APMIS

Jønsson, Rie; Ingholt, Mathias Mølbak; Krogfelt, Karen Angeliki

doi: 10.1111/apm.13504pmid: 39710986

Fritz Kauffmann (1899–1978) was a German/Danish microbiologist, who worked most of his years studying intestinal bacteria at Statens Serum Institut in Denmark. During his research, he implemented several diagnostic tools, which are still used in reference laboratories worldwide. Kauffmann was probably most known for developing the “Kauffmann‐White scheme” based on the O‐ and flagella antigens on the surface of Salmonella. He was a visionary in his field, working at the intersection of microbiology and public health, as his research enabled proper diagnosis and tracking of diseases around the world.

Löfström, Emma; Eringfält, Anna; Kötz, Arne; Tham, Johan; Undén, Johan

doi: 10.1111/apm.13489pmid: 39509082

Antibodies and avidity maturation contribute to long‐lasting immunity, and previous COVID‐19 seems to enhance the immune response after vaccination. The aim of this study was to compare the immune response after vaccination between COVID‐19 convalescents and naïve patients. Blood samples from COVID‐19 convalescents and naïve patients, taken 1, 3 and 6 months after the second dose of vaccine (mRNA‐vaccine BNT162b2), were analysed for anti‐spike IgG and avidity. Questionnaires concerning side effects were used. Thirty‐one patients in the COVID‐19 cohort and 30 patients in the naïve cohort were included. High levels of anti‐spike IgG and avidity index were seen. Anti‐spike IgG were significantly higher in the COVID‐19 cohort and declining (median 1250, 566, 282 RU/ml vs 565, 187, 65 RU/ml). Avidity did not change over time (median at 6 months 78% vs 65%). The most common side effects were pain at the injection site, malaise and headache. In conclusion, high levels of anti‐spike IgG after vaccination were seen and most patients developed high‐avidity antibodies, although antibody levels and avidity were higher in the COVID‐19 cohort. Over time, the levels of anti‐spike IgG declined, yet avidity remained high. Side effects did not differ between groups and were of short duration.

Markvart, Merete; Sørensen, Christiane E.; Ekstrand, Kim R.; Schlafer, Sebastian; Belstrøm, Daniel

doi: 10.1111/apm.13501pmid: 39563103

Dental caries is a multifactorial disease, which is the result of a complex interplay between the diet, the host, the saliva, and dental biofilms. Although the prevalence of dental caries has decreased dramatically since 1950 in many countries, it continues to be one of the most common health conditions globally. The aim of the present review is to summarize the investigations on dental caries performed by the late Noble prize winner Henrik Dam and his colleagues in the middle of the 20th century, and to relate the knowledge and state of the art at the time to current concepts on dental caries. Henrik Dam is mostly known for his discovery of Vitamin K, but he also conducted experimental studies on dental caries that focused on the role of Vitamin K, the diet, and saliva in the development of dental caries. The discoveries of Henrik Dam contributed to our understanding of the role of saliva and different dietary components, such as fat and proteins, in caries development and prevention.

Julin, Clara; Nielsen, Signe Ledou; Grantzau, Trine Lønbo; Ahmad, Syed Azhar; Cowland, Jack Bernard; Bonde, Jesper; Nørgaard, Peter

doi: 10.1111/apm.13486pmid: 39465574

Clonal hematopoiesis is highly prevalent in elderly patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), and around 20% of BPDCN patients have an associated myeloid malignancy. We present a patient with localized BPDCN and concomitant myelodysplastic syndrome (MDS), previously followed for several years due to clonal cytopenia of unknown significance. Compared targeted next‐generation sequencing (NGS) of the skin tumor and sequential bone marrow samples showed shared variants in ASXL1 and TET2 with a de novo NRAS variant in both BPDCN and MDS compared to preceding bone marrow samples. These findings illustrate a shared clonal origin of BPDCN and MDS resulting from progressive clonal hematopoiesis.

Björnberg, Amelia; Nestor, David; Peker, Nilay; Sinha, Bhanu; Couto, Natacha; Rossen, John; Sundqvist, Martin; Mölling, Paula

doi: 10.1111/apm.13511pmid: 39807079

Shotgun metagenomics offers a broad detection of pathogens for rapid blood stream infection of pathogens but struggles with often low numbers of pathogens combined with high levels of human background DNA in clinical samples. This study aimed to develop a shotgun metagenomics protocol using blood spiked with various bacteria and to assess bacterial DNA extraction efficiency with human DNA depletion. The Blood Pathogen Kit (Molzym) was used to extract DNA from EDTA‐whole blood (WB) and plasma samples, using contrived blood specimens spiked with bacteria for shotgun metagenomics diagnostics via Oxford Nanopore sequencing and PCR‐based library preparation. Results showed that bacterial reads were higher in WB than plasma. Differences for Staphylococcus aureus and Streptococcus pneumoniae were more pronounced compared to Escherichia coli. Plasma samples exhibited better method reproducibility, with more consistent droplet digital PCR results for human DNA. The study found that extraction was more efficient for Gram‐positive bacteria than Gram‐negative, suggesting that the human DNA depletion exerts a negative effect on Gram‐negative bacteria. Overall, shotgun metagenomics needs further optimisation to improve bacterial DNA recovery and enhance pathogen detection sensitivity. This study highlights some critical steps in the methodology of shotgun metagenomic‐based diagnosis of blood stream infections using Nanopore sequencing.

Hao, Li‐Sen; Ji, Jing‐Xiu; Jiang, Mei‐Yu; Song, Jie; Chen, Pan‐Pan; Zhan, Zong‐Yuan; Miao, Xiao‐Jia; Gao, Ying‐Ying; Wang, Wei; Liu, Tian

doi: 10.1111/apm.13487pmid: 39500724

Accumulating research has revealed that src‐homology domain 2‐containing protein tyrosine phosphatase‐2 (SHP2), an oncogenic protein tyrosine phosphatase, is associated with liver fibrosis. Currently, it is still unclear whether SHP2 affects liver fibrosis by influencing the apoptosis of hepatic stellate cells (HSC). In present study, we investigate effects of SHP2 expression changes on liver fibrosis, with special emphasis on the apoptosis of HSC. Using adenovirus vector, wild‐type SHP2 gene and short hairpin RNA targeting SHP2 were introduced into rats with liver fibrosis and LX‐2 cells in vitro. The expressions of type I and III collagen, pathological and functional changes, collagen deposition in rat liver and apoptosis of LX‐2 cells were detected by immunohistochemical and HE staining, automated biochemical analyzer, Masson trichrome staining, and TUNEL. This study showed that overexpression of SHP2 exacerbated dysfunction, inflammatory damage, collagen deposition and increased expression of type I and III collagen in rat liver reduced apoptosis of LX‐2 cells. On the contrary, low expression of SHP2 alleviated the aforementioned detection indicators of rats and promoted apoptosis of LX‐2 cells. In conclusion, the downregulation of SHP2 expression alleviates liver fibrosis by inducing the apoptosis of HSC, while overexpressed SHP2 exacerbates liver fibrosis by inhibiting the apoptosis of HSC.

Høiby, Niels

doi: 10.1111/apm.13480pmid: 39415557

The Swedish scientist Örjan Ouchterlony published four ground‐breaking papers 1948–1966 in Acta Pathol Microbiol Scand where he described a new method of antigen–antibody reactions in gel. He described and defined the ‘reaction of identity’ and ‘reaction of partial identity’ when he used related antigens and ‘reaction of non‐identity’ when he used non‐related antigens. His results inspired scientists in other countries to further develop and modify the ‘Ouchterlony method’ which became useful for both scientific and clinical purposes. This survey describes how the methods were discovered and how they became modified and improved and how they were used, but also underlines that the original Ouchterlony method is still used.

Yıldız, Hasan; Doğan, Serhat

doi: 10.1111/apm.13498pmid: 39529566

Resveratrol, which is thought to have a preventive effect on the formation of different types of cancer, is abundant in grapes and other foods. Resveratrol has been shown to have anti‐cancer effects by in vitro andin vivo studies, however this is the first time its effect on atypical acinar cell foci (AACF), known as precursor forms of pancreatic carcinoma, has been experimentally investigated. Male Sprague Dawley rats, each consisting of 5 experimental groups (Cont, AzCont, AzRes10, AzRes15, and AzRes20), 10 of which were 14 days old, were used in the study. In the azaserine groups (AzCont, AzRes10, AzRes15, and AzRes20), it was investigated how the development of Atypical Cell Foci (AACF) resulting from intraperitoneal injection (i.p.) of azaserine (30 mg/kg bw) in 14‐day‐old rats was affected by dietary restoration. Male rats in the resveratrol group (AzRes10, AzRes15, and AzRes20) were fed diets containing 10%, 15%, or 20% mmol resveratrol for an 8‐month experimental period 1 week after the last azaserine injection. Pancreas preparations prepared from histological sections were examined for AACF burden and analyzed via a video image analyzer. One‐way analysis of variance (ANOVA) non‐parametric statistical analyses were performed to test whether there was a difference between the averages of the experimental and control groups. The AACF load in the azaserine group (AzCont) compared to the control group (Cont) was found to be statistically significant in all categories (p < 0.05). The calculated estimated mean AACF volume (mm3) values and the AACF ratio as a percentage of the calculated organ volume were statistically significantly lower in all resveratrol groups (AzRes10, AzRes15, and AzRes20) compared to the azaserine control group (AzCont). The calculated estimated mean AACF volume (mm3) values and the AACF ratio as a percentage of the calculated organ volume were statistically significantly lower in all resveratrol groups (AzRes10, AzRes15, and AzRes20) compared to the azaserine control group (AzCont) (p < 0.05). In addition, the calculated estimated mean AACF diameter (mm) in the AzRes10 and AzRes15 groups, in the AzRes15 group the calculated estimated mean AACF number in the whole organ and the calculated average AACF number per unit area were found to be statistically significant compared to the azaserine control group (AzCont) (p < 0.05). According to the results of our study, it has been shown that atypical acinar cell foci (AACF) formed in the exocrine pancreas of rats with azaserine can be reduced by a diet containing resveratrol. It was determined that the tumor burden decreased statistically significantly (p ≤ 0.05) in resveratrol‐treated rats. Accordingly, it is thought that the inhibitory effects of resveratrol may contribute to studies that reduce the occurrence of pancreatic cancer.

Sandeep, ; Shinde, Suraj H.; Pande, Abhay H.

doi: 10.1111/apm.13515pmid: 39807071

Development of antibodies for clinical use is a complex process involving numerous aspects, with antigen specificity being the most important. Initially, polyclonal antibodies, that can recognize multiple specific and nonspecific antigens (polyreactive), were developed and were very effective in the treatments. Later on, the polyspecificity/polyreactivity of these polyclonal antibodies (binding to multiple antigens) raised concerns about therapeutic efficacy because of their nonspecific interactions and challenges, such as development of immune complexes, batch‐to‐batch variability. This highlighted the need for more targeted approaches. It was resolved by the marked invention of hybridoma technology in 1975 which resulted in the revolution in the antibody development field by offering monoclonal monospecific antibodies (bind single antigen). However, their limited application in complex pathologies sparked a paradigm shift, leading to the resurgence of polyspecific antibodies in the form of monoclonal polyspecific antibodies (Polybodies), which bind multiple antigens, but specifically. Till today, 14 Polybodies are approved for clinical use. This fluctuation in antigen specificity is directing the evolution of engineered antibodies that are going to drive the biopharmaceutical sector in the coming years. Through this write‐up, we assert the fluctuating nature of antigen specificity during the antibody development and how it will be crucial for advancing biologics.

Norrild, Bodil; Ralfkiaer, Ulrik

doi: 10.1111/apm.13452pmid: 38946015

This manuscript commemorates the 100th anniversary of APMIS, highlighting its evolution from a regional journal, founded in 1924 as Acta Pathologica et Microbiologica Scandinavica, to an international platform fostering global collaboration in pathology, microbiology, and immunology. The journal's inception was driven by Ulrik Quensel's vision in 1919, leading to the establishment of the Northern Pathological Society and the launch of the journal in 1924. APMIS has consistently published landmark research, including significant contributions from prominent. These studies have advanced understanding in fields such as pathology, microbiology, and immunology. The journal expanded its scope in the 1970s to include immunology, rebranding as APMIS in the mid‐1980s. Recent decades have seen a continued commitment to cutting‐edge research and an increasing impact factor. As APMIS transitions to an Open Access model under Wiley, it will be renamed the PMI Journal (Pathology, Microbiology, and Immunology) to reflect its global reach and dedication to scientific excellence. This centennial celebration acknowledges the contributions of editors, authors, and readers, looking forward to future advancements in biomedical research.