bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic periadolescent leuprolide exposure affects the development of reproductive physiology and behavior of female and male rats differently, but both mature after treatment termination
Authors: Guarraci Fay A. , Avendano Layla , Kelly Megan , Estoesta Cleriza , Sencherey Bernard , Valdivia Hannah S. , Gale Amanda , Yepez Lily , Belfield Jasmine B. , Carter Kristen M. , Williams Natalie , Gore Andrea C. 
Published: January 2023

Abstract
Background
GnRH agonists have been used to halt the development of puberty in children with precocious puberty since the 1980s. Recently, drugs like Lupron Depot® (leuprolide acetate), have been used to suppress pubertal progression in adolescents who are questioning their gender identity. However, few preclinical studies have been conducted to investigate potential effects of using GnRH agonists in this context.

Methods
The present study tested the effects of daily leuprolide treatment (50 µg/kg, postnatal day (PD) 25–50) on pubertal onset in female (i.e., vaginal opening) and male (i.e., preputial separation) Long-Evans rats. The first estrous cycle immediately after vaginal opening was also measured. Sexual behavior and sexual motivation were tested using the partner-preference paradigm. Female rats were tested during the first behavioral estrus after treatment ended (between PD 51–64). Male rats were tested weekly for four consecutive weeks starting three days after treatment ended (PD 53).

Results
Consistent with previous findings, leuprolide significantly delayed pubertal onset in both female and male rats. In addition, the first estrous cycle during the treatment period was disrupted by leuprolide, as indicated by a failure to cycle into estrus after vaginal opening until treatment ended. However, leuprolide affected neither sexual motivation nor fertility when female rats were tested within 14 days of leuprolide treatment ending. In contrast, the development of copulatory behavior and sexual motivation was significantly delayed by leuprolide in male rats; however, mature reproductive behavior was observed by the fourth week post-treatment.

Conclusions
Taken together with previous findings, the present results indicate that male rats may be more sensitive to periadolescent leuprolide administration, taking longer to overcome the effects of leuprolide than female rats. Nevertheless, not long after leuprolide treatment is discontinued, sex-typical reproductive physiology and behavior emerge fully in female and male rats, indicating that the drug’s effects are not permanent. If translatable to humans, leuprolide may be a reversible option to give adolescents more time to consider their gender identity with minimal long-term effects on sexual development.
Transfer factor calculated using dermal exposure and dislodgeable foliar residue and exposure assessment for reentry worker after pesticide application in cucumber field
Authors: Choi Hoon 
Published: January 2023

AbstractThis study aimed to determine the transfer factor (TF) of methidathion for cucumber harvesters in greenhouses using the dermal exposure rates (DERs) and dislodgeable foliar residues (DFRs) measured simultaneously in my previous works. The DERs recalculated using the reference body surface area for the Korean adult males were 31.5–1281.1 μg/h, and the DFR values were 12.1–222.5 ng/cm2 over 7 d after application. A strong correlation between the DERs and DFRs was observed, with a regression coefficient of 0.9982. The TF for cucumber harvesters in greenhouses was determined to be 6020.4 cm2/h, which was five times higher than that proposed by the US Environmental Protection Agency (EPA). Additionally, based on TF value of methidathion, the reentry intervals (REIs) with or without personal protective equipment (PPE) were estimated for 82 pesticides registered on cucumber. The REIs with PPE, obtained from acceptable operator exposure levels and TF value, were less than 0 d, indicating the lowest risk possibility. However, REIs without PPE were estimated between 0.04 and 4.4 d for seven pesticides, including chlorothalonil, emamectin benzoate, flubendiamide, fluquinconazole, iminoctadine tris(albesilate), propineb, and pyridaben. In conclusion, cucumber harvesters should wear PPE for health safety when they reenter the greenhouse to harvest cucumbers following application of pesticides.
Radiomics based of deep medullary veins on susceptibility-weighted imaging in infants: predicting the severity of brain injury of neonates with perinatal asphyxia
Authors: Zhuang Xiamei , Lin Huashan , Li Junwei , Yin Yan , Dong Xiao , Jin Ke 
Published: January 2023

Abstract
Objective
This study aimed to apply radiomics analysis of the change of deep medullary veins (DMV) on susceptibility-weighted imaging (SWI), and to distinguish mild hypoxic-ischemic encephalopathy (HIE) from moderate-to-severe HIE in neonates.

Methods
A total of 190 neonates with HIE (24 mild HIE and 166 moderate-to-severe HIE) were included in this study. All of them were born at 37 gestational weeks or later. The DMVs were manually included in the regions of interest (ROI). For the purpose of identifying optimal radiomics features and to construct Rad-scores, 1316 features were extracted. LASSO regression was used to identify the optimal radiomics features. Using the Red-score and the clinical independent factor, a nomogram was constructed. In order to evaluate the performance of the different models, receiver operating characteristic (ROC) curve analysis was applied. Decision curve analysis (DCA) was implemented to evaluate the clinical utility.

Results
A total of 15 potential predictors were selected and contributed to Red-score construction. Compared with the radiomics model, the nomogram combined model incorporating Red-score and urea nitrogen did not better distinguish between the mild HIE and moderate-to-severe HIE group. For the training cohort, the AUC of the radiomics model and the combined nomogram model was 0.84 and 0.84. For the validation cohort, the AUC of the radiomics model and the combined nomogram model was 0.80 and 0.79, respectively. The addition of clinical characteristics to the nomogram failed to distinguish mild HIE from moderate-to-severe HIE group.

Conclusion
We developed a radiomics model and combined nomogram model as an indicator to distinguish mild HIE from moderate-to-severe HIE group.
ALKBH5 prevents hepatocellular carcinoma progression by post-transcriptional inhibition of PAQR4 in an m6A dependent manner
Authors: Wang Weijian , Huang Qibo , Liao Zhibin , Zhang Hongwei , Liu Yachong , Liu Furong , Chen Xiaoping , Zhang Bixiang , Chen Yan , Zhu Peng 
Published: January 2023

Abstract
Background
N6-methyladenosine (m6A) is a prevalent modification of mRNA and is known to play important roles in tumorigenesis in many types of cancer. The function of N6-methyladenosine (m6A) RNA methylation depends on a variety of methyltransferases and demethylases. AlkB homolog 5 (ALKBH5) is a demethylase, and its biological function has not been completely explored in HCC.

Results
ALKBH5 is downregulated and has antitumor effects in HCC cells. In addition, Progestin and AdipoQ Receptor 4 (PAQR4) was identified as a downstream target of ALKBH5 based on transcriptome sequencing and validation studies. We found that ALKBH5 decreases PAQR4 mRNA and protein expression in an N6-methyladenosine (m6A)-dependent manner. The study also showed that ALKBH5 changes PAQR4 expression via the m6A reader IGF2BP1. In both in vivo and in vitro experiments, PAQR4 showed a strong association with the development of HCC. Finally, we found that PAQR4 interacts with AKT and enhances PI3K/AKT pathway activation.

Conclusions
ALKBH5 inhibits HCC growth by downregulating PAQR4 expression in an m6A-dependent manner, therefore suppressing PI3K/AKT pathway activation.
Transmissible H-aggregated NIR-II fluorophore to the tumor cell membrane for enhanced PTT and synergistic therapy of cancer
Authors: Yu Haoli , Wang Yuesong , Chen Yan , Cui Mengyuan , Yang Fang , Wang Peng , Ji Min 
Published: January 2023

AbstractPhotothermal therapy (PTT) combined with second near-infrared (NIR-II) fluorescence imaging (FI) has received increasing attention owing to its capacity for precise diagnosis and real-time monitoring of the therapeutic effects. It is of great clinical value to study organic small molecular fluorophores with both PTT and NIR-II FI functions. In this work, we report a skillfully fluorescent lipid nanosystem, the RR9(RGDRRRRRRRRRC) peptide-coated anionic liposome loaded with organic NIR-II fluorophore IR-1061 and chemotherapeutic drug carboplatin, which is named RRIALP-C4. According to the structural interaction between IR-1061 and phospholipid bilayer demonstrated by molecular dynamics simulations, IR-1061 is rationally designed to possess the H-aggregated state versus the free state, thus rendering RRIALP-C4 with the activated dual-channel integrated function of intravital NIR-II FI and NIR-I PTT. Functionalization of RRIALP-C4 with RR9peptide endows the specifically targeting capacity for αvβ3-overexpressed tumor cells and, more importantly, allows IR-1061 to transfer the H-aggregated state from liposomes to the tumor cell membrane through enhanced membrane fusion, thereby maintaining its PTT effect in tumor tissues. In vivo experiments demonstrate that RRIALP-C4 can effectively visualize tumor tissues and systemic blood vessels with a high sign-to-background ratio (SBR) to realize the synergistic treatment of thermochemotherapy by PTT synergistically with temperature-sensitive drug release. Therefore, the strategy of enhanced PTT through H-aggregation of NIR-II fluorophore in the tumor cell membrane has great potential for developing lipid nanosystems with integrated diagnosis and treatment function.
Hysterectomy and women’s health in India: evidence from a nationally representative, cross-sectional survey of older women
Authors: Desai Sapna , Singh Roopal Jyoti , Govil Dipti , Nambiar Devaki , Shukla Ankita , Sinha Hemali Heidi , Ved Rajani , Bhatla Neerja , Mishra Gita D. 
Published: January 2023

Abstract
Background
Hysterectomy, particularly when conducted in women younger than 45 years, has been associated with increased risk of non-communicable diseases. In India, research indicates that hysterectomy is a common procedure for women, but there have been no studies on its long-term effects. We examined patterns of hysterectomy amongst women in India and associations with their health and well-being in later life.

Methods
This analysis utilised the first wave of the Longitudinal Study on Aging in India, a nationally representative study of adults that included a module on health and well-being.
We analysed data on 35,083 women ≥45 years in India. We estimated prevalence of hysterectomy and performed multivariable logistic regression to identify associated risk factors and to examine the association between hysterectomy status and eight self-reported chronic conditions, hospitalisation and mobility.

Results
The prevalence of hysterectomy among women >=45 years was 11.4 (95% CI: 10.3, 12.6), with higher odds among urban women (aOR: 1.39; 1.17,1.64) and higher economic status (highest compared to lowest quintile: aOR: 1.95; 1.44, 2.63). Hysterectomy history was associated with four chronic conditions: hypertension (aOR: 1.51; 95% CI: 1.28, 1.79), high cholesterol (aOR: 1.43; 1.04, 1.97), diabetes (aOR: 1.69; 1.28, 2.24), and bone/joint disease (aOR: 1.54; 1.20, 1.97) and higher odds of any hospitalisation in the past year (aOR: 1.69; 1.36, 2.09).

Conclusions
In India, evidence suggests that hysterectomy is associated with major chronic conditions. The assessment for hysterectomy as a treatment option for gynaecological morbidity should consider potential health consequences in later life.
Work trajectories and status attainment process: a study using sequence analysis
Authors: Zhou Yang 
Published: January 2023

AbstractApplying sequence analysis methods to work trajectories recorded in the 2012 China Labor Force Dynamics Survey, this study examines the types of work trajectories in China’s urban labor market in three dimensions: employment status, organizational type, and work position. The findings suggest that along with the market transition, China’s urban labor market is experiencing diverse and complex job mobility patterns. This study identifies four types of work trajectories: the merit-based work trajectory, the blue-collar’s work trajectory in the private sector, the blue-collar’s work trajectory in state-owned enterprises, and the self-employed trajectory. These four typical work trajectories have significantly different influences on individuals’ attainment of socioeconomic status and elite status. This study sheds light on the microprocesses in status attainment by examining the role of work trajectories from a longitudinal perspective.
The nature and sources of international variation in formal institutions related to initial coin offerings: preliminary findings and a research agenda
Authors: Kshetri Nir 
Published: January 2023

AbstractAs prior researchers have suggested, a firm’s success in an international market depends on how well its strategy fits the nonmarket environment, such as formal institutions. This paper examines the determinants of formal institutions around new areas of economic activities. Specifically, we propose a framework for understanding how the quality of formal institutions in promoting entrepreneurship drives the focus of such institutions concerning initial coin offering (ICO), which is emerging as a popular fundraising method. The paper uses inductive analysis to examine how nonmarket factors—such as a jurisdiction’s tax haven nature, regulators’ perceptions of ICOs as threats to national or political interests, and trade and industry associations—might moderate the relationship between the quality of institutions and the focus of such institutions regarding ICOs. One of this study’s key findings is that an economy’s quality of entrepreneurship-related institutions, perceived threats to national/political interests, and tax haven nature lead to different policy orientations. Consequently, regulators assign different importance when promoting crypto-entrepreneurship and dealing with associated risks. Regulators focusing mainly on promoting crypto-ventures have taken measures to enrich the blockchain ecosystem and provided tax and non-tax incentives to attract such ventures. Regulators focusing mainly on dealing with crypto-venture risks rely on a regulatory sandbox and close regulatory monitoring of such ventures.
Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling
Authors: Watanabe Hirofumi , Mokuda Sho , Tokunaga Tadahiro , Kohno Hiroki , Ishitoku Michinori , Araki Kei , Sugimoto Tomohiro , Yoshida Yusuke , Yamamoto Toshihiro , Matsumoto Mayuko , Masumoto Junya , Hirata Shintaro , Sugiyama Eiji 
Published: January 2023

Abstract
Background
Blood coagulation factor XIII (FXIII) promotes cross-linking between fibrin molecules at the final stage of the blood coagulation cascade. However, its expression in cells or tissues and function, particularly factor XIII subunit B (FXIII-B), remains controversial. Hemorrhagic FXIII deficiency following anti-interleukin-6 (IL-6) receptor antibody treatment has been reported in patients with rheumatoid arthritis (RA). Patients receiving this biologics have reduced FXIII activity when compared to the activity in those treated with other biologics. The relationship between pro-inflammatory cytokines and FXIII expression remains unknown.

Methods
To investigate the expression pattern of FXIII in synovial tissues, immunohistochemistry, RT-qPCR, and western blotting were performed. FXIII-A expressed monocyte-derived macrophages were treated with recombinant IL-6 and anti-IL-6 receptor antibody. RNA sequencing of FXIII-B-overexpressing cells was performed to clarify the function of FXIII-B.

Results
The immunohistochemical analysis of synovial tissues revealed that factor XIII subunit A (FXIII-A) was expressed in M2 macrophages, and FXIII-B was expressed in fibroblast-like synoviocytes. IL-6 stimulation upregulated FXIII-A expression in IL-4-induced monocyte-derived macrophages, and the anti-IL-6 receptor antibody suppressed FXIII-A expression. FXIII-B was more abundantly secreted in the supernatant of fibroblast-like synoviocytes compared with that of other cells. RNA sequencing showed that FXIII-B elevated the expression of genes associated with anti-apoptotic molecules and chemokines.

Conclusions
Our findings highlight that synovial tissue is one of the sources of FXIII production. We also have demonstrated IL-6-dependent FXIII-A expression and the novel potential functions of FXIII-B.
Etomidate-Induced Myoclonus in Sprague-Dawley Rats Involves Neocortical Glutamate Accumulation and N-Methyl-d-Aspartate Receptor Activity
Authors: Feng Yan , Chang Pan , Kang Yi , Liao Ping , Li Chen-yang , Liu Jin , Zhang Wen-sheng 
Published: January 2023

BACKGROUND:
Etomidate-induced myoclonus, a seizure-like movement, is of interest to anesthetists. However, its origin in the brain and its underlying mechanism remain unclear.

METHODS:
Adult male Sprague-Dawley rats were anesthetized with etomidate, propofol, or lidocaine plus etomidate. We assessed the incidence of myoclonus, behavioral scores, and levels of glutamate and γ-aminobutyric acid (GABA) in the neocortex and hippocampus. To determine the origin and how N-methyl-d-aspartate receptors (NMDARs) modulate etomidate-induced neuroexcitability, the local field potential and muscular tension were monitored. Calcium imaging in vitro and immunoblotting in vivo were conducted to investigate the mechanisms underlying myoclonus.

RESULTS:
The incidence of etomidate (1.5 mg/kg in vivo)-induced myoclonus was higher than that of propofol (90% vs 10%, P = .0010) and lidocaine plus etomidate (90% vs 20%, P = .0050). Etomidate at doses of 3.75 and 6 mg/kg decreased the mean behavioral score at 1 (mean difference [MD]: 1.80, 95% confidence interval [CI], 0.58–3.02; P = .0058 for both), 2 (MD: 1.60, 95% CI, 0.43–2.77; P = .0084 and MD: 1.70, 95% CI, 0.54–2.86; P = .0060), 3 (MD: 1.60, 95% CI, 0.35–2.85; P = .0127 and MD: 1.70, 95% CI, 0.46–2.94; P = .0091) minutes after administration compared to etomidate at a dose of 1.5 mg/kg. In addition, 0.5 and 1 µM etomidate in vitro increased neocortical intracellular calcium signaling; this signaling decreased when the concentration increased to 5 and 10 μM. Etomidate increased the glutamate level compared to propofol (mean rank difference: 18.20; P = .003), and lidocaine plus etomidate (mean rank difference: 21.70; P = .0002). Etomidate in vivo activated neocortical ripple waves and was positively correlated with muscular tension amplitude (Spearman’s r = 0.785, P < .0001). Etomidate at 1.5 mg/kg decreased the K-Cl cotransporter isoform 2 (KCC2) level compared with propofol (MD: −1.15, 95% CI, −1.47 to −0.83; P < .0001) and lidocaine plus etomidate (MD: −0.64, 95% CI, −0.96 to −0.32; P = .0002), DL-2-amino-5-phosphopentanoic acid (AP5) suppressed these effects, while NMDA enhanced them.

CONCLUSIONS:
Etomidate-induced myoclonus or neuroexcitability is concentration dependent. Etomidate-induced myoclonus originates in the neocortex. The underlying mechanism involves neocortical glutamate accumulation and NMDAR modulation and myoclonus correlates with NMDAR-induced downregulation of KCC2 protein expression.
Socioeconomic Effects on Lumbar Fusion Outcomes
Authors: Touponse Gavin , Li Guan , Rangwalla Taiyeb , Beach Isidora , Zygourakis Corinna 
Published: January 2023

BACKGROUND:
Recent studies suggest that socioeconomic status (SES) influences outcomes after spinal fusion. The influence of SES on postoperative outcomes is increasingly relevant as rates of lumbar fusion rise.

OBJECTIVE:
To determine the influence of SES variables including race, education, net worth, and homeownership on postoperative outcomes.

METHODS:
Optum's deidentified Clinformatics Data Mart Database was used to conduct a retrospective review of SES variables for patients undergoing first-time, inpatient lumbar fusion from 2003 to 2021. Primary outcomes included hospital length of stay (LOS) and 30-day reoperation, readmission, and postoperative complication rates. Secondary outcomes included postoperative emergency room visits, discharge status, and total hospital charges.

RESULTS:
In total, 217 204 patients were identified. On multivariate analysis, Asian, Black, and Hispanic races were associated with increased LOS (Coeff. [coefficient] 0.92, 95% CI 0.68-1.15; Coeff. 0.61, 95% CI 0.51-0.71; Coeff. 0.43, 95% CI 0.32-0.55). Less than 12th grade education (vs greater than a bachelor's degree) was associated with increased odds of reoperation (OR [odds ratio] 1.88, 95% CI 1.03-3.42). Decreased net worth was associated with increased odds of readmission (OR 1.32, 95% CI 1.25-1.40) and complication (OR 1.14, 95% CI 1.10-1.20). Renting a home (vs homeownership) was associated with increased LOS, readmissions, and total charges (Coeff. 0.30, 95% CI 0.17-0.43; OR 1.19, 95% CI 1.11-1.30; Coeff. 13 200, 95% CI 9000-17 000).

CONCLUSION:
Black race, less than 12th grade education, <$25K net worth, and lack of homeownership were associated with poorer postoperative outcomes and increased costs. Increasing perioperative support for patients with these sociodemographic risk factors may improve postoperative outcomes.
Incorporation of 53BP1 into phase-separated bodies in cancer cells during aberrant mitosis
Authors: Bleiler Marina , Cyr Aiyana , Wright Dennis L. , Giardina Charles 
Published: January 2023

ABSTRACT
53BP1 (also known as TP53BP1) is a key mediator of the non-homologous end joining (NHEJ) DNA repair pathway, which is the primary repair pathway in interphase cells. However, the mitotic functions of 53BP1 are less well understood. Here, we describe 53BP1 mitotic stress bodies (MSBs) formed in cancer cell lines in response to delayed mitosis. These bodies displayed liquid–liquid phase separation characteristics, were close to centromeres, and included lamin A/C and the DNA repair protein RIF1. After release from mitotic arrest, 53BP1 MSBs decreased in number and moved away from the chromatin. Using GFP fusion constructs, we found that the 53BP1 oligomerization domain region was required for MSB formation, and that inclusion of the 53BP1 N terminus increased MSB size. Exogenous expression of 53BP1 did not increase MSB size or number but did increase levels of MSB-free 53BP1. This was associated with slower mitotic progression, elevated levels of DNA damage and increased apoptosis, which is consistent with MSBs suppressing a mitotic surveillance by 53BP1 through sequestration. The 53BP1 MSBs, which were also found spontaneously in a subset of normally dividing cancer cells but not in non-transformed cells (ARPE-19), might facilitate the survival of cancer cells following aberrant mitoses.
This article has an associated First Person interview with the first author of the paper.