bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report: Implantable cardioverter-defibrillator implantation with optimal medical treatment for lethal ventricular arrhythmia caused by recurrent coronary artery spasm due to tyrosine kinase inhibitors
Authors: Jin Jifu , Xia Guang , Luo Yu , Cai Ying , Huang Ying , Yang Zhiyun , Yang Qinghui , Yang Bing
Published: March 2023

Coronary artery spasm (CAS) may induce lethal ventricular arrhythmia due to severe and prolonged vessel constriction. Tyrosine kinase inhibitors are associated with the occurrence of CAS. Optimal medical treatment is the first-line therapeutic option for the management of CAS, whereas patients who experienced aborted sudden cardiac death (SCD) may benefit from implantable cardioverter-defibrillator (ICD) implantation. We report a case of a 63-year-old Chinese man receiving tyrosine kinase inhibitor treatment for liver cancer who presented with recurrent chest discomfort and syncope with an elevation of high-sensitivity troponin T. Emergent coronary angiography showed sub-total occlusion of the left anterior descending artery without other signs of CAS. Percutaneous transluminal coronary angioplasty with a drug-coated balloon was performed successfully with the guidance of intravascular ultrasound. After 5 months, the patient returned to the emergency room for chest discomfort and another episode of syncope. The electrocardiogram showed ST-segment elevation in the inferior and V5–V6 leads compared to the previous event. Coronary angiography was repeated immediately and showed significant luminal stenosis at the midportion of the right coronary artery (RCA), whereas, after administration of intracoronary nitroglycerine, a remarkable recovery of RCA patency was noticed. A diagnosis of CAS was made, and soon after that, the patient rapidly developed ventricular arrhythmia in the coronary care unit. After successful resuscitation, the patient recovered completely and received long-acting calcium channel blockers as well as nitrates therapy. ICD implantation was performed considering the high risk of recurrence of life-threatening ventricular arrhythmia. During the follow-up period, the patient has been free of angina, syncope, or ventricular arrhythmia, and ICD interrogation showed no ventricular tachycardia or ventricular fibrillation. We first reported the case of a patient with CAS induced by regorafenib treatment complicated with severe atherosclerotic coronary disease who survived from sudden cardiac arrest. ICD implantation is indicated in patients who experienced aborted SCD for the prevention of the next lethal ventricular arrhythmia.
Unveiling the outer core composition with neutrino oscillation tomography
Authors: Maderer Lukas , Kaminski Edouard , Coelho João A. B. , Bourret Simon , Van Elewyck Véronique
Published: March 2023

In the last 70 years, geophysics has established that the Earth’s outer core is an FeNi alloy containing a few percent of light elements, whose nature and amount remain controversial. Besides the classical combinations of silicon and oxygen, hydrogen has been advocated as the only light element that could account alone for both the core density and velocity profiles. Here we show how this question can be addressed from an independent viewpoint, by exploiting the tomographic information provided by atmospheric neutrinos, weakly-interacting particles produced in the atmosphere and constantly traversing the Earth. We evaluate the potential of the upcoming generation of atmospheric neutrino detectors for such a measurement, showing that they could efficiently detect the presence of 1 wt% hydrogen in the Earth’s core in 50 years of concomitant data taking. We then identify the main requirements for a next-generation detector to perform this measurement in a few years timescale, with the further capability to efficiently discriminate between FeNiH and FeNiSixOy core composition models in less than 15 years.
Correction of precipitation measurement for weighing precipitation gauges in a glacierized basin in the Tianshan Mountains
Authors: Jia Yufeng , Li Zhongqin , Wang Feiteng , Chen Puchen
Published: March 2023

Precipitation is one of the most important climatological data for global hydrothermal cycle and climate change. The accuracy of precipitation data not only directly affects the hydrological processes, but also plays an important role in the climate and hydrology at regional and global scales. According to the in situ datasets, the precipitation measurement in automatic weather stations for Geonor T-200B was corrected by the World Meteorological Organization Solid Precipitation Intercomparison Experiment (WMO-SPICE) transfer functions. The parameters of transfer functions were tested and recalibrated by the local datasets. The results showed that the transfer functions showed better performance after recalibrating parameters by the local datasets. The root-mean-square error (RMSE) and mean bias decreased by an average of 34% and 42%, respectively. The corrected snowfall increased by 7% (14 mm) at the test station. Then, the new parameters were used in other automatic weather stations to correct precipitation, and it was found that solid precipitation was underestimated by 13% on the glacier surface affected by wind speed. Moreover, according to the corrected precipitation datasets observed in automatic weather stations and national meteorological stations, the precipitation–altitude relationship in the Urumqi River Basin was analyzed. The annual precipitation gradient was 115 mm km-1, and the maximum seasonal altitude occurred in summer with a value of 35 mm km-1 and in autumn with the lowest value of 1 mm km-1. When considering precipitation on the glacier surface, the yearly precipitation gradient was increased with the value of 158 mm km -1 in 2019.
Stress-associated weight gain, fibromyalgia symptoms, cardiometabolic markers, and human growth hormone suppression respond to an amino acid supplement blend: Results of a prospective, cohort study
Authors: Pekarovics Susan , Beres Adam , Kelly Colleen , Billes Sonja K. , Heaton Amy L.
Published: March 2023

Introduction

An orally administered amino acid-based test supplement was recently shown to increase human growth hormone (hGH) in healthy adults. This prospective, observational, single-center, single-arm cohort study investigated the effects of 24 weeks of daily oral administration of the test supplement in individuals with stress-related weight gain, fibromyalgia (FM) and stress-related low-normal hGH production (15-30th percentile for age-appropriate levels) on insulin-like growth factor 1 (IGF-1), an indicator of hGH levels caused by stress related stimulation of somatostatin.

Methods

Participants continued to receive standard care. The primary endpoint was the change from baseline to endpoint (Week 24) in serum IGF-1. Additional endpoints included the change in body weight, clinical symptoms (assessed with the Revised Fibromyalgia Impact Questionnaire [FIQR], range 0-100, and Perceived Stress Scale [PSS], range 0-40), fasting cardiometabolic markers, tolerability, and safety. The study enrolled 84 fibromyalgia patients with low-normal age-adjusted IGF-1 serum levels. High mean ± Standard Deviation (SD) baseline FIQR and PSS scores of 76 ± 16 and 32 ± 5, respectively, indicated poor to moderate symptom management with standard care. All individuals completed 24 weeks.

Results

Serum IGF-1 levels increased with a Week 24 mean± Standard Error (SE) change of 28.4 ± 3.0 ng/mL (p<0.001). Body weight was reduced with a Week 24 mean ± SE change of -5.5 ± 0.3 kg (p<0.001) (a 6.5% weight loss from baseline). The change from baseline in FIQR and PSS scores were -29.1 ± 1.1 and -20.0 ± 0.8, respectively (both p<0.001), indicating a substantial improvement. Statistically significant improvements from baseline to Week 24 were observed in systolic and diastolic blood pressure, HbA1c, LDL and HDL cholesterol, and triglycerides (all p<0.001). The supplement was well tolerated; no adverse events were reported.

Discussion

Sustained augmentation of IGF-1 with the test supplement may represent a novel method of improving clinical symptoms, including stress-related weight gain, in individuals with fibromyalgia and stress-associated low-normal hGH.
Pharmacological management of cherubism: A systematic review
Authors: Cailleaux Pierre-Emmanuel , Porporatti André Luís , Cohen-Solal Martine , Kadlub Natacha , Coudert Amélie E.
Published: March 2023

Objective

The aim of this systematic review was to determine if there exists an efficacious drug treatment for cherubism, based on published studies.

Methods

This systematic review included observational case studies reporting pharmacological management of cherubism. We developed specific search strategies for PubMed (including Medline), ScienceDirect, Web of Science. We evaluated the methodological quality of the included studies using criteria from the Joanna Briggs Institute’s critical appraisal tools.

Results

Among the 621 studies initially identified by our search script, 14 were selected for inclusion, of which five were classified as having a low risk of bias, four as having an unclear risk, and five a high risk. Overall, 18 cherubism patients were treated. The sample size in each case study ranged from one to three subjects. This review identified three types of drugs used for cherubism management: calcitonin, immunomodulators and anti-resorptive agents. However, the high heterogeneity in case reports and the lack of standardized outcomes precluded a definitive conclusion regarding the efficacy of any treatment for cherubism.

Conclusions

The present systematic review could not identify an effective treatment for cherubism due to the heterogeneity and limitations of the included studies. However, in response to these shortcomings, we devised a checklist of items that we recommend authors consider in order to standardize the reporting of cherubism cases and specifically when a treatment is given toward identification of an efficacious cherubism therapy.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351044, identifier CRD42022351044.
The protective activity of natural flavonoids against osteoarthritis by targeting NF-κB signaling pathway
Authors: Ye Yongjun , Zhou Jianguo
Published: March 2023

Osteoarthritis (OA) is a typical joint disease associated with chronic inflammation. The nuclear factor-kappaB (NF-κB) pathway plays an important role in inflammatory activity and inhibiting NF-κB-mediated inflammation can be a potential strategy for treating OA. Flavonoids are a class of naturally occurring polyphenols with anti-inflammatory properties. Structurally, natural flavonoids can be divided into several sub-groups, including flavonols, flavones, flavanols/catechins, flavanones, anthocyanins, and isoflavones. Increasing evidence demonstrates that natural flavonoids exhibit protective activity against the pathological changes of OA by inhibiting the NF-κB signaling pathway. Potentially, natural flavonoids may suppress NF-κB signaling-mediated inflammatory responses, ECM degradation, and chondrocyte apoptosis. The different biological actions of natural flavonoids against the NF-κB signaling pathway in OA chondrocytes might be associated with the differentially substituted groups on the structures. In this review, the efficacy and action mechanism of natural flavonoids against the development of OA are discussed by targeting the NF-κB signaling pathway. Potentially, flavonoids could become useful inhibitors of the NF-κB signaling pathway for the therapeutic management of OA.
Total versus partial adrenalectomy in bilateral pheochromocytoma – a systematic review and meta-analysis
Authors: Zawadzka Karolina , Tylec Piotr , Małczak Piotr , Major Piotr , Pędziwiatr Michał , Pisarska-Adamczyk Magdalena
Published: March 2023

Background

In patients with bilateral pheochromocytoma, partial adrenalectomy offers the chance to preserve adrenal function and avoid the need for lifelong steroid supplementation. However, the risk of tumour recurrence raises questions about this procedure. The aim of our study was to compare partial and total adrenalectomy in bilateral pheochromocytoma through a systematic review with meta-analysis.

Methods

A systematic search was carried out using databases (MEDLINE, EMBASE, Scopus, Web of Science, CENTRAL) and registers of clinical trials (ClinicalTrials.gov, European Trials Register, WHO International Trials Registry Platform). This meta-analysis included studies up to July 2022 without language restrictions. A random effects model meta-analysis was performed to assess the risk of tumor recurrence, steroid dependence and morbidity in these patients.

Results

Twenty-five studies were included in the analysis involving 1444 patients. The relative risk (RR) of loss of adrenal hormone function during follow-up and the need for steroid therapy was 0.32 in patients after partial adrenalectomy: RR 0.32, 95% Confidence Interval (CI): 0.26-0.38, P < 0.00001, I2 = 21%. Patients undergoing partial adrenalectomy had a lower odds ratio (OR) for developing acute adrenal crisis: OR 0.3, 95% CI: 0.1-0.91, P=0.03, I2 = 0%. Partial adrenalectomy was associated with a higher risk of recurrence than total adrenalectomy: OR 3.72, 95% CI: 1.54-8.96, P=0.003, I2 = 28%.

Conclusion

Partial adrenalectomy for bilateral pheochromocytoma is a treatment that offers a chance of preserving adrenal hormonal function, but is associated with a higher risk of local tumor recurrence. There was no difference for the risk of metastasis and in overall mortality among the group with bilateral pheochromocytomas undergoing total or partial adrenalectomy.

This study is in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (A Measurement Tool to Assess Systematic Reviews) Guidelines (10, 11).

Systematic review registration

https://osf.io/zx3se.
Comparison between D-loop methylation and mtDNA copy number in patients with Aicardi-Goutières Syndrome
Authors: Dragoni Francesca , Garau Jessica , Orcesi Simona , Varesio Costanza , Bordoni Matteo , Scarian Eveljn , Di Gerlando Rosalinda , Fazzi Elisa , Battini Roberta , Gjurgjaj Altea , Rizzo Bartolo , Pansarasa Orietta , Gagliardi Stella
Published: March 2023

Introduction

Aicardi-Goutières Syndrome (AGS) is a rare encephalopathy with early onset that can be transmitted in both dominant and recessive forms. Its phenotypic covers a wide range of neurological and extraneurological symptoms. Nine genes that are all involved in nucleic acids (NAs) metabolism or signaling have so far been linked to the AGS phenotype. Recently, a link between autoimmune or neurodegenerative conditions and mitochondrial dysfunctions has been found. As part of the intricate system of epigenetic control, the mtDNA goes through various alterations. The displacement (D-loop) region represents one of the most methylated sites in the mtDNA. The term "mitoepigenetics" has been introduced as a result of increasing data suggesting that epigenetic processes may play a critical role in the control of mtDNA transcription and replication. Since we showed that RNASEH2B and RNASEH2A-mutated Lymphoblastoid Cell Lines (LCLs) derived from AGS patients had mitochondrial alterations, highlighting changes in the mtDNA content, the main objective of this study was to examine any potential methylation changes in the D-loop regulatory region of mitochondria and their relationship to the mtDNA copy number in peripheral blood cells of AGS patients with mutations in various AGS genes and healthy controls.

Materials and methods

We collected blood samples from 25 AGS patients and we performed RT-qPCR to assess the mtDNA copy number and pyrosequencing to measure DNA methylation levels in the D-loop region.

Results

Comparing AGS patients to healthy controls, D-loop methylation levels and mtDNA copy number increased significantly. We also observed that in AGS patients, the mtDNA copy number increased with age at sampling, but not the D-loop methylation levels, and there was no relationship between sex and mtDNA copy number. In addition, the D-loop methylation levels and mtDNA copy number in the AGS group showed a non-statistically significant positive relation.

Conclusion

These findings, which contradict the evidence for an inverse relationship between D-loop methylation levels and mtDNA copy number, show that AGS patients have higher D-loop methylation levels than healthy control subjects. Additional research is needed to identify the function of these features in the etiology and course of AGS.
Grazing disturbance significantly decreased soil organic carbon contents of alpine grasslands on the Tibetan Plateau
Authors: Yang Hua , Zhang Yonggang , Li Wei , Xu Qingmin , Zhou Huakun , Du Yangong
Published: March 2023

Ecological security barriers on the Tibetan Plateau are threatened by climate change and human activities, such as grassland degradation and reduction of carbon fixation capacity. Understanding the influence of grazing on soil organic carbon (SOC) content and its regulating factors is important for improving the ecological barrier function of alpine grasslands. In this meta-analysis, we analysed the effects of grazing on SOC. The results indicate that grazing disturbance significantly reduced the SOC content by 13.93%, with an effect size of −0.15 ± 0.04 (p < 0.001). The effect of light grazing was not significant. The reduction range gradually increased with increasing grazing intensity. The effect of grazing activity on SOC content was driven mainly by pH and total nitrogen through a structural equation model. Future nitrogen deposition scenarios would significantly increase alpine meadow SOC on the Tibetan Plateau.
The chemical composition of the secretions, their antibacterial activity, and the pygidial gland morphology of selected European Carabini ground beetles (Coleoptera: Carabidae)
Authors: Vesović Nikola , Nenadić Marija , Vranić Sofija , Vujisić Ljubodrag , Milinčić Katarina M. , Todosijević Marina , Dimkić Ivica , Janakiev Tamara , Ćurčić Nina B. , Stevanović Nataša , Mihajlović Ljiljana , Vukoičić Danijela Ž. , Ćurčić Srećko
Published: March 2023

The pygidial glands of carabids produce strong-smelling vapours. In this study, we examined the chemical composition of the gland secretions and the structure of the glands in five species of Carabini ground beetles (one species from the subtribe Calosomatina and four species from the subtribe Carabina): Calosoma (Calosoma) maderae (Fabricius, 1775), Carabus (Carabus) granulatus Linnaeus, 1758, C. (Limnocarabus) clathratus Linnaeus, 1760, C. (Carabus) ulrichii Germar, 1823, and C. (Procerus) gigas Creutzer, 1799. Additionally, we tested the antibacterial potential of the pygidial gland secretions of the two latter species against 11 bacterial strains. In order to detect the chemical content of the secretions, we used gas chromatography–mass spectrometry (GC–MS). The secretion extracts were applied against selected strains of medically important bacteria. We used bright-field microscopy to examine the morphology of the glands. We discovered a total of 11 chemical compounds in the pygidial gland extracts of the ground beetles we analysed. Ten of these compounds were identified as seven carboxylic acids, two hydrocarbons, and one aromatic aldehyde, while one chemical remained unidentified. Most of the components were isolated from the secretion of C. (L.) clathratus (nine), while the lowest number of compounds was found in C. (P.) gigas (two). Methacrylic acid was the most dominant compound by percentage in all five species, while angelic acid was also detected in all samples. As expected, salicylaldehyde was exclusively found in the species of the genus Calosoma Weber, 1801. The secretion of C. (P.) gigas was shown to achieve the highest level of antibacterial activity against Pseudomonas aeruginosa, Salmonella enterica, and S. typhimurium (even the same level as the positive control streptomycin), while the secretion of C. (C.) ulrichii achieved the highest antimicrobial potential against Staphylococcus epidermidis, S. aureus, Listeria monocytogenes, and Bacillus cereus. The most noticeable difference in the structure of the glands between the two genera is that the reservoir in Calosoma is more significantly narrowed as it leads into the efferent duct, compared to that of Carabus.
Effects of warming and isolation from precipitation on the soil carbon, nitrogen, and phosphorus, and their stoichiometries in an alpine meadow in the Qinghai–Tibet Plateau: A greenhouse warming study
Authors: Tong Yongpeng , Long Yanjun , Yang Zhen’an
Published: March 2023

Introduction

In the Qinghai–Tibet Plateau (QTP), alpine meadows are among the most noticeable reflection of global climate change. However, effects of global warming on soils hosting alpine meadows in the QTP, such as reduced moisture because of low precipitation, remain unclear.

Methods

Here, the soil moisture content (SMC), pH, dissolved organic carbon (DOC), ammonium nitrogen (NH4+–N), nitrate nitrogen (NO3−–N) and available phosphorus (AP) contents in the QTP were analyzed. The changes in and stoichiometries of total carbon, nitrogen, and phosphorus (TC, TN, and TP), microbial biomass carbon, nitrogen, and phosphorus (MBC, MBN, and MBP), β-1,4-glucosidase (BG), β-1,4-N-acetylglucoaminosidase (NAG), leucine aminopeptidase (LAP), and acid phosphatase (ACP) in the 0–30 cm layer of soils associated with warming in a greenhouse in the QTP from 2015 to 2020 were characterized.

Results

We found that warming in the greenhouse significantly decreased the SMC, NO3−–N, MBC, MBN, MBP, BG, LAP, ACP, and enzymatic C:N ratio. The warming increased the DOC, NH4+–N, AP, MBC:MBN, and enzymatic N:P ratios noticeably. The pH, TC, TN, TP, C:N, C:P, N:P, MBC:MBP, MBN:MBP, and enzymatic C:P ratios were minimally affected.

Conclusion

The results showed that warming and isolation from precipitation promoted mineralization of N and P in the soil but did not significantly alter the cycling of elements in soils in an alpine meadow.
Hereditary orotic aciduria identified by newborn screening
Authors: Staretz-Chacham Orna , Damseh Nadirah S. , Daas Suha , Abu Salah Nasser , Anikster Yair , Barel Ortal , Dumin Elena , Fattal-Valevski Aviva , Falik-Zaccai Tzipora C. , Hershkovitz Eli , Josefsberg Sagi , Landau Yuval , Lerman-Sagie Tally , Mandel Hanna , Rock Rachel , Rostami Nira , Saraf-Levy Talya , Shaul Lotan Nava , Spiegel Ronen , Tal Galit , Ulanovsky Igor , Wilnai Yael , Korman Stanley H. , Almashanu Shlomo
Published: March 2023

Introduction: Hereditary orotic aciduria is an extremely rare, autosomal recessive disease caused by deficiency of uridine monophosphate synthase. Untreated, affected individuals may develop refractory megaloblastic anemia, neurodevelopmental disabilities, and crystalluria. Newborn screening has the potential to identify and enable treatment of affected individuals before they become significantly ill.

Methods: Measuring orotic acid as part of expanded newborn screening using flow injection analysis tandem mass spectrometry.

Results: Since the addition of orotic acid measurement to the Israeli routine newborn screening program, 1,492,439 neonates have been screened. The screen has identified ten Muslim Arab newborns that remain asymptomatic so far, with DBS orotic acid elevated up to 10 times the upper reference limit. Urine organic acid testing confirmed the presence of orotic aciduria along with homozygous variations in the UMPS gene.

Conclusion: Newborn screening measuring of orotic acid, now integrated into the routine tandem mass spectrometry panel, is capable of identifying neonates with hereditary orotic aciduria.
I kappa B kinase interacting protein as a promising biomarker in pan-cancer: A multi-omics analysis
Authors: Bi Chenyang , Wang Zhe , Xiao Yafei , Zhao Ying , Guo Runjiang , Xiong Luyao , Ji Zhiyu , Li Yifan , Li Quanying , Qin Changjiang
Published: March 2023

Background: Human chromosome 12 contains I kappa B kinase interacting protein (IKBIP) is also commonly known as IKIP. The involvement of IKBIP in the growth of tumors has only been discussed in a small number of publications.

Purpose: To explore the role that IKBIP plays in the development of a wide variety of neoplasms, as well as the tumor immunological microenvironment.

Methods: UALCAN, HPA, Genotype Tissue Expression, Cancer Genome Maps, and other datasets were used to analyze IKBIP expression. We thoroughly investigated the predictive importance of IKBIP in pan-cancer, clinical traits, and genetic anomalies. We studied whether there is a link between IKBIP and immune-related genes, microsatellite instability (MSI), and the incidence of tumor mutational burden (TMB). The link between immune cell infiltration and IKBIP expression was examined using data on immune cell infiltration from ImmuCellAI, TIMER2, and earlier studies. Finally, gene set enrichment analysis (GSEA) was performed to determine the signaling pathways associated with IKBIP.

Results: IKBIP is highly expressed in most cancers and is negatively associated with the prognosis of several major cancer types. Furthermore, IKBIP expression was linked to TMB in 13 cancers and MSI in seven cancers. Additionally, IKBIP is associated with numerous immunological and cancer-promoting pathways. Simultaneously, various cancer types have unique tumor-infiltrating immune cell profiles.

Conclusion: IKBIP has the potential to act as a pan-cancer oncogene and is crucial for both carcinogenesis and cancer immunity. Elevated IKBIP expression implies an immunosuppressive environment and may be used as a prognostic biomarker and therapeutic target.
Why is farming important for rural livelihood security in the global south? COVID-19 and changing rural livelihoods in Nepal's mid-hills
Authors: Khatri Dil , Marquardt Kristina , Fischer Harry , Khatri Sanjaya , Singh Devanshi , Poudel Dilli Prasad
Published: March 2023

Over the last three decades, Nepal has experienced a rapid transition in rural livelihoods, from largely subsistence farming to more diversified off-farm employment and remittances. Despite this, subsistence farming continues to be a central part of rural production. Why does farming persist in the face of other, more remunerative, off-farm employment options? In this article we argue that subsistence food production continues to be important for rural livelihood security by providing food needs from farming, thus helping households to cope with uncertainties in off-farm employment and international labor migration. Taking the COVID-19 pandemic as an example of a high level of livelihood stress, the paper provides insights and further explanations on the logic of maintaining subsistence food production as part of rural households' livelihood security. Drawing on in-depth qualitative study, complemented with a quantitative survey from eight villages in rural Nepal, we examine the impact of the pandemic on farming and off-farm activities and explore the reasons behind peoples' choice of livelihood strategies and how these vary between different social groups. We show that there was only limited impact of the dramatic disruptions caused by the global pandemic on subsistence farming, however it brought substantial challenges for emerging semi-commercial farming and off-farm incomes, including both local and migratory wage labor. During the pandemic, people increased their reliance on locally produced food, and subsistence farming served as a critical safety net. Our analysis underscores the continued importance of subsistence production amidst contemporary shifts toward off-farm employment among rural households. We also find a growing interest in semi-commercial farming among farmers with better access to land who seek state support to develop such production. This suggests that it is important for agricultural development policy to recognize and support subsistence farming alongside emerging commercial agriculture production as an integral foundation of future farming and rural livelihood security.
Epigenetic immune monitoring for COVID-19 disease course prognosis
Authors: Samans Björn , Rosselló Chornet Marta , Rosselló Chornet Araceli , Jung Janine , Schildknecht Konstantin , Lozza Laura , Alos Zaragoza Lourdes , Hernández Laforet Javier , Babel Nina , Olek Sven
Published: March 2023

Background

The course of COVID-19 is associated with severe dysbalance of the immune system, causing both leukocytosis and lymphopenia. Immune cell monitoring may be a powerful tool to prognosticate disease outcome. However, SARS-CoV-2 positive subjects are isolated upon initial diagnosis, thus barring standard immune monitoring using fresh blood. This dilemma may be solved by epigenetic immune cell counting.

Methods

In this study, we used epigenetic immune cell counting by qPCR as an alternative way of quantitative immune monitoring for venous blood, capillary blood dried on filter paper (dried blood spots, DBS) and nasopharyngeal swabs, potentially allowing a home-based monitoring approach.

Results

Epigenetic immune cell counting in venous blood showed equivalence with dried blood spots and with flow cytometrically determined cell counts of venous blood in healthy subjects. In venous blood, we detected relative lymphopenia, neutrophilia, and a decreased lymphocyte-to-neutrophil ratio for COVID-19 patients (n =103) when compared with healthy donors (n = 113). Along with reported sex-related differences in survival we observed dramatically lower regulatory T cell counts in male patients. In nasopharyngeal swabs, T and B cell counts were significantly lower in patients compared to healthy subjects, mirroring the lymphopenia in blood. Naïve B cell frequency was lower in severely ill patients than in patients with milder stages.

Conclusions

Overall, the analysis of immune cell counts is a strong predictor of clinical disease course and the use of epigenetic immune cell counting by qPCR may provide a tool that can be used even for home-isolated patients.
Design of a multi-epitopic vaccine against Epstein-Barr virus via computer-based methods
Authors: Larijani Amirhossein , Kia-Karimi Ali , Roostaei Davoud
Published: March 2023

Background

Scientific findings have shown that Epstein-Barr virus (EBV) plays a key role in the development of some tumor diseases. Therefore, this study intends to take a practical step in controlling the pathogenicity of this virus by designing an effective vaccine based on the virus Capsid Envelope and Epstein–Barr nuclear immunogen (EBNA) Proteins Epitopes. Currently, there are no effective drugs or vaccines to treat or prevent EBV infection. So, we applied a computer-based strategy to design an epitope vaccine

Results

We designed a powerful multi-epitope peptide vaccine against EBV using in silico analysis. The vaccine is made up of 844 amino acids derived from three different types of proteins (Envelope, Capsid, EBNA) found in two different viral strains. responses. These epitopes have a high immunogenic capacity and are not likely to cause allergies. To enhance the vaccine immunogenicity, we used rOv-ASP-1, a recombinant Onchocerca volvulus activation associated protein-1, as an adjuvant and linked it to the vaccine’s N and C terminus. The physicochemical and immunological properties of the vaccine structure were evaluated. The proposed vaccine was stable, with a stability index of 33.57 and a pI of 10.10, according to bioinformatic predictions. Docking analysis revealed that the vaccine protein binds correctly with immunological receptors.

Conclusion

Our results demonstrated that the multi-epitope vaccine might be potentially immunogenic and induce humoral and cellular immune responses against EBV. This vaccine can interact appropriately with immunological receptors Also, it has a high-quality structure and suitable characteristics such as high stability.
Intratumor microbiota as a novel potential prognostic indicator in mesothelioma
Authors: Pentimalli Francesca , Krstic-Demonacos Marija , Costa Caterina , Mutti Luciano , Bakker Emyr Yosef
Published: March 2023

Introduction

Despite increased attention on immunotherapy, primarily immune checkpoint blockade, as a therapeutic approach for mesothelioma (MMe), its efficacy and tolerability remain questioned. One potential explanation for different responses to immunotherapy is the gut and intratumor microbiota; however, these remain an underexplored facet of MMe. This article highlights the cancer intratumor microbiota as a novel potential prognostic indicator in MMe.

Methods

TCGA data on 86 MMe patients from cBioPortal underwent bespoke analysis. Median overall survival was used to divide patients into “Low Survivors” and “High Survivors”. Comparison of these groups generated Kaplan-Meier survival analysis, differentially expressed genes (DEGs), and identification of differentially abundant microbiome signatures. Decontamination analysis refined the list of signatures, which were validated as an independent prognostic indicator through multiple linear regression modelling and Cox proportional hazards modelling. Finally, functional annotation analysis on the list of DEGs was performed to link the data together.

Results

107 genera signatures were significantly associated with patient survival (positively or negatively), whilst clinical characteristic comparison between the two groups demonstrated that epithelioid histology was more common in “High Survivors” versus biphasic in “Low Survivors”. Of the 107 genera, 27 had published articles related to cancer, whilst only one (Klebsiella) had MMe-related published articles. Functional annotation analysis of the DEGs between the two groups highlighted fatty acid metabolism as the most enriched term in “High Survivors”, whilst for “Low Survivors” the enriched terms primarily related to cell cycle/division. Linking these ideas and findings together is that the microbiome influences, and is influenced by, lipid metabolism. Finally, to validate the independent prognostic value of the microbiome, multiple linear regression modelling as well as Cox proportional hazards modelling were employed, with both approaches demonstrating that the microbiome was a better prognostic indicator than patient age or stage of the cancer.

Discussion

The findings presented herein, alongside the very limited literature from scoping searches to validate the genera, highlight the microbiome and microbiota as a potentially rich source of fundamental analysis and prognostic value. Further in vitro studies are needed to elucidate the molecular mechanisms and functional links that may lead to altered survival.
The Gulf of Mexico in trouble: Big data solutions to climate change science
Authors: Sunkara Vishwamithra , McKenna Jason , Kar Soumyashree , Iliev Iliyan , Bernstein Diana N.
Published: March 2023

The latest technological advancements in the development and production of sensors have led to their increased usage in marine science, thus expanding data volume and rates within the field. The extensive data collection efforts to monitor and maintain the health of marine environments supports the efforts in data driven learning, which can help policy makers in making effective decisions. Machine learning techniques show a lot of promise for improving the quality and scope of marine research by detecting implicit patterns and hidden trends, especially in big datasets that are difficult to analyze with traditional methods. Machine learning is extensively used on marine science data collected in various regions, but it has not been applied in a significant way to data generated in the Gulf of Mexico (GOM). Machine learning methods using ocean science data are showing encouraging results and thus are drawing interest from data science researchers and marine scientists to further the research. The purpose of this paper is to review the existing approaches in studying GOM data, the state of the art in machine learning techniques as applied to the GOM, and propose solutions to GOM data problems. We review several issues faced by marine environments in GOM in addition to climate change and its effects. We also present machine learning techniques and methods used elsewhere to address similar problems and propose applications to problems in the GOM. We find that Harmful Algal Blooms (HABs), hypoxia, and sea-level rises have not received as much attention as other climate change problems and within the machine learning literature, the impacts on estuaries and coastal systems, as well as oyster mortality (also major problems for the GOM) have been understudied – we identify those as important areas for improvement. We anticipate this manuscript will act as a baseline for data science researchers and marine scientists to solve problems in the GOM collaboratively and/or independently.
Extreme sea level changes over the tropical western Pacific in 1.5 °C and 2.0 °C warmer climates
Authors: Zheng Yuhang , Zhuang Wei , Du Yan
Published: March 2023

The tropical western Pacific and the adjacent South China Sea are home to many low-lying islands and coastal zones that are vulnerable to flood hazards resulting from extreme sea level (ESL) changes. Based on the hourly sea level recorded by 15 tide gauges during the period 1980-2018, this study evaluates the historical trend of ESLs over this region. On this basis, a regression model for hourly future sea-level prediction is established by combining the atmospheric reanalysis products, the tidal harmonics, and the outputs of three climate models archived by the Coupled Model Intercomparison Project Phase 6 (CMIP6) to evaluate the future ESL changes in 1.5 °C and 2.0 °C warmer climates. The historical trend of ESLs show that the ESLs along the coasts and islands of the tropical western Pacific have significantly risen during the past decades, which is mainly contributed by the mean sea level rise. And results from the historical observations and the prediction model show that in a warming climate from 1980 to 2050, both the mean sea levels and ESLs rise with fluctuations. The mean sea level change plays an important role in the secular trend of ESLs, while the interannual-to-decadal variability of ESLs is significantly affected by tides and extreme weather events. Under the warming scenario of 1.5°C, the changes in the return levels of ESL relative to the historical period are generally small at most tide gauge sites. Compared with the situations under 1.5°C warming, the return levels of ESL at most selected tide gauges will rise more significantly under the 2.0°C warming scenario, so the frequency of the current 100-year return level will reduce to less than 10 years at most stations. The above results suggest that this additional 0.5°C warming will cause a huge difference in the ESLs along the coasts and islands of the tropical western Pacific. As proposed in the Paris climate agreement, it is very necessary to limit anthropogenic warming to 1.5°C instead of 2.0°C, which will substantially reduce the potential risk of flood disasters along the coasts and islands of the tropical western Pacific.
The advancements in targets for ferroptosis in liver diseases
Authors: Xiang Xiaohong , Gao Jianbo , Su Danyang , Shi Doudou
Published: March 2023

Ferroptosis is a type of regulated cell death caused by iron overload and lipid peroxidation, and its core is an imbalance of redox reactions. Recent studies showed that ferroptosis played a dual role in liver diseases, that was, as a therapeutic target and a pathogenic factor. Therefore, herein, we summarized the role of ferroptosis in liver diseases, reviewed the part of available targets, such as drugs, small molecules, and nanomaterials, that acted on ferroptosis in liver diseases, and discussed the current challenges and prospects.
Heparin-based versus bivalirudin-based anticoagulation in pediatric extracorporeal membrane oxygenation: A systematic review
Authors: Valdes Carlos A. , Sharaf Omar M. , Bleiweis Mark S. , Jacobs Jeffrey P. , Mumtaz Mohammed , Sharaf Ramy M. , Jeng Eric I. , Peek Giles J.
Published: March 2023

Introduction

Optimal anticoagulation therapy is essential for the prevention of thrombotic and hemorrhagic complications in pediatric patients supported with extracorporeal membrane oxygenation (ECMO). Recent data have demonstrated bivalirudin has the potential to surpass and replace heparin as the anticoagulant of choice.

Methods

We conducted a systematic review comparing the outcomes of heparin-based versus bivalirudin-based anticoagulation in pediatric patients supported on ECMO to identify the preferred anticoagulant to minimize bleeding events, thrombotic complications, and associated mortality. We referenced the PubMed, Cochrane Library, and Embase databases. These databases were searched from inception through October 2022. Our initial search identified 422 studies. All records were screened by two independent reviewers using the Covidence software for adherence to our inclusion criteria, and seven retrospective cohort studies were identified as appropriate for inclusion.

Results

In total, 196 pediatric patients were anticoagulated with heparin and 117 were anticoagulated with bivalirudin while on ECMO. Across the included studies, it was found that for patients treated with bivalirudin, trends were noted toward lower rates of bleeding, transfusion requirements, and thrombosis with no difference in mortality. Overall costs associated with bivalirudin therapy were lower. Time to therapeutic anticoagulation varied between studies though institutions had different anticoagulation targets.

Conclusion

Bivalirudin may be a safe, cost-effective alternative to heparin in achieving anticoagulation in pediatric ECMO patients. Prospective multicenter studies and randomized control trials with standard anticoagulation targets are needed to accurately compare outcomes associated with heparin versus bivalirudin in pediatric ECMO patients.
Sugarcane straw returning is an approaching technique for the improvement of rhizosphere soil functionality, microbial community, and yield of different sugarcane cultivars
Authors: Wang Mengrong , Qi Xiaohang , Shi Yujie , Zhao Junyang , Ahmad Shakeel , Akhtar Kashif , Chen Baoshan , Lian Tengxiang , He Bing , Wen Ronghui
Published: March 2023

Sugarcane straw returned to the field has rapidly increased due to the bane on straw burning in China. Straw returning of new sugarcane cultivars has been practiced in the fields. Still, its response has not been explored on soil functionality, microbial community and yield of different sugarcane cultivars. Therefore, a comparison was made between an old sugarcane cultivar ROC22 and a new sugarcane cultivar Zhongzhe9 (Z9). The experimental treatments were: without (R, Z), with straw of the same cultivar (RR, ZZ), and with straw of different cultivars (RZ, ZR). Straw returning improved the contents of soil total nitrogen (TN by 73.21%), nitrate nitrogen (NO3—N by 119.61%), soil organic carbon (SOC by 20.16%), and available potassium (AK by 90.65%) at the jointing stage and were not significant at the seedling stage. The contents of NO3—N was 31.94 and 29.58%, available phosphorus (AP 53.21 and 27.19%), and available potassium (AK 42.43 and 11.92%) in RR and ZZ were more than in RZ and ZR. Straw returning with the same cultivar (RR, ZZ) significantly increased the richness and diversity of the rhizosphere microbial community. The microbial diversity of cultivar Z9 (treatment Z) was greater than that of cultivar ROC22 (Treatment R). In the rhizosphere, the relative abundance of beneficial microorganisms Gemmatimonadaceae, Trechispora, Streptomyces, Chaetomium, etc., increased after the straw returned. Sugarcane straw enhanced the activity of Pseudomonas and Aspergillus and thus increased the yield of sugarcane., The richness and diversity of the rhizosphere microbial community of Z9 increased at maturity. In ROC22, bacterial diversity increased, and fungal diversity decreased. These findings collectively suggested that the impact of Z9 straw returning was more beneficial than ROC22 on the activity of rhizosphere microorganism’s soil functionality and sugarcane production.
Interaction between a fluoroquinolone derivative KG022 and RNAs: Effect of base pairs 3′ adjacent to the bulged residues
Authors: Ichijo Rika , Kamimura Takashi , Kawai Gota
Published: March 2023

RNA-targeted small molecules are a promising modality in drug discovery. Recently, we found that a fluoroquinolone derivative, KG022, can bind to RNAs with bulged C or G. To clarify the RNA specificity of KG022, we analyzed the effect of the base pair located at the 3′side of the bulged residue. It was found that KG022 prefers G-C and A-U base pairs at the 3′side. Solution structures of the complexes of KG022 with the four RNA molecules with bulged C or G and G-C or A-U base pairs at the 3′side of the bulged residue were determined to find that the fluoroquinolone moiety is located between two purine bases, and this may be the mechanism of the specificity. This work provides an important example of the specificity of RNA-targeted small molecules.
Sodium valproate-induced nocturnal enuresis in epilepsy: Three case reports and a review of the literature
Authors: Zhang Xiaorong , Lu Wei , Mo Xiaoye
Published: March 2023

Background

Enuresis is an uncommon adverse effect of sodium valproate therapy that is unknown to most clinicians. This study provides an overview of the literature on enuresis associated with sodium valproate therapy, discussing the clinical manifestations and possible mechanisms of this side effect.

Methods

We reported three cases of enuresis induced by sodium valproate and reviewed the published enuresis cases associated with sodium valproate therapy retrieved from databases.

Case presentation and results

Three new patients with epilepsy who presented with enuresis following sodium valproate therapy were reported, and 55 published cases of nocturnal enuresis associated with sodium valproate were evaluated. The average age of these patients varied from 4 to 20 years. A total of 48 cases had generalized seizures, seven had focal seizures, and three had unknown seizures. In all the patients, the plasma concentration of sodium valproate was 80.76 ± 14.80 μg/mL, within the therapeutic range when enuresis occurred. With discontinuation or reduction of the drug, all the patients recovered completely.

Conclusion

Sodium valproate-induced enuresis is a rare and reversible side effect, occurring at a younger age, characterized by the generalized onset of seizures, and a rather high dose. The possible mechanisms include insufficient secretion of anti-diuretic hormones, sleep disorder, and hyperactivity of the parasympathetic system. Clinicians should be aware of this uncommon side effect to avoid an incorrect adjustment of the treatment direction.