bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Studies in Pediatric Gastrointestinal Surgery: Theory and Practice
Authors:   , Stellato Rebecca Kirsten
Published: November 2023

This thesis described the current state of longitudinal data analysis in the pediatric gastrointestinal (GI) surgical literature. Studies on two procedures were performed to gather the best available evidence for minimally invasive pediatric upper GI surgery. The studies were performed using the best possible design and analysis given the constraints.

Chapter one provided an introduction to the current state of methodology and statistics, especially regarding longitudinal data analysis, in the pediatric GI surgical literature. Several challenges in the reporting and analysis of the effects of pediatric surgical studies were summarized, such as the preponderance of case studies, the small number of patients in studies, ethical issues regarding a vulnerable population, poor reporting of methodology, and the suspicion that the statistical analysis of repeated measures is not always appropriate. In addition, the effects of two surgical procedures were described: anti-reflux surgery (LARS) for children with severe gastrointestinal reflux disease that does not respond to medication; and gastrostomy placement (GP) for children with severe feeding problems.

To identify potential methodological problems in the pediatric surgical literature, a literature review was performed on all scientific articles that reported on repeated measures in a pediatric GI surgical study in the years 2010-2019. The results were presented in chapter two. A large majority of the studies examined reported on the number of included patients, which was generally low (median sample size 40). Most also clearly stated the objective of the study and interpreted the results in that context. Poor adherence to reporting was found on several items related to data collection and analysis: sample size justification; reliability and validity of methods; statistical methods used; numbers of participants at each wave; and generalizability of results were not, or not clearly, reported in a majority of the articles examined. This information is crucial to the assessment of the quality of the study.

Furthermore, more than half the pediatric GI surgery studies classified as “longitudinal” or “cohort” in PubMed did not make efficient use of that design by collecting either time-to-event data or repeated measures on one or more outcomes. In the majority of the articles that did collect repeated measures, we observed inefficient, inappropriate or incorrect analysis of longitudinal data. The inefficient use of the cohort/longitudinal design identified in many publications on pediatric GI surgery has likely led to reduced power of the studies. In addition, inappropriate or incorrect analysis of repeated measures data at best make inefficient use of the available information, and at worst may have led to biased estimates of treatment effects. While these methodological issues are important in any medical study, they are especially so in studies on vulnerable (pediatric) populations….

The remainder of the summary can be found in the thesis.
Compression Run Length Encoding On Watermarking Using a Combination of DCT, DWT and SVD
Authors: Abdussalam Abdussalam , Pramudya Elkaf Rahmawan
Published: November 2023

This study focus on identifying medical images by proposing the Discrete Wavelet Transform (DWT), Discrete Cosine Transform (DCT) and Singular Value Decomposition (SVD) transformation watermarking technique and prove an increase the quality of watermarked images is good in terms of imperceptibility. Due to reduce the need for data memory compression is applied to the host image, where the compression technique chosen is lossless so that the compressed host image experiences a decrease in file size while maintaining data integrity, to maintain image degradation perceptions and diagnostic quality standards during the watermarking process. Here, we use DWT-DCT-SVD and Run Length Encoding (RLE). A good Peak Signal to Noise Ratio (PSNR) more than 30 dB using over than 200 compression size. The extracted watermark image is quite good with a fairly high PSNR value. The highest compression result size is in 32.2511.
Poverty Modeling in East Java Province Using the Spatial Seemingly Unrelated Regression (Sur) Method
Authors: Wibowo Dibyo Adi , Hidajat Moch Sjamsul , Widyatmoko Widyatmoko
Published: November 2023

Poverty is a complex problem because it relates to various aspects of human life. In Indonesia, there is one province that has a very high percentage of poverty, namely East Java Province. Although from year to year the poverty rate has decreased, when viewed from the national level it is still very far from the government's expectations of reducing the poverty rate. Cases of poverty can be modeled by Econometrics. Econometric models are often applied to problems involving one or more related equations. One method that can be used to solve several interrelated equations because there is a correlation error regression between one another, namely Seemingly Unrelated Regression which is usually abbreviated as SUR, in this case Spatial Seemingly Unrelated Regression (SUR-Spatial) is development that takes into account the spatial influence between locations. From the results of tests conducted in the SUR-Spatial Lagrange Multiplier model, the poverty data generated by the East Java Province is the SUR-Spatial Autoregressive Model (SUR-SAR). So with the SUR-SAR model it can be seen that the variable that has a significant effect on the percentage of poor people is the growth rate of Gross Regional Domestic Product based on the constant price of the minimum wage for each district, as well as the average length of school years. Meanwhile, the Poverty Depth Index has an effect because of the growth rate of Gross Regional Domestic Product on the basis of constant prices and the average length of schooling. The Poverty Severity Index is influenced by the growth rate of Gross Regional Domestic Product at constant prices and average years of schooling.
Dijkstra-based Official Motorcycle Repair Shop Application for Determining the Shortest Route
Authors: Sucipto Adi , Doheir Mohamed
Published: November 2023

Servicing on 2-wheeled vehicles is needed so that the condition remains prime and minimizes the symptoms of component damage. Motorcycle service activities have an impact on the automotive world, especially in the City of Kudus. There are also many motorized vehicle users who do not know the closest route to the nearest Authorized Motorcycle Workshop in the holy city and choose Engine Fuel (BBM) that is in accordance with the type of vehicle they have. shorter service life because the RON (Research Octane Number) or octane number for each motorized vehicle is different, the octane number represents the resistance of the fuel to engine compression. With the development of information science in the current era, an Android-based application was created to search for the closest route to an official motorcycle repair shop in the Kudus City using the Djikstra Algorithm and having a BBM recommendation feature that is suitable for motorbike users' vehicles in the Kudus City.
Decision Support System For Determining The Best Employee Using The Visekriterijumsko Kompromisno Rangiranje Method (Case Study At Distribution Center Guardian)
Authors: Auliyah Risma , Maulana Donny , Afriantoro Irfan
Published: November 2023

The quality of human resources is one of the supporting factors to increase the performance productivity of a corporate agency. Highly competent human resources can support the level of performance, with performance appraisal, the achievements of each employee will be obtained. To obtain fast and accurate information on employee performance that meets the expected criteria. To find out this, with a multi-criteria decision-making method by solving complex and unstructured situations into parts and compiling them using the Visekriterijumsko Kompromisno Rangiranje (VIKOR) method on Decision Support Systems (SPK), the determination of the best employee can be calculated based on the calculation of the weight their respective criteria, so that they can quickly select the best employees in the company. From the final results of the VIKOR method, ranking 1 is Sukron, with a value of 0.
The consumption of white bread and its impact on the health of the population in the Republic of Kosova!
Authors: MAXHUNI Prof. assoc. dr. Shurki , GJOKAJ Prof. assoc. dr. Ekrem
Published: November 2023

The wrong mentality of the majority of the population in Kosova, who consume white bread and not whole-meal bread, dates back 50 years! This action is the result of not knowing the population's right to nutrition, and how to feed towards a proper and necessary diet for the body. se: While the bakers say that the population is looking for this bread production and we respond to the demand of the consumers, the citizens do not know exactly why they consume white bread and not the integral one! The surveys were done in 7 centers and cities of the Republic of Kosova. with 10 bakeries each (70 bakeries in total) in Prishtina, Mitrovica, Pejë, Gjakova, Prizren, Ferizaj, and Gjilan for the production of types of bread, and were surveyed by 200 citizens in each city (a total 1400 citizens). Of them, 50% are women and 50% are men.
The Development Of Variety Dance Movement Videos To Ease Teachers In Process Of Creating Dance
Authors: Milinia Fitri , Asmarani Ratih
Published: November 2023

The development of learning media in the form dance Movement Videos as an effort to facilitate teachers in the process of creating dance works is based on several factors, including: 1) being affected by the Covid-19 pandemic, 2) the ability of dance teachers who are not yet qualified in cerating dance works, 3) and the absence of dance learning media, so the development of learning media in the form of videos of various dance moves at SDN Palang. Based on the problems that have been described, the development aims to produce a valid Variety of Dance video media for teachers at SDN Palang. The development of this video media uses the ADDIE model with five stages including: 1) needs analysis, 2) Design, 3) Development, 4) Implementation, and 5) Evaluation. The Evaluation of the video media of various dance movments was carried out by media experts, educators as users and students of SDN Palang. The results of the research on the development of video media for various dance movements showed that the percentage obtained from  the validation results of media experts with a score of 90 % was included in the very valid category and was suitable for use without revision. The results of material expert validation get a score of 75 % which is included in the very valid category and is suitable for use without revision. Judging from the response as many as 7 educators have an average of 85.57 %. Meanwhile, from the responses, 5 students had an average of 86.7 %. This means that educators and students give a positive response, then the high percentage proves that the media is said to be effective and acceptable.
The Effectiveness of Jigsaw Cooperative Learning Model toward Thematic Learning Outcomes of Economic Activities
Authors: Nazila Diva Rohmatin , Raharja Hawwin
Published: November 2023

This research is motivated by the low achievement of student learning outcomes in the content of Social Science lessons. The aim of this study is to describe the effect of the Jigsaw Cooperative Learning (CL) Model so that the teaching and learning atmosphere is more fun, increasing student activity in asking questions and discussing. This study uses a quantitative approach with pre-experimental research methods, using a population of fourth grade students at SDN Pesanggrahan. This type of research is a one group pretest-posttest design. The research was conducted in three stages, namely pretest, treatment and posttest. Data collection technique is by test and questionnaire. The instrument in this study was an initial test (Pretest) and a final test (posttest). The results of this study can be concluded that 1) The ability to understand the material of Economic Activities Before using the Jigsaw Type Cooperative Learning (CL) Model for class IV at SDN Pesanggrahan is generally categorized as moderate with the class average score obtained by students with a value of 66.14. 2) The ability to understand the material of economic activities after using the Jigsaw Type Cooperative Learning (CL) Model for class IV at SDN Pesanggrahan is categorized as capable with the average score obtained by students with a value of 88.86. 3) The effect of learning on Economic Activities using the Jigsaw Type Cooperative Learning (CL) Model for class IV at Pesanggrahan Elementary School shows that there is an increase in the percentage of the pretest and posttest at 34.4%
The Effectiveness of f Tiktok Content on the Students’ Behavior in Elementary School
Authors: Hijjah Alifa rahmatul , Pratiwi Emy yunita rahma
Published: November 2023

The emergence of diverse social media, one of which is TikTok which has a variety of content in it and can be accessed by various groups, including students. So that unknowingly it can affect student behavior. This study aims to determine the influence of content on the TikTok application on grade III students of SDN Kesamben 2 Ngoro Jombang.This research is a quantitative research using a correlation approach with Ex post fact research design. The population is all grade III students of SDN Kesamben 2 Ngoro Jombang totaling 16 students. Data collection method using questionnaires and documentation. The results of this study show that: (1) The level of use of the TikTok application in grade III SDN Kesamben 2 Ngoro Jombang is in the medium category with a percentage of 50.0%. (2) The behavior of students III SDN Kesamben 2 Ngoro Jombang is in the medium category with a percentage of 62.5%. (3) There is an influence between the content in the TikTok application on the behavior of grade III students of SDN Kesamben 2 Ngoro, Jombang based on the t test with a significance value of 0.014 < 0.05. And based on the results of a simple linear regression test states that every addition of 1% content on the TikTok app will increase Student Behavior by 0.752.

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Keywords: TikTok Content, Student Behavior
The Effectiveness of Course Review Horay (CRH) Learning Model on The Student’s Learning Outcomes on The Science Learning in The Fifth Grade of SDN Godong Jombang
Authors: Laili Astiya , Peatiwi Emy Yunita Rahma
Published: November 2023

The implementation of natural science learning in the fifth grade of SDN Godong Jombang still uses teacher-centered approaches such as lecture and debriefing methods. It causes students to become passive, bored, and uninterested in following natural science learning. Besides, the lecture and debriefing methods make students have difficulty to comprehend the natural science material. Thus, it requires innovation to perform the natural science learning in the class, such as course review horay learning method. This research aims to discover the effect of the course review horay learning method on the studentâ€™s learning outcomes on the natural science learning in the fifth grade of SDN Godong Jombang. The research method is quantitative with a pre-experimental design in the form of one group pretest posttest design. The data collection technique in this research is tests. The data analysis techniques in this research are validity, normality, and hypothesis tests. The research results showed that the mean of the pretest score is 62,50, meanwhile the mean of posttest score is 86,43. Based on the hypothesis test and pretest posttest results analyzed using paired sample t test through SPSS 20 application, the significant result is 0,000 < 0,05 and tcalculate > ttable (11.337 > 1,703), so that Ha is accepted, and H0 is rejected. It showed a significance effect of using course review horay learning model on the studentâ€™s learning outcomes on the natural science learning in the fifth grade of SDN Godong Jombang.
Kurang Energi Kronik (KEK) Berhubungan dengan Kejadian Anemia Remaja Putri
Authors: Wirawanti Ika Wirya
Published: November 2023

Latar Belakang:  Anemia dapat menurunkan produktivitas kerja ataupun kemampuan akademis di sekolah. Anemia juga akan berpengaruh besar bagi ibu dan bayi pada saat kehamilan dan persalinan. Tujuan: Tujuan penelitian ini adalah untuk mengetahui hubungan antara Kurang Energi Kronik (KEK) dengan kejadian anemia pada remaja putri. Metode: Penelitian ini merupakan penelitian kuantitatif dengan menggunakan desain cross sectional. Pengumpulan data dilakukan dengan populasi penelitian yaitu siswi SMP Negeri 17 Makassar dengan jumlah sampel penelitian sebanyak 50 orang. Pengambilan sampel dilakukan dengan menggunakan teknik purposive sampling dengan kriteria inklusi yaitu remaja putri berumur 12-15 tahun, sudah menstruasi, dan bersedia menjadi subjek penelitian dengan menandatangani informed consent. Penelitian ini terdiri atas variabel independen yaitu Kurang Energi Kronik (KEK), serta variabel dependen yaitu anemia. Data diperoleh secara langsung yaitu data karakteristik menggunakan kuisioner karakteristik, data anemia melalui pengambilan sampel darah kapiler dengan metode finger prick pada jari, dan data KEK melalui pengukuran Lingkar Lengan Atas (LILA) menggunakan pita LILA. Data yang diperoleh kemudian dianalisis menggunakan uji statistik Chi-Squaredengan bantuan SPSS. Hasil:  Hasil penelitian menunjukkan bahwa 22% responden mengalami KEK, 60% responden mengalami anemia, dan semua responden yang mengalami KEK juga mengalami anemia yaitu sebanyak 11 orang. Hasil uji chi-square menunjukkan bahwa ada hubungan antara Kurang Energi Kronik (KEK) dengan kejadian anemia pada remaja putri dengan nilai p=0,002. Kesimpulan: Ada hubungan antara KEK dengan kejadian anemia pada remaja putri sehingga remaja putri disarankan untuk selalu memenuhi kecukupan kebutuhan zat gizi dan konsumsi tablet tambah darah untuk menghindari anemia.
Hubungan Sikap Ahli Gizi, Sikap Pramusaji Dan Cita Rasa Makanan Terhadap Kepuasan Pasien
Authors: Supriyono  , Setyaningrum Yahmi , Nirbaya Arindra
Published: November 2023

Latar Belakang: Kepuasan pasien merupakan salah satu parameter kualitas Rumah Sakit. Faktor yang mempengaruhi kepuasan pasien perlu diteliti. Kepuasan pasien diduga dipengaruhi oleh sikap ahli gizi, sikap pramusaji, cita rasa makanan. Tujuan: menganalisa hubungan hubungan sikap ahli gizi, sikap pramusaji dan cita rasa makanan terhadap kepuasan pasien. Metode: Desain penelitian ini menggunakan desain cross sectional. Jumlah sampel sebanyak 30 responden dengan teknik quota sampling. Instrumen pengumpulan data menggunakan kuesioner sikap, citarasa dan kepuasan. Hasil: uji statistik Spearman menunjukkan ada hubungan sikap ahli gizi (p-value = 0,001; r = 0,580), aroma lauk hewani (p-value = 0,011; r = 0,465), rasa lauk hewani (p-value = 0,010; r = 0,335), tekstur lauk hewani p-value = 0,001; r = 0,556), warna lauk hewani (p-value = 0,012; r = 0,452) terhadap kepuasan pasien. Tidak ada hubungan yang signifikan antara sikap pramusaji terhadap kepuasan pasien (p-value = 0,963; r = -0,009). Kesimpulan: Peningkatan skor sikap ahli gizi dan skor cita rasa makanan berhubungan signifikan dengan peningkatan kepuasan pasien.
Brucellosis involving the aorta and iliac arteries: a systematic review of 130 cases
Authors: Li Xiao , Li Xiaoyu , Cheng Zhihua
Published: November 2023

Objective: Brucellosis, the most common bacterial zoonosis, poses a serious threat to public health in endemic regions. Cardiovascular complications of brucellosis, mostly pericarditis or endocarditis, are the leading cause of brucellosis-related death. Complications involving the aorta and iliac arteries are extremely rare but can be life-threatening. Our objective was to identify and review all reported cases of aortic and iliac involvement in brucellosis to provide a deep, up-to-date understanding of the clinical characteristics and management of the disease.

Methods: Online searches in PubMed, Web of Science, China National Knowledge Infrastructure, and the Chinese Wanfang database were conducted to collect articles reporting cases of brucellosis with aortic and iliac artery involvement. All data in terms of patient demographics, diagnostic methods, clinical manifestations, and treatment regimens and outcomes were extracted and analyzed in this systematic review.

Results: A total of 79 articles were identified, reporting a total of 130 cases of brucellosis with aortic and iliac artery involvement. Of the 130 cases, 110 (84.5%) were male individuals and 100 (76.9%) were over 50 years old. The patients had an overall mortality rate of 12.3%. The abdominal aorta was most commonly involved, followed by the ascending aorta, iliac artery, and descending thoracic aorta. Arteriosclerosis, hypertension, and smoking were the most common comorbidities. There were 71 patients (54.6%) who presented with systemic symptoms of infection at the time of admission. Endovascular therapy was performed in 56 patients (43.1%), with an overall mortality rate of 3.6%. Open surgery was performed in 52 patients (40.0%), with an overall mortality rate of 15.4%.

Conclusion: Aortic and iliac involvement in brucellosis is extremely rare but can be life-threatening. Its occurrence appears to be associated with the male gender, an older age, arteriosclerosis, and smoking. Although the number of reported cases in developing countries has increased significantly in recent years, its incidence in these countries may still be underestimated. Early diagnosis and therapeutic intervention are critical in improving patient outcomes. Endovascular therapy has become a preferred surgical treatment in recent years, and yet, its long-term complications remain to be assessed.
Analyzing the cellular plasma membrane by fast and efficient correlative STED and platinum replica EM
Authors: Puchkov Dmytro , Müller Paul Markus , Lehmann Martin , Matthaeus Claudia
Published: November 2023

The plasma membrane of mammalian cells links transmembrane receptors, various structural components, and membrane-binding proteins to subcellular processes, allowing inter- and intracellular communication. Therefore, membrane-binding proteins, together with structural components such as actin filaments, modulate the cell membrane in their flexibility, stiffness, and curvature. Investigating membrane components and curvature in cells remains challenging due to the diffraction limit in light microscopy. Preparation of 5–15-nm-thin plasma membrane sheets and subsequent inspection by metal replica transmission electron microscopy (TEM) reveal detailed information about the cellular membrane topology, including the structure and curvature. However, electron microscopy cannot identify proteins associated with specific plasma membrane domains. Here, we describe a novel adaptation of correlative super-resolution light microscopy and platinum replica TEM (CLEM-PREM), allowing the analysis of plasma membrane sheets with respect to their structural details, curvature, and associated protein composition. We suggest a number of shortcuts and troubleshooting solutions to contemporary PREM protocols. Thus, implementation of super-resolution stimulated emission depletion (STED) microscopy offers significant reduction in sample preparation time and reduced technical challenges for imaging and analysis. Additionally, highly technical challenges associated with replica preparation and transfer on a TEM grid can be overcome by scanning electron microscopy (SEM) imaging. The combination of STED microscopy and platinum replica SEM or TEM provides the highest spatial resolution of plasma membrane proteins and their underlying membrane and is, therefore, a suitable method to study cellular events like endocytosis, membrane trafficking, or membrane tension adaptations.
Geochemistry and metagenomics analyses of bacterial community structure in selected waste dumpsites in Lagos Metropolis, Nigeria
Authors: Saibu Salametu , Adebusoye Sunday A. , Oyetibo Ganiyu O. , Rodrigues Debora F.
Published: November 2023

Dumpsites are reservoirs of persistent organic pollutants (POPs) and heavy metals (HMs), constituting environmental hazards to humanity. Autochthonous microorganisms in dumpsites exhibit various degrees of responses to contaminants. Unfortunately, there is a dearth of information on the types and concentration of pollutants and the array of microorganisms in these dumpsites which may play important roles in the metabolism of such pollutants or other community processes. Therefore, determining the microbial community structure in such contaminated sites across a municipality is essential for profiling the taxa that would serve as consensus degraders of the pollutants. In this study, soil samples from three dumpsites (Cele, CS; Solous, SS; and Computer Village, CVS) were characterized for geochemical properties using GC-MS, MP-AES, and other analytical protocols, while the dynamics of bacterial communities were evaluated based on their 16S rRNA gene barcodes. A significant difference in the bacterial communities was observed among the dumpsites in relation to the extent of pollution caused by POPs and HMs. CVS, with the highest HM contamination, was rich in Actinobacteria (41.7%) and Acidobacteria (10.2%), in contrast to CS and SS. Proteobacteria (34.1%) and Firmicutes (20%) were the dominant phyla in CS (highest POP contamination), while Bacteroidetes (45.5%) and Proteobacteria (39.9%) were dominant in SS soil. Bacillus was the dominant genus in the most polluted dumpsite. Canonical correspondence analysis revealed that polycyclic aromatic hydrocarbons (PAHs) and HMs shaped the structure of the bacterial operational taxonomic units (OTUs) in the most polluted dumpsite. Out of a total of 706 OTUs, 628 OTUs exhibited a significant correlation (>50%) with benzo(b)fluoranthene, azobenzene, dibenzofurans, pyrene, dibenzo(a,l)pyrene, Cu, and Zn. In particular, Proteobacteria (Achromobacter sp. and Serratia sp.), Bacteroidetes (Zhouia sp.), and Firmicutes (Bacillus sp.) were suggested to be pivotal to the ecophysiology of dumpsite soils contaminated with POPs and HMs. The results generally underscored the importance of metagenomic and physicochemical analyses of polluted systems in enabling correlations for useful prediction of drivers of such ecosystems. This will further improve our understanding of the metabolic potential and adaptation of organisms in such systems.
Identification of novel immune cell signature in gastroesophageal reflux disease: altered mucosal mast cells and dendritic cell profile
Authors: Ustaoglu Ahsen , Daudali Fatema Arif , D’afflitto Manfredi , Murtough Stephen , Lee Chung , Moreno Estefania , Blaydon Diana C. , Kelsell David P. , Sifrim Daniel , Woodland Philip , Peiris Madusha
Published: November 2023

Introduction

Heartburn pathogenesis in GERD remains incompletely understood. We aimed to identify differences in the immune cell signature and sensory mucosal markers between reflux phenotypes and healthy asymptomatic subjects.

Methods

Thirty-seven patients with heartburn symptoms were phenotyped endoscopically and with objective reflux studies into erosive reflux disease (ERD) (N=10), nonerosive reflux disease (NERD) (N=9), functional heartburn (FH) (N=9), and Barrett’s esophagus (BO) (N=9). Bulk mRNA-sequencing(RNA-seq) was conducted on RNA extracted from endoscopic biopsies, and immune cell deconvolution analysis was performed using CIBERSORT. RNA-seq findings were validated by immunofluorescent staining for CD1a, nerve growth factor (NGF), and mast cell tryptase in corresponding patient biopsies.

Results

Transcriptomic analysis detected higher mast cell abundance in BO, ERD, and NERD compared to healthy controls (p<0.05), with decreased dendritic cell infiltration in BO, ERD, and NERD patients compared to healthy controls and FH patients. CD1a-positive dendritic cell infiltration was significantly higher in the healthy esophageal mucosa at protein level compared to BO (p=0.0005), ERD (p=0.0004), and FH patients (p=0.0096). Moreover, NGF co-expression on mast cells in GERD patients was significantly higher than in healthy controls (p=0.0094).

Discussion

The mucosa in patients with GERD had a significant increase in NGF expression on mast cells, suggesting an upregulation of signalling for neuronal sprouting in GERD. Moreover, decreased dendritic cell abundance in GERD esophageal mucosa may play a role in reduced oral tolerance and development of subsequent immune responses which may participate in esophageal sensitivity.
Single-cell transcriptomics reveals heterogeneity in esophageal squamous epithelial cells and constructs models for predicting patient prognosis and immunotherapy
Authors: Li Chenglin , Song Wei , Zhang Jialing , Luo Yonggang
Published: November 2023

Background

Esophageal squamous cell carcinoma (ESCC), characterized by its high invasiveness and malignant potential, has long been a formidable challenge in terms of treatment.

Methods

A variety of advanced analytical techniques are employed, including single-cell RNA sequencing (scRNA-seq), cell trajectory inference, transcription factor regulatory network analysis, GSVA enrichment analysis, mutation profile construction, and the inference of potential immunotherapeutic drugs. The purpose is to conduct a more comprehensive exploration of the heterogeneity among malignant squamous epithelial cell subgroups within the ESCC microenvironment and establish a model for predicting the prognosis and immunotherapy outcomes of ESCC patients.

Results

An analysis was conducted through scRNA-seq, and three Cluster of malignant epithelial cells were identified using the infer CNV method. Cluster 0 was found to exhibit high invasiveness, whereas Cluster 1 displayed prominent characteristics associated with epithelial-mesenchymal transition. Confirmation of these findings was provided through cell trajectory analysis, which positioned Cluster 0 at the initiation stage of development and Cluster 1 at the final developmental stage. The abundance of Cluster 0-2 groups in TCGA-LUAD samples was assessed using ssGSEA and subsequently categorized into high and low-expression groups. Notably, it was observed that Cluster 0-1 had a significant impact on survival (p<0.05). Furthermore, GSVA enrichment analysis demonstrated heightened activity in hallmark pathways for Cluster 0, whereas Cluster 1 exhibited notable enrichment in pathways related to cell proliferation. It is noteworthy that a prognostic model was established utilizing feature genes from Cluster 0-1, employing the Lasso and stepwise regression methods. The results revealed that in TCGA and GSE53624 cohorts, the low-risk group demonstrated significantly higher overall survival and increased levels of immune infiltration. An examination of four external immunotherapy cohorts unveiled that the low-risk group exhibited improved immunotherapeutic efficacy. Additionally, more meaningful treatment options were identified for the low-risk group.

Conclusion

The findings revealed distinct interactions between malignant epithelial cells of ESCC and subgroups within the tumor microenvironment. Two cell clusters, strongly linked to survival, were pinpointed, and a signature was formulated. This signature is expected to play a crucial role in identifying and advancing precision medicine approaches for the treatment of ESCC.
Crisis averted: a world united against the menace of multiple drug-resistant superbugs -pioneering anti-AMR vaccines, RNA interference, nanomedicine, CRISPR-based antimicrobials, bacteriophage therapies, and clinical artificial intelligence strategies to safeguard global antimicrobial arsenal
Authors: Saeed Umar , Insaf Rawal Alies , Piracha Zahra Zahid , Tariq Muhammad Nouman , Sohail Azka , Abbasi Umer Ali , Fida Rana Muhammad Shahmeer , Gilani Syed Shayan , Noor Seneen , Noor Elyeen , Waheed Yasir , Wahid Maryam , Najmi Muzammil Hasan , Fazal Imran
Published: November 2023

The efficacy of antibiotics and other antimicrobial agents in combating bacterial infections faces a grave peril in the form of antimicrobial resistance (AMR), an exceedingly pressing global health issue. The emergence and dissemination of drug-resistant bacteria can be attributed to the rampant overuse and misuse of antibiotics, leading to dire consequences such as organ failure and sepsis. Beyond the realm of individual health, the pervasive specter of AMR casts its ominous shadow upon the economy and society at large, resulting in protracted hospital stays, elevated medical expenditures, and diminished productivity, with particularly dire consequences for vulnerable populations. It is abundantly clear that addressing this ominous threat necessitates a concerted international endeavor encompassing the optimization of antibiotic deployment, the pursuit of novel antimicrobial compounds and therapeutic strategies, the enhancement of surveillance and monitoring of resistant bacterial strains, and the assurance of universal access to efficacious treatments. In the ongoing struggle against this encroaching menace, phage-based therapies, strategically tailored to combat AMR, offer a formidable line of defense. Furthermore, an alluring pathway forward for the development of vaccines lies in the utilization of virus-like particles (VLPs), which have demonstrated their remarkable capacity to elicit a robust immune response against bacterial infections. VLP-based vaccinations, characterized by their absence of genetic material and non-infectious nature, present a markedly safer and more stable alternative to conventional immunization protocols. Encouragingly, preclinical investigations have yielded promising results in the development of VLP vaccines targeting pivotal bacteria implicated in the AMR crisis, including Salmonella, Escherichia coli, and Clostridium difficile. Notwithstanding the undeniable potential of VLP vaccines, formidable challenges persist, including the identification of suitable bacterial markers for vaccination and the formidable prospect of bacterial pathogens evolving mechanisms to thwart the immune response. Nonetheless, the prospect of VLP-based vaccines holds great promise in the relentless fight against AMR, underscoring the need for sustained research and development endeavors. In the quest to marshal more potent defenses against AMR and to pave the way for visionary innovations, cutting-edge techniques that incorporate RNA interference, nanomedicine, and the integration of artificial intelligence are currently under rigorous scrutiny.
Microglia influence immune responses and restrict neurologic disease in response to central nervous system infection by a neurotropic murine coronavirus
Authors: Syage Amber , Pachow Collin , Cheng Yuting , Mangale Vrushali , Green Kim N. , Lane Thomas E.
Published: November 2023

Intracranial (i.c.) inoculation of susceptible mice with a glial-tropic strain of mouse hepatitis virus (JHMV), a murine coronavirus, results in an acute encephalomyelitis followed by viral persistence in white matter tracts accompanied by chronic neuroinflammation and demyelination. Microglia serve numerous functions including maintenance of the healthy central nervous system (CNS) and are among the first responders to injury or infection. More recently, studies have demonstrated that microglia aid in tailoring innate and adaptive immune responses following infection by neurotropic viruses including flaviviruses, herpesviruses, and picornaviruses. These findings have emphasized an important role for microglia in host defense against these viral pathogens. In addition, microglia are also critical in optimizing immune-mediated control of JHMV replication within the CNS while restricting the severity of demyelination and enhancing remyelination. This review will highlight our current understanding of the molecular and cellular mechanisms by which microglia aid in host defense, limit neurologic disease, and promote repair following CNS infection by a neurotropic murine coronavirus.
Frequency of metastases within the hypothalamic–pituitary area and the associated high-risk factors in patients with brain metastases
Authors: Xie Peng , Hu Huiling , Cao Xiong , Lan Ning , Zhang Huanyu , Yan Ruifeng , Yue Peng , Hu Wenteng , Qiao Hui
Published: November 2023

Objective

Brain radiotherapy often results in impairment of hypothalamic–pituitary (HT-P) function, which in turn causes secretory dysfunction of related hormones. In this paper, the frequency of metastasis in the HT-P area and its high-risk factors in patients with brain metastasis were retrospectively analyzed, and thus provide experimental evidence for protecting HT-P area during whole brain radiotherapy (WBRT).

Methods

A retrospective analysis was performed on the data of patients with brain metastasis diagnosed by cranial magnetic resonance imaging (MRI) at the First Hospital of Lanzhou University from 2017 to 2020. The anatomical positions of the hypothalamus and pituitary were delineated, followed by their expansion by 5 mm outwards, respectively, in the three-dimensional direction, and the hypothalamus +5 mm and pituitary +5 mm were obtained as the avoidance area, in which the frequency of brain metastasis was evaluated. Univariate and multivariate logistic regression models were used to analyze the high risk factors of brain metastasis in HT-P area.

Results

A total of 3,375 brain metastatic lesions from 411 patients were included in the analysis. The rates of brain metastasis in the hypothalamus +5 mm and pituitary +5 mm in the whole group of cases were 2.9% (12/411) and 1.5% (6/411) respectively; the frequency of lesions was 0.4% (13/3375) and 0.2% (6/3375) respectively. Univariate and multivariate analyses showed that the number of brain metastases (OR = 14.946; 95% CI = 4.071–54.880; p < 0.001), and the occurrence of brain metastasis in the pituitary (OR = 13.331; 95% CI = 1.511–117.620; p = 0.020) were related to brain metastasis in the hypothalamus, and that the only relevant factor for brain metastasis in the pituitary was the occurrence of that in the hypothalamus (OR = 0.069; 95% CI = 0.010–0.461; p = 0.006). There was no correlation between tumor pathological types, the maximum diameter, the total volume of brain metastatic lesions and the risk of brain metastasis in hypothalamus and pituitary.

Conclusion

The frequency of brain metastasis in the HT-P area is extremely low. The risk of brain metastases in the hypothalamus is correlated with their number. The larger the number of metastatic lesions, the higher the frequency of brain metastasis. Protection of the HT-P area during WBRT may be unlikely to compromise the tumor recurrence rate for patients with a relatively small number of brain metastases.
Prevalence and prognosis of acute ischemic stroke coexisting with unruptured intracranial aneurysms
Authors: Yan Yujia , An Xingwei , Ren Hecheng , Luo Bin , Han Jin , Jin Song , Liu Li , Huang Ying
Published: November 2023

Objectives

The prevalence of unruptured intracranial aneurysms (UIAs) in the acute ischemic stroke (AIS) cohort is probably higher than in the general population. This study investigated the prevalence of UIAs in AIS patients and the management risk and prognosis when treating AIS.

Methods

From January 2020 to January 2023, we conducted a single-center retrospective study at Tianjin Huanhu Hospital. Each patient underwent both brain MRI and MRA/CTA to diagnose AIS and UIAs. Clinical, radiologic, and therapeutic data during hospitalization and prognosis were analyzed. Propensity-score matching (PSM) was performed to evaluate the risk of in-hospital adverse events, unfavorable outcomes at discharge when receiving post-stroke treatment and stroke recurrence.

Results

In all, 2,181 AIS patients were included, of whom 270 had UIAs (12.4%; 95%CI 11.0–13.8%). From the unmatched and matched cohort, the incidence of in-hospital adverse events and unfavorable outcomes at discharge in patients with UIAs were not significantly different; the risk of stroke recurrence was significantly higher in patients with UIAs than in those without (unmatched: aHR, 1.71 [1.08–2.70]; matched: aHR, 2.55 [1.16–5.58]). Multivariable Cox regression models showed that aneurysm size and the presence of homoregional infarction associated with higher risk of recurrence (unmatched: aHR, 1.31 [1.21–1.41] and aHR, 3.50 [1.52–8.10]; matched: aHR, 1.28 [1.18–1.40]; p < 0.001 and aHR, 3.71 [1.12–12.34]).

Conclusion

The UIAs may not increase the risk of in-hospital adverse events and unfavorable outcomes at discharge in receiving post-stroke treatment, but it may associated with a high risk of stroke recurrence.
Relationship between BMI and prognosis of chronic heart failure outpatients in Vietnam: a single-center study
Authors: Nguyen Hoai Thi Thu , Ha Thuong Thi Thu , Tran Hieu Ba , Nguyen Dung Viet , Pham Hung Manh , Tran Phuong Minh , Pham Tuan Minh , Allison Thomas G. , Reid Christopher M. , Kirkpatrick James N.
Published: November 2023

Background

Insufficient data exists regarding the relationship between body mass index (BMI) and the prognosis of chronic heart failure (CHF) specifically within low- and middle-income Asian countries. The objective of this study was to evaluate the impact of BMI on adverse outcomes of ambulatory patients with CHF in Vietnam.

Methods

Between 2018 and 2020, we prospectively enrolled consecutive outpatients with clinically stable CHF in an observational cohort, single-center study. The participants were stratified according to Asian-specific BMI thresholds. The relationships between BMI and adverse outcomes (all-cause death and all-cause hospitalization) were analyzed by Kaplan–Meier survival curves and Cox proportional-hazards model.

Results

Among 320 participants (age 63.5 ± 13.3 years, 57.9% male), the median BMI was 21.4 kg/m2 (IQR 19.5–23.6), and 10.9% were underweight (BMI <18.50 kg/m2). Over a median follow-up time of 32 months, the cumulative incidence of all-cause mortality and hospitalization were 5.6% and 19.1%, respectively. After multivariable adjustment, underweight patients had a significantly higher risk of all-cause mortality than patients with normal BMI (adjusted hazard ratios = 3.03 [95% CI: 1.07–8.55]). Lower BMI remained significantly associated with a worse prognosis when analyzed as a continuous variable (adjusted hazard ratios = 1.27 [95% CI: 1.03–1.55] per 1 kg/m2 decrease for all-cause mortality). However, BMI was not found to be significantly associated with the risk of all-cause hospitalization (p > 0.05).

Conclusion

In ambulatory patients with CHF in Vietnam, lower BMI, especially underweight status (BMI < 18.5 kg/m2), was associated with a higher risk of all-cause mortality. These findings suggest that BMI should be considered for use in risk classification, and underweight patients should be managed by a team consisting of cardiologists, nutritionists, and geriatricians.
Non-therapeutic plasma levels in individuals utilizing curcumin supplements in daily life
Authors: Kroon Maurice A. G. M. , Berbee Jacqueline K. , Majait Soumia , Swart Eleonora L. , van Tellingen Olaf , van Laarhoven Hanneke W. M. , Kemper E. Marleen
Published: November 2023

Introduction

The spice curcumin and its metabolites are widely used by cancer patients but have not shown proven health benefits in clinical studies, likely due to low plasma concentrations after oral intake. However, public interest in curcumin continues to grow, and companies claim enhanced absorption in their formulations. This study aims to determine if daily oral intake of curcumin leads to sufficient plasma concentrations for health effects. The study was registered in the Dutch Clinical Trial Register with ID NL5931.

Methods

We used a validated HPLC-MS/MS method to measure curcumin and its metabolites in 47 individuals using their own curcumin formulations. Questionnaires assessed other supplement and medication use. Plasma samples were collected before and 1.5 h after intake, analyzing curcumin and metabolite levels with and without β-glucuronidase pretreatment to measure conjugated and unconjugated forms.

Results

Plasma concentrations of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin, ranged between 1.0 and 18.6 ng/mL. Adding β-glucuronidase resulted in an increase of unconjugated curcumin plasma levels to 25.4 ng/mL; however still significantly below (1000-fold) a plasma concentration that is expected to have a beneficial health effect. The use of adjuvants like piperine did not result in higher curcumin plasma concentrations.

Discussion

Our study shows that using oral curcumin supplements still does not result in therapeutic plasma levels. Health care practitioners need to be critical toward the claimed beneficial systemic health effects of current curcumin supplement use by their patients.

Clinical Trial Registration

https://onderzoekmetmensen.nl/en/trial/25480, NL5931.
Doxorubicin impairs cognitive function by upregulating AMPAR and NMDAR subunit expression and increasing neuroinflammation, oxidative stress, and apoptosis in the brain
Authors: Alhowail Ahmad H. , Aldubayan Maha A.
Published: November 2023

Introduction: The anticancer drug doxorubicin (DOX) is used for various malignancies. However, it also causes cognitive impairment in cancer survivors. In order to determine the mechanisms underlying the acute effects of DOX, we assessed the mRNA and protein expression of glutamate receptors and proteins involved in cognitive function and apoptosis.

Methods: Fear-conditioning memory tests were performed in rats after a single intraperitoneal injection of DOX (25 mg/kg) to evaluate short-term memory function. Rat brain samples were collected, and GluA1 mRNA and protein expression; NR2A and NR2B mRNA expression; and COX-2, NF-kB, TNF-α, and MDA, Bax, and caspase-3 levels were assessed via reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays.

Results: We observed a decreased number of entries in Y-maze, decreased exploration time to the novel object in the novel object recognition (NOR), and decreased freezing time in the fear-conditioning memory tests in DOX-treated rats relative to those in control rats, demonstrating cognitive impairment. GluA1, NR2B, and NR2A expression and MDA, NF-κB, Bax, COX-2, TNF-α, and caspase-3 levels in the brain were significantly elevated in DOX-treated rats.

Conclusion: DOX induced cognitive impairment in the rats via neuronal toxicity by upregulating AMPAR and NMDAR expression and increasing neuroinflammation, oxidative stress, and apoptosis in the brain.