bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of online mindfulness-based interventions for cancer patients: a systematic review and meta-analysis
Authors: Fan Meiling , Wang Yang , Zheng Lufang , Cui Miao , Zhou Xiuling , Liu Zengxia
Published: August 2023

Purpose

Cancer is the second leading cause of mortality worldwide. Cancer negatively affects individuals’ quality of life and overall health. Mindfulness-based interventions appear to be promising in the reduction of cancer- and treatment-related symptoms. This review aimed to determine the effectiveness of online mindfulness-based interventions on distress, anxiety, depression, stress, mindfulness, sleep disturbance, quality of life, rumination, fear of cancer recurrence, fatigue and post-traumatic growth among adult cancer patients.

Methods

A literature search was conducted across five electronic databases. Only randomized controlled trials were eligible. Two reviewers independently screened the studies, extracted data, and performed quality assessment using the Cochrane risk of bias assessment tool. Meta-analyses were conducted using review manager software, and standardized mean difference was used to determine intervention effects. Heterogeneity was examined using the I2 statistics.

Results

Ten studies were included with a total of 962 participants. Analyses revealed that online mindfulness-based interventions was effective in reducing distress (I2 = 98%；standardized mean difference = −2.21，95% confidence interval: −3.84 to 0.57；P = 0.008)， depression (I2 = 45%；standardized mean difference = −0.33，95% confidence interval: −0.64 to −0.03；P = 0.03), stress (I2 = 97%；standardized mean difference = −2.14，95% confidence interval: −4.24 to −0.03；P = 0.05) and sleep disturbance (I2 = 54%；standardized mean difference = −0.30，95% confidence interval: −0.59 to −0.01；P = 0.04), and improving quality of life (I2 = 94%；standardized mean difference = 0.92，95% confidence interval: 0.09–1.76；P = 0.03). The online mindfulness-based interventions had no significant effects on anxiety, mindfulness, rumination, fear of cancer recurrence, fatigue and post-traumatic growth. Subgroup analyses revealed that online mindfulness-based interventions resulted in higher effect sizes for distress when delivered by website than application, significantly higher effect sizes were also found for online mindfulness-based interventions with guidance, but not on treatment or cancer type. For sleep disturbance, and quality of life, no significant differences between subgroups were found.

Conclusion

These results provide preliminary support that online mindfulness-based interventions may be feasible and acceptable, which can be used as an adjuvant therapy for the management of cancer-related symptoms among cancer patients.
The Cancer Moonshot Immuno-Oncology Translational Network at 5: accelerating cancer immunotherapies
Authors: Annapragada Ananth , Sikora Andrew G , Marathe Himangi , Liu Song , Demetriou Michael , Fong Lawrence , Gao Jinming , Kufe Donald , Morris Zachary S , Vilar Eduardo , Sharon Elad , Hutson Alan , Odunsi Kunle
Published: August 2023

The Immuno-Oncology Translational Network (IOTN) was established in 2018 as part of the Cancer Moonshot. In 2022, President Joe Biden set new goals to reduce the cancer death rate by half within 25 years and improve the lives of people with cancer and cancer survivors. The IOTN is focused on accelerating translation of cancer immunology research, from bench to bedside, and improving immunotherapy outcomes across a wide array of cancers in the adult population. The unique structure and team science approach of the IOTN is designed to accelerate discovery and evaluation of novel immune-based therapeutic and prevention strategies. In this article, we describe IOTN progress to date, including new initiatives and the development of a robust set of resources to advance cancer immunology research. We summarize new insights by IOTN researchers, some of which are ripe for translation for several types of cancers. Looking to the future, we identify barriers to the translation of immuno-oncology concepts into clinical trials and key areas for action and improvements that are suitable for high-yield investments. Based on these experiences, we recommend novel National Institutes of Health funding mechanisms and development of new resources to address these barriers.
Temperature-dependence mechanical characteristics investigation of Cu wire and corresponding high strain rate plasticity behaviors enabled by Johnson–Cook constitutive model
Authors: Liu De-Shin , Wen Po-Chun , Zhuang Zhen-Wei , Chao Yung-Ching , Huang Pei-Chen
Published: August 2023

The temperature-dependence mechanical characteristics of 4N Cu wire with 25, 30 and 38 μm diameters are investigated via the utilization of micro-tensile tests. Measured data revealed that the concerned mechanical characteristics, Young's modulus and yield stresses, are significantly degraded under high testing temperature, and the variation of aforementioned characteristics degradation are almost linear proportional to the temperature increment. Trapezoidal and standard triangle loop formation of Cu wire are simulated based on the finite element method, the simulated looping profiles of Cu wires are compared to the Au wires and the Cu wire is regarded as the improved solution for the high loop height wire formation. Moreover, the Johnson–Cook constitutive model is utilized to describe the plasticity of Cu wire in accordance with the experimental data under different temperature levels. Accordingly, the comprehensive mechanical characteristics’ investigation of 4N Cu wire are systemically demonstrated and explored.
A Measure of Caregivers’ Distress-Promoting Behaviors During Toddler Vaccination: Validation of the OUCHIE-RV
Authors: Badovinac Shaylea D , Flora David B , Edgell Heather , Flanders Dan , Garfield Hartley , Weinberg Eitan , Savlov Deena , Pillai Riddell Rebecca R
Published: August 2023

Objective

The current study discusses the development and preliminary validation of an observational measure of caregivers’ distress-promoting behavior (OUCHIE-RV) in the context of toddler routine vaccination.

Methods

Measure validation was based on a sample of caregiver–toddler dyads (N = 223) from a longitudinal cohort-sequential study who were observed during toddlers’ 12-, 18-, or 24-month routine vaccinations. Validity was assessed using correlations and cross-lagged path analysis and associations were tested between OUCHIE-RV composite scores and toddlers’ pain-related distress as well as caregivers’ state anxiety, soothing behaviors, heart rate, and heart rate variability. Interrater reliability was examined using intraclass correlations (ICC) and kappa coefficients.

Results

Results of a cross-lagged path analysis indicated positive concurrent (β = .27 to β = .37) and cross-lagged predictive associations (β = .01 to β = .34) between OUCHIE-RV composite scores (reflecting the frequency and intensity of caregivers’ distress-promoting behavior) and toddlers’ pain-related distress. OUCHIE-RV composite scores were negatively associated with caregivers’ concurrent use of physical comfort (r = −.34 to −.24) and rocking (r = −.36 to −.19) and showed minimal associations with caregivers’ use of verbal reassurance (r = .06 to .12), state anxiety (r = −.02 to r = .09), heart rate (r = −.15 to r = .05), and heart rate variability (r = −.04 to r = .13). Interrater reliability was strong (Cohen’s k = .86 to .97, ICC = .77 to .85).

Conclusions

Findings provide support for the validity and reliability of the OUCHIE-RV as a research tool for measuring caregiver behaviors that promote toddlers’ pain-related distress during routine vaccinations and contribute to a better understanding of the dynamics of caregiver–toddler interaction in acute pain contexts.
A flexible mixed model for age-dependent performance: application to golf
Authors: Baker Rose D , McHale Ian G
Published: August 2023

We present a new mixed linear model for the relationship between age and performance. The model allows for random effects at the nodes of a barycentric interpolation, such that performance evolves with age in a non-prescriptive way. We use the model to investigate the effects of age on performance in golf and find that performance peaks in the 30s and then declines after that. We disaggregate performance into its constituent components and find that driving, which tends to require power and speed, deteriorates consistently from the early 20s, whilst putting, which requires touch and finesse, remains strong until the late 40s. Our model can be used in other settings, and requires only that measures of performance exist.
Synergistic action of indole-3-carbinol with membrane-active agents against multidrug-resistant Gram-negative bacteria
Authors: Wang Tso-Ping , Yeh Tzu-Hui , Lo Chung-Cheng , Lin Kuan-Hua , Huang Mei-Han , Lo Horng-Ren
Published: August 2023

The purpose of this study was to evaluate the antimicrobial activity of indole-3-carbinol (I3C) with membrane-active agents, namely carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and ethylenediaminetetraacetic acid (EDTA) against multidrug-resistant (MDR) Gram-negative bacteria and bacterial persisters. The determination of minimal inhibitory concentration (MIC) showed that I3C was effective against Acinetobacter baumannii (3.13‒6.25 × 10−3 mol l−1), Klebsiella pneumoniae (8 × 10−3 mol l−1), Pseudomonas aeruginosa (6.25‒12.5 × 10−3 mol l−1), and Escherichia coli (6.25‒12.5 × 10−3 mol l−1). Our study demonstrated that EDTA synergistically enhanced the bactericidal activity of I3C against most MDR Gram-negative bacteria isolates and contributed to an 8- to 64-fold MIC reduction compared with that of I3C alone, yet CCCP only displayed synergy with I3C against P. aeruginosa and A. baumannii. The EDTA–I3C combination also significantly reduced the viable number of testing bacteria (P = 7.2E-05), effectively reduced bacterial persisters, and repressed bacterial growth compared with that the use of I3C alone. Our data demonstrate that use of EDTA as adjuvant molecules can effectively improve the antibacterial activity of I3C and may help to reduce the development of antimicrobial resistance.
Mapping circumgalactic medium observations to theory using machine learning
Authors: Appleby Sarah , Davé Romeel , Sorini Daniele , Lovell Christopher C , Lo Kevin
Published: August 2023

We present a random forest (RF) framework for predicting circumgalactic medium (CGM) physical conditions from quasar absorption line observables, trained on a sample of Voigt profile-fit synthetic absorbers from the simba cosmological simulation. Traditionally, extracting physical conditions from CGM absorber observations involves simplifying assumptions such as uniform single-phase clouds, but by using a cosmological simulation we bypass such assumptions to better capture the complex relationship between CGM observables and underlying gas conditions. We train RF models on synthetic spectra for H i and selected metal lines around galaxies across a range of star formation rates, stellar masses, and impact parameters, to predict absorber overdensities, temperatures, and metallicities. The models reproduce the true values from simba well, with normalized transverse standard deviations of 0.50–0.54 dex in overdensity, 0.32–0.54 dex in temperature, and 0.49–0.53 dex in metallicity predicted from metal lines (not H i), across all ions. Examining the feature importance, the RF indicates that the overdensity is most informed by the absorber column density, the temperature is driven by the line width, and the metallicity is most sensitive to the specific star formation rate. Alternatively examining feature importance by removing one observable at a time, the overdensity and metallicity appear to be more driven by the impact parameter. We introduce a normalizing flow approach in order to ensure the scatter in the true physical conditions is accurately spanned by the network. The trained models are available online.
Barless flocculent galaxies: a dynamic puzzle
Authors: Zakharova Daria , Sotnikova Natalia Ya , Smirnov Anton A , Savchenko Sergey S
Published: August 2023

We draw attention to the bright galaxies that do not show a bar in their structure but have a flocculent spiral structure. Using the THINGS and HERACLES kinematic data for four barless galaxies (NGC 2841, NGC 3512, NGC 5055, NGC 7331), we built their mass models including dark haloes. We concluded that the fraction of the dark matter does not exceed 50 per cent within the optical radii of the galaxies. This is too little to explain the lack of a bar in these galaxies. In an attempt to understand the featureless structure of these galaxies, we constructed several N-body models with an initially reduced content of dark matter. We concluded that, in addition to the low mass of the dark halo, the decisive factor that leads to a barless disc is the start from an initially unstable state. An isolated dynamically cold disc (with the Toomre parameter Q < 0.5) settled into rotational equilibrium passes through the short stage of violent instability with fragmentation and formation of stellar clumps. After that, it evolves passively and ends up with a featureless structure. We assume that the barless flocculent galaxies studied in this work may be descendants of galaxies at high redshifts with rotation curves that are consistent with the high mass fraction of baryons relative to the total dark matter halo.
Evidence that bivalve burrowing is mediated by serotonin receptors: activation of foot inflation and protrusion by serotonin, serotonergic ligands and SSRI-type antidepressants in three species of freshwater bivalve
Authors: Fong Peter P , Blaszczyk Rebecca A , Butler Mary G , Stergio Jake W
Published: August 2023

Foot inflation and protrusion in bivalve molluscs is part of a sequence of events necessary for burrowing into the substrate. Although this process been observed after exogenous exposure to the neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] and by some selective serotonin reuptake inhibitor (SSRI) type antidepressants, no study has shown that foot inflation and protrusion as a precursor to burrowing is under serotonergic control. In order to elucidate the physiological mechanism mediating this response, we tested over 2,000 freshwater bivalves in three species by exposing them to 5-HT, two 5-HT receptor agonists, two receptor antagonists and five antidepressants. Fingernail clams (Sphaerium striatinum), Asian clams (Corbicula fluminea) and unionid mussels (Elliptio complanata) all showed significant foot inflation or foot protrusion when exposed to 5-HT and the serotonergic agonists 8-OH-DPAT and alpha-methyl 5-HT. Some SSRI-type antidepressants (fluoxetine and fluvoxamine) also significantly induced these responses in all three species but were not as potent at the concentrations tested. In S. striatinum and C. fluminea, a 2-h exposure to the 5-HT2 receptor antagonists mianserin and cyproheptadine effectively blocked foot inflation induced by 5-HT and 8-OH-DPAT. The 5-HT receptor mediating this response is thus sensitive to mammalian 5-HT1 and 5-HT2 receptor ligands, supporting the hypothesis that serotonin mediates the initial step in burrowing.
Transitions in vascular ultrasonography findings of temporal arteritis in a GCA case with progressive temporal headache and visual impairment
Authors: Kawamoto Toshio , Ogasawara Michihiro , Murayama Go , Matsuki-Muramoto Yuko , Hayashi Eri , Harada Mariko , Kusaoi Makio , Matsushita Masakazu , Yamaji Ken , Tamura Naoto
Published: August 2023

The European League Against Rheumatism and the American College of Rheumatology have stated that the halo sign on vascular ultrasonography (v-US) is relevant in diagnosing giant cell arteritis (GCA) and is equivalent to temporal artery biopsy. However, there are only a few reports about transitions in v-US findings after glucocorticoid (GC) therapy. We report the transitions in the v-US findings in a case of GCA after GC therapy. The patient had rapidly progressive symptoms, and there were concerns about blindness. After GC therapy, we first observed improvement in headache and visual impairment symptoms within 1 week, followed by rapid improvement in laboratory findings within 2 weeks. Subsequently, there were improvements in v-US findings after more than 2 months. In conclusion, these findings showed a dissociation between improvements in clinical symptoms and v-US findings of the temporal artery. Additionally, this case suggests that regular examination of v-US findings is useful in evaluating GCA with evident vascular wall thickness before GC therapy.
Wrist arthrodesis combined with a bulk bone allograft for implant loosening after total wrist arthroplasty: A case report
Authors: Nasu Yoshihisa , Nishida Keiichiro , Natsumeda Masamitsu , Nakahara Ryuichi , Harada Ryozo , Ozaki Toshifumi
Published: August 2023

Total wrist arthroplasty (TWA) is a challenging procedure for wrist joints severely destroyed by rheumatoid arthritis. The most common postoperative complication of TWAs is the loosening of the carpal component. Revision surgeries for failed TWAs can be complicated owing to severe bone loss and concomitant soft-tissue problems. Here, we report a case (68-year-old woman with a history of rheumatoid arthritis for 24 years) of severe aseptic loosening of semi-constrained TWA and its salvage surgery. During the primary arthroplasty procedure, severe instability at the second through fifth carpometacarpal joints was observed and arthrodesis of these joints was required. The radiographs obtained 9 months after surgery showed loosening of the carpal component. Subsequently, she suffered a stroke, resulting in a loss of follow-up, and higher stress was loaded on her upper extremities during standing and walking. In the radiograph taken at her revisit 25 months after the primary surgery, the subsidence of the carpal component progressed and loosening of the radial component was observed. Total wrist arthrodesis was performed using a bulk bone allograft of the femoral head, combined with a penetrating Wrist Fusion Rod®. Rapid bone union was achieved without soft-tissue irritation. We conclude that wrist arthrodesis with a bulk bone allograft combined with an intramedullary nail is a reasonable option for failed total wrist arthroplasty.
Integrated 3D genome, epigenome and transcriptome analyses reveal transcriptional coordination of circadian rhythm in rice
Authors: Zhang Ying , Chen Guoting , Deng Li , Gao Baibai , Yang Jing , Ding Cheng , Zhang Qing , Ouyang Weizhi , Guo Minrong , Wang Wenxia , Liu Beibei , Zhang Qinghua , Sung Wing-Kin , Yan Jiapei , Li Guoliang , Li Xingwang
Published: August 2023

Photoperiods integrate with the circadian clock to coordinate gene expression rhythms and thus ensure plant fitness to the environment. Genome-wide characterization and comparison of rhythmic genes under different light conditions revealed delayed phase under constant darkness (DD) and reduced amplitude under constant light (LL) in rice. Interestingly, ChIP-seq and RNA-seq profiling of rhythmic genes exhibit synchronous circadian oscillation in H3K9ac modifications at their loci and long non-coding RNAs (lncRNAs) expression at proximal loci. To investigate how gene expression rhythm is regulated in rice, we profiled the open chromatin regions and transcription factor (TF) footprints by time-series ATAC-seq. Although open chromatin regions did not show circadian change, a significant number of TFs were identified to rhythmically associate with chromatin and drive gene expression in a time-dependent manner. Further transcriptional regulatory networks mapping uncovered significant correlation between core clock genes and transcription factors involved in light/temperature signaling. In situ Hi-C of ZT8-specific expressed genes displayed highly connected chromatin association at the same time, whereas this ZT8 chromatin connection network dissociates at ZT20, suggesting the circadian control of gene expression by dynamic spatial chromatin conformation. These findings together implicate the existence of a synchronization mechanism between circadian H3K9ac modifications, chromatin association of TF and gene expression, and provides insights into circadian dynamics of spatial chromatin conformation that associate with gene expression rhythms.
Cross-Species Metabolomic Analyses in the Brassicaceae Reveals Common Responses to Ultraviolet-B Exposure
Authors: Jing Yue , Watanabe Mutsumi , Aarabi Fayezeh , Fernie Alisdair R , Borghi Monica , Tohge Takayuki
Published: August 2023

Exposure to UV-B radiation, an intrinsic component of solar light, is detrimental to all living organisms as chromophore units of DNA, RNA and proteins readily absorb high-energy photons. Indirect damage to the same molecules and lipids is mediated by elevated reactive oxygen species (ROS) levels, a side effect of exposure to UV-B stress. To protect themselves from UV-B radiation, plants produce phytochemical sunscreens, among which flavonoids have shown to be particularly effective. The core aglycone of flavonoid molecules is subjected to chemical decoration, such as glycosylation and acylation, further improving sunscreen properties. In particular, acylation, which adds a phenolic ring to flavonoid molecules, enhances the spectral absorption of UV-A and UV-B rays, providing to this class of compounds exceptional shielding power. In this study, we comprehensively analyzed the responses to UV-B radiation in four Brassicaceae species, including Arabidopsis thaliana, Brassica napus, Brassica oleracea, and Brassica rapa. Our study revealed a complete reprogramming of the central metabolic pathway in response to UV-B radiation characterized by increased production of functional precursors of specialized metabolites with UV-B shielding properties, indicating a targeted effort of plant metabolism to provide increased protection. The analysis of specialized metabolites and transcripts revealed the activation of the phenylpropanoid–acetate pathway, leading to the production of specific classes of flavonoids and a cross-species increase in phenylacylated-flavonoid glucosides with synapoyl glycoside decorations. Interestingly, our analysis also revealed that acyltransferase genes of the class of serine carboxypeptidase-like (SCPLs) proteins are costitutively expressed, but downregulated in response to UV-B radiation, possibly independently of the ELONGATED HYPOCOTYL 5 (HY5) signaling pathway.
Mitochondria as a therapeutic: a potential new frontier in driving the shift from tissue repair to regeneration
Authors: Main Evan N , Cruz Thaiz M , Bowlin Gary L
Published: August 2023

Fibrosis, or scar tissue development, is associated with numerous pathologies and is often considered a worst-case scenario in terms of wound healing or the implantation of a biomaterial. All that remains is a disorganized, densely packed and poorly vascularized bundle of connective tissue, which was once functional tissue. This creates a significant obstacle to the restoration of tissue function or integration with any biomaterial. Therefore, it is of paramount importance in tissue engineering and regenerative medicine to emphasize regeneration, the successful recovery of native tissue function, as opposed to repair, the replacement of the native tissue (often with scar tissue). A technique dubbed ‘mitochondrial transplantation’ is a burgeoning field of research that shows promise in in vitro, in vivo and various clinical applications in preventing cell death, reducing inflammation, restoring cell metabolism and proper oxidative balance, among other reported benefits. However, there is currently a lack of research regarding the potential for mitochondrial therapies within tissue engineering and regenerative biomaterials. Thus, this review explores these promising findings and outlines the potential for mitochondrial transplantation-based therapies as a new frontier of scientific research with respect to driving regeneration in wound healing and host–biomaterial interactions, the current successes of mitochondrial transplantation that warrant this potential and the critical questions and remaining obstacles that remain in the field.
Seller Debt in Acquisitions of Private Firms: A Security Design Approach
Authors: Jansen Mark , Phalippou Ludovic , Noe Thomas
Published: August 2023

We propose a security design model in which a potential acquirer approaches a firm with a value-add plan. The target has a single owner, who possesses private information: he alone knows whether his firm is compatible with the plan. The owner agrees that the acquirer will add value but believes that the value-add will not be as much as what the acquirer expects. Although the acquirer can choose any monotone limited liability security to offer along with cash, we show that, under general conditions, any security that is employed always takes the form of nonrecourse debt provided by the seller.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online
Diverse Hedge Funds
Authors: Lu Yan , Naik Narayan Y , Teo Melvyn
Published: August 2023

Hedge fund teams with heterogeneous educational backgrounds, academic specializations, work experiences, genders, and races, outperform homogeneous teams after adjusting for risk and fund characteristics. An event study of manager team transitions, instrumental variable regressions, and an analysis of managers who simultaneously operate solo- and team-managed funds address endogeneity concerns. Diverse teams deliver superior returns by arbitraging more stock anomalies, avoiding behavioral biases, and minimizing downside risks. Moreover, diversity allows hedge funds to circumvent capacity constraints and generate persistent performance. Our results suggest that diversity adds value in asset management.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online
The Rise of Star Firms: Intangible Capital and Competition
Authors: Ayyagari Meghana , Demirgüç-Kunt Asli , Maksimovic Vojislav
Published: August 2023

The large divergence in the returns of top-performing star firms and the rest of the economy is substantially reduced when we account for the mismeasurement of intangible capital. Star firms produce and invest more per dollar in invested capital, have more valuable innovations as measured by the market value of patents, and are as exposed to competitive shocks as nonstars. Star firms have higher markups that are predicted early in their life cycle at a time when they are small. Overall, after we correct for the mismeasurement of intangibles, the evidence points to the superior ability of star firms.
Heart valve disease in primary antiphospholipid syndrome
Authors: Niznik Stanley , Rapoport Micha J , Avnery Orly , Kidon Mona , Shavit Ronen , Ellis Martin H , Agmon-Levin Nancy
Published: August 2023

Objectives

APS-associated heart valve disease (HVD) is well described. Nonetheless, limited data exist on clinical parameters associated with the course of primary APS (pAPS) patients with HVD. The goal of this study was to assess clinical features and related outcomes in patients with APS-associated HVD.

Methods

In this multicentre retrospective study, we identified 33 pAPS patients with HVD (pAPS-HVD group) and compared their clinical course with 128 pAPS patients with normal heart valves on echocardiography (pAPS-control group).

Results

pAPS-HVD patients had more cerebrovascular events (56.3% vs 25%, P = 0.005) and livedo reticularis (24.2% vs 7.8%, P = 0.013) than pAPS-controls. Furthermore, catastrophic-APS (CAPS) (12.1% vs 2.4%, P = 0.034), recurrent thrombosis (33.3% vs 4.7%, P < 0.001) and need for advanced therapy (i.e. IVIG, plasmapheresis or rituximab) were more frequent in pAPS-HVD patients. Anti-β2-glycoprotein 1 IgG (84.8% vs 63.2%, P = 0.034), anti-cardiolipin IgG (90.9% vs 64.8%, P = 0.005) and triple positive aPL (75.8% vs 56.5%, P = 0.047) were commoner in pAPS-HVD patients vs pAPS-controls. Ten of the 33 patients with pAPS-HVD underwent valve surgery, which was associated with male gender, smoking, arterial limb ischaemia and livedo reticularis.

Conclusion

pAPS-HVD patients had a more severe APS clinical course including CAPS and thrombotic events as well as a specific serology, namely IgG isotype aPL antibodies and triple positivity. Our data suggest that pAPS-HVD represents a high-risk subgroup of APS patients.
Differential processing of risk and reward in delinquent and non-delinquent youth
Authors: Duell Natasha , Perino Michael T , McCormick Ethan M , Telzer Eva H
Published: August 2023

The present study examined the behavioral and neural differences in risky decision-making between delinquent (n = 23) and non-delinquent (n = 27) youth ages 13–17 years (M = 16, SD = 0.97) in relation to reward processing. While undergoing functional neuroimaging, participants completed an experimental risk task wherein they received feedback about the riskiness of their behavior in the form of facial expressions that morphed from happy to angry. Behavioral results indicated that delinquent youth took fewer risks and earned fewer rewards on the task than non-delinquent youth. Results from whole-brain analyses indicated no group differences in sensitivity to punishments (i.e. angry faces), but instead showed that delinquent youth evinced greater neural tracking of reward outcomes (i.e. cash-ins) in regions including the ventral striatum and inferior frontal gyrus. While behavioral results show that delinquent youth were more risk-averse, the neural results indicated that delinquent youth were also more reward-driven, potentially suggesting a preference for immediate rewards. Results offer important insights into differential decision-making processes between delinquent and non-delinquent youth.
Political Representation and Intersectionality: Perspectives of Ethnically/Racially Minoritized Citizens
Authors: de Jong Judith C , Mügge Liza M
Published: August 2023

How do ethnically/racially minoritized citizens feel represented by increasingly diverse parliaments? We approach this question intersectionally and study how ethnically/racially minoritized citizens (i) constitute and politicize self-identifications and interests, (ii) assess political representation, and (iii) discuss who represents them. We draw on twelve focus groups with Turkish, Moroccan, and Surinamese-Dutch citizens (N = 65), and find that citizens’ political self-identifications, rather than predefined group labels, are key to understanding assessments of representation. Citizens prefer politicians who act on their substantive concerns but feel that mainstream parties sometimes fail to do so. Parties led by ethnically/racially minoritized politicians and social movements fill this void by contesting the status quo. An intersectional perspective reveals that symbolic representation by descriptive representatives specifically matters for young women of color who lack role models.
Building better foundations: the Dubai International Financial Centre foundation law consultation
Authors: Saleem Shabana , Moldoveanu Mihaela Cornelia
Published: August 2023

The current proposed amendments to the Dubai International Financial Centre (DIFC) Foundations Law No 3 of 2018 (consolidated version of 2022) (“Foundations Law”) come at an opportune time and are testament to the wider progressive measures taken by the DIFC legislator, and to the growing popularity of foundations. The DIFC consultation paper introduces specific amendments to enhance this legislation. If implemented, the amended law will help meet the needs of the ever-growing private client base that increasingly uses foundations as a preferred structuring and succession-planning option. This article focuses on the key tenets of the DIFC consultation paper’s proposed amendments to the Foundation Law.
Donatio mortis causa: the gift that keeps on giving
Authors: Moorhouse Ellie
Published: August 2023

Applying the doctrine of donatio mortis causa is relevant yet risky. This article takes a deep dive into the risks associated with deathbed gifts and the reasons for their continued relevance in English and Welsh law.
Discovery of phytochelatins in human urine: Evidence for function in selenium disposition and protection against cadmium
Authors: Jarrell Zachery R. , Liu Ken H. , Dennis Kristine K. , Hu Xin , Martin Greg S. , Jones Dean P. , Go Young‐Mi
Published: August 2023

This report identifies, for the first time, a phytochelatin compound, phytochelatin 2 [γ‐E‐C‐γ‐E‐C‐G], and related metabolites in human urine. Phytochelatins are metal‐binding peptides produced by plants. They are present in nearly all human diets, due to their ubiquity in plants. The urinary concentration of phytochelatin 2 among 143 adults was in the low micromolar range, and phytochelatin 2 and its metabolites had differential correlations with urinary selenium and toxic metals. Activities of ingested phytochelatins are largely undescribed. Observed urinary metal interactions were investigated further in cell and animal models. Selenite reacted with phytochelatin to form a phytochelatin selenotrisulfide, and the preformed selenotrisulfide showed increased selenium uptake by renal proximal tubule cells. In vivo studies further showed that oral phytochelatin increased renal selenium content and decreased lung cadmium in mice. Presence of phytochelatin in human urine combined with its function in selenium and heavy metal distribution present a new route by which diet may influence metal disposition and bioavailability.
Invasion is accompanied by dietary contraction in Ponto-Caspian amphipods
Authors: Copilaș-Ciocianu Denis , Garbaras Andrius , Šidagytė-Copilas Eglė
Published: August 2023

A species’ expansion beyond the native range is often assumed to be associated with an increased dietary niche breadth. However, empirical evidence remains limited due to a scarcity of studies comparing both the parental and invaded ranges. Here, we test the trophic niche expansion hypothesis by examining stable isotopes and functional morphology across native (NW Black Sea) and invaded (SE Baltic Sea) ranges of two amphipods,Dikerogammarus villosusandPontogammarus robustoides, originating from the Ponto-Caspian region – a major source of species invading Holarctic inland waters. Stable isotopes revealed that both species underwent a twofold contraction of the dietary niche with a shift towards decreased carnivory in the invaded range. This dietary shift was morphologically mirrored by an overall reduction of prey grasping appendages, antennae, and mouthpart palps. The magnitude of dietary and morphological change was greater inD. villosus. Our findings indicate that previous experimental reports of aggressive predation inD. villosusreflect opportunistic foraging and align with local stable isotope studies which generally indicate a low trophic position. We conclude that Ponto-Caspian species can undergo rapid, if non-intuitive, changes in both diet and functional morphology outside the native range, likely contributing to their invasive potential.
Extract from Polygala fallax Hemsl. Protects Kidneys in db/db Mice by Inhibiting the TLR4/MyD88/NF-κB Signaling Pathway
Authors: Bao Yukun , Wang Zeyue , Xu Qing , Wang Lixin , Wen Yi , Deng Peng , Xu Qin
Published: August 2023

Diabetic nephropathy (DN) is a chronic kidney disease caused by the loss of renal function. The extract of Polygala fallax Hemsl (EPF) possesses anti-inflammatory a nd other pharmacological effects. Objective: To investigate the effect and potenti al mechanism of EPF in the treatment of diabetic nephropathy-associated inflammati on. Materials and methods: Db/db mice were administered varying doses of EPF (15, 30, 60 mg/kg), after which the kidney organ index and glucose tolerance were calcu lated. Urine microalbumin was detected in urine collected over 24 hours. Serum FBG, Cr, and BUN levels were measured, and H&E and PAS staining were used to observe pathological changes in the kidney. The expression of TLR4, MyD88, NF-κB, and MMP −9 in kidney tissue was measured using immunohistochemistry, quantitative real-tim e PCR, and western blotting. Additionally, the expression of TNF-α, MCP-1, IL-6, IL-18, and IL-1βinflammatory factors in the serum was measured by ELISA. Results : EPF significantly decreased the renal organ index and ameliorated glucose intole rance symptoms in db/db mice, reduced 24-hour mALB, FBG, Cr, and BUN serum levels, and mitigated renal pathological changes. Moreover, EPF significantly inhibited th e expression of TLR4, MyD88, NF-κB, MMP-9, and related inflammatory factors TNF-α, MCP-1, IL-6, IL-18, and IL-1βin kidney tissue. Discussion and conclusions: E PF from P. fallax exhibits low toxicity and is safe for use. For the first time, it was discovered that EPF might reduce renal inflammation by inhibiting the TLR4/M yD88/NF-κB signaling pathway in vivo, thereby protecting the kidneys of db/db mic e from damage.
CDK19 and CDK8 Mediator kinases drive androgen-independentin vivogrowth of castration-resistant prostate cancer
Authors: Li Jing , Hilimire Thomas A. , Liu Yueying , Wang Lili , Liang Jiaxin , Gyorffy Balazs , Sikirzhytski Vitali , Ji Hao , Zhang Li , Cheng Chen , Ding Xiaokai , Kerr Kendall R. , Dowling Charles E. , Chumanevich Alexander A. , Schools Gary P. , Lim Chang-uk , Zi Xiaolin , Porter Donald C. , Broude Eugenia V. , McInnes Campbell , Wilding George , Lilly Michael B. , Roninson Igor B. , Chen Mengqian
Published: August 2023

Castration-resistant prostate cancer (CRPC) remains incurable due to its high plasticity. We found that Mediator kinases CDK8 and CDK19, pleiotropic regulators of transcriptional reprogramming, are differentially affected by androgen, which downregulates CDK8 and upregulates CDK19. Accordingly, expression of CDK8 decreases while CDK19 increases during prostate carcinogenesis, but both CDK19 and CDK8 are upregulated in metastatic CRPC. Genetic inactivation of CDK8 and CDK19 suppresses CRPC tumor growth in castrated male mice and renders CRPC responsive to androgen deprivation. Restoration of active CDK19 or CDK8 kinases reverses this phenotype, indicating that CRPC becomes dependent on Mediator kinase activity forin vivogrowth under the conditions of androgen deprivation. Selective CDK8/19 inhibitors suppress androgen-independent growth of cell line-based and patient-derived CRPC xenografts, whereas prolonged inhibitor treatment induces tumor regression and even leads to cures. Mediator kinase activity was found to affect tumor and stromal gene expression preferentially in castrated mice, orchestrating castration-induced transcriptional reprogramming. These results warrant the exploration of Mediator kinase inhibitors for CRPC therapy.
It is the Frequency that Matters --- Effects of Electromagnetic Fields on the Release and Content of Extracellular Vesicles
Authors: Wang Yihua , Worrell Gregory A. , Wang Hai-Long
Published: August 2023

Extracellular vesicles (EVs) are small membrane-bound structures that originate from various cell types and carry molecular cargo to influence the behavior of recipient cells. The use of EVs as biomarkers and delivery vehicles for diagnosis and treatment in a wide range of human disease is a rapidly growing field of research and clinical practice. Four years ago, we postulated the hypothesis that electromagnetic fields (EMF) will influence the release and content of EVs (1). Since then, we have optimized several technical aspects of our experimental setup. We used a bioreactor system that allows cells to grow in a three-dimensional environment mimickingin-vivoconditions. We designed a custom-made EMF stimulation device that encompasses the bioreactor and delivers uniform EMFs. We established a three-step EV purification protocol that enables high-density production of EVs. We then performed mass spectrometry-based proteomics analysis on EV-related proteins and used high-resolution nanoparticle flowcytometry for single-vesicle analysis. We demonstrate that electrical stimulations of current amplitudes at physiological level that are currently applied in therapeutic deep brain stimulation can modulate EV content in a frequency-dependent manner, which may have important implications for basic biology and medical applications. First, it raises intriguing questions about how the endogenous electrical activity of neuronal and other cellular assemblies influence the production and composition of EVs. Second, it reveals an additional underlying mechanism of how therapeutic electrical stimulations can modulate EVs and treat human brain disorders. Third, it provides a novel approach of utilizing electrical stimulations in generating specific EV cargos.
TCF7L2: a potential key regulator of antidepressant effects on hippocampal astrocytes in depression model mice
Authors: Koga Yusaku , Kajitani Naoto , Miyako Kotaro , Takizawa Hitoshi , Boku Shuken , Takebayashi Minoru
Published: August 2023

Aim

Clinical and preclinical studies suggest that hippocampal astrocyte dysfunction is involved in the pathophysiology of depression; however, the underlying molecular mechanisms remain unclear. Here, we attempted to identify the hippocampal astrocytic transcripts associated with antidepressant effects in a mouse model of depression.

Methods

We used a chronic corticosterone-induced mouse model of depression to assess the behavioral effects of amitriptyline, a tricyclic antidepressant. Hippocampal astrocytes were isolated using fluorescence-activated cell sorting, and RNA sequencing was performed to evaluate the transcriptional profiles associated with depressive effects and antidepressant responses.

Results

Depression model mice exhibited typical depression-like behaviors that improved after amitriptyline treatment; the depression group mice also had significantly reduced GFAP-positive astrocyte numbers in hippocampal subfields. Comprehensive transcriptome analysis of hippocampal astrocytes showed opposing responses to amitriptyline in depression group and control mice, suggesting the importance of using the depression model. Transcription factor 7 like 2 (TCF7L2) was the only upstream regulator gene altered in depression model mice and restored in amitriptyline-treated depression model mice. In fact, TCF7L2 expression was significantly decreased in the depression group. The level of TCF7L2 long non-coding RNA, which controls mRNA expression of the TCF7L2 gene, was also significantly decreased in this group and recovered after amitriptyline treatment. The Gene Ontology biological processes associated with astrocytic TCF7L2 included proliferation, differentiation, and cytokine production.

Conclusion

We identified TCF7L2 as a gene associated with depression- and antidepressant-like behaviors in response to amitriptyline in hippocampal astrocytes. Our findings could provide valuable insights into the mechanism of astrocyte-mediated antidepressant effects.
Neuronal Connectivity as a Determinant of Cell Types and Subtypes
Authors: Liu Lijuan , Yun Zhixi , Manubens-Gil Linus , Chen Hanbo , Xiong Feng , Dong Hongwei , Zeng Hongkui , Hawrylycz Michael , Ascoli Giorgio A. , Peng Hanchuan
Published: August 2023

Classifications of single neurons at brain-wide scale is a powerful way to characterize the structural and functional organization of a brain. We acquired and standardized a large morphology database of 20,158 mouse neurons, and generated a whole-brain scale potential connectivity map of single neurons based on their dendritic and axonal arbors. With such an anatomy-morphology-connectivity mapping, we defined neuron connectivity types and subtypes (both called “c-types” for simplicity) for neurons in 31 brain regions. We found that neuronal subtypes defined by connectivity in the same regions may share statistically higher correlation in their dendritic and axonal features than neurons having contrary connectivity patterns. Subtypes defined by connectivity show distinct separation with each other, which cannot be recapitulated by morphology features, population projections, transcriptomic, and electrophysiological data produced to date. Within this paradigm, we were able to characterize the diversity in secondary motor cortical neurons, and subtype connectivity patterns in thalamocortical pathways. Our finding underscores the importance of connectivity in characterizing the modularity of brain anatomy, as well as the cell types and their subtypes. These results highlight that c-types supplement conventionally recognized transcriptional cell types (t-types), electrophysiological cell types (e-types), and morphological cell types (m-types) as an important determinant of cell classes and their identities.
Agent-based modeling of nuclear chromosome ensemble identifies determinants of homolog pairing during meiosis
Authors: Chriss Ariana , Börner G. Valentin , Ryan Shawn D.
Published: August 2023

During meiosis, pairing of homologous chromosomes (homologs) ensures the formation of haploid gametes from diploid precursor cells, a prerequisite for sexual reproduction. Pairing during meiotic prophase I facilitates crossover recombination and homolog segregation during the ensuing reductional cell division. Mechanisms that ensure stable homolog alignment in the presence of an excess of non-homologous chromosomes have remained elusive, but rapid chromosome movements during prophase I appear to play a role in the process. Apart from homolog attraction, provided by early intermediates of homologous recombination, dissociation of non-homologous associations also appears to contribute to homolog pairing, as suggested by the detection of stable non-homologous chromosome associations in pairing-defective mutants. Here, we have developed an agent-based model for homolog pairing derived from the dynamics of a naturally occurring chromosome ensemble. The model simulates unidirectional chromosome movements, as well as collision dynamics determined by attractive and repulsive forces arising from close-range physical interactions. In addition to homolog attraction, chromosome number and size as well as movement velocity and repulsive forces are identified as key factors in the kinetics and efficiency of homologous pairing. Dissociation of interactions between non-homologous chromosomes may contribute to pairing by crowding homologs into a limited nuclear area thus creating preconditions for close-range homolog attraction. Predictions from the model are readily compared to experimental data from budding yeast, parameters can be adjusted to other cellular systems and predictions from the model can be tested via experimental manipulation of the relevant chromosomal features.

Author summary

Pairing of homologous chromosomes (homologs) is a key feature of multiple cellular processes including gene expression control, chromosome break repair, and chromosome segregation. Homolog pairing during meiosis is shared among all sexually reproducing eukaryotes. Mechanistic determinants of homology-specific chromosome alignment are presently unknown. We have developed an agent-based model where contributions of the entire chromosome set to the pairing process is taken into account, comprising both homologous and non-homologous chromosomal encounters. Incorporating natural chromosome lengths, the model accurately recapitulates efficiency and kinetics of homolog pairing observed for wild-type and mutant meiosis in budding yeast, and can be adapted to nuclear dimensions and chromosome sets of other organisms.