bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Reliable is the Assessment of Fusion Status Following ACDF Using Dynamic Flexion-Extension Radiographs?
Authors: Martin Christopher T. , Yoon Sangwook Tim , Alluri Ram Kiran , Benzel Edward C. , Bono Chris M. , Cho Samuel K. , Chou Dean , Chen Xiaolong , Cheung Jason P.Y. , Cabrera Juan P. , Ćorluka Stipe , Demetriades Andreas K. , Gary Matthew F. , Ghogawala Zoher , Hamouda Waeel , Han Inbo , Hauri Dimitri , Hsieh Patrick C. , Jain Amit , Kim Jun S. , Le Hai V. , Louie Philip K. , Luo Zhuojing , Meisel Hans-Jörg , Muthu Sathish , Ryu Dal-Sung , Sansur Charles A. , Schoenfeld Andrew J. , Scaramuzzo Laura , Schroeder Gregory D. , Rajasekaran Shanmuganathan , Sotiris Veranis , Vadalà Gianluca , Vergroesen Pieter-Paul A. , Wang Jeffrey C. , Wu Yabin , Riew K. Daniel ,   AO Spine Knowledge Forum Degenerative
Published: December 2024

Study Design Reliability study. Objectives The radiographic diagnosis of non-union is not standardized. Prior authors have suggested using a cutoff of <1 mm interspinous process motion (ISPM) on flexion-extension radiographs, but the ability of practicing surgeons to make these measurements reliably is not clear. Methods 29 practicing spine surgeons measured ISPM on 19 levels of ACDF from 9 patients. Surgeons relied on these measurements to report on fusion status. Inter-observer correlation co-efficients (ICC), standard error (SEM) and the minimum detectable difference (MD) of these measurements were calculated. We screened for clerical errors by checking measurements more than one standard deviation from the group mean. Results The ICC for ISPM was .76 (.64; .88) with a SEM of 1 mm and a MD of 2.76 mm. Agreement on fusion status was moderate, with an ICC of .6 (.44; .76). After screening for and removing clerical errors, the ICC improved to .82 (.71; .91), SEM improved to .83 mm, and MD improved to 2.29 mm. Six reviewers had an ICC >.9. The ICC from these high performing reviewers was .94 (.9; .97), SEM was .45 mm, and MD was 1.26 mm. Conclusions The MD of 2.29 mm in our study group was not precise enough to support a cutoff of <1 mm ISPM as the sole measurement technique in screening for non-union after ACDF, and there was only moderate agreement amongst surgeons on fusion status based on dynamic radiographs. More stringent techniques are necessary to avoid mis-diagnosing non-union in clinical studies. Future studies should consider auditing measurements to identify clerical errors.
Peripheral defects precede neuromuscular pathology in the Smn2B/− mouse model of spinal muscular atrophy
Authors: Reilly Aoife , Beauvais Ariane , Al-Aarg Majd , Yaworski Rebecca , Sutton Emma R. , Thebault Simon , Kothary Rashmi 
Published: December 2024

Background: Spinal Muscular Atrophy (SMA) is an inherited neurodegenerative disease caused by the loss or mutation of the survival motor neuron 1 (SMN1) gene. Though classically regarded as a motor neuron disorder, reports are increasingly describing the involvement of non-neuronal organs in SMA. The Smn2B/− mouse is a model of SMA that displays a peripheral phenotype including metabolic defects. Objective: Here, we characterized several neuronal and non-neuronal defects in the Smn2B/− mouse throughout development to better understand the progression of the disease and the relationship between tissue defects. Methods: We collected tissues from mutant Smn2B/− mice and Smn2B/+ littermate controls at several timepoints and evaluated spinal cord motor neuron loss, neuromuscular junction pathology, muscle fiber size, liver steatosis, and pancreatic islet cell composition. Blood glucose and plasma neurofilament light chain (NfL) were also measured. Results: Smn2B/− mice displayed several peripheral defects prior to motor neuron loss and showed early elevations in neurofilament light chain (NfL) protein. Conclusions: This work provides an important framework for guiding future research with this mouse model and demonstrates that the liver may be an early target in the development of SMA.
Predictors of Late Antenatal Care Initiation: A Multicentre Cross-Sectional Study in Ghana
Authors: Gbene Jonathan , Takase Mohammed Augustine , Ayangba Valentine , Azumah Abanga Williams , Hamza Anwar Sadat , Alechana Justina Atogichiga , Dzantor Edem Kojo , Tarkang Elvis E. 
Published: December 2024

Background Despite free maternal healthcare, about 50% of pregnant women in Ghana initiate their antenatal clinic (ANC) late. Aim This study aimed to identify the factors that contribute to the late initiation of ANC among pregnant women in the Jasikan District, Ghana. Method A cross-sectional study was conducted between December 2021 and May 2022 in multiple health facilities. Multistage sampling was employed to select 352 pregnant women attending ANC in selected health facilities. A structured questionnaire was used to collect the data. The data was analyzed using Stata version 14.0. Descriptive statistics was used to describe the study variables and multivariable logistic regression models were performed to determine the predictors of late ANC initiation at p < .05 and 95% confidence interval (CI). Results Approximately 45.7% of the participants initiated ANC late. Age less than 20 years, older age groups (40–49 [odds ratio (OR): 18.0, 95%CI: 3.68–88.0, p < .001]; 30–39 [OR: 6.4, 95%CI: 1.76–22.87, p = .005] and 20–29 [OR: 4.6, 95%CI: 1.30–15.98, p = .018]) were associated with late initiation of ANC. Having a higher number of children (4 [OR: 2.8, 95%CI: 1.36–5.79, p = .005] and 3 [OR: 2.5, 95%CI: 1.33–4.58, p = .004]) were predictors of late ANC initiation as compared to having one child. Women who sought for advice from women leaders (OR: 3.5, 95%CI: 1.18–10.12, p = .02) were about three (3) times more likely to initiate ANC late as compared to those who sought for advice from friends. Women who felt poorly received at ANC (OR: 7.7, 95%CI: 2.188–27.078, p = .001) were about eight (8) times more likely to initiate ANC late as compared to those who felt well received. Again, those who spent over six (6) hours during ANC visits (OR: 18.4, 95%CI: 4.246–79.734, p < .001) had an 18 times higher risk of initiating ANC late relative to those who spent less than 3 h. Conclusion The study findings highlight the need for interventions that addresses the social and cultural factors, negative perceptions of ANC, and long waiting times at health facilities to improve early initiation of ANC. Such interventions can assume health education and promotion to address the sociocultural and unfavorable perceptions toward ANC. The sector ministry and the health facilities may consider expanding ANC service centers to reduce long waiting times.
Development and Validation of the Blastic Plasmacytoid Dendritic Cell Neoplasm Prognostic Score
Authors: Haddad Philip A , Gaddam Shiva Jashwanth , Gupta Ankita 
Published: December 2024

Background
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon and highly aggressive hematologic malignancy primarily characterized by its frequent involvement of the skin and potential to rapidly progress to systemic disease. Initially misclassified under various categories, such as blastic NK-cell lymphoma, and later as a subset of acute myeloid leukemia (AML), BPDCN has now been distinctly recognized as a unique myeloid neoplasm. Despite recent advancements in understanding its pathogenesis and clinical behavior, the prognosis of BPDCN remains poor and highly variable among patients. Accurate prognostic tools are crucial for improving patient management and outcomes. This study focuses on developing and validating a clinical prognostic score for BPDCN, aiming to stratify patients better based on their risk and guide therapeutic decision-making.
Methods
Using a constructed BPDCN database of 273 cases, we analyzed demographics and clinicopathologic factors. Of these, 218 cases had complete survival and outcomes data. Cox proportional-hazards models and Log-rank tests were used to identify factors impacting overall survival (OS). Factors with significant impact on OS were scored based on their hazard ratios. A validation cohort of 106 BPDCN-confirmed cases was used to test the score. Subsequently, both cohorts were combined and split into adult and pediatric cohorts for further testing and validation across age groups.
Results
The median OS for the initial, validation, adult, and pediatric cohorts were 16, 15, 12, and 60 months, respectively. The following dichotomous variables significantly impacted OS: Age &gt; 60 (10 vs. 30 months), lymphadenopathy (14 vs. 42 months), bone marrow involvement (14 vs. NR months), splenomegaly (10 vs. 16 months), disseminated skin disease (13 vs. NR months). Variables were assigned points: 1 point for each variable, except age &gt; 60, splenomegaly, and disseminated skin disease, which were given 2 points due to their high hazard ratios. The risk model categorized patients into low (0-2 points), intermediate (3-4 points), and high-risk (5-8 points) groups. Median OS for these groups were NR, 24, and 10 months, respectively (p &lt; 0.0001). The BPS similarly identified 3 risk groups in the validation cohort(38 vs. 13 vs. 9 months, p = 0.0001), adult cohort (22 vs. 13 vs. 9 months, p &lt; 0.0001), and pediatric cohort(NR vs. 36 vs. 9 months, p = 0.002).
Conclusion
The BPDCN prognostic score (BPS) is a promising tool that effectively stratifies patients into 3 distinct risk categories with significant differences in overall survival. This score was validated in multiple cohorts, including adult and pediatric groups, but requires prospective validation for further confirmation.
Development of a Machine Learning-Based Risk Score for Predicting Atrial Fibrillation in Treatment-Naive CLL Patients Initiating BTK Inhibitor Therapy
Authors: Tadmor Tamar , Melamed Guy , Alapi Hilel , Gazit Sivan , Patalon Tal , Rokach Lior 
Published: December 2024

Background: One of the limiting toxicities of BTKi therapy is the development of atrial fibrillation (AF), with an incidence of 3% to 16%.
Aim: To identify patients with chronic lymphocytic leukemia (CLL) who are at high risk of developing AF, using a machine learning approach.
Methods: The CLL cohort was based on data obtained from electronic medical records from Maccabi, the second-largest healthcare organization in Israel. We evaluated more than 100 variables to develop the scoring schema. The optimal scoring model was determined using the code available at https://github.com/ustunb/risk-slim, implemented in Python 3.5 and CPLEX 12.6.
Results: A total of 3964 patients with a CLL diagnosis were available in the database. 208 patients started a BTKi during the study period, 16 of whom developed AF during follow-up. In addition to well-established factors (age, sex, and hypertension) that are used in many existing AF scores that were developed for the general population, the algorithm detected other factors that were associated with a high risk for AF, in particular: type of BTKi used, low eGFR (&lt;30 mL/min/1.73m2), elevated absolute monocytes (&gt;1100/µL), elevated CRP, elevated CK, and elevated B2MG (&gt;2.5 mg/L). Based on the total score, we identified 3 main AF risk groups as following: low (0-6), intermediate (7-11) and high (≥12). The median AFS were 28 and 56 months for the high-risk and intermediate-risk groups, respectively, and was not reached for the low-risk group. The difference between the groups was statistically significant (P=0.0013).
The proposed scoring model reached a C-index of 0.744+/-0.082 and it outperformed the score ranking of Shanafelt et al that obtained a C-index of 0.626+/-0.138 on the same data. The improvement was found to be statistically significant (P=0.024).
Conclusion: Our novel score has a high concordance index to predict the development of AF in patients with CLL treated with BTKi.
Loss of IRF2BP2 Drives an Actionable IL-1β/IL-1R Signaling Loop in DLBCL
Authors: Tabatabai Areya , Klein Sebastian , Höfmann Svenja , Zhou Tanja , Theiss Felix , Flümann Ruth , Möllmann Michael , Hartnack Maximilian , Kesper Stefanie , Arora Aastha , Knittel Gero , Reinhardt Hans Christian 
Published: December 2024

Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous disease and is the most common lymphoid malignancy in adults (Swerdlow et al., 2016, Alizadeh et al., 2000). It is traditionally divided into two subtypes based on the cell-of-origin: Activated B cell-like (ABC) DLBCL and germinal center B cell-like (GCB) DLBCL (Alizadeh et al., 2000). DLBCL can be further subdivided into clusters A53, ST2, N1, BN2, EZB, and MCD based on the mutational profiles of the tumors (Schmitz et al., 2018, Wright et al., 2020). While cure rates of ~65% are achievable in DLBCL patients with frontline combination chemo-immune therapy (e.g. R-CHOP), treating relapsed or refractory disease remains a challenge, particularly in ABC-DLBCL and MCD patients (Pfreundschuh et al., 2011, Tilly et al., 2015, Schmitz et al., 2018).
Interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a transcriptional repressor that is frequently mutated in MCD patients, with many of these mutations predicted to be loss-of-function (Schmitz et al., 2018). Besides human DLBCL tumors, in previously published MCD mouse models, which harbor a B cell-specific loss of Prdm1, expression of mutant Myd88p.L252P, overexpression of BCL2, and in some cases expression of a Cd79b ITAM mutation, Irf2bp2 is also one of the most frequently co-mutated genes (Knittel et al., 2016, Flümann et al., 2023, Flümann et al., 2024). However, the role of IRF2BP2 in lymphoma biology and as a potential tumor suppressor gene in DLBCL has not been investigated.
To understand the role of IRF2BP2 in the germinal center reaction, we analyzed the B cell compartment of autochthonous mice which harbor a B cell specific knockout of Irf2bp2 at a premalignant age. We observed a dramatic decrease in germinal center B cells in Irf2bp2 knockout mice compared to controls, as well as a higher relative memory B cell output and reduced class switch recombination. This preliminary dataset suggests that Irf2bp2 may play a role in the dynamics of the germinal center reaction and B cell differentiation.
Moreover, we show that CRISPR/Cas9-mediated loss of IRF2BP2 in human ABC-DLBCL cell lines leads to increased proliferation and NF-KB signaling, compared to IRF2BP2-proficient cells. Additionally, we find that IRF2BP2 knockout ABC-DLBCL cells express higher interleukin-1 beta (IL1β) and are sensitive to anti-IL1β inhibition both in vitro and in vivo, while IRF2BP2-proficient cells remain insensitive. Furthermore, murine lymphoma cell lines derived from MCD mouse models, which harbor a spontaneous Irf2bp2 mutation are also sensitive to anti-IL1β inhibition in vitro and retain sensitivity over several weeks. Our findings suggest that IL1β is the primary mediator of increased NF-KB signaling upon IRF2BP2 perturbation and anti-IL1β therapy could be a potential treatment strategy for IRF2BP2-mutant patients.
Medicaid Expansion and Cancer-Specific Survival Among Individuals with Acute Lymphoblastic Leukemia
Authors: Akinyemi Oluwasegun Austine , Abobarin-Aofolaju Olufunmilayo , Adeoye Tayo , Abodunrin Faith , Adubi Oreoluwa , Ikugbayigbe Seun , Odusanya Eunice , Fasokun Mojisola , Michael Miriam , Hughes Kakra 
Published: December 2024

INTRODUCTION
Medicaid expansion under the Affordable Care Act (ACA) has aimed to improve healthcare access and outcomes for low-income individuals across the United States. Acute Lymphoblastic Leukemia (ALL), a rapidly progressing hematological malignancy, demands timely and comprehensive medical intervention to optimize patient survival rates. Despite advancements in treatment, disparities in cancer-specific survival persist (CSS), particularly among socioeconomically disadvantaged populations.

OBJECTIVE
This study investigates the impact of Medicaid expansion on CSS among individuals diagnosed with ALL, aiming to explore the extent to which increased healthcare access through Medicaid expansion may influence survival outcomes in this vulnerable patient population.

METHODOLOGY
We utilized the Surveillance, Epidemiology, and End Results (SEER) cancer registry to examine the impact of Medicaid expansion on CSS among individuals diagnosed with ALL. A difference-in-difference analysis (DID) was conducted to evaluate the effect of the policy on survival outcomes. Texas, a state that has not implemented Medicaid expansion, was compared with California, which adopted the policy in 2014. The analysis adjusted for significant covariates including age, sex, race/ethnicity, socioeconomic status, and treatment modalities. By comparing pre- and post-expansion periods in these two states, we aimed to isolate the impact of Medicaid expansion on CSS in ALL patients.

RESULT
Among 22,303 patients, 60.0% were in California (13,384), while 40.0% were in Texas (8,919). The pre-ACA period included 14,129 patients (62.0% in California and 38.0% in Texas), and 8,174 patients were in the post-ACA period (56.6% in California and 43.4% in Texas). In the post-ACA implementation period, there was a 23.5% reduction in the hazard of deaths (HR=0.77, 95% CI 0.70-0.85). Medicaid expansion significantly improved cancer-specific survival among individuals with ALL across different race/ethnicity and income levels (DID=-0.69, 95% CI -1.18 to -0.19). The most significant improvements were observed among minority groups: Blacks (DID=-0.80, 95% CI -1.39 to -0.21) and Hispanics (DID=-0.72, 95% CI -1.35 to -0.22), as well as individuals with lower income levels (DID=-0.66, 95% CI -1.14 to -0.18).

CONCLUSION
The implementation of the ACA and its Medicaid expansion component led to a substantial improvement in cancer-specific survival among individuals with acute lymphoblastic leukemia in California compared to non-expansion Texas.
Analysis of the Nervous System Adverse Events Associated with Blinatumomab: A Real-World Study Using the FDA Adverse Event Reporting System Database
Authors: Gao Wen , Lu Yaxiao , Wang Xianhuo , Zhang Huilai 
Published: December 2024

Background: Nervous system toxicity (NST) is one of the most frequent and dangerous side effects of blinatumomab, which is the world's first bispecific antibody drug targeting both CD19 and CD3. Current clinical trial data do not fully reflect the real-world situation. Therefore, this study evaluated the NST of blinatumomab therapy using the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).
Methods: Data were retrieved from FAERS for the period from October 1, 2014 to September 30, 2023. The reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence interval progressive neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms were used for data mining. The time to onset (TTO) and clinical outcomes due to blinatumomab-associated NST were assessed.
Results: In the FAERS database, 5,962 adverse reaction case reports primarily implicating blinatumomab were extracted. Male individuals accounted for the highest proportion (2,396 cases, 40.19%) of patients, patients aged 18-45 years old were the most prevalent (1,205 cases, 20.21%), and the majority of reports originated from the United States (3,494 cases, 58.60%), with the highest number of cases reported in 2021 (844 cases, 14.16%). Employing the ROR, PRR, BCPNN, and MGPS methods collectively identified 43 signals of nervous system adverse reactions. Among these adverse reactions, neurotoxicity, neurological symptoms, agnosia, intention tremor, and immune effector cell-associated neurotoxicity syndrome had the highest ROR values. For the neurological events, the median TTO was 3 days, with a range from 1 to 17 days. The highest fatality rate for neurological events was observed in increased intracranial pressure disorders, which also had the highest co-occurrence rate with cytokine release syndrome (CRS) at 36%.
Conclusions: Most NST (79%) did not overlap with cytokine release syndrome.The presence of CRS led to a higher fatality rate in patients experiencing neurological toxicities. In clinical practice, thorough medication evaluation should be conducted prior to administering blinatumomab, especially for high-risk patients with pre-existing neurological conditions.
Keywords: Blinatumomab, Nervous system toxicity, Pharmacovigilance, FDA Adverse Event Reporting System (FAERS)
A Multicenter Clinical Study of Cccg - APL-2017 in the Treatment of Children with Acute Promyelocytic Leukemia
Authors: Chang Lixian , GAO Ju , Lei Xiaoying , He Yingyi , Zhuang Shuquan , Li Chunhuai , Weng Kaizhi , Wang Lingzhen , Guo Xia , Liu Qihui , Wang Pengfei , Zhuang Yong , Yan Mei , Liu Wei , Chen Hui , Zhang Min , Shen Shuhong , Zhu Xiaofan , Ju Xiuli , Zhang Li , Wang Zhuo 
Published: December 2024

The standard therapy for childhood acute promyelocytic leukemia (APL) involves the combination of all-trans retinoic acid (ATRA) with arsenic trioxide (ATO) or Compound Huangdai tablet (Realgar-Indigo Naturalis formula, RIF). However, the effectiveness and safety of combining RIF with ATRA in a larger population of pediatric APL patients remains undocumented. Additionally, there is variability in the oral timing and dosage of RIF in different studies, which should be standardized.
We conducted a multicenter clinical trial (ChiCTR-OIC-16010014) in China. Individuals newly diagnosed with APL were categorized into two risk groups based on their initial white blood cell (WBC) count. Those with a WBC count exceeding 5×10^9/L received hydroxycarbamide at a dosage ranging from 20 to 50 mg/kg per day until their WBC levels dropped to 10×10^9/L or lower. The primary outcomes assessed were event-free survival (EFS) and overall survival (OS) over six years.
We recruited 200 patients diagnosed with APL. After a median follow-up time of 43.2 months, it was observed that the six-year OS rate was 100% in the low-risk cohort and 97.6% in the high-risk cohort. The six-year EFS rate was found to be 98.3% in the low-risk group and 97.6% in the high-risk group. It was observed that plasma levels of arsenic remained stable after the administration of RIF at a dosage of 60 mg/kg/d for seven days and returned to baseline levels within fourteen days after discontinuation of RIF administration. Furthermore, treatment strategies aimed at controlling WBC counts to maintain levels at or below 30×10^9/L were found to reduce the incidence of induced differentiation syndrome (DS) or alleviate its associated symptoms.
In conclusion, The CCCG-APL-2017 regimen, which combines RIF with ATRA, demonstrates both efficacy and safety in treating children with APL. A dosage of 60mg/kg/d of RIF is considered sufficient for the management of pediatric APL.