bluuebunny/crossref_metadata_2025 huggingface dataset:
RANCANGAN APLIKASI GUEST BOOK DI DESA LAU GUMBA BERBASIS WEB
Authors: Mayasari Nova , Hermansyah Hermansyah , Prasetyo Dimas
Published: June 2024

Desa Lau Gumba merupakan Desa yang terletak di Kecamatan Brastagi Kabupaten KaroProvinsi Sumatera Utara yang cukup di kenal karena memiliki objek wisata yang cukup menarik untuk dikunjungi. Banyaknya pengunjung atau tamu yang berkunjung ke Desa Lau Gumba baik tamu dari masyarakat setempat untuk mengurus keperluaan tertentu atau wisatawan atau investor atau warga pendatang yang sedang bekerja di Daerah Desa Lau Gumba tersebut selalu tercatat pada daftar kunjungan buku tamu. Pencatatan buku tamu masih dilakukan secara manual pada pencatatan buku tamu. Hal ini menyulitkan kepala Desa Lau Gumba mengidentifikasi tamu tamu yang dating ke kantor Desa Lau Gumba, karena harus mencari satu persatu daftar nama tamu yang berkunjung ke kantor kepala Desa Lau Gumba tersebut. Permasalahan yang didapat kepala Desa Lau Gumba pada saat melaksakan rapat mingguan atau bulanan dengan Camat Berastagi sulit untuk memberikan laporan daftar tamu yang mengunjungi kantor kepala Desa Lau Gumba karena data data tamu yang dicatat ke dalam buku tamu secara mannual tidak terstruktur penyusunan data tamu yang berkunjung ke kantor kepala Desa Lau Gumba.. Hal ini dibutuhkan teknologi informasi yang dapat menyajikan data data tamu kantor kepala Desa Lau Gumba secara terstruktur dan sistematis sehingga mempermudah kepala Desa Lau Gumba meberikan laporan kepada Camat Berastagi pada saat rapat mingguan dan bulanan. Metode yang di pakai dalam peneltian ini dengan menggunakan UML (Unifed Modeling Language), program PHP, java dan database MySQL sebagai penyimpanan data. Sistem buku tamu ini memiliki dua program yaitu program admin untuk mengelola data tamu berbasis web dan program user untuk menampilkan tamu tamu yang pernah berkunjung ke Desa Lau Gumba berbasis mobile android. Sistem buku tamu ini bertujuan untuk memberikan kemudahan dan kecepatan kepada kepala Desa Lau Gumba memaparkan serta mendokumentasikan tamu tamu yang berkunjung ke kantor kepala Desa Lau Gumba Kecamatan Berastagi Kabupaten Karo.
Edukasi Nilai-Nilai Pendidikan Agama Kristen bagi Siswa dalam Membangun Sikap Toleransi Beragama di SMP Negeri 20 Pamulang Tangerang Selatan
Authors: Boiliu Fredik Melkias , Tefbana Abraham , Maharani Asti , Pisdon Imanuel , Purba Sara Yemima , Laxwanda Michael Theodore Badra , Handayani Sari , Harefa Dewi Sriniat , Henukh Tini Martinus , Siahaan Vera Oktavia , Kurniawan Yasrid Prayogo
Published: June 2024

Program Pengabdian kepada Masyarakat (PkM) di SMP Negeri 20 Pamulang, Tangerang Selatan, bertujuan untuk memberikan pemahaman nilai-nilai Pendidikan Agama Kristen kepada siswa, dalam upaya membangun sikap saling menghormati antar agama. Dengan pendekatan ini, siswa-siswa tidak hanya meningkatkan pemahaman mengenai nilai-nilai Kristen, tetapi juga memasukkan prinsip-prinsip toleransi terhadap kepercayaan agama lain ke dalam diri mereka. Metode yang digunakan dalam kegiatan PkM ini adalah ceramah, tanya jawab dan diskusi. Hasil PkM menunjukkan adanya peningkatan kesadaran siswa mengenai perlunya menghormati keragaman keagamaan. Siswa menambah wawasan dan arahan yang tepat, membangun komunikasi melalui dialog antar umat agama yang bersatu, dan memajukan penghormatan terhadap keragaman keyakinan agama. Dengan demikian, dapat disimpulkan bahwa pendidikan agama Kristen memiliki potensi untuk menjadi sarana yang efektif dalam mendorong sikap toleransi antar agama di lingkungan sekolah, dan juga sebagai pondasi dalam membangun masyarakat yang lebih damai dan inklusif secara keseluruhan.
Rancang Bangun Sistem Deteksi Binatang Penyebab Gangguan Distribusi SUTM Berbasis IoT
Authors: Rifai Sofyan , Sulistiyanti Sri , Yudamson Afri , Nasrullah Emir
Published: June 2024

Distribusi listrik tegangan menengah di Indonesia didominasi oleh saluran tegangan menengah (SUTM). SUTM adalah konstruksi distribusi tenaga listrik non-isolasi dengan tegangan berkisar antara 5kV hingga 20kV menghubungkan gardu induk dengan pelanggan. SUTM sering mengalami gangguan sesaat hingga permanen akibat faktor binatang seperti kukang dan tupai. Penelitian ini berfungsi untuk merancang suatu sistem deteksi binatang berbasis IoT untuk mencegah dan memperingatkan dalam bentuk gambar jika terdapat binatang atau suhu berlebih di jaringan SUTM. Sistem deteksi ini menggunakan sensor PIR HC-SR501 untuk mengidentifikasi gerakan binatang, sensor DHT22 untuk deteksi suhu, buzzer ultrasonik untuk mencegah binatang, dan ESP32-CAM untuk mengambil gambar. Data yang diperoleh terkirim di Thingsboard menggunakan mikrokontroler  ESP32, serta gambar terkirim pada aplikasi Telegram. Uji coba dilakukan secara subsistem dan keseluruhan dengan simulasi dan pengujian langsung di lapangan pada gardu hubung SUTM. Hasil pengujian menunjukkan bahwa sistem dapat mendeteksi pergerakan binatang dengan sudut deteksi hingga ∠63,4° dan sensor DHT22 dapat memantau suhu dengan nilai akurasi suhu 98,78%. Buzzer ultrasonik dapat mengusir binatang dengan frekuensi 35kHz. Delay pengambilan gambar ESP32-CAM ketika variabel terpenuhi bervariasi tergantung pada provider yang digunakan, dengan Telkomsel memiliki rata-rata delay terkecil sebesar 1,39 detik,  provider Axis rata-rata delay sebesar 1,89 detik dan provider Tri memiliki rata-rata delay sebesar 2,34 detik
Drowsiness Detection in the Advanced Driver-Assistance System using YOLO V5 Detection Model
Authors: Fauzan Ridho Muhammad , Fransiskus Panca  , Welly Yandi  , Almeera Amsana Rachmani
Published: June 2024

The development of Artificial Intelligence (AI) in the automobile industry, particularly in the Advanced Driver-Assistance System (ADAS), has been increasing rapidly in recent years. One of the essential features of ADAS is the drowsiness alert system, which monitors the state of the driver's eyes. This article presents a study on the development of ADAS that focuses on drowsiness detection using deep learning through a Convolutional Neural Network (CNN) approach. The study utilized the YOLO V5 model for object detection, which was trained using custom datasets containing images annotated with two labels: "Mengantuk" (Drowsy) and "Bangun" (Awake) The goal was to recognize whether the driver was drowsy or awake. The results of the study showed that the modified YOLO V5 CNN Model had high accuracy based on evaluation metrics in terms of accuracy, precision, and recall in detecting drowsiness around the area of the eyes, with a Mean Average Precision (mAP) of 99.5% and an F1-Score of 99.8%. For better understanding and visualization, the model was tested using real-time detection through a web camera, using Jetson Nano as the inference device. The model detected drowsiness in real time, with a confidence rate of 80% to 97%
Sistem Prediksi Pergerakan Harga Valuta Asing Menggunakan Kecerdasan Buatan Metode SARSA
Authors: Reinard Vinsensius , Fat Joni , Suraidi
Published: June 2024

Pada era modern komputer dimanfaatkan untuk melakukan komputasi kecepatan tinggi. Tidak terhindar pasar valuta asing juga mengalami transisi tersebut. Sistem yang dibuat menggunakan kecerdasan buatan metode state action reward state action (SARSA) yang memprediksi dengan tepat 52% atau lebih sesuai dengan metode evaluasi. Evaluasi keberhasilan prediksi dilakukan dengan membandingkan prediksi pada state  dan state . State didefinisikan menjadi 3. State 3 adalah harga > sma+k, state 2 adalah sma+k < harga < sma-k, dan state 1 adalah harga < sma-k. Variabel sma adalah rata-rata 200 harga closed terakhir dari periode waktu 5 menit. Konstanta k bernilai 0.0005. Sistem menggunakan bahasa pemrograman Python dan terhubung ke pasar valuta asing. Pengujian dilakukan pada 2023-11-10 22:05:00 sampai 2023-11-18 06:55:00. Metode uji yang digunakan adalah metode forward testing. Forward testing adalah sistem uji menggunakan data live market. Metode kecerdasan buatan SARSA memprediksi dengan rata-rata keberhasilan 63.08% pada sampel data EUR/USD, GBP/USD, USD/CAD, USD/CHF, AUD/USD, dan USD/JPY. Prediksi berhasil paling tinggi adalah pasangan USD/CHF dengan tingkat keberhasilan 72.39%, sedangkan yang paling rendah pada GBP/USD dengan tingkat keberhasilan 59.66%. Sistem prediksi yang dibuat berkemampuan untuk aktif ketika pasar valas aktif. Sistem memprediksi dengan mengeluarkan state selanjutnya.
BUILDING RELIGIOUS AWERENESS THROUGH EDUCATIONAL TECHNOLOGY IN THE ERA OF INDUSTRIAL REVOLUTION 4.0
Authors: Hidayatulloh Hidayatulloh , Nuraeni Heni Ani
Published: June 2024

The industrial revolution became a challenge for someone who could not take advantage of it and became an opportunity to change the growth mindset for productive thinkers. This research aims to discuss efforts to biild religious awareness through educational technology in the era of industrial revolution 4.0. This research will explore how technology can be used effectively to increase religious understanding and awareness at various levels of education, from elementary to highest levels. This research method uses library research using content analysis techniques. The research results to build religious awareness require three aspects: first, it requires integration between technology and religious values. Second, involving teachers and religious leaders in the use of educational technology. Third, providing broad access for all levels of society to educational technology. It is hoped that this research can serve as a guide for developing better religious education policies, as well as providing insight for educational practitioners, technology developers and the general public regarding the importance of technology in the Islamic religious context.
Note for the Small Gaps
Authors: Vega Frank
Published: June 2024

A prime gap is the difference between two successive prime numbers. The nth prime gap, denoted $g_{n}$ is the difference between the (n + 1)st and the nth prime numbers, i.e. $g_{n}=p_{n+1}-p_{n}$. A twin prime is a prime that has a prime gap of two. The twin prime conjecture states that there are infinitely many twin primes. There isn't a verified solution to twin prime conjecture yet. In this note, using the Chebyshev function, we prove that $\liminf_{n\to \infty }{\frac {g_{n}+g_{n-1}}{\log (p_{n}) + \log (p_{n} + 2)}} \geq 1,$ under the assumption that the twin prime conjecture is false. It is well-known the proof of Daniel Goldston, J{\'a}nos Pintz and Cem Yildirim which implies that $\liminf_{n\to \infty }{\frac {g_{n}}{\log p_{n}}}=0$. In this way, we reach an intuitive contradiction. Consequently, by reductio ad absurdum, we can conclude that the twin prime conjecture is true.
Taha's 2nd Solution of Collatz Sequence
Authors: Muhammad Taha
Published: June 2024

Abstract of Taha's 2nd Solution of Collatz Sequence let Collatz Sequence of (r)=S(r) let Collatz Sequence loop of (r)=lS(r) S(n)={(n/2)=k≤n-1,…,(h) or…},n∈N_even,k,h∈N_+⋯Fact 1 S(n)={(n/2)or (3n+1),…}⇒S(n)⊇S((n/2) or (3n+1) ),n∈N_+⋯Fact 2 ⇒ lS(n)= lS((n/2) or (3n+1) )…Fact 3 Example: S(5)={16,8,4,2,1}⇒ ∴S(5)⊇S(16)⊇S(8)⊇S(4)⊇S(2)⊇ S(1)…Fact 1⇒ lS(5)=lS(16)=lS(8)=lS(4)=lS(2)=lS(1)…Fact 2
ANALISIS LAPORAN KEUANGAN UNTUK MENILAI KINERJA KEUANGAN PEMERINTAH DAERAH KABUPATEN TAPANULI UTARA
Authors: Purba Sahala , Panggabean Michael Armando , Br Purba Tesalonika , Manalu Enny , Sitanggang Cindy Arsita
Published: June 2024

Tujuan penelitian ini untuk meningkatkan kinerja pemerintah dan meningkatkan efektivitas akhir dari pengelolaan keuangan daerah, diteliti secara deskriptif kuantitatif dengan subjek riset informasi. Data yang digunakan dalam penelitian ini adalah laporan keuangan Pemerintah Daerah Kabupaten Tapanuli Utara tahun 2013-2022. Hasil penelitian ini menyatakan bahwa rasio kemandirian keuangan tergolong sangat rendah sekali sebesar 10,43%, rasio ketergantungan keuangan tergolong rendah sekali sebesar 8,91%, rasio derajat desentralisasi fiskal tergolong rendah sebesar 10,63%, rasio efektivitas PAD dan efektivitas pajak daerah tergolong sangat efisisen sebesar 108,23% dan 110,29%, rasio efisiensi PAD dan efisiensi pajak daerah tergolong sangat efisien sebesar 2,45%, dan rasio derajat kontribusi BUMD sudah baik sebesar 8,251% . Berdasarkan analisis, laporan keuangan Pemerintah Daerah Kabupaten Tapanuli Utara tahun 2013-2022 dapat dinyatakan secara umum bahwa Kabupaten Tapanuli Utara belum cukup baik dalam pelaksanaan dan pengelolaan keuangan. Sesuai hasil yang diperoleh, dapat disimpulkan bahwa kondisi kinerja keuangan Pemerintah Daerah Kabupaten Tapanuli Utara masih belum ideal.
UKURAN PERUSAHAAN, PROFITABILITAS DAN KEBIJAKAN DIVIDEN TERHADAP NILAI PERUSAHAAN MELALUI FINANCIAL DISTRESS
Authors: Hikmah Hikmah , Haldy Muhammad
Published: June 2024

This research aims to determine the influence of company size, company size and dividend policy on company value with financial distress as a mediating variable. The population in this study are mining companies listed on the Indonesia Stock Exchange (BEI) for the 2019-2023 period. The total sample tested was 30 companies, multiplied by 5 years of observations selected using purposive sampling techniques. The data analysis technique uses Partial Least Square (PLS) with the SmartPLS 4 program. The research results show that the variables of company size and dividend policy have a positive and significant effect on company value, while profitability has a negative and insignificant effect on company value. Company size, dividend policy have effect on financial distress, while profitability has no significant effect on financial distress, while the effect of financial stress on company value has a negative and significant effect.
Brown algae (Phaeophyceae) stressors and illnesses: a review for a sustainable aquaculture under climate change
Authors: Ruiz Martínez Eliana , Schroeder Declan C. , Thuestad Gunnar , Hoell Ingunn A.
Published: June 2024

Brown algae (Phaeophyceae) dominate intertidal and shallow subtidal areas globally, where larger species form extensive underwater forests. These structurally complex and highly productive habitats enhance local biodiversity and support food webs in coastal areas through secondary production, thereby shaping local oceanography and ecology. Macroalgal aquaculture is an important and growing sector, where approximately 40% of all cultivated algae belong to Phaeophyceae. However, both cultured and natural brown algae have been under increasing pressure due to climate-driven factors, such as ocean warming, eutrophication, and herbivore outbreaks. We conducted a comprehensive literature review on abiotic (temperature, light intensity, and UV radiation, nutrients, water motion, salinity, and substrata and sediment) and biotic (bacteria, viruses, fungi, eukaryotic endophytes and endoparasites, epiphytes, and grazers) stressors and illnesses in marine brown macroalgae, as well as brown algae defense mechanisms, and discuss how these parameters may affect the production of a sustainable crop for the aquaculture industry under future climate change scenarios.
BRET-based biosensors for SARS-CoV-2 oligonucleotide detection
Authors: Sultana Asfia , Geethakumari Anupriya M. , Islam Zeyaul , Kolatkar Prasanna R. , Biswas Kabir H.
Published: June 2024

The need for the early detection of emerging pathogenic viruses and their newer variants has driven the urgent demand for developing point-of-care diagnostic tools. Although nucleic acid-based methods such as reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and loop-mediated isothermal amplification (LAMP) have been developed, a more facile and robust platform is still required. To address this need, as a proof-of-principle study, we engineered a prototype—the versatile, sensitive, rapid, and cost-effective bioluminescence resonance energy transfer (BRET)-based biosensor for oligonucleotide detection (BioOD). Specifically, we designed BioODs against the SARS-CoV-2 parental (Wuhan strain) and B.1.617.2 Delta variant through the conjugation of specific, fluorescently modified molecular beacons (sensor module) through a complementary oligonucleotide handle DNA functionalized with the NanoLuc (NLuc) luciferase protein such that the dissolution of the molecular beacon loop upon the binding of the viral oligonucleotide will result in a decrease in BRET efficiency and, thus, a change in the bioluminescence spectra. Following the assembly of the BioODs, we determined their kinetics response, affinity for variant-specific oligonucleotides, and specificity, and found them to be rapid and highly specific. Furthermore, the decrease in BRET efficiency of the BioODs in the presence of viral oligonucleotides can be detected as a change in color in cell phone camera images. We envisage that the BioODs developed here will find application in detecting viral infections with variant specificity in a point-of-care-testing format, thus aiding in large-scale viral infection surveillance.
Optimizing Nodal, Wnt and BMP signaling pathways for robust and efficient differentiation of human induced pluripotent stem cells to intermediate mesoderm cells
Authors: Magro-Lopez Esmeralda , Vazquez-Alejo Elena , Espinar-Buitrago María de la Sierra , Muñoz-Fernández María Ángeles
Published: June 2024

Several differentiation protocols have enabled the generation of intermediate mesoderm (IM)-derived cells from human pluripotent stem cells (hPSC). However, the substantial variability between existing protocols for generating IM cells compromises their efficiency, reproducibility, and overall success, potentially hindering the utility of urogenital system organoids. Here, we examined the role of high levels of Nodal signaling and BMP activity, as well as WNT signaling in the specification of IM cells derived from a UCSD167i-99-1 human induced pluripotent stem cells (hiPSC) line. We demonstrate that precise modulation of WNT and BMP signaling significantly enhances IM differentiation efficiency. Treatment of hPSC with 3 μM CHIR99021 induced TBXT+/MIXL1+ mesoderm progenitor (MP) cells after 48 h of differentiation. Further treatment with a combination of 3 μM CHIR99021 and 4 ng/mL BMP4 resulted in the generation of OSR1+/GATA3+/PAX2+ IM cells within a subsequent 48 h period. Molecular characterization of differentiated cells was confirmed through immunofluorescence staining and RT-qPCR. Hence, this study establishes a consistent and reproducible protocol for differentiating hiPSC into IM cells that faithfully recapitulates the molecular signatures of IM development. This protocol holds promise for improving the success of protocols designed to generate urogenital system organoids in vitro, with potential applications in regenerative medicine, drug discovery, and disease modeling.
Investigating gut microbiota–blood and urine metabolite correlations in early sepsis-induced acute kidney injury: insights from targeted KEGG analyses
Authors: Xu Yaya , Xu Jiayue , Zhu Yueniu , Mao Haoyun , Li Jiru , Kong Xiangmei , Zhu Xiaodong , Zhang Jianhua
Published: June 2024

Background

The interplay between gut microbiota and metabolites in the early stages of sepsis-induced acute kidney injury (SA-AKI) is not yet clearly understood. This study explores the characteristics and interactions of gut microbiota, and blood and urinary metabolites in patients with SA-AKI.

Methods

Utilizing a prospective observational approach, we conducted comparative analyses of gut microbiota and metabolites via metabolomics and metagenomics in individuals diagnosed with SA-AKI compared to those without AKI (NCT06197828). Pearson correlations were used to identify associations between microbiota, metabolites, and clinical indicators. The Comprehensive Antibiotic Resistance Database was employed to detect antibiotic resistance genes (ARGs), while Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways informed on metabolic processes and microbial resistance patterns.

Results

Our study included analysis of four patients with SA-AKI and five without AKI. Significant disparities in bacterial composition were observed, illustrated by diversity indices (Shannon index: 2.0 ± 0.4 vs. 1.4 ± 0.6, P = 0.230; Simpson index: 0.8 ± 0.1 vs. 0.6 ± 0.2, P = 0.494) between the SA-AKI group and the non-AKI group. N6, N6, N6-Trimethyl-L-lysine was detected in both blood and urine metabolites, and also showed significant correlations with specific gut microbiota (Campylobacter hominis and Bacteroides caccae, R > 0, P < 0.05). Both blood and urine metabolites were enriched in the lysine degradation pathway. We also identified the citrate cycle (TCA cycle) as a KEGG pathway enriched in sets of differentially expressed ARGs in the gut microbiota, which exhibits an association with lysine degradation.

Conclusions

Significant differences in gut microbiota and metabolites were observed between the SA-AKI and non-AKI groups, uncovering potential biomarkers and metabolic changes linked to SA-AKI. The lysine degradation pathway may serve as a crucial link connecting gut microbiota and metabolites.
Reclaiming the Xhotsa: climate adaptation and ecosystem restoration via the return of Sumas Lake
Authors: Finn Riley J. R. , Ned - Kwilosintun Murray , Ballantyne Leah , Hamilton Ian , Kwo Janice , Seymour-Hourie Rayanna , Carlson Deborah , Walters Kristen E. , Grenz Jennifer , Martin Tara G.
Published: June 2024

Sumas Lake (Xhotsa), located in the Fraser Valley, British Columbia, Canada, was the heart of Semá:th Nation Territory and the epicenter of a complex Indigenous food system. For the Semá:th people, the lake represented life and livelihood. In 1924, the lake was stolen and drained in an instance of land theft that occurred during a nationwide campaign of land dispossession and genocide, decimating an ecology that supported a rich and diverse Indigenous food system and replacing it with a settler food system. A century later, in November 2021 climate change induced flooding caused the lake to return, resulting in the evacuation of thousands of people and causing millions in damages to homes and infrastructure. Since the flood, the response has been a continuation of the status quo to protect settler agricultural lands via increased investment in hard structures that control the flow of water based on assumptions of the predictability of future flow conditions. We offer a missing narrative by bringing together an analysis of Indigenous laws and oral tradition with an assessment of the economic costs of “managed retreat”, defined as the purposeful relocation of people and infrastructure out of harm’s way. We find that the cost of buying out properties in the lakebed and allowing the lake to return is close to half the cost ($1 billion) of maintaining the status quo ($2.4 billion), while facilitating climate adaptation, and restoration of a floodplain ecosystem that supported thriving populations of people, salmon, sturgeon, ducks, and food and medicinal plants– including many species which are now endangered. Returning Sumas Lake by centering ‘Water Back’ as a climate resiliency solution, enacts both food systems and ecological reconciliation, addressing the harms caused by the loss of the lake to the Semá:th People that is still felt to this day. In a time when climate change induced flooding is predicted to increase, this study demonstrates how the inclusion of Indigenous laws and knowledges are critical to the development of solutions toward a more sustainable and just future.
A Mendelian randomization study of the effect of mental disorders on cardiovascular disease
Authors: Yu Yunfeng , Yang Xinyu , Wu Jingyi , Hu Gang , Bai Siyang , Yu Rong
Published: June 2024

Objective

The effect of mental disorders (MD) on cardiovascular disease (CVD) remains controversial, and this study aims to analyze the causal relationship between eight MD and CVD by Mendelian randomization (MR).

Methods

Single nucleotide polymorphisms of attention-deficit/hyperactivity disorder (ADHD), anorexia nervosa (AN), anxiety disorder (ANX), autism spectrum disorder (ASD), bipolar disorder (BD), depression, obsessive-compulsive disorder (OCD), schizophrenia (SCZ), and CVD were obtained from UK Biobank and FinnGen. Exposure-outcome causality was tested using inverse variance weighted (IVW), MR-Egger, and weighted median. Horizontal pleiotropy and heterogeneity were assessed by MR-Egger intercept and Cochran's Q, respectively, while stability of results was assessed by leave-one-out sensitivity analysis.

Results

MR analysis showed that ANX (IVW [odds ratio (OR) 1.11, 95% confidence intervals (CI) 1.07–1.15, p < 0.001]; MR-Egger [OR 1.03, 95% CI 0.92–1.14, p = 0.652]; weighted median [OR 1.09, 95% CI 1.03–1.14, p = 0.001]), ASD (IVW [OR 1.05, 95% CI 1.00–1.09, p = 0.039]; MR-Egger [OR 0.95, 95% CI 0.84–1.07, p = 0.411]; weighted median [OR 1.01, 95% CI 0.96–1.06, p = 0.805]), depression (IVW [OR 1.15, 95% CI 1.10–1.19, p < 0.001]; MR-Egger [OR 1.10, 95% CI 0.96–1.26, p = 0.169]; weighted median [OR 1.13, 95% CI 1.08–1.19, p < 0.001]) were significantly associated with increased risk of CVD, whereas ADHD, AN, BD, OCD, and SCZ were not significantly associated with CVD (p > 0.05). Intercept analysis showed no horizontal pleiotropy (p > 0.05). Cochran's Q showed no heterogeneity except for BD (p = 0.035). Sensitivity analysis suggested that these results were robust.

Conclusions

ANX, ASD, and depression are associated with an increased risk of CVD, whereas AN, ADHD, BD, OCD, and SCZ are not causally associated with CVD. Active prevention and treatment of ANX, ASD, and depression may help reduce the risk of CVD.
Identifying molecular subgroups of patients with preeclampsia through bioinformatics
Authors: Zhang Huijie , Ma Jianglei , Gao Xueli
Published: June 2024

Preeclampsia (PE) is a pregnancy-related disorder associated with serious complications. Its molecular mechanisms remain undefined; hence, we aimed to identify molecular subgroups of patients with PE using bioinformatics to aid treatment strategies. R software was used to analyze gene expression data of 130 patients with PE and 138 healthy individuals from the Gene Expression Omnibus database. Patients with PE were divided into two molecular subgroups using the unsupervised clustering learning method. Clinical feature analysis of subgroups using weighted gene co-expression network analysis showed that the patients in subgroup I were primarily characterized by early onset of PE, severe symptoms at disease onset, and induced labor as the main delivery method. Patients in subgroup II primarily exhibited late PE onset, relatively mild symptoms, and natural delivery as the main delivery method. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the significant enrichment of calcium ion channels in subgroup II indicated the potential efficacy of calcium antagonists and magnesium sulfate therapy. In conclusion, the establishment of PE molecular subgroups can aid in diagnosing and treating PE.
An overview of the treatments for hypertrophic cardiomyopathy
Authors: Xu Wenna , Zhu Fuyu , Zhang Yue , Li Peng , Sheng Yanhui
Published: June 2024

Hypertrophic cardiomyopathy (HCM) is a very prevalent inherited disease with a wide global distribution and a prevalence rate of approximately 0.2% in the general population. Left ventricular hypertrophy (LVH) caused by sarcomere mutation is the primary reason of HCM. The histopathology feature is that cardiomyocyte hypertrophy, myocyte disorder and myocardial fibrosis lead to diminished diastolic function, left ventricular outflow tract obstruction (LVOTO) and arrhythmia, all of which result in serious cardiac complications. Previously, HCM was considered a malignant disease that was almost untreatable. With the improvement of medical standards and increasing awareness of HCM, it has become a highly treatable disease in contemporary times, with a significant decrease in mortality rates. However, there are still significant unmet requirements in the therapy of HCM. This paper draws on more than 100 references from the past four decades and summarizes current advances in the treatment of HCM. The article will review the pathogenesis and types, recent development in pharmacotherapy, invasive treatments and gene therapies, as well as dilemma and future development of HCM.
Gastroesophageal reflux disease may causally associate with the increased atrial fibrillation risk: evidence from two-sample Mendelian randomization analyses
Authors: Wang Lei , Lu Yi Wei
Published: June 2024

Background

The risk of atrial fibrillation (AF) is increased in individuals with gastroesophageal reflux disease (GERD), according to observational research. The causal significance of this association is still unclear. This study sought to assess GERD's role as a potential contributing factor in AF.

Methods

With the use of a two-sample Mendelian randomization (MR) technique, we assessed the causal relationship between GERD and AF. The association of genetic variants with GERD was examined using data from a recent genome-wide association study (GWAS) that included 602,604 people. Data on the association between genetic variations and AF was obtained from a second GWAS with 1,030,836 participants. The effect sizes were examined based on the inverse-variance weighted method. Additional statistical techniques, including MR-Egger, simple mode, weighted mode, MR Pleiotropy Residual Sum, outlier, and weighted median were used in the sensitivity analysis.

Results

MR analyses in inverse-variance weighted models, using 76 single nucleotide polymorphisms (SNPs) as markers, revealed a relationship between genetically predicted GERD and a greater AF incidence [odds ratio (OR): 1.165, 95% CI 1.102–1.231; P = 7.637 × 10−8]. According to MR-Egger, there was no evidence of gene pleiotropy that could be found (intercept = 0.003, P = 0.581). The findings of the sensitivity study, which used several MR methods, were found to be reliable.

Conclusion

The MR analysis revealed a correlation between GERD and increased AF incidence, supporting the idea that treating patients with GERD as early as possible might reduce their chance of developing AF.
Molecular landscape for risk prediction and personalized therapeutics of castration-resistant prostate cancer: at a glance
Authors: Jian Jingang , Wang Xin’an , Zhang Jun , Zhou Chenchao , Hou Xiaorui , Huang Yuhua , Hou Jianquan , Lin Yuxin , Wei Xuedong
Published: June 2024

Prostate cancer (PCa) is commonly occurred with high incidence in men worldwide, and many patients will be eventually suffered from the dilemma of castration-resistance with the time of disease progression. Castration-resistant PCa (CRPC) is an advanced subtype of PCa with heterogeneous carcinogenesis, resulting in poor prognosis and difficulties in therapy. Currently, disorders in androgen receptor (AR)-related signaling are widely acknowledged as the leading cause of CRPC development, and some non-AR-based strategies are also proposed for CRPC clinical analyses. The initiation of CRPC is a consequence of abnormal interaction and regulation among molecules and pathways at multi-biological levels. In this study, CRPC-associated genes, RNAs, proteins, and metabolites were manually collected and integrated by a comprehensive literature review, and they were functionally classified and compared based on the role during CRPC evolution, i.e., drivers, suppressors, and biomarkers, etc. Finally, translational perspectives for data-driven and artificial intelligence-powered CRPC systems biology analysis were discussed to highlight the significance of novel molecule-based approaches for CRPC precision medicine and holistic healthcare.
Reduced anti-Müllerian hormone action in cumulus-oocyte complexes is beneficial for oocyte maturation without affecting oocyte competence
Authors: Xu Fuhua , Bagnjuk Konstantin , Marti-Gutierrez Nuria , Srinivasan Sathya , Mayerhofer Artur , Lee David , Pejovic Tanja , Mitalipov Shoukhrat , Xu Jing
Published: June 2024

Anti-Müllerian hormone (AMH) is a key paracrine/autocrine factor regulating folliculogenesis in the postnatal ovary. As antral follicles mature to the preovulatory stage, AMH production tends to be limited to cumulus cells. Therefore, the present study investigated the role of cumulus cell-derived AMH in supporting maturation and competence of the enclosed oocyte. Cumulus-oocyte complexes (COCs) were isolated from antral follicles of rhesus macaque ovaries for in vitro maturation with or without AMH depletion. Oocyte meiotic status and embryo cleavage after in vitro fertilization were assessed. In vitro maturation with AMH depletion was also performed using COCs from antral follicles of human ovarian tissue. Oocyte maturation and morphology were evaluated. The direct AMH action on mural granulosa cells of the preovulatory follicle was further assessed using human granulosa cells cultured with or without AMH supplementation. More macaque COCs produced metaphase II oocytes with AMH depletion than those of the control culture. However, preimplantation embryonic development after in vitro fertilization was comparable between oocytes derived from COCs cultured with AMH depletion and controls. Oocytes resumed meiosis in human COCs cultured with AMH depletion and exhibited a typical spindle structure. The confluency and cell number decreased in granulosa cells cultured with AMH supplementation relative to the control culture. AMH treatment did not induce cell death in cultured human granulosa cells. Data suggest that reduced AMH action in COCs could be beneficial for oocyte maturation. Cumulus cell-derived AMH is not essential for supporting oocyte competence or mural granulosa cell viability.
Lateral parabrachial nucleus astrocytes control food intake
Authors: Mishra Devesh , Richard Jennifer E. , Maric Ivana , Shevchouk Olesya T. , Börchers Stina , Eerola Kim , Krieger Jean-Philippe , Skibicka Karolina P.
Published: June 2024

Food intake behavior is under the tight control of the central nervous system. Most studies to date focus on the contribution of neurons to this behavior. However, although previously overlooked, astrocytes have recently been implicated to play a key role in feeding control. Most of the recent literature has focused on astrocytic contribution in the hypothalamus or the dorsal vagal complex. The contribution of astrocytes located in the lateral parabrachial nucleus (lPBN) to feeding behavior control remains poorly understood. Thus, here, we first investigated whether activation of lPBN astrocytes affects feeding behavior in male and female rats using chemogenetic activation. Astrocytic activation in the lPBN led to profound anorexia in both sexes, under both ad-libitum feeding schedule and after a fasting challenge. Astrocytes have a key contribution to glutamate homeostasis and can themselves release glutamate. Moreover, lPBN glutamate signaling is a key contributor to potent anorexia, which can be induced by lPBN activation. Thus, here, we determined whether glutamate signaling is necessary for lPBN astrocyte activation-induced anorexia, and found that pharmacological N-methyl D-aspartate (NMDA) receptor blockade attenuated the food intake reduction resulting from lPBN astrocyte activation. Since astrocytes have been shown to contribute to feeding control by modulating the feeding effect of peripheral feeding signals, we further investigated whether lPBN astrocyte activation is capable of modulating the anorexic effect of the gut/brain hormone, glucagon like peptide -1, as well as the orexigenic effect of the stomach hormone - ghrelin, and found that the feeding effect of both signals is modulated by lPBN astrocytic activation. Lastly, we found that lPBN astrocyte activation-induced anorexia is affected by a diet-induced obesity challenge, in a sex-divergent manner. Collectively, current findings uncover a novel role for lPBN astrocytes in feeding behavior control.
Hydrological and climate intensification induces conservative behavior in the Hydrochorea corymbosa xylem production in a Central Amazon floodplain forest
Authors: de Sá Priscila Amaral , Schöngart Jochen , Wittmann Florian , Piedade Maria Teresa Fernandez , Tomazello-Filho Mario , Oliveira Rafael S. , Horna Viviana , Parolin Pia , Durgante Flavia Machado
Published: June 2024

Introduction

Trees from flooded forests have to adjust their xylem hydraulic structure to face the annual flooding and the climatic conditions of the atmosphere. Usually, this adjustment of anatomical tissues in the tropics is driven by drought events inducing conservative behavior and can be recorded annually in tree rings. However, how the flood pulse and the climatic conditions influence the xylem hydraulic structure in floodplain trees is unknown.

Methods

To fill this gap, we explore if flooded periods and monthly climate variation affect the annual tree growth and xylem anatomy structure for the tree species Hydrochorea corymbosa (Fabaceae) from the várzea flooded forest in the Central Amazon. We developed a 41-year ring width chronology (1971–2018) and a 30-year time series of xylem anatomy parameters (1988–2018) as mean hydraulic vessel diameter (Dh), vessel frequency (VF), and parenchyma quantity (PQ). We correlated the series with monthly hydrological and climatic data.

Results

The hydrological regime did not correlate with annual tree growth in that species as we previously expected but showed correlations with the xylem anatomical structure. High flood levels during the end of the flooding period induced conservative patterns of the anatomical structure, with a negative correlation with Dh (rho June = −0.40, p < 0.05) and a positive correlation with the PQ (rho September/October = 0.42, p < 0.05). These responses show that these trees are responding to flooding similar to the tree responses to drought. Regarding the climatic variation, the annual tree growth showed a negative correlation with the vapor pressure deficit (VPD), after the second half of the flooded period with the strongest correlation happening during the non-flooded period (rho December = −0.66, p < 0. 01). These conservative patterns in tree behavior also happened when the maximum temperature negatively affected the vessel diameter (rho September = −0.42, p < 0.05).

Discussion

In that case, we recognized two different moments that the environment is inducing conservative patterns in the xylem structure of those trees: 1) increasing the flood levels and 2) the high evaporative demand during the non-flooded period. In this way, the intensification of the hydrological regime, as well as the strong drought conditions during the non-flooded periods, can be a risk for H. corymbosa in the Central Amazonian floodplains.
Scleroderma and scleroderma-like syndromes
Authors: Romanowska-Próchnicka Katarzyna , Dziewit Martyna , Lesiak Aleksandra , Reich Adam , Olesińska Marzena
Published: June 2024

Systemic sclerosis is a systemic connective tissue disease whose main pathophysiological mechanism is a progressive fibrosis of internal organs and skin leading to thickening and induration. Blood vessels may also be involved. However, systemic scleroderma is not the only disease causing cutaneous sclerosis. There is a group of diseases that mimic scleroderma in their clinical presentation - these are scleroderma-like syndromes. A distinction can be made between syndromes of inflammatory/autoimmune, genetic, metabolic, toxic, drug-induced, occupational, paraneoplastic and syndromes caused by deposition disorders. In the following paper, we have reviewed the literature on scleroderma-like syndromes. We have outlined the factors predisposing to the development of each disease, its pathogenesis, clinical presentation, diagnostic and treatment process and the differences between each syndrome and systemic scleroderma.
Regulatory and memory T lymphocytes infiltrating prostate tumors predict long term clinical outcomes
Authors: Molina Oscar Eduardo , LaRue Hélène , Simonyan David , Hovington Hélène , Vittrant Benjamin , Têtu Bernard , Fradet Vincent , Lacombe Louis , Bergeron Alain , Fradet Yves
Published: June 2024

Introduction

The localization, density but mostly the phenotype of tumor infiltrating lymphocytes (TIL) provide important information on the initial interaction between the host immune system and the tumor. Our objective was to assess the prognostic significance of T (CD3+), T regulatory (Treg) (FoxP3+) and T memory (Tmem) (CD45RO+) infiltrating lymphocytes and of genes associated with TIL in prostate cancer (PCa).

Methods

Immunohistochemistry (IHC) was used to assess the infiltration of CD3+, FoxP3+ and CD45RO+ cells in the tumor area, tumor margin and adjacent normal-like epithelium of a series of 98 PCa samples with long clinical follow-up. Expression of a panel of 31 TIL-associated genes was analyzed by Taqman Low-Density Array (TLDA) technology in another series of 50 tumors with long clinical follow-up. Kaplan-Meier and Cox proportional hazards regression analyses were performed to determine association of these markers with biochemical recurrence (BCR), need for definitive androgen deprivation therapy (ADT) or lethal PCa.

Results

TIL subtypes were present at different densities in the tumor, tumor margin and adjacent normal-like epithelium, but their density and phenotype in the tumor area were the most predictive of clinical outcomes. In multivariate analyses, a high density of Treg (high FoxP3+/CD3+ cell ratio) predicted a higher risk for need of definitive ADT (HR=7.69, p=0.001) and lethal PCa (HR=4.37, p=0.04). Conversely, a high density of Tmem (high CD45RO+/CD3+ cell ratio) predicted a reduced risk of lethal PCa (HR=0.06, p=0.04). TLDA analyses showed that a high expression of FoxP3 was associated with a higher risk of lethal PCa (HR=5.26, p=0.02). Expression of CTLA-4, PD-1, TIM-3 and LAG-3 were correlated with that of FoxP3. Amongst these, only a high expression of TIM-3 was associated with a significant higher risk for definitive ADT in univariate Cox regression analysis (HR=3.11, p=0.01).

Conclusion

These results show that the proportion of Treg and Tmem found within the tumor area is a strong and independent predictor of late systemic progression of PCa. Our results also suggest that inhibition of TIM-3 might be a potential approach to counter the immunosuppressive functions of Treg in order to improve the anti-tumor immune response against PCa.
A local drug delivery system prolongs graft survival by dampening T cell infiltration and neutrophil extracellular trap formation in vascularized composite allografts
Authors: Arenas Hoyos Isabel , Helmer Anja , Yerly Anaïs , Lese Ioana , Hirsiger Stefanie , Zhang Lei , Casoni Daniela , Garcia Luisana , Petrucci MariaFrancesca , Hammer Sabine E. , Duckova Tereza , Banz Yara , Montani Matteo , Constantinescu Mihai , Vögelin Esther , Bordon Gregor , Aleandri Simone , Prost Jean-Christophe , Taddeo Adriano , Luciani Paola , Rieben Robert , Sorvillo Nicoletta , Olariu Radu
Published: June 2024

Introduction

The standard treatment for preventing rejection in vascularized composite allotransplantation (VCA) currently relies on systemic immunosuppression, which exposes the host to well-known side effects. Locally administered immunosuppression strategies have shown promising results to bypass this hurdle. Nevertheless, their progress has been slow, partially attributed to a limited understanding of the essential mechanisms underlying graft rejection. Recent discoveries highlight the crucial involvement of innate immune components, such as neutrophil extracellular traps (NETs), in organ transplantation. Here we aimed to prolong graft survival through a tacrolimus-based drug delivery system and to understand the role of NETs in VCA graft rejection.

Methods

To prevent off-target toxicity and promote graft survival, we tested a locally administered tacrolimus-loaded on-demand drug delivery system (TGMS-TAC) in a multiple MHC-mismatched porcine VCA model. Off-target toxicity was assessed in tissue and blood. Graft rejection was evaluated macroscopically while the complement system, T cells, neutrophils and NETs were analyzed in graft tissues by immunofluorescence and/or western blot. Plasmatic levels of inflammatory cytokines were measured using a Luminex magnetic-bead porcine panel, and NETs were measured in plasma and tissue using DNA-MPO ELISA. Lastly, to evaluate the effect of tacrolimus on NET formation, NETs were induced in-vitro in porcine and human peripheral neutrophils following incubation with tacrolimus.

Results

Repeated intra-graft administrations of TGMS-TAC minimized systemic toxicity and prolonged graft survival. Nevertheless, signs of rejection were observed at endpoint. Systemically, there were no increases in cytokine levels, complement anaphylatoxins, T-cell subpopulations, or neutrophils during rejection. Yet, tissue analysis showed local infiltration of T cells and neutrophils, together with neutrophil extracellular traps (NETs) in rejected grafts. Interestingly, intra-graft administration of tacrolimus contributed to a reduction in both T-cellular infiltration and NETs. In fact, in-vitro NETosis assessment showed a 62–84% reduction in NETs after stimulated neutrophils were treated with tacrolimus.

Conclusion

Our data indicate that the proposed local delivery of immunosuppression avoids off-target toxicity while prolonging graft survival in a multiple MHC-mismatch VCA model. Furthermore, NETs are found to play a role in graft rejection and could therefore be a potential innovative therapeutic target.
Research on the impact of marine economic development in coastal areas on regional economic resilience: evidence from China
Authors: Wang Hao , Yang Jicong , Wu Hongsen , Niu Congcong
Published: June 2024

Marine economy is a valuable pillar for the development of coastal areas. It is of profound significance to explore the influence of marine economy development on economic resilience of coastal areas. This paper constructs an economic resilience assessment framework based on resistance, adaptability, and evolutionary power, adopts the entropy method to calculate the economic resilience development level in China’s coastal areas from 2006 to 2019, and examines in detail the driving factors affecting the economic resilience from the indicator level. Furthermore, panel regression models are used to explore the influence of marine economic development on the economic resilience of China’s coastal areas and its mechanism of action. The results show that: (1) China’s coastal areas have an overall trend of rising economic resilience. The spatiotemporal differentiation characteristics of different economic resilience factors are significant. (2) Factors such as regional economic scale, innovation input, industrial transformation, resident income, consumption scale, degree of marketization, and financial scale are key factors to enhance the economic system resilience of coastal areas. (3) There is a significant positive impact of the marine economy on the economic resilience of coastal areas, and this promotion effect is regulated and constrained by the level of diversification of marine industries and the level of concentration of marine industries. (4) Heterogeneity analysis shows that there are significant individual differences in the impact of Marine economy on economic resilience, and its marginal effect first increases and then decreases. The corresponding policy implications are further analyzed based on the research results.