bluuebunny/crossref_metadata_2025 huggingface dataset:
Pertumbuhan In Vitro Biji Jeruk Siam Pontianak (Citrus nobilis var. microcarpa) dengan Penambahan Ekstrak Jagung dan NAA pada Media MS
Authors: Sari Felia Mulia , Ifadatin Siti , Mukarlina Mukarlina
Published: January 2024

Penelitian ini bertujuan untuk mengetahui pengaruh penambahan ekstrak jagung dan NAA untuk menghasilkan pertumbuhan terbaik pada kultur in vitro biji jeruk siam Pontianak. Penelitian ini menggunakan Rancangan Acak Lengkap (RAL) Faktorial dengan dua faktor. Faktor pertama, ekstrak jagung (J) dengan 4 taraf konsentrasi 0% (J0); 7,5% (J1); 10% (J2) dan 12,5% (J3). Faktor kedua, NAA (N) dengan 4 taraf konsentrasi 0 M (N0); 10-7M (N1); 5.10-7M (N2) dan 10-6M (N3). Hasil penelitian menunjukkan bahwa kombinasi ekstrak jagung dan NAA mampu meningkatkan perkecambahan dengan persentase 100% dan jumlah akar terbanyak yakni sebanyak 6 akar; mempercepat waktu muncul kecambah dan waktu muncul tunas yakni 9,33 dan 13,33 hari. Penambahan NAA tunggal mampu meningkatkan jumlah tunas dan jumlah daun pada tunas dari biji poliembrioni pada kultur biji jeruk siam Pontianak yakni 3,33 tunas dan 2,16 helai daun.
PVSK m. 4/A Kapsamında Durdurma ve Kimlik Sorma
Authors: ALPSOY Zeliha
Published: January 2024

Durdurma ve kimlik sorma birbirinden farklı işlemler olmakla birlikte mevzuatımıza bakıl- dığında kanun koyucunun farklı bu iki işlemi aynı madde kapsamında düzenleme eğiliminde olduğu görülmektedir. Her iki işlem de çeşitli kanunlarda düzenlenmekle birlikte çalışmada Polis Vazife ve Salahiyetleri Kanunu (PVSK) m. 4/A temel alınarak konu incelenmiştir.
Durdurma ve kimlik sorma işlemleri kolluk tarafından icra edilen işlemlerdir. Bu nedenle çalışmada önce kolluk kavramı ve kolluk türleri hakkında bilgi verilmiştir. Kolluğa ilişkin verilen bilgilerin ardından çalışmanın ilk ayağını oluşturan durdurma işlemi incelenmiştir. Durdurma üst başlığı altında işlemin ilişkili olduğu hak ve özgürlükler, işlemin benzer işlemlerden farkları, makul sebep kavramı, durdurma sebepleri ve durdurma yetkisinin kullanılması incelenmiştir.
Çalışmada özellikle durdurma işlemi ile kısıtlanan hak ve özgürlükler ortaya konulmaya çalışıl- mış konuya ilişkin tartışmalara yer verilmiştir.
Durdurma işleminin incelenmesinin ardından çalışmanın diğer ayağı olan kimlik sorma iş- lemi incelenmiştir. Bu başlık altında kimlik kavramı ile kimlik sorma işlemiyle bağlantılı hak ve özgürlükler üzerinde durulmuştur.
Her iki işleme ilişkin doktrindeki görüşlere yer verildikten sonra konu yargı kararları açı- sından da değerlendirilmiştir.
Çalışmanın son kısmında hukuka aykırı icra edilen durdurma ve kimlik sorma işlemlerinin sonuçları ve bu işlemleri denetlenme yolları incelenmiştir.
Kişinin hukuk kurallarına uyuyor olması, bu işlemlerin kendisi hakkında uygulanmayacağı anlamına gelmemektedir. Bu nedenle ceza hukuku kapsamında yer alan diğer tedbirlere naza- ran karşılaşılma ihtimali daha yüksek olan bu işlemlerin hukuki çerçevesinin bilinmesi öğreti ve uygulama bakımından yararlı olacaktır.
STRATEGI PERSONAL BRANDING DALAM AJANG PUSTAKAWAN BERPRESTASI
Authors: Saputra Nurwidianto Yuli
Published: January 2024

Dibutuhkan branding yang baik untuk mengubah persepsi masyarakat (pemustaka) tentang pustakawan dan mereka juga mesti mendapat perspektif baru yang lebih segar. Maka tujuan penelitian ini untuk mengetahui strategi personal branding dan bentuk hambatannya dalam ajang pustakawan berprestasi. Metode penelitian yang digunakan melalui pendekatan kualitatif yang bersifat studi pustaka. Hasil penelitian menunjukkan pustakawan memiliki kesadaran serta kemauan untuk mengubah mindset terhadap profesi mereka sehingga peran personal atau individu dibangun dari diri sendiri bukan dari sekedar tuntutan. Hambatan yang dihadapi berupa kepasifan pustakawan, inkonsisten, terkendala waktu, terkurung dalam lingkup kerja. Saran pada penelitian ini diperlukan strategi dan langkah sederhana dalam menguatkan kesadaran personal branding pustakawan, seperti penguatan karakter diri, konsistensi, membuat perbedaan, tau akan passionnya, dan yang terakhir membangun jejaring baik melalui teknologi informasi (internet; media sosial) maupun dengan pertemuan rutin guna memupuk persepsi positif pada diri pustakawan.
Genomic analysis of population history for Hawaiian monk seals
Authors: Hauser S , Robinson S , Latch E
Published: January 2024

The Hawaiian monk seal Neomonachus schauinslandi, one of the world’s most endangered pinnipeds, has faced decades of declines and has been the focus of intensive conservation efforts. A myriad of conservation threats has led to range-wide population declines, but population trends among islands can vary widely in response to heterogeneous threats. Populations in the Northwestern Hawaiian Islands have been declining, whereas Main Hawaiian Islands numbers are expanding. Molecular data can provide information to disentangle population structure and dynamics; however, previous studies have yielded insufficient resolution in such a genetically depauperate species. Advances in genomic technology and affordability offer a novel opportunity to revisit questions about Hawaiian monk seal trends with high-resolution markers that provide better discrimination ability in low-diversity species. Here, we investigated region- and island-level population structuring and connectivity. We used BestRAD sequencing on 169 seals from 14 islands that span the archipelago to estimate genetic diversity, genetic differentiation, population structure, and migration rates. We did not find robust evidence for island-level population structure. For the first time, our data set provided resolution to differentiate regional populations with low but significant genetic differentiation. Further, DAPC illustrated population structure with evidence for connectivity, which mirrored our migration rate estimates. Future conservation decisions will need to consider the balance of maintaining connectivity between regions while not homogenizing and losing valuable, yet rare, regional unique variation.
Implementasi Algoritma AHP Untuk Membantu Menentukan Topik Kegiatan Kajian Pada Masjid Nur-Hikmah
Authors: Izza Irma Nur , Sukya Fadelis
Published: January 2024

Masjid Nur Hikmah terletak di jalan Gunung Agung Nomor 225, Dermo, Kec. Mojoroto, Kabupaten Kediri, Jawa Timur. Masjid ini belum memiliki aplikasi untuk tata kelola penentuan materi dakwah secara otomatis. Beberapa kegiatan di Masjid Nur Hikmah dan manajemen penjadwalannya masih dilaksanakan secara manual. Oleh karena itu, dibuatlah aplikasi tata kelola penentuan materi dakwah berbasis web yang dapat memberikan kemudahan kepada pengurus masjid dalam mengelola materi dakwah dan menyampaikannya kepada warga sekitar dengan lebih mudah pula. Aplikasi dikembangkan dengan menambahkan fitur pemberian referensi materi dakwah menggunakan Sistem Pendukung Keputusan. Metode yang digunakan dalam memberikan referensi tersebut adalah metode AHP. Hasil referensi akan dipilih oleh pengurus masjid dan disapaikan kepada warga menggunakan fitur WhatsApp. Pengembangan aplikasi E-Masjid Nur Hikmah berbasis web ini menggunakan Bahasa pemrograman PHP dengan Framework Codeigniter. Selain itu digunakan pula HTML, CSS, dan Bootstrap sebagai Bahasa pemrograman pendukung. Selanjutnya, RDBSM yang digunakan sebagai media penyimpanan data menggunakan database MySQL dan didukung dengan browser Google Chrome bertujuan mempermudah warga dalam mencari informasi masjid melalui website yang ada. Hasil dari penelitian ini adalah aplikasi E-Masjid yang dapat mengelola jadwal kegiatan dakwah di masjid, jadwal kegiatan imam masjid dan memberikan rekomendasi materi dakwah berdasarkan kriteria seperti usia, umur, jenis pekerjaan dan Pendidikan terakhir.
Prediction of anticancer drug resistance using a 3D microfluidic bladder cancer model combined with convolutional neural network-based image analysis
Authors: Tak Sungho , Han Gyeongjin , Leem Sun-Hee , Lee Sang-Yeop , Paek Kyurim , Kim Jeong Ah
Published: January 2024

Bladder cancer is the most common urological malignancy worldwide, and its high recurrence rate leads to poor survival outcomes. The effect of anticancer drug treatment varies significantly depending on individual patients and the extent of drug resistance. In this study, we developed a validation system based on an organ-on-a-chip integrated with artificial intelligence technologies to predict resistance to anticancer drugs in bladder cancer. As a proof-of-concept, we utilized the gemcitabine-resistant bladder cancer cell line T24 with four distinct levels of drug resistance (parental, early, intermediate, and late). These cells were co-cultured with endothelial cells in a 3D microfluidic chip. A dataset comprising 2,674 cell images from the chips was analyzed using a convolutional neural network (CNN) to distinguish the extent of drug resistance among the four cell groups. The CNN achieved 95.2% accuracy upon employing data augmentation and a step decay learning rate with an initial value of 0.001. The average diagnostic sensitivity and specificity were 90.5% and 96.8%, respectively, and all area under the curve (AUC) values were over 0.988. Our proposed method demonstrated excellent performance in accurately identifying the extent of drug resistance, which can assist in the prediction of drug responses and in determining the appropriate treatment for bladder cancer patients.
Recent insights into the functions and mechanisms of antisense RNA: emerging applications in cancer therapy and precision medicine
Authors: Rehman Shahab Ur , Ullah Numan , Zhang Zhenbin , Zhen Yongkang , Din Aziz-Ud , Cui Hengmi , Wang Mengzhi
Published: January 2024

The antisense RNA molecule is a unique DNA transcript consisting of 19–23 nucleotides, characterized by its complementary nature to mRNA. These antisense RNAs play a crucial role in regulating gene expression at various stages, including replication, transcription, and translation. Additionally, artificial antisense RNAs have demonstrated their ability to effectively modulate gene expression in host cells. Consequently, there has been a substantial increase in research dedicated to investigating the roles of antisense RNAs. These molecules have been found to be influential in various cellular processes, such as X-chromosome inactivation and imprinted silencing in healthy cells. However, it is important to recognize that in cancer cells; aberrantly expressed antisense RNAs can trigger the epigenetic silencing of tumor suppressor genes. Moreover, the presence of deletion-induced aberrant antisense RNAs can lead to the development of diseases through epigenetic silencing. One area of drug development worth mentioning is antisense oligonucleotides (ASOs), and a prime example of an oncogenic trans-acting long noncoding RNA (lncRNA) is HOTAIR (HOX transcript antisense RNA). NATs (noncoding antisense transcripts) are dysregulated in many cancers, and researchers are just beginning to unravel their roles as crucial regulators of cancer’s hallmarks, as well as their potential for cancer therapy. In this review, we summarize the emerging roles and mechanisms of antisense RNA and explore their application in cancer therapy.
Effects of OxyR regulator on oxidative stress, Apx toxin secretion and virulence of Actinobacillus pleuropneumoniae
Authors: Guo Fangfang , Quan Rong , Cui Yifang , Cao Xiaoya , Wen Tong , Xu Fuzhou
Published: January 2024

Introduction

Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia, poses a significant threat to global swine populations due to its high prevalence, mortality rates, and substantial economic ramifications. Understanding the pathogen's defense mechanisms against host-produced reactive oxygen species is crucial for its survival, with OxyR, a conserved bacterial transcription factor, being pivotal in oxidative stress response.

Methods

This study investigated the presence and role of OxyR in A. pleuropneumoniae serovar 1-12 reference strains. Transcriptomic analysis was conducted on an oxyR disruption mutant to delineate the biological activities influenced by OxyR. Additionally, specific assays were employed to assess urease activity, catalase expression, ApxI toxin secretion, as well as adhesion and invasion abilities of the oxyR disruption mutant on porcine 3D4/21 and PT cells. A mice challenge experiment was also conducted to evaluate the impact of oxyR inactivation on A. pleuropneumoniae virulence.

Results

OxyR was identified as a conserved regulator present in A. pleuropneumoniae serovar 1-12 reference strains. Transcriptomic analysis revealed the involvement of OxyR in multiple biological activities. The oxyR disruption resulted in decreased urease activity, elevated catalase expression, enhanced ApxI toxin secretion—attributed to OxyR binding to the apxIBD promoter—and reduced adhesion and invasion abilities on porcine cells. Furthermore, inactivation of oxyR reduced the virulence of A. pleuropneumoniae in a mice challenge experiment.

Discussion

The findings highlight the pivotal role of OxyR in influencing the virulence mechanisms of A. pleuropneumoniae. The observed effects on various biological activities underscore OxyR as an essential factor contributing to the pathogenicity of this bacterium.
How and when do Pt- and Pd-semimetal minerals crystallize from saturated sulfide liquids?
Authors: Helmy Hassan M. , Botcharnikov Roman , Ballhaus Chris , Buhre Stephan
Published: January 2024

Platinum and Pd-arsenides, antimonides, tellurides, bismuthinides, and sulfides are the major hosts of Pt and Pd in magmatic and hydrothermal Cu-Ni-sulfide ores. Textural relationships among such minerals in nature often provide contradictory messages about the mechanism and timing of their formation. To know how and when Pt and Pd mineral phases crystallize from sulfide-saturated liquids and how their compositions and textures evolve during cooling, we undertook controlled cooling experiments in evacuated silica tubes. A Cu-Ni-Fe sulfide mixture, similar in composition to the average Merensky Reef sulfide magma, was charged (in a 9:1 wt.% proportion) with one of the PtAs2, PtTe2, PtSb2, PtBi2, PdAs2, PdTe2, PdSb, and PdBi2 compounds, heated to 1,100°C, and slowly cooled (15°C/day) to room temperature. The run products were sampled at 950°C, 750°C, and 25°C by quenching the silica tubes in water. The results show that Pt formed stable phases with As, Te, and Sb above 950°C and with Bi and S below 750°C. The Pt phases were found mostly in the decomposed intermediate solid solution (ISS), and all the phases survived to 25°C with no compositional changes. At 950°C, Pd formed arsenide, telluride, and antimonide immiscible melts that coexisted with monosulfide solid solution (MSS) and sulfide melt. The composition of the Pd-semimetal melt droplets changed during cooling by equilibration with the host sulfide. Palladium mineral phases formed at temperatures below 750°C directly from the immiscible semimetal-rich melts where they kept the rounded shapes of the melt droplets. Ni-sulfarsenides preceded the formation of Pd arsenides. No Ni tellurides, antimonides, or bismuthinides formed in any of the systems, implying that their formation requires higher semimetal/Pt + Pd ratios. The decomposition of MSS and ISS to base metal sulfides led to significant textural changes in Pt and Pd mineral grains. The compositions of Pt and Pd phases are inherited from the magmatic stage, and their textures are low-temperature (<450°C) features.
A two-sample mendelian randomization analysis excludes causal relationships between non-alcoholic fatty liver disease and kidney stones
Authors: Li Xintao , Xie Yongpeng , Tang Lu , Li Di , Wang Jun , Sheng Haibo , Chen Kaikai , Xiao Shuwei , Li Jianye , Yang Minghui
Published: January 2024

Objectives

Non-alcoholic fatty liver disease (NAFLD) has been linked to an increased risk of kidney stones in prior observational studies, However, the results are inconsistent, and the causality remains to be established. We aimed to investigate the potential causal relationship between NAFLD and kidney stones using two-sample Mendelian randomization (MR).

Methods

Genetic instruments were used as proxies for NAFLD. Summary-level data for the associations of exposure-associated SNPs with kidney stones were obtained from the UK Biobank study (6536 cases and 388,508 controls) and the FinnGen consortium (9713 cases and 366,693 non-cases). MR methods were conducted, including inverse variance weighted method (IVW), MR-Egger, weighted median, and MR-PRESSO. MR-Egger Regression Intercept and Cochran’s Q test were used to assess the directional pleiotropy and heterogeneity.

Results

cALT-associated NAFLD did not exhibit an association with kidney stones in the Inverse variance weighted (IVW) methods, in both the FinnGen consortium (OR: 1.02, 95%CI: 0.94-1.11, p = 0.632) and the UKBB study (OR: 1.000, 95%CI: 0.998-1.002, p = 0.852). The results were consistent in European ancestry (FinnGen OR: 1.05, 95%CI: 0.98-1.14, p = 0.144, UKBB OR: 1.000, 95%CI: 0.998-1.002, p = 0.859). IVW MR analysis also did not reveal a significant causal relationship between NAFLD and the risk of kidney stone for the other three NAFLD-related traits, including imaging-based, biopsy-confirmed NAFLD, and more stringent biopsy-confirmed NAFLD. The results remained consistent and robust in the sensitivity analysis.

Conclusions

The MR study did not provide sufficient evidence to support the causal associations of NAFLD with kidney stones.
Simulation of fishery energy consumption and carbon emissions in Zhoushan City based on the long-range energy alternatives planning system model
Authors: Xu Xieqin , Gui Feng , Zhao Sheng
Published: January 2024

To understand the current situation and development trend of energy consumption and carbon emissions in the fishery industry, a Long-Range Energy Alternatives Planning System (LEAP)-fishery model for Zhoushan City was constructed, and the trends of energy consumption and carbon emissions in the Zhoushan City fishery industry were analyzed under the business-as-usual scenario, the low-carbon scenario, and the strengthened low-carbon scenario. The results show that under the business-as-usual scenario, the future energy consumption of Zhoushan City’s fisheries in general shows an increasing trend, and the composition of energy consumption in all scenarios is primarily dominated by fossil energy, with diesel and coal predominating. In terms of the structure of end-use energy consumption, fishing vessels and aquaculture consume the most energy, with energy consumption exceeding 30% of total energy consumption in all scenarios. In terms of the emission reduction contribution rate, which the promotion of clean energy generation, the improvement of energy efficiency, and the reduction of aquaculture production play key roles in the low-carbon development of the fishery industry. From an economic perspective, carbon reduction measures such as reduction of aquaculture production and increased efficiency of energy delivery would have significant economic benefits, but these measures have limitations. Finally, suggestions are made to optimize the energy structure, improve the implementation of energy intensity and total energy control, and strengthen public awareness of energy conservation to reduce carbon emissions from the fishery industry, thus making the research in this paper relevant to real-world situations.
Electricity–gas multi-agent planning method considering users’ comprehensive energy consumption behavior
Authors: Liu Wentao , Zhou Baorong , Ou Mingyu , Zhao Wenmeng , Huang Guanglei , Mao Tian
Published: January 2024

With the advent of the energy Internet and the swift growth of unified energy systems, the comprehensive energy demand of users has gradually become a problem that cannot be ignored for the planning of integrated energy systems. Aiming at this problem, this paper suggests a multi-agent planning approach for electricity and gas, considering users’ holistic energy consumption behavior. First, utilizing a combined subjective and objective weighting method, this study establishes a utility model for users’ energy consumption characteristics. The analysis of comprehensive energy consumption behavior is conducted through an evolutionary game. On this basis, the planning revenue model for electricity grid and gas network investors is formulated, and the game mechanism of different investors is analyzed. A dynamic game model of electricity–gas multi-agent planning considering comprehensive energy consumption behavior is proposed. Ultimately, the model is resolved using an iterative exploration approach. The validity and efficacy of the proposed method are confirmed through a simulation example.
Phytoplankton community structure and water quality assessment in Xuanwu Lake, China
Authors: Qu Senhu , Zhou Junxiao
Published: January 2024

Phytoplankton community structure influences the water quality of freshwater lakes and attracts the attention worldwide. The physicochemical parameters including dissolved oxygen (DO), total nitrogen, total phosphorus, NH4+-N and CODMn and biological index such as Chl.a concentrations were measured in water of different sites of Xuanwu Lake, China in varied seasons. The Trophic level index (TLI) was calculated to evaluate the trophic status of the lake based on critical water quality parameters. The phytoplankton community structure and biomass in the water was also identified and detected. Obvious change of physicochemical parameters and biological index was detected in varied sampling time. The results showed that TN, TP, NH4+-N, CODMn and Chl.a had higher concentrations in June and August with higher temperature. Obtained Trophic level index values from key water quality indicators revealed that Xuanwu Lake exhibited a state of mesotrophic level in December 2021, mild eutrophic level in October and February, and remained in a state of moderate eutrophication during other periods having higher temperature. Chlorophyta exhibited the highest species diversity and accounted for 48.1% of the entire community. Cyanobacteria had higher density compared to other phytoplankton, which suggesting the potential ecological risk in the lake. These findings aligned with the outcomes of the analysis of the phytoplankton community structure, underscoring a certain degree of correlation between the primary water quality indicators and phytoplankton abundance in Xuanwu Lake. That is, higher discharge of contaminant including nutrients potentially dominated the phytoplankton community structure. The continuous monitoring of phytoplankton community and water quality enabled the assessment of its trophic status of urban lake. Appropriate measures such as adjustment of phytoplankton community structure were proposed to mitigate the eutrophication status of lake. The investigation indicated that phytoplankton variation was the important indicator of water quality and supplied direct evidence for the water quality management and ecosystem restoration of urban lakes.
The burden of cystic fibrosis in North Africa
Authors: El Makhzen Nada , Daimi Houria , Bouguenouch Laila , Abriel Hugues
Published: January 2024

Background: Over 200 pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with cystic fibrosis (CF)—the most prevalent autosomal recessive disease globally, the p.Phe508del variant being the most commonly observed.

Main text: Recent epidemiological studies suggest a higher global prevalence of CF than previously thought. Nevertheless, comprehensive CF data remains extremely scarce among African populations, contributing to a significant information gap within the African healthcare system. Consequently, the underestimation of CF among children from African populations is likely. The goal of this article is to review the pathogenesis of CF and its prevalence in the countries of North Africa.

Conclusion: The prevalence of CF in North African countries is likely underestimated due to the complexity of the disease and the lack of a timely, proper clinical and genetic investigation that allows the early identification of CF patients and thus facilitates therapeutic recommendations. Therefore, specific genetic and epidemiological studies on African individuals showing CF symptoms should be conducted to enhance the diagnostic yield of CF in Africa.
PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease
Authors: Kocheise Lorenz , Piseddu Ignazio , Vonderlin Joscha , Tjwa Eric T. , Buescher Gustav , Meunier Lucy , Goeggelmann Pia , Fianchi Francesca , Dumortier Jérôme , Riveiro Barciela Mar , Gevers Tom J. G. , Terziroli Beretta-Piccoli Benedetta , Londoño Maria-Carlota , Frankova Sona , Roesner Thomas , Joerg Vincent , Schmidt Constantin , Glaser Fabian , Sutter Jan P. , Fründt Thorben W. , Lohse Ansgar W. , Huber Samuel , von Felden Johann , Sebode Marcial , Schulze Kornelius
Published: January 2024

Introduction

Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years. However, immune−related adverse events (irAE) are a frequent concern in clinical practice. The safety profile of ICI for the treatment of malignancies in patients diagnosed with autoimmune and cholestatic liver disease (AILD) remains unclear. Due to this uncertainty, these patients were excluded from ICI clinical trials and ICI are withheld from this patient group. In this retrospective multicenter study, we assessed the safety of ICI in patients with AILD.

Methods

We contacted tertiary referral hospitals for the identification of AILD patients under ICI treatment in Europe via the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Fourteen centers contributed data on AILD patients with malignancies being treated with ICI, another three centers did not treat these patients with ICI due to fear of irAEs.

Results

In this study, 22 AILD patients under ICI treatment could be identified. Among these patients, 12 had primary biliary cholangitis (PBC), five had primary sclerosing cholangitis (PSC), four had autoimmune hepatitis (AIH), and one patient had an AIH-PSC variant syndrome. Eleven patients had hepatobiliary cancers and the other 11 patients presented with non-hepatic tumors. The applied ICIs were atezolizumab (n=7), durvalumab (n=5), pembrolizumab (n=4), nivolumab (n=4), spartalizumab (n=1), and in one case combined immunotherapy with nivolumab plus ipilimumab. Among eight patients who presented with grade 1 or 2 irAEs, three demonstrated liver irAEs. Cases with grades ≥ 3 irAEs were not reported. No significant changes in liver tests were observed during the first year after the start of ICI.

Discussion

This European multicenter study demonstrates that PD-1/PD-L1 inhibitors appear to be safe in patients with AILD. Further studies on the safety of more potent dual immune checkpoint therapy are needed. We conclude that immunotherapy should not categorically be withheld from patients with AILD.
The interaction effects of light and noise on the acoustic parameters of underwater vocalisations of wild spotted seals (Phoca largha) in Liaodong Bay, China1
Authors: Yang Liangliang
Published: January 2024

Some marine mammals can adjust acoustic parameters of their sound signals in response to changes in sunlight and ambient noise. Evidence was found in several toothed whales; however, relatively little research has focused on true seals. Spotted seals (Phoca largha) are highly vociferous during the breeding season. Four major underwater call types, drums, growls, knocks, and sweeps, have been identified in the acoustic repertoire of wild spotted seals in Liaodong Bay, China. This study investigated the potential effects of light (day and night) and noise (105–135 dB re 1 μPa, broadband 50–8,000 Hz) conditions on the centroid frequency (CF), root-mean-square bandwidth (BW), duration (DU), and received level (RL) parameters of their underwater vocalisations using a series of generalised linear models (GLMs). Results showed that there were significant interaction effects of light and noise on knock CFs and the BWs for all call types. Specifically, knock CFs decreased and BWs for all call types became narrower when noise increased at night but kept stable during daytime. No significant interactions were found in other acoustic parameters. However, the results of univariate GLM analyses showed that the spotted seals could lengthen their vocalisations at night and increase the vocalisation RLs in response to higher noise levels (the Lambard effect), regardless of call type. To our knowledge, this is the first study to demonstrate that the spotted seals, a poorly studied species in Chinese waters, have some capabilities to adjust their vocalisations in response to changes in light and noise conditions. The results are helpful to understand how seals interact with their habitats and useful when developing mitigation strategies to minimise disturbance of light and noise from human activities in Liaodong Bay, China.
A systematic review and meta-analysis of liver venous deprivation versus portal vein embolization before hepatectomy: future liver volume, postoperative outcomes, and oncological safety
Authors: Chaouch Mohamed Ali , Mazzotta Alessandro , da Costa Adriano Carneiro , Hussain Mohammad Iqbal , Gouader Amine , Krimi Bassem , Panaro Fabrizio , Guiu Boris , Soubrane Olivier , Oweira Hani
Published: January 2024

Introduction

This systematic review aimed to compare liver venous deprivation (LVD) with portal vein embolization (PVE) in terms of future liver volume, postoperative outcomes, and oncological safety before major hepatectomy.

Methods

We conducted this systematic review and meta-analysis following the PRISMA guidelines 2020 and AMSTAR 2 guidelines. Comparative articles published before November 2022 were retained.

Results

The literature search identified nine eligible comparative studies. They included 557 patients, 207 in the LVD group and 350 in the PVE group. This systematic review and meta-analysis concluded that LVD was associated with higher future liver remnant (FLR) volume after embolization, percentage of FLR hypertrophy, lower failure of resection due to low FLR, faster kinetic growth, higher day 5 prothrombin time, and higher 3 years’ disease-free survival. This study did not find any difference between the LVD and PVE groups in terms of complications related to embolization, FLR percentage of hypertrophy after embolization, failure of resection, 3-month mortality, overall morbidity, major complications, operative time, blood loss, bile leak, ascites, post hepatectomy liver failure, day 5 bilirubin level, hospital stay, and three years’ overall survival.

Conclusion

LVD is as feasible and safe as PVE with encouraging results making some selected patients more suitable for surgery, even with a small FLR.

Systematic review registration

The review protocol was registered in PROSPERO before conducting the study (CRD42021287628).
ADS024, a single-strain live biotherapeutic product of Bacillus velezensis alleviates dextran sulfate-mediated colitis in mice, protects human colonic epithelial cells against apoptosis, and maintains epithelial barrier function
Authors: Irwin Sophie , Chupina Estrada Andrea , Nelson Becca , Bullock Ashlen , Limketkai Berkeley , Ho Wendy , Acton Susan , Chesnel Laurent , Koon Hon Wai
Published: January 2024

Epithelial cell apoptosis and compromised gut barrier function are features of inflammatory bowel disease. ADS024 is a single-strain live biotherapeutic product (LBP) of Bacillus velezensis under development for treating ulcerative colitis (UC). The cytoprotective effects of the sterile filtrate of ADS024’s secreted products on UC patient-derived colonic tissues, human primary colonic epithelial cells (HPEC), and human colonic epithelial T84 cells were evaluated. ADS024 filtrate significantly inhibited apoptosis and inflammation with reduced Bcl-2 Associated X-protein (BAX) and tumor necrosis factor (TNF) mRNA expression in fresh colonic explants from UC patients. Exposure to UC patient-derived serum exosomes (UCSE) induced apoptosis with increased cleaved caspase 3 protein expression in HPECs. ADS024 filtrate diminished the UCSE-mediated apoptosis by inhibiting cleaved caspase 3. TNFα and interferon-gamma (IFNγ) damaged epithelial barrier integrity with reduced transepithelial electrical resistance (TEER). ADS024 filtrate partially attenuated the TEER reduction and restored tight junction protein 1 (TJP1) expression. Oral live ADS024 treatment reduced weight loss, disease activity, colonic mucosal injury, and colonic expression of interleukin 6 (IL-6) and TNFα in dextran sodium sulfate (DSS)-treated mice with colitis. Thus, ADS024 may protect the colonic epithelial barrier in UC via anti-inflammatory, anti-apoptotic, and tight-junction protection mechanisms.
Helicobacter pylori infection in humans and phytotherapy, probiotics, and emerging therapeutic interventions: a review
Authors: Liu Mengkai , Gao Hui , Miao Jinlai , Zhang Ziyan , Zheng Lili , Li Fei , Zhou Sen , Zhang Zhiran , Li Shengxin , Liu He , Sun Jie
Published: January 2024

The global prevalence of Helicobacter pylori (H. pylori) infection remains high, indicating a persistent presence of this pathogenic bacterium capable of infecting humans. This review summarizes the population demographics, transmission routes, as well as conventional and novel therapeutic approaches for H. pylori infection. The prevalence of H. pylori infection exceeds 30% in numerous countries worldwide and can be transmitted through interpersonal and zoonotic routes. Cytotoxin-related gene A (CagA) and vacuolar cytotoxin A (VacA) are the main virulence factors of H. pylori, contributing to its steep global infection rate. Preventative measures should be taken from people’s living habits and dietary factors to reduce H. pylori infection. Phytotherapy, probiotics therapies and some emerging therapies have emerged as alternative treatments for H. pylori infection, addressing the issue of elevated antibiotic resistance rates. Plant extracts primarily target urease activity and adhesion activity to treat H. pylori, while probiotics prevent H. pylori infection through both immune and non-immune pathways. In the future, the primary research focus will be on combining multiple treatment methods to effectively eradicate H. pylori infection.
The IRAK-M death domain: a tale of three surfaces
Authors: Gürkan Berke , Poelman Hessel , Pereverzeva Liza , Kruijswijk Danielle , de Vos Alex F. , Groenen Anouk G. , Nollet Edgar E. , Wichapong Kanin , Lutgens Esther , van der Poll Tom , Du Jiangfeng , Wiersinga W. Joost , Nicolaes Gerry A. F. , van ‘t Veer Cornelis
Published: January 2024

The anti-inflammatory interleukin-1 receptor associated kinase-M (IRAK-M) is a negative regulator of MyD88/IRAK-4/IRAK-1 signaling. However, IRAK-M has also been reported to activate NF-κB through the MyD88/IRAK-4/IRAK-M myddosome in a MEKK-3 dependent manner. Here we provide support that IRAK-M uses three surfaces of its Death Domain (DD) to activate NF-κB downstream of MyD88/IRAK-4/IRAK-M. Surface 1, with central residue Trp74, binds to MyD88/IRAK-4. Surface 2, with central Lys60, associates with other IRAK-M DDs to form an IRAK-M homotetramer under the MyD88/IRAK-4 scaffold. Surface 3; with central residue Arg97 is located on the opposite side of Trp74 in the IRAK-M DD tetramer, lacks any interaction points with the MyD88/IRAK-4 complex. Although the IRAK-M DD residue Arg97 is not directly involved in the association with MyD88/IRAK-4, Arg97 was responsible for 50% of the NF-κB activation though the MyD88/IRAK-4/IRAK-M myddosome. Arg97 was also found to be pivotal for IRAK-M’s interaction with IRAK-1, and important for IRAK-M’s interaction with TRAF6. Residue Arg97 was responsible for 50% of the NF-κB generated by MyD88/IRAK-4/IRAK-M myddosome in IRAK-1/MEKK3 double knockout cells. By structural modeling we found that the IRAK-M tetramer surface around Arg97 has excellent properties that allow formation of an IRAK-M homo-octamer. This model explains why mutation of Arg97 results in an IRAK-M molecule with increased inhibitory properties: it still binds to myddosome, competing with myddosome IRAK-1 binding, while resulting in less NF-κB formation. The findings further identify the structure-function properties of IRAK-M, which is a potential therapeutic target in inflammatory disease.
Spike desensitisation as a mechanism for high-contrast selectivity in retinal ganglion cells
Authors: Chang Le , Ran Yanli , Yang Mingpo , Auferkorte Olivia , Butz Elisabeth , Hüser Laura , Haverkamp Silke , Euler Thomas , Schubert Timm
Published: January 2024

In the vertebrate retina, several dozens of parallel channels relay information about the visual world to the brain. These channels are represented by the different types of retinal ganglion cells (RGCs), whose responses are rendered selective for distinct sets of visual features by various mechanisms. These mechanisms can be roughly grouped into synaptic interactions and cell-intrinsic mechanisms, with the latter including dendritic morphology as well as ion channel complement and distribution. Here, we investigate how strongly ion channel complement can shape RGC output by comparing two mouse RGC types, the well-described ON alpha cell and a little-studied ON cell that is EGFP-labelled in the Igfbp5 mouse line and displays an unusual selectivity for stimuli with high contrast. Using patch-clamp recordings and computational modelling, we show that a higher activation threshold and a pronounced slow inactivation of the voltage-gated Na+ channels contribute to the distinct contrast tuning and transient responses in ON Igfbp5 RGCs, respectively. In contrast, such a mechanism could not be observed in ON alpha cells. This study provides an example for the powerful role that the last stage of retinal processing can play in shaping RGC responses.
The effect of transcranial alternating current stimulation on functional recovery in patients with stroke: a narrative review
Authors: Yang Seoyon , Yi You Gyoung , Chang Min Cheol
Published: January 2024

Stroke is a common neurological disorder worldwide that can cause significant disabilities. Transcranial alternating current stimulation (tACS) is an emerging non-invasive neuromodulation technique that regulates brain oscillations and reshapes brain rhythms. This study aimed to investigate the effect of tACS on functional recovery in patients with stroke. The MEDLINE (PubMed), Cochrane Library, Embase, SCOPUS, and Web of Science databases were searched for English-language articles on tACS and stroke, published up to October 20, 2023. The following key search phrases were combined to identify potentially relevant articles: ‘tACS,’ ‘transcranial alternating current stimulation,’ ‘stroke,’ ‘cerebral infarct,’ and ‘intracerebral hemorrhage.’ The inclusion criteria for study selection were as follows: (1) studies involving patients with stroke and (2) studies that used tACS for functional recovery. A total of 34 potentially relevant studies were identified. Five articles were included in this review after reading the titles and abstracts and assessing their eligibility based on the full-text articles. Among the included studies, one investigated the improvement in overall functional status in patients with stroke after tACS, and two investigated the effect of tACS on motor function and gait patterns. Moreover, one study reported the efficacy of tACS on aphasia recovery, and one study evaluated the effect of tACS on hemispatial neglect. Our findings suggest that tACS improves functional recovery in patients with stroke. The application of tACS was associated with improved overall functional recovery, sensorimotor impairment, aphasia, and hemispatial neglect. The potential clinical application of tACS should be supported by high-quality, evidence-based studies.
Nano casein–pectin complex: exploring physicochemical, organoleptic properties, and LAB viability in skimmed milk and low-fat yoghurt
Authors: Gomaa Mohamed A. E. , Allam Marwa G. , Mokhtar Esraa , Ayad Eman H. E. , Darwish Saeid M. , Darwish Amira M. G.
Published: January 2024

Protein complexes with a nutritional value, heat stability, and gelling properties with no negative impact on culture viability have promising application prospects in the fermentation industry. The aim of the study was to investigate the possibility of applying physical modification seeking high-protein-fortified yoghurt production using the nano casein–pectin NCP complex as an active colloidal system with enhanced structural and thermal properties and monitor the quality properties of the physicochemical, heat stability, rheological, starter culture viability and sensory evaluation of fortified products comparing with the plain control throughout the cold storage. High-energy ball milling (HEBM) technique was used to produce nanoparticles of casein powder and smaller particles of pectin individually, and particle size and zeta potential was assessed. Deferent Nano casein-pectin (NCP) complex formulations were prepared, their physicochemical properties were assessed including protein quality via Amino Acid Analyzer (AAA), viscosity, thermogravimetric analysis (TGA), and then used in fortification of skimmed milk and low-fat yoghurt to monitor the fortification effects. The particle sizes showed to be ≈166 nm and 602.6 nm for nano-casein and pectin, respectively. Milk fortification with the NCP complex has significantly increased the nutritional value represented in increased protein content (7.19 g/100 g in NCP5); Ca, P, and S content (2,193.11, 481.21, and 313.77 ppm); and amino acid content with first limiting amino acids; histidine (0.89 mg/g), methionine (0.89 mg/g), and low content of hydrophobic amino acids (HAAs) may cause aggregation. NPC fortification enhanced physicochemical properties announced in enhanced viscosity (62. mP.s in NCP5) and heat stability (up to 200°C) compared with control skimmed milk (SM). NCP yoghurt fortification significantly increased protein content to 11 mg/100 g in T5, enhanced viscosity to 48.44 mP.s in T3, decreased syneresis to 16% in T5, and enhanced LAB viability which was translated in preferable sensorial properties. Applying fortification with nanoparticles of the casein–pectin (NCP) complex balanced the amino acid content and improved physicochemical, rheological, nutritional, and sensorial properties and LAB viability, which can be recommended further in functional food applications.
Vitamin D status and its associations with bone mineral density, bone turnover markers, and parathyroid hormone in Chinese postmenopausal women with osteopenia and osteoporosis
Authors: Chen Xi , Shen Li , Gao Chao , Weng Rou , Fan Yier , Xu Shuqin , Zhang Zhenlin , Hu Weiwei
Published: January 2024

Background

Vitamin D is a key factor in bone metabolism, yet vitamin D insufficiency and deficiency are prevalent among postmenopausal women, with potential repercussions on bone mineral density (BMD), bone turnover markers (BTMs), and parathyroid hormone (PTH). Nonetheless, the findings from existing studies exhibit inconsistency, and a notable gap exists in the availability of large-scale investigations.

Methods

In this real-world study, 8,532 postmenopausal women over 50 years old with a diagnosis of osteopenia (50.9%) and osteoporosis (49.1%) at the first visit were enrolled in this study. Serum 25(OH)D level, PTH, osteocalcin (OC) and Beta-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), were measured. BMD at all sites, including the lumbar spine, femoral neck, and total hip were obtained by dual-energy X-ray absorptiometry (DXA). The associations of serum 25(OH)D level with BMDs and BTMs were investigated using spearman correlation analysis and analysis of general linear model adjusted by age and body mass index.

Results

The serum 25(OH)D level was 22.17 ± 9.75 ng/mL among all patients included in this study. For the osteopenia group, the serum 25(OH)D level was 22.40 ± 9.41 ng/mL, while for the osteoporosis group, it measured 21.93 ± 10.08 ng/mL. In the osteopenia group, the prevalence of vitamin D deficiency, insufficiency and sufficiency was 45.8, 34.6, and 19.6%, respectively, which was close to that of the osteoporosis group (47.4, 34.3, and 18.3%) (p = 0.202). Spearman correlation analysis unveiled negative associations between serum 25(OH)D concentrations and both BTMs and PTH within both the osteopenia and osteoporosis group. In the osteoporosis group, there were positive correlations between 25(OH)D levels and femoral neck BMD (r = 0.040, p = 0.010) and total hip BMD (r = 0.053, p = 0.001). Furthermore, we found that for the osteopenia group, greater vitamin D levels were associated with greater femoral neck BMD (p = 0.020) and total hip BMD (p = 0.008) and lower β-CTX (p < 0.001), OC (p < 0.001), and PTH (p < 0.001). The same trends were seen in osteoporosis patients (p < 0.05), and with greater lumbar spine BMD with higher levels of 25(OH)D (p = 0.009).

Conclusion

This study showed high prevalence of vitamin D deficiency and insufficiency in Chinese postmenopausal women with osteopenia and osteoporosis and the relationships between vitamin D and BMD, BTMs and PTH. The results contribute to a more comprehensive understanding of how vitamin D may impact bone health.
Association between dietary inflammatory index and anemia in US adults
Authors: Ma Huimiao , Deng Wenqi , Chen Haiyan , Ding Xiaoqing
Published: January 2024

Background and aims

Anemia is a widespread global health concern, and recent research has unveiled a link between anemia and inflammation. The Dietary Inflammation Index (DII) is a novel tool used to assess the overall inflammatory potential of an individual’s diet. However, until now, there have been no studies demonstrating a connection between DII and anemia. This study aimed to explore the relationship between DII and the risk of anemia among Americans, as well as to examine the influence of other risk factors on this association.

Methods

Data from 32,244 patients were collected from the National Health and Nutrition Examination Survey (NHANES) database spanning from 1999 to 2018. Using multivariable logistic regression, we examined the correlation between DII and anemia. Subgroup analyses and smoothed curve analyses were conducted to further investigate the association between DII and anemia.

Results

The analysis revealed a significant positive association between higher DII scores and increased anemia risk in the American population (Odds Ratio [OR] = 1.06, 95% Confidence Interval [CI] = 1.03 to 1.09, p < 0.0001). This association remained consistent in subgroup analyses, encompassing various age groups, distinct Body Mass Index (BMI) categories, varying diabetes mellitus statuses, histories of hypertension, females, individuals with a RIP <3.5, and Non-Hispanic Black individuals. Notably, the association was particularly significant among non-smokers. Smoothed curve fitting analysis demonstrated a linear relationship between DII and the prevalence of anemia.

Conclusion

Our findings underscore a positive correlation between the inflammatory potential of one’s diet and the risk of anemia, especially when coupled with other risk factors. Consequently, reducing the consumption of pro-inflammatory foods may serve as one of the effective measures against the development of anemia. Given the variations in gender, age, BMI, and chronic diseases observed in our study, tailored policies could better cater to the specific needs of diverse populations.