bluuebunny/crossref_metadata_2025 huggingface dataset:
Literary Translation: Old and New Challenges
Authors: Yousef Tawfiq
Published: October 2023

This paper discusses the main challenges that face literary translation and literary translators. These challenges have been divided into three main categories: Linguistic, cultural, and human. The first type of challenges comes from the nature of the discipline itself since it involves the difficult task of dealing with phonological, syntactic, lexical, semantic, stylistic and pragmatic issues occurring in literary texts whose language is additionally characterized by its linguistic deviation from the norm, especially in its use of figurative language. The second source of challenges stems from the fact that literary translation is primarily concerned with translating culture-bound expressions and concepts which pose one of the most difficult tasks for translators when trying to render them into a foreign language. The third type of challenges is related to the barriers facing literary translation including lack of government funding, poor literary translator training, language and cultural hegemony, cultural insularity and indifference towards translated literature. The discussion focuses on the situation of literary translation in the Arab world and in the English-speaking world with some illustrative examples and statistics..
Profil Kromatografi Dan Penentuan Kadar Flavonoid Total Fraksi N-Heksan Daun Kalangkala (Litsea angulata Bl) Menggunakan Spektrofotometri UV-Vis
Authors: Astuti Puspita , Rohama Rohama , Budi Setia
Published: October 2023

ABSTRAKLatar Belakang: Kalangkala (Litsea angulata Bl) merupakan tanaman khas Kalimantan Selatan yang secara empiris digunakan masyarakat dalam pengobatan bisul. Salah satu senyawa yang terkandung yaitu flavonoid, flavonoid memiliki banyak aktivitas farmakologi salah satunya sebagai antibakteri. Flavonoid dapat tersari dengan beberapa pelarut berdasarkan tingkat kepolarannya salah satunya yaitu n-heksan yang memiliki sifat non polar.Tujuan: Mengetahui profil kromatografi dan kadar flavonoid total fraksi n-Heksan daun Kalangkala (Litsea angulata Bl) dengan menggunakan metode Spektrofotometri UV-Vis.Metode: Penelitian ini menggunakan metode observasional analitik untuk mengetahui profil kromatografi flavonoid dan observasional deskriptif dalam penentuan kadar flavonoid total fraksi n-Heksan daun Kalangkala (Litsea angulata Bl) menggunakan Spektrofotometri UV-Vis. Hasil: Hasil penelitian dari identifikasi senyawa menunjukkan daun Kalangkala (Litsea angulata Bl) positif mengandung flavonoid. Sedangkan pada profil kromatografi, eluen yang mampu mendeteksi senyawa flavonoid yaitu n-Heksan : Etil asetat (8:12) dengan noda sebanyak tujuh noda. Hasil penentuan kadar flavonoid total fraksi n-Heksan daun Kalangkala (Litsea angulata Bl) sebesar 8,367 mg QE(Quersetin Equivalen)/g.Simpulan: Profil Kromatografi Lapis Tipis (KLT) dari fraksi n-Heksan daun Kalangkala (Litsea angulata Bl) menunjukkan senyawa flavonoid dengan eluen terbaik n-Heksan : Etil asetat (8:12) serta kadar flavonoid total fraksi n-Heksan daun Kalangkala (Litsea angulata Bl) sebesar 8,367 mg QE(Quersetin Equivalen)/g.

Kata Kunci: Litsea angulata Bl, Flavonoid Total, n-Heksan.
Potensi Filtrat Jeruk Nipis (Citrus aurantiifolia) Terhadap Penurunan Kadar Ammonia Pada Ikan Patin (Pangasius pangasius)
Authors: Safitri Maynada , Alawiyah Tuti , Nugraha Dyan Fitri
Published: October 2023

Latar Belakang: Sungai Barito mengalami pencermaran dikarenakan pembuangan limbah dari pabrik, secara tidak langsung mempengaruhi mahkluk hidup di sungai dan sekitarnya salah satunya ikan patin. Ikan patin merupakan ikan yang potensi konsumsinya cukup tinggi di masyarakat, namun pemanfaatannya belum optimal, karena adanya sejumlah urea pada daging yang mudah terurai menjadi ammonia, pengurangan kadar ammonia pada daging dapat dilakukan dengan berbagai cara, yaitu dengan menggunakan bahan alami, salah satunya jeruk nipis yang didalamnya terdapat kandungan asam sitrat yang mampu menurunkan kadar ammonia.

Tujuan: Penelitian ini bertujuan untuk melihat potensi filtrat jeruk nipis (Citrus aurantiifolia) dalam penurunan kadar ammonia (NH3) pada ikan patin (Pangasius pangasius).

Metode: Penelitian menggunakan True Experimental dengan pendekatan Post Test Only Control Group Design. Metode yang dilakukan yaitu uji kuantitatif  menggunakan Spektrofotometri UV-Vis. Analisis data menggunakan Kruskal-Wallis dan Mann-Whitney.

Hasil: Hasil yang diperoleh bahwa semua sampel positif mengandung ammonia dan filtrat jeruk nipis berpotensi mampu menurunkan kadar ammonia dengan total penurunan pada konsentrasi sebesar 25% = 1,36 ppm, 50% = 1,01 ppm, 75% = 0,69 ppm, dan 100% = 0,19 ppm. Penurunan kadar ammonia disebabkan adanya proses denaturasi yang tejadi karena kandungan asam sitrat pada filtrat jeruk nipis.

Simpulan: Pemberian filtrat jeruk nipis dengan konsentrasi yang berbeda yaitu, 25%, 50%, 75%, dan 100%  menunjukan adanya pengaruh yang signifikan terhadap penurunan kadar ammonia pada ikan patin. Dan konsentrasi yang paling baik terhadap penurunan kadar ammonia yaitu pada konsentrasi 100%.
Pengaruh Edukasi Dengan Pendekatan Persepsi Kerentanan Dan Persepsi Manfaat Dalam Perubahan Perilaku Pasien Hipertensi Di Kecamatan Dusun Tengah
Authors: Damayanti Novi , Nugraha Dyan Fitri , Aryzki Saftia
Published: October 2023

Latar Belakang: Penyakit hipertensi merupakan penyakit yang paling banyak diderita oleh masyarakat Indonesia, karena tingkat kepatuhan mengkonsumsi obat adalah salah satu perilaku yang menunjukkan bahwa rendahnya angka kepatuhan dapat membuat meningkatnya angka kekambuhan penyakit hipertensi sehingga bisa berakibat terhadap komplikasi. Ada beberapa pendekatan yang bisa diberikan untuk meningkatkan kepatuhan minum obat antihipertensi, yaitu dapat diberikan sebuah  edukasi dengan pendekatan persepsi kerentanan dan persepsi manfaat melalui sebuah media berbasis video.

Tujuan: Penelitian ini bertujuan untuk mengetahui pengaruh edukasi dengan pendekatan persepsi kerentanan dan persepsi manfaat dalam perubahan perilaku pasien hipertensi di Kecamatan Dusun Tengah.

Metode: Penelitian true eksperimental dengan pendekatan pretest and posttest control group design. Pengambilan sampel dilakukan dengan stratified random sampling. Sampel penelitian berjumlah 88 pasien. Data diperoleh dengan kuesioner yang dibagikan. Ada dua kelompok yang digunakan yaitu kelompok kontrol dan kelompok intervensi.

Hasil: Hasil analisis statistik menggunakan uji regresi ordinal dengan nilai p-value 0,000 yang menunjukkan adanya pengaruh yang signifikan terhadap pemberian edukasi dengan pendekatan persepsi kerentanan dan persepsi manfaat dalam perubahan perilaku pasien hipertensi melalui sebuah media video.

Simpulan: Terdapat pengaruh pemberian edukasi dengan pendekatan persepsi kerentanan dan persepsi manfaat melalui media video dalam perubahan perilaku pasien hipertensi di Kecamatan Dusun Tengah.
Pengetahuan Masyarakat Terhadap Tanaman Obat Keluarga (TOGA) di Kelurahan Pemurus Luar
Authors: Zhahera Ghina , Melviani Melviani , Nastiti Kunti
Published: October 2023

Latar belakang: Perkembangan pengetahuan bidang kedokteran yang melahirkan berbagai jenis obat yang mengandung kimia, kepercayaan masyarakat terhadap kemampuan obat herbal semakin turun. Salah satu faktor yang menyebabkan hilangnya kepercayaan masyarakat terhadap khasiat obat- obatan tradisional adalah terputusnya pengetahuan tentang obat-obatan tradisional yang dimiliki oleh nenek moyang bangsa Indonesia. pengetahuan tentang tanaman obat keluarga ini perlu terus dikembangankan sehingga terus terjadi proses penciptaan pengetahuan diantara kelompok masyarakat yang mengembangkan nya.

Tujuan: Mengetahui pengetahuan masyarakat terhadap Tanaman Obat Keluarga (TOGA).

Metode: Penelitian deskriptif dengan analisis Univariat. Pengambilan sampel dengan teknik purvosive sampling. Sampel dari penelitian sebanyak 97 responden. data diperoleh dari kuesioner yang dibagikan ke masyarakat.

Hasil:Pengetahuan masyarakat pada jenis-jenis tanaman obat keluarga 49% dengan kategori baik, tentang manfaat tanaman obat keluarga 84% dengan kategori baik, tentang cara pengolahan tanaman obat keluarga 45% dengan kategori baik, dan masyarakat terhadap cara pakai tanaman obat keluarga 48% dengan kategori cukup baik. Penggunaan tanaman obat keluarga di masyarakat terdapat 27 tanaman obat keluarga.

Kesimpulan: Pengetahuan masyarakat terhadap tanaman obat keluarga di Kelurahan Pemurus Luar rata-rata dengan pengetahuan baik.

 

Kata Kunci: Pengetahuan, Tanaman Obat Keluarga
Prediksi Toksisitas Dan Farmakokinetika Untuk Mendapatkan Kandidat Obat Antidiabetes
Authors: Nursanti Okta
Published: October 2023

Jahe dan sereh merupakan tanaman yang berkhasiat salah satunya yaitu sebagai anti diabetes tipe 2, senyawa jahe dan sereh yang berkhasiat sebagai antidiabetes antara lain cineol, farnesol, geraniol, linalool, limonen, pinen, terpineol dan zingeron. Tujuan dari penelitian ini adalah memprediksi aktivitas dan farmakokinetik dan toksisitas senyawa yang terdapat di dalam tanaman Jahe dan Sereh. Untuk pencarian ligan uji menggunakan ChEBI, untuk mengetahui prediksi toksisitas senyawa menggunakan Protox Web server, untuk prediksi farmakokinetik menggunakan pkCSM. Dari hasil penelitian  uji toksisitas, farmakokinetik ke delapan senyawa yang ada pada jahe dan sereh mempunyai aktivitas antidiabetes yang aman.
Kata kunci : Jahe, Sereh, Protox web server, pkCSM, Antidiabetes
Platelet factor 4 improves survival in a murine model of antibiotic-susceptible and methicillin-resistant Staphylococcus aureus peritonitis
Authors: Podolnikova Nataly P. , Lishko Valeryi K. , Roberson Robert , Koh Zhiqian , Derkach Dmitry , Richardson David , Sheller Michael , Ugarova Tatiana P.
Published: October 2023

The complement receptor CR3, also known as integrin Mac-1 (CD11b/CD18), is one of the major phagocytic receptors on the surface of neutrophils and macrophages. We previously demonstrated that in its protein ligands, Mac-1 binds sequences enriched in basic and hydrophobic residues and strongly disfavors negatively charged sequences. The avoidance by Mac-1 of negatively charged surfaces suggests that the bacterial wall and bacterial capsule possessing net negative electrostatic charge may repel Mac-1 and that the cationic Mac-1 ligands can overcome this evasion by acting as opsonins. Indeed, we previously showed that opsonization of Gram-negative Escherichia coli with several cationic peptides, including PF4 (Platelet Factor 4), strongly augmented phagocytosis by macrophages. Here, we investigated the effect of recombinant PF4 (rPF4) on phagocytosis of Gram-positive Staphylococcus aureus in vitro and examined its impact in a mouse model of S. aureus peritonitis. Characterization of the interaction of rPF4 with nonencapsulated and encapsulated S. aureus showed that rPF4 localizes on the bacterial surface, thus making it available for Mac-1. Furthermore, rPF4 did not have direct bactericidal and bacteriostatic activity and was not toxic to host cells. rPF4 enhanced phagocytosis of S. aureus bioparticles by various primary and cultured Mac-1-expressing leukocytes by several folds. It also increased phagocytosis of live nonencapsulated and encapsulated bacteria. Notably, the augmentation of phagocytosis by rPF4 did not compromise the intracellular killing of S. aureus by macrophages. Using a murine S. aureus peritonitis model, we showed that treatment of infected mice with rPF4 caused a significant increase in the clearance of antibiotic-susceptible S. aureus and its methicillin-resistant (MRSA) variant and markedly improved survival. These findings indicate that rPF4 binding to the bacterial surface circumvents its antiphagocytic properties, improving host defense against antibiotic-susceptible and antibiotic-resistant bacteria.
Review of microbiota gut brain axis and innate immunity in inflammatory and infective diseases
Authors: Yuan Chongshan , He Yuhong , Xie Kunyu , Feng Lianjun , Gao Shouyang , Cai Lifu
Published: October 2023

The microbiota gut brain (MGB) axis has been shown to play a significant role in the regulation of inflammatory and infective diseases. Exploring the structure and communication mode of MGB axis is crucial for understanding its role in diseases, and studying the signaling pathways and regulatory methods of MGB axis regulation in diseases is also of profound significance for future clinical research. This article reviews the composition, communication mechanism of MGB axis and its role in inflammatory and infective diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis (MS), autism spectrum disorder (ASD), depression, psoriasis, irritable bowel syndrome (IBS), and inflammatory bowel diseases (IBD). In addition, our investigation delved into the regulatory functions of the inflammasome, IFN-I, NF-κB, and PARK7/DJ-1 innate immune signaling pathway in the context of inflammatory and infective diseases. Ultimately, we discussed the efficacy of various interventions, including fecal microbiota transplantation (FMT), antibiotics, probiotics, prebiotics, synbiotics, and postbiotics, in the management of inflammatory and infective diseases. Understanding the role and mechanism of the MGB axis might make positive effects in the treatment of inflammatory and infective diseases.
A systemic transformation of an arts and sciences curriculum to nurture inclusive excellence of all students through course-based research experiences
Authors: Delogu Franco , Nelson Michelle , Timmons Shannon C. , Weinstein Melinda , Bhattacharya Bhubanjyoti , Jaussen Paul , Al-Hamando Mazin , Al-Azary Hamad , Anyaiwe Oriehi , Appleby LaVetta , Bukaita Wisam , Cartwright Christopher , Chung Chan-Jin , Cleere Suzanne , Cole Matthew , Collins Sibrina , Faulkner Ty , Glembocki Margaret M. , Harris Christopher C. , Johnston Matthew , Kao Vivian , Kiernan Julia , Kuzmanov Aleksandra , Lauren Paula , Liu Tao , Meyer Eric , Morgan-Paisley Kineta , Morrissette Jeffery , Moschelli George , Muqbil Irfana , Nelson Patrick , Pell Bruce , Schaefer Joy , Schantz Randy , Shargel Daniel , Siddiq Fauzia , Zhou Meng , Zwiesler-Vollick Julie , Yu Na , Moore Hsiao-Ping
Published: October 2023

Introduction

We describe herein a large-scale, multidisciplinary course-based undergraduate research experience program (CRE) developed at Lawrence Technological University (LTU). In our program, all students enrolled in CRE classes participate in authentic research experiences within the framework of the curriculum, eliminating self-selection processes and other barriers to traditional extracurricular research experiences.

Methods

Since 2014, we have designed and implemented more than 40 CRE courses in our College of Arts and Sciences involving more than 30 instructors from computer science, mathematics, physics, biology, chemistry, English composition, literature, philosophy, media communication, nursing, and psychology.

Results

Assessment survey data indicates that students who participate in CRE courses have an enhanced attitude towards research and discovery, as well as increased self-efficacy. This intervention is particularly relevant for non-traditional students, such as students who commute and/or have significant work or childcare commitments, who often experience limited access to research activities.

Discussion

Herein we highlight the importance of a systemic institutional change that has made this intervention sustainable and likely to outlast the external funding phase. Systemic change can emerge from a combination of conditions, including: (1) developing a critical mass of CRE courses by providing instructors with both incentives and training; (2) developing general principles on which instructors can base their CRE activities; (3) securing and maintaining institutional support to promote policy changes towards a more inclusive institution; and (4) diversifying the range of the intervention, both in terms of initiatives and disciplines involved.
Aesthetic values in home and consumer studies – investigating the secret ingredient in food education
Authors: Berg Gita , Lundqvist Eva , Sydner Ylva Mattsson
Published: October 2023

Food is a part of everyday life, and formal food education is included in compulsory education in many countries, for example through the subject Home and Consumer Studies (HCS). While food education is often underpinned by public health concerns such as preventing non-communicable diseases and promoting cooking skills, there has been little focus on aesthetic aspects of teaching and learning about food. This study therefore aims to gain understanding of aesthetic values as a part of HCS food educational practices. Aesthetic values are here regarded as socially and culturally shared, and related to notions of pleasure and taste. As this study uses a pragmatist approach, aesthetic values are seen as constituted in encounters, encompassing experiencing individual(s), artifacts, and context. By thematically analyzing empirical data from an exploratory case study, including classroom observations, student focus groups, and teacher interviews, we show how values are constituted as culinary, production, and bodily aesthetics. Culinary aesthetics involved cooking processes, cooking skills, and presentation of food and meals. Production aesthetics involved foods’ origin and degree of pre-processing, whereas bodily aesthetics related to bodily consequences of eating. Aesthetic values were vital features of the educational practices studied and played a key role in bringing the practices forward. They also indicated what counted as valid, or desired, outcomes and thereby steered events in certain directions. The study highlights the significance of aesthetic values and argues in favor of acknowledging aesthetics in planning, undertaking, and evaluating HCS food education.
Combined signature of N7-methylguanosine regulators with their related genes and the tumor microenvironment: a prognostic and therapeutic biomarker for breast cancer
Authors: Li Tingjun , Chen Zhishan , Wang Zhitang , Lu Jingyu , Chen Debo
Published: October 2023

Background

Identifying predictive markers for breast cancer (BC) prognosis and immunotherapeutic responses remains challenging. Recent findings indicate that N7-methylguanosine (m7G) modification and the tumor microenvironment (TME) are critical for BC tumorigenesis and metastasis, suggesting that integrating m7G modifications and TME cell characteristics could improve the predictive accuracy for prognosis and immunotherapeutic responses.

Methods

We utilized bulk RNA-sequencing data from The Cancer Genome Atlas Breast Cancer Cohort and the GSE42568 and GSE146558 datasets to identify BC-specific m7G-modification regulators and associated genes. We used multiple m7G databases and RNA interference to validate the relationships between BC-specific m7G-modification regulators (METTL1 and WDR4) and related genes. Single-cell RNA-sequencing data from GSE176078 confirmed the association between m7G modifications and TME cells. We constructed an m7G-TME classifier, validated the results using an independent BC cohort (GSE20685; n = 327), investigated the clinical significance of BC-specific m7G-modifying regulators by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, and performed tissue-microarray assays on 192 BC samples.

Results

Immunohistochemistry and RT-qPCR results indicated that METTL1 and WDR4 overexpression in BC correlated with poor patient prognosis. Moreover, single-cell analysis revealed relationships between m7G modification and TME cells, indicating their potential as indicators of BC prognosis and treatment responses. The m7G-TME classifier enabled patient subgrouping and revealed significantly better survival and treatment responses in the m7Glow+TMEhigh group. Significant differences in tumor biological functions and immunophenotypes occurred among the different subgroups.

Conclusions

The m7G-TME classifier offers a promising tool for predicting prognosis and immunotherapeutic responses in BC, which could support personalized therapeutic strategies.
A novel Fas ligand plays an important role in cell apoptosis of Crassostrea hongkongensis: molecular cloning, expression profiles and functional identification of ChFasL
Authors: Qin Yanping , Wan Weitao , Li Jiangwei , Wang Zhongyu , Yang Yue , Li Jun , Ma Haitao , Yu Ziniu , Xiang Zhiming , Zhang Yuehuan
Published: October 2023

Background

Apoptosis regulates normal development, homeostasis, immune tolerance and response to environmental stress by eliminating unwanted or diseased cells, and plays a key role in non-specific immunity of invertebrates. The exogenous pathway mediated by death receptors and death ligands is a very important pathway for cell apoptosis. Death ligands are mainly members of the tumour necrosis factor (TNF) family, of which FasL is an important member. The deep involvement of FasL in vertebrates cell apoptosis and immunity has been reported many times, but there is limited research on the FasL gene in shellfish, and its functional importance in oyster cell apoptosis and immunity remains unclear.

Methods

The full length of ChFasL was identified and cloned based on the genome of Crassostrea hongkongensis. Quantitative PCR was used to detect the relative expression of ChFasL in different developmental stages and tissues, as well as the changes of relative expression in hemocytes after bacterial infection. The expression position of ChFasL in HEK293T cells was also located by subcellular localization, and the effect of increased recombinant protein content on the activity of reporter genes p53 and p21 was studied by dual-fluorescence reporter gene. Finally, the changes of apoptosis rate in hemocytes after ChFasL silencing was identified by RNA interference technology.

Results

We identified a novel FasL gene from C. hongkongensis and named it ChFasL. We found that ChFasL has potential N-linked glycosylation site, a transmembrane domain and a TNF region, which was a typical characteristics of TNF family. ChFasL was expressed in all developmental stages of larvae and in all tissues of oysters. After stimulation by V. alginolyticus or S. haemolyticus, its relative expression in hemocytes increased significantly, suggesting that ChFasL was deeply engaged in the immune response process of C. hongkongensis to external microbial stimulation. The results of subcellular localization showed that ChFasL was mainly distributed in the cytoplasm of HEK293T cells. With the overexpression of the recombinant protein pcDNA3 1- ChFasL, the activity of p53 and p21 significantly increased, showing a positive regulatory effect. Moreover, after dsRNA successfully reduced the relative expression of ChFasL, the apoptosis rate of hemocytes was significantly lower than that the dsGFP group.

Conclusion

These results comprehensively confirmed the important role of ChFasL in the apoptosis process of C. hongkongensis, which provided the basis and premise for the in-depth understanding of the immune function of apoptosis in molluscs, and also contributed to the research on the pathogenic death mechanism and disease resistance breeding of marine bivalves.
Development and validation of risk prediction and neural network models for dilated cardiomyopathy based on WGCNA
Authors: Yu Wei , Li Lingjiao , Tan Xingling , Liu Xiaozhu , Yin Chengliang , Cao Junyi
Published: October 2023

Background

Dilated cardiomyopathy (DCM) is a progressive heart condition characterized by ventricular dilatation and impaired myocardial contractility with a high mortality rate. The molecular characterization of DCM has not been determined yet. Therefore, it is crucial to discover potential biomarkers and therapeutic options for DCM.

Methods

The hub genes for the DCM were screened using Weighted Gene Co-expression Network Analysis (WGCNA) and three different algorithms in Cytoscape. These genes were then validated in a mouse model of doxorubicin (DOX)-induced DCM. Based on the validated hub genes, a prediction model and a neural network model were constructed and validated in a separate dataset. Finally, we assessed the diagnostic efficiency of hub genes and their relationship with immune cells.

Results

A total of eight hub genes were identified. Using RT-qPCR, we validated that the expression levels of five key genes (ASPN, MFAP4, PODN, HTRA1, and FAP) were considerably higher in DCM mice compared to normal mice, and this was consistent with the microarray results. Additionally, the risk prediction and neural network models constructed from these genes showed good accuracy and sensitivity in both the combined and validation datasets. These genes also demonstrated better diagnostic power, with AUC greater than 0.7 in both the combined and validation datasets. Immune cell infiltration analysis revealed differences in the abundance of most immune cells between DCM and normal samples.

Conclusion

The current findings indicate an underlying association between DCM and these key genes, which could serve as potential biomarkers for diagnosing and treating DCM.
A potential adverse role for leptin and cardiac leptin receptor in the right ventricle in pulmonary arterial hypertension: effect of metformin is BMPR2 mutation-specific
Authors: Talati Megha , Brittain Evan , Agrawal Vineet , Fortune Niki , Simon Katie , Shay Sheila , Zeng Xiaofang , Freeman Michael L. , West James , Hemnes Anna
Published: October 2023

Introduction

Pulmonary arterial hypertension is a fatal cardiopulmonary disease. Leptin, a neuroendocrine hormone released by adipose tissue, has a complex relationship with cardiovascular diseases, including PAH. Leptin is thought to be an important factor linking metabolic syndrome and cardiovascular disorders. Given the published association between metabolic syndrome and RV dysfunction in PAH, we sought to determine the association between leptin and RV dysfunction. We hypothesized that in PAH-RV, leptin influences metabolic changes via leptin receptors, which can be manipulated by metformin.

Methods

Plasma leptin was measured in PAH patients and healthy controls from a published trial of metformin in PAH. Leptin receptor localization was detected in RV from PAH patients, healthy controls, animal models of PH with RV dysfunction before and after metformin treatment, and cultured cardiomyocytes with two different BMPR2 mutants by performing immunohistochemical and cell fractionation studies. Functional studies were conducted in cultured cardiomyocytes to examine the role of leptin and metformin in lipid-driven mitochondrial respiration.

Results

In human studies, we found that plasma leptin levels were higher in PAH patients and moderately correlated with higher BMI, but not in healthy controls. Circulating leptin levels were reduced by metformin treatment, and these findings were confirmed in an animal model of RV dysfunction. Leptin receptor expression was increased in PAH-RV cardiomyocytes. In animal models of RV dysfunction and cultured cardiomyocytes with BMPR2 mutation, we found increased expression and membrane localization of the leptin receptor. In cultured cardiomyocytes with BMPR2 mutation, leptin moderately influences palmitate uptake, possibly via CD36, in a mutation-specific manner. Furthermore, in cultured cardiomyocytes, the Seahorse XFe96 Extracellular Flux Analyzer and gene expression data indicate that leptin may not directly influence lipid-driven mitochondrial respiration in BMPR2 mutant cardiomyocytes. However, metformin alone or when supplemented with leptin can improve lipid-driven mitochondrial respiration in BMPR2 mutant cardiomyocytes. The effect of metformin on lipid-driven mitochondrial respiration in cardiomyocytes is BMPR2 mutation-specific.

Conclusion

In PAH, increased circulating leptin can influence metabolic signaling in RV cardiomyocytes via the leptin receptor; in particular, it may alter lipid-dependent RV metabolism in combination with metformin in a mutation-specific manner and warrants further investigation.
Prevalence of multidrug-resistant hypervirulent Klebsiella pneumoniae without defined hypervirulent biomarkers in Anhui, China: a new dimension of hypervirulence
Authors: Ali Md Roushan , Yang Yu , Dai Yuanyuan , Lu Huaiwei , He Zhien , Li Yujie , Sun Baolin
Published: October 2023

Klebsiella pneumoniae is an opportunistic pathogen that mainly causes nosocomial infections and hospital-associated pneumonia in elderly and immunocompromised people. However, multidrug-resistant hypervirulent K. pneumoniae (MDR-hvKp) has emerged recently as a serious threat to global health that can infect both immunocompromised and healthy individuals. It is scientifically established that plasmid-mediated regulator of mucoid phenotype genes (rmpA and rmpA2) and other virulence factors (aerobactin and salmochelin) are mainly responsible for this phenotype. In this study, we collected 23 MDR-hvKp isolates and performed molecular typing, whole genome sequencing, comparative genomic analysis, and phenotypic experiments, including the Galleria mellonella infection model, to reveal its genetic and phenotypic features. Meanwhile, we discovered two MDR-hvKp isolates (22122315 and 22091569) that showed a wide range of hypervirulence and hypermucoviscosity without rmpA and rmpA2 and any virulence factors. In phenotypic experiments, isolate 22122315 showed the highest hypervirulence (infection model) with significant mucoviscosity, and conversely, isolate 22091569 exhibited the highest mucoviscosity (string test) with higher virulence compared to control. These two isolates carried carbapenemase (blaKPC − 2), β-lactamase (blaOXA − 1, blaTEM − 1B), extended-spectrum β-lactamase (ESBL) genes (blaCTX − M − 15, blaSHV − 106), outer membrane protein-coding genes (ompA), fimbriae encoding genes (ecpABCDER), and enterobactin coding genes (entAB, fepC). In addition, single nucleotide polymorphism analysis indicated that both isolates, 22122315 and 22091569, were found to have novel mutations in loci FEBNDAKP_03184 (c. 2084A > C, p. Asn695Thr), and EOFMAFIB_02276 (c. 1930C > A, p. Pro644Thr), respectively. Finally, NCBI blast analysis suggested these mutations are located in the wzc of the capsule polysaccharide (cps) region and are responsible for putative tyrosine kinase. This study would be a strong reference for enhancing the current understanding of identifying the MDR-hvKp isolates that lacked both mucoid regulators and virulence factors.
Predictive value of spinal CSF volume in the preoperative assessment of patients with idiopathic normal-pressure hydrocephalus
Authors: Kudelić Nenad , Koprek Ivan , Radoš Milan , Orešković Darko , Jurjević Ivana , Klarica Marijan
Published: October 2023

Introduction

The pathophysiology, diagnosis, and management of idiopathic normal pressure hydrocephalus (iNPH) remain unclear. Although some prognostic tests recommended in iNPH guidelines should have high sensitivity and high predictive value, there is often no positive clinical response to surgical treatment.

Materials and methods

In our study, 19 patients with clinical and neuroradiological signs of iNPH were selected for preoperative evaluation and possible further surgical treatment according to the guidelines. MR volumetry of the intracranial and spinal space was performed. Patients were exposed to prolonged external lumbar drainage in excess of 10 ml per hour during 3 days. Clinical response to lumbar drainage was assessed by a walk test and a mini-mental test.

Results

Twelve of 19 patients showed a positive clinical response and underwent a shunting procedure. Volumetric values of intracranial space content in responders and non-responders showed no statistically significant difference. Total CSF volume (sum of cranial and spinal CSF volumes) was higher than previously published. No correlation was found between spinal canal length, CSF pressure, and CSF spinal volume. The results show that there is a significantly higher CSF volume in the spinal space in the responder group (n = 12) (120.5 ± 14.9 ml) compared with the non-responder group (103.1 ± 27.4 ml; n = 7).

Discussion

This study demonstrates for the first time that CSF volume in the spinal space may have predictive value in the preoperative assessment of iNPH patients. The results suggest that patients with increased spinal CSF volume have decreased compliance. Additional prospective randomized clinical trials are needed to confirm our results.
How does the recurrence-related morphology characteristics of the Pcom aneurysms correlated with hemodynamics?
Authors: Hu Xiaolong , Deng Peng , Ma Mian , Tang Xiaoyu , Qian Jinghong , Wu Gang , Gong Yuhui , Gao Liping , Zou Rong , Leng Xiaochang , Xiang Jianping , Wu Jiandong , Ding Zhiliang
Published: October 2023

Introduction

Posterior communicating artery (Pcom) aneurysm has unique morphological characteristics and a high recurrence risk after coil embolization. This study aimed to evaluate the relationship between the recurrence-related morphology characteristics and hemodynamics.

Method

A total of 20 patients with 22 Pcom aneurysms from 2019 to 2022 were retrospectively enrolled. The recurrence-related morphology parameters were measured. The hemodynamic parameters were simulated based on finite element analysis and computational fluid dynamics. The hemodynamic differences before and after treatment caused by different morphological features and the correlation between these parameters were analyzed.

Result

Significant greater postoperative inflow rate at the neck (Qinflow), relative Qinflow, inflow concentration index (ICI), and residual flow volume (RFV) were reported in the aneurysms with wide neck (>4 mm). Significant greater postoperative RFV were reported in the aneurysms with large size (>7 mm). Significant greater postoperative Qinflow, relative Qinflow, and ICI were reported in the aneurysms located on the larteral side of the curve. The bending angle of the internal carotid artery at the initiation of Pcom (αICA@PCOM) and neck diameter had moderate positive correlations with Qinflow, relative Qinflow, ICI, and RFV.

Conclusion

The morphological factors, including aneurysm size, neck diameter, and αICA@PCOM, are correlated with the recurrence-inducing hemodynamic characteristics even after fully packing. This provides a theoretical basis for evaluating the risk of aneurysm recurrence and a reference for selecting a surgical plan.
Oral diet management for carcinoma at the base of tongue with radiotherapy and chemotherapy associated dysphagia: a case report
Authors: Ding Zhen , Zhou Lingmei , Jin Kemei , Wu Runjinxing , Gui Yihua
Published: October 2023

Introduction

Tongue cancer is one of the common malignancy of the head and neck, and directly impacts chewing, swallowing, and other eating activities. Based on the evidence-based guidelines and clinical management, this paper presents nutrition management experience of a patient with tongue cancer who had a dysphagia and feeding reflux while undergoing radiotherapy and chemotherapy.

Methods

Nutritional risk screening and comprehensive nutritional assessment were performed based on the patient’s medical history, and personalized nutritional programs were developed under the guidance of the clinical pharmaceutical consensus of parenteral nutrition and nutritional treatment guidelines for patients with tumors during radiotherapy. For the management of oral feeding, the patient’s swallowing function was evaluated to manage oral feeding. Thickening powders were used to improve the consistency of the patient’s food, which successfully achieved oral feeding of the patient.

Results

The patient finally ate five meals a day by mouth, and energy requirements were met using industrialized nutritional supplements, and homogenized food was added in between the meals. The energy provided by enteral nutrition can reached approximately 60–75%. The patient’s weight and albumin levels had increased significantly at the time of discharge.

Discussion

The nutritional management of patients with dysphagia should be jointly managed by clinicians, nurses, nutritionists, and family members to effectively improve the quality of life (QOL) and nutritional status of patients. To ensure adequate nutritional supply, appropriate swallowing training may delay the deterioration of the chewing function and improve the eating experience of such patients.
Saffron extract interferes with lipopolysaccharide-induced brain activation of the kynurenine pathway and impairment of monoamine neurotransmission in mice
Authors: Monchaux de Oliveira Camille , Morael Jennifer , Guille Alexandrine , Amadieu Camille , Vancassel Sylvie , Gaudout David , Capuron Lucile , Pourtau Line , Castanon Nathalie
Published: October 2023

Background

Although activation of inflammatory processes is essential to fight infections, its prolonged impact on brain function is well known to contribute to the pathophysiology of many medical conditions, including neuropsychiatric disorders. Therefore, identifying novel strategies to selectively counter the harmful effects of neuroinflammation appears as a major health concern. In that context, this study aimed to test the relevance of a nutritional intervention with saffron, a spice known for centuries for its beneficial effect on health.

Methods

For this purpose, the impact of an acute oral administration of a standardized saffron extract, which was previously shown to display neuromodulatory properties and reduce depressive-like behavior, was measured in mice challenged with lipopolysaccharide (LPS, 830 μg/kg, ip).

Results

Pretreatment with saffron extract (6.5 mg/kg, per os) did not reduce LPS-induced sickness behavior, preserving therefore this adaptive behavioral response essential for host defense. However, it interfered with delayed changes of expression of cytokines, chemokines and markers of microglial activation measured 24 h post-LPS treatment in key brain areas for behavior and mood control (frontal cortex, hippocampus, striatum). Importantly, this pretreatment also counteracted by that time the impact of LPS on several neurobiological processes contributing to inflammation-induced emotional alterations, in particular the activation of the kynurenine pathway, assessed through the expression of its main enzymes, as well as concomitant impairment of serotonergic and dopaminergic neurotransmission.

Conclusion

Altogether, this study provides important clues on how saffron extract interferes with brain function in conditions of immune stimulation and supports the relevance of saffron-based nutritional interventions to improve the management of inflammation-related comorbidities.
Surgery after combination therapy with a tyrosine kinase inhibitor and anti-PD-1 antibody in sarcomatoid hepatocellular carcinoma: case report and literature review
Authors: Liang Bin , Huang Tao , Kuang Shao-Lei , Xie Guang-Yuan , Liu Tian-Qi , Chen Yuan-Yuan
Published: October 2023

Introduction

Although surgery is the preferred treatment for sarcomatoid hepatocellular carcinoma (SHC), the prognosis remains considerably poor due to early postoperative recurrence and metastasis. Reports on surgery after combined treatment with a tyrosine kinase inhibitor and anti-programmed cell death (PD)-1 antibody are unavailable.

Case presentation

A 69-year-old male patient with SHC was admitted to our hospital for treatment of a liver tumor that was detected on ultrasonography. Abdominal computed tomography with triple-phase enhancement revealed a lesion in the right hepatic lobe that measured 86.0 mm × 75.0 mm × 71.0 mm. Biopsy revealed a pathological diagnosis of liver sarcoma or sarcomatoid carcinoma. The patient subsequently received transcatheter arterial chemo-embolization, as he did not consent to surgery. More than two months later, he received a combination of lenvatinib with camrelizumab, as computed tomography showed an increase in the lesion size (to 123.0 mm × 90.0 mm × 80.0 mm) and lateral growth posterior to the upper pole of the right kidney. Liver resection was performed after 6 months of systemic therapy; pathological examination confirmed a diagnosis of SHC and showed extensive necrosis of tumor cells. Combined treatment with lenvatinib and camrelizumab was continued for 6 months after surgery. The patient has survived for over 24 months after initial diagnosis and is currently tumor-free.

Conclusion

Combined systemic therapy with a tyrosine kinase inhibitor and anti-PD-1 antibody may represent a feasible treatment strategy for improving resectability in cases of unresectable SHC. The outcomes with this combination may also be explored in cases of resectable SHC that have a high-risk of recurrence; this may improve the therapeutic effect.
Regorafenib alone or in combination with high/low-dose radiotherapy plus toripalimab as third-line treatment in patients with metastatic colorectal cancer: protocol for a prospective, randomized, controlled phase II clinical trial (SLOT)
Authors: Zhou Shujuan , Wang Chenchen , Shen Lijun , Wang Yan , Zhang Hui , Wu Ruiyan , Wang Yaqi , Chen Yajie , Xuan Yan , Xia Fan , Zhang Zhen , Wan Juefeng
Published: October 2023

Combination strategies to improve immunotherapy response in microsatellite stable metastatic colorectal cancer (MSS mCRC) remain an unmet need. Several single-arm clinical trials have shown promising synergistic effects between regorafenib and ICIs; however, some contradictory results have also been reported. Randomized controlled trials are needed to further validate the combination of regorafenib with ICIs. In addition, low-dose radiotherapy has been demonstrated to induce local immune responses by reprogramming the tumor microenvironment when combined with high-dose radiotherapy and ICIs. In this study, we designed a prospective, randomized, controlled phase II trial to investigate the efficacy and safety of regorafenib in combination with high/low-dose radiotherapy plus toripalimab in MSS mCRC compared to regorafenib alone. Patients with MSS metastatic adenocarcinoma of the colon or rectum will be enrolled and randomly assigned into two arms: a control arm and an experimental arm. Patients in the control arm will receive regorafenib monotherapy (120 mg once daily on days 1-21 of each 28 days cycle). Patients in the experimental arm will first receive one cycle of regorafenib (80 mg once daily on days 1-21 of each 28 days cycle) and toripalimab (240mg, q3w), followed by high-dose (4-8 fractions of 8-12Gy) and low-dose (1-10Gy at 0.5-2Gy/fraction) radiotherapy, and then continue regorafenib and toripalimab treatment. The primary endpoint is the objective response rate, and the secondary endpoints are disease control rate, duration of remission, median progress-free survival, median overall survival, and adverse events. Recruitment started in August 2023 and is ongoing.

Clinical Trial Registration

https://clinicaltrials.gov/study/NCT05963490?cond=NCT05963490&rank=1, identifier NCT05963490.
Outcomes of the addition of oral administration of curcumin-phospholipid to hyaluronic acid-based tear substitute for the treatment of dry eye disease
Authors: Borselli Massimiliano , Ferrari Fausto F. , Bianchi Pietro , Rossi Costanza , Scalzo Giovanna Carnovale , Mangialavori Domenica , Scorcia Vincenzo , Giannaccare Giuseppe
Published: October 2023

The aim of this study is to report the clinical outcomes of oral supplementation with curcumin-phospholipid in addition to hyaluronic acid-based tear substitute for the management of dry eye disease (DED). Patients with a diagnosis of DED confirmed by pathological values of both NIKBUT <10 s. and OSDI Questionnaire score > 12 were included. Patients were randomized to receive 2 different treatments: 0.25% hyaluronic acid-based tear substitute 3 time daily (Group 1) or as above plus curcumin-phosphatidylcholine complex tablets once a day (Group 2). Patients were evaluated at baseline (T0) and after 90 days of treatment (T1) by means of Keratograph for the measurement of NIKBUT, TMH, meibomian gland dropout and bulbar redness. Overall, data from 90 eyes of 45 patients were included. Group 1 consisted of 48 eyes of 24 patients, while group 2 included 42 eyes of 21 patients. When comparing median values of both groups at T0, no statistically significant differences were found for all parameters; instead for T1, statistically significant differences were found for redness and OSDI compared to Group 1. In group 1, a statistically significant reduction after the treatment was detected for Nikbut average and OSDI questionnaire; while in group 2, a statistically significant reduction after treatment was recorded for Nikbut average, bulbar redness and OSDI questionnaire. The addition of an oral supplement containing curcumin-phospholipid may help in a greater improvement of bulbar redness and subjective ocular symptoms compared to the treatment with tear substitutes alone for the management of DED.
Statistical considerations in long-term efficacy evaluation of anti-cancer therapies
Authors: Li Ruobing , Zhang Jingyi , Wang Jingzhao , Wang Jun
Published: October 2023

Anti-cancer therapy has been a significant focus of research. Developing and marketing various types and mechanisms of anti-cancer therapies benefit a variety of patients significantly. The long-term benefit to patients in evaluating the risk-benefit ratio of anti-cancer therapy has become a significant concern. This paper discusses the evaluation of long-term efficacy within the estimand framework and summarizes the various strategies for addressing potential intercurrent events. Non-proportional hazards of survival data may arise with novel anti-cancer therapies, leading to potential bias in conventional evaluation methods. This paper reviews statistical methods for addressing this issue, including novel endpoints, hypothesis testing, and efficacy estimation methods. We also discuss the influences of treatment switching. Although advanced methods have been developed to address the non-proportional hazard, they still have limitations that require continued collaborative efforts to resolve issues.
Surveying an energy landscape
Authors: Schnabel Stefan , Janke Wolfhard
Published: October 2023

We derive a formula that expresses the density of states of a system with continuous degrees of freedom as a function of microcanonical averages of squared gradient and Laplacian of the Hamiltonian. This result is then used to propose a novel flat-histogram Monte Carlo algorithm, which is tested on a three-dimensional system of interacting Lennard-Jones particles, the O(n) vector spin model on hypercubic lattices in D = 1 to 5 dimensions, and the O(3) Heisenberg model on a triangular lattice featuring frustration effects.