المؤلفون: Albert Grinshpun, Douglas Russo, Wen Ma, Ana Verma, Francisco Hermida-Prado, Shira Sherman, Giorgio Gaglia, Sheheryar Kabraji, Gregory Kirkner, Melissa E. Hughes, Nancy U. Lin, Zachary Sandusky, Agostina Nardone, Cristina Guarducci, Quang-De Nguyen, Sandro Santagata, Zsuzsanna Nagy, Rinath Jeselsohn

المصدر: npj Breast Cancer, Vol 10, Iss 1, Pp 1-12 (2024)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract The ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These mutations confer endocrine resistance that remains estrogen receptor (ER) dependent. We hypothesized that in the presence of the ER mutations, continued ER blockade with endocrine therapies that target mutant ER is essential for tumor suppression even with chemotherapy treatment. Here, we conducted comprehensive pre-clinical in vitro and in vivo experiments testing the efficacy of adding fulvestrant to fluorouracil (5FU) and the 5FU pro-drug, capecitabine, in models of wild-type (WT) and mutant ER. Our findings revealed that while this combination had an additive effect in the presence of WT-ER, in the presence of the Y537S ER mutation there was synergy. Notably, these effects were not seen with the combination of 5FU and selective estrogen receptor modulators, such as tamoxifen, or in the absence of intact P53. Likewise, in a patient-derived xenograft (PDX) harboring a Y537S ER mutation the addition of fulvestrant to capecitabine potentiated tumor suppression. Moreover, multiplex immunofluorescence revealed that this effect was due to decreased cell proliferation in all cells expressing ER and was not dependent on the degree of ER expression. Taken together, these results support the clinical investigation of the combination of ER antagonists with capecitabine in patients with metastatic hormone receptor-positive breast cancer who have experienced progression on endocrine therapy and targeted therapies, particularly in the presence of an ESR1 activating mutation.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2374-4677Test

الوصول الحر: https://doaj.org/article/7c7a103652a4404eac1f649798184d56Test

المؤلفون: Sara Del Tufo, Umberto Atripaldi, Antonella Nicastro, Iacopo Panarese, Davide Ciardiello, Valerio Nardone, Francesco Selvaggi, Roberto Grassi, Salvatore Cappabianca, Erika Martinelli, Alfonso Reginelli

المصدر: Radiology Case Reports, Vol 19, Iss 9, Pp 3626-3630 (2024)

مصطلحات موضوعية: Rectal cancer, Biomarkers, Perineural invasion, MRI, Staging, Medical physics. Medical radiology. Nuclear medicine, R895-920

الوصف: 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.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S193004332400428XTest; https://doaj.org/toc/1930-0433Test

الوصول الحر: https://doaj.org/article/eec5cbb29fdd4342a5a6cb660c4ec7b4Test

المؤلفون: Stefano Nardone, Roberto De Luca, Antonino Zito, Nataliya Klymko, Dimitris Nicoloutsopoulos, Oren Amsalem, Cory Brannigan, Jon M. Resch, Christopher L. Jacobs, Deepti Pant, Molly Veregge, Harini Srinivasan, Ryan M. Grippo, Zongfang Yang, Mark L. Zeidel, Mark L. Andermann, Kenneth D. Harris, Linus T. Tsai, Elda Arrigoni, Anne M. J. Verstegen, Clifford B. Saper, Bradford B. Lowell

المصدر: Nature Communications, Vol 15, Iss 1, Pp 1-21 (2024)

مصطلحات موضوعية: Science

الوصف: Abstract The “dorsal pons”, or “dorsal pontine tegmentum” (dPnTg), is part of the brainstem. It is a complex, densely packed region whose nuclei are involved in regulating many vital functions. Notable among them are the parabrachial nucleus, the Kölliker Fuse, the Barrington nucleus, the locus coeruleus, and the dorsal, laterodorsal, and ventral tegmental nuclei. In this study, we applied single-nucleus RNA-seq (snRNA-seq) to resolve neuronal subtypes based on their unique transcriptional profiles and then used multiplexed error robust fluorescence in situ hybridization (MERFISH) to map them spatially. We sampled ~1 million cells across the dPnTg and defined the spatial distribution of over 120 neuronal subtypes. Our analysis identified an unpredicted high transcriptional diversity in this region and pinpointed the unique marker genes of many neuronal subtypes. We also demonstrated that many neuronal subtypes are transcriptionally similar between humans and mice, enhancing this study’s translational value. Finally, we developed a freely accessible, GPU and CPU-powered dashboard ( http://harvard.heavy.ai:6273Test/ ) that combines interactive visual analytics and hardware-accelerated SQL into a data science framework to allow the scientific community to query and gain insights into the data.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/f281b415638047cf935491423b9003e6Test

المؤلفون: Filippo Nardone

المصدر: Nuova Antologia Militare, Vol 5, Iss 17, Pp 321-382 (2024)

مصطلحات موضوعية: History (General) and history of Europe, Military Science

الوصف: This article examines the historiographical interpretation of Italian infantries during the period from the 12th to the early 14th century by the prominent Italian polemologist Piero Pieri (1893-1979), whose work stands as the sole comprehensive analysis on this subject and has served as a major source of inspiration for subsequent scholars. However, given the passage of 90 years and the accumulation of new research, his work requires revision. Specifically, this article challenges Pieri’s rigid temporal and regional categorization, which separates a superior Lombard infantry of the Swabian era, characterized by militarized citizenry, from an inferior Tuscan infantry of the Late Communal period, characterized by bourgeois and peasant levies. This piece rejects Pieri’s criterion for assessing infantry quality in a decontextualized manner and highlights the remarkable homogeneity and excellence of Italian armies in the early 14th century. It asserts that these armies reflect a more cohesive and state-oriented Communal development compared to the more primitive system of the Swabian era. The article also explores the interregional similarity of Italian warfare through mercenarism and underscores the considerable superiority of Italian Communal armies over other European infantries in the early 14th century.

وصف الملف: electronic resource

العلاقة: https://www.tabedizioni.it/web/content/296916Test; https://doaj.org/toc/2704-9795Test

الوصول الحر: https://doaj.org/article/bc5d2986aead4ce5a80f3c7703d58e17Test

المؤلفون: Wen Zhu, Alanya J. Nardone, Lucciano A. Pearce

المصدر: Frontiers in Chemical Biology, Vol 3 (2024)

مصطلحات موضوعية: GMP synthetase, CTP synthetase, asparagine synthetase, NAD+ synthetase, FGAS, carbamoyl phosphatase synthetase, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Bifunctional enzymes, characterized by their dual active sites, enable efficient chemical conversion and substrate channeling using elegant coupling mechanisms to coordinate the two active sites. In humans, several bifunctional enzymes synthesize de novo carbon-nitrogen bonds by hydrolyzing glutamine and ATP in distinct active sites. Notable examples include guanosine monophosphate synthetase, cytidine triphosphate synthetase, phosphoribosylformyl-glycinamidine synthase, asparagine synthetase, and nicotinamide adenine dinucleotide synthetase. A more complex example of multifunctional glutamine-hydrolyzing synthetases in humans is carbamoyl phosphate synthetase. These enzymes are crucial for the biosynthesis of amino acids, nucleic acids, and co-factors, thereby playing pivotal roles in human health. This review delineates recent progress in understanding the structural characteristics, regulatory mechanisms, and disease relevance of glutamine-hydrolyzing synthetases in humans. Insights into their catalysis and activity regulation offer potential pathways for developing novel therapeutics.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fchbi.2024.1410435/fullTest; https://doaj.org/toc/2813-530XTest

الوصول الحر: https://doaj.org/article/42644666b67e4367ad1434d0f5b9e510Test

المؤلفون: Giuseppe Carlo Iorio, Nerina Denaro, Lorenzo Livi, Isacco Desideri, Valerio Nardone, Umberto Ricardi

المصدر: Frontiers in Oncology, Vol 14 (2024)

مصطلحات موضوعية: HNC (head and neck cancer), radiotherapy, radiation oncology, cancer care, personalized oncology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2024.1437237/fullTest; https://doaj.org/toc/2234-943XTest

الوصول الحر: https://doaj.org/article/b062b8ebbb45481fb05450797817f508Test

المؤلفون: Olga Maria Nardone, Massimo Martinelli, Roberto de Sire, Giulio Calabrese, Anna Caiazzo, Anna Testa, Antonio Rispo, Erasmo Miele, Alessia La Mantia, Ermelinda D’Alessandro, Maria Teresa Fioretti, Lara Limansky, Mario Ferrante, Imma Di Luna, Annamaria Staiano, Fabiana Castiglione

المصدر: Therapeutic Advances in Gastroenterology, Vol 17 (2024)

مصطلحات موضوعية: Diseases of the digestive system. Gastroenterology, RC799-869

الوصف: Background: The transition from pediatric to adult healthcare in individuals with inflammatory bowel disease (IBD) poses significant challenges mainly due to the high burden of IBD during adolescence, a critical period of psychosocial development. So far, there are few longitudinal data linking transition readiness to long-term disease outcomes. Objective: We aimed to assess patients’ readiness to transition and its impact on clinical outcomes, quality of life, and adherence to therapy. Design: An observational, prospective study was conducted in a tertiary adult and pediatric center, including adolescents aged ⩾17 years with a diagnosis of IBD, who underwent a ‘structured transition’ program including two joint adult–pediatric visits. Methods: Transition readiness skills were assessed with the Transition Readiness Assessment Questionnaire (TRAQ). All patients completed the TRAQ at the time of recruitment, which occurred during the initial joint adult–pediatric visit, to determine those deemed ready for transition versus those not ready. The Morisky Medication Adherence Scale and the 36-Item Short Form Health Survey Questionnaire (SF-36) were also completed at baseline and after 12 months. Clinical outcomes were collected at the 12-month follow-up. Results: In all, 80 patients were enrolled who had transitioned through a structured transition clinic and completed 12 months of follow-up. In total, 54 patients were ready for the transition, with a mean TRAQ = 3.2 ± 0.5. The number of clinical relapses and hospitalizations at 12 months was lower in ready compared to not-ready patients ( p = 0.004 and p = 0.04, respectively). SF-36 did not differ between ready and not-ready patients and pre- and post-transition clinics ( p > 0.05). Based on the receiver operating characteristic curve, a TRAQ cutoff ⩾3.16 could predict medication adherence with a sensibility of 77%, a specificity of 82%, and an AUC of 0.81 (0.71–0.91; p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1756-2848Test

الوصول الحر: https://doaj.org/article/7f76782baed044d1a3336a6a5fb7c781Test

المؤلفون: Olga Maria Nardone, Giulio Calabrese, Alessia La Mantia, Rossella Caso, Anna Testa, Fabiana Castiglione

المصدر: Frontiers in Medicine, Vol 11 (2024)

مصطلحات موضوعية: disability, holistic care, bowel urgency, fatigue, sexual dysfunction, fertility, Medicine (General), R5-920

الوصف: In recent years, the concept of disability has increasingly garnered attention as a crucial long-term target of inflammatory bowel disease (IBD) management. The treatment paradigm has changed dramatically from full control of the disease (clinical and endoscopic remission) toward physical and emotional well-being with the goal of preventing disability and normalizing quality of life. However, in certain cases, despite achieving good disease control, patients may still experience symptoms associated with disability, and reduced emotional wellness. These symptoms can significantly impact various biopsychosocial factors, including interpersonal relationships, educational or work-related activities, body image, and sexual functioning. Nevertheless, they often remain overlooked in the context of IBD care. In this narrative review, we aim to shed light on the burden of certain disability-related symptoms such as bowel urgency, sexual dysfunction, impaired fertility and fatigue, emphasizing the importance of acknowledging and validating them in a clinical setting. There is a demanding need for comprehensive care for IBD patients, with IBD clinicians being mindful of the psychosocial challenges faced by their patients. Providing timely and appropriate management of these challenges alongside IBD treatment is key to achieving holistic remission and enhancing the overall quality of life while reducing disability.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmed.2024.1416054/fullTest; https://doaj.org/toc/2296-858XTest

الوصول الحر: https://doaj.org/article/cb94cbfc6d40451dac619c68bd518600Test

المؤلفون: Vanessa N. Frey, Patrick B. Langthaler, Nora Renz, Georg Zimmermann, Christopher Höhn, Kerstin Schwenker, Aljoscha Thomschewski, Alexander B. Kunz, Yvonne Höller, Raffaele Nardone, Eugen Trinka

المصدر: Frontiers in Medical Technology, Vol 6 (2024)

مصطلحات موضوعية: movement preparation, paraplegia, physical activity, transcranial magnetic stimulation, cortical excitability, Medical technology, R855-855.5

الوصف: BackgroundPatients with spinal cord injury (SCI) show abnormal cortical excitability that might be caused by deafferentation. We hypothesize a reduced short-interval intracortical inhibition preceding movement in patients with SCI compared with healthy participants. In addition, we expect that neuroplasticity induced by different types of sports can modulate intracortical inhibition during movement preparation in patients with SCI.MethodsWe used a reaction test and paired-pulse transcranial magnetic stimulation to record cortical excitability, assessed by measuring amplitudes of motor-evoked potentials in preparation of movement. The participants were grouped as patients with SCI practicing wheelchair dancing (n = 7), other sports (n = 6), no sports (n = 9), and healthy controls (n = 24).ResultsThere were neither significant differences between healthy participants and the patients nor between the different patient groups. A non-significant trend (p = .238), showed that patients engaged in sports have a stronger increase in cortical excitability compared with patients of the non-sportive group, while the patients in the other sports group expressed the highest increase in cortical excitability.ConclusionThe small sample sizes limit the statistical power of the study, but the trending effect warrants further investigation of different sports on the neuroplasticity in patients with SCI. It is not clear how neuroplastic changes impact the sensorimotor output of the affected extremities in a patient. This needs to be followed up in further studies with a greater sample size.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmedt.2024.1297552/fullTest; https://doaj.org/toc/2673-3129Test

الوصول الحر: https://doaj.org/article/5fbb0d2f36ef47dfa9ac7ea5c70907f0Test

المؤلفون: Federico Gagliardi, Anna Russo, Camila Scharf, Alessandro Pinto, Mario Faenza, Emma D'Ippolito, Giuseppe Argenziano, Teresa Troiani, Alfonso Reginelli, Valerio Nardone

المصدر: Clinical and Translational Radiation Oncology, Vol 46, Iss , Pp 100774- (2024)

مصطلحات موضوعية: non-melanoma skin cancer (NMSC), Radiotherapy, high-frequency ultrasound (HFUS), Dermascopy, Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: This series introduces the clinical management of difficult-to-treat non-melanoma skin cancers (NMSCs) through a multidisciplinary approach, emphasizing the integration of dermoscopy and Ultra high-frequency ultrasound (UHFUS) for accurate diagnosis and treatment planning, particularly in cases referred for radiotherapy (RT). Dermoscopy aids in diagnosing both pigmented and non-pigmented skin lesions, guiding treatment margins and reducing the benign-to-malignant biopsy ratio. UHFUS provides valuable insights into tumor size, depth, and vascularity, complementing clinical evaluations and assisting in RT planning. Three challenging cases are presented, highlighting the pivotal role of dermoscopy and UHFUS in decision-making and treatment optimization. Collaboration between dermatologists, radiation oncologists, and radiologists enhances diagnostic accuracy, tailoring treatment plans to individual patient needs and preferences, ultimately improving patient outcomes and experience. The integration of these imaging techniques holds promise for optimizing non-surgical treatments like RT and monitoring treatment progress, offering a personalized approach to NMSC management.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S240563082400051XTest; https://doaj.org/toc/2405-6308Test

الوصول الحر: https://doaj.org/article/094cfcff06fa4d50bd08b90f03d08d78Test