Human Factor Research Articles

India's flood risk assessment and mapping with multi-criteria decision analysis and GIS integration

ABSTRACT India's diverse geography poses significant flood risks, addressed in this study through the geographic information system and multi-criteria decision analysis. This comprehensive flood risk assessment considers seven parameters: mean annual precipitation, elevation, slope, drainage density (DD), land use and land cover, proximity to roads, and distance to rivers. The findings indicate that flood vulnerability is primarily influenced by rainfall, elevation, and slope, with DD, land use, and proximity to roads and rivers also playing crucial roles. Experts weighed these factors to create a thorough flood risk map using the normalized rank index and normalized weight index, categorizing areas into five risk levels: very high, high, moderate, low, and very low. The study reveals that 3.40% of the area is at very high risk, 32.65% at high risk, 39.72% at moderate risk, 20.97% at low risk, and 3.25% at very low risk. These results highlight how human and natural factors interact to influence flood risk, with vulnerable areas characterized by low elevations, steep slopes, high drainage densities, and proximity to rivers or roads. The findings provide valuable insights for policymakers, scientists, and local authorities to develop strategies to mitigate flood losses across India's varied landscapes.

Airway management in pediatrics: improving safety

AbstractAirway management in children poses unique challenges due to the different anatomy, physiology, and pathophysiology across the pediatric age span. The recently published joint European Society of Anaesthesiology and Intensive Care-British Journal of Anaesthesia (ESAIC-BJA) neonatal and infant airway management guidelines provide recommendations and suggestions to support clinicians in deciding the best strategy. These guidelines represent a framework with the most recent and up-to-date evidence, from the initial assessment to the management of normal and difficult airways up to the extubation phase. However, such guidelines have intrinsic limitations due to the lack of supporting evidence in various fields of airway management. Pediatric institutions should adopt guidelines after careful internal review according to the local circumstances, including caseload, equipment and expertise. The current narrative review focused on providing references and practical tips on pediatric airway management, which is still not completely elucidated. Moreover, the authors put particular emphasis on the influence of human factors on the overall success of tracheal intubation, the incidence of complications, and the outcomes for patients.

Abstract A017: HER2 overexpression initiates breast tumorigenesis non-cell-autonomously by altering energy metabolism in the tissue microenvironment

Abstract Breast cancer is the most common cancer globally, with approximately 70% of pre-malignant breast tumors, known as ductal carcinoma in situ (DCIS), and 20% of invasive breast tumors overexpressing human epidermal growth factor receptor 2 (HER2). While the biological role of HER2 in invasive breast cancer has been extensively studied, its impact on breast cancer stem cells (BCSCs) and early-stage tumorigenesis, particularly within the tumor microenvironment, remains unclear. Here, we explore the role of HER2 overexpression in driving cellular events within the tumor microenvironment during the premalignant stage of breast tumorigenesis, using in vitro, in vivo, and ex vivo models. We conducted multi-omics analyses on mammary ducts from a HER2+ breast cancer mouse model at the pre-cancerous stage. Our results showed that HER2/Neu overexpression alters glucose and lipid metabolism and pentose phosphate pathway in mammary epithelial cells. Ex vivo organ culture of mammary ducts confirmed that these metabolic changes lead to increased reactive oxygen species (ROS) levels within the tumor microenvironment suggesting that oxidative stress and subsequent DNA damage are early events in HER2-driven tumorigenesis. Immunostaining of histological sections from mouse mammary glands further revealed that elevated oxidative stress and DNA damage not only in HER2+ cells but also in neighboring HER2- cells. Moreover, whole genome sequencing of tumor cells confirmed that both HER2+ and HER2- tumor cells have similar mutational burden. This suggests a non-cell-autonomous effect, where HER2 overexpression in one cell population affects the tumor microenvironment and adjacent cells, contributing to early-stage cancer development. To investigate the involvement of BCSCs during tumor initiation, we performed mammosphere assays on primary cells from HER2+ mouse models and clinical DCIS samples. Our findings showed that neither BCSCs nor their cells of origin express HER2 in both DCIS samples and murine mammary glands and tumors. This suggests that HER2 overexpression may not directly drive BCSC formation but rather creates a genotoxic microenvironment that facilitates the transformation of HER2- cell populations through a non-cell-autonomous mechanism. In summary, our findings indicate that HER2 overexpression contributes to the creation of a genotoxic tumor microenvironment by altering cellular energy metabolism and increasing ROS levels. This, in turn, may lead to the transformation of BCSCs in HER2- cell populations during early breast tumorigenesis. Understanding the role of HER2 overexpression in shaping the tumor microenvironment could provide new insights into therapeutic and preventive strategies against breast cancer. Citation Format: Sevim B. Gurler, Oliver Wagstaff, Lili Dimitrova, Fuhui Chen, Robert Pedley, William Weston, Ian J. Donaldson, Brian A. Telfer, David Novo, Kyriaki Pavlou, George Taylor, Yaqing Ou, Kaye Williams, Andrew Gilmore, Keith Brennan, Ahmet Ucar. HER2 overexpression initiates breast tumorigenesis non-cell-autonomously by altering energy metabolism in the tissue microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A017.

Real-world application of disitamab vedotin (RC48-ADC) in patients withbreast cancer with different HER2 expression levels: efficacy and safety analysis.

Disitamab vedotin (RC48-ADC), an antibody-drug conjugate (ADC), combines specific antibody disitamab with cytotoxicity monomethyl auristatin E to effectively target the human epidermal growth factor receptor 2 (HER2) protein on tumor cells for precise elimination. Recent studies have demonstrated that RC48-ADC offers therapeutic benefits for patients with HER2-positive and HER2-low-expression breast cancer (BC). However, a thorough exploration of its efficacy and safety in real-world settings for patients with metastatic breast cancer (mBC) is currently lacking. This retrospective, multicenter, real-world study included patients with mBC who received RC48-ADC from September 2021 to March 2024. These patients include HER2-positive BC and HER2-low-expression BC. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), restricted mean survival time, objective response rate (ORR), and disease control rate (DCR). Factors affecting efficacy and the occurrence of treatment-related adverse events (TRAE) were evaluated. The study included a cohort of 89 patients with mBC, with 48 of those being identified as HER2-positive. As of March 2024, 22 deaths were recorded, with an immature median OS. Total PFS varied from 1.0 to 31.2 months, with a median of 5.5 months (95% CI, 4.368-6.632). HER2-positive patients exhibited prolonged PFS compared with HER2-low-expression patients (6.6 months vs 4.1 months, P = .023). The overall ORR stood at 25.8% (95% CI, 0.178-0.358), with higher rates observed in HER2-positive patients compared with HER2-low-expression patients (31.3% vs 19.5%). Similarly, the overall DCR was 78.7% (95% CI, 0.691-0.859), with HER2-positive patients demonstrating superior DCR compared with HER2-low-expression patients (83.3% vs 73.2%). Notably, HER2 expression emerged as the primary determinant of RC48-ADC efficacy. The most prevalent TRAE among all patients included leukopenia (21.3%) and alopecia (20.2%). RC48-ADC showcases promising efficacy and manageable safety in patients with both HER2-positive and HER2-low-expression mBC.

Human Factors, Human-Centered Design, and Usability of Sensor-Based Digital Health Technologies: Scoping Review.

Increasing adoption of sensor-based digital health technologies (sDHTs) in recent years has cast light on the many challenges in implementing these tools into clinical trials and patient care at scale across diverse patient populations; however, the methodological approaches taken toward sDHT usability evaluation have varied markedly. This review aims to explore the current landscape of studies reporting data related to sDHT human factors, human-centered design, and usability, to inform our concurrent work on developing an evaluation framework for sDHT usability. We conducted a scoping review of studies published between 2013 and 2023 and indexed in PubMed, in which data related to sDHT human factors, human-centered design, and usability were reported. Following a systematic screening process, we extracted the study design, participant sample, the sDHT or sDHTs used, the methods of data capture, and the types of usability-related data captured. Our literature search returned 442 papers, of which 85 papers were found to be eligible and 83 papers were available for data extraction and not under embargo. In total, 164 sDHTs were evaluated; 141 (86%) sDHTs were wearable tools while the remaining 23 (14%) sDHTs were ambient tools. The majority of studies (55/83, 66%) reported summative evaluations of final-design sDHTs. Almost all studies (82/83, 99%) captured data from targeted end users, but only 18 (22%) out of 83 studies captured data from additional users such as care partners or clinicians. User satisfaction and ease of use were evaluated for 83% (136/164) and 91% (150/164) of sDHTs, respectively; however, learnability, efficiency, and memorability were reported for only 11 (7%), 4 (2%), and 2 (1%) out of 164 sDHTs, respectively. A total of 14 (9%) out of 164 sDHTs were evaluated according to the extent to which users were able to understand the clinical data or other information presented to them (understandability) or the actions or tasks they should complete in response (actionability). Notable gaps in reporting included the absence of a sample size rationale (reported for 21/83, 25% of all studies and 17/55, 31% of summative studies) and incomplete sociodemographic descriptive data (complete age, sex/gender, and race/ethnicity reported for 14/83, 17% of studies). Based on our findings, we suggest four actionable recommendations for future studies that will help to advance the implementation of sDHTs: (1) consider an in-depth assessment of technology usability beyond user satisfaction and ease of use, (2) expand recruitment to include important user groups such as clinicians and care partners, (3) report the rationale for key study design considerations including the sample size, and (4) provide rich descriptive statistics regarding the study sample to allow a complete understanding of generalizability to other patient populations and contexts of use.

Diachronic and historical evolution of the Al-Hoceima Bay coastline, Moroccan Mediterranean Sea

Al-Hoceima Bay, located on the northern coast of Morocco, holds significant environmental importance. It also faces environmental challenges, including the pressures resulting from urban sprawl and growing number of tourists, as well as the impacts of climate change. The objective of this study is to assess the coastal changes in Al- Hoceima Bay since 1964, considering both natural and human factors. This study is based on the diachronic analysis of aerial photographs taken over a period of 56 years, utilising the digital shoreline analysis system statistical technique to calculate the shoreline’s mobility index for each period. The results demonstrate significant erosion at the Tayth beach (−1.50 m∙y−1) and Souani beach (approximately −1.90 m∙y−1), whereas accretion was experienced at the Sfiha beach at a rate of about +1.11 m∙y−1 and at the Lharch beach at a rate of +0.92 m∙y−1. The mouth of the Nekôr River experienced the highest retreat at −3.15 m∙y−1, followed by Ghiss at −2.00 m∙y−1. These findings indicate the impact of human interventions, such as the construction of the Mohamed Ben Abdelkarim El Khattabi dam on Oued Nekôr since 1981, as well as climate changes that have led to decreased flow, particularly at Oued Ghiss. These combined climatic and anthropogenic impacts have exacerbated erosion and disrupted the sediment balance along the shoreline of Al-Hoceima Bay.

Case series of pure mucinous breast carcinoma: A rare histopathological subtype

Pure mucinous breast carcinoma (PMBC) is even rarer and accounts for about 2% of all primary breast carcinoma. It is composed entirely of tumour cells with abundant extracellular mucin and without admixing of infiltrating ductal carcinoma. We studied a total of ten cases of Pure Mucinous Breast Carcinoma. Here we describes each case of demographic features and histopathological features of PMBC. The results of immunohistochemistry of Estrogen receptor (ER), Progesterone receptor (PR), Human epidermal growth factor receptor 2(HER-2neu) were also noted in this case series. All the cases were female and above 50 years of age. Out of 10 cases, 6 cases have the tumour’s location on the left side of the breast and 4 cases have the tumour’s location on the right side of the breast. All the cases belong to the lower grading and staging of the tumour. Only one case had positive lymph node status.Hormone receptor status of all the cases has ER & PR positive expression, HER-2neu negative expression and low Ki 67 labelling index. To conclude, PMBC was associated with lower-grade tumours, lower-stage, infrequent lymph node metastasis and luminal type A hormonal receptor status. These favourable findings suggest that PMBC has a better prognosis and may give a better response to hormonal therapy.

Porcine Airway Organoid-Derived Well-Differentiated Epithelial Cultures as a Tool for the Characterization of Swine Influenza a Virus Strains

Swine influenza A viruses (IAVsw) are important causes of disease in pigs but also constitute a public health risk. IAVsw strains show remarkable differences in pathogenicity. We aimed to generate airway organoids from the porcine lower respiratory tract and use these to establish well-differentiated airway epithelial cell (WD-AEC) cultures grown at an air–liquid interface (ALI) for in vitro screening of IAVsw strain virulence. Epithelial cells were isolated from bronchus tissue of juvenile pigs, and airway organoids were cultured in an extracellular matrix in a culture medium containing human growth factors. Single-cell suspensions of these 3D organoids were seeded on Transwell filters and differentiated at ALI to form a pseudostratified epithelium containing ciliated cells, mucus-producing cells and tight junctions. Inoculation with a low dose of IAVsw in a low volume inoculum resulted in virus replication without requiring the addition of trypsin, and was quantified by the detection of viral genome loads in apical washes. Interestingly, inoculation of an H3N2 strain known to cause severe disease in pigs induced a greater reduction in trans-epithelial resistance and more damage to tight junctions than H1N2 or H1N1 strains associated with mild disease in pigs. We conclude that the porcine WD-AEC model is useful in assessing the virulence of IAVsw strains.

The impact of preoperative treatment on mismatch repair protein and HER2 expression in colorectal cancer: an analysis of paired samples.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, highlighting the necessity for multifaceted treatment strategies, including preoperative treatment (PT), which can enhance surgical outcomes and provide prognostic insights. This study aims to clarify the impact of PT-induced changes in mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) expression, potentially informing tailored treatment strategies and improving clinical outcomes for CRC patients. This retrospective study analyzed 120 paired samples from CRC patients who underwent preoperative treatment, comparing pre- and post-treatment specimens. A control group of 60 untreated surgical specimens was also included. Immunohistochemistry assessed MMR proteins (MSH6, MSH2, MLH1, PMS2) and HER2 expression. MSI status was determined in samples with low MMR expression. Compared to pre-treatment samples, post-treatment samples exhibited lower levels of MSH6, MSH2, and total MMR expression, along with higher levels of HER2 expression. However, when compared to the untreated control group, there were no significant differences in the expression of MSH6, total MMR, and HER2. All samples that exhibited weak MMR expression and those that shifted to deficient mismatch repair (dMMR) status following treatment had stable microsatellite status. No clear clinicopathological characteristics or prognostic factors were found to be associated with changes in MMR and HER2 expression, except for the use of fluorouracil or capecitabine, which was related to changes in total MMR scores. ypTNM stage and TRG scores were identified as independent factors affecting disease progression in our study. PT is associated with a reduction in MMR expression, notably for the MSH2 protein, while it does not appear to influence HER2 expression.

Social technologies in management of modern Russian society

The article attempts to characterize the problem field of scientific research of the Department of Social Technologies of the Sociological Faculty of Moscow State University as part of the study of social technologies in the management of modern Russian society, with an emphasis on the technology of modernization of the Russian society and transformation of management practices in the context of new external challenges (primarily related to the active introduction of digital information and communication technologies).Modern Russian society is developing in the context of external and internal challenges requiring the transformation of management practices and the development of new social technologies. In connection with the need to implement the task set by the authorities of choosing a way of further development and rethinking the system of spiritual and moral values, the problem of the development, selection and application of social technologies of socio-cultural, economic and political modernization of Russian society has been actualized. Looking retrospectively at the process of modernization of Russia, one can clearly see the “pendulum” of development — in the direction of borrowing “Western” experience and implementing reforms by western standards or, on the contrary, “return to the roots” and implementing counter-reforms. In the current geopolitical situation, we can state that there has been a demand not only for a return to traditional values and conservative ideology, but also for a rethinking of Russia as a “distinct civilization”.Serious challenges (socio-demographic changes, digitalization, algorithmization, robotization, development of artificial intelligence, machine learning, shering economy, etc.) facing society and its social institutions today, require rethinking management practices and social technologies. The digitalization of social management is increasingly challenging the identification and analysis of the social consequences of introducing artificial intelligence, replacing human labor with machine and algorithms. When we talk about changing the nature of management in a digitalized society, we see an increasing penetration of artificial intelligence technologies into the field of management and the development of algorithmic control. Algorithms are now used in public administration, social services and social services, education, health. The autonomy and autonomization of algorithmic solutions raise serious questions about reducing the role of the human factor in management, which is alarming, especially in spheres that have traditionally been built around the human being. In addition, machines do not just study a person, they try to push him to make certain decisions, to a given behavioral response to a given stimulus, open new possibilities for manipulation. With the active introduction of digital technologies in all spheres of public life and in the management system, there are fears of total digital control. As digital platforms gain more instrumental power and access to personal data, so does the resistance of users of digital platforms due to a lack of control over the “fate” of the data provided. All this can lead to an increase in social tensions, which cannot be ignored when implementing management practices and choosing modern social technologies of management of society.

Enzyme-free and highly sensitive detection of human epidermal growth factor receptor-2 based on MNAzyme signal amplification in breast cancer.

As a common cancer biomarker, human epidermal growth factor receptor-2 (HER2) is highly expressed in breast cancer. Consequently, developing a simple and accurate HER2 sensing platform is of great significance for early diagnosis and treatment of breast cancer. Herein, we developed a rapid enzyme-free fluorescent assay biosensor based on MNAzyme signal amplification for breast cancer biomarker, HER2. The MNAzyme consists of multiple parts, including complementary DNA (cDNA) and two parts of DNAzyme (partzyme A/B). Initially, cDNA is blocked by combining with the HER2 aptamer to form a double-stranded DNA. When HER2 is present, cDNA is released as a result of the binding between HER2 and its aptamer. Due to the complementary sequences among cDNA and partzyme A/B, the MNAzyme is successfully assembled to cleave the substrate, recovering the fluorescence output. The MNAzyme biosensor exhibited a low detection limit of 0.02 ng mL-1 and excellent selectivity. Furthermore, the proposed biosensor can also change the recognition element by changing the aptamer sequence to detect various biomarkers, holding great potential for cancer diagnosis and other related biomedical applications.

Analysis of Synergistic Changes in PM2.5 and O3 Concentrations Based on Structural Equation Model Study

Given the increasing importance of effectively identifying synergistic changes between PM2.5 and O3 and comprehensively analyzing their impact on air quality management in China, we employ the Sen+Mann–Kendall (Sen+M-K) trend test in this study to examine the temporal and spatial variation trends of PM2.5 and O3 in the Yangtze River Delta (YRD), from 2003 to 2020. We identified the regions where these pollutants exhibited synergistic changes and established the pathways between the pollutants and their potential drivers, using geographically weighted random forest algorithms and structural equation modeling. The study results revealed as follows: (1) Overall, the PM2.5 concentrations show a decreasing trend, while the O3 concentrations exhibit an increasing trend, in the YRD. Analysis of the combined trends indicates that approximately 95% of the area displays opposing trends for PM2.5 and O3, with only about 4% in the southern region showing synergistic trends for both pollutants. (2) Drought and the average temperature are the main drivers of the changes in PM2.5 and O3 concentrations in areas experiencing synergistic changes. Their combined effects alleviate the aggregation of PM2.5 and reduce the formation of VOCs, indirectly reducing the generation of pollutants. The negative effect of the average temperature on the O3 concentration may indicate the existence of nonlinear effects and complex interaction effects between the drivers. NOx and VOCs play important dual roles in the generation and conversion of pollutants, although their overall impact is smaller than meteorological factors. They produce significant indirect effects through their interaction with meteorological and other human factors, further affecting the concentrations of PM2.5 and O3. In areas without coordinated changes, the main impact of meteorological factors remains unchanged, and the relationship between the two anthropogenic emission sources and their effects on PM2.5 and O3 are complex, with different directions and levels involved. This study provides detailed insights into the drivers of air quality changes in the YRD and offers a scientific basis for environmental management authorities to develop more comprehensive and targeted strategies for balancing the control of PM2.5 and O3 pollution.

Selecting Targets for Molecular Imaging of Gastric Cancer: An Immunohistochemical Evaluation.

Tumor-targeted positron emission tomography (PET) and fluorescence-guided surgery (FGS) could address current challenges in pre- and intraoperative imaging of gastric cancer. Adequate selection of molecular imaging targets remains crucial for successful tumor visualization. This study evaluated the potential of integrin αvβ6, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM) and human epidermal growth factor receptor-2 (HER2) for molecular imaging of primary gastric cancer, as well as lymph node and distant metastases. Expression of αvβ6, CEACAM5, EGFR, EpCAM and HER2 was determined using immunohistochemistry in human tissue specimens of primary gastric adenocarcinoma, healthy surrounding stomach, esophageal and duodenal tissue, tumor-positive and tumor-negative lymph nodes, and distant metastases, followed by quantification using the total immunostaining score (TIS). Positive biomarker expression in primary gastric tumors was observed in 86% for αvβ6, 72% for CEACAM5, 77% for EGFR, 93% for EpCAM and 71% for HER2. Tumor expression of CEACAM5, EGFR and EpCAM was higher compared to healthy stomach tissue expression, while this was not the case for αvβ6 and HER2. Tumor-positive lymph nodes could be distinguished from tumor-negative lymph nodes, with accuracy ranging from 82 to 93% between biomarkers. CEACAM5, EGFR and EpCAM were abundantly expressed on distant metastases, with expression in 88-95% of tissue specimens. Our findings show that CEACAM5, EGFR and EpCAM are promising targets for molecular imaging of primary gastric cancer, as well as visualization of both lymph node and distant metastases. Further clinical evaluation of PET and FGS tracers targeting these antigens is warranted.

Engineering Saccharomyces cerevisiae for continuous secretory production of hEGF in biofilm.

Human epidermal growth factor (hEGF) plays a crucial role in promoting cell growth and has various clinical applications. Due to limited natural sources and the high cost of chemical synthesis, researchers are now exploring genetic engineering as a potential method for hEGF production. In this particular study, a novel hEGF expression system was developed using Saccharomyces cerevisiae. This system involved optimizing the promoter and signal peptide and deleting protease-coding genes PEP4, PRB1, and YAP3, overexpressing chaperones KAR2 and PDI1 in the protein secretion pathway, which led to a 2.01-fold increase in hEGF production compared to the wild type strain. Furthermore, biofilm-forming genes FLO11 and ALS3 were integrated to create a biofilm strain with adhesive properties. A biofilm-based immobilized continuous fermentation model was established to leverage the characteristics of this biofilm strain. Each batch of this model yielded 130mg/L of hEGF, with a production efficiency of 2.71mg/L/h - surpassing the production efficiency of traditional free fermentation (1.62mg/L/h). This study presents a promising fermentation model for efficient hEGF production based on biofilm characteristics, offering valuable insights for the application of biofilm fermentation in the production of small molecule peptides.

Extracellular ATP Release Triggered by 131I-Trastuzumab Mitigates Radiation-Induced Reduction in Cell Viability through the P2Y6 Receptor in SKOV3 Cells.

Intracellular ATP is released outside cells by various stimuli and is involved in cytoprotection by activating purinergic receptors. However, it remains unclear whether targeted radionuclide therapy induces extracellular ATP release. Here, we prepared 131I-labeled trastuzumab (131I-trastuzumab) and examined extracellular ATP release and its roles in 131I-trastuzumab's growth inhibitory effects. 131I-trastuzumab was prepared by labeling with the chloramine-T method. The binding of 131I-trastuzumab to cells was investigated using the human epidermal growth factor receptor 2 (HER2)-positive cells (SKOV3) and the HER2-negative cell (MCF7). Extracellular ATP was determined by measuring chemiluminescence using a luciferin-luciferase reagent. The growth inhibitory effects of 131I-trastuzumab were investigated by colony formation assay. 131I-trastuzumab bound exclusively to SKOV3 cells. Treatment with 131I-trastuzumab at 4 MBq/mL and higher concentrations significantly increased extracellular ATP levels, whereas non-radioactive trastuzumab didn't. This suggested that ATP release was specifically induced by radiation derived from 131I. The growth inhibitory effects of 131I-trastuzumab were significantly enhanced by pretreatment with apyrase (ecto-ATPase) or MRS2578 (a P2Y6-selective antagonist), whereas they were significantly reduced by treatment with a P2Y6-selective agonist. In conclusion, 131I-trastuzumab induced extracellular ATP release, and the released ATP was shown to be involved in mitigating radiation-induced reduction in cell viability through P2Y6 receptor.

The efficacy and safety of the prophylactic application of PEG-rhG-CSF in radiotherapy with weekly concurrent chemotherapy for cervical cancer.

To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing neutropenia during concurrent radiotherapy combined with weekly chemotherapy in patients with cervical cancer. From September 2019 to November 2020, 180 patients with cervical cancer who required concurrent chemoradiotherapy (CCRT) were enrolled in this study. The patients were randomly divided into the following three groups at a ratio of 1:1:1: Group A (PEG-rhG-CSF), Group B (PEG-rhG-CSF + rhG-CSF) and the control group (rhG-CSF). Cisplatin or carboplatin was administered weekly. The primary endpoint was the incidence of grade 3/4 neutropenia. The secondary endpoints were the incidence of febrile neutropenia (FN), delay of radiotherapy, chemotherapy dose reduction, rate of PFS at 2 years and 3 years, and incidence of adverse reactions. Sixty patients were randomly assigned to each group. Two patients in Group B withdrew from the trial for personal reasons. The incidence of grade 1/2 neutropenia in the Control group was significantly lower than that in Group A and Group B (P < 0.001). However, the incidence of grade 3/4 neutropenia in the Control group was significantly greater than that in Group A and Group B (P < 0.001). There was no significant difference in the incidence of FN among the three groups (P = 0.771). The rate of platinum dose reduction in Group A (6.7%) and Group B (5.2%) was significantly lower than that in the Control group (30.0%) (P < 0.001). The delay rate of radiotherapy in Group A (10%) and Group B (13.8%) was obviously inferior to that in the Control group (31.7%) (P = 0.006). The 2-year PFS rates of Group A, Group B, and the Control group were 93.3%, 98.3%, and 91.7%, respectively, with no statistically significant difference (P = 0.270). The 3-year PFS rates were 89.8%, 94.1%, and 84.9%, respectively, with no statistically significant difference (P = 0.178). No treatment-related serious adverse events occurred in any of the patients. In Group A and Group B, The prophylactic application of PEG-rhG-CSF during conventional chemoradiotherapy combined with weekly chemotherapy for patients with cervical cancer can reduce the incidence of grade 3/4 neutropenia and does not increase the incidence of adverse reactions when compared to Control group. chictr.org.cn, ChiCTR1900026309, registered 29 September 2019-prospectively registered.

Survival outcomes for HER2-low breast cancer: Danish national data.

We investigated the prognosis of breast cancer (BC) with low expression of human epidermal growth factor receptor 2 (HER2), as previous studies have found varying impacts on survival of HER2-low BC compared with HER2 0 BC (HER2 IHC score of 0). HER2-low is defined as a score of 1+ or 2+ in an immunohistochemical (IHC) assay without HER2 gene amplification. Patients with HER2 0 or HER2-low BC from the national Danish Breast Cancer Group database were examined by multivariable survival analysis in a retrospective noninterventional investigation. Patients were grouped as either HER2 0 or HER2-low. The primary endpoint was time to recurrence (TR), and the secondary endpoints were overall survival (OS) and distant recurrence-free interval (DRFI). 41,610 patients were included (12,981 with HER2 0 BC and 28,629 with HER2-low BC). HER2-low BC was associated with a lower risk of recurrence (hazard ratio [HR]: 0.92, p = 0.03). Regarding secondary endpoints, HER2-low disease was linked to improved overall OS (HR: 0.94, p = 0.02). No statistically significant effect of HER2-low was found for DRFI, along with no differential effect of HER2-low according to estrogen receptor (ER) status. HER2-low BC was found to show an improved HR for OS and DRFI compared with HER2 0 BC; however, further studies are need to establish whether it represents a separate biological entity.

DLL4-targeted CAR-T therapy sensitizes neoadjuvant chemotherapy via eliminating cancer stem cells and reshaping immune microenvironment in HER2+ breast cancer

BackgroundNeoadjuvant therapy with trastuzumab, pertuzumab and paclitaxel (THP) has significantly improved the prognosis of patients with human epidermal growth factor receptor 2 (HER2)+ breast cancer (BC). However, there remains a...

Automated radiofluorination of HER2 single domain antibody: the road towards the clinical translation of [18F]FB-HER2 sdAb.

With the next generation of Human Epidermal Growth Factor Receptor 2 (HER2) -targeting therapies, such as antibody-drug conjugates, showing benefit in "HER2 low" and even "HER2 ultralow" patients, the need for novel methods to quantify HER2 expression accurately becomes even more important for clinical decision making. A HER2 PET/CT imaging assessment could evaluate HER2 positive disease locations while improving patient care, reducing the need for invasive biopsies. A single-domain antibody (sdAb)-based PET tracer could combine the high specificity of sdAbs with short-lived radionuclides such as fluorine-18 (18F) and gallium-68 (68Ga). SdAb-based PET tracers have clinically been used via a 68Ga-chelator approach. However, the distribution of 68Ga-labelled pharmaceuticals to peripheral PET centres is more challenging to organize due to the short half-life of 68Ga, most certainly when the available activity is limited by a generator. Cyclotron produced 68Ga has removed this limitation. Distribution of 18F-labelled pharmaceuticals remains less challenging due to its slightly longer half-life, and radiofluorination of sdAbs via N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) has shown to be a promising strategy for developing sdAb-based PET tracers. Although [18F]SFB automation has been reported, automating protein conjugation proves challenging. Herein we report the fully automated, cartridge-based production of [18F]FB-HER2 sdAb on a single synthesis module. [18F]FB-HER2 sdAb (> 6GBq) was obtained after a fully automated production (95min), with a RCP > 95%, apparent molar activity > 20GBq/µmol and decay-corrected radiochemical yield (RCY d.c.) of 14 ± 2% (n = 4). Further upscaling amounted to production batches of 16GBq with an apparent molar activity > 40GBq/µmol and RCY d.c. of 8 ± 1% (n = 4). Ex vivo biodistribution and PET imaging showed specific HER2-positive tumour targeting and low kidney retention. The [18F]FB-HER2 sdAb tracer was produced with clinically relevant activities using a fully automated production method. The automated production method was designed to ease the translation to the clinic and has the potential to be used not only in mono-centre but also multi-centre clinical trials with one central production site. [18F]FB-HER2 sdAb showed a favourable biodistribution pattern and could be a valuable alternative to 68Ga-labelled sdAb-based PET tracers in the clinic.

Eye Tracking and Human Influence Factors’ Impact on Quality of Experience of Mobile Gaming

Mobile gaming accounts for more than 50% of global online gaming revenue, surpassing console and browser-based gaming. The success of mobile gaming titles depends on optimizing applications for the specific hardware constraints of mobile devices, such as smaller displays and lower computational power, to maximize battery life. Additionally, these applications must dynamically adapt to the variations in network speed inherent in mobile environments. Ultimately, user engagement and satisfaction are critical, necessitating a favorable comparison to browser and console-based gaming experiences. While Quality of Experience (QoE) subjective evaluations through user surveys are the most reliable method for assessing user perception, various factors, termed influence factors (IFs), can affect user ratings of stimulus quality. This study examines human influence factors in mobile gaming, specifically analyzing the impact of user delight towards displayed content and the effect of gaze tracking. Using Pupil Core eye-tracking hardware, we captured user interactions with mobile devices and measured visual attention. Video stimuli from eight popular games were selected, with resolutions of 720p and 1080p and frame rates of 30 and 60 fps. Our results indicate a statistically significant impact of user delight on the MOS for most video stimuli across all games. Additionally, a trend favoring higher frame rates over screen resolution emerged in user ratings. These findings underscore the significance of optimizing mobile gaming experiences by incorporating models that estimate human influence factors to enhance user satisfaction and engagement.