Value of Long-term Follow-up in Surgically Excised Lesions of Uncertain Malignant Potential in the Breast - Is 5 Years Necessary?

Introduction: B3 lesions are a heterogeneous group of breast lesions of uncertain malignant potential which usually require excision. The aim was to assess the efficacy of 5 years routine radiological or clinical follow-up of patients who had "high-risk" B3 lesions surgically excised, by analyzing recurrence and subsequent development of invasive/in-situ cancer.

Patients And Methods: A 10-year retrospective review from 2010 to 2019 was performed of B3 lesions diagnosed on core needle biopsy, including patients who proceeded to surgical excision with a high-risk lesion on final histology.

AJEDI in Science: Leveraging Instructor Communities to Create Antiracist Curricula.

Gateway college science courses continue to exclude students from science, disproportionately discriminating against students of color. As the higher education system strives to reduce discrimination, we need a deliberate, iterative process to modify, supplement, or replace current modalities. By incorporating antiracist, just, equitable, diverse, and inclusive (AJEDI) principles throughout course design, instructors create learning environments that provide an antidote to historically oppressive systems.

The OCT RNFL Probability Map and Artifacts Resembling Glaucomatous Damage.

Purpose: The purpose of this study was to improve the diagnostic ability of the optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) probability (p-) map by understanding the frequency and pattern of artifacts seen on the p-maps of healthy control (HC) eyes resembling glaucomatous damage.

Methods: RNFL p-maps were generated from wide-field OCT cube scans of 2 groups of HC eyes, 200 from a commercial normative group (HC-norm) and 54 from a prospective study group, as well as from 62 patient eyes, which included 32 with early glaucoma (EG). These 32 EG eyes had 24-2 mean deviation (MD) better than -6 dB and perimetric glaucoma as defined by 24-2 and 10-2 criteria.

Clinically guided core biopsy and cutaneous punch biopsy in the evaluation of breast lesions: a necessary test or an obsolete skill?

Objective: The vast majority of breast cancers are diagnosed via image-guided procedures yet despite significant advances, imaging does not identify all breast malignancies. Clinically suspicious breast lesions with normal breast imaging remain a cause for concern. The aim of this study is to determine the diagnostic value of clinical core and cutaneous punch biopsies in the diagnosis of breast malignancy in clinically suspicious lesions with normal breast imaging.

Teaching "Crafty Microbiology": Safely Teaching Hands-On Microbiology Skills at Home.

Using nontoxic craft items and disposable lab consumables, we have developed nine modules to teach fundamental, hands-on microbiology lab skills safely at home. These "Crafty" teaching modules can be paired with virtual instruction and/or data collected by an instructor to replicate traditional microbiology lab exercises that characterize an unknown microbe. Materials and procedures used were carefully chosen to best mimic the texture of media, represent microbial diversity, assess aseptic technique, and produce analyzable data from results.

Breast cancer patients with a negative axillary ultrasound may have clinically significant nodal metastasis.

Introduction: The non-invasive nature of the preoperative axillary ultrasound (AUS) fits the current trend of increasingly conservative axillary management. Recent publications suggest that early disease patients with clinically and radiologically negative axillae do not require sentinel lymph node biopsy (SLNB). This study aims to determine the true extent of axillary node disease in negative preoperative AUS patients.

Phase Ib Trial of Copanlisib, A Phosphoinositide-3 Kinase (PI3K) Inhibitor, with Trastuzumab in Advanced Pre-Treated HER2-Positive Breast Cancer "PantHER".

Background: Activation of the phosphoinositide-3 kinase (PI3K) pathway is a resistance mechanism to anti-human epidermal growth factor receptor 2 (HER2) therapy. This phase Ib trial was conducted to determine the maximum tolerated dose (MTD) of copanlisib, an intravenous (IV) pan-class I PI3K inhibitor, combined with trastuzumab.

Methods: Patients with advanced HER2-positive breast cancer and disease progression following at least one prior line of HER2 therapy in the metastatic setting were treated with copanlisib (45 or 60 mg) IV on days 1, 8 and 15 of a 28-day cycle with a fixed dose of trastuzumab 2 mg/kg weekly.

Assessing analytical methods to monitor isoAsp formation in monoclonal antibodies.

A ubiquitous post-translational modification observed in proteins is isomerization of aspartic acid to isoaspartic acid (isoAsp). This non-enzymatic post-translational modification occurs spontaneously in proteins and plays a role in aging, autoimmune response, cancer, neurodegeneration, and other diseases. Formation of isoAsp is also a significant issue for recombinant monoclonal antibody based protein therapeutics particularly when isomerization occurs in a complementarity-determining region due to potential impact to the clinical efficacy.

Effects of anionic polyacrylamide products on gill histopathology in juvenile rainbow trout (Oncorhynchus mykiss).

Anionic polyacrylamide (PAM) products are commonly used to remove suspended materials from turbid waters and to help mitigate soil erosion. In the present study, juvenile rainbow trout (Oncorhynchus mykiss) were exposed to 3 mg/L to 300 mg/L of 10 commercially available PAM products (Clearflow Water Lynx Polymer Log and Clearflow Soil Lynx Granular Polymer; Clearflow Enviro Systems Group), and gill histological parameters were measured following either 7 d or 30 d of polymer exposure. A cationic polymer product (≤0.

Genetic exchange of fimbrial alleles exemplifies the adaptive virulence strategy of Porphyromonas gingivalis.

Porphyromonas gingivalis is a gram-negative anaerobic bacterium, a member of the human oral microbiome, and a proposed "keystone" pathogen in the development of chronic periodontitis, an inflammatory disease of the gingiva. P. gingivalis is a genetically diverse species, and is able to exchange chromosomal DNA between strains by natural competence and conjugation.

Genetic diversity in the oral pathogen Porphyromonas gingivalis: molecular mechanisms and biological consequences.

Porphyromonas gingivalis is a Gram-negative anaerobic bacterium that colonizes the human oral cavity. It is implicated in the development of periodontitis, a chronic periodontal disease affecting half of the adult population in the USA. To survive in the oral cavity, these bacteria must colonize dental plaque biofilms in competition with other bacterial species.

Natural competence is a major mechanism for horizontal DNA transfer in the oral pathogen Porphyromonas gingivalis.

Unlabelled: Porphyromonas gingivalis is a Gram-negative anaerobe that resides exclusively in the human oral cavity. Long-term colonization by P. gingivalis requires the bacteria to evade host immune responses while adapting to the changing host physiology and alterations in the composition of the oral microflora.

An Agrobacterium VirB10 mutation conferring a type IV secretion system gating defect.

Agrobacterium VirB7, VirB9, and VirB10 form a "core complex" during biogenesis of the VirB/VirD4 type IV secretion system (T4SS). VirB10 spans the cell envelope and, in response to sensing of ATP energy consumption by the VirB/D4 ATPases, undergoes a conformational change required for DNA transfer across the outer membrane (OM). Here, we tested a model in which VirB10 regulates substrate passage by screening for mutations that allow for unregulated release of the VirE2 secretion substrate to the cell surface independently of target cell contact.

Trifluoromethylphenyl as P2 for ketoamide-based cathepsin S inhibitors.

The trifluoromethylphenyl P2 motif from previously reported heteroarylnitrile series has been successfully applied for the design and synthesis of highly potent novel ketoamide-based cathepsin S inhibitors. The key in this process is the change of the torsion angle between the P2 phenyl ring and the attached secondary amide by adding a small Cl, F, or Me group at the 2-position.

Optimisation of 2-cyano-pyrimidine inhibitors of cathepsin K: improving selectivity over hERG.

Several structure-guided optimisation strategies were explored in order to improve the hERG selectivity profile of cathepsin K inhibitor 1, whilst maintaining its otherwise excellent in vitro and in vivo profile. Ultimately, attenuation of clogP and pK(a) properties proved a successful approach and led to the discovery of a potent analogue 23, which, in addition to the desired selectivity over hERG (>1000-fold), displayed a highly attractive overall profile.

Photochemical degradation of citrate buffers leads to covalent acetonation of recombinant protein therapeutics.

Novel acetone and aldimine covalent adducts were identified on the N-termini and lysine side chains of recombinant monoclonal antibodies. Photochemical degradation of citrate buffers, in the presence of trace levels of iron, is demonstrated as the source of these modifications. The link between degradation of citrate and the observed protein modifications was conclusively established by tracking the citrate decomposition products and protein adducts resulting from photochemical degradation of isotope labeled (13)C citrate by mass spectrometry.

Evidence for VirB4-mediated dislocation of membrane-integrated VirB2 pilin during biogenesis of the Agrobacterium VirB/VirD4 type IV secretion system.

Agrobacterium VirB2 pilin is required for assembly of the VirB/VirD4 type IV secretion system (T4SS). The propilin is processed by signal sequence cleavage and covalent linkage of the N and C termini, and the cyclized pilin integrates into the inner membrane (IM) as a pool for assembly of the secretion channel and T pilus. Here, by use of the substituted cysteine accessibility method (SCAM), we defined the VirB2 IM topology and then identified distinct contributions of the T4SS ATPase subunits to the pilin structural organization.

2-Phenyl-9H-purine-6-carbonitrile derivatives as selective cathepsin S inhibitors.

Starting from previously disclosed equally potent cathepsin K and S inhibitor 4-propyl-6-(3-trifluoromethylphenyl)pyrimidine-2-carbonitrile 1, a novel 2-phenyl-9H-purine-6-carbonitrile scaffold was identified to provide potent and selective cathepsin S inhibitors.

Tuned methods for conjugate addition to a vinyl oxadiazole; synthesis of pharmaceutically important motifs.

The addition of various nucleophiles to a vinyl 1,2,4-oxadiazole is described. Following optimisation, individual protocols tuned for the use of each specific class of reagent have been developed to allow the installation of nitrogen, sulfur, oxygen, and carbon nucleophiles, and leading to the preparation of a series of compounds containing the pharmaceutically important oxadiazole motif.

Design and optimization of a series of novel 2-cyano-pyrimidines as cathepsin K inhibitors.

Morphing structural features of HTS-derived chemotypes led to the discovery of novel 2-cyano-pyrimidine inhibitors of cathepsin K with good pharmacokinetic profiles, for example, compound 20 showed high catK potency (IC(50)=4nM), >580-fold selectivity over catL and catB, and oral bioavailability in the rat of 52%.

Agrobacterium VirB10 domain requirements for type IV secretion and T pilus biogenesis.

Agrobacterium tumefaciens VirB10 couples inner membrane (IM) ATP energy consumption to substrate transfer through the VirB/D4 type IV secretion (T4S) channel and also mediates biogenesis of the virB-encoded T pilus. Here, we determined the functional importance of VirB10 domains denoted as the: (i) N-terminal cytoplasmic region, (ii) transmembrane (TM) alpha-helix, (iii) proline-rich region (PRR) and (iv) C-terminal beta-barrel domain. Mutations conferring a transfer- and pilus-minus (Tra(-), Pil(-)) phenotype included PRR deletion and beta-barrel substitution mutations that prevented VirB10 interaction with the outer membrane (OM) VirB7-VirB9 channel complex.

Extension of hepatic necrosis secondary to current arcing to surgical clips: a potential complication of radiofrequency ablation.

The authors present a case report of a 67-year-old woman who underwent radiofrequency ablation of recurrent hepatic metastases. She was managed 2 years previously with a right hemi-hepatectomy. Subsequent to RF ablation she developed hepatic necrosis extending in a linear fashion to two of the metallic surgical clips at the free edge of the liver, consistent with current arcing.

Small bowel imaging: CT enteroclysis or barium enteroclysis? Critically appraised topic.

Barium enteroclysis has been traditionally used in the diagnosis of small bowel Crohn's disease. Recently CT enteroclysis has been developed as an alternative imaging technique for small bowel Crohn's disease. A search and critical appraisal of the literature was performed to determine which technique is better for diagnosis of Crohn's disease.

MRI as a problem-solving tool in unexplained failed total hip replacement following conventional assessment.

Objective: To evaluate MRI as a problem-solving tool for patients with an unexplained failed total hip replacement following conventional radiological assessment.

Methods And Materials: Patients' informed consent was obtained in all cases. Institutional review board approval was obtained.

MRI features after radiofrequency ablation of osteoid osteoma with cooled probes and impedance-control energy delivery.

Objective: The purposes of our study were to determine the temporal changes in MR signal in bone after radiofrequency ablation of osteoid osteoma and the size of the zone of marrow signal change produced by the radiofrequency technique and to compare the size of the zone with published data for radiofrequency ablation with manual-control protocols.

Materials And Methods: Radiofrequency ablation was performed in 10 patients with a clinical and radiologic diagnosis of osteoid osteoma. A cooled radiofrequency probe was inserted in the nidus.