bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel antibody competition binding assay identifies distinct serological profiles associated with protection
Authors: Bolton Jessica S. , MacGill Randall S. , Locke Emily , Regules Jason A. , Bergmann-Leitner Elke S. 
Published: December 2023

IntroductionPre-erythrocytic malaria vaccines hold the promise of inducing sterile protection thereby preventing the morbidity and mortality associated with Plasmodium infection. The main surface antigen of P. falciparum sporozoites, i.e., the circumsporozoite protein (CSP), has been extensively explored as a target of such vaccines with significant success in recent years. Systematic adjuvant selection, refinements of the immunization regimen, and physical properties of the antigen may all contribute to the potential of increasing the efficacy of CSP-based vaccines. Protection appears to be dependent in large part on CSP antibodies. However due to a knowledge gap related to the exact correlates of immunity, there is a critical need to improve our ability to down select candidates preclinically before entering clinical trials including with controlled human malaria infections (CHMI).MethodsWe developed a novel multiplex competition assay based on well-characterized monoclonal antibodies (mAbs) that target crucial epitopes across the CSP molecule. This new tool assesses both, quality and epitope-specific concentrations of vaccine-induced antibodies by measuring their equivalency with a panel of well-characterized, CSP-epitope-specific mAbs.ResultsApplying this method to RTS,S-immune sera from a CHMI trial demonstrated a quantitative epitope-specificity profile of antibody responses that can differentiate between protected vs. nonprotected individuals. Aligning vaccine efficacy with quantitation of the epitope fine specificity results of this equivalency assay reveals the importance of epitope specificity.DiscussionThe newly developed serological equivalence assay will inform future vaccine design and possibly even adjuvant selection. This methodology can be adapted to other antigens and disease models, when a panel of relevant mAbs exists, and could offer a unique tool for comparing and down-selecting vaccine formulations.
Case Report: CD19 CAR T-cell therapy following autologous stem cell transplantation: a successful treatment for R/R CD20-negative transformed follicular lymphoma with TP53 mutation
Authors: Zhang Jinjing , Cai Dali , Gao Ran , Miao Yuan , Cui Yan , Liu Zhenghua , Zhang Heyang , Yan Xiaojing , Su Nan 
Published: December 2023

BackgroundFollicular lymphoma (FL), a common indolent B-cell lymphoma, has the potential to transform into an aggressive lymphoma, such as diffuse large B-cell lymphoma (DLBCL). The outcome of patients with transformed follicular lymphoma (tFL) is poor, especially in patients with transformed lymphoma after chemotherapy and patients with progression within 24 months (POD24). Chimeric antigen receptor (CAR) T-cell therapy combined with autologous stem cell transplantation (ASCT) has promising antitumor efficacy.Case presentationHere, we described a 39-year-old male patient who was initially diagnosed with FL that transformed into DLBCL with POD24, CD20 negativity, TP53 mutation, and a bulky mass after 3 lines of therapy, all of which were adverse prognostic factors. We applied a combination approach: CD19 CAR T-cell infusion following ASCT. Ibrutinib was administered continuously to enhance efficacy, DHAP was administered as a salvage chemotherapy, and ICE was administered as a bridging regimen. The patient underwent BEAM conditioning on days -7~ -1, a total of 3.8 × 106/kg CD34+ stem cells were infused on days 01~02, and a total of 108 CAR T cells (relmacabtagene autoleucel, relma-cel, JWCAR029) were infused on day 03. The patient experienced grade 2 cytokine release syndrome (CRS), manifesting as fever and hypotension according to institutional standards. There was no immune effector cell-associated neurotoxicity syndrome (ICANS) after CAR T-cell infusion. Finally, the patient achieved CMR at +1 month, which has been maintained without any other adverse effects.ConclusionThis case highlights the amazing efficacy of CD19 CAR T-cell therapy following ASCT for R/R tFL, thus providing new insight on therapeutic strategies for the future.
Druggable genomic landscapes of high-grade gliomas
Authors: Ghanem Paola , Fatteh Maria , Kamson David Olayinka , Balan Archana , Chang Michael , Tao Jessica , Blakeley Jaishri ,   The Johns Hopkins Molecular Tumor Board Investigators, Canzoniero Jenna , Grossman Stuart A. , Marrone Kristen , Schreck Karisa C. , Anagnostou Valsamo 
Published: December 2023

BackgroundDespite the putatively targetable genomic landscape of high-grade gliomas, the long-term survival benefit of genomically-tailored targeted therapies remains discouraging.MethodsUsing glioblastoma (GBM) as a representative example of high-grade gliomas, we evaluated the clonal architecture and distribution of hotspot mutations in 388 GBMs from the Cancer Genome Atlas (TCGA). Mutations were matched with 54 targeted therapies, followed by a comprehensive evaluation of drug biochemical properties in reference to the drug’s clinical efficacy in high-grade gliomas. We then assessed clinical outcomes of a cohort of patients with high-grade gliomas with targetable mutations reviewed at the Johns Hopkins Molecular Tumor Board (JH MTB; n = 50).ResultsAmong 1,156 sequence alterations evaluated, 28.6% represented hotspots. While the frequency of hotspot mutations in GBM was comparable to cancer types with actionable hotspot alterations, GBMs harbored a higher fraction of subclonal mutations that affected hotspots (7.0%), compared to breast cancer (4.9%), lung cancer (4.4%), and melanoma (1.4%). In investigating the biochemical features of targeted therapies paired with recurring alterations, we identified a trend toward higher lipid solubility and lower IC50 in GBM cell lines among drugs with clinical efficacy. The drugs’ half-life, molecular weight, surface area and binding to efflux transporters were not associated with clinical efficacy. Among the JH MTB cohort of patients with IDH1 wild-type high-grade gliomas who received targeted therapies, trametinib monotherapy or in combination with dabrafenib conferred radiographic partial response in 75% of patients harboring BRAF or NF1 actionable mutations. Cabozantinib conferred radiographic partial response in two patients harboring a MET and a PDGFRA/KDR amplification. Patients with IDH1 wild-type gliomas that harbored actionable alterations who received genotype-matched targeted therapy had longer progression-free (PFS) and overall survival (OS; 7.37 and 14.72 respectively) than patients whose actionable alterations were not targeted (2.83 and 4.2 months respectively).ConclusionWhile multiple host, tumor and drug-related features may limit the delivery and efficacy of targeted therapies for patients with high-grade gliomas, genotype-matched targeted therapies confer favorable clinical outcomes. Further studies are needed to generate more data on the impact of biochemical features of targeted therapies on their clinical efficacy for high-grade gliomas.
A critical systematic review of K-12 neurology/neuroscience pipeline programs
Authors: Minen Mia T. , Lebowitz Naomi , Ekhtman Jane , Oza Khushalee , Yusaf Ishah , Katara Aarti , Aymon Ramisha , Plovnick Caitlin 
Published: December 2023

BackgroundEarly exposure to neuroscience is imperative to strengthening the neuroscience and neurology pipeline and may present an avenue for increasing the number of practicing neurologists and diversifying the neuroscience workforce. Our objective was to systematically review existing K-12 neuroscience education and outreach programs to understand what educational programs have been developed and implemented.MethodsWe conducted an electronic database search of PubMed, EMBASE, PsycINFO, Education Source, and ERIC. All eligible articles were systematically reviewed to examine the type of program developed, target age group, implementation, and efficacy.ResultsOur search produced 2,574 results, from which 23 articles were deemed eligible. The breakdown by age group was as follows: 5 elementary school, 8 middle school, 8 high school, and 2 general K-12 range of students. Six articles described programs intended for URM students. All programs were found to be successful in exposing students to neuroscience and inspiring interest in pursuing a career in the field of neurology.DiscussionFurther efforts are necessary to analyze the long-term effectiveness of K-12 neuroscience education and outreach programs in overcoming the shortage of neurologists and explore the impact of mentorship for various age groups among K-12.Systematic review registrationhttps://doi.org/10.17605/OSF.IO/2G8CN.
Denoising Diffusion Probabilistic Models and Transfer Learning for citrus disease diagnosis
Authors: Li Yuchen , Guo Jianwen , Qiu Honghua , Chen Fengyi , Zhang Junqi 
Published: December 2023

ProblemsPlant Disease diagnosis based on deep learning mechanisms has been extensively studied and applied. However, the complex and dynamic agricultural growth environment results in significant variations in the distribution of state samples, and the lack of sufficient real disease databases weakens the information carried by the samples, posing challenges for accurately training models.AimThis paper aims to test the feasibility and effectiveness of Denoising Diffusion Probabilistic Models (DDPM), Swin Transformer model, and Transfer Learning in diagnosing citrus diseases with a small sample.MethodsTwo training methods are proposed: The Method 1 employs the DDPM to generate synthetic images for data augmentation. The Swin Transformer model is then used for pre-training on the synthetic dataset produced by DDPM, followed by fine-tuning on the original citrus leaf images for disease classification through transfer learning. The Method 2 utilizes the pre-trained Swin Transformer model on the ImageNet dataset and fine-tunes it on the augmented dataset composed of the original and DDPM synthetic images.Results and conclusionThe test results indicate that Method 1 achieved a validation accuracy of 96.3%, while Method 2 achieved a validation accuracy of 99.8%. Both methods effectively addressed the issue of model overfitting when dealing with a small dataset. Additionally, when compared with VGG16, EfficientNet, ShuffleNet, MobileNetV2, and DenseNet121 in citrus disease classification, the experimental results demonstrate the superiority of the proposed methods over existing approaches to a certain extent.
The prolonged effect of film mulch and P application on lucerne forage yield in a semiarid environment
Authors: Kong Meng , Gu Yan-Jie , Han Cheng-Long , Shi Xiao-Peng , Kang Jing , Siddique Kadambot H. M. , Li Feng-Min , Yuan Zi-Qiang 
Published: December 2023

IntroductionLimited water and soil phosphorus (P) availability often hampers lucerne productivity in semiarid regions. Plastic film mulch and P application typically enhance young lucerne (2–3 years) productivity by increasing soil water use and P availability. However, the prolonged impact of film mulch and P application on lucerne productivity as the stand ages remains unclear.MethodsThis study conducted a 9-year field experiment on the semiarid Loess Plateau to investigate how film mulch and P application affect lucerne forage yield, soil water content, and soil fertility. The field experiment used a split-plot design with randomized blocks, in which the whole plots were with (M1) and without plastic film mulch (M0), and the split plots were four P rates (0 (P0), 9.7 (P1), 19.2 (P2), and 28.8 (P3) kg P ha−1).Results and discussionThe M1 treatment produced significantly higher lucerne forage yields than the M0 treatment during the first five years, but the yield-increasing effect of film mulch gradually diminished over time, with no effect in Years 6–8, and lower yields than the M0 treatment in Year 9. Phosphorus fertilization significantly increased forage yield after Year 3 in the M0 treatment, but only in Years 3–5 in the M1 treatment. In Years 2–5, film mulch significantly increased soil organic carbon, total nitrogen (N), inorganic N, and microbial biomass carbon in P0, P1, and P2 but not in P3. However, in Years 7–9, film mulch significantly decreased soil available potassium (K), organic carbon mineralization, lucerne density, and shoot K concentration, but did not reduce soil N and P availability at any level P of application. Moreover, plastic film mulch significantly increased the soil water content at 0–300 cm deep from Year 7 onwards. In conclusion, film mulch ceased to enhance lucerne production beyond year 6, which could not be attributed to soil water content, N or P availability but was partially associated with reduced soil K availability. Consequently, future research should focus on soil K availability, and K addition should be considered after five years in lucerne pastures mulched with plastic film in semiarid areas.
Exploring the efficacy of traditional Chinese medicine exercise in alleviating anxiety and depression in older adults: a comprehensive study with randomized controlled trial and network meta-analysis
Authors: Dong Yangjian , Kuang Xiaoqin , Dong Lili , Chao Guodong , Qi Juancai , Zhang Xinxin , Yao Jiwei 
Published: December 2023

BackgroundAnxiety and depression pose a significant global health challenge for elderly individuals. Research has demonstrated the potential of traditional Chinese medicine (TCM) exercise therapies in alleviating these conditions. However, ongoing debate and uncertainty persist regarding the optimal therapy and its impact on anxiety and depression. This study aims to evaluate and prioritize TCM exercise therapies for anxiety and depression in older adults, to identify the most effective intervention, and to provide a basis for informed decision-making in clinical practice.MethodsWe conducted a comprehensive search of electronic databases including The Web of Science, PubMed, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wang Fang, and Wei Pu database up to July 2022. Two researchers independently reviewed all included studies and extracted relevant data. Traditional meta-analysis was performed using Review Manager version 5.4, while network meta-analysis was conducted using STATA software version 15.1 to generate network evidence plots and funnel plots.ResultA total of 30 trials, involving 2,806 participants, met the eligibility criteria. The traditional meta-analysis revealed that TCM exercise significantly improved anxiety (SMD = −0.82, 95% CI = −1.39, −0.26, p = 0.004) and depression (SMD = −0.63, 95% CI = −0.85, −0.41, p &lt; 0.01) compared to the control group. In the network meta-analysis, Tai Chi exercise was ranked as the most effective intervention for anxiety (68.3%), followed by Yi Jin Jing (63.6%). For depression, the Tai Chi exercise was ranked as the most effective (87.8%), followed by the Ba Duan Jin exercise (74.1%).ConclusionTCE exercise can improve anxiety and depression in older adults, Among the four TCE exercise therapies included, Tai Chi exercise showed better efficacy than other types of treatment. Nevertheless, further research is required to validate the effectiveness of this exercise therapy through larger and more rigorous clinical trials.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023438697.
Temperature fluctuation and acute myocardial infarction in Beijing: an extended analysis of temperature ranges and differences
Authors: Tang Siqi , Fu Jia , Liu Yanbo , Zhao Yakun , Chen Yuxiong , Han Yitao , Zhao Xinlong , Liu Yijie , Jin Xiaofeng , Fan Zhongjie 
Published: December 2023

PurposeFew studies examined the relationship between temperature fluctuation metrics and acute myocardial infarction (AMI) hospitalizations within a single cohort. We aimed to expand knowledge on two basic measures: temperature range and difference.MethodsWe conducted a time-series analysis on the correlations between temperature range (TR), daily mean temperature differences (DTDmean), and daily mean-maximum/minimum temperature differences (TDmax/min) and AMI hospitalizations, using data between 2013 and 2016 in Beijing, China. The effects of TRn and DTDmeann over n-day intervals were compared, respectively. Subgroup analysis by age and sex was performed.ResultsA total of 81,029 AMI hospitalizations were included. TR1, TDmax, and TDmin were associated with AMI in J-shaped patterns. DTDmean1 was related to AMI in a U-shaped pattern. These correlations weakened for TR and DTDmean with longer exposure intervals. Extremely low (1st percentile) and high (5°C) DTDmean1 generated cumulative relative risk (CRR) of 2.73 (95% CI: 1.56–4.79) and 2.15 (95% CI: 1.54–3.01). Extremely high TR1, TDmax, and TDmin (99th percentile) correlated with CRR of 2.00 (95% CI: 1.73–2.85), 1.71 (95% CI: 1.40–2.09), and 2.73 (95% CI: 2.04–3.66), respectively. Those aged 20–64 had higher risks with large TR1, TDmax, and TDmin, while older individuals were more affected by negative DTDmean1. DTDmean1 was associated with a higher AMI risk in females.ConclusionTemperature fluctuations were linked to increased AMI hospitalizations, with low-temperature extremes having a more pronounced effect. Females and the older adult were more susceptible to daily mean temperature variations, while younger individuals were more affected by larger temperature ranges.
Factors Contributing to Resilience Among First Generation Migrants, Refugees and Asylum Seekers: A Systematic Review
Authors: Lindert Jutta , Samkange-Zeeb Florence , Jakubauskiene Marija , Bain Paul A. , Mollica Richard 
Published: December 2023

Objectives: We aimed at 1) collating and evaluating the current evidence on factors contributing to resilience of adult transnational migrants, 2) identifying methodological factors which contribute to the findings, 3) identifying and analyzing promotive and preventive factors contributing to the findings.Methods: A systematic search for relevant studies published until 2021 was conducted in PubMed, PsycINFO, PTSDPubs, and Web of Science. Both, quantitative and qualitative peer-reviewed observational studies reporting on resilience and wellbeing, sense of coherence, or post-traumatic growth outcomes among transnational migrants (aged 18+). Risk of Bias was assessed using the Critical Appraisal Skills Program for qualitative studies and the Appraisal Tool for cross-sectional studies. Due to the heterogeneity of studies we did a narrative review.Results: Database search yielded 3,756 unique records, of those n = 80 records, representing n = 76 studies met the inclusion criteria. The studies provided knowledge on resilience for n = 9,845 transnational migrants across 23 countries. All studies except two were cross sectional. N = 45 reported on resilience, n = 4 on Sense of Coherence and n = 15 on Post-Traumatic Growth. The study methods were not related to the findings. Future orientation, hope and religion/spirituality, caring for others and having opportunities were shown to be more pertinent to resilience outcomes than institutional care structures.Conclusion: Our findings highlight that mental health professionals and policymakers should try to support positive perspectives for the future and encourage policies tailored towards giving refugees opportunities to work, learn and care and to help others.
Positive Changes in Fruit Quality, Leaf Antioxidant Defense System, and Soil Fertility of Beni-Madonna Tangor Citrus (Citrus nanko × C. amakusa) after Field AMF Inoculation
Authors: Zhou Li-Jun , Wang Yu , Alqahtani Mashael Daghash , Wu Qiang-Sheng 
Published: December 2023

Citrus plants rely heavily on arbuscular mycorrhizal fungi (AMF) due to their lack of root hairs. Most experiments have been conducted with AMF inoculation under potted conditions, while field inoculation of AMF on citrus, especially a high economic hybrid tangor variety Beni-Madonna (Citrus nanko × C. amakusa), has been rarely recorded. This study aimed to analyze the effects of two AMF inoculations (a single Funneliformis mosseae and a mixture of F. mosseae, Diversispora versiformis, and Rhizophagus intraradices) on the internal and external fruit quality, leaf antioxidant defense system, and soil fertility and structure of top-worked Beni-Madonna tangor citrus trees. Three and a half years after AMF inoculations, soil hyphal length and root mycorrhizal colonization rate increased by 61.2–101.8% and 15.85–29.6% in inoculated plants, respectively. Inoculated trees had higher external fruit coloration value, fruit horizontal diameter, and fruit weight, and lower fruit rigidity than uninoculated trees. AMF-inoculated trees had higher glucose levels of fruit peels, fructose and sucrose levels of fruit fleshes, and the ratio of fruit soluble solids/titratable acids, as well as lower titratable acids concentrations than non-AMF-inoculated trees. AMF inoculation significantly increased leaf nitrogen balance index, chlorophyll index, peroxidase, catalase, superoxide dismutase, and glutathione reductase activities, as well as reduced glutathione and oxidized glutathione concentrations, resulting in lower hydrogen peroxide and malondialdehyde levels when compared to the uninoculated treatment. In addition, inoculated trees presented higher soil nutrient levels, including organic carbon, available K, and Olsen-P as, well as soil aggregate stability (based on mean weight diameter) than uninoculated trees. This study concluded that field AMF inoculation improved fruit quality, enhanced leaf antioxidant defense system, and improved soil fertility of Beni-Madonna trees, with mixed AMF being prominent in improving fruit quality and F. mosseae being prominent in enhancing leaf antioxidant defense system and improving soil fertility.
Genome-Wide Identification, Characterization, and Expression Analysis of the Copper-Containing Amine Oxidase Gene Family in Mangrove Kandelia obovata
Authors: Hussain Quaid , Ye Ting , Shang Chenjing , Li Sihui , Nkoh Jackson Nkoh , Li Wenyi , Hu Zhangli 
Published: December 2023

Copper-containing amine oxidases (CuAOs) are known to have significant involvement in the process of polyamine catabolism, as well as serving crucial functions in plant development and response to abiotic stress. A genome-wide investigation of the CuAO protein family was previously carried out in sweet orange (Citrus sinensis) and sweet cherry (Prunus avium L.). Six CuAO (KoCuAO1-KoCuAO6) genes were discovered for the first time in the Kandelia obovata (Ko) genome through a genome-wide analysis conducted to better understand the key roles of the CuAO gene family in Kandelia obovata. This study encompassed an investigation into various aspects of gene analysis, including gene characterization and identification, subcellular localization, chromosomal distributions, phylogenetic tree analysis, gene structure analysis, motif analysis, duplication analysis, cis-regulatory element identification, domain and 3D structural variation analysis, as well as expression profiling in leaves under five different treatments of copper (CuCl2). Phylogenetic analysis suggests that these KoCuAOs, like sweet cherry, may be subdivided into three subgroups. Examining the chromosomal location revealed an unequal distribution of the KoCuAO genes across four out of the 18 chromosomes in Kandelia obovata. Six KoCuAO genes have coding regions with 106 and 159 amino acids and exons with 4 and 12 amino acids. Additionally, we discovered that the 2.5 kb upstream promoter region of the KoCuAOs predicted many cis elements linked to phytohormones and stress responses. According to the expression investigations, CuCl2 treatments caused up- and downregulation of all six genes. In conclusion, our work provides a comprehensive overview of the expression pattern and functional variety of the Kandelia obovata CuAO gene family, which will facilitate future functional characterization of each KoCuAO gene.