bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-Line Treatments for Extensive-Stage Small-Cell Lung Cancer With Immune Checkpoint Inhibitors Plus Chemotherapy: A Network Meta-Analysis and Cost-Effectiveness Analysis
Authors: Kang Shuo , Wang Xinchen , Zhang Yue , Zhang Boyuan , Shang Fangjian , Guo Wei 
Published: January 2022

BackgroundImmune checkpoint inhibitors (ICIs) plus chemotherapy were unlikely to be considered cost-effective compared with chemotherapy as the first-line treatment of patients with extensive-stage small-cell lung cancer (ES-SCLC) in China due to its high costs. However, the cost-effectiveness of the comparison between the regimens of ICIs plus chemotherapy were remained unclear yet. The aim of this study was to evaluate the efficacy and cost-effectiveness of ICIs plus chemotherapy as the first-line treatment for ES-SCLC from the perspective of the Chinese healthcare system.MethodsA network meta-analysis (NMA) was conducted to indirect compare the clinical benefits between the ICIs plus chemotherapy regimens. A decision-analytic model was established to evaluate the cost-effectiveness from the Chinese healthcare system, the clinical efficacy and safety data were obtained from the clinical trials and the results of NMA. Cost and utility values were gathered from the local charges and previously studies. Key outputs of the NMA were overall survival (OS) and progression-free survival (PFS). Incremental cost-effectiveness ratios (ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed to explore the robustness of the model outcomes.ResultsFive clinical trials (IMpower133, CASPIAN, KEYNOTE-604, CA184-156, and EA5161) of 1,255 patients received first-line ICIs plus chemotherapy strategies were analyzed in the NMA. NMA showed that nivolumab plus chemotherapy was ranked higher than other strategies. The cost-effectiveness analysis showed that atezolizumab plus chemotherapy achieved relatively higher health benefits and lower costs. One-way sensitivity analyses revealed that the cost of ICIs had the substantial impact on model outcomes. The probabilistic sensitivity analyses suggested that the probability of atezolizumab plus chemotherapy could be considered cost-effective was more than 50% at the willingness-to-pay (WTP) threshold of $31,313/QALY in China. In scenario analyses, when the price of nivolumab reduced 80%, the probability of nivolumab plus chemotherapy being cost-effective was more than 50%.ConclusionsThe NMA and cost-effectiveness revealed that atezolizumab plus chemotherapy is the most favorable first-line treatment for previously untreated ES-SCLC patients compared other ICIs plus chemotherapy regimens in China. The price reduction of nivolumab would make nivolumab plus chemotherapy be the most cost-effective option in future possible context.
Prognostic Value and Correlation With Tumor Immune Infiltration of a Novel Metabolism-Related Gene Signature in Pancreatic Cancer
Authors: Chen Hui , Zu Fuqiang , Zeng Taofei , Chen Ziang , Wei Jinhong , Liu Peng , Li Zeyu , Zhou Lei , Wang Huaitao , Tan Hao , Tan Xiaodong 
Published: January 2022

BackgroundEnergy metabolism has been considered as one of the novel features of neoplasms. This study aimed to establish the prognostic signature for pancreatic cancer (PC) based on metabolism-related genes (MRGs).MethodsWe obtained MRGs from the Molecular Signatures Database (MSigDB) and gene sequence data in the Cancer Genome Atlas (TCGA) databases. Then, differentially expressed MRGs (DE-MRGs) were identified utilizing the R software. We built the prognostic model via multivariate Cox regression. Moreover, external validation of the prognostic signature was also performed. Nomogram was created to predict the overall survival (OS). Next, this study analyzed the prognostic value, clinical relationship, and metabolism-related signaling pathways of the prognostic signature. The role in tumor infiltration was further evaluated. Eventually, the expression level of the three MRGs along with the function of NT5E was validated.ResultsTwenty-two MRGs were chosen, eight of which were identified to be most significantly correlated with the prognosis of PC. Meanwhile, a 3-MRG prognostic signature was established, and we verified this prognostic model in two separate external cohorts. What is more, the nomogram was used to predict 1-/2-/3-year OS of PC patients. In addition, the immune cell infiltration and expression of immune checkpoint were significantly influenced by the risk score. Finally, three MRGs were highly expressed in PC cell lines, and NT5E was associated with the proliferation and migration ability of PC.ConclusionTo sum up, the study established and validated a 3-MRG prognostic signature for PC, and the signature could be utilized to predict the prognosis and assist the individualized clinical management of patients with PC.
Sohlh2 Inhibits the Malignant Progression of Renal Cell Carcinoma by Upregulating Klotho via DNMT3a
Authors: Liu Yang , Cui Weiwei , Zhang Ruihong , Zhi Sujuan , Liu Lanlan , Liu Xuyue , Feng Xiaoning , Chen Yanru , Zhang Xiaoli , Hao Jing 
Published: January 2022

BackgroundRenal cell carcinoma is the most common malignant tumor of the kidney. The 5-year survival of renal cell carcinoma with distant metastasis is very low. Sohlh2 is a newly discovered tumor suppressor gene playing inhibitory roles in a variety of tumors, but its role in renal cell carcinoma has not been reported.MethodsTo clarify the role of Sohlh2 in the occurrence and development of renal cell carcinoma, we constructed stably transfected human renal cell carcinoma cell lines with Sohlh2 overexpression and Sohlh2 knockdown, separately. First, we studied the effects of Sohlh2 on proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of renal cell carcinoma cells in vitro and in vivo. Then, we detected whether Sohlh2 functions through DNMT3a/Klotho using Western blotting, qPCR, and Cell Counting Kit-8 (CCK-8) assay. Finally, we collected 40 resected renal cell carcinoma samples to study the relevance between Sohlh2, DNMT3a, and Klotho by immunohistochemistry.ResultsOur results showed that Sohlh2 was downregulated in renal cell carcinoma, and its expression level was negatively correlated with tumor staging. Both in vitro and in vivo experiments confirmed that Sohlh2 overexpression inhibited the proliferation, migration, invasion, metastasis, and EMT of renal cell carcinoma. Sohlh2 functions through demethylation of Klotho by downregulating the expression of DNA methyltransferase of DNMT3a. In renal cell carcinoma, Sohlh2 was positively correlated with Klotho and negatively correlated with DNMT3a.ConclusionSohlh2 functions as a tumor suppressor gene in renal cell carcinoma by demethylation of Klotho via DNMT3a. Sohlh2 correlated with Klotho positively and with DNMT3a negatively in renal cell carcinoma. Our study suggests that Sohlh2 and DNMT3a/Klotho can be used as potential targets for the clinical treatment of renal cell carcinoma.
A Model for Identifying Optimal Patients for Primary Tumor Resection in Patients With Metastatic Bladder Cancer
Authors: Hu Jintao , Zheng Zhenming , Zheng Junjiong , Xie Weibin , Su Huabin , Yang Jingtian , Xu Zixin , Shen Zefeng , Yu Hao , Fan Xinxiang , Kong Jianqiu , Han Jinli 
Published: January 2022

BackgroundA survival benefit was observed in metastatic bladder cancer patients who underwent primary tumor resection, but it was still confusing which patients are suitable for the surgery. For this purpose, we developed a model to screen stage M1 patients who would benefit from primary tumor resection.MethodsPatients with metastatic bladder cancer were screened from the Surveillance, Epidemiology, and End Results database (2004–2016) and then were divided into surgery (partial or complete cystectomy) group and non-surgery group. To balance the characteristics between them, a 1:1 propensity score matching analysis was applied. A hypothesis was proposed that the received primary tumor resection group has a more optimistic prognosis than the other group. The multivariable Cox model was used to explore the independent factors of survival time in two groups (beneficial and non-beneficial groups). Logistic regression was used to build a nomogram based on the significant predictive factors. Finally, a variety of methods are used to evaluate our model.ResultsA total of 7,965 patients with metastatic bladder cancer were included. And 3,314 patients met filtering standards, of which 545 (16.4%) received partial or complete cystectomy. Plots of the Kaplan–Meier and subgroup analyses confirmed our hypothesis. After propensity score matching analysis, a survival benefit was still observed that the surgery group has a longer median overall survival time (11.0 vs. 6.0 months, p &lt; 0.001). Among the surgery cohort, 303 (65.8%) patients lived longer than 6 months (beneficial group). Differentiated characteristics included age, gender, TNM stage, histologic type, differentiation grade, and therapy, which were integrated as predictors to build a nomogram. The nomogram showed good discrimination in both training and validation cohorts (area under the receiver operating characteristic curve (AUC): 0.806 and 0.742, respectively), and the calibration curves demonstrated good consistency. Decision curve analysis showed that the nomogram was clinically useful. Compared with TNM staging, our model shows a better predictive value in identifying optimal patients for primary tumor resection.ConclusionsA practical predictive model was created and verified, which might be used to identify the optimal candidates for the partial or complete cystectomy group of the primary tumor among metastatic bladder cancer.
DDIT: An Online Predictor for Multiple Clinical Phenotypic Drug-Disease Associations
Authors: Lu Lu , Qin Jiale , Chen Jiandong , Wu Hao , Zhao Qiang , Miyano Satoru , Zhang Yaozhong , Yu Hua , Li Chen 
Published: January 2022

Background: Drug repurposing provides an effective method for high-speed, low-risk drug development. Clinical phenotype-based screening exceeded target-based approaches in discovering first-in-class small-molecule drugs. However, most of these approaches predict only binary phenotypic associations between drugs and diseases; the types of drug and diseases have not been well exploited. Principally, the clinical phenotypes of a known drug can be divided into indications (Is), side effects (SEs), and contraindications (CIs). Incorporating these different clinical phenotypes of drug–disease associations (DDAs) can improve the prediction accuracy of the DDAs.Methods: We develop Drug Disease Interaction Type (DDIT), a user-friendly online predictor that supports drug repositioning by submitting known Is, SEs, and CIs for a target drug of interest. The dataset for Is, SEs, and CIs was extracted from PREDICT, SIDER, and MED-RT, respectively. To unify the names of the drugs and diseases, we mapped their names to the Unified Medical Language System (UMLS) ontology using Rest API. We then integrated multiple clinical phenotypes into a conditional restricted Boltzmann machine (RBM) enabling the identification of different phenotypes of drug–disease associations, including the prediction of as yet unknown DDAs in the input.Results: By 10-fold cross-validation, we demonstrate that DDIT can effectively capture the latent features of the drug–disease association network and represents over 0.217 and over 0.072 improvement in AUC and AUPR, respectively, for predicting the clinical phenotypes of DDAs compared with the classic K-nearest neighbors method (KNN, including drug-based KNN and disease-based KNN), Random Forest, and XGBoost. By conducting leave-one-drug-class-out cross-validation, the AUC and AUPR of DDIT demonstrated an improvement of 0.135 in AUC and 0.075 in AUPR compared to any of the other four methods. Within the top 10 predicted indications, side effects, and contraindications, 7/10, 9/10, and 9/10 hit known drug–disease associations. Overall, DDIT is a useful tool for predicting multiple clinical phenotypic types of drug–disease associations.
Integrating Network Analysis and Metabolomics to Reveal Mechanism of Huaganjian Decoction in Treatment of Cholestatic Hepatic Injury
Authors: Dong Qin , Chen Jiao , Jiang Yan-Ping , Zhu Zong-Ping , Zheng Yong-Feng , Zhang Jin-Ming , Zhang Zhen , Chen Wen-Qing , Sun Shi-Yi , Pang Lan , Yan Xin , Liao Wan , Fu Chao-Mei 
Published: January 2022

Huaganjian decoction (HGJD) was first recorded in the classic “Jing Yue Quan Shu” during the Ming dynasty, and it has been extensively applied in clinical practice to treat liver diseases for over 300 years in China. However, its bioactive constituents and relevant pharmacological mechanism are still unclear. In this study, a strategy integrating network analysis and metabolomics was applied to reveal mechanism of HGJD in treating cholestatic hepatic injury (CHI). Firstly, we observed the therapeutic effect of HGJD against CHI with an alpha-naphthylisothiocyanate (ANIT) induced CHI rat model. Then, we utilized UPLC-Q-Exactive MS/MS method to analyze the serum migrant compounds of HGJD in CHI rats. Based on these compounds, network analysis was conducted to screen for potential active components, and key signaling pathways interrelated to therapeutic effect of HGJD. Meanwhile, serum metabolomics was utilized to investigate the underlying metabolic mechanism of HGJD against CHI. Finally, the predicted key pathway was verified by western blot and biochemical analysis using rat liver tissue from in vivo efficacy experiment. Our results showed that HGJD significantly alleviated ANIT induced CHI. Totally, 31 compounds originated from HGJD have been identified in the serum sample. PI3K/Akt/Nrf2 signaling pathway related to GSH synthesis was demonstrated as one of the major pathways interrelated to therapeutic effect of HGJD against CHI. This research supplied a helpful strategy to determine the potential bioactive compounds and mechanism of traditional Chinese medicine.
Retroperitoneal Robot-Assisted Laparoscopic Partial Nephrectomy for Horseshoe Kidney: A Case Report
Authors: Zhang Dongxu , Lu Youyi , Sun Fengze , Yao Huibao , Wu Jitao , Wang Jipeng 
Published: January 2022

BackgroundHorseshoe kidney (HSK) has always been a challenge for urologists depending on its particular anatomy. We report a case of renal tumor in a patient with HSK, who underwent tumor resection by retroperitoneal robot-assisted laparoscopic partial nephrectomy.Case PresentationA 47-year-old man with HSK presented to our hospital with a solid renal mass. Computed tomography urography (CTU) showed a 4.3 × 4.4-cm mass in the upper pole of the right kidney. The patient received retroperitoneal robot-assisted laparoscopic partial nephrectomy on the basis of CT three-dimensional (3D) reconstructions.ConclusionThe present case report highlights the feasibility of retroperitoneal robot-assisted laparoscopic partial nephrectomy for horseshoe kidney and the advantages of preoperative CT scan with three-dimensional reconstructions.
Superoxide Dismutases in Eukaryotic Microorganisms: Four Case Studies
Authors: de Obeso Fernandez del Valle Alvaro , Scheckhuber Christian Quintus 
Published: January 2022

Various components in the cell are responsible for maintaining physiological levels of reactive oxygen species (ROS). Several different enzymes exist that can convert or degrade ROS; among them are the superoxide dismutases (SODs). If left unchecked, ROS can cause damage that leads to pathology, can contribute to aging, and may, ultimately, cause death. SODs are responsible for converting superoxide anions to hydrogen peroxide by dismutation. Here we review the role of different SODs on the development and pathogenicity of various eukaryotic microorganisms relevant to human health. These include the fungal aging model, Podospora anserina; various members of the genus Aspergillus that can potentially cause aspergillosis; the agents of diseases such as Chagas and sleeping disease, Trypanosoma cruzi and Trypanosoma brucei, respectively; and, finally, pathogenic amoebae, such as Acanthamoeba spp. In these organisms, SODs fulfill essential and often regulatory functions that come into play during processes such as the development, host infection, propagation, and control of gene expression. We explore the contribution of SODs and their related factors in these microorganisms, which have an established role in health and disease.
Soft Ionic Pressure Sensor with Aloe Vera Gel for Low-Pressure Applications
Authors: Sujeesh Vishnu , Ponraj Godwin , Ren Hongliang 
Published: January 2022

Ionic pressure sensors are made of ionic compounds suspended in a suitable solvent mixture. When external pressure is exerted on them, it is reflected as a change in electrical parameters due to physical deformation and a redistribution of ions within the sensing medium. Variations in the composition and material of the sensing medium result in different pressure sensors with varying operating ranges and sensitivity. This work presents the design and fabrication procedure of a novel soft-pressure sensor for a very low-pressure range (<20 mm Hg) using Aloe vera gel and Glycerin as the solvent for the ionic sensing medium. We also provide a comparative study on the performance of sensor prototypes with varying solvent concentrations and geometric parameters based on a series of characterization experiments. Maximum sensitivity (7.498×10−4 Ω/mmHg) was observed when using 40% glycerin in the sensing medium, filled in a toroidal geometry with outer and inner channel diameters of 8 mm and 7 mm, respectively. The proposed sensor is entirely soft and can be designed to conform to any desired geometry.
Concomitant Identification of Muddy Brown Granular Casts and Low Fractional Excretion of Urinary Sodium in AKI
Authors: Varghese Vipin , Rivera Maria S. , Alalwan Ali , Alghamdi Ayman M. , Ramanand Akanksh , Khan Sumayyah M. , Najul-Seda Jose E. , Velez Juan Carlos Q. 
Published: January 2022

Background
Fractional excretion of urinary sodium (FENa) is a widely utilized clinical test to evaluate acute kidney injury (AKI). A low FENa (<1%) is deemed consistent with prerenal azotemia and inconsistent with acute tubular injury (ATI). Muddy brown granular casts (MBGC) on microscopic examination of urinary sediment (MicrExUrSed) are highly suggestive of ATI. We hypothesized that there is poor concordance between the presence of MBGC and FENa in ATI.

Methods
We conducted a prospective observational study in patients with AKI seen during inpatient consultation. We extracted patients who underwent assessment of percentage of low power fields (LPFs) with MBGC by MicrExUrSed and concomitant measurement of FENa. Diagnostic concordance between MBGC and FENa and their individual prognostic value were examined.

Results
Our cohort included 270 patients, 111 (41%) of whom were women. Median age was 61 years (range 27–92 years), and median serum creatinine was 3.7 mg/dl ( range1.2–22.0 mg/dl). MBGC were found in 49% (133/270). FENa <1% (inconsistent with ATI) was found in 50/133 (38%), 38/115 (33%), and 16/45 (36%) of those with >0%, ≥10%, and ≥50% LPFs with MBGC, respectively. Concordance between FENa and MBGC for ATI diagnosis was deemed fair (estimated κ-coefficient=0.2), and poor (κ=–0.11) within a subgroup of patients with preexisting chronic kidney disease (n=139). In patients with biopsy-proven ATI (n=49), MBGC had 100% specificity and 100% positive predictive value for ATI. MBGC were associated with greater risk for ≥50% increase in creatinine from baseline at discharge (acute kidney disease [AKD]).

Conclusions
About two of five patients with MBGC identified by MicrExUrSed presented with FENa <1%. Presence of MBGC was consistent with ATI, as verified by biopsy, and were predictive of AKD. These data suggest that the sole reliance in low FENa to exclude ATI should be abandoned, and MicrExUrSed should be pursued for AKI diagnosis.
Praksis Pengharapan di Masa Sulit
Authors: RIYANTO FX. EKO ARMADA 
Published: January 2022

In this article, the author sheds light on the theme of “hope” in three sections, namely: the praxis of hope, hope in Emmanuel Levinas’ philosophy, and hope in the theology of Johann Baptist Metz. Despite its crucial role in human existence, hope is rarely discussed in philosophy. Difficult life events, such as this covid-19 pandemic, challenge us reflect more deeply on hope. The author emphasizes that hope should be treated as “a faithful friend”, not merely as an abstract concept. With hope along the journey, we are empowered to survive in the midst of suffering, to face the waves of anxiety, and to transcend our frailty. By taking inspiration from Levinas’ philosophy and Metz’s theology, the author underlines that genuine hope encourages people to open themselves to God and the other(s).
An Analysis on The Creation of Condusive Working Envi-ronment Conditions at Bob PT Bumi Siak Pusako-Pertamina Hulu
Authors: Wahyuni Siska Sri 
Published: January 2022

This research aimed to know the corporation policies, physical and non-physical work environment factors, obstacles and solutions which was faced and carried out made in the creation of a conducive working environment at BOB PT Bumi Siak Pusako-Pertamina Hulu. This research was held at the BOB PT Bumi Siak Pusako-Pertamina Hulu, Zamrud on September 2019. The results of this research indicate that in creating a conducive working environment the corporation makes policies such as the corporation's policy on occupational safety and health, make policies for employees enters at 07.00 until 05.00 pm and enters 10 on/off days, provide counselling related to work environment issues, adherence to the Corporation Regulations, and adherence to the work standards that had been outlined in the SOP. Cleanliness, room area and lighting, room temperature, health facilities, sports, worship facilities, and libraries were included in discussions of physical work environment factors, moreover, about non-physical environment factors such as relationship of superiors with subordinates and relationships between employees. There are obstacles like job exchanges that must be explained in detail, workers from outside the area so they do not have to travel from home to work, government regulations that alter profit every day. To resolve the issue, we arranged to meet more frequently, tried to rest at the guesthouse, and complied with government regulations.
Improvement in laser-based micro-processing of carbon nanotube film devices
Authors: Suzuki Daichi , Serien Daniela , Obata Kotaro , Sugioka Koji , Narazaki Aiko , Terasaki Nao 
Published: January 2022

Abstract
Carbon nanotubes (CNTs) are considered remarkable low-dimensional materials that can overcome the problems associated with bulk semiconductors. The development of CNT processing technology complementing conventional processing technology is required to advance research on CNT devices. We assessed the potential and application of laser-based micro-processing for patterning micrometre-thick CNT films. We discovered that the laser ablation method can pattern micrometre-thick CNT films in micrometre spatial resolution and can directly pattern the CNT films inside the protective film—features not achievable by competing processing technologies. Thus, the laser ablation method is uniquely advantageous and applicable in manufacturing functional CNT devices.