bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling the association between long non-coding RNAs (RP5-833A20.1, DYNLRB2-2, and APOA1-AS) and ischemic stroke: exploring biomarkers, and clinical implications
Authors: Bayat Mahnaz , Mokhtari Mahsa , Mokhtari Mohammad Javad , Gharbi Negin , Tabrizi Reza , Salehi Mohammad Saied , Karimi Najmeh , Rahimi Moosa , Hooshmandi Etrat , Zafarmand Seyedeh Shaghayegh , Owjfard Maryam , Lashanizadegan Ramin , Dara Mahintaj , Borhani-Haghighi Afshin 
Published: February 2025

Abstract

Background
RP5-833A20.1, DYNLRB2-2, and APOA1 antisense are pivotal in atherosclerotic plaque pathogenesis. This study examined whether changes in these circulating lncRNAs could serve as biomarkers for high-risk ischemic stroke (IS) patients with intracranial atherosclerotic disease (ICAD).

Methods
Sixty-three IS patients, presenting within the first 24 h after stroke onset, and 60 controls were included in the study. The circulating levels of RP5-833A20.1, DYNLRB2-2, and APOA1 antisense in IS patients were assessed using real-time polymerase chain reaction (RT-PCR).

Results
Significant decreases in the circulating levels of DYNLRB2-2 and RP5-833A20.1 were observed in IS patients compared to controls (P < 0.05). However, no significant difference in APOA1 antisense levels was noted between the two groups. Subgroup analysis revealed higher RP5-833A20.1 expression in IS patients with lower National Institutes of Health Stroke Scale (NIHSS) scores (0–6) compared to those with higher scores (3.59 ± 0.783 vs. 1.05 ± 0.505, P = 0.006). After adjusting for relevant covariates, multiple logistic regression indicated an inverse association between RP5-833A20.1 and the risk of IS (adjusted OR = 0.846, P = 0.028). Linear regression analyses further demonstrated a negative correlation between RP5-833A20.1 expression and NIHSS (beta = − 0.398, P = 0.006), which was confirmed by a significant negative Spearman correlation (r = − 0.41, P = 0.0007). DYNLRB2-2 exhibited a non-significant negative relationship with NIHSS.

Conclusion
The findings suggest a significant decrease in the circulating levels of RP5-833A20.1 and DYNLRB2-2 in IS patients with ICAD, potentially indicating a protective effect against ischemic stroke. These lncRNAs hold promise as valuable biomarkers for identifying high-risk IS patients, emphasizing the need for further exploration and validation in larger cohorts to elucidate their roles in IS pathogenesis and clinical applications.
Assessing the association of rare MDR1 variants (rs944806668, rs1816042256, and rs1295312177) with steroid response in Iraqi children with idiopathic nephrotic syndrome
Authors: Abd Alridha Ali Mohammed , Kadhim Dheyaa Jabbar , Alkhazrajy Ayad Hussein Ali 
Published: February 2025

Abstract

Background
Several studies have linked the development of steroid-resistant nephrotic syndrome (SRNS) to variations in the multidrug resistance 1 gene (MDR1). However, disparities in findings have been noted among children of different ethnic origins.

Objectives
This study aimed to examine the relationship between MDR1 variants [rs944806668 (V1), rs1816042256 (V2), and rs1295312177 (V3)] and the risk of developing SRNS in Iraqi patients with idiopathic nephrotic syndrome (INS).

Methods
This case–control study included children with steroid-sensitive INS (n = 30) and SRNS (n = 30) from the Babylon Hospital for Maternity and Pediatrics. Sanger sequencing was used to determine the participants’ genotypes.

Results
Children with the V2 T/C genotype were more likely to develop SRNS [odds ratio (OR) and 95% confidence interval (95% CI): 10.8 (3.26–35.72), p < 0.001] than those with the wild genotype. However, no significant association with steroid response was observed for the V1 genotypes and alleles [OR (95% CI): 0.58 (0.18–1.91) and 0.63 (0.21–1.9), respectively; p > 0.05]. Moreover, children with the wild–variant–variant genotype combination of the V1, V2, and V3 variants exhibited a significantly higher risk of developing SRNS [OR (95% CI) 34 (4.91–235.61), p < 0.001] than those with the wild–wild–wild genotype combination.

Conclusion
These findings highlight the need to incorporate pharmacogenetic screening into the clinical management of SRNS. Children with nephrosis having the V2 T/C and V3 A/T genotypes, whether individually or in combination, are likely to resist prednisolone therapy, implying the need for alternative therapeutic approaches. Further studies are required to elucidate the potential implications of MDR1 variants for personalized drug therapy in children with INS.
Contribution of intravoxel incoherent motion MRI to diffusion-weighted MRI in differentiating benign from malignant breast masses
Authors: Rashed Dina , Settein Magdy Elsayed Mohamed , Batouty Nihal M. 
Published: February 2025

Abstract

Background
The differentiation of benign and malignant breast masses is a critical aspect of breast cancer diagnosis. The aim of this study was to assess the capability of IVIM variables to discriminate between benign and malignant breast lesions by obtaining diffusion and perfusion data from normal tissues of breast and breast lesions through intravoxel incoherent motion (IVIM) imaging utilising biexponentially analysis of multiple b-value diffusion-weighted imaging (DWI) and comparing these variables to the apparent diffusion coefficient (ADC) derived from monoexponentially analysis.

Results
In this prospective work, each subject provided informed consent. Forty-two patients with fifty-two lesions with 31 malignancies and 21 benign lesions were scanned using 1.5 T MRI and DWI with 12 b-values (range 0–1000 s/mm2). Tissue diffusivity (D), perfusion fraction (f), and pseudo-diffusion coefficient (D
p) were determined by segmented biexponentially analysis. The ADC (b = 0 and 1000 s/mm2) was computed using monoexponentially fitting of the DWI information. D, f, D
p, and ADC values have been acquired for normal tissues of the breast, benign lesions, and malignancies. The contrast of these four variables among each pair indicated that the D and ADC values of malignancies had been substantially lower compared female patients of benign tumours and normal tissues (P < 0.001). The f of malignancies was substantially greater contrasted to that of benign lesions (P < 0.001); nevertheless, no substantial variation in D
p was seen between both groups. D, f, and values of ADC exhibited superior sensitivity and specificity in distinguishing benign lesions from malignancies, with areas under the curve (AUC) of 0.945, 0.883, and 0.796, correspondingly. At the same time, D
p showed the lowest AUC of 0.515.

Conclusions
IVIM may play a crucial role in differentiating malignancies and benign lesions of the breast by providing separate quantitative measurements of D for cellularity and D
p and f for vascularity.
Prognosis of p16 and Human Papillomavirus Discordant Oropharyngeal Cancers and the Exploration of Using Natural Language Processing to Analyze Free-Text Pathology Reports
Authors: Shin Ethan , Choi Justin , Hung Tony K.W. , Poon Chester , Riaz Nadeem , Yu Yao , Kang Jung Julie 
Published: February 2025

PURPOSE
Treatment deintensification for human papillomavirus–positive (HPV+)-associated oropharyngeal cancer (OPC) has been the catalyst of experts worldwide. In situ hybridization is optimal to identify HPV+ OPC, but immunohistochemistry for its surrogate p16INK4a (p16) is standard-of-care given its availability and sensitivity. HPV testing is not required for clinical management, so treatments are often administered on the basis of p16 status alone. However, the prognosis of p16/HPV discordant tumors is uncertain.

MATERIALS AND METHODS
This cohort study included 727 consecutive patients with OPC with digitized unstructured pathology reports receiving curative radiation therapy at an academic cancer center. Natural language processing (NLP) methods were used to classify biomarker status and compared against manually derived classification. Patients were excluded if either p16 or HPV testing was not performed or equivocal. Primary end points were progression-free survival (PFS), cancer-specific survival (CSS), and overall survival.

RESULTS

NLP classified p16 and HPV status from a majority (91%) of reports. Accuracy, positive predictive value, sensitivity, and
F
-score for NLP-derived p16/HPV were 84%/82%, 91%/87%, 90%/89%, and 90%/88%, respectively. Four groups were identified: p16-positive (p16+)/HPV+ (75%), p16+/HPV-negative (HPV–; 13%), p16-negative (p16–)/HPV– (10%), and p16–/HPV+ (2%). There was no statistically significant difference in outcomes between p16+/HPV– and p16–/HPV– patients (5-year PFS 76.1%
v
68.9%;
P
= .12; 5-year CSS 81.5%
v
84.9%;
P
= .22). Number needed to harm calculations estimated one excess cancer-related death for every 10 p16+/HPV– patients, compared with that expected with p16+/HPV+ patients.

CONCLUSION
NLP classified head and neck cancer pathology reports with high concordance with gold-standard categorization, but a conspicuous portion of reports could not be interpreted. p16/HPV discordant OPC constitutes a noteworthy minority of patients. The inferior prognosis of p16+/HPV– suggests that p16 alone for prognostication is insufficient—especially when considering treatment de-escalation.
Expression of tissue factor (TF) in penile squamous cell carcinoma (PSCC) and enrichment in HPV-negative cases.
Authors: Johns Andrew , Jackson Jamaal Christopher , Campos Clemente Leticia , Solis Luisa Maren , Rao Priya , Manuel Christopher Matthew , Qiao Wei , Campbell Matthew T. , Chahoud Jad , Zacharias Niki Marie , Pettaway Curtis Alvin 
Published: February 2025

10

Background:
Advanced/metastatic PSCC is an aggressive malignancy with limited treatment options. An antibody-drug conjugate (ADC) targeting TF is approved for treatment of advanced cervical cancer and may benefit patients with PSCC. We evaluated TF expression in PSCC which could support a future clinical trial of a TF-targeting agent for PSCC.
Methods:
We identified 33 pts with PSCC who underwent primary surgery at MD Anderson from 1999-2017 and had archived primary tumor tissue available for analysis. HPV-positive status was determined by either PCR testing or high-risk HPV in situ hybridization assay. A tissue microarray (TMA) was constructed with 3 cores per tumor. Anti-TF-1 antibody staining was performed by immunohistochemistry and mean H-scores for membrane and cytoplasm staining were assessed (range 0-300) for each tumor. Median H-scores were described and compared between HPV-positive and negative tumors. Percentage of pts with tumors staining positive for TF (≥10% of tumor cells with at least 1+ intensity in cytoplasm and/or membrane) was determined. Association of TF expression with tumor grade, presence of metastatic disease, lymphovascular invasion (LVI), perineural invasion (PNI), recurrence free survival (RFS), and overall survival (OS) was assessed.
Results:
17 pts (51.5%) had HPV-positive disease; 19 pts (57.6%) had metastatic disease. 27 tumors (81.8%) stained positive for tissue factor. Median overall membrane TF H-score was 47 (range 1-232). HPV-negative tumors had significantly higher membrane expression of TF (median H-score 70, range 1-232) than HPV-positive tumors (median H-score 19, range 1-123; p=0.004). While analyses were limited by small sample size, we did not find a significant association of TF H-score with tumor grade, presence of metastatic disease, LVI, PNI, RFS, or OS.
Conclusions:
TF expression was highly prevalent in this PSCC pt cohort. HPV-negative tumors had significantly higher TF expression than HPV-positive tumors; this finding requires further study. These data support further investigation of TF-targeted therapy, such as an ADC, for treatment of PSCC.

Variable
Overall population
HPV-positive(17 patients)
HPV-negative(16 patients)

Median (range) H-score

Membrane
47 (1-232)
19 (1-123)
70 (1-232)

Cytoplasm
29 (2-180)
18 (2-98)
59 (2-180)

Positive TF expression (Percent of patients with ≥1 core having ≥10% of tumor cells with at least 1+ intensity in either cytoplasm or membrane)
27/33 (81.8%)
12/17 (70.6%)
15/16 (93.8%)
DNA damage repair alterations as predictive biomarker for platinum-based chemotherapy in metastatic urothelial cancer.
Authors: Sternschuss Michal , Paynter Alexander , Xu Wenxin , Nichols Chelsea , Hoppe Jennifer , Davis Nancy B , Jiang Di Maria , Shah Neil J. 
Published: February 2025

853

Background:
DNA damage repair gene alterations (DDRa), especially
ERCC2
mutations, have been associated with improved clinical outcomes in patients with urothelial cancer (UC) treated with cisplatin-based neoadjuvant chemotherapy. The predictive value of DDR alterations for platinum-based chemotherapy in metastatic disease is not well-defined.
Methods:
We analyzed the American Association of Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative consortium (BPC), including patients with UC treated at 4 academic centers in North America between 2013 and 2018, with Next Generation Sequencing (NGS) data available. We assessed overall survival among patients treated with first line platinum-based chemotherapy for metastatic UC, and compared the outcomes based on DDRa status using Cox models adjusted with risk-set adjustment for delayed entry. DDRa were defined as any mutation defined as “likely oncogenic” or “oncogenic” in OncoKB for the genes
ERCC2, ERCC5, BRCA1, BRCA2, RECQL4, ATM, ATR, RAD51C
and
FANCC
.
Results:
Of 716 patients with UC, 103 (14%) had any DDRa, and 32 (4.5%) had an
ERCC2
mutation. Among 566 patients (79%) who developed metastatic disease at any time during follow up, median age was 66 years, 22% were female and 25% had upper tract UC. The median overall survival (mOS) from diagnosis of metastatic disease was 15.1 months (95% CI 12.6-18.6). For patients treated with first line platinum-based chemotherapy (n=258), the presence of DDRa was associated with significantly improved mOS compared with absence of DDRa: 22.7 versus 11.2 months, hazard ratio (HR) 0.54 (95% CI 0.34-0.86, p=0.009). Similar trends were seen when analyzing patients treated with cisplatin or carboplatin, separately.
Conclusions:
DDRa were associated with improved survival in metastatic UC patients treated with platinum-based chemotherapy. Further studies are needed to explore the prognostic and predictive value of DDRa as the role of platinum-based chemotherapy evolves in the enfortumab vedotin and pembrolizumab era.

DDRa
No DDRa

First Line treatment for metastatic UC
N
Median OS months (95% CI)
N
Median OS months (95% CI)
HR (95% CI)
P value

Any platinum-based chemotherapy
32
22.7 (14.5, 66.9)
226
11.2 (9.4, 15.1)
0.54 (0.34, 0.86)
0.009

Cisplatin-based chemotherapy
22
25.9 (14.5, NR)
142
13.6 (10.4, 18.8)
0.57 (0.32, 1.01)
0.06

Carboplatin- based chemotherapy
10
17.4 (7.26, NR)
84
9.9 (6.6, 12.7)
0.53 (0.25, 1.17)
0.12

CI= Confidence interval; DDRa= DNA damage repair alteration; HR=Hazard ratio; NR=Not reached; OS= Overall survival; UC= Urothelial Carcinoma.
Development and validation of a novel prediction model for osteoporosis
Authors: Wang Jinpeng , Shan Lianfeng , Hang Jing , Li Hongyang , Meng Yan , Cao Wenhai , Gu Chunjian , Dai Jinna , Tao Lin 
Published: February 2025

AimsWe aimed to develop and validate a novel prediction model for osteoporosis based on serotonin, fat-soluble vitamins, and bone turnover markers to improve prediction accuracy of osteoporosis.MethodsPostmenopausal women aged 55 to 65 years were recruited and divided into three groups based on DXA (normal, osteopenia, and osteoporosis). A total of 109 participants were included in this study and split into healthy (39/109, 35.8%), osteopenia (35/109, 32.1%), and osteoporosis groups (35/109, 32.1%). Serum concentrations of serotonin, fat-soluble vitamins, and bone turnover markers of participants were measured. Stepwise discriminant analysis was performed to identify efficient predictors for osteoporosis. The prediction model was developed based on Bayes and Fisher’s discriminant functions, and validated via leave-one-out cross-validation. Normal and empirical volume under the receiver operating characteristic (ROC) surface (VUS) tests were used to evaluate predictive effects of variables in the prediction model.ResultsSignificant variables including oestrogen (E2), total procollagen type 1 amino-terminal propeptide (TP1NP), parathyroid hormone (PTH), BMI, vitamin K, serotonin, osteocalcin (OSTEOC), vitamin A, and vitamin D3 were used for the development of the prediction model. The training accuracy for normal, osteopenia, and osteoporosis is 74.4% (29/39), 80.0% (28/35), and 85.7% (30/35), respectively, while the total training accuracy is 79.8% (87/109). The internal validation showed excellent performance with 72.5% testing accuracy (72/109). Among these variables, serotonin and vitamin K exert important roles in the prediction of osteoporosis.ConclusionWe successfully developed and validated a novel prediction model for osteoporosis based on serum concentrations of serotonin, fat-soluble vitamins, and bone turnover markers. In addition, interactive communication between serotonin and fat-soluble vitamins was observed to be critical for bone health in this study.Cite this article: Bone Joint Res 2025;14(2):111–123.
Analytical performance evaluation and optimization of serum 25(OH)D LC-MS/MS measurement
Authors: Zhou Weiyan , Gong Meiliang , Mao Yuanli , Yuan Xiaofen , Deng Yuhang , Zhang Qianwen , Guo Wei , Qiu Ling , Huang Xianzhang , Cao Zheng , Xia Jun , She Xuhui , Cong Yulong , Zhang Chuanbao , Liu Huafen , Chen Wenxiang 
Published: February 2025

Abstract

Objectives
Measuring serum 25-hydroxyvitamin D is key in clinical labs, but inter-laboratory variations risk diagnostic errors. This study evaluates the performance of current in-house liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods used in top Chinese clinical laboratories and proposes an optimized method for improving serum 25(OH)D measurement accuracy and reliability.

Methods
Seven serum pools with different concentrations of 25(OH)D were prepared and sent to 12 participating laboratories for multiple repeat analysis with their current in-house LC-MS/MS methods and then an optimized LC-MS/MS method. Precision was assessed in terms of coefficient of variance (CV), and trueness was assessed in terms of bias referring to the U.S. National Institute of Standards and Technology (NIST) reference measurement procedure (RMP). The analytical performances of the two methods were compared and evaluated.

Results
Eighty percent and 90 % of the laboratories achieved the defined performance criteria (CV, <12.5 %; mean bias, <8.3 %) with the optimized method for the measurement of 25(OH)D2 and 25(OH)D3, compared with 43 % and 57 % of the laboratories meeting the criteria with their in-house methods, respectively. Precision and trueness improved after applying the optimized method. Although the optimized method didn’t not ensure that all laboratory samples meet the measurement uncertainty (MU) criteria (MU<13.6 %), particularly for low-concentration samples, it significantly reduced the MU compared to the in-house method.

Conclusions
Precision, trueness and MU improved after applying the optimized method. Nonetheless, more efforts are needed to ensure the reliability and accuracy of 25(OH)D measurements in clinical laboratories in China.
Evidence-based assessment of the application of Six Sigma to infectious disease serology quality control
Authors: Dimech Wayne , Vincini Giuseppe 
Published: February 2025

Abstract

Objectives
Recently, four publications have applied Sigma metrics to infectious disease serology testing. Three studies applied Sigma metrics to assays in a blood bank setting, whereas one used anti-toxoplasma testing in a diagnostic laboratory. One of the four studies applied the approach to microtitre plate enzyme immunoassays, whereas the other three were on fully automated chemiluminescent assay. The approaches used by each study differed in the approach used to calculate imprecision, measured as a percentage coefficient of variation, and bias. All four studies used the difference between the mean of the quality control result and the assay cut-off to describe the total allowable error.

Methods
This paper compares and critically reviews the methods used to calculate the Sigma value for each assay in the four studies and provides an evidence-based assessment of these approaches using real-world quality control data obtained from the National Serology Reference Laboratory, Australia (NRL) QConnect™ quality control program.

Results
The assessment found that there was a lack of standardisation in the application of Sigma metrics for infectious disease testing, including examples of inappropriate assumptions being used. Westgard Sigma Rules suggest that assays found to have a Sigma value of six or greater can be monitored using two quality control measures and applying a single mean ± three standard deviation rule.

Conclusions
Although this approach will significantly reduce the number of false rejections generated by using the full range of Westgard rules, we provide evidence that even this approach can potentially cause true errors to be missed.
Pompey, Theophanes and the Contest for Empire
Authors: Degen Julian 
Published: February 2025

Abstract
This paper outlines a new framework for the historical study of Roman imperialism in the East as a dialogue between the empire and local elites. It is argued that Pompey created in his representation a persona of himself that Near Eastern nobles considered legitimate. This representation ultimately helped him to stabilise Roman hegemony over Armenia, which had already developed into a contested borderland with the Parthians. From the fragments aligned with the lost account of Theophanes, there is a strong indication that Alexander was the dominating feature in Pompey’s representation in the East. This applies in particular to Pompey’s presentation of the so-called ‘Transcaucasian campaign’. In the course of this campaign, the Romans approached the northern limits of the world, which allowed Pompey to claim universalism by using the myths that were woven around Alexander. Universalism had been at the heart of the discourse on empire that prevailed in the Near East during the first millennium BCE and, therefore, was crucial to any imperial formation in the Near East that preceded the Romans, especially to Alexander, his successors, and Rome’s eastern enemies.
Base sizes for finite linear groups with solvable stabilisers
Authors: Baykalov Anton A. 
Published: February 2025

Abstract
Let 𝐺 be a transitive permutation group on a finite set with solvable point stabiliser and assume that the solvable radical of 𝐺 is trivial.
In 2010, Vdovin conjectured that the base size of 𝐺 is at most 5.
Burness proved this conjecture in the case of primitive 𝐺.
The problem was reduced by Vdovin in 2012 to the case when 𝐺 is an almost simple group.
Now the problem is further reduced to groups of Lie type through work of Baykalov and Burness.
In this paper, we prove the strong form of the conjecture for all almost simple groups with socle isomorphic to

PSL
n

⁢

(
q
)

\mathrm{PSL}_{n}(q)

, and the remaining classical groups will be handled in two forthcoming papers.