bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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 (<65, ≥65 and <75, and ≥75 years).

Results

Of 5506 patients, 2265 (41.1%) were <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

RecA-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

More 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

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

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.
Optimal Timing of Fungicide Application to Manage Fusarium Head Blight in Winter Barley
Authors: Cowger Christina , Read Quentin D. , Clark Logan , Dong Yanhong
Published: April 2023

Fusarium head blight (FHB) is among the chief threats to profitable barley production, and fungicide applications are one of two main strategies for reducing FHB damage to barley crops. However, there is very little published information on optimal timing of such applications. A 4-year field study was conducted with winter barley in Raleigh, North Carolina, to compare three timings for fungicide application: 50% spike emergence (Zadoks growth stage or GS 55), 100% spike emergence (GS 59), and 6 days after GS 59. Three winter barley cultivars with varying levels of FHB resistance were grown for four successive years (2018 to 2021) in a split-plot experiment and inoculated each spring with Fusarium-infected corn spawn. Three fungicides were compared: propiconazole + pydiflumetofen (Miravis Ace), prothioconazole + tebuconazole (Prosaro), and metconazole (Caramba). Correlations among visual symptoms and assays of harvested grain were modest and were weakened by fungicide applications. Across years and cultivars, deoxynivalenol (DON) and percent Fusarium-infected kernels were most reduced relative to the nontreated control by fungicide applications at the latest timing (GS 59 + 6 days). The early (GS 55) timing resulted in DON not significantly different from the nontreated control. Based on these results, it is recommended that to minimize damage from FHB, fungicide should be applied to winter barley several days after GS 59 (100% spike emergence), and not before GS 59.
Effects of Nitrogen Application Rate and Plant Density on Severity of Tar Spot of Corn
Authors: Check Jill C. , Byrne Adam M. , Singh Maninder P. , Steinke Kurt , Widdicombe William D. , Chilvers Martin I.
Published: April 2023

Tar spot of corn, caused by the fungus Phyllachora maydis, is an economically important foliar disease recently reported in the United States and Canada. Due to the recent introduction of Phyllachora maydis, the impacts of cultural management practices on disease development are still unknown. Separate field studies were conducted to determine the effects of nitrogen (N) application rate and plant density on disease development. Field trials were conducted across six site years in Michigan with two corn hybrids of differing disease susceptibility. The relative area under the disease progress curve was used to compare disease development between N application rates and plant densities. Nitrogen application rate had no significant effect on disease at any location. Plant density and disease had a significant ( P < 0.05) inverse relationship at five of six site years, with an average 41% decrease in the relative area under the disease progress curve for every 1,000 plants per hectare increase. The economically optimal planting density ranged from 73 to 77 thousand plants per hectare for US$150 to 300 per metric ton corn prices, demonstrating that relatively low planting densities were more profitable despite greater disease. Therefore, other disease management practices including hybrid selection may be more effective at protecting yield than increasing plant density.
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

Sertoli 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.

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.
Functional variant rs10175368 which affects the expression of CYP1B1 plays a protective role against breast cancer in a Chinese Han population
Authors: Liu Jiarui , Zhang Lijia , Tang Mingwen , Chen Xinyu , Yang Caiyun , Li Yong , Feng Jin , Deng Yan , Wang Xin , Zhang Yi
Published: April 2023

Objective

Cytochrome P450 1B1 (CYP1B1) genetic variants are relevant in the pathogenesis of breast cancer. Exploring the relationships between CYP1B1 functional variants and breast cancer could improve our understanding of breast cancer molecular pathophysiology.

Methods

This is a two-stage hospital-based case–control study of a Chinese Han population. Genotyping was performed to identify candidate gene variants. 3DSNP, ANNOVAR, and RegulomeDB were used to determine functional single nucleotide polymorphisms (SNPs). The relationship between candidate variants and breast cancer risk was evaluated through unconditional logistic regression analysis. The PancanQTL platform was used to perform cis and trans expression quantitative trait loci (eQTL) analysis of positive SNPs. The GSCA platform was then used to compare the gene expression levels of potential target genes between breast cancer tissue and normal tissue adjacent to the cancer.

Results

rs10175368-T acted as a protective factor against breast cancer based on an additive model [odds ratio (OR) = 0.722, 95% confidence interval (CI) = 0.613–0.850; P < 0.001], and was identified as a protective factor in the postmenopausal population (OR = 0.601; 95% CI, 0.474–0.764; P < 0.001). eQTL analysis and analysis of differential expression in carcinoma and paracancerous tissues revealed that the expression level of CYP1B1-AS1 was associated with rs10175368 and that CYP1B1-AS1 had significantly higher expression levels in breast cancer tissues than in paracancerous tissues.

Conclusion

We show, for the first time in a Chinese Han population, that the functional variant rs10175368 plays a protective role against breast cancer, especially in the postmenopausal population.
Immune plasticity in pregnancy-associated breast cancer tumorigenesis
Authors: Venetis Konstantinos , Sajjadi Elham , Peccatori Fedro A. , Guerini-Rocco Elena , Fusco Nicola
Published: April 2023

Pregnancy-associated breast cancer (PrBC) is a rare tumor that requires complex management. The coexistence of cancer and pregnancy involves several proliferative, invasive, and immune tolerance mechanisms that are shared between the two conditions. In normal pregnancy, successful fetal development is achieved through suppression of the maternal immune response toward the fetus. Similar immunosuppressive patterns during the malignant transformation supporting tumor growth, progression, and metastasis are also exhibited by tumors. An improved understanding of the immunosuppressive mechanisms and pathways underlying the immunological synergy in PrBC could lead to the identification of novel biomarkers that potentially improve patients’ clinical management. In this review article, we outline some of the paramount features of immune plasticity during pregnancy, discussing the similarities shared between normal pregnancy and breast cancer in terms of immune suppression mechanisms. Emphasis is also placed on how the current knowledge of the immune milieu of these conditions may be translated into consequent therapeutic opportunities.
Emerging role of long non-coding RNAs JPX in malignant processes and potential applications in cancers
Authors: Wang Yuanyuan , Bai Huihui , Jiang Meina , Zhou Chengwei , Gong Zhaohui
Published: April 2023

Long non-coding RNAs (lncRNAs) reportedly function as important modulators of gene regulation and malignant processes in the development of human cancers. The lncRNA JPX is a novel molecular switch for X chromosome inactivation and differentially expressed JPX has exhibited certain clinical correlations in several cancers. Notably, JPX participates in cancer growth, metastasis, and chemoresistance, by acting as a competing endogenous RNA for microRNA, interacting with proteins, and regulating some specific signaling pathways. Moreover, JPX may serve as a potential biomarker and therapeutic target for the diagnosis, prognosis, and treatment of cancer. The present article summarizes our current understanding of the structure, expression, and function of JPX in malignant cancer processes and discusses its molecular mechanisms and potential applications in cancer biology and medicine.
Characterization of HBV surface antigen isoforms in the natural history and treatment of HBV infection
Authors: Rodgers Mary A. , Shah Pir A. , Anderson Mark , Vallari Ana S. , Gersch Jeffrey , Mbanya Dora , Sauleda Oliveras Silvia , Choudhry Saad , Leary Thomas P. , Kuhns Mary C. , Dawson George J. , Cloherty Gavin A. , Lau Daryl T.Y.
Published: April 2023

Background:

The loss of HBV HBsAg or functional cure is a desirable goal of hepatitis B management. The relative abundances of HBsAg isoforms may offer additional diagnostic and predicting values. To evaluate the clinical utility of HBsAg isoforms, we developed novel prototype assays on the ARCHITECT automated serology platform that specifically detects total-HBsAg (T-HBsAg), large (L-HBsAg), and middle (M-HBsAg) products of the S gene to determine the isoform composition of human specimens from acute and chronic HBV infection and during long-term nucleos(t)ide analog therapy.

Results:

In the early phase of acute HBV infection, L-HBsAg and M-HBsAg emerged within days and were in parallel to T-HBsAg during the entire course of infection. M-HBsAg levels were consistently higher than L-HBsAg levels. Patients with HBeAg(+) chronic hepatitis B had higher T-HBsAg, M-HBsAg, and L-HBsAg levels compared with HBeAg(−) patients. Correlations of M-HBsAg and L-HBsAg to T-HBsAg were similar in both. In contrast, there was no strong correlation between L-HBsAg or M-HBsAg with HBV DNA levels. During long-term nucleos(t)ide analog treatment, changes in HBsAg isoform abundance were proportional to T-HBsAg regardless of treatment responses for both HBeAg(+) and HBeAg(−) chronic hepatitis B. A larger sample size may be necessary to detect a significant difference.

Conclusion:

HBsAg isoform compositions parallel T-HBsAg levels in both acute and chronic hepatitis B infection. L-HBsAg and M-HBsAg individual biomarkers do not appear to provide an additional diagnostic benefit for staging chronic disease or monitoring response to treatment with current therapies.
Hemodynamic Tolerance of New Resistance Training Methods in Patients With Heart Failure and Coronary Artery Disease
Authors: Gillet Alexis , Lamotte Michel , Forton Kevin , Roussoulières Ana , Dewachter Céline , Bouziotis Jason , Deboeck Gaël , van de Borne Philippe
Published: April 2023

Purpose:

The purpose of this study was to determine and compare the effectiveness of three different resistance training (RT) methods for cardiac rehabilitation.

Methods:

Individuals with heart failure with reduced ejection fraction (HFrEF, n = 23) or coronary artery disease (CAD, n = 22) and healthy controls (CTRL, n = 29) participated in this randomized crossover trial of RT exercises at 70% of the one-maximal repetition on a leg extension machine. Peak heart rate (HR) and blood pressure (BP) were measured noninvasively. The three RT methods were five sets of increasing repetitions from three to seven (RISE), of decreasing repetitions from seven to three (DROP), and three sets of nine repetitions (USUAL). Interset rest intervals were 15 sec for RISE and DROP and 60 sec for USUAL.

Results:

Peak HR differed on average by <4 bpm between methods in the HFrEF and CAD groups (P < .02). Rises in systolic BP (SBP) in the HFrEF group were comparable across methods. In the CAD group, mean SBP at peak exercise increased more in RISE and DROP than in USUAL (P < .001), but the increase was ≤10 mm Hg. In the CTRL group, SBP was higher for DROP than for USUAL (152 ± 22 vs 144 ± 24 mm Hg, respectively; P < .01). Peak cardiac output and perceived exertion did not differ between methods.

Conclusions:

The RISE, DROP, and USUAL RT methods induced a similar perception of effort and similar increases in peak HR and BP. The RISE and DROP methods appear more efficient as they allow a comparable training volume in a shorter time than the USUAL method.
In vivo screening identifies SPP2, a secreted factor that negatively regulates liver regeneration
Authors: Lin Yu-Hsuan , Zeng Qiyu , Jia Yuemeng , Wang Zixi , Li Lin , Hsieh Meng-Hsiung , Cheng Qiang , Pagani Chase A. , Livingston Nicholas , Lee Jeon , Zhang Yu , Sharma Tripti , Siegwart Daniel J. , Yimlamai Dean , Levi Benjamin , Zhu Hao
Published: April 2023

Background and Aims:

The liver is remarkably regenerative and can completely recover even when 80% of its mass is surgically removed. Identification of secreted factors that regulate liver growth would help us understand how organ size and regeneration are controlled but also provide candidate targets to promote regeneration or impair cancer growth.

Approach and Results:

To enrich for secreted factors that regulate growth control, we induced massive liver overgrowth with either YAP or MYC. Differentially expressed secreted factors were identified in these livers using transcriptomic analysis. To rank candidates by functionality, we performed in vivo CRISPR screening using the Fah knockout model of tyrosinemia. We identified secreted phosphoprotein-2 (SPP2) as a secreted factor that negatively regulates regeneration. Spp2-deficient mice showed increased survival after acetaminophen poisoning and reduced fibrosis after repeated carbon tetrachloride injections. We examined the impact of SPP2 on bone morphogenetic protein signaling in liver cells and found that SPP2 antagonized bone morphogenetic protein signaling in vitro and in vivo. We also identified cell-surface receptors that interact with SPP2 using a proximity biotinylation assay coupled with mass spectrometry. We showed that SPP2’s interactions with integrin family members are in part responsible for some of the regeneration phenotypes.

Conclusions:

Using an in vivo CRISPR screening system, we identified SPP2 as a secreted factor that negatively regulates liver regeneration. This study provides ways to identify, validate, and characterize secreted factors in vivo.
Evidence-based objective performance criteria for the evaluation of hip and knee replacement devices and technologies
Authors: Nieuwenhuijse Marc J. , Randsborg Per-Henrik , Hyde Jensen H. , Xi Wenna , Franklin Patricia , Sun Limin , Zheng Xinyan , Banerjee Samprit , Mao Jialin , Aryal Suvekshya , Chan Priscilla , Chen Amanda , Liebeskind Alexander , Bonangelino Pablo , Voorhorst Paul , Gressler Laura E. , Devlin Vincent , Peat Raquel , Marinac-Dabic Danica , Paxton Elizabeth , Sedrakyan Art
Published: April 2023

Background:

Objective performance criteria (OPC) is a novel method to provide minimum performance standards and improve the regulated introduction of original or incremental device innovations in order to prevent patients from being exposed to potentially inferior designs whilst allowing timely access to improvements. We developed 2-year safety and effectiveness OPC for total hip and knee replacement (THR and TKR).

Methods:

Analyses of large databases were conducted using various data sources: a systematic literature review; a direct data analysis from The Functional Outcomes Research for Comparative Effectiveness in Total Joint Replacement and Quality Improvement Registry (FORCE-TJR) and the Kaiser Permanente Implant Registry (KPIR); and claims data analyses from longitudinal discharge data in New York and California states. The literature review included U.S. patients (≥18 years) who received THR or TKR for primary end-stage osteoarthritis and prospectively collected data on patient-reported outcome measures (PROMs) from at least 100 subjects and/or 2-year implant survival for at least 250 implants. Random effects models were used for meta-analysis.

Results:

Data were available from a total of 951 100 patients. After screening of 7979 abstracts, 294 studies underwent full-text review and 31 studies contributed to the evidence synthesis (333 995 implants). Direct data analysis of FORCE-TJR contributed 9223 joint replacement patients to the construction of OPC for effectiveness; KPIR contributed 262 044 patients for the construction of OPC for safety. Claims database analysis contributed 345 838 patients to the construction of safety OPC. OPC for safety were constructed for cumulative incidences of 2-year all-cause and septic revision (THR/TKR 2.0%/1.6% and 0.6%/0.7%), and OPC for effectiveness were constructed based on four disease-specific and three general health-related quality of life PROMs (HOOS/KOOS 87.1/80.6; HSS/KSS function 94.4/90.6; SF-12/SF-36, PCS 46.5/41.9, EQ-5D 0.88/0.84).

Conclusion:

This study is the first to construct a 2-year OPC for the safety and effectiveness of THR and TKR based on U.S. real-world data. Based on these OPC, potential benchmarks for (single-arm study) evaluation of new device innovations are suggested for a regulated and safe introduction to the (commercial) market.
Benchmarking: a novel measuring tool for outcome comparisons in surgery
Authors: Wu Yi , Li Shizhen , Yuan Jingxiong , Zhang Hang , Wang Min , Zhang Zhenxiong , Qin Renyi
Published: April 2023

Introduction:

Benchmarking, a novel measuring tool for outcome comparisons, is a recent concept in surgery. The objectives of this review are to examine the concept, definition, and evolution of benchmarking and its application in surgery.

Methods:

The literature about benchmarking was reviewed through an ever-narrowing search strategy, commencing from the concept, definition, and evolution of benchmarking to the application of benchmarking and experiences of benchmarking in surgery. PubMed, Web of Science, Embase, and Science Direct databases were searched until 20 September 2022, in the English language according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines.

Results:

In the first phase of the literature search, the development of benchmarking was identified. The definitions of benchmarking evolved from a surveying term to a novel quality-improvement tool to assess the best achievable results in surgery. In the second phase, a total of 23 studies were identified about benchmarking in surgery, including esophagectomy, hepatic surgery, pancreatic surgery, rectum resection, and bariatric surgery. All studies were multicenter analyses from national, international, or global expert centers. Most studies (87.0%) adopted the definition that benchmark was the 75th percentile of the median values of centers. Performance metrics to define benchmarks were clinically relevant intraoperative and postoperative outcome indicators.

Conclusion:

Benchmarking in surgery is a novel quality-improvement tool to define and measure the best achievable results, establishing a meaningful reference to evaluate surgical performance.
Exploring objective factors to predict successful outcomes after laparoscopic Nissen fundoplication
Authors: Park Sangjun , Park Shin-Hoo , Kim Min Seo , Kwak Jisoo , Lee Inhyeok , Kwon Yeongkeun , Lee Chang Min , Choi Hyuk Soon , Keum Bora , Yang Kyung-Sook , Park Joong-Min , Park Sungsoo
Published: April 2023

Background:

Currently, the reported parameters that predict the resolution of symptoms after surgery are largely subjective and unreliable. Considering that fundoplication rebuilds the structural integrity of the lower esophageal sphincter (LES), the authors focused on searching for objective and quantitative predictors for the resolution of symptoms based on the anatomical issues and whether an antireflux barrier can be well established or not.

Materials and methods:

The authors reviewed the prospectively collected data of 266 patients with gastroesophageal reflux disease (GERD) who had undergone laparoscopic Nissen fundoplication (LNF). All patients were diagnosed with GERD using preoperative esophagogastroduodenoscopy, 24-h ambulatory esophageal pH monitoring, and high-resolution esophageal manometry. The patients received GERD symptom surveys using the validated Korean Antireflux Surgery Group questionnaire twice: preoperatively and 3 months after the surgery.

Results:

After excluding patients with insufficient follow-up data, 152 patients were included in the analysis. Multivariate logistic regression analyses revealed that a longer length of the LES and lower BMI determined better resolution of typical symptoms after LNF (all P<0.05). Regarding atypical symptoms, higher resting pressure of LES and DeMeester score greater than or equal to 14.7 were associated with better resolution after the surgery (all P<0.05). After LNF, typical symptoms improved in 34 out of 37 patients (91.9%) with a length of LES >greater than .05 cm, BMI less than 23.67 kg/m2, and atypical symptoms were resolved in 16 out of 19 patients (84.2%) with resting pressure of LES greater than or equal to 19.65 mm Hg, DeMeester score greater than or equal to 14.7.

Conclusion:

These results show that the preoperative length and resting pressure of LES is important in the objective prediction of symptom improvement after LNF.
The impact of patient safety incidents during hip and knee replacements on patients’ health related quality of life: a before and after study using longitudinal data linked to patient-reported outcome measures
Authors: Xiao Mimi , Kristensen Søren Rud , Marti Joachim , Mossialos Elias
Published: April 2023

Background:

The burden of patient safety incidents (PSIs) is often characterized by their impact on mortality, morbidity, and treatment costs. Few studies have attempted to estimate the impact of PSIs on patients’ health-related quality of life (HRQoL) and the studies that have made such estimates primarily focus on a narrow set of incidents. The aim of this paper is to estimate the impact of PSIs on HRQoL of patients undergoing elective hip and knee surgery in England.

Patients and methods:

A unique linked longitudinal data set consisting of patient-reported outcome measures for patients with hip and knee replacements linked to Hospital Episode Statistics (HES) collected between 2013/14 and 2016/17 was examined. Patients with any of nine US Agency for Healthcare Research and Quality (AHRQ) PSI indicators were identified. HRQoL was measured using the general EuroQol five dimensions questionnaire (EQ-5D) before and after surgery. Exploiting the longitudinal structure of the data, exact matching was combined with difference in differences to estimate the impact of experiencing a PSI on HRQoL and its individual dimensions, comparing HRQoL improvements after surgery in similar patients with and without a PSI in a retrospective cohort study. This design compares the change in HRQoL before and after surgery in patients who experience a PSI to those who do not.

Results:

The sample comprised 190 697 and 204 649 observations for patients undergoing hip replacement and knee replacement respectively. For six out of nine PSIs, patients who experienced a PSI reported improvements in HRQoL that were 14–23% lower than those who did not experience a PSI during surgery. Those who experienced a PSI were also more likely to report worse health states after surgery than those without a PSI on all five dimensions of HRQoL.

Conclusion:

PSIs are associated with a substantial negative impact on patients’ HRQoL.
Patient decision support interventions for candidates considering elective surgeries: a systematic review and meta-analysis
Authors: Cheng Ling Jie , Bansback Nick , Liao Meixia , Wu Vivien Xi , Wang Wenru , Liu Gabriel Ka Po , Hey Hwee Weng Dennis , Luo Nan
Published: April 2023

Background:

The increase in elective surgeries and varied postoperative patient outcomes has boosted the use of patient decision support interventions (PDSIs). However, evidence on the effectiveness of PDSIs are not updated. This systematic review aims to summarize the effects of PDSIs for surgical candidates considering elective surgeries and to identify their moderators with an emphasis on the type of targeted surgery.

Design:

Systematic review and meta-analysis.

Methods:

We searched eight electronic databases for randomized controlled trials evaluating PDSIs among elective surgical candidates. We documented the effects on invasive treatment choice, decision-making–related outcomes, patient-reported outcomes, and healthcare resource use. The Cochrane Risk of Bias Tool version 2 and Grading of Recommendations, Assessment, Development, and Evaluations were adopted to rate the risk of bias of individual trials and certainty of evidence, respectively. STATA 16 software was used to conduct the meta-analysis.

Results:

Fifty-eight trials comprising 14 981 adults from 11 countries were included. Overall, PDSIs had no effect on invasive treatment choice (risk ratio=0.97; 95% CI: 0.90, 1.04), consultation time (mean difference=0.04 min; 95% CI: −0.17, 0.24), or patient-reported outcomes, but had a beneficial effect on decisional conflict (Hedges’ g=−0.29; 95% CI: −0.41, −0.16), disease and treatment knowledge (Hedges’ g=0.32; 95% CI: 0.15, 0.49), decision-making preparedness (Hedges’ g=0.22; 95% CI: 0.09, 0.34), and decision quality (risk ratio=1.98; 95% CI: 1.15, 3.39). Treatment choice varied with surgery type and self-guided PDSIs had a greater effect on disease and treatment knowledge enhancement than clinician-delivered PDSIs.

Conclusions:

This review has demonstrated that PDSIs targeting individuals considering elective surgeries had benefited their decision-making by reducing decisional conflict and increasing disease and treatment knowledge, decision-making preparedness, and decision quality. These findings may be used to guide the development and evaluation of new PDSIs for elective surgical care.
Treatment for acute uncomplicated diverticulitis without antibiotherapy: systematic review and meta-analysis of randomized clinical trials
Authors: Correa Bonito Alba , Cerdán Santacruz Carlos , Di Martino Marcello , Blanco Terés Lara , Gancedo Quintana Álvaro , Martín-Pérez Elena , Biondo Sebastiano , García Septiem Javier
Published: April 2023

Background:

Use of antibiotics in selected cases of acute uncomplicated diverticulitis (AUD) has recently been questioned.

Objective:

The aim of this study is to examine the safety and efficacy of treatment regimens without antibiotics compared with that of traditional treatments with antibiotics in selected patients with AUD.

Data sources:

PubMed, Medline, Embase, Web of Science, and the Cochrane Library

Methods:

A systematic review was performed according to PRISMA and AMSTAR guidelines by searching through Medline, Embase, Web of Science, and the Cochrane Library for randomized clinical trials (RCTs) published before December 2022. The outcomes assessed were the rates of readmission, change in strategy, emergency surgery, worsening, and persistent diverticulitis.

Study selection:

RCTs on treating AUD without antibiotics published in English before December 2022 were included.

Intervention:

Treatments without antibiotics were compared with treatments with antibiotics.

Main outcome measures:

The outcomes assessed were the rates of readmission, change in strategy, emergency surgery, worsening, and persistent diverticulitis.

Results:

The search yielded 1163 studies. Four RCTs with 1809 patients were included in the review. Among these patients, 50.1% were treated conservatively without antibiotics. The meta-analysis showed no significant differences between nonantibiotic and antibiotic treatment groups with respect to rates of readmission [odds ratio (OR)=1.39; 95% CI: 0.93–2.06; P=0.11; I
2=0%], change in strategy (OR=1.03; 95% CI: 0.52–2,02; P=0.94; I
2=44%), emergency surgery (OR=0.43; 95% CI: 0.12–1.53; P=0.19; I
2=0%), worsening (OR=0.91; 95% CI: 0.48–1.73; P=0.78; I
2=0%), and persistent diverticulitis (OR=1.54; 95% CI: 0.63–3.26; P=0.26; I
2=0%).

Limitations:

Heterogeneity and a limited number of RCTs.

Conclusions:

Treatment for AUD without antibiotic therapy is safe and effective in selected patients. Further RTCs should confirm the present findings.