bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary biological data of Sahel wetland ecosystems in Burkina Faso: Implications for ecological health assessment
Authors: Kaboré Idrissa , Tampo Lallébila , Bancé Victor , Daboné Clément , Mano Komandan , Ayoro Halamoussa Joëlle , Ouéda Adama
Published: November 2022

Birds, amphibians, fish, and macroinvertebrates are useful indicators of ecological conditions and ensure considerable conservation value and tools for decision making in management of wetland ecosystems. However, the use of these organisms to monitor wetland ecosystems has rarely been explored in Western Africa. Whereas, we are currently facing to growing multiple anthropogenic pressures and climate warming that impact negatively our wetlands and the biodiversity. Notably, there is an urgent need of cost-effective tools for wetland ecosystems health assessment in Burkina Faso. In this study, we examined the taxonomic composition of birds, amphibians, fish, and macroinvertebrates and explored their potential use for monitoring wetland ecosystems. From our findings, measures of taxa composition and diversity respond to the gradients of anthropogenic alterations. Our results revealed that the highest diversity of fish and macroinvertebrates taxa was recorded in protected sites, whereas the lowest diversity was obtained in degraded sites. Additionally, the findings showed a strong and positive correlation between macroinvertebrates taxa and key water variables, whereas fish taxa were strongly correlated to xylal (deadwood) substrates. Most of bird’s species were recorded in tree-shrubs, and amphibians of protected wetlands were distinguished by identifying indicator taxa through indicator value index. African wetland ecosystems and biodiversity may be sustainably preserved through responsive monitoring programs of wetlands by limnologists.
PID control: Resilience with respect to controller implementation
Authors: Alfaro V. M. , Vilanova R.
Published: November 2022

One of the major drawbacks of the basic parallel formulations of a PID controller is the effects of proportional and derivative kick. In order to minimize these effects, modified forms of parallel controller structures such as PI-D and I-PD are usually considered in practice. In addition, there is a usual servo/regulation tradeoff regarding closed-loop control system operation. Appropriate tuning is needed for each situation. One way of focusing explicitly on load disturbance is by the appropriate selection of a controller equation. A gap is generated here between the conception of a tuning rule and its final application that may need deployment on different controller equations. There is no danger when we go from PI-D to I-PD as we just change reference processing. However, there will be a loss of performance. The potential loss of performance, depending on the final controller equations used, motivates the authors to introduce the idea of resilient PID tuning: minimize the effects of changing the controller equation on the achieved performance/robustness. Today, this can be seen as a complement to the well-known controller fragility concept. On the basis of this scenario, this paper motivates the analysis of a tuning rule from such a point of view and also emphasizes the benefits that a better process model may provide from such an aspect.
Neurocognitive function in patients with atrial fibrillation undergoing pulmonary vein isolation
Authors: Zwimpfer Leon , Aeschbacher Stefanie , Krisai Philipp , Coslovsky Michael , Springer Anne , Paladini Rebecca E. , Girod Marc , Hufschmid Janik , Knecht Sven , Badertscher Patrick , Beer Jürg H. , Bonati Leo H. , Zuern Christine S. , Roten Laurent , Reichlin Tobias , Sticherling Christian , Conen David , Osswald Stefan , Kühne Michael
Published: November 2022

Background

Atrial fibrillation (AF) is associated with cognitive dysfunction. However, neurocognitive function in AF patients undergoing pulmonary vein isolation (PVI) has not been well studied. The aim of this analysis is to compare neurocognitive function in patients who did or did not undergo PVI.

Materials and methods

We used data from the Swiss Atrial Fibrillation Cohort study (Swiss-AF), a prospective, observational, multicenter study in Switzerland. Patients with documented AF were enrolled and data of 1,576 patients without history of PVI and with complete information on PVI status and neurocognitive function were used. Information on PVI was collected at baseline and during 1 year of follow-up. Neurocognitive testing was performed at baseline and after 1 year of follow-up, using the Montreal Cognitive Assessment (MoCA), trail making test (TMT) A and B, digit symbol substitution test (DSST) and semantic fluency test (SFT). To investigate the association of PVI with neurocognitive function, we use propensity score matching (1:3) and inverse probability of treatment weighting (IPTW).

Results

The mean age of this population was 74 ± 8 years, 27.1% were women. Overall, 88 (5.5%) patients underwent PVI during 1 year of follow-up. Using ITPW (n = 1576), PVI was weakly associated with the MoCA score after adjusting for time since PVI, baseline MoCA score and other covariates (β (95%CI) 1.19 (0.05; 2.32), p = 0.04). In the propensity matched comparison (n = 352), there was no significant association between PVI and the MoCA score (β (95%CI) 1.04 (−0.19; 2.28), p = 0.1). There were no significant associations between PVI and cognitive function when using the TMT A and B, DSST or SFT independent of the method used.

Conclusion

In this population of AF patients, there was no consistent evidence of an association between PVI and neurocognitive function.

Clinical trial registration

[https://clinicaltrials.gov/], identifier [NCT02105844].
Predictors of adherence of enhanced external counterpulsation in patients with coronary heart disease after discharge: A mixed-methods study
Authors: Yin Yuhuan , He Qinli , Zhang Rong , Cheng Hu , Zhang Yiyin , Zhang Juxia
Published: November 2022

Background

Although enhanced external counter pulsation (EECP) has been included in the cardiac rehabilitation prescription for coronary heart disease (CHD) in China, because the total treatment duration of a course of EECP is 36–36 h, the average hospital stay of CHD patients is short, and the adherence after discharge remains unclear. The purpose of this study is to investigate the adherence to EECP in CHD patients after discharge, and analyze the related influencing factors.

Methods

A retrospective mixed method study combining qualitative and quantitative methods. Quantitative component included CHD patients who had received EECP treatment between March 2020 and August 2021. The qualitative component included in-depth interviews with patients who did not adhere to EECP after discharge. Binary Logistic regression was used to analyze the predictors of EECP adherence after discharge. In-depth interviews with patients were conducted to explore the reasons for dropping out of the EECP after discharge.

Results

Among 1,304 patients, only 24.23% adhered to EECP treatment after discharge. Binary logistic regression results showed that patients with disease duration < 2 years (OR = 3.13, 95%CI: 2.31–4.24), high school or below (OR = 2.81, 95%CI: 1.98–4.01), distance between residence and hospital more than 20km (OR = 2.08, 95%CI: 1.47–2.96), age over 60 (OR = 2.00, 95%CI: 1.46–2.74), female (OR = 1.64, 95%CI: 1.78–2.29), and angina pectoris (OR = 1.65, 95%CI: 1.16–2.34) were more likely to not adhere to EECP treatment after discharge. However, patients with monthly family income over 8000¥ (OR = 0.46, 95%CI: 0.28–0.75) were more likely to adhere to EECP treatment after discharge than those with household monthly income below 4,000¥. In the qualitative results, the reasons why patients do not adhere to EECP after discharge mainly include insufficient understanding, restricted objective conditions and psychosocial factors.

Conclusions

The adherence of CHD patients to EECP treatment after discharge was poor. It is necessary to develop effective intervention measures, such as brochures or videos to improve patients' understanding of the importance of adherence to EECP treatment after discharge. In addition, offering EECP treatment during off-hours and weekends may also improve adherence in more young patients.
The role of miRNAs in the diagnosis of stable atherosclerosis of different arterial territories: A critical review
Authors: Teixeira Ana Rita , Ferreira Vera Vaz , Pereira-da-Silva Tiago , Ferreira Rui Cruz
Published: November 2022

Atherosclerotic disease is a major cause of morbidity and mortality worldwide. Atherosclerosis may be present in different arterial territories and as a single- or multi-territorial disease. The different phenotypes of atherosclerosis are attributable only in part to acquired cardiovascular risk factors and genetic Mendelian inheritance. miRNAs, which regulate the gene expression at the post-transcriptional level, may also contribute to such heterogeneity. Numerous miRNAs participate in the pathophysiology of atherosclerosis by modulating endothelial function, smooth vascular cell function, vascular inflammation, and cholesterol homeostasis in the vessel, among other biological processes. Moreover, miRNAs are present in peripheral blood with high stability and have the potential to be used as non-invasive biomarkers for the diagnosis of atherosclerosis. However, the circulating miRNA profile may vary according to the involved arterial territory, considering that atherosclerosis expression, including the associated molecular phenotype, varies according to the affected arterial territory. In this review, we discuss the specific circulating miRNA profiles associated with atherosclerosis of different arterial territories, the common circulating miRNA profile of stable atherosclerosis irrespective of the involved arterial territory, and the circulating miRNA signature of multi-territorial atherosclerosis. miRNAs may consist of a simple non-invasive method for discriminating atherosclerosis of different arterial sites. The limitations of miRNA profiling for such clinical application are also discussed.
Low-density lipoprotein-cholesterol lowering effect of a nutraceutical regimen with or without ezetimibe in hypercholesterolaemic patients with statin intolerance
Authors: Ward Natalie C. , Reid Christopher M. , Watts Gerald F.
Published: November 2022

Background

Statins are the most widely prescribed medication to lower low-density lipoprotein cholesterol (LDL-c). However, a significant portion of patients are unable to tolerate them due to side effects, most commonly muscle related. Nutraceuticals, natural plant derivatives with lipid-lowering properties, may provide an alternative to lower LDL-c in these patients.

Aims

To investigate whether a nutraceutical regimen, either alone or in combination with ezetimibe, can lower LDL-c in patients with hypercholesterolemia who are intolerant to statins.

Methods

Participants were recruited into a double-blind, randomized, placebo-controlled intervention study. Treatments were (i) placebo, (ii) nutraceutical (500 mg berberine, 200 mg red yeast rice (RYR), 2 g plant sterols)/daily, (iii) ezetimibe (10 mg)/daily, or (iv) the combination of nutraceutical and ezetimibe/daily. At baseline and week 8, all participants provide a fasting blood sample for assessment of lipid profile and safety bloods.

Results

Fifty participants were randomized, with 44 completing the treatment period. Following adjustment for baseline levels and compared with placebo, LDL-c was significantly reduced (all p < 0.0001) with ezetimibe (−1.02 mmol/L), nutraceutical (−1.15 mmol/L) and the nutraceutical and ezetimibe combination (−1.92 mmol/L). Non-HDL cholesterol was significantly reduced (all p < 0.0001) with ezetimibe (−1.29 mmol/L), nutraceutical (−1.37 mmol/L) and the nutraceutical and ezetimibe combination (−2.18 mmol/L). Remnant cholesterol and triglycerides was significantly reduced with the nutraceutical and ezetimibe combination (p = 0.018).

Conclusion

A nutraceutical regimen (berberine, RYR and plant sterols) and ezetimibe independently and additively lower LDL-c in patients with hypercholesterolemia who are intolerant to statins.
Numerical study of the risk of thrombosis in the left atrial appendage of chicken wing shape in atrial fibrillation
Authors: Yang Jun , Song Chentao , Ding Huirong , Chen Mu , Sun Jian , Liu Xiaohua
Published: November 2022

Atrial fibrillation (AF) is a common and life-threatening disease. For the patients with AF, more than 90% of the thrombi are formed in the left atrial appendage (LAA), thrombus dislodgement can cause vascular embolism, making them is becoming a high-risk group for stroke. Therefore, identifying the patients with high risk of thrombosis is crucial for advanced stroke warning. To better investigate the mechanism behind thrombus formation in the LAA, this study reconstructed the 3-D Left Atrium (LA) models of six AF volunteer patients by corresponding Computed Tomography (CT) images. Combine the advantages of Computational Fluid Dynamics (CFD), the blood flow field in LA both in AF and sinus heart rate states were studied. The risk of thrombus was evaluated based on the blood viscosity, shear rate thrombus prediction model and Time Average Wall Shear Stress (TAWSS), Oscillatory Shear Index (OSI), and Relative Residence Time (RRT) values. The results showed that the left atrium had lower blood flow velocity and TAWSS values at the LAA in both AF and sinus rhythm, thus the LAA is the most thrombogenic region in the LA. Besides, the RRT value of LAA was generally higher in AF than in sinus rhythm. Therefore, AF carries a higher risk of thrombosis.
Prolyl-hydroxylase inhibitor-induced regeneration of alveolar bone and soft tissue in a mouse model of periodontitis through metabolic reprogramming
Authors: Zebrowitz Elan , Aslanukov Azamat , Kajikawa Tetsuhiro , Bedelbaeva Kamila , Bollinger Sam , Zhang Yong , Sarfatti David , Cheng Jing , Messersmith Phillip B. , Hajishengallis George , Heber-Katz Ellen
Published: November 2022

Bone injuries and fractures reliably heal through a process of regeneration with restoration to original structure and function when the gap between adjacent sides of a fracture site is small. However, when there is significant volumetric loss of bone, bone regeneration usually does not occur. In the present studies, we explore a particular case of volumetric bone loss in a mouse model of human periodontal disease (PD) in which alveolar bone surrounding teeth is permanently lost and not replaced. This model employs the placement of a ligature around the upper second molar for 10 days leading to inflammation and bone breakdown and closely replicates the bacterially induced inflammatory etiology of human PD to induce bone degeneration. After ligature removal, mice are treated with a timed-release formulation of a small molecule inhibitor of prolylhydroxylases (PHDi; 1,4-DPCA) previously shown to induce epimorphic regeneration of soft tissue in non-regenerating mice. This PHDi induces high expression of HIF-1α and is able to shift the metabolic state from OXPHOS to aerobic glycolysis, an energetic state used by stem cells and embryonic tissue. This regenerative response was completely blocked by siHIF1a. In these studies, we show that timed-release 1,4-DPCA rapidly and completely restores PD-affected bone and soft tissue with normal anatomic fidelity and with increased stem cell markers due to site-specific stem cell migration and/or de-differentiation of local tissue, periodontal ligament (PDL) cell proliferation, and increased vascularization. In-vitro studies using gingival tissue show that 1,4-DPCA indeed induces de-differentiation and the expression of stem cell markers but does not exclude the role of migrating stem cells. Evidence of metabolic reprogramming is seen by the expression of not only HIF-1α, its gene targets, and resultant de-differentiation markers but also the metabolic genes Glut-1, Gapdh, Pdk1, Pgk1 and Ldh-a in the periodontal tissue.
A novel nomogram containing efficacy indicators to predict axillary pathologic complete response after neoadjuvant systemic therapy in breast cancer
Authors: Shi Wenjie , Huang Xiaofeng , Wang Ye , Wan Xinyu , He Jinzhi , Xu Yinggang , Zhang Weiwei , Chen Rui , Xu Lu , Zha Xiaoming , Wang Jue
Published: November 2022

Background

Neoadjuvant systemic therapy (NST) could make some clinically node-positive (cN+) breast cancer patients achieve axillary pathologic complete response (pCR). This study aimed to identify the patients who are likely to achieve axillary pCR and help surgeons make surgical decisions on the axilla.

Methods

The cN+ breast cancer patients who received NST from 2015 to 2021 at The First Affiliated Hospital of Nanjing Medical University were enrolled. Univariate and multivariate logistic regression analyses were performed, and a nomogram was constructed based on the results of multivariate logistic regression analysis to predict the probability of axillary pCR and validated.

Results

The axillary pCR was achieved in 208 (38.7%) patients. Patients who had a higher radiological response rate of breast tumor (P = 0.039), smaller longest diameter of positive node after NST (P = 0.028), ER-negative status (P = 0.006), HER2-positive status (P = 0.048) and breast pCR (P < 0.001) were more likely to achieve axillary pCR. The nomogram had an area under the receiver operating characteristic curve (AUC) of 0.792 (95% CI: 0.744–0.839), and the calibration curve showed good agreement.

Conclusion

A nomogram was constructed to predict the axillary pCR of cN+ patients receiving NST based on baseline and efficacy indicators to assist surgeons in making surgical decisions on the axilla.
A spatial agent-based model for hydraulic fracturing water distribution
Authors: Lin Tong , Lin Zhulu , Lim Siew Hoon , Jia Xinhua , Chu Xuefeng
Published: November 2022

Agent-based modeling (ABM) has been employed to understand and capture the complexity of the coupled human-nature processes in water resource systems. One of the challenges is to model human decisions in the coupled human and natural systems. Hydraulic fracturing water uses were distributed through a depot-based water allocation system in the Bakken region of western North Dakota, United States. In this study, a spatially explicit ABM was developed to simulate this unique water allocation system. In the ABM, institution theory was used to model the State’s regulatory policies and procedures, while evolutionary programming was employed to allow the water-depot owners (or agents) to select appropriate strategies when applying for water permits. Cognitive maps simulated the water-depot agents’ ability and willingness to compete for more water sales. All agents had their influence boundaries that restricted their competitive behavior toward their neighbors, but not for non-neighboring agents. The decision-making process was constructed and parameterized with both quantitative and qualitative information. The ABM was calibrated against real-world water-use data, and the calibration results showed that the spatial ABM performed well in simulating the total number of water depots as well as the locations and water uses of water depots at the county level. By linking institution theory, evolutionary programming, and cognitive maps, our study exhibited a new exploration of modeling the highly complex dynamics of the decision-making process involved in coupled human-nature water resource systems.
Low-intensity electromagnetic field as a new engineering oriented bioaugmentation strategy for anammox granules
Authors: Wang Zhibin , Liu Pengpeng , Zhou Jing , Ismail Sherif , Ahmad Shakeel , Awad Hanem M. , Ni Shou-Qing
Published: November 2022

Improving the relative abundance of bacteria and their activity is still the basis for the efficient operation of anammox process. Here, biomagnetic effect was used to promote anammox granules. Batch test results show that the application of an electromagnetic field (EMF) with a strength of 0.09 μT increased the nitrogen removal performance of anammox by 32.44% while higher strength EMF of 0.20 and 0.25 μT inhibited the activity of anammox bacteria. Long-term experiment indicated that the addition of EMF with a strength of 0.09 μT greatly improved nitrogen removal performance of the granular sludge, especially the total nitrogen removal performance increased by 15.3%. After 120 days of reactor operation, the nitrogen loading rate was increased to 6.4 kg N/m3/d, and the total nitrogen removal rate of the reactors with and without EMF addition reached 4.92 kg N/m3/d and 4.25 kg N/m3/d, respectively. Throughout the experiment, the removal rate of NH4+-N and NO2−-N of anammox reactor with 0.09 μT EMT addition was always higher than that without EMF addition. The high-throughput sequencing analysis showed that the proportion of Candidatus Brocadia in reactors with and without EMF addition were 21.3% and 15.8%, respectively. The application of EMF with an intensity of 0.09 μT increased the relative abundance of the main anammox bacteria. 70 kos were enriched under EMF conditions, including ko00780 (Biotin metabolism), ko00540 (Lipopolysaccharide biosynthesis), ko00590 (Arachidonic acid metabolism). 51 kos like ko03030 (DNA replication) decreased after EMF addition. This study demonstrates the feasibility of EMF to promote anammox and expands the application of EMF in wastewater treatment.
Synthesis of porous materials by the modification of coal fly ash and its environmentally friendly use for the removal of heavy metals from wastewater
Authors: Hussain Zawar , Zhang Hao , Chang Na , Wang Haitao
Published: November 2022

Wastewater is a complex mixture of many pollutants, where the high-risk pollutants are heavy metals (HMs) in industrial wastewater due to their difficult removal. In this study, the waste CFA was used as the main raw material for production of new innovated flocculants porous particles by modification of coal fly ash (CFA) using a multi-step base–acid–base (NaOH–HCl–NaOH) modification method. The morphological structure and elemental composition of the prepared MCFA were analyzed through characterization analysis, i.e., SEM, EDX, FT-IR, BET, XPS, and XRD. Results found that the surface area of the flocculant particles of MCFA was increased from 5.241 to 32.011 m2/g, which increased the adsorption process of HMs (Mn2+, Cu2+, Ni2+, and Pb2+). The maximum removal efficiencies (Re %) of MCFA for Mn2+, Cu2+, Ni2+, and Pb2+ were recorded at 94.26%, 95.88%, 71.04%, and 99.91%, respectively. The Freundlich isotherm model was fitted for the adsorption process, and the maximum adsorption amounts of MCFA for Mn2+, Cu2+, Ni2+, and Pb2+ were 558.9219, 0.4341, 210.9737, and 12.1957 mg/g, respectively. Moreover, the kinetic model indicated that physicochemical adsorption occurred between the adsorbate materials and the adsorbent.
ESG performance, investors’ heterogeneous beliefs, and cost of equity capital in China
Authors: Tang Hua
Published: November 2022

Previous studies on the relationship between environmental, social and governance (ESG) information disclosure and cost of equity (COE) have found mixed results. They conclude that this relationship may be affected by some attributes of the company inside. In this study, we examine whether investors’heterogeneous beliefs moderates the relationship between ESG performance and COE. Our sample starts with ESG-rating firms included in Huazheng index of the Wind China financial database (WIND) for years 2015–2020. We collect financial information and relevant data from the China Stock Market and Accounting Research database (CSMAR). Using a two-way fixed effect multiple regression model, we report a negative moderate effect of both ESG performance on COE. We also find that COE Is higher when the firm financing constraints increase. Investors’heterogeneous beliefs with a lower (rather than higher) level tends to pay close attention from ESG performance by stakeholders and financing constraints decreases, which then leads to the reduction of investors’ expected risk. We therefore conclude that firms that manage actions on ESG issues have a better choices of release investors disagreements which in turn reduces their equity financing costs.
RTS,S vaccination is associated with reduced parasitemia and anemia among children diagnosed with malaria in the outpatient department of a district hospital in rural Malawi
Authors: Todd Jacob L. , Topazian Hillary M. , Zulu Madalitso , Mafunga Pilirani , Mapanje Clement , Kaphatika James G. , Chagomerana Maganizo B. , Hoffman Irving , Juliano Jonathan J. , Mvalo Tisungane
Published: November 2022

The RTS,S/AS01 malaria vaccine was recently approved by the World Health Organization, but real-world effectiveness is still being evaluated. We measured hemoglobin concentration and parasite density in vaccinated and unvaccinated children who had been diagnosed with malaria by rapid diagnostic test (mRDT) in the outpatient department of a rural hospital in Malawi. Considering all mRDT positive participants, the mean hemoglobin concentration among unvaccinated participants was 9.58 g/dL. There was improvement to 9.82 g/dL and 10.36 g/dL in the 1 or 2 dose group (p = 0.6) and the 3 or 4 dose group (p = 0.0007), respectively. Among a microscopy positive subset of participants, mean hemoglobin concentration of unvaccinated participants was 9.55 g/dL with improvement to 9.82 g/dL in the 1 or 2 dose group (p = 0.6) and 10.41 g/dL in the 3 or 4 dose group (p = 0.003). Mean parasite density also decreased from 115,154 parasites/μL in unvaccinated children to 87,754 parasites/μL in children who had received at least one dose of RTS,S (p = 0.04). In this study population, vaccination was associated with significant improvements in both hemoglobin concentration and parasite density in the setting of real-world administration of the RTS,S/AS01 vaccine.
Neontological and paleontological congruence in the evolution of Podocarpaceae (coniferales) reproductive morphology
Authors: Leslie Andrew B. , Benson Roger B. J.
Published: November 2022

Introduction

Podocarpaceae are a diverse, primarily tropical conifer family that commonly produce large leaves and highly reduced, fleshy seed cones bearing large seeds. These features may result from relatively recent adaptation to closed-canopy angiosperm forests and bird-mediated seed dispersal, although determining precisely when shifts in leaf and seed cone morphology occurred is difficult due to a sparse fossil record and relatively few surviving deep lineages.

Methods

We compare the fossil record of Podocarpaceae with results from ancestral state reconstruction methods and correlated character models using neontological data and a previously published molecular time-tree.

Results

Ancestral state reconstructions suggest that small leaves, small seeds, and multi-seeded cones are ancestral in crown Podocarpaceae, with reduced cones bearing few seeds appearing in the Early Cretaceous and the correlated evolution of large leaves and large seeds occurring from the Late Cretaceous onwards. The exact timing of these shifts based on neontological data alone are poorly constrained, however, and estimates of leaf and seed size are imprecise.

Discussion

The fossil record is largely congruent with results based on the molecular time-tree, but provide important constraints on the range of leaf and seed sizes that were present in Cretaceous Podocarpaceae and the time by which changes in cone morphology and seed size likely occurred. We suggest in particular that reduced seed cones appeared in the Early Cretaceous and are linked to the contemporaneous diversification of small bodied avialans (birds), with shifts to larger seed sizes occurring after the Cretaceous in association with the spread of closed-canopy angiosperm forests.
Case report: Identification of a frameshift mutation in GC enrichment and the GCC repeat region of the androgen insensitivity receptor (AR) gene in a patient with complete androgen insensitivity syndrome by whole-exome sequencing (WES) combined with specific PCR and deep sequencing
Authors: He Xiaojing , Ma Qingya , Zhang Qiaoli , Hong Xutao , Qi Ming , Li Yongkai , Li Xiaodong
Published: November 2022

Background: Androgen insensitivity syndrome (AIS) is an X-linked recessive hereditary disease caused due to a reduced or absent function of the androgen receptor (AR) protein encoded by the AR gene (OMIM-Gene# 313,700). Genetic testing is important in the diagnosis, clinical management, and prevention of AIS (MIM# 300,068). The AR (HGNC: 644) pathogenic variant detection rate ranges from 65% to 95% for patients with complete AIS (CAIS) and 40%–45% for patients with partial androgen insensitivity syndrome (PAIS). Identification of a pathogenic mutation in the AR confirms the diagnosis of AIS, especially in the milder forms that may have a phenotypic overlap with other disorders of sex development. Improvement of the molecular diagnostic rate of AIS is urgently required in clinical practice. We reported the results of the molecular diagnosis of a patient with CAIS who failed previously in either the traditional Sanger sequencing or next-generation sequencing (NGS). Using whole-exome sequencing (WES) combined with a special polymerase chain reaction (PCR) and deep sequencing, we successfully identified a pathogenic variant, a hemizygous mutation (c.1395-1396insGA), in the GC-enriched and unstable GCC repeat regions of the AR gene of the proband.

Conclusion: The results may be advantageous for the improvement of the detection rate of AIS, as well as other inherited disorders whose disease-causing genes contain GC-enriched and unstable GCC repeat regions.
Cancer-associated fibroblast-related gene signatures predict survival and drug response in patients with colorectal cancer
Authors: Zhang Lei , Xu Chao , Wang Si-Han , Ge Qin-Wen , Wang Xiao-Wei , Xiao Pan , Yao Qing-Hua
Published: November 2022

Background: Cancer-associated fibroblasts (CAFs) play an important role in the tumorigenesis, immunosuppression and metastasis of colorectal cancer (CRC), and can predict poor prognosis in patients with CRC. The present study aimed to construct a CAFs-related prognostic signature for CRC.

Methods: The clinical information and corresponding RNA data of CRC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Estimation of STromal and Immune cells in MAlignant Tumor tissues (ESTIMATES) and xCell methods were applied to evaluate the tumor microenvironment infiltration from bulk gene expression data. Weighted gene co-expression network analysis (WGCNA) was used to construct co-expression modules. The key module was identified by calculating the module-trait correlations. The univariate Cox regression and least absolute shrinkage operator (LASSO) analyses were combined to develop a CAFs-related signature for the prognostic model. Moreover, pRRophetic and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms were utilized to predict chemosensitivity and immunotherapy response. Human Protein Atlas (HPA) databases were employed to evaluate the protein expressions.

Results: ESTIMATES and xCell analysis showed that high CAFs infiltration was associated with adverse prognoses. A twenty-gene CAFs-related prognostic signature (CAFPS) was established in the training cohort. Kaplan-Meier survival analyses reveled that CRC patients with higher CAFs risk scores were associated with poor prognosis in each cohort. Univariate and multivariate Cox regression analyses verified that CAFPS was as an independent prognostic factor in predicting overall survival, and a nomogram was built for clinical utility in predicting CRC prognosis. Patients with higher CAFs risk scores tended to not respond to immunotherapy, but were more sensitive to five conventional chemotherapeutic drugs.

Conclusion: In summary, the CAFPS could serve as a robust prognostic indicator in CRC patients, which might help to optimize risk stratification and provide a new insight into individual treatments for CRC.
Lactate regulators contribute to tumor microenvironment and predict prognosis in lung adenocarcinoma
Authors: Shang Shipeng , Wang Mi-zhou , Xing Zhiyuan , He Ningning , Li Shangyong
Published: November 2022

Background

Lactic acid, as a product of glycolysis, increases tumor cell migration and the invasion of tumor cells in the tumor microenvironment. Besides this, lactic acid promotes the expression of programmed death-1 expression (PD-1) in regulatory T cells, which could cause the failure of PD-1 blockade therapy. However, the implications of lactic acid in the tumor microenvironment of lung adenocarcinoma (LUAD) remain largely unclear.

Methods

We performed unsupervised consensus clustering to identify lactic-associated subtypes using expression profile of lactate regulators in LUAD. Differentially expressed genes (DEGs) associated with lactic-associated subtypes was used to construct lactate signature (LaSig) using LASSO regression algorithm. Immune infiltration analysis was conducted by ESTIMATER and drug sensitivity was estimated by R package called “pRRophetic”. The difference between two groups was calculated using Wilcox rank sum test and correlation analysis was calculated using Pearson correlation coefficient.

Results

In this study, we evaluated DNA methylation and the mutation frequency of lactate regulators and found lactate regulators showed low mutation frequency in the TCGA-LUAD cohort, except TP53. At the RNA level, the expression level of lactate regulators was significantly associated with the immune cell component. In particular, expression of LDHA was positively correlated with CD4 T cell, CD8 T cell, M1 macrophages, and the enrichment score of multiple immune pathways. Two clusters were defined using the gene expression level of lactate regulators, and LDHA was significantly upregulated in cluster 1 with poor overall survival. A lactate signature (LaSig) had a robust performance in predicting the survival rate and immunotherapy response of LUAD patients. Moreover, patients in the high LaSig group may be more likely to benefit from these drugs (Cisplatin, Erlotinib, Gemcitabine, and Vinblastine) than those in the low LaSig group.

Conclusion

In summary, our study explores the role of lactate regulators in guiding the clinical treatment of lung adenocarcinoma and provides additional help to supplement traditional molecular subtypes.
Applications of single-cell RNA sequencing in atopic dermatitis and psoriasis
Authors: Xia Dengmei , Wang Yiyi , Xiao Yue , Li Wei
Published: November 2022

Single-cell RNA sequencing (scRNA-seq) is a novel technology that characterizes molecular heterogeneity at the single-cell level. With the development of more automated, sensitive, and cost-effective single-cell isolation methods, the sensitivity and efficiency of scRNA-seq have improved. Technological advances in single-cell analysis provide a deeper understanding of the biological diversity of cells present in tissues, including inflamed skin. New subsets of cells have been discovered among common inflammatory skin diseases, such as atopic dermatitis (AD) and psoriasis. ScRNA-seq technology has also been used to analyze immune cell distribution and cell-cell communication, shedding new light on the complex interplay of components involved in disease responses. Moreover, scRNA-seq may be a promising tool in precision medicine because of its ability to define cell subsets with potential treatment targets and to characterize cell-specific responses to drugs or other stimuli. In this review, we briefly summarize the progress in the development of scRNA-seq technologies and discuss the latest scRNA-seq-related findings and future trends in AD and psoriasis. We also discuss the limitations and technical problems associated with current scRNA-seq technology.
Sustained viral response and relapse after discontinuation of oral antiviral drugs in HBeAg-positive patients with chronic hepatitis B infection
Authors: Sun Fangfang , Li Zhenhua , Hu Leiping , Deng Wen , Jiang Tingting , Wang Shiyu , Bi Xiaoyue , Lu Huihui , Yang Liu , Lin Yanjie , Zeng Zhan , Shen Ge , Liu Ruyu , Chang Min , Wu Shuling , Gao Yuanjiao , Hao Hongxiao , Xu Mengjiao , Chen Xiaoxue , Zhang Lu , Lu Yao , Dong Jianping , Xie Yao , Li Minghui
Published: November 2022

Objective

To investigate the sustained virological response and relapse in chronic hepatitis B (CHB) patients with hepatitis B e antigen (HBeAg) positive after stopping oral antiviral drugs, and to monitor the disease progression and the incidence of adverse events such as liver cirrhosis and hepatocellular carcinoma.

Methods

This is a prospective observational study. Patients who continued nucleos(t)ide analogue (NA) treatment after achieving HBeAg seroconversion for more than 3 years were enrolled. After signing the informed consent form, patients stopped NA treatment and received follow-up. During the follow-up, the antiviral treatment information of the patients was collected, and the follow-up observation was carried out every 3 months since the enrollment. We monitored the virological indexes, liver and kidney function, serology and liver imaging during follow-up. The purpose of this study was to explore the sustained virological response rate, HBV DNA recurrence rate, clinical relapse rate and the related factors after drug withdrawal.

Results

A total of 82 patients were enrolled, including 42 males (51.22%) and 40 females (48.78%), with a median age of 34.00 (31.00, 37.25) years. All enrolled patients were followed up for 1 year. At the end of the follow-up, 36.59% (30/82) of patients had sustained virological response, 63.41% (52/82) of patients had HBV DNA reactivation, 17.07% (14/82) of patients had clinical relapse, and 10.98% (9/82) of patients had HBeAg reversion. During the follow-up, there were no adverse events such as liver cirrhosis and hepatocellular carcinoma. The median level of hepatitis B surface antigen (HBsAg) in patients with sustained virological response was lower than that in patients with HBV DNA reactivation (2.92 vs.3.18 log10IU/ml, Z=-1.492/P=0.136), and the median level of baseline HBsAg in patients with HBV DNA reactivation was lower than that in patients with clinical relapse (3.01 vs.3.45 log10IU/mL, Z=-1.795/P=0.073), but the difference was not significant. There was no significant statistical difference between patients with sustained virological response and HBV DNA reactivation of the median total treatment time [69.50 (56.25, 86.00) vs.62.50 (44.00, 88.50) months, Z=-0.689/P=0.491], and the consolidation treatment time [41.50 (36.75, 54.75) vs.40.50 (36.00, 53.75) months, Z=-0.419/P=0.675].

Conclusion

The sustained virological response rate of HBeAg positive CHB patients after stopping oral antiviral treatment is lower, and it is more common in patients with lower HBsAg levels. Patients still need to be closely monitored after stopping NA therapy.
BMAL1/FOXA2-induced rhythmic fluctuations in IL-6 contribute to nocturnal asthma attacks
Authors: Tang Lingling , Liu Li , Sun Xianhong , Hu Po , Zhang Hui , Wang Bohan , Zhang Xiaona , Jiang Jinjin , Zhao Xia , Shi Xiaolu
Published: November 2022

The circadian clock is closely associated with inflammatory reactions. Increased inflammatory cytokine levels have been detected in the airways of nocturnal asthma. However, the mechanisms that contribute to the nocturnal increase in inflammatory responses and the relationship with circadian clock remain unknown.

Methods

Inflammatory cytokine levels were measured in asthma patients with and without nocturnal symptoms. Allergic airway disease was induced in mice by ovalbumin (OVA), and different periods of light/dark cycles were used to induce circadian rhythm disorders. Serum shock was used to stimulate the rhythmic expression in human bronchial epidermal cells (16HBE). The expression and oscillation of circadian clock genes and inflammatory cytokines in 16HBE cells subjected to brain and muscle ARNT-like protein-1 (BMAL1) and Forkhead Box A2 (FOXA2) knockdown and treatment with a FOXA2 overexpression plasmid were assessed.

Results

Serum IL-6 was found to be significantly higher in asthmatic patients with nocturnal symptoms than those without nocturnal symptoms. The OVA-induced asthma model with a circadian rhythm disorder and 16HBE cells treated with serum shock showed an increase in IL-6 levels and a negative correlation with BMAL1 and FOXA2. The knockdown of BMAL1 resulted in a lower correlation between IL-6 and other rhythm clock genes. Furthermore, knockdown of the BMAL1 and FOXA2 in 16HBE cells reduced the expression and rhythmic fluctuations of IL-6.

Conclusions

Our findings suggest that there are increased IL-6 levels in nocturnal asthma resulting from inhibition of the BMAL1/FOXA2 signalling pathway in airway epithelial cells.
Dysregulation of iron metabolism modulators in virologically suppressed HIV-infected patients
Authors: Garrido-Rodríguez Vanesa , Álvarez-Ríos Ana Isabel , Olivas-Martínez Israel , Pozo-Balado María del Mar , Bulnes-Ramos Ángel , Leal Manuel , Pacheco Yolanda María
Published: November 2022

Background

Iron metabolism plays an essential role in cellular functions. Since virologically suppressed chronic HIV-infected subjects under effective antiretroviral treatment (ART) exhibit a persistent immune dysfunction that leads to comorbidities, iron homeostasis may be relevant in this context. We aimed to explore iron metabolism in virologically suppressed chronic HIV infected subjects under a successful ART.

Methods

In this retrospective study, traditional iron metabolism biomarkers (total iron, ferritin, transferrin, and transferrin saturation index), as well as soluble transferrin receptor (sTfR), hepcidin, and inflammatory markers were determined in virologically suppressed chronic HIV-infected subjects under at least 2 years of ART (HIV) who also had >350 CD4-T-cells/mm3 (N=92) from Spain. As controls, we collected non-HIV age-matched healthy donors (Young, N=25) and elderly subjects (>65 years old; Elderly; N=25). Additionally, an external group of non-HIV patients with ferritin<50 ng/mL diagnosed with absolute iron deficiency (Ferropenic group; N=84) was included. Comparisons between groups were performed using Kruskal-Wallis or Mann-Whitney U-tests, while associations between variables were explored by Spearman’s rho correlation coefficient.

Results

We selected samples from HIV-infected subjects (aged 42[34-47], 95% males), young age-matched (aged 40[30-58], 60% males), and elderly controls (aged 82[78-88], 100% males). Compared to both healthy (Young and Elderly) groups, HIV exhibited decreased iron, transferrin saturation, and sTfR, and increased ferritin, but similar hepcidin levels. Notably, associations between sTfR and iron (Young, r=-0.587, p=0.002; Elderly, r=-0.496, p=0.012) or transferrin saturation index (Young, r=-0.581, p=0.002; Elderly, r=-0.489, p=0.013) were negative in both controls while positive in HIV (r=0.464, p<0.0001 and r=0.421, p<0.0001, respectively). Moreover, the expected negative correlation between hepcidin and sTfR, observed in controls (Young, r=-0.533, p=0.006; Elderly, r=-0.473, p=0.017), was absent in HIV (r=0.082; p=0.438). Interestingly, the HIV inflammatory profile differed from the Elderly one, who despite their inflammaging-related profile, succeed in maintaining these associations. Furthermore, subjects from the ferropenic group (aged 42[32-51], 5% males), showing significantly lower levels of hepcidin and higher sTfR, as expected, reflected similar correlations as those Young and Elderly, in contrast to HIV.

Conclusions

Virologically suppressed chronic HIV-infected patients under successful ART exhibit altered levels of iron metabolism modulators suggesting a complex functional iron deficiency.
Patterns of participation restriction among older adults at risk of falls and relationship with intrinsic capacity: A latent cluster analysis
Authors: Merchant Reshma Aziz , Chan Yiong Huak , Aprahamian Ivan , Morley John E.
Published: November 2022

Introduction

The concept of participation restriction was first described by the World Health Organization in 2001 as a component of The International Classification of Functioning, Disability and Health Framework. Both falls and fear of falling (FOF) are associated with social isolation, depression, anxiety, poor quality of life and cognitive impairment resulting in participation restriction. Life-space mobility (LSM) is an important indicator for participation restriction which depends on multiple inter-related factors. We aimed to determine participation patterns using latent cluster analysis (LCA) in older adults at risk of falls, its relationship with intrinsic capacity (IC) and its risk prediction.

Methods

Cross-sectional study of 154 community dwelling older adults ≥ 60 years with falls or risk of falls was conducted. Questionnaires were administered on demographics, hearing, LSM, frailty (FRAIL scale), anorexia of aging (SNAQ), cognition (Montreal Cognitive Assessment, MoCA), FOF (Falls Efficacy Scale-International), physical function, and assessment for handgrip strength (HGS), gait speed, 5-times sit to stand (STS), vision and times-up-and-go (TUG) were performed. Six IC domains (vision and hearing, cognition, nutrition, mobility and depression) were measured.

Results

Three pattern of participation cluster were identified, high (n = 63, 40.9%), moderate (n = 83, 53.9%) and low (n = 8, 33 5.2%). Individuals in the high participation cluster were significantly younger, had higher LSM scores and lower FES-I scores, more robust, fewer ADL and IADL limitations, lower prevalence of low HGS, higher gait speed and shorter TUG. In the fully adjusted model compared to the high participation cluster, moderate participation was significantly associated with low MoCA scores (OR 4.2, 95% CI 1.7–10.4, p = 0.02), poor STS (OR 7.1, 95% CI 3.0–17.0, p < 0.001) whereas low participation was associated with anorexia of aging (OR 9.9, 95% CI 1.6–60.9, p = 0.014), poor STS (OR 19.1, 95% CI 2.0–187.5, p = 0.011) and hearing impairment (OR 9.8, 95% CI 1.4–70.8, p = 0.024). Participants with 3 out of 6 IC decline had a probability of greater than 80% to belong to the low/moderate participation class.

Discussion

Physical function, cognition, hearing and nutrition were significantly associated with low and/or moderate participation class. Future studies are needed to evaluate improvement in participation of those with falls or at risk for falls through restoration of IC.