bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic treatment with a combination of hepatocyte growth factor and JNK inhibitor ameliorates cavernosal veno-occlusive dysfunction: a rat model of cavernous nerve injury
Authors: Lee Junghoon , Son Hwancheol , Kim Soo Woong , Cho Min Chul 
Published: April 2023

AbstractBackgroundStructural alterations of the penis, including cavernosal apoptosis and fibrosis, induce venous leakage into the corpus cavernosum or cavernosal veno-occlusive dysfunction, a key pathophysiology associated with erectile dysfunction after radical prostatectomy. We hypothesized that the effect of JNK inhibitors on reducing apoptosis and hepatocyte growth factor (HGF) on inducing tissue regeneration could be another treatment mechanism of erectile dysfunction after radical prostatectomy.AimTo investigate whether JNK inhibition combined with intracavernosal administration of HGF can completely preserve cavernosal veno-occlusive function (CVOF) in a rat model of erectile dysfunction induced via bilateral cavernosal nerve crush injury (CNCI).MethodsA total of 42 male Sprague-Dawley rats were randomly assigned to sham control (group S), CNCI (group I), and CNCI treated with a combination of JNK inhibitor and HGF (group J + H) for 5 weeks after surgery.OutcomesRats in each group were evaluated via dynamic infusion cavernosometry (DIC), caspase-3 activity assay, Masson trichrome staining, immunohistochemical staining of α-smooth muscle actin, and immunoblotting at 5 weeks after surgery.ResultsRegarding CVOF, group I showed decreased papaverine response, increased maintenance, and drop rates of DIC when compared with group S. Group J + H showed significant improvement in the 3 DIC parameters vs group I. No differences in the 3 DIC parameters were found between group J + H and group S. Regarding the structural integrity of the corpus cavernosum, group I showed increased caspase-3 activity, decreased smooth muscle (SM):collagen ratio, decreased SM content, decreased protein expression of PECAM-1, and decreased phosphorylation of c-Jun and c-Met. Group J + H showed significant attenuation in histologic and molecular derangement as compared with group I. There were no differences in caspase-3 activity, SM content, SM:collagen ratio, PECAM-1 protein expression, c-Jun phosphorylation, and c-Met phosphorylation between groups J + H and S.Clinical ImplicationsOur results suggest that antiapoptotic and regenerative therapy for the corpus cavernosum is a potential mechanism of penile rehabilitation after radical prostatectomy.Strengths and LimitationsThis study provides evidence that combination treatment of JNK inhibitor and HGF preserves erectile function by restoring corporal SM and endothelium. However, additional human studies are needed to confirm the clinical effect.ConclusionChronic treatment with JNK inhibitor and HGF may preserve CVOF to levels comparable to sham control by preserving the structural integrity of the corpus cavernosum and so represents a potential therapeutic option for preventing the development of cavernosal veno-occlusive dysfunction.
Risk of hospitalized infections in older elderly patients with rheumatoid arthritis treated with tocilizumab or other biological/targeted synthetic disease-modifying antirheumatic drugs: Evaluation of data from a Japanese claims database
Authors: Harigai Masayoshi , Fujii Takao , Sakai Ryoko , Igarashi Ataru , Shoji Ayako , Yamaguchi Hiroko , Iwasaki Katsuhiko , Makishima Misako , Yoshida Amika , Okada Norihiro , Yamashita Katsuhisa , Kawahito Yutaka 
Published: April 2023

ABSTRACT

Objective
We compared the incidence rates of hospitalized infections (HIs) between tocilizumab (TCZ) and other biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in adults aged ≥75 years with rheumatoid arthritis (RA).

Methods
We used a Japanese claims database from Medical Data Vision Co., Ltd (Tokyo, Japan) to perform a retrospective longitudinal population-based study in patients with RA who were prescribed b/tsDMARDs between 2014 and 2019. We calculated adjusted risk ratios (aRRs) for HIs in three age groups (&lt;65, ≥65 and &lt;75, and ≥75 years).

Results
Of 5506 patients, 2265 (41.1%) were &lt;65 years, 1709 (31.0%) were 65–74 years, and 1532 (27.8%) were ≥75 years. Crude incidence rates (/100 person-years) of HIs were 3.99, 7.27, and 10.77, respectively. In the oldest group, aRRs (95% confidence interval) for HIs (b/tsDMARDs versus TCZ) were as follows: etanercept, 2.40 (1.24–4.61); adalimumab, 1.90 (0.75–4.83); golimumab, 1.21 (0.66–2.23); and abatacept, 0.89 (0.49–1.62). In the other age groups, the noticeable difference was a lower aRR of etanercept versus TCZ in the youngest group (0.30, 0.11–0.85).

Conclusion
In patients with RA aged ≥75 years, b/tsDMARDs have a similar risk of HIs to tocilizumab except for etanercept.
Assembly mechanism and cryoEM structure of RecA recombination nucleofilaments fromStreptococcus pneumoniae
Authors: Hertzog Maud , Perry Thomas Noé , Dupaigne Pauline , Serres Sandra , Morales Violette , Soulet Anne-Lise , Bell Jason C , Margeat Emmanuel , Kowalczykowski Stephen C , Le Cam Eric , Fronzes Rémi , Polard Patrice 
Published: April 2023

AbstractRecA-mediated homologous recombination (HR) is a key mechanism for genome maintenance and plasticity in bacteria. It proceeds through RecA assembly into a dynamic filament on ssDNA, the presynaptic filament, which mediates DNA homology search and ordered DNA strand exchange. Here, we combined structural, single molecule and biochemical approaches to characterize the ATP-dependent assembly mechanism of the presynaptic filament of RecA from Streptococcus pneumoniae (SpRecA), in comparison to the Escherichia coli RecA (EcRecA) paradigm. EcRecA polymerization on ssDNA is assisted by the Single-Stranded DNA Binding (SSB) protein, which unwinds ssDNA secondary structures that block EcRecA nucleofilament growth. We report by direct microscopic analysis of SpRecA filamentation on ssDNA that neither of the two paralogous pneumococcal SSBs could assist the extension of SpRecA nucleopolymers. Instead, we found that the conserved RadA helicase promotes SpRecA nucleofilamentation in an ATP-dependent manner. This allowed us to solve the atomic structure of such a long native SpRecA nucleopolymer by cryoEM stabilized with ATPγS. It was found to be equivalent to the crystal structure of the EcRecA filament with a marked difference in how RecA mediates nucleotide orientation in the stretched ssDNA. Then, our results show that SpRecA and EcRecA HR activities are different, in correlation with their distinct ATP-dependent ssDNA binding modes.
Overcoming ‘original sin’ to secure policy space
Authors: Shin Hyun Song 
Published: April 2023

AbstractMore than two decades after the emerging market crises of the 1990s, foreign investors are now active investors in emerging-market local-currency-denominated sovereign bonds. In this sense, emerging market governments have overcome ‘Original Sin’—the dictum that emerging market borrowers cannot borrow from foreigners in their own currency. However, although the borrowers no longer bear the risk of currency mismatches, the mismatch has migrated to the lenders’ balance sheet in the sense that investors evaluate gains and losses in terms of dollars or other major currencies. This paper examines the associated risks and potential remedies to financial stability risks stemming from this migration of currency mismatch from the borrower to the lender.
CycC1;1–WRKY75 complex-mediated transcriptional regulation of SOS1 controls salt stress tolerance in Arabidopsis
Authors: Lu Kai-Kai , Song Ru-Feng , Guo Jia-Xing , Zhang Yu , Zuo Jia-Xin , Chen Hui-Hui , Liao Cai-Yi , Hu Xiao-Yu , Ren Feng , Lu Ying-Tang , Liu Wen-Cheng 
Published: April 2023

Abstract
SALT OVERLY SENSITIVE1 (SOS1) is a key component of plant salt tolerance. However, how SOS1 transcription is dynamically regulated in plant response to different salinity conditions remains elusive. Here, we report that C-type Cyclin1;1 (CycC1;1) negatively regulates salt tolerance by interfering with WRKY75-mediated transcriptional activation of SOS1 in Arabidopsis (Arabidopsis thaliana). Disruption of CycC1;1 promotes SOS1 expression and salt tolerance in Arabidopsis because CycC1;1 interferes with RNA polymerase II recruitment by occupying the SOS1 promoter. Enhanced salt tolerance of the cycc1;1 mutant was completely compromised by an SOS1 mutation. Moreover, CycC1;1 physically interacts with the transcription factor WRKY75, which can bind to the SOS1 promoter and activate SOS1 expression. In contrast to the cycc1;1 mutant, the wrky75 mutant has attenuated SOS1 expression and salt tolerance, whereas overexpression of SOS1 rescues the salt sensitivity of wrky75. Intriguingly, CycC1;1 inhibits WRKY75-mediated transcriptional activation of SOS1 via their interaction. Thus, increased SOS1 expression and salt tolerance in cycc1;1 were abolished by WRKY75 mutation. Our findings demonstrate that CycC1;1 forms a complex with WRKY75 to inactivate SOS1 transcription under low salinity conditions. By contrast, under high salinity conditions, SOS1 transcription and plant salt tolerance are activated at least partially by increased WRKY75 expression but decreased CycC1;1 expression.
Quantitatively relating magnetic resonance T1 and T2 to glycosaminoglycan and collagen concentrations mediated by penetrated contrast agents and biomacromolecule-bound water
Authors: Gao Jingming , Xu Xian , Yu Xiaoye , Fu Ye , Zhang Hongjie , Gu Siyi , Cao Dinglingge , Guo Quanyi , Xu Liming , Ding Jiandong 
Published: April 2023

Abstract
Magnetic resonance imaging (MRI) is a promising non-invasive method to assess cartilage regeneration based on the quantitative relationship between MRI features and concentrations of the major components in the extracellular matrix (ECM). To this end, in vitro experiments are performed to investigate the relationship and reveal the underlying mechanism. A series of collagen (COL) and glycosaminoglycan (GAG) solutions at different concentrations are prepared, and T1 and T2 relaxation times are measured with or without a contrast agent (Gd-DTPA2−) by MRI. Fourier transform infrared spectrometry is also used to measure the contents of biomacromolecule-bound water and other water, allowing theoretical derivation of the relationship between biomacromolecules and the resulting T2 values. It has been revealed that the MRI signal in the biomacromolecule aqueous systems is mainly influenced by the protons in hydrogens of biomacromolecule-bound water, which we divide into inner-bound water and outer-bound water. We have also found that COL results in higher sensitivity of bound water than GAG in T2 mapping. Owing to the charge effect, GAG regulates the penetration of the contrast agent during dialysis and has a more significant effect on T1 values than COL. Considering that COL and GAG are the most abundant biomacromolecules in the cartilage, this study is particularly useful for the real-time MRI-guided assessment of cartilage regeneration. A clinical case is reported as an in vivo demonstration, which is consistent with our in vitro results. The established quantitative relation plays a critical academic role in establishing an international standard ISO/TS24560-1:2022 ‘Clinical evaluation of regenerative knee articular cartilage using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping’ drafted by us and approved by International Standard Organization.
SRSF2 in Sertoli cells is essential for testicular development and spermatogenesis in mice
Authors: Xie Xiaomei , Sun Longjie , Duan Yixi , Lv Zheng , Yao Xiaohong , Wang Chaofan , Chen Xuexue , Tian Shuang , Yan Lu , Shao Yujing , Luo Haoshu , Liu Jiali 
Published: April 2023

AbstractSertoli cells are essential for testis development and normal spermatogenesis by providing support and nutrients. Pre‐messenger RNA (pre‐mRNA) processing is the basic mechanism required for gene expression, and members of the serine/arginine‐rich protein (SR) family are key components of the machines that perform these basic processing events. Serine/arginine‐rich splicing factor 2 (SRSF2) is an important member of the SR family; however, the physiological functions of SRSF2 in Sertoli cells are still unclear. Here, we found that SRSF2 was localized in the nuclei of Sertoli and germ cells in male mice at all stages by breeding Amh‐Cre mice obtained with Srsf2‐specific knockout in Sertoli cells to define the function of SRSF2 in Sertoli cells. The experimental results showed that specific deletion of SRSF2 impaired fetal Sertoli cell proliferation and induced abnormal apoptosis and severe DNA damage in seminiferous tubules, resulting in severe testicular dysplasia, seminiferous tubule atrophy, and almost no normal seminiferous tubules at postnatal day 14. Eventually, these changes resulted in failure to produce normal sperm and infertility. Further RNA‐seq results showed that many key genes related to proliferation and apoptosis were downregulated; Racgap1 mRNA undergoes exon skipping. Thus, SRSF2‐dependent Sertoli cells are essential for testicular development and male reproduction.
Emerging synovial cell states in rheumatoid arthritis as potential therapeutic targets
Authors: Mantel Ian , Fein Miriam R. , Donlin Laura T. 
Published: April 2023

Purpose of review
To summarize recently discovered novel cell states in rheumatoid arthritis (RA) synovium that could have important implications for disease treatment.

Recent findings
The use of multiomic technologies, including single-cell and spatial transcriptomics and mass cytometry, has led to the discovery of several novel cell states, which could have important implications for the treatment of RA. These cells can be found in patient blood, synovial fluid, or synovial tissue and span several immune cell subsets as well as stromal cell types. These diverse cell states may represent the targets of current or future therapeutics, while their fluctuations may inform the ideal timing for therapy. Future efforts are needed to implicate how each cell state functions in the pathophysiologic network within affected joints and how medications perturb each cell state and ultimately the tissue.

Summary
Multiomic molecular technologies have afforded the discovery of numerous novel cellular states in RA synovium; the next challenge will be to link these states to pathophysiology and treatment response.
Male Versus Female Authorship in Flagship Pediatric Orthopaedic Journals From 2002 to 2021
Authors: Videckis Anthony J. , Malyavko Alisa , Kraft Denver B. , Tabaie Sean A. 
Published: April 2023

Background:
The evolution of female authorship in orthopaedic journals is reportedly rising, however, trends in pediatric orthopaedic publications have not been specifically studied, despite a higher proportion of female pediatric orthopaedic surgeons compared with orthopaedics at large. This study aimed to investigate trends in female first and senior authorship in 3 flagship pediatric orthopaedic journals over the past 20 years.

Methods:
All manuscripts from the “Journal of Pediatric Orthopaedics, Journal of Pediatric Orthopaedics Part B, and Journal of Children’s Orthopaedics” from 2002 to 2021 were evaluated from Ovid MEDLINE, and the data were extracted. We utilized the sex “Application Program Interface” algorithm to determine the sex of the first and senior authors. χ2 tests were used to analyze the demographics of the first and senior author cohorts. Fisher exact test was used to assess the trends in male and female authorship, controlling for year and journal.

Results:
Of a total, 5499 individual first authors and 5794 senior authors were identified. Sex was determined for 83.5% of the authors. Female first authorship increased significantly from 2002 to 2021 (8.8% to 22.4%, P < 0.001), with women being more likely to publish as first authors in more recent years in each journal (P < 0.001). Female senior authorship did not increase significantly over the same time period (10.8% to 12.8%, P = 0.238). There was significantly more male than female first and senior authors for all journals (P <0.001 for both first and senior authors).

Conclusions:
While female first authorship in prominent pediatric orthopaedic journals has increased significantly from 2002 to 2021, senior authorship has remained stagnant. In addition, female pediatric orthopaedic surgeons publish at rates lower than their prevalence in the field. This study serves as a benchmark for future studies looking at sex and authorship in hopes of better understanding the underlying complex issues.

Level of Evidence:
Level III.
The Utilization of Intraoperative Neurophysiological Monitoring for Lumbar Decompression and Fusion Surgery in New York State
Authors: Dodo Yusuke , Okano Ichiro , Zelenty William D. , Paek Samuel , Sarin Michele , Haffer Henryk , Muellner Maximilian , Chiapparelli Erika , Shue Jennifer , Soffin Ellen , Lebl Darren R. , Cammisa Frank P. , Girardi Federico P. , Sokunbi Gbolabo , Sama Andrew A. , Hughes Alexander P. 
Published: April 2023

Study Design.
Retrospective database analysis.

Objective.
To elucidate trends in the utilization of intraoperative neurophysiological monitoring (IONM) during elective lumbar surgery procedures and to investigate the association between the use of IONM and surgical outcomes.

Background.
The routine use of IONM in elective lumbar spine procedures has recently been called into question due to longer operative time, higher cost, and other substitute advanced technologies.

Methods.
The Statewide Planning and Research Cooperative System database was accessed to perform this retrospective study. The trends of IONM use for lumbar decompression and fusion procedures were investigated from 2007 to 2018. The association between IONM use and surgical outcomes was investigated from 2017 to 2018. Multivariable logistic regression analyses, as well as propensity score matching (PS-matching), were conducted to assess IONM association in neurological deficits reduction.

Results.
The utilization of IONM showed an increase in a linear fashion from 79 cases in 2007 to 6201 cases in 2018. A total of 34,592 (12,419 monitored and 22,173 unmonitored) patients were extracted, and 210 patients (0.6%) were reported for postoperative neurological deficits. Unadjusted comparisons demonstrated that the IONM group was associated with significantly fewer neurological complications. However, the multivariable analysis indicated that IONM was not a significant predictor of neurological injuries. After the PS-matching of 23,642 patients, the incidence of neurological deficits was not significantly different between IONM and non-IONM patients.

Conclusion.
The utilization of IONM for elective lumbar surgeries continues to gain popularity. Our results indicated that IONM use was not associated with a reduction in neurological deficits and will not support the routine use of IONM for all elective lumbar surgery.
Sex-related Differences in Epidemiology, Treatment, and Economic Burden of Traumatic Spinal Cord Injury in China (2013–2018)
Authors: Shang Shenghui , Wang Chaoyu , Wang Wei , Wang Jinghua , Lou Yongfu , Zhang Chi , Wang Wenzhao , Kang Yi , Jian Huan , Lv Yigang , Hou Mengfan , Zhao Hua , Chen Lingxiao , Zhou Hengxing , Feng Shiqing 
Published: April 2023

Study Design.
Retrospective epidemiological study.

Objective.
To describe differences based on biological sex in the epidemiology and treatment of the economic burden of traumatic spinal cord injury (TSCI) in China (2013–2018).

Summary of Background Data.
Although there have been many regional single-center studies on TSCI in China, there are few reports involving multicenter data, especially those that report on discrepancies related to biological sex.

Materials and Methods.
This study is a nationally representative hospital-based retrospective study. The treatment data of TSCI patients in 30 hospitals in 11 provinces/cities from January 2013 to December 2018 were analyzed. Sociodemographic characteristics, accident and related injury characteristics, treatment methods, and hospital costs were obtained. Regression models were used to evaluate differences in the outcomes of interest based on biological sex and other factors.

Results.
There were 13,465 individuals with TSCI, with a mean age of 50.0 years, and females (52.2) older than males (49.3). Overall, the average ratio of males to females was 3.1:1, ranging from 3.0:1 in 2013 to 2.8:1 in 2018. The overall proportion of patients with TSCI increased from 2013 to 2018 [annual percentage change (APC)=6.8%, 95% CI, 3.3–10.4] (P < 0.05). The percent increase in females (APC=8.2%, 95% CI, 5.6–10.8) was greater than that of males (APC=6.3%, 95% CI, 2.1–10.6). Overall, high-level falls mainly affected males (30.8%), and low-level falls mainly occurred in females (36.6%). Females demonstrated a higher frequency of thoracolumbar trauma and less severe neurological impairment.

Conclusions.
This study suggests that although the main population of TSCI is male, the average ratio of males to females is decreasing. The frequency of TSCI may be increasing faster in females than in males. Therefore, it is necessary to develop sex-specific public prevention measures. In addition, more medical resources should be devoted to improving the ability of hospitals to perform early surgery.
Therapeutic Plasma Exchange Is Associated With Improved Major Adverse Kidney Events in Children and Young Adults With Thrombocytopenia at the Time of Continuous Kidney Replacement Therapy Initiation
Authors: Fuhrman Dana Y. , Thadani Sameer , Hanson Claire , Carcillo Joseph A. , Kellum John A. , Park Hyun Jung , Lu Liling , Kim-Campbell Nahmah , Horvat Christopher M. , Arikan Ayse Akcan 
Published: April 2023

OBJECTIVES:
Therapeutic plasma exchange (TPE) has been shown to improve organ dysfunction and survival in patients with thrombotic microangiopathy and thrombocytopenia associated with multiple organ failure. There are no known therapies for the prevention of major adverse kidney events after continuous kidney replacement therapy (CKRT). The primary objective of this study was to evaluate the effect of TPE on the rate of adverse kidney events in children and young adults with thrombocytopenia at the time of CKRT initiation.

DESIGN:
Retrospective cohort.

SETTING:
Two large quaternary care pediatric hospitals.

PATIENTS:
All patients less than or equal to 26 years old who received CKRT between 2014 and 2020.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
We defined thrombocytopenia as a platelet count less than or equal to 100,000 (cell/mm3) at the time of CKRT initiation. We ascertained major adverse kidney events at 90 days (MAKE90) after CKRT initiation as the composite of death, need for kidney replacement therapy, or a greater than or equal to 25% decline in estimated glomerular filtration rate from baseline. We performed multivariable logistic regression and propensity score weighting to analyze the relationship between the use of TPE and MAKE90. After excluding patients with a diagnosis of thrombotic thrombocytopenia purpura and atypical hemolytic uremic syndrome (n = 6) and with thrombocytopenia due to a chronic illness (n = 2), 284 of 413 total patients (68.8%) had thrombocytopenia at CKRT initiation (51% female). Of the patients with thrombocytopenia, the median (interquartile range) age was 69 months (13–128 mo). MAKE90 occurred in 69.0% and 41.5% received TPE. The use of TPE was independently associated with reduced MAKE90 by multivariable analysis (odds ratio [OR], 0.35; 95% CI, 0.20–0.60) and by propensity score weighting (adjusted OR, 0.31; 95% CI, 0.16–0.59).

CONCLUSIONS:
Thrombocytopenia is common in children and young adults at CKRT initiation and is associated with increased MAKE90. In this subset of patients, our data show benefit of TPE in reducing the rate of MAKE90.