bluuebunny/crossref_metadata_2025 huggingface dataset:
DRUG PRICING DETERMINANTS IN THE REGIONAL PHARMACEUTICAL MARKET (A CASE STUDY FROM THE SVERDLOVSK REGION)
Authors:   Ural State University of Economics, Ekaterinburg, Russia, Begicheva Svetlana , Kalabina Elena ,   Ural State University of Economics, Ekaterinburg, Russia, Nazarov Dmitry ,   Ural State University of Economics, Ekaterinburg, Russia
Published: August 2024

Significance. It is known that the state pharmaceutical policy is aimed at ensuring the availability of medicines, their quality and rational use to all segments of the population. A significant share of the maximum retail price of medicines is accounted for by trade markups. Reaching over 40% of the final price, trade markups act as a regulator of the price affordability to end consumers. The purpose of the study was to analyze determinants influencing the level of wholesale and retail trade markups included in the price of drugs for treating cardiovascular diseases on the List of vital and essential drugs, and set by wholesalers and retailers in the regional pharmaceutical market of the Sverdlovsk region. Material and methods. The study was based on data from the Monitoring over assortment and prices of vital and essential drugs in the Sverdlovsk Region covering the period from January to October 2021 and containing over 65 thousand observations on prices of medicines for treating cardiovascular diseases. The sample covers data from 75 pharmacies. To identify statistically significant determinants influencing the level of trade markups in drug prices, the quantile regression method was used. Results. The study results made it possible to conclude that the level of wholesale markups on vital and essential drugs for treating cardiovascular diseases is statistically significantly affected by such factors as variety of product names within the therapeutic class and dosage of the drug, as well as selling season. The analysis made it possible to identify the determinants that influence retail markups included in prices of vital and essential drugs, namely: selling season, whether the pharmacy has a social status, and location of the pharmacy. In addition, it has been proven that wholesale markups for generics are higher than for branded drugs, and wholesale markups for foreign drugs are higher than for domestic ones. In pharmacies, distributor price waves are leveling out and large markups are characteristic of original drugs compared to generics and domestic drugs compared to drugs by foreign manufacturers.
Hamka’s Sufism in The Literary Work “Tenggelamnya Kapal Van Der Wijck” on Schleiermacher’s Hermeneutics Perspective
Authors: Al Farouqy AR. Miftah , Syaifuddin Helmi , Barizi Ahmad
Published: August 2024

Hamka was a prolific poet scholar who brought the idea of reforming Sufism, known as neo-Sufism. As a poet, he wrote many literary works, such as “Tenggelamnya Kapal Van der Wijck” which was written at the same time as modern Sufism, also contains elements of Sufism.  This research aims to (1) identify Hamka's sufistic texts in “The Sinking of van Der Wijck”, (2) analyze the sufistic meaning in it’s work on Schleiermacher's hermeneutic perspective. “Tenggelamnya Kapal Van der Wijck” is one of Hamka's literary works that is considered to contain sufistic values. The authors analyzed the sufistic texts in Schleirmacher’s hermeneutics perspective, a relevant approach to derive the meaning of Hamka’s literary texts. This research is in the form of qualitative research and is categorized as library research with a text analysis method. Data is obtained through documentary techniques, and data sources are taken from books and secondary notes that are relevant to the research theme. The data is then analyzed using Schleiermacher's hermeneutic working principles by means of grammatical and psychological interpretations. The result of this study is (1) Hamka's Sufism in “Tenggelamnya Kapal Van der Wijck” found in the text of the story in the aspects of: natural beauty, a quest for true happiness, good manners, and love. (2) After going through interpretation and analysis stages using perspective of Schleirmacher’s hermeneutics, the meaning of these aspects of sufistic text is love, which is natural giving (fiṭrah), and must be maintained by declaring self to Allah, natural beauty as an introduction to reaching maqām riḍā, good manners as a means of knowing Allah, and true happiness is ma'rifatullāh
Ajaran Isyrāqi: Studi Kritis-Epistemologis Filsafat Iluminasi Suhrawardi
Authors: Nur Laini Hasna Ulfa , Soleh Achmad Khudori
Published: August 2024

This research examines the epistemology of Isyrāqi philosophy critically-systematically, examining details from the source of thought, methods to verification and implications of Suhrawardi's Isyrāqi philosophy. In explaining, the author uses qualitative research, which is presented descriptively-analytically with an epistemological-philosophical perspective Nicholas Rescher. As a result, this research shows three things: First, Isyrāqi philosophy comes from the extraction of five major schools; pre-Islamic philosophy (Greece), Islamic peripatetik philosophy, especially Ibn Sina, ancient Iranian thought, Sufistic thought of Mansur al-Hallaj and al-Ghazali, and Zoroastrianism. Second, to reach isyrāqi knowledge, Suhrawardi requires to involve spiritual practice (mujāhadah) and asceticism, which is detailed in four stages in an orderly manner. Including the preparation stage, the reception stage, then the development stage (proof), and finally the immortalization stage. Third, for Suhrawardi, knowledge can be said to be final by combining two things: 1) The intellectual power of reason (discursive knowledge), and 2) Intuitive knowledge; witnessing and revelation (musyāhadah wal mukāsyafah). Light as a symbol of true truth in Isyrāqi teachings, and the tool to obtain light is intuition, while the ratio is used to explain the intuition. Suhrawardi was not satisfied with the peripatetik concept of emanation which emphasizes the role of the intellect ('aql) in the process of reaching knowledge. According to him, the role of intuition (dzawq) and mystical revelation manifested through absolute light are fundamental realities. The implications of Suhrawardi's Isyraqī ultimately paved the way for the development of Islamic philosophy afterwards, among others it is shown in the thoughts of Ibn Arabi (1165-1240) and Mulla Sadra (1573-1641).
Paying Off Debt or Forgiving Debt? Semantic and Intertextual Analysis on Lord’s Prayer in Smith-Van Dyck Arabic Bible Translation
Authors: Yahya Yuangga Kurnia , Rochma Siti Nikmatul , Mahmudah Umi
Published: August 2024

The Smith and Van Dyck Arabic Bible Translation, which first appeared in 1865, is the most widely used translation in the Christian Arab community. The expressions that appear in the translation have some quite striking differences with other Arabic translations of the Bible. This research will focus on one of the messages in Lord's Prayer, specifically Matthew 6:12 about prayer for forgiveness and forgiveness to others which has different diction from the Jesuit Arabic Bible of 1881. This study will use a post-colonialism perspective in Bible studies through semantic and intertextual analysis. This research concluded two main things. First, the quality of the SVD Bible translation from English to Arabic, as seen in Matthew 6:12 has a low level of accuracy and legibility. This can be seen from the choice of words "نغفر” as well as the use of verbs in the future form for source language texts that use the past tense. Second, the results of the SVD Bible translation also provide an overview of Western Christian ideology, which is quite dominant. The representation of this is the choice of the word "sin" rather than "debt", because debt is not a problem in a capitalist lifestyle. In fact, this mindset normalizes the existence of debt to meet the needs of human life. This shows that the translation movement carried out in the 19th century AD became one of the media for spreading the ideas of capitalism and colonialism to various colonial areas.
Analisis Sejarah Kolonialisme Belanda dalam Perkembangan Orientalisme di Indonesia
Authors: Sakti Mohammad Djaya Aji Bima , Setiawan Muhammad Nurrosyid Huda , Nasution Alhafidh , Ramadhan Amar
Published: August 2024

This research aims to analyze the relevance and influence of Dutch colonialism and it’s relevant to the development of orientalism in Indonesia. By using the ideas of the theory of orientalism that was promoted by Edward Said, this research will attempt to explore how Dutch colonialism has influenced and shaped cultural patterns with a shifting of paradigm and had the impact of changing identity in Indonesia for a long time. Through a qualitative approach, this research seeks to analyze Dutch colonial impact and legacies and tries to reveal the strategies by which these Orientalist though are still indirectly practiced today. This research provides an illustration that orientalism and colonialism are two interrelated interests and have had quite a dominant influence in the history of these two organizations in Indonesia. Colonialism became the initial basis for the orientalism movement to develop, because with its presence, orientalism could freely carry out several goals and orientations of its movement, which included Christianization and westernization.
Taurine and proline promote lung tumour growth by co-regulating Azgp1/mTOR signalling pathway
Authors: Pan Hu-Dan , Li Run-Ze , Liang Tuliang , Mi Jia-Ning , Ma Gang-Yuan , Xiao Yao , Yang Xi , Huang Chen , Li Jia-Xin , Xie Ying , Yan Pei-Yu , Yao Xiao-Jun , LEUNG Lai Han , Liu Liang
Published: August 2024

Accurate metabolic biomarkers are still scarce and essential for prognosis of lung cancer progression and prognosis. Previous studies have found that two metabolites including taurine and proline are abnormally elevated in lung cancer patients with different stages. This study aimed to elucidate their functional role in lung cancer progression, providing valuable insights into potential therapeutic targets for intervention. Taurine and proline could promote lung tumour growth for the first time, suggesting poor prognosis for lung cancer progression. In transcriptome analysis, both taurine and proline down-regulated the expression of gene Zinc-α2-glycoprotein (Azgp1). Azgp1, down-regulated in lung cancer patients, was significantly associated with key targets of the taurine and proline metabolic pathways. Azgp1 could also significantly affect downstream lipid metabolic pathways in lung cancer. In metabolome analysis, taurine and proline could alter lipid metabolism mediated by mammalian target of rapamycin (mTOR). Moreover, taurine and proline were found to be able to suppress Azgp1 expression and activate mTOR expression. Overexpression of Azgp1, in turn, significantly inhibited lung cancer progression, accompanied by the inhibition of mTOR expression. These results suggested a pro-cancer role of both taurine and proline in lung cancer and identified the Azgp1/mTOR axis as an under-reported pathway involving lung cancer progression.
Factors that facilitate or hinder the use of the facial rehabilitation webtool MEPP 2.0: a comparative study in the Quebecer health system
Authors: Martineau Sarah , Barbeau Jacinthe , Paquin Alyssia , Marcotte Karine
Published: August 2024

Background: Recently, our research team developed an open source and free website called the MEPP website (for the Mirror Effect Plus Protocol) to efficiently provide mirror therapy for patients with facial palsy. Previous studies demonstrated that the first version of the MEPP website improved user experience and likely optimized patients’ performance during facial therapy. Nevertheless, compliance was found to be low despite a generally positive opinion of the website, and in light of our earlier findings, MEPP 2.0—a revised and enhanced version of the MEPP 0.1—was created. The purpose of this study was to examine and contrast various factors that help or impede institutional partners of the Quebec health care system from using the MEPP 2.0 website in comparison to its initial version.
Methods: Forty-one patients with facial palsyand nineteen clinicians working with this population were enrolled in a within-subject crossover study. For both the MEPP 1.0 and MEPP 2.0, user experience was assessed for all participants. Embodiment was assessed in patients, and factors influencing clinical use were assessed by clinicians. Qualitative comments about their experiences were also gathered. Descriptive statistics and reliability measures were calculated. Differences between the two MEPP versions were assessed using the linear mixed model.
Results: Overall, patients appreciated more the MEPP 2.0 (OR = 4.57; p < 0.001), and all clinicians preferred the MEPP 2.0 over the MEPP 1.0. For patients, it seems that facial ownership, as well as possession and control of facial movements, was significantly better with the MEPP 2.0. For clinicians, the MEPP 2.0 specifically allowed them to self-evaluate their intervention and follow up with more objectivity. The use of the MEPP 2.0 was also modulated by what their patients reported. Qualitatively, options to access an Android app and needs for improving the exercises bank were mentioned as hindering factors.
Conclusions: The updated version of the MEPP website, the MEPP 2.0, was preferred by our different partners.
Trial registration:
https://www.isrctn.com/ISRCTN10885397
The trial was registered before the start of the study on the 1st December 2023
Generative Language Reconstruction from Brain Recordings
Authors: Ye Ziyi , Ai Qingyao , Liu Yiqun , de Rijke Maarten , Zhang Min , Lioma Christina , Ruotsalo Tuukka
Published: August 2024

Language reconstruction from non-invasive brain recordings has been a long-standing challenge. Existing research has addressed this challenge with a classification setup, where a set of language candidates are pre-constructed and then matched with the representation decoded from brain recordings. Here, we propose a new method that addresses language reconstruction through auto-regressive generation, which directly uses the representation decoded from functional magnetic resonance imaging (fMRI) as the input for a large language model (LLM), removing the reliance on the accuracy of pre-constructed candidates. While an LLM can already generate high-quality content, our approach produces results more closely aligned with the visual or auditory language stimuli in response to which brain recordings are sampled, especially for content deemed “surprising” for the LLM. Furthermore, we show that the proposed approach can be used in an auto-regressive manner to reconstruct a 10-minute-long stimulus, which outperforms previous methods with a classification setup. Our findings demonstrate the effectiveness of employing brain language interfaces in a generative setup and delineate a promising path to investigating language formation in the human brain.
USP21-EGFR signaling axis is functionally implicated in metastatic colorectal cancer
Authors: LEE Ki-Young , Shin Ji Hye , Kim Mi-Jeong , Kim Ji Young , Choi Bongkum , Kang Yeeun , Kim Seo Hyun , Lee Ha-Jeong , Kwan Dohee , Cho Yong Beom , Kim Kyeong Kyu , Chun Eunyoung
Published: August 2024

The emerging significance of ubiquitin-specific peptidase 21 (USP21) in stabilizing Fra-1 (FOSL1) has shed light on their involvement in promoting colorectal cancer (CRC) metastasis. Additionally, EGFR signaling has been linked reciprocally with Fra-1 activation in an MMP-dependent manner. However, the functional implications of the USP21-EGFR signaling axis in metastatic CRC (mCRC) remain incompletely understood. RNA-Seq data from tumor tissues (n = 27) and matched normal tissues (n = 27) from 27 mCRC patients were analyzed to investigate the clinical correlation between USP21 and EGFR expression. Functional studies including CRISPR/Cas9 gene editing method to generate USP21-knockout (USP21-KO) CRC cells, in vitro cancer progression and tumor formation assays, in vivo xenograft assays in NSG mice, and therapeutic assays with the USP21 inhibitor, BAY-805, were conducted. Elevated levels of USP21 and EGFR expression in mCRC patients correlated with poorer survival outcomes. Mechanistically, USP21 was found to enhance EGFR stability by deubiquitinating EGFR, resulting in reduced EGFR levels in USP21-KO colon cancer cells. USP21-KO colon cancer cells exhibited significantly attenuated cell proliferation, migration, colony formation, and 3D tumor spheroid formation in response to EGF. Furthermore, tumorigenic activity in vivo was notably diminished in NSG mice xenografted with USP21-KO colon cancer cells. Notably, the USP21 inhibitor, BAY-805, demonstrated a remarkable inhibitory effect on the formation of 3D tumor spheroids in colorectal cancer cells stimulated with EGF. These findings provide valuable insights into the potential of USP21 as both a therapeutic target and a predictive biomarker for intervening in mCRC induced by EGF.
Prehospital management and outcomes of patients calling with chest pain as the main complaint
Authors: Ahmed Sughra , Gnesin Filip , Christensen Helle Collatz , Blomberg Stig Nikolaj , Folke Fredrik , Kragholm Kristian , Bøggild Henrik , Lippert Freddy , Torp-Pedersen Christian , Møller Amalie Lykkemark
Published: August 2024

Background
Chest pain is a frequent cause of health care contacts. We examined the prehospital management, in-hospital discharge diagnoses, and mortality of patients calling a non-emergency and emergency medical service with chest pain.
Methods
We included all calls to a non-emergency medical helpline (calls to 1813) and emergency medical service (1-1-2 calls) with a primary complaint of chest pain from 2014–2018 in Copenhagen, Denmark. The outcomes were: emergency response (ambulance dispatch, other transports/self-transport/home visits, self-care, and unknown/cancelled response), in-hospital diagnosis within 7 days after the call (cardiovascular, pulmonary, or other non-cardiovascular/pulmonary) and 30-day mortality.
Results
Among 4,838,232 calls, 91,671 were registered with chest pain by medical dispatchers. The first call for each patient was kept for analysis (n = 66,672). In total, 91.4% were referred to the hospital, 75.8% (n = 50,627) received an ambulance and 15.6% (n = 10,383) received other transport/self-transport/home visits. In total, 26.9% (n = 17,937) were diagnosed with a cardiovascular disease (Acute Coronary Syndrome (ACS): 11.1%), 5.2% (n = 3,490) a pulmonary disease, 52.8% (n = 35.242) other non-cardiovascular/pulmonary disease, and 15.1% (n = 10,093) received no diagnosis. Among ambulance-transported patients, the prevalence of cardiovascular discharge diagnoses was higher (32.1%) and fewer received no diagnosis (11.0%). Cardiovascular disease was rare among patients not transported by ambulance and patients who were not referred to hospital at all (2-13.4%) and in patients ≤ 40 years of age (< 10%). The 30-day mortality was low regardless of the diagnosis (0.6-4%), and 65,704 were still alive 30 days later.
Conclusion
Nearly all patients calling with chest pain were referred to treatment and among ambulance-transported patients, one-third received a cardiovascular diagnosis. While current practices appear reasonable, improved differentiation of chest pain in telephone consultations could potentially reduce burden of non-acute chest pain consultations.
High vanA Conservation in Vancomycin-Resistant Enterococcus faecalis, Enterococcus faecium, and Staphylococcus aureus: Case Insights
Authors: Kaur Arshmeet
Published: August 2024

Healthcare-associated, vancomycin-resistant Enterococci and Staphylococcus aureus have become increasingly concerning to public health. Previous research onvanA-type vancomycin resistance has focused on characterizing isolates and identifying evolutionarily conserved motifs within the vanA gene to discover potential drug targets. This study is the first in the literature to compare the vanA gene across Enterococcus faecium, Enterococcus faecalis, and Staphylococcus aureus. We analyze data from two patients, collected seven years apart, each experiencing distinct healthcare conditions. The first is a urinary tract infection patient in long-term care in 2004. The second is a liver transplant patient who developed a vancomycin-resistant Enterococci (VRE) infection post-transplant in 2011. We leverage BLAST analysis to examine the genetic diversity and conservation of the vanA gene across strains of all three species from both patients. Additionally, we confirm findings of previous studies conducted independently on each patient.
Analysis of the Oncogenic Role of Methyltransferase Like 3 (METLL3) in Head and Neck Squamous Cell Carcinoma (HNSCC)
Authors: Wang Han , Huang Yinzhu , Piao Yan , Xuan Qingya , Li Xianying , Han Zhezhu , Jin Chengri
Published: August 2024

Purpose
This study focused on the role of methyltransferase-like 3 (METLL3) in head and neck squamous cell carcinoma (HNSCC), analysing its regulatory function in cancer progression, and its feasibility as a potential biomarker and therapeutic target.
Methods
We performed Gene expression, Survival prognosis, Genetic alteration, Immune infiltration, and METTL3-related gene enrichment analysis of METTL3 gene in HNSCC through TIMER2.0 and GEPIA2 databases.
Results
We found that METTL3 expression was significantly higher in HNSCC tumour tissues compared to that in adjacent normal tissues and was associated with poorer disease-free survival, indicating a 50% increased risk of recurrence in patients with high expression. Genetic alteration analysis revealed a low frequency of METTL3 mutations, primarily missense mutations, in HNSCC, suggesting a complex relationship between METTL3expression and the biological characteristics of the tumour. Additionally, the expression of METTL3 was closely related to immune cell infiltration, particularly CD8+ T-cell infiltration, which is especially significant in the immune environment of HNSCC.
Conclusion
These findings not only confirm METTL3's critical role in the pathogenesis of HNSCC but also highlight its potential as a therapeutic target, providing a scientific basis for the development of treatment strategies targeting METTL3, which may help improve treatment outcomes for HNSCC patients.
Use of Computer Vision Analysis for Labeling Inattention Periods in Eeg Recordings With Visual Stimuli
Authors: Isaev Dmitry , Major Samantha , Carpenter Kimberly L.H. , Grapel Jordan , Chang Zhuoqing , Martino Matias Di , Carlson David , Dawson Geraldine , Sapiro Guillermo
Published: August 2024

Electroencephalography (EEG) recordings with visual stimuli require detailed coding to determine the periods of participant’s attention. Here we propose to use a supervised machine learning model and off-the-shelf video cameras only. We extract computer vision-based features such as head pose, gaze, and face landmarks from the video of the participant, and train the machine learning model (multi-layer perceptron) on an initial dataset, then adapt it with a small subset of data from a new participant. Using a sample size of 23 autistic children, and training on additional 2560 labeled frames (equivalent to 85.3 seconds of the video) of a new participant, the median area under the receiver operating characteristic curve for inattention detection was 0.989 (IQR 0.984–0.993) and the median inter-rater reliability (Cohen’s kappa) with a trained human annotator was 0.888. Agreement with consensus annotation on four participants labeled independently by two human annotators was in the 0.827–0.960 range. Our results demonstrate the feasibility of automatic tools to detect inattention during EEG recordings, and its potential to reduce the subjectivity and time burden of human attention coding. The tool for model adaptation and visualization of the computer vision features is made publicly available to the research community.
CD56neg CD16+ cells represent a distinct mature NK cell subset with altered phenotype and are associated with adverse clinical outcome upon expansion in AML.
Authors: Chretien Anne-Sophie , Wlosik Julia , Orlanducci Florence , Richaud Manon , Demerle Clemence , Amara Amira Ben , Rouviere Marie-Sarah , Livrati Philippe , Gorvel Laurent , Hospital Marie Anne , Dulphy Nicolas , Devillier Raynier , Vey Norbert , Olive Daniel
Published: August 2024

CD56neg CD16+ Natural Killer (NK) cells have been reported to expand in chronic diseases and acute myeloid leukemia (AML). However, their biological role is still unclear. Using mass cytometry, spectral flow cytometry, bulk RNA-seq and in vitro assays, we characterized CD56neg CD16+ NK cells that expand in AML. We confirmed that CD56neg CD16+ NK cells represent a unique NK cell subset coexpressing Eomes and T-bet. CD56neg CD16+ NK cells could recover CD56 expression in vitro where they displayed unaltered NK cell functions. We previously demonstrated that CD56neg CD16+ NK cells expansion at diagnosis was associated with adverse clinical outcome in AML. Here, we validated our findings in a validation cohort of N=38 AML patients. AML patients with CD56neg CD16+ NK cells expansion at diagnosis had decreased overall survival (HR[CI95]=5.5[1.2-24.5], p=0.0251) and relapse-free survival (HR[CI95]=13.1[1.9-87.5], p=0.0079) compared to AML patients without expansion after 36 months follow-up. RNA-seq unveiled that CD56neg CD16+ NK cells were mature circulating NK cells with functional capacities. Upon expansion, CD56neg CD16+ NK cells from AML patients showed altered proteomic phenotype, with high expression of TIM-3 and Siglec-7. Taken together, our results suggest that CD56neg CD16+ NK cells are a relevant target for future NK-cell-based immunotherapies.
Development and verification of a machine learning-driven predictive model for cognitive impairment in Age-related Hearing Loss
Authors: Zheng Zhanhang , Li Ruilin , Su Jiping , Su Yuhong , Tu Huiqiong , Zhang Yuanyuan , Lv Huiling , Qin Shuhong , Wang Wenjuan , Wu Chenxingzi
Published: August 2024

Objective: The objective is to utilize machine learning algorithms to create a predictive model for cognitive impairment in age-relate hearing loss.
Methods:For this study, we gathered demographic information, conducted audiometric examinations, assessed cognitive abilities, and performed blood biochemical tests using data from NHANES. We then identified patients who fit the criteria based on the NHANES criteria. The LASSO regression method was employed to identify the determinants of cognitive impairment in age-related hearing loss. Additionally, five different machine learning algorithms were utilized to develop a predictive model for cognitive impairment in this population. Data from clinical trials were gathered between January 2024 and May 2024 to externally validate the model's dependability.
Results:The study comprised a total of 521 elderly adults with hearing loss, out of which 140 (26.8%) had cognitive impairment. The LASSO regression method was used to filter five factors: education level, alkaline phosphatase, globulin, creatinine, and eosinophil percentage. All of these predictors were then included in the machine learning approach for training the model.The XGB model exhibited consistent performance in both the training set (AUC=0.881) and the test set (AUC=0.868), while also demonstrating a moderate level of discrimination (AUC=0.706).
Conclusion:This study successfully developed a predictive model for cognitive impairment in age-related hearing loss using machine learning. The model demonstrates a satisfactory level of reliability and validity across several datasets. The utilization of machine learning models can serve as a potent instrument for healthcare providers in detecting cognitive impairment in the senior hearing loss population at an early stage.
Caerin 1.1 and 1.9 peptides halt B16 melanoma metastatic tumours via expanding cDC1 and reprogramming tumour macrophages
Authors: Fu Quanlan , Luo Yuandong , Li Junjie , Li Hejie , Liu Xiaosong , Chen Zhu , Ni Guoying , Wang Tianfang
Published: August 2024

Background
Cancer immunotherapy, particularly immune checkpoint inhibitors (ICBs) such as anti-PD-1 antibodies, has revolutionized cancer treatment, although response rates vary among patients. Previous studies have demonstrated that caerin 1.1 and 1.9, host-defence peptides from the Australian tree frog, enhance the effectiveness of anti-PD-1 and therapeutic vaccines in a murine TC-1 model by activating tumour-associated macrophages intratumorally.
Methods
We employed a murine B16 melanoma model to investigate the therapeutic potential of caerin 1.1 and 1.9 in combination with anti-CD47 and a therapeutic vaccine (triple therapy, TT). Tumour growth of caerin-injected primary tumours and distant metastatic tumours was assessed, and survival analysis conducted. Single-cell RNA sequencing (scRNAseq) of CD45+ cells isolated from distant tumours was performed to elucidate changes in the tumour microenvironment induced by TT.
Results
The TT treatment significantly reduced tumour volumes on the treated side compared to untreated and control groups, with notable effects observed by Day 21. Survival analysis indicated extended survival in mice receiving TT, both on the treated and distant sides. scRNAseq revealed a notable expansion of conventional type 1 dendritic cells (cDC1s) and CD4+CD8+ T cells in the TT group. Tumour-associated macrophages in the TT group shifted toward a more immune-responsive M1 phenotype, with enhanced communication observed between cDC1s and CD8+ and CD4+CD25+ T cells. Additionally, TT downregulated M2-like macrophage marker genes, particularly in MHCIIhi and tissue-resident macrophages, suppressing Cd68 and Arg1 expression across all macrophage types. Differential gene expression analysis highlighted pathway alterations, including upregulation of oxidative phosphorylation and MYC target V1 in Arg1hi macrophages, and activation of pro-inflammatory pathways in MHCIIhi and tissue-resident macrophages.
Conclusion
Our findings suggest that caerin 1.1 and 1.9, combined with immunotherapy, effectively modulate the tumour microenvironment in primary and secondary tumours, leading to reduced tumour growth and enhanced systemic immunity. Further investigation into these mechanisms could pave the way for improved combination therapies in advanced melanoma treatment.
Clinical effectiveness of unilateral single-armed vasoepididymostomy in obstructive azoospermia: a single- center experience
Authors: Zhou Yihong , Dong Jianjun , Yao Chencheng , Zhao Liangyu , Huang Yuhua , Tian Ruhui , Dai Yingbo , Tang Yuxin , Zhao Fujun , Li Zheng , Li Peng , Zhi Er lei
Published: August 2024

Background
Vasoepididymostomy (VE) is an important surgical treatment to achieve natural conception for patients with obstructive azoospermia (OA), and only unilateral VE can be performed under certain conditions, such as OA patients with congenital unilateral absence of the vas deferens (CUAVD) and some acquired OA. There is a lack of relevant reports assessing the clinical outcomes of unilateral VE in OA patients with different causes. This study is aimed to describe the clinical features and evaluate treatments and outcomes of unilateral single-armed VE in OA patients.
Methods
From December 2015 to June 2021, 46 OA patients (including 13 CUAVD-associated OA and 33 acquired OA) underwent unilateral single-armed VE in Shanghai General Hospital (Shanghai, China). Patient information, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated.
Results
Obstruction in distal of unilateral vas deferens (16/46) was the most common cause for OA patients underwent unilateral VE, and CUAVD accounts for 28.4% (13/46). The overall patency rate was 50.0% (23/46), with 38.5% (5/13) for the CUAVD group and 54.5% (18/33) for the acquired group (p > 0.05). The natural pregnancy rates in CUAVD group and acquired group were 20.0% and 33.3%, respectively (p > 0.05).
Conclusions
These findings suggest unilateral single-armed VE can achieve high patency and pregnancy rates in OA patients, whether for CUAVD or acquired OA patients.
Sirtuin-1: A marker of contrast-induced nephropathy following percutaneous coronary intervention?
Authors: ARDIC Melis , GUL Cuma Bulent
Published: August 2024

Objectives
Contrast-induced acute kidney injury (CI-AKI) is a serious complication of clinical practice after cardiac catheterization. Sirtuin-1 is a crucial regulator of the protection of the kidney against ischemia/reperfusion injury, inflammation, and vasoconstriction. In the present study, we sought to investigate whether Sirtuin-1 may be an early diagnostic marker of CIN.
Methods
76 patients admitted for elective percutaneous coronary interventions (PCI) for stable angina were enrolled between July 2022 and November 2022, and 50 patients were eligible to study. Sirtuin-1 values were measured by the Elisa kit before, 24 and 72 hours after the PCI.
Results
There is no statistically significant difference between CI-AKI (n = 17) and non-AKI (n = 33) groups regarding Sirtuin-1 between patient samples obtained before and after PCI.
Conclusions
These findings refute the hypothesis that Sirtuin-1 may be clinically beneficial as a biomarker for CI-AKI following radiological procedures requiring intravascular administration of iodinated contrast media.
FGFR2 mediated BEND3 phosphorylation disrupts BEND3/HDAC1 axis and promotes liver metastasis of colorectal cancer
Authors: Han Yi , Gong Xiaoyong , Zhao Jian , Ye Feng , Song Zijia , Sun Silei , Zhang Yong , Li Jianfang , Shi Minmin , Ji Xiaopin , Fang Yi , Jing Xiaoqian
Published: August 2024

Background
Tumor metastasis has been regarded as the leading risk factor for tumor patients. BEN-domain (BEND) family proteins have not been well elucidated in tumor metastasis.
Methods
To uncover the roles of BEND family proteins (BEND2-7) in colorectal cancer (CRC), we first mined their mRNA expression in both tumor and normal tissues from CRC patients, and plotted the survival curve. Through in vitro cell migration, invasion and in vivo tumor metastasis experiments, we confirmed that BEND3 acted as a tumor suppressor by dampening CRC-liver metastasis. Using RNA sequencing, we profiled the BEND3-targeted genes. To explore the mechanism how BEND3 represses target genes, an immunoprecipitation-mass assay was applied to reveal BEND3-interacting proteins.
Results
We speculated BEND3 as a candidate suppressor for CRC-liver metastasis using datamining. RNA-profiling showed BEND3 downregulated genes which partially enriched in two KEGG pathways: extracellular matrix organization and focal adhesion. MMP9 and CLDN18, as the representative genes for extracellular matrix organization and focal adhesion, respectively, were ascertained to be upregulated in BEND3-depleted cells. We then identified HDAC1 as a potential interactor of BEND3 and the upstream signal FGF2/FGFR2 which could disrupt BEND3/HDAC1 axis depending on FGFR2-mediated phosphorylation of BEND3 at Y153 and then trigger an activated chromatin state on the enhancer of MMP9 and CLDN18. Finally, the phosphorylation of BEND3 at Y153 positively correlates with MMP9 and CLDN18 and predicts a worse prognosis for CRC patients.
Conclusions
This is the first study that reveals the suppressive role of BEND3 in CRC and our results has preliminarily established it as a prognostic biomarker and a potential target in CRC-liver metastasis.
Evaluation of the Fragility Curve for Steel Structures with Linked Columns Frame System under Sequences of Critical Earthquakes
Authors: Golestani Yaser , Rajabi Elham
Published: August 2024

Fragility curves as a powerful tool assess the possible damage to existing structures and estimate the probability of structural damage exceeding a given level of seismic damage for several levels of seismic ground motions. This paper tries to evaluate the seismic vulnerability of steel structures containing relatively new Linked Column Frame using the fragility curves under the critical multiple earthquakes, which are not considered by most of the seismic design codes. Therefore, 10 LCF steel frames with shear/flexural behavior and length of 2 meters have been designed and implemented in OpenSees software. After selecting consecutive critical earthquakes, the fragility curves for single and consecutive scenarios have been calculated. For more comprehensively evaluation of the mentioned structures, the effect of various parameters including the number of stories and behavior of the linked beams has been investigated. The results indicate an increase in the probability of collapse under a seismic sequence compared to a single earthquake. This increase is more obvious in the performance level corresponding to the collapse threshold. So that the collapse prevention of 7-story frame with flexural linked beam exposed to consecutive earthquakes is 17% higher than the single case.
Depression Prevalence and Associated Factors Among Adolescents with Sickle Cell Anemia in Dar es Salaam, Tanzania: A Cross-Sectional Study
Authors: Athman Linda Paul , Jonathan Agnes , Mussa Fatima , kipasika Honesta , Mahawi Isihaka , Urio Florence , Ally Mwashungi , Mutagonda Ritha , Chirande Lulu , Makani Julie , Balandya Emmanuel
Published: August 2024

Background: Depression commonly arises among adolescents who have experienced long-standing psychosocial difficulties especially those facing chronic illnesses like Sickle Cell Anemia (SCA). SCA is a global health concern, and Tanzania is one of the countries with a high incidence, estimated at 8,000 to 11,000 births per year. This study aims to assess the magnitude and factors associated with depression among adolescents with SCA.
Methodology: A cross-sectional analytical study conducted on adolescents aged 11-19 years attending sickle cell clinics in referral hospitals in Dar-es-salaam Tanzania, from October 2023-March 2024. A validated Patient Health Questionnaire (PHQ-9) tool was used to screen for depression. Univarite and multivariate regression model was used to determine factors associated with clinical depression.A P value of less than 0.05 was considered statistically significant.
Results: Among 326 adolescents enrolled, the majority (64.7%) were 10-14 years of age. A total of 216 (54 %) had depression; when categorized into severity, 167 (38.7 %) had mild, 48 (14.7 %) had moderate and 1 (0.3%) had severe depression. Clinical depression, encompassing moderate to severe depression, was prevalent in 49 (15%) adolescents. Painful episodes were significantly associated with depression (aOR = 2.49) (95% CI: 1.17 - 5.29, p = 0.01).
Conclusion: Depression is common among adolescents with SCA in our setting. Painful episodes experienced by these adolescents were significantly associated with depression. This study highlights the need for screening adolescents with SCA for depression and integration of mental health services in sickle cell clinics.
Bacterial Spectrum and Antimicrobial Susceptibility Pattern of Peripheral and Central Bacterial Keratitis in South Korea for Ten Years
Authors: Jee Donghyun , Han Su Yeon , Kim Hyun Seung , Kim Eun Chul
Published: August 2024

Purpose: To evaluate the bacterial spectrum and antimicrobial susceptibility pattern of bacterial keratitis in South Korea for ten years.
Methods: 143 eyes of 143 patients who have been diagnosed with bacterial keratitis from January 2010 to April 2019 were retrospectively enrolled. Corneal scraping was done for Gram stain in all patients, and cultures were plated on blood, chocolate, Sabouraud dextrose agar, and thioglycolate broth. Empirical fourth generation fluoroquinolone or fortified vancomycin and ceftazidime were treated for every patient.
Results: Ocular trauma (n=29, 24.0%) and contact lens (n=18, 14.9%) were the most common causes in patients with bacterial keratitis. Most of the bacterial keratitis was gram-positive (n=85, 70%) and the gram-negative is only 6% (7 eyes). Most of central and peripheral keratitis were Gram positive (n=57, 65% and n=29, 85%). There was no gram-negative stain in peripheral keratitis. Vancomycin and ciprofloxacin were the most susceptible (n=68, 56.2% and n=51, 42.1%) and least resistant (n=0, 0% and n=18, 14.9%) in the antibiotic susceptibility test. Treatment time (month) and best corrected visual acuity after treatment in the gatifloxacin group were better than those in the moxifloxacin group (P<0.05).
Conclusion: The most common cause of bacterial keratitis was ocular trauma and contact lenses. There was a different bacterial spectrum in central and peripheral keratitis. Gatifloxacin was more effective for early corneal healing and recovery of visual acuity than moxifloxacin.
Quantitative semen analysis using fluorometric lateral-flow assay system for male fertility diagnosis
Authors: Cho Il-Hoon , Lee Jisuk , Jun Jin Hyun , Kadam Ulhas S. , Song Seung-Hun H. , Kim Dong Hyung
Published: August 2024

About one-third of infertility cases are attributed to male lifestyle-associated factors such as smoking, drug abuse, obesity, and psychological stress. These factors have been suggested as potential contributors to male infertility. High-quality semen is essential for successful fertility, and poor semen quality is a significant hurdle in achieving this outcome. Therefore, it is necessary to evaluate the concentration and quality of semen on-site without visiting a hospital. In this study, we developed two analytical systems using a fluorescence lateral-flow sperm (FLF-sperm) assay for the rapid and quantitative evaluation of sperm concentrations and quality. The sperm-specific protein (SP-10) was chosen as a target analyte to determine sperm counts. An immunostrip was fabricated to obtain quantitative fluorescence signals in a sandwich format. The SP-10 assay provides highly sensitive detection with a detection limit of 1.28 x 106/mL and produces a reactive signal proportional to the sperm concentration in clinical semen samples. Additionally, we established a sensing system using enzymatic cleavage to detect sperm quality based on hyaluronidase (HAdase) activity values, covering sperm concentrations from 1.8 x 106/mL to 140 x 106/mL. These quantitative sperm analysis systems allow users to easily interpret sperm counts and quality on-site for diagnosing male infertility and monitoring treatment progress.
The impact of COVID-19 on nurse staffing levels and healthcare- associated infections in medical institutions: A retrospective cohort study
Authors: Han Kyu-Tae , Kim Seungju
Published: August 2024

Background: In Korea, various policies had been introduced to improve the nursing shortage problem even before COVID-19, but there is still a shortage of nurses, and it is unclear how this, combined with the impact of infectious diseases, has affected staff nursing grades and healthcare-associated infections(HAIs). This study aimed to evaluate changes in nurse staffing levels in medical institutions in Korea and their impact on HAIs during the COVID-19 pandemic.
Methods: A total of 100,417 patients who were admitted to an intensive care unit(ICU) or general ward after a diagnosis or confirmation of COVID-19 from 2020 to 2022 were included in this study. To evaluate the effect of nurses on HAIs, nurse-to-bed(patient) ratio and fixed night shift nurses were considered as nurse factors. A HAI is defined as a patient with a diagnosed or confirmed COVID-19 infection more than seven days after admission or within seven days after discharge. To evaluate the association between nurse staffing levels and HAIs, survival analyses were performed using Cox proportional hazards models, adjusting for covariates.
Results: Of the patients admitted to an ICU or general ward, 4.5% and 12.2% had in-hospital COVID-19 infection, respectively. Survival analysis showed that HAIs increased as the number of patients per nurse increased for both general ward and ICU patients. Additionally, compared with medical institutions that do not operate fixed night shift nurses, HAIs increased as the proportion of night nurses increased, but decreased to less than 10%.
Conclusions: This study shows that securing nurses and operating an appropriate proportion of night nursing staff is important for infection control within medical institutions. In the event of an infectious disease outbreak, infection prevention activities through appropriate staffing are important, and healthcare-associated infections can be reduced by securing appropriate nurse staffing and maintaining an appropriate proportion of nurses on night shifts.
Effects of Different Non-invasive Respiratory Support in Preventing Reintubation in Patients at High Risk for Extubation Failure: A Systematic Review and Meta-Analysis
Authors: Guo Danyang , Jia Ping , Li Shaowei , Wang Li , Wang Zhenzhen , Mao Xiaorong
Published: August 2024

Background: Patients at high risk for extubation failure are subject to suffering reintubation or respiratory failure after extubation that adversely affects outcomes. It’s essential that rapidly identifying respiratory failure and correctly applying respiratory support for adequate treatment to avoid reintubation for patients. The high-flow nasal cannula (HFNC) is a safer and more comfortable respiratory support than noninvasive mechanical ventilation (NIV). However, whether HFNC is superior to NIV for preventing reintubation in patients at high risk of extubation failure is unclear. The present study aims to investigate the efficacy of HFNC for preventing reintubation in various high risk populations.
Methods: In this systematic review and meta analysis, we searched PubMed, Embase, Web of Science, Cochrane Library, and CNKI for studies from Jan 1, 2019, to Jan 1, 2024. Two independent reviewers screened studies, extracted the data from the reports, and assessed the risk of bias. The primary outcomes were the reintubation rate within 7 days and effect size calculated as risk ratio (RR; 95% Cl), the secondary outcomes were the rate of mortality(RR; 95% Cl) and ICU length of stay (SMD; 95% Cl) and respiratory rate (SMD; 95%).
Results: A total of 1,289 patients were included in 9 studies, of which 6 were randomized controlled trials and 3 were observational studies. A significant decrease in the mortality risk was found in the HFNC group(RR 0.6822 [95% Cl: 0.4795-0.9706]) compared to the NIV group. However, there was no significant difference in reintubation rate (RR 1.1729, 95% CI: 0.8679–1.5851) and ICU length of stay (SMD 0.0256, 95% CI: -0.0195–0.0708). All adverse events associated with NIV were reported in three studies.
Conclusion: For patients who are at high risk of extubation failure, the HFNC can decrease the risk of mortality, to some extent, compared to NIV, but the reintubation rate and ICU length of stay were not superior to NIV.