5'-DMT-C(Ac)-Suc-CPG; 500 Å (RNA)

In this paper, we expand on the notion of combinatorial presheaf, first introduced explicitly by Aguiar and Mahajan in 2010 but already present in the literature in some other points of view. We do this by adapting the algebraic framework of species to the study of substructures in combinatorics. Afterwards, we consider functions that count the number of patterns of objects and endow the linear span of these functions with a product and a coproduct. In this way, any well-behaved family of combinatorial objects that admits a notion of substructure generates a Hopf algebra, and this association is functorial. For example, the Hopf algebra on permutations studied by Vargas in 2014 and the Hopf algebra on symmetric functions are particular cases of this construction. A specific family of pattern Hopf algebras of interest are the ones arising from commutative combinatorial presheaves. This includes the presheaves on graphs, posets and generalized permutahedra. Here, we show that all the pattern Hopf algebras corresponding to commutative presheaves are free. We also study a remarkable non-commutative presheaf structure on marked permutations, i.e. permutations with a marked element. These objects have a natural product called inflation, which is an operation motivated by factorization theorems for permutations. In this paper, we find new factorization theorems for marked permutations. We use these theorems to show that the pattern Hopf algebra for marked permutations is also free, using Lyndon words techniques.

In the present study, SibuDAB, an albumin-binding PSMA ligand, was investigated in combination with actinium-225 and the data were compared with those of [225Ac]Ac-PSMA-617. In vitro, [225Ac]Ac-SibuDAB and [225Ac]Ac-PSMA-617 showed similar tumor cell uptake and PSMA-binding affinities as their 177Lu-labeled counterparts. The in vitro binding to serum albumin in mouse and human blood plasma, respectively, was 2.8-fold and 1.4-fold increased for [225Ac]Ac-SibuDAB as compared to [177Lu]Lu-SibuDAB. In vivo, this characteristic was reflected by the longer retention of [225Ac]Ac-SibuDAB in the blood than previously seen for [177Lu]Lu-SibuDAB. Similar to [225Ac]Ac-PSMA-617, [225Ac]Ac-SibuDAB was well tolerated at 30 kBq per mouse. Differences in blood cell counts were observed between treated mice and untreated controls, but no major variations were observed between values obtained for [225Ac]Ac-SibuDAB and [225Ac]Ac-PSMA-617. [225Ac]Ac-SibuDAB was considerably more effective to treat PSMA-positive tumor xenografts than [225Ac]Ac-PSMA-617. Only 5 kBq per mouse were sufficient to eradicate the tumors, whereas tumor regrowth was observed for mice treated with 5 kBq [225Ac]Ac-PSMA-617 and only one out of six mice survived until the end of the study. The enhanced therapeutic efficacy of [225Ac]Ac-SibuDAB as compared to that of [225Ac]Ac-PSMA-617 and reasonable safety data qualify this novel radioligand as a candidate for targeted α-therapy of prostate cancer.

Worldwide, cervical cancer is a leading cause of mortality among women, causing 265,653 deaths annually. Squamous cell carcinoma (SCC) accounts for 75% of cervical cancer cases in the USA, while adenocarcinoma (AC) accounts for 25%. The incidence of SCC is decreasing in the USA, yet AC is increasing. Many differences exist between cervical SCC and AC including anatomic origin, risk factors, prognosis, dissemination, sites of recurrence, and rates of metastasis. Despite differences, current treatment algorithms do not distinguish between cervical SCC and AC. To date, prospective research directed toward AC is limited. We review published differences in response to neoadjuvant chemotherapy and concomitant chemotherapy with radiation, the role of adjuvant radical hysterectomy, and optimal chemotherapy for cervical AC. Cervical AC is sufficiently distinct from SCC to warrant specific treatment recommendations; however, lack of data evaluating AC limit recommendations. Additional prospective AC cervix specific research is needed.