committee collaborated to design a monthly workshop series, enlisting support from human resources personnel, undergraduate student affairs offices, and senior graduate trainees with relevant expertise. The year-long workshop series covered a range of topics: personal branding, science communication, scientific storytelling, conflict resolution, time management, and job market preparation. Based on survey data, the inaugural series was well-received and cited as highly effective by attendees. Survey dissemination and analysis will continue in subsequent years to address new topics and anticipate emerging themes in the shifting career development landscape. Implementation of this workshop series demonstrates the ability of graduate programs to enhance trainee soft skills by leveraging the expertise of internal and local professional personnel.

Key Clinical Message Patients with intrathecal catheters for pain medication infusion should be aware of the possible complication of acute flaccid paralysis. While exceedingly rare, it should prompt immediate medical attention to rule out compressive pathology requiring intervention.

The gap between endoscopy and histology is getting closer with the introduction of sophisticated endoscopic technologies. Furthermore, unprecedented advances in artificial intelligence (AI) have enabled objective assessment of endoscopy and digital pathology, providing accurate, consistent, and reproducible evaluations of endoscopic appearance and histologic activity. These advancements result in improved disease management by predicting treatment response and long-term outcomes. AI will also support endoscopy in raising the standard of clinical trial study design by facilitating patient recruitment and improving the validity of endoscopic readings and endoscopy quality, thus overcoming the subjective variability in scoring. Accordingly, AI will be an ideal adjunct tool for enhancing, complementing, and improving our understanding of ulcerative colitis course. This review explores promising AI applications enabled by endoscopy and histology techniques. We further discuss future directions, envisioning a bright future where AI technology extends the frontiers beyond human limits and boundaries.