bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics and outcomes of patients with chondroblastoma undergoing surgery with various adjuvant procedures: a retrospective study of 59 cases
Authors: Hirozane Toru , Sekita Tetsuya , Kobayashi Eisuke , Mori Tomoaki , Asano Naofumi , Udaka Toru , Tajima Takashi , Nakagawa Rumi , Kikuta Kazutaka , Yoshiyama Akira , Morioka Hideo , Watanabe Itsuo , Anazawa Ukei , Susa Michiro , Horiuchi Keisuke , Suzuki Yoshihisa , Morii Takeshi , Nakayama Robert 
Published: January 2025

Abstract

Background
Chondroblastoma is classified as a benign bone tumor. However, postoperative local recurrence remains a concern. We analyzed the factors contributing to chondroblastoma local recurrence and the clinical challenges associated with treating these patients.

Methods
This retrospective study examined 59 patients followed up at our hospitals for ≥ 1 year after surgery during 1990–2020. The most common lesion site was the epiphyses of long bones (42 cases, 71%), including the femur, tibia, and humerus. Curettage was performed in 57 cases; 2 cases with an iliac lesion underwent resection. The median postoperative follow-up period was 47 months. Clinical features of chondroblastoma were retrospectively investigated, and local recurrence and postoperative functional outcomes were assessed.

Results
Local recurrence occurred in 9% (5/57) of patients after curettage but not in the resected cases. The median time to local recurrence was 14 months. The local recurrence-free survival (LRFS) rate for all patients was 92.7% at 2 years and 88.3% at 5 years. All patients with local recurrence were aged < 17 years at the time of surgery. Local recurrence was observed in the proximal humerus in two cases and the calcaneus, acetabulum, and distal femur in one case each. None of the adjuvant procedures (high-speed burr, ablation, bone replacement materials, and preoperative denosumab) helped reduce local recurrence risk (P > 0.05). Trends toward fewer local recurrences were observed in the group treated using the high-speed burr and in the group not treated using bone replacement materials. Among the groups treated with bone replacement materials, artificial bone achieved the best LRFS rate, followed by allograft and autograft. At the final follow-up, the mean Musculoskeletal Tumor Society score was 29.8 (range: 25–30), indicating excellent postoperative functional outcomes. Joint degeneration was observed in five patients. Patients with local recurrence had a high degree of disability and joint deformity (P < 0.05). Two patients received preoperative denosumab and neither experienced local recurrence nor functional impairments.

Conclusions
Good oncological and functional outcomes were achieved. Age < 17 years was associated with a high risk of local recurrence after curettage (P = 0.0198). Patients with local recurrence exhibited poorer functional outcomes. High-speed burr may help reduce the recurrence risk. If bone grafts are necessary, materials with low biocompatibility, including artificial bone, may be optimal. Managing patients with chondroblastoma should encompass curative and functional aspects.
Health economics assessment of statin therapy initiation thresholds for atherosclerosis prevention in China: a cost-effectiveness analysis
Authors: Feng Tianyu , Zhang Xiaolin , Xu Jiaying , Gao Shang , Yu Xihe 
Published: January 2025

Abstract

Background
Recent updates to the Chinese guidelines for dyslipidemia management have reduced the 10-year risk threshold for starting statins in the primary prevention of atherosclerotic heart disease. This study aims to evaluate the potential negative effects of different statin initiation thresholds on diabetes risk in the Chinese population, while also analyzing their health economic implications.

Methods
I We developed a microsimulation model based on event probabilities to assess the cost-effectiveness of statin therapy. The model utilized the China-PAR prediction tool for ASCVD risk and incorporated data from a nationally representative survey and published meta-analyses of middle-aged and elderly Chinese populations. Four strategies were evaluated: a 7.5% 10-year risk threshold, the current guideline strategy, and a 15% threshold. For each strategy, we calculated the incremental cost per quality-adjusted life year (QALY) to gain insights into the economic impact of each approach.

Result
The incremental cost per QALY for the 10% 10-year risk threshold strategy, compared to the untreated, was $52,218.75. The incremental cost per QALY for the guideline strategy, compared to the 7.5% 10-year risk threshold strategy, was $464,614.36. These results were robust in most sensitivity analyses.

Conclusion
Maintaining the recommended thresholds outlined in the current guidelines for the management of dyslipidemia may represent a cost-effective option for China at present. Variations in statin prices and the risk of statin-induced diabetes have significant impacts on the cost-effectiveness outcomes.
Performance analysis of Leica Biosystems p16 monoclonal antibody in oropharyngeal squamous cell carcinoma
Authors: Thavaraj Selvam , Robinson Max , Dayal Shubham , Bowen Claire 
Published: January 2025

Abstract

Background
Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer death globally, with newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC) cases rising to 54,000 in the US alone in the year 2022. Recently, human papilloma virus (HPV) infection was more prevalent in OPSCC patients than the traditionally known carcinogens such as tobacco or alcohol. HPV 16 is the most common causative HPV strain, which is found in 5–10% of HNSCC patients. HPV 16’s E6 and E7 oncoproteins bind and inactivate p53 and retinoblastoma (Rb) tumor-suppressing genes. This causes aberrant over-expression of the cell cycle inhibitor gene, p16, leading to tumorigenesis. Leica Biosystems (LBS) has developed a p16 antibody (6H12 clone) for qualitatively identifying the p16 protein in formalin-fixed paraffin-embedded (FFPE) tissue by immunohistochemical staining. This method comparison study tested the concordance rates between ready-to-use (RTU) LBS p16/LBS RTU p16 antibody and Roche Tissue Diagnostics (RTD) CINtec p16 Histology immunohistochemical (IHC) assays by measuring overall agreement (OA), average positive agreement (APA), and average negative agreement (ANA) rates in 170 OPSCC FFPE cases. Interobserver agreement of the 2 assays and LBS RTU p16 comparison with the standard HPV molecular assays (DNA ISH and PCR) were also assessed.

Methods
One hundred and seventy (170) unique oropharyngeal cancer cases were stained for qualitative analysis by the LBS p16 antibody on BOND III. This assay was compared to Ventana’s RTD E6H4 (CINtec) clone on Benchmark XT. A stained core was considered p16 positive if the Histoscore (H score) was ≥ 140 and negative if H < 140.

Results
Across the pathologists, the agreement rate between the 2 assays ranged from OA, 98.7 – 98.8%, ANA, 98.8 -98.9%, and APA, 98.6%. For LBS RTU p16, the interobserver agreement was OA, 98.7%, ANA, 98.8%, and APA, 98.6%; while for RTD CINtec p16 assay, the concordance was OA, 98.7%, ANA, 98.8% and APA, 98.6%. In comparison to the HPV molecular testing, DNA ISH, and PCR, across pathologists, LBS p16 clone (LBS RTU p16) showed a concordance rate of 85.8-86.9% and 87.6-88.8%, respectively.

Conclusion
LBS p16 monoclonal antibody demonstrated high concordance with CINtec p16 IHC assay across all the endpoints, suggesting a potential use of LBS RTU p16 clone in detecting p16 protein in oropharyngeal cancer cases.
Surgery impairs glymphatic activity and cognitive function in aged mice
Authors: Chen Kai , Du Xingyu , Chao Melissa A. , Xie Zhongcong , Yang Guang 
Published: January 2025

Abstract
Delirium is a common complication in elderly surgical patients and is associated with an increased risk of dementia. Although advanced age is a major risk factor, the mechanisms underlying postoperative delirium remain poorly understood. The glymphatic system, a brain-wide network of perivascular pathways, facilitates cerebrospinal fluid (CSF) flow and supports the clearance of metabolic waste. Impairments in glymphatic function have been observed in aging brains and various neurodegenerative conditions. Using in vivo two-photon imaging, we examined the effects of surgery (laparotomy) on glymphatic function in adult (6 months) and aged (18 months) mice 24 h post-surgery. In adult mice, CSF tracer entry into the brain parenchyma along periarteriolar spaces occurred rapidly following intracisternal tracer injection, with no significant differences between sham and surgery groups. In contrast, aged mice exhibited delayed tracer influx, with further impairments observed in the surgery group compared to sham controls. This glymphatic dysfunction correlated with poorer T-maze performance in aged mice. These findings suggest that surgery exacerbates glymphatic impairment in aging brains, potentially hindering brain waste clearance and contributing to postoperative delirium.
GPR137-RAB8A activation promotes ovarian cancer development via the Hedgehog pathway
Authors: Tang Chao , Li Lin , Zhu Chongying , Xu Qiang , An Zihao , Xu Shouying , Lin Chao 
Published: January 2025

Abstract

Background
Ovarian cancer (OC) progression is one of the commonest cause of female cancer death. While treatments in clinic includes primary surgery and targeted chemotherapy, curative and survival trends in OC have not significantly improved. Thus, further investigation of the mechanisms regarding OC carcinogenesis and discovery of novel targets is of great importance.

Methods
Human ovarian tissue specimens, RNA sequencing, GEPIA database and bioinformatics analyses were used to analyze the gene correlation, and to identify and validate potential downstream candidates. The biological effects of GPR137-RAB8A-Hedgehog(HH) were investigated using in vitro and in vivo models and methods including qRT-PCR, RNA stability assay, RNA immunoprecipitation assay, GLI-luciferase reporter assay, nucleo-cytoplasmic separation assay, membrane-cytoplasmic separation assay, western blot, co-immunoprecipitation, immunofluorescence staining, cell counting kit-8 assay, wound healing assay, matrigel invasion assay, colony formation assay, xenografts assay, in situ transplantation tumor model of ovarian cancer in nude mice, and immunohistochemistry staining.

Results
GPR137 expression was significantly higher in collected clinical OC tissues, compared with the adjacent normal tissues. Consistently, suppression of GPR137 inhibited human SK-OV-3 and A2780 OC cell proliferation, migration, invasion, and colony formation, whereas overexpression of GPR137 in human OC HO8910 cell exerted the opposite effects on cell biological behaviors. Mechanistically, RAB8A was identified as a downstream target of GPR137, and GPR137 promotes RAB8A expression by promoting RAB8A mRNA stability. By RNA-sequencing and experiments in vitro using multiple ovarian cancer cell models as well as in vivo using subcutaneous xenografts assay and in situ transplantation ovarian cancer model in nude mice, we further demonstrated that RAB8A positively mediated OC progression through activating HH signaling pathway by disassociating the protein–protein complex formation of GLI and SuFu (Suppressor of Fused), which reciprocally enhanced GPR137 activity, forming a regulation loop between HH signaling and GPR137.

Conclusions
Collectively, this study depicts the role of GPR137-RAB8A-HH cascade in the development of OC, deepening our understanding of tumor biomechanics regarding OC progression and providing novel targets for OC therapy in future.
Prediction of pathological complete response after neoadjuvant chemotherapy for HER2-negative breast cancer patients with routine immunohistochemical markers
Authors: Häberle Lothar , Erber Ramona , Gass Paul , Hein Alexander , Niklos Melitta , Volz Bernhard , Hack Carolin C. , Schulz-Wendtland Rüdiger , Huebner Hanna , Goossens Chloë , Christgen Matthias , Dörk Thilo , Park-Simon Tjoung-Won , Schneeweiss Andreas , Untch Michael , Nekljudova Valentina , Loibl Sibylle , Hartmann Arndt , Beckmann Matthias W. , Fasching Peter A. 
Published: January 2025

Abstract

Background
Pathological complete response (pCR) is an established surrogate marker for prognosis in patients with breast cancer (BC) after neoadjuvant chemotherapy. Individualized pCR prediction based on clinical information available at biopsy, particularly immunohistochemical (IHC) markers, may help identify patients who could benefit from preoperative chemotherapy.

Methods
Data from patients with HER2-negative BC who underwent neoadjuvant chemotherapy from 2002 to 2020 (n = 1166) were used to develop multivariable prediction models to estimate the probability of pCR (pCR-prob). The most precise model identified using cross-validation was implemented in an online calculator and a nomogram. Associations among pCR-prob, prognostic IHC3 distant recurrence and disease-free survival were studied using Cox regression and Kaplan–Meier analyses. The model’s utility was further evaluated in independent external validation cohorts.

Results
273 patients (23.4%) achieved a pCR. The most precise model had across-validated area under the curve (AUC) of 0.84, sensitivity of 0.82, and specificity of 0.71. External validation yielded AUCs between 0.75 (95% CI, 0.70–0.81) and 0.83 (95% CI, 0.78–0.87). The higher the pCR-prob, the greater the prognostic impact of pCR status (presence/absence): hazard ratios decreased from 0.55 (95% central range, 0.07–1.77) at 0% to 0.20 (0.11–0.31) at 50% pCR-prob. Combining pCR-prob and IHC3 score further improved the precision of disease-free survival prognosis.

Conclusions
A pCR prediction model for neoadjuvant therapy decision-making was established. Combining pCR and recurrence prediction allows identification of not only patients who benefit most from neoadjuvant chemotherapy, but also patients with a very unfavorable prognosis for whom alternative treatment strategies should be considered.
Prevalence and drivers of malaria infection among asymptomatic and symptomatic community members in five regions with varying transmission intensity in mainland Tanzania
Authors: Chacha Gervas A. , Francis Filbert , Mandai Salehe S. , Seth Misago D. , Madebe Rashid A. , Challe Daniel P. , Petro Daniel A. , Pereus Dativa , Moshi Ramadhani , Budodo Rule , Kisambale Angelina J. , Mbwambo Ruth B. , Bakari Catherine , Aaron Sijenunu , Mbwambo Daniel , Kajange Stella , Lazaro Samuel , Kapologwe Ntuli , Mandara Celine I. , Ishengoma Deus S. 
Published: January 2025

Abstract

Background
Despite implementation of effective interventions in the past two decades, malaria is still a major public health problem in Tanzania. This study assessed the prevalence and drivers of malaria infections among symptomatic and asymptomatic members of selected communities from five regions with varying endemicity in mainland Tanzania.

Methods
A cross-sectional community survey was conducted in five districts, including one district/region in Kagera, Kigoma, Njombe, Ruvuma and Tanga from July to August 2023. Participants aged ≥ 6 months were recruited and tested using rapid diagnostic tests (RDTs). Demographic, anthropometric, clinical, parasitological, type of house, and socio-economic status (SES) data were captured using structured questionnaires. Associations between parasite prevalence and potential drivers were determined by logistic regression, and the results were presented as crude (cOR) and adjusted odds ratios (aOR), with 95% confidence intervals (CIs).

Results
Among 10,228 individuals tested, 3515 (34.4%) had positive results by RDTs. The prevalence of malaria varied from 21.6% in Tanga to 44.4% in Kagera, and from 14.4% to 68.5% among the different villages (P < 0.001). The odds of malaria infections were higher in males (aOR = 1.32, 95% CI 1.19–1.48, P < 0.001), under-fives (aOR = 2.02, 95% CI 1.74–2.40, P < 0.001), schoolchildren [aged 5–9 years (aOR = 3.23, 95% CI 1.19–1.48, P < 0.001) and 10–14 years (aOR = 3.53, 95% CI 3.03–4.11, P < 0.001)], and non-bednet users (aOR = 1.49, 95% CI 1.29–1.72, P < 0.001). Individuals from households with low SES (aOR = 1.40, 95% CI 1.16–1.69, P < 0.001), or living in houses with open windows (aOR = 1.24, 95% CI 1.06–1.45, P < 0.001) and/or holes on the walls (aOR = 1.43, 95% CI 1.14–1.81, P < 0.001) also had higher odds.

Conclusions
Malaria prevalence varied widely across regions and villages, and the odds of infections were higher in males, schoolchildren, non-bednet users, and individuals with low SES or living in houses with open windows and/or holes on the walls. The identified vulnerable groups and hotspots should be targeted with specific interventions to reduce the disease burden and support the ongoing malaria elimination efforts in Tanzania.

Graphical Abstract
Stability of a delayed prey–predator model with fear, stochastic effects and Beddington–DeAngelis functional response
Authors: Zhao Jinxing , Shao Yuanfu 
Published: January 2025

Abstract
In view of the importance of predator-dependent functional response and fear of prey induced by powerful predators, we construct a delayed prey–predator model with fear and Beddington–DeAngelis functional response. The existence, uniqueness, and global asymptotic stability of equilibrium points are investigated and some criteria are established. Next, Hopf bifurcation analysis is executed, and the critical values of such bifurcation parameters as fear and delay for the determinate system are obtained. Then we extend it to a random environment and study the boundedness of expectation of solutions and the global asymptotic stability. Finally, the main findings are validated by numerical examples. It is worth noting that the specific influences of fear by predator, time delay, and white noise are explored numerically. Simulation figures intuitively exhibit that fear, delay, and white noise bring serious influences on the stability of the system. Fear from predator leads to a lower equilibrium state of prey and predator, and it can change the system stability from unstable to stable after exceeding a certain critical value. The time delay has a significant impact on the system stability by producing Hopf bifurcations accompanied by limit cycles, and even lead to multiple stabilities. Larger white noise can change the system stability from stable to unstable.
Up-flow anaerobic sludge blanket bioreactor for the production of carboxylates: effect of inocula on process performance and microbial communities
Authors: Lago Adrián , Greses Silvia , Moreno Inés , González-Fernández Cristina 
Published: January 2025

Abstract
This research investigated the acidogenic fermentation (AF) of sugar cane molasses in an up-flow anaerobic sludge blanket (UASB) reactor for the production of carboxylates. The first step was to assess the optimum process temperature (25, 35 or 55 ºC) using two different granular inocula, one from a brewery company (BGS) and other from a paper plant company (PGS). These experiments determined that the most suitable temperature for carboxylates production was 25 ºC, obtaining higher bioconversions (27.3 ± 0.3% using PGS and 39.2 ± 0.2% using BGS), despite the low pH value recorded (4.0-4.2). Then, both inocula were tested in UASB reactors. As a consequence of the operational conditions (25 ºC, pH = 5.5-6, organic loading rate (OLR) = 3 gCOD·L-1·d-1 and hydraulic retention time (HRT) = 10 d), the microbial communities changed from those typical for biogas production to those specialised in the production of volatile fatty acids (VFAs). Indeed, the highest bioconversion efficiency (70.1%) was obtained with BGS, where uncultured Eubacteriaceae family microorganisms (56.0%) prevailed, enhancing the production of butyric acid (59.5 ± 2.4%w/w). Consequently, this inoculum was used to further identify the OLR threshold that should not be exceeded to attain optimal carboxylates production. OLR of 6 gCOD·L-1·d-1 resulted in a decrease in bioconversion efficiency (59.5%). The VFAs pool was dominated by butyric acid (63.0 ± 1.4%w/w at an OLR of 4.5 gCOD·L-1·d-1 and 52.8 ± 2.2%w/w at 6 gCOD·L-1·d-1). The microbial community became even more specialised, increasing the presence of Firmicutes and Actinobacteriota phyla, proving that the imposed conditions favoured the production of VFAs when operating semicontinuously fed UASB reactors.
An animal model of severe acute respiratory distress syndrome for translational research
Authors: Chu Kuo-An , Lai Chia-Yu , Chen Yu-Hui , Kuo Fu-Hsien , Chen I.-Yuan , Jiang You-Cheng , Liu Ya-Ling , Ko Tsui-Ling , Fu Yu-Show 
Published: January 2025

Abstract

Background
Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine. Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of transplanted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.

Results
In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within seven days after the injury, we found that arterial blood oxygen saturation (SpO2) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2) amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A histological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.

Conclusions
This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.