bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and immunogenicity of BK-SE36/CpG malaria vaccine in healthy Burkinabe adults and children: a phase 1b randomised, controlled, double-blinded, age de-escalation trial
Authors: Ouédraogo Alphonse , Bougouma Edith Christiane , Palacpac Nirianne Marie Q. , Houard Sophie , Nebie Issa , Sawadogo Jean , Berges Gloria D. , Soulama Issiaka , Diarra Amidou , Hien Denise , Ouedraogo Amidou Z. , Konaté Amadou T. , Kouanda Seni , Myoui Akira , Ezoe Sachiko , Ishii Ken J. , Sato Takanobu , D’Alessio Flavia , Leroy Odile , Tiono Alfred B. , Cousens Simon , Horii Toshihiro , Sirima Sodiomon B. 
Published: October 2023

BackgroundBK-SE36/CpG is a recombinant blood-stage malaria vaccine candidate based on the N-terminal Plasmodium falciparum serine repeat antigen5 (SE36), adsorbed to aluminium hydroxide gel and reconstituted, prior to administration, with synthetic oligodeoxynucleotides bearing CpG motifs. In healthy Japanese adult males, BK-SE36/CpG was well tolerated. This study assessed its safety and immunogenicity in healthy malaria-exposed African adults and children.MethodsA double-blind, randomised, controlled, age de-escalating clinical trial was conducted in an urban area of Ouagadougou, Burkina Faso. Healthy participants (n=135) aged 21-45 years (Cohort 1), 5-10 years (Cohort 2) and 12-24 months (Cohort 3) were randomised to receive three vaccine doses (Day 0, 28 and 112) of BK-SE36/CpG or rabies vaccine by intramuscular injection.ResultsOne hundred thirty-four of 135 (99.2%) subjects received all three scheduled vaccine doses. Vaccinations were well tolerated with no related Grade 3 (severe) adverse events (AEs). Pain/limitation of limb movement, headache in adults and fever in younger children (all mild to moderate in intensity) were the most frequently observed local and systemic AEs. Eighty-three of BK-SE36/CpG (91%) recipients and 37 of control subjects (84%) had Grade 1/2 events within 28 days post vaccination. Events considered by the investigator to be vaccine related were experienced by 38% and 14% of subjects in BK-SE36/CpG and control arms, respectively. Throughout the trial, six Grade 3 events (in 4 subjects), not related to vaccination, were recorded in the BK-SE36/CpG arm: 5 events (in 3 subjects) within 28 days of vaccination. All serious adverse events (SAEs) (n=5) were due to severe malaria (52-226 days post vaccination) and not related to vaccination. In all cohorts, BK-SE36/CpG arm had higher antibody titres after Dose 3 than after Dose 2. Younger cohorts had stronger immune responses (12–24-month-old &gt; 5-10 years-old &gt; 21-45 years-old). Sera predominantly reacted to peptides that lie in intrinsically unstructured regions of SE36. In the control arm, there were no marked fold changes in antibody titres and participants’ sera reacted poorly to all peptides spanning SE36.ConclusionBK-SE36/CpG was well-tolerated and immunogenic. These results pave the way for further proof-of-concept studies to demonstrate vaccine efficacy.Clinical trial registrationhttps://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1921, PACTR201701001921166.
Case Report: Limbic encephalitis following treatment with durvalumab for small-cell lung cancer
Authors: Moss Thomas T. , Stavem Knut , Aandahl Astrid , Gløersen Anne S. , Grønberg Bjørn H. , Neumann Kirill , Vedeler Christian A. , Lundqvist Christofer 
Published: October 2023

BackgroundDurvalumab is an immune checkpoint Inhibitor (ICIs) that is used in the treatment of malignant tumors, such as lung cancer and melanoma. ICIs are associated with immune-related adverse events including autoimmune encephalitis, although both paraneoplastic phenomena and ICI treatment may lead to autoimmunity.Case presentationWe describe a 72-year old male patient with small-cell lung cancer, who during adjuvant treatment with Durvalumab developed GABABR1 and GAD65 antibodies and both diabetes and autoimmune limbic encephalitis. Because he was followed prospectively as part of a treatment study, we had access to repeated serum samples and cognitive assessments over time prior to developing encephalitis and diabetes, in addition to later assessments. A high titer of GABABR1 antibodies appeared early, while GAD65 antibodies appeared later with a lower titer in parallel with the development of diabetes. As he subsequently developed clinical signs of encephalitis, verified by EEG and brain MRI, he also had CSF GABABR1 antibodies. Durvalumab was discontinued and steroid treatment with subsequent plasmapheresis were started, resulting in reduction of both CSF and serum antibody levels. Clinical signs of encephalitis gradually improved.ConclusionThis case illustrates the importance of being aware of possible serious autoimmune adverse reactions, including neurological syndromes such as encephalitis, when treating patients with high risk of para-neoplasia with ICIs. In addition, the case shows the development of autoantibodies over time.
Latent diffusion augmentation enhances deep learning analysis of neuro-morphology in limbal stem cell deficiency
Authors: Gibson David , Tran Thai , Raveendran Vidhur , Bonnet Clémence , Siu Nathan , Vinet Micah , Stoddard-Bennett Theo , Arnold Corey , Deng Sophie X. , Speier William 
Published: October 2023

IntroductionLimbal Stem Cell Deficiency (LSCD) is a blinding corneal disease characterized by the loss of function or deficiency in adult stem cells located at the junction between the cornea and the sclera (i.e., the limbus), namely the limbal stem cells (LSCs). Recent advances in in vivo imaging technology have improved disease diagnosis and staging to quantify several biomarkers of in vivo LSC function including epithelial thickness measured by anterior segment optical coherence tomography, and basal epithelial cell density and subbasal nerve plexus by in vivo confocal microscopy. A decrease in central corneal sub-basal nerve density and nerve fiber and branching number has been shown to correlate with the severity of the disease in parallel with increased nerve tortuosity. Yet, image acquisition and manual quantification require a high level of expertise and are time-consuming. Manual quantification presents inevitable interobserver variability.MethodsThe current study employs a novel deep learning approach to classify neuron morphology in various LSCD stages and healthy controls, by integrating images created through latent diffusion augmentation. The proposed model, a residual U-Net, is based in part on the InceptionResNetV2 transfer learning model.ResultsDeep learning was able to determine fiber number, branching, and fiber length with high accuracy (R2 of 0.63, 0.63, and 0.80, respectively). The model trained on images generated through latent diffusion on average outperformed the same model when trained on solely original images. The model was also able to detect LSCD with an AUC of 0.867, which showed slightly higher performance compared to classification using manually assessed metrics.DiscussionThe results suggest that utilizing latent diffusion to supplement training data may be effective in bolstering model performance. The results of the model emphasize the ability as well as the shortcomings of this novel deep learning approach to predict various nerve morphology metrics as well as LSCD disease severity.
Contrast enhanced CT on PET/CT imaging in clinical routine: an international survey
Authors: Annunziata Salvatore , Testart Nathalie , Auf der Springe Katharina , Cuzzocrea Marco , Nicod Lalonde Marie , Schaefer Niklaus , Prior John O. , Garibotto Valentina , Treglia Giorgio 
Published: October 2023

AimTo perform an international survey about PET/CT imaging with contrast enhanced CT (PET/ceCT) in clinical routine worldwide.MethodsA questionnaire of ten questions was prepared for health professionals, addressing the following issues: (1) general demographic, hospital, and department information; (2) use and diffusion of PET/ceCT worldwide; (3) factors influencing the use of PET/ceCT. An invitation to the survey was sent to the corresponding authors of NM scientific articles indexed in SCOPUS in 2022 and dedicated to PET/CT imaging. Data were analysed per individual responder.Results191 individual responders worldwide participated in this survey. Most of the responders are using PET/ceCT in their center (74%). Interestingly, the relative use of PET/ceCT over the total PET/CT scans has an anti-Gaussian distribution (&lt;20% ceCT and &gt; 80% ceCT were most represented). Most of responders are using PET/ceCT in oncological settings (62%) and irrespectively from radiopharmaceuticals (62%). In most cases, PET/ceCT scans are reported by NM physicians alone or together by NM physicians and radiologists with an integrated report (31%).ConclusionPET/ceCT imaging is largely used worldwide. Local factors can affect the choice of PET/ceCT in respect to conventional PET/CT imaging. Further cost–benefit analysis could be useful to consider other possible influencing variables, such as technologies, dosimetry, department organization and economics.
AVEN: a novel oncogenic biomarker with prognostic significance and implications of AVEN-associated immunophenotypes in lung adenocarcinoma
Authors: Fan Dengxia , Yang Moses , Lee Hye Jung , Lee Jeong Hee , Kim Hong Sook 
Published: October 2023

Introduction: AVEN, an apoptosis and caspase activation inhibitor, has been associated with adverse clinical outcomes and poor prognosis in Acute myeloid leukemia (AML). Targeting AVEN in AML improves apoptosis sensitivity and chemotherapy efficacy, making it a promising therapeutic target. However, AVEN’s role has not been studied in solid tumors. Therefore, our study investigated AVEN as a prognostic biomarker in a more comprehensive manner and developed an AVEN-derived prognostic model in Lung adenocarcinoma (LUAD).Method: Pan-cancer analysis was performed to examine AVEN expression in 33 cancer types obtained from the TCGA database. GEPIA analysis was used to determine the predictive value of AVEN in each cancer type with cancer-specific AVEN expression. Lung Adenocarcinomas (LUAD) patients were grouped into AVENhigh and AVENlow based on AVEN expression level. Differentially expressed genes (DEGs) and pathway enrichment analysis were performed to gain insight into the biological function of AVEN in LUAD. In addition, several deconvolution tools, including Timer, CIBERSORT, EPIC, xCell, Quanti-seq and MCP-counter were used to explore immune infiltration. AVEN-relevant prognostic genes were identified by Random Survival Forest analysis via univariate Cox regression. The AVEN-derived genomic model was established using a multivariate-Cox regression model and GEO datasets (GSE31210, GSE50081) were used to validate its prognostic effect.Results: AVEN expression was increased in several cancer types compared to normal tissue, but its impact on survival was only significant in LUAD in the TCGA cohort. High AVEN expression was significantly correlated with tumor progression and shorter life span in LUAD patients. Pathway analysis was performed with 838 genes associated with AVEN expression and several oncogenic pathways were altered such as the Cell cycle, VEGFA-VEGFR2 pathway, and epithelial-mesenchymal-transition pathway. Immune infiltration was also analyzed, and less infiltrated B cells was observed in AVENhigh patients. Furthermore, an AVEN-derived genomic model was established, demonstrating a reliable and improved prognostic value in TCGA and GEO databases.Conclusion: This study provided evidence that AVEN is accumulated in LUAD compared to adjacent tissue and is associated with poor survival, high tumor progression, and immune infiltration alteration. Moreover, the study introduced the AVEN-derived prognostic model as a promising prognosis tool for LUAD.
Prognostic factors and predictive nomogram models for early death in elderly patients with hepatocellular carcinoma: a population-based study
Authors: Zhou Hao , Chen Junhong , Liu Kai , Xu Hongji 
Published: October 2023

Background: Owing to an aging society, there has been an observed increase in the average age of patients diagnosed with hepatocellular carcinoma (HCC). Consequently, this study is centered on identifying the prognostic factors linked with early death among this elderly demographic diagnosed with HCC. Additionally, our focus extends to developing nomograms capable of predicting such outcomes.Methods: The Surveillance, Epidemiology and End Results (SEER) database underpinned this study, showcasing participants aged 75 and above diagnosed with HCC within the timeframe from 2010 to 2015. These participants were divided randomly, at a 7:3 ratio, into training and validation cohorts. Univariable and multivariable logistic regressions were applied to the training cohort in the identification of prognostic indicators of early death, forming the basis for nomogram development. To measure the efficacy of these nomograms within both cohorts, we resorted to Receiver Operating Characteristic (ROC) curves, along with GiViTI calibration belt and Decision Curve Analysis (DCA).Results: The study involved 1,163 elderly individuals diagnosed with HCC, having reported instances of 397 all-cause early deaths and 356 HCC-specific early deaths. The sample group was divided into two cohorts: a training group consisting of 815 individuals, and a validation cohort, comprised of 348 individuals. Multifactorial analysis identified grade, T-stage, surgery, radiation, chemotherapy, bone and lung metastasis as significant predictors of mortality from all causes. Meanwhile, race, grade, T-stage, surgery, radiation, chemotherapy, and bone metastasis were revealed to be estimative factors for cancer-specific mortality. Subsequently, these factors were used to develop nomograms for prediction. GiViTI calibration belt corroborated the acceptable coherence of the nomograms, DCA confirmed their valuable clinical applicability, and ROC curves evidenced satisfactory discriminative capacity within both training and validation cohorts.Conclusion: The nomograms utilized in this study proved instrumental in detecting early death among elderly individuals afflicted with HCC. This tool could potentially assist physicians in formulating individualized treatment strategies.
Social withdrawal and anxiety-like behavior have an impact on zebrafish adult neurogenesis
Authors: Perdikaris Panagiotis , Prouska Paulina , Dermon Catherine R. 
Published: October 2023

IntroductionAccumulating evidence highlights the key role of adult neurogenesis events in environmental challenges, cognitive functions and mood regulation. Abnormal hippocampal neurogenesis has been implicated in anxiety-like behaviors and social impairments, but the possible mechanisms remain elusive.MethodsThe present study questioned the contribution of altered excitation/inhibition as well as excessive neuroinflammation in regulating the neurogenic processes within the Social Decision-Making (SDM) network, using an adult zebrafish model displaying NMDA receptor hypofunction after sub-chronic MK-801 administration. For this, the alterations in cell proliferation and newborn cell densities were evaluated using quantitative 5-Bromo-2′-Deoxyuridine (BrdU) methodology.ResultsIn short-term survival experiments. MK-801-treated zebrafish displayed decreased cell proliferation pattern within distinct neurogenic zones of telencephalic and preoptic SDM nodes, in parallel to the social withdrawal and anxiety-like comorbidity. BrdU+ cells co-expressed the pro-inflammatory marker IL-1β solely in MK-801-treated zebrafish, indicating a role of inflammation. Following the cessation of drug treatment, significant increases in the BrdU+ cell densities were accompanied by the normalization of the social and anxiety-like phenotype. Importantly, most labeled cells in neurogenic zones showed a radial glial phenotype while a population of newborn cells expressed the early neuronal marker TOAD or mGLuR5, the latter suggesting the possible involvement of metabotropic glutamate receptor 5 in neurogenic events.DiscussionOverall, our results indicate the role of radial glial cell proliferation in the overlapping pathologies of anxiety and social disorders, observed in many neuropsychiatric disorders and possibly represent potential novel targets for amelioration of these symptoms.
Three-stage pattern of rapid increase, plateau, and subsequent decline in vitamin D concentration during pregnancy among Chinese women: a large-scale survey
Authors: Wang Huabin , Zhang Feifang , Li Bingxian , Fu Miao , Shan Xiaoyun , Ma Yongjun 
Published: October 2023

BackgroundThere is an incomplete understanding of fluctuations in vitamin D (VitD) concentration during pregnancy among Chinese women. Furthermore, previous research has yielded conflicting results in this area. This study aims to investigate the changes in VitD status and deficiency in Chinese pregnant women across various age groups, gestational weeks, and as well as seasonal variations through conducting a large-scale survey.MethodsA toal of 11,220 Chinese pregnant women between 2021 and April 2023 were included in this study. Generalized additive models (GAM), stratified analysis, and restricted cubic splines (RCS) were used to analyze changes in VitD status and deficiency risk during pregnancy.ResultsOf the participants, 45.2% had deficient concentration of 25-hydroxyvitamin D. VitD concentration and deficiency rate do not show linear changes with age and gestational weeks. With increasing gestational weeks, VitD concentration rapidly increased in women with gestational age &lt; 20 weeks, remained stable between 20 and 30 weeks, and decreased beyond 30 weeks; however, the odds of VitD deficiency showed three different patterns: a rapid decline, a stable period, and a mild increase, respectively. Based on the stratified regression analysis, VitD deficiency odds increased by 16% with each additional week of gestation in pregnant women with gestational age &gt; 30 weeks, OR = 1.16 (1.10–1.22), p &lt; 0.001. Interaction effect analysis indicated that pregnant women over 35 years with gestational weeks between 20 and 30 had the lowest odds of VitD deficiency.ConclusionVitD concentration undergo three phases during pregnancy: rapid increase, plateau, and subsequent decrease. VitD deficiency odds was highest in pregnant women under 25 with gestational ages &lt;20 and lowest in pregnant women over 35 with gestational ages between 20 and 30. The odds of deficiency increase slightly in pregnant women with gestational ages beyond 30 weeks, indicating that they may require additional VitD supplementation.
Effects of MRI radiomics combined with clinical data in evaluating lymph node metastasis in mrT1-3a staging rectal cancer
Authors: Dong Xue , Ren Gang , Chen Yanhong , Yong Huifang , Zhang Tingting , Yin Qiufeng , Zhang Zhongyang , Yuan Shijun , Ge Yaqiong , Duan Shaofeng , Liu Huanhuan , Wang Dengbin 
Published: October 2023

ObjectiveTo investigate the value of a clinical-MRI radiomics model based on clinical characteristics and T2-weighted imaging (T2WI) for preoperatively evaluating lymph node (LN) metastasis in patients with MRI-predicted low tumor (T) staging rectal cancer (mrT1, mrT2, and mrT3a with extramural spread ≤ 5 mm).MethodsThis retrospective study enrolled 303 patients with low T-staging rectal cancer (training cohort, n = 213, testing cohort n = 90). A total of 960 radiomics features were extracted from T2WI. Minimum redundancy and maximum relevance (mRMR) and support vector machine were performed to select the best performed radiomics features for predicting LN metastasis. Multivariate logistic regression analysis was then used to construct the clinical and clinical-radiomics combined models. The model performance for predicting LN metastasis was assessed by receiver operator characteristic curve (ROC) and clinical utility implementing a nomogram and decision curve analysis (DCA). The predictive performance for LN metastasis was also compared between the combined model and human readers (2 seniors).ResultsFourteen radiomics features and 2 clinical characteristics were selected for predicting LN metastasis. In the testing cohort, a higher positive predictive value of 75.9% for the combined model was achieved than those of the clinical model (44.8%) and two readers (reader 1: 54.9%, reader 2: 56.3%) in identifying LN metastasis. The interobserver agreement between 2 readers was moderate with a kappa value of 0.416. A clinical-radiomics nomogram and decision curve analysis demonstrated that the combined model was clinically useful.ConclusionT2WI-based radiomics combined with clinical data could improve the efficacy in noninvasively evaluating LN metastasis for the low T-staging rectal cancer and aid in tailoring treatment strategies.
Pembrolizumab and trastuzumab in combination with FLOT in the perioperative treatment of HER2-positive, localized esophagogastric adenocarcinoma—a phase II trial of the AIO study group (AIO STO 0321)
Authors: Tintelnot Joseph , Stein Alexander , Al-Batran Salah-Eddin , Ettrich Thomas , Götze Thorsten , Grün Barbara , Haag Georg Martin , Heuer Vera , Hofheinz Ralf-Dieter , Homann Nils , Bröring Tobias Sebastian , Cruz Mariana Santos , Kurreck Annika , Lorenzen Sylvie , Moosmann Nicolas , Müller Christian , Schuler Markus , Siegler Gabriele , Binder Mascha , Gökkurt Eray 
Published: October 2023

BackgroundEsophagogastric adenocarcinoma (EGA) presents a substantial global health challenge as the number of cases continues to rise. The current standard approach for treating localized EGA involves a combination of triplet chemotherapy, which consists of a platinum compound, a fluoropyrimidine, and a taxane (known as FLOT), followed by surgery. In cases of metastatic EGA with HER2-positive status or in certain studies with localized EGA, the use of HER2-targeted antibodies such as trastuzumab has shown improved responses. Recently, the addition of programmed cell death protein 1 (PD-1) inhibitors, such as pembrolizumab, when combined with 5-FU, platinum-based chemotherapy, and trastuzumab, has demonstrated significant enhancements in response rates for HER2-positive metastatic EGA. However, there is currently insufficient evidence regarding this treatment approach in localized HER2-positive disease.MethodsThe PHERFLOT study is an open-label, single-arm, multicenter, exploratory phase II trial designed to assess the efficacy, safety, and tolerability of perioperative pembrolizumab, FLOT, and trastuzumab in patients with previously untreated localized HER2-positive EGA. In total, 30 patients will be recruited. The co-primary end points are pathological complete response rate and disease-free survival rate after 2 years. Secondary objectives include safety and tolerability, efficacy in terms of progression-free survival and objective response rate and translational markers, such as blood-based signatures (e.g., immune repertoire changes or emergence of anti-HER2 resistance variants) or microbiota signatures that may correlate with immune activation and therapy response.DiscussionRecent evidence from phase II clinical trials demonstrated improved efficacy through the addition of trastuzumab to perioperative FLOT. Furthermore, in advanced or metastatic EGA, the combination of trastuzumab, FLOT, and the PD1-inhibitor pembrolizumab significantly improved treatment response. The PHERFLOT study aims to assess the efficacy and safety of this treatment approach in HER2-positive–localized EGA, potentially identifying a promising new perioperative regimen for localized EGA, which then needs to be confirmed within a randomized trial. Furthermore, the accompanying translational program of the study might help to improve the stratification of suitable patients and to identify potential translational targets for future clinical trials.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT05504720.