bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternatives to antibiotics
Authors:   , Beenker Wouter Antonius Gerardus
Published: June 2023

Antibiotic resistance is a growing problem, leading to ineffective antibiotic treatments, causing bacterial infections to be lethal again. Therefore, new alternatives are needed to fight bacterial infections. Targeting bacterial quorum sensing, might be a promising approach.

Quorum sensing (QS) is a bacterial communication system via which bacteria regulate their gene expression based on cell density. In other words, when there are a lot of bacteria, different genes are activated that are beneficial for collaboration. These genes include genes involved in virulence factor production (which cause tissue damage) and biofilm formation (which makes the bacteria less susceptible for antibiotics). Therefore, inhibition of QS might have beneficial effects, including less tissue damage and higher susceptibility to antibiotics. QS inhibitors have also shown positive outcomes in animal models. However, the role of QS during human infections is still underexplored.

In this thesis, we focused on the potential of QS inhibition as alternative treatment against bacterial infection. We searched for novel QS inhibitors using a library of more than 10,000 fungal filtrates. This showed that natural compounds produced by fungi still hold great promise to find novel QS inhibitors since various active compounds were identified. Paecilomycone showed the greatest potential by limiting production of virulence factors and biofilm formation in P. aeruginosa, a bacteria that is notorious for causing infections in immunocompromised patients, including individuals with CF.

In addition, we set up a new platform to study the role of QS during infection using co-cultures of P. aeruginosa bacteria with airway organoids. This research showed that organoids can indeed be used to study the interplay between epithelium and bacteria. The epithelium showed a strong immune response after infection with P. aeruginosa, while P. aeruginosa bacteria upregulated genes involved in infection. However, genes involved with QS were inhibited. This suggests that the role of QS during human infection might be limited.

Therefore, we need to focus on learning more about the role of QS during human infection before developing QS into the clinic.
Components of cigarette smoke inhibit expansion of oocyte-cumulus complexes from porcine follicles
Authors: Vršanská S , Nagyová E , Mlynarčíková A , Ficková M , Kolena J
Published: June 2023

The role of alkaloids in cigarette smoke was investigated in the cumulus expansion of oocyte-cumulus complexes (OCC) isolated from large antral porcine follicles. Suppression of the cumulus expansion stimulated by FSH was observed in the presence of different concentration of cadmium, anabasine and nicotine but not its metabolite cotinine. There were comparable inhibitory effects of cadmium and nicotine on the synthesis and accumulation of hyaluronic acid in the cell/matrix compartment of OCC. The inhibitory effect of tested compounds on the cumulus expansion was accompanied by decreased progesterone synthesis by cumulus cells during 42 h incubation of OCC with FSH. The results suggest that cigarette smoking may affect intrafollicular processes, which are responsible for normal ovulation and fertilization.
The Role of Heat Shock Proteins and Autophagy in Mechanisms Underlying Effects of Sulforaphane on Doxorubicin-Induced Toxicity in HEK293 Cells
Authors: BOŤANSKÁ B , PECNÍKOVÁ V , FOGARASSYOVÁ M , BARANČÍK M
Published: June 2023

Doxorubicin (DOX) is a cytostatic agent belonging to anthracycline group. Important role in mechanism associated with negative effects of DOX plays an oxidative stress. Heat shock proteins (HSPs) are part of mechanisms initiated in response to stressful stimuli and play an important role in cellular responses to oxidative stress through interaction with components of redox signaling. The present work was aimed to study the role of HSPs and autophagy in mechanisms underlying effects of sulforaphane (SFN), a potential activator of Nrf-2, on doxorubicin-induced toxicity in human kidney HEK293 cells. We investigated effects of SFN and DOX on proteins associated with regulation of heat shock response, redox signaling, and autophagy. Results show that SFN significantly reduced cytotoxic effects of DOX. The positive effects of SFN on DOX-induced changes were associated with up-regulation of Nrf-2 and HSP60 protein levels. In the case of another heat shock protein HSP40, SFN increased its levels when was administered alone but not in conditions when cells were exposed to the effects of DOX. Sulforaphane also reversed negative effects of DOX on activities of superoxide dismutases (SODs) and up-regulation of autophagy markers (LC3A/B-II, Atg5, and Atg12). In conclusion, the changes observed in HSP60 are of particular importance in terms of protecting cells from the effects of DOX. Finding that under conditions where SFN reduced cytotoxic effects of DOX were significantly increased protein levels of both Nrf-2 and HSP60 point to the role of HSP60 in mechanisms of redox signaling underlying effects of SFN on DOX-induced toxicity in HEK293 cells. Moreover, data confirmed an important role of autophagy in effects of SFN on DOX-induced toxicity.
Effects of Iron Nanoparticles Administration on Ischemia/Reperfusion Injury in Isolated Hearts of Male Wistar Rats
Authors: KINDERNAY L , FERENCZYOVÁ K , FARKAŠOVA V , BARTEKOVÁ M , BERNÁTOVÁ I , RAVINGEROVÁ T
Published: June 2023

Iron is an essential mineral participating in numerous biological processes in the organism under physiological conditions. However, it may be also involved in the pathological mechanisms activated in various cardiovascular diseases including myocardial ischemia/reperfusion (I/R) injury, due to its involvement in reactive oxygen species (ROS) production. Furthermore, iron has been reported to participate in the mechanisms of iron-dependent cell death defined as “ferroptosis”. On the other hand, iron may be also involved in the adaptive processes of ischemic preconditioning (IPC). This study aimed to elucidate whether small amounts of iron may modify the cardiac response to I/R in isolated perfused rat hearts and their protection by IPC. Pretreatment of the hearts with iron nanoparticles 15 min prior to sustained ischemia (iron preconditioning, Fe-PC) did not attenuate post-I/R contractile dysfunction. Recovery of left ventricular developed pressure (LVDP) was significantly improved only in the group with combined pretreatment with iron and IPC. Similarly, the rates of contraction and relaxation [+/-(dP/dt)max] were almost completely restored in the group preconditioned with a combination of iron and IPC but not with iron alone. In addition, the severity of reperfusion arrhythmias was reduced only in the iron+IPC group. No changes in protein levels of “survival” kinases of the RISK pathway (Reperfusion Injury Salvage Kinase) were found except for reduced caspase 3 levels in both preconditioned groups. The results indicate that a failure to precondition rat hearts with iron may be associated with the absent upregulation of RISK proteins and the pro-ferroptotic effect manifested by reduced glutathione peroxidase 4 (GPX4) levels. However, combination with IPC suppressed the negative effects of iron resulting in cardioprotection.
A Study on University Professors’ Perception on Educational Applicability of ChatGPT in English Classes
Authors:   The Korean Society of Culture and Convergence, Cha Minyoung , Im Hee-Joo
Published: June 2023

The purpose of this paper is to examine professors’ perceptions on chatGPT and provide some suggestions about them. To that end, a total of fifteen professors belonging to universities in Chungcheong-namdo participated in the online survey. The findings of this study are as follows. First, the meaning or concept of chatGPT was already known, and most of the participants had experience using it. Also, professors thought chatGPT is a useful educational tool and showed strong willingness to use in classes. However, the professors mentioned conducting teaching-learning activities by using chatGPT could be difficult. Second, It was believed that the expected effect of using chatGPT could serve as motivation, learning aid, and interaction. However, as expected difficulties, concerns such as limitations in English proficiency, risk of absolute trust, and ethical risks were raised. The study provided some suggestions to educators and administrators.
A Study on the Soundscape of Pleasure Appeared in Shin Yun-bok's Hyewonjeonshincheop
Authors:   The Korean Society of Culture and Convergence, Noh Shihun
Published: June 2023

The purpose of this study is to analyze how Shin Yun-bok tried to change the perspective on pleasure through the paintings in his Hyewonjeonshincheop and how he used sound and silence in the conversion by examining the soundscape of pleasure in the album. Among the frequency of soundscape elements extracted from pictures and poems (111), the frequency of pleasure factor (58) was slightly more than half, and human sound (25) and social sound (26) accounted for the majority of pleasure sounds. The elements of the soundscape of pleasure are divided into “source of pleasure” and “enjoyment,” “pleasure of sense” and “pleasure dependent on association,” “sexual desire” and “entertainment,” and function to reinforce the theme of pleasure by letting us feel how much the characters are absorbed in pleasure, and to awaken other related senses and harmonize with them to experience pleasure synesthetically. As well described in the auditory images of Hyewonjeonshincheop, “status,” “oppressive system,” and “competition” at the time were obstacles to the pursuit of pleasure by the upper class. Shin Yun-bok tried to change the perspective on pleasure by treating “sexual desire” at the same level as “entertainment” and making people realize that there is no high or low in the pursuit of pleasure, and by dealing with the phenomenon of inversion that appears when the pursuit reaches its peak.
Landscapes and Soundscapes of Islands Expressed in Elementary School Songs in the Island Region of Jeollanam-do
Authors:   The Korean Society of Culture and Convergence, Han Myung Ho
Published: June 2023

This study aims to examine the characteristics of landscapes and soundscapes of the islands expressed in elementary school songs located in Sinan-gun, Wando-gun, and Jindo-gun of Jeollanam-do. School songs from 36 schools in Shinan-gun, 36 schools in Wando-gun, and 32 schools in Jindo-gun were investigated. Topography and water have the highest appearance rate of landscape elements, and among elements of topography, mountains and the sea have the highest frequency of appearance. The soundscape elements expressed in school songs are composed of natural sound, artificial sound, human sound, and tranquility, and natural sound has the highest frequency of occurrence. The soundscape elements of nature represent the topographical characteristics of the island region, and the elements of artificial sound, human sound, and tranquility express the life of children or the sound environment of the school. The landscape of the island expressed in the school song sings the appearance and location of the school, the spirit and mind of children, hope for the future, the soul and patriotic spirit of local ancestors, and the beauty of the natural scenery of the island and school in Jeollanam-do. In addition, the identity of the island is expressed by including the history and tradition of gardens and historical sites in the lyrics of school songs.
Aspects of the Personal Relationship Network of Women in the Mid-Joseon Dynasty Seen through Miam-ilgi
Authors:   The Korean Society of Culture and Convergence, Kim Girim
Published: June 2023

The purpose of this thesis is to examine the aspects of women's personal network in the Miam-ilgi and to clarify the aspects of women's lives in the mid-Joseon Dynasty. Miam-ilgi is a diary written by Yoo Hee-chun, who recorded the personal information of the people he met, the personal relationship network between women, and her activities. Women's personal network was formed through their husband's official colleagues, their wives, and their husband's concubines. The range was extended to the woman's eighth degree of parental family. Women acted as beneficiaries and donors, giving and receiving goods in the personal network. In addition, she made various demands such as exemption from military service, succession to descendants, and government positions. Furthermore, women expanded their networks by including men in their families in their networks. This is different from the late Joseon Dynasty, when women's personal networks were formed mainly through husband's in-laws
The Acceptance of the Lee Kun-hee Collection and the Exhibition of Donated Works from the Perspective of the Collection Story
Authors:   The Korean Society of Culture and Convergence, Lee Kwangpyo
Published: June 2023

This study sought to examine the achievements and limitations of the exhibition of donated works of the Lee Kun-hee collection and to explore the sustainable direction in the process of accepting and enjoying the Lee Kun-hee collection. To this end, the flow and characteristics of 18 exhibitions of Lee Kun-hee collection donated works were analyzed. Over time, the exhibition of donated works has diversified into collaborative exhibitions and theme exhibitions, and has developed into an exhibition that makes spectators think about the meaning of the Lee Kun-hee collection. Nevertheless, almost all exhibitions failed to show the story of the Lee Kun-hee collection and only displayed donated works themselves. Based on this analysis, it was emphasized that in order for the acceptance and enjoyment of the Lee Kun-hee collection to continue, various stories of collector Lee Kun-hee should be discovered and actively reflected in the exhibition of donated works.
Penyebab Mortalitas Lansia Selama Masa Perawatan Rumah Sakit COVID-19: A Systematic Review
Authors: Astuti Agnes Dewi , Aridamayanti Bernadetta Germia
Published: June 2023

Background: The first case of COVID-19 was first reported in China in December 2019 and spread rapidly to various countries. On July 13, 2020, COVID-19 was officially declared a world pandemic by the WHO. COVID19 affects more than 210 countries in the world and kills millions of people with 21% of deaths occurring in the elderly. Objective: To describe the risk factors and causes of elderly mortality during the period of treatment or quarantine in the hospital by COVID-19. Methods: The database used as a reference, among others, is Scopus, PubMed and Science Direct, which is limited to publications in the last 2 years from 2020 to 2021, full text articles selected in English. Meanwhile, the keywords used in the article search are "COVID-19" AND "elderly clinical of SARS-CoV-2" AND "pandemic mortality". This systematic review used 5 articles that met the inclusion criteria. Results: Risk factors or causes of elderly mortality during COVID-19 hospital treatment include chormobid such as dementia, respiratory disorders such as asthma, diabetes mellitus, chronic kidney disease and hypertension. Conclusions: Various non-communicable diseases that accompany COVID-19 will be a risk factor and even a leading cause of death in the elderly during hospital treatment.

Keywords: COVID-19; elderly clinical of SARS-CoV-2; pandemic mortality

ABSTRAK

Latar belakang: Kasus pertama COVID-19 pertama kali dilaporkan di China pada Desember 2019 dan menyebar dengan cepat ke berbagai negara. Pada 13 Juli 2020, COVID-19 resmi diumumkan sebagai pandemik dunia oleh WHO. COVID-19 mempengaruhi lebih dari 210 negara yang ada di dunia dan membunuh jutaan jiwa dengan 21% kasus kematian paling banyak terjadi pada lansia. Tujuan: Untuk menjabarkan faktor risiko maupun penyebab kejadian mortalitas lansia selama masa perawatan atau karantina di rumah sakit oleh COVID-19. Metode: Database yang digunakan sebagai referensi antara lain adalah Scopus, PubMed dan Science Direct yang dibatasi dalam publikasi 2 tahun terakhir terhitung sejak dari 2020 hingga 2021, full text article yang dipilih menggunakan bahasa Inggris. Sedangkan, kata kunci yang digunakan pada pencarian artikel adalah “COVID-19” AND “elderly clinical of SARS-CoV-2” AND “pandemic mortality”. Systematic review ini menggunakan 5 artikel yang sesuai dengan kriteria inklusi. Hasil: Faktor Risiko ataupun penyebab mortalitas lansia selama masa perawatan COVID-19 dirumah sakit antara lain adalah kormobid seperti demensia, gangguan pernapasa seperti asma, diabetes melitus, penyakit ginjal kronis dan hipertensi. Simpulan: Berbagai macam penyakit tidak menular yang disertai dengan COVID-19 akan menjadi faktor risiko bahkan penyebab utama kematian pada lansia selama masa perawatan di rumah sakit.

Kata kunci: COVID-19; elderly clinical of SARS-CoV-2; pandemic mortality
Faktor Jenis Kelamin dan Status Imunisasi terhadap Kejadian Pneumonia pada Balita di RSUD dr. Soedarso
Authors: A'yuni Zera Qurrota , Mamesah Lilis Sri Supiatun , Marhana Isnin Anang
Published: June 2023

Introduction: The incidence of pneumonia in toddlers was recorded as the second highest case in the Pediatric Inpatient Room at the dr. Soedarso Regional General Hospital, West Borneo Province. Purpose: Analyzing the relationship between sex and immunization status on the incidence of pneumonia in toddlers at the dr. Soedarso Regional General Hospital, West Borneo Province. Methods: The study used a case control design with 31 cases and 31 controls. Sampling using a total sampling technique with a ratio of 1:1. The case group was toddlers diagnosed with pneumonia by the Patient Responsible Doctor who was recorded in the medical record. The control group was toddlers were not diagnosed with pneumonia by the Patient Responsible Doctor who was recorded in the medical record . This study used bivariate analysis. The statistical test is the Chi-Square Test. Results: The most data for toddlers is owned by toddlers with male sex (54.8%).Most of the data for toddlers is owned by toddlers with incomplete immunization status (82.3%). The results of the bivariate analysis showed that there was no significant correlation between sex and immunization status on the incidence of pneumonia in toddlers. Conclusion: There was no significant correlation between sex and immunization status on the incidence of pneumonia in toddlers at the dr. Soedarso Regional General Hospital, West Borneo Province. This research still needs further research to explore other factors that can cause pneumonia in toddlers.
Peran Orang Tua untuk Meningkatkan Pengetahuan dan Sikap Remaja terhadap Pernikahan Usia Dini
Authors: Hamidiyanti Baiq Yuni Fitri , Pratiwi Intan Gumilang , Suseno Mutiara Rachmawati , Faiqah Syajaratuddur , Sulianty Ati
Published: June 2023

Introduction: Factors causing early marriage in NTB include coercion from parents. For example, interviews with six young women who married early showed that two people married because of promiscuity, and two married because of coercion by their parents. One married because they liked each other, and one person had to get married, afraid of being a disgrace to the family and society because going home too late. Late night with his girlfriend. Objective: to analyze the effect of developing parental role models to increase adolescent knowledge and attitudes towards early marriage in West Lombok Regency. Method: quasi-experiment with pretest-posttest research design with Mann-Whitney test. The research location is in Sigerongan, West Lombok Regency, and carried out for three months with a population of male and female adolescents aged 15-19 years and a sample of 40 adolescents who were grouped into two groups. The sampling method used simple random sampling. Result: there is a significant difference in the value of knowledge between the intervention group and the control group. Conclusion: there is a significant difference between the intervention group and the control group, and there are differences in the post-test results of adolescent attitudes towards early marriage in the intervention group and the control group.
Efektifitas the Safe Delivery App (SDA) secara Blended Learning terhadap Pengetahuan Bidan
Authors: Baska Dwie Yunita , Wahyuni Elly , Savitri Wewet
Published: June 2023

Instroduction: Globally on the industrial revolution of 4.0 mobile learning (mLearning) tools were familiar and attracted considerable attention for healthcare workers as a means of continuous training. The Safe Delivery App’s innovation (SDA) is a smartphone mLearning app that contains information and skills for trained health workers, can be accessed directly, quckly, and based on evidence-based Basic Emergency Obstetric and Neonatal Care (BEmONC) content. Purpose: This study assessed the effect of the SDA intervention by blended learning on midwives’ knowledge. Methods: The study used a quasi-experimental group pre-and post-test design with control group. The research sample consisted of 48 midwives with randomized sampling grouping through by-wheel trial numbers, timing 3 to 6 month. An independent sample t-test was used to statistically, Confidence interval (Cls) and effect size by Cohen’s d were used. Results: The use of The SDA App has proven to be significantly effective in creasing knowledge, the mean differences before-after 5,39 (SD=2,37); 95% Cl 2,29 ± 4,28, p-value <0,001 and d=1,38 in one of the modules. Conclusion: The SDA App has proven very effective improved the quality of human resources for midwives, hope these benefits will be further disseminated wider by all heatlh cares provider.
Human adenovirus DNA polymerase is evolutionarily and functionally associated with human telomerase reverse transcriptase based on in silico molecular characterization that implicate abacavir and zidovudine
Authors: Fatoki Toluwase Hezekiah
Published: June 2023

Human adenoviruses (HAdVs) are non-enveloped, small double stranded DNA (dsDNA) viruses that cause asymptomatic infections, clinical syndromes and significant susceptibility to infections in immunocompromised people. The aim of the present study was to identify critical host proteins and HAdV hypothetical proteins that could be developed as potential host-viral targets for antiHAdV therapy. Here, the function of selected hypothetical proteins of HAdV based on phylogenetic relationship with the therapeutic targets of antiretroviral drugs of human immunodeficiency virus (HIV) was predicted computationally, and characterized the molecular dynamics and binding affinity of DNA polymerase of HAdV. Thirty-eight hypothetical proteins (HPs) of human adenovirus (HAdV) were used in this study. The results showed that HAdV DNA polymerase (P03261) is related to Human TERT (O14746) and HLA-B (P01889) genes. The protein-protein interaction of human five molecular targets (PNP, TERT, CCR5, HLA-B, and NR1I2) of ARVDs are well-coordinated/networked with CD4, AHR, FKBP4, NR3C1, HSP90AA1, and STUB1 proteins in the anti-HIV infection mechanism. The results showed that the free energy score of abacavir and zidovudine binding to HAdV DNA polymerase are −5.8 and −5.4 kcal mol-1 respectively. Also, the control drug, cidofovir and ganciclovir have less binding affinity for DNA polymerase of HAdV when compare to that of abacavir and zidovudine. Similarity was observed in the binding of abacavir and zidovudine to HAdV DNA polymerase (ASP742, ALA743, LEU772, ARG773 and VAL776). In conclusion, combination of abacavir and zidovudine was predicted to be potential therapy for controlling HAdV infection targeting HAdV DNA polymerase.
Methods for infection prevention in the built environment—a mini-review
Authors: Salonen Noora , Ahonen Merja , Sirén Kai , Mäkinen Riika , Anttila Veli-Jukka , Kivisaari Meija , Salonen Kalle , Pelto-Huikko Aino , Latva Martti
Published: June 2023

The COVID-19 pandemic has shown that infection prevention actions need to be more efficient in public indoor environments. In addition to SARS-CoV-2, the cause of COVID-19, many pathogens, including other infectious viruses, antibiotic-resistant bacteria, and premise plumbing pathogens, are an invisible threat, especially in public indoor spaces. The indoor hygiene concept for comprehensive infection prevention in built environments highlights that the indoor environment should be considered as a whole when aiming to create buildings with increased infection prevention capacity. Within indoor environments, infections can indirectly spread through surfaces, air, and water systems. Many methods, such as antimicrobial technologies and engineering solutions, targeting these indoor elements are available, which aim to increase the hygiene level in indoor environments. The architectural design itself lays a foundation for more efficient infection prevention in public buildings. Touchless solutions and antimicrobial coatings can be applied to frequently touched surfaces to prevent indirect contact infection. Special ventilation solutions and air purification systems should be considered to prevent airborne infection transmissions. Proper design and use of water supply systems combined with water treatment devices, if necessary, are important in controlling premise plumbing pathogens. This article gives a concise review of the functional and available hygiene-increasing methods—concentrating on indoor surfaces, indoor air, and water systems—to help the professionals, such as designers, engineers, and maintenance personnel, involved in the different stages of a building’s lifecycle, to increase the infection prevention capacity of public buildings.
Retinal degeneration in rpgra mutant zebrafish
Authors: Liu Xiliang , Han Shanshan , Liu Fei , Yu Shanshan , Qin Yayun , Li Jingzhen , Jia Danna , Gao Pan , Chen Xiang , Tang Zhaohui , Liu Mugen , Huang Yuwen
Published: June 2023

Introduction: Pathogenic mutations in RPGRORF15, one of two major human RPGR isoforms, were responsible for most X-linked retinitis pigmentosa cases. Previous studies have shown that RPGR plays a critical role in ciliary protein transport. However, the precise mechanisms of disease triggered by RPGRORF15 mutations have yet to be clearly defined. There are two homologous genes in zebrafish, rpgra and rpgrb. Zebrafish rpgra has a single transcript homologous to human RPGRORF15; rpgrb has two major transcripts: rpgrbex1-17 and rpgrbORF15, similar to human RPGRex1-19 and RPGRORF15, respectively. rpgrb knockdown in zebrafish resulted in both abnormal development and increased cell death in the dysplastic retina. However, the impact of knocking down rpgra in zebrafish remains undetermined. Here, we constructed a rpgra mutant zebrafish model to investigate the retina defect and related molecular mechanism.

Methods: we utilized transcription activator-like effector nuclease (TALEN) to generate a rpgra mutant zebrafish. Western blot was used to determine protein expression. RT-PCR was used to quantify gene transcription levels. The visual function of embryonic zebrafish was detected by electroretinography. Immunohistochemistry was used to observe the pathological changes in the retina of mutant zebrafish and transmission electron microscope was employed to view subcellular structure of photoreceptor cells.

Results: A homozygous rpgra mutant zebrafish with c.1675_1678delins21 mutation was successfully constructed. Despite the normal morphological development of the retina at 5 days post-fertilization, visual dysfunction was observed in the mutant zebrafish. Further histological and immunofluorescence assays indicated that rpgra mutant zebrafish retina photoreceptors progressively began to degenerate at 3-6 months. Additionally, the mislocalization of cone outer segment proteins (Opn1lw and Gnb3) and the accumulation of vacuole-like structures around the connecting cilium below the OSs were observed in mutant zebrafish. Furthermore, Rab8a, a key regulator of opsin-carrier vesicle trafficking, exhibited decreased expression and evident mislocalization in mutant zebrafish.

Discussion: This study generated a novel rpgra mutant zebrafish model, which showed retinal degeneration. our data suggested Rpgra is necessary for the ciliary transport of cone-associated proteins, and further investigation is required to determine its function in rods. The rpgra mutant zebrafish constructed in this study may help us gain a better understanding of the molecular mechanism of retinal degeneration caused by RPGRORF15 mutation and find some useful treatment in the future.
The diagnostic value of electrocardiogram-based machine learning in long QT syndrome: a systematic review and meta-analysis
Authors: Wu Min-Juan , Wang Wen-Qin , Zhang Wei , Li Jun-Hua , Zhang Xing-Wei
Published: June 2023

Introduction

To perform a meta-analysis to discover the performance of ML algorithms in identifying Congenital long QT syndrome (LQTS).

Methods

The searched databases included Cochrane, EMBASE, Web of Science, and PubMed. Our study considered all English-language studies that reported the detection of LQTS using ML algorithms. Quality was assessed using QUADAS-2 and QUADAS-AI tools. The bivariate mixed effects models were used in our study. Based on genotype data for LQTS, we performed a subgroup analysis.

Results

Out of 536 studies, 8 met all inclusion criteria. The pooled area under the receiving operating curve (SAUROC) for detecting LQTS was 0.95 (95% CI: 0.31–1.00); sensitivity was 0.87 (95% CI: 0.83–0.90), and specificity was 0.91 (95% CI: 0.88–0.93). Additionally, diagnostic odd ratio (DOR) was 65 (95% CI: 39–109). The positive likelihood ratio (PLR) was 9.3 (95% CI: 7.0–12.3) and the negative likelihood ratio (NLR) was 0.14 (95% CI: 0.11–0.20), with very low heterogeneity (I2 = 16%).

Discussion

We found that machine learning can be used to detect features of rare cardiovascular disease like LQTS, thus increasing our understanding of intelligent interpretation of ECG. To improve ML performance in the classification of LQTS subtypes, further research is required.

Systematic Review Registration

identifier PROSPERO CRD42022360122.
Strain-based forward modeling and inversion of seismic moment tensors using distributed acoustic sensing (DAS) observations
Authors: Lecoulant Jean , Ma Yuanyuan , Dettmer Jan , Eaton David
Published: June 2023

This study used a waveform inversion of distributed acoustic sensing (DAS) data, acquired in two horizontal monitoring wells, to estimate the moment tensor (MT) of two induced microearthquakes. An analytical forward model was developed to simulate far-field tangential strain generated by an MT source in a homogeneous and anisotropic medium, averaged over the gauge length along a fiber of arbitrary orientation. To prepare the data for inversion, secondary scattered waves were removed from the field observations, using f-k filtering and time-windowing. The modeled and observed primary arrivals were aligned using a cut-and-paste approach. The MT parameters were inverted via a least-squares approach, and their uncertainties were determined through bootstrap analysis. Using simulated data with additive noise derived from the field data and the same fiber configuration as the monitoring wells, the inversion method adequately resolved the MT. Despite the assumption of Gaussian noise, which underlies the least-squares inversion approach, the method was robust in the presence of heavy-tailed noise observed in field data. When the inversion was applied to field data, independent inversion results using P-waves, S-waves, and both waves together yielded results that were consistent between the two events and for different wave types. The agreement of the inversion results for two events resulting from the same stress field illustrated the reliability of the method. The uncertainties of the MT parameters were small enough to make the inversion method useful for geophysical interpretation. The variance reduction obtained from the data predicted for the most probable MT was satisfying, even though the polarity of the P-waves was not always correctly reproduced.
Biochemical association of regulatory variant of KLF14 genotype in the pathogenesis of cardiodiabetic patients
Authors: Alanazi Abdullah Salah , Rasheed Sumbal , Rehman Kanwal , Mallhi Tauqeer Hussain , Akash Muhammad Sajid Hamid , Alotaibi Nasser Hadal , Alzarea Abdulaziz Ibrahim , Tanveer Nida , Khan Yusra Habib
Published: June 2023

Background and purpose

The study focuses on examining the relationship between a single nucleotide polymorphism (SNP) in KLF14 rs4731702 and risk of type 2 diabetes mellitus (T2DM) and dyslipidemia in different ethnic populations. The purpose of this study was to evaluate the association between KLF14 rs4731702 and serum lipid profile and to determine the frequency distribution of KLF14 rs4731702 among T2DM and cardiometabolic patients.

Methods

A total of 300 volunteers were recruited, consisting of three groups: 100 healthy individuals, 100 individuals diagnosed with T2DM, and 100 individuals diagnosed with cardiometabolic disorders. Biochemical analysis of blood samples was conducted to assess various biomarkers related to glycemic control and lipid profile. This involved measuring levels of glucose, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and ApoA1. Genotyping analysis was performed to investigate KLF14 rs4731702 polymorphism. The Tetra ARMS-PCR method was employed for genotyping analysis.

Results

The results of biochemical profiling revealed a significant association between altered glycemic biomarkers and lipid profile in diseased patients compared to healthy participants. The frequencies of KLF14 rs4731702 alleles and genotypes were compared between the control group and T2DM group. A statistically significant difference was observed, indicating a potential association between KLF14 rs4731702 and T2DM. In the dominant inheritance model of KLF14 rs4731702 SNP, a statistically significant difference [odds ratio (95% confidence interval)] of 0.56 (0.34 –0.96) was found between the control and T2DM subjects. This suggests that the presence of certain genotypes influences the risk of T2DM. In T2DM patients, individuals carrying the C allele exhibited compromised insulin sensitivity, decreased HDL-C and ApoA1 levels, and increased serum glucose, TG, and LDL-C concentrations. Conversely, TT genotype carriers demonstrated increased levels of HDL-C and ApoA1, lower insulin resistance, serum glucose, LDL-C, and TG levels.

Conclusion

The study’s findings indicate that dyslipidemia in T2DM patients is associated with reduced KLF14 functionality due to CC and CT genotypes, leading to insulin resistance and an increased risk of cardiovascular diseases. Additionally, risk of KLF14 rs4731702 polymorphism was found to increase with age and was more prevalent in female than in male individuals. These insights contribute to understanding genetic factors influencing the development and progression of T2DM and dyslipidemia in different ethnic populations.
Effect of coffee consumption on thyroid function: NHANES 2007-2012 and Mendelian randomization
Authors: Zhao Guoxu , Wang Zhao , Ji Jinli , Cui Rongjun
Published: June 2023

Background

Coffee is one of the most consumed beverages worldwide, but the effects on the thyroid are unknown. This study aims to examine the association between coffee and thyroid function.

Methods

Participant data (≥ 20 years, n = 6578) for the observational study were obtained from NHANES 2007-2012. Analysis was performed using weighted linear regression models and multiple logistic regression models. Genetic datasets for Hyperthyroidism and Hypothyroidism were obtained from the IEU database and contained 462,933 European samples. Mendelian randomization (MR) was used for the analysis, inverse variance weighting (IVW) was the main method of analysis.

Results

In the model adjusted for other covariates, participants who drank 2-4 cups of coffee per day had significantly lower TSH concentrations compared to non-coffee drinkers (b=-0.23, 95% CI: -0.30, -0.16), but no statistically significant changes in TT4, FT4, TT3 and FT3. In addition, participants who drank <2 cups of coffee per day showed a low risk of developing subclinical hypothyroidism. (OR=0.60, 95% CI: 0.41, 0.88) Observational studies and MR studies have demonstrated both that coffee consumption has no effect on the risk of hyperthyroidism and hypothyroidism.

Conclusions

Our study showed that drinking <2 cups of coffee per day reduced the risk of subclinical hypothyroidism and drinking 2-4 cups of coffee reduced serum TSH concentrations. In addition, coffee consumption was not associated with the risk of hyperthyroidism and hypothyroidism.
A mechanistic model of a PWR-based nuclear power plant in response to external hazard-induced station blackout accidents
Authors: Liu Tao , Wu Zeyun , Bensi Michelle , Ma Zhegang
Published: June 2023

Natural hazard-induced nuclear accidents, such as the Fukushima Daiichi Accident that occurred in Japan in 2011, have significantly increased reactor safety studies in understanding nuclear power plant (NPP) responses to external hazard events such as earthquakes and floods. Natural hazards could cause the loss of offsite power in nuclear power plants, potentially leading to a Station Blackout (SBO) accident that significantly contributes to the overall risk of nuclear power plant accidents. Despite the fact that extensive research has been conducted on the station blackout accident for nuclear power plant, further understanding of these events is needed, particularly in the context of the dynamic nature of external hazards such as external flooding. This paper estimates the progression of station blackout events for a generic pressurized water reactor (PWR) in response to external flooding events. The original RELAP5-3D model of the Westinghouse four-loop design pressurized water reactor was adopted and modified to simulate the external flood-induced station blackout accident, including the short-term and long-term station blackout scenarios. A sensitivity analysis of long-term station blackout, examining reactor operation times and analyzing key parameters over time, was also conducted in this work. The results of the analyses, especially the critical timing parameters of key event sequences, provide useful insights about the time during the external flooding event, which is important for plant operators to make timely decisions to prevent potential core damage. This paper represents significant progress toward developing an integrated risk assessment framework for further identifying and assessing the effects of the critical sources of uncertainties of nuclear power plant under external hazard-induced events.
The Daily Pattern of Expression of Leptin and Ghrelin O-Acyl Transferase Under Various Lighting Schedules in the Whole Brain of Zebrafish (Danio rerio)
Authors: Mondal Gopinath , Khan Zeeshan Ahmad , Devi Sijagurumayum Dharmajyoti , Labala Rajendra Kumar , Chattoraj Asamanja
Published: June 2023

Graphical Abstract

Light dark cycle influences the levels of Leptin and Ghrelin O-Acyl Transferase (GOAT).
Rheumatoid meningitis: a rare neurological complication of rheumatoid arthritis
Authors: Fan Siyuan , Zhao Jiuliang , Hou Bo , Liu Mange , Niu Jingwen , Zhou Yan , Mao Chenhui , Ren Haitao , Feng Feng , Li Mengtao , Zeng Xiaofeng , Zhu Yicheng , Guan Hongzhi
Published: June 2023

Objective

To describe the clinical and neuroimaging characteristics of rheumatoid meningitis (RM) in Chinese patients.

Methods

The patients admitted to our hospital with the diagnosis of RM in the past 8 years were retrospectively analyzed.

Results

Six patients with RM were identified among 933 patients admitted with rheumatoid arthritis (RA). The symptoms of meningitis occurred after onset of arthritis in five patients and before onset in one. Headache (n=6), hyperacute focal neurological deficits (n=4) and seizures (n=3) were the most prevalent symptoms. The nadir modified Rankin Scale score was ≥3 in five patients. Rheumatoid factor was elevated in all patients, and interleukin-6 levels in cerebrospinal fluid were dramatically elevated in three of four tested patients. Magnetic resonance imaging of the brain revealed that the meninges were affected in all patients and the cerebral parenchyma was affected in one patient. The lesions were generally located in the frontoparietal region and showed restricted diffusion along the adjacent subarachnoid space. RM occurred during disease-modifying therapy in four patients. In the acute episode, three patients improved on tocilizumab and the other three improved on pulse corticosteroids. For maintenance therapy, two patients received combined therapy of tocilizumab and other immunosuppressive agents, one received adalimumab and methotrexate, and two received low-dose oral corticosteroids with an immunosuppressive agent. Five patients had a good outcome, and one died of Pneumocystis jirovecii pneumonia after stabilization of his neurologic conditions. No relapse of RM occurred on immunotherapy during follow-up.

Conclusions

Chinese patients with RM share some remarkable clinical and neuroimaging features and respond well to appropriate immunotherapy. Tocilizumab could be a treatment option for this severe complication of RA.
The paradox of autoimmunity and autoinflammation in inherited neutrophil disorders – in search of common patterns
Authors: Krzyzanowski Damian , Oszer Aleksandra , Madzio Joanna , Zdunek Maciej , Kolodrubiec Julia , Urbanski Bartosz , Mlynarski Wojciech , Janczar Szymon
Published: June 2023

Congenital defects of neutrophil number or function are associated with a severe infectious phenotype that may require intensive medical attention and interventions to be controlled. While the infectious complications in inherited neutrophil disorders are easily understood much less clear and explained are autoimmune and autoinflammatory phenomena. We survey the clinical burden of autoimmunity/autoinflammation in this setting, search for common patterns, discuss potential mechanisms and emerging treatments.
Targeting macrophage Syk enhances responses to immune checkpoint blockade and radiotherapy in high-risk neuroblastoma
Authors: Rohila Deepak , Park In Hwan , Pham Timothy V. , Jones Riley , Tapia Elisabette , Liu Kevin X. , Tamayo Pablo , Yu Alice , Sharabi Andrew B. , Joshi Shweta
Published: June 2023

Background

Neuroblastoma (NB) is considered an immunologically cold tumor and is usually less responsive to immune checkpoint blockade (ICB). Tumor-associated macrophages (TAMs) are highly infiltrated in NB tumors and promote immune escape and resistance to ICB. Hence therapeutic strategies targeting immunosuppressive TAMs can improve responses to ICB in NB. We recently discovered that spleen tyrosine kinase (Syk) reprograms TAMs toward an immunostimulatory phenotype and enhances T-cell responses in the lung adenocarcinoma model. Here we investigated if Syk is an immune-oncology target in NB and tested whether a novel immunotherapeutic approach utilizing Syk inhibitor together with radiation and ICB could provide a durable anti-tumor immune response in an MYCN amplified murine model of NB.

Methods

Myeloid Syk KO mice and syngeneic MYCN-amplified cell lines were used to elucidate the effect of myeloid Syk on the NB tumor microenvironment (TME). In addition, the effect of Syk inhibitor, R788, on anti-tumor immunity alone or in combination with anti-PDL1 mAb and radiation was also determined in murine NB models. The underlying mechanism of action of this novel therapeutic combination was also investigated.

Results

Herein, we report that Syk is a marker of NB-associated macrophages and plays a crucial role in promoting immunosuppression in the NB TME. We found that the blockade of Syk in NB-bearing mice markedly impairs tumor growth. This effect is facilitated by macrophages that become immunogenic in the absence of Syk, skewing the suppressive TME towards immunostimulation and activating anti-tumor immune responses. Moreover, combining FDA-approved Syk inhibitor, R788 (fostamatinib) along with anti-PDL1 mAb provides a synergistic effect leading to complete tumor regression and durable anti-tumor immunity in mice bearing small tumors (50 mm3) but not larger tumors (250 mm3). However, combining radiation to R788 and anti-PDL1 mAb prolongs the survival of mice bearing large NB9464 tumors.

Conclusion

Collectively, our findings demonstrate the central role of macrophage Syk in NB progression and demonstrate that Syk blockade can “reeducate” TAMs towards immunostimulatory phenotype, leading to enhanced T cell responses. These findings further support the clinical evaluation of fostamatinib alone or with radiation and ICB, as a novel therapeutic intervention in neuroblastoma.
Now you see me, now you don’t: verifying the absence of alien invasive yellow crazy ant Anoplolepis gracilipes in South Africa
Authors: Ndaba Abusisiwe , Munyai Thinandavha Caswell , Mbanyana Nokuthula , van Noort Simon , Janion-Scheepers Charlene
Published: June 2023

Anoplolepis gracilipes is an invasive species that is a major threat to native ecosystems worldwide. It has been listed as one of the top 100 worst invasive species in the world and is well known for its negative impact on native arthropods and some vertebrates. This study aimed to confirm the presence or absence of A. gracilipes in some major South African harbours. We did so by surveying four harbours in the Western Cape and KwaZulu-Natal provinces, using pitfall trapping, yellow pan traps, and baiting. In addition, ant collections from Iziko Museums of South Africa (Cape Town, South Africa), University of KwaZulu-Natal (Pietermaritzburg campus, South Africa), Iimbovane Outreach Project (Stellenbosch University, South Africa), and AfriBugs CC (Pretoria, South Africa) were examined for specimens of A. gracilipes. The invasive species A. gracilipes was not detected from any of the sampled harbours during this study, nor in the main ant collections in South Africa. The only, and potentially erroneous published record of A. gracilipes in South Africa, is from Durban harbour and subsequent possibly erroneous citizen science observations are from other coastal sites such as Gansbaai, Knysna, Table Bay, and Kalk Bay. This is a positive outcome for conservation authorities as this species is highly invasive and, if introduced, will likely outcompete native fauna and result in ecosystem collapse. Although A. gracilipes was not detected in the samples from this study, early detection and eradication of this species should be prioritised. This can be achieved through existing pest monitoring programs at harbours, and continued border biosecurity measures.