Machine Learning Assessment of Gestational Age in Accelerated Maturation, Delayed Maturation, Villous Edema, Chorangiosis, and Intrauterine Fetal Demise.

CONTEXT.­: Assessment of placental villous maturation is among the most common tasks in perinatal pathology. However, the significance of abnormalities in morphology is unclear and interobserver variability is significant. OBJECTIVE.­: To develop a machine learning model of placental maturation across the second and third trimesters and quantify the impact of different pathologist-diagnosed abnormalities of villous morphology. DESIGN.­: Digitize placental villous slides from more than 2500 placentas at 12.0 to 42.6 weeks. Build whole slide learning models to estimate obstetrician-determined gestational age for cases with appropriate maturation and normal morphology. Define the model output as "placental age" and compare it to the chronologic gestational age. RESULTS.­: Our model showed an r2 of 0.864 and mean absolute error of 1.62 weeks for placentas with appropriate maturation in the test set. Pathologist diagnosis of accelerated maturation was associated with a 2.56-week increase in placental age (±2.91 weeks, P < .001), while delayed maturation was associated with a 0.92-week decrease in placental age (±1.82 weeks, P < .001). Intrauterine fetal demise causes diverse changes to placental age, driven by the nature of the demise. We tested the impact of training a model, using all live births. The resulting r2 was 0.874 and mean absolute error was 1.73 weeks. Furthermore, by including cases with abnormal maturation in the training data, the effect size of accelerated maturation was blunted to only 0.56 ± 2.35 weeks (P < .001). CONCLUSIONS.­: We show that various abnormalities of villous maturation and morphology correlate with abnormalities in placental age. This "no pathologist" model could be useful in situations where pathologists are unavailable or the need for consistency outweighs the utility of expertise.

Low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma, outcome of advanced disease: retrospective study from the Ultra-Rare Sarcoma Working Group.

BACKGROUND: To present findings from a retrospective study conducted by the Ultra-Rare Sarcoma Working Group on metastatic low-grade fibromyxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), and hybrid (H)-LGFMS/SEF across 28 global centres. METHODS: Patients treated at participating institutions from January 2000 to September 2022 were retrospectively selected. Diagnosis was confirmed by expert pathologists. Primary endpoint was progression-free survival (PFS-1) from metastasis detection to first progression or death. PFS-2 was calculated from therapy initiation. RESULTS: A total of 101 patients were identified (32 LGFMS, 50 SEF, 19 H-LGFMS/SEF). Median (m) follow-up was 62.1 months. mPFS-1 was 28.7, 11.8, and 20.3 months for LGFMS, SEF, and H-LGFMS/SEF, respectively. mOS was 145.8, 41.9, and 113.5 months, respectively. Treatments included anthracycline-based chemotherapy, gemcitabine-based chemotherapy (G), pazopanib, trabectedin, others. mPFS-2 was: 20.1, 5.5, and 3.5 months in H-LGFMS/SEF, SEF, and LGFMS, respectively, with anthracyclines; 19.5, 7.7, and 6.9 months in LGFMS, SEF, and H-LGFMS/SEF, respectively, with pazopanib; 12.0, 9.7, and 3.1 months in H-LGFMS/SEF, LGFMS, and SEF, respectively. Occasional responses occurred with ifosfamide/oral cyclophosphamide, and prolonged stable disease with immune checkpoint inhibitors. CONCLUSIONS: In this series, the largest available, metastatic LGFMS, SEF, and H-LGFMS/SEF showed different courses. Systemic agents have modest efficacy, informing future trials of novel agents for these tumours.

Phase I PIANO trial-PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes.

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) induces direct DNA damage and immunogenic cell death in patients with gastric cancer peritoneal metastases (GCPM). Combining PIPAC-OX with immune checkpoint inhibition remains untested. We conducted a phase I first-in-human trial evaluating the safety and efficacy of PIPAC-OX combined with systemic nivolumab (NCT03172416). METHODS: Patients with GCPM who experienced disease progression on at least first-line systemic therapy were recruited across three centers in Singapore and Belgium. Patients received PIPAC-OX at 90 mg/m2 every 6 weeks and i.v. nivolumab 240 mg every 2 weeks. Translational studies were carried out on GCPM samples acquired during PIPAC-OX procedures. RESULTS: In total, 18 patients with GCPM were prospectively recruited. The PIPAC-OX and nivolumab combination was well tolerated with manageable treatment-related adverse events, although one patient suffered from grade 4 vomiting. At second and third PIPAC-OX, respectively, the median decrease in peritoneal cancer index (PCI) was -5 (interquartile range: -12 to +1) and -7 (interquartile range: -6 to -20) and peritoneal regression grade 1 or 2 was observed in 66.7% (6/9) and 100% (3/3). Translational analyses of 43 GCPM samples revealed enrichment of immune/stromal infiltration and inflammatory signatures in peritoneal tumors after PIPAC-OX and nivolumab. M2 macrophages were reduced in treated peritoneal tumor samples while memory CD4+, CD8+ central memory and naive CD8+ T-cells were increased. CONCLUSIONS: The first-in-human trial combining PIPAC-OX and nivolumab demonstrated safety and tolerability, coupled with enhanced T-cell infiltration within peritoneal tumors. This trial sets the stage for future combinations of systemic immunotherapy with locoregional intraperitoneal treatments.

Nutrient starvation activates ECM remodeling gene enhancers associated with inflammatory bowel disease risk in fibroblasts.

Nutrient deprivation induces a reversible cell cycle arrest state termed quiescence, which often accompanies transcriptional silencing and chromatin compaction. Paradoxically, nutrient deprivation is associated with activated fibroblast states in pathological microenvironments in which fibroblasts drive extracellular matrix (ECM) remodeling to alter tissue environments. The relationship between nutrient deprivation and fibroblast activation remains unclear. Here, we report that serum deprivation extensively activates transcription of ECM remodeling genes in cultured fibroblasts, despite the induction of quiescence. Starvation-induced transcriptional activation accompanied large-scale histone acetylation of putative distal enhancers, but not promoters. The starvation-activated putative enhancers were enriched for non-coding genetic risk variants associated with inflammatory bowel disease (IBD), suggesting that the starvation-activated gene regulatory network may contribute to fibroblast activation in IBD. Indeed, the starvation-activated gene PLAU, encoding uPA serine protease for plasminogen and ECM, was upregulated in inflammatory fibroblasts in the intestines of IBD patients. Furthermore, the starvation-activated putative enhancer at PLAU, which harbors an IBD risk variant, gained chromatin accessibility in IBD patient fibroblasts. This study implicates nutrient deprivation in transcriptional activation of ECM remodeling genes in fibroblasts and suggests nutrient deprivation as a potential mechanism for pathological fibroblast activation in IBD.

Investigating the Formation of Polymer-Nanoparticle Complex Coacervate Hydrogels Using Polymerization-Induced Self-Assembly-Derived Nanogels with a Succinate-Functional Core.

This paper reports polymer-nanoparticle-based complex coacervate (PNCC) hydrogels prepared by mixing anionic nanogels synthesized by polymerization-induced self-assembly (PISA) and cationic branched poly(ethylenimine) (bPEI). Specifically, poly(3-sulfopropyl methacrylate)58-b-poly(2-(methacryloyloxy)ethyl succinate)500 (PKSPMA58-PMES500) nanogels were prepared by reversible addition-fragmentation chain-transfer (RAFT)-mediated PISA. These nanogels swell on increasing the solution pH and form free-standing hydrogels at 20% w/w and pH ≥ 7.5. However, the addition of bPEI significantly improves the gel properties through the formation of PNCCs. Diluted bPEI/nanoparticle mixtures were analyzed by dynamic light scattering (DLS) and aqueous electrophoresis to examine the mechanism of PNCC formation. The influence of pH and the bPEI-to-nanogel mass ratio (MR) on the formation of these PNCC hydrogels was subsequently investigated. A maximum gel strength of 1300 Pa was obtained for 20% w/w bPEI/PKSPMA58-PMES500 PNCC hydrogels prepared at pH 9 with an MR of 0.1, and shear-thinning behavior was observed in all cases. After the removal of shear, these PNCC gels recovered rapidly, with the recovery efficiency being pH-dependent.

SARS-CoV-2 spike aggravates lupus nephritis and lung fibrosis in systemic lupus erythematosus.

OBJECTIVE: COVID-19 induces the development of autoimmune diseases, including SLE, which are characterised by inflammation, autoantibodies and thrombosis. However, the effects of COVID-19 on SLE remain unclear. METHODS: We investigated the effects of COVID-19 on SLE development and progression in three animal models. Plasmids encoding SARS-CoV-2 spike protein and ACE2 receptor were injected into R848-induced BALB/C lupus mice, R848-induced IL-1 receptor antagonist knockout (KO) lupus mice and MRL/lpr mice. Serum levels of albumin and autoantibodies, lymphocyte phenotypes and tissue histology were evaluated. RESULTS: In R848-induced BALB/C lupus mice, the SARS-CoV-2 spike protein increased autoantibody and albumin levels compared with vehicle and mock treatments. These mice also exhibited splenomegaly, which was further exacerbated by the spike protein. Flow cytometric analysis revealed elevated T helper 1 cell counts, and histological analysis indicated increased levels of the fibrosis marker protein α-smooth muscle actin. In KO mice, the spike protein induced splenomegaly, severe kidney damage and pronounced lung fibrosis. In the MRL/lpr group, spike protein increased the serum levels of autoantibodies, albumin and the thrombosis marker chemokine (C-X-C motif) ligand 4. CONCLUSION: COVID-19 accelerated the development and progression of lupus by inducing autoantibody production, fibrosis and thrombosis.

Patient-Reported Outcomes After Switching to a 2-Drug Regimen of Fixed-Dose Combination Dolutegravir/Lamivudine: 48-Week Results from the SALSA Study.

Patient-reported outcomes (PROs) facilitate communication between patients and providers, enhancing patient-centered care. We report PROs for virologically suppressed people living with HIV-1 who switched to dolutegravir/lamivudine (DTG/3TC) or continued their 3- or 4-drug current antiretroviral regimen (CAR) in the phase 3 SALSA study. Secondary endpoints included change from baseline in HIV Treatment Satisfaction Questionnaire (status version; HIVTSQs) and HIV Symptom Distress Module (HIV-SDM) at Weeks 4, 24, and 48. A post hoc analysis assessed change in HIVTSQs and HIV-SDM by age (≥ 50 and < 50 years). Higher HIVTSQs scores represent greater treatment satisfaction (range, 0-60); lower HIV-SDM scores indicate less symptom bother (range, 0-80). Participants in the DTG/3TC (n = 246) and CAR (n = 247) groups reported comparable baseline HIVTSQs total scores (mean [SD], 55.2 [6.5] and 55.8 [5.5], respectively). Beginning at Week 4, mean HIVTSQs scores in the DTG/3TC group further increased vs. CAR and were sustained through Week 48. Baseline mean (SD) HIV-SDM symptom bother scores were comparable between the DTG/3TC (9.0 [9.9]) and CAR (7.9 [9.3]) groups. Small improvements in HIV-SDM scores favoring DTG/3TC were observed at Weeks 4 and 24 and sustained through Week 48 (though not significant between groups). Participants aged ≥ 50 and < 50 years who switched to DTG/3TC reported higher satisfaction and less symptom distress vs. CAR; these results were generally comparable between age groups. Participants who switched to DTG/3TC reported rapid and sustained improvements in treatment satisfaction compared with those who continued CAR, reinforcing the benefits of DTG/3TC beyond virologic suppression (NCT04021290; registration date, 7/11/2019).

Associations of quality of social support and accurate beliefs about curability among older adults with advanced cancer.

INTRODUCTION: Supporting older adults with advanced cancer to better understand their disease and its prognosis is important for shared decision-making. Social support is a potentially modifiable factor that may influence disease understanding. In this study, we examined the associations of quantity and quality of social support with patients' beliefs about the curability of their advanced cancer. MATERIALS AND METHODS: We performed a secondary analysis of a cluster-randomized trial that recruited older adults aged ≥70 with advanced incurable cancer. At enrollment, patients completed the Older Americans Resources and Services (OARS) Medical Social Support form that measures both quantity (number of close friends and relatives) and quality of social support. Quality of social support was measured using 12 questions in instrumental and emotional support, each ranging from 1 (none of the time) to 5 (all of the time). Higher cumulative scores indicated greater quality of support. For beliefs about curability, patients were asked, "What do you believe are the chances that your cancer will go away and never come back with treatment?" Responses were 0 %, <50 %, 50/50, >50 %, and 100 %. Ordinal logistic regression was used to investigate the association of quantity and quality of social support with beliefs about curability, adjusting for potential confounders. RESULTS: We included 347 patients; mean age was 76.4 years and 91 % were white. Quantity of social support was not associated with belief in curability [adjusted odds ratio (AOR) 1.03, 95 % confidence interval (CI) (0.92, 1.16)]. For every unit increase in the quality of social support (OARS Medical Social Support score), the odds of believing in curability decreased by 26.7 % [AOR 0.73, 95 % CI (0.56, 0.97)]. DISCUSSION: Our study demonstrated that the quality, but not the quantity, of social support was associated with patients' beliefs about curability. These findings suggest that bolstering social support may directly enhance disease understanding. This insight informs supportive care interventions that specifically address disease comprehension among patients.

IL-21 drives skin and lung inflammation and fibrosis in a model for systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, abnormal inflammation, and fibrosis of the skin and internal organs, notably the skin and lungs, significantly impairing quality of life. There is currently no cure for SSc, and its etiology remains largely unknown, presenting a primary barrier to effective treatment. We investigated the role of interleukin-21 (IL-21) in the pathogenesis of SSc. METHODS: We assessed the expression levels of fibrosis-related genes in human dermal fibroblasts exposed to IL-21 and TGF beta. We also induced SSc in wild-type C57BL/6 mice and IL-21 knockout (KO) mice with a C57BL/6 background using bleomycin (Bleomycin). Histological analyses were conducted on skin and lung tissues from these mice. The distribution and expression levels of fibrosis-related proteins in the tissues were examined via immunohistochemistry and quantitative real-time PCR. Furthermore, we measured the frequency of Th1, Th2, and Th17 cells among splenocytes through flow cytometry. RESULTS: IL-21 activation led to STAT3 phosphorylation more than TGF beta in dermal fibroblasts. In IL-21 KO mice with BLM-induced SSc, skin thickness and lung fibrosis were reduced. The absence of IL-21 in these mice resulted in suppressed expression of fibrosis-related genes, including Col1a1, Col1a2, Col3a1, CTGF, α-SMA, STAT3, and TGFß, in the skin and lungs. It also led to a decreased frequency of Th1, Th2, and Th17 cells, as well as a lower Th17/Treg ratio among splenocytes, factors known to contribute to the development of SSc. CONCLUSIONS: IL-21 contributes to the development of SSc by promoting the expression of fibrosis-related genes and modulating the levels of CD4+ T cells.

Duodenal transcriptomics demonstrates signatures of tissue inflammation and immune cell infiltration in children with environmental enteric dysfunction across global centers.

BACKGROUND: Environmental enteric dysfunction (EED) is an inflammatory condition of the small intestine that is prevalent in children residing in low- and middle-income countries. EED is accompanied by profound histopathologic changes in the small bowel, loss of absorptive capacity, increased intestinal permeability, increased microbial translocation, and nutrient loss. OBJECTIVES: We sought to identify dysregulated genes and pathways that might underlie pediatric EED. METHODS: RNA-sequencing libraries were generated from endoscopically obtained duodenal tissue from undernourished children with EED from 3 prospective cohorts of children with EED. The EED transcriptome was defined in comparison to North American children without EED. Weighted gene coexpression network analysis (WGCNA) was tested for gene modules associated with EED and its histologic features. RESULTS: The 1784 upregulated genes in EED were highly enriched for immune and inflammatory processes, including IL-17 and JAK-STAT signaling, and cytokine-cytokine receptor interactions. The 1388 downregulated genes included genes corresponding to xenobiotic metabolism, detoxification, and antioxidant capacities. A gene coexpression module enriched for antimicrobial responses and chemokine activity was significantly associated with villous blunting, goblet cell depletion, and overall histologic severity of EED. CONCLUSIONS: The transcriptome signatures of EED include specific innate and adaptive immune responses that are consistently elevated across study centers, coupled with reduced detoxification and antioxidant capacities. These data may have implications for targeted interventions to improve EED outcomes.

Effect of diet on the gut mycobiome and potential implications in inflammatory bowel disease.

The gut microbiome is a complex, unique entity implicated in the prevention, pathogenesis, and progression of common gastrointestinal diseases. While largely dominated by bacterial populations, advanced sequencing techniques have identified co-inhabiting fungal communities, collectively referred to as the mycobiome. Early studies identified that gut inflammation is associated with altered microbial composition, known as gut dysbiosis. Altered microbial profiles are implicated in various pathological diseases, such as inflammatory bowel disease (IBD), though their role as a cause or consequence of systemic inflammation remains the subject of ongoing research. Diet plays a crucial role in the prevention and management of various diseases and is considered to be an essential regulator of systemic inflammation. This review compiles current literature on the impact of dietary modulation on the mycobiome, showing that dietary changes can alter the fungal architecture of the gut. Further research is required to understand the impact of diet on gut fungi, including the metabolic pathways and enzymes involved in fungal fermentation. Additionally, investigating whether dietary modulation of the gut mycobiome could be utilized as a therapy in IBD is essential.

Pan-tumor validation of a NGS fraction-based MSI analysis as a predictor of response to Pembrolizumab.

Microsatellite instability high (MSI-H) and mismatch repair deficient (dMMR) tumor status have been demonstrated to predict patient response to immunotherapies. We developed and validated a next-generation sequencing (NGS)-based companion diagnostic (CDx) to detect MSI-H solid tumors via a comprehensive genomic profiling (CGP) assay, FoundationOne®CDx (F1CDx). To determine MSI status, F1CDx calculates the fraction of unstable microsatellite loci across >2000 loci using a fraction-based (FB) analysis. Across solid tumor types, F1CDx demonstrated a high analytical concordance with both PCR (n = 264) and IHC (n = 279) with an overall percent agreement (OPA) of 97.7% and 97.8%, respectively. As part of a retrospective bridging clinical study from KEYNOTE-158 Cohort K and KEYNOTE-164, patients with MSI-H tumors as determined by F1CDx demonstrated an objective response rate (ORR) of 43.0% to pembrolizumab. In real-world cancer patients from a deidentified clinicogenomic database, F1CDx was at least equivalent in assessing clinical outcome following immunotherapy compared with MMR IHC. Demonstrated analytical and clinical performance of F1CDx led to the pan-tumor FDA approval in 2022 of F1CDx to identify MSI-H solid tumor patients for treatment with pembrolizumab. F1CDx is an accurate, reliable, and FDA-approved method for the identification of MSI-H tumors for treatment with pembrolizumab.

Prognostic impact of intraoperative rupture in early-stage epithelial ovarian cancer: an ancillary study of GORILLA-3002.

OBJECTIVE: To evaluate whether intraoperative rupture affects oncological outcomes in patients with early-stage epithelial ovarian cancer (EOC). METHODS: A multicenter retrospective study was conducted on patients with early-stage EOC based on surgical and final pathological reports between 2007 and 2021. Oncologic outcomes were compared between the unruptured group (International Federation of Gynaecology and Obstetrics [FIGO] stage IA/IB) and ruptured group (FIGO stage IC1). The primary endpoint was progression-free survival (PFS). Propensity score matching (PSM) was performed to adjust for the imbalance in prognostic factors between the groups. RESULTS: Overall, 197 (58.3 %) patients comprised the unruptured group (FIGO stage IA/IB), and 141 (41.7 %) were in the intraoperatively ruptured group (FIGO stage IC1). No significant difference in the 5-year PFS was observed between the two groups before PSM (92.65 % vs. 92.80 %, P = 0.93). After PSM, the 5-year PFS showed a noticeable decrease in the ruptured group compared to the unruptured group, although this difference showed borderline statistical significance (96.90 % vs. 89.82 %, P = 0.061). This trend was particularly discernible in cases with aggressive tumor characteristics; intraoperative rupture remained an independent prognostic factor for shorter PFS in patients with high-grade histology (adjusted hazard ratio = 14.4, 95 % confidence interval = 2.8-74.1). CONCLUSIONS: Although not statistically significant, intraoperative rupture may negatively affect PFS in these patients after PSM. Therefore, rupture during surgery should be avoided as it can cause upstaging and unnecessary chemotherapy.

Risk factors for the recurrence in patients with early endometrioid endometrial cancer achieving complete remission for fertility-sparing hormonal treatment.

OBJECTIVE: This study aimed to assess the recurrence risk factors in patients with early-stage endometrioid endometrial cancer (EC) who achieved a complete response (CR) through fertility-sparing hormonal treatment (FST). METHODS: We retrospectively analyzed patients who received FST for presumed stage IA and grade 1 endometrioid EC at two institutions. Medroxyprogesterone (MPA)- and levonorgestrel-releasing intrauterine devices (LNG-IUD) were used concurrently. Maintenance therapy involved maintaining the LNG-IUDs in situ for those who did not attempt to conceive immediately after achieving CR. Cox regression analysis was used to identify clinicopathological variables for recurrence-free survival (RFS) following CR. RESULTS: Among 178 patients with endometrioid EC who received FST, 142 (79.8 %) achieved CR. The median time to achieve CR and the median FST duration were 10 months (range 1-34) and 14 months (range 3-49), respectively. During the median follow-up period of 44 months (range 6-143), 59.9 % (85/142) of patients had recurrence, with a median RFS of 14 months (range 1-123) after CR. In multivariable analysis, age > 35-years (hazard ratio (HR) 1.892, 95 % confidence interval (CI) 1.224-2.923; P < 0.05) and pregnancy after the first CR (HR 0.203, 95 % CI 0.093-0.444; P < 0.05) were significantly associated with RFS. CONCLUSIONS: Older age and non-pregnancy status may be risk factors for recurrence after CR. Therefore, patients with these conditions should undergo stringent follow-up, including imaging and histological examinations, to detect recurrence after CR.

Toward a responsible future: recommendations for AI-enabled clinical decision support.

BACKGROUND: Integrating artificial intelligence (AI) in healthcare settings has the potential to benefit clinical decision-making. Addressing challenges such as ensuring trustworthiness, mitigating bias, and maintaining safety is paramount. The lack of established methodologies for pre- and post-deployment evaluation of AI tools regarding crucial attributes such as transparency, performance monitoring, and adverse event reporting makes this situation challenging. OBJECTIVES: This paper aims to make practical suggestions for creating methods, rules, and guidelines to ensure that the development, testing, supervision, and use of AI in clinical decision support (CDS) systems are done well and safely for patients. MATERIALS AND METHODS: In May 2023, the Division of Clinical Informatics at Beth Israel Deaconess Medical Center and the American Medical Informatics Association co-sponsored a working group on AI in healthcare. In August 2023, there were 4 webinars on AI topics and a 2-day workshop in September 2023 for consensus-building. The event included over 200 industry stakeholders, including clinicians, software developers, academics, ethicists, attorneys, government policy experts, scientists, and patients. The goal was to identify challenges associated with the trusted use of AI-enabled CDS in medical practice. Key issues were identified, and solutions were proposed through qualitative analysis and a 4-month iterative consensus process. RESULTS: Our work culminated in several key recommendations: (1) building safe and trustworthy systems; (2) developing validation, verification, and certification processes for AI-CDS systems; (3) providing a means of safety monitoring and reporting at the national level; and (4) ensuring that appropriate documentation and end-user training are provided. DISCUSSION: AI-enabled Clinical Decision Support (AI-CDS) systems promise to revolutionize healthcare decision-making, necessitating a comprehensive framework for their development, implementation, and regulation that emphasizes trustworthiness, transparency, and safety. This framework encompasses various aspects including model training, explainability, validation, certification, monitoring, and continuous evaluation, while also addressing challenges such as data privacy, fairness, and the need for regulatory oversight to ensure responsible integration of AI into clinical workflow. CONCLUSIONS: Achieving responsible AI-CDS systems requires a collective effort from many healthcare stakeholders. This involves implementing robust safety, monitoring, and transparency measures while fostering innovation. Future steps include testing and piloting proposed trust mechanisms, such as safety reporting protocols, and establishing best practice guidelines.

Taphonomic signatures of early scavenging by black and turkey vultures.

Scavenging is critical for nutrient cycling and maintenance of healthy ecosystems. While there is substantial research into the identification of taphonomic signatures from facultative mammalian scavengers, early stage scavenging signatures by vultures remain unknown. Further, some vulture species are opportunistic predators, highlighting the need to define signatures observed in the course of normal scavenging behavior. We placed stillborn neonatal calves in an unoccupied pasture and used motion-trigger camera traps to quantify scavenging effort, then conducted necropsies to evaluate the effect of black vulture (Coragyps atratus) and turkey vulture (Cathartes aura) scavenging effort on carcass consumption. We measured the order of consumption of different tissue types to delineate which anatomic structures vultures consume first. Scavenging trials with higher numbers of vultures feeding on the carcass for longer were associated with decreased remaining tongue and abdominal viscera, and a larger umbilical wound. Greater maximum flock sizes were associated with decreased remaining tongue and abdominal viscera, a larger umbilical wound, and greater biomass consumption. Black vultures targeted the perineum and tongue earlier, while turkey vultures targeted the eyes, perineum, and tongue. These results are consistent with the idea that vultures prefer tissues that are easy to access and contain high nutrient content. These patterns form a distinctive taphonomic signature that can be used to identify early scavenging by black and turkey vultures. Our results demonstrate that criteria commonly used to identify livestock depredation by black vultures only document vulture presence and not predation. This distinction implies that new and more definitive criteria need to be developed and put into practice for more accurate decision criteria in livestock depredation compensation programs.