APMIS

Tunheim, Gro; Baranowska‐Hustad, Marta; Lund‐Johansen, Fridtjof; Fossum, Even; Bhandari, Sabin; Kukule, Liva; Møller, Thea Kristine Rogne; Vikse, Elisabeth L.; Bekkevold, Terese; Oftung, Fredrik; Robertson, Anna Hayman; Næss, Lisbeth M.

doi: 10.1111/apm.70102pmid: 41376258

Antibody levels induced by SARS‐CoV‐2 infection have been reported to be associated with specific symptoms, disease severity, and viral load. In this study we investigated whether antibody responses were associated with virus type (Alpha B.1.1.7 or non‐variants of concern (non‐VOC)), viral load and clinical outcome in unvaccinated non‐hospitalized adults with PCR‐confirmed SARS‐CoV‐2 infection. Serum samples, questionnaires and symptom diaries were collected longitudinally (Day 0–180) between May 2020 and June 2021. IgG levels against ancestral Wuhan antigens and antibodies inhibiting RBD‐ACE2 interaction were measured by multiplex immunoassay and flowcytometry, respectively. Antibody neutralization assays were performed with B.1 and B.1.1.7 viruses. Viral load was measured by digital‐droplet PCR, and virus isolates were sequenced. Factors influencing IgG levels were investigated using Bayesian multilevel models. Alpha‐cases had 2.6–3.2‐fold higher IgG levels against RBD, nucleocapsid, and spike on Day 14, and higher antibody‐mediated inhibition of ACE2‐RBD interaction compared to non‐VOC cases. Alpha‐cases displayed 1.8‐ and 5.4‐fold higher neutralizing antibody titers than non‐VOC cases against B.1 and B1.1.7, respectively, but both non‐VOC and Alpha cases displayed the lowest ratio of binding to neutralizing antibodies against their infecting virus type. Alpha cases reported more symptoms than non‐VOC cases, but the severity of disease was similar. Nausea was significantly associated with higher IgG levels, while no association was found for viral load, despite Alpha cases having higher viral loads than non‐VOC cases. This study shows higher antibody responses induced by the more transmissible Alpha virus compared to earlier non‐VOC variants after mild SARS‐CoV‐2 infection. Reporting of nausea was positively associated with IgG levels.

Fu, Xueqing; Yin, Liu

doi: 10.1111/apm.70095pmid: 41332235

Ultrasonic examinations showed significant limitations in the early detection and prognostic prediction of sepsis‐induced myocardial dysfunction (SIMD), needing assisting biomarkers. The diagnostic and prognostic potential of miR‐324‐3p in SIMD was evaluated in this study, aiming to explore a novel biomarker. The functional role of miR‐324‐3p in regulating myocardial cell injury was assessed in H9c2 cells. The study enrolled 210 sepsis patients, including 98 patients diagnosed with SIMD. The significance of miR‐324‐3p in SIMD risk prediction, screening, and prognosis prediction was evaluated. Moreover, ultrasonic parameters, involving LVEF, LVDd, LAD, and FS, were compared between sepsis and SIMD patients, and the diagnostic and prognostic values of these parameters were also assessed. Silencing miR‐324‐3p exerted significantly protective effects on myocardial cell injury. Increasing serum miR‐324‐3p was observed in SIMD patients and was positively correlated with Dallas grades. LVEF, LVDd, LAD, and FS also showed significance in discriminating SIMD patients, but a single parameter cannot possess both satisfactory sensitivity and specificity. Serum miR‐324‐3p could help improve the diagnostic accuracy, sensitivity, and specificity of ultrasonic parameters in screening SIMD, and miR‐324‐3p was also identified as an independent risk factor for the adverse prognosis of SIMD patients.

Li, Wei; Zhang, Yijian; Yang, Hongwei; Guo, Junyu; Wang, Boqian

doi: 10.1111/apm.70097pmid: 41376260

Arum, Alexander; Andreasen, Emilie Korsgaard; Pedersen, Helle; Nielsen, Trine Dahl; Frandsen, Peter; Pedersen, Birgitte Tønnes; Hogdall, Estrid; Bonde, Jesper

doi: 10.1111/apm.70109pmid: 41334677

Elimination of cervical cancer requires broad access to and participation in cervical screening. Self‐sampling has emerged as a robust technology that simplifies access; however, few self‐sampling devices are independently validated regarding sample quality. This study compares the quality of three self‐sampling devices: Evalyn (Rovers), currently used in Denmark, the FLOQSwab (Copan) and the modified FLOQSwab: SensiGrip. Women residing in the Capital Region of Denmark, accepting screening by self‐sampling, were offered a kit containing the following combinations of devices: (1) Evalyn, FLOQSwab, (2) Evalyn, SensiGrip or (3) FLOQSwab, SensiGrip. Returned kits were analyzed using the validated BD Onclarity HPV assay on the COR instrument (BD). A total of 1677 women participated. Sample quality was similar across devices, also when stratifying into age groups. Two hundred thirty‐two women (13.9%) tested positive for one or more oncogenic HPV types. Pairwise concordance analysis for each group showed an overall agreement between 93.5% and 95%. Analytical and diagnostic performance of samples collected by the three self‐sampling devices resulted in similar quality and HPV detection. Hence the sample quality is not a determinant in the choice of sampling device and focus on other factors such as cost, women's preference or size and weight can take precedence.

Prytz, Karolina Liljedahl; Magnuson, Anders; Sundqvist, Martin; Kurland, Lisa; Källman, Jan

doi: 10.1111/apm.70129pmid: 41457009

Blood stream infections are associated with high mortality and morbidity. NEWS2 is a quick scoring system including bedside measurable vital signs. This study aimed to investigate the ability of NEWS2 ≥ 5p to identify sepsis, per Sepsis‐3 criteria, among adult patients with community‐acquired infection and positive blood cultures. It also explored if NEWS2 ≥ 5p could indicate infection etiology based on bacterial species in blood culture. This retrospective study included 555 patients with positive blood cultures. 425 of 555 (76.6%) patients had sepsis. The sensitivity of NEWS2 ≥ 5p for detecting sepsis was 86.6% and was not statistically associated with infection etiology. Patients with S. pneumoniae had a higher median NEWS2 score than those with other bacterial species. The 28‐day mortality rate was 12.1%, and the sensitivity of NEWS2 ≥ 5p for detecting 28‐day mortality was 91.0%. NEWS2 ≥ 5p was detected in a high proportion of sepsis cases among patients with blood stream infections, independent of bacterial species, and is a quick tool for identifying high sepsis likelihood in the emergency department.

Morais, Hannah Gil de Farias; Colares, Débora Frota; Sousa, Julliany Taverny; Martins, Helder Domiciano Dantas; Paz, Alexandre Rolim; Morais, Everton Freitas; Bonan, Paulo Rogerio Ferreti; Freitas, Roseana de Almeida

doi: 10.1111/apm.70126pmid: 41405445

Xu, Guangfei; Li, Hewen; Huang, Ting; Xu, Liang; Liu, Danian; Ji, Bo

doi: 10.1111/apm.70096pmid: 41332237

Ischemic stroke (IS), a life‐threatening disease, carries a high risk of disability and death. Reverse transcription quantitative real‐time polymerase chain reaction was utilized to measure the PART1 and miR‐638 expression in patients with IS and oxygen–glucose deprivation/reoxygenation (OGD/R) model. Superoxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH), interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) levels were determined by enzyme‐linked immunosorbent assay kit. Cell viability was assessed using the cell counting kit‐8 assay. Apoptotic cells were analyzed by flow cytometry. To explore the interaction between PART1 and miR‐638, luciferase reporter and RNA immunoprecipitation (RIP) assays were carried out. In patients with IS and OGD/R‐treated cells, PART1 exhibited upregulation, whereas miR‐638 showed downregulation; there was a negative correlation between these two molecules. Knockdown of PART1 increased cell viability, decreased apoptosis, lowered MDA, LDH, IL‐6 and TNF‐α levels, and increased SOD activity. PART1 negatively regulated miR‐638 expression, and inhibition of miR‐638 reduced the protective effect of the knockdown of PART1 on OGD/R‐treated cells. This study demonstrated that knockdown of PART1 inhibits IS‐induced neurological injury by regulating miR‐638 expression, which promotes the understanding of IS disease and provides new options for the treatment of the disease.

Wu, Di; Qu, Yan; Zhang, Yichuan; Li, Ruiting

doi: 10.1111/apm.70108pmid: 41365609

Long non‐coding RNAs (lncRNAs) are crucial regulators of hepatocellular carcinoma (HCC) development. The objective of the present investigation was to examine the lncRNA HOXC‐AS1 levels in HCC and to explore the function of the HOXC‐AS1/miR‐876‐3p/NR3C1 axis in HCC. Relative HOXC‐AS1, miR‐876‐3p, and NR3C1 levels in tumor and paracancerous specimens were assessed by quantitative RT‐PCR. sh‐HOXC‐AS1 was transfected into HCC cells to analyze its effects on HCC. The detection of cell growth, migration, and invasiveness was conducted by the CCK‐8 assay along with Transwell analysis. Flow cytometry was employed to assess cell apoptosis. To evaluate the prognostic significance of HOXC‐AS1, a Kaplan–Meier survival analysis was carried out. HOXC‐AS1 was increased in HCC specimens in comparison with paracancerous tissues. Patients with high HOXC‐AS1 levels had lower disease‐free survival and overall survival rates than cases with low HOXC‐AS1 levels (p < 0.001). Silencing HOXC‐AS1 reduced the growth, migration, and invasiveness of HCC cells while promoting their apoptosis. As the direct target gene, miR‐876‐3p is negatively related to HOXC‐AS1 levels. miR‐876‐3p could reverse the functions of HOXC‐AS1 for HCC cells by targeting NR3C1. Upregulation of HOXC‐AS1 promotes HCC progression through the miR‐876‐3p/NR3C1 axis.

Trivedi, Pinal; Singh, Shrinkhla; Dowari, Sikhasmita; Jedhe, Nikita; Rana, Khushboo; Srivastava, Ratika; Gajjar, Devarshi

doi: 10.1111/apm.70120pmid: 41399284

Fusarium Keratitis is a corneal infection that causes blindness if left untreated. Immune profiling of Fusarium‐infected corneas may facilitate the development of an effective immunotherapy. The ex vivo caprine (goat) cornea model examines immune cell and cytokine activity in response to Fusarium keratitis. Dissected caprine corneas maintained in ex vivo culture conditions were infected with the clinical Fusarium isolate (CSH_1) to study local immune responses. Immuno‐phenotyping was performed using immune cell markers CD45, CD11b, and HLA‐DR/DQ, followed by quantification of IL‐1ß, IL‐6, IFN‐γ, TGF‐ß, IL‐4, IL‐10, and MCP‐1 through ELISA. The efficacy of antifungals was evaluated by sectioning drug‐treated infected corneas by H&E staining and cytokine profiling to assess the immunomodulatory effect of antifungal treatment. Results show that CD45+ lymphocytes, recognized as a universal marker for immune cells, were abundant in the cornea. Activated myeloid cells (CD 11b+HLA DR/DQ+) and cytokines IL‐1ß, IL‐6, IFN‐γ, TGF‐ß, IL‐4, IL‐10, and MCP‐1 were significantly elevated in infected corneas relative to uninfected samples. Among the drugs tested, posaconazole showed complete inhibition of Fusarium, while natamycin and amphotericin B showed the least inhibition and moderate inhibition was shown by voriconazole. The ex vivo model offers a valuable framework for evaluating pre‐clinical efficacy of different treatment protocols for fungal keratitis on local tissue.

Mattila, Taneli T.; Patankar, Madhura; Väyrynen, Juha P.; Klintrup, Kai; Mäkelä, Jyrki; Tuomisto, Anne; Nieminen, Pentti; Mäkinen, Markus J.; Karttunen, Tuomo J.

doi: 10.1111/apm.70105pmid: 41332218

Mucin 1 (MUC1) is overexpressed in colorectal cancer (CRC), yet its prognostic value is controversial. In vitro, MUC1 promotes anoikis resistance. Putative anoikis‐resistant (AR) structures are clusters of carcinoma cells surviving without matrix contact, and are associated with adverse prognosis. We explored the prognostic role of MUC1 in CRC and its association with putative AR structures. We studied 118 patients with CRC, including 52 with nodal metastases. Immunohistochemical MUC1 expression was analyzed in primary tumors and nodal metastases by estimating the proportions of MUC1‐positive carcinoma cells within different subpopulations. In primary tumors, MUC1 expression was increased in most putative AR structure types, and abundant AR structures were associated with elevated MUC1. MUC1 in primary tumors was not prognostic. In nodal metastases, MUC1 levels correlated with those in primary tumors but were lower. High MUC1 levels in both primary tumors and metastases were associated with worse prognosis as compared with expression decreasing in nodal metastases. High MUC1 expression in nodal metastases was associated with synchronous distant metastasis and adverse prognosis. In conclusion, primary tumor MUC1 is not prognostic. In nodal metastases, high MUC1 associates with distant metastasis and poor outcomes. Putative AR structures show high MUC1 expression supporting its role in anoikis resistance.