prasterone (Mylis)

Two cases of pregnancy during the fourth year of 68 mg etonogestrel implant use.

Warling Allysa A, Page Lauren S LS, Nelson Hallie H, Lazorwitz Aaron A

The United States Food and Drug Administration recently expanded approval of the 68 mg radiopaque etonogestrel (ENG) contraceptive implant (Nexplanon, Organon, Oss, The Netherlands) from three years to five years, based on clinical trial data showing no pregnancies in years four or five of use. We present two cases of pregnancy in year four of implant use. Two patients presented to our medical center's emergency department with ENG implants in situ and were found to have positive pregnancy tests. The first patient had her implant placed three years and one month prior to presentation, and had an intrauterine pregnancy. The second patient had her implant placed three years and five months prior to presentation, and had a tubal ectopic pregnancy. The first patient underwent a medical termination of pregnancy and implant removal and replacement three days after initial presentation. Her original implant was removed intact. The second patient underwent a laparoscopic right salpingectomy and implant removal and replacement one day after initial presentation. Her original implant was removed intact. These cases suggest that both intrauterine and ectopic pregnancies can occur in year four of ENG implant use. Further work should be conducted to determine risk factors for implant failure, especially in years four and five of use.

Improved molecular serogroup typing reveals locally circulating Leptospira serogroups in wildlife in Yamaguchi, Japan.

Kiuno Kazuki K, Koizumi Nobuo N, Kakita Tetsuya T, Takabe Kyosuke K et al.

Leptospirosis is a globally distributed zoonotic disease caused by pathogenic Leptospira spp., which are classified into numerous serogroups. Accurate serogroup identification is essential for epidemiological understanding and public health interventions in endemic regions. The microscopic agglutination test (MAT) is the conventional serological method for serogroup identification; however, it is labor-intensive and depends on extensive reference strain panels. Molecular serogroup typing (MST) has been proposed as an alternative approach, but its performance for region-specific strains has not been sufficiently evaluated. In this study, we improved an MST method optimized for Japanese Leptospira isolates and applied it to determine the serogroups of pathogenic Leptospira spp. detected in kidneys of wild boars (Sus scrofa) and sika deer (Cervus nippon) collected in Yamaguchi Prefecture, Japan, between 2016 and 2025. Pathogenic Leptospira DNA was detected in 23 of the 190 wild boars (12.1%) and 22 of the 275 sika deer (8.0%) by real-time PCR targeting lipL32. The improved MST identified serogroups Autumnalis, Australis, Canicola, and Hebdomadis in both host species, with Autumnalis predominating. In contrast, MAT using standard reference strains detected antibodies mainly against Hebdomadis and Australis, indicating discrepancies in the predominant serogroups between molecular and serological results. Notably, MAT using a local Autumnalis strain successfully detected Autumnalis antibodies in both hosts. These findings demonstrate that the improved MST complements serological testing.

Correction to: Two-year outcomes of more than 30 000 elderly patients with atrial fibrillation: results from the All Nippon AF In the Elderly (ANAFIE) Registry.

Proteomic dynamics in endochondral ossification: insights from antler tip analysis.

Xi Xi X, Cao Xinyue X, Zhou Yuying Y, Tian Zichen Z et al.

The antler primary growth center, located at the distal tip of the growing antler, comprises five consecutive tissue zones beneath the velvet skin. Because the outermost reserve mesenchyme contains blastema progenitor cells with multipotent differentiation capacity, antler regeneration recapitulates embryonic skeletal development through endochondral ossification (ECO). The molecular mechanisms governing cell fate decisions and tissue morphogenesis across these zones remain poorly understood. We profiled the proteome of the sika deer (Cervus nippon) antler growth center across all five tissue zones using the Orbitrap Astral platform in data-independent acquisition (DIA) mode. Protein identification and quantification were performed with DIA-NN. Proteome dynamics were analyzed by integrating three complementary clustering approaches including weighted gene co-expression network analysis (WGCNA), Fuzzy C-means clustering, and monotonic feature selection. Differentially expressed proteins were annotated by gene ontology (GO) enrichment analysis. Transcriptomic data from the same tissue zones were reanalyzed to assess mRNA-protein concordance. A total of 8,173 proteins were identified across the five tissue zones, representing the most comprehensive proteomic coverage of the antler growth center. Clustering analyses resolved distinct protein expression modules corresponding to sequential ECO stages from mesenchymal proliferation in the reserve mesenchyme to cartilage mineralization in the innermost zone. Deep proteome coverage enabled detection of low-abundance chondrogenic transcription factors SOX9, SOX6, and RUNX3, whose spatial expression matched their known roles in chondrogenesis. At the protein level, the reserve mesenchyme co-expressed 11 embryonic and 23 mesenchymal stem cell markers, indicating that antler stem cells represented a unique mesenchymal stem cell (MSC) population possessing partial embryonic stem cell (ESC)-like features. This study provides a spatially resolved proteomic atlas of the complete antler growth center and identifies key regulatory proteins at each stage of endochondral ossification. The findings offer new insights into progenitor cell characteristics, transcription factor activity, and protein dynamics during bone development, with potential relevance to bone repair and regenerative medicine.