bluuebunny/crossref_metadata_2025_split huggingface dataset:
External validation and revision of the Lafontaine criteria for unstable distal radius fractures: a retrospective study
Authors: Dissaneewate Pornpanit , Thanavirun Phatklao , Tangjaroenpaisan Yanin , Dissaneewate Kantapon 
Published: February 2025

Abstract

Background
The Lafontaine criteria are the most commonly cited criteria for predicting unstable distal radius fractures. However, formal validation of the performance of these criteria remains limited. Therefore, we aimed to evaluate the Lafontaine criteria as a diagnostic prediction rule for distal radius fractures, assess the inter-rater reliability and predictive ability of various parameters for distal radius instability, and develop new criteria for fracture instability using reliable and highly predictive factors.

Methods
This retrospective study included 274 adult patients with acute distal radius fractures treated with closed reduction and immobilisation between January 2019 and December 2022. Patients who underwent immediate surgery, were lost to follow-up before 4 weeks, or had unacceptable alignment after reduction were excluded. The Lafontaine criteria were validated using the area under the receiver operating characteristic curve (AUROC). Criteria with an AUROC > 0.7 were considered acceptable. The criteria were updated using risk factors with stronger associations in the multivariable logistic regression analysis, and the inter-rater reliability of potential predictors was evaluated.

Results
The median age of the patients was 63 years; 78% were female. Redisplacement occurred in 39% of the cases. The AUROC for the Lafontaine criteria was 0.65 (95% confidence interval [CI] 0.57–0.74). Multivariable logistic regression showed that age 56–74 years (odds ratio [OR] 3.92, 95% CI 1.82–9.16, p < 0.001) age > 74 years (OR 6.34, 95% CI 2.66–16.2, p < 0.001), associated ulna fracture (OR 1.61, 95% CI 0.92–2.84, p = 0.10), and initial radial shortening > 3 mm (OR 5.78, 95% CI 3.11–11.2, p < 0.001) were the strongest predictive factors of fracture instability. These predictors demonstrated substantial inter-rater reliability, making them suitable for clinical use. Updating the model with these risk factors resulted in an AUROC of 0.74 (95% CI 0.66–0.82).

Conclusions
The performance of the Lafontaine criteria in discriminating unstable distal radius fractures was unacceptable in our study cohort. The updated criteria using age group (< 56 years, 56–74 years, and > 74 years), associated ulnar fractures, and initial radial shortening > 3 mm was found to have moderate discrimination; however, further research is warranted to improve the prediction and measurement reliability of fracture instability.
Genomic analysis of the SMN1 gene region in patients with clinically diagnosed spinal muscular atrophy: a retrospective observational study
Authors: Kato Tamaki , Yokomura Mamoru , Osawa Yutaka , Matsuo Kensuke , Kubo Yuji , Homma Taihei , Saito Kayoko 
Published: February 2025

Abstract

Background
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease. Most patients with SMA have a mutation in the survival motor neuron 1 (SMN1) gene on chromosome 5q. With current genetic testing, SMN1 copy number is determined; a diagnosis is reached when the copy number is zero. When the SMN1 copy number is 1, exons and intron/exon boundaries of the allele are examined for single-nucleotide variants (SNVs). Genetically undiagnosed cases of SMA exist when 2 copies of SMN1 exist or when a SNV is in the deep intron. Furthermore, SMN1 is highly homologous to SMN2; therefore, it is expected that many SNVs have not been elucidated.

Methods
This retrospective observational study conducted in Japan used pre-collected DNA samples from patients with clinically diagnosed SMA. Enrollment period was January 28, 2020 to September 30, 2021. SNV analysis of SMN1 (exon 1–8 and intron 1–7) was conducted by long-range polymerase chain reaction and next-generation sequencing.

Results
From 336 DNA samples collected from patients, 62 patient samples were included in the SNV analysis. Two patients have been genetically diagnosed (a heterozygous variant in intron 6 with 1 copy of SMN1; a homozygous missense mutation in exon 3 with 2 copies of SMN1). Three SNVs in intron 6, c.834+1506A>G (n = 9), c.834+1751G>A (n = 2), and c.835-367C>A (n = 5) were identified; all were numerically, and c.834+1506A>G and c.835-367C>A were significantly, more frequent in patients with 0 copies versus those with ≥ 1 copy of exon 7 in SMN1. We confirmed 3 hybrid SMN gene types in 5 patients that contained SMN2 gene sequence (aaTgg) flanked by upstream “t” and downstream “G” SMN1 sequence.

Conclusions
In this study of patients with clinically diagnosed SMA, 2 cases with genetic SMN types were identified that would not have been identified through current genetic testing, which examines SMN1 deletions only. Furthermore, for 1 patient with a homozygous SMN1 missense mutation, SMA was not suspected by the current copy number screening method. This study demonstrated the importance of performing full-length sequencing for clinically diagnosed SMA to complement current screening methods.

Trial registration: University Hospital Medical Information Network Clinical Trials Registry (Number: UMIN000040095).
VSIG4+ tumor-associated macrophages mediate neutrophil infiltration and impair antigen-specific immunity in aggressive cancers through epigenetic regulation of SPP1
Authors: Pan Zongfu , Chen Jinming , Xu Tong , Cai Anqi , Han Bing , Li Ying , Fang Ziwen , Yu Dingyi , Wang Shanshan , Zhou Junyu , Gong Yingying , Che Yulu , Zou Xiaozhou , Cheng Lei , Tan Zhuo , Ge Minghua , Huang Ping 
Published: February 2025

Abstract
V-set and immunoglobulin domain-containing 4 (VSIG4) positive tumor-associated macrophage (VSIG4+ TAM) is an immunosuppressive subpopulation newly identified in aggressive cancers. However, the mechanism how VSIG4+ TAMs mediate immune evasion in aggressive cancers have not been fully elucidated. In our study, we found targeting VSIG4+ TAMs by VSIG4 deficiency or blockade remarkably limited tumor growth and metastasis, especially those derived from anaplastic thyroid cancer (ATC) and pancreatic cancer, two extremely aggressive types. Moreover, the combination of VSIG4 blockade with a BRAF inhibitor synergistically enhanced anti-tumor activity in ATC-tumor bearing mice. VSIG4 deficiency recovered the antigen presentation (B2m, H2-k1, H2-d1) of TAMs and activated antigen-specific CD8+ T cells by promoting their in vivo proliferation and intratumoral infiltration. Notably, loss of VSIG4 in TAMs significantly reduced the production of lactate and histone H3 lysine 18 lactylation, resulting the decreased transcription of SPP1 mediated by STAT3, which collectively disrupted the cell-cell interactions between TAMs and neutrophils. Further combination of VSIG4 with SPP1 blockade synergistically boosted anti-tumor activity. Overall, our studies demonstrate the epigenetic regulation function of VSIG4 confers on TAMs an alternative pattern, beyond the checkpoint role of VSIG4, to shape the immunosuppressive tumor microenvironment and impair antigen-specific immunity against aggressive cancers.

Graphical abstract
Hospitalizations for bronchiolitis among infants before and after the SARS-CoV-2 pandemic: an area-based study of the Emilia-Romagna Region, Italy
Authors: Ballardini Elisa , Manfrini Marco , Fattori Silvia , Pellacani Elena , Ćosić Branislava , Gargano Giancarlo , Berardi Alberto 
Published: February 2025

Abstract

Background
Bronchiolitis is the most frequent lower respiratory tract infection and a leading cause of hospitalization in infants. Our aim was to assess the incidence and characteristics of bronchiolitis requiring hospital admission in an Italian region before and after the SARS-CoV-2 pandemic.

Methods
This area-based retrospective study analyses 4,396 hospital discharge records (HDR) of children under 1 year of age admitted with a diagnosis of bronchiolitis (ICD9-CM codes 466.11 and 466.19), in Emilia-Romagna (Italy) from January1st, 2018 to December 31th, 2021. Weighted t-testing and Z-testing was carried out.

Results
in the study period, 2–4% of infants were admitted for bronchiolitis (10% of all admissions under 1 year) and 59% of them were aged less than 90 days. After a significant decrease in 2020, bronchiolitis resurged in 2021, and Respiratory Syncytial Virus (RSV) cases reached 82%. RSV cases were more likely to undergo non-invasive ventilation (NIV), oxygen supplementation and to receive i.v. (intravenous) infusions. There was an overall increasing trend in NIV and oxygen supplementation, and a decreasing trend in chest X-rays.

Conclusions
This area-based study shows reduced hospital admissions due to bronchiolitis during the SARS-CoV-2 pandemic and a resurgence of RSV infection after the easing of preventive measures. We also provide information on length of stay and need for hospital treatments. These area-based information will be helpful in assessing the impact of future universal prevention measures.
The utilization of the multimodal immunotherapy for the opsoclonus–myoclonus syndrome can reduce relapses and permanent neurological sequelae
Authors: He Fang , Kessi Miriam , Zhang Ciliu , Peng Jing , Yin Fei , Yang Lifen 
Published: February 2025

Abstract

Background
There is no known effective treatment strategy to prevent relapses and avert permanent neurological sequelae in opsoclonus–myoclonus syndrome (OMS). To describe the treatment strategy that reduced relapses and led to remission of OMS without permanent neurological sequelae.

Methods
This cross-sectional study was conducted at the Department of Pediatrics, Xiangya Hospital, Central South University. Patients diagnosed with OMS from January 2014 to July 2022 were enrolled. Exposures included treatment with multimodal immunotherapy. Main outcomes and measures included the OMS severity grading scale and DQ/IQ scores. The clinical data was collected and analysed.

Results
Of the six recruited patients, three were (50.00%) males. The median age of onset was 15.50 months. Preceding manifestation was present in one patient and two cases had neuroblastoma. The mean duration from disease onset to the initiation of therapies was 1.86 months. The combinations of ≥ two therapies were used: combination of the intravenous immunoglobulin (IVIG) plus intravenous dexamethasone plus rituximab was used for three (50.00%) patients and the combination of the IVIG plus intravenous dexamethasone plus rituximab plus mycophenolate mofetil for one (16.67%) case. Besides, the combination of the intravenous methylprednisolone (IVMP, which was switched to intravenous dexamethasone later) plus rituximab was utilized for one (16.67%) case and the combination of the IVIG and IVMP for one (16.67%) patient. Total numbers of the therapies used comprised of dual therapy (33.33%), triple therapy (50.00%), and other multiple agents (16.67%). Besides, surgical resections were done for the cases with tumors. The disease course was monophasic for five cases and five cases achieved remission. OMS scores improved significantly at the end of follow up. Five (83.33%) patients did not have permanent neurological sequelae.

Conclusions
The combination of the intravenous dexamethasone plus IVIG plus rituximab for the OMS can reduce relapses and permanent neurological sequelae.
SpatialLeiden: spatially aware Leiden clustering
Authors: Müller-Bötticher Niklas , Sahay Shashwat , Eils Roland , Ishaque Naveed 
Published: February 2025

Abstract
Clustering can identify the natural structure that is inherent to measured data. For single-cell omics, clustering finds cells with similar molecular phenotype after which cell types are annotated. Leiden clustering is one of the algorithms of choice in the single-cell community. In the field of spatial omics, Leiden is often categorized as a “non-spatial” clustering method. However, we show that by integrating spatial information at various steps Leiden clustering is rendered into a computationally highly performant, spatially aware clustering method that compares well with state-of-the art spatial clustering algorithms.
Application of spectrophotometry in novel simultaneous dissolution profiling of a single pill triple therapy of amlodipine, perindopril and indapamide; whiteness evaluation
Authors: Soudi Aya T. 
Published: February 2025

Abstract
Simple, diverse univariate spectrophotometric methods were developed and validated for the determination of amlodipine besylate (AM), perindopril arginine (PE), and indapamide (ID). The first method involved direct measurement of AM absorbance at 365 nm within a concentration range of 2.00–40.00 µg/mL, where PE and ID exhibited no spectral interference. To eliminate the contribution of AM from the ternary mixture, its spectrum was divided by a reference spectrum of AM (12 µg/mL), followed by mathematical subtraction of the resulting constant. The spectrum was then multiplied by the AM divisor to yield a corrected spectrum of the PE and ID binary mixture, allowing their quantification. Various approaches were used to quantify both drugs, including measurement of their second (2DD) and first derivative (1DD) spectra at 231.30 nm and 251.00 nm, respectively. Additionally, the ratio difference (RD) technique and dual wavelength (DW) method were employed. The concentration ranges for PE and ID were 5.00–100.00 µg/mL and 1.00–20.00 µg/mL, respectively. Among these methods, the DW technique was the simplest, so it was chosen for dissolution monitoring of PE and ID. These methods were successfully applied to determine AM, PE, and ID in bulk powder, as well as in Triplixam® tablets, without interference from excipients and in different used dissolution media. The whiteness of the method was evaluated, demonstrating its excellent environmental, analytical and practical efficiency.
The tryptophan-aspartate (WD) repeat domain of bovine Coronin-1A promotes mycobacterial survival by inhibiting calcium signaling-mediated phagosome-lysosome fusion
Authors: Yang Jing , Li Zhunan , Li Aicong , Liu Yayi , Zhang Xinyan , Zhang Yong , Gao Yuanpeng 
Published: February 2025

Abstract
Bovine tuberculosis is a chronic consumptive zoonosis, causing significant economic losses and critical public health risks. Coronin-1A is a host cytoskeleton-associated protein that is crucial for understanding the inhibition of phagosome-lysosome fusion by Mycobacterium tuberculosis (M.tb) to evade host innate immune clearance. However, the involvement of bovine Coronin-1A (bCoronin-1A) in M.tb infection and whether it can be manipulated so as to enhance host resistance against bovine tuberculosis remains to be seen. Here, we explored the role of bCoronin-1A in phagosome-lysosome fusion in M.tb-infected macrophages. We found that bCoronin-1A was upregulated at both the transcriptional and protein levels following M.tb infection of embryonic bovine lung (EBL) cells. Notably, bCoronin-1A was recruited to M.tb-containing phagosomes where it hindered phagosome-lysosome fusion, leading to increased intracellular mycobacterial survival. Further investigation revealed that mycobacterial lipoamide dehydrogenase C (LpdC) interacted with a single tryptophan-aspartate (WD) unit within the WD repeat domain of bCoronin-1A to sequester it on the phagosomes. The WD repeat domain mediated a decrease in intracellular calcium levels, which reduced levels of calmodulin-dependent kinase II (CaMKII) and its activated forms, thereby inhibiting lysosomal delivery. Overall, our findings revealed that bCoronin-1A had a critical impact on mycobacterial survival in macrophages by inhibiting calcium-mediated phagosome-lysosome fusion. This suggests that targeting bCoronin-1A as a key factor influencing mycobacterial survival may be an effective breeding strategy to develop tuberculosis-resistant dairy cows.
Seroprevalence of brucellosis in camels and humans in the Al-Qassim region of Saudi Arabia and its implications for public health
Authors: Almuzaini Abdulaziz M. , Aljohani Abdullah S. M. , Alajaji Ahmed I. , Elbehiry Ayman , Abalkhail Adil , Almujaidel Abdulrahman , Aljarallah Sahar N. , Sherif Hazem R. , Marzouk Eman , Draz Abdelmaged A. 
Published: February 2025

Abstract
Brucellosis is a significant zoonotic disease caused by intracellular, gram-negative bacteria from the genus Brucella. Although camels are classified as secondary hosts for Brucella species, they are among the most susceptible and vulnerable animals to brucellosis, particularly Brucella abortus (B. abortus) and Brucella melitensis (B. melitensis). The present study aimed to investigate the epidemiology of camel brucellosis as a zoonotic disease by determining the seroprevalence of brucellosis in both camels and humans, assessing potential risk factors (e.g., age, size, and location), and conducting molecular characterization of Brucella spp. associated with abortion in camels. The Rose Bengal Test (RBT), Antigen Rapid Brucella Antibody Test (ARBT), indirect enzyme-linked immunosorbent assay (I-ELISA), and complement fixation test (CFT) were used to detect brucellosis in both camels and humans. Additionally, a molecular method using polymerase chain reaction was used as a confirmatory technique. A total of 625 camel serum samples and 100 human serum samples were collected in sterile vacuum tubes from various camel farms and individuals across different localities in the Al Qassim region. Additionally, samples from 10 confirmed Brucella-infected camels (including the uterus and supramammary lymph nodes) were analyzed. The results indicated that the overall prevalence of brucellosis in camel sera was 9.72%, as determined by RBT, and 8.16%, as determined by ARBT. In contrast, the overall prevalence of brucellosis in human sera from febrile patients was found to be 17% via RBT. Notably, 57.98% of camel sera that tested positive for Brucella antibodies via RBT were also positive according to I-ELISA and CFT. Furthermore, 42.1%, 70.58%, and 47.05% of human sera that were positive for Brucella antibodies as determined by RBT were also positive according to I-ELISA and CFT, respectively. The highest seropositivity for camel brucellosis was observed in female camels, particularly in the Unaizah area of the Qassim region and among the Homr breed. The prevalence of human brucellosis was highest among females and individuals who consumed raw milk. At the molecular level, B. melitensis biovar 3 was detected in the examined tissues. In conclusion, intervention measures are vital for reducing brucellosis in humans and camels. Public awareness campaigns should highlight the importance of protective clothing when handling aborted she-camels and the need to boil or pasteurize milk. Additionally, studies should differentiate between vaccinated and nonvaccinated camels, and standardizing serological tests for diagnosing brucellosis should be prioritized.
TOPBP1 as a potential predictive biomarker for enhanced combinatorial efficacy of olaparib and AZD6738 in PDAC
Authors: Tang Xiao-Mei , Shi Min-Min , Wang Jia-Cheng , Gu Yi-Jin , Dai Yu-Ting , Yang Qin-Xin , Liu Jia , Ren Ling-Jie , Liu Xin-Yun , Yang Chun , Ma Fang-Fang , Liu Ji-Bing , Yu Hong , Fu Da , Wang Yun-Feng 
Published: February 2025

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and often lethal malignancy, requiring the development of enhanced therapeutic approaches. The DNA damage response (DDR) pathway is frequently altered during PDAC development, leading to an increased occurrence of DNA damage. DNA topoisomerase II-binding protein 1 (TOPBP1) plays a supportive role in regulating the DDR pathway, and its overexpression has been linked to the tumorigenesis of various cancers. This study investigated the biological role of TOPBP1 in PDAC pathogenesis and evaluated its clinical relevance in guiding treatment regimens. We examined the relationship between TOPBP1 expression, DDR pathway modulation, and therapeutic response in PDAC cell lines, primary cells, and subcutaneous mouse models. We found that elevated TOPBP1 expression was positively correlated with increased histologic grade and reduced patient survival in PDAC. TOPBP1 knockdown increased the sensitivity of PDAC cells to olaparib treatment and improved therapeutic efficacy in both PDAC cell lines and subcutaneous mouse models. Combination treatment with olaparib and AZD6738 effectively induced P53-dependent apoptosis via inhibiting the ATR pathway and enhancing signaling through the ATM pathway, which significantly reduced the viability of pancreatic cell lines. Notably, this combination therapy was more effective in PDAC cell lines exhibiting high TOPBP1 expression, indicating that TOPBP1 may serve as a useful predictive biomarker. In conclusion, TOPBP1 is a potential marker for optimizing the olaparib and AZD6738 combination therapy in PDAC. This study highlights the clinical significance of TOPBP1 in the treatment of PDAC and emphasizes the potential implications for a broader population of patients.
Biochemical analysis of miR-217 and miR-532 in patients with fibromyalgia
Authors: Ayoub Shymaa E. , Ahmed Azza M. , Abdelwahed Mostafa Y. , Khalefa Abeer A. , Awaji Aeshah A. , Zekry Samer S. , Ibrahim Enas G. , Eid Hana M. , Elasmer Shimaa M. , Fares Reham 
Published: February 2025

Abstract
About 5% of the population suffers from fibromyalgia (FM), a chronic multi-symptom pain illness whose pathophysiology is still unknown. We aimed to be the first to investigate the possible association of sera levels of miR-217 and miR-532 in patients with fibromyalgia and correlate their expression levels to different clinical and biochemical disease criteria. This study included 80 participants who splitted into two groups: 40 fibromyalgia sufferers (12 male and 28 female), and 40 healthy volunteers (10 male and 30 female) who served as the control group. Venous blood samples were collected from all subjects. The miR-217 and miR-532 serum expressions were detected using quantitative real-time PCR (qRT-PCR). According to our data, the fold changes of miR-217 and miR-532 in fibromyalgia patients were significantly lower than in controls, for miR-217 (median = 0.1359, IQR: 0.038–0.287, P < 0.001) and miR-532 [median = 0.2199, IQR: (0.114–0.421), P < 0.001]. In addition, there was a significant negative relationship between Aspartate transaminase (AST) and both miR-217 and miR-532 (r = − 0.480, P = P < 0.001 r = − 0.462, P = P < 0.001), respectively. Serum miR-217 and miR-532 could serve as potential diagnostic biomarkers for fibromyalgia.