bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial results of the INSPIRE clinical trial—investigating radiation dosimetry for differentiated thyroid cancer patients
Authors: Taprogge Jan , Abreu Carla , Vávrová Lenka , Carnegie-Peake Lily , Rushforth Dominic , Gape Paul , Gear Jonathan , Murray Iain , Wong Kee H. , Newbold Kate , Yusuf Siraj , Flux Glenn 
Published: May 2023

IntroductionThe optimal strategy for differentiated thyroid cancer (DTC) patients treated with radioiodine (RAI) following thyroidectomy remains controversial. Multi-centre clinical studies are essential to identify strategies to improve patient outcomes while minimising treatment-induced toxicity.Materials and MethodsThe INSPIRE clinical trial (ClinicalTrials.gov Identifier: NCT04391244) aims to investigate patient-specific dosimetry for DTC patients and to determine the range of absorbed doses delivered to target and non-target tissues and their relationship with treatment outcome and toxicity.ResultsWe report here initial results of the first 30 patients enrolled onto the INSPIRE trial. A large range of absorbed doses are observed for both thyroid remnants and salivary glands, with median values of 4.8 Gy (Range 0.2 – 242 Gy) and 0.3 Gy (Range 0.1 to 1.7 Gy), respectively.DiscussionThe preliminary study results are encouraging and could help to improve our understanding of absorbed doses to thyroid remnants and normal organs following RAI therapy. Such knowledge could potentially enable patient-specific treatment planning with improved clinical outcomes and quality-of-life of patients.
RUNX2 promotes gastric cancer progression through the transcriptional activation of MGAT5 and MMP13
Authors: Wang Ying , Tan Zhibo , Li Xiaoyu , Zhang Lili , Pei Xiaojuan 
Published: May 2023

IntroductionRUNX2 is overexpressed in gastric cancer but the mechanism(s) through which it promotes tumor progression remain undefined. Here, we investigated the role of RUNX2 on gastric cancer pathogenesis at the molecular level.MethodsThe qRT-PCR and western bolt were utilized to examine the mRNA and protein levels. CCK-8, Transwell and wound healing assays were used to measure cell proliferation, invasion and migration. CHIP-PCR gel electrophoresis was used to verify RUNX2 as a transcription factor for MMP13 and MGAT5. The in vivo assay was utilized to assess tumor growth. In vivo assay was used to evaluate tumor growth, aberrant expression of RUNX2 and lung metastasis of gastric cancer.ResultsRUNX2 is overexpressed in MKN-45 and AGS cells. Genetic RUNX2 silencing reduced the proliferation, invasion and migration of MKN-45 and AGS cells. Analysis of the gastric cancer samples from the database revealed a significant positive correlation between MGAT5, MMP13, and RUNX2 expression. JASPAR analysis revealed that there was a potential binding site of RUNX2 in the promoter regions of MGAT5 and MMP13, and the experimental results confirmed that RUNX2 could regulate the expression of MGAT5 and MMP13 respectively. In vivo assays confirmed the aberrant expression of RUNX2 in mouse models of gastric cancer and reduced growth and lung metastasis in RUNX2 silenced xenograft tumors assessed.ConclusionCollectively, these data reveal that RUNX2 enhances MGAT5 and MMP13 expression in gastric cancer cells and represents a biomarker and potential therapeutic target for gastric cancer therapy.
Association of early immune-related adverse events with treatment efficacy of neoadjuvant Toripalimab in resectable advanced non-small cell lung cancer
Authors: Tao Ye , Li Xiang , Liu Bing , Wang Jia , Lv Chao , Li Shaolei , Wang Yuzhao , Chen Jinfeng , Yan Shi , Wu Nan 
Published: May 2023

BackgroundNeoadjuvant immunotherapy with anti-PD-1 was proved promising in resectable non-small cell lung cancer (NSCLC). Immune-related adverse events (irAEs) have been preliminarily implicated their association with treatment efficacy. Here we elucidated the early onset of irAEs associated with better clinical outcomes in a prospective study (Renaissance study).MethodsWe conducted the prospective study of NSCLC patients treated by neoadjuvant Toripalimab (240mg, every 3 weeks) plus double platinum-based chemotherapy from December 2020 to March 2022 at Peking University Cancer Hospital. Patients were enrolled if they have resectable IIB-IIIB NSCLC without EGFR/ALK mutation. Data were analyzed to explore the relationship between clinical outcome and irAEs after neoadjuvant treatment. A multidisciplinary team including physicians, surgeons, and radiologists, confirmed the irAEs according to the clinical manifestation. The relationship between irAEs and pathological outcomes was analyzed. The Renaissance study was approved by the Peking University Ethic board (2020YJZ58) and registered at https://clinicaltrials.gov/ as NCT04606303.ResultsFifty-five consecutive patients were enrolled with a male-to-female ratio of 10:1, the median age was 62 years old (IQR: 45-76), of which 44 patients (80%) were diagnosed with squamous cell carcinoma. Forty-eight of 55 patients finally received thoracic surgery with a median preoperative waiting time of 67 days (IQR 39-113 days). Pathological results demonstrated that 31 (64.6%) patients achieved major pathological response (MPR) and 24 (50.0%) achieved complete pathological response (pCR). Among 48 patients who received R0 resection, immunotherapy-related thyroid dysfunction, rash/pruritus and enteritis occurred in 11 patients (22.9%), 7 patients (14.6%), and 1 patient (2.1%), respectively. Six patients (54.5%) with thyroid dysfunction achieved MPR with 5 (45.5%) achieved pCR, and a median time to onset was 45 days (IQR 21-91 days). Six patients (85.7%) with rash or pruritus achieved MPR and 5 patients (71.4%) achieved pCR, with median time to onset being 8 days (IQR 6-29 days). Furthermore, irAEs had no significant influence on operation time (170.6 min vs 165.7 min, P=0.775), intraoperative blood loss (67.4 mL vs 64.3 mL, P=0.831) and preoperative waiting time (93 days vs 97 days, P=0.630) when comparing with patients without irAEs (Figure 1).ConclusionThe immunotherapy-related rash is potentially associated with pathological outcomes in NSCLC patients after neoadjuvant chemo-immunotherapy, suggesting easy-to-find irAEs, such as rash, can be used as indicators to predict response to neoadjuvant chemo-immunotherapy.Clinical trial registrationclinicaltrials.gov/, identifier NCT04606303.
Development of a machine learning framework for radiation biomarker discovery and absorbed dose prediction
Authors: Andersson Björn , Langen Britta , Liu Peidi , Dávila López Marcela 
Published: May 2023

BackgroundMolecular radiation biomarkers are an emerging tool in radiation research with applications for cancer radiotherapy, radiation risk assessment, and even human space travel. However, biomarker screening in genome-wide expression datasets using conventional tools is time-consuming and underlies analyst (human) bias. Machine Learning (ML) methods can improve the sensitivity and specificity of biomarker identification, increase analytical speed, and avoid multicollinearity and human bias.AimTo develop a resource-efficient ML framework for radiation biomarker discovery using gene expression data from irradiated normal tissues. Further, to identify biomarker panels predicting radiation dose with tissue specificity.MethodsA strategic search in the Gene Expression Omnibus database identified a transcriptomic dataset (GSE44762) for normal tissues radiation responses (murine kidney cortex and medulla) suited for biomarker discovery using an ML approach. The dataset was pre-processed in R and separated into train and test data subsets. High computational cost of Genetic Algorithm/k-Nearest Neighbor (GA/KNN) mandated optimization and 13 ML models were tested using the caret package in R. Biomarker performance was evaluated and visualized via Principal Component Analysis (PCA) and dose regression. The novelty of ML-identified biomarker panels was evaluated by literature search.ResultsCaret-based feature selection and ML methods vastly improved processing time over the GA approach. The KNN method yielded overall best performance values on train and test data and was implemented into the framework. The top-ranking genes were Cdkn1a, Gria3, Mdm2 and Plk2 in cortex, and Brf2, Ccng1, Cdkn1a, Ddit4l, and Gria3 in medulla. These candidates successfully categorized dose groups and tissues in PCA. Regression analysis showed that correlation between predicted and true dose was high with R2 of 0.97 and 0.99 for cortex and medulla, respectively.ConclusionThe caret framework is a powerful tool for radiation biomarker discovery optimizing performance with resource-efficiency for broad implementation in the field. The KNN-based approach identified Brf2, Ddit4l, and Gria3 mRNA as novel candidates that have been uncharacterized as radiation biomarkers to date. The biomarker panel showed good performance in dose and tissue separation and dose regression. Further training with larger cohorts is warranted to improve accuracy, especially for lower doses.
Comprehensive transcriptomic analysis and meta-analysis identify therapeutic effects of N-acetylcysteine in nonalcoholic fatty liver disease
Authors: Yang Keungmo , Kim Hee-Hoon , Shim Young-Ri , Ryu Tom , Kim Chang Wook 
Published: May 2023

Introduction: The continuous rise in the prevalence of nonalcoholic fatty liver disease (NAFLD) is emerging as a global health issue. Although the protective effects of N-acetylcysteine (NAC), an antioxidant, against various diseases have been reported, it is still unclear whether NAC has therapeutic potential in NAFLD. Thus, the present meta-analysis aimed to investigate the efficacy of NAC on NAFLD in preclinical studies.Methods: By searching PubMed, Web of Science, and Cochrane Library, 13 studies were included. The methodological quality was assessed based on the SYstematic Review Centre for Laboratory animal Experimentation guideline, and heterogeneity was evaluated with I2 and p values. Publication bias was assessed by Egger’s test and sensitivity analysis was performed.Results: The results showed that NAC treatment significantly improved systemic and hepatic lipid metabolism (p &lt; 0.01), inflammation-related liver injury (p &lt; 0.01), glucose intolerance (p &lt; 0.05), and hepatic steatosis (p &lt; 0.01) by restoring hepatic glutathione (GSH) (p &lt; 0.05) and GSH reductase (p &lt; 0.05) levels compared to controls in NAFLD-induced animals. Consistently, in bulk, single-cell, and spatial transcriptomics data, the abovementioned target pathways of NAC were strongly associated with NAFLD development in mice and patients.Conclusion: Our study suggests that NAC has therapeutic potential for NAFLD and should be considered for future clinical trials.
A combined approach of DNA metabarcoding collectively enhances the detection efficiency of medicinal plants in single and polyherbal formulations
Authors: Travadi Tasnim , Shah Abhi P. , Pandit Ramesh , Sharma Sonal , Joshi Chaitanya , Joshi Madhvi 
Published: May 2023

IntroductionEmpirical research has refined traditional herbal medicinal systems. The traditional market is expanding globally, but inadequate regulatory guidelines, taxonomic knowledge, and resources are causing herbal product adulteration. With the widespread adoption of barcoding and next-generation sequencing, metabarcoding is emerging as a potential tool for detecting labeled and unlabeled plant species in herbal products.MethodsThis study validated newly designed rbcL and ITS2 metabarcode primers for metabarcoding using in-house mock controls of medicinal plant gDNA pools and biomass pools. The applicability of the multi-barcode sequencing approach was evaluated on 17 single drugs and 15 polyherbal formulations procured from the Indian market.ResultsThe rbcL metabarcode demonstrated 86.7% and 71.7% detection efficiencies in gDNA plant pools and biomass mock controls, respectively, while the ITS2 metabarcode demonstrated 82.2% and 69.4%. In the gDNA plant pool and biomass pool mock controls, the cumulative detection efficiency increased by 100% and 90%, respectively. A 79% cumulative detection efficiency of both metabarcodes was observed in single drugs, while 76.3% was observed in polyherbal formulations. An average fidelity of 83.6% was observed for targeted plant species present within mock controls and in herbal formulations.DiscussionIn the present study, we achieved increasing cumulative detection efficiency by combining the high universality of the rbcL locus with the high-resolution power of the ITS2 locus in medicinal plants, which shows applicability of multilocus strategies in metabarcoding as a potential tool for the Pharmacovigilance of labeled and unlabeled plant species in herbal formulations.
Monitoring weed mechanical and chemical damage stress based on chlorophyll fluorescence imaging
Authors: Quan Longzhe , Chen Keyong , Chen Tianbao , Li Hailong , Li Wenchang , Cheng Tianyu , Xia Fulin , Lou Zhaoxia , Geng Tianyu , Sun Deng , Jiang Wei 
Published: May 2023

Currently, mechanical and chemical damage is the main way to carry out weed control. The use of chlorophyll fluorescence (CF) technology to nondestructively monitor the stress physiological state of weeds is significant to reveal the damage mechanism of mechanical and chemical stresses as well as complex stresses. Under simulated real field environmental conditions, different species and leaf age weeds (Digitaria sanguinalis 2-5 leaf age, and Erigeron canadensis 5-10 leaf age) were subjected to experimental treatments for 1-7 days, and fluorescence parameters were measured every 24 h using a chlorophyll fluorometer. The aim of this study was to investigate the changes in CF parameters of different species of weeds (Digitaria sanguinalis, Erigeron canadensis) at their different stress sites under chemical, mechanical and their combined stresses. The results showed that when weeds (Digitaria sanguinalis and Erigeron canadensis) were chemically stressed in different parts, their leaf back parts were the most severely stressed after 7 days, with photosynthetic inhibition reaching R=75%. In contrast, mechanical stress differs from its changes, and after a period of its stress, each parameter recovers somewhat after 1 to 2 days of stress, with heavy mechanical stress R=11%. Complex stress had the most significant effect on CF parameters, mainly in the timing and efficiency of changes in Fv/Fm, Fq’/Fm’, ETR, Rfd, NPQ and Y(NO), with R reaching 71%-73% after only 3-4 days of complex stress, and its changes in complex stress were basically consistent with the pattern of changes in its chemical stress. The results of the study will help to understand the effects of mechanical and chemical stresses and combined stresses on CF parameters of weeds and serve as a guide for efficient weed control operations and conducting weed control in the future.
Moderate nitrogen application improved salt tolerance by enhancing photosynthesis, antioxidants, and osmotic adjustment in rapeseed (Brassica napus L.)
Authors: Wang Long , Zheng Jingdong , Zhou Guisheng , Li Jing , Qian Chen , Lin Guobin , Li Yiyang , Zuo Qingsong 
Published: May 2023

Salt stress is a major adverse environmental factor limiting plant growth. Nitrogen (N) application is an effective strategy to alleviate the negative effects of salt stress on plants. To improve the knowledge of the mechanism of N application on alleviating salt stress on rapeseed seedlings, a pot experiment was conducted with four N application treatments (0, 0.1, 0.2, and 0.3 g N kg−1 soil, referred to as N0, N1, N2, and N3, respectively) and exposed to non-salt stress (0 g NaCl kg−1 soil, referred to as S0) and salt stress (3 g NaCl kg−1 soil, referred to as S1) conditions. The results indicated that in comparison with non-salt stress, salt stress increased the Na content (236.53%) and reactive oxygen species (ROS) production such as hydrogen peroxide (H2O2) (30.26%), resulting in cell membrane lipid peroxidation characterized by an increased content of malondialdehyde (MDA) (122.32%) and suppressed photosynthetic rate (15.59%), finally leading to inhibited plant growth such as shorter plant height, thinner root neck, lower leaf area, and decreased dry weight. N application improved the plant growth, and the improvement by N application under salt stress was stronger than that under non-salt stress, suggesting that rapeseed seedlings exposed to salt stress are more sensitive to N application and require N to support their growth. Moreover, seedlings exposed to salt stress under N application showed lower ROS accumulation; increased photosynthesis; higher antioxidants such as catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and ascorbic acid (AsA); and greater accumulation of osmotic substances including soluble protein, soluble sugar, and proline, as compared with seedlings without N application. In particular, the best improvement by N application under salt stress occurred at the N2 level, while too high N application could weaken the improvement due to inhibited N metabolism. In summary, this study suggests that moderate N application can improve photosynthesis, antioxidants, and osmoregulation to alleviate the adverse effects of salt stress in rapeseed seedlings.
Global trends and hotspots in the digital therapeutics of autism spectrum disorders: a bibliometric analysis from 2002 to 2022
Authors: Wu Xuesen , Deng Haiyin , Jian Shiyun , Chen Huian , Li Qing , Gong Ruiyu , Wu Jingsong 
Published: May 2023

IntroductionAutism spectrum disorder (ASD) is a severe neurodevelopmental disorder that has become a major cause of disability in children. Digital therapeutics (DTx) delivers evidence-based therapeutic interventions to patients that are driven by software to prevent, manage, or treat a medical disorder or disease. This study objectively analyzed the current research status of global DTx in ASD from 2002 to 2022, aiming to explore the current global research status and trends in the field.MethodsThe Web of Science database was searched for articles about DTx in ASD from January 2002 to October 2022. CiteSpace was used to analyze the co-occurrence of keywords in literature, partnerships between authors, institutions, and countries, the sudden occurrence of keywords, clustering of keywords over time, and analysis of references, cited authors, and cited journals.ResultsA total of 509 articles were included. The most productive country and institution were the United States and Vanderbilt University. The largest contributing authors were Warren, Zachary, and Sarkar, Nilanjan. The most-cited journal was the Journal of Autism and Developmental Disorders. The most-cited and co-cited articles were Brian Scarselati (Robots for Use in Autism Research, 2012) and Ralph Adolphs (Abnormal processing of social information from faces in autism, 2001). “Artificial Intelligence,” “machine learning,” “Virtual Reality,” and “eye tracking” were common new and cutting-edge trends in research on DTx in ASD.DiscussionThe use of DTx in ASD is developing rapidly and gaining the attention of researchers worldwide. The publications in this field have increased year by year, mainly concentrated in the developed countries, especially in the United States. Both Vanderbilt University and Yale University are very important institutions in the field. The researcher from Vanderbilt University, Warren and Zachary, his dynamics or achievements in the field is also more worth our attention. The application of new technologies such as virtual reality, machine learning, and eye-tracking in this field has driven the development of DTx on ASD and is currently a popular research topic. More cross-regional and cross-disciplinary collaborations are recommended to advance the development and availability of DTx.
The impact of COVID-19 on a South African pediatric cardiac service: implications and insights into service capacity
Authors: Aldersley Thomas , Brooks Andre , Human Paul , Lawrenson John , Comitis George , De Decker Rik , Fourie Barend , Manganyi Rodgers , Pribut Harold , Salie Shamiel , Swanson Lenise , Zühlke Liesl 
Published: May 2023

Background and ObjectivesThe Western Cape public pediatric cardiac service is under-resourced. COVID-19 regulations are likely to have long-term effects on patient care but may provide insight into service capacity requirements. As such, we aimed to quantify the impact of COVID-19 regulations on this service.MethodsAn uncontrolled retrospective pre-post study of all presenting patients over two, one-year periods; the pre-COVID-19 period (01/03/2019–29/02/2020) and the peri-COVID-19 period (01/03/2020–28/02/2021).ResultsAdmissions decreased by 39% (624 to 378) and cardiac surgeries decreased by 29% (293 to 208) in the peri-COVID-19 period, with an increase in urgent cases (PR:5.99, 95%CI:3.58–10.02, p &lt; 0.001). Age at surgery was lower in the peri-COVID-19 period, 7.2 (2.4–20.4) vs. 10.8 (4.8–49.2) months (p &lt; 0.05), likewise, age at surgery for transposition of the great arteries (TGA) was lower peri-COVID-19, 15 (IQR:11.2–25.5) vs. 46 (IQR:11–62.5) days (p &lt; 0.05). Length of stay 6 (IQR:2–14) vs. 3 days (IQR:1–9) (p &lt; 0.001), complications (PR:1.21, 95%CI:1.01–1.43, p &lt; 0.05), and age-adjusted delayed-sternal-closure rates (PR:3.20, 95%CI:1.09–9.33, p &lt; 0.05) increased peri-COVID-19.ConclusionCardiac procedures were significantly reduced in the peri-COVID-19 period which will have implications on an overburdened service and ultimately, patient outcomes. COVID-19 restrictions on elective procedures freed capacity for urgent cases, demonstrated by the absolute increase in urgent cases and significant decrease in age at TGA-surgery. This facilitated intervention at the point of physiological need, albeit at the expense of elective procedures, and also revealed insights into capacity requirements of the Western Cape. These data emphasize the need for an informed strategy to increase capacity and reduce backlog whilst ensuring minimal morbidity and mortality.