bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression profiles analysis identifies specific interferon-stimulated signatures as potential diagnostic and predictive indicators of JAK2V617F+ myelofibrosis
Authors: Zhao Yanhong , Wang Di , Liang Yipeng , Xu Changlu , Shi Lihong , Tong Jingyuan 
Published: August 2022

Objective: This study aimed to identify specific dysregulated genes with potential diagnostic and predictive values for JAK2V617F+ myelofibrosis.Methods: Two gene expression datasets of CD34+ hematopoietic stem and progenitor cells (HSPCs) from patients with JAK2V617F+ myeloproliferative neoplasm (MPN) [n = 66, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)] and healthy controls (HC) (n = 30) were acquired from the GEO (Gene Expression Omnibus) database. The differentially expressed genes (DEGs) were screened between each JAK2V617F+ MPN entity and HC. Subsequently, functional enrichment analyses, including Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Gene Set Enrichment Analysis (GSEA), were conducted to decipher the important biological effects of DEGs. Protein–protein interaction (PPI) networks of the DEGs were constructed to identify hub genes and significant modules. Another two gene expression profiles of patients with JAK2V617F+ MPN [n = 23, including PV, ET, secondary myelofibrosis (SMF), and PMF] and HC (n = 6) from GEO were used as external validation datasets to prove the reliability of the identified signatures.Results: KEGG analysis revealed the upregulated genes in three JAK2V617F+ MPN entities compared with HC were essentially enriched in inflammatory pathways and immune response signaling pathways, and the number of these pathways enriched in PMF was obviously more than that in PV and ET. Following the PPI analysis, 10 genes primarily related to inflammation and immune response were found upregulated in different JAK2V617F+ MPN entities. In addition, Reactome enrichment analysis indicated that interferon signaling pathways were enriched specifically in PMF but not in PV or ET. Furthermore, several interferon (IFN)-stimulated genes were identified to be uniquely upregulated in JAK2V617F+ PMF. The external datasets validated the upregulation of four interferon-related genes (OAS1, IFITM3, GBP1, and GBP2) in JAK2V617F+ myelofibrosis. The receiver operating characteristic (ROC) curves indicate that the four genes have high area under the ROC curve (AUC) values when distinguishing JAK2V617F+ myelofibrosis from PV or ET.Conclusion: Four interferon-stimulated genes (OAS1, IFITM3, GBP1, and GBP2) exclusively upregulated in JAK2V617F+ myelofibrosis might have the potential to be the auxiliary molecular diagnostic and predictive indicators of myelofibrosis.
Role of leukocytes and systemic inflammation indexes (NLR, PLR, MLP, dNLR, NLPR, AISI, SIR-I, and SII) on admission predicts in-hospital mortality in non-elderly and elderly COVID-19 patients
Authors: Ghobadi Hassan , Mohammadshahi Jafar , Javaheri Nazli , Fouladi Nasrin , Mirzazadeh Yasaman , Aslani Mohammad Reza 
Published: August 2022

BackgroundSystemic inflammation indices, including neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR), derived neutrophil/lymphocyte ratio (dNLR), neutrophil/lymphocyte*platelet ratio (NLPR), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIR-I), and systemic inflammation index (SII) are well-expressed inflammatory indices that have been used to predict the severity and mortality of various inflammatory diseases. This study aimed to investigate the role of systemic inflammatory markers in predicting mortality in non-elderly and elderly COVID-19 patients.MethodsIn a retrospective study, laboratory parameters were examined for 1,792 COVID-19 patients (elderly = 710 and non-elderly = 1,082). The ability of inflammatory markers to distinguish the severity of COVID-19 was determined by receiver operating characteristic (ROC) analysis, and survival probability was determined by the mean of Kaplan–Meier curves, with the endpoint being death.ResultsIn the non-survivor non-elderly and elderly patients, the parameters PLR, MLR, dNLR, NLPR, AISI, SIR-I, and SII were significantly higher than in the surviving patients. WBC count (HR = 4.668, 95% CI = 1.624 to 13.413, P &lt; 0.01), neutrophil count (HR = 6.395, 95% CI = 2.070 to 19.760, P &lt; 0.01), dNLR (HR = 0.390, 95% CI = 0.182 to 0.835, P &lt; 0.05), and SII (HR = 10.725, 95% CI = 1.076 to 106.826, P &lt; 0.05) were significantly associated with survival. On the other hand, in elderly patients, it was found that WBC count (HR = 4.076, 95% CI = 2.176 to 7.637, P &lt; 0.001) and neutrophil count (HR = 2.412, 95% CI = 1.252 to 4.647, P &lt; 0.01) were significantly associated with survival.ConclusionWBC count and neutrophil count in non-elderly and elderly patients, were reliable predictors of mortality.
The alteration of left ventricular strain in later-onset spinal muscular atrophy children
Authors: Cui Yiqin , Feng Yijie , Xia Yu , Fu Xingpeng , Gong Ming , Qian Jingjing , Yu Jin , Ye Jingjing , Gao Feng , Cheng Hongqiang , Mao Shanshan 
Published: August 2022

BackgroundPatients with spinal muscular atrophy (SMA) may suffer from multisystem injury, including an impaired cardiovascular system. However, M-mode echocardiography, the current dominant echocardiographic modality, is limited in the detection of myocardial injury. We considered the use of left ventricular strain imaging in detecting myocardial injury and explored the serum lipid profile related to cardiovascular disease in later-onset SMA children.MethodsA case-control study involving 80 patients with later-onset SMA and 80 age-, gender-, and body surface area-matched control children was conducted in a single tertiary pediatric hospital in China. Data on the left ventricular strain measured using two-dimensional speckle tracking echocardiography, left ventricular function parameters assessed by M-mode echocardiography, and serum lipid profile of these two groups were retrospectively collected for differential analysis.ResultsThe mean age of the 80 SMA patients were (6.87 ± 2.87) years, of which 46 were type 2 and 34 were type 3 patients. The global longitudinal strain (GLS) of the SMA group (−18.7 ± 2.9%, p &lt; 0.001) was lower than that of the control group; the time to peak longitudinal strain (TTPLS) of the SMA group (22.9 ± 13.6 ms, p &lt; 0.001) was higher than that of the control group, while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), measured by the Teichholz method of M-mode echocardiography, showed no significant differences between the two groups. In addition, independent indicators for cardiovascular risk, including total cholesterol (TC)/HDL, low-density lipoprotein (LDL)/HDL, and Apo B/Apo A1 levels, were higher in SMA children than in the control group.ConclusionCompared with healthy controls, later-onset SMA children presented with reduced GLS and prolonged TTPLS while the LVEF and LVFS values were within normal range. In particular, whether a reduced GLS or prolonged TTPLS in later-onset SMA compared to the control group can predict the risk of future cardiomyopathy remains to be investigated.
Threshold effect of plasma total homocysteine levels on cognitive function among hypertensive patients in China: A cross-sectional study
Authors: Wang Li , Chen Jianduan , Li Junpei , Hu Feng , Xie Yanyou , Zhou Xinlei , Shen Si , Zhou Wei , Zhu Lingjuan , Wang Tao , Tu Jianglong , Bao Huihui , Cheng Xiaoshu 
Published: August 2022

BackgroundIncreased plasma total homocysteine (tHcy) is an influencing factor of cognitive impairment in the general population. However, studies on the relationship between the risk of cognitive impairment and plasma tHcy levels in patients with hypertension are limited. This study aimed to explore the association between plasma tHcy levels and cognitive function assessed by MMSE scores among hypertensive patients in China.MethodsA total of 9,527 subjects from the Chinese Hypertension Registry Study participated in this study. Plasma tHcy levels were quantified by high-performance liquid chromatography using a fluorescence detector. Cognitive assessment was performed using the Mini-Mental State Examination (MMSE). Linear regression models, two piecewise linear regression models, and smoothing curve fitting were applied to determine the relationship between plasma tHcy levels and cognitive function.ResultsThis analysis included 9,527 Chinese hypertensive adults. Based on the results of linear regression models, a negative relationship was identified between plasma tHcy levels and MMSE scores [beta coefficient (β) per standard deviation (SD) increase: −0.26, 95% confidence interval (CI) −0.35, −0.16, P &lt; 0.001]. The fully adjusted smooth curve fitting presented a nonlinear between plasma tHcy levels and MMSE scores. The threshold effect analysis showed that the inflection point of tHcy was about 27.1 μmol/L. The effect size [β (95% CI)] per SD increase in plasma tHcy concentrations on MMSE scores was −0.93 (−1.24, −0.6) on the left side and −0.07 (−0.24, 0.10) on the right side of the inflection point (P-value for log-likelihood ratio (LLR) test was &lt;0.001). Moreover, subgroup analyses revealed that sex could influence the negative association between plasma tHcy levels and MMSE scores up to a specific threshold (P-value for interaction &lt;0.001). Linear regression models indicated that there was an enhanced inverse association between tHcy levels and MMSE scores in female patients with tHcy concentrations less than 26.9 μmol/L compared to male patients with tHcy concentrations less than 32.0 μmol/L.ConclusionsPlasma tHcy levels had a threshold effect on MMSE scores among hypertensive patients in China. Increased plasma tHcy levels were independently inversely associated with cognitive decline among hypertensive patients with tHcy concentrations &lt;27.1 μmol/L.
Quantitative susceptibility mapping of basal ganglia iron is associated with cognitive and motor functions that distinguish spinocerebellar ataxia type 6 and type 3
Authors: Marvel Cherie L. , Chen Lin , Joyce Michelle R. , Morgan Owen P. , Iannuzzelli Katherine G. , LaConte Stephen M. , Lisinski Jonathan M. , Rosenthal Liana S. , Li Xu 
Published: August 2022

BackgroundIn spinocerebellar ataxia type 3 (SCA3), volume loss has been reported in the basal ganglia, an iron-rich brain region, but iron content has not been examined. Recent studies have reported that patients with SCA6 have markedly decreased iron content in the cerebellar dentate, coupled with severe volume loss. Changing brain iron levels can disrupt cognitive and motor functions, yet this has not been examined in the SCAs, a disease in which iron-rich regions are affected.MethodsIn the present study, we used quantitative susceptibility mapping (QSM) to measure tissue magnetic susceptibility (indicating iron concentration), structural volume, and normalized susceptibility mass (indicating iron content) in the cerebellar dentate and basal ganglia in people with SCA3 (n = 10) and SCA6 (n = 6) and healthy controls (n = 9). Data were acquired using a 7T Philips MRI scanner. Supplemental measures assessed motor, cognitive, and mood domains.ResultsPutamen volume was lower in both SCA groups relative to controls, replicating prior findings. Dentate susceptibility mass and volume in SCA6 was lower than in SCA3 or controls, also replicating prior findings. The novel finding was that higher basal ganglia susceptibility mass in SCA6 correlated with lower cognitive performance and greater motor impairment, an association that was not observed in SCA3. Cerebellar dentate susceptibility mass, however, had the opposite relationship with cognition and motor function in SCA6, suggesting that, as dentate iron is depleted, it relocated to the basal ganglia, which contributed to cognitive and motor decline. By contrast, basal ganglia volume loss, rather than iron content, appeared to drive changes in motor function in SCA3.ConclusionThe associations of higher basal ganglia iron with lower motor and cognitive function in SCA6 but not in SCA3 suggest the potential for using brain iron deposition profiles beyond the cerebellar dentate to assess disease states within the cerebellar ataxias. Moreover, the role of the basal ganglia deserves greater attention as a contributor to pathologic and phenotypic changes associated with SCA.
Automatic quantification of retinal photoreceptor integrity to predict persistent disease activity in neovascular age-related macular degeneration using deep learning
Authors: Song Xian , Xu Qian , Li Haiming , Fan Qian , Zheng Yefeng , Zhang Qiang , Chu Chunyan , Zhang Zhicheng , Yuan Chenglang , Ning Munan , Bian Cheng , Ma Kai , Qu Yi 
Published: August 2022

PurposeUsing deep learning (DL)-based technique, we identify risk factors and create a prediction model for refractory neovascular age-related macular degeneration (nAMD) characterized by persistent disease activity (PDA) in spectral domain optical coherence tomography (SD-OCT) images.Materials and methodsA total of 671 typical B-scans were collected from 186 eyes of 186 patients with nAMD. Spectral domain optical coherence tomography images were analyzed using a classification convolutional neural network (CNN) and a fully convolutional network (FCN) algorithm to extract six features involved in nAMD, including ellipsoid zone (EZ), external limiting membrane (ELM), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelium detachment (PED), and subretinal hyperreflective material (SHRM). Random forest models were probed to predict 1-year disease activity (stable, PDA, and cured) based on the quantitative features computed from automated segmentation and evaluated with cross-validation.ResultsThe algorithm to segment six SD-OCT features achieved the mean accuracy of 0.930 (95% CI: 0.916–0.943), dice coefficients of 0.873 (95% CI: 0.847–0.899), a sensitivity of 0.873 (95% CI: 0.844–0.910), and a specificity of 0.922 (95% CI: 0.905–0.940). The six-metric model including EZ and ELM achieved the optimal performance to predict 1-year disease activity, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.980, the accuracy of 0.930, the sensitivity of 0.920, and the specificity of 0.962. The integrity of EZ and ELM significantly improved the performance of the six-metric model than that of the four-metric model.ConclusionThe prediction model reveals the potential to predict PDA in nAMD eyes. The integrity of EZ and ELM constituted the strongest predictive factor for PDA in nAMD eyes in real-world clinical practice. The results of this study are a significant step toward image-guided prediction of long-term disease activity in the management of nAMD and highlight the importance of the automatic identification of photoreceptor layers.
COVID-19 in cancer patients with diabetes in Pakistan: Clinical features and management
Authors: Asghar Kashif , Abu Bakar Muhammad , Ashfaq Sara , Alvi Asim Munir , Shafiq Waqas , Azmat Umal , Siddiqi Ahmed Imran , Farooq Asim , Raza Rabail , Siddique Kashif 
Published: August 2022

BackgroundDiabetes and cancer are the leading causes of mortality all over the world. Infectious diseases are more common and/or life-threatening in patients with diabetes. Cancer patients with diabetes are individuals that are more susceptible to the current COVID-19 pandemic. We investigated the clinical features of survivor and non-survivor COVID-19-infected cancer patients with diabetes.Patients and MethodsWe did a retrospective study of 43 diabetic cancer patients with PCR-confirmed COVID-19 infection from Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan between March 03, 2020, and May 18, 2021. These patients either were discharged from the hospital or had died by Jun 16, 2021. Clinicopathological and radiological features were compared between survivors and non-survivors by fisher’s exact test and chi-square test.ResultsForty-three diabetic cancer patients with SARS-CoV-2 infection were enrolled and the majority were males 26 (60.5%). The overall mean age was 61.67 ± 11.80. 39 (90.7%) had solid tumors and 3 (7.0%) had hematological malignancies. Fever (74.4%) and dyspnea (58.1%) were the most common symptoms. Complications were reported in 36 (83.7%) patients; during the course of the disease. Additionally, all the deceased patients (n=15) had acquired the complications. 11 (25.6%) patients were admitted to an intensive care unit (ICU). Furthermore, 29 (67.4%) out of 43 patients showed abnormal features in the radiological findings. We found significantly elevated levels of C-reactive protein (P=0.005), serum lactate (P=0.01), albumin (P=0.02), alkaline phosphate (P=0.03), and neutrophil count (P=0.04) in the non-survivors as compared to the survivors.ConclusionCancer patients with diabetes are a vulnerable population in the current pandemic. Identifying how diabetes in cancer patients affects the severity of SARS-CoV-2 infection is crucial for the clinical management of these patients. Rigorous scrutiny of clinicopathological features of COVID-19 infected cancer patients with diabetes especially values of C-reactive protein, lactate, albumin, alkaline phosphate, neutrophils, and regular monitoring of blood glucose levels may play a critical role in the outcome of the disease.
Establishing a novel model of malignant airway stenosis in rabbit
Authors: Lin Xiaoxiao , Zhou Liqin , Zhou Wanting , Li Yuping , Jin Xuru , Ye Min , Chen Chengshui 
Published: August 2022

BackgroundMalignant central airway stenosis is a life-threatening condition. However, treatment of malignant airway stenosis remains challenging. There is currently a severe lack of an excellent animal model of malignant airway stenosis to facilitate treatment approaches. This is the first study to establish a rabbit model of malignant airway stenosis for bronchoscopic interventional studies.Materials and methodsNew Zealand White rabbits were used in this study, randomly divided into group A (18 rabbits) and group B (6 rabbits). A VX2 fragment suspension was injected into the submucosal layer of rabbits’ airway by bronchoscopy. Bronchoscopic examinations were performed once a week after VX2 tumor implantation to observe tumor growth and the degree of airway stenosis. Randomly, three rabbits were generally dissected after a weekly bronchoscopic examination in group A. The rabbits that reached grade III airway stenosis underwent stent implantation in group B.ResultsA total of 24 rabbits were successfully implanted with the VX2 fragment suspension in the airway without significant adverse events, and the success rate of the tumor growth was 100%. The degree of airway stenosis reaching grade III took 2 to 3 weeks after implantation of the VX2 tumor. The median survival time of rabbit models without stent implantation and rabbits with stent implantation was 32.5 and 32.0 days, respectively.ConclusionsThe implanting method is safe and effective for the establishment of a rabbit model of malignant airway stenosis. When the tumor grows to 2 to 3 weeks, the rabbit model is available for stent implantation. We recommend the models for more preclinical animal studies on bronchoscopic interventional treatments.
Genotypes and clinical intervention of patients with neurofibromatosis type 1 associated dystrophic scoliosis
Authors: Li Haichong , Zhang Wenyan , Yao Ziming , Guo Ruolan , Hao Chanjuan , Zhang Xuejun 
Published: August 2022

ObjectiveTo analyze the genotypic characteristics of patients with neurofibromatosis type 1 (NF1) associated dystrophic scoliosis and to summarize the outcomes of the surgical treatment of these patients.MethodsExome sequencing (ES) combined with multiplex ligation-dependent probe amplification (MLPA) was used for genotypic identification. All patients underwent surgical treatments for spinal deformities, and the outcomes of the surgery was summarized by analyzing the clinical and imaging parameters before and after the surgery.ResultsFourteen patients (six males and eight females) were clinically diagnosed as NF1 associated dystrophic scoliosis with common symptoms including café-au-lait spots, paravertebral tumors, and dystrophic scoliosis. NF1 mutations were detected in 12 (85.7%) patients, including four nonsense mutations, three splicing mutations, three frameshift mutations, and two exon deletions. The first surgical procedure included growing-rod surgery in 10 patients and posterior spinal fusion in four patients. The follow-up duration was 2.3 years (1.0–10.3 years), and the Cobb angle of the main curve improved from 61.5° (30°-125°) pre-operatively to 14.5° (0°-42°) at the last follow-up, with an average correction rate of 74.0% (44–100%). Instrumentation-related complications occurred in four patients during the follow-up period.ConclusionsIn patients with dystrophic scoliosis who met the clinical diagnostic criteria for NF1, the mutation detection rate of ES combined with MLPA was 85.7%. There was no mutation hotspot in NF1 gene, molecular diagnosis could offer information about genetic counseling, prenatal diagnosis and eugenics. Surgical treatment according to patient's age and severity could effectively correct the spinal deformities.
Evaluation of whole-genome sequence to predict drug resistance of nine anti-tuberculosis drugs and characterize resistance genes in clinical rifampicin-resistant Mycobacterium tuberculosis isolates from Ningbo, China
Authors: Che Yang , Lin Yi , Yang Tianchi , Chen Tong , Sang Guoxin , Chen Qin , He Tianfeng 
Published: August 2022

SettingControlling drug-resistant tuberculosis in Ningbo, China.ObjectiveWhole-genome sequencing (WGS) has not been employed to comprehensively study Mycobacterium tuberculosis isolates, especially rifampicin-resistant tuberculosis, in Ningbo, China. Here, we aim to characterize genes involved in drug resistance in RR-TB and create a prognostic tool for successfully predicting drug resistance in patients with TB.DesignDrug resistance was predicted by WGS in a “TB-Profiler” web service after phenotypic drug susceptibility tests (DSTs) against nine anti-TB drugs among 59 clinical isolates. A comparison of consistency, sensitivity, specificity, and positive and negative predictive values between WGS and DST were carried out for each drug.ResultsThe sensitivities and specificities for WGS were 95.92 and 90% for isoniazid (INH), 100 and 64.1% for ethambutol (EMB), 97.37 and 100% for streptomycin (SM), 75 and 100% for amikacin (AM), 80 and 96.3%for capreomycin (CAP), 100 and 97.22% for levofloxacin (LFX), 93.33 and 90.91% for prothionamide (PTO), and 70 and 97.96% for para-aminosalicylic acid (PAS). Around 53 (89.83%) and 6 (10.17%) of the isolates belonged to lineage two (East-Asian) and lineage four (Euro-American), respectively.ConclusionWhole-genome sequencing is a reliable method for predicting resistance to INH, RIF, EMB, SM, AM, CAP, LFX, PTO, and PAS with high consistency, sensitivity, and specificity. There was no transmission that occurred among the patients with RR-TB in Ningbo, China.