106 research outputs found
The New NIL Market May Decrease Overseas Professional Basketball Recruitment of United States Talent
At only nineteen years old, Cade Cunningham earned a $10.05 million salary to join the Detroit Pistons as the first overall pick in the 2021 National Baseball Association (the âNBAâ) Draft. The remaining top ten picks also earned multi-million-dollar salaries at similarly young ages. With the potential to make millions in their early twenties, it is no wonder why thousands of high school-aged basketball players dream of playing in the NBA one day. In addition to the fierce competition and limited opportunities, there is one major hurdle that young players need to overcome to realize this dream: the NBAâs âone-and-doneâ rule.
This post was originally published on the Cardozo International & Comparative Law Review on October 19, 2022. The original post can be accessed via the Archived Link button above
Radiofrequency Ablation in Vertebral Body Metastasis with and without Percutaneous Cement Augmentation: A Systematic Review Addressing the Need for SPINE Stability Evaluation
Vertebral body metastases (VBM) are one of the most frequent sites of bone metastasis, and their adequate therapeutic management still represents an insidious challenge for both oncologists and surgeons. A possible alternative treatment for VBM is radiofrequency ablation (RFA), a percutaneous technique in which an alternating current is delivered to the tumor lesion producing local heating and consequent necrosis. However, RFA alone could alter the biomechanics and microanatomy of the vertebral body, thus increasing the risk of post-procedure vertebral fractures and spine instability, and indeed the aim of the present study is to investigate the effects of RFA on spine stability. A systematic review according to PRISMA-P guidelines was performed, and 17 papers were selected for the systematic review. The results show how RFA is an effective, safe, and feasible alternative to conventional radiotherapy for the treatment of VBM without indication for surgery, but spine stability is a major issue in this context. Although exerting undeniable benefits on pain control and local tumor recurrence, RFA alone increases the risk of spine instability and consequent vertebral body fractures and collapses. Concomitant safe and feasible therapeutic strategies such as percutaneous vertebroplasty and kyphoplasty have shown synergic positive effects on back pain and improvement in spine stability
Intrinsically disordered amphiphilic peptides as potential targets in drug delivery vehicles
Intrinsically disordered proteins/peptides play a crucial role in many physiological and pathological
events and may assume a precise conformation upon binding to a specific target. Recently, we have
described the conformational and functional properties of two linear ester peptides provided with the
following sequences: Y-G-E-C-P-C-K-OAllyl (PepK) and Y-G-E-C-P-C-E-OAllyl (PepE). Both peptides
are characterized by the presence of the ââCPCââ motif together with a few amino acids able to promote
disorder. The CPC sequence is a binding motif for the CXCR4 receptor that represents a well-known
target for cancer therapies. In this paper, we report on synthetic amphiphilic peptides that consist of
lipophilic derivatives of PepE and PepK bearing two stearic alkyl chains and/or an ethoxylic spacer.
These peptide amphiphiles form stable supramolecular aggregates; they present conformational features
that are typical of intrinsically disordered molecules as shown by CD spectroscopy. Solution
fluorescence and DLS studies have been performed to evaluate Critical Micellar Concentrations and the
dimension of supramolecular aggregates. Moreover, preliminary in vitro cell-based assays have been
conducted to investigate the molecular recognition processes involving the CXCR4 receptor. In the
end, the results obtained have been compared with the previous data generated by the corresponding
non-amphiphilic peptides (PepE and PepK)
Conformational Ensembles Explored Dynamically from Disordered Peptides Targeting Chemokine Receptor CXCR4
This work reports on the design and the synthesis of two short linear peptides both containing a few amino acids with disorder propensity and an allylic ester group at the C-terminal end. Their structural properties were firstly analyzed by means of experimental techniques in solution such as CD and NMR methods that highlighted peptide flexibility. These results were further confirmed by MD simulations that demonstrated the ability of the peptides to assume conformational ensembles. They revealed a network of transient and dynamic H-bonds and interactions with water molecules. Binding assays with a well-known drug-target, i.e., the CXCR4 receptor, were also carried out in an attempt to verify their biological function and the possibility to use the assays to develop new specific targets for CXCR4. Moreover, our data indicate that these peptides represent useful tools for molecular recognition processes in which a flexible conformation is required in order to obtain an interaction with a specific target
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CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development
The C-type lectin receptor CLEC-2 signals through a pathway that is critically dependent on the tyrosine kinase Syk. We show that homozygous loss of either protein results in defects in brain vascular and lymphatic development, lung inflation and perinatal lethality. Furthermore, we find that conditional deletion of Syk in the haematopoietic lineage, or conditional deletion of CLEC-2 or Syk in the megakaryocyte/platelet lineage, also causes defects in brain vascular and lymphatic development, although the mice are viable. In contrast, conditional deletion of Syk in other haematopoietic lineages had no effect on viability or brain vasculature and lymphatic development. We show that platelets, but not platelet releasate, modulate the migration and intercellular adhesion of lymphatic endothelial cells through a pathway that is dependent on CLEC-2 and Syk. These studies demonstrate that megakaryocyte/platelet expression of CLEC-2 and Syk is required for normal brain vasculature and lymphatic development and that platelet CLEC-2 and Syk directly modulate lymphatic endothelial cell behaviour in vitro
Safety and effectiveness of RBD-specific polyclonal equine F(abÂŽ)2 fragments for the treatment of hospitalized patients with severe Covid-19 disease: A retrospective cohort study
Background Passive immunotherapy has been evaluated as a therapeutic alternative for patients with COVID-19 disease. Equine polyclonal immunotherapy for COVID-19 (EPIC) showed adequate safety and potential efficacy in a clinical trial setting and obtained emergency use authorization in Argentina. We studied its utility in a real world setting with a larger population. Methods We conducted a retrospective cohort study at âHospital de Campaña Escuela-Hogar" (HCEH) in Corrientes, Argentina, to assess safety and effectiveness of EPIC in hospitalized adults with severe COVID-19 pneumonia. Primary endpoints were 28-days all-cause mortality and safety. Mortality and improvement in modified WHO clinical scale at 14 and 21 days were secondary endpoints. Potential confounder adjustment was made by logistic regression weighted by the inverse of the probability of receiving the treatment (IPTW) and doubly robust approach. Findings Subsequent clinical records of 446 non-exposed (Controls) and 395 exposed (EPIC) patients admitted between November 2020 and April 2021 were analyzed. Median age was 58 years and 56.8% were males. Mortality at 28 days was 15.7% (EPIC) vs. 21.5% (Control). After IPTW adjustment the OR was 0.66 (95% CI: 0.46â0.96) P = 0.03. The effect was more evident in the subgroup who received two EPIC doses (complete treatment, n = 379), OR 0.58 (95% CI 0.39 to 0.85) P = 0.005. Overall and serious adverse events were not significantly different between groups. Conclusions In this retrospective cohort study, EPIC showed adequate safety and effectiveness in the treatment of hospitalized patients with severe SARS-CoV-2 disease.Fil: Farizano Salazar, Diego H.. Hospital de Campaña Escuela Hogar; ArgentinaFil: Achinelli, Fernando. Hospital de Campaña Escuela Hogar; ArgentinaFil: Colonna, Mariana. Inmunova; ArgentinaFil: PĂ©rez, LucĂa. Hospital Italiano; ArgentinaFil: GimĂ©nez, AnalĂa A.. Hospital de Campaña Escuela Hogar; ArgentinaFil: Ojeda, Maria Alejandra. Hospital de Campaña Escuela Hogar; ArgentinaFil: Miranda Puente, Susana N.. Hospital de Campaña Escuela Hogar; ArgentinaFil: SĂĄnchez Negrette, LĂa. Hospital de Campaña Escuela Hogar; ArgentinaFil: Cañete, Florencia. Hospital de Campaña Escuela Hogar; ArgentinaFil: Martelotte Ibarra, Ornela I.. Hospital de Campaña Escuela Hogar; ArgentinaFil: Sanguineti, Santiago. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BioquĂmicas de Buenos Aires. FundaciĂłn Instituto Leloir. Instituto de Investigaciones BioquĂmicas de Buenos Aires; ArgentinaFil: Spatz, Linus. Inmunova; ArgentinaFil: Goldbaum, Fernando Alberto. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BioquĂmicas de Buenos Aires. FundaciĂłn Instituto Leloir. Instituto de Investigaciones BioquĂmicas de Buenos Aires; ArgentinaFil: Massa, Carolina. Inmunova; ArgentinaFil: Rivas, Marta. Inmunova; ArgentinaFil: Pichel, Mariana. Inmunova; ArgentinaFil: Hiriart, Yanina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - La Plata. Instituto de Estudios InmunolĂłgicos y FisiopatolĂłgicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios InmunolĂłgicos y FisiopatolĂłgicos; ArgentinaFil: Zylberman, Vanesa. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Gallego, Sandra Veronica. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Universidad Nacional de CĂłrdoba. Facultad de Medicina. Instituto de VirologĂa Dr. J. M. Vanella; ArgentinaFil: Konigheim, Brenda Salome. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Universidad Nacional de CĂłrdoba. Facultad de Medicina. Instituto de VirologĂa Dr. J. M. Vanella; ArgentinaFil: FernĂĄndez, Francisco. No especifĂca;Fil: Deprati, MatĂas. No especifĂca;Fil: Roubicek, Ian. Inmunova; ArgentinaFil: Giunta, Diego Hernan. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Hospital Italiano; ArgentinaFil: Nannini, Esteban. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Rosario. Instituto de InmunologĂa Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias MĂ©dicas. Instituto de InmunologĂa Clinica y Experimental de Rosario; ArgentinaFil: Lopardo, Gustavo. No especifĂca;Fil: Belloso, Waldo Horacio. Hospital Italiano; Argentin
RBD-specific polyclonal F(abÂŽ)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial
Background: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. Methods: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). Findings: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65 1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5 28% [-3 95; 14 50]; p = 0 15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14 2 (§ 0 7) days in the INM005 group and 16 3 (§ 0 7) days in the placebo group, hazard ratio 1 31 (95% CI 1 0 to 1 74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6 9% the INM005 group and 11 4% in the placebo group (risk difference [95% IC]: 0 57 [0 24 to 1 37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. Interpretation: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.Fil: Lopardo, Gustavo. Municipalidad de Vicente Lopez (buenos Aires). Hospital Municipal Doctor Bernardo Houssay.; ArgentinaFil: Belloso, Waldo H.. Hospital Italiano; ArgentinaFil: Nannini, Esteban. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Colonna, Mariana. Inmunova; ArgentinaFil: Sanguineti, Santiago. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Inmunova; ArgentinaFil: Zylberman, Vanesa. Inmunova; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Muñoz, Luciana. Inmunova; ArgentinaFil: Dobarro, MartĂn. Sanatorio Sagrado CorazĂłn; ArgentinaFil: Lebersztein, Gabriel. Sanatorio Sagrado CorazĂłn; ArgentinaFil: Farina, Javier. Gobierno de la Provincia de Buenos Aires. Hospital de Alta Complejidad Cuenca Alta Doctor Nestor Carlos Kirchner.; ArgentinaFil: Vidiella, Gabriela. Sanatorio Agote. Dr. Luis Agote; ArgentinaFil: Bertetti, Anselmo. Sanatorio Guemes Sociedad Anonima.; ArgentinaFil: Crudo, Favio. Universidad Nacional de San Antonio de Areco; ArgentinaFil: Alzogaray, Maria Fernanda. Instituto Medico Platense.; ArgentinaFil: Barcelona, Laura. Municipalidad de Vicente Lopez (buenos Aires). Hospital Municipal Doctor Bernardo Houssay.; ArgentinaFil: Teijeiro, Ricardo. Gobierno de la Ciudad AutĂłnoma de Buenos Aires. Hospital General de Agudos Doctor Ignacio Pirovano; ArgentinaFil: Lambert, Sandra. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. NĂ©stor Carlos Kirchner Samic; ArgentinaFil: Scublinsky, DarĂo. Clinica Zabala.; ArgentinaFil: Iacono, Marisa. Provincia del Neuquen. Hospital Provincial Neuquen "dr. E. Castro Rendon"; ArgentinaFil: Stanek, Vanina. Hospital Italiano; ArgentinaFil: Solari, RubĂ©n. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Cruz, Pablo. No especifĂca;Fil: Casas, Marcelo MartĂn. Clinica Adventista Belgrano; ArgentinaFil: Abusamra, Lorena. Hospital Municipal Dr. Diego Thompson; ArgentinaFil: Luciardi, HĂ©ctor Lucas. Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Hosp. Centro de Salud "zenon Santillan"; ArgentinaFil: Cremona, Alberto. Hospital Italiano de La Plata; ArgentinaFil: Caruso, Diego. Hospital Español; ArgentinaFil: de Miguel, Bernardo. No especifĂca;Fil: Perez Lloret, Santiago. Pontificia Universidad CatĂłlica Argentina "Santa MarĂa de los Buenos Aires"; Argentina. Universidad Abierta Interamericana. SecretarĂa de InvestigaciĂłn. Centro de Altos Estudios En Ciencias Humanas y de la Salud - Sede Buenos Aires; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: MillĂĄn, Susana. No especifĂca;Fil: Kilstein, Yael. No especifĂca;Fil: Pereiro, Ana. FundaciĂłn Mundo Sano; ArgentinaFil: Sued, Omar. FundaciĂłn HuĂ©sped; ArgentinaFil: Cahn, Pedro. FundaciĂłn HuĂ©sped; ArgentinaFil: Spatz, Linus. Inmunova; ArgentinaFil: Goldbaum, Fernando Alberto. Inmunova; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BioquĂmicas de Buenos Aires. FundaciĂłn Instituto Leloir. Instituto de Investigaciones BioquĂmicas de Buenos Aires; Argentina. Universidad Nacional de San Martin. Centro de Rediseño E Ingenieria de Proteinas.; Argentin
Cancer cure for 32 cancer types: results from the EUROCARE-5 study.
BACKGROUND: Few studies have estimated the probability of being cured for cancer patients. This study aims to estimate population-based indicators of cancer cure in Europe by type, sex, age and period. METHODS: 7.2 million cancer patients (42 population-based cancer registries in 17 European countries) diagnosed at ages 15-74 years in 1990-2007 with follow-up to 2008 were selected from the EUROCARE-5 dataset. Mixture-cure models were used to estimate: (i) life expectancy of fatal cases (LEF); (ii) cure fraction (CF) as proportion of patients with same death rates as the general population; (iii) time to cure (TTC) as time to reach 5-year conditional relative survival (CRS) >95%. RESULTS: LEF ranged from 10âyears for chronic lymphocytic leukaemia patients to 5âyears for women with breast cancer. The CF was 94% for testis, 87% for thyroid cancer in women and 70% in men, 86% for skin melanoma in women and 76% in men, 66% for breast, 63% for prostate and <10% for liver, lung and pancreatic cancers. TTC was <5âyears for testis and thyroid cancer patients diagnosed below age 55âyears, and <10âyears for stomach, colorectal, corpus uteri and melanoma patients of all ages. For breast and prostate cancers, a small excess (CRSâ<â95%) remained for at least 15âyears. CONCLUSIONS: Estimates from this analysis should help to reduce unneeded medicalization and costs. They represent an opportunity to improve patients' quality of life
Cancer cure for 32 cancer types: results from the EUROCARE-5 study.
BACKGROUND: Few studies have estimated the probability of being cured for cancer patients. This study aims to estimate population-based indicators of cancer cure in Europe by type, sex, age and period. METHODS: 7.2 million cancer patients (42 population-based cancer registries in 17 European countries) diagnosed at ages 15-74 years in 1990-2007 with follow-up to 2008 were selected from the EUROCARE-5 dataset. Mixture-cure models were used to estimate: (i) life expectancy of fatal cases (LEF); (ii) cure fraction (CF) as proportion of patients with same death rates as the general population; (iii) time to cure (TTC) as time to reach 5-year conditional relative survival (CRS) >95%. RESULTS: LEF ranged from 10âyears for chronic lymphocytic leukaemia patients to 5âyears for women with breast cancer. The CF was 94% for testis, 87% for thyroid cancer in women and 70% in men, 86% for skin melanoma in women and 76% in men, 66% for breast, 63% for prostate and <10% for liver, lung and pancreatic cancers. TTC was <5âyears for testis and thyroid cancer patients diagnosed below age 55âyears, and <10âyears for stomach, colorectal, corpus uteri and melanoma patients of all ages. For breast and prostate cancers, a small excess (CRSâ<â95%) remained for at least 15âyears. CONCLUSIONS: Estimates from this analysis should help to reduce unneeded medicalization and costs. They represent an opportunity to improve patients' quality of life
First Results of the Ce(n,Îł)Ce Cross-Section Measurement at n_TOF
An accurate measurement of the Ce(n,Îł) energy-dependent cross-section was performed at the n_TOF facility at CERN. This cross-section is of great importance because it represents a bottleneck for the s-process nucleosynthesis and determines to a large extent the cerium abundance in stars. The measurement was motivated by the significant difference between the cerium abundance measured in globular clusters and the value predicted by theoretical stellar models. This discrepancy can be ascribed to an overestimation of the Ce capture cross-section due to a lack of accurate nuclear data. For this measurement, we used a sample of cerium oxide enriched in Ce to 99.4%. The experimental apparatus consisted of four deuterated benzene liquid scintillator detectors, which allowed us to overcome the difficulties present in the previous measurements, thanks to their very low neutron sensitivity. The accurate analysis of the p-wave resonances and the calculation of their average parameters are fundamental to improve the evaluation of the Ce Maxwellian-averaged cross-section
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