bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Differences in Treatment Response and Survival Time of Lung Adenocarcinoma Patients Based on a Prognostic Risk Model of Glycolysis-Related Genes
Authors: Zhao Rongchang , Ding Dan , Ding Yan , Han Rongbo , Wang Xiujuan , Zhu Chunrong 
Published: May 2022

Background:Multiple factors influence the survival of patients with lung adenocarcinoma (LUAD). Specifically, the therapeutic outcomes of treatments and the probability of recurrence of the disease differ among patients with the same stage of LUAD. Therefore, effective prognostic predictors need to be identified.Methods:Based on the tumor mutation burden (TMB) data obtained from The Cancer Genome Atlas (TCGA) database, LUAD patients were divided into high and low TMB groups, and differentially expressed glycolysis-related genes between the two groups were screened. The least absolute shrinkage and selection operator (LASSO) and Cox regression were used to obtain a prognostic model. A receiver operating characteristic (ROC) curve and a calibration curve were generated to evaluate the nomogram that was constructed based on clinicopathological characteristics and the risk score. Two data sets (GSE68465 and GSE11969) from the Gene Expression Omnibus (GEO) were used to verify the prognostic performance of the gene. Furthermore, differences in immune cell distribution, immune-related molecules, and drug susceptibility were assessed for their relationship with the risk score.Results:We constructed a 5-gene signature (FKBP4, HMMR, B4GALT1, SLC2A1, STC1) capable of dividing patients into two risk groups. There was a significant difference in overall survival (OS) times between the high-risk group and the low-risk group (p&lt; 0.001), with the low-risk group having a better survival outcome. Through multivariate Cox analysis, the risk score was confirmed to be an independent prognostic factor (HR = 2.709, 95% CI = 1.981–3.705,p&lt; 0.001), and the ROC curve and nomogram exhibited accurate prediction performance. Validation of the data obtained in the GEO database yielded similar results. Furthermore, there were significant differences in sensitivity to immunotherapy, cisplatin, paclitaxel, gemcitabine, docetaxel, gefitinib, and erlotinib between the low-risk and high-risk groups.Conclusion:Our results reveal that glycolysis-related genes are feasible predictors of survival and the treatment response of patients with LUAD.
Pooled Prevalence and Determinants of Completion of Maternity Continuum of Care in Sub-Saharan Africa: A Multi-Country Analysis of Recent Demographic and Health Surveys
Authors: Hunie Asratie Melaku , Belay Daniel Gashaneh 
Published: May 2022

BackgroundImproving the coverage of completion of the maternity continuum of care is the priority area of sub-Saharan African countries to achieve the sustainable development goal. Despite this, information is scant about the pooled prevalence of completion of the maternity continuum of care and its determinants in sub-Saharan African countries. Therefore, this study aimed to assess the pooled prevalence of completion of the maternity continuum of care and its determinants among women in sub-Saharan African countries.MethodsThe study was conducted based on Demographic and Health Survey (DHS) data from 33 sub-Saharan African countries from 2010 to 2020. The total sample size of 337,297 postpartum period women with children aged 0–36 months (about 3 years) was employed in the analysis by STATA version 14. A multilevel logistic regression model was fitted, and intraclass correlation coefficient (ICC), median odds ratio (MOR), proportion change in variance (PCV), and deviance were used for model fitness and comparison. Adjusted odds ratio (AOR) with its 95% confidence interval (CI) was presented. Variables with a value of p &lt; 0.05 were declared significant determinants of completion of the maternity continuum of care.ResultsThe pooled prevalence of completion of the maternity continuum of care was 35.81%; [95% CI, 35.64%, 35.9%]. Higher educational level [AOR = 3.62; 95% CI 2.25, 4.46], wanted pregnancy [AOR = 2.51; 95% CI 1.82, 3.12], history of terminated pregnancy [AOR = 3.21; 95% CI 2.86, 4.21], distance to the nearby health facility [AOR = 2.11; 95% CI 1.68, 2.36], women as primary decision maker [AOR = 2.15; 95% CI 2.02, 2.87], nouse of traditional medication during pregnancy [AOR = 1.01; 95% CI 1.00, 1.45], antenatal care (ANC) visit within second trimester [AOR = 2.76; 95% CI 2.01, 3.47], informed about pregnancy complication [AOR = 2.73; 95% CI 2.10, 3.21], healthcare provider support [AOR = 1.77; 95% CI 1.02, 2.44], and being eastern and western African [AOR = 1.55; 95% CI 1.11, 2.44 and AOR = 2.01; 95% CI 1.88, 2.76, respectively] were determinant factors of completion of maternity continuum of care.ConclusionsThe completion of the maternity continuum of care in sub-Sahara African countries was low. Emphasis on women's education, type, history of pregnancy, distance to the nearby health facility, region, assessing the exposure of traditional medication, and informed about pregnancy complications, healthcare provider's support can improve the prevalence of completion of the maternity continuum of care.
Case Report: A Missense Mutation of KIT in Hyperpigmentation and Lentigines Unassociated With Systemic Disorders: Report of a Chinese Pedigree and a Literature Review
Authors: Yang Lu , Liu Yuehua , Wang Tao 
Published: May 2022

BackgroundKIT is a proto-oncogene that is involved in the proliferation, survival, and regulation of melanocytes, mast cells, and the interstitial cells of Cajal. Mutations of KIT have been reported to be associated with hyperpigmentation and lentigines, mastocytosis, and gastrointestinal stromal tumors (GISTs). Some hotspot mutations of KIT have been reported to be associated with mastocytosis and GISTs, while the relationship between KIT mutations and hyperpigmentation and lentigines has not been fully elucidated.MethodsIn this study, we presented a three-generation Chinese pedigree with progressive hyperpigmentation and generalized lentigines inherited in an autosomal dominant pattern. High-throughput sequencing was performed to capture genetic variations in peripheral blood samples of the proband. Also, Sanger sequencing was performed to further verify the result. We also reviewed previous literature on KIT mutations with hyperpigmentation and lentigines.ResultsA missense mutation of the KIT gene was identified: c. 2485G &gt; C, which was co-segregated in the proband and his insulted father. Germline KIT mutations presenting as generalized hyperpigmentation and lentigines without systemic disorders are rare, with only two reports of c. 2485G &gt; C mutation associated with this phenotype in previous literature.ConclusionOur pedigree, together with those two reports, indicates a possible phenotype-genotype correlation of this germline KIT mutation, which might be helpful for genetic counseling, further functional segregation of KIT, and design of targeted therapy in the future.
Clinical Practice Guidelines for the Management of Behavioral and Psychological Symptoms of Dementia: A Systematic Review With AGREE II
Authors: Ma Huixuan , Lu Xinliang , Zhou Aihong , Wang Fen , Zuo Xiumei , Zhan Minmin , Zou Qi , Gong Shuting , Chen Yufei , Lyu Jihui , Jia Longfei , Jia Jianping , Wei Cuibai 
Published: May 2022

BackgroundHigh-quality clinical practice guidelines (CPGs) are important for the effective treatment of behavioral and psychological symptoms of dementia (BPSD). However, recommendations provided by different quality guidelines may lead to varied clinical practice outcomes.ObjectiveTo assess the quality of available CPGs for the management of BPSD and summarize the best recommendations for treating BPSD.MethodsThis was a systematic review of CPGs for the management of BPSD with data obtained from electronic databases and evaluated using the Appraisal of Guidelines for Research and Evaluation II instrument, consisting of six domains: “Scope and purpose”, “Stakeholder involvement”, “Rigor of development”, “Clarity of presentation”, “Applicability”, and “Editorial independence”. The criteria for high-quality guidelines were set as: the score of high-quality guidelines in the “Rigor of development” domain should be ≥60% and as well as a score of &gt;60% in at least three other domains. High-quality guidelines were selected for recommendation extraction, and the final recommendations were formed in combination with the latest meta-analysis and randomized clinical-trial results.ResultsIn term of median scores in each domain for the six included CPGs, “Scope and purpose” (87.5%) scored better than all others, whereas “Applicability” (46.5%) was the domain with the lowest score. Four CPGs (2015 APA, 2018 NICE, 2018 CANADA, 2020 EAN) met the criteria of high-quality guidelines and were used to extract recommendations. From these four CPGs, nine specific recommendations related to the management of BPSD were summarized, of which seven were related to pharmacological treatment and two to non-pharmacological treatment. These recommendations covered the applicability of antipsychotic drugs, medication recommendations, withdrawal times, and several suitable non-pharmacological therapies.ConclusionThe quality of CPGs for the management of BPSD requires improvement, especially for the “Applicability” domain. For psychotic-like symptoms in dementia, the use of antipsychotics should be based on the individual's risk-benefit ratio, and the use of atypical antipsychotics seems to be a better choice. Non-pharmacological treatments may be suitable for emotional symptoms and sleep disorders.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020209204.
Nodopathies in the Early Diagnosis of Axonal Forms of Guillain-Barré Syndrome
Authors: Urdiales-Sánchez Sara , González-Montaña José-Ramiro , Diaz-Pérez Ricardo , Calvo-Calleja Pablo , Gutiérrez-Trueba María-Antonia , Urdiales-Urdiales Javier 
Published: May 2022

Introduction:Guillain-Barré syndrome (GBS) has been classified into demyelinating and axonal subtypes or forms, such as acute motor axonal neuropathy (AMAN) and regional pharyngeal-cervical-brachial variant (PCBv).ObjectiveTo study the relationship between motor nerve conduction blocks (CBs) and prognosis in AMAN and PCBv.Patients and MethodsWe retrospectively analyzed six cases of AMAN and PCBv with serial nerve conduction studies (NCS) and electromyography (EMG).ResultsThe serial NCS (1st−2nd and 3rd week) showed, as the most constant data, a decreased amplitude of the compound muscle action potential (CMAP) in 100% of cases. CBs were present in 66.6% of cases. EMG (3rd week) showed signs of severe denervation in 33.3%. All patients were treated from the 1st−2nd week of evolution with intravenous immunoglobulins (IVIGs). Patients with CBs (1st−2nd and 3rd week), showed reversible CBs or reversible conduction failure (RCF) and complete recovery at 1 month. Patients without CBs, with persistent reduced distal CMAP amplitude (dCMAP), showed severe acute denervation due to axonal degeneration (3rd week and 1st−3rd month) and a slow recovery of several months.ConclusionsNot all axonal forms of GBS have a poor prognosis. This study of AMAN and PCBv shows that patients with CBs can have reversible CBs or RCF, and good prognosis. Patients without CBs, with persistent reduction of dCMAP amplitude decrement, have severe acute denervation, and a worse prognosis. AMAN and PCBv have a continuous spectrum ranging from CBs due to dysfunction/disruption of Nodes of Ranvier, called nodopathies, with reversible CBs or RCF and good prognosis, to axonal degeneration with worse prognosis.
Abnormal Fractional Amplitude of Low Frequency Fluctuation Changes in Patients With Dry Eye Disease: A Functional Magnetic Resonance Imaging Study
Authors: Liang Rong-Bin , Liu Li-Qi , Shi Wen-Qing , Sun Tie , Ge Qian-Min , Li Qiu-Yu , Shu Hui-Ye , Zhang Li-Juan , Shao Yi 
Published: May 2022

PurposeTo investigate spontaneous brain activity in patients with dry eye (DE) and healthy control (HC) using the fractional amplitude of low frequency fluctuation (fALFF) technique with the aim of elucidating the relationship between the clinical symptoms of DE and changes in brain function.Material and MethodsA total of 28 patients with DE and 28 matched healthy volunteers (10 males and 18 females in each group) were enrolled. Resting-state functional magnetic resonance imaging scans were performed in both groups. Then all subjects were required to complete a comprehensive Hospital Anxiety and Depression Scale (HADS). Receiver operating characteristic (ROC) curve analysis was used to evaluate the differences in fALFF values between the two groups and their diagnostic value. Linear correlations between HADS and fALFF values in different brain regions of DE patients were analyzed using the Pearson correlation coefficient.ResultsPatients with DE had significantly higher fALFF values in the left calcarine sulcus (CS) than the HC group, while fALFF values in the bilateral middle frontal gyrus (MFG) and right MFG/right inferior frontal gyrus (IFG) were significantly lower in DE patients than in HC group. fALFF values had a high diagnostic value for differentiating patients with DE from the HC group (P &lt; 0.001). Right MFG and right MFG/IFG were significantly correlated with HADS values.ConclusionOur study found that DE mainly involved functional disorders in the brain areas of the left CS, bilateral MFG and right MFG/right IFG, which helped us to find possible clinical features of DE disease and reflected the potential pathological mechanism of DE.
Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration
Authors: Sfera Adonis , Thomas Karina G. , Andronescu Christina V. , Jafri Nyla , Sfera Dan O. , Sasannia Sarvin , Zapata-Martín del Campo Carlos M. , Maldonado Jose C. 
Published: May 2022

Graphical AbstractBoth HIV-1 and cART alter the lysosomes, increasing intracellular iron and the risk of ferroptosis. Dysfunctional lysosomes release the ferroptosis drivers iron, Ca2+ and cathepsin B (catB), promoting neuronal and oligodendrocyte loss, reflected in the white and gray matter pathology. The host responds to lysosomal damage by activating an epigenetic axis comprised of bromodomain 4 (BRD4) and microRNA-29 family (miR-29) that promptly suppresses lysosomal function, lowering ferritinophagy. As there is an inverse relationship between miR-29 and BRD4, HIV-1 inhibition of miR-29, upregulates BRD4, blocking ferritinophagy. The BRD4/miR-29 system also inhibits iron regulatory protein-2 (IRP-2) and augments cystine/glutamate antiporter xCT (SLC7A11), lowering the odds of ferroptosis.
Bevacizumab, With Sorafenib and Cyclophosphamide Provides Clinical Benefit for Recurrent or Refractory Osseous Sarcomas in Children and Young Adults
Authors: Bodea Jessica , Caldwell Kenneth J. , Federico Sara M. 
Published: May 2022

ObjectiveChildren and adolescents with recurrent and metastatic solid tumors have a poor outcome. A previous phase 1 study (ANGIO1) targeting angiogenesis with bevacizumab, sorafenib, and cyclophosphamide, demonstrated a signal of activity in a subset of patients. Here we report the results of a cohort of pediatric and young adult patients treated at the recommended phase 2 doses.MethodsElectronic medical records of patients with refractory or recurrent solid tumors who received ANGIO1 therapy were reviewed. Treatment cycles lasted 21 days and included bevacizumab, sorafenib, and cyclophosphamide. Toxicities were assessed using Common Terminology Criteria for Adverse Events, v5.0. Responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST1.1).ResultsThirty-nine patients (22 male, 17 female; median age 15 years; range 1-22 years) received the treatment regimen. The most common diagnoses included bone sarcomas (n=21; 14 Ewing sarcoma, 7 osteosarcoma) and soft tissue sarcomas (n=9; 2 rhabdomyosarcoma, 3 synovial sarcoma, 2 desmoplastic small round cell tumors, and 2 high-grade sarcoma). The most common Grade 3 non-hematologic toxicities included hypertension (2, 5.4%) and hematuria (2, 5.4%). Five patients (13.5%) had a pneumothorax (3 at progressive disease, 1 post lung biopsy, and 1 spontaneous). Common Grade 3/4 hematologic toxicities were lymphopenia (19, 51%) and leukopenia (13, 35%). Sixteen patients (43.2%) developed palmar-plantar erythrodysesthesia Grade 2 or less. A total of 297 cycles were administered. Twenty-three patients required a dose reduction of cyclophosphamide, sorafenib or bevacizumab during therapy, all of whom continued to have clinical benefit following dose modification. One patient (Ewing sarcoma) achieved a complete response after 11 cycles; 2 patients (Ewing sarcoma, high grade sarcoma) achieved a partial response following cycles 2 and 4, respectively and 20 patients had stable disease as a best response.ConclusionsIntravenous bevacizumab combined with oral sorafenib and metronomic cyclophosphamide was tolerated and required minimal supportive care or additional clinic visits. Disease stabilization for prolonged time periods was observed in greater than half of the treated patients. Patients with bone sarcoma demonstrated a signal of activity suggesting possible benefit from incorporation of the therapy as a maintenance regimen in upfront setting, or as a palliative regimen.
A Nomogram Combined Radiomics and Clinical Features as Imaging Biomarkers for Prediction of Visceral Pleural Invasion in Lung Adenocarcinoma
Authors: Zha Xinyi , Liu Yuanqing , Ping Xiaoxia , Bao Jiayi , Wu Qian , Hu Su , Hu Chunhong 
Published: May 2022

ObjectivesTo develop and validate a nomogram model based on radiomics features for preoperative prediction of visceral pleural invasion (VPI) in patients with lung adenocarcinoma.MethodsA total of 659 patients with surgically pathologically confirmed lung adenocarcinoma underwent CT examination. All cases were divided into a training cohort (n = 466) and a validation cohort (n = 193). CT features were analyzed by two chest radiologists. CT radiomics features were extracted from CT images. LASSO regression analysis was applied to determine the most useful radiomics features and construct radiomics score (radscore). A nomogram model was developed by combining the optimal clinical and CT features and the radscore. The model performance was evaluated using ROC analysis, calibration curve and decision curve analysis (DCA).ResultsA total of 1316 radiomics features were extracted. A radiomics signature model with a selection of the six optimal features was developed to identify patients with or without VPI. There was a significant difference in the radscore between the two groups of patients. Five clinical features were retained and contributed as clinical feature models. The nomogram combining clinical features and radiomics features showed improved accuracy, specificity, positive predictive value, and AUC for predicting VPI, compared to the radiomics model alone (specificity: training cohort: 0.89, validation cohort: 0.88, accuracy: training cohort: 0.84, validation cohort: 0.83, AUC: training cohort: 0.89, validation cohort: 0.89). The calibration curve and decision curve analyses suggested that the nomogram with clinical features is beyond the traditional clinical and radiomics features.ConclusionA nomogram model combining radiomics and clinical features is effective in non-invasively prediction of VPI in patients with lung adenocarcinoma.
Blocking CD47 Shows Superior Anti-tumor Therapeutic Effects of Bevacizumab in Gastric Cancer
Authors: Shi Chenyang , Li Jiaxin , Fan Guorong , Liu Yu 
Published: May 2022

Background: Bevacizumab (Avastin®), a humanized antiangiogenic monoclonal antibody, is widely used in the clinical treatment of tumour diseases. However, recent research has shown that the beneficial antiangiogenic effects of these agents have been limited in a number of patients due to complex immunosuppressive mechanisms. Here, we report a synergistic antitumour strategy through simultaneous blockade of VEGF and CD47 signalling to enhance the curative effect of advanced gastric cancer.Method: A BGC-823 gastric tumour model was chosen to evaluate antitumour efficacy. Macrophage migration and phagocytosis were evaluated to determine immune-related resistance to bevacizumab therapy. Synergistic antitumour activity was observed on the basis of tumour volume, tumour weight, tumour inhibition rate, tumour angiogenesis and tumour metastasis when bevacizumab was combined with an anti-CD47 monoclonal antibody.Results: Our study demonstrated that synergistic therapy targeting CD47 and VEGF reversed macrophage migration and phagocytosis, which were inhibited by antiangiogenic therapy and enhanced antitumour effects. Moreover, blockade of CD47 induced by antiangiogenic therapy inhibited tumour metastasis.Conclusion: Our data provide an effective strategy to attenuate resistance to bevacizumab therapy, promoting clinical cancer treatment with antiangiogenic drugs in combination with CD47-targeting inhibitors.
Changes in Climate Vulnerability and Projected Water Stress of The Gambia's Food Supply Between 1988 and 2018: Trading With Trade-Offs
Authors: Hadida Genevieve , Ali Zakari , Kastner Thomas , Carr Tony W. , Prentice Andrew M. , Green Rosemary , Scheelbeek Pauline 
Published: May 2022

BackgroundThe coexistence of under- and overnutrition is of increasing public health concern in The Gambia. Fruits, vegetables and pulses are essential to healthy and sustainable diets, preventing micronutrient deficiencies and non-communicable diseases, while cereals significantly contribute to energy intake. However, environmental changes are predicted to intensify, reducing future yields of these crops if agricultural productivity and resilience are not improved. The Gambia is highly climate-vulnerable and import-dependent, but the extent of its reliance on other climate-vulnerable countries for its supply of nutritionally important crops is currently unknown.MethodsWe used United Nations Food and Agriculture Organization data, with novel origin-tracing algorithms applied, to analyse The Gambia's supply of cereals, fruits, vegetables and pulses between 1988 and 2018. The climate vulnerability of countries was assessed using Notre Dame Global Adaptation Initiative (ND-GAIN) index scores, and projected water stress (2040) assessed using World Resources Institute (WRI) scores. Multilevel generalized linear mixed-effects models were used to identify changes in the overall climate vulnerability and projected water stress of supply.ResultsBetween 1988 and 2018, The Gambia's supply of cereals, fruits, vegetables and pulses diversified, with the proportion domestically produced falling (Cereals: 61.4%–27.7%; Fruits: 93.0%–55.7%; Vegetables: 24.6%–16.3%; Pulses: 100.0%–76.0%). The weighted-average ND-GAIN scores improved (indicating less climate vulnerability) for supply of all crops except cereals, but the weighted-average WRI score for supply deteriorated (indicating increased projected water stress) for all crops except vegetables. When just considering imports, weighted-average ND-GAIN scores deteriorated for fruits and cereals while showing no significant change for other food groups, and the WRI score deteriorated for cereals only.ConclusionsDespite some notable improvements in the environmental vulnerability of The Gambia's supply of nutritionally important crops (particularly vegetables), considerable, and in some cases increasing, proportions of their supply are produced in countries that are vulnerable to climate change and future water stress. This may have implications for the availability, affordability, and hence consumption of these crops in The Gambia, ultimately exacerbating existing nutritional challenges. Exploring the options to strengthen supply resilience—such as altering trade patterns, agricultural techniques and diets—should be prioritized.