The 10 most-cited articles in Annals of the New York Academy of Sciences, 2023

Language models (LMs) like GPT-3, PaLM, and ChatGPT are the foundation for almost all major language technologies, but their capabilities, limitations, and risks are not well understood. We present Holistic Evaluation of Language Models (HELM) to improve the transparency of LMs. LMs can serve many purposes and their behavior should satisfy many desiderata. To navigate the vast space of potential scenarios and metrics, we taxonomize the space and select representative subsets. We evaluate models on 16 core scenarios and 7 metrics, exposing important trade-offs. We supplement our core evaluation with seven targeted evaluations to deeply analyze specific aspects (including world knowledge, reasoning, regurgitation of copyrighted content, and generation of disinformation). We benchmark 30 LMs, from OpenAI, Microsoft, Google, Meta, Cohere, AI21 Labs, and others. Prior to HELM, models were evaluated on just 17.9% of the core HELM scenarios, with some prominent models not sharing a single scenario in common. We improve this to 96.0%: all 30 models are now benchmarked under the same…

Accurate and affordable tools for diagnosing anemia and its main determinants are essential for understanding the magnitude and distribution of the problem and the appropriate interventions needed for its timely prevention and treatment. The objective of this review is to address methods, equipment, and sample-related and quality control aspects of hemoglobin measurement for anemia diagnosis. Also, other iron-, infectious-, and genetic-related causes of anemia are addressed in individuals and populations. The best practice for hemoglobin determination is the use of venous blood, analyzed on automated hematology analyzers, with high-quality control measures in place. The importance of a correct anemia diagnosis is highlighted by the cost of a misdiagnosis. A false-negative diagnosis may result in missing out and not treating anemia, its causes, and its adverse effects. On the other hand, a false-positive diagnosis may result in the provision of unneeded treatment or referral for expensive laboratory tests to determine a cause of anemia, wasting valuable resources and risking causing…

A functional interplay of bottom-up and top-down processing allows an individual to appropriately respond to the dynamic environment around them. These processing modalities can be represented as attractor states using a dynamical systems model of the brain. The transition probability to move from one attractor state to another is dependent on the stability, depth, neuromodulatory tone, and tonic changes in plasticity. However, how does the relationship between these states change in disease states, such as anxiety or depression? We describe bottom-up and top-down processing from Marr's computational-algorithmic-implementation perspective to understand depressive and anxious disease states. We illustrate examples of bottom-up processing as basolateral amygdala signaling and projections and top-down processing as medial prefrontal cortex internal signaling and projections. Understanding these internal processing dynamics can help us better model the multifaceted elements of anxiety and depression.

Anemia is a major public health concern. Young children, menstruating adolescent girls and women, and pregnant women are among the most vulnerable. Anemia is the consequence of a wide range of causes, including biological, socioeconomic, and ecological risk factors. Primary causes include: iron deficiency; inherited red blood cell disorders; infections, such as soil-transmitted helminthiasis, schistosomiasis, and malaria; gynecological and obstetric conditions; and other chronic diseases that lead to blood loss, decreased erythropoiesis, or destruction of erythrocytes. The most vulnerable population groups in low- and middle-income countries are often at the greatest risk to suffer from several of these causes simultaneously as low socioeconomic status is linked with an increased risk of anemia through multiple pathways. Targeted and effective action is needed to prevent anemia. Understanding the causes and risk factors of anemia for different population subgroups within a country guides the design and implementation of effective strategies to prevent and treat anemia. A coordinated…

More than 100 countries have communicated or adopted new Nationally Determined Contributions (NDCs) and net-zero target pledges. We investigate the impact on global, national, sectoral, and individual greenhouse gas emissions projections under different scenarios based on the announced NDCs and net-zero pledges using the IMAGE integrated assessment model. Our results show that while the net-zero pledges, if implemented, could be an important step forward, they are still not enough to achieve the Paris Agreement goals of well below 2°C and preferably 1.5°C by the end of the century. Still, our net-zero scenarios project significant all-sector decarbonization, in particular, electricity; however, certain sectors like industry and transport prove hard to completely abate.

Astrocytes are the most abundant glial cell type in the central nervous system and are essential to the development, plasticity, and maintenance of neural circuits. Astrocytes are heterogeneous, with their diversity rooted in developmental programs modulated by the local brain environment. Astrocytes play integral roles in regulating and coordinating neural activity extending far beyond their metabolic support of neurons and other brain cell phenotypes. Both gray and white matter astrocytes occupy critical functional niches capable of modulating brain physiology on time scales slower than synaptic activity but faster than those adaptive responses requiring a structural change or adaptive myelination. Given their many associations and functional roles, it is not surprising that astrocytic dysfunction has been causally implicated in a broad set of neurodegenerative and neuropsychiatric disorders. In this review, we focus on recent discoveries concerning the contributions of astrocytes to the function of neural networks, with a dual focus on the contribution of astrocytes to synaptic…

Huntington's disease (HD) is a fatal, monogenic, autosomal dominant neurodegenerative disease caused by a polyglutamine-encoding CAG expansion in the huntingtin (HTT) gene that results in mutant huntingtin proteins (mHTT) in cells throughout the body. Although large parts of the central nervous system (CNS) are affected, the striatum is especially vulnerable and undergoes marked atrophy. Astrocytes are abundant within the striatum and contain mHTT in HD, as well as in mouse models of the disease. We focus on striatal astrocytes and summarize how they participate in, and contribute to, molecular pathophysiology and disease-related phenotypes in HD model mice. Where possible, reference is made to pertinent astrocyte alterations in human HD. Astrocytic dysfunctions related to cellular morphology, extracellular ion and neurotransmitter homeostasis, and metabolic support all accompany the development and progression of HD, in both transgenic mouse and human cellular and chimeric models of HD. These findings reveal the potential for the therapeutic targeting of astrocytes so as to restore…

Emotion regulation is essential to survive in a world full of challenges with rapidly changing contextual demands. The ability to flexibly shift between different emotional control strategies is critical to successfully deal with these demands. Recently, decision neuroscience has shown the importance of monitoring alternative control strategies. However, this insight has not been incorporated into current neurocognitive models of emotional control. Here, we integrate insights from decision and affective sciences into a novel viewpoint on emotion control, the Flexible Emotion Control Theory (FECT). This theory explains how an individual can flexibly change emotion-regulatory behavior to adapt to varying goals and contextual demands. Crucially, FECT proposes that rapid switching between alternative emotional control strategies requires concurrent evaluation of current as well as alternative (unchosen) options. The neural implementation of FECT relies on the involvement of distinct prefrontal structures, including the lateral frontal pole (FPl) and its connections with other cortical…

Human cytomegalovirus (HCMV) is a prevalent herpesvirus, infecting the majority of the human population. Like other herpesviruses, it causes lifelong infection through the establishment of latency. Although reactivation from latency can cause significant morbidity and mortality in immunocompromised hosts, our understanding of HCMV latency and how it is maintained remains limited. Here, we discuss the characterized latency reservoir in hematopoietic cells in the bone marrow and the gaps in our knowledge of mechanisms that facilitate HCMV genome maintenance in dividing cells. We further review clinical evidence that strongly suggests the tissue origin of HCMV reactivation, and we outline similarities to murine cytomegalovirus where latency in tissue-resident cells has been demonstrated. Overall, we think these observations call for a rethinking of HCMV latency reservoirs and point to potential sources of HCMV latency that reside in tissues.

The present study aimed to analyze the different components of state mathematics anxiety that students experienced while solving calculation problems by manipulating their stress levels. A computerized mathematical task was administered to 165 fifth-graders randomly assigned to three different groups: positive, negative, and control conditions, in which positive, negative, or no feedback during the task was given, respectively. Behavioral (task performance), emotional (negative feelings), cognitive (worrisome thoughts and perceived competence), and psychophysiological responses (skin conductance and vagal withdrawal) were analyzed. Behavioral responses did not differ in the positive and negative conditions, while the latter was associated with children's reportedly negative emotional states, worries, and perceived lack of competence. The stress induced in the negative condition led to an increase in skin conductance and cardiac vagal withdrawal in children. Our data suggest the importance of considering students' interpretation of mathematics-related experiences, which might affect…