Exploring genome-wide differentiation and signatures of selection in Italian and North American Holstein populations

Among Italian dairy cattle, the Holstein is the most reared breed for the production of Parmigiano Reggiano protected designation of origin cheese, which represents one of the most renowned products in the entire Italian dairy industry. In this work, we used a medium-density genome-wide data set consisting of 79,464 imputed SNPs to study the genetic structure of Italian Holstein breed, including the population reared in the area of Parmigiano Reggiano cheese production, and assessing its distinctiveness from the North American population. Multidimensional scaling and ADMIXTURE approaches were used to explore the genetic structure among populations. We also investigated putative genomic regions under selection among these 3 populations by combining 4 different statistical methods based either on allele frequencies (single marker and window-based) or extended haplotype homozygosity (EHH; standardized log-ratio of integrated EHH and cross-population EHH). The genetic structure results allowed us to clearly distinguish the 3 Holstein populations; however, the most remarkable difference was observed between Italian and North American stock. Selection signature analyses identified several significant SNPs falling within or closer to genes with known roles in several traits such as milk quality, resistance to disease, and fertility. In particular, a total of 22 genes related to milk production have been identified using the 2 allele frequency approaches. Among these, a convergent signal has been found in the VPS8 gene which resulted to be involved in milk traits, whereas other genes (CYP7B1, KSR2, C4A, LIPE, DCDC1, GPR20, and ST3GAL1) resulted to be associated with quantitative trait loci related to milk yield and composition in terms of fat and protein percentage. In contrast, a total of 7 genomic regions were identified combining the results of standardized log-ratio of integrated EHH and cross-population EHH. In these regions candidate genes for milk traits were also identified. Moreover, this was also confirmed by the enrichment analyses in which we found that the majority of the significantly enriched quantitative trait loci were linked to milk traits, whereas the gene ontology and pathway enrichment analysis pointed to molecular functions and biological processes involved in AA transmembrane transport and methane metabolism pathway. This study provides information on the genetic structure of the examined populations, showing that they are distinguishable from each other. Furthermore, the selection signature analyses can be considered as a starting point for future studies in the identification of causal mutations and consequent implementation of more practical application

Whole-exome analysis in osteosarcoma to identify a personalized therapy

Osteosarcoma is the most common pediatric primary non-hematopoietic bone tumor. Survival of these young patients is related to the response to chemotherapy and development of metastases. Despite many advances in cancer research, chemotherapy regimens for osteosarcoma are still based on non-selective cytotoxic drugs. It is essential to investigate new specific molecular therapies for osteosarcoma to increase the survival rate of these patients. We performed exomic sequence analyses of 8 diagnostic biopsies of patients with conventional high grade osteosarcoma to advance our understanding of their genetic underpinnings and to correlate the genetic alteration with the clinical and pathological features of each patient to identify a personalized therapy. We identified 18,275 somatic variations in 8,247 genes and we found three mutated genes in 7/8 (87%) samples (KIF1B, NEB and KMT2C). KMT2C showed the highest number of variations; it is an important component of a histone H3 lysine 4 methyltransferase complex and it is one of the histone modifiers previously implicated in carcinogenesis, never studied in osteosarcoma. Moreover, we found a group of 15 genes that showed variations only in patients that did not respond to therapy and developed metastasis and some of these genes are involved in carcinogenesis and tumor progression in other tumors. These data could offer the opportunity to get a key molecular target to identify possible new strategies for early diagnosis and new therapeutic approaches for osteosarcoma and to provide a tailored treatment for each patient based on their genetic profile

Liquid biopsy in bladder cancer: State of the art and future perspectives

Bladder cancer is the most common malignancy of the urinary tract. Cystoscopy represents the gold standard in the diagnosis of suspicious bladder lesions. However, the procedure is invasive and burdened by pain, discomfort and infective complications. Cytology, which represents an alternative diagnostic possibility is limited by poor sensitivity. Considering the limitations of both procedures, and the necessity to perform multiple evaluations in patients who are in follow-up for bladder cancer, an improved non-invasive methodology is required in the clinical management of this disease. Liquid biopsy, e.g. the detection of clinical biomarkers in urine, represent a promising novel and non-invasive approach that could overcome those limitations and be integrated into the current clinical practice. The aim of this review is to summarize the state of the art of this approach and the latest novelties regarding detection, prognosis and surveillance of bladder cancer

Conceptual Design of a Liquid Helium Vertical Test-Stand for 2m long Superconducting Undulator Coils

Superconducting Undulators (SCUs) can produce higher photon flux and cover a wider photon energy range compared to permanent magnet undulators (PMUs) with the same vacuum gap and period length. To build the know-how to implement superconducting undulators for future upgrades of the European XFEL facility, the test stand SUNDAE1 for the characterization of SCU is being developed. The purpose of SUNDAE1 is the training, tuning and development of new SCU coils by means of precise magnetic field measurements. The experimental setup will allow the characterization of magnets up to 2m in length. These magnets will be immersed in a Helium bath at 4K or 2K temperature. In this article, we describe the experimental setup and highlight its expected performances

SUNDAE1: A Liquid Helium Vertical Test-Stand for 2m Long Superconducting Undulator Coils

Superconducting Undulators (SCUs) can produce higher photon flux and cover a wider photon energy range compared to permanent magnet undulators (PMUs) with the same vacuum gap and period length. To build the know-how to implement superconducting undulators for future upgrades of the European XFEL facility, two magnetic measurement test stands named SUNDAE 1 and 2 (Superconducting UNDulAtor Experiment) are being developed. SUNDAE1 will facilitate research and development on magnet design thanks to the possibility of training new SCU coils and characterizing their magnetic field. The experimental setup will allow the characterization of magnets up to 2m in length. These magnets will be immersed in a Helium bath at 2K or 4K temperature. In this article, we describe the experimental setup and highlight its expected performances

Energetics of the Einstein-Rosen spacetime

A study covering some aspects of the Einstein--Rosen metric is presented. The electric and magnetic parts of the Weyl tensor are calculated. It is shown that there are no purely magnetic E--R spacetimes, and also that a purely electric E--R spacetime is necessarily static. The geodesics equations are found and circular ones are analyzed in detail. The super--Poynting and the ``Lagrangian'' Poynting vectors are calculated and their expressions are found for two specific examples. It is shown that for a pulse--type solution, both expressions describe an inward radially directed flow of energy, far behind the wave front. The physical significance of such an effect is discussed.Comment: 19 pages Latex.References added and updated.To appear in Int.J.Theor.Phy

Surgical and survival outcomes with perioperative or neoadjuvant immune-checkpoint inhibitors combined with platinum-based chemotherapy in resectable NSCLC: A systematic review and meta-analysis of randomised clinical trials

: The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised trials comparing neoadjuvant or perioperative chemoimmunotherapy to neoadjuvant chemotherapy in resectable NSCLC. Nine reports from 6 studies were included. Receipt of surgery was more frequent in the experimental arm (odds ratio, OR 1.39) as was pCR (OR 7.60). EFS was improved in the experimental arm (hazard ratio, HR 0.55) regardless of stage, histology, PD-L1 expression (PD-L1 negative, HR 0.74) and smoking exposure (never smokers, HR 0.67), as was OS (HR 0.67). Grade > = 3 treatment-related adverse events were more frequent in the experimental arm (OR 1.22). The experimental treatment improved surgical outcomes, pCR rates, EFS and OS in stage II-IIIB, EGFR/ALK negative resectable NSCLC; confirmatory evidence is warranted for stage IIIB tumours and with higher maturity of the OS endpoint

Effects of phylogenetic associations on environmental and temporal niche partitioning among sympatric mammals

Mammals have evolved to occupy spatial and temporal niches in order to optimize resource utilization and minimize predation risk or competition. Subsequently, niche partitioning may be influenced by phylogenetic associations, which could have substantial consequences for ecosystem structure and function. We use the output from occupancy models based on camera trapping data to construct a tri-partite network describing the environmental and temporal partitioning of activity among twelve sympatric mammals in the Apennine Mountains of central Italy. We further evaluate if there were any effects of phylogenetic associations on the contributions of species to the properties of this spatio-temporal network. The Apennines form a pristine region in central Italy with a relatively intact Mediterranean mammal fauna. The mammal community in our study consisted of species ranging in size from 300 gs to over 200 kg, and included herbivores, omnivores and predators. There was limited structuring of the network describing environmental and temporal niche use. Furthermore, we did not find any phylogenetic signal in species contributions to network structures, and phylogenetic relatedness among species was not associated with their similarities in environmental or spatial niche use. However, animals appeared to have partitioned environmental niches more than temporal ones, suggesting that spatial variation in resource availability may have been more important than temporal avoidance of predation risk or competition in shaping activity within this mammal community. Our study highlights the need to evaluate under which conditions evolutionary history is influencing contemporary ecological processes

Mixed cryoglobulinemia

Mixed cryoglobulinemia (MC), type II and type III, refers to the presence of circulating cryoprecipitable immune complexes in the serum and manifests clinically by a classical triad of purpura, weakness and arthralgias. It is considered to be a rare disorder, but its true prevalence remains unknown. The disease is more common in Southern Europe than in Northern Europe or Northern America. The prevalence of 'essential' MC is reported as approximately 1:100,000 (with a female-to-male ratio 3:1), but this term is now used to refer to a minority of MC patients only. MC is characterized by variable organ involvement including skin lesions (orthostatic purpura, ulcers), chronic hepatitis, membranoproliferative glomerulonephritis, peripheral neuropathy, diffuse vasculitis, and, less frequently, interstitial lung involvement and endocrine disorders. Some patients may develop lymphatic and hepatic malignancies, usually as a late complication. MC may be associated with numerous infectious or immunological diseases. When isolated, MC may represent a distinct disease, the so-called 'essential' MC. The etiopathogenesis of MC is not completely understood. Hepatitis C virus (HCV) infection is suggested to play a causative role, with the contribution of genetic and/or environmental factors. Moreover, MC may be associated with other infectious agents or immunological disorders, such as human immunodeficiency virus (HIV) infection or primary Sjögren's syndrome. Diagnosis is based on clinical and laboratory findings. Circulating mixed cryoglobulins, low C4 levels and orthostatic skin purpura are the hallmarks of the disease. Leukocytoclastic vasculitis involving medium- and, more often, small-sized blood vessels is the typical pathological finding, easily detectable by means of skin biopsy of recent vasculitic lesions. Differential diagnoses include a wide range of systemic, infectious and neoplastic disorders, mainly autoimmune hepatitis, Sjögren's syndrome, polyarthritis, and B-cell lymphomas. The first-line treatment of MC should focus on eradication of HCV by combined interferon-ribavirin treatment. Pathogenetic treatments (immunosuppressors, corticosteroids, and/or plasmapheresis) should be tailored to each patient according to the progression and severity of the clinical manifestations. Long-term monitoring is recommended in all MC patients to assure timely diagnosis and treatment of the life-threatening complications. The overall prognosis is poorer in patients with renal disease, liver failure, lymphoproliferative disease and malignancies

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients