bluuebunny/crossref_metadata_2025_split huggingface dataset:
The combined signatures of telomere and immune cell landscape provide a prognostic and therapeutic biomarker in glioma
Authors: Han Xu , Yan Zihan , Fan Kaiyu , Guan Xueyi , Hu Bohan , Li Xiang , Ou Yunwei , Cui Bing , An Lingxuan , Zhang Yaohua , Gong Jian 
Published: August 2023

BackgroundGliomas, the most prevalent primary malignant tumors of the central nervous system in adults, exhibit slow growth in lower-grade gliomas (LGG). However, the majority of LGG cases progress to high-grade gliomas, posing challenges for prognostication. The tumor microenvironment (TME), characterized by telomere-related genes and immune cell infiltration, strongly influences glioma growth and therapeutic response. Therefore, our objective was to develop a Telomere-TME (TM-TME) classifier that integrates telomere-related genes and immune cell landscape to assess prognosis and therapeutic response in glioma.MethodsThis study encompassed LGG patients from the TCGA and CCGA databases. TM score and TME score were derived from the expression signatures of telomere-related genes and the presence of immune cells in LGG, respectively. The TM-TME classifier was established by combining TM and TME scores to effectively predict prognosis. Subsequently, we conducted Kaplan-Meier survival estimation, univariate Cox regression analysis, and receiver operating characteristic curves to validate the prognostic prediction capacity of the TM-TME classifier across multiple cohorts. Gene Ontology (GO) analysis, biological processes, and proteomaps were performed to annotate the functional aspects of each subgroup and visualize the cellular signaling pathways.ResultsThe TM_low+TME_high subgroup exhibited superior prognosis and therapeutic response compared to other subgroups (P&lt;0.001). This finding could be attributed to distinct tumor somatic mutations and cancer cellular signaling pathways. GO analysis indicated that the TM_low+TME_high subgroup is associated with the neuronal system and modulation of chemical synaptic transmission. Conversely, the TM_high+TME_low subgroup showed a strong association with cell cycle and DNA metabolic processes. Furthermore, the classifier significantly differentiated overall survival in the TCGA LGG cohort and served as an independent prognostic factor for LGG patients in both the TCGA cohort (P&lt;0.001) and the CGGA cohort (P&lt;0.001).ConclusionOverall, our findings underscore the significance of the TM-TME classifier in predicting prognosis and immune therapeutic response in glioma, shedding light on the complex immune landscape within each subgroup. Additionally, our results suggest the potential of integrating risk stratification with precision therapy for LGG.
Therapeutic cancer vaccination against mutant calreticulin in myeloproliferative neoplasms induces expansion of specific T cells in the periphery but specific T cells fail to enrich in the bone marrow
Authors: Holmström Morten Orebo , Andersen Morten , Traynor Sofie , Ahmad Shamaila Munir , Lisle Thomas Landkildehus , Handlos Grauslund Jacob , Skov Vibe , Kjær Lasse , Ottesen Johnny T. , Gjerstorff Morten Frier , Hasselbalch Hans Carl , Andersen Mads Hald 
Published: August 2023

BackgroundTherapeutic cancer vaccination against mutant calreticulin (CALR) in patients with CALR-mutant (CALRmut) myeloproliferative neoplasms (MPN) induces strong T-cell responses against mutant CALR yet fails to demonstrate clinical activity. Infiltration of tumor specific T cells into the tumor microenvironment is needed to attain a clinical response to therapeutic cancer vaccination.AimDetermine if CALRmut specific T cells isolated from vaccinated patients enrich in the bone marrow upon completion of vaccination and explore possible explanations for the lack of enrichment.MethodsCALRmut specific T cells from four of ten vaccinated patients were expanded, enriched, and analyzed by T-cell receptor sequencing (TCRSeq). The TCRs identified were used as fingerprints of CALRmut specific T cells. Bone marrow aspirations from the four patients were acquired at baseline and at the end of trial. T cells were enriched from the bone marrow aspirations and analyzed by TCRSeq to identify the presence and fraction of CALRmut specific T cells at the two different time points. In silico calculations were performed to calculate the ratio between transformed cells and effector cells in patients with CALRmut MPN.ResultsThe fraction of CALRmut specific T cells in the bone marrow did not increase upon completion of the vaccination trial. In general, the T cell repertoire in the bone marrow remains relatively constant through the vaccination trial. The enriched and expanded CALRmut specific T cells recognize peripheral blood autologous CALRmut cells. In silico analyses demonstrate a high imbalance in the fraction of CALRmut cells and CALRmut specific effector T-cells in peripheral blood.ConclusionCALRmut specific T cells do not enrich in the bone marrow after therapeutic cancer peptide vaccination against mutant CALR. The specific T cells recognize autologous peripheral blood derived CALRmut cells. In silico analyses demonstrate a high imbalance between the number of transformed cells and CALRmut specific effector T-cells in the periphery. We suggest that the high burden of transformed cells in the periphery compared to the number of effector cells could impact the ability of specific T cells to enrich in the bone marrow.
Effects of temperature, salinity and diet on embryonic and early larval development in Littorina littorea (Gastropoda: Littorinimorpha)
Authors: Lillebjerka Tora , Malzahn Arne M. , Kjørsvik Elin , Hagemann Andreas 
Published: August 2023

IntroductionThe common periwinkle Littorina littorea is a delicacy in southern Europe. Enabling aquaculture production would be measure to avoid future over-harvesting and ensure a constant market supply.MethodsHowever, knowledge gaps in reproductive biology needs to be filled to allow setting up rearing protocols.ResultsWe investigated effects of temperature and salinity on embryonic development by incubating eggs at ten different temperatures in steps every 2°C, form 5 to 23°C) and four salinities (20 – 40). Embryonic development was clearly temperature dependent; eggs hatched after three days at the highest temperature while it took 16 days to hatch at the lowest temperature. Calculating effective day-degrees (DDeff) allowed expressing the thermal history of the embryogenesis and concluding that this species hatches on average at 61 (SD 3.7) DDeff. Larval growth- and developmental rates showed a different response to the temperature extremes as snails with the smallest shell lengths at hatch were found for the highest and lowest temperatures (204.5, SD = 11.6, and 202.9µm, SD = 13.7 respectively). Viable larvae only hatched at temperatures above 9°C. Larvae hatched at lower temperatures did not develop a shell or swimming lobes. Salinity and temperature significantly influenced time-to-hatch and hatching success; the lowest salinity (20PSU) lead to later hatching (80-100DDeff) and lower hatching success compared to higher salinities (25, 30, and 40, hatch around 40-50 DDeff). Neither hatch rate nor time-to-hatch showed differences among the higher salinities, suggesting a salinity threshold below 25. There was no significant interaction between salinity and temperature on time-to-hatch or hatching success. Larval diet had a significant effect on growth rates during the planktonic stage. Veliger larvae fed on two different live microalgae mono-diets (Dunaliella tertiolecta and Rhodomonas baltica) successfully passed their pelagic phase at the same time with no differences in growth rates, while veliger larvae fed on either of two preserved microalgae products (Nannochloropis sp. and Tetrasemis sp. frozen pastes) were not growing.DiscussionWe conclude that embryonal development can be successfully completed at temperatures between 7 and 20°C, while lower or higher temperatures should be avoided. Successfully hatched larvae can be fed on mono-microalgae diets until settlement.
Inter-rater reliability of the extended Composite Quality Score (CQS-2)
Authors: Mickenautsch Steffen , Rupf Stefan , Miletić Ivana , Strähle Ulf Tilman , Sturm Richard , Kimmie-Dhansay Faheema , Vidosusić Kata , Yengopal Veerasamy 
Published: August 2023

AimTo establish the inter-rater reliability of the Composite Quality Score (CQS-2) and to test the null hypothesis that it did not differ significantly from that of the first CQS version (CQS-1).Materials and methodsFour independent raters were selected to rate 45 clinical trial reports using CQS-1 and CQS-2. The raters remained unaware of each other’s participation in this study until all rating had been completed. Each rater received only one rating template at a time in a random sequence for CQS-1 and CQS-2 rating. Raters completed each template and sent these back to the principal investigator. Each rater received their next template 2 weeks after submission of the completed previous template. The inter-rater reliabilities for the overall appraisal score of the CQS-1 and the CQS-2 were established by using the Brennan-Prediger coefficient (BPC). The coefficients of both CQS versions were compared by using the two-sample z-test. During secondary analysis, the BPCs for every criterion and each corroboration level for both CQS versions were established.ResultsThe BPC for the CQS-1 was 0.85 (95% CI: 0.64–1.00) and for the CQS-2 it was 1.00 (95% CI: 0.94–1.00), suggesting a very high inter-rater reliability for both. The difference between the two CQS versions was statistically not significant (p = 0.17). The null hypothesis was accepted.ConclusionThe CQS-2 is still under development, This study shows that it is associated with a very high inter-rater reliability, which did not statistically significantly differ from that of the CQS-1. The promising results of this study warrant further investigation in the applicability of the CQS-2 as an appraisal tool for prospective controlled clinical therapy trials.
Novel insights into genetic characteristics of blaGES-encoding plasmids from hospital sewage
Authors: Ota Yusuke , Prah Isaac , Mahazu Samiratu , Gu Yoshiaki , Nukui Yoko , Koike Ryuji , Saito Ryoichi 
Published: August 2023

IntroductionThe prevalence of Guiana extended-spectrum (GES)-type carbapenemase producers is increasing worldwide, and hospital water environments are considered as potential reservoirs. However, the genetic features underlying this resistance are not yet fully understood. This study aimed to characterize blaGES-encoding plasmids from a single-hospital sewage sample in Japan.MethodsCarbapenemase producers were screened using carbapenemase-selective agar and polymerase chain reaction. Whole-genome sequencing analyzes were performed on the carbapenemase-producing isolates.ResultsEleven gram-negative bacteria (four Enterobacter spp., three Klebsiella spp., three Aeromonas spp., and one Serratia spp.) with blaGES-24 (n = 6), blaGES-6 (n = 4), and blaGES-5 (n = 1) were isolated from the sewage sample. Five blaGES-24 and a blaGES-5 were localized in IncP-6 plasmids, whereas three blaGES-6 plasmids were localized in IncC plasmids with IncF-like regions. The remaining blaGES-6 and blaGES-24 were, respectively, localized on IncFIB-containing plasmids with IncF-like regions and a plasmid with an IncW-like replication protein. The IncP-6 and IncW-like plasmids had a close genetic relationship with plasmids from Japan, whereas the IncC/IncF-like and IncFIB/IncF-like plasmids were closely related to those from the United States and Europe. All blaGES genes were located on the class 1 integron cassette of the Tn3 transposon-related region, and the IncC/IncF-like plasmid carried two copies of the integron cassette. Eight of the eleven blaGES-encoding plasmids contained toxin-antitoxin system genes.DiscussionThe findings on the plasmids and the novel genetic content from a single wastewater sample extend our understanding regarding the diversity of resistance and the associated spread of blaGES, suggesting their high adaptability to hospital effluents. These findings highlight the need for the continuous monitoring of environmental GES-type carbapenemase producers to control their dissemination.
Exploring the relationship between patient-relevant outcomes and Alzheimer’s disease progression assessed using the clinical dementia rating scale: a systematic literature review
Authors: Cummings Jeffrey , Hahn-Pedersen Julie Hviid , Eichinger Christian Stefan , Freeman Caroline , Clark Alice , Tarazona Luis Rafael Solís , Lanctôt Krista 
Published: August 2023

BackgroundPeople with Alzheimer’s disease (AD) have difficulties in performing activities of daily living (ADLs) as the disease progresses, commonly experience neuropsychiatric symptoms (NPS), and often have comorbidities such as cardiovascular disease. These factors all contribute to a requirement for care and considerable healthcare costs in AD. The Clinical Dementia Rating (CDR) scale is a widely used measure of dementia staging, but the correlations between scores on this scale and patient-/care partner-relevant outcomes have not been characterized fully. We conducted a systematic literature review to address this evidence gap.MethodsEmbase, MEDLINE, and the Cochrane Library were searched September 13, 2022, to identify published studies (no restriction by date or country) in populations with mild cognitive impairment due to AD or AD dementia. Studies of interest reported data on the relationships between CDR Global or CDR–Sum of Boxes (CDR-SB) scores and outcomes including NPS, comorbidities, ADLs, nursing home placement, healthcare costs, and resource use.ResultsOverall, 58 studies met the inclusion criteria (42 focusing on comorbidities, 14 on ADLs or dependence, five on nursing home placement, and six on economic outcomes). CDR/CDR-SB scores were correlated with the frequency of multiple NPS and with total scores on the Neuropsychiatric Inventory. For cardiovascular comorbidities, no single risk factor was consistently linked to AD progression. Increasing CDR/CDR-SB scores were correlated with decline in multiple different measures of ADLs and were also associated with nursing home placement and increasing costs of care.ConclusionNPS, ADLs, and costs of care are clearly linked to AD progression, as measured using CDR Global or CDR-SB scores, from the earliest stages of disease. This indicates that scores derived from the CDR are a meaningful way to describe the severity and burden of AD for patients and care partners across disease stages.
Targeting the metabolic profile of amino acids to identify the key metabolic characteristics in cerebral palsy
Authors: Wang Dan , Song Juan , Cheng Ye , Xu Yiran , Song Lili , Qiao Yimeng , Li Bingbing , Xia Lei , Li Ming , Zhang Jin , Su Yu , Wang Ting , Ding Jian , Wang Xiaoyang , Wang Sujuan , Zhu Changlian , Xing Qinghe 
Published: August 2023

BackgroundCerebral palsy (CP) is a neurodevelopmental disorder characterized by motor impairment. In this study, we aimed to describe the characteristics of amino acids (AA) in the plasma of children with CP and identify AA that could play a potential role in the auxiliary diagnosis and treatment of CP.MethodsUsing high performance liquid chromatography, we performed metabolomics analysis of AA in plasma from 62 CP children and 60 healthy controls. Univariate and multivariate analyses were then applied to characterize different AA. AA markers associated with CP were then identified by machine learning based on the Lasso regression model for the validation of intra-sample interactions. Next, we calculated a discriminant formula and generated a receiver operating characteristic (ROC) curve based on the marker combination in the discriminant diagnostic model.ResultsA total of 33 AA were detected in the plasma of CP children and controls. Compared with controls, 5, 7, and 10 different AA were identified in total participants, premature infants, and full-term infants, respectively. Of these, β-amino-isobutyric acid [p = 2.9*10(−4), Fold change (FC) = 0.76, Variable importance of protection (VIP) = 1.75], tryptophan [p = 5.4*10(−4), FC = 0.87, VIP = 2.22], and asparagine [p = 3.6*10(−3), FC = 0.82, VIP = 1.64], were significantly lower in the three groups of CP patients than that in controls. The combination of β-amino-isobutyric acid, tryptophan, and taurine, provided high levels of diagnostic classification and risk prediction efficacy for preterm children with an area under the curve (AUC) value of 0.8741 [95% confidence interval (CI): 0.7322–1.000]. The discriminant diagnostic formula for preterm infant with CP based on the potential marker combination was defined by p = 1/(1 + e−(8.295–0.3848* BAIBA-0.1120*Trp + 0.0108*Tau)).ConclusionFull-spectrum analysis of amino acid metabolomics revealed a distinct profile in CP, including reductions in the levels of β-amino-isobutyric acid, tryptophan, and taurine. Our findings shed new light on the pathogenesis and diagnosis of premature infants with CP.
A comparative absorption study of sucrosomial® orodispersible vitamin D3 supplementation vs. a reference chewable tablet and soft gel capsule vitamin D3 in improving circulatory 25(OH)D levels in healthy adults with vitamin D deficiency—Results from a prospective randomized clinical trial
Authors: Bano Aasiya , Abrar Saida , Brilli Elisa , Tarantino Germano , Bugti Ali Akbar , Fabbrini Marco , Conti Gabriele , Turroni Silvia , Bugti Mahroo , Afridi Fauzia , Mureed Shah , Zada Hakeem , Din Ujjan Ikram , Ashraf Saadia , Ghafoor Aamir , Khan Saeed , Khan Amjad 
Published: August 2023

BackgroundVitamin D (Vit D) deficiency (VDD), associated with diverse health conditions, is commonly treated with Vit D3 supplements. However, the gastrointestinal (GI) absorption of Vit D3 in different formulations has not been well studied.ObjectiveWe aimed to compare the absorption of an innovative phospholipids-sucrester matrix biodelivery vehicle-based (sucrosomial®) orodispersible Vit D3 preparation against a reference chewable tablet and soft gel capsule (SGC) Vit D3 formulations in Vit D-deficient healthy adults.MethodsIn study 1, 25 subjects were randomized to receive a weekly single dose of 200,000 IU of sucrosomial® Vit D3 (n = 12) or chewable tablet Vit D3 (n = 13) for 3 weeks. In study 2, 20 subjects were randomized to receive a single dose of 200,000 IU every other week of sucrosomial® Vit D3 (n = 10) or SGC Vit D3 (n = 10) for 6 weeks. Circulatory 25-hydroxyvitamin D3 [25(OH)D] levels were reassessed after 2, 3, and 6 weeks in study 1 and after 4 and 6 weeks in study 2.ResultsIn study 1, after 2 weeks, circulatory 25(OH)D levels increased significantly in both Vit D3 treatment groups (p &lt; 0.0001) but improved markedly in the sucrosomial® Vit D3 group, with no further considerable change after 3 and 6 weeks in both groups. Overall, at all three follow-ups, sucrosomial® Vit D3 treatment achieved significantly higher and sustained 25(OH)D levels (p &lt; 0.001). In study 2, after 4 weeks, both Vit D3 treatment groups showed significant improvement in circulatory 25(OH)D levels (p &lt; 0.0001) but substantially higher in the sucrosomial® group with statistically significant differences between the two treatment groups (p = 0.02). At the 6-week follow-up, only subjects in the sucrosomial® Vit D3 group showed a further increase in circulatory 25(OH)D levels (p = 0.049), but no further significant changes in the levels of the SGC Vit D3 group (p = 0.062), showing a statistically significant difference between the two treatment groups (p = 0.002). The Vit D3 treatment was well tolerated by all participants, and no treatment-emergent effects or serious adverse events were reported.ConclusionOur results suggest that the sucrosomial® Vit D3 preparation absorbs efficiently in the GI system, achieving adequately higher and sustained circulatory Vit D levels in VDD, and thus can effectively contribute to the body protection against VDD-associated health conditions.Clinical trial registrationclinicaltrials.gov, identifier: NCT05706259.
Morphometry-based radiomics for predicting therapeutic response in patients with gliomas following radiotherapy
Authors: Sherminie Lahanda Purage G. , Jayatilake Mohan L. , Hewavithana Badra , Weerakoon Bimali S. , Vijithananda Sahan M. 
Published: August 2023

IntroductionGliomas are still considered as challenging in oncologic management despite the developments in treatment approaches. The complete elimination of a glioma might not be possible even after a treatment and assessment of therapeutic response is important to determine the future course of actions for patients with such cancers. In the recent years radiomics has emerged as a promising solution with potential applications including prediction of therapeutic response. Hence, this study was focused on investigating whether morphometry-based radiomics signature could be used to predict therapeutic response in patients with gliomas following radiotherapy.Methods105 magnetic resonance (MR) images including segmented and non-segmented images were used to extract morphometric features and develop a morphometry-based radiomics signature. After determining the appropriate machine learning algorithm, a prediction model was developed to predict the therapeutic response eliminating the highly correlated features as well as without eliminating the highly correlated features. Then the model performance was evaluated.ResultsTumor grade had the highest contribution to develop the morphometry-based signature. Random forest provided the highest accuracy to train the prediction model derived from the morphometry-based radiomics signature. An accuracy of 86% and area under the curve (AUC) value of 0.91 were achieved for the prediction model evaluated without eliminating the highly correlated features whereas accuracy and AUC value were 84% and 0.92 respectively for the prediction model evaluated after eliminating the highly correlated features.DiscussionNonetheless, the developed morphometry-based radiomics signature could be utilized as a noninvasive biomarker for therapeutic response in patients with gliomas following radiotherapy.
HER-2 ultra-low breast cancer: exploring the clinicopathological features and prognosis in a retrospective study
Authors: Shi Jiajie , Zhang Liqiu , Geng Cuizhi 
Published: August 2023

ObjectiveTo explore the clinicopathological features of patients with ultra-low expression of human epidermal growth factor 2 (HER-2) in breast cancer and its impact on prognosisMethodsData from 1024 patients with primary breast cancer having HER-2 ultra-low expression from January 01, 2018, to December 31, 2018, were collected and analyzed retrospectively. The clinicopathological features and prognosis were compared using a chi-squared test or Fisher exact probability method. COX regression analysis and log-rank test were used to explore the factors related to the postoperative 5-year survival rate. All analytical data were defined as statistically significant (P &lt; 0.05).ResultsOverall survival (OS) was higher in the HER-2 ultra-low group compared to the low expression group (P = 0.022). The tumor diameter, lymph node metastasis (LNM), and Ki67 expression were factors affecting DFS in the HER-2 ultra-low expression group (P &lt; 0.05). The tumor diameter and LNM were risk factors affecting the OS (P &lt; 0.05) in the HER-2 ultra-low expression group. LNM and Ki67 expression were risk factors affecting DFS (P &lt; 0.05) in the HER-2 low expression group. LNM was considered an independent risk factor affecting OS (P &lt; 0.05).ConclusionBreast cancer with HER-2 ultra-low expression has differences in the clinicopathological features. Breast cancer with HER-2 low expression is more aggressive and has a worse prognosis. This study provides a reference to consider in the treatment of HER-2-low and -ultra-low expression breast cancer.