bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengaruh Pemberian Artificial Sweeteners Stevia terhadap Berat Badan, Profil Jaringan Lemak, Nilai Glukosa Darah, dan Kadar Malondialdehyde (MDA) pada Tikus Galur Wistar serta Tinjauannya Menurut Pandangan Islam
Authors: Dhani Retno Noviar , Mukhtar Diniwati , Istiwara Endy Muhammad , Royhan Aan
Published: November 2023

Penyakit kardiovaskular (CVD) merupakan penyebab utama kematian yang dipengaruhi oleh peningkatan kadar MDA dan pola makan yang tidak seimbang. Di Indonesia, CVD merupakan 1/3 dari penyebab utama morbiditas dan mortalitas. Konsumsi artificial sweeteners stevia dapat dijadikan upaya pencegahan faktor risiko terjadinya penyakit kardiovaskular. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian artificial sweeteners stevia terhadap berat badan, profil jaringan lemak, nilai glukosa darah, dan kadar Malondialdehyde (MDA) pada Tikus Galur Wistar. Jenis penelitian ini adalah laboratorium eksperimental menggunakan desain one group pre-test, post-test, dan control group yang dibagi menjadi tiga kelompok (kontrol, artificial sweeteners stevia, dan gula dapur) selama 4 minggu. Subjek penelitian ini adalah Tikus Galur Wistar sebanyak 30 ekor. Pemberian artificial sweeteners stevia pada tikus galur wistar memberikan hasil yang signifikan terhadap peningkatan berat badan dan profil jaringan lemak (p<0,05). Namun, tidak signifikan terhadap nilai glukosa darah (sewakt u) (p>0,05) dan kadar Malondialdehyde (MDA) (p>0,05). Terdapat pengaruh positif dari pemberian artificial sweetener stevia terhadap tikus galur wistar. Ditinjau dari perspektif Islam, konsumsi artificial sweetener stevia yaitu halal dan boleh digunakan untuk dikonsumsi karena mengandung banyak manfaat positif terhadap kesehatan dibandingkan mudharat yang akan diterima oleh manusia. Diperlukan penelitian lebih lanjut dengan durasi yang lebih lama mengenai variabel yang tidak terkontrol terkait keterbatasan dalam penelitian ini.
Analisis Kandungan DNA Babi pada Produk Daging Olahan di Pasar-Pasar Kelurahan Cempaka Putih dan Tinjauannya Menurut Pandangan Islam
Authors: Salsabila Nurul , Suciati Yulia , Astiwara Endy Muhammad
Published: November 2023

Pendahuluan: Berdasarkan syariat islam, status kehalalan suatu makanan menjadi syarat bagi umat muslim dalam mengambil keputusan untuk mengonsumsi suatu makanan. Banyak masyarakat terutama umat muslim resah terhadap pencampuran bahan non-halal seperti pencampuran daging babi ke dalam produk daging olahan, padahal di Indonesia produk daging olahan seperti bakso, sosis, nugget, dan kornet termasuk salah satu produk makanan yang banyak dikonsumsi. Belum ada informasi tentang analisis cemaran DNA babi pada produk daging olahan terutama produk bakso di pasar-pasar Kelurahan Cempaka Putih. Maka dari itu, tujuan dari penelitian ini ialah menganalisa keberadaan cemaran DNA babi pada produk daging olahan berupa produk bakso di pasar-pasar Kelurahan Cempaka Putih serta tinjauannya menurut islam. Metode: Metode analisis yang digunakan pada penelitian ini adalah Real Time Polymerase Chain Reaction (RT-PCR) dengan menggunakan QIAGEN Mericon Pig Kit. Hasil: Hasil penelitian menunjukkan bahwa seluruh sampel produk bakso (5 sampel uji) tidak mengandung DNA babi. Kesimpulan: Mayoritas ulama sepakat bahwa memanfaatkan babi dan seluruh unsur-unsur babi adalah haram, dengan tidak adanya sampel yang tercemar DNA babi maka produk sampel bakso di Pasar-Pasar Kelurahan Cempaka Putih aman untuk dikonsumsi umat muslim.
Perbandingan Berat Feses Template Kato-Katz Standar dengan Template Kato-Katz Akrilik Untuk Pemeriksaan Telur Cacing
Authors: Maulana Muhammad
Published: November 2023

KATA KUNCI          Berat feses, Template Kato-Katz ABSTRAK                 Pemeriksaan infeksi kecacingan dapat dilakukan dengan 2 metode, yaitu secara kualitatif dan kuantitatif. Pemeriksaan kualitatif yaitu metode direct slide, sedangkan pemeriksaan kuantitatif yaitu metode Kato-Katz. Kemajuan pada bidang teknik kimia memperkenalkan material baru yaitu akrilik. Akrilik bisa  diaplikasikan di bidang kesehatan contohnya pada pembuatan template Kato-Katz. Tujuan dari penelitian ini adalah untuk mengetahui perbandingan berat feses template Kato Katz standar ketebalan template 1,5 mmdan diameter lubang 6 mmdengan template Kato-Katz akrilik ketebalan template 2 mmdan diameter lubang 6 mmuntuk pemeriksaan telur cacing serta memperoleh nilai  faktor perkalian, untuk mendapatkan nilai EPG (Egg Per Gram). Jenis penelitian ini adalah Survey Analitik dengan rancangan Study Komparatif,  jumlah populasi sebanyak 30 orang dengan sebanyak 30 sampel dan cara pengambilan menggunakan Teknik Total Sampling. Berat feses ditimbang menggunakan timbangan analitik menggunakan template standar lalu dibandingkan dengan berat feses menggunakan template akrilik. Didapatkan hasil rata-rata berat feses dengan template standar sebesar 41,80 mg dan berat template akrilik sebesar 43,22 mg, faktor perkalian yang didapat pada template standar adalah 24 dan pada template akrilik adalah 23. Berdasarkan uji statistik yang dilihat dari nilai sig. (2-tailed) didapatkan nilai signifikasi 0,000 yang menujukkan P<? (?=0,05), artinya terdapat perbedaan yang bermakna antara berat feses template Kato-Katz standar dengan template Kato-Katz akrilik untuk pemeriksaan telur cacing. Disarankan kepada peneliti selanjutnya melakukan penelitian pengaruh setiap jenis konsistensi feses dan menggunakan pengaturan yang lebih beragam.
Hubungan Kepadatan Parasit Malaria dengan Jumlah Trombosit pada Penderita Malaria di Kecamatan Cempaka
Authors: Farras Muhammad Denny
Published: November 2023

Malaria disebabkan oleh parasit Plasmodium dan disebarkan ke manusia lewat gigitan nyamuk betina Anopheles yang telah terinfeksi. Kepadatan parasit malaria adalah jumlah parasit malaria dalam setiap mikroliter darah pasien yang terinfeksi. Pada penderita malaria, terjadi peningkatan antibodi antiplatelet IgG yang menyebabkan fagositosis trombosit dan menyebabkan turunnya jumlah trombosit dalam tubuh. Tujuan penelitian ini adalah untuk mengetahui hubungan kepadatan parasit malaria dengan jumlah trombosit pada penderita malaria di Kecamatan Cempaka. Jenis penelitian ini yaitu Survey Analitik dengan rancangan penelitian cross sectional, dengan jumlah populasi dan jumlah sampel sebanyak 17 sampel dengan teknik sampling Total Sampling. Variabel kepadatan parasit malaria didapat dari pemeriksaan mikroskopis malaria dengan sampel darah vena. Variabel jumlah trombosit didapat dari pemeriksaan trombosit metode Hematology Analyzer. Pada responden didapatkan kepadatan parasit yaitu 195- 67.883 parasit/uL dengan rata-rata 17.527 parasit/uL. Jumlah trombosit 58.000- 321.000 sel/uL dengan rata-rata 156.235 sel/uL. Berdasarkan uji statistik metode Spearman, didapatkan p value= 0,031 dengan koefisien korelasi -0,525 yang berarti terdapat hubungan yang signifikan antara kepadatan parasit malaria dengan jumlah trombosit pada penderita malaria di Kecamatan Cempaka. Kesimpulan pada penelitian ini yaitu kepadatan pada 17 orang responden adalah 195-67.883 parasit/uL, jumlah trombosit 58.000-321.000 sel/uL, dan terdapat hubungan antara kepadatan parasit dan jumlah trombosit pada penderita malaria di Kecamatan Cempaka. Saran kepada peneliti selanjutnya untuk melakukan penelitian dengan variabel eritrosit.KEYWORDS Malaria, Platelets, Parasite Density
The Relationship Between Mother's Attitude and Behavior to The Nutritional Status of Preschool Children in Kalanganyar District, Lebak, Banten and Its Overview from An Islamic
Authors: Fakhiroh Lulu , Indrawati Isna , Istiwara Endy Muhammad
Published: November 2023

Background: The nutritional status of children under five is one measure of the success of health development, therefore it is necessary to pay attention to the nutrition of children under five. Factors that affect nutritional status can be divided into direct and indirect factors. Direct factors are determined by food intake and infectious diseases, while indirect factors include the availability of food in the family, parenting patterns, health services and environmental conditions. The purpose of this study was to describe the nutritional status of preschool children in Kalanganyar Lebak District, Banten. To find out the picture of parenting style on the nutritional status of preschool children in the District of Kalanganyar Lebak, Banten. To determine the relationship between maternal parenting behavior and the nutritional status of preschool children in Kalanganyar Lebak District, Banten. The method in this study used a quantitative type with correlation analytic, namely to see the relationship between attitudes and behavior of mother's parenting pattern towards the nutritional status of preschool children in Kalanganyar District, Lebak, Banten. Result: The results of this study from the bivariate test showed a p value of 0.0024 <0.05 which means that there is a relationship between mother's parenting behavior and children's nutritional status. The results of the bivariate analysis test showed a p value of 0.034 <0.05 which means that there is a relationship between mother's parenting behavior and children's nutritional status. Conclusion: The conclusion from this study is that there is a relationship between maternal parenting behavior and the nutritional status of preschool children in Kalanganyar District, Lebak Banten. There is a relationship between mother's parenting behavior and nutritional status of preschool children in the Kalanganyar sub-district, Lebak, Banten.
Kesadaran Masyarakat Terhadap Faktor Risiko Penyakit Zoonosis di Desa Koncang Pandeglang Banten dan Tinjauannya Menurut Pandangan Islam
Authors: Halida Ezayffa Hizfar , Hardjanti Ambar , Arifandi Firman
Published: November 2023

Pendahuluan: Zoonosis adalah penyakit menular yang ditularkan dari hewan ke masyarakat, begitu juga sebaliknya. Untuk mencegah terpaparnya penyakit zoonosis, masyarakat perlu memiliki kesadaran terhadap faktor-faktor yang berisiko menyebabkan penyakit tersebut. Penelitian ini bertujuan untuk mengetahui tingkat kesadaran masyarakat, meliputi pengetahuan, sikap dan perilaku, mengetahui hubungan pengetahuan dan perilaku, serta hubungan sikap dan perilaku masyarakat terhadap faktor risiko penyakit zoonosis di Desa Koncang Pandeglang Banten dan tinjauannya menurut pandangan Islam.  Metodologi: Jenis penelitian ini adalah kuantitatif yang menggunakan metode penelitian survei dengan pendekatan cross sectional. Cara penetapan sampel adalah Purposive Random Sampling. Sampel pada penelitian ini adalah masyarakat Desa Koncang dengan total 49 responden. Pengambilan data dilakukan dengan teknik wawancara.Hasil: Dari hasil analisa, didapatkan 51% responden memiliki tingkat pengetahuan yang sangat baik terhadap faktor risiko penyakit zoonosis. 49% responden memiliki sikap yang baik. 55% responden memiliki perilaku yang sangat baik. Perilaku seluruh responden tergolong baik, dan hanya 7 orang memiliki pengetahuan yang buruk, dan 1 orang memiliki sikap yang buruk. Hasi uji Chi Square pada hubungan antara pengetahuan dan perilaku menunjukkan hasil 0,75 (p>0,05). Sedangkan pada hubungan antara sikap dan perilaku menunjukkan hasil 0,276 (p>0.05).Kesimpulan: Secara keseluruhan, masyarakat Desa Koncang memiliki pengetahuan, sikap dan perilaku yang baik terhadap faktor risiko penyakit zoonosis. Tidak terdapat hubungan yang signifikan antara pengetahuan dan perilaku masyarakat terhadap faktor risiko penyakit zoonosis. Menunjukkan hasil yang serupa, tidak terdapat hubungan yang signifikan antara sikap dan perilaku masyarakat terhadap faktor risiko penyakit zoonosis.
Hubungan antara Status Gizi dengan Tingkat Perkembangan Anak yang Teridentifikasi Stunting di Wilayah Jakarta Selatan Tahun 2022
Authors: Tuty  , Mangunatmadja Irawan
Published: November 2023

Stunting merupakan salah satu faktor risiko yang kuat terhadap keterlambatan perkembangan. Gangguan perkembangan bersifat multifaktorial tetapi saat ini belum terdapat hubungan yang jelas antara perkembangan dengan status gizi. Melalui studi ini, peneliti ingin melihat hubungan antara status gizi dan perkembangan pada anak usia balita. Penelitian potong lintang pada anak berusia kurang dari 5 tahun dengan stunting dilakukan pada 9 Puskesmas di Jakarta Selatan sejak Januari hingga Juli 2022. Pada subjek dilakukan pengukuran antropometri dan pemeriksaan perkembangan menggunakan Ages and Stages Questionnaires (ASQ) versi 3. Status gizi pasien diolah menggunakan aplikasi WHO antropometri dan analisis data menggunakan SPSS. Terdapat 136 subjek yang sesuai dengan kriteria inklusi, dengan total subjek akhir didapatkan 100 subjek. Karakteristrik demografi subjek sedikit didominasi jenis kelamin perempuan (51%), median usia subjek adalah 34 bulan berkisar antara 5 – 56 bulan, dan status gizi didominasi gizi baik (60%). Perkembangan yang tidak normal didapatkan pada 64 subjek (64%) dengan keterlambatan perkembangan global pada 29% subjek. Tidak terdapat hubungan yang signifikan antara status gizi dengan gangguan perkembangan pada subjek (p = 0,598). Terdapat hubungan yang signifikan antara nilai Z-score Weight-for-Height (WHZ) dengan aspek perkembangan komunikasi (p = 0,07) dan motorik kasar (p = 0,015). Status gizi tidak memengaruhi keterlambatan perkembangan secara keseluruhan tetapi memiliki hubungan dengan aspek komunikasi dan motorik kasar. Studi lebih lanjut mengenai status gizi dan tingkat perkembangan perlu dilakukan.
Essensi Ruhul Islam dalam Tantangan Spiritual Era Kontemporer
Authors: Ahmadi
Published: November 2023

Pentingnya memahami dan membahas esensi ruhul Islam dalam era kontemporer (masa kini) tidak dapat diabaikan. Dalam konteks masa kini, di mana kita dihadapkan dengan berbagai perubahan sosial, teknologi, dan tuntutan kehidupan modern, sangat penting untuk memahami bagaimana nilai-nilai dan prinsip-prinsip Islam dapat diterapkan secara relevan dalam kehidupan kita. Era kontemporer ditandai dengan kemajuan teknologi, globalisasi, dan perubahan sosial yang cepat, seringkali mempengaruhi nilai-nilai spiritual dan keyakinan agama seseorang. Tantangan spiritual dalam era kontemporer meliputi materialisme, konsumerisme, sekularisme, kemajuan teknologi, dan pluralisme serta toleransi, perpecahan golongan umat islam terkait dengan adanya ajaran-ajaran islam yang menyimpang makin sering terjadi. Penting bagi umat Islam untuk kembali memperdalam, memahami dan mewujudkan essensi Ruhul Islam dalam praktik kehidupan kontemporer. Essensi Ruhul Islam mengacu pada pemahaman dan penghayatan yang benar akan Islam sebagai agama. Tujuan penelitian ini adalah untuk menganalisis dan memahami secara mendalam esensi Ruhul Islam dan nilai-nilai spiritual yang diemban oleh ajaran Islam, sehingga nilai-nilai tersebut dapat membantu individu Muslim menghadapi tantangan spiritual yang dihadapi dalam era kontemporer. Metode penelitian yang digunakan adalah studi literatur yakni analisis terhadap sumber-sumber literatur yang relevan dengan topik penelitian. Hasil Penelitian menunjukkan bahwa penerapkan esensi Ruhul Islam dapat membawa dampak positif pada kualitas spiritual dan kenyakinan beragama individu Muslim, membantu kita menghadapi tantangan dan cobaan dengan lebih baik, serta mencapai kedamaian pikiran dan jiwa dalam menghadapi tekanan kehidupan kontemporer.
Lipid Nanoparticle-Mediated Delivery of CRISPR-Cas9 for Therapeutic Gene Correction
Authors:   , Walther Johanna
Published: November 2023

The thesis “Lipid Nanoparticle-Mediated Delivery of CRISPR-Cas9 for Therapeutic Gene Correction” delves into the potential of CRISPR-Cas9 as a gene therapy tool for treating hereditary disorders. Originally a bacterial defense mechanism, CRISPR-Cas9 has been modified into a precision gene editing tool. It functions like molecular scissors, creating specific DNA breaks that trigger DNA repair processes, which, when coupled with repair DNA, can correct gene mutations causing hereditary diseases. However, the challenge lies in safely and efficiently delivering CRISPR-Cas9 to affected organs in patients.

The thesis explores the use of lipid nanoparticles, small, virus-sized particles composed of naturally occurring body fats, as a viable delivery system for CRISPR-Cas9. The work in this thesis demonstrates that the designed lipid nanoparticles can effectively transport CRISPR-Cas9 into both cultured cells and later in liver cells of mice as well. Moreover, the results show that the delivered CRISPR-Cas9 generates precise genome edits. Furthermore, it addresses the potential immune responses against CRISPR-Cas9, given it bacterial origin, and introduces a strategy to mitigate such reactions.

In summary, this thesis presents a promising approach to deliver CRISPR-Cas9 to diseased cells, enabling the precise correction of pathogenic gene mutations, marking a significant advancement in the field of gene therapy for hereditary disorders.
Invisible Women: Data Bias in a World Designed for Men
Authors: HAVAN Cumhur
Published: November 2023

Caroline Criado Perez's "Invisible Women: Data Bias in a World Designed for Men" addresses a pervasive issue of gender data bias and its far-reaching implications in various spheres of society. Through a meticulously researched and thought-provoking analysis, Perez sheds light on the historical, cultural, and systemic factors that have contributed to this data gap. This academic book review examines the key arguments, strengths, and contributions of "Invisible Women," while also evaluating its impact on the broader field of gender studies and policy-making.
Cheminformatics and artificial intelligence for accelerating agrochemical discovery
Authors: Djoumbou-Feunang Yannick , Wilmot Jeremy , Kinney John , Chanda Pritam , Yu Pulan , Sader Avery , Sharifi Max , Smith Scott , Ou Junjun , Hu Jie , Shipp Elizabeth , Tomandl Dirk , Kumpatla Siva P.
Published: November 2023

The global cost-benefit analysis of pesticide use during the last 30 years has been characterized by a significant increase during the period from 1990 to 2007 followed by a decline. This observation can be attributed to several factors including, but not limited to, pest resistance, lack of novelty with respect to modes of action or classes of chemistry, and regulatory action. Due to current and projected increases of the global population, it is evident that the demand for food, and consequently, the usage of pesticides to improve yields will increase. Addressing these challenges and needs while promoting new crop protection agents through an increasingly stringent regulatory landscape requires the development and integration of infrastructures for innovative, cost- and time-effective discovery and development of novel and sustainable molecules. Significant advances in artificial intelligence (AI) and cheminformatics over the last two decades have improved the decision-making power of research scientists in the discovery of bioactive molecules. AI- and cheminformatics-driven molecule discovery offers the opportunity of moving experiments from the greenhouse to a virtual environment where thousands to billions of molecules can be investigated at a rapid pace, providing unbiased hypothesis for lead generation, optimization, and effective suggestions for compound synthesis and testing. To date, this is illustrated to a far lesser extent in the publicly available agrochemical research literature compared to drug discovery. In this review, we provide an overview of the crop protection discovery pipeline and how traditional, cheminformatics, and AI technologies can help to address the needs and challenges of agrochemical discovery towards rapidly developing novel and more sustainable products.
Antiviral options and therapeutics against influenza: history, latest developments and future prospects
Authors: Meseko Clement , Sanicas Melvin , Asha Kumari , Sulaiman Lanre , Kumar Binod
Published: November 2023

Drugs and chemotherapeutics have helped to manage devastating impacts of infectious diseases since the concept of ‘magic bullet’. The World Health Organization estimates about 650,000 deaths due to respiratory diseases linked to seasonal influenza each year. Pandemic influenza, on the other hand, is the most feared health disaster and probably would have greater and immediate impact on humanity than climate change. While countermeasures, biosecurity and vaccination remain the most effective preventive strategies against this highly infectious and communicable disease, antivirals are nonetheless essential to mitigate clinical manifestations following infection and to reduce devastating complications and mortality. Continuous emergence of the novel strains of rapidly evolving influenza viruses, some of which are intractable, require new approaches towards influenza chemotherapeutics including optimization of existing anti-infectives and search for novel therapies. Effective management of influenza infections depend on the safety and efficacy of selected anti-infective in-vitro studies and their clinical applications. The outcomes of therapies are also dependent on understanding diversity in patient groups, co-morbidities, co-infections and combination therapies. In this extensive review, we have discussed the challenges of influenza epidemics and pandemics and discoursed the options for anti-viral chemotherapies for effective management of influenza virus infections.
Carbon source–dependent capsule thickness regulation in Streptococcus pneumoniae
Authors: Werren Joel P. , Mostacci Nadja , Gjuroski Ilche , Holivololona Lalaina , Troxler Lukas J. , Hathaway Lucy J. , Furrer Julien , Hilty Markus
Published: November 2023

Background

The polysaccharide capsule of Streptococcus pneumoniae plays a major role in virulence, adherence to epithelial cells, and overall survival of the bacterium in the human host. Galactose, mannose, and N-acetylglucosamine (GlcNAc) are likely to be relevant for metabolization in the nasopharynx, while glucose is the primary carbon source in the blood. In this study, we aim to further the understanding of the influence of carbon sources on pneumococcal growth, capsule biosynthesis, and subsequent adherence potential.

Methods

We tested the growth behavior of clinical wild-type and capsule knockout S. pneumoniae strains, using galactose, GlcNAc, mannose, and glucose as carbon source for growth. We measured capsule thickness and quantified capsule precursors by fluorescein isothiocyanate (FITC)–dextran exclusion assays and 31P-nuclear magnetic resonance measurements, respectively. We also performed epithelial adherence assays using Detroit 562 cells and performed a transcriptome analysis (RNA sequencing).

Results

We observed a reduced growth in galactose, mannose, and GlcNAc compared to growth in glucose and found capsular size reductions in mannose and GlcNAc compared to galactose and glucose. Additionally, capsular precursor measurements of uridine diphosphate-(UDP)-glucose and UDP-galactose showed less accumulation of precursors in GlcNAc or mannose than in glucose and galactose, indicating a possible link with the received capsular thickness measurements. Epithelial adherence assays showed an increase in adherence potential for a pneumococcal strain, when grown in mannose compared to glucose. Finally, transcriptome analysis of four clinical isolates revealed not only strain specific but also common carbon source-specific gene expression.

Conclusion

Our findings may indicate a careful adaption of the lifestyle of S. pneumoniae according to the monosaccharides encountered in the respective human niche.
Does sacubitril/valsartan work in children with heart failure?—a pilot study
Authors: Xu Yahe , Zhang Mingjie , Chen Yijun , Chen Xi , Song Wenting , Zhu Limin , Liu Liping , Gong Xiaolei , Zhang Yuqi , Xu Zhuoming
Published: November 2023

Background

Sacubitril/valsartan is an angiotensin receptor neprilysin antagonist (ARNI) approved for adult heart failure (HF). Its safety and efficacy in pediatric HF patients with cardiomyopathy or congenital heart disease are poorly understood. A pilot study was conducted to assess the clinical response, efficacy and safety of sacubitril/valsartan in this population at a tertiary care hospital in China.

Methods

Clinical parameters of patients who received sacubitril/valsartan from January 2019 to March 2023 were retrospectively collected and analyzed. Children over 1 month with a left ventricular ejection fraction (LVEF) <45% were included. Clinical efficacy was evaluated by echocardiographic LVEF, N-terminal pro-brain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) HF classification, HF re-admission, and death or transplantation. The initial dose was either 0.2 mg/kg bid or 0.4 mg/kg bid, with a target dose of 2.3 mg/kg bid or 3.1 mg/kg bid.

Results

Forty-five patients (60% male) with a median age of 7.86 years were enrolled. Among them, 23 had congenital heart disease and 22 had cardiomyopathies. The median maintenance dose was 0.76 mg/kg. The primary endpoint of LVEF up to 45% was reached by 24 patients (53.3%). The median NT-proBNP was significantly decreased from 5,501.5 pg/ml to 2,241.5 pg/ml (P < 0.001), more in congenital heart disease than in cardiomyopathies (P = 0.032). The NYHA HF class was improved or remained stable in 42 cases (93.3%). During a median follow-up of 1.23 years, 13 patients (28.9%) were re-hospitalized due to HF, and 9 patients (20%) died or underwent transplantation. Hypotension was the main adverse event, occurring in 8 patients.

Conclusions

Sacubitril/valsartan may be effective in children with HF, but its safety and outcomes may differ depending on the etiology and anatomy of HF. Early post-operative congenital heart disease patients had less tolerance, more hypotension but better recovery and outcomes, while mid- and late- post-operative congenital heart disease patients and cardiomyopathy patients had less side effects but poorer clinical outcomes.
Symmetrical peripheral gangrene: potential mechanisms and therapeutic approaches in severe COVID-19
Authors: Wang Manzhi , Sun Tao , Dong Liang , Huang Shengshi , Liu Ju
Published: November 2023

Symmetrical peripheral gangrene is a rare condition that is characterized by ischemic damage and tissue death (gangrene) in the extremities. Recent reports have shed light on SPG in patients with severe COVID-19. This condition presents with symmetrical cyanosis of the extremities and common COVID-19 symptoms and what the most frightening is within a few days, cutaneous necrosis occurred and patients died. Skin biopsy results have shown the presence of microthrombi in small vessels. The formation of SPG in COVID-19 patients results from immunothrombosis, endothelial dysfunction, and procoagulant platelets, leading to a hypercoagulation state and microvascular thrombosis. Thrombotic microangiopathy, shock, disseminated intravascular coagulation, and anticoagulant depletion promote the development of SPG in COVID-19. At the early stage, SPG patients with COVID-19 exhibit similar clinical manifestations. TMA causes early damage to microvasculature in SPG, and the shock state further exacerbates the ischemic injury due to local hypo-perfusion. The disturbed procoagulant-anticoagulant balance caused by DIC and anticoagulant depletion, combined with the pre-ischemic state brought on by TMA and shock, leads to the rapid formation of extensive microthrombi in the late stage of COVID-19 associated SPG. This review will delve into the clinical features, possible mechanisms, and potential therapeutic managements for COVID-19 associated SPG.
Reducing carbon emission in the goat farms by switching from conventional goat farming to green goat farm typology
Authors: Canan Selime
Published: November 2023

The carbon footprint of goat farms associated with the management type and the income sacrifice to switch to green goat farms are still not precise in the literature. Therefore, the objectives of this study were 1) to assess the environmental impacts of goat farming associated with management typology in Türkiye and 2) to explore the link between farm-level income sacrifice and the amount of greenhouse gas (GHG) reduction. Goat farm-level data were collected from randomly selected 284 goat farms through a questionnaire. Environmental impacts of goat farming associated with the management typology were examined using the life cycle assessment (LCA). The GHG emissions were calculated both for the whole goat farm associated with the management type and for individual goat products such as milk, meat, mohair, and replacement. The research results showed that Turkish goat farms emitted GHG emissions for the production of per kg of meat, milk, and mohair by 9.85 kg CO2-eq, 8 kg CO2-eq, and 0.28 kg CO2-eq, respectively. Goat farms in management type 1 emitted the highest GHG emission in a year, while that of goat farms in type 5 was the lowest. The research results also showed that the environmental impact and farm-level income sacrifice per kg GHG emission reduction to reach the level of environmentally friendly goat farms varied according to the management type of goat farms. Typical Turkish goat farms gained agricultural income by 2.47 USD per kg of GHG emission. The amount of agricultural income gained per kg GHG emission varied according to typology. Based on the research results, typical Turkish goat farms faced with an income sacrifice of 2.85 USD per kg GHG emission reduction to reach the level of environmentally friendly goat farms having minimum GHG emission in a year. Turkish goat farms emitted 0.49 kg CO2-eq per USD of agricultural production expenses. The study suggests switching from a conventional management type to environmentally friendly management type goat farms. Facilitating the accessibility of financial resources may enhance the switching process through benefiting investments in infrastructure, equipment, and research and development. Creating resource-efficient and environmentally friendly goat farms by subsidizing the goat farms may decrease GHG emissions.
Intra-annual carbon fluxes and resource use efficiency of subtropical urban forests: insights from Chongming Island ecological observatory
Authors: Zheng Ji , Han Yujie , Sun Ningxiao , Ye Yize , Yan Jingli , Zhang Wenwen , Yin Shan
Published: November 2023

Understanding the carbon budget within cities is crucial in the context of carbon peaking and carbon neutrality. This study investigates the carbon source-sink dynamics of urban forest ecosystems using carbon flux observations from the Chongming Island Ecological Observatory in Shanghai. The study aims to reveal the intra-annual variations of carbon fluxes and explore the changes in resource use efficiency of urban forest ecosystems within the framework of the big-leaf model. The results reveal distinct patterns in temperature (Tair), relative humidity (RH), radiation, and vapor pressure deficit (VPD). Diurnal cycles of net ecosystem exchange (NEE), gross primary production (GPP), and ecosystem respiration (Reco) exhibit seasonal variations, with higher amplitudes observed from April to September. The observed forest ecosystem acts as a moderate carbon sink (318.47 gC m−2 year−1), with the highest carbon uptake occurring in May and the highest carbon emission in February. During the growing season, the total carbon sink was 225.37 gC m−2, composed of GPP 1337.01 gC m−2 and Reco 1111.64 gC m−2. Water-use efficiency (WUE) and light-use efficiency (LUE) exhibit seasonal variations, while carbon-use efficiency (CUE) declines after May. These findings contribute to our understanding of urban forest carbon dynamics and their potential role in carbon management strategies.
The unique immune ecosystems in pediatric brain tumors: integrating single-cell and bulk RNA-sequencing
Authors: Cao Liangliang , Xie Wanqun , Ma Wenkun , Zhao Heng , Wang Jiajia , Liang Zhuangzhuang , Tian Shuaiwei , Wang Baocheng , Ma Jie
Published: November 2023

Background

The significant progress of immune therapy in non-central nervous system tumors has sparked interest in employing the same strategy for adult brain tumors. However, the advancement of immunotherapy in pediatric central nervous system (CNS) tumors is not yet on par. Currently, there is a lack of comprehensive comparative studies investigating the immune ecosystem in pediatric and adult CNS tumors at a high-resolution single-cell level.

Methods

In this study, we comprehensively analyzed over 0.3 million cells from 171 samples, encompassing adult gliomas (IDH wild type and IDH mutation) as well as four major types of pediatric brain tumors (medulloblastoma (MB), ependymoma (EPN), H3K27M-mutation (DIPG), and pediatric IDH-mutation glioma (P-IDH-M)). Our approach involved integrating publicly available and newly generated single-cell datasets. We compared the immune landscapes in different brain tumors, as well as the detailed functional phenotypes of T-cell and myeloid subpopulations. Through single-cell analysis, we identified gene sets associated with major cell types in the tumor microenvironment (gene features from single-cell data, scFes) and compared them with existing gene sets such as GSEA and xCell. The CBTTC and external GEO cohort was used to analyze and validate the immune-stromal-tumor patterns in pediatric brain tumors which might potentially respond to the immunotherapy.

Results

From the perspective of single-cell analysis, it was observed that major pediatric brain tumors (MB, EPN, P-IDH-M, DIPG) exhibited lower immune contents compared with adult gliomas. Additionally, these pediatric brain tumors displayed diverse immunophenotypes, particularly in regard to myeloid cells. Notably, the presence of HLA-enriched myeloid cells in MB was found to be independently associated with prognosis. Moreover, the scFes, when compared with commonly used gene features, demonstrated superior performance in independent single-cell datasets across various tumor types. Furthermore, our study revealed the existence of heterogeneous immune ecosystems at the bulk-RNA sequencing level among different brain tumor types. In addition, we identified several immune-stromal-tumor patterns that could potentially exhibit significant responses to conventional immune checkpoint inhibitors.

Conclusion

The single-cell technique provides a rational path to deeply understand the unique immune ecosystem of pediatric brain tumors. In spite of the traditional attitudes of “cold” tumor towards pediatric brain tumor, the immune-stroma-tumor patterns identified in this study suggest the feasibility of immune checkpoint inhibitors and pave the way for the upcoming tide of immunotherapy in pediatric brain tumors.
Mechanism underlying polyvalent IgG-induced regulatory T cell activation and its clinical application: Anti-idiotypic regulatory T cell theory for immune tolerance
Authors: Victor Jefferson Russo , Nahm Dong-Ho
Published: November 2023

The regulatory T (Treg) cells constitute a functionally defined subpopulation of T cells that modulate the immune system and maintain immune tolerance through suppression of the development of autoimmune responses to self-antigens and allergic reactions to external antigens. Reduction in the number or function of Treg cells has been suggested as a key immune abnormality underlying the development of autoimmune and allergic diseases. In vitro studies have demonstrated that purified polyvalent immunoglobulin G (IgG) from multiple healthy blood donors can exert immunomodulatory effects on Treg cells. Incubation of polyvalent human IgG with purified CD4+CD25high T cells increased the intracellular expression of interleukin (IL)-10. Intravenous administration of polyvalent human IgG induced significant expansions of CD4+ Foxp3+ Treg cells and clinical improvements in patients with autoimmune diseases. In human clinical trials, intramuscular administration of autologous total IgG significantly increased the percentage of IL-10-producing CD4+ Treg cells in the peripheral blood of healthy subjects and provided significant clinical improvements in patients with atopic dermatitis. These results suggest a clinical usefulness of polyvalent IgG-induced activation of Treg cells in human subjects. This review proposes a new hypothesis for immune tolerance mechanism by integrating the pre-existing “idiotypic network theory” and “Treg cell theory” into an “anti-idiotypic Treg cell theory.” Based on this hypothesis, an “active anti-idiotypic therapy” for allergic and autoimmune diseases using autologous polyvalent IgG (as immunizing antigens) is suggested as follows: (1) Intramuscular or subcutaneous administration of autologous polyvalent IgG produces numerous immunogenic peptides derived from idiotypes of autologous IgG through processing of dendritic cells, and these peptides activate anti-idiotypic Treg cells in the same subject. (2) Activated anti-idiotypic Treg cells secrete IL-10 and suppress Th2 cell response to allergens and autoimmune T cell response to self-antigens. (3) These events can induce a long-term clinical improvements in patients with allergic and autoimmune diseases. Further studies are needed to evaluate the detailed molecular mechanism underlying polyvalent IgG-induced Treg cell activation and the clinical usefulness of this immunomodulatory therapy for autoimmune and allergic diseases.
Semaphorin 7A is protective during inflammatory peritonitis through integrin receptor signaling
Authors: Körner Andreas , Köhler David , Schneider Mariella , Roth Judith M. , Granja Tiago F. , Eggstein Claudia , Mirakaj Valbona , Rosenberger Peter
Published: November 2023

Introduction

The study explores the role of endothelial Semaphorin 7A (SEMA7A) in inflammatory processes. SEMA7A is known for enhancing inflammation during tissue hypoxia and exhibiting anti-inflammatory properties in the intestinal system during colitis. This research extends the understanding of SEMA7A's function by examining its role in inflammatory peritonitis and intestinal inflammation.

Methods

The research involved inducing peritonitis in SEMA7A knockout (SEMA7A-/-) and wild-type (WT) animals through Zymosan A (ZyA) injection. The inflammatory response was assessed by measuring cell count and cytokine release. In parallel, the study investigated the expression of SEMA7A in intestinal epithelial cells under inflammatory stimuli and its impact on interleukin 10 (IL-10) production using an in vitro co-culture model of monocytes and epithelial cells. Additionally, the distribution of SEMA7A target receptors, particularly ITGAV/ITGB1 (CD51/CD29), was analyzed in WT animals.

Results

The results revealed that SEMA7A-/- animals exhibited increased inflammatory peritonitis compared to the WT animals. Inflammatory conditions in intestinal epithelial cells led to the induction of SEMA7A. The co-culture experiments demonstrated that SEMA7A induced IL-10 production, which depended on integrin receptors and was independent of PLXNC1 expression. Furthermore, ITGAV/ITGB1 emerged as the predominant SEMA7A receptor in the intestinal area of WT animals.

Discussion

These findings underscore the multifaceted role of SEMA7A in inflammatory processes. The differential responses in peritonitis and intestinal inflammation suggest that SEMA7A's function is significantly influenced by the expression and distribution of its target receptors within different organ systems. The study highlights the complex and context-dependent nature of SEMA7A in mediating inflammatory responses.
Transcriptomic response to salinity variation in native and introduced mud-tidal gastropod Batillaria attramentaria
Authors: Patra Ajit Kumar , Ho Phuong-Thao , Won Yong-Jin
Published: November 2023

The introduced Asian mud-tidal gastropod Batillaria attramentaria has been reported to quickly dominate its new habitat, Elkhorn Slough, USA, which has a different osmotic condition from its native habitat. This species has also been reported to have a substantial impact on the ecosystem of the new habitat. In this study, we compared the gene expression profiles in response to temporary salinity variation in native (Asian) and introduced (North American) snails and elucidated the genetic mechanism underlying such rapid adaptation of the introduced species. We examined the transcriptomes of four B. attramentaria populations, including three from the native habitats and one from the introduced habitat, in response to salinity variation. We found that 2,353, 2,505, 10,362, and 16,381 genes were differentially expressed due to their lineages (Kuroshio vs. Tsushima), origins (native vs. introduced), locations (Korea, Japan, or the USA), and salinity variations (stressful: 13, 23, and 43 PSU vs. optimal: 33 PSU), respectively. We found that GO-enriched differentially expressed genes involved in the detection of various abiotic and biotic stimuli through sensory perception and genes involved in response to abiotic stimulus and stress were upregulated when exposed to lower-salinity conditions in all locations. The results indicated that B. attramentaria has adapted well to varied salinity conditions and evolved after around 100 years of invasion in Elkhorn Slough. This study provides valuable transcriptomic data on salinity stress response genes in the tidal gastropod and contributes to the research on the adaptive evolution of coastal gastropods.
Evaluation of mangrove restoration effectiveness using remote sensing indices - a case study in Guangxi Shankou Mangrove National Natural Reserve, China
Authors: Wang Yuhang , Wang Xifei , Khan Shahbaz , Zhou Demin , Ke Yinghai
Published: November 2023

As one of the most productive marine ecosystems in the coastal wetlands, mangrove forests have been severely threatened by intensive human activities. Many countries and regions have carried out mangrove restoration projects. The evaluation of mangrove restoration effectiveness is of great significance for scientific decision-making for restoration engineering and wetland management. In this study, we presented a remote-sensing-based Mangrove Restoration Effectiveness Index (MREI) to evaluate mangrove restoration effectiveness. We took the Guangxi Shankou Mangrove National Natural Reserve (GSMNNR) in China, a UNESCO Biosphere Reserve, as our study area, where four phases of afforestation were implemented during 1990-2022. The MREI was developed based on Landsat-series images by considering the change in mangrove area and the Normalized Difference Vegetation Index (NDVI) from the start year to the end year of each afforestation phase (evaluation period). We further evaluated the Persistence of Restoration Effectiveness (PRE) based on the MREI change trajectory during the whole evaluation period, and the Process-based Restoration Effectiveness Index (PREI) was developed to evaluate the restoration effectiveness at village scale. The results showed that MREI can effectively represent the trajectory of mangrove restoration and showed consistent pattern with high-spatial-resolution imagery. From 1990 to 2022, the mangrove forest area increased from 235.26 ha in 1990 to 873.27 ha in 2022, and 84.59% of the mangrove forest was converted from tidal flats in the reserve. The average value of MREI in the five evaluation phases were 0.48, 0.24, 0.29, 0.17, and 0.72, respectively. The dynamic change of MREI showed that 5.24% of the zones had poor PRE, 44.17% of the zones had excellent PRE. From the perspective of spatial distribution, the Zones with PREI values ranging from high to low were follows: Zone A, E, J, G, C, H, I (D), F, B. Overall, the high value zones of PREI were mainly distributed in the central of the Dandou Sea and the northern part of the Yingluo Bay. The low value zones were distributed in the northwest of the Dandou Sea. We expect the MREI and PREI have great potential to be applied to other regions to evaluate mangrove restoration effectiveness.
Parametric comparison of different lobe rotor geometry for positive displacement turbine in water distribution network
Authors: Baratian Iman , Ghobadian Barat , Banakar Ahmad
Published: November 2023

The application of hydro turbines for harnessing water energy within distribution networks, as an alternative to pressure relief valves, is steadily increasing. These turbines are particularly suitable for recovering energy from incompressible subsonic fluid flows. In this research paper, three models of positive displacement lobe machine designed to function as water turbines were extensively examined and compared. The three selected turbine types included the circular lobe turbine, the cycloidal arc lobe turbine and the epicycloid arc lobe turbine. These turbines were meticulously designed and developed for their respective applications. Under identical operational conditions, optimization processes were applied to enhance volumetric efficiency and power efficiency for all three turbine variants, each having a different number of blades. A computer program was devised to facilitate the optimization and calculation of blade geometries under various operating conditions. This research delved into the impact of blade geometry type and the number of blades on turbine efficiency and size. The data obtained from the present investigation were systematically analyzed, and the performance of the different turbines were compared. Notably, the circular lobe turbine was found to be the largest among the three, occupying more space. The cycloidal arc requiring a greater amount of material resulting in rotor volume, which subsequently resulted in a higher overall cost. In contrast, the cycloidal arc lobe turbine emerged as the smallest variant, demanding less space for operation. Efficiency-wise, the cycloidal arc lobe turbine exhibited the highest efficiency with two blades, while the circular lobe turbine displayed the lowest efficiency with six blades. Moreover, among the turbines with the same number of lobes, the cycloidal arc lobe turbine consistently demonstrated superior efficiency compared to the circular lobe turbine.
Characterization of the zinc finger μ-protein HVO_0758 from Haloferax volcanii: biological roles, zinc binding, and NMR solution structure
Authors: Üresin Deniz , Pyper Dennis J. , Borst Andreas , Hadjeras Lydia , Gelhausen Rick , Backofen Rolf , Sharma Cynthia , Schwalbe Harald , Soppa Jörg
Published: November 2023

It is increasingly recognized that very small proteins (μ-proteins) are ubiquitously found in all species of the three domains of life, and that they fulfill important functions. The halophilic archaeon Haloferax volcanii contains 282 μ-proteins of less than 70 amino acids. Notably, 43 of these contain two C(P)XCG motifs, suggesting their potential to complex a zinc ion. To explore the significance of these proteins, 16 genes encoding C(P)XCG proteins had been deleted, and the majority of mutants exhibited phenotypic differences to the wild-type. One such protein, HVO_2753, was thoroughly characterized in a previous study. In the present study an in-depth analysis of a second protein, HVO_0758, was performed. To achieve this goal, the HVO_0758 protein was produced heterologously in Escherichia coli and homologously in H. volcanii. The purified protein was characterized using various biochemical approaches and NMR spectroscopy. The findings demonstrated that HVO_0758 is indeed a bona fide zinc finger protein, and that all four cysteine residues are essential for folding. The NMR solution structure was solved, revealing that HVO_0758 is comprised of an N-terminal alpha helix containing several positively charged residues and a globular core with the zinc finger domain. The transcriptomes of the HVO_0758 deletion mutant and, for comparison, the HVO_2753 deletion mutant were analyzed with RNA-Seq and compared against that of the wild-type. In both mutants many motility and chemotaxis genes were down-regulated, in agreement to the phenotype of the deletion mutants, which had a swarming deficit. The two H. volcanii zinc-finger μ-proteins HVO_0758 and HVO_2753 showed many differences. Taken together, two zinc finger μ-proteins of H. volcanii have been characterized intensively, which emerged as pivotal contributors to swarming behavior and biofilm formation.