bluuebunny/crossref_metadata_2025_split huggingface dataset:
CNS bridging radiotherapy achieves rapid cytoreduction before CAR T-cell therapy for aggressive B-cell lymphomas
Authors: Cederquist Gustav Y. , Schefflein Javin , Devlin Sean M. , Shah Gunjan L. , Shouval Roni , Hubbeling Harper , Tringale Kathryn , Alarcon Tomas Ana , Fregonese Beatrice , Hajj Carla , Boardman Alexander , Luna De Abia Alejandro , Corona Magdalena , Cassanello Giulio , Dahi Parastoo B. , Lin Richard J. , Ghione Paola , Salles Gilles , Perales Miguel-Angel , Palomba M. Lia , Falchi Lorenzo , Scordo Michael , Grommes Christian , Yahalom Joachim , Imber Brandon S. 
Published: June 2024

Abstract
Chimeric antigen receptor (CAR) T-cell therapy (CART) for central nervous system lymphoma (CNSL) is a promising strategy, yet responses are frequently not durable. Bridging radiotherapy (BRT) is used for extracranial lymphoma in which it can improve CART outcomes through cytoreduction of high-risk lesions. We hypothesized that BRT would achieve similar, significant cytoreduction before CART for CNSL (CNS-BRT). We identified patients with CNSL with non-Hodgkin B-cell lymphoma who received CNS-BRT before commercial CART. Cytoreduction from CNS-BRT was calculated as change in lesion size before CART. Twelve patients received CNS-BRT, and the median follow-up among survivors is 11.8 months (interquartile range, 8.5-21.9). Ten patients had CNSL (9 secondary, 1 primary) and 2 patients had epidural disease (evaluable for toxicity). All 10 patients with CNSL had progressive disease at the time of CNS-BRT. Of 12 patients, 1 experienced grade ≥3 cytokine release syndrome, and 3 of 12 patients experienced grade ≥3 immune effector cell–associated neurotoxicity syndrome. CNS-BRT achieved a 74.0% (95% confidence interval, 62.0-86.0) mean reduction in lesion size from baseline (P = .014) at a median of 12 days from BRT completion and before CART infusion. Best CNS response included 8 complete responses, 1 partial response, and 1 progressive disease. Three patients experienced CNS relapse outside the BRT field. Preliminary data suggest CNS-BRT achieves rapid cytoreduction and is associated with a favorable CNS response and safety profile. These data support further study of BRT as a bridging modality for CNSL CART.
Prediction of the future number of fall-related emergency medical services calls in older individuals
Authors: Uemura Shuji , Nakayama Ryuichi , Koyama Masayuki , Taguchi Yukiko , Bunya Naofumi , Sawamoto Keigo , Ohnishi Hirofumi , Narimatsu Eichi 
Published: June 2024

Abstract
Background
Falls among older individuals contribute significantly to the rise in ambulance transport use. To recognize the importance of future countermeasures, we estimated the projected number and percentage of fall-related emergency medical service (EMS) calls.

Methods
We examined the sex, age group, and location of falls among patients aged ≥ 65 years who contacted emergency services in Sapporo City from 2013 to 2021. Annual fall-related calls per population subgroup were calculated, and trends were analyzed. Four models were used to estimate the future number of fall-related calls from the 2025–2060 projected population: (1) based on the 2022 data, estimates from the 2013–2022 data using (2) Poisson progression, (3) neural network, (4) estimates from the 2013–2019 data using neural network. The number of all EMS calls was also determined using the same method to obtain the ratio of all EMS calls.

Results
During 2013–2022, 70,262 fall-related calls were made for those aged ≥ 65 years. The rate was higher indoors among females and outdoor among males in most age groups and generally increased with age. After adjusting for age, the rate increased by year. Future estimates of the number of fall calls are approximately double the number in 2022 in 2040 and three times in 2060, with falls accounting for approximately 11% and 13% of all EMS calls in 2040 and 2060, respectively.

Conclusion
The number of fall-related EMS calls among older people is expected to increase in the future, and the percentage of EMS calls will also increase; therefore, countermeasures are urgently needed.
Drug repurposing based on the DTD-GNN graph neural network: revealing the relationships among drugs, targets and diseases
Authors: Li Wenjun , Ma Wanjun , Yang Mengyun , Tang Xiwei 
Published: June 2024

Abstract
Motivation
The rational modelling of the relationship among drugs, targets and diseases is crucial for drug retargeting. While significant progress has been made in studying binary relationships, further research is needed to deepen our understanding of ternary relationships. The application of graph neural networks in drug retargeting is increasing, but further research is needed to determine the appropriate modelling method for ternary relationships and how to capture their complex multi-feature structure.

Results
The aim of this study was to construct relationships among drug, targets and diseases. To represent the complex relationships among these entities, we used a heterogeneous graph structure. Additionally, we propose a DTD-GNN model that combines graph convolutional networks and graph attention networks to learn feature representations and association information, facilitating a more thorough exploration of the relationships. The experimental results demonstrate that the DTD-GNN model outperforms other graph neural network models in terms of AUC, Precision, and F1-score. The study has important implications for gaining a comprehensive understanding of the relationships between drugs and diseases, as well as for further research and application in exploring the mechanisms of drug-disease interactions. The study reveals these relationships, providing possibilities for innovative therapeutic strategies in medicine.
Whole transcriptome analysis to identify non-coding RNA regulators and hub genes in sperm of non-obstructive azoospermia by microarray, single-cell RNA sequencing, weighted gene co-expression network analysis, and mRNA-miRNA-lncRNA interaction analysis
Authors: Karoii Danial Hashemi , Azizi Hossein , Skutella Thomas 
Published: June 2024

Abstract
Background
The issue of male fertility is becoming increasingly common due to genetic differences inherited over generations. Gene expression and evaluation of non-coding RNA (ncRNA), crucial for sperm development, are significant factors. This gene expression can affect sperm motility and, consequently, fertility. Understanding the intricate protein interactions that play essential roles in sperm differentiation and development is vital. This knowledge could lead to more effective treatments and interventions for male infertility.

Materials and methods
Our research aim to identify new and key genes and ncRNA involved in non-obstructive azoospermia (NOA), improving genetic diagnosis and offering more accurate estimates for successful sperm extraction based on an individual’s genotype.

Results
We analyzed the transcript of three NOA patients who tested negative for genetic sperm issues, employing comprehensive genome-wide analysis of approximately 50,000 transcript sequences using microarray technology. This compared gene expression profiles between NOA sperm and normal sperm. We found significant gene expression differences: 150 genes were up-regulated, and 78 genes were down-regulated, along with 24 ncRNAs up-regulated and 13 ncRNAs down-regulated compared to normal conditions. By cross-referencing our results with a single-cell genomics database, we identified overexpressed biological process terms in differentially expressed genes, such as “protein localization to endosomes” and “xenobiotic transport.” Overrepresented molecular function terms in up-regulated genes included “voltage-gated calcium channel activity,” “growth hormone-releasing hormone receptor activity,” and “sialic acid transmembrane transporter activity.” Analysis revealed nine hub genes associated with NOA sperm: RPL34, CYB5B, GOL6A6, LSM1, ARL4A, DHX57, STARD9, HSP90B1, and VPS36.

Conclusions
These genes and their interacting proteins may play a role in the pathophysiology of germ cell abnormalities and infertility.
Transcriptome and metabolome analysis reveals mechanism of light intensity modulating iridoid biosynthesis in Gentiana macrophylla Pall.
Authors: Fu Huanhuan , Wang Yaomin , Mi Fakai , Wang Li , Yang Ye , Wang Fang , Yue Zhenggang , He Yihan 
Published: June 2024

AbstractLight intensity is a key factor affecting the synthesis of secondary metabolites in plants. However, the response mechanisms of metabolites and genes in Gentiana macrophylla under different light intensities have not been determined. In the present study, G. macrophylla seedlings were treated with LED light intensities of 15 µmol/m2/s (low light, LL), 90 µmol/m2/s (medium light, ML), and 200 µmol/m2/s (high light, HL), and leaves were collected on the 5th day for further investigation. A total of 2162 metabolites were detected, in which, the most abundant metabolites were identified as flavonoids, carbohydrates, terpenoids and amino acids. A total of 3313 and 613 differentially expressed genes (DEGs) were identified in the LL and HL groups compared with the ML group, respectively, mainly enriched in KEGG pathways such as carotenoid biosynthesis, carbon metabolism, glycolysis/gluconeogenesis, amino acids biosynthesis, plant MAPK pathway and plant hormone signaling. Besides, the transcription factors of GmMYB5 and GmbHLH20 were determined to be significantly correlated with loganic acid biosynthesis; the expression of photosystem-related enzyme genes was altered under different light intensities, regulating the expression of enzyme genes involved in the carotenoid, chlorophyll, glycolysis and amino acids pathway, then affecting their metabolic biosynthesis. As a result, low light inhibited photosynthesis, delayed glycolysis, thus, increased certain amino acids and decreased loganic acid production, while high light got an opposite trend. Our research contributed significantly to understand the molecular mechanism of light intensity in controlling metabolic accumulation in G. macrophylla.
Combining transcriptome and metabolome analysis to understand the response of sorghum to Melanaphis sacchari
Authors: Zhao Xin-Rui , Zhao Dong-Ting , Zhang Ling-Yu , Chang Jin-Hua , Cui Jiang-Hui 
Published: June 2024

Abstract
Background
The sorghum aphid Melanaphis sacchari (Zehntner) (Homoptera: Aphididae) is an important insect in the late growth phase of sorghum (Sorghum bicolor L.). However, the mechanisms of sorghum response to aphid infestation are unclear.

Results
In this paper, the mechanisms of aphid resistance in different types of sorghum varieties were revealed by studying the epidermal cell structure and performing a transcriptome and metabolome association analysis of aphid-resistant and aphid-susceptible varieties. The epidermal cell results showed that the resistance of sorghum to aphids was positively correlated with epidermal cell regularity and negatively correlated with the intercellular space and leaf thickness. Transcriptome and metabolomic analyses showed that differentially expressed genes in the resistant variety HN16 and susceptible variety BTX623 were mainly enriched in the flavonoid biosynthesis pathway and differentially expressed metabolites were mainly related to isoflavonoid biosynthesis and flavonoid biosynthesis. The q-PCR results of key genes were consistent with the transcriptome expression results. Meanwhile, the metabolome test results showed that after aphidinfestation, naringenin and genistein were significantly upregulated in the aphid-resistant variety HN16 and aphid-susceptible variety BTX623 while luteolin was only significantly upregulated in BTX623. These results show that naringenin, genistein, and luteolin play important roles in plant resistance to aphid infestation. The results of exogenous spraying tests showed that a 1‰ concentration of naringenin and genistein is optimal for improving sorghum resistance to aphid feeding.

Conclusions
In summary, the physical properties of the sorghum leaf structure related to aphid resistance were studied to provide a reference for the breeding of aphid-resistant varieties. The flavonoid biosynthesis pathway plays an important role in the response of sorghum aphids and represents an important basis for the biological control of these pests. The results of the spraying experiment provide insights for developing anti-aphid substances in the future.
Response surface methodology mediated optimization of phytosulfokine and plant growth regulators for enhanced protoplast division, callus induction, and somatic embryogenesis in Angelica Gigas Nakai
Authors: Lee Han-Sol , Han Jong-Eun , Bae Eun-Kyung , Jie Eun Yee , Kim Suk Weon , Kwon Hyuk Joon , Lee Hak Sung , Yeon Soo-Ho , Murthy Hosakatte Niranjana , Park So-Young 
Published: June 2024

AbstractBackgroundAngelica Gigas(Purple parsnip) is an important medicinal plant that is cultivated and utilized in Korea, Japan, and China. It contains bioactive substances especially coumarins with anti-inflammatory, anti-platelet aggregation, anti-cancer, anti-diabetic, antimicrobial, anti-obesity, anti-oxidant, immunomodulatory, and neuroprotective properties. This medicinal crop can be genetically improved, and the metabolites can be obtained by embryonic stem cells. In this context, we established the protoplast-to-plant regeneration methodology inAngelica gigas.ResultsIn the present investigation, we isolated the protoplast from the embryogenic callus by applying methods that we have developed earlier and established protoplast cultures using Murashige and Skoog (MS) liquid medium and by embedding the protoplast in thin alginate layer (TAL) methods. We supplemented the culture medium with growth regulators namely 2,4-dichlorophenoxyaceticacid (2,4-D, 0, 0.75, 1.5 mg L− 1), kinetin (KN, 0, 0.5, and 1.0 mg L− 1) and phytosulfokine (PSK, 0, 50, 100 nM) to induce protoplast division, microcolony formation, and embryogenic callus regeneration. We applied central composite design (CCD) and response surface methodology (RSM) for the optimization of 2,4-D, KN, and PSK levels during protoplast division, micro-callus formation, and induction of embryogenic callus stages. The results revealed that 0.04 mg L− 12,4-D + 0.5 mg L− 1KN + 2 nM PSK, 0.5 mg L− 12,4-D + 0.9 mg L− 1KN and 90 nM PSK, and 1.5 mg L− 12,4-D and 1 mg L− 1KN were optimum for protoplast division, micro-callus formation and induction embryogenic callus. MS basal semi-solid medium without growth regulators was good for the development of embryos and plant regeneration.ConclusionsThis study demonstrated successful protoplast culture, protoplast division, micro-callus formation, induction embryogenic callus, somatic embryogenesis, and plant regeneration inA. gigas. The methodologies developed here are quite useful for the genetic improvement of this important medicinal plant.
Barriers and enablers to improving integrated primary healthcare for non-communicable diseases and mental health conditions in Ethiopia: a mixed methods study
Authors: Bekele Alemayehu , Alem Atalay , Seward Nadine , Eshetu Tigist , Gebremariam Tewodros Haile , Getachew Yeneneh , Mengiste Wondosen , Medhin Girmay , Fairall Lara , Sevdalis Nick , Prince Martin , Fekadu Abebaw , Hanlon Charlotte 
Published: June 2024

Abstract
Background
The Ethiopian Primary Healthcare Clinical Guidelines (EPHCG) seek to improve quality of primary health care, while also expanding access to care for people with Non-Communicable Diseases and Mental Health Conditions (NCDs/MHCs). The aim of this study was to identify barriers and enablers to implementation of the EPHCG with a particular focus on NCDs/MHCs.

Methods
A mixed-methods convergent-parallel design was employed after EPHCG implementation in 18 health facilities in southern Ethiopia. Semi-structured interviews were conducted with 10 primary healthcare clinicians and one healthcare administrator. Organisational Readiness for Implementing Change (ORIC) questionnaire was self-completed by 124 health workers and analysed using Kruskal Wallis ranked test to investigate median score differences. Qualitative data were mapped to the Consolidated Framework for Implementation Science (CFIR) and the Theoretical Domains Framework (TDF). Expert Recommendations for Implementing Change (ERIC) were employed to select implementation strategies to address barriers.

Results
Four domains were identified: EPHCG training and implementation, awareness and meeting patient needs (demand side), resource constraints/barriers (supply side) and care pathway bottlenecks. The innovative facility-based training to implement EPHCG had a mixed response, especially in busy facilities where teams reported struggling to find protected time to meet. Key barriers to implementation of EPHCG were non-availability of resources (CFIR inner setting), such as laboratory reagents and medications that undermined efforts to follow guideline-based care, the way care was structured and lack of familiarity with providing care for people with NCDs-MHCs. Substantial barriers arose because of socio-economic problems that were interlinked with health but not addressable within the health system (CFIR outer setting). Other factors influencing effective implementation of EPHCG (TDF) included low population awareness about NCDs/MHCs and unaffordable diagnostic and treatment services (TDF). Implementation strategies were identified. ORIC findings indicated high scores of organisational readiness to implement the desired change with likely social desirability bias.

Conclusion
Although perceived as necessary, practical implementation of EPHCG was constrained by challenges across domains of internal/external determinants. This was especially marked in relation to expansion of care responsibilities to include NCDs/MHCs. Attention to social determinants of health outcomes, community engagement and awareness-raising are needed to maximize population impact.
Artificial intelligence-driven computer aided diagnosis system provides similar diagnosis value compared with doctors’ evaluation in lung cancer screening
Authors: Gao Shan , Xu Zexuan , Kang Wanli , Lv Xinna , Chu Naihui , Xu Shaofa , Hou Dailun 
Published: June 2024

Abstract
Objective
To evaluate the consistency between doctors and artificial intelligence (AI) software in analysing and diagnosing pulmonary nodules, and assess whether the characteristics of pulmonary nodules derived from the two methods are consistent for the interpretation of carcinomatous nodules.

Materials and Methods
This retrospective study analysed participants aged 40–74 in the local area from 2011 to 2013. Pulmonary nodules were examined radiologically using a low-dose chest CT scan, evaluated by an expert panel of doctors in radiology, oncology, and thoracic departments, as well as a computer-aided diagnostic(CAD) system based on the three-dimensional(3D) convolutional neural network (CNN) with DenseNet architecture(InferRead CT Lung, IRCL). Consistency tests were employed to assess the uniformity of the radiological characteristics of the pulmonary nodules. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy. Logistic regression analysis is utilized to determine whether the two methods yield the same predictive factors for cancerous nodules.

Results
A total of 570 subjects were included in this retrospective study. The AI software demonstrated high consistency with the panel's evaluation in determining the position and diameter of the pulmonary nodules (kappa = 0.883, concordance correlation coefficient (CCC) = 0.809, p = 0.000). The comparison of the solid nodules' attenuation characteristics also showed acceptable consistency (kappa = 0.503). In patients diagnosed with lung cancer, the area under the curve (AUC) for the panel and AI were 0.873 (95%CI: 0.829–0.909) and 0.921 (95%CI: 0.884–0.949), respectively. However, there was no significant difference (p = 0.0950). The maximum diameter, solid nodules, subsolid nodules were the crucial factors for interpreting carcinomatous nodules in the analysis of expert panel and IRCL pulmonary nodule characteristics.

Conclusion
AI software can assist doctors in diagnosing nodules and is consistent with doctors' evaluations and diagnosis of pulmonary nodules.
Clinical application of intraoperative ultrasound superb microvascular imaging in brain tumors resections: contributing to the achievement of total tumoral resection
Authors: Cai Siman , Xing Hao , Wang Yuekun , Wang Yu , Ma Wenbin , Jiang Yuxin , Li Jianchu , Wang Hongyan 
Published: June 2024

Abstract
Background
To investigate whether the intraoperative superb microvascular imaging(SMI) technique helps evaluate lesion boundaries compared with conventional grayscale ultrasound in brain tumor surgery and to explore factors that may be associated with complete radiographic resection.

Methods
This study enrolled 57 consecutive brain tumor patients undergoing surgery. During the operation, B-mode and SMI ultrasound evaluated the boundaries of brain tumors. MRI before and within 48h after surgery was used as the gold standard to evaluate gross-total resection(GTR). The ultrasound findings and GTR results were analyzed to determine the imaging factors related to GTR.

Results
A total of 57 patients were enrolled in the study, including 32 males and 25 females, with an average age of 53.4 ± 14.1 years old(range 19 ~ 80). According to the assessment criteria of MRI, before and within 48 h after the operation, 37(63.9%) cases were classified as GTR, and 20(35.1%) cases were classified as GTR. In comparing tumor interface definition between B-mode and SMI mode, SMI improved HGG boundary recognition in 5 cases(P = 0.033). The results showed that the tumor size ≥ 5 cm and unclear ultrasonic boundary were independent risk factors for nGTR (OR>1, P<0.05).

Conclusions
As an innovative intraoperative doppler technique in neurosurgery, SMI can effectively demarcate the tumor’s boundary and help achieve GTR as much as possible.
Development and validation of a LASSO prediction model for cisplatin induced nephrotoxicity: a case-control study in China
Authors: Zhang Jingwei , Luo Xuyang , Fan Yi , Zhou Wei , Ma Shijie , Kang Yuwei , Yang Wei , Geng Xiaoxia , Zhang Heping , Deng Fei 
Published: June 2024

Abstract
Background
Early identification of high-risk individuals with cisplatin-induced nephrotoxicity (CIN) is crucial for avoiding CIN and improving prognosis. In this study, we developed and validated a CIN prediction model based on general clinical data, laboratory indications, and genetic features of lung cancer patients before chemotherapy.

Methods
We retrospectively included 696 lung cancer patients using platinum chemotherapy regimens from June 2019 to June 2021 as the traing set to construct a predictive model using Absolute shrinkage and selection operator (LASSO) regression, cross validation, and Akaike’s information criterion (AIC) to select important variables. We prospectively selected 283 independent lung cancer patients from July 2021 to December 2022 as the test set to evaluate the model’s performance.

Results
The prediction model showed good discrimination and calibration, with AUCs of 0.9217 and 0.8288, sensitivity of 79.89% and 45.07%, specificity of 94.48% and 94.81%, in the training and test sets respectively. Clinical decision curve analysis suggested that the model has value for clinical use when the risk threshold ranges between 0.1 and 0.9. Precision-Recall (PR) curve shown in recall interval from 0.5 to 0.75: precision gradually declines with increasing Recall, up to 0.9.

Conclusions
Predictive models based on laboratory and demographic variables can serve as a beneficial complementary tool for identifying high-risk populations with CIN.