Single-cell analysis of phenotypic plasticity could improve the development of more effective therapeutics. Still, the development of tools to measure single-cell heterogeneity has lagged due to difficulties in manipulating and culturing single cells. Here, we describe a single-cell culture and phenotyping platform that employs a starburst microfluidic network and automatic liquid handling system to capture single cells for long-term culture and multi-dimensional analysis and quantify their clonal properties via their surface biomarker and secreted cytokine/growth factor profiles. Studies performed on this platform found that cells derived from single-cell cultures maintained phenotypic equilibria similar to their parental populations. Single-cell cultures exposed to chemotherapeutic drugs stochastically disrupted this balance to favor stem-like cells. They had enhanced expression of mRNAs and secreted factors associated with cell signaling, survival, and differentiation. This single-cell analysis approach can be extended to analyze more complex phenotypes and screen responses to therapeutic targets.

Objective: We explored the experiences of women in senior or leadership roles in navigating and leading during acute public health emergencies. Methods: Women leaders in the World Health Organization Western Pacific Region attending the Global Outbreak Alert and Response Network’s Outbreak Response Leadership Training (11–18 September 2024) were invited to participate in this phenomenological study. Eleven interviews were conducted with training attendees and observational data were gathered. Inductive thematic analysis was conducted to identify key themes. Results: Four themes associated with women-centric experiences in public health emergency response were identified: disproportionate expectations in the workplace; the use of authoritarian decision-making during planning and implementation; encompassing different perspectives and leadership styles compared to men; and requesting additional opportunities and equitable prospects for career growth. Four themes that reflect non-gender-exclusive challenges experienced during emergency responses were also detailed. Themes observed were related to: barriers to efficiency; consequences of working within this field; and needs and necessities during emergency response. Discussion: This study highlights both gender-specific and systemic challenges experienced by women leaders in public health emergency responses, revealing how sociocultural norms and operational barriers intersect during times of crisis. We identified opportunities to assist women leaders through the recognition and promotion of different leadership styles, establishing a support network for women, and addressing systemic and organizational barriers that impact women.

Child ; Humans ; Liver Neoplasms/pathology* ; World Health Organization

Humans ; Stomach Neoplasms/pathology* ; Gastric Mucosa/pathology* ; Adenocarcinoma/pathology*

Objective: To investigate the evolution and clinical significance of HER2 low expression status in HER2 negative patients in primary and recurrent/metastatic breast cancers. Methods: The data and archived sections of 259 breast cancer patients with recurrence/metastasis and HER2-negative primary foci were collected from January 2015 to January 2022 at the Fourth Hospital of Hebei Medical University, and the HER2 status of primary and recurrence/metastasis foci was determined by immunohistochemistry (IHC), among which IHC 2+patients were subject to fluorescence in situ hybridization (FISH). The HER2 status was classified as HER2-0 group; patients with IHC 1+, IHC 2+and no FISH amplification were classified as HER2 low expression group; and patients with IHC 3+, IHC 2+and FISH amplified were classified as HER2-positive group. The changes of HER2 status in patients with HER2 low expression in primary versus recurrent/metastatic breast cancer foci were compared, and their clinicopathologic characteristics and prognosis were analyzed. Results: The overall concordance rate between primary and recurrent/metastatic HER2 status in breast cancer was 60.6% (157/259, κ=0.178). A total of 102 patients (102/259, 39.4%) had inconsistent primary and recurrent/metastatic HER2 status; 37 patients (37/259, 14.3%) had HER2-0 at the primary foci and HER2-low expression at the recurrent/metastatic; and 56 patients (56/259, 21.6%) had HER2-low expression in the primary foci and HER2-0 in the recurrent/metastatic. The recurrent/metastatic foci became low-expressing compared with the recurrent/metastatic foci which remained HER2-0 patients, with longer overall survival time, higher ER and PR positivity, lower Ki-67 positivity index, and lower tumor histological grade; all with statistically significant differences (all P<0.05). In the primary HER2-low group, patients with recurrent/metastatic foci became HER2-0 while those with recurrent/metastatic foci remained low expression; there were no statistically significant differences in clinicopathological features and overall survival time (all P>0.05). Conclusions: Unstable HER2 status in patients with HER2-0 and low expression in primary versus recurrent/metastatic breast cancer foci, and HER2-0 in the primary foci but low HER2 expression status in recurrence/metastasis is associated with favourable prognosis, and testing HER2 status in recurrence/metastasis can provide more treatment options for such patients.
Humans ; Breast Neoplasms/genetics* ; Clinical Relevance ; In Situ Hybridization, Fluorescence ; Female

Adult ; Humans ; Stomach ; Histiocytosis, Langerhans-Cell/diagnosis*

Humans ; Kidney/pathology*

Male ; Humans ; Spermatic Cord ; Mesothelioma ; Mesothelioma, Malignant

Humans ; Glomerulonephritis, Membranoproliferative/pathology* ; Fibronectins

Child ; Humans ; Neoplasms/genetics* ; World Health Organization