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Article ; Online: Cyclotris(paraquat-p-phenylenes).

Anamimoghadam, Ommid / Cooper, James A / Nguyen, Minh T / Guo, Qing-Hui / Mosca, Lorenzo / Roy, Indranil / Sun, Junling / Stern, Charlotte L / Redfern, Louis / Farha, Omar K / Stoddart, J Fraser

Angewandte Chemie (International ed. in English)

2019 Volume 58, Issue 39, Page(s) 13778–13783

Abstract: ... triangular, threefold symmetric, viologen-containing macrocycles. Cyclotris(paraquat-p-phenylene) (CTPQT ...

Abstract	Reported here is the synthesis, solid-state characterization, and redox properties of new triangular, threefold symmetric, viologen-containing macrocycles. Cyclotris(paraquat-p-phenylene) (CTPQT
Language	English
Publishing date	2019-08-29
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
DOI	10.1002/anie.201907329
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Article ; Online: A phase 1 study in healthy participants to characterize the safety and pharmacology of inclacumab, a fully human anti-P-selectin antibody, in development for treatment of sickle cell disease.

Mayer, Christina Lourdes / Koeck, Kathleen / Hottmann, Margot / Redfern, Andrew / Davis, Mark / Barth, Aline / Geng, Xin / Hoppe, Carolyn / Yue, Patrick

European journal of clinical pharmacology

2023 Volume 79, Issue 9, Page(s) 1219–1228

Abstract: ... of intravenous (IV) inclacumab, a fully human IgG4 anti-P-selectin monoclonal antibody in development ... activated platelet-leukocyte aggregate (PLA) formation, P-selectin inhibition, plasma soluble P-selectin, and anti ... P-selectin inhibition > 90% was observed up to 12 weeks post-dose. The mean ratio of free to total ...

Abstract	Purpose: We evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of intravenous (IV) inclacumab, a fully human IgG4 anti-P-selectin monoclonal antibody in development for the treatment of sickle cell disease, at doses up to and exceeding those previously tested in healthy individuals. Methods: In this phase 1, open-label, single-ascending-dose study, 15 healthy participants were enrolled into cohorts receiving 20 mg/kg (n = 6) or 40 mg/kg (n = 9) IV inclacumab and observed for up to 29 weeks post-dose. Safety, PK parameters, thrombin receptor-activating peptide (TRAP)-activated platelet-leukocyte aggregate (PLA) formation, P-selectin inhibition, plasma soluble P-selectin, and anti-drug antibodies were characterized. Results: Two inclacumab-related treatment-emergent adverse events were reported in 1 participant; no dose-limiting toxicities were observed. Plasma PK parameters were generally dose-proportional, with a terminal half-life of 13 to 17 days. Mean TRAP-activated PLA formation decreased within 3 h from the start of infusion, and inhibition was sustained for ~ 23 weeks. Mean P-selectin inhibition > 90% was observed up to 12 weeks post-dose. The mean ratio of free to total soluble P-selectin decreased rapidly from pre-dose to end of infusion, then increased gradually to 78% of the baseline ratio by week 29. Treatment-emergent anti-drug antibodies were observed in 2 of 15 participants (13%), without apparent impact on safety, PK, or PD. Conclusions: Inclacumab was well tolerated, with PK as expected for a monoclonal antibody against a membrane-bound target and a long duration of PD effects after both single IV doses, supporting a prolonged dosing interval. Trial registration: ACTRN12620001156976; registered November 4, 2020.
MeSH term(s)	Humans ; Healthy Volunteers ; Antibodies, Monoclonal/adverse effects ; Anemia, Sickle Cell/drug therapy ; Anemia, Sickle Cell/chemically induced ; Selectins ; Polyesters ; Double-Blind Method ; Dose-Response Relationship, Drug
Chemical Substances	inclacumab (A6734I702L) ; Antibodies, Monoclonal ; Selectins ; Polyesters
Language	English
Publishing date	2023-07-12
Publishing country	Germany
Document type	Clinical Trial, Phase I ; Journal Article
ZDB-ID	121960-1
ISSN	1432-1041 ; 0031-6970
ISSN (online)	1432-1041
ISSN	0031-6970
DOI	10.1007/s00228-023-03514-3
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Article ; Online: Bone mineral density fall during aromatase inhibitor treatment may predict lower breast cancer recurrence.

Martin, Hilary / Redfern, Andrew

Cancer medicine

2024

Abstract: ... with substantially less reduction, was significant (HR = 3.02, 95% CI 1.15-7.90 p = 0.025). Hip BMD reduction was ... with the greatest (p = 0.10).: Conclusions: The findings suggest an association may exist between lumbar spine ...

Abstract	Purpose: Aromatase inhibitors (AIs) are associated with reduction in bone mineral density (BMD). The use of bone strengthening agents zoledronic acid and denosumab are associated with improved breast cancer outcomes for post-menopausal patients treated with AIs. This study investigates whether change in BMD with AI therapy is associated with breast cancer recurrence. Methods: A cohort of patients treated at a single institution diagnosed with hormone receptor-positive breast cancer with baseline BMD and subsequent BMD test while receiving adjuvant aromatase inhibitor therapy were studied. Demographic, treatment and outcome data was obtained. Simple and multiple linear regression analysis was performed to investigate predictors of annual percent BMD change at the LS and hip. Univariate and multivariate Cox proportional hazards modelling were undertaken to investigate predictors of breast cancer recurrence. Results: 353 patients eligible patients were identified. In multivariate analysis of lumbar spine BMD change, the difference between those in quartile 1, which showed the greatest reduction in BMD, and quartile 3, with substantially less reduction, was significant (HR = 3.02, 95% CI 1.15-7.90 p = 0.025). Hip BMD reduction was also not significantly associated with breast cancer recurrence. The two quartiles with the least reduction in hip BMD showing a non-significant reduced risk of recurrence relative to the quartile with the greatest (p = 0.10). Conclusions: The findings suggest an association may exist between lumbar spine BMD change and breast cancer recurrence for patients treated with adjuvant AI. Further research is required to determine whether BMD change can be utilised as a biomarker.
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.6846
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Article ; Online: Potential pro-inflammatory impact of scleral lens midday fogging on human corneal epithelial cells: An in vitro study.

Walker, Maria K / Lema, Carolina / Redfern, Rachel

Contact lens & anterior eye : the journal of the British Contact Lens Association

2024 , Page(s) 102187

Abstract: ... revealed no significant association (r = +0.48, P = 0.09).: Conclusions: The results suggest that the FR ...

Abstract	Purpose: Midday fogging (MDF) occurs when particulate material accumulates in the fluid reservoir (FR) beneath scleral lenses (SL), and its impact on epithelial cells is unknown. This study examines the in vitro pro-inflammatory effect of the FR on human corneal epithelial cells in varying degrees of MDF. Methods: Normal SL neophytes were recruited to wear SL 8 h daily for 4 days. Following 8 h on days 1 and 4, optical coherence tomography (OCT) images were acquired for MDF quantification using ImageJ, and the FR was collected. FR samples from the same eye were later pooled, diluted 2-fold and applied on human telomerase-immortalized corneal epithelial (hTCEpi) cells cultured on Terasaki microwell plates. Tumor necrosis factor (TNF)-α and culture media were used as positive and negative controls, respectively. After a 30-minute treatment, the nuclear factor-kappa B (NF-κB) pathway was measured by NF-κB-p65 immunofluorescence and images were analyzed with ImageJ. Pearson's correlation was conducted to determine the association between median nuclear fluorescence and MDF. Results: Fourteen FR samples with a mean volume of 22 ± 16 µl were tested. Mean MDF severity following 8 h of SL wear was 25 ± 17 units (range 7 - 64). The median nuclear fluorescence (NF-κB-p65 translocation) in cultured hTCEpi cells ranged from 31.43 to 45.16 while the negative and positive controls were 44.71 ± 1.72 and 108.77 ± 68.38, respectively. Although a potential positive trend between MDF and median nuclear fluorescence was observed, Pearson's correlation analysis revealed no significant association (r = +0.48, P = 0.09). Conclusions: The results suggest that the FR can trigger NF-κB-p65 translocation in hTCEpi cells, which may be associated with MDF severity. This study introduces the use of Terasaki microwell plates for immunofluorescence studies of the FR. The technique is simple, minimizes sample usage, and does not require expensive instrumentation.
Language	English
Publishing date	2024-05-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2004847-6
ISSN	1476-5411 ; 1367-0484
ISSN (online)	1476-5411
ISSN	1367-0484
DOI	10.1016/j.clae.2024.102187
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Article ; Online: Vitamin A and its natural derivatives.

Redfern, Chris P F

Methods in enzymology

2020 Volume 637, Page(s) 1–25

Abstract: Vitamin A and derivatives, the natural retinoids, underpin signaling pathways of cellular differentiation, and are key chromophores in vision. These functions depend on transfer across membranes, and carrier proteins to shuttle retinoids to specific cell ...

Abstract	Vitamin A and derivatives, the natural retinoids, underpin signaling pathways of cellular differentiation, and are key chromophores in vision. These functions depend on transfer across membranes, and carrier proteins to shuttle retinoids to specific cell compartments. Natural retinoids, ultimately derived from plant carotenoids by metabolism to all-trans retinol, are lipophilic and consist of a cyclohexenyl (β-ionone) moiety linked to a polyene chain. This structure constrains the orientation of retinoids within lipid membranes. Cis-trans isomerization at double bonds of the polyene chain and s-cis/s-trans rotational isomerization at single bonds define the functional dichotomy of retinoids (signaling/vision) and specificities of interactions with specific carrier proteins and receptors. Metabolism of all-trans retinol to 11-cis retinal, transfer to photoreceptors, and removal and recycling of all-trans retinal generated by photoreceptor irradiation, is the key process underlying vision. All-trans retinol transferred into cells is metabolized to all-trans retinoic acid and shuttled to the cell nucleus to regulate gene expression controlling organ, tissue and cell differentiation, and cellular homeostasis. Research methods need to address the potential of photoisomerization in vitro to confound research results, and data should be interpreted in the context of membrane-association properties of retinoids and physiological concentrations in vivo. Despite a century of research, there are many fundamental questions of retinoid cellular biochemistry and molecular biology still to be answered. Computational modeling techniques will have an important role for understanding the nuances of vitamin A signaling and function.
MeSH term(s)	Carotenoids ; Retina ; Retinaldehyde ; Retinoids ; Vitamin A
Chemical Substances	Retinoids ; Vitamin A (11103-57-4) ; Carotenoids (36-88-4) ; Retinaldehyde (RR725D715M)
Language	English
Publishing date	2020-03-19
Publishing country	United States
Document type	Journal Article
ISSN	1557-7988
ISSN (online)	1557-7988
DOI	10.1016/bs.mie.2020.02.002
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Article ; Online: Initial Experience Using Magseed for Breast Lesion Localization Compared With Wire-Guided Localization: Analysis of Volume and Margin Clearance Rates.

Redfern, Roberta E / Shermis, Robin B

Annals of surgical oncology

2022 Volume 29, Issue 6, Page(s) 3776–3783

Abstract: ... characteristics did not vary by group. Considering only lumpectomy cases, total volume resected (13.7 vs. 17.1; p ... 0.003) and calculated resection ratios (1.8 vs. 2.5; p = 0.02) were significantly lower ...

Abstract	Background: Detection of nonpalpable lesions requiring surgical intervention has increased during the past several decades. Techniques have evolved to help surgeons locate lesions in the operating room. Disadvantages of wire localization has led to the use of new approaches for surgical guidance. Magnetic seeds have been suggested to improve workflow and cosmetic result. Methods: This retrospective cohort study analyzed consecutive patients undergoing lumpectomy or excisional biopsy with the guidance of wire localization or magnetic seeds. The optimal and total resected volumes were calculated from pathology records, and the calculated resection volumes were compared by localization approach. Margin positivity and need for reoperation were reviewed and compared. Results: Each group included 148 patients. The majority were treated with lumpectomy and did not undergo preoperative chemotherapy. The operative characteristics did not vary by group. Considering only lumpectomy cases, total volume resected (13.7 vs. 17.1; p = 0.003) and calculated resection ratios (1.8 vs. 2.5; p = 0.02) were significantly lower in the magnetic seed group. The rates of positive margins (10% vs. 14%) and reoperation (12.8% vs. 17.3%) were non-significantly lower than in the wire localization cases. Conclusions: Magnetic seeds were successfully used for lesion localization in this cohort. Pathologic examination of specimens suggested that the surgeons were able to remove closer to optimal volumes of tissue than those using wire-guided intervention. Removal of less tissue did not result in higher rates of margin positivity or a need for re-intervention to achieve negative margin status. Magnetic seeds are a feasible and non-inferior approach that overcomes many drawbacks of other localization methods.
MeSH term(s)	Biopsy ; Breast Neoplasms/surgery ; Female ; Humans ; Margins of Excision ; Mastectomy, Segmental/methods ; Reoperation ; Retrospective Studies
Language	English
Publishing date	2022-01-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-022-11327-4
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Article ; Online: Despite Greater Improvement in Pain and Function Among Obese Patients Shortly After Total Knee Arthroplasty, There is No Difference in Patient-Reported Outcomes and Satisfaction Between Body Mass Index Classes at 1 Year Postoperatively.

Pasqualini, Ignacio / Huffman, Nickelas / Redfern, Roberta E / Piuzzi, Nicolas S

The Journal of arthroplasty

2024

Abstract: ... P < .0001). However, KOOS JR, satisfaction, and pain did not vary by BMI class postoperatively ... patients reported the greatest improvements in KOOS JR (23.24 ± 15.67, P < .0001) and pain scores (-3.56 ... 2.65, P < .0001) at 90 days. Significantly greater improvement with increasing BMI was also present ...

Abstract	Background: Although obesity may be associated with an increased risk of perioperative and postoperative complications after total knee arthroplasty (TKA), body mass index (BMI) cutoffs for TKA patient selection remain a controversial topic. This study aimed to investigate patient-reported outcomes, satisfaction, and pain among BMI classes at 3 months and 1 year following TKA. Methods: A total of 2,365 patients were categorized into Centers for Disease Control BMI classes according to preoperative values. The BMI distribution over the cohort demonstrated 7 underweight, 340 healthy weight, 731 overweight, 666 Class I, 391 Class II, and 230 Class III obesity. Preoperative and postoperative Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR), satisfaction, and pain scores were compared by BMI class by Analysis of Variance with pairwise comparisons. Results: Preoperative KOOS JR scores and satisfaction scores were both significantly greater for healthy weight patients compared to Class III patients (P < .0001). However, KOOS JR, satisfaction, and pain did not vary by BMI class postoperatively. Changes in scores from baseline suggest larger improvements with increasing BMI class, where Class III patients reported the greatest improvements in KOOS JR (23.24 ± 15.67, P < .0001) and pain scores (-3.56 ± 2.65, P < .0001) at 90 days. Significantly greater improvement with increasing BMI was also present at 1-year postoperatively for KOOS JR scores. A total of 85.8% of Class III patients reached the Minimal Clinically Important Difference for KOOS JR at 90 days compared to 76.8% of the healthy weight group (P = .03). Differences between BMI groups in the proportion reaching Minimal Clinically Important Difference at 1 year were not significant. Conclusions: Patients of higher BMI reported greater and earlier improvements in satisfaction, knee function, and pain following TKA. Shared decision-making remains paramount to preoperative surgical evaluation. However, rationing of this surgical intervention based on BMI alone may not be warranted.
Language	English
Publishing date	2024-02-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	632770-9
ISSN	1532-8406 ; 0883-5403
ISSN (online)	1532-8406
ISSN	0883-5403
DOI	10.1016/j.arth.2024.01.043
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Article ; Online: Iron alloys of volatile elements in the deep Earth's interior.

Tian, Yifan / Zhang, Peiyu / Zhang, Wei / Feng, Xiaolei / Redfern, Simon A T / Liu, Hanyu

Nature communications

2024 Volume 15, Issue 1, Page(s) 3320

Abstract: Investigations into the compositional model of the Earth, particularly the atypical concentrations of volatile elements within the silicate portion of the early Earth, have attracted significant interest due to their pivotal role in elucidating the ... ...

Abstract	Investigations into the compositional model of the Earth, particularly the atypical concentrations of volatile elements within the silicate portion of the early Earth, have attracted significant interest due to their pivotal role in elucidating the planet's evolution and dynamics. To understand the behavior of such volatile elements, an established 'volatility trend' has been used to explain the observed depletion of certain volatile elements. However, elements such as Se and Br remain notably over-depleted in the silicate Earth. Here we show the results from first-principles simulations that explore the potential for these elements to integrate into hcp-Fe through the formation of substitutional alloys, long presumed to be predominant constituents of the Earth's core. Based on our findings, the thermodynamic stability of these alloys suggests that these volatile elements might indeed be partially sequestered within the Earth's core. We suggest potential reservoirs for volatile elements within the deep Earth, augmenting our understanding of the deep Earth's composition.
Language	English
Publishing date	2024-04-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-47663-0
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Article ; Online: Improved patient reported outcomes with the direct anterior approach versus the posterior approach for total hip arthroplasty in the early post-operative period.

Sarhan, Omar / Megalla, Martinus / Imam, Nareena / Ren, Anna N / Redfern, Roberta E / Klein, Gregg R

Archives of orthopaedic and trauma surgery

2024 Volume 144, Issue 5, Page(s) 2373–2380

Abstract: ... group through 6 months (p = 0.03 and p = 0.005). At 1 year post-operatively, HOOS JR and EQ-5D-5L did ... not vary between groups (p = 0.48 and p = 0.56), nor did changes from baseline (p = 0.47 and p = 0.11 ... through 6 months (p = 0.03) and EQ-5D-5L through 3 months (p = 0.005), but not at 12 months (p = 0.89 and p ...

Abstract	Background: Patients undergoing total hip arthroplasty (THA) with the direct anterior approach (DAA) may experience faster recovery but may also have better baseline health than those who undergo THA with the posterior approach (PA). This study aimed to compare patient-reported outcome measures (PROMs) between the DAA and PA while controlling for baseline factors. Methods: This is a secondary data analysis from a prospective cohort study of patients utilizing a smartphone-based care management platform following THA. The primary outcomes were HOOS JR and EQ-5D-5L through 1 year and change from baseline. Longitudinal regression models were created to control for baseline characteristics and investigate the impact of surgical approach on PROMs. Results: Of 1364 THAs evaluated, 731 (53.6%) were female, and 840 (61.6%) used the PA. Patients in the PA group were of similar age but had higher body mass index and comorbidity scores. Pre-operative HOOS JR and EQ-5D-5L were comparable, but higher post-operatively in the DAA group through 6 months (p = 0.03 and p = 0.005). At 1 year post-operatively, HOOS JR and EQ-5D-5L did not vary between groups (p = 0.48 and p = 0.56), nor did changes from baseline (p = 0.47 and p = 0.11). After controlling baseline characteristics, DAA was significantly associated with higher average HOOS JR through 6 months (p = 0.03) and EQ-5D-5L through 3 months (p = 0.005), but not at 12 months (p = 0.89 and p = 0.56). Conclusion: THA patients undergoing DAA demonstrate earlier improvements in HOOS JR and EQ-5D-5L. However, these differences may not be clinically significant and are not evident at 1-year post-operative. Patient selection and surgeon training may continue to affect outcomes by surgical approach.
MeSH term(s)	Humans ; Arthroplasty, Replacement, Hip/methods ; Female ; Patient Reported Outcome Measures ; Male ; Aged ; Middle Aged ; Prospective Studies ; Postoperative Period
Language	English
Publishing date	2024-03-23
Publishing country	Germany
Document type	Journal Article ; Comparative Study
ZDB-ID	80407-1
ISSN	1434-3916 ; 0003-9330 ; 0344-8444
ISSN (online)	1434-3916
ISSN	0003-9330 ; 0344-8444
DOI	10.1007/s00402-024-05271-z
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Article ; Online: Characteristics and Outcomes of Cardiac Rehabilitation Patients With and Without Cancer: Insights From Western Sydney.

Hollings, Matthew / Gordon, Nicole / Redfern, Julie / Thomas, Liza / Singleton, Anna / Tu, Qiang / Zecchin, Robert

Heart, lung & circulation

2024

Abstract: ... oncology patients were older (68.8±10.6 vs 59.8±13.7yrs, p<0.001), more likely female (33% vs 21%, p<0.001 ... born in Australia (46% vs 35%, p=0.004), non-partnered (34% vs 25%, p=0.002) and had a prior history ... of hypertension (65% vs 56%, p=0.010) or stroke (8% vs 5%, p=0.045). After adjusting for age and sex, the overall ...

Abstract	Aim: Increased cardiovascular events are common in cancer survivors and contribute to an emerging cardio-oncology patient group requiring secondary prevention strategies including cardiac rehabilitation (CR). This study aimed to compare characteristics and outcomes for patients participating in CR with and without an existing cancer diagnosis. Method: Observational cohort study including consecutive patients enrolled in a single-centre outpatient CR program in Western Sydney between 2018-2022. Clinical history, demographics and CR outcome data were collected as part of standard care at program enrolment and completion. Patients with and without a cancer diagnosis were compared at enrolment and outcomes were analysed in both groups. Results: A total of 1,792 patients enrolled in CR, 191 (11%) had a documented history of cancer; prostate (18%), skin (12%), colon (9%) and breast (8%) malignancies were most prevalent. The most common treatments were surgical resection (80%) and chemotherapy or radiotherapy (37%). Cardio-oncology patients were older (68.8±10.6 vs 59.8±13.7yrs, p<0.001), more likely female (33% vs 21%, p<0.001), born in Australia (46% vs 35%, p=0.004), non-partnered (34% vs 25%, p=0.002) and had a prior history of hypertension (65% vs 56%, p=0.010) or stroke (8% vs 5%, p=0.045). After adjusting for age and sex, the overall cohort improved their mean peak exercise capacity and waist circumference after CR, however there were no differences between groups. There were also no between-group differences for adherence and completion of CR program or any other cardiovascular risk factors. Sub-analyses revealed a clinically meaningful improvement in waist circumference for cancer patients with a history of radiation therapy and a blunted peak exercise capacity adaptation for those with a history of chemotherapy treatment. Conclusions: Despite differences in demographic and clinical characteristics of CR patients with and without cancer, all patients showed significant and clinically relevant improvements in peak exercise capacity and waist circumference after CR. Results also highlighted potential associations between specific cancer treatments and changes in fitness outcomes, which warrants further evaluation.
Language	English
Publishing date	2024-01-16
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2020980-0
ISSN	1444-2892 ; 1443-9506
ISSN (online)	1444-2892
ISSN	1443-9506
DOI	10.1016/j.hlc.2023.11.017
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