bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the Bioaccessibility of Functional Ice Cream with Blueberry Enriched with Whey Protein Gel
Authors: Pehlivanoğlu Halime , Sunal Zeynep , Yaman Mustafa , Aksoy Aslı
Published: May 2024

Ice cream is a complex product obtained by blowing air through special equipment and then freezing a physicochemical mixture consisting of milk, sugar, emulsifier, stabilizer, oil, color and flavoring substances. Recently, especially with the pandemic experienced all over the world, consumers have begun to turn to functional foods that have high nutritional value and are important for health. Functional foods, in addition to its nutritional effects, are defined as foods that have health protective, corrective and/or disease risk reducing effects, depending on one or more effective ingredients, and these effects are scientifically and clinically proven. In order for a product to have functional properties, it must contain bioactive ingredients, probiotic microorganisms and also have a prebiotic effect. For this reason, our study aimed to provide functional properties to ice cream with blueberries, which are rich in phenolic compounds, and to examine the phenolic substance bioaccessibility of this functional ice cream under mouth, stomach and small intestine conditions simulated with the in vitro gastrointestinal digestion model system. In this context, functional ice cream was produced by trapping the phenolic rich blueberry fruit in six different concentrations of whey protein gel, and the amount of phenolic substance and protein amount were determined after in vitro digestion. While the phenolic substance content of protein gel ice cream in the small intestine environment was between 261-485 µg/100 g and an average of 114 µg/100 g in the control sample, in the oral environment these values were determined as 85-251 µg/100 g in protein gel ice cream and 291 µg/100 g in the control sample. As a result of our study, it was determined that the amount of gallic acid phenolic substance and bioaccessibility of ice cream samples produced with protein gel increased from the oral environment to the small intestine. In the control sample (blueberry ice cream without protein gel), it was observed that the amount of phenolic substance was highest in the oral environment and decreased as it went to the small intestine environment. According to the FAO Guidelines for Use of Nutrition Claims, samples with a whey protein gel ratio of 16%, 18% and 20% can be considered as "protein sources". Thus, in this study, functionalized in terms of protein content and phenolic substance, increased bioaccessibility and high protein ice cream production was carried out.
DISCRETION IN THE APPLICATION OF SPECIAL MEDICAL AND SOCIAL MEASURES TO CONVICTS WITH DRUG ADDICTION
Authors: Grishko Aleksandr
Published: May 2024

The article examines the mechanism of applying special medical and social measures to convicts with drug addiction. Based on the analysis of the current Russian legislation, as well as the legislation of a number of foreign countries, the author comes to the conclusion that there are currently many gaps in the application of the institute under study. Changes of a theoretical and practical nature are proposed, consisting in improving the conceptual apparatus by introducing the terms voluntary, compulsory and compulsory treatment for drug addiction, as well as special norms in the Federal Law "On Probation in the Russian Federation".
The Keep. Uncanny Propriation: Derrida’s Marrano Objection
Authors: Moreiras Alberto
Published: May 2024

This essay attempts to offer some reflections on what it is that Jacques Derrida found uncomfortable in Martin Heidegger’s thought at the level of fundamental gestures. The region of disagreement is located in Derrida’s self-identification in a marrano register at an autographic level. This paper studies the notions of propriation and expropriation in Heidegger’s late texts and compares them to Derrida’s ‘uncanny propriation’ as a marrano notion. I offer four propositions regarding Derrida’s marranismo, which I align with Derrida’s proposal for desecularization, tentatively described as a ‘messianic engagement with the khora’. I conclude with a proposal for the development of ontic models of marrano action that would antecede the theory/practice divide.
Propriety, Facticity, Normativity
Authors: Liakos David
Published: May 2024

In Donner le temps II, Derrida argues that Heidegger is a thinker of ‘propriety’, which suggests that Heidegger is committed to a metaphysical strategy of assigning essential characteristics to entities and to being. This essay interrogates this claim from Derrida’s reading in Donner le temps II of Heidegger’s analytic of Dasein. Drawing on Giorgio Agamben’s critique of Derrida on this issue, we will distinguish propriety from facticity. This investigation reveals that Heidegger conceives of Dasein as facing a range of possible commitments which can become determinate but are not determined. In turn, this conception of facticity provides the basis for Heidegger’s thinking of normativity, that is, a measure for success or failure which does not assign propriety to Dasein’s character, as Steven Crowell has argued. The essay concludes that Derrida’s critique of propriety and departure from phenomenology complicate the possibility of a viable deconstructive conception of normativity.
‘The Key Thing’: Fairy Tale Lore and Intertexts in Little Red and Other Stories
Authors: Fogarty Anne
Published: May 2024

‘Little Red Riding Hood’ is not only an intertext for the first story in Little Red and Other Stories but for the entire volume. An iconic fairy tale, known primarily in the version by the brothers Grimm, it is also one of the most commented on and reworked stories. While most retellings give precedent either to Little Red Riding Hood or the wolf, Ní Dhuibhne’s revisiting of the tale accords importance too to the role of the grandmother. She counters the tendency to appropriate fairy tales and sideline their enticement and wisdom by excavating their deep content especially the affects and primal predicaments that they depict. Fairy tale motifs in her short story collection allow the articulation of emotions that could not otherwise be voiced, provide a means of parsing everyday experience, and open a portal onto the magical and the numinous.
Family History and a Migratory Legend in County Cavan
Authors: Bourke Angela
Published: May 2024

Éilís Ní Dhuibhne’s elegant essay, ‘“The Old Woman as Hare”: Structure and Meaning in an Irish Legend’, published in Folklore, delivers the outcome of considerable reading and thinking in just six pages of text, while notes and references take up another two. Gendered readings of Irish oral tradition were rare in the early nineties, especially in such readable form. I happily urged this example of Éilís’s work on my students of Modern Irish and retained most of her findings in memory. Rereading it thirty years later, however, I’m led among the small drumlin farms of north-west Cavan, where my maternal grandparents, Patrick and Ellen Magee, grew up. Éilís’s own writings range widely, as seams of scholarship, family, memory and landscape enrich and illuminate each other. My essay reflects on my own family research, visits late in life to the border counties, and material written down in one Co. Cavan school in 1937/38 for the National Folklore Collection, and now available on www.duchas.ie .
Teaching Creative Writing: Éilís Ní Dhuibhne, Theorist and Practitioner
Authors: Ryan James
Published: May 2024

This article reviews Éilís Ní Dhuibhne’s career as a teacher of creative writing at University College Dublin and demonstrates her formidable contribution to the theory and practice of creative writing teaching. It draws from the 2011 symposium which she organised on the teaching and learning of creative writing in Ireland, and the subsequent publication Imagination in the Classroom, which she co-edited. Together the symposium and publication can be seen as the context in which the teaching of creative writing in Irish higher-level institutions assumed the mantle of an autonomous, professional discipline.
Éilís na Gaeilge
Authors: Póirtéir Cathal
Published: May 2024

Many readers of Éilís Ní Dhuibhne’s short stories and novels in English may not have read her creative work in the Irish language. In this short essay I aim to make more readers aware of her contribution to literature in Irish and of where her work is situated within the overall range of modern literature in Irish. ‘Éilís na Gaeilge’ is a somewhat different writer than her English language doppelganger. Her Irish language novels, for example, are predominantly works of popular fiction such as murder mysteries. Much of her work in Irish is aimed at – or at least accessible to – a young adult readership and deals directly and indirectly with social issues that affect their lives. She is an exceptional writer who had already developed a national and international reputation writing in English before devoting much of her writing life to work in Irish. This essay aims to cast some light on the range and quality of Éilís Ní Dhuibhne’s creative work in Irish and to encourage those who can to engage with that work as well as with her more widely known stories in English.
BİR AYRIMCILIK TEMELİ OLARAK VATANDAŞLIĞIN İNSAN HAKLARI HUKUKU BAKIMINDAN GÖRÜNÜMLERİ
Authors: Körpe Vahit Mert
Published: May 2024

Uluslararası hukuk bakımından özellikle ırk temelli ayrımcılığın önlenmesi açısından en önemli insan hakları belgelerinden birisi olan Her Türlü Irk Ayrımcılığının Ortadan Kaldırılmasına İlişkin Sözleşme (ICERD) ırk ayrımcılığını “siyasi, ekonomik, sosyal, kültürel veya toplumsal yaşamın herhangi bir alanında, insan hakları ve temel özgürlüklerin tanınmasını, uygulanmasını, bu hak ve özgürlüklerden yararlanılmasını ortadan kaldırmak veya zayıflatmak amacına ya da etkisine yönelik ırk, renk, soy ya da ulusal veya etnik kökene dayalı her türlü ayrım, dışlama, kısıtlama ya da tercih” olarak belirtmiştir. Ancak bu genel tanım ele alındığında dahi çoğu uluslararası insan haklarına ilişkin belgede vatandaşlık kıstasına göre yapılan ayrımların bu kategoride değerlendirilemeyeceği belirtilmiş ve vatandaşlık “meşru” bir ayrımcılık ölçütü olarak yargı kararlarında ve iç hukuk mevzuatında kabul edilmiştir. Bu çalışmamızda da bir ayrım kriteri olarak vatandaşlık kavramının uluslararası ve bölgesel insan hakları hukuku mekanizmaları bakımından niteliği incelenip bu ayrımın olası sınırları ve etkilerine yer verilecektir.
Dual targeting negative enrichment strategy for highly sensitive and purity detection of CTCs
Authors: Gao Siying , Li Xuejie , Hu Zhiyuan , Wang Zihua , Hao Xiaopeng
Published: May 2024

Circulating tumor cells (CTCs) have significant clinical value in early tumor detection, dynamic monitoring and immunotherapy. CTC detection stands out as a leading non-invasive approach for tumor diagnostics and therapeutics. However, the high heterogeneity of CTCs and the occurrence of epithelial-mesenchymal transition (EMT) during metastasis pose challenges to methods relying on EpCAM-positive enrichment. To address these limitations, a method based on negative enrichment of CTCs using specific leukocyte targets has been developed. In this study, aiming to overcome the low purity associated with immunomagnetic beads targeting solely the leukocyte common antigen CD45, we introduced CD66b-modified immunomagnetic beads. CD66b, a specific target for neutrophils with abundant residues, was chosen as a complementary approach. The process involved initial collection of nucleated cells from whole blood samples using density gradient centrifugation. Subsequently, magnetically labeled leukocytes were removed by magnetic field, enabling the capture of CTCs with higher sensitivity and purity while retaining their activity. Finally, we selected 20 clinical blood samples from patients with various cancers to validate the effectiveness of this strategy, providing a new generalized tool for the clinical detection of CTCs.
Scaling carbon removal systems: deploying direct air capture amidst Canada’s low-carbon transition
Authors: Cortinovis Stephanie Rose , Craik Neil , Moreno-Cruz Juan , Motlaghzadeh Kasra , Schweizer Vanessa
Published: May 2024

Carbon dioxide removal (CDR) technologies, such as direct air carbon capture and storage (DACCS), will be critical in limiting the rise of the average global temperature over the next century. Scaling up DACCS technologies requires the support of a complex array of policies and infrastructure across multiple overlapping policy areas, such as climate, energy, technology innovation and resource management. While the literature on DACCS and other CDR technologies acknowledges the path-dependent nature of policy development, it has tended to focus on abstract policy prescriptions that are not rooted in the specific political, social and physical (infrastructural) context of the implementing state. To address this gap, this paper provides a country-level study of the emerging DACCS policy regime in Canada. Drawing on the existing literature that identifies idealized (acontextual) policy objectives that support DACCS development and effective regulation, we identify the actionable policy objectives across six issue domains: general climate mitigation strategies; energy and resource constraints; carbon storage and transport regulation and infrastructure; financing scale-up and supporting innovation; removal and capture technology availability and regulation; and addressing social acceptability and public interest. Using a database of Canadian climate policies (n = 457), we identify policies within the Canadian (federal and provincial) policy environment that map to the idealized policy objectives within each of these domains. This exercise allows us to analyze how key policy objectives for DACCS development are represented within the Canadian system, and enables us to identify potential niches, and landscape influences within the system, as well as gaps and potential barriers to the system transition process. This paper contributes to our understanding of national DACCS policy development by providing a framework for identifying components of the DAC system and linking those components to desired policy outcomes and may provide a basis for future cross-country comparisons of national-level DACCS policy.
Sodium–glucose cotransporter-2 inhibitors improve cardiovascular outcomes post-acute coronary syndrome complicated by acute heart failure
Authors: Rahhal Alaa , Hamamyh Tahseen , Chapra Ammar , Zaza Khaled J. , Najim Mostafa , Hemadneh Mohammad , Faraj Hazem , Kanjo Wael , Yasin Ahmed , Toba Haneen , Mohammed Wafa , Hamad Mohammad Khair , Al-Tikrety Nawras , Baraa Habib Mhd , Awaisu Ahmed , Mahfouz Ahmed , Alyafei Sumaya , Arabi Abdul Rahman , Patel Ashfaq , Al-Hijji Mohammed
Published: May 2024

Background

Acute coronary syndrome (ACS) remains a risk factor for heart failure (HF). Therefore, we aimed to assess the cardioprotective role of sodium–glucose cotransporter-2 (SGLT2) inhibitors post-ACS in patients with acute HF (AHF) and diabetes.

Methods

We conducted a retrospective observational cohort study employing propensity score matching. This study involved patients with diabetes admitted with ACS complicated by AHF, defined as either new clinical HF requiring diuretics during the index admission or having an ejection fraction (EF) of <40%. The study population was divided into two groups; (1) SGLT2 inhibitor users and (2) SGLT2 inhibitor non-users. The Cox proportional hazard regression analysis was used to evaluate the outcomes.

Results

A total of 465 patients (93% male; mean age, 55 ± 10 years) were included in this study. Using a 1 : 1 propensity score matching, 78 patients were included per arm with an absolute standardized difference of <0.1 for all baseline characteristics. The use of SGLT2 inhibitors resulted in lower composite outcomes of ACS, HF hospitalization, and all-cause mortality at 1 month and 12 months [1 month: 2.6% vs. 11.5%, HR = 0.20 (0.04–0.94), p = 0.041; 12 months: 14.1% vs. 23.1%, HR = 0.46 (0.22–0.99), p = 0.046].

Conclusion

The findings suggest that SGLT2 inhibitors may confer cardioprotective effects in ACS-induced AHF, thereby widening the spectrum for indications of SGLT2 inhibitors.
Symptom clusters and unplanned hospital readmission in Chinese patients with acute myocardial infarction on admission
Authors: Mao Yijun , Shi Yuqiong , Qiao Wenfang , Zhang Zhuo , Yang Wei , Liu Haili , Li Erqing , Fan Hui , Liu Qiang
Published: May 2024

Backgroud

Acute myocardial infarction (AMI) has a high morbidity rate, high mortality rate, high readmission rate, high health care costs, and a high symptomatic, psychological, and economic burden on patients. Patients with AMI usually present with multiple symptoms simultaneously, which are manifested as symptom clusters. Symptom clusters have a profound impact on the quality of survival and clinical outcomes of AMI patients.

Objective

The purpose of this study was to analyze unplanned hospital readmissions among cluster groups within a 1-year follow-up period, as well as to identify clusters of acute symptoms and the characteristics associated with them that appeared in patients with AMI.

Methods

Between October 2021 and October 2022, 261 AMI patients in China were individually questioned for symptoms using a structured questionnaire. Mplus 8.3 software was used to conduct latent class analysis in order to find symptom clusters. Univariate analysis is used to examine characteristics associated with each cluster, and multinomial logistic regression is used to analyze a cluster membership as an independent predictor of hospital readmission after 1-year.

Results

Three unique clusters were found among the 11 acute symptoms: the typical chest symptom cluster (64.4%), the multiple symptom cluster (29.5%), and the atypical symptom cluster (6.1%). The cluster of atypical symptoms was more likely to have anemia and the worse values of Killip class compared with other clusters. The results of multiple logistic regression indicated that, in comparison to the typical chest cluster, the atypical symptom cluster substantially predicted a greater probability of 1-year hospital readmission (odd ratio 8.303, 95% confidence interval 2.550–27.031, P < 0.001).

Conclusion

Out of the 11 acute symptoms, we have found three clusters: the typical chest symptom, multiple symptom, and atypical symptom clusters. Compared to patients in the other two clusters, those in the atypical symptom cluster—which included anemia and a large percentage of Killip class patients—had worse clinical indicators at hospital readmission during the duration of the 1-year follow-up. Both anemia and high Killip classification suggest that the patient's clinical presentation is poor and therefore the prognosis is worse. Intensive treatment should be considered for anemia and high level of Killip class patients with atypical presentation. Clinicians should focus on patients with atypical symptom clusters, enhance early recognition of symptoms, and develop targeted symptom management strategies to alleviate their discomfort in order to improve symptomatic outcomes.
Transcatheter PFO closure for cryptogenic stroke: current approaches and future considerations
Authors: Eltelbany Moemen , Gattani Raghav , Ofosu-Somuah Araba , Damluji Abdulla , Epps Kelly C. , Batchelor Wayne B.
Published: May 2024

Patent Foramen Ovale (PFO) is a common congenital atrial septal defect present in 20%–35% of the general population. Although generally considered a benign anatomic variant, a PFO may facilitate passage of a thrombus from the venous to arterial circulation, thereby resulting in cryptogenic stroke or systemic embolization. A PFO is detected in nearly one half of patients presenting with cryptogenic stroke and often considered the most likely etiology when other causes have been excluded. In this review, we discuss the contemporary role of transcatheter closure of PFO in the treatment of cryptogenic stroke, including devices currently available for commercial use in the United States (Amplatzer PFOTM Occluder and GoreTM Cardioform Septal Occluder) and a novel suture-mediated device (NobleStitchTM EL) under clinical investigation. To provide the best care for cryptogenic stroke patients, practitioners should be familiar with the indications for PFO closure and corresponding treatment options.
Effect of low dose honey on the apoptosis and inflammation gene expression in corneal limbal stem cells and keratocytes and its efficacy as an ophthalmic formulation in the treatment of dry eye: in-vitro and clinical study
Authors: Sanie-Jahromi Fatemeh , Khaki Mehdi , Heydari Mojtaba , Nowroozzadeh Mohammad Hossein , Akbarizadeh Amin Reza , Daneshamouz Saeid , NejatyJahromy Yaser , Nejabat Maryam , Mahmoudi Ahmad , Zareei Athar , Nejabat Mahmood
Published: May 2024

Background

The use of honey as an eye treatment encounters challenges due to its high osmolarity, low pH, and difficulties in sterilization. This study addresses these issues by employing a low concentration of honey, focusing on both in-vitro experiments and clinical trials for treating dry eye disease in corneal cells.

Methods

In the in-vitro experiment, we investigated the impact of a 1% honey-supplemented medium (HSM) on limbal stem cells (LSCs) and keratocytes using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and real-time polymerase chain reaction (PCR) for BCL-2, BAX, and IL-1β gene expression. Simultaneously, in the clinical trial, 80 participants were divided into two groups, receiving either a 1% w/v honey ophthalmic formulation or a placebo for 3 months. Study outcomes included subjective improvement in dry eye symptoms, tear break-up time (TBUT), and Schirmer’s test results.

Results

MTT results indicated that 1% HSM did not compromise the survival of corneal cells and significantly reduced the expression of the IL-1β gene. Additionally, participants in the honey group demonstrated a higher rate of improvement in dry eye symptoms and a significant enhancement in TBUT values at the three-month follow-up. However, there was no significant difference between the study groups in terms of Schirmer’s test values. No adverse events were observed or reported.

Conclusion

In conclusion, 1% honey exhibits anti-inflammatory and anti-infective properties, proving effective in ameliorating dry eye symptoms and enhancing tear film stability in patients with dry eye disease.

Clinical Trial Registration: https://irct.behdasht.gov.ir/trial/63800.
Genome-wide CRISPR/Cas9 screen reveals JunB downmodulation of HIV co-receptor CXCR4
Authors: Schulze William J. , Gregory Devon A. , Johnson Marc C. , Lange Margaret J.
Published: May 2024

HIV-1 relies extensively on host cell machinery for replication. Identification and characterization of these host-virus interactions is vital to our understanding of viral replication and the consequences of infection in cells. Several prior screens have identified host factors important for HIV replication but with limited replication of findings, likely due to differences in experimental design and conditions. Thus, unidentified factors likely exist. To identify novel host factors required for HIV-1 infection, we performed a genome-wide CRISPR/Cas9 screen using HIV-induced cell death as a partitioning method. We created a gene knockout library in TZM-GFP reporter cells using GeCKOv2, which targets 19,050 genes, and infected the library with a lethal dose of HIV-1NL4-3. We hypothesized that cells with a knockout of a gene critical for HIV infection would survive while cells with a knockout of a non-consequential gene would undergo HIV-induced death and be lost from the population. Surviving cells were analyzed by high throughput sequencing of the integrated CRISPR/Cas9 cassette to identify the gene knockout. Of the gene targets, an overwhelming majority of the surviving cells harbored the guide sequence for the AP-1 transcription factor family protein, JunB. Upon the generation of a clonal JunB knockout cell line, we found that HIV-1NL4-3 infection was blocked in the absence of JunB. The phenotype resulted from downregulation of CXCR4, as infection levels were recovered by reintroduction of CXCR4 in JunB KO cells. Thus, JunB downmodulates CXCR4 expression in TZM-GFP cells, reducing CXCR4-tropic HIV infection.
Intrasegmental recombination as an evolutionary force of Lassa fever virus
Authors: He Cheng-Qiang , Kong Chao , He Mei , Chen Guan-Xiang , Liu Shu-Min , Ding Nai-Zheng
Published: May 2024

Lassa fever (LF), caused by Lassa virus (LASV), is one of the most dangerous diseases to public health. Homologous recombination (HR) is a basic genetic power driving biological evolution. However, as a negative-stranded RNA virus, it is unknown whether HR occurs between LASVs and its influence on the outbreak of LF. In this study, after analyzing 575 S and 433 L segments of LASV collected in Africa, we found that LASV can achieve HR in both of its segments. Interestingly, although the length of S segment is less than half of the L segment, the proportion of LASVs with S recombinants is significantly higher than that with L recombinants. These results suggest that HR may be a feature of LASV, which can be set by natural selection to produce beneficial or eliminate harmful mutations for the virus, so it plays a role in LASV evolution during the outbreak of LF.
Unraveling metabolic characteristics and clinical implications in gastric cancer through single-cell resolution analysis
Authors: Wang Wenyue , Li Conghui , Dai Yuting , Wu Qingfa , Yu Weiqiang
Published: May 2024

Background: Gastric cancer is a highly prevalent malignant neoplasm. Metabolic reprogramming is intricately linked to both tumorigenesis and cancer immune evasion. The advent of single-cell RNA sequencing technology provides a novel perspective for evaluating cellular metabolism. This study aims to comprehensively investigate the metabolic pathways of various cell types in tumor and normal samples at high resolution and delve into the intricate regulatory mechanisms governing the metabolic activity of malignant cells in gastric cancer.

Methods: Utilizing single-cell RNA sequencing data from gastric cancer, we constructed metabolic landscape maps for different cell types in tumor and normal samples. Employing unsupervised clustering, we categorized malignant cells in tumor samples into high and low metabolic subclusters and further explored the characteristics of these subclusters.

Results: Our research findings indicate that epithelial cells in tumor samples exhibit significantly higher activity in most KEGG metabolic pathways compared to other cell types. Unsupervised clustering, based on the scores of metabolic pathways, classified malignant cells into high and low metabolic subclusters. In the high metabolic subcluster, it demonstrated the potential to induce a stronger immune response, correlating with a relatively favorable prognosis. In the low metabolic subcluster, a subset of cells resembling cancer stem cells (CSCs) was identified, and its prognosis was less favorable. Furthermore, a set of risk genes associated with this subcluster was discovered.

Conclusion: This study reveals the intricate regulatory mechanisms governing the metabolic activity of malignant cells in gastric cancer, offering new perspectives for improving prognosis and treatment strategies.
Immunomodulatory effects of laser-synthesized nanodiamonds on peripheral blood mononuclear cells: evaluation of unconjugated, PEGylated, and antibody-conjugated formulations
Authors: Alexander Elena , Leong Kam W.
Published: May 2024

The application of laser-synthesized nanodiamonds (LNDs) is of great interest to biomedical researchers and drug developers because this emerging method of synthesis yields nanodiamonds of consistent size (<5 nm diameter) and surface chemistry that can be functionalized to perform a staggering range of highly specialized tasks. The present study assessed the threshold at which LNDs in various conjugations and concentrations triggered immune responses and cytotoxicity in peripheral mononuclear blood cells from healthy donors, as assessed by changes in ATP concentrations and induced secretion of the cytokines IFN-γ, IL-6 and TNF-α. Conjugations assessed were raw (unconjugated) NDs, PEGylated (PEG5k-NDs), and antibody conjugated to goat anti-mouse antibodies (IgG-NDs). Concentrations of each conjugation were prepared and tested at 50.0, 10.0, 2.0, 0.4, and 0.08 μg/mL. Results showed that pegylated and raw NDs were well tolerated, with the indicators of inflammation or minimal cytotoxicity emerging only at the highest concentrations tested (50.0 μg/mL). IgG-NDs showed signs of inflammatory responses at the two highest concentrations tested (10.0 and 50.0 μg/mL). There was some evidence that the dilutant vehicle used for ND suspension may have contributed to the immune response. All three ND configurations increased ATP concentration in a dose-dependent manner, up to a concentration of 10.0 μg/mL. At the highest concentration (50.0 μg/mL), the ND solutions showed minimal signs of cytotoxicity. Conclusion from this testing suggest that LNDs are likely to offer substantial utility in biomedical applications because of their capacity to evade the immune response at concentrations at least as high as 2.0 μg/mL and potentially up to 50.0 μg/mL.
Odorant receptor co-receptors affect expression of tuning receptors in Drosophila
Authors: Long Teng , Mohapatra Pratyajit , Ballou Sydney , Menuz Karen
Published: May 2024

Insects detect odorants using two large families of heteromeric receptors, the Odorant Receptors (ORs) and Ionotropic Receptors (IRs). Most OR and IR genes encode odorant-binding “tuning” subunits, whereas four (Orco, Ir8a, Ir25a, and Ir76b) encode co-receptor subunits required for receptor function. Olfactory neurons are thought to degenerate in the absence of Orco in ants and bees, and limited data suggest this may happen to some olfactory neurons in Drosophila fruit flies as well. Here, we thoroughly examined the role of co-receptors on olfactory neuron survival in Drosophila. Leveraging knowledge that olfactory neuron classes are defined by the expression of different tuning receptors, we used tuning receptor expression in antennal transcriptomes as a proxy for the survival of distinct olfactory neuron classes. Consistent with olfactory neuron degeneration, expression of many OR-family tuning receptors is decreased in Orco mutants relative to controls, and transcript loss is progressive with age. The effects of Orco are highly receptor-dependent, with expression of some receptor transcripts nearly eliminated and others unaffected. Surprisingly, further studies revealed that olfactory neuron classes with reduced tuning receptor expression generally survive in Orco mutant flies. Furthermore, there is little apoptosis or neuronal loss in the antenna of these flies. We went on to investigate the effects of IR family co-receptor mutants using similar approaches and found that expression of IR tuning receptors is decreased in the absence of Ir8a and Ir25a, but not Ir76b. As in Orco mutants, Ir8a-dependent olfactory neurons mostly endure despite near-absent expression of associated tuning receptors. Finally, we used differential expression analysis to identify other antennal genes whose expression is changed in IR and OR co-receptor mutants. Taken together, our data indicate that odorant co-receptors are necessary for maintaining expression of many tuning receptors at the mRNA level. Further, most Drosophila olfactory neurons persist in OR and IR co-receptor mutants, suggesting that the impact of co-receptors on neuronal survival may vary across insect species.
Expiratory braking defines the breathing patterns of asphyxiated neonates during therapeutic hypothermia
Authors: Papoff Paola , Caresta Elena , D’Agostino Benedetto , Midulla Fabio , Petrarca Laura , Giannini Luigi , Pisani Francesco , Montecchia Francesco
Published: May 2024

Introduction

Although neonatal breathing patterns vary after perinatal asphyxia, whether they change during therapeutic hypothermia (TH) remains unclear. We characterized breathing patterns in infants during TH for hypoxic-ischemic encephalopathy (HIE) and normothermia after rewarming.

Methods

In seventeen spontaneously breathing infants receiving TH for HIE and in three who did not receive TH, we analyzed respiratory flow and esophageal pressure tracings for respiratory timing variables, pulmonary mechanics and respiratory effort. Breaths were classified as braked (inspiratory:expiratory ratio ≥1.5) and unbraked (<1.5).

Results

According to the expiratory flow shape braked breaths were chategorized into early peak expiratory flow, late peak expiratory flow, slow flow, and post-inspiratory hold flow (PiHF). The most braked breaths had lower rates, larger tidal volume but lower minute ventilation, inspiratory airway resistance and respiratory effort, except for the PiHF, which had higher resistance and respiratory effort. The braked pattern predominated during TH, but not during normothermia or in the uncooled infants.

Conclusions

We speculate that during TH for HIE low respiratory rates favor neonatal braked breathing to preserve lung volume. Given the generally low respiratory effort, it seems reasonable to leave spontaneous breathing unassisted. However, if the PiHF pattern predominates, ventilatory support may be required.
QL1604 combined with bevacizumab as an innovative first-line treatment for HCC patient with extensive metastasis who showed remarkable effect: a case report
Authors: Wan Yanzhi , Tan Keqin , Zhu Hong
Published: May 2024

Hepatocellular carcinoma (HCC) is a common and highly malignant tumor with poor outcomes, especially when it metastasizes. In this report, we present the case of a 64-year-old male patient diagnosed with recurrence and multiple metastases of HCC 7 years after surgery. As the tumor invaded the spinal canal and pressed on the spinal cord, the patient experienced paralysis in the lower limbs. After undergoing surgical resection for spinal decompression, the patient chose an innovative regimen: QL1604 200 mg every 3 weeks plus bevacizumab 675 mg every 3 weeks as first-line treatment. From July 2022 to February 2024, the patient has regularly received the treatment. During the treatment, the paralysis symptoms of the patient gradually improved, and the motor function of the lower limbs completely returned to normal. When re-evaluated his spinal cord injury, the Frankel grade of the patient was downgraded from C to E. The tumor shrank to reach a state of PR and lasted for one and a half years. QL1604 combined with bevacizumab demonstrated excellent efficacy and minimal side effects in this patient. This new combined therapy holds potential as a first-line treatment strategy.
Application of biological agents in the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis
Authors: Liu Weijun , Tian Guanyuan , Chen Chao , Zhang Mingying , Chen Zhanmao , Chen Tietao , Lin Zhibin , Wu Wuzhong , Wu Yiqaing , Wu Kefei , Liu Qinghua
Published: May 2024

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been traditionally treated using glucocorticoids and immunosuppressants. However, these treatment modes are associated with high recurrence AAV rates and adverse reactions. Therefore, treatment strategies for AAV need to be urgently optimized. The efficacy and safety of biological agents in the treatment of vasculitis have been clinically validated. This review comprehensively summarizes the evidence-based support for the clinical use of existing biological agents in AAV. The findings reveal that multiple biological agents not only effectively reduce the adverse reactions associated with glucocorticoids and immunosuppressants but also demonstrate significant therapeutic efficacy. Notably, rituximab, an anti-CD20 antibody, has emerged as a first-line treatment option for AAV. Mepolizumab has shown promising results in relapsed and refractory eosinophilic granulomatosis with polyangiitis. Other biological agents targeting cytokines, complement, and other pathways have also demonstrated clinical benefits in recent studies. The widespread application of biological agents provides new insights into the treatment of AAV and is expected to drive further clinical research. These advancements not only improve patient outcomes but also offer more possibilities and hope in the field of AAV treatment.
Natural compound Alternol actives multiple endoplasmic reticulum stress-responding pathways contributing to cell death
Authors: Liu Wang , He Chenchen , Li Changlin , Ye Shazhou , Zhao Jiang , Zhu Cunle , Wang Xiangwei , Ma Qi , Li Benyi
Published: May 2024

Background: Alternol is a small molecular compound isolated from the fermentation of a mutant fungus obtained from Taxus brevifolia bark. Our previous studies showed that Alternol treatment induced reactive oxygen species (ROS)-dependent immunogenic cell death. This study conducted a comprehensive investigation to explore the mechanisms involved in Alternol-induced immunogenic cell death.

Methods: Prostate cancer PC-3, C4-2, and 22RV1 were used in this study. Alternol interaction with heat shock proteins (HSP) was determined using CETSA assay. Alternol-regulated ER stress proteins were assessed with Western blot assay. Extracellular adenosine triphosphate (ATP) was measured using ATPlite Luminescence Assay System.

Results: Our results showed that Alternol interacted with multiple cellular chaperone proteins and increased their expression levels, including endoplasmic reticulum (ER) chaperone hypoxia up-regulated 1 (HYOU1) and heat shock protein 90 alpha family class B member 1 (HSP90AB1), as well as cytosolic chaperone heat shock protein family A member 8 (HSPA8). These data represented a potential cause of unfolded protein response (UPR) after Alternol treatment. Further investigation revealed that Alternol treatment triggered ROS-dependent (ER) stress responses via R-like ER kinase (PERK), inositol-requiring enzyme 1α (IRE1α). The double-stranded RNA-dependent protein kinase (PKR) but not activating transcription factor 6 (ATF6) cascades, leading to ATF-3/ATF-4 activation, C/EBP-homologous protein (CHOP) overexpression, and X-box binding protein XBP1 splicing induction. In addition, inhibition of these ER stress responses cascades blunted Alternol-induced extracellular adenosine triphosphate (ATP) release, one of the classical hallmarks of immunogenic cell death.

Conclusion: Taken together, our data demonstrate that Alternol treatment triggered multiple ER stress cascades, leading to immunogenic cell death.
Relationship between learners’ L2 Motivational Self System and parental investment behavior in learners’ English learning
Authors: Zhang Yu , Lu Xiaobing , Liu Honggang
Published: May 2024

Students’ motivation and learning behavior are significantly impacted by parents’ participation and investment. It has been demonstrated that parental investment behavior could exert a direct effect on students’ L2 Motivational Self System (L2MSS) mediated by parental investment belief. Nevertheless, the relationship between components of parental investment behavior and students’ language learning motivation remains a topic necessitating further scholarly investigation. In response to this gap, we conducted a quantitative study involving a survey of 900 high school students to explore the relationship between students’ English learning motivation, as conceptualized by the L2 Motivational Self System and parental investment behavior based on a four-component model. The findings in this study indicated that high school students exhibited moderate levels of L2MSS and relatively low levels of parental investment behavior. Moreover, students’ L2MSS was found to have a significant positive correlation with the global parental investment behavior, with parental emotional investment behavior emerging as a positive predictor of high school students’ L2MSS. These results underscore the importance of parental provision of sufficient economic, relationship, knowledge, and emotional support in cultivating a nurturing and supportive familial context conducive to the development of students’ positive future selves.
Impulsivity and reward and punishment sensitivity among patients admitted to a specialized inpatient eating disorder treatment program
Authors: Martinelli Mary K. , Schreyer Colleen C. , Vanzhula Irina A. , Guarda Angela S.
Published: May 2024

Introduction

Eating disorders (EDs) are conceptualized as disorders of under- and over-control, with impulsivity reflecting under-control. Extant research indicates that impulsivity and related factors such as reward sensitivity and punishment sensitivity may serve as trait-level transdiagnostic risk and/or maintenance factors in EDs. Findings on impulsivity and reward and punishment sensitivity by diagnosis are mixed and research on the relationship between these factors and ED symptoms, hospital course, and treatment outcomes is limited.

Methods

Participants (N = 228) were patients admitted to a specialized inpatient behavioral treatment program for EDs who agreed to participate in a longitudinal study and completed self-report measures of impulsivity, reward sensitivity, and punishment sensitivity at admission. Weight and ED symptomatology were measured at admission and discharge. Hospital course variables included length of stay and premature treatment dropout.

Results

Impulsivity was lower in individuals with anorexia nervosa (AN) restricting type compared to those with AN binge/purge type or bulimia nervosa; no other group differences were observed. Higher impulsivity was associated with greater bulimic symptoms on the Eating Disorder Inventory 2 (EDI-2) at admission. Impulsivity was not related to ED symptoms, weight outcomes, length of hospital stay, or treatment dropout at program discharge.

Conclusion

Impulsivity may help distinguish restrictive versus binge/purge EDs, but does not necessarily relate to discharge outcomes in an intensive inpatient ED program. Findings from this study provide novel contributions to the literature on personality traits in EDs and have important clinical implications. Results suggest that patients with higher levels of impulsivity or reward and punishment sensitivity can be expected to respond to inpatient treatment. Suggestions for future research are discussed.
Decision tree-Markov model of perinatal depression screening: a cost–utility analysis
Authors: Yang Yehuan , Zheng Ruimin , Yang Li , Huang Xing , Zhang Tong
Published: May 2024

Background

Perinatal depression affects the physical and mental health of pregnant women. It also has a negative effect on children, families, and society, and the incidence is high. We constructed a cost–utility analysis model for perinatal depression screening in China and evaluated the model from the perspective of health economics.

Methods

We constructed a Markov model that was consistent with the screening strategy for perinatal depression in China, and two screening strategies (screening and non-screening) were constructed. Each strategy was set as a cycle of 3 months, corresponding to the first trimester, second trimester, third trimester, and postpartum. The state outcome parameters required for the model were obtained based on data from the National Prospective Cohort Study on the Mental Health of Chinese Pregnant Women from August 2015 to October 2016. The cost parameters were obtained from a field investigation on costs and screening effects conducted in maternal and child health care institutions in 2020. The cost–utility ratio and incremental cost–utility ratio of different screening strategies were obtained by multiplicative analysis to evaluate the health economic value of the two screening strategies. Finally, deterministic and probabilistic sensitivity analyses were conducted on the uncertain parameters in the model to explore the sensitivity factors that affected the selection of screening strategies.

Results

The cost–utility analysis showed that the per capita cost of the screening strategy was 129.54 yuan, 0.85 quality-adjusted life years (QALYs) could be obtained, and the average cost per QALY gained was 152.17 yuan. In the non-screening (routine health care) group, the average cost was 171.80 CNY per person, 0.84 QALYs could be obtained, and the average cost per QALY gained was 205.05 CNY. Using one gross domestic product per capita in 2021 as the willingness to pay threshold, the incremental cost–utility ratio of screening versus no screening (routine health care) was about −3,126.77 yuan, which was lower than one gross domestic product per capita. Therefore, the screening strategy was more cost-effective than no screening (routine health care). Sensitivity analysis was performed by adjusting the parameters in the model, and the results were stable and consistent, which did not affect the choice of the optimal strategy.

Conclusion

Compared with no screening (routine health care), the recommended perinatal depression screening strategy in China is cost-effective. In the future, it is necessary to continue to standardize screening and explore different screening modalities and tools suitable for specific regions.
Spatio-temporal distributions and determinants of diarrhea among under-five children in Ethiopia
Authors: Tiku Meskerem , Zeru Melkamu A. , Belay Denekew Bitew
Published: May 2024

Objective

The purpose of this study was to evaluate the spatio-temporal pattern of Ethiopia’s childhood diarrheal disease and identify its contributing factors.

Methods

We conducted analyses on secondary data from four Ethiopian Demographic and Health Surveys conducted between 2000 and 2016. Moran’s I was used to determine spatial dependence and spatial models were used to evaluate variables associated with diarrhea in under-five children at the zonal level.

Results

Childhood diarrhea showed spatial clustering in Ethiopia (Moran’s I; p < 0.05). The spatial regression model revealed significant factors at the zonal level: children born at home (eθ = 1.355, 95% CI: 1.052–1.544, p < 0.001), low birth weight (eθ = 1.18, 95% CI: 1.017–1.691, p < 0.05), and unimproved source of water (eθ = 0.8568, 95% CI: 0.671–1.086, p < 0.01).

Conclusion

The prevalence of diarrhea among under-five children varied over time by zone, with the Assosa, Hundene, and Dire Diwa zones having the highest rates. Home births and low birth weight contributed to the prevalence of childhood diarrhea. In high-risk zones of Ethiopia, reducing childhood diarrhea requires integrated child health interventions and raising awareness about the potential hazards associated with unimproved water sources.