Ten simple rules for implementing open and reproducible research practices after attending a training course.

Open, reproducible, and replicable research practices are a fundamental part of science. Training is often organized on a grassroots level, offered by early career researchers, for early career researchers. Buffet style courses that cover many topics can inspire participants to try new things; however, they can also be overwhelming. Participants who want to implement new practices may not know where to start once they return to their research team. We describe ten simple rules to guide participants of relevant training courses in implementing robust research practices in their own projects, once they return to their research group. This includes (1) prioritizing and planning which practices to implement, which involves obtaining support and convincing others involved in the research project of the added value of implementing new practices; (2) managing problems that arise during implementation; and (3) making reproducible research and open science practices an integral part of a future research career. We also outline strategies that course organizers can use to prepare participants for implementation and support them during this process.

Autism and autistic traits in those who died by suicide in England.

BACKGROUND: Autism and autistic traits are risk factors for suicidal behaviour. AIMS: To explore the prevalence of autism (diagnosed and undiagnosed) in those who died by suicide, and identify risk factors for suicide in this group. METHOD: Stage 1: 372 coroners' inquest records, covering the period 1 January 2014 to 31 December 2017 from two regions of England, were analysed for evidence that the person who died had diagnosed autism or undiagnosed possible autism (elevated autistic traits), and identified risk markers. Stage 2: 29 follow-up interviews with the next of kin of those who died gathered further evidence of autism and autistic traits using validated autism screening and diagnostic tools. RESULTS: Stage 1: evidence of autism (10.8%) was significantly higher in those who died by suicide than the 1.1% prevalence expected in the UK general alive population (odds ratio (OR) = 11.08, 95% CI 3.92-31.31). Stage 2: 5 (17.2%) of the follow-up sample had evidence of autism identified from the coroners' records in stage 1. We identified evidence of undiagnosed possible autism in an additional 7 (24.1%) individuals, giving a total of 12 (41.4%); significantly higher than expected in the general alive population (1.1%) (OR = 19.76, 95% CI 2.36-165.84). Characteristics of those who died were largely similar regardless of evidence of autism, with groups experiencing a comparably high number of multiple risk markers before they died. CONCLUSIONS: Elevated autistic traits are significantly over-represented in those who die by suicide.

Autistic Traits, Empathizing-Systemizing, and Gender Diversity.

Previous research indicates a link between autism and transgender and gender-diverse identities, though the association is not yet fully understood. The current study examined autistic traits (Autism Spectrum Quotient [AQ]), empathizing (Empathizing Quotient-Short [EQ-S]), and systemizing (Systemizing Quotient-Short [SQ-S]) in a sample of 89 adults and aimed to test whether gender-diverse individuals exhibit cognitive profiles consistent with predictions derived from the Extreme Male Brain (EMB) theory. As most research has considered only cisgender people, we recruited a more diverse sample by contacting > 200 UK LGBTQ+ organizations and posting on social media. A range of non-cisgender identities (e.g., transgender male, transgender female, non-binary, genderqueer, transmasculine) and non-heterosexual orientations (e.g., bisexual) were represented, and participants were categorized into one of four groups: (1) assigned female at birth but does not identify as female (transgender AFAB) (n = 32), (2) cisgender female (n = 21), (3) assigned male at birth but does not identify as male (transgender AMAB) (n = 18), and (4) cisgender male (n = 18). After controlling for age and autism diagnostic status, transgender AFAB participants had marginally higher AQ scores, and significantly higher SQ-S and systemizing-relative-to-empathizing (D) scores, compared with the cisgender female group. No such differences were detected between the transgender AMAB and cisgender male groups. Our findings are broadly in line with predictions derived from the EMB theory, though as no transgender AFAB participants reported being heterosexual, it was not possible to determine whether these effects relate specifically to gender identity, to sexual orientation, or to both.

A longitudinal examination of perinatal testosterone, estradiol and vitamin D as predictors of handedness outcomes in childhood and adolescence.

The developmental origins of handedness remain elusive, though very early emergence suggests individual differences manifesting in utero could play an important role. Prenatal testosterone and Vitamin D exposure are considered, yet findings and interpretations remain equivocal. We examined n = 767 offspring from a population-based pregnancy cohort (The Raine Study) for whom early biological data and childhood/adolescent handedness data were available. We tested whether 18-week maternal circulatory Vitamin D (25[OH]D), and testosterone and estradiol from umbilical cord blood sampled at birth predicted variance in direction of hand preference (right/left), along with right- and left-hand speed, and the strength and direction of relative hand skill as measured by a finger-tapping task completed at 10 (Y10) and/or 16 (Y16) years. Although higher concentrations of Vitamin D predicted more leftward and less lateralized (regardless of direction) relative hand skill profiles, taken as a whole, statistically significant findings typically did not replicate across time-point (Y10/Y16) or sex (male/female) and were rarely detected across different (bivariate/multivariate) levels of analysis. Considering the number of statistical tests and generally inconsistent findings, our results suggest that perinatal testosterone and estradiol contribute minimally, if at all, to subsequent variance in handedness. Vitamin D, however, may be of interest in future studies.

Evidence of assortative mating for theory of mind via facial expressions but not language.

Assortative mating is a phenomenon in which romantic partners typically resemble each other at a level greater than chance. There is converging evidence that social behaviours are subject to assortative mating, though less is known regarding social cognition. Social functioning requires the ability to identify and understand the mental states of others, i.e., theory of mind. The present study recruited a sample of 102 heterosexual couples via an online survey to test if theory of mind as measured using facial expressions (Reading the Mind in the Eyes Test) or language (Stiller-Dunbar Stories Task) is associated with assortative mating. Results provide evidence of assortative mating for theory of mind via facial expressions, though there was no such effect for theory of mind via language. Assortative mating for theory of mind via facial expressions was not moderated by length of relationship nor by partner similarity in age, educational attainment, or religiosity, all variables relevant to social stratification. This suggests assortative mating for theory of mind via facial expressions is better explained by partners being alike at the start of their relationship (initial assortment) rather than becoming similar through sustained social interaction (convergence), and by people seeking out partners that are like themselves (active assortment) rather than simply pairing with those from similar demographic backgrounds (social homogamy).

An examination of the influence of prenatal sex hormones on handedness: Literature review and amniotic fluid data.

Competing theories have posited roles for foetal androgen exposure in the development of human handedness. However, due to practical and ethical considerations, few studies have used hormonal measures to examine this possibility. The current paper reviews this literature and reveals a generally inconsistent pattern of results. We also present data from a longitudinal study of prenatal sex hormone exposure and subsequent handedness. More specifically, we examine correlations between testosterone and estradiol measured from second trimester amniotic fluid and hand preference (Dutch language version of the Edinburgh Handedness Inventory) and hand skill asymmetry (pegboard task) measured at 15 years of age. Prenatal sex hormone exposure was not associated with the direction of hand preference in either males or females. However, in females, high levels of prenatal testosterone were associated with weaker lateralisation of hand skill, and high levels of prenatal estradiol were associated with weaker hand preference. In addition, high levels of prenatal testosterone were associated with increased task duration (i.e., slow hand speed) for the right and left hands of males. The pattern of results observed here is not entirely consistent with any of the main theories linking sex hormones with handedness, suggesting that an association between these variables may be more complex than initially thought.

No evidence for a difference in 2D:4D ratio between youth with elevated prenatal androgen exposure due to congenital adrenal hyperplasia and controls.

The second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine 513 serial radiographs of the left hand obtained clinically in 90 youth with classical CAH (45 female) and 70 control youth (31 female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase of 2D:4D through development). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: ß = -0.001 (-0.008, 0.006); females: ß = -0.004 [-0.015, 0.007]; males: ß = 0.001, [-0.008, 0.011]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research.

Where next for laterality research? Looking back and looking forward.

While paying attention to the recommendations of Ocklenburg, Berretz, Packheiser, and Friedrich (2020) in the target article, researchers in the field of laterality should attempt to: (1) solve the long-standing puzzle of the relationship between handedness and language lateralization; (2) further explore the genetic bases of manual and cerebral asymmetry and of their associations with psychiatric and neurodevelopmental conditions; (3) explore the adaptive significance of laterality for humans and non-humans and elucidate the relationships of asymmetry across species; and (4) embrace developing technologies to investigate the interaction between the hemispheres during the performance of everyday tasks.

Digit ratio (2D:4D) and handedness: A meta-analysis of the available literature.

The Geschwind-Behan-Galaburda and sexual differentiation models predict an association between elevated foetal androgen exposure and left-handedness whereas the callosal hypothesis predicts the opposite. We present a meta-analysis of correlations between handedness and digit ratio (2D:4D), a putative marker of prenatal testosterone. Left-handedness predicted low (male-typical) right-hand digit ratio (R2D:4D), high (female-typical) left-hand digit ratio (L2D:4D), and low R2D:4D-L2D:4D directional asymmetry (D[R-L]). Effect sizes were extremely small and not moderated by sex or method of measuring handedness or 2D:4D. The same general pattern was observed after excluding the very large study (110,329 males, 90,412 females) of Manning and Peters ([2009]. Digit ratio (2D:4D) and hand preference for writing in the BBC Internet Study. Laterality: Asymmetries of Body, Brain and Cognition, 14(5), 528-540. doi:10.1080/13576500802637872); however, no significant effects for R2D:4D were observed once these samples were removed. The results do not confirm any theory linking prenatal androgens with handedness, so we speculate they instead reflect the mechanical action of writing causing subtle changes in the musculature and/or fat pads of the fingers. Gripping a pen/pencil might cause an increase in 2D relative to 4D (and/or decrease in 4D relative to 2D) resulting in higher ratios on the writing-hand; furthermore, this could differ between left- and right-handers due to writing in the left-to-right direction (as in English) having asymmetrical effects depending on which hand is used.

Digit ratio (2D:4D) and congenital adrenal hyperplasia (CAH): Systematic literature review and meta-analysis.

The ratio of length between the second and fourth fingers (2D:4D) is commonly used as an indicator of prenatal sex hormone exposure. Several approaches have been used to try to validate the measure, including examining 2D:4D in people with congenital adrenal hyperplasia (CAH), a suite of conditions characterised by elevated adrenal androgen production secondary to defective steroidogenesis. We present a systematic review and meta-analysis that examines the relationship between these two variables. Twelve articles relating to nine CAH cohorts were identified, and 2D:4D comparisons have been made between cases and controls in eight of these cohorts. Altogether, at least one 2D:4D variable has been compared between n = 251 females with CAH and n = 358 unaffected females, and between n = 108 males with CAH and n = 204 unaffected males. A previous meta-analysis (Hönekopp and Watson, 2010) reported lower right hand (R2D:4D) and left hand (L2D:4D) digit ratios in patients with CAH relative to sex-matched controls. Our meta-analysis showed the same pattern, with medium effect sizes for R2D:4D and small effect sizes for L2D:4D. Differences of small magnitude were also observed for M2D:4D, and no significant effects were observed for D[R-L]. Notably, the only effects that remained statistically significant when stratified by sex were R2D:4D in males and L2D:4D in females, and the average effect size had reduced by 46.70% since the meta-analysis of Hönekopp and Watson (2010). We also found that individual comparisons in this literature were considerably underpowered, and that patterns of sexual dimorphism in 2D:4D were similar in CAH samples as in typically developing populations. Findings are discussed in relation to the prenatal androgen hypothesis as well as alternative explanations.

A comparison of self-measured and researcher-measured digit ratio (2D:4D).

The largest investigation of digit ratio (2D:4D), the BBC Internet Study, reported on finger lengths measured by participants themselves, yet data validating this technique are scarce and the reliability has been questioned. The current study aimed to calculate reliability and repeatability statistics for self-measured 2D:4D and to examine the correlations with researcher-measures. One hundred and seventy-eight undergraduate psychology students attending a practical class self-measured their finger lengths with rulers; a researcher using digital Vernier calipers measured the second and fourth fingers of a random sub-sample (n = 97). Reliability and repeatability of self-measured 2D:4D were high, as were correlations with researcher-measurements. In each case, lower values were observed for the right-left difference in 2D:4D (D[R-L]). Self-measured L2D:4D and M2D:4D were significantly higher than the equivalent researcher measurements, suggesting that direct comparison could be problematic. Self-measurements and directly made researcher-measurements of 2D:4D are strongly correlated, though self-measured D[R-L] is unreliable.

Modulation of Glucagon Receptor Pharmacology by Receptor Activity-modifying Protein-2 (RAMP2).

The glucagon and glucagon-like peptide-1 (GLP-1) receptors play important, opposing roles in regulating blood glucose levels. Consequently, these receptors have been identified as targets for novel diabetes treatments. However, drugs acting at the GLP-1 receptor, although having clinical efficacy, have been associated with severe adverse side-effects, and targeting of the glucagon receptor has yet to be successful. Here we use a combination of yeast reporter assays and mammalian systems to provide a more complete understanding of glucagon receptor signaling, considering the effect of multiple ligands, association with the receptor-interacting protein receptor activity-modifying protein-2 (RAMP2), and the role of individual G protein α-subunits. We demonstrate that RAMP2 alters both ligand selectivity and G protein preference of the glucagon receptor. Importantly, we also uncover novel cross-reactivity of therapeutically used GLP-1 receptor ligands at the glucagon receptor that is abolished by RAMP2 interaction. This study reveals the glucagon receptor as a previously unidentified target for GLP-1 receptor agonists and highlights a role for RAMP2 in regulating its pharmacology. Such previously unrecognized functions of RAMPs highlight the need to consider all receptor-interacting proteins in future drug development.

ENO2, a Glycolytic Enzyme, Contributes to Prostate Cancer Metastasis: A Systematic Review of Literature.

Prostate cancer (PCa) is the second leading cause of male cancer deaths in the UK and the fifth worldwide. The presence of distant PCa metastasis can reduce the 5-year survival rate from 100% to approximately 30%. Enolase 2 (ENO2), a crucial glycolytic enzyme in cancer metabolism, is associated with the metastasis of multiple cancers and is also used as a marker for neuroendocrine tumours. However, its role in PCa metastasis remains unclear. In this study, we systematically reviewed the current literature to determine the association between ENO2 and metastatic PCa. Medline, Web of Science, and PubMed were searched for eligible studies. The search yielded five studies assessing ENO2 expression in PCa patients or cell lines. The three human studies suggested that ENO2 expression is correlated with late-stage, aggressive PCa, including castrate-resistant PCa (CRPC), metastatic CRPC, and neuroendocrine PCa (NEPC). This was further supported by two in vitro studies indicating that ENO2 expression can be regulated by the tumour microenvironment, such as androgen deprived conditions and the presence of bone-forming osteoblasts. Therefore, ENO2 may functionally contribute to PCa metastasis, possibly due to the unique metabolic features of PCa, which are glycolysis dependent only at the advanced metastatic stage.

Neighbor of Brca1 gene (Nbr1) functions as a negative regulator of postnatal osteoblastic bone formation and p38 MAPK activity.

The neighbor of Brca1 gene (Nbr1) functions as an autophagy receptor involved in targeting ubiquitinated proteins for degradation. It also has a dual role as a scaffold protein to regulate growth-factor receptor and downstream signaling pathways. We show that genetic truncation of murine Nbr1 leads to an age-dependent increase in bone mass and bone mineral density through increased osteoblast differentiation and activity. At 6 mo of age, despite normal body size, homozygous mutant animals (Nbr1(tr/tr)) have approximately 50% more bone than littermate controls. Truncated Nbr1 (trNbr1) co-localizes with p62, a structurally similar interacting scaffold protein, and the autophagosome marker LC3 in osteoblasts, but unlike the full-length protein, trNbr1 fails to complex with activated p38 MAPK. Nbr1(tr/tr) osteoblasts and osteoclasts show increased activation of p38 MAPK, and significantly, pharmacological inhibition of the p38 MAPK pathway in vitro abrogates the increased osteoblast differentiation of Nbr1(tr/tr) cells. Nbr1 truncation also leads to increased p62 protein expression. We show a role for Nbr1 in bone remodeling, where loss of function leads to perturbation of p62 levels and hyperactivation of p38 MAPK that favors osteoblastogenesis.

The indirect effect of self-compassion in the association between autistic traits and anxiety/depression: A cross-sectional study in autistic and non-autistic adults.

LAY ABSTRACT: Previous research on non-autistic adults suggests self-compassion may serve to reduce mental health problems and promote psychological well-being. Correlations between autistic traits and self-compassion have been observed in non-clinical populations. In this study, we were interested in extending previous research by exploring relationships between autistic traits, self-compassion and anxiety/depression in autistic adults without intellectual disability. The findings revealed that on average autistic people reported lower self-compassion than non-autistic people. Once we accounted for levels of self-compassion in our statistical model, this resulted in a complete loss of statistical significance in the relationships between autistic traits and anxiety/depression. Self-compassion may be a useful target for clinical intervention in autistic adults with co-occurring mental health difficulties.

Handedness in twins reared apart: A review of the literature and new data.

Reared-apart twin studies are a powerful means for identifying the relative contributions of heredity and environment to variation in human physical and behavioural traits. One such characteristic is handedness, for which it has long been noted that approximately 20% of twin pairs are comprised of one right-handed cotwin and one left-handed cotwin. Reared-together twin studies suggest a slightly greater concordance in monozygotic (MZT) than dizygotic (DZT) twins, implying that genetics influences hand preference. We report here two studies of handedness in reared-apart twins. Study 1 synthesizes the available data and estimates that at least N = 560 same-sex reared-apart twin pairs (for which zygosity is known with reasonable confidence) have been identified. Of these, handedness data are available for both members of n = 415 pairs. We observed similar levels of concordance/discordance for reared-apart monozygotic (MZA) and dizygotic (DZA) twins. However, although direction of handedness (right or left) has frequently been examined, strength of handedness (strong or weak) has not. Study 2 examined strength of hand preference and relative hand skill, as well as right- and left-hand speed, information available for participants in the Minnesota Study of Twins Reared Apart (MISTRA). We provide evidence of heritability for right-hand and left-hand speed. We also found hand preference strength was more alike than chance in DZA, but not MZA, twins. Findings are discussed in relation to genetic and environmental influences on human handedness.

Longitudinal Associations Between Autistic Traits, Self-compassion, Anxiety and Depression in Autistic and Non-autistic Adults Without Intellectual Disability.

PURPOSE: Previous cross-sectional research suggests self-compassion may mediate associations between autistic traits and mental health in autistic and non-autistic adults. However, no research to date has examined these relationships longitudinally. In this study, we used a cross-lagged panel analysis to examine correlations over time between autistic traits, self-compassion, and anxiety/depression. METHODS: Participants were from the UK and included autistic (n = 228 at T1, n = 156 at T2, and n = 165 at T3) and non-autistic adults (n = 228 at T1, n = 122 at T2, and n = 124 at T3) without intellectual disability. Participants were recruited through an online participation platform and completed demographics, the Autism Spectrum Quotient (AQ), the Self-Compassion Scale (SCS), and the Hospital Anxiety and Depression Scale (HADS) at baseline (T1), 6 months (T2), and 12 months (T3). RESULTS: In the autistic sample, negative correlations were observed between self-compassion and subsequent anxiety/depression across all models and timepoints, and these relationships were not reciprocal (i.e., earlier depression and anxiety did not predict future self-compassion). In the non-autistic sample, the findings generally suggested bi-directional relationships between self-compassion and anxiety/depression. In both groups, an indirect pathway between T1 autistic traits and T3 anxiety/depression via T2 self-compassion was confirmed. CONCLUSION: Considering the high prevalence of anxiety and depression among autistic people, and that self-compassion can be cultivated through practice, these findings suggest that self-compassion could be a useful therapeutic target to promote mental health in the autistic population.

The association of prenatal amniotic sex hormones and digit ratio (2D:4D) in children aged 5 to 70 months: A longitudinal study.

The sex difference of the 2D:4D digit ratio (female > male)-a proposed marker for prenatal testosterone exposure-is well established. Studies suggest it already exists in utero and is of moderate effect size in adulthood. However, evidence for the claim that 2D:4D reflects prenatal androgen action is limited, and the sex difference may exhibit lability during childhood. In the present study, 244 mothers were recruited in the course of an amniocentesis examination (performed between gestational weeks 14 and 18). Prenatal testosterone (T) and estradiol (E) levels were determined from amniotic fluid for boys and girls. The majority (97.4%, n = 114) of available female T levels (n = 117) were found below the level of quantification. Therefore, only male amniotic fluid data (n = 117) could be included for the analysis of associations between amniotic sex hormones (T levels and T to E ratio (T/E)) and 2D:4D. The families were then invited to each of the five consecutive follow-ups (ages: 5, 9, 20, 40, and 70 months) where children's 2D:4D was measured for both hands. The alternative marker D[r-l] reflects the directional asymmetry of 2D:4D (right subtracted by left 2D:4D) and was subsequently calculated as an additional measure for prenatal T exposure. No significant correlations between amniotic T or the T/E ratio (measured between week 14 and 18 of gestation) with 2D:4D respectively D[r-l] were observed for any time point. There was a significant sex difference (females > males) and a significant age effect with moderate correlations of 2D:4D between time points. 2D:4D increased between 20 and 40 months and between 40 and 70 months of age. The findings raise questions regarding the applicability of 2D:4D as a marker for prenatal androgen action and are discussed in terms of the reliability of obtained digit ratio data as well as in terms of the developmental timing of amniocentesis.

Judgements of attractiveness of the opposite sex and nostril differences in self-rated mood: The effects of androstenol.

Androstenol has been reported to influence judgements of attractiveness and to affect participants' mood. In the present study, participants were asked to sniff androstenol or a control odour (pure ethanol) unilaterally with the left or right nostril. Subsequently, they rated the attractiveness of photographs of the opposite sex and their own feelings on four mood scales. Participants rated the photographs as significantly more attractive after sniffing androstenol compared with the control odour. This did not depend upon androstenol being perceived as pleasant. Androstenol made male participants feel more lively, and both male and female participants more sexy, when sniffed through the right compared with the left nostril. Participants rated themselves as more irritable and aggressive when exposed to androstenol through the left nostril. The findings are discussed in relation to the effects of arousal on attraction and in the context of current theories of hemispheric differences in emotion.