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Background: The single-arm phase II APT trial established trastuzumab and paclitaxel (TH) as the standard adjuvant regimen for small human epidermal growth factor receptor 2 (HER2+) tumors. However, paclitaxel causes alopecia and has high rates of neuropathy and hypersensitivity reactions. In patients with metastatic HER2+ breast cancer (BC), the combination of trastuzumab and vinorelbine (TV) is effective and well tolerated. There is a need for alternative non-anthracycline/taxane-based regimens for patients with HER2+ early-stage BC, especially for those with contraindications or who wish to avoid side effects of taxane-based regimens. Here we describe our institutional experience with adjuvant TV for patients with early-stage HER2+ BC. Methods: Clinicopathological characteristics, treatment details, and outcomes of patients with localized HER2+ BC treated with adjuvant TV from 2007 to 2021 at a large academic medical institution were collected. Study endpoints included invasive disease-free survival (IDFS), overall survival (OS), and safety/tolerability. IDFS and OS were measured from start date of TV treatment to date of event/last follow-up and date of death/last follow-up, respectively. Results: A total of 30 patients were treated with TV. All patients received trastuzumab at standard dosing and vinorelbine at a starting dose of 25 mg/m2 either on days 1/8 or on days 1/8/21 (weekly) of a 21-day cycle with four planned cycles. Median age at diagnosis was 59 years (range: 36–81). 90.3% of patients had anatomic pathologic stage IA BC and 9.7% stage IIA BC. Of the 30 patients, 24 of them opted to pursue TV due to concerns related to alopecia, neuropathy, and other toxicities, and 6 switched from treatment with TH to TV due to toxicities. Eight patients experienced neutropenia with no cases of febrile neutropenia. No patients experienced alopecia or long-term neuropathy. With a median follow-up of 68 months (5.7 years), the 5-year IDFS rate was 90.9%, with one local and one distant recurrence. The 5-year OS was 100%. Conclusions: Trastuzumab in combination with vinorelbine in the adjuvant, early-stage setting for low-risk HER2+ BC demonstrated clinical efficacy and appeared to be well tolerated. TV warrants further evaluation as an alternative regimen to TH for patients with early-stage HER2+ BC. [ABSTRACT FROM AUTHOR]

In this study, variations in eye lens dose across different types of protective operator eyewear as well as the most appropriate protective methods when conducting endoscopic retrograde cholangiopancreatography were evaluated. The eye lens doses of 10 types of commercially available protective eyewear were compared. The ratio of the measured value near the eye to the measured value at the eye lens position ranged from 0.65 to 5.40 and it varied according to the mounting position of the dosemeter as well as the type of protective eyewear. Thus, the eye lens dose may have been overestimated or underestimated. Regardless of the working conditions, a face shield type of protective eyewear is recommended to reduce the eye lens dose. Moreover, it is preferable to attach a lens dosemeter near the eye to measure and evaluate the eye lens dose. [ABSTRACT FROM AUTHOR]

Purpose: To explore the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with breast cancer based on type of anticancer treatment. Methods: Patients with breast cancer had anti-spike antibody concentrations measured ⩾14 days after receiving a full SARS-CoV-2 vaccination series. The primary endpoint was IgA/G/M anti-spike antibody concentration. Multiple regression analysis was used to analyze log10-transformed antibody titer concentrations. Results: Between 29 April and 20 July 2021, 233 patients with breast cancer were enrolled, of whom 212 were eligible for the current analysis. Patients who received mRNA-1273 (Moderna) had the highest antibody concentrations [geometric mean concentration (GMC) in log10: 3.0 U/mL], compared to patients who received BNT162b2 (Pfizer) (GMC: 2.6 U/mL) (multiple regression adjusted p = 0.013) and Ad26.COV2.S (Johnson & Johnson/Janssen) (GMC: 2.6 U/mL) (p = 0.071). Patients receiving cytotoxic therapy had a significantly lower antibody titer GMC (2.5 U/mL) compared to patients on no therapy or endocrine therapy alone (3.0 U/mL) (p = 0.005). Patients on targeted therapies (GMC: 2.7 U/mL) also had a numerically lower GMC compared to patients not receiving therapy/on endocrine therapy alone, although this result was not significant (p = 0.364). Among patients who received an additional dose of vaccine (n = 31), 28 demonstrated an increased antibody response that ranged from 0.2 to >4.4 U/ mL. Conclusion: Most patients with breast cancer generate detectable anti-spike antibodies following SARS-CoV-2 vaccination, though systemic treatments and vaccine type impact level of response. Further studies are needed to better understand the clinical implications of different antibody levels, the effectiveness of additional SARS-CoV-2 vaccine doses, and the risk of breakthrough infections among patients with breast cancer. [ABSTRACT FROM AUTHOR]

Patients with metastatic triple‐negative breast cancer have a poor prognosis. Sacituzumab govitecan (IMMU‐132) is an antibody‐drug conjugate that contains the irinotecan active metabolite, SN‐38, linked to a humanized monoclonal antibody targeting trophoblast cell surface antigen 2, which is overexpressed in many solid tumors. In a basket design phase I/II study, sacituzumab govitecan demonstrated promising single‐agent therapeutic activity in multiple cancer cohorts, leading to accelerated approval by the U.S. Food and Drug Administration of sacituzumab govitecan‐hziy (TRODELVY) for the treatment of patients with metastatic triple‐negative breast cancer who had received at least two prior therapies in the metastatic setting. Recently, results of the phase III trial, ASCENT, were confirmatory. There is limited available information on the adverse event management with sacituzumab govitecan needed to maximize the dose and duration of effective therapy while maintaining patient quality of life. This review summarizes the clinical development and the practical management of patients receiving sacituzumab govitecan. Sacituzumab govitecan has a well‐defined and manageable toxicity profile, and rapid recognition and appropriate early and proactive management will allow clinicians to optimize sacituzumab govitecan treatment for patients. Implications for Practice: Sacituzumab govitecan (TRODELVY) is a novel antibody‐drug conjugate composed of the active metabolite of irinotecan (SN‐38) conjugated to a monoclonal antibody targeting trophoblast cell surface antigen 2, an epithelial cell surface antigen overexpressed in many cancers. Because of the rapid approval of sacituzumab govitecan, there is limited available information on adverse event (AE) management with this agent. As such, this article reviews the clinical development of the drug, the AE profile, and provides recommendations regarding AE management to help optimize therapy with sacituzumab govitecan. Sacituzumab govitecan (IMMU‐132) is an antibody‐drug conjugate that contains the irinotecan active metabolite, SN‐38, linked to a humanized monoclonal antibody targeting trophoblast cell surface antigen 2 (Trop‐2), which is overexpressed in many solid tumors. This review summarizes the clinical development and the practical management of patients receiving sacituzumab govitecan. [ABSTRACT FROM AUTHOR]

Pathogenic spirochetes from genus Leptospira are etiologic agents of leptospirosis. Cellular vaccines against Leptospira infection often elicit mainly response against the LPS antigen of the serovars present in the formulation. There is no suitable protein candidate capable of replacing whole-cell vaccines, thus requiring new approaches on vaccine development to improve leptospirosis prevention. Our goal was to develop a whole-cell vaccine sorovar-independent based on LPS removal and conservation of protein antigens exposure, to evaluate the protective capacity of monovalent or bivalent vaccines against homologous and heterologous virulent Leptospira in hamster. Leptospire were subjected to heat inactivation, or to LPS extraction with butanol and in some cases further inactivation with formaldehyde. Hamsters were immunized and challenged with homologous or heterologous virulent serovars, blood and organs were collected from the survivors for bacterial quantification, chemokine evaluation, and analysis of sera antibody reactivity and cross-reactivity by Western blot. Immunization with either heated or low LPS vaccines with serovar Copenhageni or Canicola resulted in 100% protection of the animals challenged with homologous virulent bacteria. Notably, different from the whole-cell vaccine, the low LPS vaccines produced with serovar Canicola provided only partial protection in heterologous challenge with the virulent Copenhageni serovar. Immunization with bivalent formulation results in 100% protection of immunized animals challenged with virulent serovar Canicola. All vaccines produced were able to eliminate bacteria from the kidney of challenged animals. All the vaccines raised antibodies capable to recognize antigens of serovars not present in the vaccine formulation. Transcripts of IFNγ, CXCL16, CCL5, CXCL10, CXCR6, and CCR5, increased in all immunized animals. Conclusion: Our results showed that bivalent vaccines with reduced LPS may be an interesting strategy for protection against heterologous virulent serovars. Besides the desirable multivalent protection, the low LPS vaccines are specially promising due to the expected lower reatogenicity. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To examine the predictive value of ultrasound parameters for antepartum non‐reassuring fetal status (NRFS) in fetal growth restriction (FGR) cases after late preterm. Methods: Retrospective review of singleton FGR cases before 37 weeks gestation who delivered after 34 weeks gestation was performed. The association between ultrasound parameters that was assessed from 34 to 36 weeks gestation and the development of antepartum NRFS that was diagnosed by nonstress test and biophysical profile was analyzed by using multivariate Cox proportional hazards analyses. Results: A total of 214 patients were included in final data analyses. Antepartum NRFS occurred in 23 cases (10.7%) including five cases of placental abruption. Lower standard deviation (SD) of estimated fetal weight (EFW), lower cerebroplacental ratio (CPR) and the presence of oligohydramnios were independently associated with antepartum NRFS. The prevalence of antepartum NRFS was highest (50.4%) in the group of EFW ≤−2.5 SD with CPR ≤1.45. Conclusion: Ultrasound parameters of lower SD of EFW, lower CPR and oligohydramnios were predictive for antepartum NRFS in FGR after late preterm. [ABSTRACT FROM AUTHOR]

Abstract: Recently, circularly polarized luminescence (CPL)‐active systems have become a very hot and interesting subject in chirality‐ and optics‐related areas. The CPL‐active systems are usually available by two approaches: covalently combining a luminescent centre to chiral motif or associating the guest of luminescent probe to a chiral host. However, all the chiral components in CPL materials were organic, although the luminescent components were alternatively organics or inorganics. Herein, the first totally inorganic CPL‐active system by “luminescent guest–chiral host” strategy is proposed. Luminescent sub‐10 nm lanthanide oxides (Eu2O3 or Tb2O3) nanoparticles (guests) were encapsulated into chiral non‐helical SiO2 nanofibres (host) through calcination of chiral SiO2 hybrid nanofibres, trapping Eu3+ (or Tb3+). These lanthanide oxides display circular dichroism (CD) optical activity in the ultraviolet wavelength and CPL signals around at 615 nm for Eu3+ and 545 nm for Tb3+. This work has implications for inorganic‐based CPL‐active systems by incorporation of various luminescent guests within chiral inorganic hosts. [ABSTRACT FROM AUTHOR]

An LBO (LiBO) walled ionization chamber was designed to monitor the epithermal neutron fluence in boron neutron capture therapy clinical irradiation. The thermal and epithermal neutron sensitivities of the device were evaluated using accelerator neutrons from the Be(d, n) reaction at a deuteron energy of 4 MeV (4 MeV d-Be neutrons). The response of the chamber in terms of the electric charge induced in the LBO chamber was compared with the thermal and epithermal neutron fluences measured using the gold-foil activation method. The thermal and epithermal neutron sensitivities obtained were expressed in units of pC cm, i.e., from the chamber response divided by neutron fluence (cm). The measured LBO chamber sensitivities were 2.23 × 10 ± 0.34 × 10 (pC cm) for thermal neutrons and 2.00 × 10 ± 0.12 × 10 (pC cm) for epithermal neutrons. This shows that the LBO chamber is sufficiently sensitive to epithermal neutrons to be useful for epithermal neutron monitoring in BNCT irradiation. [ABSTRACT FROM AUTHOR]

A novel and efficient method for the activation of the C(sp3)–C(sp3) bond was developed. The C(sp3)–C(sp3) bond in 3- benzhydryl pentane-2,4-dione was easily cleaved in the presence of NaHSO4/SiO2 to form benzhydryl cation which reacted with aromatic compounds at 110 °C for five to six hours to afford triarylmethanes in good yields. This reaction using Brønsted acids was applicable for the alkylation of electron-rich aromatics containing alkyl halides as a side chain. [ABSTRACT FROM AUTHOR]

The prokaryotic ubiquitous Toxin-Antitoxin (TA) operons encode a stable toxin and an unstable antitoxin. The most accepted hypothesis of the physiological function of the TA system is the reversible cessation of cellular growth under stress conditions. The major TA family, VapBC is present in the spirochaete Leptospira interrogans. VapBC modules are classified based on the presence of a predicted ribonucleasic PIN domain in the VapC toxin. The expression of the leptospiral VapC in E. coli promotes a strong bacterial growth arrestment, making it difficult to express the recombinant protein. Nevertheless, we showed that long term induction of expression in E. coli enabled the recovery of VapC in inclusion bodies. The recombinant protein was successfully refolded by high hydrostatic pressure, providing a new method to obtain the toxin in a soluble and active form. The structural integrity of the recombinant VapB and VapC proteins was assessed by circular dichroism spectroscopy. Physical interaction between the VapC toxin and the VapB antitoxin was demonstrated in vivo and in vitro by pull down and ligand affinity blotting assays, respectively, thereby indicating the ultimate mechanism by which the activity of the toxin is regulated in bacteria. The predicted model of the leptospiral VapC structure closely matches the Shigella's VapC X-ray structure. In agreement, the ribonuclease activity of the leptospiral VapC was similar to the activity described for Shigella's VapC, as demonstrated by the cleavage of tRNAfMet and by the absence of unspecific activity towards E. coli rRNA. This finding suggests that the cleavage of the initiator transfer RNA may represent a common mechanism to a larger group of bacteria and potentially configures a mechanism of post-transcriptional regulation leading to the inhibition of global translation. [ABSTRACT FROM AUTHOR]

Hermansky-Pudlak Syndrome (HPS) is a rare, genetic, multisystem disorder characterized by oculocutaneous albinism (OCA), bleeding diathesis, immunodeficiency, granulomatous colitis, and pulmonary fibrosis. HPS pulmonary fibrosis (HPS-PF) occurs in 100% of patients with subtype HPS-1 and has a similar presentation to idiopathic pulmonary fibrosis. Upon onset, individuals with HPS-PF have approximately 3 years before experiencing signs of respiratory failure and eventual death. This review aims to summarize current research on HPS along with its associated pulmonary fibrosis and its implications for the development of novel treatments. We will discuss the genetic basis of the disease, its epidemiology, and current therapeutic and clinical management strategies. We continue to review the cellular processes leading to the development of HPS-PF in alveolar epithelial cells, lymphocytes, mast cells, and fibrocytes, along with the molecular mechanisms that contribute to its pathogenesis and may be targeted in the treatment of HPS-PF. Finally, we will discuss emerging new cellular and molecular approaches for studying HPS, including lentiviral-mediated gene transfer, induced pluripotent stem cells (iPSCs), organoid and 3D-modelling, and CRISPR/Cas9-based gene editing approaches. [ABSTRACT FROM AUTHOR]

Abstract: Invited for the cover of this issue is the group of Ren‐Hua Jin at the Kanagawa University and co‐workers at Nara Institute of Science and Technology. The image depicts lanthanide metals encapsulated within temperature‐resistant chiral silica emitting polarized light. Read the full text of the article at 10.1002/chem.201705862. [ABSTRACT FROM AUTHOR]