Molecular Anthropology in the genomic era

Molecular Anthropology is a relatively young field of research. In fact, less than 50 years have passed since the symposium ''Classification and Human Evolution'' ( 1962, Burg Wartenstein, Austria), where the term was formally introduced by Emil Zuckerkandl. In this time, Molecular Anthropology has developed both methodologically and theoretically and extended its applications, so covering key aspects of human evolution such as the reconstruction of the history of human populations and peopling processes, the characterization of DNA in extinct humans and the role of adaptive processes in shaping the genetic diversity of our species. In the current scientific panorama, molecular anthropologists have to face a double challenge. As members of the anthropological community, we are strongly committed to the integration of biological findings and other lines of evidence (e.g. linguistic and archaeological), while keeping in line with methodological innovations which are moving the approach from the genetic to the genomic level. In this framework, the meeting "DNA Polymorphisms in Human Populations: Molecular Anthropology in the Genomic Era" ( Rome, December 3-5, 2009) offered an opportunity for discussion among scholars from different disciplines, while paying attention to the impact of recent methodological innovations. Here we present an overview of the meeting and discuss perspectives and prospects of Molecular Anthropology in the genomic era

Relevant genetic differentiation among Brazilian populations of Anastrepha fraterculus (Diptera, Tephritidae)

We used a population genetic approach to detect the presence of genetic diversity among six populations of A. fraterculus across Brazil. To this aim, we used Simple Sequence Repeat (SSR) markers, which may capture the presence of differentiative processes across the genome in distinct populations. Spatial analyses of molecular variance were used to identify groups of populations that are both genetically and geographically homogeneous while also being maximally differentiated from each other. The spatial analysis of genetic diversity indicates that the levels of diversity among the six populations vary significantly on an eco-geographical basis. Particularly, altitude seems to represent a differentiating adaptation, as the main genetic differentiation is detected between the two populations present at higher altitudes and the other four populations at sea level. The data, together with the outcomes from different cluster analyses, identify a genetic diversity pattern that overlaps with the distribution of the known morphotypes in the Brazilian area.Fil: Manni, Mosè. Università degli Studi di Pavia; ItaliaFil: Lima, Kátia Manuela. Universidade Estadual de Santa Cruz; BrasilFil: Rosalba Guglielmino, Carmela. Università degli Studi di Pavia; ItaliaFil: Lanzavecchia, Silvia Beatriz. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Centro de Investigación de Ciencias Veterinarias y Agronómicas. Instituto de Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Juri, Marianela Lucia. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Centro de Investigación de Ciencias Veterinarias y Agronómicas. Instituto de Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vera, Maria Teresa. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cladera, Jorge. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Centro de Investigación de Ciencias Veterinarias y Agronómicas. Instituto de Genética; ArgentinaFil: Scolari, Francesca. Università degli Studi di Pavia; ItaliaFil: Gomulski, Ludvik. Università degli Studi di Pavia; ItaliaFil: Bonizzoni, Mariangela. Università degli Studi di Pavia; ItaliaFil: Gasperi, Giuliano. Università degli Studi di Pavia; ItaliaFil: Gomes Silva, Janisete. Universidade Estadual de Santa Cruz; BrasilFil: Malacrida, Anna Rodolfa. Università degli Studi di Pavia; Itali

3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine

Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-l-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-gamma mediated STAT1/NF-kappa Beta pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1 beta, IFN-gamma, and IL-17 production, and inhibiting generation of effector CD8(+) T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance. 3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. Here the authors identify 3-HKA as a biogenic amine and show it has anti-inflammatory properties that can protect mice against psoriasis and nephrotoxic nephritis.Peer reviewe

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

5G Architecture for Cross-border Mobility Services: The 5G-Routes Project Approach

Data travels across multiple system architectures to supply Cooperative, Connected and Automated Mobility (CCAM) services. The latter arrives to road users as a notification or warning message as “Reduce the speed, accident at 500 meters”, for example. 5G-Routes project approach aims at delivering Use Cases (UC) in multi-administrative domain scenarios where a UC 5G deployment can be transferred from one Mobile Network Operator (MNO) domain to another as the users moves. The present paper analyses the use of the 5G-Routes Project Architecture for the deployment of the UC 2.1 CCAM services to be tested in a cross-border environment in the countries of Latvia and Estonia. 5G and UC2.1 CCAM Services used to improve road users’ safety through traffic light maneuver (TLM), road and lane topology (MAPEM), collective perception (CPM), cooperative awareness (CAM), decentralized environmental notification (DENM) services

A literature review of clinical tests for lumbar instability in low back pain: validity and applicability in clinical practice.

Background Several clinical tests have been proposed on low back pain (LBP), but their usefulness in detecting lumbar instability is not yet clear. The objective of this literature review was to investigate the clinical validity of the main clinical tests used for the diagnosis of lumbar instability in individuals with LBP and to verify their applicability in everyday clinical practice. Methods We searched studies of the accuracy and/or reliability of Prone Instability Test (PIT), Passive Lumbar Extension Test (PLE), Aberrant Movements Pattern (AMP), Posterior Shear Test (PST), Active Straight Leg Raise Test (ASLR) and Prone and Supine Bridge Tests (PB and SB) in Medline, Embase, Cinahl, PubMed, and Scopus databases. Only the studies in which each test was investigated by at least one study concerning both the accuracy and the reliability were considered eligible. The quality of the studies was evaluated by QUADAS and QAREL scales. Results Six papers considering 333 LBP patients were included. The PLE was the most accurate and informative clinical test, with high sensitivity (0.84, 95%CI: 0.69 - 0.91) and high specificity (0.90, 95%CI: 0.85 -0.97). The diagnostic accuracy of AMP depends on each singular test. The PIT and the PST demonstrated by fair to moderate sensitivity and specificity [PIT sensitivity = 0.71 (95%CI:0.51 - 0.83), PIT specificity = 0.57 (95%CI: 039\u20130.78); PST sensitivity = 0.50 (95%CI: 0.41 - 0.76), PST specificity = 0.48 (95%CI: 0.22 - 0.58)]. The PLE showed a good reliability (k = 0.76), but this result comes from a single study. The inter-rater reliability of the PIT ranged by slight (k = 0.10 and 0.04), to good (k = 0.87). The inter-rater reliability of the AMP ranged by slight (k = 120.07) to moderate (k = 0.64), whereas the inter-rater reliability of the PST was fair (k = 0.27). Conclusions The data from the studies provided information on the methods used and on the validity of the instability tests. These results suggest that PLE is the most appropriate tests to detect lumbar instability in specific LBP. However, due to the lack of available papers on other lumbar conditions, these findings should be confirmed with studies on non-specific LBP

Angioimmunoblastic t-cell lymphoma: report on 282 cases from the prospective international t-cell lymphoma project

Angioimmunoblastic T-cell lymphoma (AITL) is a rare and unique subtype of peripheral T-cell lymphoma (PTCL) with distinct clinicopathologic features. Clinical presentation is varied with an aggressive course and dismal outcomes. Curative treatment modalities in AITLs are still an unmet need. In this study, we aimed to advance our understanding of clinical characteristics, prognostic factors, treatment strategies in patients with AITL in the international prospective T-Cell Project (TCP).We did a sub-analysis of 282 patients with AITL out of 1,553 cases enrolled between 2006 and 2018 in the TCP, a global prospective registry of patients with PTCL involving 74 institutions in 13 countries in Europe, North/South America, and Asia. Eligible patients were >18 years old with baseline clinical data necessary for disease staging, treatment type, and follow-up for at least 5 years. The primary and secondary endpoints were 5-year OS and PFS. Additionally, we analyzed prognostic factors and POD24. The TCP is registered on ClinicalTrials.gov, NCT01142674.The median age at diagnosis was 64 years (range 22–88) and 63% of patients were >60 years old. The advanced stage had 90% of patients and 60% were males. According to the IPI, PIT, and PIAI, the majority of cases were in the high-risk groups. Anthracyclinecontaining chemotherapy was received by 81% of patients, and 27 (12.5%) underwent HDT/ASCT as consolidation. Five-year OS and PFS were 44% and 32%, respectively. CR was achieved in 106 patients. ASCT was associated with superior OS (89% vs 52%, p = 0.05) and PFS (79% vs 31, p = 0.02). In multivariate analysis, older age (p=0.003), ECOG PS >2 (p=0.0001), CRP>ULN (p=0.003) and Beta2 microglobulin >ULN (p=0.002) showed an independent prognostic value on PFS. Finally, POD24 was a powerful predictor of outcome: the 5-year PFS for patients with or without POD24 was 2% and 48%, respectively (p=0.0001).Our data confirmed the poor outcome of AITL, mostly in patients exhibiting POD24, and the promising efficacy of ASCT in CR1. Moreover, the collected data gave a better understanding of the need for more effective therapies and the importance to continue prospective studies in a real-world population201S253S25