Miracle-dz/UniFAR-FTUs huggingface dataset:
Complex adaptive landscape for a “Simple” structure: The role of trade‐offs in the evolutionary dynamics of mandibular shape in ground squirrels

Trade‐offs are inherent features of many biomechanical systems and are often seen as evolutionary constraints. Structural decoupling may provide a way to escape those limits in some systems but not for structures that transmit large forces, such as mammalian mandibles. For such structures to evolve in multiple directions on a complex adaptive landscape, different regions must change shape while maintaining structural integrity. We evaluated the complexity of the adaptive landscape for mandibular shape in Marmotini, a lineage of ground squirrels that varies in the proportions of seeds and foliage in their diets, by comparing the fit of models based on traits that predict changes in mandibular loading. The adaptive landscape was more complex than predicted by a two‐peak model with a single dietary shift. The large number of adaptive peaks reflects a high diversity of directions of shape evolution. The number of adaptive peaks also reflects a multiplicity of functional trade‐offs posed by the conflicting demands of processing foods with various combinations of material properties. The ability to balance trade‐offs for diets with different proportions of the same foods may account for diversification and disparity of lineages in heterogeneous environments. Rather than constraints, trade‐offs may be the impetus of evolutionary change.
Differences in clinical features associated with cannabis intoxication in presentations to European emergency departments according to patient age and sex

Abstract Objective To investigate if clinical features associated with acute cannabis intoxication in patients presenting to Emergency Departments for medical assistance differ according to patient age and sex. Methods We analysed presentations in the Euro-DEN Plus dataset from 2014 to 2019 in which cannabis was the only drug involved (except for alcohol), and age, sex and alcohol co-ingestion had been recorded. Age was considered as categorical (five groups; <20, 20–29, 30–39, 40–49 and ≥50 years), and sex as binary variable (male/female). We evaluated 12 key clinical features recorded during emergency department (ED) care. Risks of presenting with each of these clinical features according to patient age and sex were calculated by logistic regression models, and adjusted for sex, age and alcohol co-ingestion. Results 4,268 of 43,633 Euro-DEN presentations (9.8%) fulfilled the inclusion criteria (median age: 26 years (IQR = 20–34), 70% male, 52% co-ingested alcohol). The frequency of clinical features was: anxiety 28%, vomiting 24%, agitation 23%, palpitations 14%, reduced consciousness 13%, acute psychosis 9%, hallucinations 9%, chest pain 7%, headache 6%, hypotension 4%, hypertension 3% and seizures 2%. Patients younger than 20 years more frequently had vomiting (34.7% of cases), reduced consciousness (21.5%), and headache (10.8%); and less frequently acute psychosis (5.5%). Patients older than 49 years more often had hypotension (6.5%) and less frequently vomiting (20%), anxiety (14%), agitation (14%) and reduced consciousness (10%). Males more frequently presented with hypertension (3.7 vs. 1.5%; OR = 2.311, 95%CI = 1.299–3.816), psychosis (10.4 vs 6.3%; 1.948, 1.432–2.430), chest pain (8.1 vs 4.5%; 1.838, 1.390–2.430) and seizures (2.5 vs 1.4%; 1.805, 1.065–3.060), and less frequently with vomiting (21.8 vs 28.2%; 0.793, 0.677–0.930), anxiety (25.4 vs 32.3%; 0.655, 0.561–0.766) and hypotension (2.9 vs 5.8%; 0.485, 0.350–0.671). Conclusions The prevalence of some clinical features typically associated with acute cannabis intoxication differed according to age and sex. The causes for these differences should be further investigated in order to better understand the pathophysiology of cannabis-related acute toxicity, and they may be relevant particularly for developing prevention campaigns and for treatment in specific sex and/or age groups.
Eosinophilic solid and cystic renal cell carcinoma and renal cell carcinomas with TFEB alterations: a comparative study

Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) is a recently described renal tumour entity with frequent cytokeratin (CK)20 positivity, commonly harbouring TSC mutations. In contrast, frequency of CK20 expression and presence of TSC mutations are unclear in TFEB‐amplified RCC and TFEB‐translocated RCC, which frequently express Melan A. Herein, we provide a comparative analysis of six ESC RCC with four TFEB‐amplified/translocated RCC.
Muscle‐tendon architecture in Kenyans and Japanese: Potential role of genetic endowment in the success of elite Kenyan endurance runners

The specificity of muscle‐tendon and foot architecture of elite Kenyan middle‐ and long‐distance runners has been found to contribute to their superior running performance. To investigate the respective influence of genetic endowment and training on these characteristics, we compared leg and foot segmental lengths as well as muscle‐tendon architecture of Kenyans and Japanese males (i) from infancy to adulthood and (ii) non‐athletes versus elite runners.
A prospective cohort study of racial/ethnic variation in the association between change in cystatin C and dietary quality in older Americans

Abstract Using a sample of US adults aged 65 years and older, we examined the role of dietary quality in cystatin C change over 4 years and whether this association varied by race/ethnicity. The Health and Retirement Study provided observations with biomarkers collected in 2012 and 2016, participant attributes measured in 2012, and dietary intake assessed in 2013. The sample was restricted to respondents who were non-Hispanic/Latino White (n 789), non-Hispanic/Latino Black (n 108) or Hispanic/Latino (n 61). Serum cystatin C was constructed to be equivalent to the 1999–2002 National Health and Nutrition Examination Survey (NHANES) scale. Dietary intake was assessed by a semi-quantitative FFQ with diet quality measured using an energy-adjusted form of the Alternative Healthy Eating Index-2010 (AHEI-2010). Statistical analyses were conducted using autoregressive linear modelling adjusting for covariates and complex sampling design. Cystatin C slightly increased from 1·2 mg/l to 1·3 mg/l over the observational period. Greater energy-adjusted AHEI-2010 scores were associated with slower increase in cystatin C from 2012 to 2016. Among respondents reporting moderately low to low dietary quality, Hispanic/Latinos had significantly slower increases in cystatin C than their non-Hispanic/Latino White counterparts. Our results speak to the importance of considering racial/ethnic determinants of dietary intake and subsequent changes in health in ageing populations. Further work is needed to address measurement issues including further validation of dietary intake questionnaires in diverse samples of older adults.
Identification of HPCAL1 as a specific autophagy receptor involved in ferroptosis

ABSTRACT Selective macroautophagy/autophagy maintains cellular homeostasis through the lysosomal degradation of specific cellular proteins or organelles. The pro-survival effect of selective autophagy has been well-characterized, but the mechanism by which it drives cell death is still poorly understood. Here, we use a quantitative proteomic approach to identify HPCAL1 (hippocalcin like 1) as a novel autophagy receptor for the selective degradation of CDH2 (cadherin 2) during ferroptosis. HPCAL1-dependent CDH2 depletion increases susceptibility to ferroptotic death by reducing membrane tension and favoring lipid peroxidation. Site-directed mutagenesis aided by bioinformatic analyses revealed that the autophagic degradation of CDH2 requires PRKCQ (protein kinase C theta)-mediated HPCAL1 phosphorylation on Thr149, as well as a non-classical LC3-interacting region motif located between amino acids 46–51. An unbiased drug screening campaign involving 4208 small molecule compounds led to the identification of a ferroptosis inhibitor that suppressed HPCAL1 expression. The genetic or pharmacological inhibition of HPCAL1 prevented ferroptosis-induced tumor suppression and pancreatitis in suitable mouse models. These findings provide a framework for understanding how selective autophagy promotes ferroptotic cell death.Abbreviations: ANXA7: annexin A7; ARNTL: aryl hydrocarbon receptor nuclear translocator like; CCK8: cell counting kit-8; CDH2: cadherin 2; CETSAs: cellular thermal shift assays; CPT2: carnitine palmitoyltransferase 2; DAMP, danger/damage-associated molecular pattern; DPPH: 2,2-diphenyl-1-picrylhydrazyl; DFO: deferoxamine; EBNA1BP2: EBNA1 binding protein 2; EIF4G1: eukaryotic translation initiation factor 4 gamma 1; FBL: fibrillarin; FKBP1A: FKBP prolyl isomerase 1A; FTH1: ferritin heavy chain 1; GPX4: glutathione peroxidase 4; GSDMs: gasdermins; HBSS: Hanks’ buffered salt solution; HMGB1: high mobility group box 1; HNRNPUL1: heterogeneous nuclear ribonucleoprotein U like 1; HPCAL1: hippocalcin like 1; H1-3/HIST1H1D: H1.3 linker histone, cluster member; IKE: imidazole ketone erastin; KD: knockdown; LDH: lactate dehydrogenase; LIR: LC3-interacting region; MAGOH: mago homolog, exon junction complex subunit; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MDA: malondialdehyde; MLKL: mixed lineage kinase domain like pseudokinase; MPO: myeloperoxidase; MTOR: mechanistic target of rapamycin kinase; OE: overexpressing; OSTM1: osteoclastogenesis associated transmembrane protein 1; PRKC/PKC: protein kinase C; PRKAR1A: protein kinase cAMP-dependent type I regulatory subunit alpha; PRDX3: peroxiredoxin 3; PTGS2: prostaglandin-endoperoxide synthase 2; ROS: reactive oxygen species; SLC7A11: solute carrier family 7 member 11; SLC40A1: solute carrier family 40 member 1; SPTAN1: spectrin alpha, non-erythrocytic 1; STS: staurosporine; UBE2M: ubiquitin conjugating enzyme E2 M; ZYX: zyxin
Genomic changes underlying repeated niche shifts in an adaptive radiation

In adaptive radiations, single lineages rapidly diversify by adapting to many new niches. Little is known yet about the genomic mechanisms involved, that is, the source of genetic variation or genomic architecture facilitating or constraining adaptive radiation. Here, we investigate genomic changes associated with repeated invasion of many different freshwater niches by threespine stickleback in the Haida Gwaii archipelago, Canada, by resequencing single genomes from one marine and 28 freshwater populations. We find 89 likely targets of parallel selection in the genome that are enriched for old standing genetic variation. In contrast to theoretical expectations, their genomic architecture is highly dispersed with little clustering. Candidate genes and genotype‐environment correlations match the three major environmental axes predation regime, light environment, and ecosystem size. In a niche space with these three dimensions, we find that the more divergent a new niche from the ancestral marine habitat, the more loci show signatures of parallel selection. Our findings suggest that the genomic architecture of parallel adaptation in adaptive radiation depends on the steepness of ecological gradients and the dimensionality of the niche space.
Daylength Shapes Entrainment Patterns to Artificial Photoperiods in a Subterranean Rodent

Photoperiodism plays an important role in the synchronization of seasonal phenomena in various organisms. In mammals, photoperiod encoding is mediated by differential entrainment of the circadian system. The limits of daily light entrainment and photoperiodic time measurement can be verified in organisms that inhabit extreme photic environments, such as the subterranean. In this experimental study, we evaluated entrainment of circadian wheel-running rhythms in South American subterranean rodents, the Anillaco tuco-tucos (Ctenomys aff. knighti), exposed to different artificial photoperiods, from extremely long to extremely short photophases (LD 21:3, LD 18:6, LD 15:9, LD 9:15, LD 6:18 and LD 3:21). Artificial photoperiods synchronized their activity/rest rhythms and clear differences occurred in (a) phase angles of entrainment relative to the LD cycle and (b) duration of the daily activity phase α. These photoperiod-dependent patterns of entrainment were similar to those reported for epigeous species. Release into constant darkness conditions revealed aftereffects of entrainment to different photoperiods, observed in α but not in the free-running period τ. We also verified if animals coming from summer and winter natural photoperiods entrained equally to the artificial photoperiods by evaluating their phase angle of entrainment, α and τ aftereffects. To this end, experimental animals were divided into “Matching” and “Mismatching” groups, based on whether the experimental photoperiod (short-day [L < 12 h] or long-day [L > 12 h]) matched or not the natural photoperiod to which they had been previously exposed. No significant differences were found in the phase angle of entrainment, α and τ aftereffects in each artificial photoperiod. Our results indicate that the circadian clocks of tuco-tucos are capable of photoperiodic time measurement despite their natural subterranean habits and that the final entrainment patterns achieved by the circadian clock do not depend on the photoperiodic history.
Numerical and experimental study of multimode failure phenomena in GFRP laminates of different lay-ups

ABSTRACT Induced delamination due to low velocity impact results in degradation of load-carrying capacity of composite structures especially when loading is predominantly in compression. In this paper, size, shape and orientation of delamination that occur due to low velocity impact is obtained by numerical modelling and results are validated through experiments. Initially, numerical model is validated for single-mode fracture tests like double cantilever beam and end-notch flexure. Multimode failure phenomenon like low velocity impact was also simulated for different lay-ups such as cross-ply, angle-ply and quasi-isotropic and validated through experiments. Low velocity impact testing of laminates was done using drop weight impactor, and experimentally obtained force–time and energy–time history were compared with numerical results. Good match is obtained between simulations and experiments. Delamination size was also compared and it is found that numerical model correctly predicts the size, shape and orientation of delamination for all lay-ups.
The experiences of carers in supporting a person living with dementia to participate in virtual cognitive stimulation therapy during the COVID-19 pandemic

Abstract Objectives Cognitive stimulation therapy (CST) is an evidence-based group intervention for people with dementia. In response to the COVID-19 pandemic, many existing CST groups moved virtually and this required carers of people living with dementia to assist with setting up the appropriate technology. This study aimed to explore the roles and experiences of carers in accessing virtual CST (vCST). Methods This qualitative study used semi-structured individual interviews, via telephone or videoconference, to explore the roles and experiences of carers. Interviews were recorded, transcribed verbatim and thematically analysed. Results Twelve family carers (age: 51–75 years) reported a range of experiences, from novice to expert knowledge in terms of accessing digital devices (mainly laptops and iPads) and connecting to Zoom. Accessing vCST provided carers an immediate application of new knowledge. Carers reported positive responses to vCST that provided their family member living with dementia with social contact and cognitive stimulation during lockdown. Conclusion Accessing vCST required carers to have an existing adequate level of technological competence in order to learn and use the Zoom platform. Adult learning principles can be used to improve carers’ digital literacy required for vCST and other telehealth initiatives.
The Development, Content Validation, and Pilot Testing of the Paraphilic Interests and Disorders Scale

The prevalence rates of paraphilic interests and disorders in the general population have been understudied, in large part due to the lack of a standardized assessment measure. As a result, the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 provides little information regarding the prevalence of paraphilic disorders. The present study involved the development of a self-report measure, Paraphilic Interests and Disorders Scale (PIDS), that can be used to assess for the eight paraphilic interests/disorders in the DSM-5 for use with general population samples. Study 1 established the content validity of the PIDS using feedback from 22 experts in the field, and recommendations from these experts were utilized to modify the measure. In Study 2, the PIDS was piloted on 100 individuals in the general population, which supported the feasibility of implementation and its limited-efficacy. While the PIDS requires further psychometric support, the current research suggests the PIDS is a promising tool to gather self-report, population-based data on DSM-5 paraphilic interests and disorders.
Improving Web-Based Treatment Intake for Multiple Mental and Substance Use Disorders by Text Mining and Machine Learning: Algorithm Development and Validation

Background Text mining and machine learning are increasingly used in mental health care practice and research, potentially saving time and effort in the diagnosis and monitoring of patients. Previous studies showed that mental disorders can be detected based on text, but they focused on screening for a single predefined disorder instead of multiple disorders simultaneously. Objective The aim of this study is to develop a Dutch multi-class text-classification model to screen for a range of mental disorders to refer new patients to the most suitable treatment. Methods On the basis of textual responses of patients (N=5863) to a questionnaire currently used for intake and referral, a 7-class classifier was developed to distinguish among anxiety, panic, posttraumatic stress, mood, eating, substance use, and somatic symptom disorders. A linear support vector machine was fitted using nested cross-validation grid search. Results The highest classification rate was found for eating disorders (82%). The scores for panic (55%), posttraumatic stress (52%), mood (50%), somatic symptom (50%), anxiety (35%), and substance use disorders (33%) were lower, likely because of overlapping symptoms. The overall classification accuracy (49%) was reasonable for a 7-class classifier. Conclusions A classification model was developed that could screen text for multiple mental health disorders. The screener resulted in an additional outcome score that may serve as input for a formal diagnostic interview and referral. This may lead to a more efficient and standardized intake process.
Thermo‐sensitive mitochondrial trifunctional protein deficiency presenting with episodic myopathy

Mitochondrial trifunctional protein (MTP) is involved in long‐chain fatty acid β‐oxidation (lcFAO). Deficiency of one or more of the enzyme activities as catalyzed by MTP causes generalized MTP deficiency (MTPD), long‐chain hydroxyacyl‐CoA dehydrogenase deficiency (LCHADD), or long‐chain ketoacyl‐CoA thiolase deficiency (LCKATD). When genetic variants result in thermo‐sensitive enzymes, increased body temperature (e.g. fever) can reduce enzyme activity and be a risk factor for clinical decompensation. This is the first description of five patients with a thermo‐sensitive MTP deficiency. Clinical and genetic information was obtained from clinical files. Measurement of LCHAD and LCKAT activities, lcFAO‐flux studies and palmitate loading tests were performed in skin fibroblasts cultured at 37°C and 40°C. In all patients (four MTPD, one LCKATD), disease manifested during childhood (manifestation age: 2–10 years) with myopathic symptoms triggered by fever or exercise. In four patients, signs of retinopathy or neuropathy were present. Plasma long‐chain acylcarnitines were normal or slightly increased. HADHB variants were identified (at age: 6–18 years) by whole exome sequencing or gene panel analyses. At 37°C, LCHAD and LCKAT activities were mildly impaired and lcFAO‐fluxes were normal. Remarkably, enzyme activities and lcFAO‐fluxes were markedly diminished at 40°C. Preventive (dietary) measures improved symptoms for most. In conclusion, all patients with thermo‐sensitive MTP deficiency had a long diagnostic trajectory and both genetic and enzymatic testing were required for diagnosis. The frequent absence of characteristic acylcarnitine abnormalities poses a risk for a diagnostic delay. Given the positive treatment effects, upfront genetic screening may be beneficial to enhance early recognition.
High Power Optically Pumped Semiconductor Lasers for Sodium Guidestar Applications

Optically pumped semiconductor lasers (OPSLs) are shown to provide a much more compact and less expensive source for illumination of the sodium layer of the mesosphere for use as a sodium laser guidestar via single and two photon excitation schemes. This represents a revolution in laser guidestar technology as the cost, size, and power requirements for a laser guidestar system are shown to have been decreased by an order of magnitude with guidestar performance shown to be similar to previous sources. Sodium laser guidestar sources for broadband simultaneous illumination of multiple lines are developed and simulated. Simulations are then compared to actual returns for multi-line sodium laser guidestars. The simultaneous multi-line laser guidestar is shown to be superior to the single line laser guidestar for equal output powers both via modeling and via on sky returns performed at Starfire Optical Range (SOR) with a combination of a legacy narrowband laser guidestars and a broadband OPSL guidestar. The multi-line OPSL guidestars are shown to provide the first continuous wave source for use as a polychromatic laser guidestar (PLGS) to correct for tip and tilt aberrations. Different methods for utilization of the PLGS
Traumatic brain injury and risk of subsequent attempted suicide and violent crime

Abstract Background Traumatic brain injury (TBI) can cause long-lasting sequelae that may increase the risk of suicidal or criminal behaviour, but large-scale longitudinal studies are lacking on the link between TBI and events of suicide attempt and violent crime. This study examined the incidence of suicide attempt and violent crime following hospital contact for TBI in a nationwide cohort study. Methods We used nationwide register data covering all individuals aged 10+ living in Denmark during 1980–2016 (n = 7 783 951). Of these, 587 522 individuals had a hospital contact for TBI. Incidence rate ratios (IRR) were calculated by Poisson regression analyses while adjusted for relevant covariates including other fractures and psychiatric diagnoses. Results Individuals with TBI had higher rates of suicide attempt (females IRR, 2.78; 95% CI 2.71–2.85; males IRR, 3.00; 95% CI 2.93–3.08) compared to individuals without TBI in adjusted analyses. Multiple TBI and temporal proximity to TBI were associated with higher rates of suicide attempt. Individuals with TBI had higher rates of violent crime (females IRR, 2.43; 95% CI 2.36–2.49; males IRR, 1.80, 95% CI 1.78–1.82) compared with individuals without TBI. Higher rates of violent crime were found after multiple TBI and temporal proximity to TBI. Conclusions This nationwide cohort study found higher rates of suicide attempt and violent crime among individuals with prior hospital diagnosed TBI, compared with individuals without TBI. This emphasises the need for preventive efforts immediately after TBI diagnosis, which might mitigate the risks of a trajectory toward suicidal or violent behaviours.