bluuebunny/crossref_metadata_2025 huggingface dataset:
A Complement-Related Gene Signature for Predicting Overall Survival and Immunotherapy Efficacy in Sarcoma Patients
Authors: Zhang Lin , Lin Weihao , Zhou Yang , Shao Fei , Gao Yibo , He Jie
Published: April 2022

The prognoses of sarcomas are poor and the responses of them to systemic therapies are limited and controversial. Thus, there is an urgent need to stratify the risk factors and identify the patients who may benefit from systemic therapies. Here, we developed a reliable, complement-based gene signature to predict the prognosis of sarcoma patients. Survival-related complement genes were identified by univariate Cox analyses and were used to build a gene signature, which was further selected using the least absolute shrinkage and selection operator model, and determined using a stepwise Cox proportional hazards regression model. The whole sarcoma cohort of TCGA was randomly divided into a training set and a test set. The signature was constructed using the training set and validated subsequently in the test set, the whole TCGA sarcoma cohort, and another two independent cohorts from the TARGET and GEO databases, respectively. Furthermore, the prognostic value of the signature was also validated in an independent cohort from our center. This model effectively predicted prognoses across the training set, different validation cohorts, and different clinical subgroups. Next, immune cell infiltration analysis, GO and KEGG analysis, and gene set enrichment analysis were performed to explore possible underlying mechanisms of this signature. Moreover, this signature may predict the response to immunotherapy. Collectively, the current complement-related gene signature can predict overall survival and possible immunotherapy response of sarcoma patients; it may serve as a powerful prognostic tool to further optimize clinical treatment and prognosis management for sarcoma patients.
Tumor Microenvironment Profiling Identifies Prognostic Signatures and Suggests Immunotherapeutic Benefits in Neuroblastoma
Authors: Feng Chenzhao , Li Ting , Xiao Jun , Wang Jing , Meng Xinyao , Niu Huizhong , Jiang Bin , Huang Lei , Deng Xiaogeng , Yan Xueqiang , Wu Dianming , Fang Yifan , Lin Yu , Chen Feng , Wu Xiaojuan , Zhao Xiang , Feng Jiexiong
Published: April 2022

The tumor microenvironment (TME) influences disease initiation and progression. Cross-talks of cells within TME can affect the efficacy of immunotherapies. However, a precise, concise, and comprehensive TME landscape in neuroblastoma (NB) has not been established. Here, we profiled the TME landscape of 498 NB-related patients on a self-curated gene list and identified three prognostic TMEsubgroups. The differentially expressed genes in these three TMEsubgroups were used to construct a genetic signature of the TME landscape and characterize three GeneSubgroups. The subgroup with the worst overall survival prognosis, the TMEsubgroup/GeneSubgroup3, lacked immune cell infiltration and received the highest scores of MYCN- and ALK-related signatures and lowest scores of immune pathways. Additionally, we found that the GeneSubgroup3 might be benefited from anti-GD2 instead of anti-PD-1 therapy. We further created a 48-gene signature, the TMEscore, to infer prognosis and validated it in three independent NB cohorts and a pan-cancer cohort of 9,460 patients. We did RNA-seq on 16 samples and verified that TMEscore was higher in patients with stage 3/4 than stage 1/2 diseases. The TMEscore could also predict responses for several immunotherapies. After adding clinical features, we found that the nomogram-based score system, the TMEIndex, surpassed the current risk system at predicting survivals. Our analysis explained TME at the transcriptome level and paved the way for immunotherapies in NB.
Abrogating the Interaction Between p53 and Mortalin (Grp75/HSPA9/mtHsp70) for Cancer Therapy: The Story so far
Authors: Elwakeel Ahmed
Published: April 2022

p53 is a transcription factor that activates the expression of a set of genes that serve as a critical barrier to oncogenesis. Inactivation of p53 is the most common characteristic in sporadic human cancers. Mortalin is a differentially sub-cellularly localized member of the heat shock protein 70 family of chaperones that has essential mitochondrial and extra-mitochondrial functions. Elevated mortalin levels in multiple cancerous tissues and tumor-derived cell lines emphasized its key role in oncogenesis. One of mortalin’s major oncogenic roles is the inactivation of p53. Mortalin binds to p53 sequestering it in the cytoplasm. Hence, p53 cannot freely shuttle to the nucleus to perform its tumor suppressor functions as a transcription factor. This protein-protein interaction was reported to be cancer-specific, hence, a selective druggable target for a rationalistic cancer therapeutic strategy. In this review article, the chronological identification of mortalin-p53 interactions is summarized, the challenges and general strategies for targeting protein-protein interactions are briefly discussed, and information about compounds that have been reported to abrogate mortalin-p53 interaction is provided. Finally, the reasons why the disruption of this druggable interaction has not yet been applied clinically are discussed.
Chemical Reactivity and Optical and Pharmacokinetics Studies of 14 Multikinase Inhibitors and Their Docking Interactions Toward ACK1 for Precision Oncology
Authors: Srivastava Ruby
Published: April 2022

Activated Cdc42-associated kinase 1 (ACK1/TNK2) has a significant role in cell endocytosis, survival, proliferation, and migration. Mutations in ACK1 are closely associated with the occurrence and development of cancers. In this work, a conceptual density functional theory (CDFT)-based computational peptidology (CDFT-CP) method is used to study the chemical reactivity of 14 multikinase inhibitors. Optical properties of these inhibitors are studied by time-dependent density functional theory (TDDFT). Various biological and pharmacokinetic parameters are studied by Osiris, Molinspiration, and BOILED-Egg in SwissADME software tools. Physicochemical and biopharmaceutical (PCB), Salmonella typhimurium reverse mutation assay (AMES) mutagenicity, toxicity, and risk prediction are estimated by Simulations plus ADMET Predictor 10.2 software. MD simulations for an active model of ACK1 is carried out by the CABS-flex 2.0 web server, and potential binding pockets for ACK1 are searched using the PrankWeb server. SwissTargetPrediction is used to predict the potential targets for the multikinase inhibitors. Docking studies are carried out for ACK1–multikinase inhibitors using Autodock 4.2 software. Noncovalent interactions for ACK1–multikinase inhibitor complexes are studied using the Protein–Ligand Interaction Profiler (PLIP) server. Results indicated higher binding affinities and strong noncovalent interactions in ACK1–multikinase inhibitor complexes.
Clinical Implications of Plasma Galectin-3 in Heart Failure With Preserved Ejection Fraction: A Meta-Analysis
Authors: Shi Yujiao , Dong Guoju , Liu Jiangang , Shuang Xiong , Liu Chunqiu , Yang Chenguang , Qing Wang , Qiao Wenbo
Published: April 2022

Background

Heart failure with preserved ejection fraction (HFpEF) is an increasing public health concern. Currently, data regarding the clinical application value of plasma Galectin-3 (Gal-3) in HFpEF are contradictory. Therefore, we performed the following meta-analysis to appraise the clinical implications of serum Gal-3 in HFpEF, including its capacity to predict new-onset disease, long-term unfavorable endpoints, and the degree of cardiac structural abnormality and left ventricular diastolic dysfunction (LVDD).

Methods

PubMed, Embase, Scopus, and Web of Science were retrieved exhaustively from their inception until November 30, 2021, to obtain studies assessing the correlation between plasma Gal-3 and the clinical features of HFpEF (new-onset HFpEF, adverse outcomes, and echocardiographic parameters related to abnormal cardiac structure and LVDD).

Results

A total of 24 papers containing 27 studies were ultimately included in the present research. The results of the meta-analysis revealed that high plasma Gal-3 levels are strongly associated with the following clinical characteristics of HFpEF: (i) the increased risk of new-onset HFpEF (HR: 1.11; 95% CI: 1.04-1.19; p = 0.910, I2 = 0%; P = 0.002); (ii) the high risk of adverse outcomes of HFpEF patients [all-cause death (HR: 1.55; 95% CI: 1.27-1.87; p = 0.138, I2 = 42%; P = 0.000) and the composite events [all-cause death and HF hospitalization (HR: 1.50; 95% CI: 1.30-1.74; p = 0.001, I2 = 61%; P = 0.000) or cardiovascular (CV) death and HF hospitalization (HR: 1.71; 95% CI: 1.51-1.94; p = 0.036, I2 = 58%; P = 0.000)]; (iii) echocardiographic indices [E/e ratio (r: 0.425, 95% CI: 0.184-0.617; p = 0.000, I2 = 93%; P = 0.001) and DT (r: 0.502, 95% CI: 0.061-0.779; p = 0.001 I2 = 91%; P = 0.027)].

Conclusions

Plasma Gal-3 might be employed as an additional predictor for new-onset HFpEF, the adverse prognosis in HFpEF patients (all-cause death, the composite endpoints of all-cause death and HF hospitalization or CV death and HF hospitalization), and the severity of LVDD in HFpEF populations.
Comparison of Mortality Outcomes in Acute Myocardial Infarction Patients With or Without Standard Modifiable Cardiovascular Risk Factors
Authors: Sia Ching-Hui , Ko Junsuk , Zheng Huili , Ho Andrew Fu-Wah , Foo David , Foo Ling-Li , Lim Patrick Zhan-Yun , Liew Boon Wah , Chai Ping , Yeo Tiong-Cheng , Yip James W. L. , Chua Terrance , Chan Mark Yan-Yee , Tan Jack Wei Chieh , Figtree Gemma , Bulluck Heerajnarain , Hausenloy Derek J.
Published: April 2022

Background

Acute myocardial infarction (AMI) cases have decreased in part due to the advent of targeted therapies for standard modifiable cardiovascular disease risk factors (SMuRF). Recent studies have reported that ST-elevation myocardial infarction (STEMI) patients without SMuRF (termed “SMuRF-less”) may be increasing in prevalence and have worse outcomes than “SMuRF-positive” patients. As these studies have been limited to STEMI and comprised mainly Caucasian cohorts, we investigated the changes in the prevalence and mortality of both SMuRF-less STEMI and non-STEMI (NSTEMI) patients in a multiethnic Asian population.

Methods

We evaluated 23,922 STEMI and 62,631 NSTEMI patients from a national multiethnic registry. Short-term cardiovascular and all-cause mortalities in SMuRF-less patients were compared to SMuRF-positive patients.

Results

The proportions of SMuRF-less STEMI but not of NSTEMI have increased over the years. In hospitals, all-cause and cardiovascular mortality and 1-year cardiovascular mortality were significantly higher in SMuRF-less STEMI after adjustment for age, creatinine, and hemoglobin. However, this difference did not remain after adjusting for anterior infarction, cardiopulmonary resuscitation (CPR), and Killip class. There were no differences in mortality in SMuRF-less NSTEMI. In contrast to Chinese and Malay patients, SMuRF-less patients of South Asian descent had a two-fold higher risk of in-hospital all-cause mortality even after adjusting for features of increased disease severity.

Conclusion

SMuRF-less patients had an increased risk of mortality with STEMI, suggesting that there may be unidentified nonstandard risk factors predisposing SMuRF-less patients to a worse prognosis. This group of patients may benefit from more intensive secondary prevention strategies to improve clinical outcomes.
The Evolving Story of Multifactorial Chylomicronemia Syndrome
Authors: Paquette Martine , Bernard Sophie
Published: April 2022

Multifactorial chylomicronemia syndrome (MCS or type V hyperlipoproteinemia) is the most frequent cause of severe hypertriglyceridemia and is associated with an increased risk of acute pancreatitis, cardiovascular disease, and non-alcoholic steatohepatitis. The estimated prevalence of MCS in the North American population is 1:600–1:250 and is increasing due to the increasing prevalence of obesity, metabolic syndrome, and type 2 diabetes. Differentiating between familial chylomicronemia syndrome and MCS is crucial due to their very different treatments. In recent years, several cohort studies have helped to differentiate these two conditions, and recent evidence suggests that MCS itself is a heterogeneous condition. This mini-review will summarize recent literature on MCS, with a specific focus on the genetic determinants of the metabolic risk and the latest developments concerning the pharmacological and non-pharmacological treatment options for these patients. Possible research directions in this field will also be discussed.
Coordinated slag Disposal From Horizontal Boreholes During Hydraulic Cutting Based on Two-Phase Flow Theory
Authors: Zhang Yongjiang , Ji Fei , Zou Quanle
Published: April 2022

The purpose of the study is to explore the mechanism of coordinated slag disposal in the hydraulic cutting process, ensure the safety implementation of the hydraulic cutting operation and increase the success rate of hydraulic cutting. In the ultra-high pressure hydraulic cutting technique, the method for determining the cutting pressure is ambiguous, the coordination mechanism of various factors (including cutting pressure and coal-dropping speed) lingers unclarified; the slag disposal mechanism during hydraulic cutting is inexplicit. Aiming at these problems, a model for coordinated slag disposal during hydraulic cutting based on coal‐water two-phase flow was established. The critical flow velocity in the moving laminar flow regime is taken as that during the coordinated slag disposal from boreholes. The relationship curve between the coal-dropping speed and cutting pressure under different Protodyakonov coefficients of coal seams was obtained. Hence, the model for coordinated slag disposal during hydraulic cutting was established; the selection interval of reasonable pressure for coordinated slag disposal during hydraulic cutting was determined. The reasonable cutting pressure for slag disposal in coal seams with a Protodyakonov coefficient of 0.48 was determined as about 80 MPa. During the cutting test, the average net gas extraction from the boreholes for hydraulic cutting was 4.5 times larger than that from the conventional boreholes. Furthermore, the gas permeability coefficient of the boreholes for hydraulic cutting increased by 25 times; the effective extraction radius was more than doubled. It indicated that the model for reasonably selecting the cutting pressure based on the coordinated slag disposal theory can effectively guide the selection of the cutting pressure on site. While solving various problems occurring in the hydraulic cutting process on site, the model can be used to improve the cutting effect, which provides a theoretical basis for reasonably selecting the pressure during ultra-high pressure hydraulic cutting.
Sulfur and Oxygen Isotope Records of Sulfate-Driven Anaerobic Oxidation of Methane in Diffusion-Dominated Marine Sediments
Authors: Chen Tingting , Strauss Harald , Fang Yunxin , Lin Zhiyong , Sun Xiaoming , Liu Jiarui , Lu Yang , Yang Xin , Lin Haixin , Wu Zhongwei , Lin Xiao
Published: April 2022

Organoclastic sulfate reduction (OSR) and sulfate-driven anaerobic oxidation of methane (SD-AOM) are the two major microbial pathways for sulfate consumption in marine sulfur cycle. The relative changes of sulfur and oxygen isotope ratios in pore water sulfate are affected by the mode of microbial sulfate reduction and have been applied as an indicator for assessing methane excess environments. However, so far, this isotope proxy fails to distinguish sulfate reduction processes fueled by the oxidation of organic matter or by diffusing methane. To better understand the mechanism of sulfur and oxygen isotope partitioning during OSR and SD-AOM, coupled sulfur and oxygen isotopic compositions of pore water sulfate (δ34SSO4 and δ18OSO4) were investigated from four methane diffusing sites (CL56, CL57, CL59, and CL60) of the South China Sea, supplemented by carbon isotopic composition of dissolved inorganic carbon (DIC) and sulfur isotopic composition of pyrite in bulk sediments. Pore water sulfate and DIC concentrations, as well as calculated net sulfate reduction rates suggest that the sulfate reduction at site CL57 was mainly dominated by OSR, whereas sites CL56, CL59, and CL60 were likely impacted by both OSR and SD-AOM. Furthermore, the trend of cross-plotting δ18OSO4 versus δ34SSO4 values from site CL57 was distinguishable from sites CL56, CL59, and CL60, although all study sites show similar patterns to those derived from methane limited environments. This further indicates the trajectory of sulfur and oxygen isotope partitioning was affected by the mode of sulfate reduction (i.e., OSR vs. SD-AOM). At site CL57, the low net sulfate reduction rate would lead to enhanced oxidation of intermediate sulfur species during OSR, thus leading to a higher slope in the δ18OSO4 vs. δ34SSO4 cross-plot (1.26). In contrast, the higher net sulfate reduction rates at sites CL56, CL59, and CL60 due to the impact from SD-AOM would lead to lower slopes in the δ18OSO4 vs. δ34SSO4 cross-plots (0.78 ± 0.11). This study provides new insights into the sulfur and oxygen isotope systematics during microbial sulfate reduction processes in methane diffusing environments.
Influencing Factor Analysis on the Fractured Tight Sandstone Gas Reservoir Characteristics: A Case Study of Bozi 3 Gas Reservoir in the Tarim Basin
Authors: Liu Zhaolong , Zhang Yongling , Zhang Yongzhong , Zhao Libin , Peng Peng , Liu Hualin , Chang Baohua , Huang Weigang , Zhou Peng
Published: April 2022

The Bozi 3 gas reservoir in the Tarim Basin is a typical ultra-deep fractured tight sandstone gas reservoir, in which the main formations are the Cretaceous Bashijiqike Formation and the Baxigai Formation. The reservoir has the characteristics of deep burial, tight reservoir matrix, well-developed fractures, large differences in well productivity, and regional pressure distribution. These characteristics bring development challenges in well deployment, production allocation, gas production rate optimization, and production improvement. The main reservoir of Bozi 3 is deposited in the braided river delta, fan delta, and shallow lake environment with adequate provenance and a strong hydrodynamic environment, which provides favorable depositional conditions for the formation of thick sandbodies. Although the buried depth of the Bozi 3 gas reservoir is over 6,000 m, it has undergone an evolutionary process of long-term shallow burial in the early stage and rapid deep burial in the late stage, which protects the primary pore, and the finally formed reservoir has the characteristics of an extra-low pore and ultra-low permeability pore structure. Late tectonic movements caused the Bozi 3 gas reservoir to experience strong uplift under a strong nappe-thrust environment, forming a large number of high-angle fractures around the faults. Although the fracture distribution is inhomogeneous, tensile fractures at the top anticline have a low-filling degree and good effectiveness, which effectively improve Bozi 3 reservoir properties. Through analysis of the reservoir characteristics and influencing factors of the Bozi 3 gas reservoir, it is concluded that the difference in reservoir characteristics is the main reason for the large difference in production of adjacent wells and zonal distribution of formation pressure at the early development. This study can also provide a reliable geological basis for well deployment, production allocation rationalization, and gas production rate optimization in the study area.
Investigating the Pore Structure Characteristics and Reservoir Capacities of Lower Jurassic Continental Shale Reservoirs in the Northeastern Sichuan Basin, China
Authors: Jiang Tao , Jin Zhijun , Liu Guangxiang , Hu Zongquan , Chen Xuanhua , Liu Zhongbao , Wang Guanping
Published: April 2022

The Lower Jurassic shale in the northeastern Sichuan Basin is one of the main research intervals of continental shale gas. The shale pore structure is an important indicator for evaluating the reservoir capacities of shale reservoirs. We concentrate on the pore structure to indicate reservoir capacity using several testing methods, for example, N2 adsorption-high-pressure mercury pore size combined experiments, X-ray diffraction (XRD) experiments, and the total organic carbon (TOC) method. The results show that the clay mineral content of the continental shale is high. The pore type is mainly a mineral matrix pore, followed by an organic matter pore, and the microcracks are locally developed; the distribution interval of the main pore size is mesoporous, between 10 and 50 nm; the pore volumes and specific surface areas of the continental shale reservoirs are negatively correlated or unrelated to the TOC, mainly due to the failure of pore development in the organic vitrinite and fusinite and the occupation of pore volume and adsorption sites by the soluble organic matter. The larger pores are mainly formed by clay minerals; the reservoir capacities of the continental shale reservoirs were evaluated using a two-factor evaluation method of the pore volume and specific surface area. It was found that the continental shale mainly comprises free reservoirs and has a storage gas capability level of II–IV. The research results elucidate the pore structure characteristics and reservoir capacities of the continental shale reservoirs in the northeastern Sichuan Basin, having important theoretical and guiding significance for the gas-bearing evaluation and dessert target optimization of the continental shale in the study area.
Using Technology to Personalize Middle School Math Instruction: Evidence From a Blended Learning Program in Five Public Schools
Authors: Nitkin David , Ready Douglas D. , Bowers Alex J.
Published: April 2022

Schools are increasingly using technology to personalize instruction. Programs such as Khan Academy and Zearn produce a vast array of data on students’ behaviors and outcomes when engaged in technology-based instruction. However, these datasets rarely include equally detailed information from when students engage in non-technological learning activities. This study explores the implementation of an innovative model for adolescent mathematics instruction that includes detailed data from both technological and non-technological learning modalities. Much of the research on the implementation of technology-based personalization has focused on the effects of technology programs as isolated interventions rather than within blended models that combine instructional technology with significant changes to teacher-led instruction. Furthermore, existing studies of blended, personalized programs very rarely utilize daily programmatic data to push inside the “black box” of day-to-day interactions among students, teachers, and content. We attempt to address these gaps by using hierarchical cluster analysis, cluster trees, and clustergram heatmaps to explore and visualize data from 170,075 daily lesson assignments and assessments generated by 1,238 unique fifth through eighth grade students across five schools implementing an innovative model for blended and personalized middle school math instruction. We explore three research questions: (1) To what degree did the daily implementation of this program reflect its stated goal of personalizing instruction? (2) Did student outcomes vary based on exposure to each of the learning modalities utilized by this program? (3) Did student outcomes vary based on the academic proficiency of students entering the program? These analyses support three main findings: (a) The instructional reform succeeds in creating a highly personalized student experience, but was likely hampered in implementation by policy and logistical constraints; (b) Participation in a learning modality focused on long-term projects was associated with a lower degree of personalization but higher student outcomes than the other six learning modalities utilized by the program, particularly for some latent clusters of students; and (c) Initially higher-performing students earned higher scores on daily assessments than initially lower-performing students, despite the program’s intended goal of fostering equity in student outcomes through personalization of content to meet each student’s supposed level of readiness.
Profiles of Good Teaching Practices in STEM Disciplines: An Analysis of Mixed Methods of Academic and Assessment Variables of Teaching in the First Cycle of Civil Engineering
Authors: Salvo-Garrido Sonia , Sagner-Tapia Johanna , Bravo-Sanzana Mónica , Torralbo Camila
Published: April 2022

A relevant area to improve the quality of undergraduate education are the STEM disciplines: science, technology, engineering, and mathematics. These disciplines have seen a drop in student interest and participation internationally. This study aimed to determine profiles of good teaching practices based on responses from a teaching evaluation survey and academic context variables of students in STEM disciplines using a mixed-methods design. The study was conducted at a state university in southern Chile, framed in the first cycle of STEM disciplines, the Faculty of Engineering and Sciences using data from 2016 to 2017. The quantitative results revealed four groups analyzed by cluster, together with the most frequent responses according to the highest and lowest scores. The qualitative results yielded five groups of codes of greatest frequency in the twelve analysis units, which were the students’ comments divided into mathematics, physical sciences, and chemistry courses. The findings suggest a need to continue developing pedagogical knowledge in STEM teachers and highlight student involvement. Actions for improvement could focus on orienting teaching skills: (a) with a special emphasis on pedagogical content knowledge to promote active learning; (b) in the knowledge of the classroom culture and its problems associated with poor outcomes, offering the students equal opportunities for academic performance in STEM; and (c) in the management of a learning environment suitable for all students, inclusive classrooms, alleviating the burden of academic success being only on students. Finally, the teaching evaluation instrument needs to be improved.
Surgical Outcome and Evaluation of Strategies in the Management of Growth Hormone-Secreting Pituitary Adenomas After Initial Transsphenoidal Pituitary Adenectomy Failure
Authors: Yan Jiun-Lin , Chen Mao-Yu , Chen Yao-Liang , Chuang Chi-Cheng , Hsu Peng-Wei , Wei Kuo-Chen , Chang Chen-Nen
Published: April 2022

Acromegaly is a systemic disease that requires multidisciplinary treatment to achieve the best clinical outcome. This study aimed to evaluate the outcomes of the endoscopic transsphenoidal approach (TSA) as the primary treatment for somatotroph adenomas and further investigate patients who had suboptimal surgical results. This retrospective study included 83 patients with somatotroph adenomas treated by TSA at our institution from 1999 to 2010. Biochemical remission was defined as hGH <1 and <2.5 ng/ml. Factors associated with failure of TSA and strategy of secondary treatments for refractory and recurrent disease were analyzed. The mean age of patients was 41.1 ± 11.3 years, and the mean follow-up time was 54.2 ± 44.3 months. Approximately 44.5% of patients had residual tumors after TSA. Larger tumor size, higher GH level before the operation, and the existence of residual tumors were associated with TSA failure. Forty-one patients had an inadequate response to TSA or a recurrent lesion, and of these patients, 37 had residual tumor after TSA. Octreotide results in good outcomes in the treatment of DGSA patients, and SRS/EXRT generates good results in treating patients who receive second treatments when remission cannot be reached 6 months after TSA operation.
Case Report: Hypercholesterolemia “Lean Mass Hyper-Responder” Phenotype Presents in the Context of a Low Saturated Fat Carbohydrate-Restricted Diet
Authors: Norwitz Nicholas G. , Soto-Mota Adrian , Feldman David , Parpos Stefanos , Budoff Matthew
Published: April 2022

Emerging evidence suggests that “leanness” and good metabolic health markers may predict larger increases in LDL cholesterol (LDL-C) in response to carbohydrate restriction. Specifically, a recent cohort study demonstrated an inverse association between BMI and LDL-C change among individuals on carbohydrate-restricted diets and identified a subgroup of “Lean Mass Hyper-Responders” (LMHR) who exhibit exceptional increases in LDL-C, in the context of low triglycerides and high HDL-C. We present the case of one subject, LM, who adopted a ketogenic diet for management of ulcerative colitis. He subsequently experienced an increase in LDL-C from 95 to 545 mg/dl, at peak, in association with HDL-C >100 mg/dl and triglycerides ~40 mg/dl, typical of the emergent LMHR phenotype. Assessments of LM’s dietary intake, lipid panels, and BMI are consistent with prior data and suggest that the LMHR phenomenon is not dependent on saturated fat intake but inversely associates with BMI changes. Finally, computed tomography angiography conducted on LM after over 2 years of hypercholesterolemia revealed no evidence of calcified or non-calcified plaque.
Axon Guidance Molecules in the Islets of Langerhans
Authors: Waters Bayley J. , Blum Barak
Published: April 2022

The islets of Langerhans, responsible for regulating blood glucose in vertebrates, are clusters of endocrine cells distributed throughout the exocrine pancreas. The spatial architecture of the different cell types within the islets controls cell-cell communication and impacts their ability to collectively regulate glucose. Islets rely on a range of chemotactic and adhesive cues to establish and manage intercellular relationships. Growing evidence indicates that axon guidance molecules such as Slit-Robo, Semaphorin-Neuropilin, Ephrin-Eph, and Netrins, influence endocrine progenitors’ cell migration to establish correct architecture during islet morphogenesis, as well as directly regulating physical cell-cell communication in the mature islet to coordinate hormone secretion. In this mini-review, we discuss what is known and not yet known about how axon guidance molecules contribute to islet morphogenesis and function.
Production Analysis of Horizontal Wells in a Two-Region Composite Reservoir Considering Formation Damage
Authors: Li Jingsong , Wang Tao
Published: April 2022

The horizontal well is extensively used to exploit oil at the Bohai offshore oilfield, China. It has been proved by practice that formation damage always happens during the production of wells. However, it is a challenging task to evaluate the formation damage for horizontal wells. In this paper, a flow model considering formation damage is established for horizontal wells. The reservoir geometry is divided into two regions: the inner region represents the region of formation damage and the outer region that without damage. The finite element method is used to solve the flow model. The well production rate can be determined by using the material balance method. For different scenarios, such as when the horizontal well is completely in the inner region or when the horizontal well passes through two regions, the effects of some key parameters such as damage radius, damage region permeability, and well position on the oil production rate and pressure distribution characteristics are analyzed. The results show that a smaller damage radius, higher damage zone permeability, and a horizontal well closer to or in greater contact with the outer region result in a higher oil production rate and faster pressure drop propagation. The presented model and obtained results enrich production analysis of horizontal wells in a two-region composite reservoir considering formation damage, which has significance for efficient offshore reservoir development.
Spatial Variability of Selected Soil Properties in Long-Term Drained and Restored Peatlands
Authors: Negassa Wakene , Baum Christel , Beyer Florian , Leinweber Peter
Published: April 2022

Drained peatlands have been rewetted for restoration in Europe and North America for about 25 years. However, information on spatial variability of soil chemical and biochemical properties in long-term drained and restored peatlands is insufficient to design appropriate research methods and soil sampling protocols for monitoring biogeochemical processes. The study aimed to examine the influence of long-term drainage and rewetting of peatlands on smallscale spatial variability of the soil chemical properties and enzyme activities. We collected 400 soil samples from the 0–15 cm and 15–30 cm soil depths of a drained and a corresponding rewetted peatland. The number of grid cells was 100 for each of the drained and the rewetted peatland, and the size of each grid cell was 3 m × 3 m. We analyzed 17 soil parameters from the surfaces and 14 from the subsurface of both sites. The variability (range, SD, and CV) of all the soil properties was higher in the drained peatland than in the restored peatlands except for the soil pH. The geostatistical analysis revealed only the soil pH, acid phosphatase, β-glucosidase, and arylsulfatase activities disclosed the strong spatial dependency at the ≤5 m semivariance range in the drained peatland. However, more than 80% of the soil properties showed a strong spatial dependence within the 4–20 m semivariance ranges in the restored peatland. The strong spatial dependencies of all the soil properties in the long-term restored peatland conclusively call for the spatial soil sampling and geostatistical data analysis methods to capture substantial spatial variability that has important implications in degraded peatland restoration.
Hedge and Alder-Based Agroforestry Systems: Potential Interventions to Carbon Sequestration and Better Crop Productivity in Indian Sub-Himalayas
Authors: Parmar Brajendra , Vishwakarma Anand , Padbhushan Rajeev , Kumar Amarendra , Kumar Rajkishore , Kumari Ragini , Kumar Yadav Brahmdeo , Giri S. P. , Kaviraj Megha , Kumar Upendra
Published: April 2022

Agroforestry systems (AFSs) have potential to combat climate change and to ensure food security. AFSs can sequester carbon and amend the organic matter, thereby enhancing the crop productivity. Carbon sequestration depends on the type of AFSs, climate, cropping pattern, and management practices. The aim of this study was to evaluate different AFSs for their potential to sequester carbon and impact on soil organic matter (SOM) in the eastern sub-Himalayas, India. Hedge-, alder-, and guava-based AFSs were established along with control (without any tree), and the maize–mustard–potato cropping pattern was followed in each AFS. Soil samples were collected after the fifth crop cycle and further analyzed. The results showed that crop productivity was significantly higher in all the AFSs than control. On average, soil organic carbon (SOC) was found to be significantly higher by 62 and 64% in hedge-based AFSs as compared to guava-based AFSs and control, respectively, andat parwith alder-based AFSs. Particulate organic carbon (POC) was higher in all the three AFSs than in the control. For microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) contents, the trend of AFSs was expressed as alder-based AFS > hedge-based AFS > guava-based AFS > control. Hedge- and alder-based AFSs had higher SOC stocks than guava-based AFSs and control. Carbon dioxide equivalent (CO2eq.) emissions were greater in control than hedge-based AFSs (35.2 Mg ha−1), followed by alder-based AFSs (28.6 Mg ha−1), and the lowest was observed in guava-based AFSs. On an average, hedge species accumulated more nitrogen (N), phosphorus (P), and potassium (K), which were 60, 12, and 28 kg ha−1yr−1, respectively. This conclusively proved that AFSs were significantly affecting SOM pools and crop productivity and had a significant role in carbon retention in the soil. Overall, hedge- and alder-based AFSs retained higher soil carbon, and hence, hedge- and alder-based AFSs may be promoted to achieve climate-smart agriculture practices in the acid soils of the Indian sub-Himalayan region.
Optimized Variables for Environmental Dynamics: China’s Renewable Energy Policy
Authors: Wang Yujing , You Yanqun , Teng Yu
Published: April 2022

The purpose of this study is to determine the impacts of foreign direct investment (FDI), renewable energy (RE), energy consumption index (ECI), Globalization (GLO), and green technology innovation (GTI) on environmental pollution using a time series data from 1980 to 2019, using DARDL assessor to look at how markers with high levels of petroleum derivatives distorted the explanatory variable in China. The results showed that GTI contaminated environmental sustainability (ES). The polluted safe house notion claimed that FDI has a negative impact on the country’s inherent character. Finally, people are waking up to the importance of ES. Single-headed causalities from GTI to carbon emissions were detected in the middle of the other causes and fossil fuel byproducts need to change into green energy resources to reduce environmental pollution. Finally, the research proved that FDI is a major source of environmental pollution in China. According to the findings of the DARDL research, foreign direct investment and urbanization, green technological innovations, and China’s environmental pollution policy direction are all congruent with each other.
Ojibwe Perspectives Toward Proper Wolf Stewardship and Wisconsin’s February 2021 Wolf Hunting Season
Authors: Gilbert Jonathan H. , David Peter , Price Michael W. , Oren Jenny
Published: April 2022

In February 2021, the Wisconsin DNR implemented a wolf season in which > 20% of the population was killed in 63 h. Wisconsin’s Ojibwe tribes had a visceral reaction to this killing. This paper provides a perspective for this reaction by reviewing the Ojibwe relationship with Ma’iingan. This relationship maintains that Ma’iingan and Ojibwe are to be considered relatives whose fates are intertwined. Ma’iingan and Ojibwe have lived parallel histories, suffering from the effects of colonization, the decimation of wolf populations and decline of tribal culture. The Ojibwe tribes ceded vast territories in treaties with the United States while retaining common use rights, including the right to hunt and fish. These rights were reaffirmed just as wolves were reestablishing themselves in Wisconsin. The tribes continue to strengthen their culture, while wolf populations continue to recover. By examining these comparative histories, it becomes apparent that “whatever happens to one happens to the other.” Unfortunately, Ma’iingan were not adjudicated during the Wisconsin treaty case, creating uncertainty over how the relationship between the Ojibwe and Ma’iingan is to be respected by the state. The tribes believe their treaty right includes protection for wolves, so that wolves can fulfill their cultural and ecological purposes. Tribes maintain that Ma’iingan should determine their own population levels, in order to provide ecological and cultural benefits. A respectful and appreciative relationship with Ma’iingan should be maintained so that the future well-being of both Ma’iingan and the Ojibwe will be assured.
Evidence-Based Smart Transition Strategies for Long-Distance Commuters in Beijing
Authors: Zhao Xu , Zhang Zhehao , Guo Wenbo , Zhou Yufang , Papaix Claire , Sun Qingfeng
Published: April 2022

Building a sustainable and eco-friendly transport system is crucial to tackling global challenges such as climate change, as transport can be seen as one of the main sources of air pollution and CO2 emissions in megacities, particularly in developing countries. By bringing together multiple modes of travel, and combining different transport provider options into a single service, Mobility-as-a-Service (MaaS) could offer an effective way to help build a sustainable city by improving public transport services. However, the strategies used to develop MaaS, vary in different cities based on their specific multimodal transport facilities and service. Many residents of Beijing have to contend with long-distance commuting, which may adversely affect individuals’ travel experience and satisfaction and is, therefore, a key issue for transport development in Beijing. Using Beijing as a case study, we carried out in-depth interviews and thereby captured long-distance commuters’ concerns and needs concerning their commuting experiences. Our findings show that long-distance commuters are primarily concerned about the following multimodal commuting scenarios: “Underground + bicycle”, “Underground + taxi”, “Underground + private car”, and “Underground + bus”. Therefore, we suggest that the priority should be to develop a MaaS model for Beijing that focuses on the integration of multimodal transport connected to the underground rail system.
Genetic Polymorphisms in microRNA Genes Targeting PI3K/Akt Signal Pathway Modulate Cervical Cancer Susceptibility in a Chinese Population
Authors: Chen Kerong , Yan Zhiling , Dong Xudong , Liang Yan , Yao Yueting , Zhang Shao , Liu Weipeng , Li Chuanyin , Yao Yufeng , Shi Li
Published: April 2022

Polymorphisms in microRNA (miRNA) genes could influence the expression of miRNAs that regulate the PI3K/Akt signalling pathway and play crucial roles in cancer susceptibility. To investigate the association of single nucleotide polymorphisms (SNPs) in miRNA genes of PI3K/Akt with cervical intraepithelial neoplasia (CIN) and cervical cancer (CC), nine SNPs located in miRNA genes were selected for genotyping, and the association of these SNPs with CIN and CC risk was evaluated. A total of 1,402 participants were enrolled in the current study, including 698 healthy individuals in the control group, 431 patients with CC, and 273 patients with CIN. Nine SNPs in miRNA genes (rs107822 in miR-219a, rs10877887 in let-7i, rs2292832 in miR-149, rs353293 in miR-143, rs3746444 in miR-499, rs3803808 in miR-132, rs4078756 in miR-10b, rs629367 in let-7a, and rs7372209 in miR-26a) were genotyped using MassArray, and the association of these SNPs with CIN and CC were analysed. The results showed that the frequencies of rs107822 in miR-219a and rs2292832 in miR-149 were significantly different between the control and CC groups (p < 0.005). The C allele of rs107822 in miR-219a was associated with an increased risk of CC (OR = 1.29, 95%CI:1.09–1.54) whereas the C allele of rs2292832 in miR-149 was associated with a decreased risk of CC (OR = 0.77, 95%CI:0.64–0.92). The results of inheritance model analysis showed that the best-fit inheritance models for rs107822 and rs2292832 were log-additive. The 2CC + CT genotype of rs107822 could be a risk factor for CC when compared with the TT genotype (OR = 1.28, 95%CI:1.08–1.51). The 2CC + CT genotype of rs2292832 could be a protective factor against CC when compared with the TT genotype (OR = 0.76, 95%CI:0.64–0.92). However, no association of these SNPs with CIN was found in the current study. Our results suggest that rs107822 in the promoter region of miR-219a and rs2292832 in pre-miR-149 region are associated with the risk of CC.
Selection and Evaluation of Candidate Reference Genes for Quantitative Real-Time PCR in Aboveground Tissues and Drought Conditions in Rhododendron Delavayi
Authors: Zhang Lu , Cai Yanfei , Zhang Mingchao , Du Guanghui , Wang Jihua
Published: April 2022

There has been no systematic identification and screening of candidate reference genes for normalization of quantitative real-time PCR (qRT-PCR) results in Rhododendron delavayi to date. Therefore, the present study used GAPDH, Act, EF1, Tub-, Tub-5, UEC1, TATA, TATA-2, UEP, TIP41, and Ubiquitin to predict their stabilities on different aboveground tissues (matured leaves (ML), stem tips (STM), and flower buds (FB)) at different developmental stages (young and adult plants) using five statistical algorithms: Delta Ct method, BestKeeper, geNorm, Normfinder, and RefFinder. The findings were confirmed using ML obtained from plants that had been stressed by drought. By using RefFinder with ML samples collected under drought conditions, it was determined that the top five most stable reference genes were GAPDH > UEC1 > Actin > Tubulin- > Tubulin—5, whereas the least stable reference gene was Ubiquitin. In addition, under control conditions, UEC1, UEC2, Actin, and GAPDH were selected as the highest stable potential reference genes at the juvenile stage of R. delavayi with ML and STM. When ML and STM were combined with drought-stressed samples, TIP41, GAPDH, or their combination proved to be the most effective qRT-PCR primers. The findings will aid in the improvement of the precision and reliability of qRT-PCR data and laying the groundwork for future gene functional studies in R. delavayi.
Providing a Helping Hand: Metabolic Regulation of T Follicular Helper Cells and Their Association With Disease
Authors: Mayberry Colleen L. , Logan Natalie A. , Wilson John J. , Chang Chih-Hao
Published: April 2022

T follicular helper (Tfh) cells provide support to B cells upon arrival in the germinal center, and thus are critical for the generation of a robust adaptive immune response. Tfh express specific transcription factors and cellular receptors including Bcl6, CXCR5, PD-1, and ICOS, which are critical for homing and overall function. Generally, the induction of an immune response is tightly regulated. However, deviation during this process can result in harmful autoimmunity or the inability to successfully clear pathogens. Recently, it has been shown that Tfh differentiation, activation, and proliferation may be linked with the cellular metabolic state. In this review we will highlight recent discoveries in Tfh differentiation and explore how these cells contribute to functional immunity in disease, including autoimmune-related disorders, cancer, and of particular emphasis, during infection.