CHAMMI: A benchmark for channel-adaptive models in microscopy imaging

Most neural networks assume that input images have a fixed number of channels (three for RGB images). However, there are many settings where the number of channels may vary, such as microscopy images where the number of channels changes depending on instruments and experimental goals. Yet, there has not been a systemic attempt to create and evaluate neural networks that are invariant to the number and type of channels. As a result, trained models remain specific to individual studies and are hardly reusable for other microscopy settings. In this paper, we present a benchmark for investigating channel-adaptive models in microscopy imaging, which consists of 1) a dataset of varied-channel single-cell images, and 2) a biologically relevant evaluation framework. In addition, we adapted several existing techniques to create channel-adaptive models and compared their performance on this benchmark to fixed-channel, baseline models. We find that channel-adaptive models can generalize better to out-of-domain tasks and can be computationally efficient. We contribute a curated dataset (https://doi.org/10.5281/zenodo.7988357) and an evaluation API (https://github.com/broadinstitute/MorphEm.git) to facilitate objective comparisons in future research and applications.Comment: Accepted at NeurIPS Track on Datasets and Benchmarks, 202

Let Models Speak Ciphers: Multiagent Debate through Embeddings

Discussion and debate among Large Language Models (LLMs) have gained considerable attention due to their potential to enhance the reasoning ability of LLMs. Although natural language is an obvious choice for communication due to LLM's language understanding capability, the token sampling step needed when generating natural language poses a potential risk of information loss, as it uses only one token to represent the model's belief across the entire vocabulary. In this paper, we introduce a communication regime named CIPHER (Communicative Inter-Model Protocol Through Embedding Representation) to address this issue. Specifically, we remove the token sampling step from LLMs and let them communicate their beliefs across the vocabulary through the expectation of the raw transformer output embeddings. Remarkably, by deviating from natural language, CIPHER offers an advantage of encoding a broader spectrum of information without any modification to the model weights. While the state-of-the-art LLM debate methods using natural language outperforms traditional inference by a margin of 1.5-8%, our experiment results show that CIPHER debate further extends this lead by 1-3.5% across five reasoning tasks and multiple open-source LLMs of varying sizes. This showcases the superiority and robustness of embeddings as an alternative "language" for communication among LLMs

Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis

Infantile hemangiomas (IHs) are non-malignant, largely cutaneous vascular tumors affecting approximately 5–10% of children to varying degrees. During the first year of life, these tumors are strongly proliferative, reaching an average size ranging from 2 to 20 cm. These lesions subsequently stabilize, undergo a spontaneous slow involution and are fully regressed by 5 to 10 years of age. Systemic treatment of infants with the non-selective β-adrenergic receptor blocker, propranolol, has demonstrated remarkable efficacy in reducing the size and appearance of IHs. However, the mechanism by which this occurs is largely unknown. In this study, we sought to understand the molecular mechanisms underlying the effectiveness of β blocker treatment in IHs. Our data reveal that propranolol treatment of IH endothelial cells, as well as a panel of normal primary endothelial cells, blocks endothelial cell proliferation, migration, and formation of the actin cytoskeleton coincident with alterations in vascular endothelial growth factor receptor-2 (VEGFR-2), p38 and cofilin signaling. Moreover, propranolol induces major alterations in the protein levels of key cyclins and cyclin-dependent kinase inhibitors, and modulates global gene expression patterns with a particular affect on genes involved in lipid/sterol metabolism, cell cycle regulation, angiogenesis and ubiquitination. Interestingly, the effects of propranolol were endothelial cell-type independent, affecting the properties of IH endothelial cells at similar levels to that observed in neonatal dermal microvascular and coronary artery endothelial cells. This data suggests that while propranolol markedly inhibits hemangioma and normal endothelial cell function, its lack of endothelial cell specificity hints that the efficacy of this drug in the treatment of IHs may be more complex than simply blockage of endothelial function as previously believed

Case Report: An exceptional response to neoadjuvant radiotherapy and chemotherapy in undifferentiated pleomorphic sarcoma following checkpoint inhibitor use

Undifferentiated pleomorphic sarcoma (UPS), a subtype of soft tissue sarcoma (STS), is an uncommon malignancy associated with a poor prognosis. As with other forms of sarcoma, surgical resection remains the only form of treatment with curative potential. The role of perioperative systemic therapy has not been definitively elucidated. Due to high recurrence rates and metastatic potential, management of UPS can pose a difficult task for clinicians. In cases of unresectable UPS due to anatomic limitations and in patients with comorbidities and poor performance status (PS), management options are limited. We describe a patient with UPS involving the chest wall with poor PS who achieved complete response (CR) following neoadjuvant chemotherapy and radiation in the setting of prior immune-checkpoint inhibitor (ICI) therapy

Artificial Intelligence Model Predicts Sudden Cardiac Arrest Manifesting With Pulseless Electric Activity Versus Ventricular Fibrillation

BACKGROUND: There is no specific treatment for sudden cardiac arrest (SCA) manifesting as pulseless electric activity (PEA) and survival rates are low; unlike ventricular fibrillation (VF), which is treatable by defibrillation. Development of novel treatments requires fundamental clinical studies, but access to the true initial rhythm has been a limiting factor. METHODS: Using demographics and detailed clinical variables, we trained and tested an AI model (extreme gradient boosting) to differentiate PEA-SCA versus VF-SCA in a novel setting that provided the true initial rhythm. A subgroup of SCAs are witnessed by emergency medical services personnel, and because the response time is zero, the true SCA initial rhythm is recorded. The internal cohort consisted of 421 emergency medical services-witnessed out-of-hospital SCAs with PEA or VF as the initial rhythm in the Portland, Oregon metropolitan area. External validation was performed in 220 emergency medical services-witnessed SCAs from Ventura, CA. RESULTS: In the internal cohort, the artificial intelligence model achieved an area under the receiver operating characteristic curve of 0.68 (95% CI, 0.61-0.76). Model performance was similar in the external cohort, achieving an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.59-0.84). Anemia, older age, increased weight, and dyspnea as a warning symptom were the most important features of PEA-SCA; younger age, chest pain as a warning symptom and established coronary artery disease were important features associated with VF. CONCLUSIONS: The artificial intelligence model identified novel features of PEA-SCA, differentiated from VF-SCA and was successfully replicated in an external cohort. These findings enhance the mechanistic understanding of PEA-SCA with potential implications for developing novel management strategies

Author Correction: Early Pastoral Economies and Herding Transitions in Eastern Eurasia (Scientific Reports, (2020), 10, 1, (1001), 10.1038/s41598-020-57735-y)

This Article contains a typographical error in the Introduction section under subheading ‘Understanding Early Horse Domestication and Transport’ where, “Historical records refer to horse-mounted warriors in western Asia by the 8th century BCE, while archaeological finds from localities like Arzhan 2 in southern Tuva show specialized horse equipment (bronze snaffle bits) and equine vertebral pathologies linked with mounted riding in Central Asia by the late 9th century BCE31.” should read: “Historical records refer to horse-mounted warriors in western Asia by the 8th century BCE, while archaeological finds from localities like Arzhan in southern Tuva show specialized horse equipment (bronze snaffle bits) and equine vertebral pathologies linked with mounted riding in Central Asia by the late 9th century BCE31.”

Early Pastoral Economies and Herding Transitions in Eastern Eurasia

While classic models for the emergence of pastoral groups in Inner Asia describe mounted, horse-borne herders sweeping across the Eurasian Steppes during the Early or Middle Bronze Age (ca. 3000–1500 BCE), the actual economic basis of many early pastoral societies in the region is poorly characterized. In this paper, we use collagen mass fingerprinting and ancient DNA analysis of some of the first stratified and directly dated archaeofaunal assemblages from Mongolia’s early pastoral cultures to undertake species identifications of this rare and highly fragmented material. Our results provide evidence for livestock-based, herding subsistence in Mongolia during the late 3rd and early 2nd millennia BCE. We observe no evidence for dietary exploitation of horses prior to the late Bronze Age, ca. 1200 BCE – at which point horses come to dominate ritual assemblages, play a key role in pastoral diets, and greatly influence pastoral mobility. In combination with the broader archaeofaunal record of Inner Asia, our analysis supports models for widespread changes in herding ecology linked to the innovation of horseback riding in Central Asia in the final 2nd millennium BCE. Such a framework can explain key broad-scale patterns in the movement of people, ideas, and material culture in Eurasian prehistory

Early Pastoral Economies and Herding Transitions in Eastern Eurasia

While classic models for the emergence of pastoral groups in Inner Asia describe mounted, horse-borne herders sweeping across the Eurasian Steppes during the Early or Middle Bronze Age (ca. 3000-1500 BCE), the actual economic basis of many early pastoral societies in the region is poorly characterized. In this paper, we use collagen mass fingerprinting and ancient DNA analysis of some of the first stratified and directly dated archaeofaunal assemblages from Mongolia's early pastoral cultures to undertake species identifications of this rare and highly fragmented material. Our results provide evidence for livestock-based, herding subsistence in Mongolia during the late 3rd and early 2nd millennia BCE. We observe no evidence for dietary exploitation of horses prior to the late Bronze Age, ca. 1200 BCE - at which point horses come to dominate ritual assemblages, play a key role in pastoral diets, and greatly influence pastoral mobility. In combination with the broader archaeofaunal record of Inner Asia, our analysis supports models for widespread changes in herding ecology linked to the innovation of horseback riding in Central Asia in the final 2nd millennium BCE. Such a framework can explain key broad-scale patterns in the movement of people, ideas, and material culture in Eurasian prehistory

Socio-economic disadvantage is associated with heavier drinking in high but not middle-income countries participating in the International Alcohol Control (IAC) Study

INTRODUCTION AND AIMS: To investigate if socio-economic disadvantage, at the individual- and country-level, is associated with heavier drinking in some middle- and high-income countries. DESIGN AND METHODS: Surveys of drinkers were undertaken in some high- and middle-income countries. Participating countries were Australia, England, New Zealand, Scotland (high-income) and Peru, Thailand and Vietnam (middle-income). Disadvantage at the country-level was defined as per World Bank (categorised as middle-or high-income); individual-level measures were (i) years of education and (ii) whether and individual was under or over the poverty line in each country. Measures of heavier drinking were (i) proportion of drinkers that consumed 8+ drinks and (ii) three drinking risk groups (lower, increasing and higher). Multi-level logistic regression models were used. RESULTS: Individual-level measures of disadvantage, lower education and living in poverty, were associated with heavier drinking, consuming 8+ drinks on a typical occasion or drinking at the higher risk level, when all countries were considered together. Drinkers in the middle-income countries had a higher probability of consuming 8+ drinks on a typical occasion relative to drinkers in the high-income countries. Interactions between country-level income and individual-level disadvantage were undertaken: disadvantaged drinkers in the middle-income countries were less likely to be heavier drinkers relative to those with less disadvantage in the high-income countries. DISCUSSION AND CONCLUSIONS: Associations between socio-economic disadvantage and heavier drinking vary depending on country-level income. These findings highlight the value of exploring cross-country differences in heavier drinking and disadvantage and the importance of including country-level measurements to better elucidate relationships

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit