Simultaneous adaptive smoothing of relaxometry and quantitative magnetization transfer mapping

Attempts for in-vivo histology require a high spatial resolution that comes with the price of a decreased signal-to-noise ratio. We present a novel iterative and multi-scale smoothing method for quantitative Magnetic Resonance Imaging (MRI) data that yield proton density, apparent transverse and longitudinal relaxation, and magnetization transfer maps. The method is based on the propagation-separation approach. The adaptivity of the procedure avoids the inherent bias from blurring subtle features in the calculated maps that is common for non-adaptive smoothing approaches. The characteristics of the methods were evaluated on a high-resolution data set (500 μ isotropic) from a single subject and quantified on data from a multi-subject study. The results show that the adaptive method is able to increase the signal-to-noise ratio in the calculated quantitative maps while largely avoiding the bias that is otherwise introduced by spatially blurring values across tissue borders. As a consequence, it preserves the intensity contrast between white and gray matter and the thin cortical ribbon

Potential Mechanisms of Ovarian Protection with Gonadotropin-Releasing Hormone Agonist in Breast Cancer Patients: A Review

The use of chemotherapy in premenopausal cancer patients may lead to chemotherapy-induced premature ovarian failure. Pharmacological temporary ovarian suppression obtained with the gonadotropin-releasing hormone agonist (GnRHa) administered concomitantly with chemotherapy has been investigated as a technique capable to reduce the gonadotoxicity, reducing the risk of developing premature menopause. In recent years, important evidence has become available on the efficacy and safety of this strategy that should now be considered a standard option for ovarian function preservation in premenopausal breast cancer patients. However, in women interested in fertility preservation, this is not an alternative to cryopreservation strategies, which remains the first option to be proposed. The purpose of this review is to summarize the mechanisms of GnRHa in the preservation of fertility in premenopausal cancer patient candidates to receive chemotherapy, highlighting the areas of doubt that require further investigation

Management of young women with early breast cancer

Breast cancer is still the most frequent cancer diagnosed in women aged 6440 years and the primary cause of death in this age group. The management of these patients needs a dedicated approach involving a multidisciplinary team that takes into account their treatment and survivorship issues. The present review aims to provide a perspective on the many challenges associated with treatment of young women with early breast cancer. We will focus on the standard (neo)adjuvant treatment, highlighting the paucity of age-specific results about the available genomic signatures, the groundbreaking landscape of adjuvant endocrine therapy and the relevant issue of the fertility preservation

Bioinspired Fingertip for Anthropomorphic Robotic Hands

Background: An artificial fingertip with mechanical features and appearance similar to the human fingertip could represent a significant step forward towards the development of the next generation artificial hands. However, so far, a fingertip showing a good trade-off among mechanical features, appearance and anthropomorphism, along with its 3D computational model, is still missing

A combined fermentative-chemical approach for the scalable production of pure E. coli monophosphoryl lipid A

Lipid A is the lipophilic region of lipopolysaccharides and lipooligosaccharides, the major components of the outer leaflet of most part of Gram-negative bacteria. Some lipid As are very promising immunoadjuvants. They are obtained by extraction from bacterial cells or through total chemical synthesis. A novel, semisynthetic approach to lipid As is ongoing in our laboratories, relying upon the chemical modification of a natural lipid A scaffold for the fast obtainment of several other lipid As and derivatives thereof. The first requisite for this strategy is to have this scaffold available in large quantities through a scalable process. Here, we present an optimized fed-batch fermentation procedure for the gramscale production of lipid A from Escherichia coli K4 and a suitable phenol-free protocol for its purification. A study for regioselective de-O-phosphorylation reaction was then performed to afford pure monophosphoryl lipid A with an attenuated endotoxic activity, as evaluated by cytokine production in human monocytic cell line THP-1 in vitro. The reported method for the large-scale obtainment ofmonophoshoryl lipid A from the fed-batch fermentation broth of a recombinant strain of E. coli may permit the access to novel semisynthetic lipid A immunoadjuvant candidates

T-DM1 Efficacy in Patients With HER2-positive Metastatic Breast Cancer Progressing After a Taxane Plus Pertuzumab and Trastuzumab: An Italian Multicenter Observational Study

reserved21T-DM1 improves progression-free survival (PFS) and overall survival (OS) in patients with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer progressing on prior trastuzumab plus a taxane. A paucity of data is available on T-DM1 efficacy after dual anti-HER2 blockade with pertuzumab and trastuzumab plus a taxane, which represents the current first-line standard of care. The present study is a retrospective/prospective evaluation of the efficacy and activity of second-line T-DM1 after front-line pertuzumab-based therapy.mixedConte, Benedetta; Fabi, Alessandra; Poggio, Francesca; Blondeaux, Eva; Dellepiane, Chiara; D'Alonzo, Alessia; Buono, Giuseppe; Arpino, Grazia; Magri, Valentina; Naso, Giuseppe; Presti, Daniele; Mura, Silvia; Fontana, Andrea; Cognetti, Francesco; Molinelli, Chiara; Pastorino, Simona; Bighin, Claudia; Miglietta, Loredana; Boccardo, Francesco; Lambertini, Matteo; Del Mastro, LuciaConte, Benedetta; Fabi, Alessandra; Poggio, Francesca; Blondeaux, Eva; Dellepiane, Chiara; D'Alonzo, Alessia; Buono, Giuseppe; Arpino, Grazia; Magri, Valentina; Naso, Giuseppe; Presti, Daniele; Mura, Silvia; Fontana, Andrea; Cognetti, Francesco; Molinelli, Chiara; Pastorino, Simona; Bighin, Claudia; Miglietta, Loredana; Boccardo, Francesco; Lambertini, Matteo; Del Mastro, Luci

Prospective study to optimize care and improve knowledge on ovarian function and/or fertility preservation in young breast cancer patients: Results of the pilot phase of the PREgnancy and FERtility (PREFER) study

Background: Despite the availability of different strategies for ovarian function and/or fertility preservation in young breast cancer patients candidates for chemotherapy, limited data are available on patients\u2019 actual need of these options. Patients and methods: The PREFER study is a prospective cohort study including premenopausal women with newly diagnosed early stage breast cancer between the age of 18 and 45 years and candidates for chemotherapy. The study aimed to investigate patients' preferences and their choices of the different available strategies for ovarian function and/or fertility preservation (i.e. acceptance rate) and reasons for refusal. Results: A total of 131 consecutive patients referred from a single breast unit were included. Median age was 38.9 years with 92 patients (70.3%) diagnosed at 64 40 years. The majority of patients (122, 93.1%) were concerned about the risk of treatment-induced premature ovarian insufficiency (POI) and/or infertility. A total of 120 (91.6%) patients underwent temporary ovarian suppression with gonadotropin-releasing hormone agonists during chemotherapy for ovarian function preservation. Among patients with 6440 years, only 11 (12.0%) decided to access cryopreservation strategies for fertility preservation. The main reason for not accessing the fertility unit was completion of family planning before breast cancer diagnosis; for patients who accessed the fertility unit, fear of the procedure was the main reason to refuse the proposed cryopreservation strategies. Conclusion: Despite the majority of young breast cancer patients are concerned about the risk of treatment-induced POI and/or infertility, only a limited number of them required to access the fertility unit to undergo cryopreservation strategies

A Semisynthetic Approach to New Immunoadjuvant Candidates: Site-Selective Chemical Manipulation of Escherichia coli Monophosphoryl Lipid A

A semisynthetic approach to novel lipid A derivatives from Escherichia coli (E. coli) lipid A is reported. This methodology stands as an alternative to common approaches based exclusively on either total synthesis or extraction from bacterial sources. It relies upon the purification of the lipid A fraction from fed-batch fermentation of E. coli, followed by its structural modification through tailored, siteselective chemical reactions. In particular, modification of the lipid pattern and functionalization of the phosphate group as well as of the sole primary hydroxyl group were accomplished, highlighting the unusual reactivity of the molecule. Preliminary investigations of the immunostimulating activity of the new semisynthetic lipidA derivatives show that some of them stand out as promising, new immunoadjuvant candidates