Miracle-dz/UniFAR-FTUs huggingface dataset:
Interfacing behavioral and neural circuit models for habit formation

Habits are an important mechanism by which organisms can automate the control of behavior to alleviate cognitive demand. However, transitions to habitual control are risky because they lead to inflexible responding in the face of change. The question of how the brain controls transitions into habit is thus an intriguing one. How do we regulate when our repeated actions become automated? When is it advantageous or disadvantageous to release actions from cognitive control? Decades of research have identified a variety of methods for eliciting habitual responding in animal models. Progress has also been made to understand which brain areas and neural circuits control transitions into habit. Here, I discuss existing research on behavioral and neural circuit models for habit formation (with an emphasis on striatal circuits), and discuss strategies for combining information from different paradigms and levels of analysis to prompt further progress in the field.
Differences in patient-reported outcomes between medial opening-wedge high tibial osteotomy and total knee arthroplasty

Purpose: To compare patient subjective satisfaction between medial opening-wedge high tibial osteotomy (HTO) and total knee arthroplasty (TKA). Methods: This study enrolled 110 knees, including comprising 49 knees in the HTO group, and 61 knees in the TKA group. We assessed the overall satisfaction using a three-point questionnaire. The satisfaction questionnaire included three questions: (1) How satisfied are you with the results of your knee surgery? (2) How satisfied are you with your most recent knee surgery for reducing your pain? and (3) How satisfied are you with your most recent knee surgery for improving your ability to perform functions? Furthermore, we assessed knee pain and function by using the Knee Society Function Score (KSS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) systems. Results: Overall, 93.8% of patients from the HTO group and 95.1% from the TKA group indicated subjective satisfaction (very satisfied and satisfied) with their surgeries. For pain relief, the HTO group showed significantly better outcomes for overall satisfaction (p = 0.04 in walking on a flat surface and p = 0.02 in going upstairs or downstairs). For restored function, the HTO group scored significantly better on ascending stairs than the TKA group (p = 0.007). Functional outcomes using the KSS scoring system did not show significant differences between the two groups. The KOOS pain score was significantly higher in the TKA group (89.9 ± 6.4) than in the HTO group (80.3 ± 12.5). Conclusion: HTO and TKA have comparable outcomes with respect to overall patient satisfaction. Level of evidence: Level III, therapeutic case series.
Long-term efficacy after closure of patent foramen ovale for ischemic neurological events in young adults

Abstract Background: The efficacy of patent foramen ovale (PFO) closure remains controversial, and it is unclear which patient groups are best benefited. We performed this meta-analysis to clarify the efficacy of PFO closure of younger patients for prevention of recurrent ischemic neurological events. Methods: We systematically searched for studies of PFO closure for younger patients under the age of 55, and pooled available data on PFO closure of younger vs older patients and on PFO closure of younger patients vs medical therapy. The primary endpoints were the composite outcome of recurrent ischemic neurological events [stroke and/or transient ischemic attack (TIA)]. The secondary endpoints included recurrent stroke, TIA, atrial fibrillation (AF) and bleeding events. We calculated the odds ratios (OR) and 95% confidence interval (CI) using fixed-effect and random-effect models. Results: Three randomized controlled trials (RCT) and 13 observational studies were eligible. Compared with older patients undergoing PFO closure, younger patients undergoing closure had a lower risk of composite outcome (OR: 0.40, 95% CI: 0.28 to .56; P < .001) and AF (OR: 0.25, 95% CI: 0.10–0.61; P = .003). Compared with medical therapy, PFO closure of younger patients reduced the risk of composite outcome (OR: 0.50, 95% CI: 0.33–0.75; P<.001); there was no statistical difference in total complications of AF and bleeding events (OR: 2.15, 95% CI: 0.15–30.37; P = .57). Separate analysis of stroke and TIA showed that PFO closure in younger patients was more effective in preventing stroke (OR: 0.45, 95% CI: 0.28–0.72; P < .001) and TIA (OR: 0.35, 95% CI: 0.21–0.58); P < . 001) compared with older patients. Compared with medical therapy, PFO closure of younger patients reduced the risk of stroke (OR: 0.26, 95% CI: 0.13–0.51; P < .001); but there was no difference in the risk of TIA (OR: 1.07, 95% CI: 0.16–7.01; P = .94). Conclusions: Compared with PFO closure of older patients and medical therapy, PFO closure of younger patients can benefit more for the prevention of recurrent ischemic neurological events. Our results indicate that PFO closure is the best treatment strategy for younger patients under the age of 55.
Stomatal optimization based on xylem hydraulics (SOX) improves land surface model simulation of vegetation responses to climate

Summary Land surface models (LSMs) typically use empirical functions to represent vegetation responses to soil drought. These functions largely neglect recent advances in plant ecophysiology that link xylem hydraulic functioning with stomatal responses to climate. We developed an analytical stomatal optimization model based on xylem hydraulics (SOX) to predict plant responses to drought. Coupling SOX to the Joint UK Land Environment Simulator (JULES) LSM, we conducted a global evaluation of SOX against leaf‐ and ecosystem‐level observations. SOX simulates leaf stomatal conductance responses to climate for woody plants more accurately and parsimoniously than the existing JULES stomatal conductance model. An ecosystem‐level evaluation at 70 eddy flux sites shows that SOX decreases the sensitivity of gross primary productivity (GPP) to soil moisture, which improves the model agreement with observations and increases the predicted annual GPP by 30% in relation to JULES. SOX decreases JULES root‐mean‐square error in GPP by up to 45% in evergreen tropical forests, and can simulate realistic patterns of canopy water potential and soil water dynamics at the studied sites. SOX provides a parsimonious way to incorporate recent advances in plant hydraulics and optimality theory into LSMs, and an alternative to empirical stress factors.
Characteristics that make trophy hunting of giant pandas inconceivable

In November 1928, Theodore Jr. and Kermit Roosevelt led an expedition to China with the expressed purpose of being the first Westerners to kill the giant panda (Ailuropoda melanoleuca). The expedition lasted 8 months and resulted in the brothers shooting a giant panda in the mountains of Sichuan Province. Given the concurrent attention in the popular press describing this celebrated expedition, the giant panda was poised to be trophy hunted much like other large mammals around the world. Today, however, the killing of giant pandas, even for the generation of conservation revenue, is unthinkable for reasons related to the species itself and the context, in time and space, in which the species was popularized in the West. We found that the giant panda's status as a conservation symbol, exceptional charisma and gentle disposition, rarity, value as a nonconsumptive ecotourism attraction, and endemism are integral to the explanation of why the species is not trophy hunted. We compared these intrinsic and extrinsic characteristics with 20 of the most common trophy‐hunted mammals to determine whether the principles applying to giant pandas are generalizable to other species. Although certain characteristics of the 20 trophy‐hunted mammals aligned with the giant panda, many did not. Charisma, economic value, and endemism, in particular, were comparatively unique to the giant panda. Our analysis suggests that, at present, exceptional characteristics may be necessary for certain mammals to be excepted from trophy hunting. However, because discourse relating to the role of trophy hunting in supporting conservation outcomes is dynamic in both science and society, we suspect these valuations will also change in future.
A survey of outpatient Internal Medicine clinician perceptions of diagnostic error

Abstract Background Little is known about how practicing Internal Medicine (IM) clinicians perceive diagnostic error, and whether perceptions are in agreement with the published literature. Methods A 16-question survey was administered across two IM practices: one a referral practice providing care for patients traveling for a second opinion and the other a traditional community-based primary care practice. Our aim was to identify individual- and system-level factors contributing to diagnostic error (primary outcome) and conditions at greatest risk of diagnostic error (secondary outcome). Results Sixty-five of 125 clinicians surveyed (51%) responded. The most commonly perceived individual factors contributing to diagnostic error included atypical patient presentations (83%), failure to consider other diagnoses (63%) and inadequate follow-up of test results (53%). The most commonly cited system-level factors included cognitive burden created by the volume of data in the electronic health record (EHR) (68%), lack of time to think (64%) and systems that do not support collaboration (40%). Conditions felt to be at greatest risk of diagnostic error included cancer (46%), pulmonary embolism (43%) and infection (37%). Conclusions Inadequate clinician time and sub-optimal patient and test follow-up are perceived by IM clinicians to be persistent contributors to diagnostic error. Clinician perceptions of conditions at greatest risk of diagnostic error may differ from the published literature.
Comparison of Caregiver Engagement in Telepractice and In-person Family-Centered Early Intervention.

Telepractice-specifically, the use of high-speed internet and interactive videoconferencing technology to deliver real-time audio and video communications between the family and the practitioner-is gaining acceptance as an alternative means of providing family-centered early intervention to families of children who are deaf and hard of hearing. This study examined whether caregivers' reported perceptions of self-efficacy and involvement differed when early intervention was delivered in-person and through telepractice. The Scale of Parental Involvement and Self-Efficacy (SPISE) was used to evaluate perceptions of two groups of caregivers: one that received early intervention in-person (n = 100) and a group who received services through telepractice (n = 41). Results indicated that mode of delivery of services was not related to caregivers' perceptions of their self-efficacy or involvement. Further analysis revealed that although certain caregiver or child characteristics did influence some aspects of caregivers' beliefs about their self-efficacy or involvement, the effect of those variables was similar across both modes of delivery.
Designing cyclic competence-stimulating peptide (CSP) analogs with pan-group quorum-sensing inhibition activity in Streptococcus pneumoniae

Significance Streptococcus pneumoniae is a prevalent human pathogen that is a major cause of community-acquired pneumonia. S. pneumoniae utilizes the competence regulon to initiate its attack on the human host. In the current manuscript, we report 1) the design of cyclic competence-stimulating peptide analogs capable of inhibiting the competence regulon in S. pneumoniae with activities at the low nanomolar range; 2) structural analysis that elucidated the molecular mechanism of lead analogs; and 3) pharmacological evaluation of a lead analog that revealed that the peptide can attenuate S. pneumoniae-mediated acute pneumonia in vivo. Our results highlight the potential of inhibiting the competence regulon as a therapeutic approach to combat pneumococcus infections. Streptococcus pneumoniae is an opportunistic human pathogen that utilizes the competence regulon, a quorum-sensing circuitry, to acquire antibiotic resistance genes and initiate its attack on the human host. Interception of the competence regulon can therefore be utilized to study S. pneumoniae cell−cell communication and behavioral changes, as well as attenuate S. pneumoniae infectivity. Herein we report the design and synthesis of cyclic dominant negative competence-stimulating peptide (dnCSP) analogs capable of intercepting the competence regulon in both S. pneumoniae specificity groups with activities at the low nanomolar range. Structural analysis of lead analogs provided important insights as to the molecular mechanism that drives CSP receptor binding and revealed that the pan-group cyclic CSPs exhibit a chimeric hydrophobic patch conformation that resembles the hydrophobic patches required for both ComD1 and ComD2 binding. Moreover, the lead cyclic dnCSP, CSP1-E1A-cyc(Dap6E10), was found to possess superior pharmacological properties, including improved resistance to enzymatic degradation, while remaining nontoxic. Lastly, CSP1-E1A-cyc(Dap6E10) was capable of attenuating mouse mortality during acute pneumonia caused by both group 1 and group 2 S. pneumoniae strains. This cyclic pan-group dnCSP is therefore a promising drug lead scaffold against S. pneumoniae infections that could be administered individually or utilized in combination therapy to augment the effects of current antimicrobial agents.
Group metacognitive therapy for adolescents with anxiety and depressive disorders: A pilot study.

OBJECTIVE(S) The metacognitive model suggests that beliefs about cognition maintain repetitive negative thinking (RNT), a transdiagnostic process that underlies commonly comorbid, emotional disorders. To date, there has been the limited application of metacognitive therapy (MCT) to adolescents. This study aimed to evaluate a six-session group transdiagnostic MCT program for adolescents with anxiety and/or depressive disorders. METHOD Participants (N = 10; 3 male, 7 female; average age 15.2 years) completed measures of metacognition and RNT at assessment, baseline period, during treatment, and at 1- and 3-month follow-ups. RESULTS Nine participants attended all six treatment sessions and one discontinued after four sessions. At posttreatment and follow-ups, the majority of participants no longer met diagnostic criteria for anxiety or depressive disorders and evidenced a clinically significant or reliable change in metacognitions and RNT. CONCLUSIONS Results suggest that group MCT is promising in terms of acceptability and effectiveness for adolescents with anxiety and/or depressive disorders.
Ginsenoside Rg3 attenuates the osimertinib resistance by reducing the stemness of non‐small cell lung cancer cells

In the present study, we found that Ginsenoside Rg3 attenuated the stemness of non‐small cell lung cancer (NSCLC) cells, evident by decreasing spheroid formation ability, ALDH1 activity and stemness marker expression. Furthermore, osimertinib‐resistant NSCLC cells displayed a stronger stemness than the parental cells. Ginsenoside Rg3 reduced the stemness and osimertinib resistance of osimertinib‐resistant cells. RNA‐sequencing revealed that Hippo signaling was shown on the top of the most upregulated pathways regulated by Ginsenoside Rg3 in NSCLC cells, and YAP/TAZ expression was suppressed by Ginsenoside Rg3. Notably, the inhibitor of Hippo signaling attenuated the effects of Ginsenoside Rg3 on the stemness of NSCLC cells. Therefore, Ginsenoside Rg3 attenuates the osimertinib resistance of NSCLC cells via suppressing the stemness, which is dependent on Hippo pathway.
Bacterial pore‐forming toxin pneumolysin: Cell membrane structure and microvesicle shedding capacity determines differential survival of immune cell types

Bacterial infectious diseases can lead to death or to serious illnesses. These outcomes are partly the consequence of pore‐forming toxins, which are secreted by the pathogenic bacteria (eg, pneumolysin of Streptococcus pneumoniae). Pneumolysin binds to cholesterol within the plasma membrane of host cells and assembles to form trans‐membrane pores, which can lead to Ca2+ influx and cell death. Membrane repair mechanisms exist that limit the extent of damage. Immune cells which are essential to fight bacterial infections critically rely on survival mechanisms after detrimental pneumolysin attacks. This study investigated the susceptibility of different immune cell types to pneumolysin. As a model system, we used the lymphoid T‐cell line Jurkat, and myeloid cell lines U937 and THP‐1. We show that Jurkat T cells are highly susceptible to pneumolysin attack. In contrast, myeloid THP‐1 and U937 cells are less susceptible to pneumolysin. In line with these findings, human primary T cells are shown to be more susceptible to pneumolysin attack than monocytes. Differences in susceptibility to pneumolysin are due to (I) preferential binding of pneumolysin to Jurkat T cells and (II) cell type specific plasma membrane repair capacity. Myeloid cell survival is mostly dependent on Ca2+ induced expelling of damaged plasma membrane areas as microvesicles. Thus, in myeloid cells, first‐line defense cells in bacterial infections, a potent cellular repair machinery ensures cell survival after pneumolysin attack. In lymphoid cells, which are important at later stages of infections, less efficient repair mechanisms and enhanced toxin binding renders the cells more sensitive to pneumolysin.
Genetic Susceptibility Determines β-Cell Function and Fasting Glycemia Trajectories Throughout Childhood: A 12-Year Cohort Study (EarlyBird 76)

OBJECTIVE Previous studies suggested that childhood prediabetes may develop prior to obesity and be associated with relative insulin deficiency. We proposed that the insulin-deficient phenotype is genetically determined and tested this hypothesis by longitudinal modeling of insulin and glucose traits with diabetes risk genotypes in the EarlyBird cohort. RESEARCH DESIGN AND METHODS EarlyBird is a nonintervention prospective cohort study that recruited 307 healthy U.K. children at 5 years of age and followed them throughout childhood. We genotyped 121 single nucleotide polymorphisms (SNPs) previously associated with diabetes risk, identified in the adult population. Association of SNPs with fasting insulin and glucose and HOMA indices of insulin resistance and β-cell function, available from 5 to 16 years of age, were tested. Association analysis with hormones was performed on selected SNPs. RESULTS Several candidate loci influenced the course of glycemic and insulin traits, including rs780094 (GCKR), rs4457053 (ZBED3), rs11257655 (CDC123), rs12779790 (CDC123 and CAMK1D), rs1111875 (HHEX), rs7178572 (HMG20A), rs9787485 (NRG3), and rs1535500 (KCNK16). Some of these SNPs interacted with age, the growth hormone–IGF-1 axis, and adrenal and sex steroid activity. CONCLUSIONS The findings that genetic markers influence both elevated and average courses of glycemic traits and β-cell function in children during puberty independently of BMI are a significant step toward early identification of children at risk for diabetes. These findings build on our previous observations that pancreatic β-cell defects predate insulin resistance in the onset of prediabetes. Understanding the mechanisms of interactions among genetic factors, puberty, and weight gain would allow the development of new and earlier disease-management strategies in children.
Correlation between immunoglobulin dose administered and plasma neutralization of streptococcal superantigens in patients with necrotizing soft tissue infections.

Analyses of plasma collected pre- and post-administration of intravenous immunoglobulin G (IVIG) from patients with Group A Streptococcus necrotizing soft tissue infections demonstrated a negative correlation between IVIG dose and toxin-triggered T-cell proliferation (r=-0.67, p<0.0001). One 25g-dose IVIG was sufficient to yield patient plasma neutralizing activity against streptococcal superantigens.
Consequences of HSF knockdown on gene expression during the heat shock response in Tigriopus californicus

ABSTRACT Although the existence of a cellular heat shock response is nearly universal, its relationship to organismal thermal tolerance is not completely understood. Many of the genes involved are known to be regulated by the highly conserved heat shock transcription factor-1 (HSF-1), yet the regulatory network is not fully characterized. Here, we investigated the role of HSF-1 in gene expression following thermal stress using knockdown of HSF-1 by RNA interference in the intertidal copepod Tigriopus californicus. We observed some evidence for decreased transcription of heat shock protein genes following knockdown, supporting the widely acknowledged role of HSF-1 in the heat shock response. However, the majority of differentially expressed genes between the control and HSF-1 knockdown groups were upregulated, suggesting that HSF-1 normally functions to repress their expression. Differential expression observed in genes related to chitin and cuticle formation lends support to previous findings that these processes are highly regulated following heat stress. We performed a genome scan and identified a set of 396 genes associated with canonical heat shock elements. RNA-seq data did not find those genes to be more highly represented in our HSF-1 knockdown treatment, indicating that requirements for binding and interaction of HSF-1 with a given gene are not simply predicted by the presence of HSF-1 binding sites. Further study of the pathways implicated by these results and future comparisons among populations of T. californicus may help us understand the role and importance of HSF-1 in the heat shock response and, more broadly, in organismal thermal tolerance. Summary: In an investigation of its role in the heat shock response of an intertidal copepod, HSF-1 affected a complex gene suite both in response to and independent of heat stress.
Infants' attachment insecurity predicts attachment-relevant emotion regulation strategies in adulthood.

Infant attachment is theorized to lay the foundation of emotion regulation across the life span. However, testing this proposition requires prospective designs examining whether attachment assessed in infancy predicts emotion regulation strategies observed in adult relationships. Using unique data from the Minnesota Longitudinal Study of Risk and Adaptation, we examined whether infant attachment assessed at 12 and 18 months in the Strange Situation were associated with attachment-relevant emotion regulation strategies coded from video-recorded conflict discussions with romantic partners at ages 20, 23, 26, and/or 35. The current research first integrated the developmental and emotion regulation literatures to identify three specific attachment-relevant emotion regulation strategies. Balanced-regulation involves being open, approach-orientated, and engaging in collaborative problem-solving. Hypo-regulation involves suppressing emotions, disengaging from close others, and engaging in superficial problem-solving. Hyper-regulation involves exaggerating emotional expressions, ruminating, and being self-focused in processing issues. Compared to stable secure infants (secure at 12 and 18 months), stable insecure infants (insecure at 12 and 18 months) displayed worse balanced-regulation and greater hypo-regulation strategies, and unstable insecure infants (insecure at 12 or 18 months) displayed greater hyper-regulation strategies, in relationship-threatening situations 20-35 years later. Conceptually replicating these results, greater friendship insecurity at age 16 predicted worse balanced-regulation and greater hypo- and hyper-regulation strategies during relationship-threatening situations in adulthood. These findings highlight that infant attachment insecurity is associated with distinct emotion regulation strategies in adulthood 20-35 years later. (PsycINFO Database Record (c) 2020 APA, all rights reserved).