Miracle-dz/UniFAR-FTUs huggingface dataset:
The Performance of Multivariate Methods for Two-Group Comparisons with Small Samples and Incomplete Data

Abstract In intervention studies having multiple outcomes, researchers often use a series of univariate tests (e.g., ANOVAs) to assess group mean differences. Previous research found that this approach properly controls Type I error and generally provides greater power compared to MANOVA, especially under realistic effect size and correlation combinations. However, when group differences are assessed for a specific outcome, these procedures are strictly univariate and do not consider the outcome correlations, which may be problematic with missing outcome data. Linear mixed or multivariate multilevel models (MVMMs), implemented with maximum likelihood estimation, present an alternative analysis option where outcome correlations are taken into account when specific group mean differences are estimated. In this study, we use simulation methods to compare the performance of separate independent samples t tests estimated with ordinary least squares and analogous t tests from MVMMs to assess two-group mean differences with multiple outcomes under small sample and missingness conditions. Study results indicated that a MVMM implemented with restricted maximum likelihood estimation combined with the Kenward–Roger correction had the best performance. Therefore, for intervention studies with small N and normally distributed multivariate outcomes, the Kenward–Roger procedure is recommended over traditional methods and conventional MVMM analyses, particularly with incomplete data.
Conclusions and questions from a non-randomised comparison of routine clinical services implementing different treatment models for borderline personality disorder

Our study (Barnicot & Crawford 2018) was a non-randomised comparison of outcomes in routine clinical services implementing different treatment models for borderline personality disorder (BPD): mentalization-based therapy (MBT) and dialectical behaviour therapy (DBT). Our study’s contribution lies primarily in its novelty as currently the only head-to-head comparison of these treatment models, and its potential to generate exploratory findings for further testing in a definitive randomised controlled trial. We thank Luyten and colleagues for their useful commentary.
Adolescents’ Attitudes and Intentions toward Help-Seeking and Computer-Based Treatment for Depression

Objective Many depressed adolescents do not seek professional help despite there being evidence-based treatments for depression, such as cognitive behavioral therapy or computer-based therapy. To increase professional help-seeking behavior in depressed adolescents, it is necessary to positively change help-seeking attitudes. This study aimed to explore the effect of sub-groups of help-seeking attitudes, gender, and depression level on adolescents’ help-seeking intentions and their perceptions of computer-based psychotherapy. Methods Participants were 246 adolescents aged 13–18 years recruited from six middle and high schools in South Korea. Measures were self-administered questionnaires, and included the Patient Health Questionnaire-9, the Attitudes Toward Seeking Professional Psychological Help Scale, the Intention to Seek Counseling Inventory, Preferences for Depression Treatment, and the Perceptions of Computerized Therapy Questionnaire. Results Help-seeking intentions were positively related with female gender and the recognition of the need for help. A higher level of confidence in therapists was related to high preference for computer-based therapy and face-to-face therapy. Adolescents with more severe depression were more likely to prefer pharmacotherapy. The perceptions of computer-based therapy were more positive in male adolescents, and in adolescents with a higher level of confidence in therapists yet a lower level of interpersonal openness. Conclusion To promote adolescents’ help-seeking behavior, improvement of the recognition of the need for help is required, especially among male adolescents. Computer-based therapy provides an alternative for male adolescents with high confidence in therapists yet low interpersonal openness. Consideration of the help-seeking attitudes and gender is needed when providing therapeutic intervention to depressed adolescents.
Effect of reimbursement restriction policy on the use of benzodiazepines in the Netherlands: an interrupted time series analysis

Objectives Use of benzodiazepines has health risks. Reimbursement was restricted in the Netherlands from January 2009 onwards with the goal to reduce chronic use and healthcare expenditures. The aim of this study is to assess the initial and long-term effects of this policy on benzodiazepine use. Design Interrupted time series analysis, segmented regression models, Kaplan-Meier survival analysis and Cox proportional hazards analysis. Setting A 10% random sample of benzodiazepine dispensings by outpatient pharmacies between January 2002 and August 2015 were obtained from the PHARMO database. This database covered a catchment area representing about 3.6 million residents in 2015. Participants 2 500 800 benzodiazepine prescriptions from 128 603 patients were included. Intervention Reimbursement restriction policy from January 2009 onwards. Outcome measures Changes in: the volume of dispensed prescriptions and doses, the incidence, prevalence of incidental, regular and chronic use and discontinuation rates of benzodiazepines. Results The volume of dispensed prescriptions and doses decreased by 12.5% (95% CI 9.0% to 15.9%) and 15.1% (95% CI 11.4% to 17.3%) respectively in January 2009 compared with December 2008. A clear initial effect on the overall incidence (−14.7%; 95% CI −19.8% to 9.6%) and the prevalence of incidental (−17.8%; 95% CI −23.9% to 11.7%), regular (−20.0%; 95% CI −26.1% to 13.9%) and chronic (−16.0%; 95% CI −23.1% to 8.9%) use was observed. A statistically significant reduction in the monthly trend per 1000 medication users was observed for the overall incidence (−0.017; 95% CI −0.031 to 0.003) and the prevalence of incidental (−3.624; 95% CI −4.996 to 2.252) but not for regular (−0.304; 95% CI −1.204 to 0.596) and chronic (0.136; 95% CI −0.858 to 1.130) use. Patients who started treatment before policy had a slightly higher probability of discontinuation (HR=1.013; 95% CI 1.004 to 1.022). Conclusions The reimbursement policy had a significant initial effect on the volume, incidence and prevalence of benzodiazepine use. In addition, there is a statistically significant reduction in the monthly trend of overall incidence and of the prevalence of incidental use. No statistically significant reduction in the monthly trend of chronic use, the main purpose of the reimbursement restriction, could be demonstrated.
Population adaptation in efficient balanced networks

Adaptation is a key component of efficient coding in sensory neurons. However, it remains unclear how neurons can provide a stable representation of external stimuli given their history-dependent responses. Here we show that a stable representation is maintained if efficiency is optimized by a population of neurons rather than by neurons individually. We show that spike-frequency adaptation and E/I balanced recurrent connectivity emerge as solutions to a global cost-accuracy tradeoff. The network will re-distribute sensory responses from highly excitable neurons to less excitable neurons as the cost of neural activity increases. This does not change the representation at the population level, despite causing dynamic changes in individual neurons. By applying this framework to an orientation coding network, we reconcile neural and behavioral findings. Our approach underscores the common mechanisms behind the diversity of neural adaptation and its role in producing a reliable representation of the stimulus while minimizing metabolic cost.
Gender-Typed and Gender-Segregated Play Among Tanzanian Hadza and Congolese BaYaka Hunter-Gatherer Children and Adolescents.

Few data exist on gender-typed and gender-segregated play in hunter-gatherer societies, despite their unique demographic and cultural features which may influence children's gendered play. Using naturalistic observations of Hadza (N = 46, 41% female) and BaYaka (N = 65, 48% female) hunter-gatherer 3- to 18-year-olds from Tanzania and the Republic of Congo, we showed that access to playmates was negatively associated with playing in mixed-gender groups. Young boys did not engage in more rough-and-tumble play than girls, but adolescent boys participated in this type of play more than adolescent girls. Children were also more likely to participate in work-themed play which conformed to gender norms within their society. Findings are discussed within the context of gendered division of labor, child autonomy, and demography.
The role of cognitive processing in the relationship of posttraumatic stress symptoms and depression among older Holocaust survivors: a moderated-mediation model

ABSTRACT Background and Objectives: Trauma often affects cognitive processes; however, little is known about their role in the relationship between posttraumatic stress and depression among traumatized people. This study aimed to examine three cognitive processes (intrusive rumination, deliberate rumination, and looming cognitive style) and the moderated-mediation effect of these processes in the relationship between posttraumatic stress and depression. Design: The study design was multiple-group cross-sectional. Methods: Participants included 159 Holocaust survivors and 87 matched participants without Holocaust experience. Participants completed questionnaires that assessed levels of rumination, looming cognitive style, posttraumatic stress, and depression. Results: Holocaust survivors reported higher levels of intrusive and deliberate rumination and looming, as well as higher levels of posttraumatic stress and depression than the non-exposed participants. Structural equation modeling revealed a direct association between posttraumatic stress and depression among the non-exposed group. Among the Holocaust survivors, higher levels of posttraumatic stress were related to more depression through the mediators of looming and intrusive rumination, and lower levels of posttraumatic stress were related to lower levels of depression through deliberate rumination. Conclusion: Findings suggest that trauma influences unique cognitive processes that affect the relationship between posttraumatic stress and depression.
Emerging role of miRNAs in renal fibrosis

ABSTRACT As one type of the most common endogenous short noncoding RNAs (ncRNAs), microRNAs (miRNAs) act as posttranscriptional regulators of gene expression and have great potential biological functions in the physiological and pathological processes of various diseases. The role of miRNAs in renal fibrosis has also attracted great attention in the previous 20 years, and new therapeutic strategies targeting miRNAs appear to be promising. Some researchers have previously reviewed the roles of miRNA in renal fibrosis disease, but numerous studies have emerged over the recent 5 years. It is necessary to update and summarize research progress in miRNAs in renal fibrosis. Thus, in this review, we summarize progress in miRNA-mediated renal fibrosis over the last 5 years and evaluate the biological functions of some miRNAs in different stages of renal fibrosis. Furthermore, we also expound the recent clinical applications of these miRNAs to provide new insights into the treatment of renal fibrosis disease.
SSBP1 mutations cause mtDNA depletion underlying a complex optic atrophy disorder.

Inherited optic neuropathies include complex phenotypes, mostly driven by mitochondrial dysfunction. We report an optic atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with mitochondrial DNA (mtDNA) depletion without accumulation of multiple deletions. By whole-exome sequencing, we identified mutations affecting the mitochondrial single strand binding protein (SSBP1) in four families with dominant and one with recessive inheritance. We show that SSBP1 mutations in patient-derived fibroblasts variably affect its amount and alter multimer formation, but not the binding to ssDNA. SSBP1 mutations impaired mtDNA, nucleoids and 7S-DNA amounts as well as mtDNA replication, impacting replisome machinery. The variable mtDNA depletion in cells reflected in severity of mitochondrial dysfunction, including respiratory efficiency, OXPHOS subunits and complexes amount and assembly. mtDNA depletion and cytochrome c oxidase-negative cells were found ex-vivo in biopsies of affected tissues, like kidney and skeletal muscle. Reduced efficiency of mtDNA replication was also reproduced in vitro, confirming the pathogenic mechanism. Furthermore, ssbp1 suppression in zebrafish induced signs of nephropathy and reduced optic nerve size, the latter phenotype complemented by wild-type mRNA but not by SSBP1 mutant transcripts. This previously unrecognized disease of mtDNA maintenance implicates SSBP1 mutations as cause of human pathology.
Neural Signal to Violations of Abstract Rules Using Speech-Like Stimuli

Abstract As the evidence of predictive processes playing a role in a wide variety of cognitive domains increases, the brain as a predictive machine becomes a central idea in neuroscience. In auditory processing, a considerable amount of progress has been made using variations of the Oddball design, but most of the existing work seems restricted to predictions based on physical features or conditional rules linking successive stimuli. To characterize the predictive capacity of the brain to abstract rules, we present here two experiments that use speech-like stimuli to overcome limitations and avoid common confounds. Pseudowords were presented in isolation, intermixed with infrequent deviants that contained unexpected phoneme sequences. As hypothesized, the occurrence of unexpected sequences of phonemes reliably elicited an early prediction error signal. These prediction error signals do not seemed to be modulated by attentional manipulations due to different task instructions, suggesting that the predictions are deployed even when the task at hand does not volitionally involve error detection. In contrast, the amount of syllables congruent with a standard pseudoword presented before the point of deviance exerted a strong modulation. Prediction error’s amplitude doubled when two congruent syllables were presented instead of one, despite keeping local transitional probabilities constant. This suggests that auditory predictions can be built integrating information beyond the immediate past. In sum, the results presented here further contribute to the understanding of the predictive capabilities of the human auditory system when facing complex stimuli and abstract rules.
Photosynthetic Responses of Turf‐forming Red Macroalgae to High CO2 Conditions

Seaweeds are important components of near‐shore ecosystems as primary producers, foundation species, and biogeochemical engineers. Seaweed communities are likely to alter under predicted climate change scenarios. We tested the physiological responses of three perennial, turf‐building, intertidal rhodophytes, Mastocarpus stellatus, Osmundea pinnatifida, and the calcified Ellisolandia elongata, to elevated pCO2 over 6 weeks. Responses varied between these three species. E. elongata was strongly affected by high pCO2, whereas non‐calcified species were not. Elevated pCO2 did not induce consistent responses of photosynthesis and respiration across these three species. While baseline photophysiology differed significantly between species, we found few clear effects of elevated pCO2 on this aspect of macroalgal physiology. We found effects of within‐species variation in elevated pCO2 response in M. stellatus, but not in the other species. Overall, our data confirm the sensitivity of calcified macroalgae to elevated pCO2, but we found no evidence suggesting that elevated pCO2 conditions will have a strong positive or negative impact on photosynthetic parameters in non‐calcified macroalgae.
NaCl Nanoparticles as a Cancer Therapeutic

Many inorganic nanoparticles are prepared and their behaviors in living systems are investigated. Yet, common electrolytes such as NaCl are left out of this campaign. The underlying assumption is that electrolyte nanoparticles will quickly dissolve in water and behave similarly as their constituent salts. Herein, this preconception is challenged. The study shows that NaCl nanoparticles (SCNPs) but not salts are highly toxic to cancer cells. This is because SCNPs enter cells through endocytosis, bypassing cell regulations on ion transport. When dissolved inside cancer cells, SCNPs cause a surge of osmolarity and rapid cell lysis. Interestingly, normal cells are much more resistant to the treatment due to their relatively low sodium levels. Unlike conventional chemotherapeutics, SCNPs cause immunogenic cell death or ICD. In vivo studies show that SCNPs not only kill cancer cells, but also boost an anticancer immunity. The discovery opens up a new perspective on nanoparticle‐based therapeutics.
Surface vacancy on PtTe2 for promoting CO oxidation through efficiently activating O2

Platinum group metal dichalcogenides (PtTe2) with controllable thickness have been synthesized and confirmed to be promising electric and spintronic materials. Here, using the first-principles calculations, we demonstrate the potential application of PtTe2 as catalyst substrate. Taking CO oxidation as model reaction, the importance of surface vacancy is clarified. It is found that surface vacancy on PtTe2 could improve the stability and catalytic activity of the supported Pt atom. The details of CO oxidation processes indicate that surface vacancy could weaken the adsorption of reactants and speed up the formation and decomposition of OOCO intermediate on Pt catalysts. The underlying mechanisms for the improved activity are unveiled through comprehensively analyzing the charge transfer, density of states, and charge density difference. We hope that the current findings were beneficial for the research and development of efficient catalysts by collocating various single atom/cluster catalysts with different platinum group metal dichalcogenides.
Circulating versus lipopolysaccharide-induced inflammatory markers as correlates of subthreshold depressive symptoms in older adults

Abstract Objectives: Circulating cytokines have been associated with depression, but their detection has limitations, which may be overcome by direct detection of intracellular cytokines (ICCs) after lipopolysaccharide (LPS) stimulation in vitro. This study compared circulating versus LPS-induced inflammatory markers as correlates of subthreshold depressive symptoms. Methods: Secondary data analysis of a cross-sectional insomnia study in healthy community-dwelling older adults was conducted. In 117 participants (≥55 years), plasma tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP) and in vitro LPS-induced monocyte production of IL-6 and TNF-α were assayed. Depressive symptoms were assessed using the clinician-rated Inventory of Depressive Symptomatology (IDS-C). Multivariate linear regression was conducted to test the associations between inflammatory markers and subthreshold depressive symptoms in the entire sample as well as in subgroups stratified into higher and lower inflammation levels. Results: LPS-induced TNF-α (adjusted β = 0.28, p = .04), IL-6 (0.29, p = .03) and TNF-α + IL-6 (0.43, p = .001) significantly positively correlated with subthreshold depressive symptoms only in higher inflammation subgroups. No circulating biomarkers positively correlated in any subgroups. In the entire sample, no biomarkers were significantly associated with subthreshold depressive symptoms. Conclusions: LPS-induced cytokines may be more sensitive correlates of subthreshold depressive symptoms than circulating cytokines, particularly in older adults with higher systemic inflammation. Clinical Trials Registry: ClinicalTrials.gov NCT00280020.
LRRK2 binds to the Rab32 subfamily in a GTP-dependent manner via its armadillo domain

ABSTRACT LRRK2 is a multi-domain Ser/Thr kinase that is associated with inherited and sporadic cases of Parkinson’s disease. Many mutations linked to disease are associated within a central ROC-COR regulatory region and the subsequent kinase domain, leading to enhanced catalytic activity. The N-terminus of human LRRK2 consists of armadillo repeat motifs (ARMs) followed by ankyrin repeats (ANKs). Recently, Rab GTPases have emerged as key players in LRRK2 function, both as substrates of the kinase, and as regulators of the catalytic activity. Rabs recruit effector proteins via their GTP-dependent switch 1 and 2 regions to distinct sub-cellular compartments to regulate membrane trafficking. LRRK2 phosphorylates Rab8, Rab10 and Rab12 in switch 2, and this activity is regulated via interactions with Rab29. Furthermore, the related Rab32-subfamily GTPases, Rab32 and Rab38, have also been shown to interact with LRRK2. Here, we have mapped the interactions of the Rab32-subfamily to the ARM domain of LRRK2. The complexes are dependent on the GTP state of the Rabs in vitro, implying that LRRK2 may be an effector of the Rab32-subfamily of small GTPases. X-ray crystal structures of the Rab32-family GTPases and subsequent mutational studies reveal that a positively charged residue in switch 1 is critical for binding of Rab32/38 to LRRK2. Homology modelling and mutational analyses of the ARM domain point to a patch of negatively charged residues that contribute to complex formation. These structural and biochemical studies provide a framework for understanding the molecular basis for Rab regulation of LRRK2 and its role in Parkinson’s disease.
The latest eating quality science - managing intramuscular fat and tenderness to improve the consumer experience

This paper discusses the new research and potential implementation phases associated with managing eating quality in Australian lamb. Firstly we discuss the need for electrical stimulation systems as part of lamb processing, especially for supply chains with a domestic focus. We then describe the new eating quality traits being developed in the Sheep CRC Information Nucleus program namely intramuscular fat, shear force tenderness and consumer evaluation using Meat Standards Australia taste panels. Finally we discuss future ways the Industry will underpin and guarantee eating quality of lamb cuts.
TalkBankDB: A Comprehensive Data Analysis Interface to TalkBank

TalkBank, a CLARIN B Centre, is the host for a collection of multilingual multimodal corpora designed to foster fundamental research in the study of human communication. It contains tens of thousands of audio and video recordings across many languages linked to richly annotated transcriptions, all in the CHAT transcription format. The purpose of the TalkBankDB project is to provide an intuitive on-line interface for researchers to explore TalkBank's media and transcripts, specify data to be extracted, and pass these data on to statistical programs for further analysis.