bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iguratimod versus salazosulfapyridine in rheumatoid arthritis patients with an inadequate response to methotrexate: Adjusted with propensity score matching
Authors: Nozaki Yuji , Oribe Motohiro , Tomita Daisuke , Itami Tetsu , Hayashi Shinya , Maeda Toshihisa , Fukuda Koji , Kuroda Ryosuke , Funahashi Keiko , Matsubara Tsukasa , Kinoshita Koji , Matsumura Itaru 
Published: June 2022

ABSTRACT

Objectives
Methotrexate (MTX) is recommended as a first-line conventional synthetic disease-modifying antirheumatic drug (csDMARD) for treating rheumatoid arthritis (RA). This retrospective study sought to identify an add-on csDMARD treatment strategy for RA patients with MTX-inadequate response (IR).

Methods
We collected the cases of RA patients treated with salazosulfapyridine (SASP) or iguratimod (IGU) as the additional csDMARD for MTX-IR during a 24-month follow-up. We performed propensity score matching to evaluate the retention rate, clinical efficacy, and safety profile (n = 54, each group).

Results
The retention rates at 24 months were 38.5% (MTX+SASP group) and 67.8% (MTX+IGU group). At 3 and 6 months, the MTX+IGU group’s 28 joint-disease activity score (DAS28) was significantly decreased versus the MTX+SASP group, and at 3 months the MTX+IGU group’s good-responder percentage (22.9%) was significantly higher versus the MTX+SASP group’s good-responder percentage (10.7%). Conversely, compared to the MTX+SASP group, the MTX+IGU group showed a greater reduction in the estimated glomerular filtration rate from baseline during follow-up.

Conclusions
IGU is a useful add-on csDMARD for RA patients with MTX-IR; its high retention rate and good clinical response make it a useful combination therapy for controlling RA disease activity. However, the renal function should be monitored during follow-up.
LTBK-02. Safety of growth hormone replacement therapy in childhood craniopharyngioma
Authors: van Schaik Jiska , Kormelink Eline , Schouten-van Meeteren Netteke , de Vos-Kerkhof Evelien , Bakker Boudewijn , Fiocco Marta , Hoving Eelco , Tissing Wim , van Santen Hanneke 
Published: June 2022

Abstract
Introduction: Treatment for childhood-onset craniopharyngioma (cCP) has shifted from complete to limited resection aiming to avoid additional hypothalamic morbidity. Up to 90% of cCP patients develop growth hormone deficiency (GHD). GH replacement therapy (GHRT) is of high importance for linear growth and metabolic state. Hardly any studies evaluated the optimal time to start GHRT in relation to tumor progression or recurrence. Our aim was to assess the effect of GHRT in cCP on tumor progression/recurrence.
Methods: Patients with cCP diagnosed between 2001 and 2022, with at least one year of follow-up were included. Tumor progression/recurrence was defined as tumor progression/recurrence requiring intervention. Kaplan Meier and multivariable cox regression analyses were estimated for tumor progression/recurrence. Comparison was made between cCP patients with GHRT and without GHRT. Of the cCP patients receiving GHRT, those given GHRT ≤ 1 year of cCP diagnosis were compared to those given GHRT &gt;1 year after cCP diagnosis.
Results: Of 59 cCP patients, 52 were diagnosed with GHD and 51 (86.4%) received GHRT. Sixteen cCP patients (31.4%) developed tumor progression/recurrence during GHRT compared to four cCP patients (50.0%) without GHRT. Mean progression free survival (PFS) did not differ between cCP patients with or without GHRT (GHRT: 5.55 years 95% CI 3.74 - 7.36 vs. no GHRT: 3.69 years 95% CI 1.44 - 5.93). Of cCP patients who started GHRT ≤1 year after cCP diagnosis, 36.4% developed tumor progression/recurrence compared to 27.6% of cCP patients who received GHRT &gt; 1 year after diagnosis (PFS: 8.45 years CI 95% 5.54 – 11.36 vs. 7.99 years CI 95% 6.03 – 9.94). Limited surgery was associated to tumor progression/recurrence (HR 6.99 CI 95% 2.10 – 23.25).
Conclusion: GHRT does not seem to influence tumor progression/recurrence in cCP. These results support early initiation of GHRT in cCP patients to optimize linear growth and metabolic outcome.
A Petrologic Insight into Transitioning Eruption Styles from the Devil’s Rock Region, Ambae, Vanuatu
Authors: Collins Nathan , Rowe Michael C , Kilgour Geoff , Nichols Alexander R L , Schipper C Ian , Tari Dan , Garaebiti Esline 
Published: June 2022

AbstractAmbae Island is the largest volcano in the New Hebrides Arc with recent eruptive activity occurring primarily at the summit and along the island’s rift zone. The Devil’s Rock area forms a prominent outcrop on the SW coast. Eruptive deposits here are derived from both strombolian and phreatomagmatic eruptions that contain a similar olivine- and clinopyroxene-rich juvenile basaltic component. This study focuses on a particular transition from strombolian to phreatomagmatic activity to understand if the change in eruption style is a function of magmatic processes or properties (e.g. different composition, ascent rate, degassing history) or if it is driven purely by external factors (e.g. magma–water interaction and/or vent migration). Melts from the strombolian to phreatomagmatic phase record the same melt compositions and volatile contents, suggesting the same magma batch is involved throughout the eruption. More broadly, similarities in H2O, CO2 and S concentrations between olivine- and pyroxene-hosted melt inclusions from Devil’s Rock melt inclusions and those erupted during the 2017–2018 summit eruptions may indicate that a long-term shared magmatic reservoir exists beneath Ambae. Physical characteristics of juvenile tephra including groundmass crystallinity and porosity are combined with melt inclusion compositions to better understand the degassing and crystallisation history and melt evolution of this volcanic system across the transitioning eruptive sequence. Groundmass crystallisation is variable and negatively correlated with connected porosity of erupted scoria reflecting mixing of materials at the vent and inclusion of dense clasts from conduit margins. A direct comparison of crystallinities between strombolian and phreatomagmatic phases reveals higher crystallinity in the strombolian deposits, which is reflective of post-fragmentation crystallisation of clasts. This is particularly evident in the proximal strombolian materials. Qualitative crystallisation textures of melt inclusions are used in a similar fashion to groundmass crystallinities to assess the relative timing of cooling. These trends mirror those of the groundmass and suggest longer cooling times and more effective degassing for samples of the transitional materials. Based on our analysis of deposits at Devil’s Rock, the transition from a strombolian to a phreatomagmatic eruption style was likely driven by groundwater or seawater incursion into the shallow conduit, close to modern-day sea level. Overall, these results suggest a dynamic system where different magmatic cooling histories for strombolian versus phreatomagmatic eruptive phases are reflected in changing groundmass crystallinity. This highlights the propensity for transitions in eruption style over seemingly short time intervals and significantly enhancing eruption explosivity.
Evolution of the DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN subfamily in green plants
Authors: Han Jiapeng , Xie Xiaoxue , Zhang Yang , Yu Xiaofen , He Guangyuan , Li Yin , Yang Guangxiao 
Published: June 2022

Abstract
Adapting to unfavorable environments is a necessary step in plant terrestrialization and radiation. The dehydration-responsive element-binding (DREB) protein subfamily plays a pivotal role in plant abiotic stress regulation. However, relationships between the origin and expansion of the DREB subfamily and adaptive evolution of land plants are still being elucidated. Here, we constructed the evolutionary history of the DREB subfamily by compiling APETALA2/ethylene-responsive element-binding protein superfamily genes from 169 representative species of green plants. Through extensive phylogenetic analyses and comparative genomic analysis, our results revealed that the DREB subfamily diverged from the ethylene-responsive factor (ERF) subfamily in the common ancestor of Zygnemophyceae and Embryophyta during the colonization of land by plants, followed by expansions to form three different ancient archetypal genes in Zygnemophyceae species, designated as groups archetype-I, archetype-II/III, and archetype-IV. Four large-scale expansions paralleling the evolution of land plants led to the nine-subgroup divergence of group archetype-II/III in angiosperms, and five whole-genome duplications during Brassicaceae and Poaceae radiation shaped the diversity of subgroup IIb-1. We identified a Poaceae-specific gene in subgroup IIb-1, ERF014, remaining in a Poaceae-specific microsynteny block and co-evolving with a small heat shock protein cluster. Expression analyses demonstrated that heat acclimation may have driven the neofunctionalization of ERF014s in Pooideae by engaging in the conserved heat-responsive module in Poaceae. This study provides insights into lineage-specific expansion and neofunctionalization in the DREB subfamily, together with evolutionary information valuable for future functional studies of plant stress biology.
Increased incidence of pediatric narcolepsy following the 2009 H1N1 pandemic: a report from the pediatric working group of the sleep research network
Authors: Simakajornboon Narong , Mignot Emmanuel , Maski Kiran , Owens Judith , Rosen Carol , Ibrahim Sally , Hassan Fauziya , Chervin Ronald D , Perry Gayln , Brooks Lee , Kheirandish-Gozal Leila , Gozal David , Mason Thornton , Robinson Althea , Malow Beth , Naqvi Kamal , Chen Maida L , Jambhekar Supriya , Halbower Ann , Graw-Panzer Katharina , Dayyat Ehab , Lew Jenny , Melendres Cecilia , Kotagal Suresh , Jain Sejal , Super Elizabeth , Dye Thomas , Hossain Md Monir , Tadesse Dawit 
Published: June 2022

Abstract
This study was aimed to evaluate the yearly incidence of pediatric narcolepsy prior to and following the 2009 H1N1 pandemic and to evaluate seasonal patterns of narcolepsy onset and associations with H1N1 influenza infection in the United States. This was a multicenter retrospective study with prospective follow-up. Participants were recruited from members of the Pediatric Working Group of the Sleep Research Network including 22 sites across the United States. The main outcomes were monthly and yearly incident cases of childhood narcolepsy in the United States, and its relationship to historical H1N1 influenza data. A total of 950 participants were included in the analysis; 487 participants were male (51.3%). The mean age at onset of excessive daytime sleepiness (EDS) was 9.6  ±  3.9 years. Significant trend changes in pediatric narcolepsy incidence based on EDS onset (p  &lt;  .0001) occurred over the 1998–2016 period, peaking in 2010, reflecting a 1.6-fold increase in narcolepsy incidence. In addition, there was significant seasonal variation in narcolepsy incident cases, with increased cases in spring (p  &lt;  .05). Cross-correlation analysis demonstrated a significant correlation between monthly H1N1 infection and monthly narcolepsy incident cases (p  =  .397, p  &lt;  .0001) with a lag time of 8 months. We conclude that there is a significant increase in pediatric narcolepsy incidence after the 2009 H1N1 pandemic in the United States. However, the magnitude of increase is lower than reported in European countries and in China. The temporal correlation between monthly H1N1 infection and monthly narcolepsy incidence, suggests that H1N1 infection may be a contributing factor to the increased pediatric narcolepsy incidence after the 2009 H1N1 pandemics.
The role of endogenous Smad7 in regulating macrophage phenotype following myocardial infarction
Authors: Li Jun , Li Ruoshui , Tuleta Izabela , Hernandez Silvia C. , Humeres Claudio , Hanna Anis , Chen Bijun , Frangogiannis Nikolaos G. 
Published: June 2022

AbstractSmad7 restrains TGF‐β responses, and has been suggested to exert both pro‐ and anti‐inflammatory actions that may involve effects on macrophages. Myocardial infarction triggers a macrophage‐driven inflammatory response that not only plays a central role in cardiac repair, but also contributes to adverse remodeling and fibrosis. We hypothesized that macrophage Smad7 expression may regulate inflammation and fibrosis in the infarcted heart through suppression of TGF‐β responses, or via TGF‐independent actions. In a mouse model of myocardial infarction, infiltration with Smad7+ macrophages peaked 7 days after coronary occlusion. Myeloid cell‐specific Smad7 loss in mice had no effects on homeostatic functions and did not affect baseline macrophage gene expression. RNA‐seq predicted that Smad7 may promote TREM1‐mediated inflammation in infarct macrophages. However, these alterations in the transcriptional profile of macrophages were associated with a modest and transient reduction in infarct myofibroblast infiltration, and did not affect dysfunction, chamber dilation, scar remodeling, collagen deposition, and macrophage recruitment. In vitro, RNA‐seq and PCR arrays showed that TGF‐β has profound effects on macrophage profile, attenuating pro‐inflammatory cytokine/chemokine expression, modulating synthesis of matrix remodeling genes, inducing genes associated with sphingosine‐1 phosphate activation and integrin signaling, and inhibiting cholesterol biosynthesis genes. However, Smad7 loss did not significantly affect TGF‐β‐mediated macrophage responses, modulating synthesis of only a small fraction of TGF‐β‐induced genes, including Itga5, Olfml3, and Fabp7. Our findings suggest a limited role for macrophage Smad7 in regulation of post‐infarction inflammation and repair, and demonstrate that the anti‐inflammatory effects of TGF‐β in macrophages are not restrained by endogenous Smad7 induction.
A non‐polar fraction of Saponaria officinalis L. acted as a TLR4/MD2 complex antagonist and inhibited TLR4/MyD88 signaling in vitro and in vivo
Authors: Yu Ga‐Ram , Lim Dong‐Woo , Karunarathne Wisurumuni Arachchilage Hasitha Maduranga , Kim Gi‐Young , Kim Hyuck , Kim Jai‐Eun , Park Won‐Hwan 
Published: June 2022

AbstractTargeting Toll‐like receptor 4/myeloid differentiation factor 2 (TLR4/MD2) signaling is regarded as a potential strategy for treating inflammatory diseases. Saponaria officinalis L. is rich in saponin, which include quillaic acid, gypsogenin, saponarin, and hederagenin. We evaluated the pharmacological activity of a Saponaria officinalis extract in THP‐1 derived macrophages and RAW264.7 macrophages. TLR4/MyD88 complex formation and downstream signals were investigated by co‐immunoprecipitation (Co‐IP). In silico docking simulation was conducted to predict binding scores and perform 3D modeling of saponarin‐TLR4/MD2 complex. A hexane fraction of Saponaria officinalis (SH) and fr.1 (a sub‐fraction 1 of SH) inhibited mitogen‐activated protein kinase (MAPK) signaling, nuclear factor kappa b (NF‐κB) activity, cytokine production, and the expressions of marker genes specific for M1 polarization. The inhibitory effects of fr.1 and saponarin on TLR4/MyD88 complex formation were observed by western blotting TLR4 co‐immunoprecipitated proteins. Saponarin and fr.1 markedly attenuated LPS‐induced inflammatory cytokines, thus reducing mortality and morphological abnormality in zebrafish larvae. Finally, docking simulation revealed that saponarin can directly interact with TLR4/MD2 complex to inhibit downstream signalings. Our findings suggest that saponarin reduces downstream inflammatory response by disrupting TLR4/MD2 complex and blocking MyD88‐dependent inflammatory signaling.
Using the Parent Risk Screening Measure (PRISM) to Assess Pain-Related Risk Factors in Parents of Youth Seeking Treatment for Acute Musculoskeletal Pain
Authors: Holley Amy L. , Gaultney Wendy , Wilson Anna C. 
Published: June 2022

Objectives:
The Parent Risk Screening Measure (PRISM) rapidly assesses parent distress, psychosocial function, and behaviors associated with child pain-related dysfunction in parents of youth with chronic pain. Recognizing the importance of parent pain-related cognitions and responses to pain during the acute pain period, the current study examined the utility of the PRISM in screening parents of youth with acute pain.

Methods:
Participants were 175 parent-youth dyads taking part in a larger study examining risk and resilience in youth with acute musculoskeletal pain. Parents completed the PRISM and a battery of measures reporting on their child’s pain-related disability and cognitions and behaviors in response to their child’s pain. Youth reported on their pain, pain-related disability, pain-related fear, catastrophizing, and pain self-efficacy.

Results:
PRISM total scores (M=2.55, SD=2.77) were correlated with many parent and child report measures (eg, protectiveness, catastrophizing, and pain-related fear), with higher scores associated with greater symptoms. Using published PRISM cutoffs, 86.9% of parents were classified as low and 13.13% as elevated risk. t tests revealed significant differences between elevated and low-risk groups on several measures. Moreover, youth of parents in the elevated risk group were more likely to meet clinical cutoffs on pain catastrophizing and fear avoidance measures.

Discussion:
Findings suggest the PRISM is useful in screening for parent distress and behaviors associated with elevated pain symptomatology in a pediatric acute musculoskeletal pain sample. The important next steps are to identify the ideal time for administering the PRISM and to examine the associations among PRISM scores and pain outcomes over time.
Lower serum copper concentrations are associated with higher prevalence of nonalcoholic steatohepatitis: a matched case–control study
Authors: Zhang Huai , Zheng Kenneth I. , Zhu Pei-Wu , Chen Sui-Dan , Li Gang , Ma Hong-Lei , Tang Liang-Jie , Huang Ou-Yang , Byrne Christopher D. , Targher Giovanni , Wang Xiao-Dong , Zheng Ming-Hua 
Published: June 2022

Background and aim
Copper is an essential trace element involved in oxidative stress reactions and energy metabolism. While nonalcoholic fatty liver disease (NAFLD) is closely related to metabolic dysfunction, the role of copper in the development of simple steatosis (NAFL) and nonalcoholic steatohepatitis (NASH) is still unclear. We aimed to compare serum copper levels between patients with simple steatosis and those with NASH.

Methods and results
We studied 102 patients with biopsy-proven NASH (cases) and 102 NAFL controls, who were matched for age, sex, and residential city. Multivariable conditional logistic analysis was performed to explore associations between serum copper levels and the presence of NASH. Serum copper levels were significantly lower in patients with NASH than in those with matched NAFL controls (15.53 ± 2.41 μmol/l vs. 16.34 ± 3.23 μmol/l; P = 0.029). This intergroup difference in serum copper levels was more pronounced in men than in women. The per unit, per SD, and per doubling of serum copper levels were associated, respectively, with an approximately 20, 40, and 90% decrease in risk of having NASH, even after adjustment for potential confounding factors.

Conclusion
Lower serum copper concentrations are significantly associated with higher prevalence of NASH among biopsied-proven NAFLD patients, particularly in men.
Considerations for routinely testing for high Lp(a)
Authors: Nurmohamed Nick S. , Moriarty Patrick M. , Stroes Erik S.G. 
Published: June 2022

Purpose of review
Lipoprotein(a) (Lp[a]) is a likely causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve disease, confirmed by Mendelian randomization. With reliable assays, it has been established that Lp(a) is linearly associated with ASCVD. Current low-density lipoprotein cholesterol (LDL-C) lowering therapies do not or minimally lower Lp(a). This review focuses on the clinical importance and therapeutic consequences of Lp(a) measurement.

Recent findings
Development of RNA-based Lp(a) lowering therapeutics has positioned Lp(a) as one of the principal residual risk factors to target in the battle against lipid-driven ASCVD risk. Pelacarsen, which is a liver-specific antisense oligonucleotide, has shown Lp(a) reductions up to 90% and its phase 3 trial is currently underway. Olpasiran is a small interfering RNA targeting LPA messenger RNA which is being investigated in phase 2 and has already shown dose-dependent Lp(a) reductions up to 90%.

Summary
Lp(a) should be measured in every patient at least once to identify patients with very high Lp(a) levels. These patients could benefit from Lp(a) lowering therapies when approved. In the meantime, therapy in high Lp(a) patients should focus on further reducing LDL-C and other ASCVD risk factors.
Identifying Barriers to Trainees Addressing Corporal Punishment and Effective Discipline Using Simulation and Semistructured Debriefing
Authors: Slingsby Brett , Moore Jessica , Wing Robyn , Garro Aris , Brown Linda 
Published: June 2022

Objective
The objective of the current study was to examine (1) physician trainee interventions when confronted with a situation in which corporal punishment (CP) occurs in a simulated medical setting and (2) their knowledge, comfort, and experiences shared during a semistructured debriefing.

Methods
Themes were developed from simulation sessions from 2018 to 2019, where a convenience sample of training physicians was invited to participate. The simulation involved a medical visit where a caregiver becomes increasingly aggravated, eventually striking her child on the back of the head. There were a total of 7 simulations with one trainee participating while others observed. All trainees subsequently participated in a debriefing and educational session.

Results
A total of 37 physician trainees participated. Themes of not having the wording to address CP, not knowing the distinction between CP and physical abuse, previous negative experiences discussing discipline with families, and fear of offending families negatively impacted trainees' ability to intervene during the simulation. Trainees were interested in future education including simulated medical encounters to improve their responses to CP in the future.

Conclusions
Trainees felt uncomfortable with intervening when CP was observed and did not know how to provide appropriate guidance to families on discipline. Moreover, performance during the simulation and discussions during the debriefings revealed knowledge gaps regarding the difference between CP and physical abuse, how to word recommendations about CP to caregivers, and what resources should be provided. These data suggest the need for education on CP and discipline to be integrated into pediatric training.