bluuebunny/crossref_metadata_2025 huggingface dataset:
ANALISIS REGRESI DATA PANEL PADA FAKTOR-FAKTOR YANG MEMPENGARUHI TINGKAT KEMISKINAN SULAWESI TENGGARA TAHUN 2017-2020
Authors: Hijrawati Hijrawati , Adi Wibawa Gusti , Yahya Irma , Baharuddin Baharuddin , Arviana Rahman Gusti , Agusrawati Agusrawati
Published: April 2023

Tingkat kemiskinan adalah persentase jumlah penduduk yang berada di bawah garis kemiskinan. Tingkat kemiskinan yang tinggi memberikan dampak negatif bagi pembangunan ekonomi negara. Sulawesi Tenggara merupakan salah satu provinsi yang ada di Indonesia dan juga mengalami masalah kemiskinan. oleh karena itu, dalam penelitian ini membahas tentang analisis regresi data panel pada faktor-faktor yang mempengaruhi tingkat kemiskinan Provinsi Sulawesi Tenggara tahun 2017-2020. Penelitian ini dilakukan dengan tujuan untuk mengetahui faktor-faktor yang mempengaruhi tingkat kemiskinan Provinsi Sulawesi Tenggara tahun 2017-2020 menggunakan analisis regresi data panel. Analisis regresi data panel merupakan gabungan antara data cross section dan data time series. Model regresi data panel yang diperoleh dari estimasi Generalized Least Square yaitu dengan pendekatan random effect model. Hasil penelitian menunjukan bahwa variabel rata-rata lama sekolah  dan tingkat pengangguran terbuka berpengaruh signifikan terhadap tingkat kemiskinan (Y) di Provinsi Sulawesi Tenggara tahun 2017-2020.
PROFIL PENGGUNA ALAT KONTRASEPSI DI PROVINSI SULAWESI TENGGARA DENGAN ALGORITMA K-MEANS TERORGANISIR
Authors: Lapandewa Asti , Agusrawati Agusrawati , Adi Wibawa Gusti , Abapihi Bahriddin , Baharuddin Baharuddin
Published: April 2023

Tujuan penelitian ini adalah untuk mengetahui profil pengguna alat kontrasepsi berdasarkan kabupaten/kota di Provinsi Sulawesi Tenggara, karena pengguna alat kontasepsi yang bervariasi atau berbeda beda di setiap kabupaten/kota, maka untuk mengatasinya dibutuhkan metode dalam menganalisis data pengguna alat kontrasepsi. Salah satu metode yang dapat  digunakan adalah penggerombolan. Pada penelitian ini diterapkan metode penggerombolan dengan algoritma K-Means terorganisir. Hasil penggerombolan terbaik adalah algotirma  pautan tunggal dengan K-Means dengan  banyaknya gerombol ialah 3 gerombol berdasarkan Bayesian Information Criterion (BIC). Gerombol 1 termasuk dalam pengguna alat kontrasepsi rendah berisi 12 Kabupaten/Kota yaitu Buton, Bombana, Wakatobi, Kolaka Utara, Buton Utara, Konawe Utara, Kolaka Timur, Konawe Kepulauan, Muna Barat, Buton Tengah, Buton Selatan, Kota Bau-Bau, Gerombol 2 termasuk pengguna alat kontrasepsi sedang berisi 3 Kabupaten/Kota yaitu  Konawe, Kolaka, Konawe Selatan dan gerombol 3 termasuk pengguna alat kontrasepsi tinggi berisi 2 Kabupaten/Kota yaitu Muna dan Kota Kendari.
PENGARUH FORMULASI TEPUNG SAGU (Metroxylon sp.), TEPUNG TAPIOKA DAN TEPUNG BERAS MERAH (Oryza nivara) TERHADAP NILAI ORGANOLEPTIK DAN NILAI GIZI NUGGET IKAN CAKALANG (Katsuwonus pelamis
Authors: Haerul Andi , Ansharullah Ansharullah , Sadimantara Muhammad Syukri
Published: April 2023

ABSTRACT The purpose of this study was to determine the effect of sago flour, tapioca flour, and red rice flour formulations on the organoleptic characteristics and nutritional value of skipjack tuna nuggets. This study used a completely randomized design (CRD), namely A0 (100% tapioca flour), A1 (50% tapioca flour: 25% sago flour: 25% red rice flour), A2 (50% tapioca flour: 30% sago flour: 20% red rice flour), A3 (50% tapioca flour: 35% sago flour: 15% red rice flour), and A4 (50% tapioca flour: 40% sago flour: 10% red rice flour). Data were analyzed using analysis of variance (ANOVA) and continued with Duncan's multiple range test (DMRT) at a confidence level of 95% (α=0.05). The results show that the best treatment for skipjack tuna nuggets was A3 (50 % tapioca flour: 35 % sago flour: 15 % red rice flour) with average preference scores for color, aroma, texture, and taste reaching 3.80 (like), 3.61 (like), 3.84 (like), and 3.77 (like), respectively. The nutritional value analysis of the A3 skipjack tuna nugget product shows that it contained 45.73% water, 2.18% ash, 13.33% fat, 12.02% protein, and 26.74% carbohydrate, respectively. The results show that the skipjack tuna nugget product was accepted (liked) by the panelists and met the national quality standard for water, ash, fat, protein, and carbohydrate contents. Keywords: sago flour, tapioca flour, red rice flour, fish nuggets ABSTRAK Tujuan penelitian ini untuk mengetahui pengaruh formulasi tepung sagu, tepung tapioka dan tepung beras merah terhadap nilai organoleptik dan nilai gizi nugget ikan cakalang. Penelitian ini menggunakan Rancangan Acak Lengkap (RAL) yaitu A0 (tepung tapioka 100 %), A1 (tepung tapioka 50 % : tepung sagu 25 % : tepung beras merah 25 %), A2 (tepung tapioka 50 % : tepung sagu 30 % : tepung beras merah 20 %), A3 (tepung tapioka 50 % : tepung sagu 35 % : tepung beras merah 15 %), A4 (tepung tapioka 50 % : tepung sagu 40 % : tepung beras merah 10 %). Data dianalisis menggunakan analysis of varian (ANOVA) dan dilanjutkan dengan uji duncan’s multiple range test (DMRT) pada taraf kepercayaan 95 % (α=0,05).Hasil penelitian yang diperoleh menunjukkan bahwa perlakuan terbaik nugget ikan cakalang yaitu A3 (tepung tapioka 50 % : tepung sagu 35 % : tepung beras merah 15 %) dengan rata-rata kesukaan terhadap warna 3,80 (suka), aroma 3,61 (suka), tekstur 3,84 (suka) dan rasa 3,77(suka). Analisis nilai gizi produk nugget ikan cakalang terpilih A3 meliputi kadar air (45,73 %), kadar abu (2,18 %), Kadar lemak (13,33 %), kadar protein (12,02 %) dan kadar karbohidrat (26,74 %). Berdasarkan hasil penelitian produk nugget ikan cakalang dapat diterima (disukai) oleh panelis dan telah memenuhi syarat mutu SNI terhadap kadar air, kadar abu, kadar lemak, kadar protein dan kadar karbohidrat. Kata kunci: tepung sagu, tepung tapioka, tepung beras merah, nugget ikan
Staten, marknaden och industripolitikens återupprättelse: Visioner om transportsystemets klimatomställning, 2006-2022
Authors: Haikola Simon , Anshelm Jonas
Published: April 2023

Trots upprepade politiska utfästelser om att transportsystemet ska bli fossilfritt har dess omställning gått trögt. Det har länge funnits en påtaglig kontrast mellan visionerna för transportsystemets omställning och de faktiskt vidtagna åtgärderna. De dominerande förklaringarna till denna kontrast, liksom föreställningarna om vad som kan göras, har skiftat över tid och beroende på vilken regering som suttit vid makten. I grunden kretsar de emellertid alltid kring samma frågor: Hur väl rustat är det svenska planeringssystemet för att genomföra en fundamental omställning av transporterna? I vilken omfattning kräver transportsystemets omställning en mer djupgående förändring av samhället? Vilken roll bör stat och marknad ha i transportsystemets omställning? I denna bok skildrar vi hur den offentliga diskussionen om transportsystemet förändrats under de fyra olika regeringar som suttit vid makten mellan 2006-2022. Genom att följa formuleringen av politiska visioner i statliga utredningar och hur dessa visioner diskuterats i den offentliga debatten visar vi hur en period av utpräglat marknadsliberal politik utmanas av klimatkeynesianistiska idéer. Samtidigt har hela undersökningsperioden karakteriserats av betydande institutionella låsningar.
Critical Study of Rita Wahyu’s Interpretation of Matthew 1:20 - Is Jesus Christ the Holy Spirit?
Authors: Laia Harman Ziduhu , Basuki Ponco Mujiono , Wibowo Daniel Ari
Published: April 2023

An article titled “Yesus dan Roh Kudus” written by Rita Wahyu and published on the website “Sarapan Pagi Biblikal” became highly controversial in 2021, particularly regarding her interpretation of the text in Matthew 1:20. The article contains elements of Modalism, Modalistic Monarchianism, or Sabellianism, which teach about the Oneness of God, meaning that God has one nature and one person with three names: the Father, the Son, and the Holy Spirit. Rita emphasizes her thesis on the preposition ἐκ in the text, which she believes should be interpreted as “of” in English, indicating that the child in Mary’s womb is the Holy Spirit. However, research on the preposition ἐκ in Matthew 1:20 using exegetical methods based on Biblical grammattical laws shows that Rita’s interpretation lacks a basis that can be sustained exegetically. Her interpretation of the preposition is eisegesis, not exegesis. From an exegetical standpoint, the preposition ἐκ in the text indicates the source or origin of the child; the cause or agent of Mary’s pregnancy; and/or the giver of the seed of the baby in Mary’s womb, namely the Holy Spirit.
Deep‐Learning-Based Uncertainty Analysis of Flat Plate Film Cooling With Application to Gas Turbine
Authors: Wang Yaning , Qiu Xubin , Qian Shuyang , Sun Yangqing , Wang Wen , Cui Jiahuan
Published: April 2023

Nowadays, gas turbines intake jet air at high temperatures to improve the power output as much as possible. However, the excessive temperature typically puts the blade in the face of unpredictable damage. Film cooling is one of the prevailing methods applied in engineering scenarios, with the advantages of a simple structure and high cooling efficiency. This study aims to assess the uncertain effect that the three major film cooling parameters exert on the global and fixed-cord-averaged film cooling effectiveness under low, medium, and high blowing ratios br. The three input parameters include coolant hole diameter d, coolant tube inclination angle θ, and density ratio dr. The training dataset is obtained by Computational Fluid Dynamics (CFD). Moreover, a seven-layer artificial neural network (ANN) algorithm is applied to explore the complex non-linear mapping between the input flat film cooling parameters and the output fixed-cord-averaged film cooling effectiveness on the external turbine blade surface. The sensitivity experiment conducted using Monte Carlo (MC) simulation shows that the d and θ are the two most sensitive parameters in the low-blowing-ratio cases. The θ comes to be the only leading factor of sensitivity in larger blowing ratio cases. As the blowing ratio rises, the uncertainty of the three parameters d, θ, and dr all decrease. The combined effect of the three parameters is also dissected and shows that it has a more significant influence on the general cooling effectiveness than any single effect. The d has the widest variation of uncertainty interval at three blowing ratios, while the θ has the largest uncertain influence on the general cooling effectiveness. With the aforementioned results, the cooling effectiveness of the gas turbine can be furthermore enhanced.
Comparison of percutaneous closure systems for large bore vascular access sites in endovascular procedures
Authors: Košak Luka , Lulić Davorka , Jakljević Tomislav , Gobić David , Aničić Josip , Tomulić Vjekoslav
Published: April 2023

Backgrounds

The vascular closure device (VCD) is a medical device used for achieving hemostasis of vascular access sites greater than 8 Fr. We compared complications after placement of Perclose ProGlide (Abbott Vascular, USA), a percutaneous suture-mediated closure system, with MANTA VCD (Teleflex Vascular, USA), a collagen-based closure device.

Methods

This retrospective cohort study analyzed procedures performed between 2016 and 2021. We compared the incidence of bleeding complications according to the Bleeding Academic Research Consortium (BARC) and Valve Academic Research Consortium-3 (VARC-3) criteria. The comparison was made between two cohorts of patients: in the first, vascular access sites were closed with a double Perclose ProGlide system, and in the second with an 18 Fr MANTA VCD.

Results

A total of 189 patients were included in the study, out of which 63% were male and 37% were female, with a median age of 79 (72–83) years. All devices were used for femoral arterial access closure. A double Perclose ProGlide was used in 91 (48%) patients, while MANTA VCD was used in 98 patients (52%). The distribution of patients by VARC-3 and BARC bleeding criteria differs between groups (p = 0.017). A significantly higher incidence of VARC 1 (14% vs. 4%; p = 0.020) and BARC 1–2 (14% vs. 4%; p = 0.020) complications in the Perclose ProGlide cohort was observed. VARC 3 (1% vs. 5%; p = 0.213) and BARC 3b (1% vs. 5%; p = 0.213) complications showed higher, but statistically non-significant rates of major bleeding complications in the MANTA VCD cohort. The need for subsequent surgical revision did not show a significant difference between the cohorts (2% vs. 6%; p = 0.281).

Conclusion

The Perclose ProGlide cohort was associated with a significantly higher rate of milder complications. MANTA VCD cohort had a higher rate of major bleeding complications, requiring more complex treatment with a potentially larger impact on quality of life.
Active tectonics and paleo-earthquakes in north Yumu Shan, northern Tibetan Plateau: Insights from structural analysis and radiocarbon dating
Authors: Wang Ye , Chen Xuanhua , He Chengguang , Xiao Yongjun , Shao Zhaogang , Han Jian’en , Li Bing , Zhang Yiping , Ding Weicui , Xu Shenglin , Han Lele
Published: April 2023

The Yumu Shan is located at the northern margin of the Tibetan Plateau in northwest China. It is characterized by the development of several northeastward-protruding arcuate geomorphic bulge belts on its north slope. These bulge belts are distributed along the Wutongquan spring, the ancient Camel City, and the Xiaogengzi area, and south to Gaotai City in the Hexi Corridor. In this study, our detailed field mapping and structural analysis reveal northeastward active anticline folding along the curved bulge belts and related lacustrine sediments in their hinterlands. Radiocarbon dating of plant charcoal samples from lacustrine sedimentary layers yields a 14C age of AD 178 ± 42. This age is close to the time of the 180AD/Ms7.5 earthquake at Biaoshi City (i.e., the ancient Zhangye City) during the Eastern Han Dynasty. The similarity between seismic events and sedimentary age leads us to infer that the charcoal in the lacustrine layer records a major flood event related to the Biaoshi earthquake. We propose a fault-related fold model for the formation of the arcuate bulge belts and related sediments. First, a series of historical earthquake activities in the Holocene, especially the 180AD/Ms7.5 Biaoshi earthquake, may have led to active blind thrust faulting in the northern margin of the plateau. Then, blind thrusting may have resulted in fault-related anticline folding, causing the formation of geomorphic bulges. The latter acts as a flood-retaining dam, resulting in hinterland deposition of lacustrine sediments. For this reason, we suggest that seismogenic blind thrust faulting is responsible for the uplift and northward growth of the Tibetan Plateau. As the northernmost blind thrust in this area, the Xiaogengzi Fault could be considered the North Boundary Thrust (NBT), which defines exactly the northern margin of the plateau.
Anoikis in phenotypic reprogramming of the prostate tumor microenvironment
Authors: Nepali Prerna R. , Kyprianou Natasha
Published: April 2023

Prostate cancer is one of the most common malignancies in males wherein 1 in 8 men are diagnosed with this disease in their lifetime. The urgency to find novel therapeutic interventions is associated with high treatment resistance and mortality rates associated with castration-resistant prostate cancer. Anoikis is an apoptotic phenomenon for normal epithelial or endothelial cells that have lost their attachment to the extracellular matrix (ECM). Tumor cells that lose their connection to the ECM can die via apoptosis or survive via anoikis resistance and thus escaping to distant organs for metastatic progression. This review discusses the recent advances made in our understanding of the signaling effectors of anoikis in prostate cancer and the approaches to translate these mechanistic insights into therapeutic benefits for reducing lethal disease outcomes (by overcoming anoikis resistance). The prostate tumor microenvironment is a highly dynamic landscape wherein the balance between androgen signaling, cell lineage changes, epithelial-mesenchymal transition (EMT), extracellular matrix interactions, actin cytoskeleton remodeling as well as metabolic changes, confer anoikis resistance and metastatic spread. Thus, these mechanisms also offer unique molecular treatment signatures, exploitation of which can prime prostate tumors to anoikis induction with a high translational significance.
Sulfate reduction and homoacetogenesis at various hypersaline conditions: Implications for H2 underground gas storage
Authors: Schwab Laura , Prinsen Lilian , Nowack Guido , Popp Denny , Noll Matthias , Vogt Carsten , Wagner Martin
Published: April 2023

While interest in underground gas storage (UGS) of hydrogen (H2) in salt caverns is increasing in a growing H2 economy, knowledge of the microbial communities inhabiting those hypersaline environments is still scarce. High salt concentrations and limited availability of carbon (C) sources in cavern environments reduce microbial growth rates and metabolic activities. Growth conditions potentially change once H2 is stored in salt caverns. H2 is a universal electron donor that can facilitate autotrophic growth and subsequently growth of heterotrophs. In this study, a mixed culture enriched from hypersaline UGS sites was investigated in microcosm experiments with H2 atmosphere, testing the effect of different salt concentrations and C sources on methanogenesis, sulfate reduction and homoacetogenesis. Sulfate, acetate and lactate concentrations were quantified throughout a time span of 125 days of incubation and correlations with the microbial community structure and function were explored through 16S rRNA gene-based amplicon sequencing at the end of the experiment. Many of the amplicon sequence variants (ASVs) were only assigned to family or order level, reflecting that a large number of ASVs belong to previously undescribed taxa. At 4.4 M NaCl, close to cavern brine salinity, members of the Desulfovibrionales were absent when no C source other than CO2 was offered as the sole C source. This is in line with the finding that no sulfate reduction occurred at these conditions. Acetogenic Halanaerobiia dominated in these high salinity levels. Based on metagenome sequencing of four selected samples, we found that acetogenesis at autotrophic conditions relies on the activity of a halophilic homoacetogen, Acetohalobium sp. and that sulfate reduction can most likely be associated with a so far undescribed member of the Desulfonatronovibrionales. We further discuss the discrepancy between sulfate reduction at heterotrophic conditions, while no sulfate reduction was observed under autotrophic conditions although acetate was produced through the homoacetogenic activity of Acetohalobium. For the application of UGS of H2, this means that the presence and activity of the aforementioned microorganisms must be investigated, as they can eventually lead to the formation of acetate and allow sulfate reduction at relevant concentrations.
Morphological variation across space does not predict phenotypic change through time in two Neogene planktonic foraminifera species
Authors: Brombacher Anieke , Wilson Paul A. , Bailey Ian , Ezard Thomas H. G.
Published: April 2023

Introduction

Lines of least resistance, or the direction of maximum phenotypic variation, are reliable predictive tools for directions of evolutionary divergence through time. However, the consistency of trait covariation patterns through space, i.e. in different populations of the same taxa inhabiting different environmental settings, remains poorly established.

Methods

To test whether the predicted direction of evolutionary change is the same through time as it is across space, we compare within- and among-population trait covariation patterns across six Atlantic populations of two planktonic foraminifera species. Our study interval is 600,000 years long, spans the Neogene/Quaternary boundary and includes Earth’s most recent major natural shift in global climate state: the intensification of Northern Hemisphere Glaciation.

Results

We show that, despite powerful global temporal changes in climate, there is a strong spatial signal in the evolutionary response. Population-specific trait covariation slopes vary among sites, climate phases and core/edge position within the species’ biogeographic range.

Discussion

Our results imply that the direction of expected evolutionary change does not align across populations. This suggests that trait covariation patterns in the study species are driven by adaptation to local environmental settings rather than species-wide constraints. Single populations should therefore not be used to predict the response of other populations, even if they are faced with similar environmental conditions. We caution against using individual populations to project future response of other/global populations unless the underlying mechanism for trait covariation is shown to be universal.
Identification of new immune subtypes of renal injury associated with anti-neutrophil cytoplasmic antibody–associated vasculitis based on integrated bioinformatics analysis
Authors: Lin Lizhen , Ye Keng , Chen Fengbin , Xie Jingzhi , Chen Zhimin , Xu Yanfang
Published: April 2023

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease that may lead to end-stage renal disease. However, few specifific biomarkers are available for AAV-related renal injury. The aim of this study was to identify important biomarkers and explore new immune subtypes of AAV-related renal injury.

Methods: In this study, messenger RNA expression profiles for antibody-associated vasculitis and AAV-associated kidney injury were downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed to identify the most relevant module genes to AAV. Key module genes from WGCNA were then intersected with AAV- and nephropathy-related genes from the Genecards database to identify key genes for AAV-associated kidney injury. Subsequently, the expression of key genes was validated in independent datasets and the correlation of genes with clinical traits of kidney injury was verified by the Nephroseq database. Finally, non-negative matrix factorization (NMF) clustering was performed to identify the immune subtypes associated with the key genes.

Results: Eight co-key genes (AGTR2, ANPTL2, BDKRB1, CSF2, FGA, IL1RAPL2, PCDH11Y, and PGR) were identifified, and validated the expression levels independent datasets. Receiver operating characteristic curve analysis revealed that these eight genes have major diagnostic value as potential biomarkers of AAV-related renal injury. Through our comprehensive gene enrichment analyses, we found that they are associated with immune-related pathways. NMF clustering of key genes identified two and three immune-related molecular subtypes in the glomerular and tubular data, respectively. A correlation analysis with prognostic data from the Nephroseq database indicated that the expression of co-key genes was positively co-related with the glomerular filtration rate.

Discussion: Altogether, we identifified 8 valuable biomarkers that firmly correlate with the diagnosis and prognosis of AAV-related renal injury. These markers may help identify new immune subtypes for AAV-related renal injury.
Housing and integration of internally displaced persons: The case of Ukraine in 2018
Authors: Zavisca Jane R. , Mitchneck Beth , Gerber Theodore P.
Published: April 2023

Housing is a widely recognized yet understudied domain of integration of internally displaced persons (IDPs) into their new communities. This article examines the role of housing for integration of Ukrainian IDPs displaced by Russia-fueled political violence in Eastern Ukraine that started in 2014 or by Russia's annexation of Crimea that year. In Ukraine, housing holds particular significance for integration because homeownership is both widespread and a vital source of people's sense of wellbeing, security, and normalcy. Our evidence comes from an original 2018 survey of housing experiences of both IDPs and long-term residents in IDPs' new localities. The survey design enables us to assess housing integration relationally, by comparing gaps in housing status and subjective housing-related wellbeing between IDPs and locals. We find that for IDPs in protracted displacement, deprivation of culturally normative housing conditions, particularly homeownership, impeded both material and experiential housing integration. Disparities in housing status drive differences in subjective experience, ranging from satisfaction with one's housing to feeling at home in one's community. These results from our 2018 study may help anticipate challenges of the massive, nationwide displacement crisis precipitated by Russia's 2022 invasion of Ukraine. Whether Ukrainians resettle in new communities or return to their old ones, divisions between those who have homes to return to and those who do not are likely to be salient. Policies aimed at restoring housing resources, particularly pathways to homeownership, will be essential to rebuilding Ukraine.
RIPK1 in the inflammatory response and sepsis: Recent advances, drug discovery and beyond
Authors: Liu Xiaoyu , Tang A-Ling , Chen Jie , Gao Nan , Zhang Guoqiang , Xiao Cheng
Published: April 2023

Cytokine storms are an important mechanism of sepsis. TNF-α is an important cytokine. As a regulator of TNF superfamily receptors, RIPK1 not only serves as the basis of the scaffold structure in complex I to promote the activation of the NF-κB and MAPK pathways but also represents an important protein in complex II to promote programmed cell death. Ubiquitination of RIPK1 is an important regulatory function that determines the activation of cellular inflammatory pathways or the activation of death pathways. In this paper, we introduce the regulation of RIPK1, RIPK1 PANoptosome’s role in Inflammatory and sepsis, and perspectives.
Identification of cuproptosis-associated subtypes and signature genes for diagnosis and risk prediction of Ulcerative colitis based on machine learning
Authors: Tang Dadong , Pu Baoping , Liu Shiru , Li Hongyan
Published: April 2023

Background

Ulcerative colitis (UC) is a chronic and debilitating inflammatory bowel disease that impairs quality of life. Cuproptosis, a recently discovered form of cell death, has been linked to many inflammatory diseases, including UC. This study aimed to examine the biological and clinical significance of cuproptosis-related genes in UC.

Methods

Three gene expression profiles of UC were obtained from the Gene Expression Omnibus (GEO) database to form the combined dataset. Differential analysis was performed based on the combined dataset to identify differentially expressed genes, which were intersected with cuproptosis-related genes to obtain differentially expressed cuproptosis-related genes (DECRGs). Machine learning was conducted based on DECRGs to identify signature genes. The prediction model of UC was established using signature genes, and the molecular subtypes related to cuproptosis of UC were identified. Functional enrichment analysis and immune infiltration analysis were used to evaluate the biological characteristics and immune infiltration landscape of signature genes and molecular subtypes.

Results

Seven signature genes (ABCB1, AQP1, BACE1, CA3, COX5A, DAPK2, and LDHD) were identified through the machine learning algorithms, and the nomogram built from these genes had excellent predictive performance. The 298 UC samples were divided into two subtypes through consensus cluster analysis. The results of the functional enrichment analysis and immune infiltration analysis revealed significant differences in gene expression patterns, biological functions, and enrichment pathways between the cuproptosis-related molecular subtypes of UC. The immune infiltration analysis also showed that the immune cell infiltration in cluster A was significantly higher than that of cluster B, and six of the characteristic genes (excluding BACE1) had higher expression levels in subtype B than in subtype A.

Conclusions

This study identified several promising signature genes and developed a nomogram with strong predictive capabilities. The identification of distinct subtypes of UC enhances our current understanding of UC’s underlying pathogenesis and provides a foundation for personalized diagnosis and treatment in the future.
Evolving approaches to profiling the microbiome in skin disease
Authors: Chen Yang , Knight Rob , Gallo Richard L.
Published: April 2023

Despite its harsh and dry environment, human skin is home to diverse microbes, including bacteria, fungi, viruses, and microscopic mites. These microbes form communities that may exist at the skin surface, deeper skin layers, and within microhabitats such as the hair follicle and sweat glands, allowing complex interactions with the host immune system. Imbalances in the skin microbiome, known as dysbiosis, have been linked to various inflammatory skin disorders, including atopic dermatitis, acne, and psoriasis. The roles of abundant commensal bacteria belonging to Staphylococcus and Cutibacterium taxa and the fungi Malassezia, where particular species or strains can benefit the host or cause disease, are increasingly appreciated in skin disorders. Furthermore, recent research suggests that the interactions between microorganisms and the host’s immune system on the skin can have distant and systemic effects on the body, such as on the gut and brain, known as the “skin-gut” or “skin-brain” axes. Studies on the microbiome in skin disease have typically relied on 16S rRNA gene sequencing methods, which cannot provide accurate information about species or strains of microorganisms on the skin. However, advancing technologies, including metagenomics and other functional ‘omic’ approaches, have great potential to provide more comprehensive and detailed information about the skin microbiome in health and disease. Additionally, inter-species and multi-kingdom interactions can cause cascading shifts towards dysbiosis and are crucial but yet-to-be-explored aspects of many skin disorders. Better understanding these complex dynamics will require meta-omic studies complemented with experiments and clinical trials to confirm function. Evolving how we profile the skin microbiome alongside technological advances is essential to exploring such relationships. This review presents the current and emerging methods and their findings for profiling skin microbes to advance our understanding of the microbiome in skin disease.
Downregulated ESRP1/2 promotes lung metastasis of bladder carcinoma through altering FGFR2 splicing and macrophage polarization
Authors: Zhao Yuyang , Li Mingyang , Wu Wenbo , Miao Wenhao , Liu Haitao
Published: April 2023

Introduction

Lung metastasis occurs in parts of the bladder carcinoma (BC) patients but represents the highest severity and a poor outcome of the disease. The molecular mechanism underlying lung metastasis of BC is not fully understood. Fibroblast growth factor receptor 2 (FGFR2) signaling plays a substantial role in the BC cell growth and invasion. In this study, we assessed the regulation of the alternative splicing of FGFR2 by epithelial splicing regulatory proteins (ESRPs) in lung metastasis of BC.

Methods

Gene profile of BC in comparison with adjacent non-tumor bladder tissue was obtained from GEO public database to analyze the levels of differentiated genes and pathways. Moreover, the association of ESRP1 or ESRP2 with lung metastasis of BC was analyzed on our own clinic samples. The effects of altered expression of ESRP1 or ESRP2 on alternative splicing of FGFR2 IIIb and IIIc, which represents epithelial and mesenchymal-like splicing, were analyzed on BC cell lines T24 and RT4. The in vivo effects of ESRP1 or ESRP2 on lung metastasis of BC were assessed in mice subcutaneously grafted with ESRP1/2-modified BC labeled with fluorescent and luciferase reporters.

Results

We detected significant reduction of ESRP1 and ESRP2 in BC in public database of BC specimens. Moreover, analysis on our own specimens also showed strong downregulation of ESRP1 or ESRP2 in BC, and the latter was more pronounced in cases with lung metastasis. In vitro, altered levels of ESRP1 or ESRP2 caused a switch of FGFR2 splicing between FGFR2-IIIb and FGFR2-IIIc, resulting in changes in tumor cell growth and metastatic potential. In vivo, re-expression of ESRP1 or ESRP2 in BC cells not only inhibited the growth of the xenografted tumor formation in nude mice, but also reduced the occurrence of lung metastasis, partially through altering polarization of tumor-associated macrophages.

Conclusion

Our data thus suggest that reduction in ESRP1 or ESRP2 promotes lung metastasis of BC through altering FGFR2 splicing and macrophage polarization.
Oyster aquaculture cages provide fish habitat similar to natural structure with minimal differences based on farm location
Authors: Mercaldo-Allen Renee , Auster Peter J. , Clark Paul , Dixon Mark S. , Estela Erick , Liu Yuan , Milke Lisa , Phillips Gillian , Redman Dylan , Smith Barry C. , Verkade Alison , Rose Julie M.
Published: April 2023

Oyster aquaculture gear may augment natural seafloor by providing structured habitat for economically important fish species. Underwater video census was used to assess fish abundance and community composition on eastern oyster (Crassostrea virginica) shelf and bag style aquaculture off-bottom cages and within natural rock reef habitat. During 2018, underwater cameras were mounted on four study cages at a dense shellfish farm of 40-100 commercial cages (dense cage farm), on four single cages interspersed on low relief seafloor (sparse cage farm), and amongst four boulders on a rock reef (rock reef), within an embayment off Milford, Connecticut, which is part of Long Island Sound, in the United States. In 2019, cameras were similarly deployed on two study cages per farm at each of three shellfish farms off Milford, Norwalk and Westport, CT. Video was recorded hourly in eight-minute segments from 7 am to 7 pm. Data loggers monitored seawater temperature, light intensity, and current speed. Fish abundance (MaxN) was calculated for all videos. We compared fish abundance and community composition between May and September, on cage and boulder habitat, on cages at dense and sparse farms and on cages across farm locations. In 2018, abundance of black sea bass (Centropristis striata), scup (Stenotomus chrysops) and tautog (Tautoga onitis) was significantly higher on cages than boulders, regardless of cage number. Cunner (Tautogolabrus adspersus) abundance was significantly higher on boulders than cages when cage sites were grouped. However pairwise comparisons indicated that cunner were significantly higher at the sparse cage farm versus the rock reef but cunner abundance on the dense cage farm and rock reef sites was not significantly different. Abundance of black sea bass, scup, tautog, and cunner were not significantly different across 2019 farm locations. Young-of-the-year fish occurred episodically at all sites during both years, with black sea bass and scup most abundant. Fish abundance corresponded to seasonal changes in seawater temperature and was highest at the warmest temperatures. Light intensity and current speed explained less variation in fish abundance relative to temperature, and relationships were inconsistent across habitats and farm locations Our results suggest that multi-tiered oyster aquaculture cages contribute structure to seafloor environments that provide habitat for temperate reef fish similar to natural rock reefs.
Tracing timing of growth in cultured molluscs using strontium spiking
Authors: de Winter Niels J. , van Sikkeleras Sterre , Goudsmit-Harzevoort Barbara , Boer Wim , de Nooijer Lennart , Reichart Gert-Jan , Claeys Philippe , Witbaard Rob
Published: April 2023

Introduction

Growth experiments present a powerful tool for determining the effect of environmental parameters on growth and carbonate composition in biogenic calcifiers. For successful proxy calibration and biomineralization studies, it is vital to identify volumes of carbonate precipitated by these organisms at precise intervals during the experiment. Here, we investigate the use of strontium labelling in mollusc growth experiments.

Methods

Three bivalve species (Cerastoderma edule, Mytilus edulis and Ostrea edulis) were grown under monitored field conditions. The bivalves were regularly exposed to seawater with elevated concentrations of dissolved strontium chloride (SrCl2). In addition, the size of their shells was determined at various stages during the experiment using calliper measurements and digital photography. Trace element profiles were measured in cross sections through the shells of these molluscs using laser ablation ICPMS and XRF techniques.

Results

Our results show that doses of dissolved strontium equivalent to 7-8 times the background marine value (~0.6 mmol/L) are sufficient to cause reproducible peaks in shell-incorporated strontium in C. edule and M. edulis shells. No negative effects were observed on shell calcification rates. Lower doses (3-5 times background values) resulted in less clearly identifiable peaks, especially in M. edulis. Strontium spiking labels in shells of O. edulis are more difficult to detect, likely due to their irregular growth.

Discussion

Strontium spiking is a useful technique for creating time marks in cultured shells and a reproducible way to monitor shell size during the growing season while limiting physical disturbance of the animals. However, accurate reconstructions of growth rates at high temporal resolution require frequent spiking with high doses of strontium.
Alterations of the intestinal microbiota in age-related macular degeneration
Authors: Zhang Yuanyuan , Wang Tianyu , Wan Zhongqi , Bai Jianhao , Xue Yawen , Dai Rushun , Wang Minli , Peng Qing
Published: April 2023

Purpose

Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50. Recently, intestinal microbiota has been reported to be involved in the pathogenesis of ocular diseases. The purpose of this study was to discover more about the involvement of the intestinal microbiota in AMD patients.

Methods

Fecal samples from 30 patients with AMD (AMD group) and 17 age- and sex-matched healthy controls (control group) without any fundus disease were collected. DNA extraction, PCR amplification, and 16S rRNA gene sequencing of the samples were performed to identify intestinal microbial alterations. Further, we used BugBase for phenotypic prediction and PICRUSt2 for KEGG Orthology (KO) as well as metabolic feature prediction.

Results

The intestinal microbiota was found to be significantly altered in the AMD group. The AMD group had a significantly lower level of Firmicutes and relatively higher levels of Proteobacteria and Bacteroidota compared to those in the control group. At the genus level, the AMD patient group showed a considerably higher proportion of Escherichia-Shigella and lower proportions of Blautia and Anaerostipes compared with those in the control group. Phenotypic prediction revealed obvious differences in the four phenotypes between the two groups. PICRUSt2 analysis revealed KOs and pathways associated with altered intestinal microbiota. The abundance of the top eight KOs in the AMD group was higher than that in the control group. These KOs were mainly involved in lipopolysaccharide biosynthesis.

Conclusion

The findings of this study indicated that AMD patients had different gut microbiota compared with healthy controls, and that AMD pathophysiology might be linked to changes in gut-related metabolic pathways. Therefore, intestinal microbiota might serve as non-invasive indicators for AMD clinical diagnosis and possibly also as AMD treatment targets.
The novel two-component system AmsSR governs alternative metabolic pathway usage in Acinetobacter baumannii
Authors: Casella Leila G. , Torres Nathanial J. , Tomlinson Brooke R. , Shepherd Mark , Shaw Lindsey N.
Published: April 2023

In this study, we identify a novel two-component system in Acinetobacter baumannii (herein named AmsSR for regulator of alternative metabolic systems) only present in select gammaproteobacterial and betaproteobacterial species. Bioinformatic analysis revealed that the histidine kinase, AmsS, contains 14 predicted N-terminal transmembrane domains and harbors a hybrid histidine kinase arrangement in its C-terminus. Transcriptional analysis revealed the proton ionophore CCCP selectively induces PamsSR expression. Disruption of amsSR resulted in decreased intracellular pH and increased depolarization of cytoplasmic membranes. Transcriptome profiling revealed a major reordering of metabolic circuits upon amsR disruption, with energy generation pathways typically used by bacteria growing in limited oxygen being favored. Interestingly, we observed enhanced growth rates for mutant strains in the presence of glucose, which led to overproduction of pyruvate. To mitigate the toxic effects of carbon overflow, we noted acetate overproduction in amsSR-null strains, resulting from a hyperactive Pta-AckA pathway. Additionally, due to altered expression of key metabolic genes, amsSR mutants favor an incomplete TCA cycle, relying heavily on an overactive glyoxylate shunt. This metabolic reordering overproduces NADH, which is not oxidized by the ETC; components of which were significantly downregulated upon amsSR disruption. As a result, the mutants almost exclusively rely on substrate phosphorylation for ATP production, and consequently display reduced oxygen consumption in the presence of glucose. Collectively, our data suggests that disruption of amsSR affects the function of the aerobic respiratory chain, impacting the energy status of the cell, which in turn upregulates alternative metabolic and energy generation pathways.
Milk metabolomics analyses of lactating dairy cows with divergent residual feed intake reveals physiological underpinnings and novel biomarkers
Authors: Hailemariam Dagnachew , Hashemiranjbar Mohsen , Manafiazar Ghader , Stothard Paul , Plastow Graham
Published: April 2023

The opportunity to select for feed efficient cows has been limited by inability to cost-effectively record individual feed efficiency on an appropriate scale. This study investigated the differences in milk metabolite profiles between high- and low residual feed intake (RFI) categories and identified biomarkers of residual feed intake and models that can be used to predict residual feed intake in lactating Holsteins. Milk metabolomics analyses were undertaken at early, mid and late lactation stages and residual feed intake was calculated in 72 lactating dairy cows. Cows were ranked and grouped into high residual feed intake (RFI >0.5 SD above the mean, n = 20) and low residual feed intake (RFI <0.5 SD below the mean, n = 20). Milk metabolite profiles were compared between high residual feed intake (least efficient) and low residual feed intake (most efficient) groups. Results indicated that early lactation was predominantly characterized by significantly elevated levels of medium chain acyl carnitines and glycerophospholipids in high residual feed intake cows. Citrate cycle and glycerophospholipid metabolism were the associated pathways enriched with the significantly different metabolites in early lactation. At mid lactation short and medium chain acyl carnitines, glycerophospholipids and amino acids were the main metabolite groups differing according to residual feed intake category. Late lactation was mainly characterized by increased levels of amino acids in high residual feed intake cows. Amino acid metabolism and biosynthesis pathways were enriched for metabolites that differed between residual feed intake groups at the mid and late lactation stages. Receiver operating characteristic curve analysis identified candidate biomarkers: decanoylcarnitine (area under the curve: AUC = 0.81), dodecenoylcarnitine (AUC = 0.81) and phenylalanine (AUC = 0.85) at early, mid and late stages of lactation, respectively. Furthermore, panels of metabolites predicted residual feed intake with validation coefficient of determination (R2) of 0.65, 0.37 and 0.60 at early, mid and late lactation stages, respectively. The study sheds light on lactation stage specific metabolic differences between high-residual feed intake and low-residual feed intake lactating dairy cows. Candidate biomarkers that distinguished divergent residual feed intake groups and panels of metabolites that predict individual residual feed intake phenotypes were identified. This result supports the potential of milk metabolites to select for more efficient cows given that traditional residual feed intake phenotyping is costly and difficult to conduct in commercial farms.
TRAF2 as a key candidate gene in clinical hepatitis B-associated liver fibrosis
Authors: Wu Cichun , Zhang Jian , Wang Huiwen , Zhang Wei , Liu Jingqing , Zhou Nianqi , Chen Keyu , Wang Ying , Peng Shifang , Fu Lei
Published: April 2023

Objectives: Approximately 240 million individuals are infected with chronic hepatitis B virus (HBV) worldwide. HBV infection can develop into liver fibrosis. The mechanism of HBV-related liver fibrosis has not been fully understood, and there are few effective treatment options. The goal of this study was to use transcriptomics in conjunction with experimental validation to identify new targets to treat HBV-related liver fibrosis.

Methods: To identify differentially expressed genes (DEGs), five liver tissues were collected from both healthy individuals and patients with chronic hepatitis B. NovoMagic and Java GSEA were used to screen DEGs and key genes, respectively. Immunocell infiltration analysis of RNA-seq data was, and the results were confirmed by Western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry.

Results: We evaluated 1,105 genes with differential expression, and 462 and 643 genes showed down- and upregulation, respectively. The essential genes, such as tumor necrosis factor (TNF) receptor-associated factor-2 (TRAF2), were screened out of DEGs. TRAF2 expression was abnormally high in hepatic fibrosis in patients with hepatitis B compared with healthy controls. The degree of hepatic fibrosis and serum levels of glutamate transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were positively linked with TRAF2 expression. TRAF2 may be crucial in controlling T lymphocyte-mediated liver fibrosis.

Conclusion: Our findings imply that TRAF2 is essential for HBV-induced liver fibrosis progression, and it may potentially be a promising target for the treatment of hepatic fibrosis in hepatitis B.