bluuebunny/crossref_metadata_2025 huggingface dataset:
Manfaat Pendampingan Pemberdayaan Masyarakat dalam Program Pengembangan Berorganisasi di Jabodetabek
Authors: Sutarto Bambang , Supatmin Supatmin , Prabowo Budhi
Published: July 2023

The Association of Overseas Argapuri is one of the social communities in Jabodetabek society. The movement of this association can be further enhanced by providing assistance in the form of training and additional capacity building. One of the assistance that can be done is to provide training regarding the use of information technology. Having sufficient knowledge and insight into skills will later become the provision to be able to metamorphose into an independent person who can not only be useful for himself, but also be able to provide benefits to society and the universe after living in the Argapuri Migrant Association. Community service activities focus on graphic design training for members of the Agapuri overseas community. This training is expected to provide added value for the development of the Argapuri migrant community. So that the agenda for using information technology can run sustainably in the Argapuri migrant community and have a significant impact.
Deflectometry for specular surfaces: an overview
Authors: Burke Jan , Pak Alexey , Höfer Sebastian , Ziebarth Mathias , Roschani Masoud , Beyerer Jürgen
Published: July 2023

Deflectometry as a technique to assess reflective surfaces has now existed for some 40 years. Its different aspects and variations have been studied in multiple theses and research articles; reviews are available for certain subtopics. Still a field of active development with many unsolved problems, deflectometry now encompasses a large variety of application domains, hardware setup types, and processing workflows for different purposes, and spans a range from qualitative defect inspection of large vehicles to precision measurements of microscopic optics. Over these years, many exciting developments have accumulated in the underlying theory, in the systems design, and in the implementation specifics. This diversity of topics is difficult to grasp for experts and non-experts alike and may present an obstacle to a wider acceptance of deflectometry as a useful tool for research and industrial applications. This paper presents an attempt to summarize the status of deflectometry and to map relations between its notable branches. Its aim is to provide a communication basis for experienced practitioners and also to offer a convenient entry point for those interested in learning about the method. The list of references introduces some prominent trends and established research groups in order to facilitate further self-directed exploration.
Non-ammoniagenic proliferation and differentiation media for cultivated adipose tissue
Authors: Hubalek S. , Melke J. , Pawlica P. , Post M. J. , Moutsatsou P.
Published: July 2023

Ammonia (Amm), and its aqueous solved state, ammonium, which is produced from glutamine (Gln) metabolism, is a known inhibitor of stem cell proliferation in vitro. In the context of cultivated beef, primary bovine fibro-adipogenic progenitor cells (FAPs) need to be grown and differentiated for several weeks in vitro for the production of cultivated fat. In this study, the ammonium sensitivity of these cells was investigated by introducing ammonium chloride, which was found to inhibit their proliferation when above 5 mM and their adipogenic differentiation when above 2 mM. Novel serum-free proliferation and differentiation media were hence developed with the aim to suppress Amm production during expansion and adipogenesis. Glutamine substitutes, such as a-ketoglutarate (aKG), glutamate (Glt) and pyruvate (Pyr) were investigated. It was found that aKG based proliferation medium (PM) was the most effective in promoting and maintaining FAPs growth over several passages while the specific Amm production rate was reduced more than 5-fold. In terms of differentiation capacity, the substitution of glucose (Gluc) and Gln with galactose (Gal) and Pyr was shown to be the most effective in promoting FAPs differentiation into mature adipocytes, resulting in over 2-fold increase of fat volume per cell, while suppressing Amm production. Our findings suggest that FAPs do not require Gln as an essential nutrient but, on the contrary, possess all the necessary metabolic pathways to proliferate and subsequently differentiate in a Gln-free medium, resulting in decreased Amm production rates and seemingly synthesising glutamine de novo. These findings are important for prolonging the lifespan of culture medium, allowing for reduced costs and process interventions.
Natriuretic peptide biomarkers in the imminent development of preeclampsia
Authors: Marek-Iannucci Stefanie , Oliveros Estefania , Brailovsky Yevgeniy , Pirlamarla Preethi , Roman Amanda , Rajapreyar Indranee N.
Published: July 2023

Preeclampsia is the most common cause of morbidity and mortality in pregnancy, the incidence being significantly higher in low-income countries with reduced access to health care. Women with preeclampsia are at a higher risk of developing cardiovascular disease with a poorer long-term outcome. Early recognition and treatment are key to improving short- and long-term outcomes. Approximately 3%–5% of pregnant women will develop preeclampsia, with potentially fatal outcomes. Despite ongoing research, the exact pathophysiologic mechanism behind its development remains unclear. In this brief report, we describe the potential role of natriuretic peptides as biomarkers in the imminent development of preeclampsia. In a retrospective manner, we analyzed changes in the left ventricular ejection fraction and left atrial volume and increases in natriuretic peptide in correlation with the development of preeclampsia. We found that three out of four patients developed a significant increase in natriuretic peptide, which correlated with the development of preeclampsia and/or peripartum cardiomyopathy. Significant increases in natriuretic peptides around the time of delivery might be a marker for the imminent development of preeclampsia. Close monitoring of natriuretic peptide levels in the peripartum period could give important insight into the imminent development of preeclampsia in high-risk patients. Close follow-up in specialized cardio-obstetric clinics is highly recommended.
A nonlinear relationship between systemic inflammation response index and short-term mortality in patients with acute myocardial infarction: a retrospective study from MIMIC-IV
Authors: Wang Yufei , Chen Hua
Published: July 2023

Background

This investigation aimed to evaluate the efficacy of the Systemic Inflammatory Response Index (SIRI) in prognosticating short-term all-cause mortality among patients diagnosed with acute myocardial infarction (AMI) in the intensive care unit (ICU).

Methods and Results

Clinical data were obtained from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. A total of 4,291 patients were included in the cohort. Results from multivariate regression analyses showed that the quartile of the natural logarithm of SIRI (ln-SIRI) was independently associated with mortality. Compared to patients in the first quartile (Q1), patients in the second quartile (Q2) and fourth quartile (Q4) were significantly associated with an increased risk of 30-day (HR = 2.031, 95% CI: 1.604–2.571, p < 0.001 and HR = 1.703, 95% CI: 1.32–2.195, p < 0.001) and 90-day all-cause mortality (HR = 2.063, 95% CI: 1.68–2.532, p < 0.001 and HR = 1.788, 95% CI: 1.435–2.227, p < 0.001), which is consistent with the results of the Kaplan-Meier analysis and the results of multivariate regression analyses by classifying into 12 groups based on dodeciles of SIRI. Curve fitting showed a curvilinear relationship and further threshold saturation effects showed that, for 90-day mortality, each unit increased in ln-SIRI, when the ln-SIRI level is less than 2.9, the patient's mortality increases by 23.2% (OR: 1.232; 95% CI: 1.111–1.367; p < 0.001); when the ln-SIRI is greater than 2.9 and less than 4.6, the patient's mortality decreases by 44.4% (OR: 0.554; 95% CI: 0.392–0.789; p = 0.001); when ln SIR > 4.6, the patient's mortality increases by 24.7% (OR: 1.247; 95% CI: 1.108–1.404; p < 0.001). Moreover, the length of stay in the hospital was lower in patients in the third quartile (Q3) (coefficient: −1.999; 95% CI: −2.834 – −1.165, p < 0.001). The length of stay in the ICU was higher in patients in Q2 and Q4 (coefficient: 0.685;95% CI: 0.243–1.128; p = 0.0024 and coefficient: 0.989;95% CI: 0.528–1.451; p < 0.001). Furthermore, SIRI may outperform NLR in predicting short-term mortality.

Conclusion

SIRI is an independent risk factor for 30- and 90-day mortality, and length of stay in ICU for critical AMI patients.
Impact of variable seawater conductivity on ocean wave-induced electromagnetic fields simulated with finite difference method
Authors: Ge Jiaqi , Li Yuguo
Published: July 2023

Electric fields generated by the motion of ocean waves through the Earth’s ambient geomagnetic fields and the induced secondary magnetic field can be observed at the seafloor and at the sea-surface, and even in the air. Most of current studies on ocean wave-induced electromagnetic fields assume that seawater conductivity is constant, and ocean waves are treated as regular waves with a fixed amplitude and frequency. However, these assumptions are inconsistent with actual ocean conditions. In this paper, we present a finite difference algorithm for simulating the ocean wave-induced electromagnetic fields with variable seawater conductivity. We investigate impacts of variable seawater conductivity on the electromagnetic fields induced by the wind waves and swell as well as mixed ocean waves, which are treated as the superposition of a number of regular waves with different frequencies and amplitudes, and analyze the characteristics of the induced electromagnetic fields.
Thermal performance analysis of a thermocline storage tank with integrated annular distributors
Authors: Junli Chen , Yanping Zhang , Chongzhe Zou , Yulong Xiao , Yuming Ouyang
Published: July 2023

The implementation of single-tank thermocline storage systems in concentrating solar power systems is a promising solution to improve their stability and continuity. However, flow uniformity within the tank is crucial for achieving optimal thermal efficiency. Distributors have been used to homogenize flow uniformity, and their geometrical parameters significantly impact the thermal performance. In this study, a transient three-dimensional model was developed to investigate the effect of annular distributor gaps on temperature and velocity distribution during the charging and discharging processes. The results showed that the use of annular distributors prevented maldistribution of the thermocline layer, resulting in improved flow uniformity. Furthermore, the discharging efficiency initially decreased and then increased as the gap increased from 30 mm to 80 mm. The minimum discharging efficiency of 72.8% was observed at a gap of 50 mm. Therefore, this study provides an effective method for optimizing the design of annular distributors and presents a creative approach for improving the flow uniformity in thermocline storage tanks.
Habitat shifts in response to predation risk are constrained by competition within a grazing guild
Authors: Creel Scott , Becker Matthew S. , Goodheart Ben , de Merkle Johnathan Reyes , Dröge Egil , M’soka Jassiel , Rosenblatt Elias , Mweetwa Thandiwe , Mwape Henry , Vinks Milan A. , Mukula Teddy , Smit Daan , Sanguinetti Carolyn , Dart Chase , Christianson David , Schuette Paul , Simpamba Twakundine , Chifunte Clive
Published: July 2023

Introduction

Predators can affect prey not only by killing them, but also by causing them to alter their behavior, including patterns of habitat selection. Prey can reduce the risk of predation by moving to habitats where predators are less likely to detect them, less likely to attack, or less likely to succeed. The interaction of such responses to risk with other ecological processes remains relatively unstudied, but in some cases, changes in habitat use to avoid predation may be constrained by competition: larger, dominant competitors should respond freely to predation risk, but the responses of smaller, subordinate competitors may be constrained by the responses of dominant competitors. For large grazing herbivores, an alternative hypothesis proposes that smaller prey species are vulnerable to more predators, and thus should respond more strongly to predation risk.

Methods

Here, we tested these two hypotheses with 775 observations of habitat selection by four species of obligate grazers (zebra, wildebeest, puku and oribi) in the immediate presence or absence of four large carnivores (lion, spotted hyena, African wild dog and cheetah) in three ecosystems (Greater Liuwa, Greater Kafue and Luangwa Valley). Patterns of predation within this set were described by observation of 1,105 kills.

Results

Our results support the hypothesis that responses to predation risk are strongest for larger, dominant competitors. Even though zebras were killed least often, they showed the strongest shift into cover when carnivores were present. Wildebeest, puku and oribi showed weaker habitat shifts, even though they were more frequently killed. These patterns remained consistent in models that controlled for differences in the hunting mode of the predator (stalking, coursing, or intermediate) and for differences among ecosystems. There was no evidence that smaller species were subject to predation by a broader set of predators. Instead, smaller prey were killed often by smaller predators, and larger prey were killed often by larger predators.

Discussion

Broadly, our results show that responses to predation risk interact with interspecific competition. Accounting for such interactions should help to explain the considerable variation in the strength of responses to predation risk that has been observed.
An overview of DNA methylation markers for early detection of gastric cancer: current status, challenges, and prospects
Authors: Xue Ying , Huang Chao , Pei Bing , Wang ZhenZhen , Dai Yanmiao
Published: July 2023

Background: Gastric cancer (GC) is one of the most common malignancies, with a low 5-year survival rate. However, if diagnosed at an early stage, it can be cured by endoscopic treatment and has a good prognosis. While gastrointestinal X-ray and upper endoscopy are used as national GC screening methods in some GC high-risk countries, such as Japan and Korea, their radiation exposure, invasiveness, and high cost suggest that they are not the optimal tools for early detection of GC in many countries. Therefore, a cost-effective, and highly accurate method for GC early detection is urgently needed in clinical settings. DNA methylation plays a key role in cancer progression and metastasis and has been demonstrated as a promising marker for cancer early detection.

Aims and methods: This review provides a comprehensive overview of the current status of DNA methylation markers associated with GC, the assays developed for GC early detection, challenges in methylation marker discovery and application, and the future prospects of utilizing methylation markers for early detection of GC. Through our analysis, we found that the currently reported DNA methylation markers related to GC are mainly in the early discovery stage. Most of them have only been evaluated in tissue samples. The majority of non-invasive assays developed based on blood lack standardized sampling protocols, pre-analytical procedures, and multicenter validation, and they exhibit insufficient sensitivity for early-stage GC detection. Meanwhile, the reported GC DNA methylation markers are generally considered pan-cancer markers.

Conclusion: Therefore, future endeavors should focus on identifying additional methylation markers specific to GC and establishing non-invasive diagnostic assays that rely on these markers. These assays should undergo multicenter, large-scale prospective validation in diverse populations.
Unveiling 2,000 years of differentiation among Tungusic-speaking populations: a revised phylogeny of the paternal founder lineage C2a-M48-SK1061
Authors: Yu Hui-Xin , Ao Cheligeer , Zhang Xian-Peng , Liu Kai-Jun , Wang Yi-Bing , Meng Song-Lin , Li Hui , Wei Lan-Hai , Man Da
Published: July 2023

Previous studies demonstrated Y chromosome haplogroup C2a-M48-SK1061 is the only founding paternal lineage of all Tungusic-speaking populations. To infer the differentiation history of these populations, we studied more sequences and constructed downstream structure of haplogroup C2a-M48-SK1061 with better resolution. In this study, we generated 100 new sequences and co-analyzed 140 sequences of C2a-M48-SK1061 to reconstruct a highly revised phylogenetic tree with age estimates. We also performed the analysis of the geographical distribution and spatial autocorrelation of sub-branches. Dozens of new sub-branches were discovered, many sub-branches were nearly unique for Ewenki, Evens, Oroqen, Xibe, Manchu, Daur, and Mongolian. The topology of these unique sub-branches is the key evidence for understanding the complex evolutionary relationship between different Tungusic-speaking populations. The revised phylogeny provided a clear pattern for the differentiation history of haplogroup C2a-M48-SK1061 in the past 2,000 years. This study showed that the divergence pattern of founder lineage is essential to understanding the differentiation history of populations.
Risk factors for multiple sclerosis in the context of Epstein-Barr virus infection
Authors: Hedström Anna Karin
Published: July 2023

Compelling evidence indicates that Epstein Barr virus (EBV) infection is a prerequisite for multiple sclerosis (MS). The disease may arise from a complex interplay between latent EBV infection, genetic predisposition, and various environmental and lifestyle factors that negatively affect immune control of the infection. Evidence of gene-environment interactions and epigenetic modifications triggered by environmental factors in genetically susceptible individuals supports this view. This review gives a short introduction to EBV and host immunity and discusses evidence indicating EBV as a prerequisite for MS. The role of genetic and environmental risk factors, and their interactions, in MS pathogenesis is reviewed and put in the context of EBV infection. Finally, possible preventive measures are discussed based on the findings presented.
Cellular metabolism hijacked by viruses for immunoevasion: potential antiviral targets
Authors: Li Jiaqi , Wang Yanjin , Deng Hao , Li Su , Qiu Hua-Ji
Published: July 2023

Cellular metabolism plays a central role in the regulation of both innate and adaptive immunity. Immune cells utilize metabolic pathways to modulate the cellular differentiation or death. The intricate interplay between metabolism and immune response is critical for maintaining homeostasis and effective antiviral activities. In recent years, immunometabolism induced by viral infections has been extensively investigated, and accumulating evidence has indicated that cellular metabolism can be hijacked to facilitate viral replication. Generally, virus-induced changes in cellular metabolism lead to the reprogramming of metabolites and metabolic enzymes in different pathways (glucose, lipid, and amino acid metabolism). Metabolic reprogramming affects the function of immune cells, regulates the expression of immune molecules and determines cell fate. Therefore, it is important to explore the effector molecules with immunomodulatory properties, including metabolites, metabolic enzymes, and other immunometabolism-related molecules as the antivirals. This review summarizes the relevant advances in the field of metabolic reprogramming induced by viral infections, providing novel insights for the development of antivirals.
Regulation of post-translational modification of PD-L1 and advances in tumor immunotherapy
Authors: Feng Chong , Zhang Lening , Chang Xin , Qin Dongliang , Zhang Tao
Published: July 2023

The immune checkpoint molecules programmed cell death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) are one of the most promising targets for tumor immunotherapy. PD-L1 is overexpressed on the surface of tumor cells and inhibits T cell activation upon binding to PD⁃1 on the surface of T cells, resulting in tumor immune escape. The therapeutic strategy of targeting PD-1/PD-L1 involves blocking this binding and restoring the tumor-killing effect of immune cells. However, in clinical settings, a relatively low proportion of cancer patients have responded well to PD-1/PD-L1 blockade, and clinical outcomes have reached a bottleneck and no substantial progress has been made. In recent years, PD-L1 post-translation modifications (PTMs) have gradually become a hot topic in the field of PD-L1 research, which will provide new insights to improve the efficacy of current anti-PD-1/PD-L1 therapies. Here, we summarized and discussed multiple PTMs of PD-L1, including glycosylation, ubiquitination, phosphorylation, acetylation and palmitoylation, with a major emphasis on mechanism-based therapeutic strategies (including relevant enzymes and targets that are already in clinical use and that may become drugs in the future). We also summarized the latest research progress of PTMs of PD-L1/PD-1 in regulating immunotherapy. The review provided novel strategies and directions for tumor immunotherapy research based on the PTMs of PD-L1/PD-1.
Compassion fatigue and compassion satisfaction among Romanian emergency medicine personnel
Authors: Hăisan Anca , Hogaș Simona , Măirean Cornelia , Punei Mirabela-Olivia , Volovăț Simona Ruxandra , Hogaș Mihai , Kantor Cristina , Cimpoeșu Diana
Published: July 2023

Background

Contemporary scientific literature has emphasized two specific aspects of healthcare professionals: compassion satisfaction and compassion fatigue. In the context of the COVID-19 pandemic, which has placed significant strain on health systems and healthcare workers, the Russian-Ukrainian crisis appears to have a magnifying effect, particularly on mental health.

Methods

The aim of the present study was to investigate the relationship between threat perception, daily worries, and professional quality of life in a sample of Emergency Medicine Personnel during two major events mentioned above. The sample included 372 participants (56.7% nurses and 43.3% physicians) from emergency units in five county hospitals in the Eastern region of Romania.

Results

The study revealed that threats related to the pandemic were positively linked to secondary traumatic stress, and daily worries were positively linked to both secondary traumatic stress and burnout. Threats generated by the war did not manifest a direct relation with any of the indicators of professional quality of life, but daily worries generated by war positively predicted both secondary traumatic stress and burnout.

Conclusion

Both the pandemic, which involved cumulative exposure, and the war, which involved a lower and more distant level of exposure, had the potential to generate worries and predict a low quality of life. However, our results did not reveal any association between threats, worries, and compassion satisfaction. As a result, this positive indicator of quality of life remained stable despite the presence of threats and worries.
Positive experience with TNF-α inhibitor in toxic epidermal necrolysis resistant to high-dose systemic corticosteroids
Authors: Nikitina Ekaterina A. , Fomina Daria S. , Markina Ulyana A. , Andreev Sergey S. , Streltsov Yuri V. , Kruglova Tatiana S. , Lebedkina Marina S. , Karaulov Alexander V. , Lysenko Maryana A.
Published: July 2023

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, potentially life-threatening syndromes characterized by the development of necrotic epidermal and mucosal lesions. The most common etiologic cause of SJS/TEN is drug-induced mechanisms. The group of drugs with high potential risk includes sulfonamides, anticonvulsants, non-steroidal anti-inflammatory drugs (NSAIDs), allopurinol, phenobarbital, etc. There is no gold standard treatment algorithm for SJS/TEN. In medical practice, systemic glucocorticosteroids (sGCS), intravenous immunoglobulin (IVIG), plasmapheresis, and cyclosporine are used empirically and in various combinations. Recently published studies have demonstrated the efficacy of TNF-α inhibitors as a promising approach in SJS/TEN, including cases resistant to high-dose sGCS, with etanercept and infliximab being the most commonly used drugs. In a large multicenter study by Zhang J et al. (XXXX), 242 patients treated with etanercept, sGCS, or a combination of both had lower mortality compared to the control group. A shorter skin healing time was documented compared to sGCS monotherapy, thus reducing the risk of secondary infections. The published data show a high efficacy with THF-α inhibitor blockade, but the safety of TNF-α inhibitors in patients with SJS/TEN is still questionable due to the paucity of available information. As all clinical research data should be accumulated to provide reliable evidence that the use of TNF-α inhibitors may be beneficial in SJS/TEN, we report a case of etoricoxib-associated SJS with progression to TEN in a 50-year-old woman who was refractory to high-dose sGCS therapy.
The gut microbiome as a potential source of non-invasive biomarkers of chronic obstructive pulmonary disease
Authors: Li Naijian , Yi Xinzhu , Chen Chiyong , Dai Zhouli , Deng Zhishan , Pu Jinding , Zhou Yumin , Li Bing , Wang Zhang , Ran Pixin
Published: July 2023

Background

The link between gut microbial dysbiosis and the development of chronic obstructive pulmonary disease (COPD) is of considerable interest. However, little is known regarding the potential for the use of the fecal metagenome for the diagnosis of COPD.

Methods

A total of 80 healthy controls, 31 patients with COPD severity stages I or II, and 49 patients with COPD severity stages III or IV fecal samples were subjected to metagenomic analysis. We characterized the gut microbiome, identified microbial taxonomic and functional markers, and constructed a COPD disease classifier using samples.

Results

The fecal microbial diversity of patients with COPD stages I or II was higher than that of healthy controls, but lower in patients with COPD stages III or IV. Twenty-one, twenty-four, and eleven microbial species, including potential pathogens and pro-inflammatory bacteria, were significantly enriched or depleted in healthy controls, patients with COPD stages I or II, and patients with COPD stages III & IV. The KEGG orthology (KO) gene profiles derived demonstrated notable differences in gut microbial function among the three groups. Moreover, gut microbial taxonomic and functional markers could be used to differentiate patients with COPD from healthy controls, on the basis of areas under receiver operating characteristic curves (AUCs) of 0.8814 and 0.8479, respectively. Notably, the gut microbial taxonomic features differed between healthy individuals and patients in stages I-II COPD, which suggests the utility of fecal metagenomic biomarkers for the diagnosis of COPD (AUC = 0.9207).

Conclusion

Gut microbiota-targeted biomarkers represent potential non-invasive tools for the diagnosis of COPD.
Enhanced antibacterial and anticancer activities of plant extract mediated green synthesized zinc oxide-silver nanoparticles
Authors: Mohamad Sukri Siti Nur Amalina , Shameli Kamyar , Teow Sin-Yeang , Chew Jactty , Ooi Li-Ting , Lee-Kiun Soon Michiele , Ismail Nur Afini , Moeini Hassan
Published: July 2023

This study presents a green synthesis approach for the fabrication of zinc oxide-silver nanoparticles (ZnO-Ag-NPs) using Punica granatum fruit peels extract as a natural reducing and stabilizing agent. This eco-friendly method offers a sustainable alternative to conventional methods that often employ toxic or hazardous chemicals. Antibacterial and anti-cancer activities of the green synthesized nanoparticles were then assessed in vitro. X-ray diffraction confirmed the production of ZnO-Ag-NPs with increasing crystallinity in higher pH values. The ZnO-Ag-NPs were found to be agglomerated with spherical Ag-NPs. Fourier Transform Infrared (FTIR) spectra revealed a broad band in ZnO-Ag-NPs ranging from 400−1 to 530 cm−1 with reduced intensity as compared to ZnO-NPs, indicating the formation of Ag-NPs on the surface of ZnO-NPs. The synthesized ZnO-Ag-NPs exhibited potent antibacterial activity against a broad spectrum of bacterial strains, particularly Gram-positive bacteria, with superior inhibition activity compared to ZnO-NPs. Moreover, ZnO-Ag-NPs showed a dose-dependent anti-proliferative effect on colorectal-, lung-, and cervical cancer cells. ZnO-Ag-NPs showed significantly greater efficacy in inhibiting cancer cell growth at a lower concentration of 31.25 μg/mL, compared to ZnO-NPs which required over 500 μg/mL, possibly due to the presence of silver nanoparticles (Ag-NPs). The results obtained from this study demonstrate the potential of green synthesis approaches in the fabrication of therapeutic nanomaterials for cancer treatment, as well as other biomedical applications.
Optimising low-energy defibrillation in 2D cardiac tissue with a genetic algorithm
Authors: Aron Marcel , Lilienkamp Thomas , Luther Stefan , Parlitz Ulrich
Published: July 2023

Sequences of low-energy electrical pulses can effectively terminate ventricular fibrillation (VF) and avoid the side effects of conventional high-energy electrical defibrillation shocks, including tissue damage, traumatic pain, and worsening of prognosis. However, the systematic optimisation of sequences of low-energy pulses remains a major challenge. Using 2D simulations of homogeneous cardiac tissue and a genetic algorithm, we demonstrate the optimisation of sequences with non-uniform pulse energies and time intervals between consecutive pulses for efficient VF termination. We further identify model-dependent reductions of total pacing energy ranging from ∼4% to ∼80% compared to reference adaptive-deceleration pacing (ADP) protocols of equal success rate (100%).
Increased intraocular inflammation in retinal vein occlusion is independent of circulating immune mediators and is involved in retinal oedema
Authors: Zhou Yufan , Qi Jinyan , Liu Hengwei , Liang Shengnan , Guo Tingting , Chen Juan , Pan Wei , Tan Huanhuan , Wang Jie , Xu Heping , Chen Zhongping
Published: July 2023

We aim to understand the link between systemic and intraocular levels of inflammatory mediators in treatment-naïve retinal vein occlusion (RVO) patients, and the relationship between inflammatory mediators and retinal pathologies. Twenty inflammatory mediators were measured in this study, including IL-17E, Flt-3 L, IL-3, IL-8, IL-33, MIP-3β, MIP-1α, GRO β, PD-L1, CD40L, IFN-β, G-CSF, Granzyme B, TRAIL, EGF, PDGF-AA, PDGF-AB/BB, TGF-α, VEGF, and FGFβ. RVO patients had significantly higher levels of Flt-3 L, IL-8, MIP-3β, GROβ, and VEGF, but lower levels of EGF in the aqueous humor than cataract controls. The levels of Flt-3 L, IL-3, IL-33, MIP-1α, PD-L1, CD40 L, G-CSF, TRAIL, PDGF-AB/BB, TGF-α, and VEGF were significantly higher in CRVO than in BRVO. KEGG pathway enrichment revealed that these mediators affected the PI3K-Akt, Ras, MAPK, and Jak/STAT signaling pathways. Protein–Protein Interaction (PPI) analysis showed that VEGF is the upstream cytokine that influences IL-8, G-CSF, and IL-33 in RVO. In the plasma, the level of GROβ was lower in RVO than in controls and no alterations were observed in other mediators. Retinal thickness [including central retinal thickness (CRT) and inner limiting membrane to inner plexiform layer (ILM-IPL)] positively correlated with the intraocular levels of Flt-3 L, IL-33, GROβ, PD-L1, G-CSF, and TGF-α. The size of the foveal avascular zone positively correlated with systemic factors, including the plasma levels of IL-17E, IL-33, INF-β, GROβ, Granzyme B, and FGFβ and circulating high/low-density lipids and total cholesterols. Our results suggest that intraocular inflammation in RVO is driven primarily by local factors but not circulating immune mediators. Intraocular inflammation may promote macular oedema through the PI3K-Akt, Ras, MAPK, and Jak/STAT signaling pathways in RVO. Systemic factors, including cytokines and lipid levels may be involved in retinal microvascular remodeling.
The genotype–phenotype correlations of the CACNA1A-related neurodevelopmental disorders: a small case series and literature reviews
Authors: Kessi Miriam , Chen Baiyu , Pang Nan , Yang Lifen , Peng Jing , He Fang , Yin Fei
Published: July 2023

Background

Genotype–phenotype correlations of the CACNA1A-related neurodevelopmental disorders such as global developmental delay (GDD)/intellectual disability (ID), epileptic encephalopathy (EE), and autism spectrum disorder (ASD) are unknown. We aimed to summarize genotype–phenotype correlations and potential treatment for CACNA1A-related neurodevelopmental disorders.

Methods

Six children diagnosed with CACNA1A-related neurodevelopmental disorders at Xiangya Hospital, Central South University from April 2018 to July 2021 were enrolled. The PubMed database was systematically searched for all reported patients with CACNA1A-related neurodevelopmental disorders until February 2023. Thereafter, we divided patients into several groups for comparison.

Results

Six patients were recruited from our hospital. Three cases presented with epilepsy, five with GDD/ID, five with ataxia, and two with ASD. The variants included p.G701R, p.R279C, p.D1644N, p.Y62C, p.L1422Sfs*8, and p. R1664Q [two gain-of-function (GOF) and four loss-of-function (LOF) variants]. About 187 individuals with GDD/ID harboring 123 variants were found (case series plus data from literature). Of those 123 variants, p.A713T and p.R1664* were recurrent, 37 were LOF, and 7 were GOF. GOF variants were linked with severe-profound GDD/ID while LOF variants were associated with mild–moderate GDD/ID (p = 0.001). The p.A713T variant correlated with severe-profound GDD/ID (p = 0.003). A total of 130 epileptic patients harboring 83 variants were identified. The epileptic manifestations included status epilepticus (n = 64), provoked seizures (n = 49), focal seizures (n = 37), EE (n = 29), absence seizures (n = 26), and myoclonic seizures (n = 10). About 49 (42.20%) patients had controlled seizures while 67 (57.80%) individuals remained with refractory seizures. Status epilepticus correlated with variants located on S4, S5, and S6 (p = 0.000). Among the 83 epilepsy-related variants, 23 were recurrent, 32 were LOF, and 11 were GOF. Status epilepticus was linked with GOF variants (p = 0.000). LOF variants were associated with absence seizures (p = 0.000). Six patients died at an early age (3 months to ≤5 years). We found 18 children with ASD. Thirteen variants including recurrent ones were identified in those 18 cases. GOF changes were more linked to ASD.

Conclusion

The p.A713T variant is linked with severe-profound GDD/ID. More than half of CACNA1A-related epilepsy is refractory. The most common epileptic manifestation is status epilepticus, which correlates with variants located on S4, S5, and S6.
A retrospective analysis for investigating the relationship between FIGO stage IVA/IVB and cytoreductive surgery with prognosis in epithelial ovarian cancer
Authors: Liu Hong , Luo Min , Peng Chunrong , Huang Jianmei , Wang Dengfeng , Huang Jianming , Zhang Guonan
Published: July 2023

Objective

To investigate the effect of primary debulking surgery (PDS), NACT followed by interval debulking surgery (NACT-IDS), and chemotherapy alone on the prognosis of FIGO stage IV epithelial ovarian cancer (EOC) with different metastatic patterns.

Methods

We retrospectively analyzed 133 cases of FIGO stage IV EOC with pleural effusion (stage IVA), parenchymal metastases (stage IVB), or extra-abdominal lymph node metastases (stage IVB) at our Hospital between January 2014 and July 2021.

Results

Among 133 cases with stage IV disease, 16.5% (n=22) presented with pleural effusion, 46.6% (n=62) with parenchymal metastases, and 36.9% (n=49) with extra-abdominal lymph node metastases. Regardless of the metastatic patterns, the 90.2% (n=120) of cases who underwent PDS/NACT-IDS exhibited a significantly superior overall survival (OS) compared to the 9.8% cases (n=13) who received chemotherapy alone (32 vs 17 months, p=0.000). The cohort was further stratified into 58 cases (48.3%) with R0, 41 cases (34.2%) with R1, and 21 cases (17.5%) with R2. The median OS of cases with R0 was significantly better than that of cases with R1/R2 (74 vs 27 months, p=0.000). There was no significant difference in median OS between PDS and NACT-IDS (43 vs 31 months, p=0.676), as well as between FIGO IVA and IVB (35 vs 31 months, p=0.582). Additionally, the metastatic patterns and the number of neoadjuvant chemotherapy cycles (≤4 or >4) did not demonstrate any prognostic significance for median OS (p=0.820 and 33 vs 26 months, p=0.280, respectively).

Conclusion

Regardless of FIGO IVA and IVB stages or metastatic patterns, patients diagnosed with stage IV EOC may benefit from cytoreductive surgery with abdominal R0, compared with chemotherapy alone.
Incidence and time trends of childhood hematological neoplasms: a 36-year population-based study in the southern European context, 1983–2018
Authors: Trallero Jan , Sanvisens Arantza , Almela Vich Fernando , Jeghalef El Karoni Noura , Saez Lloret Isabel , Díaz-del-Campo Cristina , Marcos-Navarro Ana Isabel , Aizpurua Atxega Amaia , Sancho Uriarte Patricia , De-la-Cruz Ortega Marta , Sánchez María José , Perucha Josefina , Franch Paula , Chirlaque María Dolores , Guevara Marcela , Ameijide Alberto , Galceran Jaume , Ramírez Cristina , Camblor Marta Rodríguez , Alemán Maria Araceli , Gutiérrez Pilar , Marcos-Gragera Rafael ,   REDECAN
Published: July 2023

Background

Hematological neoplasms (HNs) are the first and most common childhood cancers globally. Currently, there is a lack of updated population-based data on the incidence of these cancers in the Spanish pediatric population. This study aimed to describe the incidence and incidence trends of HNs in children (0–14 years) in Spain using data from the Spanish Network of Cancer Registries and to compare the results with other southern European countries.

Methods

Data were extracted from 15 Spanish population-based cancer registries between 1983 and 2018. Cases were coded according to the International Classification of Diseases for Oncology, third edition, first revision, and grouped according to the International Classification of Childhood Cancer, third edition. Crude rates (CRs), age-specific rates, and age-standardized incidence rates using the 2013 European population (ASRE) were calculated and expressed as cases per 1,000,000 child-years. Incidence trends and annual percentage changes (APCs) were estimated.

Results

A total of 4,747 HNs were recorded (59.5% boys). Age distribution [n (%)] was as follows: <1 year, 266 (5.6%); 1–4 years, 1,726 (36.4%); 5–9 years, 1,442 (30.4%); and 10–14 years, 1,313 (27.6%). Leukemias were the most common group, with a CR and an ASRE of 44.0 (95%CI: 42.5; 45.5) and 44.1 (95%CI: 42.6; 45.7), respectively. The CR and ASRE of lymphomas were 20.1 (95%CI: 19.1; 21.1) and 20.0 (95%CI: 19.0; 21.1), respectively. The comparable incidence rates between our results and those of other southern European countries were similar for lymphomas, while some differences were observed for leukemias. From 1988 to 2016, the trend in leukemia incidence was stable for both sexes, with an APC of 0.0 (95%CI: −0.5; 0.7), whereas a constant overall increase was observed for lymphoma in both sexes, with an APC of 1.0 (95%CI: 0.4; 1.6).

Conclusion

Leukemias are the most common HNs in children, and their incidence has remained stable since 1988, whereas the incidence of lymphomas has increased every year. Lymphoma incidence is like that of other southern European countries, while leukemia incidence is similar only to that of southwestern European countries. Collaborative cancer registry projects allow for assessing epidemiological indicators for cancers such as HNs, which helps health authorities and clinicians provide more knowledge about these malignancies.
Parapharyngeal meningioma extending through foramen ovale: a case report
Authors: Mao Jin , Wei Kai , Yang Siyu , Hu Ling , Wang Chao
Published: July 2023

Background

Meningioma is a common non-glial tumor of the brain. Extracranial meningiomas in the parapharyngeal space are especially rare. Herein we report a case of extracranial meningioma in the parapharyngeal space and give a comprehensive description of its complete clinical course and radiological findings, which may provide helpful information in the diagnosis and treatment of extracranial meningiomas in the parapharyngeal space.

Case Presentation

A 61-year-old man presented a slowly increased mass under the left ear without pain and numbness over one year. Ultrasound examination detected a hypoechoic uneven mass behind the left parotid gland with a clear boundary, and color Doppler flow imaging revealed blood flow signals within the mass. Unenhanced computed tomography (CT) of the craniofacial region revealed a homogenous soft tissue mass in the parapharyngeal space without calcification. Magnetic resonance imaging (MRI) showed that a homogenous soft tissue mass was hyperintense on T2-weighted image, hypointense on T1-weighted image, and obviously enhanced after contrast enhancement in the parapharyngeal space. Coronal MRI showed that the lesion originated from basicranial dura extending into parapharyngeal space through the left foramen ovale at the skull base. Finally, histopathological and immunohistochemical analyses confirmed the final diagnosis of extracranial meningiomas in the parapharyngeal space.

Conclusion

Extracranial meningiomas of the parapharyngeal space are rare and often pose a diagnostic challenge. Preoperative imaging examinations, especially CT and MRI, can aid in the accurate preoperative diagnosis, especially when intracranial extensions and dural tail signs are observed.
Diagnosis and management of chagasic cardiomyopathy patients in several institutions in Argentina
Authors: Chuit Roberto , Antonietti Laura , Agüero Roberto Nicolás , Varela Gabriela Badino , Mordini Oscar Daniel , Alemandri Emilce , Abril Marcelo , Días Miguel , Yadón Zaida E. , Pizzi Hugo , Pizzi Rogelio
Published: July 2023

Introduction

According to estimates by the World Health Organization, the infection and disease caused by the protozoan parasite Trypanosoma cruzi affects almost 6 million people, and more than 1 million suffer chagasic cardiomyopathy (Ch-CMP). It is estimated that 376,000 of these individuals live in Argentina. This study describes the characteristics and medical management of individuals with Ch-CMP in Argentina.

Methods

This is a descriptive, retrospective, cross-sectional study on the diagnosis and clinical and therapeutic evaluation of patients with Ch-MCP using historical records collected from different medical institutions in the country between 1 January 2018 and 30 June 2021.

Results

During this period, 652 patients (mean age 61.2 years ± 12.9) were included, with women accounting for 60.3% of the sample. The diagnosis of cardiac insufficiency was 36.0% and 64.4% had arrhythmias. The most common cardiovascular risk factors detected were arterial hypertension (69.5%), smoking (56.6%), and diabetes (20.9%). Less than half of the subjects (45.4%) had been studied by electrocardiogram (ECG), chest X-ray, and echocardiogram. ECG studies showed conduction disorders (38.8%), left ventricular hypertrophy (28.1%), ventricular extrasystoles (22.0%), complete right bundle branch block (8.6%), and atrioventricular block (2.6%). According to the Kuschnir classification, 21.4% of the study subjects were in Grade 3.

Conclusions

The patients included in the study had a similar clinical presentation and history of the disease to those published in other studies. When evaluating the medical practices, we found that patients were inadequately studied. Although it is difficult to estimate the fraction of the total number of patients represented by the present study, the study allowed us to establish that the care received by patients was not adequate.
Safety analysis of pemigatinib leveraging the US Food and Drug administration adverse event reporting system
Authors: Zhang Ying , Ran Li , Liang Yongchao , Zhang Yanqiu , An Zhuoling
Published: July 2023

Background: Cholangiocarcinoma (CCA) is a highly lethal and aggressive epithelial tumor of the hepatobiliary system. A poor prognosis, propensity for relapse, low chance of cure and survival are some of its hallmarks. Pemigatinib, the first targeted treatment for CCA in the United States, has been demonstrated to have a significant response rate and encouraging survival data in early-phase trials. The adverse events (AEs) of pemigatinib must also be determined.

Objective: To understand more deeply the safety of pemigatinib in the real world through data-mining of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Methods: Disproportionality analysis was employed in a retrospective pharmacovigilance investigation to identify the AEs linked to pemigatinib use as signals. Data were collected between 1 January 2020 to 30 June 2022. Four data-mining methods (proportional reporting odds ratio; proportional reporting ratio; Bayesian confidence propagation neural networks of information components; empirical Bayes geometric means) were used to calculate disproportionality.

Results: A total of 203 cases using pemigatinib as the prime-suspect medication were found in our search, which involved 99 preferred terms (PTs). Thirteen signals of pemigatinib-induced AEs in seven System Organ Classes were detected after confirming the four algorithms simultaneously. Nephrolithiasis was an unexpected significant AE not listed on the drug label found in our data-mining. Comparison of the differences between pemigatinib and platinum drugs in terms of 33 PTs revealed that 13 PTs also met the criteria of the four algorithms. Ten of these PTs were identical to those compared with all other drugs, in which (excluding a reduction in phosphorus in blood) other PT signal values were higher than those of all other drugs tested. However, comparison of the differences between pemigatinib and infigratinib in terms of the 33 PTs revealed no significant signals in each algorithm method.

Conclusion: Some significant signals were detected between pemigatinib use and AEs. PTs with apparently strong signals and PTs not mentioned in the label should be taken seriously.