bluuebunny/crossref_metadata_2025_split huggingface dataset:
Land-use function evolution and eco-environmental effects in the tarim river basin from the perspective of production–living–ecological space
Authors: Wang Yang , Wang Yin , Xia Tingting , Li Yang , Li Zhi 
Published: September 2022

The identification of land type multi-functionality is a basic tool for the organization, coordination, and configuration of basin land, and provides a key criterion for determining the combination of land-use functions and the status quo of the ecological environment in the basin. However, a feasible identification method system for this purpose has not yet been established. Therefore, in this study, we construct a production–living–ecological space (PLES) classification system from the comprehensive perspective of land-use type and ecological environment. Based on remote sensing of PLES and statistical land-use status data for 2000, 2005, 2010, 2015, and 2020, we analyze the evolutionary characteristics of land-use function using the transfer matrix and center of gravity transfer methods. These are combined with the eco-environmental quality index to reveal the driving factors of eco-environmental quality spatial differentiation using the geographic detector model. The results indicate that the overall ecological environment quality index of the Tarim River Basin presents a downward trend, with a spatial differentiation pattern of high in the northwest and low in the southeast. Over the past 20 years, the ecological environment quality index has dropped by 0.852. The structural evolution and regional differentiation of PLES areas are remarkable, all of which expanded over the study period (except for the key ecological land). The center of gravity of production land presented the most obvious migration, with a total migration of 10,601.76 m to the northeast. Eco-environmental effects are found to be mainly driven by socio-economic factors, of which population density growth is the most important. The implementation of some ecological restoration projects has played a role in slowing down the degradation trend of the ecological environment quality in the Tarim River Basin; however, due to population increases and socio-economic development, the ecological environment degradation has overall been exacerbated.
Research into the biological differences and targets in lung cancer patients with diverse immunotherapy responses
Authors: Zhang Xunlang , Wu Xinhui , Huang Huang , Du Kangming , Nie Yingying , Su Peiyuan , Li Yuefei 
Published: September 2022

BackgroundImmunotherapy has gradually become an important therapy option for lung cancer patients.MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were responsible for all the public data.ResultsIn our study, we firstly identified 22 characteristic genes of NSCLC immunotherapy response using the machine learning algorithm. Molecule subtyping was then conducted and two patient subtypes were identified Cluster1 and Cluster2. Results showed that Cluster1 patients had a lower TIDE score and were more sensitive to immunotherapy in both TCGA and combined GEO cohorts. Biological enrichment analysis showed that pathways of epithelial-mesenchymal transition (EMT), apical junction, KRAS signaling, myogenesis, G2M checkpoint, E2F targets, WNT/β-catenin signaling, hedgehog signaling, hypoxia were activated in Cluster2 patients. Genomic instability between Cluster1 and Cluster2 patients was not significantly different. Interestingly, we found that female patients were more adaptable to immunotherapy. Biological enrichment revealed that compared with female patients, pathways of MYC target, G2M checkpoints, mTORC1 signaling, MYC target, E2F target, KRAS signaling, oxidative phosphorylation, mitotic spindle and P53 pathway were activated. Meanwhile, monocytes might have a potential role in affecting NSCLC immunotherapy and underlying mechanism has been explored. Finally, we found that SEC14L3 and APCDD1L were the underlying targets affecting immunotherapy, as well as patients survival.ConclusionsThese results can provide direction and guidance for future research focused on NSCLC immunotherapy.
Durable disease control and refractory bullous pemphigoid after immune checkpoint inhibitor discontinuation in metastatic renal cell carcinoma: A case report
Authors: Mari Roxane , Guerin Mathilde , Vicier Cécile , Walz Jochen , Bonnet Nathalie , Pignot Géraldine , Gravis Gwenaelle 
Published: September 2022

BackgroundImmune checkpoint inhibitors deeply modified metastatic renal cell carcinoma’s management, and confront us to adverse events that we were not used to with conventional anti-cancer therapies. We report the case of a patient who received nivolumab as second-line treatment of a metastatic clear cell renal cell carcinoma and who developed bullous pemphigoid four years after nivolumab introduction, with persistent exacerbations even after its discontinuation.Case presentationA 66-year-old man was diagnosed with lung metastasis eight years after radical nephrectomy for a clear cell renal cell carcinoma. He firstly received an anti-angiogenic agent combination, and then received anti-programmed death 1 (PD1) nivolumab as second-line treatment. Nivolumab led to prolonged disease control, but after four years of exposure the patient developed skin lesions consistent with bullous pemphigoid. After seven years of nivolumab administration and perfect disease stability, nivolumab was discontinued and surveillance was proposed. Despite nivolumab discontinuation, the patient continued to develop bullous pemphigoid exacerbations. Metastatic renal cell carcinoma was still perfectly stable more than two years after immune checkpoint discontinuation with no further anti-cancer therapy.DiscussionWe report the case of a refractory bullous pemphigoid which occurred four years after nivolumab introduction and lasted despite nivolumab discontinuation, in a patient whose metastatic renal cell carcinoma is still controlled after more than two years without any anticancer treatment. This highlights the potential association between immune-related adverse events and response to immune checkpoint inhibitors, and underlines the occurrence of late-onset and long-lasting immune-related adverse events even after discontinuation of treatment, which must encourage us to remain vigilant in the long term.
Morphogenetic dispositions for variability in acute kidney injury after cardiac surgery: Pilot study
Authors: Karan Radmila , Kovačević-Kostić Natasa , Kirćanski Bratislav , Čumić Jelena , Terzić Duško , Milićević Vladimir , Velinović Vojislav , Velinović Miloš , Obrenović-Kirćanski Biljana 
Published: September 2022

BackgroundThe aim of our study was to evaluate the degree of genetic homozygosity in cardiac surgical patients with postoperative acute kidney injury (AKI), compared to the subgroup without postoperative AKI, as well as to evaluate antropomorpho-genetic variability in cardiac surgical patients with regard to the presence and severity degree of AKI.Materials and methodsThe prospective cohort study included an analysis of 138 eligible coronary artery disease (CAD) surgical patients that were screened consecutively. The tested group was divided into three subgroups according to RIFLE criteria: Subgroup NoAKI (N = 91), risk (N = 31), and injury (N = 16). All individuals were evaluated for the presence of 19 observable recessive human traits (ORHT) as a marker of chromosomal homozygosity and variability.ResultsComparing subgroups NoAKI and risk, four ORHTs were significantly more frequent in the risk subgroup. Comparing subgroups NoAKI and injury, nine ORHTs were significantly more frequent in the injury subgroup; while comparing the injury subgroup and risk, five ORHTs were significantly more frequent in injury than in the risk subgroup. Results also showed a significant increase in the mean value of ORHTs for the injury subgroup compared to NoAKI subgroup (p = 0.039). Variability decreased proportionally to the increase in the severity of AKI (VNoAKI = 32.81%, VRisk = 30.92%, and VInjury = 28.62%).ConclusionOur findings pointed to the higher degree of recessive homozygosity and decreased variability in AKI patients vs. NoAKI individuals, thus presumably facilitating the development and severity degree expression of AKI in patients after cardiac surgery.
Fusobacterium nucleatum infection-induced neurodegeneration and abnormal gut microbiota composition in Alzheimer’s disease-like rats
Authors: Yan Caixia , Diao Qilin , Zhao Yuxi , Zhang Cheng , He Xiaoya , Huang Ruijie , Li Yan 
Published: September 2022

ObjectiveTo explore whether Fusobacterium nucleatum could lead to behavioral and pathological changes in Alzheimer’s disease (AD)-like model rat and whether they could affect the gut microbiota.MethodsThe cognitive ability and alveolar bone loss of Sprague-Dawley (SD) rats were tested by Morris water maze and Micro-CT, respectively. HE staining and immunohistochemistry were used to analyze the pathological changes and Aβ1–42 in brains. Western blot was applied to detect the expression of p-Tau 181 in the brain. Limulus amebocyte lysate assay and PCR were performed to determine serum LPS level and whether F. nucleatum accessed the brain, respectively. The gut microbiota was analyzed by the 16S rRNA gene sequence.ResultsOral infection with F. nucleatum could induce increased alveolar bone loss and learning impairment in AD-like rats. Additionally, F. nucleatum exposure increased the Aβ1–42 expression by about one-fourth (P &lt; 0.05), p-Tau181 by about one-third (P &lt; 0.05), and serum LPS (P &lt; 0.05) in AD-like rats. Moreover, F. nucleatum could change the gut microflora composition in AD-like rats, accompanied by a significant increase in the abundance of Streptococcus and Prevotella.ConclusionOral infection with F. nucleatum could contribute to abnormalities in cognitive ability and pathological change in the brain of AD-like rats, which may be related to abnormal gut microbiota composition.
Brain structural connectome in neonates with prenatal opioid exposure
Authors: Vishnubhotla Ramana V. , Zhao Yi , Wen Qiuting , Dietrich Jonathan , Sokol Gregory M. , Sadhasivam Senthilkumar , Radhakrishnan Rupa 
Published: September 2022

IntroductionInfants with prenatal opioid exposure (POE) are shown to be at risk for poor long-term neurobehavioral and cognitive outcomes. Early detection of brain developmental alterations on neuroimaging could help in understanding the effect of opioids on the developing brain. Recent studies have shown altered brain functional network connectivity through the application of graph theoretical modeling, in infants with POE. In this study, we assess global brain structural connectivity through diffusion tensor imaging (DTI) metrics and apply graph theoretical modeling to brain structural connectivity in infants with POE.MethodsIn this prospective observational study in infants with POE and control infants, brain MRI including DTI was performed before completion of 3 months corrected postmenstrual age. Tractography was performed on the whole brain using a deterministic fiber tracking algorithm. Pairwise connectivity and network measure were calculated based on fiber count and fractional anisotropy (FA) values. Graph theoretical metrics were also derived.ResultsThere were 11 POE and 18 unexposed infants included in the analysis. Pairwise connectivity based on fiber count showed alterations in 32 connections. Pairwise connectivity based on FA values showed alterations in 24 connections. Connections between the right superior frontal gyrus and right paracentral lobule and between the right superior occipital gyrus and right fusiform gyrus were significantly different after adjusting for multiple comparisons between POE infants and unexposed controls. Additionally, alterations in graph theoretical network metrics were identified with fiber count and FA value derived tracts.ConclusionComparisons show significant differences in fiber count in two structural connections. The long-term clinical outcomes related to these findings may be assessed in longitudinal follow-up studies.
A network pharmacology approach to evaluate the synergistic effect of dihydromyricetin and myricitrin in vine tea on the proliferation of B16F10 cells
Authors: Zhao Nanxing , Kong Hongming , Liu Hesheng , Shi Qing , Qi Xiangyang , Chen Qiuping 
Published: September 2022

Aim of the studyAlthough vine tea has demonstrated broad-spectrum anti-cancer properties, its main active compounds, dihydromyricetin (DMY) and myricitrin (MYT), exert weaker effects than the tea extracts. This study aimed to investigate the synergistic inhibitory effects of DMY and MYT on B16F10 cell proliferation and their synergistic inhibitory effects.MethodsThe effect of vine tea extracts (VTEs) and their active compounds on B16F10 cells was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, fluorescence staining, and flow cytometry. The synergistic effects were calculated by the combination index (CI), and its mechanism was discussed by network pharmacology.ResultsDifferent VTEs varied in their inhibition of B16F10 cell growth, with IC50 values ranging from 4.45 to 12.95 μg/mL, Among these, Guangzhou Qingyuan (Level 2), appeared to have the most potent inhibitory effect. The IC50 value of mix-use of DMY and MYT was 19.94∼64.4 μM, of which DMY: MYT = 8:1 had the minimum IC50 value of 19.94 μM. Combinations in the 1:1∼8:1 range had stronger effects than the isolated active compound. When they were mixed at the ratio of 1:4∼8:1, CI &lt; 1, showing a synergistic effect. The combination of DMY and MYT also significantly inhibited the tyrosinase activity in B16F10 cells, consistent with its impact on cell proliferation. The eight potential targets were identified by network pharmacology regulating melanin metabolism, tyrosine metabolism, and melanogenesis signaling. According to the analysis of protein-protein interactions, TP53, TNF, and TYR might be critical targets for preventing and treating melanoma.ConclusionWe found that DMY and MYT induced apoptosis of B16F10 cells, and their combined application had a significant synergistic effect. The present findings indicated that vine tea had a multi-pathway and multi-target impact on the prevention and treatment of melanoma.
Development and validation of a high-resolution T2WI-based radiomic signature for the diagnosis of lymph node status within the mesorectum in rectal cancer
Authors: Song Gesheng , Li Panpan , Wu Rui , Jia Yuping , Hong Yu , He Rong , Li Jinye , Zhang Ran , Li Aiyin 
Published: September 2022

PurposeThe aim of this study was to explore the feasibility of a high-resolution T2-weighted imaging (HR-T2WI)-based radiomics prediction model for diagnosing metastatic lymph nodes (LNs) within the mesorectum in rectal cancer.MethodA total of 604 LNs (306 metastatic and 298 non-metastatic) from 166 patients were obtained. All patients underwent HR-T2WI examination and total mesorectal excision (TME) surgery. Four kinds of segmentation methods were used to select region of interest (ROI), including method 1 along the border of LNs; method 2 along the expanded border of LNs with an additional 2–3 mm; method 3 covering the border of LNs only; and method 4, a circle region only within LNs. A total of 1,409 features were extracted for each method. Variance threshold method, Select K Best, and Lasso algorithm were used to reduce the dimension. All LNs were divided into training and test sets. Fivefold cross-validation was used to build the logistic model, which was evaluated by the receiver operating characteristic (ROC) with four indicators, including area under the curve (AUC), accuracy (ACC), sensitivity (SE), and specificity (SP). Three radiologists with different working experience in diagnosing rectal diseases assessed LN metastasis respectively. The diagnostic efficiencies with each of four segmentation methods and three radiologists were compared to each other.ResultsFor the test set, the AUCs of four segmentation methods were 0.820, 0.799, 0.764, and 0.741; the ACCs were 0.725, 0.704, 0.709, and 0.670; the SEs were 0.756, 0.634, 0.700, and 0.589; and the SPs were 0.696, 0.772, 0.717, and 0.750, respectively. There was no statistically significant difference in AUC between the four methods (p &gt; 0.05). Method 1 had the highest values of AUC, ACC, and SE. For three radiologists, the overall diagnostic efficiency was moderate. The corresponding AUCs were 0.604, 0.634, and 0.671; the ACCs were 0.601, 0.632, and 0.667; the SEs were 0.366, 0.552, and 0.392; and the SPs were 0.842, 0.715, and 0.950, respectively.ConclusionsThe proposed HR-T2WI-based radiomic signature exhibited a robust performance on predicting mesorectal LN status and could potentially be used for clinicians in order to determine the status of metastatic LNs in rectal cancer patients.
Impact of perioperative red blood cell transfusion, anemia of cancer and global health status on the prognosis of elderly patients with endometrial and ovarian cancer
Authors: Anic Katharina , Schmidt Mona Wanda , Schmidt Marcus , Krajnak Slavomir , Löwe Amelie , Linz Valerie Catherine , Schwab Roxana , Weikel Wolfgang , Brenner Walburgis , Westphalen Christiane , Rissel René , Hartmann Erik Kristoffer , Conradi Roland , Hasenburg Annette , Battista Marco Johannes 
Published: September 2022

IntroductionPerioperative red blood cell (RBC) transfusions have been associated with increased morbidity and worse oncological outcome in some solid neoplasms. In order to elucidate whether RBC transfusions themselves, the preoperative anemia of cancer (AOC), or the impaired global health status might explain this impact on patients with endometrial cancer (EC) or ovarian cancer (OC), we performed a retrospective, single-institution cohort study.Materials and methodsWomen older than 60 years with EC or OC were included. The influence of RBC transfusions, AOC, and frailty status determined by the G8 geriatric screening tool (G8 score), as well as the clinical-pathological cancer characteristics on progression-free survival (PFS) and overall survival (OS), was determined by using the Kaplan-Meier method and the Cox regression analyses.ResultsIn total, 263 patients with EC (n = 152) and OC (n = 111) were included in the study. Patients with EC receiving RBC transfusions were faced with a significantly shorter 5-year PFS (79.8% vs. 26.0%; p &lt; 0.001) and 5-year OS (82.6% vs. 25.7%; p &lt; 0.001). In multivariable analyses, besides established clinical-pathological cancer characteristics, the RBC transfusions remained the only significant prognostic parameter for PFS (HR: 1.76; 95%-CI [1.01–3.07]) and OS (HR: 2.38; 95%-CI [1.50–3.78]). In OC, the G8 score stratified the cohort in terms of PFS rates (G8-non-frail 53.4% vs. G8-frail 16.7%; p = 0.010) and AOC stratified the cohort for 5-year OS estimates (non-anemic: 36.7% vs. anemic: 10.6%; p = 0.008). Multivariable Cox regression analyses determined the G8 score and FIGO stage as independent prognostic factors in terms of PFS (HR: 2.23; 95%-CI [1.16–4.32] and HR: 6.52; 95%-CI [1.51–28.07], respectively). For OS, only the TNM tumor stage retained independent significance (HR: 3.75; 95%-CI [1.87–7.53]).DiscussionThe results of this trial demonstrate the negative impact of RBC transfusions on the prognosis of patients with EC. Contrastingly, the prognosis of OC is altered by the preoperative global health status rather than AOC or RBC transfusions. In summary, we suggested a cumulatively restrictive transfusion management in G8-non-frail EC patients and postulated a more moderate transfusion management based on the treatment of symptomatic anemia without survival deficits in OC patients.
Case report: Common clonal origin of concurrent langerhans cell histiocytosis and acute myeloid leukemia
Authors: Kazama Shintaro , Yokoyama Kazuaki , Ueki Toshimitsu , Kazumoto Hiroko , Satomi Hidetoshi , Sumi Masahiko , Ito Ichiro , Yusa Nozomi , Kasajima Rika , Shimizu Eigo , Yamaguchi Rui , Imoto Seiya , Miyano Satoru , Tanaka Yukihisa , Denda Tamami , Ota Yasunori , Tojo Arinobu , Kobayashi Hikaru 
Published: September 2022

Langerhans cell histiocytosis (LCH) and acute myeloid leukemia (AML) are distinct entities of blood neoplasms, and the exact developmental origin of both neoplasms are considered be heterogenous among patients. However, reports of concurrent LCH and AML are rare. Herein we report a novel case of concurrent LCH and AML which shared same the driver mutations, strongly suggesting a common clonal origin.An 84-year-old female presented with cervical lymphadenopathy and pruritic skin rash on the face and scalp. Laboratory tests revealed pancytopenia with 13% of blasts, elevated LDH and liver enzymes, in addition to generalised lymphadenopathy and splenomegaly by computed tomography. Bone marrow specimens showed massive infiltration of MPO-positive myeloblasts, whereas S-100 and CD1a positive atypical dendritic cell-like cells accounted for 10% of the atypical cells on bone marrow pathology, suggesting a mixture of LCH and AML. A biopsy specimen from a cervical lymph node and the skin demonstrated the accumulation of atypical cells which were positive for S-100 and CD1a. LCH was found in lymph nodes, skin and bone marrow; AML was found in peripheral blood and bone marrow (AML was predominant compared with LCH in the bone marrow).Next generation sequencing revealed four somatic driver mutations (NRAS-G13D, IDH2-R140Q, and DNMT3A-F640fs/-I715fs), equally shared by both the lymph node and bone marrow, suggesting a common clonal origin for the concurrent LCH and AML. Prednisolone and vinblastine were initially given with partial response in LCH; peripheral blood blasts also disappeared for 3 months. Salvage chemotherapy with low dose cytarabine and aclarubicin were given for relapse, with partial response in both LCH and AML. She died from pneumonia and septicemia on day 384. Our case demonstrates a common cell of origin for LCH and AML with a common genetic mutation, providing evidence to support the proposal to classify histiocytosis, including LCH, as a myeloid/myeloproliferative malignancy.