bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is there a reduction in hip destruction under a treat-to-target strategy in patients with rheumatoid arthritis?
Authors: Tsushima Hidetoshi , Takahide Sakuragi , Akasaki Yukio , Fujiwara Toshifumi , Hara Daisuke , Ikemura Satoshi , Sakuraba Kouji , Kamura Satoshi , Miyahara Hisaaki , Yamada Hisakata , Fukushi Jun-ichi , Nakashima Yasuharu 
Published: February 2023

ABSTRACT

Objectives
The treatments for rheumatoid arthritis (RA) have been greatly improved, and the tight control of disease activity yields superior clinical outcomes. This study aimed to elucidate the accompanying changes in hip destruction following the implementation of a treat-to-target strategy for patients with RA.

Methods
We extracted 190 hips over two periods, i.e. the early period (1998–2003) and the late period (2013–19), with 103 and 87 hips, respectively. The observed rheumatic changes, such as inward migration, upward migration, and femoral head collapse, were quantitatively evaluated, while osteoarthritic changes, such as the formation of a capital drop, were investigated from radiographs before primary total hip arthroplasty.

Results
A comparison of the two periods’ data showed that the degree of inward migration (−3.44 vs. −7.45 mm; P &lt; .001) and upward migration (+4.3 vs. +0.95 mm; P &lt; .001) significantly decreased in the late-period group. The collapse of the femoral head was not significantly different. The incidence of capital drops was significantly higher in the late-period group (7.8% vs. 27.5%; P &lt; .001).

Conclusions
The degree of inward and upward migration representative of rheumatic changes reduced, whereas the frequency of capital drops as osteoarthritic changes increased during the late period.
ARBUSCULAR MYCORRHIZA-INDUCED KINASES AMK8 and AMK24 associate with the receptor-like kinase KINASE3 to regulate arbuscular mycorrhizal symbiosis in Lotus japonicus
Authors: Leng Junchen , Wei Xiaotong , Jin Xinyi , Wang Longxiang , Fan Kai , Zou Ke , Zheng Zichao , Saridis Georgios , Zhao Ningkang , Zhou Dan , Duanmu Deqiang , Wang Ertao , Cui Haitao , Bucher Marcel , Xue Li 
Published: February 2023

Abstract
Arbuscular mycorrhizal (AM) symbiosis is a widespread, ancient mutualistic association between plants and fungi, and facilitates nutrient uptake into plants. Cell surface receptor-like kinases (RLKs) and receptor-like cytoplasmic kinases (RLCKs) play pivotal roles in transmembrane signaling, while few RLCKs are known to function in AM symbiosis. Here, we show that 27 out of 40 AM-induced kinases (AMKs) are transcriptionally upregulated by key AM transcription factors in Lotus japonicus. Nine AMKs are only conserved in AM-host lineages, among which the SPARK-RLK-encoding gene KINASE3 (KIN3) and the RLCK paralogues AMK8 and AMK24 are required for AM symbiosis. KIN3 expression is directly regulated by the AP2 transcription factor CTTC MOTIF-BINDING TRANSCRIPTION FACTOR1 (CBX1), which regulates the reciprocal exchange of nutrients in AM symbiosis, via the AW-box motif in the KIN3 promoter. Loss of function mutations in KIN3, AMK8, or AMK24 result in reduced mycorrhizal colonization in L. japonicus. AMK8 and AMK24 physically interact with KIN3. KIN3 and AMK24 are active kinases and AMK24 directly phosphorylates KIN3 in vitro. Moreover, CRISPR-Cas9-mediated mutagenesis of OsRLCK171, the sole homolog of AMK8 and AMK24 in rice (Oryza sativa), leads to diminished mycorrhization with stunted arbuscules. Overall, our results reveal a crucial role of the CBX1-driven RLK/RLCK complex in the evolutionarily conserved signaling pathway enabling arbuscule formation.
Microalgal glycerol-3-phosphate acyltransferase role in galactolipids and high-value storage lipid biosynthesis
Authors: Zou Song , Lu Yuanchen , Ma Haiyan , Li Yanhua , Chen Guanqun , Han Danxiang , Hu Qiang 
Published: February 2023

AbstractGlycerolipids are the most abundant lipids in microalgae, and glycerol-3-phosphate:acyl-CoA acyltransferase (GPAT) plays an important role in their biosynthesis. However, the biochemical and biological functions of algal GPAT remain poorly characterized. Here, we characterized the endoplasmic reticulum (ER)-associated GPAT of the model unicellular green alga Chlamydomonas reinhardtii (CrGPATer). Enzymatic assays indicated that CrGPATer is an sn-1 acyltransferase using a variety of acyl-CoAs as the acyl donor. Subcellular localization revealed that CrGPATer was associated with ER membranes and lipid droplets. We constructed overexpression (OE) and knockdown (KD) transgenic C. reinhardtii lines to investigate the in vivo function of CrGPATer. Lipidomic analysis indicated that CrGPATer OE enhanced the cellular content of galactolipids, especially monogalactosyldiacylglycerol, under nitrogen deficiency stress. Correspondingly, CrGPATer KD lines contained lower contents of galactolipids than the control. Feeding experiments with labeled phosphatidic acid revealed that the intermediate of the eukaryotic Kennedy pathway could be used for galactolipid biosynthesis in the chloroplasts. These results provided multiple lines of evidence that the eukaryotic Kennedy pathway mediated by CrGPATer may be involved in galactolipid biosynthesis in C. reinhardtii. OE of CrGPATer significantly increased the content of triacylglycerol and the yield of biomass. Moreover, the content and yield of 1, 3-olein-2-palmitin, a high-value lipid that can be used as an alternative for human milk fat in infant formula, were significantly enhanced in the OE transgenic lines. Taken together, this study provided insights into the biochemical and biological functions of CrGPATer and its potential as a genetic engineering target in functional lipid manufacturing.
Experimental approaches in studying active biomolecules modulating fruit ripening: Melatonin as a case study
Authors: Arabia Alba , Muñoz Paula , Pallarés Núria , Munné-Bosch Sergi 
Published: February 2023

Abstract
Phytohormones are naturally occurring small organic molecules found at low concentrations in plants. They perform essential functions in growth and developmental processes, from organ initiation to senescence, including fruit ripening. These regulatory molecules are studied using different experimental approaches, such as performing exogenous applications, evaluating endogenous levels, and/or obtaining genetically modified lines. Here, we discuss the advantages and limitations of current experimental approaches used to study active biomolecules modulating fruit ripening, focusing on melatonin. Although melatonin has been implicated in fruit ripening in several model fruit crops, current knowledge is affected by the different experimental approaches used, which have given different and sometimes even contradictory results. The methods of application and the doses used have produced different results in studies based on exogenous applications, while different measurement methods and ways of expressing results explain most of the variability in studies using correlative analyses. Furthermore, studies on genetically modified crops have focused on tomato (Solanum lycopersicum L.) plants only. However, TILLING and CRISPR methodologies are becoming essential tools to complement the results from the experimental approaches described above. This will not only help the scientific community better understand the role of melatonin in modulating fruit ripening, but it will also help develop technological advances to improve fruit yield and quality in major crops. The combination of various experimental approaches will undoubtedly lead to a complete understanding of the function of melatonin in fruit ripening in the near future, so that this knowledge can be effectively transferred to the field.
cAMP controls the balance between dormancy and activation of primordial follicles in mouse ovaries
Authors: Zheng Wenying , Zhang Tuo , Zhao Ting , Zhu Zijian , Qin Shaogang , Yan Hao , He Meina , Zhou Bo , Xia Guoliang , Zhang Hua , Wang Chao 
Published: February 2023

Abstract
In mammalian ovaries, the balance between dormancy and activation of primordial follicles determines the female fecundity and endocrine homeostasis. Recently, several functional molecules and pathways have been reported to be involved in the activation of primordial follicles. However, the homeostasis regulatory mechanisms of primordial follicle activation are still scant. Our previous study has proved that a relatively higher concentration of cyclic AMP (cAMP) is required for primordial follicle formation. Here, we identified that cAMP also plays a vital role in the balance between dormancy and activation of primordial follicles. Our results showed that the concentration of cAMP remained stable in neonatal mouse ovaries, which is due to ADCY3, the synthetase of cAMP, and PDE3A, the hydrolytic enzyme of cAMP, were synchronously increased during the activation of primordial follicles in mouse ovaries. Once the concentration of cAMP in neonatal ovaries was either elevated or reduced in vitro, the activation of primordial follicles was either accelerated or decelerated accordingly. In addition, a higher concentration of cAMP in the ovaries of puberty mice improved primordial follicle activation in vivo. Finally, cAMP promoted primordial follicle activation via canonical mTORC1–PI3K signaling cascades and PKA signaling. In conclusion, our findings reveal that the concentration of cAMP acts as a key regulator in balancing the dormancy and activation of primordial follicles in the mouse ovary.
Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling
Authors: Wei Min , Sun Yanping , Li Shouzhen , Chen Yunuo , Li Longfei , Fang Minghao , Shi Ronghua , Tong Dali , Chen Jutao , Ma Yuqian , Qu Kun , Zhang Mei , Xue Tian 
Published: February 2023

Abstract
Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.
A Welfare Analysis of Occupational Licensing in U.S. States
Authors: Kleiner Morris M , Soltas Evan J 
Published: February 2023

Abstract
We assess the welfare consequences of occupational licensing for workers and consumers. We estimate a model of labour market equilibrium in which licensing restricts labour supply but also affects labour demand via worker quality and selection. On the margin of occupations licensed differently between U.S. states, we find that licensing raises wages and hours but reduces employment. We estimate an average welfare loss of 12% of occupational surplus. Workers and consumers respectively bear 70% and 30% of the incidence. Higher willingness to pay offsets 80% of higher prices for consumers, and higher wages compensate workers for 60% of the cost of mandated investment in occupation-specific human capital. Welfare effects appear more favourable in occupations in which licensing is more common.
Wet cupping therapy in the modulation of inflammation in patients with pain
Authors: Al Jaouni Soad K , Rohaiem Sawsan M , Almuhayawi Mohammed S , Godugu Kavitha , Almughales Jamil , Kholi Sabria M , Al-Raddadi Rajaa , Bukhari Musab , Mousa Shaker A 
Published: February 2023

Abstract

Objectives
Wet cupping therapy (WCT) is a complementary treatment used for a wide range of diseases associated with pain. Inflammatory cytokines play an important role in the clinical symptoms related to pain. The objective of this study is to assess the changes in inflammatory markers (different interleukins (IL) and tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte stimulating factor (G-CSF)) in patients with pain who went a 6 weeks of WCT as a complementary approach.

Methods
This is a retrospective record review study from the Prophetic Medicine Clinics for Cupping Therapy Clinics, at King Abdulaziz University Hospital, Saudi Arabia. It consists of 93 adult patients; these patients were referred from different specialty clinics with various diagnoses due to pain for performing WCT as an integrative treatment. Measurements of various biomarkers in patients with pain before and after 6 weeks of WCT were carried out.

Key findings
Serum IL-1β, IL-5, IL-6, IL-7, IL-8, IL-12, IL-13, TNF-α, GM-CSF, G-CSF, MCP-1 and MIP-1β were significantly (P &lt; 0.001) decreased in patients after 6 weeks of WCT. Other biomarkers did not significantly change.

Conclusions
WCT showed favourable effects on pro-inflammatory markers (cytokines and chemokines) in patients with pain.
Cost and cost-effectiveness analysis of a digital diabetes prevention program: results from the PREDICTS trial
Authors: Michaud Tzeyu L , Wilson Kathryn E , Katula Jeffrey A , You Wen , Estabrooks Paul A 
Published: February 2023

Abstract
Although technology-assisted diabetes prevention programs (DPPs) have been shown to improve glycemic control and weight loss, information are limited regarding relevant costs and their cost-effectiveness. To describe a retrospective within-trial cost and cost-effectiveness analysis (CEA) to compare a digital-based DPP (d-DPP) with small group education (SGE), over a 1-year study period. The costs were summarized into direct medical costs, direct nonmedical costs (i.e., times that participants spent engaging with the interventions), and indirect costs (i.e., lost work productivity costs). The CEA was measured by the incremental cost-effectiveness ratio (ICER). Sensitivity analysis was performed using nonparametric bootstrap analysis. Over 1 year, the direct medical costs, direct nonmedical costs, and indirect costs per participant were $4,556, $1,595, and $6,942 in the d-DPP group versus $4,177, $1,350, and $9,204 in the SGE group. The CEA results showed cost savings from d-DPP relative to SGE based on a societal perspective. Using a private payer perspective for d-DPP, ICERs were $4,739 and $114 to obtain an additional unit reduction in HbA1c (%) and weight (kg), and were $19,955 for an additional unit gain of quality-adjusted life years (QALYs) compared to SGE, respectively. From a societal perspective, bootstrapping results indicated that d-DPP has a 39% and a 69% probability, at a willingness-to-pay of $50,000/QALY and $100,000/QALY, respectively, of being cost-effective. The d-DPP was cost-effective and offers the prospect of high scalability and sustainability due to its program features and delivery modes, which can be easily translated to other settings.
Populusroot salicinoid phenolic glycosides are not mobilized to support metabolism and regrowth under carbon-limited conditions
Authors: Hillabrand R M , Gordon H , Hynes B , Constabel C P , Landhäusser S M 
Published: February 2023

AbstractRemobilization of carbon storage compounds in trees is crucial for the resilience to disturbances, stress and the requirements of their perennial lifestyle, all of which can impact photosynthetic carbon gain. Trees contain abundant non-structural carbohydrates in the form of starch and sugars for long-term carbon storage, yet questions remain about the ability of trees to remobilize non-conventional carbon compounds under stress. Aspens, like other members of the genus Populus, have abundant specialized metabolites called salicinoid phenolic glycosides, which contain a core glucose moiety. In this study, we hypothesized that the glucose-containing salicinoids could be remobilized as an additional carbon source during severe carbon limitation. We made use of genetically modified hybrid aspen (Populus tremula L.× Populus albaL.) with minimal salicinoid content and compared these with control plants with high salicinoid content during resprouting (suckering) in dark (carbon-limited) conditions. As salicinoids are abundant anti-herbivore compounds, identification of such a secondary function for salicinoids may provide insight into the evolutionary pressures that drive their accumulation. Our results show that salicinoid biosynthesis is maintained during carbon limitation and suggests that salicinoids are not remobilized as a carbon source for regenerating shoot tissue. However, we found that salicinoid-producing aspens had reduced resprouting capacity per available root biomass when compared with salicinoid-deficient aspens. Therefore, our work shows that the constitutive salicinoid production in aspens can reduce the capacity for resprouting and survival in carbon-limited conditions.
OASL knockdown inhibits the progression of stomach adenocarcinoma by regulating the mTORC1 signaling pathway
Authors: Zhao Weizhu , Yang Haiying , Liu Luguang , Qu Xianlin , Ding Jishuang , Yu Hang , Xu Botao , Zhao Siwei , Xi Guangmin , Xing Ligang , Chai Jie 
Published: February 2023

AbstractThe present study investigated the effects of 2′‐5′ oligoadenylate synthetase‐like (OASL) on the biological functions of stomach adenocarcinoma (STAD) cells and tumor formation in nude mice. The differential expression levels of OASL in the different cancer types from TCGA dataset were analyzed using gene expression profiling interactive analysis. Overall survival and the receiver operating characteristic were analyzed using the KM plotter and R, respectively. Furthermore, OASL expression and its effects on the biological functions of STAD cells were detected. The possible upstream transcription factors of OASL were predicted using JASPAR. The downstream signaling pathways of OASL were analyzed using GSEA. Tumor formation experiments were performed to evaluate the effect of OASL on tumor formation in nude mice. The results showed that OASL was highly expressed in STAD tissues and cell lines. OASL knockdown markedly inhibited cell viability, proliferation, migration, and invasion and accelerated STAD cell apoptosis. Conversely, OASL overexpression had the opposite effect on STAD cells. JASPAR analysis revealed that STAT1 is an upstream transcription factor of OASL. Furthermore, GSEA showed that OASL activated the mTORC1 signaling pathway in STAD. The protein expression levels of p‐mTOR and p‐RPS6KB1 were suppressed by OASL knockdown and promoted by OASL overexpression. The mTOR inhibitor, rapamycin, markedly reversed the effect of OASL overexpression on STAD cells. Additionally, OASL promoted tumor formation and increased tumor weight and volume in vivo. In conclusion, OASL knockdown suppressed the proliferation, migration, invasion, and tumor formation of STAD cells by inhibiting the mTOR signaling pathway.
Mediation of serum albumin in the association of serum potassium with mortality in Chinese dialysis patients: a prospective cohort study
Authors: Huang Naya , Liu Yuanying , Ai Zhen , Zhou Qian , Mao Haiping , Yang Xiao , Xu Yuanwen , Yu Xueqing , Chen Wei 
Published: February 2023

Abstract

Background:
The clinical importance of hypokalemia is likely underrecognized in Chinese dialysis patients, and whether its clinical effect was mediated by serum albumin is not fully elucidated. This study aimed to explore the association between serum.

Methods:
This was a prospective nation-wide multicenter cohort study. Restricted cubic splines were used to test the linearity of serum potassium and relationships with all-cause (AC) and cardiovascular (CV) mortality and a subsequent two-line piecewise linear model was fitted to approach the nadir. A mediation analysis was performed to examine relations of albumin to potassium and mortalities.

Results:
A total of 10,027 patients were included, of whom 6605 were peritoneal dialysis and 3422 were hemodialysis patients. In the overall population, the mean age was 51.69 ± 14.8 years, 55.3%(5546/10027) were male, and the median dialysis vintage was 13.60 (4.70, 39.70) months. Baseline serum potassium was 4.30 ± 0.88 mmol/L. After a median follow-up period of 26.87 (14.77, 41.50) months, a U-shaped was found between potassium and mortality, and a marked increase in risk at lower potassium but a moderate elevation in risk at higher potassium were observed. The nadir for AC mortality risk was estimated from piecewise linear models to be a potassium concentration of 4.0 mmol/L. Interestingly, the significance of the association between potassium and mortality was attenuated when albumin was introduced into the extended adjusted model. A subsequent significant mediation by albumin for potassium and AC and CV mortalities were found (P < 0.001 for both), indicating that hypokalemia led to higher mortality mediated by low serum albumin, which was a surrogate of poor nutritional status and inflammation.

Conclusions:
Associations between potassium and mortalities were U-shaped in the overall population. The nadir for AC mortality risk was at a potassium of 4.0 mmol/L. Serum albumin mediated the association between potassium and AC and CV mortalities.
A multicenter, randomized, placebo-controlled study to select the minimum effective dose of estetrol in postmenopausal participants (E4Relief): part 2—vaginal cytology, genitourinary syndrome of menopause, and health-related quality of life
Authors: Gaspard Ulysse , Taziaux Mélanie , Jost Maud , Coelingh Bennink Herjan J.T. , Utian Wulf H. , Lobo Rogerio A. , Foidart Jean-Michel 
Published: February 2023

Abstract

Objective
A phase 2 study showed that 15 mg estetrol (E4) alleviates vasomotor symptoms (VMS). Here, we present the effects of E4 15 mg on vaginal cytology, genitourinary syndrome of menopause, and health-related quality of life.

Methods
In a double-blind, placebo-controlled study, postmenopausal participants (n = 257, 40-65 y) were randomized to receive E4 2.5, 5, 10, or 15 mg or placebo once daily for 12 weeks. Outcomes were the vaginal maturation index and maturation value, genitourinary syndrome of menopause score, and the Menopause Rating Scale to assess health-related quality of life. We focused on E4 15 mg, the dose studied in ongoing phase 3 trials, and tested its effect versus placebo at 12 weeks using analysis of covariance.

Results
Least square (LS) mean percentages of parabasal and intermediate cells decreased, whereas superficial cells increased across E4 doses; for E4 15 mg, the respective changes were −10.81% (P = 0.0017), −20.96% (P = 0.0037), and +34.17% (P < 0.0001). E4 15 mg decreased LS mean intensity score for vaginal dryness and dyspareunia (−0.40, P = 0.03, and −0.47, P = 0.0006, respectively); symptom reporting decreased by 41% and 50%, respectively, and shifted to milder intensity categories. The overall Menopause Rating Scale score decreased with E4 15 mg (LS mean, −3.1; P = 0.069) and across doses was associated with a decreasing frequency and severity of VMS (r = 0.34 and r = 0.31, P < 0.001).

Conclusions
E4 demonstrated estrogenic effects in the vagina and decreased signs of atrophy. E4 15 mg is a promising treatment option also for important menopausal symptoms other than VMS.