bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement in Clinical and Radiographic Outcomes After Isolated Realignment Surgery in Patients With Large Cystic Osteochondral Lesion of the Talar Shoulder and Concurrent Malalignment
Authors: Kim Jaeyoung , Yi Young , Lee Woo-Chun 
Published: April 2024

Background: Malalignment has been suggested as a predisposing factor for the development of osteochondral lesions of the talus (OLTs). Purpose: To evaluate the clinical and radiographic outcomes of realignment surgery in patients with a large cystic OLT of the talar shoulder and concurrent malalignment of the foot and ankle. Study Design: Case series; Level of evidence, 4. Methods: The authors reviewed consecutive patients with large cystic OLTs (diameter, >10 mm) of the talar shoulder and concurrent malalignment of the foot and ankle who underwent realignment surgery between September 2013 and April 2021. The type of realignment procedure was determined based on patient symptoms and findings on plain radiographs and weightbearing computed tomography. Clinical improvement was assessed using pre- and postoperative Foot Function Index (FFI) scores and the visual analog scale (VAS) for pain. The OLT location was categorized according to Raikin zone, and the OLT area and volume were measured and compared pre- and postoperatively. The comparative analysis was performed using the Wilcoxon signed-rank test. Results: In total, 27 ankles in 27 patients (mean age, 34.4 ± 11.9 years) were included in the analysis. There were 25 patients with a medial lesion (zone 4 [n = 19], zone 7 [n = 5], and zone 1 [n = 1]), and 2 patients with a lateral lesion (zone 6). Despite OLT location, patients’ symptoms varied; 15 (55.6%) patients reported both medial- and lateral-sided pain, 10 (37%) reported lateral-sided pain, and 2 (7%) reported medial-sided pain. Supramalleolar osteotomy was performed in 18 patients, while foot and hindfoot correction without supramalleolar osteotomy was performed in 9 patients. Postoperatively, both the median FFI (from 44.4 [interquartile range (IQR), 35.7-52.2] to 9.1 [IQR, 5.2-13.9]) and median VAS pain score (from 6 [IQR, 5-6] to 1 [IQR, 1-2]) improved significantly ( P < .0001 for both), and the median lesion size (from 25.8 mm2 [IQR, 19.3-45.2 mm2] to 13.8 mm2 [IQR, 6.8-26.5 mm2]) and median volume (from 2226.8 mm3 [IQR, 1311-3104 mm3] to 1326.5 mm3 [IQR, 714-2100 mm3]) decreased significantly ( P < .0001 for both). During the mean follow-up of 4.1 ± 2.1 years, no subsequent surgery for OLT was necessary. Conclusion: The results suggest that realignment procedures can improve the symptoms and radiographic profile of OLTs in patients with large cystic OLTs of the talar shoulder and malalignment of the foot and ankle.
NSD2 drives t(4;14) myeloma cell dependence on adenylate kinase 2 by diverting one-carbon metabolism to the epigenome
Authors: Sobh Amin , Encinas Elena , Patel Alisha , Surapaneni Greeshma , Bonilla Emilie , Kaestner Charlotte , Poullard Janai , Clerio Monica , Vasan Karthik , Freeman Tzipporah , Lv Dongwen , Dupéré-Richer Daphné , Riva Alberto , Barwick Benjamin G. , Zhou Daohong , Boise Lawrence H. , Mitsiades Constantine S. , Kim Baek , Bennett Richard L. , Chandel Navdeep S. , Licht Jonathan D. 
Published: April 2024

Abstract
Chromosomal translocation (4;14), an adverse prognostic factor in multiple myeloma (MM), drives overexpression of the histone methyltransferase nuclear receptor binding SET domain protein 2 (NSD2). A genome-wide CRISPR screen in MM cells identified adenylate kinase 2 (AK2), an enzyme critical for high-energy phosphate transfer from the mitochondria, as an NSD2-driven vulnerability. AK2 suppression in t(4;14) MM cells decreased nicotinamide adenine dinucleotide phosphate (NADP[H]) critical for conversion of ribonucleotides to deoxyribonucleosides, leading to replication stress, DNA damage, and apoptosis. Driving a large genome-wide increase in chromatin methylation, NSD2 overexpression depletes S-adenosylmethionine, compromising the synthesis of creatine from its precursor, guanidinoacetate. Creatine supplementation restored NADP(H) levels, reduced DNA damage, and rescued AK2-deficient t(4;14) MM cells. As the creatine phosphate shuttle constitutes an alternative means for mitochondrial high-energy phosphate transport, these results indicate that NSD2-driven creatine depletion underlies the hypersensitivity of t(4;14) MM cells to AK2 loss. Furthermore, AK2 depletion in t(4;14) cells impaired protein folding in the endoplasmic reticulum, consistent with impaired use of mitochondrial adenosine triphosphate (ATP). Accordingly, AK2 suppression increased the sensitivity of MM cells to proteasome inhibition. These findings delineate a novel mechanism in which aberrant transfer of carbon to the epigenome creates a metabolic vulnerability, with direct therapeutic implications for t(4;14) MM.
Patterns of CRS with teclistamab in relapsed/refractory multiple myeloma with or without prior T-cell redirection therapy
Authors: Hamadeh Issam S. , Shekarkhand Tala , Rueda Colin , Firestone Ross S. , Wang Alice X. , Korde Neha , Hultcrantz Malin L. , Lesokhin Alexander M. , Mailankody Sham , Hassoun Hani , Shah Urvi A. , Maclachlan Kylee , Rajeeve Sridevi , Patel Dhwani , Shah Gunjan L. , Scordo Michael , Lahoud Oscar B. , Chung David J. , Landau Heather J. , Giralt Sergio , Usmani Saad Z. , Tan Carlyn R. 
Published: April 2024

Abstract
Teclistamab (Tec) is a first-in-class BCMA × CD3 bispecific T-cell engager antibody approved for treating multiple myeloma progressing after at least 4 lines of therapy. The objective of this study was to evaluate the rate of cytokine release syndrome (CRS) in patients who were treated with commercial Tec and had prior exposure to other T-cell redirection therapies. A retrospective chart review was performed to identify patients who completed the Tec step-up dosing phase between November 2022 and November 2023. Patients were divided into 2 cohorts based on prior exposure to T-cell redirection therapy (cohort 1: T-cell redirection therapy experienced; cohort 2: T-cell redirection therapy naïve). The primary objective was to compare the differences in the rates of CRS between the 2 cohorts. Univariate and multivariate logistic regression analyses were performed to assess the association between CRS rates with Tec and prior treatment with T-cell redirection therapy. A total of 72 patients were included in the analysis (27 in cohort 1 and 45 in cohort 2). The CRS rates were significantly lower in cohort 1 (37%, n = 10) compared with cohort 2 (80%, n = 36; P = .0004). Based on multivariate logistic regression analysis, patients without prior exposure to T-cell redirection therapy (cohort 2) had about a fourfold increase in the incidence of CRS (95% confidence interval, 1.40-14.90; P = .0002) with Tec. In our study, prior exposure to T-cell redirection therapy reduced the risk of CRS with Tec during the step-up dosing phase. This observation will allow for the optimization of CRS prophylactic strategies for Tec.
Does local soil factor drive functional leaf trait variation? A test on Neilingding Island, South China
Authors: Tong Sen , Zhang Juanjuan , Qiao Xueting , Li Buhang , Yang Qiong , Hu Ping , Yu Shixiao 
Published: April 2024

AbstractLeaf traits were affected by soil factors and displayed varietal differences in forest. However, few examples have been reported on the Island ecosystems. We comprehensively investigated 9 leaf traits (leaf length, leaf width, leaf area, SLA, leaf fresh weight, leaf C content, leaf N content, leaf K content, leaf C:N ratio) of 54 main subtropical woody species and soil parameters (soil pH, total C content, total N content, total K content, available N content, available P content, available K content and soil moisture) in Neilingding Island, Shenzhen, southern China. Intra-and interspecific variation of leaf traits were measured and their correlations with soil parameters were explored. The interspecific variations of leaf C:N ratio, leaf N content and leaf fresh weight were higher than their intraspecific variations. The intraspecific variation of leaf K content was larger than that of interspecific one, accounting for 80.69% of the total variance. Positive correlations were found among intraspecific coefficients of variations in leaf morphological traits. The correlation analysis between the variation of intraspecific traits and the variation of soil parameters showed that changes in soil factors affected leaf morphology and stoichiometry. The interaction between soil moisture and soil available P content was the key factor on intraspecific variations of leaf traits including leaf area, leaf fresh weight, leaf C and leaf K content. We concluded that leaf traits of plants in the island were tightly related to soil parameters. Soil parameters, especially soil moisture and available P content, affected plant leaf morphology and stoichiometry at the local scale.
Characterization of genes related to the efflux pump and porin in multidrug-resistant Escherichia coli strains isolated from patients with COVID-19 after secondary infection
Authors: Ganjo Aryan R. , Balaky Salah Tofik Jalal , Mawlood Ahang Hasan , Smail Sakar B. , Shabila Nazar P. 
Published: April 2024

Abstract
Background
Escherichia coli (E. coli) is a multidrug resistant opportunistic pathogen that can cause secondary bacterial infections in patients with COVID-19. This study aimed to determine the antimicrobial resistance profile of E. coli as a secondary bacterial infection in patients with COVID-19 and to assess the prevalence and characterization of genes related to efflux pumps and porin.

Methods
A total of 50 nonduplicate E. coli isolates were collected as secondary bacterial infections in COVID-19 patients. The isolates were cultured from sputum samples. Confirmation and antibiotic susceptibility testing were conducted by Vitek 2. PCR was used to assess the prevalence of the efflux pump and porin-related genes in the isolates. The phenotypic and genotypic evolution of antibiotic resistance genes related to the efflux pump was evaluated.

Results
The E. coli isolates demonstrated high resistance to ampicillin (100%), cefixime (62%), cefepime (62%), amoxicillin-clavulanic acid (60%), cefuroxime (60%), and ceftriaxone (58%). The susceptibility of E. coli to ertapenem was greatest (92%), followed by imipenem (88%), meropenem (86%), tigecycline (80%), and levofloxacin (76%). Regarding efflux pump gene combinations, there was a significant association between the acrA gene and increased resistance to levofloxacin, between the acrB gene and decreased resistance to meropenem and increased resistance to levofloxacin, and between the ompF and ompC genes and increased resistance to gentamicin.

Conclusions
The antibiotics ertapenem, imipenem, meropenem, tigecycline, and levofloxacin were effective against E. coli in patients with COVID-19. Genes encoding efflux pumps and porins, such as acrA, acrB, and outer membrane porins, were highly distributed among all the isolates. Efflux pump inhibitors could be alternative antibiotics for restoring tetracycline activity in E. coli isolates.
Analysis of endophytic bacterial diversity in seeds of different genotypes of cotton and the suppression of Verticillium wilt pathogen infection by a synthetic microbial community
Authors: Wu Chong-Die , Fan Yong-Bin , Chen Xue , Cao Jiang-Wei , Ye Jing-Yi , Feng Meng-Lei , Liu Xing-Xing , Sun Wen-Jing , Liu Rui-Na , Wang Ai-Ying 
Published: April 2024

Abstract
Background
In agricultural production, fungal diseases significantly impact the yield and quality of cotton (Gossypium spp.) with Verticillium wilt posing a particularly severe threat.

Results
This study is focused on investigating the effectiveness of endophytic microbial communities present in the seeds of disease-resistant cotton genotypes in the control of cotton Verticillium wilt. The technique of 16S ribosomal RNA (16S rRNA) amplicon sequencing identified a significant enrichment of the Bacillus genus in the resistant genotype Xinluzao 78, which differed from the endophytic bacterial community structure in the susceptible genotype Xinluzao 63. Specific enriched strains were isolated and screened from the seeds of Xinluzao 78 to further explore the biological functions of seed endophytes. A synthetic microbial community (SynCom) was constructed using the broken-rod model, and seeds of the susceptible genotype Xinluzao 63 in this community that had been soaked with the SynCom were found to significantly control the occurrence of Verticillium wilt and regulate the growth of cotton plants. Antibiotic screening techniques were used to preliminarily identify the colonization of strains in the community. These techniques revealed that the strains can colonize plant tissues and occupy ecological niches in cotton tissues through a priority effect, which prevents infection by pathogens.

Conclusion
This study highlights the key role of seed endophytes in driving plant disease defense and provides a theoretical basis for the future application of SynComs in agriculture.
The genome of Citrus australasica reveals disease resistance and other species specific genes
Authors: Nakandala Upuli , Furtado Agnelo , Masouleh Ardashir Kharabian , Smith Malcolm W. , Williams Darren C. , Henry Robert J. 
Published: April 2024

Abstract
Background
The finger lime (Citrus australasica), one of six Australian endemic citrus species shows a high natural phenotypic diversity and novel characteristics. The wide variation and unique horticultural features have made this lime an attractive candidate for domestication. Currently no haplotype resolved genome is available for this species. Here we present a high quality, haplotype-resolved reference genome for this species using PacBio HiFi and Hi-C sequencing.

Results
Hifiasm assembly and SALSA scaffolding resulted in a collapsed genome size of 344.2 Mb and 321.1 Mb and 323.2 Mb size for the two haplotypes. The nine pseudochromosomes of the collapsed genome had an N50 of 35.2 Mb, 99.1% genome assembly completeness and 98.9% gene annotation completeness (BUSCO). A total of 41,304 genes were predicted in the nuclear genome. Comparison with C. australis revealed that 13,661 genes in pseudochromosomes were unique in C. australasica. These were mainly involved in plant-pathogen interactions, stress response, cellular metabolic and developmental processes, and signal transduction. The two genomes showed a syntenic arrangement at the chromosome level with large structural rearrangements in some chromosomes. Genetic variation among five C. australasica cultivars was analysed. Genes related to defense, synthesis of volatile compounds and red/yellow coloration were identified in the genome. A major expansion of genes encoding thylakoid curvature proteins was found in the C. australasica genome.

Conclusions
The genome of C. australasica present in this study is of high quality and contiguity. This genome helps deepen our understanding of citrus evolution and reveals disease resistance and quality related genes with potential to accelerate the genetic improvement of citrus.
Amide proton transfer weighted and diffusion weighted imaging based radiomics classification algorithm for predicting 1p/19q co-deletion status in low grade gliomas
Authors: Ma Andong , Yan Xinran , Qu Yaoming , Wen Haitao , Zou Xia , Liu Xinzi , Lu Mingjun , Mo Jianhua , Wen Zhibo 
Published: April 2024

Abstract
Background
1p/19q co-deletion in low-grade gliomas (LGG, World Health Organization grade II and III) is of great significance in clinical decision making. We aim to use radiomics analysis to predict 1p/19q co-deletion in LGG based on amide proton transfer weighted (APTw), diffusion weighted imaging (DWI), and conventional MRI.

Methods
This retrospective study included 90 patients histopathologically diagnosed with LGG. We performed a radiomics analysis by extracting 8454 MRI-based features form APTw, DWI and conventional MR images and applied a least absolute shrinkage and selection operator (LASSO) algorithm to select radiomics signature. A radiomics score (Rad-score) was generated using a linear combination of the values of the selected features weighted for each of the patients. Three neuroradiologists, including one experienced neuroradiologist and two resident physicians, independently evaluated the MR features of LGG and provided predictions on whether the tumor had 1p/19q co-deletion or 1p/19q intact status. A clinical model was then constructed based on the significant variables identified in this analysis. A combined model incorporating both the Rad-score and clinical factors was also constructed. The predictive performance was validated by receiver operating characteristic curve analysis, DeLong analysis and decision curve analysis. P < 0.05 was statistically significant.

Results
The radiomics model and the combined model both exhibited excellent performance on both the training and test sets, achieving areas under the curve (AUCs) of 0.948 and 0.966, as well as 0.909 and 0.896, respectively. These results surpassed the performance of the clinical model, which achieved AUCs of 0.760 and 0.766 on the training and test sets, respectively. After performing Delong analysis, the clinical model did not significantly differ in predictive performance from three neuroradiologists. In the training set, both the radiomic and combined models performed better than all neuroradiologists. In the test set, the models exhibited higher AUCs than the neuroradiologists, with the radiomics model significantly outperforming resident physicians B and C, but not differing significantly from experienced neuroradiologist.

Conclusions
Our results suggest that our algorithm can noninvasively predict the 1p/19q co-deletion status of LGG. The predictive performance of radiomics model was comparable to that of experienced neuroradiologist, significantly outperforming the diagnostic accuracy of resident physicians, thereby offering the potential to facilitate non-invasive 1p/19q co-deletion prediction of LGG.
Biplex quantitative PCR to detect transcriptionally active human papillomavirus 16 from patient saliva
Authors: Deutsch Fiona , Sais Dayna , Keatinge Ni , Hill Meredith , Tran Ngoc Ha , Elliott Michael , Tran Nham 
Published: April 2024

AbstractHead and neck cancers, particularly oropharyngeal cancers (OPC), have been increasingly associated with human papillomavirus (HPV) infections, specifically HPV16. The current methods for HPV16 detection primarily rely on p16 staining or PCR techniques. However, it is important to note the limitations of conventional PCR, as the presence of viral DNA does not always indicate an ongoing viral infection. Moreover, these tests heavily rely on the availability of tissue samples, which can present challenges in certain situations. In this study, we developed a RT-qPCR biplex approach to detect HPV16 oncogenes E6 and E7 RNA in saliva samples from OPC patients. Salivary supernatant was used as the liquid biopsy source. We successfully obtained RNA from salivary supernatant, preserving its integrity as indicated by the detection of several housekeeping genes. Our biplex approach accurately detected E6 and E7 RNA in HPV16-positive cell lines, tissues, and finally in OPC salivary samples. Importantly, the assay specifically targeted HPV16 and not HPV18. This biplexing technique allowed for reduced sample input without compromising specificity. In summary, our approach demonstrates the potential to detect viable HPV16 in saliva from OPC patients. Since the assay measures HPV16 RNA, it provides insights into the transcriptional activity of the virus. This could guide clinical decision-making and treatment planning for individuals with HPV-related OPC.
Targeting PCSK9 to upregulate MHC-II on the surface of tumor cells in tumor immunotherapy
Authors: Wang Hanbing , Zhang Xin , Zhang Yipeng , Shi Tao , Zhang Yue , Song Xueru , Liu Baorui , Wang Yue , Wei Jia 
Published: April 2024

Abstract
Background
Proprotein convertase subtilisin/kexin type 9 (PCSK9), the last member of the proprotein convertase family, functions as a classic regulator of low-density lipoprotein (LDL) by interacting with low-density lipoprotein receptor (LDLR). Recent studies have shown that PCSK9 can affect the occurrence and development of tumors and can be used as a novel therapeutic target. However, a comprehensive pan-cancer analysis of PCSK9 has yet to be conducted.

Methods
The potential oncogenic effects of PCSK9 in 33 types of tumors were explored based on the datasets of The Cancer Genome Atlas (TCGA) dataset. In addition, the immune regulatory role of PCSK9 inhibition was evaluated via in vitro cell coculture and the tumor-bearing mouse model. Finally, the antitumor efficacy of targeted PCSK9 combined with OVA-II vaccines was verified.

Results
Our results indicated that PCSK9 was highly expressed in most tumor types and was significantly correlated with late disease stage and poor prognosis. Additionally, PCSK9 may regulate the tumor immune matrix score, immune cell infiltration, immune checkpoint expression, and major histocompatibility complex expression. Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Combining PCSK9 inhibitors could enhance the efficacies of OVA-II tumor vaccine monotherapy.

Conclusions
Conclusively, our pan-cancer analysis provided a more comprehensive understanding of the oncogenic and immunoregulatory roles of PCSK9 and demonstrated that targeting PCSK9 could increase the efficacy of long peptide vaccines by upregulating DC infiltration and MHC-II expression on the surface of tumor cells.

Summary
This study reveals the critical oncogenic and immunoregulatory roles of PCSK9 in various tumors and shows the promise of PCSK9 as a potent immunotherapy target.
Identification of stemness-related glycosylation changes in head and neck squamous cell carcinoma
Authors: Routila E , Mahran R , Salminen S , Irjala H , Haapio E , Kytö E , Ventelä S , Petterson K , Routila J , Gidwani K , Leivo J 
Published: April 2024

Abstract
Background
Altered glycosylation is a hallmark of cancer associated with therapy resistance and tumor behavior. In this study, we investigated the glycosylation profile of stemness-related proteins OCT4, CIP2A, MET, and LIMA1 in HNSCC tumors.

Methods
Tumor, adjacent normal tissue, and blood samples of 25 patients were collected together with clinical details. After tissue processing, lectin-based glycovariant screens were performed.

Results
Strong correlation between glycosylation profiles of all four stemness-related proteins was observed in tumor tissue, whereas glycosylation in tumor tissue, adjacent normal tissue, and serum was differential.

Conclusions
A mannose- and galactose-rich glycosylation niche associated with stemness-related proteins was identified.