277 research outputs found
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
Femtosecond laser-assisted big-bubble deep anterior lamellar keratoplasty
Purpose: To determine whether type 1 big-bubble (BB) formation is influenced by the sequence of incisions created with the Victus femtosecond laser (FSL) enabled with software version 3.4 (SV 3.4) during deep anterior lamellar keratoplasty (DALK). Materials and Methods: Consecutive FSL-assisted DALK BB procedures were performed on 20 human donor corneas: 10 shaped by tunnel incision followed by lamellar incision (tunnel-lamellar group, TL) and 10 in the reverse order (lamellar-tunnel group, LT). The BB type was assessed by evaluating dynamic air movement during air inflation; bubble diameter and floor thickness were measured by anterior segment optical coherence tomography. Results: Overall, a type 1 BB formed in 85% of eyes: 100% in the TL group and 70% in the LT group. In the LT group, a type 2 BB formed in 2 corneas and one cornea was perforated during cannula insertion. Type 1 BB was achieved after one attempt in 90% of eyes in the TL group and in 57% in the LT group. Conclusion: Shaping the tunnel before rather than after lamellar incision may be more effective for obtaining a type 1 BB by air injection
Categorical rhythms in a singing primate
What are the origins of musical rhythm? One approach to the biology and evolution of music consists in finding common musical traits across species. These similarities allow biomusicologists to infer when and how musical traits appeared in our species1 . A parallel approach to the biology and evolution of music focuses on finding statistical universals in human music2 . These include rhythmic features that appear above chance across musical cultures. One such universal is the production of categorical rhythms3 , defined as those where temporal intervals between note onsets are distributed categorically rather than uniformly2 ,4 ,5 . Prominent rhythm categories include those with intervals related by small integer ratios, such as 1:1 (isochrony) and 1:2, which translates as some notes being twice as long as their adjacent ones. In humans, universals are often defined in relation to the beat, a top-down cognitive process of inferring a temporal regularity from a complex musical scene1 . Without assuming the presence of the beat in other animals, one can still investigate its downstream products, namely rhythmic categories with small integer ratios detected in recorded signals. Here we combine the comparative and statistical universals approaches, testing the hypothesis that rhythmic categories and small integer ratios should appear in species showing coordinated group singing3 . We find that a lemur species displays, in its coordinated songs, the isochronous and 1:2 rhythm categories seen in human music, showing that such categories are not, among mammals, unique to humans
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