bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of major adverse cardiovascular events in patients with acute coronary syndrome: Development and validation of a non-invasive nomogram model based on autonomic nervous system assessment
Authors: Wang Jun , Wu Xiaolin , Sun Ji , Xu Tianyou , Zhu Tongjian , Yu Fu , Duan Shoupeng , Deng Qiang , Liu Zhihao , Guo Fuding , Li Xujun , Wang Yijun , Song Lingpeng , Feng Hui , Zhou Xiaoya , Jiang Hong
Published: November 2022

Background

Disruption of the autonomic nervous system (ANS) can lead to acute coronary syndrome (ACS). We developed a nomogram model using heart rate variability (HRV) and other data to predict major adverse cardiovascular events (MACEs) following emergency coronary angiography in patients with ACS.

Methods

ACS patients admitted from January 2018 to June 2020 were examined. Holter monitors were used to collect HRV data for 24 h. Coronary angiograms, clinical data, and MACEs were recorded. A nomogram was developed using the results of Cox regression analysis.

Results

There were 439 patients in a development cohort and 241 in a validation cohort, and the mean follow-up time was 22.80 months. The nomogram considered low-frequency/high-frequency ratio, age, diabetes, previous myocardial infarction, and current smoking. The area-under-the-curve (AUC) values for 1-year MACE-free survival were 0.790 (95% CI: 0.702–0.877) in the development cohort and 0.894 (95% CI: 0.820–0.967) in the external validation cohort. The AUCs for 2-year MACE-free survival were 0.802 (95% CI: 0.739–0.866) in the development cohort and 0.798 (95% CI: 0.693–0.902) in the external validation cohort. Development and validation were adequately calibrated and their predictions correlated with the observed outcome. Decision curve analysis (DCA) showed the model had good discriminative ability in predicting MACEs.

Conclusion

Our validated nomogram was based on non-invasive ANS assessment and traditional risk factors, and indicated reliable prediction of MACEs in patients with ACS. This approach has potential for use as a method for non-invasive monitoring of health that enables provision of individualized treatment strategies.
Associations of lipid profiles with the risk of ischemic and hemorrhagic stroke: A systematic review and meta-analysis of prospective cohort studies
Authors: Gong Xiaoxian , Chen Luowei , Song Bo , Han Xiang , Xu Weihai , Wu Bo , Sheng Feng , Lou Min
Published: November 2022

Background and purpose

The associations of lipid profiles with the risk of ischemic stroke (IS) or hemorrhagic stroke (HS) are controversial. In this study, we aimed to illustrate the optimal level for lipid levels in the risk of IS and HS.

Materials and methods

We searched the electronic database of PubMed, Embase, and the Cochrane library from inception until November 2020. Prospective cohort studies published in English for the associations of lipid profiles (TC, TG, LDL-C, HDL-C, and non–HDL-C) with the risk of IS and HS were eligible for this study, and the publication status was not restricted. We calculated the pooled effect estimates using the random-effects model. We tested the associations of lipid profiles with IS and HS and compared their differences.

Results

We retrieved 50 prospective cohort studies containing 3,301,613 individuals. An increase in total cholesterol (TC) is associated with an increased IS risk (P < 0.001) and a reduced HS risk (P < 0.001). Similarly, an increase in triglyceride links with a greater IS risk (P < 0.001) but with a lower HS risk (P = 0.014). On the opposite, high-density lipoprotein cholesterol (HDL-C) correlates with a reduced IS risk (P = 0.004) but has no significant association with the HS risk (P = 0.571). Moreover, an increase in low-density lipoprotein cholesterol (LDL-C) or non–high-density lipoprotein cholesterol has no statistically significant effect on both IS and HS. The pooled effect estimates on the risk of IS and HS revealed that TC and LDL-C levels should be controlled under 6.0 and 3.5 mmol/L, respectively, to reduce worsening effects on the IS risk while maintaining potential beneficial effects on reducing the HS risk.

Conclusion

We revealed comprehensive relationships between lipid profiles and the risk of stroke, suggesting controlling the TC and LDL-C levels under 6.0 and 3.5 mmol/L, respectively, to balance both the IS and HS risk.
Prioritization of microRNA biomarkers for a prospective evaluation in a cohort of myocardial infarction patients based on their mechanistic role using public datasets
Authors: Venugopal Priyanka , George Melvin , Kandadai Sriram Damal , Balakrishnan Karthikeyan , Uppugunduri Chakradhara Rao S.
Published: November 2022

Background

MicroRNAs (miR) have proven to be promising biomarkers for several diseases due to their diverse functions, stability and tissue/organ-specific nature. Identification of new markers with high sensitivity and specificity will help in risk reduction in acute myocardial infarction (AMI) patients with chest pain and also prevent future adverse outcomes. Hence the aim of this study was to perform a detailed in silico analysis for identifying the mechanistic role of miRs involved in the pathogenesis/prognosis of AMI for prospective evaluation in AMI patients.

Methods

miR profiling data was extracted from GSE148153 and GSE24591 datasets using the GEO2R gene expression omnibus repository and analyzed using limma algorithm. Differentially expressed miRs were obtained by comparing MI patients with corresponding controls after multiple testing corrections. Data mining for identifying candidate miRs from published literature was also performed. Target prediction and gene enrichment was done using standard bioinformatics tools. Disease specific analysis was performed to identify target genes specific for AMI using open targets platform. Protein-protein interaction and pathway analysis was done using STRING database and Cytoscape platform.

Results and conclusion

The analysis revealed significant miRs like let-7b-5p, let-7c-5p, miR-4505, and miR-342-3p in important functions/pathways including phosphatidylinositol-3-kinase/AKT and the mammalian target of rapamycin, advanced glycation end products and its receptor and renin–angiotensin–aldosterone system by directly targeting angiotensin II receptor type 1, forkhead box protein O1, etc. With this approach we were able to prioritize the miR candidates for a prospective clinical association study in AMI patients of south Indian origin.
Expression pattern and diagnostic value of ferroptosis-related genes in acute myocardial infarction
Authors: Wu Jiahe , Cai Huanhuan , Lei Zhe , Li Chenze , Hu Yushuang , Zhang Tong , Zhu Haoyan , Lu Yi , Cao Jianlei , Hu Xiaorong
Published: November 2022

Background

Ferroptosis is a form of regulatory cell death (RCD) caused by iron-dependent lipid peroxidation. The role of ferroptosis in the process of acute myocardial infarction (AMI) is still unclear and requires further study. Therefore, it is helpful to identify ferroptosis related genes (FRGs) involved in AMI and explore their expression patterns and molecular mechanisms.

Methods

The AMI-related microarray datasets GSE66360 and GSE61144 were obtained using the Gene Expression Omnibus (GEO) online database. GO annotation, KEGG pathway enrichment analysis and Protein-protein interaction (PPI) analysis were performed for the common significant differential expression genes (CoDEGs) in these two datasets. The FRGs were obtained from the FerrDb V2 and the differentially expressed FRGs were used to identify potential biomarkers by receiver operating characteristic (ROC) analysis. The expression of these FRGs was verified using external dataset GSE60993 and GSE775. Finally, the expression of these FRGs was further verified in myocardial hypoxia model.

Results

A total of 131 CoDEGs were identified and these genes were mainly enriched in the pathways of “inflammatory response,” “immune response,” “plasma membrane,” “receptor activity,” “protein homodimerization activity,” “calcium ion binding,” “Phagosome,” “Cytokine-cytokine receptor interaction,” and “Toll-like receptor signaling pathway.” The top 7 hub genes ITGAM, S100A12, S100A9, TLR2, TLR4, TLR8, and TREM1 were identified from the PPI network. 45 and 14 FRGs were identified in GSE66360 and GSE61144, respectively. FRGs ACSL1, ATG7, CAMKK2, GABARAPL1, KDM6B, LAMP2, PANX2, PGD, PTEN, SAT1, STAT3, TLR4, and ZFP36 were significantly differentially expressed in external dataset GSE60993 with AUC ≥ 0.7. Finally, ALOX5, CAMKK2, KDM6B, LAMP2, PTEN, PTGS2, and ULK1 were identified as biomarkers of AMI based on the time-gradient transcriptome dataset of AMI mice and the cellular hypoxia model.

Conclusion

In this study, based on the existing datasets, we identified differentially expressed FRGs in blood samples from patients with AMI and further validated these FRGs in the mouse time-gradient transcriptome dataset of AMI and the cellular hypoxia model. This study explored the expression pattern and molecular mechanism of FRGs in AMI, providing a basis for the accurate diagnosis of AMI and the selection of new therapeutic targets.
Subsurface structures of Sianok Segment in the GSF (Great Sumatran Fault) inferred from magnetic and gravity modeling
Authors: Dahrin Darharta , Amir Harman , Suryanata Putu Billy , Bijaksana Satria , Fajar Silvia Jannatul , Ibrahim Khalil , Harlianti Ulvienin , Arisbaya Ilham , Pebrian Mutiara Qalbi , Rahman Adinda Aisyah , Kasendri Adibbian
Published: November 2022

Among the 19 segments of the Great Sumatran Fault (GSF), the Sianok segment is unique due to its proximity to active volcanoes as well as to the sizable Maninjau Caldera. Located next to the Sumani to its southeast, the Sianok segment also passes through a relatively densely populated area. To identify potential disasters in the future, it is imperative to understand the subsurface structures of the Sianok segment. In this study, ground magnetic measurements were conducted, and the data were combined with the Bouguer anomaly map. Hand samples were also collected and measured for magnetic susceptibility and density. The values were later used as initial parameters for modeling. Joint forward modeling of magnetic and gravity was then used in the modeling stage as well as in the interpretation stage. Subsurface models of 20 km in depth were then formulated based on the magnetic and gravity data. The models show shallow magma chambers beneath Maninjau Caldera, Mount Marapi, and Mount Singgalang-Tandikat. The models confirm that exposed and unexposed Permian metamorphic rocks are commonly distributed in the Sianok segment. The thickness of volcanic deposits such as tuff and andesites in the Sianok segment were found to be sizable, ranging from 1 km for tuff to 3.5 km for andesites of the Maninjau Caldera.
Multilevel and empirical reliability estimates of learning growth: A simulation study and empirical illustration
Authors: Forthmann Boris , Förster Natalie , Souvignier Elmar
Published: November 2022

Reliable learning progress information is crucial for teachers’ interpretation and data-based decision making in everyday classrooms. Slope estimates obtained from simple regression modeling or more complex latent growth models are typically used in this context as indicators of learning progress. Research on progress monitoring has used mainly two ways to estimate reliability of learning progress, namely (a) split-half reliability and (b) multilevel reliability. In this work we introduce empirical reliability as another attractive alternative to quantify measurement precision of slope estimates (and intercepts) in learning progress monitoring research. Specifically, we extended previous work on slope reliability in two ways: (a) We evaluated in a simulation study how well multilevel reliability and empirical reliability work as estimates of slope reliability, and (b) we wanted to better understand reliability of slopes as a latent variable (by means of empirical reliability) vs. slopes as an observed variable (by means of multilevel reliability). Our simulation study demonstrates that reliability estimation works well over a variety of different simulation conditions, while at the same time conditions were identified in which reliability estimation was biased (i.e., with very poor data quality, eight measurement points, and when empirical reliability was estimated). Furthermore, we employ multilevel reliability and empirical reliability to estimate reliability of intercepts (i.e., initial level) and slopes for the quop-L2 test. Multilevel and empirical reliability estimates were comparable in size with only slight advantages for latent variable scores. Future avenues for research and practice are discussed.
How to manage land use conflict between ecosystem and sustainable energy for low carbon transition?: Net present value analysis for ecosystem service and energy supply
Authors: Kim Jiwon , Park Eunbeen , Song Cholho , Hong Mina , Jo Hyun-Woo , Lee Woo-Kyun
Published: November 2022

Solar energy generation has become one of the most popular renewable energy sources for achieving global carbon neutrality. This transition to land-intensive energy generates inevitable land use conflicts with existing land cover, such as forest or agricultural land. South Korea is one of the countries currently experiencing conflicts in land use between ecosystems, food and energy. In addition, various land use problems occur, such as deforestation due to developments and an increase in idle agricultural land due to a decrease in the labor force. Thus, it is important to establish future land use policies that consider these issues. This study conducted a net present value (NPV) analysis for solving land use conflict by comparing monetary value according to different land use cases. Two land use scenarios were investigated: 1) land cover maintained (forest or agricultural land) and 2) land use change for solar energy generation. These two scenarios were compared in the target areas selected in this study to determine the criteria for the solar energy generation site. The economic values from Scenario 1were calculated primarily using ecosystem services assessment and market value, and those of Scenario 2 were calculated based on statistical data. The total suitable area for solar energy generation in Korea was 551,393 ha. As results, the NPV of forest ecosystem services was higher than that of solar energy generation in forest. In the case of idle agricultural land, agriculture caused a continuous deficit owing to carbon emissions, and accordingly, the carbon reduction effect through solar energy generation had a greater value than agricultural activities. This study attempted to resolve land use conflict by considering carbon neutrality through comparing economic values and introducing ecosystem services assessment and carbon credit price in the process of the analysis.
MiRNA-190a-5p promotes primordial follicle hyperactivation by targeting PHLPP1 in premature ovarian failure
Authors: Zhang Yuchi , Han Dongwei , Yu Xiaoyan , Shao Xinyu , Zong Chuju , Zhang Manyu , Wang Junzhi , Liang Jingwen , Ge Pengling
Published: November 2022

We previously screened 6 differentially expressed miRNAs in ovarian tissues of 4-vinylcyclohexene diepoxide (VCD)-treated premature ovarian failure (POF) model in SD rats, including miRNA-190a-5p, miRNA-98-5p, miRNA-29a-3p, miRNA-144-5p, miRNA-27b-3p, miRNA-151-5p. In this study, to investigate the mechanisms causing the onset of POF, we first identified miRNAs with earlier differential expression at consecutive time points in the VCD-treated rat POF model and explored the mechanisms by which the target miRNAs promote POF. The SD rats were injected with VCD for 15 days to induce POF. Additionally, we collected rat blood and ovaries at the same time every day for 15 consecutive days, and luteinizing hormone (LH), follicle-stimulating hormone (FSH), Anti-Mullerian hormone (AMH), and estradiol (E2) serum levels were detected by ELISA. Six miRNAs expression were measured in rat ovaries by qRT-PCR. Dual-luciferase reporter gene assays were employed to predict and verify the target gene (PHLPP1) of target miRNAs (miRNA-190a-5p). Western blot was examined to detect the expression levels of PHLPP1, AKT, p-AKT, FOXO3a, p-FOXO3a, and LHR proteins on the target gene PHLPP1 and its participation in the primordial follicular hyperactivation-related pathways (AKT-FOXO3a and AKT-LH/LHR). During the VCD modeling POF rat ovaries, miRNA-190a-5p was the first to show significant differential expression, i.e., 6th of VCD treating, and PHLPP1 was verified to be a direct downstream target of it. Starting from the 6th of VCD treatment, the more significant the up-regulation trend of miRNA-190a-5p expression, the more obvious the down-regulation trend of PHLPP1 and LHR mRNA and protein expression, accompanied by the more severe phosphorylation of AKT and FOXO3a proteins, thus continuously over-activating the rat primordial follicle to promote the development of POF. In conclusion, miRNA-190a-5p may become a potential biomarker for early screening of POF, and it can continuously activate primordial follicles in rats by targeting the expression of PHLPP1 and key proteins in the AKT-FOXO3a and AKT-LH/LHR pathways.
NBTXR3 improves the efficacy of immunoradiotherapy combining nonfucosylated anti-CTLA4 in an anti-PD1 resistant lung cancer model
Authors: Hu Yun , Paris Sébastien , Bertolet Genevieve , Barsoumian Hampartsoum B. , Wang Qi , Da Silva Jordan , Patel Nalini B. , Nguyen Nguyen , Doss Denaha J. , Huang Ailing , Hsu Ethan , Leyton Claudia S. Kettlun , Voss Tiffany A. , Masrorpour Fatemeh , Leuschner Carola , Pietz Jordan T. , Puebla-Osorio Nahum , Gandhi Saumil , Nguyen Quynh-Nhu , Wang Jing , Cortez Maria Angelica , Welsh James W.
Published: November 2022

The efficacy of immunoradiotherapy consisting of radiation therapy and immune checkpoint blockade relies on effectively promoting the systemic antitumor immune response’s activation while simultaneously reducing local factors favoring immune suppression. We previously demonstrated that NBTXR3, a nanoparticle radioenhancer, significantly improved immune responses in a murine anti-PD1-resistant metastatic lung cancer model. We hypothesize that radioactivated-NBTXR3 addition to anti-PD1 and a second-generation anti-CTLA4 could improve treatment effectiveness. To test this hypothesis, we inoculated mice with 344SQR cells in the right and left legs to establish primary and secondary tumors. The primary tumors were intratumorally injected with NBTXR3 nanoparticles on day 7, followed by three fractions of 12 Gy radiation on days 8, 9, and 10. The secondary tumors received two fractions of 1Gy radiation on days 13 and 14. Multiple rounds of anti-PD1, anti-CTLA4 or nonfucosylated anti-CTLA4 were given to the mice. Immune profiling of the tumors revealed that the combination of NBTXR3 with immunoradiotherapy significantly upregulated the activities of a wide range of antitumor immune pathways and reduced the abundance of regulatory suppressor T cells. This combination effectively eradicated the primary and secondary tumors and increased animal survival to 75%. Remarkably, previously treated with NBTXR3-containing treatment, the survivor mice exhibited a long-lasting antitumor memory immune response. This data provides compelling evidence of the efficacy of NBTXR3 to synergize with the immunoradiotherapy approach when combined with an anti-PD1 and multiple checkpoints such as a second generation anti-CTLA4 and show the potential for clinical uses of antitumor immunomodulatory effects of NBTXR3.
Prognostic value of γ‐aminobutyric acidergic synapse-associated signature for lower-grade gliomas
Authors: Jiang Hongxiang , Sun Zhiqiang , Li Fei , Chen Qianxue
Published: November 2022

Background

Synapse-associated proteins (SAPs) play important roles in central nervous system (CNS) tumors. Recent studies have reported that γ-aminobutyric acidergic (GABAergic) synapses also play critical roles in the development of gliomas. However, biomarkers of GABAergic synapses in low-grade gliomas (LGGs) have not yet been reported.

Methods

mRNA data from normal brain tissue and gliomas were obtained from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases, respectively. A validation dataset was also obtained from the Chinese Glioma Genome Atlas (CGGA) database. The expression patterns of GABAergic synapse-related genes (GSRGs) were evaluated with difference analysis in LGGs. Then, a GABAergic synapse-related risk signature (GSRS) was constructed with least absolute shrinkage and selection operator (LASSO) Cox regression analysis. According to the expression value and coefficients of identified GSRGs, the risk scores of all LGG samples were calculated. Univariate and multivariate Cox regression analyses were conducted to evaluate related risk scores for prognostic ability. Correlations between characteristics of the tumor microenvironment (TME) and risk scores were explored with single-sample gene set enrichment analysis (ssGSEA) and immunity profiles in LGGs. The GSRS-related pathways were investigated by gene set variation analysis (GSVA). Real-time PCR and the Human Protein Atlas (HPA) database were applied to explore related expression of hub genes selected in the GSRS.

Results

Compared with normal brain samples, 25 genes of 31 GSRGs were differentially expressed in LGG samples. A constructed five-gene GSRS was related to clinicopathological features and prognosis of LGGs by the LASSO algorithm. It was shown that the risk score level was positively related to the infiltrating level of native CD4 T cells and activated dendritic cells. GSVA identified several cancer-related pathways associated with the GSRS, such as P53 pathways and the JAK-STAT signaling pathway. Additionally, CA2, PTEN, OXTR, and SLC6A1 (hub genes identified in the GSRS) were regarded as the potential predictors in LGGs.

Conclusion

A new five-gene GSRS was identified and verified by bioinformatics methods. The GSRS provides a new perspective in LGG that may contribute to more accurate prediction of prognosis of LGGs.
Rational design of a novel multi-epitope peptide-based vaccine against Onchocerca volvulus using transmembrane proteins
Authors: Shey Robert Adamu , Ghogomu Stephen Mbigha , Nebangwa Derrick Neba , Shintouo Cabirou Mounchili , Yaah Ntang Emmaculate , Yengo Bernis Neneyoh , Nkemngo Francis Nongley , Esoh Kevin Kum , Tchatchoua Nelly Manuela Tatchou , Mbachick Tekoh Terriss , Dede Api Fon , Lemoge Arnaud Azonpi , Ngwese Roland Akwelle , Asa Bertha Fru , Ayong Lawrence , Njemini Rose , Vanhamme Luc , Souopgui Jacob
Published: November 2022

Almost a decade ago, it was recognized that the global elimination of onchocerciasis by 2030 will not be feasible without, at least, an effective prophylactic and/or therapeutic vaccine to complement chemotherapy and vector control strategies. Recent advances in computational immunology (immunoinformatics) have seen the design of novel multi-epitope onchocerciasis vaccine candidates which are however yet to be evaluated in clinical settings. Still, continued research to increase the pool of vaccine candidates, and therefore the chance of success in a clinical trial remains imperative. Here, we designed a multi-epitope vaccine candidate by assembling peptides from 14O. volvulus(Ov) proteins using an immunoinformatics approach. An initial 126 Ov proteins, retrieved from the Wormbase database, and at least 90% similar to orthologs in related nematode species of economic importance, were screened for localization, presence of transmembrane domain, and antigenicity using different web servers. From the 14 proteins retained after the screening, 26 MHC-1 and MHC-II (T-cell) epitopes, and linear B-lymphocytes epitopes were predicted and merged using suitable linkers. TheMycobacterium tuberculosisResuscitation-promoting factor E (RPFE_MYCTU), which is an agonist of TLR4, was then added to the N-terminal of the vaccine candidate as a built-in adjuvant. Immune simulation analyses predicted strong B-cell and IFN-γ based immune responses which are necessary for protection againstO. volvulusinfection. Protein-protein docking and molecular dynamic simulation predicted stable interactions between the 3D structure of the vaccine candidate and human TLR4. These results show that the designed vaccine candidate has the potential to stimulate both humoral and cellular immune responses and should therefore be subject to further laboratory investigation.
Evolutions of upwelling and terrestrial organic matter input in the inner shelf of the East China Sea in the last millennium revealed by long-chain alkyl diols proxies
Authors: Song Chuanhui , Dang Tianxiang , Zhang Ting , Ge Tiantian , Xiang Rong , Xing Lei , Bao Rui , Zhou Yang , Xiao Rui , Wu Baojin
Published: November 2022

Long-chain alkyl diols (LCDs) can be used as organic geochemical proxies for paleoceanographic change, especially in marginal sea areas where large volumes of sediments are deposited rapidly and continuously. However, little is known about the applicability and response on a millennium scale in relation with existing records in those sediments. We reconstruct changes in upwelling and terrestrial organic matter (OM) input in core sediments from the Zhejiang Fujian coastal station (T08) and Yangtze River Estuary station (T06) in the inner shelf of the East China Sea (ECS) over the last millennium, using the LCD based proxies: diol index 2 (DI-2), and FC321,15-diol. Our results show that DI-2 values ([(C28+C30)1,14-diols]/([(C28+C30)1,13-diols]+[(C28+C30)1,14-diols])) at T08 decrease significantly during 600–400 yr BP but increase gradually after 400 yr BP. The FC321,15-diol proxy ([C321,15-diol]×100/([(C28+C30)1,13-diols]+[(C30+C32)1,15-diols])) at T06 shows marked fluctuations during 1000–800 yr BP, followed by a significant decline during 800–500 yr BP but a subsequent increase from 500 to 300 yr BP. We find that variations in DI-2 values are broadly consistent with changes in the strength of the East Asian Summer Monsoon (EASM) and the Kuroshio Current and are likely linked to changes in the frequency and intensity of the El Niño-Southern Oscillation (ENSO). The increased strength of the EASM causes greater offshore movement of the upper layer of seawater, which in turn triggers upwelling of bottom waters formed by Kuroshio subsurface waters. We find that variations in FC321,15-diol proxy are controlled mainly by the East Asian Winter Monsoon (EAWM) and the Yangtze River discharge. By increasing the strength of the EAWM, southward transportation of material deposited in the estuary of the Yangtze River by the ECS coastal currents is promoted. In addition, we synthesize records of other organic geochemical indicators nearby core sediments in the ECS; these records emphasize the importance of reconstructing the evolutionary history of upwelling and subdividing the relative inputs of terrestrial OM. Our study provides a new means for reconstructing the evolution of upwelling and terrestrial OM input in the inner shelf of the ECS over the last millennium.
Surface elevation changes in an estuarine mangrove forest in Vanga, Kenya: Implications for management and mitigation of sea-level rise
Authors: Kimeli Amon Kibiwot , Cherono Shawlet , Baya Patience , Mathinji Margaret , Okello Judith Auma , Koedam Nico , Westphal Hildegard , Kairo James Gitundu
Published: November 2022

Mangrove ecosystems are often called “makers of land” due to their ability to promote deposition, trap, and augment sediments. Accurate location- and region-specific elevation information is required to assess and mitigate threats to mangroves caused by their vulnerability to sea-level rise. The provision of land building services by mangroves is primarily sediment-dependent. It is therefore influenced by local factors, including sediment availability and supply. In the present study from Kenya, we measured and examined the variations in surface elevation in mangroves at variable distances from the creek channel using a combination of surface-elevation tables and horizon markers for three years. Elevation changes varied with distance from the creek channel (p < 0.05), with both surface loss and gains recorded. Elevation changes varied between -80 mm (most significant subsidence) and 42 mm (highest accretion) in stations closer to the creek, while farther from the creek (~200 m away), elevation changes ranged between -68 mm (most significant subsidence) and 29 mm (highest accretion). However, net surface elevation changes over the three years showed that shallow subsidence occurred in both stations closer to the creek (-45 ± 7.2 mm) and those farthest from the creek (-20 ± 7.1 mm). At the same time, an average of 18 mm of sediments were accreted above the horizon markers translating to ~9 mm yr-1 of accretion, a rate larger than both the current global rates of sea-level rise (~3.1 mm yr-1) and local measured rates of sea-level rise (3.8 mm yr-1) in Mombasa, a tide-gauge station nearest (~100 km) to the study site. Cumulatively, sediment elevation changes in Vanga indicate that they are outpacing the current rates of sea-level rise. However, they could be vulnerable to predicted and accelerated rates. It, therefore, calls for more holistic management and monitoring of the dynamics within the mangrove forests and adjacent terrestrial hinterlands.
Case report: Rapid onset, ischemic-type gastritis after initiating oral iron supplementation
Authors: Koch Regina M. , Tchernodrinski Stefan , Principe Daniel R.
Published: November 2022

Oral iron supplements are commonly administered to patients with chronic iron deficiency anemia. This approach is generally well-tolerated, causing only mild adverse effects. Rarely, oral iron supplementation can cause more severe symptoms, one of the most concerning being acute gastritis. This predominantly affects elderly patients and is extremely uncommon in young, otherwise healthy people. Here, we report the case of a 43-year-old woman who presented with upper gastrointestinal (GI) symptoms and iron deficiency anemia and was started on oral iron supplementation following the resolution of her acute symptoms. She soon re-presented with a severe, Helicobacter pylori-negative gastritis with iron deposition on histology. These new onset symptoms resolved rapidly with cessation of iron supplements, consistent with iron pill gastritis. In addition to the limited body of literature describing iron pill gastritis, this case serves as a reminder that any patient receiving oral iron supplementation is at a potential risk for gastritis, particularly in the setting of an ongoing GI pathology. Hence, it is important to provide continued follow-up for patients receiving iron supplementation regardless of age or comorbidity, particularly in the weeks following the start of the treatment.
Recent progress in diagnosis and treatment of Human African Trypanosomiasis has made the elimination of this disease a realistic target by 2030
Authors: Álvarez-Rodríguez Andrés , Jin Bo-Kyung , Radwanska Magdalena , Magez Stefan
Published: November 2022

Human African Trypanosomiasis (HAT) is caused by unicellular flagellated protozoan parasites of the genus Trypanosoma brucei. The subspecies T. b. gambiense is mainly responsible for mostly chronic anthroponotic infections in West- and Central Africa, accounting for roughly 95% of all HAT cases. Trypanosoma b. rhodesiense results in more acute zoonotic infections in East-Africa. Because HAT has a two-stage pathogenesis, treatment depends on clinical assessment of patients and the determination whether or not parasites have crossed the blood brain barrier. Today, ultimate confirmation of parasitemia is still done by microscopy analysis. However, the introduction of diagnostic lateral flow devices has been a major contributor to the recent dramatic drop in T. b. gambiense HAT. Other techniques such as loop mediated isothermal amplification (LAMP) and recombinant polymerase amplification (RPA)-based tests have been published but are still not widely used in the field. Most recently, CRISPR-Cas technology has been proposed to improve the intrinsic diagnostic characteristics of molecular approaches. This will become crucial in the near future, as preventing the resurgence of HAT will be a priority and will require tools with extreme high positive and negative predicted values, as well as excellent sensitivity and specificity. As for treatment, pentamidine and suramin have historically been the drugs of choice for the treatment of blood-stage gambiense-HAT and rhodesiense-HAT, respectively. For treatment of second-stage infections, drugs that pass the blood brain barrier are needed, and melarsoprol has been effectively used for both forms of HAT in the past. However, due to the high occurrence of post-treatment encephalopathy, the drug is not recommended for use in T. b. gambiense HAT. Here, a combination therapy of eflornithine and nifurtimox (NECT) has been the choice of treatment since 2009. As this treatment requires IV perfusion of eflornithine, efforts were launched in 2003 by the drugs for neglected disease initiative (DNDi) to find an oral-only therapy solution, suitable for rural sub-Saharan Africa treatment conditions. In 2019 this resulted in the introduction of fexinidazole, with a treatment regimen suitable for both the blood-stage and non-severe second-stage T. b. gambiense infections. Experimental treatment of T. b. rhodesiense HAT has now been initiated as well.
Development, implementation, and evaluation of Teach Back curriculum for community health workers
Authors: Holcomb Jennifer , Ferguson Gayla M. , Thornton Logan , Highfield Linda
Published: November 2022

Teach Back is a commonly used communication method to improve patient understanding and retention of health information. The method has been shown to be effective in improving patient and healthcare system outcomes, including patient health literacy and hospital readmissions. Community health workers (CHWs) are frontline healthcare workers who can help address patient health and social needs associated with hospital readmissions. However, a gap exists in Teach Back curricula and training methods reflecting the scope of work for CHWs. The objective of this training was to provide CHWs with didactic information and skill building practice curriculum focused on the integration of Teach Back into clinical patient interactions, care coordination, and follow-up support. A multidisciplinary team of academic and clinical partners at a large academic health university developed, implemented, and evaluated a 3-week pilot Teach Back training with CHWs through a quality improvement approach. The CHWs reported overall satisfaction with the training and instructors. The academic clinical partnership allowed the training to be tailored to the daily clinical workflow as reflected in the CHWs agreement that the training was relevant and practical. With the repeated exposure to Teach Back each week, the CHWs also reported an increase in confidence and conviction in using Teach Back. Additional implementation and evaluation of the training curriculum for CHWs is needed to gain further insights into Teach Back and training best practices and translation into practice.
Instruments to evaluate non-technical skills during high fidelity simulation: A systematic review
Authors: Gawronski Orsola , Thekkan Kiara R. , Genna Catia , Egman Sabrina , Sansone Vincenza , Erba Ilaria , Vittori Alessandro , Varano Carmelita , Dall’Oglio Immacolata , Tiozzo Emanuela , Chiusolo Fabrizio
Published: November 2022

Introduction

High Fidelity Simulations (HFS) are increasingly used to develop Non-Technical Skills (NTS) in healthcare providers, medical and nursing students. Instruments to measure NTS are needed to evaluate the healthcare providers’ (HCPs) performance during HFS. The aim of this systematic review is to describe the domains, items, characteristics and psychometric properties of instruments devised to evaluate the NTS of HCPs during HFS.

Methods

A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Studies were retrieved from PubMed, Cinahl, Web of Science, Cochrane Library, ProQuest and PubPsych. Studies evaluating the measurement properties of instruments used to assess NTS during HFS training were included. Pairs of independent reviewers determined the eligibility, extracted and evaluated the data. Risk of bias and appraisal of the methodological quality of the studies was assessed using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist, and the quality of the evidence with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE).

Results

A total of 3,953 articles were screened. A total of 110 reports were assessed for eligibility and 26 studies were included. Studies were conducted in Europe/United Kingdom (n = 13; 50%), North America/Australia (n = 12; 46%) and Thailand (n = 1; 4%). The NTS instruments reported in this review included from 1 to 14 domains (median of 4, Q1 = 3.75, Q3 = 5) and from 3 to 63 items (median of 15, Q1 = 10, Q3 = 19.75). Out of 19 NTS assessment instruments for HFS, the Team Emergency Assessment Measure (TEAM) can be recommended for use to assess NTS. All the other instruments require further research to assess their quality in order to be recommended for use during HFS training. Eight NTS instruments had a positive overall rating of their content validity with at least a moderate quality of evidence.

Conclusion

Among a large variety of published instruments, TEAM can be recommended for use to assess NTS during HFS. Evidence is still limited on essential aspects of validity and reliability of all the other NTS instruments included in this review. Further research is warranted to establish their performance in order to be reliably used for HFS.
Prevalence and WGS-based characteristics of MRSA isolates in hospitals in Shanghai, China
Authors: Zhang Hongzhi , Tian Liang , Chen Taiyao , Chen Wenjie , Ge Yilin , Bi Jing , Fang Zhixin , Chen Min
Published: November 2022

Methicillin-resistant Staphylococcus aureus (MRSA) isolates remain a serious threat to global health despite a decrease in MRSA infections since 2005. MRSA isolates exhibit great diversity worldwide, and their lineages show geographic variation. In this study, we used whole genome sequencing (WGS) to analyze antibiotic resistance genes and virulence genes, spa, staphylococcal cassette chromosome mec, sequence types (STs), and core genome multilocus sequence typing (cgMLST) of MRSA isolates from patients and environmental surface in hospitals in China to determine their prevalence and molecular traits. The highest number of infections by MRSA isolates was observed in patients aged ≥60 years (69.8%, P < 0.05). We identified a total of 19 STs from 162 MRSA isolates from patients. A significant increase was observed in the incidence of ST764-t002-II MRSA infection, which is replacing ST5-t002-II MRSA as the predominant ST. Similarly, isolates from environmental surface were predominantly ST764-t002-II (47%). Notably, most ST764 isolates (97.7%) carried seb, but not arginine catabolic mobile element (ACME), which differed from ST764 isolates in Japan and Thailand. The potential danger of spreading requires rigorous surveillance of emerging ST764 MRSA isolates. We also found higher resistance to seven antimicrobials [OXA, cefoxitin (FOX), ERY, CFZ, ciprofloxacin (CIP), levofloxacin (LEV), and moxifloxacin (MXF)]. Resistance to gentamicin (38.3%), tetracycline (55.9%), and minocycline (41.5%) were also common. Phenotypic resistance to antimicrobials was associated with resistance genes to its content, and cgMLST clustering suggested a strong link between these strains. Overall, our findings revealed the prevalence and molecular characteristics of MRSA isolates in Shanghai, China, providing a theoretical reference for preventing and controlling clonal transmission of MRSA isolates in hospitals in China.
A multi-omics machine learning framework in predicting the recurrence and metastasis of patients with pancreatic adenocarcinoma
Authors: Li Shenming , Yang Min , Ji Lei , Fan Hua
Published: November 2022

Local recurrence and distant metastasis are the main causes of death in patients with pancreatic adenocarcinoma (PDAC). Microbial content in PDAC metastasis is still not well-characterized. Here, the tissue microbiome was comprehensively compared between metastatic and non-metastatic PDAC patients. We found that the pancreatic tissue microbiome of metastatic patients was significantly different from that of non-metastatic patients. Further, 10 potential bacterial biomarkers (Kurthia, Gulbenkiania, Acetobacterium and Planctomyces etc.) were identified by differential analysis. Meanwhile, significant differences in expression patterns across multiple omics (lncRNA, miRNA, and mRNA) of PDAC patients were found. The highest accuracy was achieved when these 10 bacterial biomarkers were used as features to predict recurrence or metastasis in PDAC patients, with an AUC of 0.815. Finally, the recurrence and metastasis in PDAC patients were associated with reduced survival and this association was potentially driven by the 10 biomarkers we identified. Our studies highlight the association between the tissue microbiome and recurrence or metastasis of pancreatic adenocarcioma patients, as well as the survival of patients.
Deciphering the potential of a plant growth promoting endophyte Rhizobium sp. WYJ-E13, and functional annotation of the genes involved in the metabolic pathway
Authors: Huang Xiaoping , Zeng Zhanghui , Chen Zhehao , Tong Xiaxiu , Jiang Jie , He Chenjing , Xiang Taihe
Published: November 2022

Plant growth-promoting rhizobacteria (PGPR) are well-acknowledged root endophytic bacteria used for plant growth promotion. However, which metabolites produced by PGPR could promote plant growth remains unclear. Additionally, which genes are responsible for plant growth-promoting traits is also not elucidated. Thus, as comprehensive understanding of the mechanism of endophyte in growth promotion is limited, this study aimed to determine the metabolites and genes involved in plant growth-promotion. We isolated an endophytic Rhizobium sp. WYJ-E13 strain from the roots of Curcuma wenyujin Y.H. Chen et C. Ling, a perennial herb and medicinal plant. The tissue culture experiment showed its plant growth-promoting ability. The bacterium colonization in the root was confirmed by scanning electron microscopy and paraffin sectioning. Furthermore, it was noted that the WYJ-E13 strain produced cytokinin, anthranilic acid, and L-phenylalanine by metabolome analysis. Whole-genome analysis of the strain showed that it consists of a circular chromosome of 4,350,227 bp with an overall GC content of 60.34%, of a 2,149,667 bp plasmid1 with 59.86% GC, and of a 406,180 bp plasmid2 with 58.05% GC. Genome annotation identified 4,349 putative protein-coding genes, 51 tRNAs, and 9 rRNAs. The CDSs number allocated to the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Clusters of Orthologous Genes databases were 2027, 3,175 and 3,849, respectively. Comparative genome analysis displayed that Rhizobium sp. WYJ-E13 possesses the collinear region among three species: Rhizobium acidisoli FH23, Rhizobium gallicum R602 and Rhizobium phaseoli R650. We recognized a total set of genes that are possibly related to plant growth promotion, including genes involved in nitrogen metabolism (nifU, gltA, gltB, gltD, glnA, glnD), hormone production (trp ABCDEFS), sulfur metabolism (cysD, cysE, cysK, cysN), phosphate metabolism (pstA, pstC, phoB, phoH, phoU), and root colonization. Collectively, these findings revealed the roles of WYJ-E13 strain in plant growth-promotion. To the best of our knowledge, this was the first study using whole-genome sequencing for Rhizobium sp. WYJ-E13 associated with C. wenyujin. WYJ-E13 strain has a high potential to be used as Curcuma biofertilizer for sustainable agriculture.
Diversity and functional profile of gut symbiotic bacteria between Lysinibacillus sphaericus C3-41 susceptible and resistant Culex quinquefasciatus Say as revealed by 16S rRNA gene high-throughput sequencing
Authors: Zhang Xiaolei , Meng Haoran , Hu Xiaomin , Yuan Zhiming
Published: November 2022

Previous studies have demonstrated that symbiotic gut bacteria in insects are involved in the development of insecticide resistance, but the relationship between the symbiotic gut bacteria and resistance to Lysinibacillus sphaericus C3-41 in Culex pipiens quinquefasciatus remains unclear. In this study, the abundance and diversity of gut symbionts of Cx. quinquefasciatus that were resistant (RLCql) or susceptible (SLCql) to L. sphaericus C3-41 were analyzed by high-throughput 16S rRNA sequencing. The main phyla among the symbiotic gut bacterial communities of Cx. quinquefasciatus were Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes. However, the relative abundance of Firmicutes, Proteobacteria, and unidentified Bacteria in the gut of the resistant strain of Cx. quequinfasciatus (RLCql colony) was higher compared to the susceptible strain (SLCql colony). The NMDS (Non-Metric Multi-Dimensional Scaling) and unweighted unifrac PCoA analyses also revealed significant differences between the symbiotic gut bacterial communities from the resistant and susceptible strains, suggesting that bacterial insecticides can alter bacterial composition. Ultimately, the changes in the bacterial community likely occurred after the development of resistance to L. sphaericus C3-41. These results provide guidance for further research into the mechanisms of gut symbionts involved in resistance against L. sphaericus C3-41 in Cx. quinquefasciatus.
An MRI-based joint model of radiomics and spatial distribution differentiates autoimmune encephalitis from low-grade diffuse astrocytoma
Authors: Piao Sirong , Luo Xiao , Bao Yifang , Hu Bin , Liu Xueling , Zhu Yuqi , Yang Liqin , Geng Daoying , Li Yuxin
Published: November 2022

Background

The differential diagnosis between autoimmune encephalitis and low-grade diffuse astrocytoma remains challenging. We aim to develop a quantitative model integrating radiomics and spatial distribution features derived from MRI for discriminating these two conditions.

Methods

In our study, we included 188 patients with confirmed autoimmune encephalitis (n = 81) and WHO grade II diffuse astrocytoma (n = 107). Patients with autoimmune encephalitis (AE, n = 59) and WHO grade II diffuse astrocytoma (AS, n = 79) were divided into training and test sets, using stratified sampling according to MRI scanners. We further included an independent validation set (22 patients with AE and 28 patients with AS). Hyperintensity fluid-attenuated inversion recovery (FLAIR) lesions were segmented for each subject. Ten radiomics and eight spatial distribution features were selected via the least absolute shrinkage and selection operator (LASSO), and joint models were constructed by logistic regression for disease classification. Model performance was measured in the test set using the area under the receiver operating characteristic (ROC) curve (AUC). The discrimination performance of the joint model was compared with neuroradiologists.

Results

The joint model achieved better performance (AUC 0.957/0.908, accuracy 0.914/0.840 for test and independent validation sets, respectively) than the radiomics and spatial distribution models. The joint model achieved lower performance than a senior neuroradiologist (AUC 0.917/0.875) but higher performance than a junior neuroradiologist (AUC 0.692/0.745) in the test and independent validation sets.

Conclusion

The joint model of radiomics and spatial distribution from a single FLAIR could effectively classify AE and AS, providing clinical decision support for the differential diagnosis between the two conditions.