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Cancer Innovation Aug 2024The current standard of care for advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer is pertuzumab plus trastuzumab and docetaxel as...
BACKGROUND
The current standard of care for advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer is pertuzumab plus trastuzumab and docetaxel as first-line therapy. However, with the development of newer treatment regimens, there is a lack of evidence regarding which is the optimal treatment strategy. The aim of this network meta-analysis was to evaluate the efficacy and safety of first-line regimens for advanced HER2-positive breast cancer by indirect comparisons.
METHODS
A systematic review and Bayesian network meta-analysis were conducted. The PubMed, EMBASE, and Cochrane Library databases were searched for relevant articles published through to December 2023. The hazard ratio (HR) and 95% credible interval (CrI) were used to compare progression-free survival (PFS) between treatments, and the odds ratio and 95% CrI were used to compare the objective response rate (ORR) and safety.
RESULTS
Twenty randomized clinical trials that included 15 regimens and 7094 patients were analyzed. Compared with the traditional trastuzumab and docetaxel regimen, PFS was longer on the pyrotinib and trastuzumab plus docetaxel regimen (HR: 0.41, 95% CrI: 0.22-0.75) and the pertuzumab and trastuzumab plus docetaxel regimen (HR: 0.65, 95% CrI: 0.43-0.98). Consistent with the results for PFS, the ORR was better on the pyrotinib and trastuzumab plus docetaxel regimen and the pertuzumab and trastuzumab plus docetaxel regimen than on the traditional trastuzumab and docetaxel regimen. The surface under the cumulative ranking curve indicated that the pyrotinib and trastuzumab plus docetaxel regimen was most likely to rank first in achieving the best PFS and ORR. Comparable results were found for grade ≥3 AE rates of ≥10%.
CONCLUSIONS
Our results suggest that the pyrotinib and trastuzumab plus docetaxel regimen is most likely to be the optimal first-line therapy for patients with HER2-positive breast cancer.
PubMed: 38948247
DOI: 10.1002/cai2.126 -
PeerJ 2024Leaf inclination angle (LIA) and tillering impact the winter wheat ( L.) population canopy structure. Understanding their effects on water use (WU) parameters and yield...
Leaf inclination angle (LIA) and tillering impact the winter wheat ( L.) population canopy structure. Understanding their effects on water use (WU) parameters and yield can guide water-saving strategies through population control. In this study, six near-isogenic lines (NILs) and their parents were selected as materials. These special materials were characterized by varying tillering at the current sowing density, a similar genetic background, and, particularly, a gradient in mean flag leaf LIA. The investigation focused on the jointing to early grain-filling stage, the peak water requirement period of wheat crops. Population-scale transpiration (PT) and evaporation from the soil surface (E) were partitioned from total evapotranspiration (ET) by the means of micro-lysimeters. The results showed decreased PT, E, and ET with increased population density (PD) within a narrow density range derived from varying tillering across genotypes. Significant correlations existed between PD and ET, E, and PT, especially in the wettest 2017-2018 growing season. Within such narrow PD range, all the correlations between WU parameters and PD were negative, although some correlations were not statistically significant, thereby suggesting the population structure's predominant impact. No significant correlation existed between LIA and both ET and PT within the LIA range of 35°-65°. However, significant correlations occurred between LIA and E in two growing seasons. Genotypes with similar LIA but different PD produced varied ET; while with similar PD, the four pairs of genotypes with different LIA each consumed similar ET, thus highlighting PD's more crucial role in regulating ET. The yield increased with higher LIA, and showed a significant correlation, emphasizing the LIA's significant effect on yield. However, no correlation was observed with PD, indicating the minor effect of tillering at the current sowing density. Therefore these results might offer valuable insights for breeding water-saving cultivars and optimizing population structures for effective field water conservation.
Topics: Triticum; Plant Leaves; Plant Transpiration; Soil; Seasons; Water; Genotype
PubMed: 38948218
DOI: 10.7717/peerj.17618 -
PeerJ 2024The integration of diagnostic methods holds promise for advancing the surveillance of malaria transmission in both endemic and non-endemic regions. Serological assays...
BACKGROUND
The integration of diagnostic methods holds promise for advancing the surveillance of malaria transmission in both endemic and non-endemic regions. Serological assays emerge as valuable tools to identify and delimit malaria transmission, serving as a complementary method to rapid diagnostic tests (RDT) and thick smear microscopy. Here, we evaluate the potential of antibodies directed against peptides encompassing the entire amino acid sequence of the MSP-1 Sal-I strain as viable serological biomarkers for exposure.
METHODS
We screened peptides encompassing the complete amino acid sequence of the Merozoite Surface Protein 1 (MSP-1) Sal-I strain as potential biomarkers for exposure. Here, immunodominant peptides specifically recognized by antibodies from individuals infected with were identified using the SPOT-synthesis technique followed by immunoblotting. Two 15-mer peptides were selected based on their higher and specific reactivity in immunoblotting assays. Subsequently, peptides p70 and p314 were synthesized in soluble form using SPPS (Solid Phase Peptide Synthesis) and tested by ELISA (IgG, and subclasses).
RESULTS
This study unveils the presence of IgG antibodies against the peptide p314 in most -infected individuals from the Brazilian Amazon region. B-cell epitope prediction further supports the utilization of p314 as a potential biomarker for evaluating malaria transmission, strengthened by its amino acid sequence being part of a conserved block of MSP-1. Indeed, compared to patients infected with and uninfected individuals never exposed to malaria, -infected patients have a notably higher recognition of p314 by IgG1 and IgG3.
Topics: Humans; Malaria, Vivax; Merozoite Surface Protein 1; Plasmodium vivax; Biomarkers; Antibodies, Protozoan; Immunoglobulin G; Adult; Female; Male; Middle Aged; Peptides; Enzyme-Linked Immunosorbent Assay; Young Adult; Adolescent; Amino Acid Sequence
PubMed: 38948214
DOI: 10.7717/peerj.17632 -
Plastic and Reconstructive Surgery.... Mar 2024Breast reduction is one of the most required plastic surgery procedures worldwide, improving significantly the quality of life for patients with macromastia and...
Breast reduction is one of the most required plastic surgery procedures worldwide, improving significantly the quality of life for patients with macromastia and gigantomachia. Despite various proposed approaches aiming to yield more stable results postreduction, no single technique has demonstrated unequivocal superiority. Recurrence ptosis at 6-12 months postoperative remains a challenging concern. To improve this issue, the authors propose a novel application of the poly-4-hydroxybutyrate (P4HB) scaffold on the anterior surface of the Ribeiro dermo-adipose flap. The primary aim was to establish a durable and resilient biological connection between the mammary gland and the flap, thereby promoting long-lasting outcomes in breast reduction procedures. The P4HB scaffold is a monofilament, single-layer, biologically derived, fully resorbable, rapidly integrating within breast tissue; this biological process stimulates the formation of freshly vascularized connective tissue up to a thickness of 2-3 mm. Within 18-24 months, the scaffold undergoes gradual resorption through hydrolysis-based mechanism, providing enhanced strength and resistance to the native tissue, as shown in animal model. A key innovation proposed by the authors involves the division of a 15 × 20 cm rectangular sheet of the P4HB scaffold along its diagonal, resulting in two right triangles. This modification ensures increased height of the device if compared with the traditional splitting technique of the scaffold. The strategic establishment of a biological bridge between the mammary gland and flap through the implementation of the P4HB scaffold could potentially enhance the longevity and aesthetics of breast reduction outcomes.
PubMed: 38948158
DOI: 10.1097/GOX.0000000000005676 -
World Journal of Stem Cells Jun 2024Proliferation and differentiation of intestinal stem cell (ISC) to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating...
Proliferation and differentiation of intestinal stem cell (ISC) to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating gut inflammation. However, when this disordered proliferation continues, it induces the ISC to enter a cancerous state. The gut microbiota on the free surface of the gut mucosal barrier is able to interact with ISC on a sustained basis. Microbiota metabolites are able to regulate the proliferation of gut stem and progenitor cells through transcription factors, while in steady state, differentiated colonocytes are able to break down such metabolites, thereby protecting stem cells at the gut crypt. In the future, the gut flora and its metabolites mediating the regulation of ISC differentiation will be a potential treatment for enteropathies.
PubMed: 38948097
DOI: 10.4252/wjsc.v16.i6.619 -
Materials Today. Bio Aug 2024The complex biological process of osseointegration and the bio-inertness of bone implants are the major reasons for the high failure rate of long-term implants, and have...
The complex biological process of osseointegration and the bio-inertness of bone implants are the major reasons for the high failure rate of long-term implants, and have also promoted the rapid development of multifunctional implant coatings in recent years. Herein, through the special design of peptides, we use layer-by-layer assembly technology to simultaneously display two peptides with different biological functions on the implant surface to address this issue. A variety of surface characterization techniques (ellipsometry, atomic force microscopy, photoelectron spectroscopy, dissipation-quartz crystal microbalance) were used to study in detail the preparation process of the dual peptide functional coating and the physical and chemical properties, such as the composition, mechanical modulus, stability, and roughness of the coating. Compared with single peptide functional coatings, dual-peptide functionalized coatings had much better performances on antioxidant, cellular adhesion in early stage, proliferation and osteogenic differentiation in long term, as well as in vivo osteogenesis and osseointegration capabilities. These findings will promote the development of multifunctional designs in bone implant coatings, as a coping strategy for the complexity of biological process during osteointegration.
PubMed: 38948091
DOI: 10.1016/j.mtbio.2024.101108 -
Frontiers in Oral Health 2024To determine which components in a new restorative material (Renewal MI) improve its ability to form resin tags within demineralized dentine.
OBJECTIVES
To determine which components in a new restorative material (Renewal MI) improve its ability to form resin tags within demineralized dentine.
METHODS
Varied components included polylysine (PLS), monocalcium phosphate (MCP), powder to liquid ratio (PLR), 4-methacryloyloxyethyl trimellitate anhydride (4META), and polypropylene glycol dimethacrylate (PPGDMA). Urethane dimethacrylate (UDMA), containing PPGDMA (24 wt%) and 4META (3 wt%), was mixed with glass filler with MCP (8 wt%) and PLS (5 wt%). PLR was 3:1 or 5:1. Reducing MCP and/or PLS to 4 and 2 wt% respectively or fully removing MCP, PLS, 4META or PPGDMA gave 16 formulations in total. Renewal MI, Z250 (with or without Scotchbond Universal adhesive) and Activa were used as commercial comparators. Collagen discs were obtained by totally demineralizing 2 mm thick, human, premolar, coronal dentine discs by immersion in formic acid (4M) for 48 h. The restorative materials were then applied on top ( = 3), before dissolving the collagen in sodium hypochlorite (15%). SEM/EDX was employed to determine resin tags length, composition, and surface coverage.
RESULTS
Tags were >400, 20 and 200 µm and covered 62, 55 and 39% of the adhesion interface for Renewal MI, Scotchbond and Activa, respectively. With experimental formulations, they were 200 and >400 µm long with high vs. low PLR and composed primarily of polymerized monomers. Percentages of the adhesion interface covered varied between 35 and 84%. Reducing PLS or MCP caused a decline in coverage that was linear with their concentrations. Reducing MCP had lesser effect when PLS or PLR were low. Removal of 4META caused a greater reduction in coverage than PPGDMA removal.
CONCLUSION
PLS, MCP, 4META, PPGDMA and low PLR together enhance Renewal MI tags formation in, and thereby sealing of, demineralized dentine.
PubMed: 38948090
DOI: 10.3389/froh.2024.1420541 -
Frontiers in Physiology 2024Proximal tubule (PT) cells maintain a high-capacity apical endocytic pathway to recover essentially all proteins that escape the glomerular filtration barrier. The multi...
Proximal tubule (PT) cells maintain a high-capacity apical endocytic pathway to recover essentially all proteins that escape the glomerular filtration barrier. The multi ligand receptors megalin and cubilin play pivotal roles in the endocytic uptake of normally filtered proteins in PT cells but also contribute to the uptake of nephrotoxic drugs, including aminoglycosides. We previously demonstrated that opossum kidney (OK) cells cultured under continuous fluid shear stress (FSS) are superior to cells cultured under static conditions in recapitulating essential functional properties of PT cells . To identify drivers of the high-capacity, efficient endocytic pathway in the PT, we compared FSS-cultured OK cells with less endocytically active static-cultured OK cells. Megalin and cubilin expression are increased, and endocytic uptake of albumin in FSS-cultured cells is > 5-fold higher compared with cells cultured under static conditions. To understand how differences in receptor expression, distribution, and trafficking rates contribute to increased uptake, we used biochemical, morphological, and mathematical modeling approaches to compare megalin traffic in FSS- versus static-cultured OK cells. Our model predicts that culturing cells under FSS increases the rates of all steps in megalin trafficking. Importantly, the model explains why, despite seemingly counterintuitive observations (a reduced fraction of megalin at the cell surface, higher colocalization with lysosomes, and a shorter half-life of surface-tagged megalin in FSS-cultured cells), uptake of albumin is dramatically increased compared with static-grown cells. We also show that FSS-cultured OK cells more accurately exhibit the mechanisms that mediate uptake of nephrotoxic drugs compared with static-grown cells. This culture model thus provides a useful platform to understand drug uptake mechanisms, with implications for developing interventions in nephrotoxic injury prevention.
PubMed: 38948083
DOI: 10.3389/fphys.2024.1404248 -
Frontiers in Molecular Biosciences 2024Alzheimer's disease (AD) is a progressive debilitating neurological disorder representing the most common neurodegenerative disease worldwide. Although the exact...
Alzheimer's disease (AD) is a progressive debilitating neurological disorder representing the most common neurodegenerative disease worldwide. Although the exact pathogenic mechanisms of AD remain unresolved, the presence of extracellular amyloid-β peptide 1-42 (Aβ) plaques in the parenchymal and cortical brain is considered one of the hallmarks of the disease. In this work, we investigated the Aβ fibrillogenesis timeline up to 48 h of incubation, providing morphological and chemo-structural characterization of the main assemblies formed during the aggregation process of Aβ, by atomic force microscopy (AFM) and surface enhanced Raman spectroscopy (SERS), respectively. AFM topography evidenced the presence of characteristic protofibrils at early-stages of aggregation, which form peculiar macromolecular networks over time. SERS allowed to track the progressive variation in the secondary structure of the aggregation species involved in the fibrillogenesis and to determine when the β-sheet starts to prevail over the random coil conformation in the aggregation process. Our research highlights the significance of investigating the early phases of fibrillogenesis to better understand the molecular pathophysiology of AD and identify potential therapeutic targets that may prevent or slow down the aggregation process.
PubMed: 38948077
DOI: 10.3389/fmolb.2024.1376411 -
Space Science Reviews 2024The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper... (Review)
Review
The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper mission. REASON is designed to probe Europa from exosphere to subsurface ocean, contributing the third dimension to observations of this enigmatic world. The hypotheses REASON will test are that (1) the ice shell of Europa hosts liquid water, (2) the ice shell overlies an ocean and is subject to tidal flexing, and (3) the exosphere, near-surface, ice shell, and ocean participate in material exchange essential to the habitability of this moon. REASON will investigate processes governing this material exchange by characterizing the distribution of putative non-ice material (e.g., brines, salts) in the subsurface, searching for an ice-ocean interface, characterizing the ice shell's global structure, and constraining the amplitude of Europa's radial tidal deformations. REASON will accomplish these science objectives using a combination of radar measurement techniques including , , , , , and . Building on a rich heritage from Earth, the moon, and Mars, REASON will be the first ice-penetrating radar to explore the outer solar system. Because these radars are untested for the icy worlds in the outer solar system, a novel approach to measurement quality assessment was developed to represent uncertainties in key properties of Europa that affect REASON performance and ensure robustness across a range of plausible parameters suggested for the icy moon. REASON will shed light on a never-before-seen dimension of Europa and - in concert with other instruments on Europa Clipper - help to investigate whether Europa is a habitable world.
PubMed: 38948073
DOI: 10.1007/s11214-024-01072-3