bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the Monocyte Subpopulations and M1/M2 Macrophage Ratio in Concentrated Bone Marrow Aspirate
Authors: Butler James J. , Dankert John F. , Keller Laura E. , Azam Mohammad T. , Dahmen Jari , Kerkhoffs Gino M. M. J. , Kennedy John G. 
Published: December 2024

Objective The purpose of this study was to determine the M1/M2 macrophage ratio in concentrated bone marrow aspirate (cBMA) in patients undergoing surgical intervention augmented with cBMA for osteochondral lesions of the talus (OLTs). Design Samples of peripheral blood (PB), bone marrow aspirate (BMA), and cBMA were collected during the procedure. The samples were analyzed by automated cell counting and multicolor fluorescence-activated cell sorting with specific antibodies recognizing monocytes (CD14+ CD16+) and the M1 (CD86+) and M2 (CD163+CD206+) populations within that monocyte population. Cytokine concentrations within the samples were evaluated with enzyme-linked immunosorbent assay (ELISA). The composition of cBMA was compared between 2 commercially available BMA concentration systems. Results Thirty-eight patients with a mean age of 43.2 ± 10.1 years old undergoing a surgical procedure for the treatment of OLTs involving the use of cBMA were included. cBMA had a mean fold increase of 4.7 for all white blood cells, 6.1 for monocytes, 7.9 for lymphocytes, 2.4 for neutrophils, and 9.6 for platelets when compared to BMA. The mean M1/M2 ratio for PB, BMA, and cBMA was 15.2 ± 12.0, 20.8 ± 13.3, and 22.1 ± 16.0, respectively. There was a statistically significant higher concentration of interleukin-1 receptor antagonist (IL-1Ra) in the cBMA sample (8243.3 ± 14,837.4 pg/mL) compared to both BMA (3143.0 ± 2218.5 pg/mL) and PB (1847.5 ± 1520.4 pg/mL) samples. The IL-1Ra/IL-1β ratio for PB, BMA, and cBMA was 790.6 ± 581.9, 764.7 ± 675.2, and 235.7 ± 192.1, respectively. There was no difference in the cBMA M1/M2 ratio (19.0 ± 11.1 vs 24.0 ± 18.3) between the Magellan (Isto Biologics, Hopkinton, Massachusetts) and Angel systems (Arthrex Inc, Naples, Florida). Conclusion This prospective study found that the M1/M2 ratio in cBMA was 22.1 ± 16.0, with significant patient to patient variation observed. Overall, there was no statistically significant difference in the M1/M2 ratio across PB, BMA, and cBMA samples. This is the first study to characterize the macrophage subpopulation within cBMA, which may have significant clinical implications in future studies.
Cryoablation-induced neutrophil Ca2+ elevation and NET formation exacerbate immune escape in colorectal cancer liver metastasis
Authors: Tan Hongtong , Jiang Yiquan , Shen Lujun , Nuerhashi Gulijiayina , Wen Chunyong , Gu Ling , Wang Yujia , Qi Han , Cao Fei , Huang Tao , Liu Ying , Xie Weining , Deng Wuguo , Fan Weijun 
Published: December 2024

Abstract
Background
Liver metastasis poses a significant barrier to effective immunotherapy in patients with colorectal cancer. Cryoablation has emerged as a vital supplementary therapeutic approach for these patients. However, its impact on the tumor microenvironment following the ablation of liver metastases remains unclear.

Methods
We acquired multi-omics time-series data at 1 day, 5 days, and 14 days post-cryoablation, based on tumor and peripheral blood samples from clinical patients, cell co-culture models, and a liver metastases mouse model built on the MC38 cell line in C57BL/6 J mice. This dataset included single-cell transcriptomic sequencing, bulk tissue transcriptomic sequencing, 4D-Label-Free proteomics, flow cytometry data, western blot data, and histological immunofluorescence staining of pathological specimens.

Results
We found that a neutrophil-related inflammatory state persisted for at least 14 days post-cryoablation. During this period, neutrophils underwent phenotypic changes, shifting from the N1 to the N2 type. Cryoablation also caused a significant increase in intracellular Ca2+ concentration in neutrophils, which triggered the formation of PAD4-dependent neutrophil extracellular traps (NETs), further promoting immune evasion. Moreover, animal studies demonstrated that depleting or inhibiting the CXCL2-CXCR2 signaling axis within neutrophils, or degrading NETs, could effectively restore the host’s anti-tumor immune response.

Conclusions
These findings underscore the critical role of neutrophils and their NETs in immune escape following cryoablation. Targeting the CXCL2-CXCR2-Ca2+-PAD4 axis could enhance the therapeutic response to PD-1 antibodies, providing a potential strategy to improve treatment outcomes for colorectal cancer with liver metastases.

Graphical Abstract
Greenhouse gas and volatile organic compound emissions of additive-treated whole-plant maize silage: part B—aerobic storage period and carbon footprint of silage additive use
Authors: Deeken Hauke Ferdinand , Maack Gerd-Christian , Trimborn Manfred , Büscher Wolfgang 
Published: December 2024

Abstract
Background
Silage emits climate- and environment-relevant gases during anaerobic fermentation and aerobic feed-out periods. This trial should determine the unknown CO2, methane, nitrous oxide, ethanol and ethyl acetate emissions of constant maize silage over both periods. The results will be published in two consecutive articles (Part A: anaerobic fermentation period; Part B: aerobic storage period).

Methods
Three silage treatments were observed (n = 4): The untreated control (CON) was compared to the chemical additive treatment (CHE; 0.5 g sodium benzoate and 0.3 g potassium sorbate per kg fresh matter) and the biological additive treatment (BIO; 1 × 108 colony-forming units Lentilactobacillus buchneri and 1 × 107 colony-forming units Lactiplantibacillus plantarum per kg fresh matter). During the two aerobic emission measurement periods (AEMP), the silos were ventilated mechanically to supply 2–6 (L air) min–1 to the two faces of the material (150.6 kg dry matter m–3). AEMP1 (duration 14 days) began on ensiling day 30, AEMP2 (19 days) on day 135.

Results
In AEMP1, aerobic stability differed among the treatments (p < 0.05): 5.17 ± 0.75 days for CON, 6.33 ± 0.15 days for BIO, and 7.33 ± 0.57 days for CHE. In AEMP2, only CON showed a temperature increase of 2 K above ambient temperature after 7.75 ± 0.31 days. BIO and CHE indicated higher ethanol and ethyl acetate emission rates during the first period of the heating process. Furthermore, 20.0%–70.4% of ethanol and 169.0%–953.6% of ethyl acetate quantities present in the material at the silo opening emitted as gases.

Conclusion
Methane and nitrous oxide emissions during anaerobic fermentation exceeded the quantities during aerobic storage in all treatments. However, compared with those of crop production, the total climate-relevant CO2eq emissions are small. Microbial respiration during heating leads to climate-neutral CO2 emissions and dry matter losses. Minimising these losses is promising for mitigating climate-relevant emissions directly during silage storage and indirectly during crop production since less forage input is needed. Thus, silage additives can help improve the silage carbon footprint by improving aerobic stability and silage deterioration.

Graphical Abstract
Morphometrics of human skulls and mandibles obtained from Southwestern Nigeria: implications in clinical manoeuvres
Authors: Femi-Akinlosotu Omowumi Moromoke , Igado Olumayowa Olawumi , Adeniji Kehinde Oluwaseyi 
Published: December 2024

Abstract
Background
Craniometric data can be useful in the estimation of sex, age, stature, and ethnicity. Despite Nigeria’s diverse and multifaceted demography, there is a dearth of information on detailed morphometry of specific features of the Nigerian cranium. This study sought to provide detailed descriptions of various dimensions on the Nigerian mandibular bone, nose, foramen magnum, and orbit for use in clinico-anatomical studies, dentistry, anthropology, and forensic medicine. Using 33 skulls and 17 mandibles, without gender bias, obtained from the departmental museum, 17 parameters were measured linearly on each mandible and thirty-six parameters on each skull using a digital Vernier calliper. Mean and standard deviation of data sets generated were analysed using t-test at p < 0.05.

Results
The distance between the cranial and caudal angles of the mandible was 3.48 ± 0.21 mm. The distance from the rostral point of the dental bone to the condylar, coronoid, and angular processes was 4.86 ± 0.25 mm, 2.64 ± 0.52 mm, and 3.72 ± 0.30 mm, respectively. The distance between the most medial points of the most rostral left & right mental foramina in the skulls was 4.51 ± 0.17 mm. The distance between the most medial points of the most rostral left & right mental foramina in the skulls was 4.51 ± 0.17 mm. Most orbit skull types were megaseme in nearly 61%, and orbital asymmetry was also observed. However, the right orbit (26.07 ± 2.106) was significantly higher (p < 0.0001) than left orbit (24.80 ± 1.850). The most common shape of the foramen magnum was the oval-like foramen (78%). The common nose types were platyrrhine in 50% and mesorrhine in 26%.

Conclusion
Insights from this study might provide practical reference information for mandibular and orbital reconstructive surgeries in clinical settings, skull classification in forensic science, and research purposes.
Association between three common genetic polymorphisms of xeroderma pigmentosum complementation group C (XPC) and susceptibility to opium dependency
Authors: Qasemian-Talgard Arghavan , Saadat Mostafa 
Published: December 2024

Abstract
Aim
To investigated the relationship between three common polymorphisms (rs2228000, rs2228001, and PAT) in xeroderma pigmentosum complementation group C (XPC) gene and susceptibility to opium dependence (OD).

Methods
A total of 143 (131 male, 12 female) opium dependent patients and 570 (515 male, 55 female) controls were comprised in this study. The controls and cases were sex and age-matched. The genotypes of the polymorphisms were determined by polymerase chain reaction using primers specific for each polymorphism. Statistical comparisons were performed with SPSS software (version 26) using odds ratios (OR), and their 95% confidence intervals (95% CI). Haplotype analysis was also performed using SNPAlyze(TM) version 6 software.

Results
There was no association between rs2228000 and the risk of OD in the statistical analyses. The risk of OD was associated with the other two variants. The pooled ID and DD genotypes of the PAT polymorphism significantly decreased the risk of OD (OR = 0.66, 95% CI: 0.44–0.98, p = 0.042). For the rs2228001 polymorphism, AC + AA was negatively correlated with the risk of OD (OR = 0.65, 95% CI: 0.44–0.97, p = 0.038).

Conclusion
The present findings propose that probably XPC is an appropriate candidate gene for susceptibility to opiate dependence.
Effects of steel fibers and carbon nanotubes on the flexural behavior of hybrid GFRP/steel reinforced concrete beams
Authors: Salman Amany , Hassan Ahmed , Ahmed H. I. 
Published: December 2024

Abstract
Background
Glass fiber-reinforced polymer (GFRP) bars offer a superior alternative to steel bars in concrete reinforcement but are associated with wider cracks and higher deformation rates. This study introduces a novel approach by combining steel fibers (SFs) and carbon nanotubes (CNTs) to address these drawbacks and enhance the performance of GFRP-reinforced concrete beams. The unique contribution of this study lies in the simultaneous use of SFs and CNTs, which has not been extensively investigated, particularly in the context of GFRP-reinforced concrete. The study involved testing three sets of nine specimens with different concrete mixtures and reinforcement forms.

Results
The results showed that adding 0.04% CNTs by cement weight and 0.6% SFs by volume fraction significantly improved the mechanical performance of GFRP and steel reinforced beams. GFRP reinforced beams with CNTs and SFs exhibited a reduction in crack width, a 20% increase in load-carrying capacity, and a 25% reduction in deflection compared to reference specimens. Scanning electron microscope analysis further revealed that CNTs effectively enhanced tensile load transfer, improving flexural behavior of the beams. The finite element analysis using ANSYS confirmed the experimental findings, highlighting the improved stress distribution in the modified concrete mixtures.

Conclusions
Incorporating SFs and CNTs in concrete significantly improves the mechanical performance of GFRP-reinforced beams, making them more durable and resilient. These findings suggest that the proposed approach can enhance the longevity and sustainability of concrete structures, particularly in dynamic load applications such as bridges and high-rise buildings. Further experimental and analytical studies are recommended to assess the practical implications and cost-effectiveness of these materials in large-scale construction projects.
Larotrectinib for Newly Diagnosed Infantile Fibrosarcoma and Other Pediatric
NTRK
Fusion–Positive Solid Tumors (Children's Oncology Group ADVL1823)
Authors: Laetsch Theodore W. , Voss Stephan , Ludwig Kathleen , Hall David , Barkauskas Donald A. , DuBois Steven G. , Ronan Joan , Rudzinski Erin R. , Memken Amanda , Robinson Krystal , Sorger Joel , Reid Joel M. , Bhatla Teena , Crompton Brian D. , Church Alanna J. , Fox Elizabeth , Weigel Brenda J. 
Published: December 2024

PURPOSE

The TRK inhibitor larotrectinib is US Food and Drug Administration approved for
NTRK
fusion–positive solid tumors that lack a satisfactory alternative or have progressed after treatment but has not been systematically studied as a frontline therapy with a defined duration of treatment. ADVL1823 evaluated larotrectinib in patients with newly diagnosed
NTRK
fusion–positive solid tumors with response-adapted duration of therapy and local control.

METHODS
Patients received larotrectinib twice daily in 28-day cycles for a predefined duration of treatment, ranging from 6 to 26 cycles depending on response to therapy and surgical resectability. The primary end point was the objective response rate (ORR) within six cycles in patients with infantile fibrosarcoma (IFS); patients with other histologic diagnoses were analyzed in a separate cohort. Secondary objectives included event-free survival (EFS) and overall survival (OS).

RESULTS
Thirty-three patients were enrolled: 18 with IFS and 15 with other solid tumors. The ORR within six cycles was 94% (17/18; 95% adjusted CI, 72.7 to 98.6) among children with IFS and 60% (9/15; 95% CI, 32.3 to 83.7) among children with other solid tumors. Six percent (2/33; 95% CI, 0.7 to 22.2) patients developed progressive disease while on therapy. Two-year EFS and OS among these groups were 82.2% (95% CI, 54.3 to 93.9) and 93.8% (95% CI, 63.2 to 99.1) for IFS and 80% (95% CI, 50.0 to 93.1) and 93.3% (95% CI, 61.3 to 99.0) for other solid tumors, respectively. Patients undergoing surgical resection of their tumor had prolonged EFS, with only 1 of 16 such patients experiencing disease progression. Four of 33 patients had dose-limiting toxicities.

CONCLUSION

Larotrectinib is highly active in patients with newly diagnosed
NTRK
fusion–positive solid tumors. Larotrectinib should be a frontline option for patients with IFS and other
NTRK
fusion–positive solid tumors. Local control with surgical resection remains important in the treatment of patients with IFS.
Evaluating the Economic Impact of Novel Oncology Drug Coverage Through Patient Assistance Programs
Authors: Samuel Vanessa Mara , Chan Megan , Huang Mina , Cheng Brooke , Huang Longlong , Sun Shaun Zheng , Jensen Chris , Dellamattia Shelley , Darbyshire Megan , Ko Jenny 
Published: December 2024

PURPOSE
Despite a universal public health care system, Canadian oncology patients often enroll in patient assistance programs (PAPs) to access oncology drugs that are awaiting funding decisions. Our multicenter study evaluated the pharmacoeconomic and clinical impact of PAPs for patients with cancer in British Columbia (BC).

METHODS
Eligible patients were diagnosed with cancer and enrolled in a PAP between January 2016 and December 2019 in three BC centers. Charts were reviewed for treatment details and survival data. For each drug indication, the hazard ratio from clinical trial data was multiplied by the median overall survival (mOS) or median progression-free survival (mPFS) of our cohort to estimate the mOS or mPFS if the drug was not received. Person life-years gained (PLYG) was the difference between the actual mOS or mPFS and the estimated mOS or mPFS if the drug was not received. Incremental cost-effectiveness ratios and drug costs were obtained from the Canadian Agency for Drugs and Technologies in Health. A total economic value of quality-adjusted life year (QALY) gained for each cohort was calculated and compared with the cost of drugs associated with the gain.

RESULTS
Our cohort consisted of 1,025 patients who accessed 40 oncology drugs via PAP. The median time from Health Canada approval to provincial funding was 2.04 years. In the first PAP exposure group (N = 1,025), median PLYG was 0.38 years for OS and 0.80 years for PFS. The total estimated economic value of QALY gained was $83,068,819.32, with total drug costs of $97,026.661.44.

CONCLUSION
PAPs were involved in covering up to $100 million in costs to bridge gaps between regulatory approval and public funding. Economic value and PLYG gained from PAPs are substantial.
Initiation of a Pediatric Movement Clinic in an Urban Setting
Authors: Burton Monique S. 
Published: December 2024

Abstract
Physical activity is an essential component to overall health and wellness. Disparities and barriers to equitable access to physical activity exist and are more common in urban, under resourced and minority communities. Health care providers play an essential role in supporting patients to reach ideal physical activity goals. Movement Clinic was established to address these concerns and work toward optimal wellness for all patients.
Driving after Concussion: Symptom Clusters and Neurocognition Uniquely Relate to Post-Concussion Driving Performance
Authors: Hashida Kumiko , Drattell Julia , Devos Hannes , Gore Russell , Lynall Robert , Schmidt Julianne 
Published: December 2024

ABSTRACT

Purpose
To identify clinical concussion assessment outcomes that uniquely capture simulated driving performance among acutely concussed individuals, relative to controls.

Methods
Cross-sectional design. Twenty-eight college students within 72-hours of concussion and 46 non-concussed controls participated in the study. We collected the following clinical concussion assessment outcomes: 4 concussion symptom clusters, 7 computerized neurocognitive domain scores, Standardized Assessment of Concussion (SAC) total score, Balance Error Scoring System total score, and tandem gait completion time. The following simulated driving outcomes were included (count): total collisions, speed exceedances, centerline crossings, and road edge excursions. We used separate generalized linear mixed regression models fit using a Poisson distribution with group, assessment, and interaction effects.

Results
Higher migrainous symptoms (p < 0.001), cognitive-fatigue symptoms (p = 0.041), poorer visual memory (p = 0.015), and slower reaction time (p = 0.023) in concussion group were associated with higher risk of committing speed exceedances, relative to controls. Conversely, better performance on the continuous performance test (p = 0.046) and SAC (p = 0.045) in concussion group were associated with higher risk of committing speed exceedances relative to controls. Poorer performance on psychomotor speed (p = 0.001), reaction time (p = 0.031), cognitive flexibility (p = 0.004), and executive function (p = 0.003) were associated with higher risk of committing centerline crossings in concussion group, relative to controls. Conversely, better performance on the continuous performance test (p = 0.035) and higher affective symptoms (p = 0.013) were associated with higher risk of committing centerline crossings and road edge excursions, respectively. relative to controls.

Conclusions
Our results highlight key symptom clusters and computerized neurocognitive outcomes that uniquely inform poorer simulated driving performance in acutely concussed individuals. Symptom clusters and computerized neurocognitive function might be helpful when discussing with patients about return to driving decisions post-concussion.
Pathophysiology, Diagnosis and Treatment of Tinnitus - a literature review
Authors: Piekarska Martyna , Dąbek Katarzyna , Ochwat Michał , Sudoł Maria , Mierzwa Gabriela , Kajtel Aleksandra , Skowronek Anna 
Published: December 2024

Introduction and purpose
Primary tinnitus involves the perception of various types of sounds, usually without the presence of an external or internal stimulus (we then speak of primary tinnitus). Secondary tinnitus is rare, but should be ruled out at the beginning of the diagnostic process, as it can result from a serious disease. The issue of ear noise is a widespread problem in primary care. The purpose of our article was to summarize information on tinnitus, its risk factors, pathophysiology, diagnosis and treatment.

Materials and methods
To write this article, databases such as PubMed and Google Scholar were searched using the following terms: tinnitus, tinnitus treatment, tinnitus cognitive behavioral therapy.

Description of the state of knowledge
There are many mechanisms that can lead to tinnitus. Since they often coexist with hearing loss, tinnitus is thought to be a response to sensory deprivation. In diagnosis, it is very important to take a thorough medical history to distinguish primary from secondary tinnitus, which determines further management of the patient. Due to the truncated knowledge of the pathophysiology of tinnitus, there are no clear guidelines for the treatment of tinnitus. There are various therapeutic options available, such as cognitive-behavioral therapy, sound therapy, somatosensory therapy, neuromodulation and hypnosis. They improve patients' quality of life, however, reliable data confirming reductions in tinnitus intensity is often lacking.

Conclusions
Tinnitus is a commonly encountered condition. Although significant research has been conducted, our understanding, particularly of its pathophysiology, remains incomplete. This makes it difficult to develop effective treatment.