Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative transportomics identifies Kif5a as a major regulator of neurodegeneration

Many neurons in the adult central nervous system, including retinal ganglion cells (RGCs), degenerate and die after injury. Early axon protein and organelle trafficking failure is a key component in many neurodegenerative disorders yet changes to axoplasmic transport in disease models have not been quantified. We analyzed early changes in the protein ‘transportome’ from RGC somas to their axons after optic nerve injury and identified transport failure of an anterograde motor protein Kif5a early in RGC degeneration. We demonstrated that manipulating Kif5a expression affects anterograde mitochondrial trafficking in RGCs and characterized axon transport in Kif5a knockout mice to identify proteins whose axon localization was Kif5a-dependent. Finally, we found that knockout of Kif5a in RGCs resulted in progressive RGC degeneration in the absence of injury. Together with expression data localizing Kif5a to human RGCs, these data identify Kif5a transport failure as a cause of RGC neurodegeneration and point to a mechanism for future therapeutics.
Transcriptome-wide association and prediction for carotenoids and tocochromanols in fresh sweet corn kernels

Sweet corn is consistently one of the most highly consumed vegetables in the U.S., providing a valuable opportunity to increase nutrient intake through biofortification. Significant variation for carotenoid (provitamin A, lutein, zeaxanthin) and tocochromanol (vitamin E, antioxidants) levels is present in temperate sweet corn germplasm, yet previous genome-wide association studies (GWAS) of these traits have been limited by low statistical power and mapping resolution. Here, we employed a high-quality transcriptomic dataset collected from fresh sweet corn kernels to conduct transcriptome-wide association studies (TWAS) and transcriptome prediction studies for 39 carotenoid and tocochromanol traits. In agreement with previous GWAS findings, TWAS detected significant associations for four causal genes, β-carotene hydroxylase (crtRB1), lycopene epsilon cyclase (lcyE), γ-tocopherol methyltransferase (vte4), and homogentisate geranylgeranyltransferase (hggt1) on a transcriptome-wide level. Pathway-level analysis revealed additional associations for deoxy-xylulose synthase2 (dxs2), diphosphocytidyl methyl erythritol synthase2 (dmes2), cytidine methyl kinase1 (cmk1), and geranylgeranyl hydrogenase1 (ggh1), of which, dmes2, cmk1, and ggh1 have not previously been identified through maize association studies. Evaluation of prediction models incorporating genome-wide markers and transcriptome-wide abundances revealed a trait-dependent benefit to the inclusion of both genomic and transcriptomic data over solely genomic data, but both transcriptome- and genome-wide datasets outperformed a priori candidate gene-targeted prediction models for most traits. Altogether, this study represents an important step towards understanding the role of regulatory variation in the accumulation of vitamins in fresh sweet corn kernels. Core Ideas Transcriptomic data aid the study of vitamin levels in fresh sweet corn kernels. crtRB1, lcyE, dxs2, dmes2, and cmk1 were associated with carotenoid traits. vte4, hggt1, and ggh1 were associated with tocochromanol traits. Transcriptomic data boosted predictive ability over genomic data alone for some traits. Joint transcriptome- and genome-wide models achieved the highest predictive abilities.
Ecological System Levels of Risk Factors for Intimate Partner Homicide Perpetration and Victimization: A Three-Level Meta-analysis

This study aims to identify, through an advanced three-level meta-analytic approach, the predictive validity of the different ecological systems for IPH perpetration and victimization relative to IPV, other homicides, IPH followed by suicide, and non-abused control groups. Twenty-nine studies were included, with 473 effect sizes in a unique population of 16,237. Each factor was classified into one of three ecological systems: ontogenetic, microsystem, and exosystem. The results revealed that the impact of each ecological system on the likelihood of IPH varies depending on the offender/victim gender and the comparison groups. Specifically, the largest odds ratios for intimate partner femicide (IPF) perpetration/victimization versus IPV were found at the microsystem level as well as IPF victimization versus non-abused group at the ontogenetic level of risk factors. Moderator analyses showed that the difference between male IPH and IPV perpetrators in the effect of the microsystem level of risk factors is explained in part by a set of cultural values and beliefs toward equality. We then discuss the present results’ implications for risk assessment and the prevention/treatment of IPH perpetration and victimization, as well as future research.
The possible role of pedunculopontine tegmental nucleus (PPT) opioid receptors in the cardiovascular responses in normotensive and hemorrhagic hypotensive rats

ABSTRACT Background The pedunculopontine tegmental nucleus (PPT) is involved in cardiovascular regulation. The presence of mu (μ) opioid receptors in the PPT nucleus has been determined. In the present study, the role of this nucleus in normotensive conditions and then the role of these receptors on cardiovascular function in hypotension induced by hemorrhage (HEM) were investigated. Method Animals were divided into the following groups: Group 1: control, Group 2: HEM, Group 3: morphine at dose 100 nmol (a general opioid receptor agonist), Group 4: naloxone at dose 100 nmol (a general opioid receptor antagonist), Group 5: morphine + HEM, and Group 6: naloxone + HEM. After anesthesia, two femoral arteries were cannulated to record the cardiovascular parameters and blood withdrawal. Two minutes after induction of HEM, drugs were injected into the nucleus, and cardiovascular parameters were measured. Changes (Δ) in cardiovascular responses due to drug injection and HEM were calculated and compared to control and HEM groups. Results HEM significantly reduced changes in systolic and mean arterial pressures and increased heart rate changes compared to control. Morphine microinjection in normotensive and HEM rats significantly decreased systolic blood pressure, mean arterial pressure, and heart rate, and naloxone significantly increased all these parameters. Conclusion This study showed that the PPT nucleus plays a role in modulating the cardiovascular responses induced by HEM. The µ opioid receptor of the PPT nucleus in the normotensive and HEM rats have inhibitory effects on blood pressure and heart rate mainly, and these effects are eliminated by naloxone microinjection.
Work incapacity and psychiatric patient care following attempted suicide – a cohort study of 65 097 Swedish twins

Abstract Background Research is scarce on the role of familial factors and previous psychiatric care on the association between suicide attempt and future work incapacity as well as deterioration in mental health. We aimed to investigate the associations between suicide attempt and sickness absence, disability pension and psychiatric patient care and to study the influence of previous psychiatric care and familial factors (genetics and shared environment) on the associations. Methods The study included 65 097 twins living in Sweden on 31st of December 2006, aged 19–60 years. The twins were followed 2007–2013 regarding sickness absence, disability pension, inpatient care or specialized outpatient care for a mental diagnosis. Cox regression models were performed for the whole sample, and conditional models for discordant twin pairs. The analyses were also stratified by psychiatric care before 2007. Results We found that suicide attempt predicted sickness absence, disability pension, and future mental diagnosis among the whole sample. The discordant twin pair analyses showed that the association between suicide attempt and sickness absence or disability pension was influenced by familial factors. Stratified analyses of individuals with or without psychiatric care before 2007 showed that previous psychiatric care had some impact on the associations. Conclusions A suicide attempt is a risk factor for work incapacity and psychiatric patient care. Familial factors and previous psychiatric care play a role in the associations between attempting suicide and work incapacity as well as psychiatric patient care. These factors are important when developing measures preventing work incapacity among those with a suicide attempt.
Classic and current concepts in adrenal steroidogenesis: a reappraisal

ABSTRACT Adrenal steroid biosynthesis and its related pathology are constant evolving disciplines. In this paper, we review classic and current concepts of adrenal steroidogenesis, plus control mechanisms of steroid pathways, distribution of unique enzymes and cofactors, and major steroid families. We highlight the presence of a “mineralocorticoid (MC) pathway of zona fasciculata (ZF)”, where most circulating corticosterone and deoxycorticosterone (DOC) originate together with 18OHDOC, under ACTH control, a claim based on functional studies in normal subjects and in patients with 11β-, and 17α-hydroxylase deficiencies. We emphasize key differences between CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) and the onset of a hybrid enzyme – CYP11B1/CYP11B2 –, responsible for aldosterone formation in ZF under ACTH control, in “type I familial hyperaldosteronism” (dexamethasone suppressible). In “apparent MC excess syndrome”, peripheral conversion of cortisol to cortisone is impaired by lack of 11β-hydroxysteroid dehydrogenase type 2, permitting free cortisol access to MC receptors resulting in severe hypertension. We discuss two novel conditions involving the synthesis of adrenal androgens: the “backdoor pathway”, through which dihydrotestosterone is formed directly from androsterone, being relevant for the fetoplacental setting and sexual differentiation of male fetuses, and the rediscovery of C19 11-oxygenated steroids (11-hydroxyandrostenedione and 11-ketotestosterone), active androgens and important markers of virilization in 21-hydroxylase deficiency and polycystic ovaries syndrome. Finally, we underline two enzyme cofactor deficiencies: cytochrome P450 oxidoreductase which partially affects 21- and 17α-hydroxylation, producing a combined clinical/hormonal picture and causing typical skeletal malformations (Antley-Bixler syndrome), and PAPSS2, coupled to SULT2A1, that promotes sulfation of DHEA to DHEAS, preventing active androgens to accumulate. Its deficiency results in reduced DHEAS and elevated DHEA and androgens with virilization. Future and necessary studies will shed light on remaining issues and questions on adrenal steroidogenesis.
Blunted rest-activity rhythm is associated with increased white blood-cell-based inflammatory markers in adults: an analysis from NHANES 2011-2014

ABSTRACT Circadian rhythm disruption is associated with immune system disturbance and has been observed in many health problems where chronic-inflammation acts as a major contributor. We aim to examine whether rest-activity circadian rhythm is associated with chronic inflammation using white blood-cell-based inflammatory indices including white blood cell (WBC) count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). We analyzed the data from 8089 adults (age≥20) with at least 4 days of validated accelerometer recordings and a valid WBC count from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. Non-parametric rest-activity circadian rhythm parameters were derived from the accelerometer recordings. In the models adjusting multiple covariates, a one-quantile increase in relative amplitude (i.e. more robust circadian rhythm) was associated with 1 × 108 cells/L decrease in WBC number (95% CI: 5 × 107 to 1.5 × 108, P < .001), 7 × 107 cells/L decrease in neutrophils (95% CI: 3 × 107 to 1.1 × 108, P = .003) and 15.2 × 109 /L decrease in SII (95% CI: 6 × 109 /L to 20 × 109/L, P = .019). Consistent results were also observed for the association of M10 value and L5 value with these inflammatory indices. Our results indicated that blunted rest-activity circadian rhythm is associated with increased white blood-cell-based inflammatory indices in adults, suggesting interventions aiming at enhancing circadian rhythm by lifestyle programs may be a novel approach to improve the general health.
Cryopreserved Placental Membrane Allograft Reduces the Likelihood of Developing a New or Recurring Foot Ulcer and All-Cause Mortality in Diabetic Patients When Compared with Other Cellular- and Tissue-Based Products

Objective: To compare outcomes for Medicare patients with diabetic foot ulcer(s) (DFU) receiving cryopreserved placental membrane containing viable cells (vCPM) to other Cellular- and Tissue-Based Products (CTPs). Approach: Patients with DFU and CTP use were selected in Medicare claims (2013–2017) by using a strict definition of DFU with demonstrated diabetes etiology. We compared the effectiveness of vCPM with other CTPs on: (1) reduction of post-treatment ulcer occurrence, and (2) reduction in 1 year mortality. We controlled for selection bias and differential risk characteristics between comparison groups in a two-stage inverse probability treatment weighting model. Results: Overall, 7,869 DFU episodes with CTP use met inclusion criteria: 786 received vCPM, 4,546 received another “cellular” CTP, and 2,537 received “acellular” CTP. For ulcer occurrence, we examined: 30-, 90-, 180-, and 365 days post-treatment. We found a significant reduction in ulcers at each period for vCPM compared with either alternative CTP—results range from a 36.7% percentage point reduction in ulcer occurrence at 30 days compared with cellular CTP, and a 58.5% percentage point reduction at 365 days compared with acellular CTP. Further, the application of vCPM reduces mortality within 1 year by 2.3 percentage points (13–13.8% change) compared with other CTPs. Innovation: This study examines the differences in ulcer occurrence and mortality for Medicare DFU patients receiving vCPM and other CTPs. Our strict DFU definition excludes beneficiaries without foot ulcer with demonstrated diabetes etiology. Conclusion: Among CTPs, vCPM users have reduced ulcer rates (recurrent or new) and reduced all-cause mortality compared with other “cellular” and “acellular” CTPs.
Association Between Statin Use and Daptomycin-related Musculoskeletal Adverse Events: A Mixed Approach Combining a Meta-analysis and a Disproportionality Analysis

Abstract Background There is a growing concern about the association between the combined use of daptomycin (DAP) and statins and the occurrence of musculoskeletal adverse events (MAEs), but this remains controversial. This study aimed to clarify the association between statin use and DAP-related MAEs. Methods We used a mixed approach that combines 2 methodologies. First, we conducted a meta-analysis to examine the effects of statin use on DAP-related MAEs. Second, we conducted a disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to further confirm the results of the meta-analysis and to examine the effect of each type of statin on DAP-related MAEs in a large population. Results In the meta-analysis, statin use significantly increased the incidence of DAP-related rhabdomyolysis (odds ratio [OR]: 3.83; 95% confidence interval [CI]: 1.43–10.26) but not DAP-related myopathy (OR: 1.72; 95% CI: .95–3.12). In the disproportionality analysis using the FAERS, the use of statin significantly increased the reporting OR (ROR) for DAP-related myopathy (ROR: 5.69; 95% CI: 4.31–7.51) and rhabdomyolysis (ROR: 5.77; 95% CI: 4.33–7.68). Atorvastatin, rosuvastatin, and simvastatin all increased the incidence of DAP-related myopathy and rhabdomyolysis. Conclusion The mixed approach combining a meta-analysis and disproportionality analysis showed that statin use was associated with the occurrence of DAP-related rhabdomyolysis. The appropriate use of statins and DAP should be performed with careful consideration of its safety.
As clear as glass: How figurativeness and familiarity impact simile processing in readers with and without dyslexia

For skilled readers, idiomatic language confers faster access to overall meaning compared with non-idiomatic language, with a processing advantage for figurative over literal interpretation. However, currently very little research exists to elucidate whether atypical readers—such as those with developmental dyslexia—show such a processing advantage for figurative interpretations of idioms, or whether their reading impairment implicates subtle differences in semantic access. We wanted to know whether an initial figurative interpretation of similes, for both typical and dyslexic readers, is dependent on familiarity. Here, we tracked typical and dyslexic readers’ eye movements as they read sentences containing similes (e.g., as cold as ice), orthogonally manipulated for novelty (e.g., familiar: as cold as ice, novel: as cold as snow) and figurativeness (e.g., literal: as cold as ice [low temperature], figurative: as cold as ice [emotionally distant]), with figurativeness being defined by the sentence context. Both participant groups exhibited a processing advantage for familiar and figurative similes over novel and literal similes. However, compared with typical readers, participants with dyslexia had greater difficulty processing similes both when they were unfamiliar and when the context biased the simile meaning towards a literal rather than a figurative interpretation. Our findings suggest a semantic processing anomaly in dyslexic readers, which we discuss in light of recent literature on sentence-level semantic processing.
Disclosing Cyclic(Alkyl)(Amino)Carbenes as One‐Electron Reductants: Synthesis of Acyclic(Amino)(Aryl)Carbene‐Based Kekulé Diradicaloids

Abstract Herein, we disclose cyclic(alkyl)(amino)carbenes (CAACs) to be one‐electron reductants under the formation of a transient radical cation as indicated by EPR spectroscopy. The disclosed CAAC reducing reactivity was used to synthesize acyclic(amino)(aryl)carbene‐based Thiele and Chichibabin hydrocarbons, a new class of Kekulé diradicaloids. The results demonstrate CAACs to be potent organic reductants. Notably, the acyclic(amino)(aryl)carbene‐based Chichibabin's hydrocarbon shows an appreciable population of the triplet state at room temperature, as evidenced by both variable‐temperature NMR and EPR spectroscopy.
Magnetic phase diagram of (Mo2/3RE1/3)2AlC, RE = Tb and Dy, studied by magnetization, specific heat, and neutron diffraction analysis

We report the results of magnetization, heat capacity, and neutron diffraction measurements on (Mo2/3RE1/3)2AlC with RE = Dy and Tb. Temperature and field-dependent magnetization as well as heat capacity were measured on a powder sample and on a single crystal allowing the construction of the magnetic field-temperature phase diagram. To study the magnetic structure of each magnetic phase, we applied neutron diffraction in a magnetic field up to 6 T. For (Mo2/3Dy1/3)2AlC in zero field, a spin density wave is stabilized at 16 K, with antiferromagnetic ordering at 13 K. Furthermore, we identify the coexistence of ferromagnetic and antiferromagnetic phases induced by magnetic fields for both RE = Tb and Dy. The origin of the field induced phases is resulting from the competing ferromagnetic and antiferromagnetic interactions.
Optimizing falls risk prediction for inpatient stroke rehabilitation: A secondary data analysis

ABSTRACT Background Identifying individuals at risk for falls during inpatient stroke rehabilitation can ensure timely implementation of falls prevention strategies to minimize the negative personal and health system consequences of falls. Objectives To compare sociodemographic and clinical characteristics of fallers and non-fallers; and evaluate the ability of the Berg Balance Scale (BBS) and Morse Falls Scale (MFS) to predict falls in an inpatient stroke rehabilitation setting. Methods A longitudinal study involving a secondary analysis of health record data from 818 patients with stroke admitted to an urban, rehabilitation hospital was conducted. A fall was defined as having ≥1 fall during the hospital stay. Cut-points on the BBS and MFS, alone and in combination, that optimized sensitivity and specificity for predicting falls, were identified. Results Low admission BBS score and admission to a low-intensity rehabilitation program were associated with falling (p < .05). Optimal cut-points were 29 for the BBS (sensitivity: 82.4%; specificity: 57.4%) and 30 for the MFS (sensitivity: 73.2%; specificity: 31.4%) when used alone. Cut-points of 45 (BBS) and 30 (MFS) in combination optimized sensitivity (74.1%) and specificity (42.7%). Conclusions A BBS cut-point of 29 alone appears superior to using the MFS alone or combined with the BBS to predict falls.
The simultaneous changes in motor performance and EEG patterns in beta band during learning dart throwing skill in dominant and non-dominant hand

Abstract Background: Although changes in performance during the learning of various sports skills have been studied, however, how these changes at the brain level is still unknown. The aim of this study was to investigate simultaneous changes in motor performance and EEG patterns in beta band during learning dart throwing skill in dominant and non-dominant hand. Methodology: The samples consisted of 14 non-athlete students with an average age of 23 ± 2.5, which were divided into two group dominant hand (7) and non-dominant hand (7). Repeated measures ANOVA were used to measure data at the execution level and changes in EEG activity. Results: The results of this study at the performance level showed a significant reduction in the absolute error of dart throwing and at the same time at the brain level increased EEG activity in frontal and parietal-posterior regions along with decreased central area activity in acquisition and retention stages in both groups (P<.05). Also, there was a significant difference between the activity of EEG pattern in the dominant and non-dominant hand groups except for two channels AF3 and PO4 (P<.05). Conclusion: In general, the results of this study showed that along with relatively constant changes in performance during dart skill learning, relatively constant changes in EEG activity pattern occur, so that the concept of motor learning is also visible at the brain level. Also, the results of this study supported the existence of the different motor program for dominant and non-dominant hand control in the conditions of bilateral transfer control.