bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severe and rapidly changing hypophosphatemia in cannabinoid hyperemesis syndrome: a case report
Authors: Acharya Prakash , Mishra Aakash , Kuikel Sandip , Mishra Aman , Rauniyar Robin , Khanal Kunjan , Nepal Amit Sharma , Thapaliya Sahil 
Published: June 2024

Abstract
The increasing prevalence of cannabis worldwide requires awareness of a potential, less recognized, paradoxical entity, the cannabinoid hyperemesis syndrome (CHS). This includes cyclic episodes of nausea, vomiting, and compulsive hot water bathing for alleviation in individuals with chronic cannabis use. An 18-year-old male with daily and prolonged cannabis use has excessive nausea and vomiting, is diagnosed with CHS, and is further complicated by severe and rapidly fluctuating hypophosphatemia. He was successfully managed with intravenous (IV) antiemetic (metoclopramide) and IV normal saline in the emergency department. Hypophosphatemia was treated with IV phosphorous. Although hypophosphatemia in CHS is a rare encounter, the authors share their experience to promote broader recognition and insight into successful management.
The Lifetime Impacts of the New Deal's Youth Employment Program
Authors: Aizer Anna , Early Nancy , Eli Shari , Imbens Guido , Lee Keyoung , Lleras-Muney Adriana , Strand Alexander 
Published: June 2024

Abstract
We study the lifetime effects of the first and largest American youth employment and training program in the United States—the Civilian Conservation Corps (CCC), 1933–1942. We match newly digitized enrollee records to census, World War II enlistment, Social Security, and death records. We find that longer service in the CCC led to improvements in height, health status, longevity, geographic mobility, and lifetime earnings but did not improve short-term labor market outcomes, including employment and wages. We address potential selection into CCC duration using several approaches, most importantly two newly developed control-function approaches that leverage unbiased estimates of the short-term effects of a randomized controlled trial of Job Corps (the modern version of the CCC). Our findings suggest that short- and medium-term evaluations of employment programs underestimate effects because they fail to capture lifetime effects and often ignore or underestimate health and longevity benefits that increase in magnitude at later ages.
Incidence of juvenile idiopathic arthritis in Finland, 2000–2020
Authors: Uusitupa Erika , Rahikkala Heidi , Sard Sirja , Pokka Tytti , Salo Henri , Kärki Johanna , Sokka-Isler Tuulikki , Backström Maria , Vähäsalo Paula 
Published: June 2024

Abstract

Objective
Previous epidemiological data of JIA in Finland are from the turn of the millennium. We aimed to determine the recent annual incidence of JIA in several consecutive years in Finland and to explore the differences in incidence between sexes, age groups and regions.

Methods
We analysed all children &lt;16 years of age who met the ILAR classification criteria for JIA. Cases from 2000–2020 were identified from two national registers: the Care Register for Health Care of the Finnish Institute for Health and Welfare and the Reimbursement Register containing medication data from the Social Insurance Institution of Finland; cases from 2016–2020 were identified from the Finnish Rheumatology Quality Register.

Results
The incidence of JIA was 31.7 per 100 000 (95% CI 30.2, 33.1), according to the Care Register in 2000–2020 and peaked in 2010–2014. No considerable differences in incidence rates were observed among registers. In all age groups, incidence in girls was predominant compared with boys. The incidence in girls peaked at the ages of 2 years and 14–15 years. Decreasing incidence was observed among boys 0–3 years old during the entire study period, whereas increasing incidence was observed among teenage girls and boys 4–7 years old in 2000–2013.

Conclusion
The incidence of JIA is not only very high with respect to that in other parts of the world but also higher than previously reported in Finland. The incidence varied by region and year but was not higher at the end than the beginning of the study period.
One-year effectiveness of long-term exercise therapy in people with axial spondyloarthritis and severe functional limitations
Authors: van Wissen Maria A T , van den Ende Cornelia H M , Gademan Maaike G J , Teuwen Max M H , Peter Wilfred F , Mahler Elien A M , van Schaardenburg Dirkjan , van Gaalen Floris A , Spoorenberg Anneke , van den Hout Wilbert B , van Tubergen Astrid M , Vliet Vlieland Theodora P M , van Weely Salima F E 
Published: June 2024

Abstract

Objective
To evaluate the effectiveness of long-term, personalized, supervised exercise therapy on functional ability compared with usual care in people with axial spondyloarthritis (axSpA) and severe functional limitations.

Methods
Participants were randomly 1:1 assigned to the intervention [maximal 64 sessions, with 14 additional optional sessions of supervised active exercise therapy (e.g. aerobic and muscle strengthening) with individualized goal-setting, education and self-management regarding physical activity] or usual care (care determined by clinician(s) and participants themselves). Primary endpoint was the change in the Patient-Specific Complaints activity ranked 1 [PSC1 (0–10)] at 52 weeks. Secondary endpoints were the PSC activities ranked 2 and 3, the Bath Ankylosing Spondylitis Functional Index, 6-min walk test, Patient Reported Outcome Measurement Information System-Physical Function-10 and the Short Form-36 Physical and Mental Component Summary Score (SF-36 PCS and MCS). Statistical comparisons comprised independent student t-tests and linear mixed models, based on intention-to-treat.

Results
214 participants [49% female, age 52 (s.d. 12) years], were randomized to the intervention (n = 110) or usual care (n = 104) group. In the intervention group 93% started treatment, using on average 40.5 sessions (s.d. 15.1). At 52 weeks, the difference in change in PSC1 between groups favoured the intervention group [mean difference (95% CI); −1.8 (−2.4 to −1.2)]. Additionally, all secondary outcomes, except the SF-36 MSC, showed significantly greater improvements in the intervention group with effect sizes ranging from 0.4 to 0.7.

Conclusion
Long-term, supervised exercise therapy proved more effective than usual care in improving functional disability and physical quality of life in people with axSpA and severe functional limitations.

Trial registration
Netherlands Trial Register NL8238, included in the International Clinical Trial Registry Platform (ICTRP) (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8238).
Five-year follow-up of patients with difficult-to-treat rheumatoid arthritis
Authors: Takanashi Satoshi , Takeuchi Tsutomu , Kaneko Yuko 
Published: June 2024

Abstract

Objectives
To elucidate the long-term outcomes of patients with difficult-to-treat rheumatoid arthritis (D2T RA).

Methods
We collected data on the clinical course of patients who had been identified as D2T RA in 2018 until 2023. We stratified the patients according to outcomes at the last visit: resolved D2T RA, persistent D2T RA and mortality. We compared their clinical characteristics and investigated the predictive factors for the resolution of D2T RA or mortality. Furthermore, we investigated the impact of the causes of D2T RA identified in 2018, multidrug resistance, comorbidities and socioeconomic factors on outcomes in 2023.

Results
Of 173 patients identified as D2T RA in 2018, 150 were included in the analysis. Among them, D2T RA was resolved in 67 (45%), 75 (50%) remained as D2T RA, and 8 (5%) died. Patients with resolved D2T RA were significantly younger at the latest visit (P = 0.02), had a higher proportion of treatment changes during five years (P  = 0.002), and had a higher proportion of interleukin-6 receptor inhibitors use in 2023 (P = 0.04) than those in patients with persistent D2T RA or those who died. D2T RA resolved in 38% of patients with multidrug resistance, mainly with treatment changes. Rheumatic disease comorbidity index and glucocorticoid dose escalation were independent risk factors for mortality [odds ratio (OR), 3.50; P = 0.02 and OR, 31.9; P  = 0.002, respectively].

Conclusion
Further modifications in RA treatment are useful for resolving D2T RA. Multiple comorbidities and glucocorticoid use are associated with mortality.
Religious Polarization in Europe
Authors: Wilkins-Laflamme Sarah , Voas David , Hewlett Kirstie 
Published: June 2024

Abstract
We define two types of religious polarization and investigate the extent to which they are present across European countries, based on data from the 2008 to 2017 European Values Study and hierarchical linear modeling. The first type is polarization by religiosity, with declines in the middle ground between the actively religious and the nonreligious as secularization reaches an advanced stage. The second type is issue polarization, with the religious and secular taking different positions on a range of socio-political values, including social conservatism and ethnic nationalism. We find limited evidence of bimodality in the distribution of religiosity. We find more evidence, however, of issue polarization between the religious and secular in Europe, especially in social conservatism. Religious polarization should thus be understood as a multidimensional concept where one dimension may be more prevalent than others in society.
Impact of an internet-based insomnia intervention on suicidal ideation and associated correlates in veterans at elevated suicide risk
Authors: Nazem Sarra , Sun Shengnan , Barnes Sean M , Monteith Lindsey L , Hostetter Trisha A , Forster Jeri E , Brenner Lisa A , Galfalvy Hanga , Haghighi Fatemeh 
Published: June 2024

Abstract
Improving public health approaches to suicide prevention requires scalable evidence-based interventions that can be easily disseminated. Given empirical data supporting the association between insomnia and suicide risk, internet-delivered insomnia interventions are promising candidates to meet this need. The purpose of this study was to examine whether an unguided internet-delivered cognitive-behavioral therapy for insomnia (iCBT-I) improved insomnia severity, suicidal ideation (SI), and suicide risk correlates (depression, post-traumatic stress disorder, anxiety, hostility, belongingness, hopelessness, agitation, irritability, concentration) in a sample of veterans. Secondary data analysis of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn veterans (n = 50) with clinically significant insomnia and elevated SI drawn from a larger randomized controlled trial (RCT) of an iCBT-I, Sleep Healthy Using the Internet (SHUTi). Two-sample t-tests or Wilcoxon rank sum tests were used to evaluate between-group differences (SHUTi vs. Insomnia Education Website control) in symptom improvement from baseline to post-intervention. SHUTi participants experienced a significant improvement in insomnia severity (P &lt; .001; d = −1.08) and a non-significant with small (subthreshold medium) effect size reduction of SI (P = .17, d = 0.40), compared to control participants. Significant improvement in hopelessness was observed (medium effect size), with non-significant small to medium effect size reductions in most remaining suicide risk correlates. Self-administered iCBT-I was associated with improvements in insomnia severity in veterans at elevated risk for suicide. These preliminary findings suggest that SI and suicide risk correlates may improve following an iCBT-I intervention, demonstrating the need for future well-powered iCBT-I RCTs targeted for populations at elevated suicide risk.
Cross study analyses of SEND data: toxicity profile classification
Authors: Carfagna Mark A , Ahmed Cm Sabbir , Butler Susan , Fukushima Tamio , Houser William , Jensen Nikolai , Paisley Brianna , Leuenroth-Quinn Stephanie , Snyder Kevin , Vispute Saurabh , Wang Wenxian , Ali Md Yousuf 
Published: June 2024

Abstract
A SEND toxicology data transformation, harmonization, and analysis platform were created to improve the identification of unique findings related to the intended target, species, and duration of dosing using data from multiple studies. The lack of a standardized digital format for data analysis had impeded large-scale analysis of in vivo toxicology studies. The CDISC SEND standard enables the analysis of data from multiple studies performed by different laboratories. This work describes methods to analyze data and automate cross-study analysis of toxicology studies. Cross-study analysis can be used to understand a single compound’s toxicity profile across all studies performed and/or to evaluate on-target versus off-target toxicity for multiple compounds intended for the same pharmacological target. This work involved development of data harmonization/transformation strategies to enable cross-study analysis of both numerical and categorical SEND data. Four de-identified SEND datasets from the BioCelerate database were used for the analyses. Toxicity profiles for key organ systems were developed for liver, kidney, male reproductive tract, endocrine system, and hematopoietic system using SEND domains. A cross-study analysis dashboard with a built-in user-defined scoring system was created for custom analyses, including visualizations to evaluate data at the organ system level and drill down into individual animal data. This data analysis provides the tools for scientists to compare toxicity profiles across multiple studies using SEND. A cross-study analysis of 2 different compounds intended for the same pharmacological target is described and the analyses indicate potential on-target effects to liver, kidney, and hematopoietic systems.
Sigh generation in preBötzinger Complex
Authors: Cui Yan , Bondarenko Evgeny , Perez Carolina Thörn , Chiu Delia N. , Feldman Jack L. 
Published: June 2024

AbstractWe explored neural mechanisms underlying sighing. Photostimulation of parafacial (pF) neuromedin B(NMB) or gastrin releasing peptide (GRP), or preBötzinger Complex (preBötC) NMBR or GRPR neurons elicited ectopic sighs with latency inversely related to time from preceding endogenous sigh. Of particular note, ectopic sighs could be produced without involvement of these peptides or their receptors in preBötC. Moreover, chemogenetic or optogenetic activation of preBötC SST neurons induced sighing, even in the presence of NMBR and/or GRPR antagonists. We propose that an increase in the excitability of preBötC NMBR or GRPR neurons not requiring activation of their peptide receptors activates partially overlapping pathways to generate sighs, and that preBötC SST neurons are a downstream element in the sigh generation circuit that converts normal breaths into sighs.
SK609, a novel dopamine D3 receptor agonist and norepinephrine transporter blocker with pro-cognitive actions, does not induce psychostimulant-like increases in risky choice during probabilistic discounting
Authors: Knapp Christopher P. , Fallon Brooke , Kortagere Sandhya , Waterhouse Barry D. , Floresco Stan B. , Navarra Rachel L. 
Published: June 2024

AbstractRationalePsychostimulants, such as amphetamine (AMPH) and methylphenidate (MPH), non-selectively elevate extracellular concentrations of the catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE), and are common pharmacological strategies used to improve prefrontal cortex (PFC)-dependent cognitive dysfunction. However, this approach can be problematic given AMPH has been shown to increase preference for risky choices in a rodent assay of risk/reward decision making. SK609 is a novel NE reuptake blocker that selectively activates DA D3 receptors without affinity for the DA transporter. SK609 has been shown to improve cognitive performance without increasing psychostimulant-like spontaneous locomotor activity, suggesting SK609 may benefit neurocognitive function without psychostimulant-like side effect liability.ObjectivesWe compared AMPH, MPH, and SK609 within dose ranges that display their cognitive enhancing properties in a probabilistic discounting task (PDT) of risk/reward decision making behavior to assess their potential to increase risky choice preference.MethodsRats chose between small/certain rewards delivered with 100% certainty and large/risky rewards delivered with descending probabilities across a session (100-6.25%) following administration of AMPH (0.25-1 mg/kg), MPH (2-8 mg/kg), and SK609 (4 mg/kg).ResultsAMPH and MPH increased risky choice behavior at doses previously reported to enhance cognition, whereas SK609 did not. AMPH and MPH also reduced sensitivity to non-rewarded risky choices.ConclusionsThese data highlight the combination of NE transporter blockade and selective D3 activation in pro-cognitive action without psychostimulant-like side effect liability. The absence of DA transporter blockade and non-selective dopaminergic activation are beneficial properties of SK609 that differentiates it from the traditional pro-cognitive psychostimulants.
Deciphering the Preeclampsia-Specific Immune Microenvironment: The Role of Pro-inflammatory Macrophages
Authors: Fei Haiyi , Lu Xiaowen , Shi Zhan , Liu Xiu , Yang Cuiyu , Zhu Xiaohong , Lin Yuhan , Jiang Ziqun , Wang Jianmin , Huang Dong , Liu Liu , Zhang Songying , Jiang Lingling 
Published: June 2024

AbstractPreeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between PE and GDM is still lacking. In this study, Cytometry by time of flight (CyTOF) indicated that the frequencies of memory-like Th17 cells (CD45RA-CCR7+IL-17A+CD4+), memory-like CD8+T cells (CD38+CXCR3-CCR7+Helios-CD127-CD8+) and pro-inflam Macs (CD206-CD163-CD38midCD107alowCD86midHLA-DRmidCD14+) were increased, while the frequencies of anti-inflam Macs (CD206+CD163-CD86midCD33+HLA-DR+CD14+) and granulocyte myeloid-derived suppressor cells (gMDSCs, CD11b+CD15hiHLA-DRlow) were decreased in the placenta of PE compared with that of NP, but not in that of GDM or GDM&PE. The pro-inflam Macs were positively correlated with memory-like Th17 cells and memory-like CD8+T cells but negatively correlated with gMDSCs. Single-cell RNA sequencing revealed that transferring the F4/80+CD206-pro-inflam Macs with a Folr2+Ccl7+Ccl8+C1qa+C1qb+C1qc+phenotype from the uterus of PE mice to normal pregnant mice induced the production of memory-like IL-17a+Rora+Il1r1+TNF+Cxcr6+S100a4+CD44+Th17 cells via IGF1-IGF1R, which contributed to the development and recurrence of PE. Pro-inflam Macs also induced the production of memory-like CD8+T cells but inhibited the production of Ly6g+S100a8+S100a9+Retnlg+Wfdc21+gMDSCs at the maternal-fetal interface, leading to PE-like symptoms in mice. In conclusion, this study revealed the PE-specific immune cell network, which was regulated by pro-inflam Macs, providing new ideas about the pathogenesis of PE.
TheArabidopsissplicing factor PORCUPINE/SmE1 orchestrates temperature-dependent root development via auxin homeostasis maintenance
Authors: El Arbi Nabila , Nardeli Sarah Muniz , Šimura Jan , Ljung Karin , Schmid Markus 
Published: June 2024

SummaryAppropriate abiotic stress response is pivotal for plant survival and makes use of multiple signaling molecules and phytohormones to achieve specific and fast molecular adjustments. A multitude of studies has highlighted the role of alternative splicing in response to abiotic stress, including temperature, emphasizing the role of transcriptional regulation for stress response. Here we investigated the role of the core splicing factorPORCUPINE(PCP) on temperature-dependent root development.We used marker lines and transcriptomic analyses to study the expression profiles of meristematic regulators and mitotic markers, and chemical treatments, as well as root hormone profiling to assess the effect of auxin signaling.The loss ofPCPsignificantly alters RAM architecture in a temperature-dependent manner. Our results indicate that PCP modulates the expression of central meristematic regulators and is required to maintain appropriate levels of auxin in the RAM.We conclude that alternative pre-mRNA splicing is sensitive to moderate temperature fluctuations and contributes to root meristem maintenance, possibly through the regulation of phytohormone homeostasis and meristematic activity.
Novel miRNA-inducing drugs enable differentiation of retinoic acid-resistant neuroblastoma cells
Authors: Nguyen Lien D. , Sengupta Satyaki , Cho Kevin , Floru Alexander , George Rani E. , Krichevsky Anna M. 
Published: June 2024

AbstractTumor cell heterogeneity in neuroblastoma, a pediatric cancer arising from neural crest-derived progenitor cells, poses a significant clinical challenge. In particular, unlike adrenergic (ADRN) neuroblastoma cells, mesenchymal (MES) cells are resistant to chemotherapy and retinoid therapy and thereby significantly contribute to relapses and treatment failures. Previous research suggested that overexpression or activation of miR-124, a neurogenic microRNA with tumor suppressor activity, can induce the differentiation of retinoic acid-resistant neuroblastoma cells. Leveraging our established screen for miRNA-modulatory small molecules, we validated PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, as a robust inducer of miR-124. A combination of PP121 and BDNF-activating bufalin synergistically arrests proliferation, induces differentiation, and maintains the differentiated state of MES SK-N-AS cells for 8 weeks. RNA-seq and deconvolution analyses revealed a collapse of the ADRN core regulatory circuitry (CRC) and the emergence of novel CRCs associated with chromaffin cells and Schwann cell precursors. Using a similar protocol, we differentiated and maintained MES neuroblastoma GI-ME-N and SH-EP cell lines, as well as glioblastoma LN-229 and U-251 cell lines, for over 16 weeks. In conclusion, our novel protocol suggests a promising treatment for therapy-resistant cancers of the nervous system. Moreover, these long-lived, differentiated cells provide valuable models for studying mechanisms underlying differentiation, maturation, and senescence.
Diffusion of constructed resources and specialism promotes facilitation in spatial systems
Authors: Ardichvili Alice Nadia , Barot Sébastien , Lata Jean-Christophe , Loeuille Nicolas 
Published: June 2024

AbstractSessile organisms contend with locally limiting nutrients and neighbours. Increases in nutrient concentration due to niche construction and diffusion of resources change the interaction sign between neighbours usually thought to compete for resources. We investigate conditions under which the positive effect of niche construction outweighs the negative effect of resource consumption. Following the design of facilitation experiments, we model two patches connected by resource flows, and ask whether the presence of a niche constructor in one patch eases the colonisation of the other. Niche constructors positively affect neighbouring organisms when their niches are sufficiently differentiated, and when the constructed resource diffuses more than the non-constructed resource. Our work proposes mechanisms for the emergence of facilitation, which is increasingly recognised as a key process structuring plant and microbial communities. We discuss the implications for the spatial structure of communities and their functioning, including in an agricultural context.