Aplicación del Score de Riesgo de desarrollo de hipertensión arterial esencial a corto plazo de Framingham en Santo Tomé, Argentina.

Objetivo: Valorar la utilidad del Score de Framingham en el desarrollo de la enfermedad, la influencia de los factores de riesgo cardiovasculares valorados, y conocer la frecuencia de nuevos casos de hipertensión arterial a corto plazo en la ciudad de Santo Tomé.Material y Métodos: Se realizó un trabajo de seguimiento, en la ciudad argentina de Santo Tomé (Santa Fe) de 316 personas normotensos no diabéticos, de 20 a 69 años; valorando el grado de riesgo de desarrollo de HTAe mediante el Score de Framingham de Riesgo a corto plazo y la influencia de los factores de riesgo cardiovasculares que éste considera, en el desarrollo de la enfermedad.Resultados: La edad media fue de 39,4±12,8 años, siendo el 62,3% mujeres. En relación al riesgo de desarrollar HTA a 1 y 2 años fueron de bajo riesgo el 67,7% y 55,1%; de moderado riesgo el 11,1% y 9,8%; y de alto riesgo el 21,2% y 35,1% respectivamente. La incidencia a un año de HTA fue del 11,4% en comparación a 2 años que fue significativamente menor (5,7%, IC95 0,97%-10,4% p=0,02), y la variable de mayor influencia en el desarrollo de la enfermedad fue el índice de masa corporal elevado (OR=3; IC95 1,4-6,9; p=0,004).Conclusión: En nuestra muestra el score no fue útil como predictor de desarrollo de hipertensión arterial esencial a corto plazo, pudiendo deberse al hecho de que en el mismo se incluyen factores que en nuestra muestra no influyeron en la presencia de la enfermedad.Fil: Vicco, Miguel Hernán. Provincia de Santa Fe. Ministerio de Salud. Htal J. B. Iturraspe. Area de Clinica Medica; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: César, Lucia. Provincia de Santa Fe. Ministerio de Salud. Htal J. B. Iturraspe. Area de Clinica Medica; ArgentinaFil: Musacchio, Héctor Mario. Provincia de Santa Fe. Ministerio de Salud. Htal J. B. Iturraspe. Area de Clinica Medica; ArgentinaFil: Galluccio, Federico. Provincia de Santa Fe. Ministerio de Salud. Htal J. B. Iturraspe. Area de Clinica Medica; Argentin

Seismic disasters and the demographic perspective: 1968, Belice and 1980, Irpinia-Basilicata (southern Italy) case studies

One of the challenges on disasters’ understanding is the assessment of impact from a more global perspective, adding to their scenario of injuries, deaths, homeless and economic losses, those effects that are mostly widespread and could last for a long period of time, driving to a serious disruption of a community or a society. Seismic disasters are not just the results of the energy released by the earthquake or buildings’ vulnerability: social, demographic, cultural parameters may instead play a crucial, yet underestimated, role. We carried out a pilot study to investigate the demographic perspective of the impact of 1968 Belice and 1980 Irpinia-Basilicata earthquakes on local communities. The macroseismic MCS intensities were used as a primary parameter upon which the demographic scenario was derived. Population annual growth rates, the ageing index, the child- woman ratio, and the Gini index from the demographic data census of the period 1951-2011 were analyzed to assess population dynamics, age structure evolution and its level of spatial concentration within the disasters’ areas. Demographic data were then matched to macroseismic intensities to outline a new, original analysis which describes the impact of the two seismic disasters with a broad multi-parameter perspective. The results highlight also the existence of a general marginality of most affected areas with respect to the processes of population growth, ageing and fertility, as well as for distribution of the regional population, occurring already before the disasters stroke. This marginality might have enhanced the impact of disasters by significantly increasing vulnerability

LLaMAntino: LLaMA 2 Models for Effective Text Generation in Italian Language

Large Language Models represent state-of-the-art linguistic models designed to equip computers with the ability to comprehend natural language. With its exceptional capacity to capture complex contextual relationships, the LLaMA (Large Language Model Meta AI) family represents a novel advancement in the field of natural language processing by releasing foundational models designed to improve the natural language understanding abilities of the transformer architecture thanks to their large amount of trainable parameters (7, 13, and 70 billion parameters). In many natural language understanding tasks, these models obtain the same performances as private company models such as OpenAI Chat-GPT with the advantage to make publicly available weights and code for research and commercial uses. In this work, we investigate the possibility of Language Adaptation for LLaMA models, explicitly focusing on addressing the challenge of Italian Language coverage. Adopting an open science approach, we explore various tuning approaches to ensure a high-quality text generated in Italian suitable for common tasks in this underrepresented language in the original models' datasets. We aim to release effective text generation models with strong linguistic properties for many tasks that seem challenging using multilingual or general-purpose LLMs. By leveraging an open science philosophy, this study contributes to Language Adaptation strategies for the Italian language by introducing the novel LLaMAntino family of Italian LLMs

Incorporation of anti-PD1 or anti PD-L1 agents to platinum-based chemotherapy for the primary treatment of advanced or recurrent endometrial cancer. A meta-analysis

Endometrial cancer; ImmunotherapyCàncer d'endometri; ImmunoteràpiaCáncer de endometrio; InmunoterapiaImportance Various randomized trials have explored the efficacy of combining immune checkpoint inhibitors (ICIs) with first-line chemotherapy in advanced endometrial cancer. We aimed to summarize available data and clarify the benefit of adding immunotherapy according to the DNA mismatch repair status (deficient, dMMR or proficient, pMMR) and the specific type of agent used (anti-PD1 or anti-PD-L1). Objective To assess whether the addition of ICIs to standard platinum-based chemotherapy enhances progression-free survival (PFS) for patients with advanced endometrial cancer both overall and based on DNA mismatch repair status. Data sources Electronic databases (PubMed, Embase and Cochrane Library) and conference proceedings were searched for first line, randomized and controlled trials integrating ICIs with chemotherapy for the treatment of advanced endometrial cancer published or presented by November 1, 2023. Study selection Five studies, comprising 2456 patients (1308 received ICIs with chemotherapy and 1148 treated with chemotherapy alone) met the selection criteria and were included in the analysis. Experimental arms included pembrolizumab, dostarlimab (anti-PD1) and durvalumab, atezolizumab and avelumab (anti-PD-L1) combined with standard three-weekly carboplatin-paclitaxel chemotherapy backbone. Endometrial carcinosarcoma were included in 3 out of 5 trials. Data extraction and synthesis For comparison of PFS outcomes, extrapolation of hazard ratios (HRs), 95% confidence intervals (CI) and PFS events was performed for each included study in the overall population and according to subgroups. Data analysis was conducted using a random-effects model. Results The addition of ICIs to chemotherapy improved PFS compared to chemotherapy alone in the overall population (pooled HR, 0.63; 95 % CI, 0.52––0.76; P <.001). In the dMMR subgroup the benefit was more pronounced (pooled HR, 0.34; 95 % CI, 0.27––0.44; P <.001) and not affected by drugs used with pooled HRs of 0.39 (95 % CI, 0.28––0.55; P <.001) and 0.34 (95 % CI, 0.27––0.44; P <.001) for PD-L1 and PD1 inhibitors, respectively. For pMMR patients, a statistically significant benefit in terms of PFS was confirmed only when anti-PD1 were used (anti-PD-1: HR 0.64, 95 % CI: 0.46–0.90, P =.010 vs anti-PD-L1: HR 0.87, 95 % CI: 0.73–1.03, P =.104) Conclusions and relevance This meta-analysis confirmed the advantage in terms of PFS of adding ICIs to standard platinum-based chemotherapy. While dMMR patients benefit from the incorporation of both anti PD-1 or anti PD-L1, this benefit is confined to the association of anti-PD1 agents in pMMR patients. Updated analysis of trials is awaited to clarify the impact of immunotherapy on overall survival

Coupling PAF Signaling to Dynein Regulation

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Therapeutic Potential of Tisotumab Vedotin in the Treatment of Recurrent or Metastatic Cervical Cancer: A Short Report on the Emerging Data

Cervical cancer is the fourth most common type of cancer in women worldwide. It is associated with a high death rate, despite the fact that it is a nearly 100% preventable disease because of very effective primary and secondary preventive strategies. Advanced and recurrent disease is uncurable with a high relapse risk and the second-line therapies are limited with modest response rates and short durability. Investigating alternative mechanisms of action is crucial because of the high request for effective new therapies. Tisotumab vedotin (TV) is the first antibody-drug conjugated to target a cell surface-expressed tissue factor, and preliminary data in patients with metastatic and recurrent cervical cancer have been promising. In addition, the trials showed a favorable tolerability profile, with limited incidence of grade 3 or worse adverse events. According to the data of ENGOT-cx6/GOG-3023/innovaTV 204, the US Food and Drug Administration granted expedited approval of TV on September 20, 2021, for women with recurrent or metastatic cervical cancer. Actually, two other trials testing TV alone or in combination with other agents are ongoing. ENGOT-cx8/GOG-3024/innovaTV 205 is a Phase Ib/II trial of TV in combination with platinum or bevacizumab or pembrolizumab, in patients with recurrent or metastatic cervical cancer who have not received prior systemic therapy or who have progressed after no more than two prior systemic therapies. ENGOTcx12/GOG-3057/InnovaTV 301 is a Phase 3 trial of TV vs investigator's choice chemotherapy in patients with advanced or recurrent cervical cancer who had received no more than 2 prior chemotherapy lines. The outcomes of these two trials will potentially confirm and reinforce the use of TV as a new standard of care in advanced or recurrent cervical cancer

A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian family with faciogenital dysplasia (Aarskog–Scott syndrome)

AbstractAarskog–Scott Syndrome (AAS) is an X-linked disorder characterised by short stature and multiple facial, limb and genital abnormalities. A gene, FGD1, altered in a patient with AAS phenotype, has been identified and found to encode a protein with homology to Rho/Rac guanine nucleotide exchange factors (Rho/Rac GEF). However, since this original report on identification of a mutated FGD1 gene in an AAS patient, no additional mutations in the FGD1 gene have been described. We analysed 13 independent patients with clinical diagnosis of AAS. One patient presented a mutation that results in a nucleotide change in exon 10 of the FGD1 gene (G2559>A) substituting a Gln for Arg in position 610. The mutation was found to segregate with the AAS phenotype in affected males and carrier females in the family of this patient. Interestingly, Arg-610 is located within one of the two pleckstrin homology (PH) domains of the FGD1 gene and it corresponds to a highly conserved residue which has been involved in InsP binding in PH domains of other proteins. The same residue is often mutated in the Bruton’s tyrosine kinase (Btk) gene in patients with an X-linked agammaglobulinemia. The Arg610Gln mutation represents the first case of a mutation in the PH domain of the FGD1 gene and additional evidence that mutations in PH domains can be associated to human diseases

SCIENZAPERTA: EARTH SCIENCE FOR EVERYONE... FINALLY IN MILAN!

ScienzAperta is an outreach science venue that the Istituto Nazionale di Geofisica e Vulcanologia started in 2011 as the spring of science: the doors of the headquarters of science were finally opened to public. A number of events, conferences, seminars, guided tours through the Institute and its laboratories are every year offered to general public. The venue is held in most of the cities where the Institute is located, priority to high seismic and/or volcanic risk regions. On May 2014 we held ScienzAperta for the first time in Milano and open up the doors to schools specifically dealing mostly with seismic hazard in a region where general public not necessarily think it might We offered students conferences, seminars and educational activities to highlight the fun of science and jet raise awareness on proper behaviours in case of earthquake shaking. We asked students and teachers, from elementary to high schools, to fill in a questionnaire that we use to evaluate the appreciation the venue had. One hundred years after Giuseppe Mercalli’s death we could not forget to celebrate his science the city where he was born.UnpublishedMilano3T. Pericolosità sismica e contributo alla definizione del rischiorestricte

Olaparib beyond progression compared with platinum chemotherapy after secondary cytoreductive surgery in patients with recurrent ovarian cancer: phase III randomized, open-label MITO 35b study, a project of the MITO-MANGO groups

Background Poly (ADP-ribose) polymerase inhibitors have transformed the management landscape for patients with ovarian cancer, demonstrating remarkable improvements in progression-free survival and overall survival. Unfortunately, most relapses are due to an acquired mechanism of resistance to these agents. We hypothesize that secondary cytoreductive surgery, removing resistant clones, might help to overcome the development of resistance to poly (ADP-ribose) polymerase inhibitors, prolonging their therapeutic effect. Primary Objective To determine the efficacy of olaparib beyond progression compared with standard platinum-based chemotherapy in patients with recurrent ovarian cancer progressed during or after poly (ADP-ribose) polymerase inhibitor maintenance therapy after secondary cytoreductive surgery. Study Hypothesis Olaparib administered beyond progression is more effective in increasing progression-free survival and progression-free survival 2 compared with second-line platinum-based chemotherapy in patients after secondary cytoreductive surgery. Trial Design Phase III, randomized, open-label, multicenter trial. Eligible patients will be randomized in a 1:1 ratio to receive olaparib or platinum-based chemotherapy of the investigator's choice. Major Eligibility Criteria Eligible patients must have high-grade serous or endometrioid ovarian cancer progressed during or after first-line poly (ADP-ribose) polymerase inhibitor maintenance therapy and must have undergone secondary cytoreductive surgery. Primary Endpoint The dual primary endpoints will include progression-free survival and progression-free survival 2. Progression-free survival is defined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as the time between randomization and progression or death from any cause. Progression-free survival 2 is defined by the investigator using RECIST version 1.1 as the time frame from randomization to the second progression or death from any cause after subsequent treatment. Sample Size Approximately 200 patients will be enrolled in this study. Estimated Dates for Completing Accrual and Presenting Results Enrollment will be completed in 2024. Results will be presented in 2026. Trial Registration EudraCT 2021-000245-41 NCT0525547