bluuebunny/crossref_metadata_2025 huggingface dataset:
Navigating Translational Medicine in Academia: How Can Translational Scientists Be Rewarded and Supported in Their Careers?
Authors:   , Kools Farah Rose Wilhelmina
Published: March 2024

Navigating Translational Medicine in Academia: How Can Translational Scientists Be Rewarded and Supported in Their Careers?

This is the overarching research question of my action-based PhD dissertation. During my biomedical training I became interested in the pivotal role this subset of biomedical scientists has in bringing much needed healthcare innovations into clinical settings. While learning about the complex translational pipeline and the many stakeholders involved, I couldn’t help but notice opposing forces within the careers of translational scientists. On the one hand these scientists are working towards solving unmet patient needs, on the other they are largely assessed on metrics such as publication and citation records. These records are classic metrics used to evaluate scientific careers, but in the case of translational scientists their main goal is to create patient impact which involves work outside of the research domain. Negative consequences of publication pressure, e.g., increased scientific misconduct and burnout, are challenges all researchers face. On top of that, translational scientists often lack comprehensive reward structures recognizing their specialized work beyond research activities. So how can translational scientists be rewarded and supported in their careers? We found a need for alternative performance measurements that include tasks within other domains (e.g., clinical and educational), mentorship programs to develop mentorship skills, receive and provide career support, and gain or expand an (international) network of translational scientists, and the opportunity for the development of translational competencies at graduate-level to support sustainable career pathways. We hope this dissertation can contribute towards mitigating the opposing forces within the careers of translational scientists and facilitate them in reaching their ultimate goal of impacting patients.
Bridging the Divide between Rights In Personam and Rights In Rem in Land Transactions: A Comparative Perspective of Australian and South African Law
Authors: Hepburn Samantha , Badenhorst Pieter
Published: March 2024

In transactions relating to land a distinction is made between the creation of personal or contractual rights (rights in personam) by contract, and real rights (rights in rem) via the registration process. Historically, additional, or special rights or interests have been conferred upon the vendor and purchaser to provide protection for the time period between the creation of rights in personam and the creation of rights in rem. The focus of this article is to identify and examine the nature and operation of these protective rights and compare their application in Australia and South Africa. These protective rights are recognised in different ways in both Australia and South Africa via common law, equity and legislation. It is concluded that interim protective equitable rights in Australia and a special category of personal rights under South African law provide a bridge to the creation of full in rem rights.
Enhancing Responsible Business in the Extractive Industry in Ghana: Reflections on the 2022 Appiatse Explosion
Authors: Dossah Veronica
Published: March 2024

Business-related human rights and environmental abuses are on the increase in the extractive industry (oil, gas and mining) in Ghana. The recent victim is the community of Appiatse in Ghana which suffered from an explosion of Ammonium Nitrate and Fuel Oil (ANFO). Maxam Ghana Ltd was transporting these chemicals to a mining site in Ghana. The government of Ghana found Maxam Ghana Ltd liable per its Mining Regulation (LI 2177) and imposed hefty fines on it. This paper reflects and highlights some business-related human rights issues arising from this incident. Then it suggests Responsible Business Conduct (RBC) as one of the tools that may be useful to address these issues and help achieve sustainable business operations in the extractive industry in Ghana. Essentially, RBC encourages businesses to incorporate international standards and guidelines into their business operations in addition to complying with national laws that help to respect human rights in the course of their operations.
‘He had thoughtlessly accepted certain gifts’: Corruption and Normative Behaviour for Roman Magistrates
Authors: Carlà-Uhink Filippo
Published: March 2024

It has been highlighted many times how difficult it is to draw a boundary between gift and bribe, and how the same transfer can be interpreted in different ways according to the position of the observer and the narrative frame into which it is inserted. This also applied of course to Ancient Rome; in both the Republic and Principate lawgivers tried to define the limits of acceptable transfers and thus also to identify what we might call ‘corruption’. Yet, such definitions remained to a large extent blurred, and what was constructed was mostly a ‘code of conduct’, allowing Roman politicians to perform their own ‘honesty’ in public duty – while being aware at all times that their involvement in different kinds of transfer might be used by their opponents against them and presented as a case of ‘corrupt’ behaviour.
KOMPARASI KEWENANGAN PENGADILAN NEGERI SURABAYA DALAM SENGKETA EKONOMI SYARIAH PERSPEKTIF KEPASTIAN HUKUM
Authors: Hafid Abd Hafid
Published: March 2024

Kekuasaan kehakiman adalah Lembaga yudikatif yang diberikan kewenangan dalam menyelesaikan suatu persengketaan hal ini Mahkamah Agung yang menaungi empat badan peradilan di bawahnya. Dalam Putusan pengadilan Negeri Surabaya antara perkara No: 622 Pdt.G/2021/PN.Sby dan perkara No:  835 Pdt.Bth/2021/PN.Sby merupakan satu subjek hukum dan objek hukum yang sama, akan tetapi dalam putusan Pengadilan menimbulkan amar putusan yang berbeda (kontradiktif). Artikel ini mengkaji studi komparatif tinjauan teori kepastian hukum terhadap putusan pengadilan. Dalam artikel ini penulis menggunakan metode penelitian dengan pendekatan putusan pengadilan, kepustakaan, peraturan perundang-undangan dan doktrinal. Dalam Putusan pengadilan Negeri Surabaya terdapat dua putusan yang berbeda , Pertama, putusan pengadilan dengan Register No: 622 Pdt.G/2021/PN.Sby menyatakan tidak memliki kewenangan secara absolut hal ini sesuai dengan peraturan perundang-undangan yang berlaku, Kedua, putusan Pengadilan, dengan Register No. 835 Pdt.Bth/2021/PN.Sby memilik kewenangan secara absolut hal ini tidak sesuai dengan peraturan perundang-undangan, Teori Kepastian Hukum adalah salah satu prinsip hukum yang sangat penting dalam sistem hukum di banyak Negara, termasuk Indonesia. Teori ini mengacu pada prinsip, bahwa hukum harus jelas, pasti, dan dapat dipahami oleh semua orang atau warganegara yang tunduk pada hukum tersebut, sehingga dalam putusan pengadila tersebut menimbulkan putusan yang kontradiktif, putusan yang pertama sesuai dengan peraturan hukum yang berlaku, sedangkan putusan yang kedua tidak sesuai dengan peraturan hukum.
LABA ATAU ARUS KAS SEBAGAI PARAMETEK KINERJA PERUSAHAAN BERDASARKAN SIKLUS HIDUP PERUSAHAAN
Authors: Riza Lailatul Qodriyah
Published: March 2024

This research is aimed to know earning or cash flow has value relevance with use life cycle of firm. Life cycle of firm is distinguished to four stage. They are start up stage, growth stage, maturity stage and decline stage. Cash flow are predicted to be used accounting measure in start up, growth and decline stage and than in maturity stage, earning are expected to be more value relevance as accounting measure. This research use manufacture industries in Indonesian as sample of the research. The samples have classified by Indonesian Capital Market Directory in 2008. There 128 firms are used sample in this research and with three years research, 2005-2007. And then the firms are classified to life cycle of firm with cash flow patterens metode. The result of this research can show that earning can use accouting measure in start up stage and cash flow can use accouting measure in growth stage. Accounting measure for the maturity stage is earning and cash flow. But in this research can not examine firms in decline stage because the firms sample in decline stage just six firms and three years research.
PENENTUAN HARGA JUAL PRODUK ROTI MENGGUNAKAN KONSEP BIAYA TOTAL UNTUK MEMAXIMISASI LABA PADA PERUSAHAAN ROTI MERAH DELIMA KOTA
Authors: Wahyuni
Published: March 2024

Penentuan harga jual suatu produk/jasa merupakan salah satu bagian terpenting dari suatu pengambilan keputusan bagi manajemen, karena harga jual dapat berpengaruh terhadap aspek-aspek tertentu seperti perolehan laba, volume penjualan, dan sebagainya. Harga jual yang tepat adalah harga yang terjangkau dan paling efisien bagi konsumen, oleh sebab itu dapat dikatakan bahwa harga itu penting tetapi bukan yang terpenting. Tujuan peneltian ini adalah untuk mengetahui harga jual produk roti yang ditetapkan oleh Perusahaan Roti Merah Delima bila menggunakan konsep biaya total, dan untuk mengetahui apakah penentuan harga jual yang ditetapkan tersebut dapat memaximasi laba yang diperoleh.

Pendekatan yang digunakan dalam menganalisis data adalah pendekatan deskriptif kuantitatif. Tempat penelitian di Perusahaan Roti Merah Delima Kediri. Teknik pengumpulan data yang digunakan ada tiga cara yaitu melalui observasi, interview, dan dokumentasi. Teknik analisa data yang digunakan  adalah rumus akuntansi untuk mengetahui harga jual per unit produk, rumus BEP untuk mengetahui laba per unit produk, rumus rentabilitas untuk mengetahui peningkatan laba yang diperoleh per unitnya.

Hasil analisa data menyimpulkan bahwa roti tawar kentang yang membutuhkan bahan tepung terigu sebanyak 1.800 gr juga dapat menghasilkan 8 unit roti dengan harga jual Rp 3.300 per unit, sedangkan untuk roti tawar manis dan tawar asin  yang menggunakan tepung terigu sebanyak 2.000 gr dan 2.800 gr, masing-masing dapat menghasilkan jumlah yang sama yaitu 8 unit roti dengan harga jual masing-masing sebesar Rp 2.800 untuk roti tawar manis dan Rp 2.600 untuk roti tawar asin. Laba yang diperoleh bila dalam penentuan harga jualnya UD. Merah Delima menggunakan pendekatan cost plus dengan konsep biaya total dapat maksimal, ini terbukti dengan adanya realisasi bahwa laba yang dikehendaki dapat tercapai/terealisasi.
PENGARUH KESADARAN PAJAK, TINGKAT PENDIDIKAN, DAN PERSEPSI TENTANG SANKSI PAJAK PENGUSAHA PENYEDIA JASA INTERNET TERHADAP KEPATUHAN FORMAL
Authors: Musrifah Novianti  , Mienati Somya Lasmana
Published: March 2024

This study aimed to determine the effect of tax awareness, education level, and the perception about tax penalties of entrepreneurs of internet service providers against formal compliance. The approach used is quantitative explanatory that focuses on hypothesis testing through multiple linear regression analysis. This study uses primary data in the form of questionnaires. The sample used in this study were 31 companies from the member Asosiasi Penyedia Jasa Internet Indonesia (APJII) East Java.

The partial t test indicate that tax awareness and education level of entrepreneurs of internet service providers do not significantly influence formal compliance, while the perception about tax penalties of entrepreneurs of internet service providers significantly influence formal compliance.
PERHITUNGAN PELUNASAN BUNGA FLAT ANTARA TEORI DAN PRAKTIK
Authors: Agustin Defi Nurrokhmah
Published: March 2024

Bunga flat merupakan pembebanan bunga setiap bulan tetap dari jumlah pinjamannya, demikian pula pokok pinjaman setiap bulan juga dibayar sama sehingga cicilan setiap bulan sama sampai kredit tersebut lunas. Bunga flat dapat dilunasi sebelum jatuh tempo waktu kredit. Pelunasan bunga flat dapat dihitung dengan menggunakan rumus dan tabel pelunasan.

Penelitian ini bertujuan untuk mengetahui perbandingan perhitungan pelunasan  suku bunga flat yang ada pada teori dan praktik di bank. Penelitian ini merupakan penelitian komparatif yang membandingan satu variabel dengan dua situasi yang berbeda. Jenis data yang digunakan dalam penelitian ini adalah data kuantitatif. Sumber data dalam peneltian ini adalah data sekunder. Data sekunder dalam penelitian ini adalah rumus perhitungan bunga flat menurut teori dan praktik, perhitungan pelunasan bunga flat menurut praktik dan tabel pelunasan. Analisis dilakukan dengan membandingkan perhitungan pelunasan bunga dengan jangka waktu 12 bulan, 18 bulan dan 24 bulan dengan metode bunga flat berdasarkan teori dan praktik.

Hasil penelitian menunjukkan bahwa perhitungan pelunasan perhitungan bunga flat  antara teori dan praktik adalah berbeda. Nilai perhitungan pelunasan bunga yang tinggi adalah menurut teori dengan menggunakan tabel pelunasan bunga kredit
ROLE PLAY FOR TEACHING SPEAKING IN ENGLISH FOR ACCOUNTING
Authors: Fitria Nur Hamidah
Published: March 2024

Speaking is one of English skills in teaching and learning process. It is also one of the target of the students to speak in learning English for Specific Purposes especially in English for Accounting. In achieving the target in teaching speaking, it is needed a method which is appropriate in speaking activity when the students practice to speak in the classroom. This study aims to describe the use of role play for teaching speaking especially to the students in English for Accounting. It describes speaking activities by using role play and the benefit of role play for teaching speaking in English for Accounting. Role play can be as an effective method that the ESP lecturer uses in teaching speaking of English for Accounting. It gives students more chances to act and interact with their groups and they bring liveliness and lighten up the atmosphere in speaking class.
PENGARUH INOVASI PRODUK TERHADAP VOLUME PENJUALAN PADA UD ABADI MULYA KEDIRI
Authors: Rike Kusuma Wardhani
Published: March 2024

Tujuan Penelitian ini adalah untuk mengetahui pengaruh  inovasi produk terhadap volume penjualan pada UD Abadi Mulya Kediri. Metode yang digunakan dalam penelitian ini adalah metode deskriptif kuantitatif. Dengan menggunakan metode ini peneliti akan mengetahui tingkat signifikansi antar variabel yang diteliti sehingga dapat ditarik kesimpulan yang jelas mengenai objek yang akan diteliti.

 Penelitian ini menggunakan metode deskriptif kuantitatif untuk menguji pengaruh inovasi produk terhadap volume penjualan pada UD Abadi Mulya serta menguji teori dengan pengujian suatu hipotesis apakah diterima atau ditolak.

Data yang terkumpul akan diproses menggunakan SPSS 16.0 dengan uji statistic untuk menentukan sebaran dan pengaruh variabel bebas terhadap variabel terikat. Uji yang digunakan adalah analisis regresi linier sederhana yang menunjukkan hubungan signifikan (r = 0,850) antara inovasi produk terhadap volume penjualan. Diperoleh nilai t sebesar 2.797 lebih besar dari t tabel sebesar 2.7745. Nilai rsquare sebesar 0.723 menunjukkan bahwa 72.3% varibel independen (inovasi produk) yang dapat menjelaskan variabel dependen (volume penjualan). Sedangkan sisanya sebesar 27,7% dipengaruhi atau dijelaskan oleh variabel lain yang tidak dimasukkan dalam penelitian ini.

Hasil analisa data menunjukkan bahwa inovasi produk berpengaruh secara signifikan terhadap volume penjualan. Sehingga peneliti menyarankan untuk selalu menambah variasi/inovasi produk baru untuk meningkatkan volume penjualan.
Dissection flap fenestration can reduce re-apposition force of the false lumen in type-B aortic dissection: a computational and bench study
Authors: Ahuja Aashish , Guo Xiaomei , Noblet Jillian N. , Krieger Joshua F. , Roeder Blayne , Haulon Stéphan , Chambers Sean , Kassab Ghassan
Published: March 2024

Thoracic endovascular aortic repair (TEVAR) has been widely adopted as a standard for treating complicated acute and high-risk uncomplicated Stanford Type-B aortic dissections. The treatment redirects the blood flow towards the true lumen by covering the proximal dissection tear which promotes sealing of the false lumen. Despite advances in TEVAR, over 30% of Type-B dissection patients require additional interventions. This is primarily due to the presence of a persistent patent false lumen post-TEVAR that could potentially enlarge over time. We propose a novel technique, called slit fenestration pattern creation, which reduces the forces for re-apposition of the dissection flap (i.e., increase the compliance of the flap). We compute the optimal slit fenestration design using a virtual design of experiment (DOE) and demonstrate its effectiveness in reducing the re-apposition forces through computational simulations and benchtop experiments using porcine aortas. The findings suggest this potential therapy can drastically reduce the radial loading required to re-appose a dissected flap against the aortic wall to ensure reconstitution of the aortic wall (remodeling).
3D and 4D assembly of functional structures using shape-morphing materials for biological applications
Authors: Mirzababaei Soheyl , Towery Lily Alyssa Kera , Kozminsky Molly
Published: March 2024

3D structures are crucial to biological function in the human body, driving interest in their in vitro fabrication. Advances in shape-morphing materials allow the assembly of 3D functional materials with the ability to modulate the architecture, flexibility, functionality, and other properties of the final product that suit the desired application. The principles of these techniques correspond to the principles of origami and kirigami, which enable the transformation of planar materials into 3D structures by folding, cutting, and twisting the 2D structure. In these approaches, materials responding to a certain stimulus will be used to manufacture a preliminary structure. Upon applying the stimuli, the architecture changes, which could be considered the fourth dimension in the manufacturing process. Here, we briefly summarize manufacturing techniques, such as lithography and 3D printing, that can be used in fabricating complex structures based on the aforementioned principles. We then discuss the common architectures that have been developed using these methods, which include but are not limited to gripping, rolling, and folding structures. Then, we describe the biomedical applications of these structures, such as sensors, scaffolds, and minimally invasive medical devices. Finally, we discuss challenges and future directions in using shape-morphing materials to develop biomimetic and bioinspired designs.
Licensing effects of inflammatory factors and TLR ligands on the regenerative capacity of adipose-derived mesenchymal stem cells
Authors: Szűcs Diána , Monostori Tamás , Miklós Vanda , Páhi Zoltán G. , Póliska Szilárd , Kemény Lajos , Veréb Zoltán
Published: March 2024

Introduction: Adipose tissue-derived mesenchymal stem cells are promising contributors to regenerative medicine, exhibiting the ability to regenerate tissues and modulate the immune system, which is particularly beneficial for addressing chronic inflammatory ulcers and wounds. Despite their inherent capabilities, research suggests that pretreatment amplifies therapeutic effectiveness.

Methods: Our experimental design exposed adipose-derived mesenchymal stem cells to six inflammatory factors for 24 h. We subsequently evaluated gene expression and proteome profile alterations and observed the wound closure rate post-treatment.

Results: Specific pretreatments, such as IL‐1β, notably demonstrated an accelerated wound‐healing process. Analysis of gene and protein expression profiles revealed alterations in pathways associated with tissue regeneration.

Discussion: This suggests that licensed cells exhibit potentially higher therapeutic efficiency than untreated cells, shedding light on optimizing regenerative strategies using adipose tissue-derived stem cells.
Timing dependent neuronal migration is regulated by Cdk5-mediated phosphorylation of JIP1
Authors: Fei Qinglin , Im Doo Soon , Xu Yiwen , Huang Tianwen , Qu Dianbo
Published: March 2024

The mammalian brain, especially the cerebral cortex, has evolved to increase in size and complexity. The proper development of the cerebral cortex requires the coordination of several events, such as differentiation and migration, that are essential for forming a precise six-layered structure. We have previously reported that Cdk5-mediated phosphorylation of JIP1 at T205 modulates axonal out-growth. However, the spatiotemporal expression patterns and functions of these three genes (Cdk5, Cdk5r1 or p35, and Mapk8ip1 or JIP1) in distinct cell types during cortical development remain unclear. In this study, we analyzed single-cell RNA-sequencing data of mouse embryonic cortex and discovered that Cdk5, p35, and JIP1 are dynamically expressed in intermediate progenitors (IPs). Pseudotime analysis revealed that the expression of these three genes was concomitantly upregulated in IPs during neuronal migration and differentiation. By manipulating the expression of JIP1 and phospho-mimetic JIP1 using in utero electroporation, we showed that phosphorylated JIP1 at T205 affected the temporal migration of neurons.
Unraveling intestinal microbiota’s dominance in polycystic ovary syndrome pathogenesis over vaginal microbiota
Authors: Yu Xia , Li XiaoQin , Yang Hui
Published: March 2024

Background

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disease in women, intricately linked to hormonal imbalances. The microbiota composition plays a pivotal role in influencing hormonal levels within the body. In this study, we utilized a murine model to investigate how intestinal and vaginal microbiota interact with hormones in the development of PCOS.

Methods

Twenty female mice were randomly assigned to the normal group (N) and the model group (P), where the latter received daily subcutaneous injections of 0.1 mL DHEA (6 mg/100 g). Throughout the experiment, we evaluated the PCOS mouse model by estrus cycle, serum total testosterone (T), prolactin (PRL) and luteinizing hormone (LH) levels, and ovarian pathological morphology. The microbial composition in both intestinal content and vaginal microbiota were studied by 16S rRNA gene high-throughput sequencing.

Results

Compared with the N group, the P group showed significant increases in body weight, T, and PRL, with significant decrease in LH. Ovaries exhibited polycystic changes, and the estrous cycle was disrupted. The intestinal microbiota result shows that Chao1, ACE, Shannon and Simpson indexes were decreased, Desulfobacterota and Acidobacteriota were increased, and Muribaculaceae, Limosilactobacillus and Lactobacillus were decreased in the P group. T was significantly positively correlated with Enterorhabdus, and LH was significantly positively correlated with Lactobacillus. The analysis of vaginal microbiota revealed no significant changes in Chao1, ACE, Shannon, and Simpson indices. However, there were increased in Firmicutes, Bacteroidota, Actinobacteriota, Streptococcus, and Muribaculaceae. Particularly, Rodentibacter displayed a robust negative correlation with other components of the vaginal microbiota.

Conclusion

Therefore, the response of the intestinal microbiota to PCOS is more significant than that of the vaginal microbiota. The intestinal microbiota is likely involved in the development of PCOS through its participation in hormonal regulation.
Revered and reviled: a sentiment analysis of female and male referents in three languages
Authors: Levshina Natalia , Koptjevskaja-Tamm Maria , Östling Robert
Published: March 2024

Our study contributes to the less explored domain of lexical typology, focusing on semantic prosody and connotation. Semantic derogation, or pejoration of nouns referring to women, whereby such words acquire connotations and further denotations of social pejoration, immorality and/or loose sexuality, has been a very prominent question in studies on gender and language (change). It has been argued that pejoration emerges due to the general derogatory attitudes toward female referents. However, the evidence for systematic differences in connotations of female- vs. male-related words is fragmentary and often fairly impressionistic; moreover, many researchers argue that expressed sentiments toward women (as well as men) often are ambivalent. One should also expect gender differences in connotations to have decreased in the recent years, thanks to the advances of feminism and social progress. We test these ideas in a study of positive and negative connotations of feminine and masculine term pairs such as woman - man, girl - boy, wife - husband, etc. Sentences containing these words were sampled from diachronic corpora of English, Chinese and Russian, and sentiment scores for every word were obtained using two systems for Aspect-Based Sentiment Analysis: PyABSA, and OpenAI’s large language model GPT-3.5. The Generalized Linear Mixed Models of our data provide no indications of significantly more negative sentiment toward female referents in comparison with their male counterparts. However, some of the models suggest that female referents are more infrequently associated with neutral sentiment than male ones. Neither do our data support the hypothesis of the diachronic convergence between the genders. In sum, results suggest that pejoration is unlikely to be explained simply by negative attitudes to female referents in general.
Acute myocardial infarction complicated by cardiogenic shock in Ukraine: multicentre registry analysis 2021–2022
Authors: Bilchenko Anton O. , Gritsenko Olga V. , Kolisnyk Volodymir O. , Rafalyuk Oleg I. , Pyzhevskii Andrii V. , Myzak Yaroslav V. , Besh Dmytro I. , Salo Victor M. , Chaichuk Sergii O. , Lehoida Mykhailo O. , Danylchuk Ihor V. , Polivenok Ihor V.
Published: March 2024

Background

Data on the results and management strategies in patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) in the Low and Lower-Middle Income Countries (LLMICs) are limited. This lack of understanding of the situation partially hinders the development of effective cardiogenic shock treatment programs in this part of the world.

Materials and methods

The Ukrainian Multicentre Cardiogenic Shock Registry was analyzed, covering patient data from 2021 to 2022 in 6 major Ukrainian reperfusion centres from different parts of the country. Analysis was focusing on outcomes, therapeutic modalities and mortality predictors in AMI-CS patients.

Results

We analyzed data from 221 consecutive patients with CS from 6 hospitals across Ukraine. The causes of CS were ST-elevated myocardial infarction (85.1%), non-ST-elevated myocardial infarction (5.9%), decompensated chronic heart failure (7.7%) and arrhythmia (1.3%), with a total in-hospital mortality rate for CS of 57.1%. The prevalence of CS was 6.3% of all AMI with reperfusion rate of 90.5% for AMI-CS. In 23.5% of cases, CS developed in the hospital after admission. Mechanical circulatory support (MCS) utilization was 19.9% using intra-aortic balloon pump alone. Left main stem occlusion, reperfusion deterioration, Charlson Comorbidity Index >4, and cardiac arrest were found to be independent predictors for hospital mortality in AMI-СS.

Conclusions

Despite the wide adoption of primary percutaneous coronary intervention as the main reperfusion strategy for AMI, СS remains a significant problem in LLMICs, associated with high in-hospital mortality. There is an unmet need for the development and implementation of a nationwide protocol for CS management and the creation of reference CS centers based on the country-wide reperfusion network, equipped with modern technologies for MCS.
Experimental study on stress and deformation characteristics of foundation pit considering excavation width using 3D printing technology
Authors: Liu Fengzhou , Zhang Xu , Xiang Maolong , Lyu Jingkang , Feng Rui , LIU Shouhua
Published: March 2024

A sophisticated model of the foundation pit support structure was developed via a model test that incorporated 3D printing technology. A meticulously scaled-down simulation of foundation pit excavation was conducted, utilizing the excavation width of the foundation pit as the sole variable, to evaluate and compare the impact of various foundation pit widths on the force and deformation characteristics of the foundation pit following layer-by-layer excavation. The findings indicate that the stress and deformation characteristics of the retaining structure shift from the “cantilever” mode to a composite mode of “internally convex” or “concave-convex” as the pit is excavated and internal support is installed. The change in pit width has minimal influence on the mechanical response law of the support structure during excavation. Nonetheless, the alteration in the pit width had a direct effect on both the internal force and deformation of the support structure, as well as the change in surface settlement value. In the experiment, wider pits had monitoring values that increased multiple times compared to narrower pits. The width of the foundation pit has a considerable impact on the mechanical response and stability of the pit, which is evident in the relatively lower lateral earth pressure on the outside of the retaining structure in narrower pits. This results in less stress and deformation of the pit structure. Moreover, the decrease in the passive zone of the pit contributes to better stability, indicating that the lower lateral earth pressure on the outside of the retaining structure is an innate reason for the excellent stability of narrower pits.
Envisioning sustainable sanitation planning: a unified approach of diffusion of innovation and theory of planned behavior in predicting ecosan toilet adoption in Arba Minch City, Ethiopia
Authors: Ejigu Abrham Kassa , Yeshitela Kumelachew
Published: March 2024

This study explores the adoption of ecological sanitation (ecosan) toilets in Arba Minch City, Ethiopia, using an integrated approach combining the diffusion of innovation (DOI) model and the Theory of Planned Behavior (TPB). The research aims to understand the complex associations between DOI variables (relative advantage, complexity, compatibility, trialability, and observability) and TPB constructs (attitude, subjective norm, and perceived behavioral control) in predicting residents’ behavioral attitudes and intentions. Applying Structural Equation Modeling (SEM) and bootstrapping techniques, the study investigates direct and indirect effects, offering a comprehensive analysis of the adoption process. The objectives include examining the influence of TPB and DOI constructs on residents’ intentions, unraveling direct and indirect effects on these intentions, and investigating variations among users of different toilet types in the city. The result of the study shows that attitude and perceived behavioral control are central to shaping intentions, aligning with TPB principles. Contextual factors like compatibility, relative advantage, and trayability reveal nuanced insights, deviating from conventional patterns. The study identifies attitude as a key moderator between DOI constructs and behavioral intention, enriching our understanding of the adoption process. In conclusion, the integrated DOI and TPB model provides nuanced perspectives on factors influencing behavioral attitudes and intentions toward ecosan toilet adoption. The crucial roles of perceived behavioral control and attitude underscore the importance of tailored interventions. The study’s insights are relevant for policymakers, practitioners, and development organizations working on sustainable sanitation practices in urban areas, contributing to broader sustainable development objectives.
Deciphering the causal association and co-disease mechanisms between psoriasis and breast cancer
Authors: Li Xujia , Huang Lingli , Yan Yue , Rong Yuming , Chen Xuxian , Gao Mengge , Huang Jinsheng
Published: March 2024

Background

Prior research has indicated a link between psoriasis and the susceptibility to breast cancer (BC); however, a definitive causal relationship remains elusive. This study sought to elucidate the causal connection and shared underlying mechanisms between psoriasis and BC through bidirectional Mendelian randomization (MR) and bioinformatic approaches.

Methods

We employed a bidirectional MR approach to examine the potential causal connection between psoriasis and BC. Genetic data pertaining to psoriasis and BC were sourced from extensive published genome-wide association studies. The inverse -variance weighted or wald ratio served as the primary method for estimating causal effects. Sensitivity analysis of the MR results was applied with multiple methods. Leveraged datasets from the Gene Expression Omnibus and the Cancer Genome Atlas repositories to identify common differentially expressed genes, shedding light on the shared mechanisms underlying these two conditions.

Results

The MR analysis revealed that when considering psoriasis as an exposure factor, the incidences of BC (OR=1.027) and estrogen receptor negative (ER-) BC (OR=1.054) were higher than in the general population. When using Her2+ BC as an exposure factor, the risk of psoriasis was 0.822 times higher (OR=0.822) than in the general population. Sensitivity analysis indicated that the results were robust. Transcriptome analysis showed that CXCL13 and CCL20 were activated in both BC and psoriasis. Both diseases were also linked to neutrophil chemotaxis, the IL-17 pathway, and the chemokine pathway.

Conclusion

The results suggest that psoriasis may increase the risk of BC, especially ER- BC, while reverse MR suggests a decreased risk of psoriasis in Her2+ BC. Transcriptome analysis revealed a shared mechanism between psoriasis and BC.
Increased interleukin-9 and Th9 cells in patients with refractory Graves’ disease and interleukin-9 polymorphisms are associated with autoimmune thyroid diseases
Authors: Yao Qiuming , Song Zhenyu , Wang Bin , Du Peng , Qin Qiu , Zhao Jing , Zhang Jin-an
Published: March 2024

Introduction

Autoimmune thyroid diseases (AITDs) are prevalent disorders, primarily encompassing Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Despite their common occurrence, the etiology of AITDs remains elusive. Th9 cells, a new subset of CD4+T cells with immunomodulatory properties, have been linked to the development of various autoimmune diseases. However, research on the role of Th9 cells in AITDs is limited.

Methods

We investigated the expression of Th9 cells,their functional cytokine IL-9, and transcription factor IRF4 in peripheral blood mononuclear cells (PBMCs) and plasma of AITD patients and healthy controls. Additionally, we explored the genetic association between four loci polymorphisms (rs31564, rs2069879, rs1859430, and rs2069868) of the IL-9 gene and AITDs.

Results

We reported, for the first time, that refractory GD patients exhibited elevated mRNA levels of IL-9 and IRF4 in PBMCs, increased IL-9 protein levels in plasma, and a higher proportion of Th9 cells in peripheral blood when compared to normal controls. Furthermore, human recombinant IL-9 protein was found to enhance IFN-g secretion in PBMCs from both GD patients and normal controls. At the genetic association level, after adjusting for age and sex, the rs2069879 polymorphism exhibited a significant association with AITDs under an additive model (P<0.001, OR= 0.05, 95% CI=0.03-0.08).

Discussion

Our results reveal that Th9 cells may exert a pivotal role in the pathogenesis and progression of refractory GD and HT, and IL-9 holds promise as a novel therapeutic target for the management of AITDs.
The intricate dance of non-coding RNAs in myasthenia gravis pathogenesis and treatment
Authors: Wang Benqiao , Zhu Ying , Liu Dan , Hu Chunxiang , Zhu Ruixia
Published: March 2024

Myasthenia gravis (MG) stands as a perplexing autoimmune disorder affecting the neuromuscular junction, driven by a multitude of antibodies targeting postsynaptic elements. However, the mystery of MG pathogenesis has yet to be completely uncovered, and its heterogeneity also challenges diagnosis and treatment. Growing evidence shows the differential expression of non-coding RNAs (ncRNAs) in MG has played an essential role in the development of MG in recent years. Remarkably, these aberrantly expressed ncRNAs exhibit distinct profiles within diverse clinical subgroups and among patients harboring various antibody types. Furthermore, they have been implicated in orchestrating the production of inflammatory cytokines, perturbing the equilibrium of T helper 1 cells (Th1), T helper 17 cells (Th17), and regulatory T cells (Tregs), and inciting B cells to generate antibodies. Studies have elucidated that certain ncRNAs mirror the clinical severity of MG, while others may hold therapeutic significance, showcasing a propensity to return to normal levels following appropriate treatments or potentially foretelling the responsiveness to immunosuppressive therapies. Notably, the intricate interplay among these ncRNAs does not follow a linear trajectory but rather assembles into a complex network, with competing endogenous RNA (ceRNA) emerging as a prominent hub in some cases. This comprehensive review consolidates the landscape of dysregulated ncRNAs in MG, briefly delineating their pivotal role in MG pathogenesis. Furthermore, it explores their promise as prospective biomarkers, aiding in the elucidation of disease subtypes, assessment of disease severity, monitoring therapeutic responses, and as novel therapeutic targets.
Evaluation of tumor response to immune checkpoint inhibitors by a 3D immunotumoroid model
Authors: Pezeshki Abdulmohammad , Cheville John C. , Florio Angela B. , Leibovich Bradley C. , Vasmatzis George
Published: March 2024

Background

Only 20 percent of renal and bladder cancer patients will show a significant response to immune checkpoint inhibitor (ICI) therapy, and no test currently available accurately predicts ICI response.

Methods

We developed an “immunotumoroid” cell model system that recapitulates the tumor, its microenvironment, and necessary immune system components in patient-derived spheroids to enable ex vivo assessment of tumor response to ICI therapy. Immunotumoroids were developed from surgically resected renal cell carcinomas and bladder carcinomas selected for high tumor-infiltrating lymphocytes (TILs) and survived more than a month without media exchange. Immunohistochemistry was used to detect immune and non-immune cells in cryopreserved source tumors and the resulting immunotumoroids. Immunotumoroid response to ICIs (nivolumab, pembrolizumab, and durvalumab) and chemotherapy (cisplatin, gemcitabine, and paclitaxel) was monitored in real-time with Cytotox Red staining in an Incucyte device, and the immunotumoroid response was compared to retrospective clinical drug responses.

Results

Six of the 13 cases tested grew viable immunotumoroid models, with failed cases attributed to extensive tumor tissue necrosis or excess lymphocytes preventing spheroid formation. One successfully cultured case was excluded from the study due to low TIL infiltration (<5%) in the primary tumor sample. The five remaining models contained immune cells (CD4+ and CD8+ T cells, and macrophages), non-immune cells (fibroblasts), and tumor cells. Chemotherapy and ICI drugs were tested in immunotumoroids from 5 cases and compared to clinical outcomes where data was available. Four/five models showed cell killing in response to chemotherapy and two/five showed sensitivity to ICI. In three cases, the immunotumoroid model accurately predicted the patient’s clinical response or non-response to ICIs or chemotherapy.

Conclusion

Our immunotumoroid model replicated the multicellular nature of the tumor microenvironment sufficiently for preclinical ICI screening. This model could enable valuable insights into the complex interactions between cancer cells, the immune system, and the microenvironment. This is a feasibility study on a small number of cases, and additional studies with larger case numbers are required including correlation with clinical response.
TOB1 modulates neutrophil phenotypes to influence gastric cancer progression and immunotherapy efficacy
Authors: Zhang Jinfeng , Li Yunlong , Chen Jing , Huang Tongtong , Lin Jing , Pi Yilin , Hao Huiting , Wang Dong , Liang Xiao , Fu Songbin , Yu Jingcui
Published: March 2024

Introduction

The ErbB-2.1(TOB1) signaling transducer protein is a tumor-suppressive protein that actively suppresses the malignant phenotype of gastric cancer cells. Yet, TOB1 negatively regulates the activation and growth of different immune cells. Understanding the expression and role of TOB1 in the gastric cancer immune environment is crucial to maximize its potential in targeted immunotherapy.

Methods

This study employed multiplex immunofluorescence analysis to precisely delineate and quantify the expression of TOB1 in immune cells within gastric cancer tissue microarrays. Univariate and multivariate Cox analyses were performed to assess the influence of clinical-pathological parameters, immune cells, TOB1, and double-positive cells on the prognosis of gastric cancer patients. Subsequent experiments included co-culture assays of si-TOB1-transfected neutrophils with AGS or HGC-27 cells, along with EdU, invasion, migration assays, and bioinformatics analyses, aimed at elucidating the mechanisms through which TOB1 in neutrophils impacts the prognosis of gastric cancer patients.

Results

We remarkably revealed that TOB1 exhibits varying expression levels in both the nucleus (nTOB1) and cytoplasm (cTOB1) of diverse immune cell populations, including CD8+ T cells, CD66b+ neutrophils, FOXP3+ Tregs, CD20+ B cells, CD4+ T cells, and CD68+ macrophages within gastric cancer and paracancerous tissues. Significantly, TOB1 was notably concentrated in CD66b+ neutrophils. Survival analysis showed that a higher density of cTOB1/nTOB1+CD66b+ neutrophils was linked to a better prognosis. Subsequent experiments revealed that, following stimulation with the supernatant of tumor tissue culture, the levels of TOB1 protein and mRNA in neutrophils decreased, accompanied by enhanced apoptosis. HL-60 cells were successfully induced to neutrophil-like cells by DMSO. Neutrophils-like cells with attenuated TOB1 gene expression by si-TOB1 demonstrated heightened apoptosis, consequently fostering a malignant phenotype in AGS and HCG-27 cells upon co-cultivation. The subsequent analysis of the datasets from TCGA and TIMER2 revealed that patients with high levels of TOB1 combined neutrophils showed better immunotherapy response.

Discussion

This study significantly advances our comprehension of TOB1’s role within the immune microenvironment of gastric cancer, offering promising therapeutic targets for immunotherapy in this context.
Efficacy and safety of BVAC-C in HPV type 16- or 18–positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study
Authors: Choi Chel Hun , Lee Jeong-Won , Bae Duk-Soo , Kang Eun-Suk , Cho Duck , Kim Yong-Man , Kim Kidong , Kim Jae-Weon , Kim Hee Seung , Kim Young-Tae , Lee Jung-Yun , Lim Myong Cheol , Oh Taegwon , Song Boyeong , Jeon Insu , Park Myunghwan , Kim Wu Hyun , Kang Chang-Yuil , Kim Byoung-Gie
Published: March 2024

Background

BVAC-C, a B cell– and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV–positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16– or 18–positive cervical cancer who had experienced recurrence after a platinum-based combination chemotherapy.

Patients and methods

Patients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Primary endpoints were safety and objective response rate (ORR) as assessed by an independent radiologist according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Results

Of the 30 patients available for analysis, the ORR was 19.2% (Arm 1: 20.0% (3/15), Arm 2: 33.3% (2/6), Arm3: 0%) and the DCR was 53.8% (Arm 1: 57.1%, Arm 2: 28.6%, Arm3: 14.3%). The median DOR was 7.5 months (95% CI 7.1–not reported), the median PFS was 5.8 months (95% CI 4.2–10.3), and the median OS was 17.7 months (95% CI 12.0–not reported). All evaluated patients showed not only inflammatory cytokine responses (IFN-γ or TNF-α) but also potent E6/E7-specific T cell responses upon vaccinations. Immune responses of patients after vaccination were correlated with their clinical responses.

Conclusion

BVAC-C represents a promising treatment option and a manageable safety profile in the second-line setting for this patient population. Further studies are needed to identify potential biomarkers of response.

Clinical trial registration

ClinicalTrials.gov, identifier NCT02866006.
Potential diagnostic markers shared between non-alcoholic fatty liver disease and atherosclerosis determined by machine learning and bioinformatic analysis
Authors: Wang Lihong , He Wenhui , Wang Xilin , Wang Jianrong , Wei Xiaojuan , Wu Dongzhi , Wu Yundan
Published: March 2024

Background

Evidence indicates that chronic non-alcoholic fatty liver disease (NAFLD) can increase the risk of atherosclerosis (AS), but the underlying mechanism remains unclear.

Objective

This study is intended for confirming key genes shared between NAFLD and AS, and their clinical diagnostic value to establish a foundation for searching novel therapeutic targets.

Methods

We downloaded the Gene Expression Omnibus (GEO) datasets, GSE48452 and GSE89632 for NAFLD and GSE100927, GSE40231 and GSE28829 for AS. The progression of NAFLD co-expression gene modules were recognized via weighted gene co-expression network analysis (WGCNA). We screened for differentially expressed genes (DEGs) associated with AS and identified common genes associated with NAFLD and AS using Venn diagrams. We investigated the most significant core genes between NAFLD and AS using machine learning algorithms. We then constructed a diagnostic model by creating a nomogram and evaluating its performance using ROC curves. Furthermore, the CIBERSORT algorithm was utilized to explore the immune cell infiltration between the two diseases, and evaluate the relationship between diagnostic genes and immune cells.

Results

The WGCNA findings associated 1,129 key genes with NAFLD, and the difference analysis results identified 625 DEGs in AS, and 47 genes that were common to both diseases. We screened the core RPS6KA1 and SERPINA3 genes associated with NAFLD and AS using three machine learning algorithms. A nomogram and ROC curves demonstrated that these genes had great clinical meaning. We found differential expression of RPS6KA1 in patients with steatosis and NASH, and of SERPINA3 only in those with NASH compared with normal individuals. Immune infiltration findings revealed that macrophage and mast cell infiltration play important roles in the development of NAFLD and AS. Notably, SERPINA3 correlated negatively, whereas RPS6KA1 correlated positively with macrophages and mast cells.

Conclusion

We identified RPS6KA1 and SERPINA3 as potential diagnostic markers for NAFLD and AS. The most promising marker for a diagnosis of NAFLD and AS might be RPS6KA1, whereas SERPINA3 is the most closely related gene for NASH and AS. We believe that further exploration of these core genes will reveal the etiology and a pathological relationship between NAFLD and AS.