bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation therapy for retroperitoneal sarcoma: practice patterns in North America
Authors: Ruff Samantha M. , Heh Victor , Konieczkowski David J. , Onuma Amblessed , Dunlop Hayley M. , Kim Alex C. , Grignol Valerie P. , Contreras Carlo M. , Pawlik Timothy M. , Pollock Raphael , Beane Joal D. 
Published: March 2024

Abstract
Background
The addition of radiation therapy (RT) to surgery in retroperitoneal sarcoma (RPS) remains controversial. We examined practice patterns in the use of RT for patients with RPS over time in a large, national cohort.

Methods
Patients in the National Cancer Database (2004–2017) who underwent resection of RPS were included. Trends over time for proportions were calculated using contingency tables with Cochran-Armitage Trend test.

Results
Of 7,485 patients who underwent resection, 1,821 (24.3%) received RT (adjuvant: 59.9%, neoadjuvant: 40.1%). The use of RT decreased annually by < 1% (p = 0.0178). There was an average annual increase of neoadjuvant RT by 13% compared to an average annual decrease of adjuvant RT by 6% (p < 0.0001). Treatment at high-volume centers (OR 14.795, p < 0.0001) and tumor > 10 cm (OR 2.009, p = 0.001) were associated with neoadjuvant RT. In contrast liposarcomas (OR 0.574, p = 0.001) were associated with adjuvant RT. There was no statistically significant difference in overall survival between patients treated with surgery alone versus surgery and RT (p = 0.07).

Conclusion
In the United States, the use of RT for RPS has decreased over time, with a shift towards neoadjuvant RT. However, a large percentage of patients are still receiving adjuvant RT and this mostly occurs at low-volume hospitals.
A retrospective study: exploring preoperative hyponatremia in elderly patients with hip fractures
Authors: Shi Li-Tao , Feng Zhen , Zhu Cui-Min 
Published: March 2024

Abstract
Background
This research aims to examine the frequency, age-related distribution, and intensity of preoperative hyponatremia among elderly individuals with hip fractures. This study aims to provide valuable insights into the diagnosis of preoperative hyponatremia in this patient population.

Methods
This research involved the analysis of clinical data obtained from 419 elderly individuals with hip fractures (referred to as the fracture group) and 166 elderly individuals undergoing routine health examinations (designated as the control group). A comprehensive comparison was conducted, examining baseline characteristics such as age, gender, and comorbidities between these two groups. We further investigated variations in the incidence rate of hyponatremia, age distribution, and the severity of hyponatremia. Additionally, a subgroup analysis compared patients with femoral neck fractures to those with intertrochanteric femur fractures, specifically examining the incidence rate and severity of hyponatremia in these distinct fracture types.

Results
The incidence of cerebrovascular disease was found to be higher in the fracture group as compared to the control group in our research. Nevertheless, no significant differences in general health and other comorbidities were observed between the two groups. Notably, the fracture group exhibited a greater preoperative prevalence of hyponatremia, with its severity increasing with age. Furthermore, among elderly patients with intertrochanteric femur fractures, the incidence of preoperative hyponatremia was not only higher but also more severe when compared to those with femoral neck fractures.

Conclusion
Elderly individuals experiencing hip fractures exhibit a notable prevalence of preoperative hyponatremia, predominantly mild to moderate, with an escalating occurrence linked to advancing age. This phenomenon is especially conspicuous among patients with intertrochanteric fractures, warranting dedicated clinical scrutiny. The administration of sodium supplementation is advisable for the geriatric demographic as deemed necessary. Addressing hyponatremia becomes crucial, as it may play a role in the etiology of hip fractures in the elderly, and rectifying this electrolyte imbalance could potentially serve as a preventive measure against such fractures.
Navigation versus fluoroscopy in minimalinvasive iliosacral screw placement
Authors: Prost Max , Taday Roman , Beyersdorf Carl Christoph Paul , Latz David , Windolf Joachim , Scheyerer Max Joseph , Konieczny Markus Rafael 
Published: March 2024

Abstract
Introduction
When needed operative treatment of sacral fractures is mostly performed with percutaneous iliosacral screw fixation. The advantage of navigation in insertion of pedicle screws already could be shown by former investigations. The aim of this investigation was now to analyze which influence iliosacral screw placement guided by navigation has on duration of surgery, radiation exposure and accuracy of screw placement compared to the technique guided by fluoroscopy.

Methods
68 Consecutive patients with sacral fractures who have been treated by iliosacral screws were inclouded. Overall, 85 screws have been implanted in these patients. Beside of demographic data the duration of surgery, duration of radiation, dose of radiation and accuracy of screw placement were analyzed.

Results
When iliosacral screw placement was guided by navigation instead of fluoroscopy the dose of radiation per inserted screw (155.0 cGy*cm2 vs. 469.4 cGy*cm2p < 0.0001) as well as the duration of radiation use (84.8 s vs. 147.5 s p < 0.0001) were significantly lower. The use of navigation lead to a significant reduction of duration of surgery (39.0 min vs. 60.1 min p < 0.01). The placement of the screws showed a significantly higher accuracy when performed by navigation (0 misplaced screws vs 6 misplaced screws—p < 0.0001).

Conclusion
Based on these results minimal invasive iliosacral screw placement guided by navigation seems to be a safe procedure, which leads to a reduced exposure to radiation for the patient and the surgeon, a reduced duration of surgery as well as a higher accuracy of screw placement.
Blood-based biomarkers in patients with non-small cell lung cancer treated with immune checkpoint blockade
Authors: Tsai Yo-Ting , Schlom Jeffrey , Donahue Renee N. 
Published: March 2024

Abstract
The paradigm of non-small cell lung cancer (NSCLC) treatment has been profoundly influenced by the development of immune checkpoint inhibitors (ICI), but the range of clinical responses observed among patients poses significant challenges. To date, analyses of tumor biopsies are the only parameter used to guide prognosis to ICI therapy. Tumor biopsies, however, are often difficult to obtain and tissue-based biomarkers are limited by intratumoral heterogeneity and temporal variability. In response, there has been a growing emphasis on the development of “liquid biopsy”‒ derived biomarkers, which offer a minimally invasive means to dynamically monitor the immune status of NSCLC patients either before and/or during the course of treatment. Here we review studies in which multiple blood-based biomarkers encompassing circulating soluble analytes, immune cell subsets, circulating tumor DNA, blood-based tumor mutational burden, and circulating tumor cells have shown promising associations with the clinical response of NSCLC patients to ICI therapy. These investigations have unveiled compelling correlations between the peripheral immune status of patients both before and during ICI therapy and patient outcomes, which include response rates, progression-free survival, and overall survival. There is need for rigorous validation and standardization of these blood-based assays for broader clinical application. Integration of multiple blood-based biomarkers into comprehensive panels or algorithms also has the potential to enhance predictive accuracy. Further research aimed at longitudinal monitoring of circulating biomarkers is also crucial to comprehend immune dynamics and resistance mechanisms and should be used alongside tissue-based methods that interrogate the tumor microenvironment to guide treatment decisions and may inform on the development of novel therapeutic strategies. The data reviewed here reinforce the opportunity to refine patient stratification, optimize treatments, and improve outcomes not only in NSCLC but also in the wider spectrum of solid tumors undergoing immunotherapy.
Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value
Authors: Hong Shihao , Fu Ni , Sang Shanliang , Ma Xudong , Sun Fangying , Zhang Xiao 
Published: March 2024

Abstract
Background
Ovarian cancer (OC) is a severe gynecological malignancy with significant diagnostic and therapeutic challenges. The discovery of reliable cancer biomarkers can be used to adjust diagnosis and improve patient care. However, serous OC lacks effective biomarkers. We aimed to identify novel biomarkers for OC and their pathogenic causes.

Methods
The present study used the differentially expressed genes (DEGs) obtained from the “Limma” package and WGCNA modules for intersection analysis to obtain DEGs in OC. Three hub genes were identified—claudin 3 (CLDN3), interferon regulatory factor 6 (IRF6), and prostasin (PRSS8)—by searching for hub genes through the PPI network and verifying them in GSE14407, GSE18520, GSE66957, and TCGA + GTEx databases. The correlation between IRF6 and the prognosis of OC patients was further confirmed in Kaplan-Miller Plotter. RT-qPCR and IHC confirmed the RNA and protein levels of IRF6 in the OC samples. The effect of IRF6 on OC was explored using transwell invasion and scratch wound assays. Finally, we constructed a ceRNA network of hub genes and used bioinformatics tools to predict drug sensitivity.

Results
The joint analysis results of TCGA, GTEx, and GEO databases indicated that IRF6 RNA and protein levels were significantly upregulated in serous OC and were associated with OS and PFS. Cell function experiments revealed that IRF6 knockdown inhibited SKOV3 cell proliferation, migration and invasion.

Conclusion
IRF6 is closely correlated with OC development and progression and could be considered a novel biomarker and therapeutic target for OC patients.
Simultaneous determination of bromoxynil and MCPA in commercial samples and raw materials using reversed phase high performance liquid chromatography
Authors: Yar Ahmed , Ansari Tariq Mahmood , Rehman Faariah , Raza Asad , Riaz Umair , Iqbal Rashid , Al-Mohaimeed Amal M. , Al-onazi Wedad A. , Rizwan Muhammad 
Published: March 2024

AbstractThis study encompasses a quick, efficient, repeatable and reproducible analytical method for simultaneous determination of Bromoxynil (3, 5-Dibromo-4-hydroxybenzonitrile) and MCPA (2-methyl-4-chlorophenoxyacetic acid) using RP-HPLC with UV-Detector. Bromoxynil + MCPA is one of the most selective post emergent herbicide formulations for the control of important broad leaf weeds infesting small grains (wheat, barley, oats, rye), conservation reserve program areas and grass grown for seed. Optimum weed control is achieved when Bromoxynil + MCPA is applied to actively growing weed seedlings. So, a simple, repeatable, reproducible and efficient simultaneous analytical method was developed for Bromoxynil + MCPA. The developed method was applied for the detection and quantitation of these pesticides in formulations and raw materials with excellent recoveries. It was validated according to ICH Guidelines with excellent linearity R2 = 0.992 for Bromoxynil and 0.998 for MCPA. For Bromoxynil, LOD = 1.57 mg/L and LOQ = 5.22 mg/L while for MCPA the LOD = 1.08 mg/L and LOQ = 3.62 mg/L was found. The proposed method has shown high precision (RSD %) 0.06% and 0.11% for Bromoxynil and MCPA respectively while the trueness has been calculated in terms of recovery percentage obtained as “mean value of Bromoxynil 99.53% and MCPA 100.10%” which is excellent under optimized conditions. For repeatability and reproducibility, five replicate readings of standard and sample were taken and had found within acceptable limits of relative standard deviation (RSD ≤  ± 2%). Finally, the robustness of the developed method was determined by changing flow rate and mobile phase ratios that has found within the permissible limits (% RSD NMT 1.5). So, the proposed analytical method has found to be more precise, valid and accurate at commercial scale.
Graphical Abstract
Multi-omics analysis reveals novel loci and a candidate regulatory gene of unsaturated fatty acids in soybean (Glycine max (L.) Merr)
Authors: Zhao Xunchao , Zhan Yuhang , Li Kaiming , Zhang Yan , Zhou Changjun , Yuan Ming , Liu Miao , Li Yongguang , Zuo Peng , Han Yingpeng , Zhao Xue 
Published: March 2024

Abstract
Background
Soybean is a major oil crop; the nutritional components of soybean oil are mainly controlled by unsaturated fatty acids (FA). Unsaturated FAs mainly include oleic acid (OA, 18:1), linoleic acid (LLA, 18:2), and linolenic acid (LNA, 18:3). The genetic architecture of unsaturated FAs in soybean seeds has not been fully elucidated, although many independent studies have been conducted. A 3 V multi-locus random single nucleotide polymorphism (SNP)-effect mixed linear model (3VmrMLM) was established to identify quantitative trait loci (QTLs) and QTL-by-environment interactions (QEIs) for complex traits.

Results
In this study, 194 soybean accessions with 36,981 SNPs were calculated using the 3VmrMLM model. As a result, 94 quantitative trait nucleotides (QTNs) and 19 QEIs were detected using single-environment (QTN) and multi-environment (QEI) methods. Three significant QEIs, namely rs4633292, rs39216169, and rs14264702, overlapped with a significant single-environment QTN.

Conclusions
For QTNs and QEIs, further haplotype analysis of candidate genes revealed that the Glyma.03G040400 and Glyma.17G236700 genes were beneficial haplotypes that may be associated with unsaturated FAs. This result provides ideas for the identification of soybean lipid-related genes and provides insights for breeding high oil soybean varieties in the future.
Sensitive B-cell receptor repertoire analysis shows repopulation correlates with clinical response to rituximab in rheumatoid arthritis
Authors: Pollastro Sabrina , Musters Anne , Balzaretti Giulia , Niewold Ilse , van Schaik Barbera , Hässler Signe , Verhoef Catharina M. , Pallardy Marc , van Kampen Antoine , Mariette Xavier , de Vries Niek ,   on behalf of the ABIRISK Consortium, Szely Natacha , Gleizes Aude , Abina Salima Hacein-Bey , Richez Christophe , Soubrier Martin , Avouac Jérome , Brocq Olivier , Sellam Jérémie , Huizinga Tom , Jury Elizabeth , Manson Jessica , Mauri Claudia , Matucci Andrea 
Published: March 2024

Abstract
Background
Although B-cell depleting therapy in rheumatoid arthritis (RA) is clearly effective, response is variable and does not correlate with B cell depletion itself.

Methods
The B-cell receptor (BCR) repertoire was prospectively analyzed in peripheral blood samples of twenty-eight RA patients undergoing rituximab therapy. Timepoints of achieved BCR-depletion and -repopulation were defined based on the percentage of unmutated BCRs in the repertoire. The predictive value of early BCR-depletion (within one-month post-treatment) and early BCR-repopulation (within 6 months post-treatment) on clinical response was assessed.

Results
We observed changes in the peripheral blood BCR repertoire after rituximab treatment, i.e., increased clonal expansion, decreased clonal diversification and increased mutation load which persisted up to 12 months after treatment, but started to revert at month 6. Early BCR depletion was not associated with early clinical response but late depleters did show early response. Patients with early repopulation with unmutated BCRs showed a significant decrease in disease activity in the interval 6 to 12 months. Development of anti-drug antibodies non-significantly correlated with more BCR repopulation.

Conclusion
Our findings indicate that rather than BCR-depletion it is repopulation with unmutated BCRs, possibly from naïve B cells, which induces remission. This suggests that (pre-existing) differences in B-cell turnover between patients explain the interindividual differences in early clinical effect.
Increased stress hyperglycemia ratio at hospital admission in stroke patients are associated with increased in-hospital mortality and length of stay
Authors: Shen Di , Cai Xintian , Zhu Qing , Heizhati Mulalibieke , Hu Junli , Song Shuaiwei , Yang Wenbo , Hong Jing , Li Nanfang 
Published: March 2024

Abstract
Objective
Recently, the stress hyperglycemia ratio (SHR) has been introduced as a metric to signify relative hyperglycemia. This study aimed to investigate the relationship between SHR and in-hospital mortality and length of stay occurring during hospitalization in stroke patients.

Methods
The retrospective cohort study comprised a total of 4,018 patients diagnosed with acute stroke. The SHR is expressed by the formula: SHR = ABG (mmol/L) / [1.59 × HbA1c (%) − 2.59]. Outcomes included in-hospital mortality and length of stay. Multivariable logistic and linear regression analyses were conducted. Receiver operating characteristic (ROC) analysis was performed to distinguish between the variables, and the area under the ROC curve (AUC) was compared.

Results
In this analysis, a total of 4,018 individuals participated, including 2,814 male patients, accounting for 70.0%. Overall, in-hospital mortality and length of stay tended to rise as SHR increased. A higher prevalence of in-hospital mortality was observed with each standard deviation (SD) increase of the SHR (odds ratio [OR]: 1.26, 95% confidence interval [CI]: 1.05–1.52). Moreover, after considering the confounders, a significant positive association between SHR levels and length of stay was observed (β = 0.70, 95% CI: 0.40-1.00). ROC analysis showed that among stroke patients, SHR (AUC = 0.693) was more effective than admission blood glucose (ABG) (AUC = 0.646) and glycosylated hemoglobin (HbA1c) (AUC = 0.523), which were more predictive of in-hospital mortality.

Conclusions
Elevated SHR levels are associated with increased in-hospital mortality and prolonged length of stay in stroke patients.
Integrative multi-omics characterization reveals sex differences in glioblastoma
Authors: Jang Byunghyun , Yoon Dayoung , Lee Ji Yoon , Kim Jiwon , Hong Jisoo , Koo Harim , Sa Jason K. 
Published: March 2024

Abstract
Background
Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with limited treatment modalities and poor prognosis. Recent studies have highlighted the importance of considering sex differences in cancer incidence, prognosis, molecular disparities, and treatment outcomes across various tumor types, including colorectal adenocarcinoma, lung adenocarcinoma, and GBM.

Methods
We performed comprehensive analyses of large-scale multi-omics data (genomic, transcriptomic, and proteomic data) from TCGA, GLASS, and CPTAC to investigate the genetic and molecular determinants that contribute to the unique clinical properties of male and female GBM patients.

Results
Our results revealed several key differences, including enrichments of MGMT promoter methylation, which correlated with increased overall and post-recurrence survival and improved response to chemotherapy in female patients. Moreover, female GBM exhibited a higher degree of genomic instability, including aneuploidy and tumor mutational burden. Integrative proteomic and phosphor-proteomic characterization uncovered sex-specific protein abundance and phosphorylation activities, including EGFR activation in males and SPP1 hyperphosphorylation in female patients. Lastly, the identified sex-specific biomarkers demonstrated prognostic significance, suggesting their potential as therapeutic targets.

Conclusions
Collectively, our study provides unprecedented insights into the fundamental modulators of tumor progression and clinical outcomes between male and female GBM patients and facilitates sex-specific treatment interventions.
Highlights

Female GBM patients were characterized by increased MGMT promoter methylation and favorable clinical outcomes compared to male patients.

Female GBMs exhibited higher levels of genomic instability, including aneuploidy and TMB.

Each sex-specific GBM is characterized by unique pathway dysregulations and molecular subtypes.

EGFR activation is prevalent in male patients, while female patients are marked by SPP1 hyperphosphorylation.
Impact of reimbursement systems on patient care – a systematic review of systematic reviews
Authors: Wagenschieber Eva , Blunck Dominik 
Published: March 2024

Abstract
Background
There is not yet sufficient scientific evidence to answer the question of the extent to which different reimbursement systems influence patient care and treatment quality. Due to the asymmetry of information between physicians, health insurers and patients, market-based mechanisms are necessary to ensure the best possible patient care. The aim of this study is to investigate how reimbursement systems influence multiple areas of patient care in form of structure, process and outcome indicators.

Methods
For this purpose, a systematic literature review of systematic reviews is conducted in the databases PubMed, Web of Science and the Cochrane Library. The reimbursement systems of salary, bundled payment, fee-for-service and value-based reimbursement are examined. Patient care is divided according to the three dimensions of structure, process, and outcome and evaluated in eight subcategories.

Results
A total of 34 reviews of 971 underlying primary studies are included in this article. International studies identified the greatest effects in categories resource utilization and quality/health outcomes. Pay-for-performance and bundled payments were the most commonly studied models. Among the systems examined, fee-for-service and value-based reimbursement systems have the most positive impact on patient care.

Conclusion
Patient care can be influenced by the choice of reimbursement system. The factors for successful implementation need to be further explored in future research.
The economic effect of financial compensation in China’s healthcare system: comprehensive insights regarding supply and demand factors
Authors: Guo Yi , Hong Xuezhi , Li Dongmei , An Qiannan , Fan Wenwen , Yang Minghe , Xiao Luyang 
Published: March 2024

Abstract
Objectives
We aim to analyse the effects of government subsidies on residents’ health and healthcare expenditure from the perspectives of supply and demand.

Data and methods
According to the regional division adopted in the data query system of the National Bureau of Statistics, this study divides 31 provinces and cities into three regions: eastern, central, and western. The data used are from public databases, such as the “China Statistical Yearbook,” “China Health Statistical Yearbook,” and “Government Final Account Report”. In this study, mathematical model derivation is used to construct a fixed effects model, and an empirical study based on cross-sectional data and general linear regression is conducted. To prevent endogeneity issues, this study introduces instrumental variables and uses 2SLS regression to further analyse the output results.

Results
For every 1% increase in supplementary funding on the supply side, the perinatal mortality rate decreases by 1.765%, while for every 1% increase in financial compensation on the demand side, per capita outpatient expenses increase by 0.225% and per capita hospitalization expenses increase by 0.196%. Regarding medical resources, for every 1% increase in the number of beds per 1,000 people, per capita hospitalization expenses decrease by 0.099%. In the central and eastern regions, where economic levels are higher, supply-side government funding is more effective than demand-side funding. In contrast, demand-side funding is more effective in the western region.

Conclusions
The roles of multiple influencing factors and significant regional heterogeneity are clarified. Increasing financial compensation to providers positively impacts perinatal mortality but leads to higher per capita outpatient and hospital expenditures. Finally, this study provides targeted policy recommendations and solid theoretical support for policymakers.