The pipeline of highly trained STEM (science, technology, engineering, and mathematics) professionals has narrowed in recent decades, forcing society to re-examine how schools are discovering and developing STEM talent. Of particular concern is the finding that rural students attend post-secondary schools at lower rates than their urban counterparts, and when they do attend, they are less likely to graduate from STEM programs. One reason may be that they are not prepared for advanced STEM coursework because they lack access to essential STEM talent-development programs in middle or high school. This creates excellence gaps, which exacerbate the narrowing STEM pipeline to the workforce. To address this, we formed a university–school partnership to develop an outside-of-school STEM talent development program, called STEM Excellence, for rural middle-school students who attend under-resourced schools. The aim of STEM Excellence was to increase students’ achievement and aspirations while empowering their teachers to develop local STEM programs grounded in developmental psychology theories. STEM Excellence integrated the Talent Development Megamodel Principles of ability, domains of talent, opportunity, and psychosocial variables. STEM Excellence also recognized the interplay of multiple person–environment systems as presented in the Bioecological Systems Model.

The abilities to form concepts and abstractions, and to make analogies, are key to human intelligence, but AI systems have a long way to go before they can match the abilities of humans in these areas. To develop machines that can abstract and analogize, researchers typically focus on idealized problem domains that are meant to capture the essence of human abstraction abilities without having to deal with the complexity of real-world situations. This commentary describes why solving problems in these domains remains difficult for AI systems, and discusses how AI researches can make progress on imbuing machines with these essential abilities.

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.

Dietary calcium intake is low in many countries, particularly in low- and middle-income countries (LMICs). Water is often overlooked as a source of dietary calcium despite it being universally consumed and providing good calcium bioavailability. Our objective was to assess water distribution systems in LMICs and to develop a formula to simulate the contribution of different water sources to calcium availability. We calculated the contribution of drinking water considering different calcium concentration levels to estimate total calcium availability. We consider a country's households’ access to drinking water sources and the distribution of the country's population by age and gender. Calcium availability could be increased by an average of 49 mg of calcium per person per day in the 62 countries assessed if calcium in drinking water was considered. In 22 (31%) of the countries studied, 80% of households are supplied by water sources that could increase calcium availability. Improving calcium concentration in water could be considered as a strategy in LMICs to slightly improve calcium availability.

The kidney is critical for mineral homeostasis. Calcium and magnesium reabsorption in the renal thick ascending limb (TAL) involves claudin-16 (CLDN16) and claudin-19 (CLDN19) and pathogenic variants in either gene lead to familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) with severe calcium and magnesium wasting. While both CLDN16 and CLDN19 localize to the TAL, varying expression patterns in the renal tubule have been reported using different antibodies. We, therefore, studied the localization of CLDN19 in the kidneys of wild-type and Cldn19-deleted mice using three anti-CLDN19 antibodies and examined the role of Cldn19 deletion on CLDN16 and CLDN10 localization. We find that CLDN19 localizes to basolateral membrane domains of the medullary and cortical TAL but only to the tight junction of TALs in the outer stripe of outer medulla and cortex, where it colocalizes with CLDN16. Furthermore, in TALs from Cldn19-deleted mice, CLDN16 is expressed in basolateral membrane domains but not at the tight junction. In contrast, Cldn19 ablation does not change CLDN10 localization. These findings directly implicate CLDN19 in regulating permeability in the TAL by allowing junctional insertion of CLDN16 and may explain the shared renal phenotypic characteristics in FHHNC patients.

New interdisciplinary research into genetic influences on musicality raises a number of ethical and social issues for future avenues of research and public engagement. The historical intersection of music cognition and eugenics heightens the need to vigilantly weigh the potential risks and benefits of these studies and the use of their outcomes. Here, we bring together diverse disciplinary expertise (complex trait genetics, music cognition, musicology, bioethics, developmental psychology, and neuroscience) to interpret and guide the ethical use of findings from recent and future studies. We discuss a framework for incorporating principles of ethically and socially responsible conduct of musicality genetics research into each stage of the research lifecycle: study design, study implementation, potential applications, and communication.

Changes in synaptic function are an early hallmark of neuropathological conditions that often precede symptom onset, with mounting genetic, transcriptional, and epidemiological evidence implicating microglia in this process. The correlation between infection and neurocognitive sequelae further suggests that environmental exposures modulate neuroimmune interactions and contribute to synaptic alterations. Recent studies investigating functional roles of microglia across broad neuropathological contexts including neurodegeneration, aging, neuropsychiatric and neurodevelopmental disorders, and neurotropic infections reveal convergent mechanisms underlying microglial-mediated synaptic dysfunction. We propose that early microglial changes, driven by genetic alterations coupled with environmental neuroimmune modulation, may be a common denominator that contributes to early synaptic pathologies. Here we review the evidence and discuss how microglia respond, and contribute, to synaptopathies across diverse neurological conditions, spotlighting their importance as broadly relevant therapeutic targets within neurological diseases.

Globally, dietary intake of calcium is often insufficient, and it is unclear if adequacy could be achieved by promoting calcium-rich local foods. This study used linear programming and household consumption data from Uganda, Bangladesh, and Guatemala to assess whether local foods could meet calcium population reference intakes (Ca PRIs). The most promising food-based approaches to promote dietary calcium adequacy were identified for 12- to 23-month-old breastfed children, 4- to 6-year-old children, 10- to 14-year-old girls, and nonpregnant and nonbreastfeeding (NPNB) women of reproductive age living in two regions of each country. Calcium-optimized diets achieved 75–253% of the Ca PRI, depending on the population, and were <100% for 4- to 6-year-olds in one region of each country and 10- to 14-year-old girls in Sylhet, Bangladesh. The best food sources of calcium were green leafy vegetables and milk, across geographic locations, and species of small fish, nixtamalized (lime-treated) maize products, sesame seeds, and bean varieties, where consumed. Food-based recommendations (FBRs) achieving the minimum calcium threshold were identified for 12- to 23-month-olds and NPNB women across geographic locations, and for 4- to 6-year-olds and 10-to 14-year-old girls in Uganda. However, for 4- to 6-year-olds and 10- to 14-year-old girls in Bangladesh and Guatemala, calcium-adequate FBRs could not be identified, indicating a need for alternative calcium sources or increased access to and consumption of local calcium-rich foods.

Chronic impairment in the paretic ankle following stroke often requires that individuals use compensatory patterns such as asymmetric propulsion to achieve effective walking speeds needed for community engagement. Ankle exosuit assistance can provide ankle biomechanical benefit in the lab, but such environments inherently limit the amount of practice available. Community walking studies without exosuits can provide massed practice and benefit walking speed but are limited in their ability to assist proper mechanics. In this study, we combined the positive aspects of community training with those of exosuit assistance. We developed and evaluated a community Robotic Exosuit Augmented Locomotion (cREAL) program. Four participants in the chronic stage of stroke independently used our community ankle exosuit for walking in the community 3–5 days/week for 4 weeks. We performed lab evaluations before and after the 4-week program. Two participants significantly improved their unassisted paretic propulsion by an average of 27% after the program and walked on average 4001 steps/day more in the week following the program. Despite the small number of participants, this study provides preliminary evidence for the potential of exosuits to augment gait training and rehabilitation in the community.

Adequate calcium intake is essential for health, especially for infants, children, adolescents, and women, yet is difficult to achieve with local foods in many low- and middle-income countries. Previous analysis found it was not always possible to identify food-based recommendations (FBRs) that reached the calcium population recommended intake (PRI) for these groups in Bangladesh, Guatemala, and Uganda. We have modeled the potential contribution of calcium-fortified drinking water or wheat flour to FBR sets, to fill the remaining intake gaps. Optimized diets containing fortified products, with calcium-rich local foods, achieved the calcium PRI for all target groups. Combining fortified water or flour with FBRs met dietary intake targets for adolescent girls in all geographies and allowed a reduction from 3–4 to the more feasible 1–2 FBRs. Water with a calcium concentration of 100 mg/L with FBRs was sufficient to meet calcium targets in Uganda, but higher concentrations (400–500 mg/L) were mostly required in Guatemala and Bangladesh. Combining calcium-fortified wheat flour at 400 mg/100 g of flour and the FBR for small fish resulted in diets meeting the calcium PRI in Bangladesh. Calcium-fortified water or flour could improve calcium intake for vulnerable populations, especially when combined with FBRs based on locally available foods.

Epigenetic transcriptional regulation frequently requires histone modifications. Some, but not all, of these modifications are able to template their own inheritance. Here, I discuss the molecular mechanisms by which histone modifications can be inherited and relate these ideas to new results about epigenetic transcriptional memory, a phenomenon that poises recently repressed genes for faster reactivation and has been observed in diverse organisms. Recently, we found that the histone H3 lysine 4 dimethylation that is associated with this phenomenon plays a critical role in sustaining memory and, when factors critical for the establishment of memory are inactivated, can be stably maintained through multiple mitoses. This chromatin-mediated inheritance mechanism may involve a physical interaction between an H3K4me2 reader, SET3C, and an H3K4me2 writer, Spp1− COMPASS. This is the first example of a chromatin-mediated inheritance of a mark that promotes transcription.

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 their emotional, cognitive, and psychophysiological responses.

An important first step in talent development in science, technology, engineering, and mathematics (STEM) is getting individuals excited about STEM. Females, in particular, are underrepresented in many STEM fields. Since girls’ interest in STEM declines in adolescence, interventions should begin in secondary education at the latest. One appropriate intervention is (online) mentoring. Although its short-term effectiveness has been demonstrated for proximal outcomes during secondary education (e.g., positive changes in elective intentions in STEM), studies of the long-term effectiveness of STEM mentoring provided during secondary education—especially for real-life choices of university STEM majors and professions—are lacking. In our study, we examine females’ real-life decisions about university majors and entering professions made years after they had participated in an online mentoring program (CyberMentor) during secondary education. The program's proximal positive influence on girls’ elective intentions in STEM and certainty about career plans during secondary education had previously been demonstrated in several studies with pre–post-test waitlist control group designs. Specifically, we compared the choices that former mentees (n = 410) made about university majors and entering professions several years after program participation with (1) females of their age cohort and (2) females of a group of girls comparably interested in STEM who had signed up for the program but then not participated (n = 71). Further, we examined the explanatory contribution to these later career-path-relevant, real-life choices based on (1) mentees’ baseline conditions prior to entering the program (e.g., elective intentions in STEM), (2) successful 1-year program participation, and (3) multiyear program participation. Findings indicate positive long-term effects of the program in all areas investigated.

Using latent profile analysis, we identified profiles of expectancy beliefs, perceived values, and perceived costs among 1433 first- and second-year undergraduates in an introductory chemistry course for STEMM majors. We also investigated demographic differences in profile membership and the relation of profiles to chemistry final exam achievement, science/STEMM credits completed, and graduating with a science/STEMM major. Four motivational profiles were identified: Moderately Confident and Costly (profile 1), Mixed Values-Costs/Moderate-High Confidence (profile 2), High Confidence and Values/Moderate-Low Costs (profile 3), and High All (profile 4). Underrepresented students in STEMM were more likely to be in profile 2 relative to profile 3. First-generation college students were more likely to be in profile 4 than profile 3. Finally, students likely to be in profile 3 had higher final exam grades than the other profiles and were more likely to graduate with a science major compared to profile 1. There were no differences in graduating science major between profile 3 and the other two profiles. Thus, profile 3 was most adaptive for both proximal (final exam) and distal (graduating with a science major) outcomes. Results suggest that supporting motivation early in college is important for persistence and ultimately the talent development of undergraduate STEMM students.

Familial tooth agenesis (FTA) is one of the most common craniofacial anomalies in humans. Loss-of-function mutations in PAX9 and WNT10A have been known to cause FTA with various expressivity. In this study, we identified five FTA kindreds with novel PAX9 disease-causing mutations: p.(Glu7Lys), p.(Val83Leu), p.(Pro118Ser), p.(Ser197Argfs*23), and c.771+4A>G. Concomitant PAX9 and WNT10A pathogenic variants found in two probands with severe phenotypes suggested an effect of mutational synergism. All overexpressed PAX9s showed proper nuclear localization, excepting the p.(Pro118Ser) mutant. Various missense mutations caused differential loss of PAX9 transcriptional ability. PAX9 overexpression in dental pulp cells upregulated LEF1 and AXIN2 expression, indicating a positive regulatory role for PAX9 in canonical Wnt signaling. Analyzing 176 cases with 63 different mutations, we observed a distinct pattern of tooth agenesis for PAX9-associated FTA: Maxillary teeth are in general more frequently affected than mandibular ones. Along with all second molars, maxillary bicuspids and first molars are mostly involved, while maxillary lateral incisors and mandibular bicuspids are relatively less affected. Genotypically, missense mutations are associated with fewer missing teeth than frameshift and nonsense variants. This study significantly expands the phenotypic and genotypic spectrums of PAX9-associated disorders and reveals a molecular mechanism of genetic synergism underlying FTA variable expressivity.

Inculcating the capacity to adapt successfully to failures is essential for talent development in science, technology, engineering, and mathematics (STEM) fields. Despite its importance, this capacity to learn from failure is among the least understood processes in the field of talent development. This study aims to investigate how students conceptualize and react to failures and whether there is a correlation between students’ conceptualizations of failure, emotional reactions to it, and academic performance. We invited 150 high-achieving high school students to share, interpret, and label their most memorable struggles in their STEM classes. Most of their struggles focused on the learning process itself, such as poor understanding of the subject matter, insufficient motivation or effort, or adopting ineffective learning strategies. Poor performance outcomes, such as poor test scores and bad grades, were not mentioned as frequently as the learning process. Students who labeled their struggle experiences as failures tended to focus more on performance outcomes, whereas students who labeled their struggle experiences as neither failures nor successes focused more on the learning process. Higher-achieving students were also less likely to label their struggles as failures than less-high achievers. Implications for classroom instruction are discussed with a particular focus on talent development in STEM fields.

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 harm. At the individual level, clinicians must understand the causes of absolute and functional anemia to diagnose and treat anemia at the clinical level. Actions toward anemia diagnosis and control at public health levels require global, regional, and country actions that should cover general and context-specific characteristics.

The epistemic feat that we call science is not an aseptic outcome of reasoning from an eternal viewpoint but the product of myriad epistemic communities with intersecting and interlacing scientific perspectives.

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.

Human society encompasses diverse social influences, and people experience events differently and may behave differently under such influence, including in forming an impression of others. However, little is known about the underlying neural relevance of individual differences in following others’ opinions or social norms. In the present study, we designed a series of tasks centered on social influence to investigate the underlying relevance between an individual's degree of social conformity and their neural variability. We found that individual differences under the social influence are associated with the amount of inter-trial electroencephalogram (EEG) variability over multiple stages in a conformity task (making face judgments and receiving social influence). This association was robust in the alpha band over the frontal and occipital electrodes for negative social influence. We also found that inter-trial EEG variability is a very stable, participant-driven internal state measurement and could be interpreted as mindset instability. Overall, these findings support the hypothesis that higher inter-trial EEG variability may be related to higher mindset instability, which makes participants more vulnerable to exposed external social influence. The present study provides a novel approach that considers the stability of one's endogenous neural signal during tasks and links it to human social behaviors.