De novo design of proteins housing excitonically coupled chlorophyll special pairs.

Natural photosystems couple light harvesting to charge separation using a 'special pair' of chlorophyll molecules that accepts excitation energy from the antenna and initiates an electron-transfer cascade. To investigate the photophysics of special pairs independently of the complexities of native photosynthetic proteins, and as a first step toward creating synthetic photosystems for new energy conversion technologies, we designed C2-symmetric proteins that hold two chlorophyll molecules in closely juxtaposed arrangements. X-ray crystallography confirmed that one designed protein binds two chlorophylls in the same orientation as native special pairs, whereas a second designed protein positions them in a previously unseen geometry. Spectroscopy revealed that the chlorophylls are excitonically coupled, and fluorescence lifetime imaging demonstrated energy transfer. The cryo-electron microscopy structure of a designed 24-chlorophyll octahedral nanocage with a special pair on each edge closely matched the design model. The results suggest that the de novo design of artificial photosynthetic systems is within reach of current computational methods.

Epigenetic modulators provide a path to understanding disease and therapeutic opportunity.

The discovery of epigenetic modulators (writers, erasers, readers, and remodelers) has shed light on previously underappreciated biological mechanisms that promote diseases. With these insights, novel biomarkers and innovative combination therapies can be used to address challenging and difficult to treat disease states. This review highlights key mechanisms that epigenetic writers, erasers, readers, and remodelers control, as well as their connection with disease states and recent advances in associated epigenetic therapies.

Standardizing quality utilization of interventional radiology treatments of blunt splenic injury: SQUIRTS study.

OBJECTIVES: Nonoperative management (NOM) of blunt splenic injury (BSI) is well accepted in appropriate patients. Splenic artery embolization (SAE) in higher-grade injuries likely plays an important role in increasing the success of NOM. We previously implemented a protocol requiring referral of all BSI grades III-V undergoing NOM for SAE. It is unknown the risk of complications as well as longitudinal outcomes. We aimed to examine the splenic salvage rate and safety profile of the protocol. We hypothesized the splenic salvage rate would be high and complications would be low. METHODS: A retrospective study was performed at our Level 1 trauma center over a 9-year period. Injury characteristics and outcomes in patients sustaining BSI grades III-V were collected. Outcomes were compared for NOM on protocol (SAE) and off protocol (no angiography or angiography but no embolization). Complications for angiographies were examined. RESULTS: Between January 2010 and February 2019, 570 patients had grade III-V BSI. NOM was attempted in 359 (63 %) with overall salvage rate of 91 % (328). Of these, 305 were on protocol while 54 were off protocol (41 no angiography and 13 angiography but no SAE). During the study period, for every grade of injury a pattern was seen of a higher salvage rate in the on-protocol group when compared to the off-protocol group (Grade III, 97 %(181/187) vs. 89 %(32/36), Grade IV, 91 %(98/108) vs. 69 %(9/13) and Grade V, 80 %(8/10 vs. 0 %(0/5). The overall salvage rate was 94 %(287) on protocol vs. 76 %(41) off protocol (p < 0.001, Cochran-Mantel-Haenszel test). Complications occurred in only 8 of the 318 who underwent angiography (2 %). These included 5 access complications and 3 abscesses. CONCLUSION: The use of a protocol requiring routine splenic artery embolization for all high-grade spleen injuries slated for non-operative management is safe with a very low complication rate. NOM with splenic angioembolization failure rate is improved as compared to non-SAE patients' at all higher grades of injury. Thus, SAE for all hemodynamically stable patients of all high-grade types should be considered as a primary form of therapy for such injuries.

Establishing a Cell-Free Glycoprotein Synthesis System for Enzymatic N-GlcNAcylation.

N-linked glycosylation plays a key role in the efficacy of many therapeutic proteins. One limitation to the bacterial glycoengineering of human N-linked glycans is the difficulty of installing a single N-acetylglucosamine (GlcNAc), the reducing end sugar of many human-type glycans, onto asparagine in a single step (N-GlcNAcylation). Here, we develop an in vitro method for N-GlcNAcylating proteins using the oligosaccharyltransferase PglB from Campylobacter jejuni. We use cell-free protein synthesis (CFPS) to test promiscuous PglB variants previously reported in the literature for the ability to produce N-GlcNAc and successfully determine that PglB with an N311V mutation (PglBN311V) exhibits increased GlcNAc transferase activity relative to the wild-type enzyme. We then improve the transfer efficiency by producing CFPS extracts enriched with PglBN311V and further optimize the reaction conditions, achieving a 98.6 ± 0.5% glycosylation efficiency. We anticipate this method will expand the glycoengineering toolbox for therapeutic research and biomanufacturing.

Heuristic test reveals little effect of learning and maturation on early prey capture experiences in a web-building spider.

Behaviors can vary throughout an animal's life and this variation can often be explained by changes associated with learning and/or maturing. Currently, there is little consensus regarding how these processes interact to affect behaviors. Here we proposed a heuristic approach to disentangle the effects of learning and maturation on behavior and applied it to the predatory behaviors of Physocyclus globosus spiderlings. We varied the degree of prey difficulty and familiarity spiderlings received along the first instar and across the molt to the second instar and quantified the time spiderlings spent wrapping prey, as a proxy for prey capture efficiency. We found no overall evidence for learning or maturation. Changes in efficiency were mainly due to the switch from difficult to easy prey, or vice versa. However, there was one treatment where spiderlings improved in efficiency before and after the molt, without a switch in prey type. This provides some indication that difficult prey may offer more opportunity for learning or maturation to impact behavior. Although we found little effect of learning or maturation on prey capture efficiency, we suggest that our heuristic approach is effective and could be useful in investigating these processes in other behaviors and other animals.

Critical left main coronary artery stenosis presenting as cardiac arrest in coarctation of the aorta patient.

Congenital coronary artery stenosis coexisting with aortic coarctation in nonsyndromic patients has not previously been reported. This report describes a nonsyndromic aortic coarctation patient who experienced intraoperative cardiac arrest due to a previously undiagnosed critical left main coronary artery stenosis. The patient was successfully resuscitated, underwent patch coronary ostioplasty, and was discharged home. He remains well for four months following repair.

PDZ-Binding Kinase, a Novel Regulator of Vascular Remodeling in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is high blood pressure in the lungs that originates from structural changes in small resistance arteries. A defining feature of PAH is the inappropriate remodeling of pulmonary arteries (PA) leading to right ventricle failure and death. Although treatment of PAH has improved, the long-term prognosis for patients remains poor, and more effective targets are needed. METHODS: Gene expression was analyzed by microarray, RNA sequencing, quantitative polymerase chain reaction, Western blotting, and immunostaining of lung and isolated PA in multiple mouse and rat models of pulmonary hypertension (PH) and human PAH. PH was assessed by digital ultrasound, hemodynamic measurements, and morphometry. RESULTS: Microarray analysis of the transcriptome of hypertensive rat PA identified a novel candidate, PBK (PDZ-binding kinase), that was upregulated in multiple models and species including humans. PBK is a serine/threonine kinase with important roles in cell proliferation that is minimally expressed in normal tissues but significantly increased in highly proliferative tissues. PBK was robustly upregulated in the medial layer of PA, where it overlaps with markers of smooth muscle cells. Gain-of-function approaches show that active forms of PBK increase PA smooth muscle cell proliferation, whereas silencing PBK, dominant negative PBK, and pharmacological inhibitors of PBK all reduce proliferation. Pharmacological inhibitors of PBK were effective in PH reversal strategies in both mouse and rat models, providing translational significance. In a complementary genetic approach, PBK was knocked out in rats using CRISPR/Cas9 editing, and loss of PBK prevented the development of PH. We found that PBK bound to PRC1 (protein regulator of cytokinesis 1) in PA smooth muscle cells and that multiple genes involved in cytokinesis were upregulated in experimental models of PH and human PAH. Active PBK increased PRC1 phosphorylation and supported cytokinesis in PA smooth muscle cells, whereas silencing or dominant negative PBK reduced cytokinesis and the number of cells in the G2/M phase of the cell cycle. CONCLUSIONS: PBK is a newly described target for PAH that is upregulated in proliferating PA smooth muscle cells, where it contributes to proliferation through changes in cytokinesis and cell cycle dynamics to promote medial thickening, fibrosis, increased PA resistance, elevated right ventricular systolic pressure, right ventricular remodeling, and PH.

Transcription factor Nrf1 regulates proteotoxic stress-induced autophagy.

Cells exposed to proteotoxic stress invoke adaptive responses aimed at restoring proteostasis. Our previous studies have established a firm role for the transcription factor Nuclear factor-erythroid derived-2-related factor-1 (Nrf1) in responding to proteotoxic stress elicited by inhibition of cellular proteasome. Following proteasome inhibition, Nrf1 mediates new proteasome synthesis, thus enabling the cells to mitigate the proteotoxic stress. Here, we report that under similar circumstances, multiple components of the autophagy-lysosomal pathway (ALP) were transcriptionally upregulated in an Nrf1-dependent fashion, thus providing the cells with an additional route to cope with proteasome insufficiency. In response to proteasome inhibitors, Nrf1-deficient cells displayed profound defects in invoking autophagy and clearance of aggresomes. This phenomenon was also recapitulated in NGLY1 knockout cells, where Nrf1 is known to be non-functional. Conversely, overexpression of Nrf1 induced ALP genes and endowed the cells with an increased capacity to clear aggresomes. Overall, our results significantly expand the role of Nrf1 in shaping the cellular response to proteotoxic stress.

Adaptation of the Mycobacterium tuberculosis transcriptome to biofilm growth.

Mycobacterium tuberculosis (M. tb), the causative agent of tuberculosis (TB), is a leading global cause of death from infectious disease. Biofilms are increasingly recognized as a relevant growth form during M. tb infection and may impede treatment by enabling bacterial drug and immune tolerance. M. tb has a complicated regulatory network that has been well-characterized for many relevant disease states, including dormancy and hypoxia. However, despite its importance, our knowledge of the genes and pathways involved in biofilm formation is limited. Here we characterize the biofilm transcriptomes of fully virulent clinical isolates and find that the regulatory systems underlying biofilm growth vary widely between strains and are also distinct from regulatory programs associated with other environmental cues. We used experimental evolution to investigate changes to the transcriptome during adaptation to biofilm growth and found that the application of a uniform selection pressure resulted in loss of strain-to-strain variation in gene expression, resulting in a more uniform biofilm transcriptome. The adaptive trajectories of transcriptomes were shaped by the genetic background of the M. tb population leading to convergence on a sub-lineage specific transcriptome. We identified widespread upregulation of non-coding RNA (ncRNA) as a common feature of the biofilm transcriptome and hypothesize that ncRNA function in genome-wide modulation of gene expression, thereby facilitating rapid regulatory responses to new environments. These results reveal a new facet of the M. tb regulatory system and provide valuable insight into how M. tb adapts to new environments.

Effect of Far-Red Light on Biomass Accumulation, Plant Morphology, and Phytonutrient Composition of Ruby Streaks Mustard at Microgreen, Baby Leaf, and Flowering Stages.

Far-red (FR) light influences plant development significantly through shade avoidance response and photosynthetic modulation, but there is limited knowledge on how FR treatments influence the growth and nutrition of vegetables at different maturity stages in controlled environment agriculture (CEA). Here, we comprehensively investigated the impacts of FR on the yield, morphology, and phytonutrients of ruby streaks mustard (RS) at microgreen, baby leaf, and flowering stages. Treatments including white control, white with supplementary FR, white followed by singularly applied FR, and enhanced white (WE) matching the extended daily light integral (eDLI) of FR were designed for separating the effects of light intensity and quality. Results showed that singular and supplemental FR affected plant development and nutrition similarly throughout the growth cycle, with light intensity and quality playing varying roles at different stages. Specifically, FR did not affect the fresh and dry weight of microgreens but increased those values for baby leaves, although not as effectively as WE. Meanwhile, FR caused significant morphological change and accelerated the development of leaves, flowers, and seedpods more dramatically than WE. With regard to phytonutrients, light treatments affected the metabolomic profiles for baby leaves more dramatically than microgreens and flowers. FR decreased the glucosinolate and anthocyanin contents in microgreens and baby leaves, while WE increased the contents of those compounds in baby leaves. This study illustrates the complex impacts of FR on RS and provides valuable information for selecting optimal lighting conditions in CEA.

Experience of loneliness and depression due to spousal separation by long-term care residents and their spouses: a qualitative systematic review.

OBJECTIVE: The objective of this review was to describe the experiences of loneliness and/or depression for residents and their spouses who are separated by long-term care placement. INTRODUCTION: Loneliness and depression have a pernicious influence on the overall health and well-being of older adults. Older adults' mental health is significantly affected by social relationships, including those between spouses. However, research pertaining to the experience or effect of spousal separation on long-term care residents and community-dwelling spouses' feelings of loneliness and/or depression is limited. INCLUSION CRITERIA: This systematic review included studies that recruited community-dwelling spouses and long-term care residents over 50 years of age with living spouses from whom they are separated due to long-term care placement. Studies on the experiences of loneliness and/or depression due to spousal separation with one or both spouses living in long-term care were included in this review. METHODS: Ovid MEDLINE(R) was used for the initial search. A full search strategy was developed for Ovid MEDLINE(R), CINAHL (EBSCOhost), Embase (Ovid), and PsycINFO (Ovid). The review was conducted using the JBI approach, with 2 independent reviewers performing study selection, critical appraisal, data extraction, assessment of confidence, and data synthesis. RESULTS: Eleven papers were included in this systematic review. Four synthesized findings were extracted from 10 categories and 42 findings: i) Loneliness and depression result from a lack of physical and social connection for separated long-term care residents and community-dwelling spouses; ii) Community-dwelling spouses feel unprepared and upset with spousal separation due to a lack of psychological support; iii) Behavioral strategies can prevent community-dwelling spouses and long-term care residents from developing loneliness and/or depression; and 4) Community-dwelling spouses have differing abilities to adapt and cope with feelings of loneliness and/or depression. CONCLUSION: This review provides a comprehensive synthesis of the feelings of loneliness and/or depression spouses who are separated due to long-term care admission experience. This review has demonstrated that there is a lack of literature inclusive of the voices and perspectives of all spouses affected by spousal separation in long-term care. The limitations of this review include the small number of included studies and the range of quality of included studies. Recommendations include additional research on the lived experience of spousal separation from the perspectives of long-term care residents and their community-dwelling spouses. Further, additional psychological support is needed for separated spouses guided by the suggestions and experiences of long-term care residents and their community-dwelling spouses. REVIEW REGISTRATION: PROSPERO CRD42022333014.

Replacing the Scalpel With a Computer Mouse: An Evaluation of Time Spent on Electronic Health Record for Plastic Surgery Residents and Its Impact on Resident Training.

BACKGROUND: Following the integration of the electronic health record (EHR) into the healthcare system, concern has grown regarding EHR use on physician well-being. For surgical residents, time spent on the EHR increases the burden of a demanding, hourly restricted schedule and detracts from time spent honing surgical skills. To better characterize these burdens, we sought to describe EHR utilization patterns for plastic surgery residents. METHODS: Integrated plastic surgery resident EHR utilization from March 2019 to March 2020 was extracted via Cerner Analytics at a tertiary academic medical center. Time spent in the EHR on-duty (0600-1759) and off-duty (1800-0559) in the form of chart review, orders, documentation, and patient discovery was analyzed. Statistical analysis was performed in the form of independent t tests and Analysis of Variance (ANOVA). RESULTS: Twelve plastic surgery residents spent a daily average of 94 ± 84 minutes on the EHR, one-third of which was spent off-duty. Juniors (postgraduate years 1-3) spent 123 ± 99 minutes versus seniors (postgraduate years 4-6) who spent 61 ± 49 minutes (P < 0.01). Seniors spent 19% of time on the EHR off-duty, compared with 37% for juniors (P < 0.01). Chart review comprised the majority (42%) of EHR usage, followed by patient discovery (22%), orders (14%), documentation (12%), other (6%), and messaging (1%). Seniors spent more time on patient discovery (25% vs 21%, P < 0.001), while juniors spent more time performing chart review (48% vs 36%, P = 0.19). CONCLUSION: Integrated plastic surgery residents average 1.5 hours on the EHR daily. Junior residents spend 1 hour more per day on the EHR, including more time off-duty and more time performing chart review. These added hours may play a role in duty hour violations and detract from obtaining operative skill sets.

Cell Transplantation for Repair of the Spinal Cord and Prospects for Generating Region-Specific Exogenic Neuronal Cells.

Spinal cord injury (SCI) is associated with currently irreversible consequences in several functional components of the central nervous system. Despite the severity of injury, there remains no approved treatment to restore function. However, with a growing number of preclinical studies and clinical trials, cell transplantation has gained significant potential as a treatment for SCI. Researchers have identified several cell types as potential candidates for transplantation. To optimize successful functional outcomes after transplantation, one key factor concerns generating neuronal cells with regional and subtype specificity, thus calling on the developmental transcriptome patterning of spinal cord cells. A potential source of spinal cord cells for transplantation is the generation of exogenic neuronal progenitor cells via the emerging technologies of gene editing and blastocyst complementation. This review highlights the use of cell transplantation to treat SCI in the context of relevant developmental gene expression patterns useful for producing regionally specific exogenic spinal cells via in vitro differentiation and blastocyst complementation.

Sensitivity to the initial rewarding effects of alcohol: Influence of age, sex, and ß-endorphin.

BACKGROUND: Alcohol use disorders (AUDs) are widespread, devastating and complex. About 20% of people who consume alcohol develop problem use, accounting for over 5% of worldwide deaths. While numerous animal models have facilitated understanding of the consequences of excessive drinking, translational models allow for experimental manipulation of factors thought to contribute to AUD liability. METHODS: We employ a single-exposure conditioned place preference assay (SE-CPP) to investigate the influence of age, sex and the opioid peptide ß-endorphin (bE) on the initial rewarding effects of ethanol, a strong predictor of AUDs. Adolescent (PND28-35) and adult (PND70-90) male and female, control C57BL/6J and bE-deficient mice were tested following a single injection of 1.5 g/kg of ethanol. Following the SE-CPP test, animals were deeply anesthetized, sacrificed, and perfused, and the brains were subsequently sectioned at 40 microns and processed for immunohistochemical localization of c-fos. One-sample, two-tailed t-tests were used to assess drug preference or aversion and the locomotor effects of alcohol. RESULTS: In general, adults were more sensitive to the effects of alcohol than adolescents, and outcomes depended on sex and bE. For example, among females, adolescents were stimulated by the drug, but insensitive to locomotor effects as adults, while among males, adolescents were insensitive and adults sedated. Wild-type adolescents of both sexes failed to evince initial subjective reward from the drug, but bE-deficient adolescents, and all adult subjects, preferred a context once associated with ethanol over one that had been paired with saline. c-fos immunoreactivity in multiple brain regions was attenuated in bE-deficient animals, though influences of both sex and bE grew stronger with age. CONCLUSIONS: This study demonstrates the utility of the SE-CPP paradigm for elucidating factors that contribute to the liability for AUDs, and supports the growing body of research that shows that sensitivity to the rewarding effects of alcohol changes during the course of development. Our results also suggest that developmental contributions are sex-dependent, and may also depend on the influence of endogenous opioid signaling.

MYC is sufficient to generate mid-life high-grade serous ovarian and uterine serous carcinomas in a p53-R270H mouse model.

Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment is understood. However, previous GEMMs of high-grade serous ovarian cancer (HGSOC) have had to utilize genetics rarely or never found in human HGSOC to yield ovarian cancer within the lifespan of a mouse. MYC, an oncogene, is amongst the most amplified genes in HGSOC, but it has not previously been utilized to drive HGSOC GEMMs. We coupled Myc and dominant negative mutant p53-R270H with a fallopian tube epithelium-specific promoter Ovgp1 to generate a new GEMM of HGSOC. Female mice developed lethal cancer at an average of 15.1 months. Histopathological examination of mice revealed HGSOC characteristics including nuclear p53 and nuclear MYC in clusters of cells within the fallopian tube epithelium and ovarian surface epithelium. Unexpectedly, nuclear p53 and MYC clustered cell expression was also identified in the uterine luminal epithelium, possibly from intraepithelial metastasis from the fallopian tube epithelium (FTE). Extracted tumor cells exhibited strong loss of heterozygosity at the p53 locus, leaving the mutant allele. Copy number alterations in these cancer cells were prevalent, disrupting a large fraction of genes. Transcriptome profiles most closely matched human HGSOC and serous endometrial cancer. Taken together, these results demonstrate the Myc and Trp53-R270H transgene was able to recapitulate many phenotypic hallmarks of HGSOC through the utilization of strictly human-mimetic genetic hallmarks of HGSOC. This new mouse model enables further exploration of ovarian cancer pathogenesis, particularly in the 50% of HGSOC which lack homology directed repair mutations. Histological and transcriptomic findings are consistent with the hypothesis that uterine serous cancer may originate from the fallopian tube epithelium.

Plant periderm as a continuum in structural organisation: a tracheophyte-wide survey and hypotheses on evolution.

Periderm is a well-known structural feature with vital roles in protection of inner plant tissues and wound healing. Despite its importance to plant survival, knowledge of periderm occurrences outside the seed plants is limited and the evolutionary origins of periderm remain poorly explored. Here, we review the current knowledge of the taxonomic distribution of periderm in its two main forms - canonical periderm (periderm formed as a typical ontogenetic stage) and wound periderm (periderm produced as a self-repair mechanism) - with a focus on major plant lineages, living and extinct. We supplement the published occurrences with data based on our own observations and experiments. This updated body of data reveals that the distribution of wound periderm is more widespread taxonomically than previously recognized and some living and extinct groups are capable of producing wound periderm, despite canonical periderm being absent from their normal developmental program. A critical review of canonical and wound periderms in extant and fossil lineages indicates that not all periderms are created equal. Their organisation is widely variable and the differences can be characterised in terms of variations in three structural features: (i) the consistency in orientation of periclinal walls within individual files of periderm cells; (ii) the lateral coordination of periclinal walls between adjacent cell files; and (iii) whether a cambial layer and conspicuous layering of inward and outward derivatives can be distinguished. Using a new system of scoring periderm structure based on these criteria, we characterise the level of organisation of canonical and wound periderms in different lineages. Looking at periderms through the lens provided by their level of organisation reveals that the traditional image of periderm as a single generalised feature, is best viewed as a continuum of structural configurations that are all predicated by the same basic process (periclinal divisions), but can fall anywhere between very loosely organized (diffuse periclinal growth) to very tightly coordinated (organized periclinal growth). Overall, wound periderms in both seed plants and seed-free plants have lower degrees of organisation than canonical periderms, which may be due to their initiation in response to inherently disruptive traumatic events. Wound and canonical periderms of seed plants have higher degrees of organisation than those of seed-free plants, possibly due to co-option of the programs responsible for organizing their vascular cambial growth. Given the importance of wound periderm to plant survival, its widespread taxonomic distribution, and its early occurrence in the fossil record, we hypothesise that wound periderm may have had a single origin in euphyllophytes and canonical periderm may have originated separately in different lineages by co-option of the basic regulatory toolkit of wound periderm formation. In one evolutionary scenario, wound periderm regulators activated initially by tissue tearing due to tensional stresses elicited by woody growth underwent heterochronic change that switched their activation trigger from tissue tearing to the tensional stresses that precede it, with corresponding changes in the signalling that triggered the regulatory cascade of periderm development from tearing-induced signals to signalling induced by tension in cells.

Differentiation between atypical anorexia nervosa and anorexia nervosa using machine learning.

OBJECTIVE: Body mass index (BMI) is the primary criterion differentiating anorexia nervosa (AN) and atypical anorexia nervosa despite prior literature indicating few differences between disorders. Machine learning (ML) classification provides us an efficient means of accurately distinguishing between two meaningful classes given any number of features. The aim of the present study was to determine if ML algorithms can accurately distinguish AN and atypical AN given an ensemble of features excluding BMI, and if not, if the inclusion of BMI enables ML to accurately classify between the two. METHODS: Using an aggregate sample from seven studies consisting of individuals with AN and atypical AN who completed baseline questionnaires (N = 448), we used logistic regression, decision tree, and random forest ML classification models each trained on two datasets, one containing demographic, eating disorder, and comorbid features without BMI, and one retaining all features and BMI. RESULTS: Model performance for all algorithms trained with BMI as a feature was deemed acceptable (mean accuracy = 74.98%, mean area under the receiving operating characteristics curve [AUC] = 74.75%), whereas model performance diminished without BMI (mean accuracy = 59.37%, mean AUC = 59.98%). DISCUSSION: Model performance was acceptable, but not strong, if BMI was included as a feature; no other features meaningfully improved classification. When BMI was excluded, ML algorithms performed poorly at classifying cases of AN and atypical AN when considering other demographic and clinical characteristics. Results suggest a reconceptualization of atypical AN should be considered. PUBLIC SIGNIFICANCE: There is a growing debate about the differences between anorexia nervosa and atypical anorexia nervosa as their diagnostic differentiation relies on BMI despite being similar otherwise. We aimed to see if machine learning could distinguish between the two disorders and found accurate classification only if BMI was used as a feature. This finding calls into question the need to differentiate between the two disorders.

Pitfalls in research on ecological validity of novel executive function tests: A systematic review and a call to action.

The term "ecological validity" (EV) has traditionally referred to test scores' ability to predict real-world functioning. However, a test's similarity to real-world tasks is sometimes mistaken for evidence of its ability to predict daily life, sometimes bypassing rigorous validation research. The goal of this systematic review was to examine the type and quality of evidence used to support claims of EV of novel face-valid tests of executive functions (EF). MEDLINE and PsychINFO databases were searched using the following terms: ecologic* AND neuropsychol* AND (executive function* OR executive dysfunction OR executive abilit*). Thirty-two articles that explicitly stated that their results demonstrated EV of a novel face-valid test of EF were identified. Results showed that only 60% of studies based their claims about EV on test scores' ability to predict functional outcomes, with the remaining 40% relying on other evidence (e.g., correlations with other measures, participant feedback, group differences). Among the studies that did base their conclusions on test scores' ability to predict outcomes (n = 19), an overwhelming majority relied on behavioral rating scales, utilized small sample sizes and participant-to-variable ratios, and failed to control for covariates and multiple comparisons. Poor scientific rigor was particularly pronounced in studies of "naturalistic" tests. The present systematic review reveals significant conceptual, methodological, and statistical flaws among an overwhelming majority of studies that claim to have found support for the EV of a novel face-valid test of EF. We call upon authors, reviewers, and editors to safeguard the scientific rigor of research in this area. (PsycInfo Database Record (c) 2024 APA, all rights reserved).