Citations

ABSTRACTMost discussions about discrimination and bias in anatomical research papers have been limited to terminology relating to race/ethnicity and gender/sex. However, as editors of anatomical journals, the authors of this article have frequently observed broader instances of potential discrimination and bias within anatomical research. These often stem from differences among authors' backgrounds, traditions, cultures, religions, provenance/origins, and workplace affiliations. In view of the limited discourse on this topic, we seek in this article to establish a consensus among editors of anatomical journals and to propose new Guidelines Against Discrimination and Bias in Anatomical Research Papers (GDBARP). We have identified multiple factors that can contribute to discrimination and bias, underscoring the need for greater awareness and proactive measures. It is imperative in anatomical research to respect authors, reviewers, and editors regardless of their background, culture, traditions, sex, ethnicity, language, religion, or ethical perspectives.

In 2007, the Bárány Society embarked on a project to establish definitions of vestibular syndromes and disorders based on best available evidence, referred to as the International Classification of Vestibular Disorders (ICVD). Since then, numerous publications providing consensus-driven diagnostic criteria for vestibular symptoms, syndromes, and disorders have been published. Here, we reflect on the rationale for developing the ICVD as well as its subsequent achievements, challenges, and outlook. In this summary of the work of the ICVD to date, the authors will focus on practical aspects to help improve the utility and applicability of these diagnostic criteria moving forward.

Background: The number of multiply revised anterior cruciate ligament reconstructions (rrACLRs) performed each year continues to increase. The most reliable graft type and surgical technique in the young, active patient remains to be determined. Purpose: To determine the outcomes of rrACLR using quadriceps tendon (QT) autograft with lateral extra-articular tenodesis (LET). Study Design: Case series; Level of evidence, 4. Methods: A retrospective review was performed of all competitive athletes undergoing rrACLR with QT autograft and LET at a single institution with a minimum follow-up of 2 years. Patient demographics, physical examination, and radiological findings, and previous surgical details were documented. Patient outcomes were noted, including the International Knee Documentation Committee (IKDC) and Lysholm scores, ability to return to sport and return at the same level of play, retear rate, and other complications. Results: A total of 19 rrACLRs were performed and met inclusion criteria in the 10-year study period. All participants were high school, collegiate, or professional athletes with a mean age of 22 years, and 63.2% were female. The mean follow-up was 42.3 months, and IKDC scores increased from 51.6 preoperatively to 74.7 at the final follow-up ( P < .001). Likewise, the Lysholm score increased significantly from a preoperative value of 53.6 to 76.8 at the final follow-up ( P < .001). Return to play was possible in 52.6% of the patients at a mean of 11.5 months, with 31.6% returning to the same or higher level of play. One (5.3%) patient experienced a recurrent ACL tear, and 2 (10.5%) experienced a contralateral tear. Arthrofibrosis requiring surgical intervention occurred in 26.3% of the athletes. Conclusion: Short- to midterm results demonstrated that competitive athletes who received an rrACLR using a QT autograft with LET had statistically significant improvements in both IKDC and Lysholm scores, with more than half of patients being able to return to sport and nearly a third returning at the same or higher level of play. In the setting of a third ACL reconstruction, quadriceps tendon autograft with LET is a reasonable option even in high-risk patients.

Abstract Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung tumor marked by significant molecular heterogeneity. In a study of 590 patients across two independent cohorts, we observed comparable overall survival across treatment regimens (chemotherapy, chemoimmunotherapy, immunotherapy) without unexpected adverse events. Genomic analysis identified distinct NSCLC-like (KEAP1, KRAS, STK11 mutations) and SCLC-like (RB1, TP53 mutations) LCNEC subtypes, with 80% aligning with SCLC transcriptional profiles. Serial sampling revealed stable mutational but shifting transcriptomic landscapes over time. NSCLC-like LCNECs showed elevated FGL-1 (a LAG-3 ligand) and SPINK1 expression, while SCLC-like subtypes expressed higher levels of DLL3. Immunofluorescence confirmed FGL-1 in NSCLC-like LCNECs, and H&E slide analyses indicated fewer tumor-infiltrating lymphocytes in LCNECs versus other lung cancers. These findings highlight LCNEC’s distinct immunogenomic profile, supporting future investigations into LAG-3, SPINK1, and DLL3-targeted therapies.

Abstract Glioblastoma (GBM) remains the most common and lethal adult malignant primary brain cancer with few treatment options. A significant issue hindering GBM therapeutic development is intratumor heterogeneity. GBM tumors contain neoplastic cells within a spectrum of different transcriptional states. Identifying effective therapeutics requires a platform that predicts the differential sensitivity and resistance of these states to various treatments. Here, we developed a novel framework, ISOSCELES ( I nferred cell S ensitivity O perating on the integration of S ingle- C ell E xpression and L 1000 E xpression S ignatures), to quantify the cellular drug sensitivity and resistance landscape. Using single-cell RNA sequencing of newly diagnosed and recurrent GBM tumors, we identified compounds from the LINCS L1000 database with transcriptional response signatures selectively discordant with distinct GBM cell states. We validated the significance of these findings in vitro, ex vivo, and in vivo , and identified a novel combination of an OLIG2 inhibitor and Depatux-M for GBM. Our studies suggest that ISOSCELES identifies cell states sensitive and resistant to targeted therapies in GBM and that it can be applied to identify new synergistic combinations. Highlights Integration of GBM single-cell RNA sequencing data with L1000-derived drug response signatures facilitates clustering of tumor cells and small molecules on cell-drug connectivity. Cell-drug connectivity predicts the identities of drug-sensitive and resistant cell states. In silico perturbation analysis using cell-drug connectivity predicts drug-induced changes in the cell-drug connectivity landscape in vivo. In silico perturbation analysis to predict drug-induced changes in the tumor cell-drug connectivity landscape predicts drug combinations that synergize in vivo to extend survival.

ABSTRACT Evidence indicates that the integrity of in utero development influences late life healthy or unhealthy aging; however, specific links between them are unclear. Histone chaperone HIRA is thought to play a role in both life stages, and here, we explore this role using the murine pigmentary system by investigating and comparing the effects of its lineage‐specific knockout, either conditionally during embryogenesis or postnatally. Embryonic knockout of Hira in tyrosinase+ neural crest‐derived lineages, including melanoblasts, led to reduced melanoblast numbers during embryogenesis, with single‐cell RNA sequencing analysis indicating evidence of lineage‐specificity defects. This was supported in an in vitro model using melb‐a melanoblasts in which Hira knockdown affected lineage identity and melanoblast differentiation potential, with ATAC‐seq data indicating a role of HIRA in orchestrating chromatin accessibility. Interestingly, however, newborn Hira knockout mice had wild type numbers of differentiated melanocytes, albeit functionally defective, as demonstrated by very mild hypopigmentation of the first hair coat, increased melanocyte telomere‐associated DNA damage foci, and impaired response to proliferative challenge. Moreover, as they aged, mice with embryonic melanoblast Hira knockout displayed marked defects in melanocyte stem cell maintenance and premature hair graying. Importantly, this phenotype was not observed after postnatal inducible knockout, indicating an essential role for HIRA at embryonic stages that is transmitted to adulthood, rather than a direct postnatal requirement within the pigmentary system. This genetic model shows that HIRA function during early development lays a foundation for maintaining lineage identity and subsequent maintenance of adult tissue‐specific stem cells during aging.

ABSTRACT The stromal tumor environment (STE) plays a vital yet often underrecognized role in cancer progression, shaping tumor development. It influences complex interactions among stromal cells, immune cells, extracellular matrix (ECM) components, and signaling molecules. Stromal cells regulate integrin signaling and are involved in remodeling the tumor microenvironment, driving critical processes such as cell migration, survival, angiogenesis, and proliferation. Advances in understanding the STE are creating new opportunities for early cancer detection and treatment. Innovations in molecular imaging, particularly for melanoma, are transforming cancer diagnostics by providing deeper insights into tumor biology, cellular interactions, and angiogenesis, paving the way for more personalized and timely therapeutic interventions. Among these advancements, in vivo skin fluorescent imaging (SFI) stands out as a powerful tool, offering real‐time molecular insights at the point of care with the ability to improve patient management.

Background Olfactory dysfunction (OD) is a common symptom in patients with coronavirus disease 2019 (COVID-19) with limited treatment options. Objective This pilot study aimed to investigate an acupuncture protocol in patients with COVID-19 related OD. Methods Thirty patients were randomized into 2 groups. The standard group was treated with budesonide nasal irrigation and olfactory training. The acupuncture group received ten sessions of acupuncture therapy in addition to the standard group treatment. Olfaction was assessed using the University of Pennsylvania Smell Identification Test, 10-point visual analog scale, and Sino-Nasal Outcome Test at baseline and after 3 months of treatment. Differences between study arms were compared using Fisher’s exact and Wilcoxon rank sum tests. Results Eighteen of the 30 (60%) enrolled patients completed the study, including 11 (73%) in the standard and 7 (47%) in the acupuncture group. Reasons for participant drop-out included cost of travel and time constraints. There were no acupuncture complications. Conclusions Acupuncture as an adjunct therapy for COVID-19 related OD is well tolerated. Subsequent studies with larger sample sizes are needed to assess the effect of acupuncture on OD.

Objectives Generative artificial intelligence (GAI) tools can enhance the quality and efficiency of medical research, but their improper use may result in plagiarism, academic fraud and unreliable findings. Transparent reporting of GAI use is essential, yet existing guidelines from journals and institutions are inconsistent, with no standardised principles. Design and setting International online Delphi study. Participants International experts in medicine and artificial intelligence. Main outcome measures The primary outcome measure is the consensus level of the Delphi expert panel on the items of inclusion criteria for GAMER (Rreporting guideline for the use of Generative Artificial intelligence tools in MEdical Research). Results The development process included a scoping review, two Delphi rounds and virtual meetings. 51 experts from 26 countries participated in the process (44 in the Delphi survey). The final checklist comprises nine reporting items: general declaration, GAI tool specifications, prompting techniques, tool’s role in the study, declaration of new GAI model(s) developed, artificial intelligence-assisted sections in the manuscript, content verification, data privacy and impact on conclusions. Conclusion GAMER provides universal and standardised guideline for GAI use in medical research, ensuring transparency, integrity and quality.