bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycobacterium leprae Transcriptome During In Vivo Growth and Ex Vivo Stationary Phases
Authors: Ojo Olabisi , Williams Diana L. , Adams Linda B. , Lahiri Ramanuj
Published: January 2022

Mycobacterium leprae, the causative agent of leprosy, is an obligate intracellular pathogen primarily residing within host macrophages and Schwann cells. Whole genome sequencing predicts a highly degraded genome with approximately one third of the coding capacity resulting in the loss of many catabolic pathways. Therefore, it can be assumed that M. leprae obtains many of the necessary metabolites for intracellular survival and growth from the host cells. In this study, global transcriptomic analyses were done on freshly harvested M. leprae growing in athymic mouse footpads for five months (MFP5) and compared to those held in axenic medium for 48 (ML48) and 96 (ML96) hours. Results show that all of the genes and pseudogenes were transcribed under both in vivo and in vitro conditions. 24% and 33% of gene transcript levels were significantly altered in ML48 and ML96 respectively, compared to MFP5. Approximately 45% (39/86) of lipid metabolism genes were significantly downregulated in ML96 compared to MFP5, majority of which are in the β-oxidation pathway. Cholesterol oxidase, acyl-CoA dehydrogenase, and coenzyme F420-dependent oxidoreductase, were significantly upregulated in both ML48 and ML96 compared to MFP5. 30% of cell wall and cell processes functional category genes had altered gene transcription at 96hr compared to MFP5. 40% of 57 genes associated with mycobacterial virulence showed significantly altered transcript levels with 52% significantly downregulated in ML96, including most of the Pro-Glu/Pro-Pro-Glu genes. All 111 hypothetical protein genes with unknown function were expressed. Adenosine triphosphate (ATP) synthesis in M. leprae appears to be significantly downregulated under ex vivo conditions. This is the first study comparing M. leprae global gene expression during in vivo growth and ex vivo stationery phase in axenic medium confirming that during the growth phase in the footpads of experimentally infected mice, M. leprae is metabolically active and its primary source of energy production is probably lipids.
An Intersectionality-Based Policy Analysis Examining the Complexities of Access to Wild Game and Fish for Urban Indigenous Women in Northwestern Ontario
Authors: Phillipps Breanna , Skinner Kelly , Parker Barbara , Neufeld Hannah Tait
Published: January 2022

The destruction of Indigenous food systems is a direct consequence of the settler-colonial project within Canada and has led to decreasing access to Indigenous foods, disproportionate rates of food insecurity and disconnection from Indigenous food systems and environments. We interviewed Indigenous women, non-Indigenous staff of Indigenous-serving organizations, and policymakers (i.e., those who develop, interpret, or implement wild food policy) to explore how the policy context has impacted Indigenous women and their communities’ experiences of accessing Indigenous foods in urban northwestern Ontario. We applied an Intersectionality-Based Policy Analysis (IBPA) Framework to shape our research questions and guide the thematic analysis of the data. We found that stakeholder groups had differing understandings of the issue of accessing wild foods and Indigenous food security and their actions either supported or disrupted efforts for access to wild food to promote food security or Indigenous Food Sovereignty. Policymakers cited necessary barriers to promote food safety and support conservation of wildlife. Staff of Indigenous-serving organizations approached the issue with consideration of both Western and Indigenous worldviews, while Indigenous women spoke about the ongoing impacts of colonial policy and government control over their lands and territories. The main policy areas discussed included residential school policy, food regulation, and natural resource regulation. We also investigated community-level strategies for improvement, such as a wild game license. Throughout, we tied the colonial control over ‘wildlife’ and the Western food safety discourse, with infringements on Indigenous Food Sovereignty, experiences of racism in food settings and on the land, as well as with broad control over Indigenous sovereignty in Ontario. This work contributes to an increased understanding of how Western discourses about health, food, and the environment are perpetuated through systemic racism in government policy and reiterated through policymakers' views and interpretations or actions. Government institutions must develop culturally safe partnerships with Indigenous leaders and organizations to facilitate a transfer of power that can support Indigenous Food Sovereignty.
Simultaneous Upregulation of Elastolytic and Elastogenic Factors Are Necessary for Regulated Collateral Diameter Expansion
Authors: Andraska Elizabeth , Skirtich Nolan , McCreary Dylan , Kulkarni Rohan , Tzeng Edith , McEnaney Ryan
Published: January 2022

Background: During arteriogenesis, outward remodeling of the arterial wall expands luminal diameter to produce increased conductance in developing collaterals. We have previously shown that diameter expansion without loss of internal elastic lamina (IEL) integrity requires both degradation of elastic fibers and LOX-mediated repair. The aim of this study was to investigate the expression of genes involved in remodeling of the extracellular matrix (ECM) using a model of arteriogenesis.

Methods: Sprague-Dawley rats underwent femoral artery ligation with distal arteriovenous fistula (FAL + AVF) placement. Profunda femoral arteries (PFA) were harvested for analysis at various time points. Serum desmosine, an amino acid found exclusively in elastin, was evaluated with enzyme-linked immunosorbent assay (ELISA) as a marker of tissue elastolysis. Tissue mRNA isolated from FAL + AVF exposed PFAs was compared to the contralateral sham-operated using qPCR. HCAECs were cultured under low shear stress (8 dyn·s/cm2) for 24 h and then exposed to high shear stress (40 dyn·s/cm2) for 2–6 h. Primers used included FBN-1, FBN-2, Timp-2, LOX-1, Trop-E, Cath-K, Cath-S, MMP-2, MMP-9, FBLN-4, and FBLN-5 and were normalized to GAPDH. mRNA fold changes were quantified using the 2-ΔΔCq method. Comparisons between time points were made with non-parametric ANOVA analysis with Bonferroni adjustment.

Results: PFAs showed IEL reorganization during arteriogenesis. Serum desmosine levels are significantly elevated at 2 days and one week, with a return to baseline thereafter (p < 0.01). Expression of ECM structural proteins (FBN-1, FBN-2, FBLN-4, FBLN-5, Tropoelastin, TIMP-2, LOX-1) and elastolytic proteins (MMP-2, MMP-9, Cathepsin S, Cathepsin K) exhibited an early peak (p < 0.05) relative to sham PFAs. After two weeks, expression returned to baseline. HCAECs demonstrated upregulation of FBN-2, FBLN-5, LOX-1 and Trop-E at 4 h of high shear stress, as well as elastolytic protein MMP-2.

Conclusions: Elastin degradation begins early in arteriogenesis and is mediated by local upregulation of elastolytic genes. Elastolysis appears to be simultaneously balanced by production of elastic fiber components which may facilitate stabilization of the IEL. Endothelial cells are central to initiation of arteriogenesis and begin ECM remodeling in response to altered shear stress.
Case Report: Combination of Pressure Guidewire and Optical Coherence Tomography-Guided Drug-Coated Balloon Revascularization for Renal Artery Fibromuscular Dysplasia
Authors: Li Yuxi , Wen Xinyan , Zheng Bo , Chen Ming , Ma Wei , Li Jianping
Published: January 2022

Fibromuscular dysplasia (FMD) is the second common cause of renovascular hypertension. With the advent of endovascular therapy, angiography has become a diagnostic gold standard for FMD. Optical coherence tomography (OCT) by reflecting in vivo histology may improve diagnostic and classification accuracy. Renal fractional flow reserve (rFFR), measured by pressure guidewire, may distinguish the patients who may benefit from revascularization by identifying physiologically significant stenoses. However, the role of usage of both OCT and rFFR is not well-studied. We herein report a 17-year-old male with renovascular hypertension due to FMD. Angioplasty of drug-coated balloon (DCB) guided by OCT and FFR favorably achieved blood pressure (BP) control. In conclusion, the utility of both OCT and FFR may be useful for the appropriate selection of patients with renal FMD.
Diosmin Alleviates Venous Injury and Muscle Damage in a Mouse Model of Iliac Vein Stenosis
Authors: Guo Zhiye , Du Xiaolong , Zhang Yihua , Su Chunwan , Ran Feng , Lu Qiulun
Published: January 2022

Chronic venous disease (CVD) is a progressive inflammatory disease that increases in prevalence with age. Elucidating the underlying molecular mechanism of CVD development is essential for disease prevention and treatment. This study constructed a mouse model of iliac vein stenosis to explore the mechanism of the CVD disease progression, and diosmin was administered as a positive control (as recommended by clinical practice). The mouse model was established successfully with iliac vein stenosis, leading to the expansion of the intercellular space and venous leakage. Conversely, micronized diosmin showed a dose-dependent therapeutic effect for these manifestations. Concerning the mechanism, iliac vein stenosis caused an inflammatory response in veins, while diosmin suppressed this increase. Furthermore, RNA sequencing analysis indicated that diosmin significantly improved muscle function through actin filament organization and muscle contraction. These results indicated that the mouse model of iliac vein stenosis is a reliable model to study venous diseases. Furthermore, the dose-dependent therapeutic effect of diosmin on stenosis (without toxic side-effects) suggests greater protection against venous diseases at higher doses of diosmin.
ACEI/ARB Medication During ICU Stay Decrease All-Cause In-hospital Mortality in Critically Ill Patients With Hypertension: A Retrospective Cohort Study Based on Machine Learning
Authors: Yang Boshen , Xu Sixuan , Wang Di , Chen Yu , Zhou Zhenfa , Shen Chengxing
Published: January 2022

Background: Hypertension is a rather common comorbidity among critically ill patients and hospital mortality might be higher among critically ill patients with hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg). This study aimed to explore the association between ACEI/ARB medication during ICU stay and all-cause in-hospital mortality in these patients.

Methods: A retrospective cohort study was conducted based on data from Medical Information Mart for Intensive Care IV (MIMIC-IV) database, which consisted of more than 40,000 patients in ICU between 2008 and 2019 at Beth Israel Deaconess Medical Center. Adults diagnosed with hypertension on admission and those had high blood pressure (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg) during ICU stay were included. The primary outcome was all-cause in-hospital mortality. Patients were divided into ACEI/ARB treated and non-treated group during ICU stay. Propensity score matching (PSM) was used to adjust potential confounders. Nine machine learning models were developed and validated based on 37 clinical and laboratory features of all patients. The model with the best performance was selected based on area under the receiver operating characteristic curve (AUC) followed by 5-fold cross-validation. After hyperparameter optimization using Grid and random hyperparameter search, a final LightGBM model was developed, and Shapley Additive exPlanations (SHAP) values were calculated to evaluate feature importance of each feature. The features closely associated with hospital mortality were presented as significant features.

Results: A total of 15,352 patients were enrolled in this study, among whom 5,193 (33.8%) patients were treated with ACEI/ARB. A significantly lower all-cause in-hospital mortality was observed among patients treated with ACEI/ARB (3.9 vs. 12.7%) as well as a lower 28-day mortality (3.6 vs. 12.2%). The outcome remained consistent after propensity score matching. Among nine machine learning models, the LightGBM model had the highest AUC = 0.9935. The SHAP plot was employed to make the model interpretable based on LightGBM model after hyperparameter optimization, showing that ACEI/ARB use was among the top five significant features, which were associated with hospital mortality.

Conclusions: The use of ACEI/ARB in critically ill patients with hypertension during ICU stay is related to lower all-cause in-hospital mortality, which was independently associated with increased survival in a large and heterogeneous cohort of critically ill hypertensive patients with or without kidney dysfunction.
Saving Time for Patient Care by Optimizing Physician Note Templates: A Pilot Study
Authors: Alissa Rana , Hipp Jennifer A. , Webb Kendall
Published: January 2022

Background: At times, electronic medical records (EMRs) have proven to be less than optimal, causing longer hours behind computers, shorter time with patients, suboptimal patient safety, provider dissatisfaction, and physician burnout. These concerning healthcare issues can be positively affected by optimizing EMR usability, which in turn would lead to substantial benefits to healthcare professionals such as increased healthcare professional productivity, efficiency, quality, and accuracy. Documentation issues, such as non-standardization of physician note templates and tedious, time-consuming notes in our mother-baby unit (MBU), were discussed during meetings with stakeholders in the MBU and our hospital's EMR analysts.

Objective: The objective of this study was to assess physician note optimization on saving time for patient care and improving provider satisfaction.

Methods: This quality improvement pilot investigation was conducted in our MBU where four note templates were optimized: History and Physical (H and P), Progress Note (PN), Discharge Summary (DCS), and Hand-Off List (HOL). Free text elements documented elsewhere in the EMR (e.g., delivery information, maternal data, lab result, etc.) were identified and replaced with dynamic links that automatically populate the note with these data. Discrete data pick lists replaced necessary elements that were previously free texts. The new note templates were given new names for ease of accessibility. Ten randomly chosen pediatric residents completed both the old and new note templates for the same control newborn encounter during a period of one year. Time spent and number of actions taken (clicks, keystrokes, transitions, and mouse-keyboard switches) to complete these notes were recorded. Surveys were sent to MBU providers regarding overall satisfaction with the new note templates.

Results: The ten residents' average time saved was 23 min per infant. Reflecting this saved time on the number of infants admitted to our MBU between January 2016 and September, 2019 which was 9373 infants; resulted in 2.6 hours saved per day, knowing that every infant averages two days length of stay. The new note templates required 69 fewer actions taken than the old ones (H and P: 11, PN: 8, DCS: 18, HOL: 32). The provider surveys were consistent with improved provider satisfaction.

Conclusion: Optimizing physician notes saved time for patient care and improved physician satisfaction.
Low-Temperature Hydrothermal Systems Response to Rainfall Forcing: An Example From Temperature Time Series of Fumaroles at La Soufrière de Guadeloupe Volcano
Authors: de Bremond d’Ars Jean , Gibert Dominique
Published: January 2022

Volcanoes with highly-developed and shallow hydrothermal systems may be subject to sudden increases of their surface steam emission at vents in response to either deep forcing (e.g. increase of heat flux coming from the magma chamber) or external forcing (e.g. sudden decrease of atmospheric pressure or variation of meteoric water input). Because the vent plumbing has a limited heat and mass transfer capacity, the rise of steam pressure accompanying the increase of flux may destabilize the system in order to augment its net transfer capacity. This reorganization may, for instance, take the form of an enlargement of existing conduits and vents or to the creation of new ones. In such a case, local and extremely dangerous blast phenomena are likely to occur with devastating consequences several hundreds of meters around. Even volcanoes with a moderate activity and considered safe by the local population are exposed to such abrupt and dangerous events. The detection of early warning signals through temperature monitoring in the vents is of a primary importance and a main difficulty is to correctly interpret temperature jumps in order to reduce false alarms. We analyze time series of the temperature measured in three fumaroles located at the top of La Soufrière volcano in Guadeloupe, which are characterized by their relatively low temperature around 99°C, slightly above the boiling temperature of water at this altitude. Thanks to the long duration of the records from January to August 2017 and to their short 1-s sampling interval, a multiscale analysis can be performed over several orders of magnitude. We show that, despite their complex and sometimes erratic appearance, the temperature variations observed in the vents contain components highly correlated with rain input variations. Some remarkable patterns recurrently appear at different periods and we show that the main temperature variations of more than 10°C are related to the rainfall intensity. Our results illustrate the importance of external forcing on the otherwise complex and possibly chaotic dynamics of the shallow hydrothermal system of La Soufrière. They also reveal that a careful analysis of rainfall forcing must be done to be able to draw any conclusion concerning changes caused by the underlying hydrothermal system.
Fine-Scale Structures in the Mid-Level Eyewall of Super Typhoon Rammasun (2014) Simulated With the WRF-LES Framework
Authors: Gao Zhen , Wu Liguang , Zhou Xingyang
Published: January 2022

It has been numerically demonstrated that the turbulence above the boundary is important to tropical cyclone intensification and rapid intensification, but the three-dimensional structures of the sub-grid-scale (SGS) eddy have not been revealed due to the lack of observational data. In this study, two numerical simulations of Super Typhoon Rammasun (2014) were conducted with the Advanced Weather Research and Forecast (WRF) model by incorporating the large-eddy simulation (LES) technique, in which the enhanced eyewall convection and the process of rapid intensification are captured. Consistent with previous observational studies, the strong turbulent kinetic energy (TKE) is found throughout the whole eyewall inside of the radius of maximum wind in both experiments. The simulations indicate that the strong TKE is associated with horizontal rolls with the horizontal extent of 2–4 km, which are aligned azimuthally in the intense eyewall convection. It is indicated that the three-dimensional structures of the SGS eddy can be simulated with the vertical grid spacing of ∼100 m when the horizontal grid spacing is 74 m. It is suggested that there is considerable turbulence associated with azimuthally-aligned horizontal rolls in the mid-level eyewall of tropical cyclone.
Dealing With Brain MRI Findings in Pediatric Patients With Endocrinological Conditions: Less Is More?
Authors: Baldo Francesco , Marin Maura , Murru Flora Maria , Barbi Egidio , Tornese Gianluca
Published: January 2022

Neuroimaging is a key tool in the diagnostic process of various clinical conditions, especially in pediatric endocrinology. Thanks to continuous and remarkable technological developments, magnetic resonance imaging can precisely characterize numerous structural brain anomalies, including the pituitary gland and hypothalamus. Sometimes the use of radiological exams might become excessive and even disproportionate to the patients’ medical needs, especially regarding the incidental findings, the so-called “incidentalomas”. This unclarity is due to the absence of well-defined pediatric guidelines for managing and following these radiological findings. We review and summarize some indications on how to, and even if to, monitor these anomalies over time to avoid unnecessary, expensive, and time-consuming investigations and to encourage a more appropriate follow-up of brain MRI anomalies in the pediatric population with endocrinological conditions.
A Predictive Model of Live Birth Based on Obesity and Metabolic Parameters in Patients With PCOS Undergoing Frozen-Thawed Embryo Transfer
Authors: Jiang Xiaohua , Liu Ruijun , Liao Ting , He Ye , Li Caihua , Guo Peipei , Zhou Ping , Cao Yunxia , Wei Zhaolian
Published: January 2022

Aims

To determine the clinical predictors of live birth in women with polycystic ovary syndrome (PCOS) undergoing frozen-thawed embryo transfer (F-ET), and to determine whether these parameters can be used to develop a clinical nomogram model capable of predicting live birth outcomes for these women.

Methods

In total, 1158 PCOS patients that were clinically pregnant following F-ET treatment were retrospectively enrolled in this study and randomly divided into the training cohort (n = 928) and the validation cohort (n = 230) at an 8:2 ratio. Relevant risk factors were selected via a logistic regression analysis approach based on the data from patients in the training cohort, and odds ratios (ORs) were calculated. A nomogram was constructed based on relevant risk factors, and its performance was assessed based on its calibration and discriminative ability.

Results

In total, 20 variables were analyzed in the present study, of which five were found to be independently associated with the odds of live birth in univariate and multivariate logistic regression analyses, including advanced age, obesity, total cholesterol (TC), triglycerides (TG), and insulin resistance (IR). Having advanced age (OR:0.499, 95% confidence interval [CI]: 0.257 – 967), being obese (OR:0.506, 95% CI: 0.306 - 0.837), having higher TC levels (OR: 0.528, 95% CI: 0.423 - 0.660), having higher TG levels (OR: 0.585, 95% CI: 0.465 - 737), and exhibiting IR (OR:0.611, 95% CI: 0.416 - 0.896) were all independently associated with a reduced chance of achieving a live birth. A predictive nomogram incorporating these five variables was found to be well-calibrated and to exhibit good discriminatory capabilities, with an area under the curve (AUC) for the training group of 0.750 (95% CI, 0.709 - 0.788). In the independent validation cohort, this model also exhibited satisfactory goodness-of-fit and discriminative capabilities, with an AUC of 0.708 (95% CI, 0.615 - 0.781).

Conclusions

The nomogram developed in this study may be of value as a tool for predicting the odds of live birth for PCOS patients undergoing F-ET, and has the potential to improve the efficiency of pre-transfer management.
Accelerated Development With Increased Bone Mass and Skeletal Response to Loading Suggest Receptor Activity Modifying Protein-3 as a Bone Anabolic Target
Authors: Pacharne Suruchi , Livesey Matthew , Kadmiel Mahita , Wang Ning , Caron Kathleen M. , Richards Gareth O. , Skerry Tim M.
Published: January 2022

Knockout technologies provide insights into physiological roles of genes. Studies initiated into endocrinology of heteromeric G protein-coupled receptors included deletion of receptor activity modifying protein-3, an accessory protein that alters ligand selectivity of calcitonin and calcitonin-like receptors. Initially, deletion of Ramp3-/- appeared phenotypically silent, but it has emerged that mice have a high bone mass phenotype, and more subtle alterations to angiogenesis, amylin homeostasis, and a small proportion of the effects of adrenomedullin on cardiovascular and lymphatic systems. Here we explore in detail, effects of Ramp3-/- deletion on skeletal growth/development, bone mass and response of bone to mechanical loading mimicking exercise. Mouse pups lacking RAMP3 are healthy and viable, having accelerated development of the skeleton as assessed by degree of mineralisation of specific bones, and by microCT measurements. Specifically, we observed that neonates and young mice have increased bone volume and mineralisation in hindlimbs and vertebrae and increased thickness of bone trabeculae. These changes are associated with increased osteoblast numbers and bone apposition rate in Ramp3-/- mice, and increased cell proliferation in epiphyseal growth plates. Effects persist for some weeks after birth, but differences in gross bone mass between RAMP3 and WT mice lose significance in older animals although architectural differences persist. Responses of bones of 17-week old mice to mechanical loading that mimics effects of vigorous exercise is increased significantly in Ramp3-/- mice by 30% compared with WT control mice. Studies on cultured osteoblasts from Ramp3-/- mice indicate interactions between mRNA expression of RAMPs1 and 3, but not RAMP2 and 3. Our preliminary data shows that Ramp3-/- osteoblasts had increased expression β-catenin, a component of the canonical Wnt signalling pathway known to regulate skeletal homeostasis and mechanosensitivity. Given interactions of RAMPs with both calcitonin and calcitonin-like receptors to alter ligand selectivity, and with other GPCRs to change trafficking or ligand bias, it is not clear whether the bone phenotype of Ramp3-/- mice is due to alterations in signalling mediated by one or more GPCRS. However, as antagonists of RAMP-interacting receptors are growing in availability, there appears the likelihood that manipulation of the RAMP3 signalling system could provide anabolic effects therapeutically.
Comprehensive Evaluation for Protective Coatings: Optical, Electrical, Photoelectrochemical, and Spectroscopic Characterizations
Authors: Shen Xin , Yanagi Rito , Solanki Devan , Su Haoqing , Li Zhaohan , Xiang Cheng-Xiang , Hu Shu
Published: January 2022

Numerous efficient semiconductors suffer from instability in aqueous electrolytes. Strategies utilizing protective coatings have thus been developed to protect these photoabsorbers against corrosion while synergistically improving charge separation and reaction kinetics. Recently, various photoelectrochemical (PEC) protective coatings have been reported with suitable electronic properties to ensure low charge transport loss and reveal the fundamental photoabsorber efficiency. However, protocols for studying the critical figures of merit for protective coatings have yet to be established. For this reason, we propose four criteria for evaluating the performance of a protective coating for PEC water-splitting: stability, conductivity, optical transparency, and energetic matching. We then propose a flow chart that summarizes the recommended testing protocols for quantifying these four performance metrics. In particular, we lay out the stepwise testing protocols to evaluate the energetics matching at a semiconductor/coating/(catalyst)/liquid interface. Finally, we provide an outlook for the future benchmarking needs for coatings.
A Structural Equation Modeling Approach to Disentangling Regional-Scale Landscape Dynamics in Ghana
Authors: Peeling Julie A. , Singh Aditya , Judge Jasmeet
Published: January 2022

Land cover (LC) change is an integrative indicator of changes in ecosystems due to anthropogenic or natural forcings. There is a significant interest in the investigation of spatio-temporal patterns of LC transitions, and the causes and consequences thereof. While the advent of satellite remote sensing techniques have enhanced our ability to track and measure LC changes across the globe, significant gaps remain in disentangling specific factors that influence, or in certain cases, are influenced by, LC change. This study aims to investigate the relative influence of regional-scale bioclimatology and local-scale anthropogenic factors in driving LC and environmental change in Ghana. This analysis builds upon previous research in the region that has highlighted multiple drivers of LC change in the region, especially via drivers such as deforestation, urbanization, and agricultural expansion. It used regional-scale remotely sensed, demographic, and environmental data for Ghana across 20 years and developed path models on causal factors influencing LC transitions in Ghana. A two-step process is utilized wherein causal linkages from an exploratory factor analysis (EFA) are constrained with literature-based theoretical constructs to implement a regional-scale partial least squares path model (PLSPM). The PLSPM reveals complex interrelationships among drivers of LC change that vary across the geography of Ghana. The model suggests strong effects of local urban expansion on deforestation and vegetation losses in urban and peri-urban areas. Losses of vegetation are in turn related to increases in local heating patterns indicative of urban heat island effects. Direct effects of heat islands are however masked by strong latitudinal gradients in climatological factors. The models confirm that decreases in vegetation cover results in increased land surface albedo that is indirectly related to urban and population expansion. These empirically-estimated causal linkages provide insights into complex spatio-temporal variations in potential drivers of LC change. We expect these models and spatial data products to form the basis for detailed investigations into the mechanistic underpinnings of land cover dynamics across Ghana. These analyses are aimed at building a template for methods that can be utilized to holistically design spatially-disaggregated strategies for sustainable development across Ghana.
How to Promote the Agricultural Company Through Environmental Social Responsibility to Achieve Sustainable Production?
Authors: Huang Stanley Y. B. , Yu Chun-Chieh , Lee Yue-Shi
Published: January 2022

This survey employs the multilevel growth curve model to demonstrate how to promote the development of the company’s environmental innovation in agricultural companies specializing in the agricultural production and export of agricultural products to achieve sustainable production through environmental social responsibility and environmental engagement according to the engagement theory. The empirical data are collected 30 chief executive officers and their 90 supervisors of top management teams (TMTs) of Taiwanese agricultural companies in 2 months. The empirical results demonstrate that environmental social responsibility significantly influences the top management teams’ environmental engagement development, which in turn significantly influences the agricultural company’s environmental innovation. These empirical results can not only promote the sustainable production literature in the agricultural field but also help these agricultural companies implement environmental innovation to realize sustainable production of agricultural exports.
Financial Inclusion and Carbon Reduction: Evidence From Chinese Counties
Authors: Yang Zhenkai , Yu Lu , Liu Yinwei , Yin Zhichao , Xiao Zumian
Published: January 2022

With the improvement of inclusive financial system, China’s economy has made significant development and growth. It worth in-depth investigation on environmental impact of financial inclusion, since growing GDP usually accompanied by more intensive carbon emission. This paper aims to reveal whether financial inclusion contributes to the carbon reduction in China using county-level dataset. A fixed-effect panel regression approach is adopted to examine the impact of financial inclusion on county-level regional carbon emissions. The estimation results imply that financial inclusion plays an important role in reducing carbon emissions. The mediation effect analysis reveals two channels through which financial inclusion imposes negative impact on the level of regional carbon emissions. One is to elevate the carbon sequestration capacity by increasing vegetation coverage, and the other is to improve the industrial structure through enhanced financial support. In addition to being a bridge between economic opportunity and output, financial inclusion can also act as an effective measure for addressing climate change.
Variation in Bacterial Community Structure in Rhizosphere and Bulk Soils of Different Halophytes in the Yellow River Delta
Authors: Zhao Yinghan , Li Tian , Shao Pengshuai , Sun Jingkuan , Xu Wenjing , Zhang Zehao
Published: January 2022

Soil microorganisms play the important role in driving biogeochemical cycles. However, it is still unclear on soil microbial community characteristics and microbial driving mechanism in rhizosphere and bulk soils of different halophyte species. In this study, we analyzed bacterial communities in the rhizosphere and bulk soils of three typical halophytes in the Yellow River Delta, i.e., Phragmites communis, Suaeda salsa, and Aeluropus sinensis, by high-throughput sequencing. The contents of total carbon, total nitrogen, and available phosphorus in rhizosphere soils of the three halophytes were significantly higher than those in bulk soils, which suggested a nutrient enrichment effect of the rhizosphere. Rhizosphere soil bacterial α-diversity of P. communis was higher than that in bulk soil, whereas bacterial α-diversity in rhizosphere soil of S. salsa and A. sinensis was lower than those in bulk soil. The dominant bacterial phyla were Proteobacteria, Actinobacteria, Chloroflexi, and Bacteroidetes, which accounted for 31, 20.5, 16.3, and 10.3%, respectively. LDA effect size (LEfSe) analysis showed that the bacterial species with significant differences in expression abundance was obviously different in the rhizosphere and bulk soil of three halophytes. The principal component analysis (PCoA) showed that bacterial community composition was greatly different between rhizosphere and bulk soils of P. communis and S. salsa, while no difference in A. sinensis. Changed bacterial community composition was mainly ascribed to salinity in rhizosphere and bulk soils. Additionally, salinity was positively correlated with Bacteroidetes and negatively correlated with Actinobacteria and Acidobacteria. Our study clarified the variation in bacterial community structure between rhizosphere and bulk soils with soil physicochemical properties, which proved a biological reference to indicate the characteristics of saline and alkaline land.
PDE4B Proposed as a High Myopia Susceptibility Gene in Chinese Population
Authors: Zhao Fuxin , Chen Wei , Zhou Hui , Reinach Peter S. , Wang Yuhan , Juo Suh-Hang H. , Yang Zhenglin , Xue Anquan , Shi Yi , Liang Chung-Ling , Zeng Changqing , Qu Jia , Zhou Xiangtian
Published: January 2022

Myopia is the most common cause of refractive error worldwide. High myopia is a severe type of myopia, which usually accompanies pathological changes in the fundus. To identify high myopia susceptibility genes, DNA-pooling based genome-wide association analysis was used to search for a correlation between single nucleotide polymorphisms and high myopia in a Han Chinese cohort (cases vs. controls in discovery stage: 507 vs. 294; replication stage 1: 991 vs. 1,025; replication stage 2: 1,021 vs. 52,708). Three variants (rs10889602T/G, rs2193015T/C, rs9676191A/C) were identified as being significantly associated with high myopia in the discovery, and replication stage. rs10889602T/G is located at the third intron of phosphodiesterase 4B (PDE4B), whose functional assays were performed by comparing the effects of rs10889602T/T deletion of this risk allele on PDE4B and COL1A1 gene and protein expression levels in the rs10889602T/Tdel/del, rs10889602T/Tdel/wt, and normal control A549 cell lines. The declines in the PDE4B and COL1A1 gene expression levels were larger in the rs10889602T/T deleted A549 cells than in the normal control A549 cells (one-way ANOVA, p < 0.001). The knockdown of PDE4B by siRNA in human scleral fibroblasts led to downregulation of COL1A1. This correspondence between the declines in rs10889602 of the PDE4B gene, PDE4B knockdown, and COL1A1 protein expression levels suggest that PDE4B may be a novel high myopia susceptibility gene, which regulates myopia progression through controlling scleral collagen I expression levels. More studies are needed to determine if there is a correlation between PDE4B and high myopia in other larger sample sized cohorts.
Clinical Significance and Potential Role of LSM4 Overexpression in Hepatocellular Carcinoma: An Integrated Analysis Based on Multiple Databases
Authors: Chen Liang , Lin Yun-hua , Liu Guo-qing , Huang Jing-en , Wei Wei , Yang Zhong-hua , Hu Yi-ming , Xie Jia-heng , Yu Hong-zhu
Published: January 2022

Background: Hepatocellular carcinoma (HCC) is a solid tumor with high recurrence rate and high mortality. It is crucial to discover available biomarkers to achieve early diagnosis and improve the prognosis. The effect of LSM4 in HCC still remains unrevealed. Our study is dedicated to exploring the expression of LSM4 in HCC, demonstrating its clinical significance and potential molecular mechanisms.

Methods: Clinical information and LSM4 expression values of HCC were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Survival analysis and receiver operating characteristic (ROC) curve analysis were applied to evaluate the prognostic and diagnostic significance of LSM4. Calculating pooled standardized mean difference (SMD) and performing summary receiver operating characteristic (sROC) curve analysis to further determine its expression status and diagnostic significance. LSM4-related co-expressed genes (CEGs) were obtained and explored their clinical significance in HCC. LSM4-associated pathways were identified through Gene set enrichment analysis (GSEA).

Results: Up-regulated LSM4 was detected in HCC tissues (SMD = 1.56, 95% CI: 1.29–1.84) and overexpressed LSM4 had excellent distinguishing ability (AUC = 0.91, 95% CI: 0.88–0.93). LSM4 was associated with clinical stage, tumor grade, and lymph node metastasis status (p < 0.05). Survival analysis showed that high LSM4 expression was related to poor overall survival (OS) of HCC patients. Cox regression analysis suggested that high LSM4 expression may be an independent risk factor for HCC. We obtained nine up-regulated CEGs of LSM4 in HCC tissues, and six CEGs had good prognostic and diagnostic significance. GSEA analysis showed that up-regulated LSM4 was closely related to the cell cycle, cell replication, focal adhesion, and several metabolism-associated pathways, including fatty acid metabolism.

Conclusion: Overexpressed LSM4 may serve as a promising diagnostic and prognostic biomarker of HCC. Besides, LSM4 may play a synergistic effect with CEGs in promoting the growth and metastasis of HCC cells via regulating crucial pathways such as cell cycle, focal adhesion, and metabolism-associated pathways.
T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells
Authors: Kiekens Laura , Van Loocke Wouter , Taveirne Sylvie , Wahlen Sigrid , Persyn Eva , Van Ammel Els , De Vos Zenzi , Matthys Patrick , Van Nieuwerburgh Filip , Taghon Tom , Van Vlierberghe Pieter , Vandekerckhove Bart , Leclercq Georges
Published: January 2022

T-bet and Eomes are transcription factors that are known to be important in maturation and function of murine natural killer (NK) cells. Reduced T-BET and EOMES expression results in dysfunctional NK cells and failure to control tumor growth. In contrast to mice, the current knowledge on the role of T-BET and EOMES in human NK cells is rudimentary. Here, we ectopically expressed either T-BET or EOMES in human hematopoietic progenitor cells. Combined transcriptome, chromatin accessibility and protein expression analyses revealed that T-BET or EOMES epigenetically represses hematopoietic stem cell quiescence and non-NK lineage differentiation genes, while activating an NK cell-specific transcriptome and thereby drastically accelerating NK cell differentiation. In this model, the effects of T-BET and EOMES are largely overlapping, yet EOMES shows a superior role in early NK cell maturation and induces faster NK receptor and enhanced CD16 expression. T-BET particularly controls transcription of terminal maturation markers and epigenetically controls strong induction of KIR expression. Finally, NK cells generated upon T-BET or EOMES overexpression display improved functionality, including increased IFN-γ production and killing, and especially EOMES overexpression NK cells have enhanced antibody-dependent cellular cytotoxicity. Our findings reveal novel insights on the regulatory role of T-BET and EOMES in human NK cell maturation and function, which is essential to further understand human NK cell biology and to optimize adoptive NK cell therapies.
Longitudinal High-Throughput Sequencing of the T-Cell Receptor Repertoire Reveals Dynamic Change and Prognostic Significance of Peripheral Blood TCR Diversity in Metastatic Colorectal Cancer During Chemotherapy
Authors: Chen Yi-Tung , Hsu Hung-Chih , Lee Yun-Shien , Liu Hsuan , Tan Bertrand Chin-Ming , Chin Chia-Yin , Chang Ian Yi-Feng , Yang Chia-Yu
Published: January 2022

Colorectal cancer (CRC) is a major cause of cancer mortality and morbidity. Despite advances in chemotherapy and targeted therapy, unsustainable clinical benefit was noted due to recurrence and therapy resistance. The immune status of the cancer patient may affect the effectiveness of disease treatments. The dynamic change in the T-cell receptor (TCR) repertoire might be a clinical parameter for monitoring treatment responses. In this study, we aimed to determine the characteristics and clinical significance of the TCR repertoire in patients with unresectable metastatic colorectal cancer (mCRC). Herein, we comprehensively profile 103 peripheral blood samples from 20 healthy controls and 16 CRC patients with a follow-up of 98 to 452 days to identify hypervariable rearrangements of the TCRα and TCRβ repertoires using high-throughput sequencing. We found that TCRα repertoires, TCRβ repertoires, and CDR3 clonotypes were altered in mCRC patients compared with healthy controls. The diversity of TCR repertoires and CDR3 clonotypes decreased in most mCRC patients after therapy. Furthermore, compared with baseline TCR diversity, patients whose TCR diversity dropped considerably during therapy had better treatment responses, including lower CEA and CA19-9 levels and smaller tumor sizes. TCR baseline diversity was also significantly associated with partial response (PR) status (odds ratio: 5.29, p = 0.04). In conclusion, the present study demonstrated the association between dynamic changes in TCR diversity during chemotherapy and clinical outcomes as well as the potential utility of the TCR repertoire in predicting the prognosis of cancer treatment.
Neutrophil-Mediated Immunopathology and Matrix Metalloproteinases in Central Nervous System – Tuberculosis
Authors: Poh Xuan Ying , Loh Fei Kean , Friedland Jon S. , Ong Catherine W. M.
Published: January 2022

Tuberculosis (TB) remains one of the leading infectious killers in the world, infecting approximately a quarter of the world’s population with the causative organismMycobacterium tuberculosis(M. tb). Central nervous system tuberculosis (CNS-TB) is the most severe form of TB, with high mortality and residual neurological sequelae even with effective TB treatment. In CNS-TB, recruited neutrophils infiltrate into the brain to carry out its antimicrobial functions of degranulation, phagocytosis and NETosis. However, neutrophils also mediate inflammation, tissue destruction and immunopathology in the CNS. Neutrophils release key mediators including matrix metalloproteinase (MMPs) which degrade brain extracellular matrix (ECM), tumor necrosis factor (TNF)-α which may drive inflammation, reactive oxygen species (ROS) that drive cellular necrosis and neutrophil extracellular traps (NETs), interacting with platelets to form thrombi that may lead to ischemic stroke. Host-directed therapies (HDTs) targeting these key mediators are potentially exciting, but currently remain of unproven effectiveness. This article reviews the key role of neutrophils and neutrophil-derived mediators in driving CNS-TB immunopathology.
A Personalized Rituximab Retreatment Approach Based on Clinical and B-Cell Biomarkers in ANCA-Associated Vasculitis
Authors: Arnold Jack , Vital Edward M. , Dass Shouvik , Aslam Aamir , Rawstron Andy C. , Savic Sinisa , Emery Paul , Md Yusof Md Yuzaiful
Published: January 2022

Background

Time to relapse after rituximab for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is variable, and optimal retreatment strategy has remained unclear. In AAV following rituximab induction, the study objective was to evaluate clinical and B-cell predictors of relapse in order to develop a retreatment algorithm.

Methods

A retrospective observational study was conducted in 70 rituximab-treated ANCA-associated vasculitis patients followed up for over 10 years. Complete response (CR) was defined as Birmingham Vasculitis Activity Score v3.0 = 0. Retreatment was given on clinical relapse, defined as new features or worsening of persistent disease (not by biomarker status). Peripheral B-cell subsets were measured using highly sensitive flow cytometry. Predictors were tested using multivariable Cox regression.

Results

Median time to retreatment for cycles 1–5 were 84, 73, 67, 60, and 73 weeks. Over 467 patient-years follow-up, 158 relapses occurred in 60 patients; 16 (in 15 patients) were major (renal = 7, neurological = 4, ENT = 3, and respiratory = 2). The major-relapse rate was 3.4/100 patient-years. In multivariable analysis, concomitant immunosuppressant [HR, 0.48 (95% CI, 0.24–0.94)], achieving CR [0.24 (0.12–0.50)], and naïve B-cell repopulation at 6 months [0.43 (0.22–0.84)] were associated with longer time to relapse. Personalized retreatment using these three predictors in this cohort would have avoided an unnecessary fixed retreatment in 24% of patients. Area under the receiver operating characteristic for prediction of time to relapse was greater if guided by naïve B-cell repopulation than if previously evaluated ANCA and/or CD19+ cells return at 6 months had been used, 0.82 and 0.53, respectively.

Conclusion

Our findings suggest that all patients should be coprescribed oral immunosuppressant. Those with incomplete response or with absent naïve B cells should be retreated at 6 months. Patients with complete response and naïve repopulation should not receive fixed retreatment. This algorithm could reduce unnecessary retreatment and warrant investigation in clinical trials.