The evaluation of grey literature using bibliometric indicators: A methodological proposal

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The possible prognostic role of histone deacetylase and transforming growth factor β/Smad signaling in high grade gliomas treated by radio-chemotherapy: a preliminary immunohistochemical study

Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system. Unfortunately, patients affected by this disease have a very poor prognosis, due to high level of invasiveness and resistance to standard therapies. Although the molecular profile of GBM has been extensively investigated, the events responsible for its pathogenesis and progression remain largely unknown. Histone Deacetylases (HDAC) dependent epigenetic modifications and transforming growth factor (TGF)-β/Smad pathway seem to play an important role in GBM tumorigenesis, resistance to common therapies and poor clinical outcome. The aim of this study was to evaluate the involvement and the possible interaction between these two molecular cascades in the pathogenesis and prognosis of GBM. Immunohistochemistry (IHC) was performed on microdissected GBM samples, collected from 14 patients (6 men and 8 women) ranging in age from 43 to 74 years. The patients were previously divided, on the basis of their overall survival (OS), into two groups: short and long OS. Patients with poor prognosis showed hyperexpression of HDAC4 and HDAC6, an activation of the TGF-β/Smad pathway, with high levels of IL-13, Smad2, PDGF and MMP3 expression, compared to the long survivors. The short OS group exhibits a decrease in Smad 7 expression and also low levels of p21 immunostaining, which represents a common target of the two pathways. The IHC data was confirmed by quantitative analysis and Immunoblotting. Our preliminary results suggest that both HDAC4 and HDAC6 together with the TGF-β/Smad pathway may be involved in progression of GBM and this cross talking could be a useful prognostic marker in this deadly disease

Verso una open peer review dei dati: uno studio pilota nelle scienze sociali

L’open peer review (OPR) può essere applicata a tutte le tipologie di risultati della ricerca, dagli articoli scientifici, alle proposte di progetto fino ai dataset. Tuttavia, a partire dalla sua definizione, vanno ancora analizzati i criteri e modalità per assicurare una valutazione trasparente ed efficace per il progresso della ricerca scientifica. Ciò si inquadra nell’ambito dell’Open Science che coglie l’esigenza di analizzare le trasformazioni strutturali e tecnologiche nel sistema della comunicazione scientifica odierna. E’ proprio in tale contesto che i principi di Merton – in particolare quelli di communality e organized skepticism – diventano importanti punti di riferimento. Questo studio ha lo scopo di analizzare l’applicabilità della revisione paritaria aperta dei dati della ricerca prodotti nelle discipline afferenti alle scienze sociali. Lo studio inserisce nel progetto europeo OpenUP (OPENing UP new methods, indicators and tools for peer review, dissemination of research results, and impact measurement), che intende analizzare le trasformazioni nell’attuale scenario della ricerca scientifica allo scopo di 1) identificare meccanismi, processi e strumenti innovativi per la peer review applicata a tutti i risultati della ricerca (pubblicazioni, software e dati), 2) esplorare i meccanismi della disseminazione innovativa efficaci per le imprese, l’industria, il settore educativo e la società nel suo insieme e 3) analizzare un insieme di nuovi indicatori (altmetric) che valutano l’impatto dei risultati della ricerca collegandoli ai canali per la disseminazione. OpenUp utilizza una metodologia centrata sull’utente. Questo approccio metodologico non solo coinvolge tutti gli stakeholder (ricercatori, case editrici, enti che finanziano la ricerca, istituzioni, industria e il pubblico in generale) in una serie di workshops, conferenze e corsi di formazione, ma vuole testare i risultati acquisiti in un set di studi pilota. Questi ultimi sono collegati ai tre pilastri del progetto (revisione paritaria, disseminazione innovativa dei risultati e altmetric) e sono applicati ad alcune comunità e settori della ricerca specifici: scienze umane, scienze sociali, energia e scienze della vita. Nello specifico il lavoro presentato intende descrivere la metodologia usata per sviluppare lo studio pilota sull’OPR dei dati nelle scienze sociali. In particolare si concentra sulla prima fase che intende ricostruire il contesto generale della diffusione e condivisione dei dati. Sulla base di questa analisi, saranno identificati i criteri di selezione della comunità da coinvolgere nello studio pilota, insieme alle caratteristiche e alle problematiche specifiche che verranno successivamente indagate durante il suo svolgimento. L’analisi prende in considerazione sia la prospettiva di coloro che forniscono i dati sia quella degli utenti che li utilizzano. Essa si pone nella prospettiva di considerare i principi Mertoniani ed in particolare le problematiche legate alla loro applicabilità nella condivisione e valutazione dei dati della ricerca

En defensa de los indios norteamericanos. : Traducción y presentación editorial de un capítulo de 'A century of dishonor', de Helen Hunt Jackson

El presente trabajo se ha realizado a partir de la traducción del inglés al castellano de un capítulo de la obra de A Century of Dishonor de Helen Hunt Jackson. La traducción es acompañada por un trabajo suplementario de investigación acerca del contexto sociopolítico de la época, la obra y su autora con el fin de contextualizar la traducción y de obtener un panorama más amplio sobre la historia de los indios norteamericanos y su relación con el gobierno de los Estados Unidos, marcada por innumerables injusticias e abusos perpetrados durante un siglo. En este trabajo se puede encontrar un extracto del texto traducido correspondiente al Capítulo VIII del texto original y cuyo argumento trata sobre la tribu indígena de los indios cheroquis, desde el primer encuentro con los colonos británicos del general Oglethorpe en 1733, pasando por contacto con la religión cristiana a través de los misionarios wesleyanos en 1735, hasta los efectos del nuevo gobierno real de Georgia. Los últimos episodios se centran en los acontecimientos relativos a la participación de los indios cheroquis en la revolución americana y las primeras relaciones diplomáticas con el gobierno de Estados Unidos iniciadas con la firma del tratado de Hopewell en 1785 y descritas en 1789 por el secretario de Guerra, el general KnoxEl present treball s'ha realitzat a partir de la traducció de l'anglès al castellà d'un capítol de l'obra A Century of Dishonor d'Helen Hunt Jackson. La traducció és acompanyada per un treball suplementari d'investigació sobre el context sociopolític de l'època, l'obra i la seva autora per tal de contextualitzar la traducció i d'obtenir un panorama més ampli sobre la història dels indis nord-americans i la seva relació amb el govern dels Estats Units, marcada per innombrables injustícies i abusos perpetrats durant un segle. En aquest treball es pot trobar un extracte del text traduït corresponent al Capítol VIII del text original; l'argument tracta sobre la tribu indígena dels indis cheroquis, des la primera trobada amb els colons britànics del general Oglethorpe en 1733, passant pel contacte amb la religió cristiana amb els missioners wesleyans en 1735, fins als efectes del nou govern reial de Geòrgia. Els últims episodis es centren en els esdeveniments relatius a la participació dels indis cheroquis en la revolució americana i les primeres relacions diplomàtiques amb el govern dels Estats Units iniciades amb la signatura del tractat de Hopewell en 1785 i descrites en 1789 pel secretari de Guerra, el general KnoxThis work consists of a translation from English into Spanish of a chapter of the book A Century of Dishonor by Helen Hunt Jackson. The translation is accompanied by an additional research about the socio-political context of the time and Jackson's life and work in order to contextualize the translation and offer a broader overview of the history of American Indians and their relationship with the United States government, marked by countless injustices and abuses perpetrated during a century. It is included an excerpt of the translated text corresponding to Chapter VIII of the original text and whose plot development is based on the history of the Cherokees Indians: their first meeting with the British settlers of General Oglethorpe in 1733, their contact with Christian religion introduced by the Wesleyan missionaries in 1735, until the effects of the new royal government of Georgia. The last episodes focus on the facts related to the participation of the Cherokees in the American Revolution and their first diplomatic relations with the US government initiated with the signing of Hopewell's treaty in 1785 and described in 1789 by the Secretary of War General Kno

Pharmacokinetics of dexmedetomidine combined with methadone following oral-transmucosal and intramuscular administration in dogs

Oral-transmucosal (OTM) drug delivery refers to noninvasive and painless administration of medical preparations through any oral cavity membrane to achieve systemic effects (Sattar et al., 2014). Regarding sedative drugs, OTM administration is very attractive in veterinary medicine, especially for patients difficult to inject and restrain (Messenger et al., 2016). This study aims to compare the pharmacokinetics of dexmedetomidine after OTM and intramuscular (IM) administration combined with methadone. After obtaining Ethical Committee approval and owner’s written consent, eight dogs, were administered with dexmedetomidine (10 mg/kg) and methadone (0.4 mg/kg) by OTM and other 4 dogs by IM route. Blood samples were collected at prefixed times up to four hours. Dexmedetomidine was quantified by a validated HPLC-MS method. On dexmedetomidine concentrations, a pharmacokinetic analysis was carried out with a noncompartmental approach (Phoenix WinNonlin® 7.0, Pharsight, Cary, NC). Mean ± SD terminal half-lives of dexmedetomidine were 187.42 ± 109.66 and 94.78 ± 34.08 min after OTM and IM administration, respectively. Maximum serum (Cmax) concentrations were 0.83 ± 0.32 and 9.09 ± 2.46 ng/mL for OTM and IM administration, respectively. Time to maximum concentration (Tmax) were 44.38 ± 32.16 and 21.25±11.39 min by OTM and IM administration, respectively. Area under the curve from 0 to the last measured concentration (AUClast) were 103.75 ± 30.23 and 614.87 ± 77.15 min*ng/mL for OTM and IM administration, respectively. Cmax, Tmax and AUClast values by OTM route demonstrate a lower and delayed absorption of the drug compared to IM. To complete the study, the pharmacokinetic analysis of methadone is foreseen, so as a clinical trial to compare the clinical effects of the combination of dexmedetomidine and methadone by OTM and IM administration and to establish an effective dosage of oral-transumucosal route in dogs for this association

Sex Differences in Heart Failure: What Do We Know?

: Heart failure (HF) remains an important global health issue, substantially contributing to morbidity and mortality. According to epidemiological studies, men and women face nearly equivalent lifetime risks for HF. However, their experiences diverge significantly when it comes to HF subtypes: men tend to develop HF with reduced ejection fraction more frequently, whereas women are predominantly affected by HF with preserved ejection fraction. This divergence underlines the presence of numerous sex-based disparities across various facets of HF, encompassing aspects such as risk factors, clinical presentation, underlying pathophysiology, and response to therapy. Despite these apparent discrepancies, our understanding of them is far from complete, with key knowledge gaps still existing. Current guidelines from various professional societies acknowledge the existence of sex-based differences in HF management, yet they are lacking in providing explicit, actionable recommendations tailored to these differences. In this comprehensive review, we delve deeper into these sex-specific differences within the context of HF, critically examining associated definitions, risk factors, and therapeutic strategies. We provide a specific emphasis on aspects exclusive to women, such as the impact of pregnancy-induced hypertension and premature menopause, as these unique factors warrant greater attention in the broader HF discussion. Additionally, we aim to clarify ongoing controversies and knowledge gaps pertaining to the pharmacological treatment of HF and the sex-specific indications for cardiac implantable electronic devices. By shining a light on these issues, we hope to stimulate a more nuanced understanding and promote the development of more sex-responsive approaches in HF management

Right atrial mass following transcatheter radiofrequency ablation for recurrent atrial fibrillation: thrombus, endocarditis or mixoma?

We report a case of an asymptomatic patient in whom a right atrial mass was fortuitously documented by echocardiography few months after a transcatheter radiofrequency catheter ablation for recurrent AF. No masses were seen in the cardiac chambers before the ablative procedure, raising important diagnostic and decision-making issues. The patient was referred to the surgeon and a diagnosis of right atrial myxoma was made

Excess of NPM-ALK oncogenic signaling promotes cellular apoptosis and drug dependency.

Most of the anaplastic large-cell lymphoma (ALCL) cases carry the t(2;5; p23;q35) that produces the fusion protein NPM-ALK (nucleophosmin-anaplastic lymphoma kinase). NPM-ALK-deregulated kinase activity drives several pathways that support malignant transformation of lymphoma cells. We found that in ALK-rearranged ALCL cell lines, NPM-ALK was distributed in equal amounts between the cytoplasm and the nucleus. Only the cytoplasmic portion was catalytically active in both cell lines and primary ALCL, whereas the nuclear portion was inactive because of heterodimerization with NPM1. Thus, about 50% of the NPM-ALK is not active and sequestered as NPM-ALK/NPM1 heterodimers in the nucleus. Overexpression or relocalization of NPM-ALK to the cytoplasm by NPM genetic knockout or knockdown caused ERK1/2 (extracellular signal-regulated protein kinases 1 and 2) increased phosphorylation and cell death through the engagement of an ATM/Chk2- and γH2AX (phosphorylated H2A histone family member X)-mediated DNA-damage response. Remarkably, human NPM-ALK-amplified cell lines resistant to ALK tyrosine kinase inhibitors (TKIs) underwent apoptosis upon drug withdrawal as a consequence of ERK1/2 hyperactivation. Altogether, these findings indicate that an excess of NPM-ALK activation and signaling induces apoptosis via oncogenic stress responses. A 'drug holiday' where the ALK TKI treatment is suspended could represent a therapeutic option in cells that become resistant by NPM-ALK amplification.We thank Maria Stella Scalzo for technical support, Dr Emanuela Colombo for kindly providing MEFs that lack NPM1 (MEF NPM−/−p53−/−) and control fibroblasts (MEF p53−/−), Dr Guido Serini for the use of his confocal microscopy unit at the Candiolo Cancer Institute—IRCCS, Torino, Italy. We also thank Ariad Pharmaceutical, Pfizer, Astellas and Novartis that kindly provided all drugs used in this study. This work was supported by the Regione Lombardia (ID14546A) and Fondazione Berlucchi Onlus Grant 2014 (to CGP), and by grants FP7 ERC-2009-StG (Proposal No. 242965—‘Lunely’); Associazione Italiana per la Ricerca sul Cancro (AIRC) Grant IG-12023; Koch Institute/DFCC Bridge Project Fund; Ellison Foundation Boston; Worldwide Cancer Research Association (former AICR) grant 12-0216; the Grant for Oncology Innovation by Merck-Serono and R01 CA196703-01 (to RC).This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/onc.2015.45

Prolonged pre-firing pancreatic compression with linear staplers in distal pancreatectomy: a valuable technique for post-operative pancreatic fistula prevention

Purpose: Post-operative pancreatic fistula (POPF) remains the main complication after distal pancreatectomy (DP). The aim of this study is to evaluate the potential benefit of different durations of progressive stapler closure on POPF rate and severity after DP. Methods: Patients who underwent DP between 2016 and 2023 were retrospectively enrolled and divided into two groups according to the duration of the stapler closure: those who underwent a progressive compression for < 10 min and those for ≥ 10 min. Results: Among 155 DPs, 83 (53.5%) patients underwent pre-firing compression for < 10 min and 72 (46.5%) for ≥ 10 min. As a whole, 101 (65.1%) developed POPF. A lower incidence rate was found in case of ≥ 10 min compression (34-47.2%) compared to < 10 min compression (67- 80.7%) (p = 0.001). When only clinically relevant (CR) POPFs were considered, a prolonged pre-firing compression led to a lower rate (15-20.8%) than the < 10 min cohort (32-38.6%; p = 0.02). At the multivariate analysis, a compression time of at least 10 min was confirmed as a protective factor for both POPF (OR: 5.47, 95% CI: 2.16-13.87; p = 0.04) and CR-POPF (OR: 2.5, 95% CI: 1.19-5.45; p = 0.04) development. In case of a thick pancreatic gland, a prolonged pancreatic compression for at least 10 min was significantly associated to a lower rate of CR-POPF compared to < 10 min (p = 0.04). Conclusion: A prolonged pre-firing pancreatic compression for at least 10 min seems to significantly reduce the risk of CR-POPF development. Moreover, significant advantages are documented in case of a thick pancreatic gland