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This contribution explores modern and traditional approaches to the decipherment of ancient writing systems. It surveys methods used by paleographers and epigraphers and state-of-the art applications of computational linguistics, such as models based on neural networks. It frames the contextual problems scholars encounter in dealing with ancient codes, the situations and preconditions of the unknown codes, their idiosyncrasies and peculiarities, and the potential solutions afforded by both traditional and novel methods of investigation.

BackgroundCurrently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population.MethodsThis was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Cox regression models evaluated factors associated with the risk of new clinical events/death.ResultsAmong 148 PWH followed for a median (interquartile range) of 47 (32–84) months after 4DR evidence, 38 PWH had 62 new events or died from any cause (incidence rate, 9.12/100 person-years of follow-up; 95% CI = 6.85–11.39): 12 deaths (6 AIDS-related and 6 non-AIDS-related), 18 ADEs, 32 NADEs; 20 of the 38 NADEs (45%) of the incident clinical events were malignancies. The 4-year cumulative incidence of death was 6% (95% CI, 3%–13%), and that of ≥1 event or death was 22% (95% CI, 16%–31%). A higher risk of new clinical events/death was more likely in PWH with previous clinical events (adjusted hazard ratio [aHR], 2.67; 95% CI, 1.07–6.67) and marginally associated with lower baseline CD4+/CD8+ ratio (aHR, 0.82; 95% CI, 0.65–1.02).ConclusionsPWH harboring 4DR have a high burden of disease with a worrying incidence of malignancies, strongly advising for close prevention and monitoring interventions as well as access to innovative therapeutic strategies, especially in people with a history of clinical events and low CD4+/CD8+ ratio.

Meniere's disease (MD) is characterized by the triad of fluctuating hearing loss, episodic vertigo and tinnitus, and by endolymphatic hydrops found on postmortem examinations. Since the description of endolymphatic hydrops by Hallpike and Cairns, the physiopathology of Meniere's symptoms has been based on assumption that the pathologic lesion was the cause of the symptoms. Schuknecht proposed the theory of membranous rupture causing the mixing up of endolymph and perilymph leading to the occurrence of Meniere's symptoms. Lawrence confirmed this theory with research on experimental animals. In 1995 the AAO-HNS criteria defines "Possible MD (Grade D), Probable MD (Grade C), Definite MD (Grade B) and Certain MD (Grade A). In 1995 the Committee of Barany Society proposed a classification that is similar to the AAO-HNS criteria but includes only two categories: definite MD and probable MD. A variety of medical and surgical treatments has been developed to treat or control the symptoms. The treatment can be divided into non-destructive and destructive procedures. During the last 21st IFOS Congress in Paris in June 2017, an international consensus (ICON) Round Table joining six experts of MD from different continents was designed in trying to draw a minimal consensus, which could be summarized in an algorithm. This synthesis was highly challenging and only France and Japan have drawn a consensus or recommendation applicable in their countries. Scientific literature was assessed using the Level of Evidence classification (1 to 5) and recommendations were given following the grading of recommendations assessment, development and evaluation (GRADE) scoring system. In MD, the aim of the treatment is first to reduce the frequency, and secondarily the severity of the vertigo attack, with a minimal impairment of hearing function associated with a hearing and tinnitus improvement. The treatment is symptomatic and should always be related to the main complaint of the patient. At the beginning it should be conservative. The conservative treatments are used regardless of the hearing function, while destructive ones are preferentially used in patients with hearing loss. Concerning bilateral MD the treatment should always be conservative.

Introduction: Leptin is a proteohormone produced predominantly by white adipocytes and primarily known for its key role in the control of food intake and sense of satiety. From its discover leptin has been found in different body districts, involved in always new functions and processes. In the last years numerous relationships between leptin and cancer has been found. The aim of this study is to test the leptin positivity in human primitive laryngeal squamous cell carcinoma (SCC) and in its lymph node metastasis. Materials and methods: Leptin positivity was detected by immunohistochemical analysis on pathological samples from 18 patients subjected to laryngectomy and neck dissection for SCC. Results: During the study we pointed out a statistically significant relationship (p < 0.05) between leptin positivity levels and tumor differentiation grade, in particular we observed that a decrease in tumor leptin production correlates with higher level of cancer histological dedifferentiation. Conclusion: Our research on leptin expression in laryngeal squamous neoplastic pathology is aimed to the attempt of establishing a more precise patient risk stratification thanks to a new marker able to give a contribution to the identification of patient with poor prognosis and at risk of failure of actual standard therapy.

This study reports on hospital admission and outcomes of 69 HIV-infected individuals who were diagnosed with SARS-CoV-2 infection between February and May 2020, in a network of Italian centres. Patients' characteristics and median days between symptoms and diagnosis were similar by hospital admission, whereas admitted patients had lower nadir CD4 cells and current lymphocytes count. These values were also correlated to worse COVID-19 outcome. Antiretroviral drugs did not seem to be associated with disease severity.

In the original version of this article, in Fig.2b the formatting on the x-axis of the graph has been published incorrectly.

Meniere's disease (MD) is characterized by the triad of fluctuating hearing loss, episodic vertigo and tinnitus, and by endolymphatic hydrops found on postmortem examinations. Since the description of endolymphatic hydrops by Hallpike and Cairns all the physiopathology of Meniere's symptoms have been based on assumption that the pathologic lesion was the cause of the symptoms. Paparella came out term and concept towards understanding of a disease was, "pathogenesis," which applies to all otological diseases, in general and in particular within this context of MD, which allows us to better understand this disease. After Schuknecht proposed the theory of membranous rupture causing the mixing up of endo and perilymph leading to the appearance of Meniere's symptoms. Lawrence proved this theory with research on experimental animals. In 1995 the AAO-HNS criteria defines "Possible MD, Probable MD, Definite MD and Certain MD. In 1995 the Committee of Barany Society proposed a classification that is similar to the AAO-HNS criteria, it includes only two categories: definite MD and probable MD. A variety of medical and surgical treatments have been developed to treat or control the symptoms. The treatment can be divided into non-destructive and destructive procedures.

OBJECTIVES: This study evaluated the virological efficacy of dolutegravir 50 mg twice daily in 190 HIV-1 failing antiretroviral-experienced patients with previous exposure to first-generation integrase strand transfer inhibitor (INSTI) over a 5 year follow-up using data from clinical practice. PATIENTS AND METHODS: This analysis included HIV-1-infected patients who were ≥18 years of age, treatment experienced, had HIV-1 RNA >50 copies/mL, with INSTI-resistant virus, who started dolutegravir 50 mg twice daily plus optimized background therapy (OBT), recorded in the national prospective database PRESTIGIO (www.progettoprestigio.it). Follow-up accrued from the start of dolutegravir 50 mg twice daily + OBT until virological failure (VF) or dolutegravir discontinuation for any reason or the last treatment visit on dolutegravir 50 mg twice daily treatment. VF was defined by the lack of achievement of HIV-1 RNA 100000 copies/mL (adjusted HR = 4.73, 95% CI = 1.33-16.78, P = 0.016) and with ≥1 INSTI mutations plus Q148H/K/R/N and the G140S/A/C as compared with other subjects (adjusted HR = 4.18, 95% CI = 1.32-13.23, P = 0.015). CONCLUSIONS: Our data showed a favourable long-term efficacy of dolutegravir 50 mg twice daily in association with OBT in treatment-experienced failing subjects, with INSTI-resistant virus, in the real world. A close monitoring of adherence is crucial for maintenance of virological response in this fragile subgroup of subjects.

Josep Tabernero,1 Volker Kunzmann,2 Werner Scheithauer,3 Michele Reni,4 Jack Shiansong Li,5 Stefano Ferrara,6 Kamel Djazouli7 1Medical Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain; 2Medizinische Klinik und Poliklinik II, University of Würzburg, Würzburg, Germany; 3Medizinische Universität Wien, Wien, Austria; 4San Raffaele ScientificInstitute, Milan, Italy; 5Celgene Corporation, Summit, NJ, USA; 6Celgene Corporation, Boudry, Switzerland; 7Celgene Corporation, Paris, France Purpose: The global Phase III MPACT trial demonstrated superior efficacy of nab-paclitaxel plus gemcitabine over gemcitabine alone as first-line treatment for metastatic pancreatic cancer. Region was a randomization stratification factor in the MPACT trial. This subgroup analysis of MPACT examined efficacy and safety of patients treated in Western Europe.Patients and methods: Patients received nab-paclitaxel plus gemcitabine or gemcitabine alone as first-line treatment for metastatic pancreatic cancer as previously described. A total of 76 patients were included in this analysis (n=38 for each arm).Results: Differences between the overall Western European cohort and the intention-to-treat population included lower percentages of male patients (46% and 58%, respectively) and patients with biliary stents (8% and 17%), and higher percentages of patients with Karnofsky performance status of 90–100 (78% and 60%) and primary tumors in the body of the pancreas (48% and 31%). The median overall survival was 10.7 months with nab-paclitaxel plus gemcitabine vs 6.9 months with gemcitabine alone (hazard ratio [HR]: 0.82 [95% confidence interval (CI): 0.48–1.40]; P=0.471). Median progression-free survival was 5.3 vs 3.7 months, respectively (HR: 0.70 [95% CI: 0.37–1.33]; P=0.277). The independently assessed overall response rate was 18% vs 5% (response rate ratio, 3.50 [95% CI: 0.78–15.78]; P=0.076). The most common grade≥3 adverse events with nab-paclitaxel plus gemcitabine and gemcitabine alone were neutropenia (46% vs 33%, respectively), leukopenia (35% vs 19%), anemia (22% vs 0%), asthenia (21% vs 6%), thrombocytopenia (14% vs 3%), and peripheral neuropathy (13% vs 3%).Conclusion: Although a statistically significant difference between the treatment arms was not reached for efficacy endpoints, this study does report treatment benefit and a manageable safety profile associated with nab-paclitaxel plus gemcitabine in patients treated in Western Europe with metastatic pancreatic cancer. Keywords: metastatic pancreatic cancer, nab-paclitaxel, gemcitabine, Western Europe, MPACT