Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma ...(RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1-10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1-28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1-5.1) and 14.47 months (95% CI, 7.91-21.04) in patients achieving at least MR (
< 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7-13.3) and 23.35 (NA-NA) months, respectively (
< 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies.
The totoaba (Totoaba macdonaldi) is a sciaenid (croaker) fish endemic to the Gulf of California with high commercial importance. Because it was considered at risk of extinction (since 2021 it was ...reclassified as vulnerable by the IUCN), and aquaculture procedures were developed for restocking and commercial purposes. The present study was conducted with the hypothesis that the early stages of totoaba present depensatory individual growth and an observed variance-at-age modelling approach is the best way to parametrize growth. Ten models were tested including asymptotic, non-asymptotic, exponential-like, and power-like curves including a new one that represents a modification of Schnute’s model. The model that best described the growth trajectory of larval and early juveniles of T. macdonaldi in a controlled environment is a sigmoid curve with two inflexions, related to changes in the feeding regime.
Abstract Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a median survival of 12 to 15 months after diagnosis. Acquired chemoresistance, high systemic toxicity, and low ...penetration of the blood brain barrier by many anticancer drugs contribute to the failure of anti-GBM therapies. To circumvent some of these obstacles, we tested a novel prodrug approach to evaluate anti-GBM efficacy by utilizing serum albumin-binding doxorubicin (Doxo), aldoxorubicin (Aldoxo), which is less toxic, is released from albumin in an acidic environment and accumulates in tumor tissues. A human GBM cell line that expresses a luciferase reporter (U87-luc) was stereotactically injected into the left striatum of the brain of immunodeficient mice. Following initial tumor growth for 12 days, mice were injected once a week in the tail-vein with Aldoxo 24 mg/kg or 18 mg/kg of doxorubicin equivalents—3/4 maximum tolerated dose (MTD), Doxo 6 mg/kg (3/4 MTD), or vehicle. Aldoxo-treated mice demonstrated significantly slower growth of the tumor when compared to vehicle-treated or Doxo-treated mice. Five out of eight Aldoxo-treated mice remained alive more than 60 days with a median survival of 62 days, while the median survival of vehicle- and Doxo-treated mice was only 26 days. Importantly, Aldoxo-treated mice exhibited high levels of Doxo within the tumor tissue, accompanied by low tumor cell proliferation (Ki67) and abundant intratumoral programmed cell death (cleaved caspase-3). Effective accumulation of Aldoxo in brain tumor tissues but not normal brain, its anti-tumor efficacy, and low toxicity, provide a strong rationale for evaluating this novel drug conjugate as a treatment for patients afflicted with GBM.
Obtaining the best possible estimates of individual growth parameters is essential in studies of physiology, fisheries management, and conservation of natural resources since growth is a key ...component of population dynamics. In the present work, we use data of an endangered fish species to demonstrate the importance of selecting the right data error structure when fitting growth models in multimodel inference. The totoaba (Totoaba macdonaldi) is a fish species endemic to the Gulf of California increasingly studied in recent times due to a perceived threat of extinction. Previous works estimated individual growth using the von Bertalanffy model assuming a constant variance of length-at-age. Here, we reanalyze the same data under five different variance assumptions to fit the von Bertalanffy and Gompertz models. We found consistent significant differences between the constant and nonconstant error structure scenarios and provide an example of the consequences using the growth performance index ϕ′ to show how using the wrong error structure can produce growth parameter values that can lead to biased conclusions. Based on these results, for totoaba and other related species, we recommend using the observed error structure to obtain the individual growth parameters.
The production of gluten-free (GF) laminated dough pieces is still a challenge in food industry. This work aims to evaluate changes in GF bulk dough characteristics as affected by the addition of ...hydrocolloids and the process of production of laminated products. Xanthan gum (XG), hydroxypropyl methylcellulose (HPMC) and
psyllium
(P) were added at 2.5 and 5% in GF dough made with rice and soy flour and cassava starch. Protein fractions were extracted, quantified and analyzed by electrophoresis. Rheology was evaluated by a creep and recovery test and proton mobility was explored by nuclear magnetic resonance. Tests were done on samples before and after the refrigerated rest time to assess the impact of that production step. Extractability of native proteins increased with lower doses of additives, while higher doses reduced it. The opposite behavior was observed on extractability of noncovalent proteins. Under stress, XG (J
0
: 7.7·10
–6
and 4.9·10
–6
Pa
−1
; J
1
: 7.3·10
–6
and 4.9·10
–6
Pa
−1
) and HPMC samples (J
0
: 7.0·10
–6
and 6.5 10
–6
Pa
−1
; J
1
: 8.2·10
–6
and 8.6·10
–6
Pa
−1
) showed lower instantaneous and viscoelastic compliance than control sample (J
0
: 9.8·10
–6
Pa
−1
; J
1
: 10.5 10
–6
Pa
−1
), while P had higher values (J
0
: 10.4·10
–6
and 9.8·10
–6
Pa
−1
; J
1
: 12.5·10
–6
and 12.5·10
–6
Pa
−1
). Additives promoted more viscous dough relaxation. After the refrigerated rest time, XG-2.5% elastic recover enhanced, while HPMC showed the opposite. XG decreased water proton mobility and P increased it. The refrigerated rest time enhanced water structuration.
The totoaba (Totoaba macdonaldi) is a sciaenid (croaker) fish endemic to the Gulf of California with high commercial importance. Because it was considered at risk of extinction (since 2021 it was ...reclassified as vulnerable by the IUCN), and aquaculture procedures were developed for restocking and commercial purposes. The present study was conducted with the hypothesis that the early stages of totoaba present depensatory individual growth and an observed variance-at-age modelling approach is the best way to parametrize growth. Ten models were tested including asymptotic, non-asymptotic, exponential-like, and power-like curves including a new one that represents a modification of Schnute’s model. The model that best described the growth trajectory of larval and early juveniles of T. macdonaldi in a controlled environment is a sigmoid curve with two inflexions, related to changes in the feeding regime.
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a median survival of 12 to 15 months after diagnosis. Acquired chemoresistance, high systemic toxicity, and low ...penetration of the blood brain barrier by many anticancer drugs contribute to the failure of anti-GBM therapies. To circumvent some of these obstacles, we tested a novel prodrug approach to evaluate anti-GBM efficacy by utilizing serum albumin-binding doxorubicin (Doxo), aldoxorubicin (Aldoxo), which is less toxic, is released from albumin in an acidic environment and accumulates in tumor tissues. A human GBM cell line that expresses a luciferase reporter (U87-luc) was stereotactically injected into the left striatum of the brain of immunodeficient mice. Following initial tumor growth for 12 days, mice were injected once a week in the tail-vein with Aldoxo 24 mg/kg or 18 mg/kg of doxorubicin equivalents—3/4 maximum tolerated dose (MTD), Doxo 6 mg/kg (3/4 MTD), or vehicle. Aldoxo-treated mice demonstrated significantly slower growth of the tumor when compared to vehicle-treated or Doxo-treated mice. Five out of eight Aldoxo-treated mice remained alive more than 60 days with a median survival of 62 days, while the median survival of vehicle- and Doxo-treated mice was only 26 days. Importantly, Aldoxo-treated mice exhibited high levels of Doxo within the tumor tissue, accompanied by low tumor cell proliferation (Ki67) and abundant intratumoral programmed cell death (cleaved caspase-3). Effective accumulation of Aldoxo in brain tumor tissues but not normal brain, its anti-tumor efficacy, and low toxicity, provide a strong rationale for evaluating this novel drug conjugate as a treatment for patients afflicted with GBM.
The paper investigates the dynamics between institutions and the governance of transport infrastructure projects, focusing on the planning and construction process of the CentrePort Canada Way (CCW) ...project. The CCW is regarded as a pivotal project in helping CentrePort Canada, the major inland port in Winnipeg and the province of Manitoba, to become a major inland transport and logistics hub in catalyzing and promoting international trade between Manitoba, Canada and the world. It focuses on how institutions have caused paradigm shifts in the planning culture of infrastructure projects in Manitoba, notably the Manitoba Infrastructure and Transportation (MIT)—how such shifts have transformed its initial idea, financial support, planning and construction of the CCW project. We hypothesize that institutions have influenced in an important manner on the direction of planning and development the CCW project, in both positive and negative ways. The paper offers insight to the roles of institutions on the planning and development process on large-scale transport infrastructure projects.
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