bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bulk- and single cell-RNA sequencing reveal KIF20A as a key driver of hepatocellular carcinoma progression and immune evasion
Authors: Su Zhixiong , Zhong Yaqi , He Yufang , You Lijie , Xin Fuli , Wang Lei , Liu Zhihua 
Published: November 2024

IntroductionKinesin family member 20A (KIF20A) is essential for cell proliferation and is implicated in promoting tumor progression, but its role in hepatocellular carcinoma (HCC) remains poorly studied.MethodsThrough the analysis of bulk RNA-sequencing (bulk RNA-seq) and single-cell RNA sequencing (scRNA-seq) data, the expression of KIF20A and its relationship with diagnosis, prognosis, and the immune microenvironment were examined. The association between KIF20A and the malignant progression and metastasis of HCC was confirmed through in vitro and in vivo experiments. Furthermore, patient re-staging was performed using Recursive Partitioning Analysis (RPA) to enhance clinical benefit.ResultsIn this study, we firstly found KIF20A was overexprerssed in HCC both by bulk RNA-seq and scRNA-seq, and then the overexpression of KIF20A significantly promoted the proliferation, invasion, and metastasis in vitro. In vivo, the overexpression of KIF20A promoted the growth and lung metastasis of HCC. Furthermore, gene set variation analysis of bulk RNA-seq and scRNA-seq revealed that KIF20A might be associated with cell cycle related signaling pathways of E2F and G2M, and overexpression of KIF20A inhibited the activity of p21 and bax, as well as shortened G2 phase. Importantly, we found that KIF20A could induce T cell exhaustion via the SPP1-CD44 axe using scRNA-seq. Additionally, KIF20A was also correlated with the expression of immune checkpoint inhibitors (ICIs), and KIF20Ahigh subgroup might be benefited from the ICIs therapy.ConclusionKIF20A emerges as a pivotal driver of HCC progression, intricately regulating cell cycle pathways and modulating immune responses, which position KIF20A as a promising target for HCC management.
The CRAFITY score emerges as a paramount prognostic indicator in hepatocellular carcinoma patients received Lenvatinib and Pembrolizumab
Authors: Wu Weijie , Yang Zhenyun , Zou Hao , Long Teng , Zhou Zhongguo , Zhang Yaojun , Chen Minshan , Hu Dandan 
Published: November 2024

BackgroundLevels of C-reactive protein (CRP) and alpha-fetoprotein (AFP) in immunotherapy (CRAFITY) scores are associated with the prognosis of patients with hepatocellular carcinoma (HCC). This study aimed to explore the efficacy of lenvatinib and pembrolizumab (Len-P) based on the CRAFITY score.MethodsIn this study, 228 patients with HCC who received Len-P in Sun Yat-sen University Cancer Center were included. CRAFITY 0 score was defined as AFP level below 100 ng/ml, CRP level below 1 mg/dl, CRAFITY 1 score was defined as AFP level at least 100 ng/ml or CRP level at least 1 mg/dl. CRAFITY 2 scores were defined as AFP levels exceeding 100 ng/ml and CRP levels exceeding 100 ng/ml. The primary outcome was overall survival (OS). The second outcome was tumor response rate.ResultsThe survival time of CRAFITY 0 is significantly longer than that of CRAFITY 1 and CRAFITY 2 (p =.044). Univariate analysis showed that largest tumor size (HR = 2.149; 95% CI 1.129 - 4.091; p =.02), lymph node metastasis (HR = 2.012; 95% CI 1.132- 3.579; p = .017), and CRAFITY (HR = 0.372; 95% CI 0.168-0.824; p = .015) were important risk determinants of OS in all patients. The results of multivariate analysis show that CRAFITY score is an independent risk factors for OS (HR = 0.719; 95% CI 0.377-1.374; p =.048). The ORR of CRAFITY 0, 1 and 2 scores were 36.4%, 32% and 27.4%, respectively (p = .556). The ORR of intrahepatic lesions by CRAFITY 0, 1 and 2 were 37.9%, 35%, 30.6% (p= .688).ConclusionCRAFITY score is a good predictor of prognosis in HCC patients receiving Len-P.
ProC6C, a novel multi-stage malaria vaccine, elicits functional antibodies against the minor and central repeats of the Circumsporozoite Protein in human adults
Authors: Plieskatt Jordan , Ofori Ebenezer Addo , Naghizadeh Mohammad , Miura Kazutoyo , Flores-Garcia Yevel , Borbye-Lorenzen Nis , Tiono Alfred B. , Skogstrand Kristin , Sagara Issaka , Zavala Fidel , Theisen Michael 
Published: November 2024

IntroductionProC6C is a multi-stage malaria vaccine which includes Plasmodium falciparum Circumsporozoite Protein (PfCSP), Pfs48/45 and Pfs230 sequences, designed to elicit functional antibodies that prevent sporozoite invasion of human hepatocytes (PfCSP) and parasite development in mosquitoes (Pfs48/45 and Pfs230). ProC6C formulated on Alhydrogel was evaluated in combination with Matrix-M in a Phase 1 trial in Burkina Faso. The PfCSP antibody responses were assessed for magnitude, specificity, avidity and functionality. These results compliment the prior reported safety and tolerability of ProC6C as well as the transmission reducing activity of ProC6C.MethodsThe PfCSP response of ProC6C in Burkinabes in the Phase 1 trial (PACTR202201848463189) was profiled through the three vaccine administrations of 100 µg protein on Alhydrogel® alone (AlOH) or combined with 50 µg Matrix-M™ adjuvant (AlOH/Matrix-M). Serology was completed against full-length PfCSP and major/minor repeat peptides using antibody equivalence to PfCSP monoclonal antibodies (mAb 311, mAb 317 and mAb L9). Comparison of the ProC6C responses were made to those that received RTS,S/AS01 in a study conducted in Thailand. Bio-Layer Interferometry was further used to determine antibody avidity. The human IgG was subsequently purified, pooled, and evaluated in a mouse sporozoite challenge model to determine functionality.ResultsA single administration of ProC6C-AlOH/Matrix-M seroconverted 19 of 20 volunteers against PfCSP and significantly enhanced antibody titers to major and minor repeats (and present through D180). At D70, ProC6C-AlOH/Matrix-M PfCSP antibodies were found to be similar to responder pools generated from Thai adults receiving RTS,S/AS01. Additionally, ProC6C antibodies were found to be competitive to established PfCSP antibodies such as mAb 317 and mAb L9. The purified and pooled IgG from human volunteers, used in a passive transfer mouse sporozoite challenge model, showed a median of 50% inhibition (P=0.0058). ProC6C PfCSP antibodies were functional in this in vivo assessment and consistent with inhibition seen by other Circumsporozoite vaccines in this model.DiscussionThis analysis supports continued investigation of the antibody responses elicited by the ProC6C multi-stage malaria vaccine. This Phase 1 clinical trial demonstrated the short PfCSP sequence included in ProC6C can induce significant PfCSP antibodies in humans, which importantly were determined to be functional.
Local radiotherapy in extensive-stage small-cell lung cancer sustainably boosts the clinical benefit of first-line immunotherapy: a case report
Authors: Wang Hongming , Wang Nuoni , Li Shiyan , Du Yangfeng , Wu Tao , Tian Wei , Dong Wen , Liu Xiaoyang , Zhang Yan , Zheng Jiang , Xiao Zemin , Wu Zhijun 
Published: November 2024

BackgroundExtensive-stage small-cell lung cancer (ES-SCLC) has a dismal prognosis owing to its high aggressiveness, rapid drug resistance, and early metastasis. ES-SCLC responds well to first-line chemotherapy, and chemotherapy coupled with immunotherapy can further improve overall survival. However, the long-term survival of patients remains unsatisfactory because of its high recurrence rate and the poor efficacy of second-line treatment. Although local radiotherapy is an important component of the overall treatment for ES-SCLC, its value in the age of immunotherapy remains controversial.Case descriptionA 54-year-old male with ES-SCLC achieved a complete response (CR), as determined using enhanced computed tomography (CT) after four cycles of immunochemotherapy (serplulimab, carboplatin, and etoposide). Whole-body positron emission tomography-CT was performed during maintenance treatment with serplulimab, which showed primary lung, liver, and bone metastatic lesions with CR. However, several mediastinal lymph nodes exhibited glucose metabolism uptake, and new lesions appeared on the head. The patient underwent palliative radiotherapy of the head and consolidative thoracic radiotherapy of the chest and continued maintenance treatment with serplulimab. Subsequent magnetic resonance imaging of the head suggested good control of metastatic lesions (CR). The patient received first-line immunotherapy for approximately 20 months.ConclusionsThis report presents a patient with ES-SCLC who underwent local radiotherapy in addition to serplulimab as maintenance therapy. Although the programmed death-ligand 1 (PD-L1) expression level was negative and a PD-1 inhibitor instead of a PD-L1 inhibitor was used, the patient did not experience significant pneumonia during treatment, and the efficacy of the current treatment was evident. This treatment model warrants further clinical investigation.
COVID-19 vaccine and the risk of flares in inflammatory arthritis: a systematic literature review and meta-analysis
Authors: Hoxha Ariela , Striani Giovanni , Lovisotto Marco , Simioni Paolo , Doria Andrea , Ramonda Roberta 
Published: November 2024

IntroductionCoronavirus disease 2019 (COVID-19) vaccines aroused concerns about the risk of flares and adverse events in inflammatory arthritis (IA) since the vaccine clinical trials did not specifically investigate this subset of patients.MethodsA systematic literature review and meta-analysis to summarize the data on joint disease flare and adverse events following immunization (AEFI). Two researchers independently evaluated the literature on Pubmed, Scopus, and EMBASE databases from 22nd March 2020 to 30th September 2023. A random-effects model was used to pool odds ratios (OR) (with 95% CI) for the risk of joint disease flares and adverse events. Subgroup analyses were performed to evaluate the risk of disease flare between different IA and adverse events. Heterogeneity was assessed by I2 statistic.ResultsA total of 9874 IA patients were included in the study: 6579 (66.6%) patients affected by RA and 3295 (33.4%) spondyloarthritis (SpA). The overall rate of flares was higher in RA vs. SpA (9.1% vs. 5.3%). However, the pooled estimated analysis showed no increased risk of joint disease flare following COVID-19 vaccination in patients affected by RA vs. SpA [OR 0.88, 95% CI: 0.77-1.00]. Furthermore, a subgroup analysis showed an increased risk of joint flares in psoriatic arthritis (PsA) patients vs. RA [OR 0.79, 95% CI: 0.68-0.93, p=0.004]. The pooled estimated analysis revealed no increased risk of AEFI in patients with RA vs. SpA [1.02, 95% CI: 0.63-1.65].ConclusionsOur meta-analysis summarized the current evidence on joint disease flares and COVID-19 vaccine-associated AEFI in IA patients. Pooled analysis showed an increased risk of disease flares in PsA vs. RA patients.
Multiple recommended health behaviors among medical students in Western Canada: a descriptive study of self-reported knowledge, adherence, barriers, and time use
Authors: Ip Nathanael , Scarrott Kendra , Conklin Annalijn I. 
Published: November 2024

BackgroundGeneral medical practitioners are responsible for promoting and prescribing lifestyle modification and serve as role models for healthy behaviors. We aimed to assess self-reported knowledge, adherence, barriers and time spent on all recommended health behaviors among medical students.MethodsA cross-sectional online survey of eight behavioral domains among undergraduate medical students in The University of British Columbia, Canada, was analysed using descriptive statistics and visual display.ResultsBetween March and April 2023, 137 medical students participated in the survey (74% female). Over 80% had knowledge of five health behavior recommendations, but lacked knowledge of specific dietary recommendations in particular. Over 60% reported meeting guideline-recommended levels for tobacco, weekly alcohol, daily alcohol (females only), and physical activity (males only). Large gaps existed between knowledge and adherence for physical activity, sleep, sedentariness, screen time, and dietary recommendations. Sex differences in knowledge and adherence to recommended health behaviors were identified. Time spent on wellness focused on sleep (47–49 h/week), diet (9.6 h/week), exercise (5.8 h/week), and hobbies (6.1 h/week). Forgetting recommendations (69% of females, 71% of males), and lack of time (72% of females, 52% of males) were principal barriers to knowledge and adherence.ConclusionMost medical students in Western Canada reported not meeting multiple recommended health behaviors. Time was the largest barrier to adherence and free time was spent on sleep. Medical education may require protected time and dedicated content for health behaviors to ensure future physicians can be role models of health promotion for patients.
Subphenotypic features of patients with sepsis and ARDS: a multicenter cohort study
Authors: Li Nan , Fang DeYu , Ge Feng , Zhang Lin , Liu Ying , Jin Hongxu , Shen Hao , Xie Keliang , Gao Yan 
Published: November 2024

ObjectivesPatients with sepsis are often comorbid with acute respiratory distress syndrome (ARDS), and the phenotypic characteristics of pulmonary and non-pulmonary infections leading to ARDS are still unclear. This study aimed to compare the phenotypic characteristics of ARDS resulting from pulmonary infections and other non-site infections and provide better guidance for clinical treatment.MethodsWe conducted a multicenter cohort analysis using data from the Tianjin Medical University General Hospital, Medical Information Mart for Intensive Care-IV (MIMIC-IV), and the electronic intensive care unit (eICU) databases. The study population consisted of adult patients diagnosed with sepsis and ARDS. The primary objectives were to compare the characteristics and outcomes of patients with pulmonary infection-induced ARDS and those with non-pulmonary infection-induced ARDS using Wilcoxon analysis, Kaplan–Meier curves, correlation analysis, propensity matching scores, and other statistical methods.ResultsPatients with ARDS by pulmonary infection may be more likely to have a history of chronic obstructive pulmonary disease, and abdominal infection was more likely to induce ARDS in sepsis patients with non-pulmonary infection. Pulmonary infections caused by Klebsiella pneumoniae and Acinetobacter baumannii were more likely to induce ARDS. The oxygenation index and prognosis of ARDS patients induced by pulmonary infection were worse than those caused by other infections, with lower PaO2, PaO2/FiO2, and ROX index and longer hospital stay. More ARDS patients with pulmonary infection were given mechanical ventilation therapy, with higher mortality, APACHE II, SOFA, and SAPS II. The further correlation analysis showed that the prognostic scores of ARDS patients were negatively correlated with PaO2/FiO2 and ROX index. The above results were confirmed to varying degrees by propensity matching scores, external cohort validation, and other methods.ConclusionPulmonary infection induces a worse prognosis of ARDS than other site infections in patients with sepsis and ARDS. These patients require heightened vigilance, early intervention, and possibly more aggressive management strategies.
A study of machine learning to predict NRDS severity based on lung ultrasound score and clinical indicators
Authors: Huang Chunyan , Ha Xiaoming , Cui Yanfang , Zhang Hongxia 
Published: November 2024

ObjectiveTo develop predictive models for neonatal respiratory distress syndrome (NRDS) using machine learning algorithms to improve the accuracy of severity predictions.MethodsThis double-blind cohort study included 230 neonates admitted to the neonatal intensive care unit (NICU) of Yantaishan Hospital between December 2020 and June 2023. Of these, 119 neonates were diagnosed with NRDS and placed in the NRDS group, while 111 neonates with other conditions formed the non-NRDS (N-NRDS) group. All neonates underwent lung ultrasound and various clinical assessments, with data collected on the oxygenation index (OI), sequential organ failure assessment (SOFA), respiratory index (RI), and lung ultrasound score (LUS). An independent sample test was used to compare the groups’ LUS, OI, RI, SOFA scores, and clinical data. Use Least Absolute Shrinkage and Selection Operator (LASSO) regression to identify predictor variables, and construct a model for predicting NRDS severity using logistic regression (LR), random forest (RF), artificial neural network (NN), and support vector machine (SVM) algorithms. The importance of predictive variables and performance metrics was evaluated for each model.ResultsThe NRDS group showed significantly higher LUS, SOFA, and RI scores and lower OI values than the N-NRDS group (p &lt; 0.01). LUS, SOFA, and RI scores were significantly higher in the severe NRDS group compared to the mild and moderate groups, while OI was markedly lower (p &lt; 0.01). LUS, OI, RI, and SOFA scores were the most impactful variables for the predictive efficacy of the models. The RF model performed best of the four models, with an AUC of 0.894, accuracy of 0.808, and sensitivity of 0.706. In contrast, the LR, NN, and SVM models have lower AUC values than the RF model with 0.841, 0.828, and 0.726, respectively.ConclusionFour predictive models based on machine learning can accurately assess the severity of NRDS. Among them, the RF model exhibits the best predictive performance, offering more effective support for the treatment and care of neonates.
Comparison of tissue damage and inflammation for robotic laparoscopy and conventional laparoscopy in early endometrial cancer
Authors: Meng Shengnan , Cao Yanling , Shen Qingwei , Dong Ling , Wang Nan 
Published: November 2024

IntroductionThis study was to analyze the dynamics of tissue damage and inflammatory response markers perioperatively and whether these differ between robotic laparoscopy and conventional laparoscopy in early endometrial cancer.MethodsIn a randomized controlled trial conducted at SHANGHAI FIRST MATERNITY and INFANT HOSPITAL, eighty women with early-stage, low-risk endometrial cancer were randomly assigned to receive either robotic or conventional laparoscopy. Blood samples were collected at admission, immediately before surgery, 2 h after surgery, 24 h after surgery, 48 h after surgery, and 1 week after surgery. The samples were analyzed for various biomarkers associated with inflammatory processes and tissue damage. These included high-sensitivity C-reactive protein (hs-CRP), white blood cell count (WBC), platelet count, interleukin-6 (IL-6), cortisol, creatine kinase (CK), and tumor necrosis factor-alpha (TNF-α). These markers provide insights into the underlying physiological responses and potential tissue-level changes within the study participants.ResultsThere was no significant difference in clinical and preoperative data between two groups. The results showed that the patients who underwent robotic laparoscopy had a longer pre-surgical time compared to the conventional laparoscopy group. However, the robotic group had shorter operating times, quicker vaginal cuff closures, and lower estimated blood loss compared to the conventional laparoscopy group. The hospital stays, Visual Analog Scale (VAS) score and drainage volume on the first day after operation were lower in robotic group compared to conventional laparoscopy group. hs-CRP, WBC, IL-6 and cortisol were significantly lower in the robotic group, though the differences were transient.DiscussionThis study demonstrated that robotic laparoscopy, used in early endometrial cancer treatment, leads to a reduced inflammatory response, less tissue damage, and lower stress levels, as evidenced by decreased levels of hs-CRP, IL-6, and cortisol, compared to conventional laparoscopy. These findings suggest that robot- laparoscopy may facilitate a quicker recovery and improve patient-reported outcomes.
Exploring agro-ecological significance, knowledge gaps, and research priorities in arbuscular mycorrhizal fungi
Authors: Mwampashi Lenganji Lackson , Magubika Aneth Japhet , Ringo Job Frank , Theonest Dickson J. , Tryphone George Muhamba , Chilagane Luseko Amos , Nassary Eliakira Kisetu 
Published: November 2024

This systematic review examines the global agricultural relevance and practical environmental implications of arbuscular mycorrhizal fungi (AMF) within the phylum Glomeromycota. Following PRISMA guidelines, ensuring a comprehensive and unbiased literature review, a literature search was conducted, focusing on the functional roles of AMF in enhancing crop productivity, nutrient uptake, and soil health. Key findings reveal that AMF contribute significantly to sustainable agriculture by reducing the need for chemical fertilizers and increasing plant resilience to environmental stressors like drought, salinity, or pest resistance. The review highlights the importance of AMF in forming symbiotic relationships with plants, which enhance nutrient absorption and improve soil structure, showcasing long-term benefits such as reduced erosion or improved water retention. However, the current literature lacks in-depth exploration of the taxonomy and evolutionary aspects of AMF, as well as the specific functional roles they play in different agricultural contexts, e.g., understanding evolution could enhance strain selection for specific crops. This review identifies several urgent research gaps, including a need for a more refined understanding of AMF community dynamics under varying land management practices. For example, there are gaps in and a critical evaluation of advanced molecular techniques. Such techniques are essential for studying these interactions. Addressing these gaps will enhance the integration of AMF into sustainable agricultural systems and improve ecosystem management practices across different geographical regions. Future research should prioritize developing precise molecular imaging techniques and optimizing AMF applications for different crops and soil types to maximize their ecological and agricultural benefits. This could be practical through interdisciplinary collaboration (e.g., involving molecular biologists, agronomists, etc.). In conclusion, this review advances the practical application of AMF in agriculture and its contribution to biodiversity conservation in agroecosystems. Integrating these findings into policy frameworks could encourage sustainable farming practices, promote the adoption of AMF inoculants, and foster incentives for environmentally friendly land management strategies.Systematic review registrationhttps://www.bmj.com/content/372/bmj.n71.