bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclin C-Cdk8 Kinase Phosphorylation of Rim15 Prevents the Aberrant Activation of Stress Response Genes
Authors: Willis Stephen D. , Hanley Sara E. , Doyle Steven J. , Beluch Katherine , Strich Randy , Cooper Katrina F.
Published: March 2022

Cells facing adverse environmental cues respond by inducing signal transduction pathways resulting in transcriptional reprograming. In the budding yeast Saccharomyces cerevisiae, nutrient deprivation stimulates stress response gene (SRG) transcription critical for entry into either quiescence or gametogenesis depending on the cell type. The induction of a subset of SRGs require nuclear translocation of the conserved serine-threonine kinase Rim15. However, Rim15 is also present in unstressed nuclei suggesting that additional activities are required to constrain its activity in the absence of stress. Here we show that Rim15 is directly phosphorylated by cyclin C-Cdk8, the conserved kinase module of the Mediator complex. Several results indicate that Cdk8-dependent phosphorylation prevents Rim15 activation in unstressed cells. First, Cdk8 does not control Rim15 subcellular localization and rim15∆ is epistatic to cdk8∆ with respect to SRG transcription and the execution of starvation programs required for viability. Next, Cdk8 phosphorylates a residue in the conserved PAS domain in vitro. This modification appears important as introducing a phosphomimetic at Cdk8 target residues reduces Rim15 activity. Moreover, the Rim15 phosphomimetic only compromises cell viability in stresses that induce cyclin C destruction as well as entrance into meiosis. Taken together, these findings suggest a model in which Cdk8 phosphorylation contributes to Rim15 repression whilst it cycles through the nucleus. Cyclin C destruction in response to stress inactivates Cdk8 which in turn stimulates Rim15 to maximize SRG transcription and cell survival.
A Series of Photosensitizes for Fe3+ in Aqueous Solution and Cells With Colorimetric and Fluorescent Channels: Synthesis and Performance
Authors: Xu Ming , Liao Jiang-Tao , Chen Gang , Chen Yin-Yun , Liu Dan , Wang Li-Le
Published: March 2022

Ferrum (Fe) is a widely existing metal element and nearly the most important trace element in living species, including human beings. The design of chemosensors for Fe ions faces issues related to the d-d transition of Fe(II) and Fe(III) ions, which makes them efficient electron trappers and energy quenchers. Most fluorescent dyes cannot afford such d-d quenching, showing emission turn off effect towards both Fe(II) and Fe(III) ions with poor selectivity. As a consequence, the development for Fe with emission turn on effect and good selectivity shall be continued and updated. In this work, three rhodamine-derived chemosensors modified by different lengths of alkyl chains having electron-donating N and O atoms were synthesized and explored for the selective optical sensing of Fe(III). These chemosensors showed colorimetric and fluorescent emission turn on sensing for Fe(III), showing two sensing channels. These chemosensors showed good selectivity, which was assigned to the sieving effect of alkyl chains with electron-donating N and O atoms. The N atom was found to be more effective in associating with Fe(III), compared to the O atom. Their fluorescent cell imaging experiment was carried out to confirm the possibility of being used for cell imaging.
Oral and Stool Microbiome Coalescence and Its Association With Antibiotic Exposure in Acute Leukemia Patients
Authors: Franklin Samantha , Aitken Samuel L. , Shi Yushi , Sahasrabhojane Pranoti V. , Robinson Sarah , Peterson Christine B. , Daver Naval , Ajami Nadim A. , Kontoyiannis Dimitrios P. , Shelburne Samuel A. , Galloway-Peña Jessica
Published: March 2022

Failure to maintain segregation of oral and gut microbial communities has been linked to several diseases. We sought to characterize oral-fecal microbiome community coalescence, ectopic extension of oral bacteria, clinical variables contributing to this phenomenon, and associated infectious consequences by analyzing the 16S rRNA V4 sequences of longitudinal fecal (n=551) and oral (n=737) samples from 97 patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC). Clustering observed in permutation based multivariate analysis of variance (PERMANOVA) of Bray-Curtis dissimilarity and PCoA plot of UniFrac distances between intra-patient longitudinal oral-stool sample pairs suggested potential oral-stool microbial community coalescence. Bray-Curtis dissimilarities and UniFrac distances were used to create an objective definition of microbial community coalescence. We determined that only 23 of the 92 patients exhibited oral-stool community coalescence. This was validated through a linear mixed model which determined that patients who experienced coalescence had an increased proportion of shared to unique OTUs between their oral-stool sample pairs over time compared to non-coalesced patients. Evaluation of longitudinal microbial characteristics revealed that patients who experienced coalescence had increased stool abundance of Streptococcus and Stenotrophomonas compared to non-coalesced patients. When treated as a time-varying covariate, each additional day of linezolid (HR 1.15, 95% CI 1.06 – 1.24, P <0.001), meropenem (HR 1.13, 95% CI 1.05 – 1.21, P = 0.001), metronidazole (HR 1.13, 95% CI 1.05 – 1.21, P = 0.001), and cefepime (HR 1.10, 95% CI 1.01 – 1.18, P = 0.021) increased the hazard of oral-stool microbial community coalescence. Levofloxacin receipt was associated with a lower risk of microbiome community coalescence (HR 0.75, 95% CI 0.61 – 0.93, P = 0.009). By the time of neutrophil recovery, the relative abundance of Bacteroidia (P<0.001), Fusobacteria (P=0.012), and Clostridia (P=0.013) in the stool were significantly lower in patients with oral-gut community coalescence. Exhibiting oral-stool community coalescence was associated with the occurrence of infections prior to neutrophil recovery (P=0.002), as well as infections during the 90 days post neutrophil recovery (P=0.027). This work elucidates specific antimicrobial effects on microbial ecology and furthers the understanding of oral/intestinal microbial biogeography and its implications for adverse clinical outcomes.
Streptococcus pneumoniae Strains Isolated From a Single Pediatric Patient Display Distinct Phenotypes
Authors: Agnew Hannah N. , Brazel Erin B. , Tikhomirova Alexandra , van der Linden Mark , McLean Kimberley T. , Paton James C. , Trappetti Claudia
Published: March 2022

Streptococcus pneumoniae is the leading cause of bacterial paediatric meningitis after the neonatal period worldwide, but the bacterial factors and pathophysiology that drive pneumococcal meningitis are not fully understood. In this work, we have identified differences in raffinose utilization by S. pneumoniae isolates of identical serotype and sequence type from the blood and cerebrospinal fluid (CSF) of a single pediatric patient with meningitis. The blood isolate displayed defective raffinose metabolism, reduced transcription of the raffinose utilization pathway genes, and an inability to grow in vitro when raffinose was the sole carbon source. The fitness of these strains was then assessed using a murine intranasal infection model. Compared with the CSF isolate, mice infected with the blood isolate displayed higher bacterial numbers in the nose, but this strain was unable to invade the ears of infected mice. A premature stop codon was identified in the aga gene in the raffinose locus, suggesting that this protein likely displays impaired alpha-galactosidase activity. These closely related strains were assessed by Illumina sequencing, which did not identify any single nucleotide polymorphisms (SNPs) between the two strains. However, these wider genomic analyses identified the presence of an alternative alpha-galactosidase gene that appeared to display altered sequence coverage between the strains, which may account for the observed differences in raffinose metabolic capacity. Together, these studies support previous findings that raffinose utilization capacity contributes to disease progression, and provide insight into a possible alternative means by which perturbation of this pathway may influence the behavior of pneumococci in the host environment, particularly in meningitis.
Mapping Global Research on Cyber Bullying in the Context of Cross-Cultural Collaborations: A Bibliometric and Network Analysis
Authors: Peker Adem , Yalçın Ragıp Ümit
Published: March 2022

The increasing prevalence of communication tools also increases the negative use of the individual, which will disrupt communication with others. One consequence of this negative use is defined as cyber bullying and it can negatively affect the mental health of individuals. This study adopts a descriptive bibliometric approach to map global research on cyber bullying using metadata from the Web of Science database. Analysis of publication trends at the country level shows that cyber bullying and cross-cultural research is a growing research area in recent years. In addition, researchers conduct studies on cyberbullying and intercultural cooperation in different parts of the world. Co-authoring network analyzes revealed that we conducted the most effective research on cyber bullying in the USA, and collaborations on cyber bullying research were heterogeneous, except for some regions. The visual network map shows that there is cooperation between authors and institutions in studies on cyber bullying. All the top 5 universities that make the most publications on cyber bullying are within the member states of the European Union
Case Report: Esophagectomy and Azygos Continuation of the Inferior Vena Cava: A Lethal Combination
Authors: Zhang Yan , Ding Zheng , Mu Teng , Pan Xue , Zhang Guoqing , Li Xiangnan
Published: March 2022

Azygos continuation of the inferior vena cava (IVC) is rare in the general population and even rarer among patients with esophageal carcinoma. In 90% of cases, this congenital IVC variant is isolated and does not affect the patient’s growth or development. However, thoracic surgery such as esophagectomy would be fatal if the flow through this connection was interrupted. We present a case of minimally invasive esophagectomy in a patient with azygos continuation of the IVC.
Premature Ventricular Contractions From the Left Anterior Fascicle: Electrocardiographic and Electrophysiological Characteristics, Mapping Strategy, and Immediate and Long-Term Catheter Ablation Results
Authors: Chen Hongwu , Xiao Fangyi , Ju Weizhu , Yang Gang , Zhang Fengxiang , Gu Kai , Li Mingfang , Liu Hailei , Wang Zidun , Sharma Dinesh , Cao Kejiang , Chen Minglong
Published: March 2022

Background

Left anterior fascicle (LAF) premature ventricular contractions (PVC) are rarely reported. We described the electrocardiographic and electrophysiological characteristics of PVCs originating from LAF and evaluated the results of catheter ablation.

Methods

The baseline AH and HV intervals were recorded during normal sinus rhythm (NSR), and the HV interval of LAF-PVC was measured during the procedure. During the index procedure, the conduction interval from the earliest Purkinje potential (PP) site to the His was labeled as time A, the conduction interval from the earliest site to the onset of the QRS as time B, then the HV interval during NSR (HVNSR) is A + B, and the HV interval during PVC (HVPVC) is B-A; a predicted PP time was calculated using HVNSR and HVPVC. The calculated formula is as follows: Predicted target PP = (HVNSR + HVPVC)/2. During the repeat procedure, the mapping strategy only focuses on the earliest retrograde PP due to the injury or block of LAF sustained at the index procedure.

Results

Notably, 24 patients with LAF-PVC were included. The ECG characteristics of PVC exhibited right bundle branch block (RBBB) morphology with right-axis deviation (RAD) in 18 patients and only RAD in 6 patients. The QRS durations of NSR and PVC were 78.8 ± 7.9 and 106.8 ± 12.3 ms, respectively. There was no significant difference between the predicted and mapped PP site (31.5 ± 8.1 vs. 30.6 ± 7.8 ms; P = 0.17). There was a significant difference between the mean axis deviation before and after ablation (46.3 ± 25.4° vs. 18.3 ± 44.1°; P = 0.001); however, only 10 patients had a complete LAF block. Eight patients had a recurrence, the QRS morphology of LAF-PVC became narrower (95.9 ± 17.2 vs. 105.3 ± 16.9 ms, P = 0.003), and 4 patients’s PVC QRS morphology was similar to NSR. During the repeat procedure, the earliest retrograde PP interval was longer than the index procedure in four patients (12.0 ± 1.9 vs. 37.8 ± 1.1 ms; P < 0.001).

Conclusion

The target PP site for ablation of the LAF region can be calculated using the HV interval during NSR and PVC at the index procedure. The mapping strategy at repeat procedures focused on the earliest retrograde PP interval.
Plausible Functional Diagnostics by Rational Echocardiography in the Assessment of Valvular Heart Disease - Role of Quantitative Echocardiography in the Assessment of Mitral Regurgitation
Authors: Hagendorff Andreas , Stöbe Stephan
Published: March 2022

The echocardiographic assessment of valvular heart diseases is the basic analysis of valvular defects next to clinical investigation and stethoscopy. Severity of mitral regurgitation (MR) is usually estimated by an integrated approach using semi quantitative parameters and is still one of the biggest challenges of echocardiography. Quantitative echocardiographic analysis of MR severity often fails to describe comprehensible hemodynamic conditions. However, comprehensive echocardiography based on standardized image acquisition and proper image quality is required to properly assess hemodynamic parameter comparable to cardiac magnetic resonance tomography. This review focuses on the uncertainty of MR severity assessed by echocardiography in recent trials of interventional MR treatment. In addition, the necessity to provide plausible echocardiographic data for individual decision making is highlighted. In conclusion, plausible functional diagnostics by rational echocardiography is a prerequisite in patients with valvular heart diseases.
Increased Prevalence of Elevated D-Dimer Levels in Patients on Direct Oral Anticoagulants: Results of a Large Retrospective Study
Authors: Reda Sara , Thiele Serra Elena , Müller Jens , Hamedani Nasim Shahidi , Oldenburg Johannes , Pötzsch Bernd , Rühl Heiko
Published: March 2022

Elevated D-dimer levels during anticoagulant therapy with vitamin K antagonists (VKA) are associated with an increased risk of thrombosis. It has been hypothesized that elevated D-dimer levels in patients receiving direct oral anticoagulants (DOACs) also indicate an increased risk of thrombosis recurrence, but data on the distribution of D-dimer levels in patients with VTE on DOACs are sparse. In the present study we retrospectively analyzed D-dimer levels in patients taking DOACs after first or recurrent venous thrombosis (n = 1,716, 1,126 thereof rivaroxaban, 481 apixaban, 62 edoxaban, and 47 dabigatran). Patients on VKA (n = 402) served as control group. Thrombotic events in the study population were categorized into distal deep venous thrombosis (DVT, n = 552 patients), distal DVT with pulmonary embolism (PE, n = 166), proximal DVT (n = 685), proximal DVT with PE (n = 462), PE without DVT (n = 522), DVT of the upper extremity (n = 78), cerebral venous sinus thrombosis (CVST, n = 48), and other venous thrombosis (n = 74). In VKA users a median D-dimer level of 0.20 mg/l was observed. In patients on DOACs D-dimer levels were significantly higher, with 0.26 mg/l for rivaroxaban, 0.31 mg/l for apixaban (P < 10−16 each), 0.24 mg/l for edoxaban (P = 2 × 10−5), and 0.25 mg/l for dabigatran (P = 4 × 10−4). These differences in comparison to patients on VKA treatment could not be explained by the patients' age, sex, body mass index, and type of thrombosis as these characteristics did not differ significantly between cohorts. Moreover, the prevalence of D-dimer levels above age-adjusted cut-offs [≥0.50 mg/l in ≤50-year-old patients, ≥(age × 0.01) mg/l in >50-year-old patients] was higher in patients on rivaroxaban (13.9%, RR 1.74, 95% CI 1.21–2.50), apixaban (17.0%, RR 2.14, 95% CI 1.45–3.15) and dabigatran (23.4%, RR 2.94, 95% CI 1.59–5.44) than in patients on VKA (8.0%). In patients on edoxaban D-dimer levels above the reference range were observed in 14.5%, but no statistical significance was reached in comparison to the VKA cohort. In conclusion, the obtained data suggest, that the type of oral anticoagulant should be considered in the clinical assessment of D-dimer levels in thrombosis patients. Further studies are warranted to evaluate a potential association between elevated D-dimer levels and thrombosis risk in patients on DOACs.
A Balanced Scorecard for Maximizing Data Performance
Authors: Pierce Elizabeth
Published: March 2022

A good performance monitoring system is crucial to knowing whether an organization's efforts are making their data capabilities better, the same, or worse. However, comprehensive performance measurements are costly. Organizations need to expend time, resources, and personnel to design the metrics, to gather evidence for the metrics, to assess the metrics' value, and to determine if any actions should be taken as a result of those metrics. Consequently organizations need to be strategic in selecting their portfolio of performance indicators for evaluating how well their data initiatives are producing value to the organization. This paper proposes a balanced scorecard approach to aid organizations in designing a set of meaningful and coordinated metrics for maximizing the potential of their data assets. This paper also discusses implementation challenges and the need for further research in this area.
Making Digital Health “Solutions” Sustainable in Healthcare Systems: A Practitioner Perspective
Authors: Cripps Matthew , Scarbrough Harry
Published: March 2022

Digital health solutions have the potential to bring about great improvements in the delivery and quality of services in healthcare systems. In this paper, we draw on the extensive experience of NHS (National Health Service) England to develop a practitioner perspective on the challenges of effectively implementing and sustaining such solutions. We argue that a properly sustainable approach requires a shift in both thinking and practice when it comes to the spread and adoption of such technologies. Our thinking needs to shift from a focus on the technology itself to how we bring about the changes needed to deliver more efficient and effective care for patients. In practical terms, this means focussing on the changes involved to integrate digital health solutions into the delivery of services. In particular, it requires greater attention to the motivations, constraints and specific contexts that influence users and patients. The technical expertise of innovators therefore needs to be complemented by other forms of insight into change processes, including clinical and behavioral insight, process engineering and knowledge management. In this paper, we show how these different pillars of the NHS Sustainable Healthcare approach help to ensure the effective implementation and use of digital solutions. We draw out the implications of this approach for policy-makers in healthcare systems, highlighting the need to give greater attention and resources to the downstream challenges of implementing digital health solutions.
Advances and Accuracy Assessment of Ocean Tide Models in the Antarctic Ocean
Authors: Sun Weikang , Zhou Xinghua , Zhou Dongxu , Sun Yanfei
Published: March 2022

Ocean tides in polar regions play an important role in the study of sea ice dynamics and floating ice shelves. The accuracy of existing ocean tide models in shallow waters and polar seas is much lower than that in open deep oceans. This study summarized the advances of state-of-the-art global tide models in the Antarctic Ocean, the construction of tide models around Circum-Antarctica, and five typical regions: Antarctic Peninsula, Ross Sea, Filchner–Ronne Ice Shelf (FRIS), Weddell Sea, and Amery Ice Shelf (AIS). The accuracy of FES 2014, TPXO9, EOT20, CATS 2008, and regional tide models in the Antarctic Ocean and typical areas was evaluated using tidal records and satellite altimetry data. EOT20 and ANTPEN04.01 models have higher accuracy in the Antarctic Peninsula, and the root sum square (RSS) values are 8.29 and 7.46 cm, respectively. TPXO9 has the highest accuracy in the Weddell Sea and FRIS and AIS and RSS values are 18.33 and 12.77 cm, respectively. TPXO9 and RIS_Optimal models have higher accuracy in the Ross Sea and Ross Ice Shelf (RIS), RSS values are 5.62 and 6.21 cm, respectively. The accuracy of FES 2014, TPXO9, CATS 2008, and the regional tide model in the Drake Passage, Kerguelen Islands, and Adelie–Mertz was evaluated using satellite altimetry data. The RSS values are less than 4 cm. By using the altimetry data at Sentinel-3A single-satellite crossovers in terms of the STD of the SLA, the comparison of the STDs show that FES2014 is the best.
Strategies for Gully Stabilization and Highland Protection in Chinese Loess Plateau
Authors: Liu Wanfeng , Zhang Huyuan , Zhu Jianghong , Hu Aiping
Published: March 2022

Loess tablelands are large-scale platforms with flat top surfaces in the center of Chinese Loess Plateau, such as Dongzhiyuan, which is a ∼900 km2 loess stratum, with the thickness larger than 200 m. The break of loess tablelands is widely reported due to the retreat of gully systems, resulting in serious social problems and economic losses. The retreating rate of large gullies has been 0.5–6.6 m/year over the past 2,000 years, estimated by the calculation of erosion modulus, literature archaeology, and field monitoring. The retreating rate of a small gully can reach 7.5–27.0 m/year after a rainstorm. To protect the farmland, buildings, roads, and pipelines near to the gully head areas, a project named Gully Stabilization and Highland Protection (GSHP) was launched by the local government, including the small watershed management (SWM) around loess slopes and gully channels and sponge city construction (SCC) achieved by improving the drainage system of tableland surfaces. These efforts improve the soil and water conservations, although they contribute less to controlling gully expansion. From the perspective of mutual promotion of gravity erosion and hydraulic erosion, this paper proposes a technical framework for GSHP, focusing on the avoidance of geological disaster. This case study reports on an illustrative GSHP project, the restoration of Huoxianggou gully, including the backfilled loess embankment across the gully for convenient urban transportation, and the stabilization of unstable loess slopes. After the implementation, the retreat of the gully head has been stopped, and the soil erosion rate has been reduced by 90%.
The Theory of Hyperlipidemic Memory of Type 1 Diabetes
Authors: Nwosu Benjamin Udoka
Published: March 2022

Literature Search Criteria

A literature search was conducted to identify publications addressing the early phases of lipid phenotypes in children and adults with either type 1 diabetes or type 2 diabetes. Medline, EMBASE, and Ovid were searched using the following search terms:clinical remission, partial remission, partial clinical remission, honeymoon phase, C-peptide, type 1 or 2 diabetes, children, pediatric type 1 or 2 diabetes, and paediatrics type 1 or 2 diabetes, adults, adult type 1 or type 2 diabetes.

Partial clinical remission (PR) of type 1 diabetes (T1D) is characterized by continued endogenous production of insulin and C-peptide following the diagnosis and the introduction of exogenous insulin therapy. PR is associated with improved glycemic control and reduced prevalence of diabetes complications. The theory of hyperglycemic memory was proposed to explain this concept of improved glycemic outcomes in remitters (those who experienced PR) versus non-remitters (those who did not experience PR). However, this theory is incomplete as it does not explain the dichotomy in early lipid phenotypes in T1D based on PR status, which is an understudied area in diabetology and lipidology. To fill this knowledge gap, we propose the Theory of Hyperlipidemic Memory of T1D. This theory is premised on our 5-year research on early post-diagnostic dichotomy in lipid phenotypes between remitters and non-remitters across the lifespan. It provides a more rigorous explanation for the differences in lifelong atherosclerotic cardiovascular disease (ASCVD) risk between remitters and non-remitters. We conducted 4 clinical studies in pediatric and adult subjects with diabetes mellitus to characterize the particulars of the hyperlipidemic memory. In the first investigation, we explored the impact of the presence or absence of PR on lipid parameters in children and adolescents with T1D. In the second, we investigated whether pubertal maturation influenced our findings in T1D; and whether these findings could be replicated in healthy, non-diabetic children and adolescents. In the third, we leveraged our findings from T1D and controls to investigate the mechanisms of early lipid changes in T2D by comparing the earliest lipid phenotype of subjects with type 2 diabetes (T2D) to those of remitters, non-remitters, and controls. In the fourth, we investigated the impact of PR on the earliest lipid phenotypes in adults with T1D and compared these early lipid data to those of T2D subjects and controls. This body of work across the lifespan in children, adolescents, and adults supports the Theory of Hyperlipidemic Memory. This new theory clarifies why PR largely determines the risks for early-phase dyslipidemia, mid-term microvascular disease risk, and long-term ASCVD risk in subjects with T1D.
11-Deoxycorticosterone Producing Adrenal Hyperplasia as a Very Unusual Cause of Endocrine Hypertension: Case Report and Systematic Review of the Literature
Authors: Asla Queralt , Sardà Helena , Lerma Enrique , Hanzu Felicia A. , Rodrigo María Teresa , Urgell Eulàlia , Pérez José Ignacio , Webb Susan M. , Aulinas Anna
Published: March 2022

Background and Objectives

11-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide the most relevant clinical features that clinicians dealing with patients presenting with the hallmarks of hypertension due to 11-deoxycorticosterone-producing adrenal lesions should be aware of.

Design and Methods

We report the case of a patient with an 11-deoxycorticosterone-producing adrenal lesion and provide a systematic review of all published cases (PubMed, Web of Science and EMBASE) between 1965 and 2021.

Results

We identified 46 cases (including ours). Most cases (31, 67%) affected women with a mean age of 42.9 ± 15.2 years and presented with high blood pressure and hypokalemia (average of 2.68 ± 0.62 mmol/L). Median (interquartile range) time from onset of first suggestive symptoms to diagnosis was 24 (55) months. Aldosterone levels were low or in the reference range in 98% of the cases when available. 11-deoxycorticosterone levels were a median of 12.5 (18.9) times above the upper limit of the normal reference range reported in each article and overproduction of more than one hormone was seen in 31 (67%). Carcinoma was the most common histological type (21, 45.7%). Median tumor size was 61.5 (60) mm. Malignant lesions were larger, had higher 11-deoxycorticosterone levels and shorter time of evolution at diagnosis compared to benign lesions.

Conclusions

11-deoxycorticosterone-producing adrenal lesions are very rare, affecting mostly middle-aged women with a primary aldosteronism-like clinical presentation and carcinoma is the most frequent histological diagnosis. Measuring 11-deoxycorticosterone levels, when low aldosterone levels or in the lower limit of the reference range are present in hypertensive patients, is advisable.

Systematic Review Registration

Open Science Framework, 10.17605/OSF.IO/NR7UV.
Differences in Glycemic Abnormalities Between Primary Aldosteronism and Essential Hypertension: A Systematic Review and Meta-Analysis
Authors: Manosroi Worapaka , Atthakomol Pichitchai , Wattanawitawas Pittaporn , Buranapin Supawan
Published: March 2022

Background

The relationship of glycemic abnormalities between primary aldosteronism (PA) patients and essential hypertension (EH) patients is still debatable. This meta-analysis aimed to explore differences in the prevalence of glycemic abnormalities and levels of abnormal glucose metabolism in PA and EH patients.

Methods

A search was performed using PubMed, Scopus, Cochrane and Web of Science databases from their inception through January 2022. Inclusion criteria for this study were 1) observational studies which contained specific data of interest, 2) studies including data which compared adult PA and EH patients and 3) studies which used appropriate methods to diagnose PA. Risk ratio (RR) or standardized mean difference (SMD) with a 95% confidence interval (95% CI) was calculated.

Results

Twenty-six studies involving 53,186 patients were included in the meta-analysis. Patients with PA demonstrated significantly higher overall incidence of glycemic abnormalities than patients with EH [RR 1.54; 95% CI (1.20,1.98)]. Risk of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in PA patients were higher than in EH patients [RR 1.27; 95%CI (1.08, 1.49) and RR 2.99; 95%CI (1.74, 5.16), respectively]. There was no statistically significant difference of risk between these groups for impaired fasting glucose (IFG) [RR 1.70; 95%CI (0.55, 5.26)]. Moderate heterogeneity was observed in overall glycemic abnormalities outcomes. A high level of heterogeneity was observed for IFG, while the level was low for DM and IGT.

Conclusions

PA patients have a higher risk of glycemic abnormalities than in EH patients. Further study should be conducted to investigate underlying mechanisms of glycemic abnormalities in PA.

Systematic Review Registration

www.inplasy.com, INPLASY, identifier 202220004.
Microalgae as a Natural CO2 Sequester: A Study on Effect of Tobacco Smoke on Two Microalgae Biochemical Responses
Authors: Barati Bahram , Fazeli Zafar Fatemeh , Amani Babadi Arman , Hao Chen , Qian Lili , Wang Shuang , El-Fatah Abomohra Abd
Published: March 2022

Microalgae are known as the most efficient biological sequesters of carbon dioxide (CO2). Recently, they have been exploited to enhance air quality by decreasing CO2 levels and increasing oxygen (O2) concentrations. However, in public places, there are sources of toxic chemicals such as tobacco smoke that may affect the growth of microalgae. For the first time, the current study explores the influence of tobacco smoke on the cell growth, biodiesel characteristics, and biochemical composition of two strains of model microalgae. Chlamydomonas strains were treated with tobacco smoke in a sealed box for 7 days, wherein every 1 h, one cigarette was burnt. Upon exposure of microalgae to tobacco smoke, the specific growth rate (μmax) was unaffected in CHL-2220 and remained around 0.500 days−1, whereas in CHL-2221, it decreased notably from 0.445 days−1 to 0.376 days−1. In the CHL-2221, the lipid level considerably reduced from 15.55 %DW to 13.37 %DW upon exposure to tobacco smoke. In both strains, palmitic acid was the main constituent of saturated fatty acids (SFAs) that displayed significant (p < 0.05) decreases in response to tobacco smoke exposure. In CHL-2221, oleic acid (C18:1) presented a substantial increase from 7.64 to 17.09% in response to tobacco smoke. Moreover, exposure of CHL-2220 to tobacco smoke decreased the cetane number (CN) from 30.34 to 25.28, while in CHL-2221, it increased from 26.07 to 29.73 upon treatment. Both strains demonstrated low-quality biodiesel to be used as feedstock. Conversely, their fatty acid profile revealed their promising use as nutrient food.
Total Brain Volumetric Measures and Schizophrenia Risk: A Two-Sample Mendelian Randomization Study
Authors: Zhu Dan , Wang Chunyang , Guo Lining , Si Daojun , Liu Mengge , Cai Mengjing , Ma Lin , Fu Dianxun , Fu Jilian , Wang Junping , Liu Feng
Published: March 2022

Schizophrenia (SCZ) is an idiopathic psychiatric disorder with a heritable component and a substantial public health impact. Although abnormalities in total brain volumetric measures (TBVMs) have been found in patients with SCZ, it is still unknown whether these abnormalities have a causal effect on the risk of SCZ. Here, we performed a Mendelian randomization (MR) study to investigate the possible causal associations between each TBVM and SCZ risk. Specifically, genome-wide association study (GWAS) summary statistics of total gray matter volume, total white matter volume, total cerebrospinal fluid volume, and total brain volume were obtained from the United Kingdom Biobank database (33,224 individuals), and SCZ GWAS summary statistics were provided by the Psychiatric Genomics Consortium (150,064 individuals). The main MR analysis was conducted using the inverse variance weighted method, and other MR methods, including MR-Egger, weighted median, simple mode, and weighted mode methods, were performed to assess the robustness of our findings. For pleiotropy analysis, we employed three approaches: MR-Egger intercept, MR-PRESSO, and heterogeneity tests. No TBVM was causally associated with SCZ risk according to the MR results, and no significant pleiotropy or heterogeneity was found for instrumental variables. Taken together, this study suggested that alterations in TBVMs were not causally associated with the risk of SCZ.
Comparison of Data Normalization Strategies for Array-Based MicroRNA Profiling Experiments and Identification and Validation of Circulating MicroRNAs as Endogenous Controls in Hypertension
Authors: Chekka Lakshmi Manasa S. , Langaee Taimour , Johnson Julie A.
Published: March 2022

Introduction: MicroRNAs are small noncoding RNAs with potential regulatory roles in hypertension and drug response. The presence of many of these RNAs in biofluids has spurred investigation into their role as possible biomarkers for use in precision approaches to healthcare. One of the major challenges in clinical translation of circulating miRNA biomarkers is the limited replication across studies due to lack of standards for data normalization techniques for array-based approaches and a lack of consensus on an endogenous control normalizer for qPCR-based candidate miRNA profiling studies.

Methods: We conducted genome-wide profiling of 754 miRNAs in baseline plasma of 36 European American individuals with uncomplicated hypertension selected from the PEAR clinical trial, who had been untreated for hypertension for at least one month prior to sample collection. After appropriate quality control with amplification score and missingness filters, we tested different normalization strategies such as normalization with global mean of imputed and unimputed data, mean of restricted set of miRNAs, quantile normalization, and endogenous control miRNA normalization to identify the method that best reduces the technical/experimental variability in the data. We identified best endogenous control candidates with expression pattern closest to the mean miRNA expression in the sample, as well as by assessing their stability using a combination of NormFinder, geNorm, Best Keeper and Delta Ct algorithms under the Reffinder software. The suitability of the four best endogenous controls was validated in 50 hypertensive African Americans from the same trial with reverse-transcription–qPCR and by evaluating their stability ranking in that cohort.

Results: Among the compared normalization strategies, quantile normalization and global mean normalization performed better than others in terms of reducing the standard deviation of miRNAs across samples in the array-based data. Among the four strongest candidate miRNAs from our selection process (miR-223-3p, 19b, 106a, and 126-5p), miR-223-3p and miR-126-5p were consistently expressed with the best stability ranking in the validation cohort. Furthermore, the combination of miR-223-3p and 126-5p showed better stability ranking when compared to single miRNAs.

Conclusion: We identified quantile normalization followed by global mean normalization to be the best methods in reducing the variance in the data. We identified the combination of miR-223-3p and 126-5p as potential endogenous control in studies of hypertension.
Identification of Common and Distinct Pathways in Inflammatory Bowel Disease and Colorectal Cancer: A Hypothesis Based on Weighted Gene Co-Expression Network Analysis
Authors: Derakhshani Afshin , Javadrashid Darya , Hemmat Nima , Dufour Antoine , Solimando Antonio Giovanni , Abdoli Shadbad Mahdi , Duijf Pascal H. G. , Brunetti Oronzo , Silvestris Nicola , Baradaran Behzad
Published: March 2022

Patients with inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, are at higher risk to develop colorectal cancer (CRC). However, the underlying mechanisms of this predisposition remain elusive. We performed in-depth comparative computational analyses to gain new insights, including weighted gene co-expression network analysis (WGCNA) and gene ontology and pathway enrichment analyses, using gene expression datasets from IBD and CRC patients. When individually comparing IBD and CRC to normal control samples, we identified clusters of highly correlated genes, differentially expressed genes, and module-trait associations specific for each disease. When comparing IBD to CRC, we identified common hub genes and commonly enriched pathways. Most notably, IBD and CRC share significantly increased expression of five genes (MMP10, LCN2, REG1A, REG3A, and DUOX2), enriched inflammatory and neutrophil activation pathways and, most notably, highly significant enrichment of IL-4 and IL-13 signaling. Thus, our work expands our knowledge about the intricate relationship between IBD and CRC development and provides new rationales for developing novel therapeutic strategies.
Prognosis and Dissection of Immunosuppressive Microenvironment in Breast Cancer Based on Fatty Acid Metabolism-Related Signature
Authors: Tang Yuhui , Tian Wenwen , Xie Jindong , Zou Yutian , Wang Zehao , Li Ning , Zeng Yan , Wu Linyu , Zhang Yue , Wu Song , Xie Xiaoming , Yang Lu
Published: March 2022

Fatty acid metabolism has been deciphered to augment tumorigenesis and disease progression in addition to therapy resistance via strengthened lipid synthesis, storage, and catabolism. Breast cancer is strongly associated with the biological function of fatty acid metabolism owing to the abundant presence of adipocytes in breast tissue. It has been unraveled that tumor cells exhibit considerable plasticity based on fatty acid metabolism, responding to extra-tumoral and a range of metabolic signals, in which tumor microenvironment plays a pivotal role. However, the prognostic significance of fatty acid metabolism in breast cancer remains to be further investigated. Alongside these insights, we retrieved 269 reliable fatty acid metabolism-related genes (FMGs) and identified the landscape of copy number variations and expression level among those genes. Additionally, 11 overall survival-related FMGs were clarified by univariate Cox hazards regression analysis in The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Subsequently, a prognostic signature based on 6 overall survival (OS)-related FMGs was generated using Lasso Cox hazards regression analysis in TCGA dataset and was validated in two external cohorts. The correlation between the signature and several essential clinical parameters, including T, N, and PAM50 subtypes, was unveiled by comparing the accumulating signature value in various degrees. Furthermore, an optimal nomogram incorporating the signature, age, and American Joint Committee on Cancer (AJCC) stage was constructed, and the discrimination was verified by C-index, the calibration curve, and the decision curve analysis. The underlying implications for immune checkpoints inhibitors, the landscape of tumor immune microenvironment, and the predictive significance in therapy resistance to diverse strategies were depicted ultimately. In conclusion, our findings indicate the potential prognostic connotation of fatty acid metabolism in breast cancer, supporting novel insights into breast cancer patients’ prognosis and administrating effective immunotherapy.
Interleukin-22 in Renal Protection and Its Pathological Role in Kidney Diseases
Authors: Ma Qianqian , Luan Jingyun , Bai Yu , Xu Caili , Liu Fangyu , Chen Bufeng , Ju Dianwen , Xu Hong
Published: March 2022

Chronic kidney injury has gradually become a worldwide public health problem currently affecting approximately 10% of the population and can eventually progress to chronic end-stage renal disease characteristic by the result of epithelial atrophy. Interleukin-22 (IL-22) is a cytokine produced by activated immune cells, while acting mainly on epithelial cells ranging from innate immune response to tissue regeneration to maintain barrier integrity and promote wound healing. Accumulating data suggests that IL-22 has emerged as a fundamental mediator of epithelial homeostasis in the kidney through promoting tissue repair and regeneration, inhibiting oxidative stress, and producing antimicrobial peptides. Binding of IL-22 to its transmembrane receptor complex triggers janus kinase/tyrosine kinase 2 phosphorylation, which further activates a number of downstream cascades, including signal transducer and activator of transcription 3, MAP kinase, and protein kinase B, and initiates a wide array of downstream effects. However, the activation of the IL-22 signaling pathways promotes the activation of complement systems and enhances the infiltration of chemokines, which does harm to the kidney and may finally result in chronic renal failure of different autoimmune kidney diseases, including lupus nephritis, and IgA nephropathy. This review describes current knowledge of the basic features of IL-22, including structure, cellular origin and associated signaling pathways. Also, we summarize the latest progress in understanding the physiological and pathological effects of IL-22 in the kidney, suggesting the potential strategies for the specific application of this cytokine in the treatment of kidney disease.
The Role of the Crosstalk Between Gut Microbiota and Immune Cells in the Pathogenesis and Treatment of Multiple Myeloma
Authors: Jasiński Marcin , Biliński Jarosław , Basak Grzegorz W.
Published: March 2022

Around 10% of all hematologic malignancies are classified as multiple myeloma (MM), the second most common malignancy within that group. Although massive progress in developing of new drugs against MM has been made in recent years, MM is still an incurable disease, and every patient eventually has relapse refractory to any known treatment. That is why further and non-conventional research elucidating the role of new factors in MM pathogenesis is needed, facilitating discoveries of the new drugs. One of these factors is the gut microbiota, whose role in health and disease is still being explored. This review presents the continuous changes in the gut microbiota composition during our whole life with a particular focus on its impact on our immune system. Additionally, it mainly focuses on the chronic antigenic stimulation of B-cells as the leading mechanism responsible for MM promotion. The sophisticated interactions between microorganisms colonizing our gut, immune cells (dendritic cells, macrophages, neutrophils, T/B cells, plasma cells), and intestinal epithelial cells will be shown. That article summarizes the current knowledge about the initiation of MM cells, emphasizing the role of microorganisms in that process.
Harnessing the Immunogenic Potential of Gold Nanoparticle-Based Platforms as a Therapeutic Strategy in Breast Cancer Immunotherapy: A Mini Review
Authors: Chen Xiao-Yang , Yung Lin-Yue Lanry , Tan Puay Hoon , Bay Boon Huat
Published: March 2022

Breast cancer remains the most common malignancy among women worldwide. Although the implementation of mammography has dramatically increased the early detection rate, conventional treatments like chemotherapy, radiation therapy, and surgery, have significantly improved the prognosis for breast cancer patients. However, about a third of treated breast cancer patients are known to suffer from disease recurrences and progression to metastasis. Immunotherapy has recently gained traction due to its ability to establish long-term immune surveillance, and response for the prevention of disease recurrence and extension of patient survival. Current research findings have revealed that gold nanoparticles can enhance the safety and efficacy of cancer immunotherapy, through their unique intrinsic properties of good biocompatibility, durability, convenient surface modification, as well as enhanced permeability and retention effect. Gold nanoparticles are also able to induce innate immune responses through the process of immunogenic cell death, which can lead to the establishment of lasting adaptive immunity. As such gold nanoparticles are considered as good candidates for next generation immunotherapeutic strategies. This mini review gives an overview of gold nanoparticles and their potential applications in breast cancer immunotherapeutic strategies.
Lipids in Liver Failure Syndromes: A Focus on Eicosanoids, Specialized Pro-Resolving Lipid Mediators and Lysophospholipids
Authors: Artru Florent , McPhail Mark J. W. , Triantafyllou Evangelos , Trovato Francesca Maria
Published: March 2022

Lipids are organic compounds insoluble in water with a variety of metabolic and non-metabolic functions. They not only represent an efficient energy substrate but can also act as key inflammatory and anti-inflammatory molecules as part of a network of soluble mediators at the interface of metabolism and the immune system. The role of endogenous bioactive lipid mediators has been demonstrated in several inflammatory diseases (rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, cancer). The liver is unique in providing balanced immunotolerance to the exposure of bacterial components from the gut transiting through the portal vein and the lymphatic system. This balance is abruptly deranged in liver failure syndromes such as acute liver failure and acute-on-chronic liver failure. In these syndromes, researchers have recently focused on bioactive lipid mediators by global metabonomic profiling and uncovered the pivotal role of these mediators in the immune dysfunction observed in liver failure syndromes explaining the high occurrence of sepsis and subsequent organ failure. Among endogenous bioactive lipids, the mechanistic actions of three classes (eicosanoids, pro-resolving lipid mediators and lysophospholipids) in the pathophysiological modulation of liver failure syndromes will be the topic of this narrative review. Furthermore, the therapeutic potential of lipid-immune pathways will be described.