Human Factor Research Articles

Mechanisms of action and resistance to anti-HER2 antibody-drug conjugates in breast cancer

Human epidermal growth factor 2 (HER2)-positive breast cancer (BC) represents nearly 20% of all breast tumors. Historically, these patients had a high rate of relapse and dismal prognosis. The advent of HER2-targeting monoclonal antibodies such as trastuzumab followed by pertuzumab had improved the prognosis of HER2-positive metastatic BC. More recently, antibody-drug conjugates (ADCs) are now reshaping the treatment paradigm of solid tumors, especially breast cancer. Tratsuzumab emtansine (T-DM1) was one of the first ADC developed in oncology and was approved for the management of HER2-positive metastatic BC. In a head-to-head comparison, trastuzumab deruxtecan (T-DXd) defeated T-DM1 as a second-line treatment. The efficacy of ADCs is counterbalanced by the appearance of acquired resistance to these agents. In this paper, we summarize the mechanisms of action and resistance of T-DM1 and T-DXd, as well as their clinical efficacy. Additionally, we also discuss potential strategies for addressing resistance to ADC.

Pilot Perceptions of Wire Strikes in Agricultural Aviation Operations.

INTRODUCTION: Agricultural aircraft operations are associated with unique challenges. In particular, these include maintaining awareness of obstacles associated with flight at very low altitudes. Wire strikes are a common cause of accidents in these operations.METHODS: Focus groups were completed during the 2022 Ag Aviation Expo hosted by the National Agricultural Aviation Association with pilots who had experienced wire-strike events (N = 22). The researchers coded the transcripts using a human factors framework.RESULTS: Notably, unplanned "trim passes" were a key stage of flight during wire-strike events. Cognitive risk factors that may have affected their performance included situation awareness, decision-making choices, and pressure to perform. Over half of subjects reported being aware of the wire before collision. Possible prevention strategies include not spraying the field due to safety risks, paying better attention to where they were in the field, and avoiding deviation from the planned route.DISCUSSION: Wire-strike events often occur due to momentary lapses in attention, even when the pilot is already aware of the wire. This study shows that targeted approaches to prevent wire strikes in agricultural aviation operations require addressing a number of cognitive risks and human factors, rather than implementing increased preflight surveillance. These results have implications for preventing future wire-strike accidents based directly on pilot perceptions, both within agricultural operations and general aviation more broadly.Baumgartner HM, DiDomenica R, Hu PT, Thomas S. Pilot perceptions of wire strikes in agricultural aviation operations. Aerosp Med Hum Perform. 2024; 95(6):305-312.

Isolation and Characterization of a Novel Mammary Adenocarcinoma, MCa-P1362, with Hormone Receptor Expression, Human Epidermal Growth Factor Receptor 2 Positivity, and Enrichment in Cancer and Mesenchymal Stem Cells

Preclinical models that display spontaneous metastasis are necessary to improve the therapeutic options for hormone receptor-positive breast cancers. Within this study, detailed cellular and molecular characterization was conducted on MCa-P1362, a newly established mouse model of metastatic breast cancer that is syngeneic in BALB/c mice. MCa-P1362 cancer cells express estrogen receptor, progesterone receptor, and the human epidermal growth factor receptor 2. MCa-P1362 cancer cells proliferate invitro and invivo in response to estrogen, yet do not depend on steroid hormones for growth and tumor progression. Analysis of MCa-P1362 tumor explants revealed the tumors contained a mixture of cancer cells and mesenchymal stromal cells. Through transcriptomic and functional analyses of both cancer and stromal cells, stem cells were detected within both populations. Functional studies demonstrated that MCa-P1362 cancer stem cells drove tumor initiation, whereas stromal cells from these tumors contributed to drug resistance. MCa-P1362 may serve as a useful preclinical model to investigate the cellular and molecular basis of breast tumor progression and therapeutic resistance.

Human Factors and Civility education – enhancing patient safety for Allied Health Professionals

Human Factors and Civility education – enhancing patient safety for Allied Health Professionals

The impact of grazing activities and environmental conditions on the stability of alpine grassland ecosystems

Globally, grazing activities have profound impacts on the structure and function of ecosystems. This study, based on a 20-year MODIS time series dataset, employs remote sensing techniques and the Seasonal-Trend decomposition using Loess (STL) algorithm to quantitatively assess the stability of alpine grassland ecosystems from multiple dimensions, and to reveal the characteristics of grazing activities and environmental conditions on ecosystem stability. The results indicate that only 5.77% of the area remains undisturbed, with most areas experiencing varying degrees of disturbance. Further analysis shows that grazing activities in high vegetation coverage areas are the main source of interference. In areas with concentrated interference, elevation and slope have a positive correlation with resistance stability, but a negative correlation with recovery stability. Precipitation and landscape diversity have positive effects on both resistance stability and recovery stability. Vegetation coverage and grazing intensity have a negative correlation with resistance stability, but a positive correlation with recovery stability. This highlights the complex interactions between human activities, environmental factors, and ecosystem stability. The findings emphasize the need for targeted conservation and management strategies to mitigate disturbances to ecosystems affected by human activities and enhance their stability.

Efficacy of First-Line Treatment With Pertuzumab and Trastuzumab in Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in Routine Clinical Practice.

The first-line treatment for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) involves a combination of trastuzumab, pertuzumab, and a taxane (TPH). This study assessed the efficacy of trastuzumab and pertuzumab (PH) in routine practice, following the treatment protocols of Uruguay's National Resources Fund (FNR), akin to clinical trials. Patients with advanced MBC treated with PH between 2008 and 2022 per FNR protocols were evaluated. The Kaplan-Meyer method and log-rank test were utilized for analyzing overall survival (OS). Demographic and clinical variables, including age, menopausal status, and hormone receptors (HR), were analyzed. The study included 318 PH-treated patients. The median age was 56 years, with 63.2% being postmenopausal and 60.4% HR and HER-2 positive. With a median follow-up of 17.2 months, the median OS was 29 months. OS varied based on HR status and the presence of metastases at different sites, significantly lower in patients with brain, cutaneous/subcutaneous, and pulmonary metastases. Additionally, OS was higher in patients treated at private institutions compared to public ones. This study demonstrates the disparity in oncological treatment efficacy between clinical trials and clinical reality in Uruguay, emphasizing the importance of authentic environment research for more representative and effective medicine in Latin America.

Cost-effectiveness Analysis of Intra- and Perilesional Recombinant Human Epidermal Growth Factor vs Hydrocolloid Therapy in Venous Ulcer Treatment in the Colombian Context

Cost-effectiveness Analysis of Intra- and Perilesional Recombinant Human Epidermal Growth Factor vs Hydrocolloid Therapy in Venous Ulcer Treatment in the Colombian Context

Beyond Chemoimmunotherapy in Advanced Non-Small Cell Lung Cancer: New Frontiers, New Challenges.

Chemoimmunotherapy is currently the preferred first-line treatment option for the majority of patients with advanced non-small cell lung cancer without driver genetic alterations. Most of these patients, however, will experience disease progression within the first year after treatment initiation and both patients and their physicians will be confronted with the dilemma of the optimal second-line treatment. Identification of molecular targets, such as KRASG12C, BRAFV600X, METexon14, and human epidermal growth factor receptor 2 mutations, and RET rearrangements offer therapeutic opportunities in pretreated patients with corresponding alterations. For those tumors that do not harbor oncogenic drivers, second-line treatment with docetaxel remains the current standard of care despite modest efficacy. Strategies to challenge docetaxel include the combination of immune checkpoint inhibitors (ICIs) with tyrosine inhibitors of multiple kinases or with DNA damage response inhibitors, antibody-drug conjugates, and locoregional treatments for oligoprogressive disease. Next-generation immunotherapy strategies, such as T-cell engagers, immune-mobilizing monoclonal T-cell receptors, chimeric antigen receptor cell therapy, tumor infiltrating lymphocytes, and T-cell receptor cell therapy are being currently investigated in the quest to reverse resistance to ICIs. Importantly, the advent of these new agents heralds a novel spectrum of toxicities that require both the physician's and the patient's education. Herein, we review current and future strategies aiming to outperform docetaxel after chemoimmunotherapy failure, and we provide practical information on how to best communicate to our patients the unique toxicity aspects associated with immunotherapy.

The Atypical Transport System: Natural Gas Pipeline System

The natural gas pipeline system (NGPS) is complex with a diverse network topology. This study elucidates the network characteristics of the NGPS, revealing that it shares commonalities with small-world networks, but with differences caused by its structural and operational characteristics. The combination of the low aggregation effect caused by branching structure and the offsetting effect caused by economic and geographical constraints results in a network with small world characteristics. NGPS has longer mean path than common small world network, but the aggregation factor is close to that of a standard small world network. With respect to its small-world characteristics and correlation with self-organized criticality (SOC), an in-depth study of the SOC characteristics of the NGPS was conducted utilizing a combination of traditional logarithm analysis and R/S analysis. The findings establish that there are atypical SOC characteristics, characterized by a weakened power law within a specific functional range, thereby encouraging the advancement of SCADA and other safety technologies. Because of the line-pack, which induces time lags in the NGPS, NGPS can prevent the cascade failures. The reasons for the periodicity and centrality of NGPS data are analyzed by the affecting components, with the R/S analysis verifying a weak positive correlation of the function data across different time series. The interlinking of the SOC and R/S analysis illustrates the connection between critical status, accident type, and operation index. The results prove the reasonability and importance of insurance measures, such as regular internal detection, higher grade steel pipes change and staff training et al., in a novel view of SOC. The future works in building accidents database and human factors study are proposed.

Enhancing landslide hazard prevention: Mapping vulnerability via considering the effects of human factors

Vulnerability mapping is necessary to reduce the effects of a landslide disaster. This study presents an approach to map vulnerability induced by a landslide hazard. The vulnerability was assessed by improved multi-criteria decision making (MCDM), in which the effects of human factors were incorporated. In the proposed approach, the weights of the indicators and factors were calculated using an integration method, including a grey decision-making trial and evaluation laboratory and the analytical hierarchy process (AHP) to calculate each index and factor’s weight. The effect of human factors is expressed as the ability of residents to cope with hazards in a community, which is evaluated by the adaptability index layer. The adaptability index layer includes four factors: gender ratio, age, education and medical resources. VIKOR is used to score and rank the adaptability index layer. The vulnerability is then mapped using geographic information system (GIS). A case study of historical landslides in Heyuan, China, was used for validation. The results demonstrate that 17.91% of Heyuan has the highest vulnerability, which is higher than that from the traditional method (13.76%). The model, considering adaptability, can predict areas with high vulnerability more accurately. Management recommendations are proposed via the following four specific aspects: i) urban vulnerability management and planning; ii) inter-regional differences in socio-economic vulnerability; iii) individual perceptions of landslides and iv) enhancing urban planning and strategies in similar cities.

Exploring the neutrophil-to-lymphocyte ratio as a prognostic biomarker in triple-negative breast cancer

Triple-negative breast cancer is a subtype characterized by the absence of estrogen receptor, progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 receptors, limiting treatment options primarily to chemotherapy due to lack of targeted therapies typically used for other breast cancer types, hence necessitating research for improved therapeutic strategies and outcomes. The neutrophil and lymphocyte percentages, absolute counts, and the ratio of neutrophils to lymphocytes were evaluated in peripheral blood of 81 patients with triple-negative breast cancer (TNBC) and 25 healthy controls. This study observed trend of high neutrophil percentage was observed in patients with positive lymph node status as compared to negative lymph node status. Significant high absolute neutrophil count was observed in patients with positive LN status, High BR score and presence of metastasis. A trend of high neutrophil to lymphocyte ratio was observed in patients with presence of perineural invasion, presence of necrosis, and patients with presence of metastasis.

Empirical investigation of drivers, motivations and barriers for implementation of integrated continuous improvement system: a case of Ethiopian manufacturing industries

PurposeContinuous improvement in an integrated approach is a philosophy developed over decades based on a set of management practices. It comprises enhancement methodologies that escalate success as well as diminishes letdowns. The state-of-the-art literature finds a variety of practices for the execution of continuous improvement (CI) system. However, it is rare to find an empirical study with an inclusive system that considers various practices in one frame for improving competitiveness. With this outlook, therefore, this study aims originally to identify drivers, motivations and barriers for the application of integrated CI system, and then conduct an empirical investigation within the context of Ethiopian manufacturing industries.Design/methodology/approachJustification of the problem, extensive review of literature, identification of practices, developing research framework, investigational analysis of the empirical study using reliability and descriptive statistical analysis and identifying leading drivers (unique practices and common factors), motivations and barriers are the research approaches used in this study. Furthermore, the primary data were collected through a self-administered questionnaire and were analyzed using a statistical package for social science (SPSS) 23 and the findings were triangulated to relate to the existing state-of-the-art literature.FindingsThe findings indicate 17 common factors associated with human, strategic, operational, technology, structure, resource and information factors; 21 unique practices of just-in-time (JIT), lean-six sigma (LSS), supply chain management (SCM), total productive maintenance (TPM), and total quality management (TQM) methodologies; 20 barriers connected with internal and external issues and 17 motivations linked to operational, innovation and business results are identified. In general, the empirical analysis discovers the practices are noteworthy and commonly supported by a least of 52% of the respondents. As a result, the first five prominent common factors, barriers, unique practices and motivations are also supported by a minimum of 72%, 73.9%, 65.8% and 75% of the respondents, respectively.Research limitations/implicationsEven though this is the first-ever study in the Ethiopian manufacturing sector with the focus on integrated CI practices of JIT, TQM, TPM, SCM and LSS initiatives, some limitations have existed and the major limitations of the study are, targeted merely small number manufacturing companies despite the fact that there are hundreds of companies implementing CI system in Ethiopia, and the data collected were only based on the perception of the respondents, and other information’s like annual reports was not employed to support the findings.Practical implicationsThe findings of this study underlined that the implementation of drivers in relation to common factors and unique practices supported by exterminating barriers in manufacturing industries of Ethiopia enables to enhance competitiveness through attaining operational, innovation and business results though it requires a practical case application to prove this perception-based analysis.Originality/valueThough there are a number of studies published on integrated continuous improvement, currently it is found that there is no literature focused on the identification and empirical investigation of drivers (common factors and unique practices), motivations and barriers for application of integrated CI system with the focus of JIT, TQM, TPM, SCM and LSS initiatives. Therefore, this is the first-ever study, and the empirical analysis of the study discovered that identified practices are providing valuable insights for manufacturing industries which will be on board on this voyage including institutions, practitioners and other sectors.

A clinical systematic literature review of treatments among patients with advanced and/or metastatic human epidermal growth factor receptor 2 positive breast cancer.

Aim: This systematic literature review aims to summarize the efficacy/effectiveness of treatments, including eribulin (ERI)-based and anti-human epidermal growth factor receptor 2 (HER2) treatments in advanced/metastatic HER2+ breast cancer. Methods: Three databases from 2016 to September 2021 were searched for clinical trials and observational studies in patients receiving first-line (1L) standard of care (SOC), second-line (2L) SOC or third-line or subsequent lines (3L+). Results: 2692 citations were screened, and 38 studies were included. Eleven studies were randomized-controlled trials (RCTs; 5 in 1L, 6 in 3L+), 6 were single-arm trials (5 in 1L, 1 in 3L+) and 21 were observational studies (13 in 1L, 6 in 2L, 4 in 3L+ [note that studies with subgroups for 1L, 2L, 3L+ are double-counted]). Longer overall survival (OS) was associated with 1L and 2L treatment, and for 3L+ studies that included ERI, ERI or trastuzumab (Tmab)+ERI led to longer OS than treatments of physician's choice (median OS of 11, 10 and 8.9months, respectively). Progression-free survival was 9months in Tmab+pertuzumab (Pmab)+ERI, 4months in Tmab+ERI and 3.3months in ERI. Conclusion: Available treatments provide a wide range of efficacy. However, later lines lack standardization and conclusions on comparative effectiveness are limited by differing trial designs. Thus, the chance of prolonged survival with new agents warrants further research.

Epitope binning for multiple antibodies simultaneously using mammalian cell display and DNA sequencing

Epitope binning, an approach for grouping antibodies based on epitope similarities, is a critical step in antibody drug discovery. However, conventional methods are complex, involving individual antibody production. Here, we established Epitope Binning-seq, an epitope binning platform for simultaneously analyzing multiple antibodies. In this system, epitope similarity between the query antibodies (qAbs) displayed on antigen-expressing cells and a fluorescently labeled reference antibody (rAb) targeting a desired epitope is analyzed by flow cytometry. The qAbs with epitope similar to the rAb can be identified by next-generation sequencing analysis of fluorescence-negative cells. Sensitivity and reliability of this system are confirmed using rAbs, pertuzumab and trastuzumab, which target human epidermal growth factor receptor 2. Epitope Binning-seq enables simultaneous epitope evaluation of 14 qAbs at various abundances in libraries, grouping them into respective epitope bins. This versatile platform is applicable to diverse antibodies and antigens, potentially expediting the identification of clinically useful antibodies.

Modelling error chains in offshore wind energy systems: Examining the interplay of human performance and machine state

A dynamic model of the mutual interdependency between humans and machines in offshore wind farms (OWFs) is developed in this paper. The model emphasises the importance of having early indicators to dynamically moderate human behaviour and the need to account for both human and physical subsystems and their mutual interactions for optimal asset management practices. This work simulates three distinct scenarios for: (1) examining the interconnectedness of technical and human dynamics and their implications on error and failure; (2) assessing the impact of production loss on human and organisational behaviour; and (3) evaluating human error probability as an early warning sign of production loss. The findings suggest that adopting an appropriate maintenance culture and considering human error likelihood and production rate in decision-making leads to optimising production and mitigating the risks associated with human error. The research highlights the significance of comprehending the complex interactions between human and machine factors in the operation and maintenance (O&M) of offshore wind turbines (OWTs). The proposed dynamic model helps organisations identify the underlying causes of errors, allowing them to improve their maintenance strategies.

Just the facts: integrating human and environmental factors in trauma resuscitation with Zero Point Survey.

Just the facts: integrating human and environmental factors in trauma resuscitation with Zero Point Survey.

Human mesenchymal stromal cells ameliorate cisplatin induced acute and chronic kidney injury via TSG-6.

Cisplatin is widely employed in tumor chemotherapy, but nephrotoxicity is an unavoidable side effect of cisplatin. Several studies have demonstrated that mesenchymal stromal cells (MSCs) ameliorate cisplatin-induced kidney injury, but the underlying mechanisms are unknown. In this study, the cisplatin-induced kidney injury mouse model was established by subjecting a single intraperitoneal injection with cisplatin. One hour before cisplatin injection, the mice received human bone marrow MSCs (hBM-MSCs) with or without siRNA-transfection, recombinant human tumor necrosis factor (TNF)-α-stimulated gene/protein 6 (rhTSG-6), or PBS through tail vein. In addition, cisplatin-stimulated HK-2 cells were treated with hBM-MSCs or rhTSG-6. hBM-MSCs treatment remarkably ameliorated cisplatin-induced acute and chronic kidney injury, as evidenced by significant reductions in serum creatinine (Scr), blood urea nitrogen (BUN), tubular injury, collagen deposition, α-smooth muscle actin accumulation, as well as inflammatory responses, and by remarkable increased anti-inflammatory factor expression and Treg cells infiltration in renal tissues. Furthermore, we found that only a few hBM-MSCs engrafted into damaged kidney and that the level of human TSG-6 in serum of mice increased significantly following hBM-MSCs administration. Moreover, hBM-MSCs significantly increased the viability of damaged HK-2 cells and decreased the levels of inflammatory cytokines in the culture supernatant. However, knockdown of TSG-6 gene in hBM-MSCs significantly attenuated their beneficial effects in vivo and in vitro. On the contrary, treated with rhTSG-6 achieved similar beneficial effects of hBM-MSCs. Our results indicate that systemic administration of hBM-MSCs alleviate cisplatin-induced acute and chronic kidney injury in part by paracrine TSG-6 secretion.

Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial

ObjectiveTo evaluate the efficacy and safety of tislelizumab added to chemotherapy as first line (primary) treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma compared with placebo plus chemotherapy.DesignRandomised, double blind,...

Expression of HER2 in urothelial carcinoma and its significance

Abstract Objectives We explored the expression levels and clinical significance of human epidermal growth factor receptor 2 (HER2) in urothelial carcinoma (UC) tissues. Materials and methods Patient data were reviewed, and 111 paraffin specimens of UC obtained from the Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, from 2020 to 2021 were collected. Immunohistochemistry was used to detect HER2 protein expression in all UC tumor tissues. χ 2 and Fisher exact tests were used to analyze the relationship between HER2 protein expression and clinicopathological data (sex, age, histopathological diagnosis, invasiveness, histopathological grade, maximum tumor diameter, muscle invasion, regional lymph node metastasis, and clinical stage). Results In this study, 92 cases (82.88%) showed HER2 protein expression, and there was a statistically significant difference in the distribution of HER2 positivity (immunohistochemistry 2+ and 3+) according to the pathological grades of UC (p = .021). Human epidermal growth factor receptor 2 positivity was not associated with sex, age, histopathological diagnosis, invasiveness, maximum tumor diameter, muscle invasion, regional lymph node metastasis, or clinical stage (all p < .05). Conclusions HER2 protein is highly expressed in UC, and its expression may be closely related to the high pathological grade of UC.

HER2 quantitative continuous scoring for accurate patient selection in HER2 negative trastuzumab deruxtecan treated breast cancer

Many targeted cancer therapies rely on biomarkers assessed by scoring of immunohistochemically (IHC)-stained tissue, which is subjective, semiquantitative, and does not account for expression heterogeneity. We describe an image analysis-based method for quantitative continuous scoring (QCS) of digital whole-slide images acquired from baseline human epidermal growth factor receptor 2 (HER2) IHC-stained breast cancer tissue. Candidate signatures for patient stratification using QCS of HER2 expression on subcellular compartments were identified, addressing the spatial distribution of tumor cells and tumor-infiltrating lymphocytes. Using data from trastuzumab deruxtecan-treated patients with HER2-positive and HER2-negative breast cancer from a phase 1 study (NCT02564900; DS8201-A-J101; N = 151), QCS-based patient stratification showed longer progression-free survival (14.8 vs 8.6 months) with higher prevalence of patient selection (76.4 vs 56.9%) and a better cross-validated log-rank p value (0.026 vs 0.26) than manual scoring based on the American Society of Clinical Oncology / College of American Pathologists guidelines. QCS-based features enriched the HER2-negative subgroup by correctly predicting 20 of 26 responders.