bluuebunny/crossref_metadata_2025 huggingface dataset:
Hambatan Guru Pada Pembelajaran Tematik dalam Kurikulum 2013 Di Sekolah Dasar
Authors: Azmi Nabilah Nur , Sari Irma Yunita , Prayogo Muhammad Suwignyo
Published: July 2024

Penelitian ini dilatarbelakangi dengan adanya hambatan yang dihadapi oleh guru pada pembelajaran tematik. Tujuan dari penelitian ini adalah untuk mengetahui apa saja hambatan yang telah dihadapi oleh guru pada pembelajaran tematik dalam kurikulum 2013 di Sekolah Dasar dan bagaimana solusinya. Tujuan dari penelitian ini memanfaatkan studi dokumen dan hasil penelitian sebelumnya. Data dikumpulkan melalui penelusuran jurnal elektronik seperti internet dan Google Scholar dengan kata kunci terfokus pada implementasi guru dalam menghadapi kurikulum 2013. Hasil penelitian menunjukkan bahwa hambatan yang dihadapi guru dalam pembelajaran tematik terjadi dalam tiga tahapan yakni pada tahap perencanaan, pelaksanaan, dan evaluasi. Dalam menghadapi semua hambatan yang ada, diperlukan kerjasama dan komunikasi yang baik antara semua komponen pendidikan agar hambatan dapat diatasi dengan baik.
Analisis Nilai Nilai Karakter dalam Novel Kenang Langit Karya Kirana Kejora
Authors: Rika Rika Wahyuni , Alpusari Mahmud , Mulyani Eva Astuti
Published: July 2024

Penelitian ini dilatar belakangi oleh pentingnya nilai pendidikan karakter untuk mendorong pribadi manusia yang berkapasitas, berkomitmen secara benar, juga memiliki tujuan hidup. Dengan demikian, dapat diintregasikan keseluruh aspek kehidupan yang digambarkan melalui sebuah karya sastra. Novel Kenang Langit karya Kirana Kejora memiliki unsur-unsur nilai karakter yang dapat dikaji dan di implementasikan dalam kehidupan sosial serta dalam bidang pendidikan bagi siswa. Novel Kenang Langit karya Kirana Kejora ini merupakan novel yang bertemakan tentang persahabatan. Adapaun alasan memilih Novel Kenang Langit ini karena, (a) terdapat nilai-nilai karakter yang dapat diajarkan kepada peserta didik; (b) kisah yang sangat inspiratif dan banyak motivasi; (c) banyaknya pesan moral (d) Bahasa yang dikemas secara sederhana dan menarik serta membuat novel ini menjadi sarana pembelajaran sastra yang menyenangkan di Sekolah Dasar. Tujuan penelitian ini adalah untuk mengetahui Nilai-nilai karakter yang terdapat dalam novel Kenang Langit karya Kirana Kejora. Jenis penelitian ini adalah penelitian kepustakaan (library research). Hasil penelitian menunjukkan Nilai-Nilai Pendidikan Karakter Dalam Novel Kenang Langit Karya Kirana Kejora yaitu nilai kejujuran yang terdiri dari 2 data, nilai disiplin yang terdiri dari 6 data, nilai kreatif yang terdiri dari 13 data, nilai peduli sosial yang terdiri dari 27 data, nilai tanggung jawab yang terdiri dari 4 data. Maka dapat disimpulkan bahwa Novel Kenang Langit Karya Kirana Kejora sarat akan nilai pendidikan karakter. Nilai pendidikan karakter yang paling mendominasi Novel Kenang Langit Karya Kirana Kejora adalah nilai peduli sosial dengan jumlah data sebanyak 27 data.
Kesulitan Guru dalam Pembelajaran Daring pada Mata Pelajaran Bahasa Indonesia di SDN 164 Pekanbaru
Authors: Yulianti Elsi , Antosa Zariul
Published: July 2024

Penelitian ini dilakukan untuk mengetahui kesulitan dan solusi yang dilakukan guru ketika mengalami kesulitan pada saat pembelajaran Bahasa Indonesia secara daring. Penelitian ini merupakan penelitian kualitatif melalui pendekatan deskriptif kualitatif. Dalam penelitian ini, pengumpulan data dilakukan dengan cara observasi, wawancara dan studi dokumentasi. Analisis data terdiri dari pengumpulan data, reduksi data, penyajian data dan verifikasi data. Hasil penelitian menunjukkan kesulitan yang dialami oleh guru pada saat pembelajaran Bahasa Indonesia secara daring yaitu gangguan jaringan pada peserta didik, peserta didik masih memiliki keterbatasan fasilitas terutama HP, ditemukannya peserta didik yang sulit dalam memahami pembelajaran, guru mengalami kesulitan fokus saat pembelajaran karena waktu yang singkat dan juga antusias peserta didik yang tergolong rendah, ditemukannya peserta didik yang tidak dibimbing oleh kedua orang tua pada saat pembelajaran, ada juga peserta didik yang kurang aktif dalam mengikuti pembelajaran, guru masih kurang maksimal dalam menggunakan metode pembelajaran, dan minimnya kemampuan dalam pengoptimalan aplikasi pembelajaran daring. Untuk meminimalisir kesulitan yang dialami guru tetap menyediakan tugas offline, melakukan komunikasi terus menerus atau secara rutin kepada orang tua peserta didik, sharing hiring kepada guru dan peserta didik lainnya, dan mengikuti pelatihan menggunakan teknologi atau aplikasi yang dapat digunakan pada saat pembelajaran secara daring
Penggunaan Media 3 Dimensi Bangun Ruang untuk Meningkatkan Minat Belajar Siswa pada Mata Pembelajaran Matematika
Authors: Sintia Irne , Kusmana Dinda Afrisa , Alicia Vicky Dinda Hawa , Putri Alya Ihsani , Kurnia Budi
Published: July 2024

Penelitian ini bertujuan untuk mengevaluasi efektivitas penggunaan media tiga dimensi bangun ruang dalam meningkatan minat belajar siswapada mata pembelajaran matematika. Metode penelitian yang digunakan adalah penelitian tindakan kelas yang tidak jauh berbeda dari prinsip yang digunakan dalam jenis penelitian lain. Sampel penelitian terdiri dari pemilihan sampel secara acak pada kelas 4 di SDN 1 Cimahi yang berjumlah 29 orang yang terdiri dari 15 orang anak perempuan dan 14 anak laki-laki. Hasil penelitian menunjukan bahwa penggunaan media tiga dimensi dalam pembelajaran matematika secara signifika meningkatkan minat belajar siswa. Data yang diperoleh dari hasil tes menunjukan peningkatan yang signfikan setelah interpensi media tiga dimensi ditetapkan. Siswa menunjukan antusiasme yang lebih tinggi dan keterlibatan yang lebih aktif selama proses pembelajaran, yang berkontribusi pada pemahaman yang lebih baik pada pemahaman konsep bangun ruang.
A miskolci dialíziscentrum betegeinek jellemzése, különös tekintettel a halálozásra, a testösszetételre és a kezelési módra
Authors: Ladányi Erzsébet , Csurgyók Roland , Kun Szilárd , Wittmann István
Published: July 2024

Az elhízás és a magasabb testtömegindex (BMI) egyes szerzők szerint összefüggésbe hozható bizonyos betegpopulációk jobb túlélésével. Lehetséges, hogy a magasabb BMI a dializált vesebetegekben védőhatással bírhat, ami az elhízási paradoxon (más néven: reverz epidemiológia) koncepcióját erősíti. Ennek a megfigyelésnek a hátterében felmerült a gyulladásos és a tápláltsági állapot, valamint a testösszetétel szerepe. Jelen vizsgálatunk célja az volt, hogy az elhízási paradoxont az összes okból bekövetkező mortalitás, a testösszetétel- és gyulladásos paraméterek, a tápláltsági állapot összefüggéseinek tükrében vizsgáljuk prevalens HD- és PD-kezelt betegeink körében. Vizsgálatunkban retrospektív adatelemzést végeztünk 2020. január és 2023. június között. Bioimpedanciai (BCMv) és bizonyos laboratóriumi vizsgálati eredmények kiértékelését tűztük ki célul, vizsgálva ezen eredmények és a mortalitás közti összefüggéseket. Emellett – eltérő trendeket feltételezve – tanulmányoztuk a két vesepótló modalitás közti különbségeket az idő függvényében. Összesen 765 krónikusan dializált – 701 hemodializált és 64 PD-kezelt – beteg adatainak feldolgozását végeztük el. A PD-kezelt betegek esetében jobb túlélés igazolódott. Az elhunyt betegek idősebbek és anaemiásabbak voltak. Esetükben kifejezettebb volt a szisztémás, szubklinikus gyulladás és a katabolikus állapot. A HD-kezeltek csoportjában gyakoribb volt a túlhidráltság és az elhunytak soványszövet-indexe, zsírmentes testtömege, relatív zsírmentes testtömege és a test sejttömege alacsonyabbnak bizonyult, mint a PD-kezeltek esetében. A tendenciavizsgálatok tanúsága szerint a HD-kezelés romló gyulladásos folyamattal jellemezhető és általánosságban is progresszívebb, mint a PD. Vizsgálatunk alapján, az irodalmi adatoknak megfelelően, a dializált betegek adekvát kezelésében fontos a testösszetétel, a tápláltsági, valamint a szisztémás, szubklinikus gyulladásra vonatkozó legfontosabb paraméterek követése, hiszen ezek figyelembevételével alapvetően befolyásolható a dializált betegek túlélése. Indokoltnak tartható a dializált betegek száraz testsúlyának objektív vizsgálata és fenntartása.
Metforminasszociált laktátacidózis krónikus vesebetegnél
Authors: Béres Kornélia , Ladányi Erzsébet
Published: July 2024

A laktátacidózis a metabolikus acidózis egyik ritka típusa, amely során a szervezetben kóros mennyiségben szaporodik fel a laktát, vagyis a tejsav. Csökkent folyadékbevitel, akut hasmenés, hányás, láz esetén dehidráció alakulhat ki, amely a metformint szedő betegeknél fokozza a tejsavacidózis kialakulásának veszélyét. Laktátacidózis fokozott kockázatával kell számolni emellett a veseműködés heveny romlásakor, szív-, máj- és légzőszervi megbetegedés esetén vagy szepszis kialakulásánál. Az általunk bemutatott beteg esete is rámutat a metforminnal történő kezelés potenciális kockázatára, és a megfelelő körültekintéssel való alkalmazásának fontosságára.
Exploring adaptation strategies for smallholder farmers in dryland farming systems and impact on pearl millet production under climate change in West Africa
Authors: Akinseye Folorunso M. , Zagre Inoussa , Faye Aliou , Joseph Jacob Emanuel , Worou Omonlola N. , Whitbread Anthony M.
Published: July 2024

Understanding and identifying appropriate adaptation optons for cropping systems and management practices at spatial and temporal scales is an important prerequisite for scaling. Pearl millet (Pennisetum glaucum (L) R. Br.) could be regarded as a risk-reducing measure crop under climate change when coupled with tactical agronomic management practices. In this study, we assess the impacts of adaptation strategies such as cultivar type, planting windows, and fertilizer strategies on pearl millet production under rainfed farming systems over Nigeria and Senegal using the Agricultural Production Systems Simulator (APSIM) model. The impact of climate change on millet yield was evaluated using a validated APSIM-millet module that utilized yield data collected through participatory research and extension approach (PREA) in contrasting environments. The climate model projections for the mid-century period (2040–2069) were compared against a baseline period of 1980–2009 for both locations. During the simulation, two millet varieties (improved local and dual-purpose) with two sowing regimes were considered comparing traditional farmers’ sowing window (dry sowing) and agronomic sowing window (planting based on the onset of the rainfall) at three different fertilizer levels [low (23 kg N ha−1), medium (40.5 kg N ha−1), and high (68.5 kg N ha−1) respectively]. The performance of the APSIM-millet module was found to be satisfactory as indicated by the low Root Means Square Error (RMSE) and Normalized Root Mean Square Error (NRMSE) values. The range for grain yield was between 17.7% and 25.8%, while for AGB it was between 18.6% and 21.4%. The results showed that farmers’ sowing window simulated slightly higher grain yield than the agronomic sowing window for improved local millet cultivar indicating yield increased by 8–12%. However, the projected changes in the mid-century (2040–2069) resulted in a decline in yield against baseline climate for both varieties and sowing windows, indicating the negative impact of climate change (CC) on yield productivity. The comparison between dual-purpose millet and improved local millet indicates that disseminating the improved millet variety and implementing early sowing could be an effective adaptation strategy in reducing risks and losses caused by climate change. Similarly, low magnitude impacts simulated on grain yield (< −8% in Nigeria compared to > −8% in Senegal) even though both locations are in the same agroecological zone.
A systematic overview of single-cell transcriptomics databases, their use cases, and limitations
Authors: Gondal Mahnoor N. , Shah Saad Ur Rehman , Chinnaiyan Arul M. , Cieslik Marcin
Published: July 2024

Rapid advancements in high-throughput single-cell RNA-seq (scRNA-seq) technologies and experimental protocols have led to the generation of vast amounts of transcriptomic data that populates several online databases and repositories. Here, we systematically examined large-scale scRNA-seq databases, categorizing them based on their scope and purpose such as general, tissue-specific databases, disease-specific databases, cancer-focused databases, and cell type-focused databases. Next, we discuss the technical and methodological challenges associated with curating large-scale scRNA-seq databases, along with current computational solutions. We argue that understanding scRNA-seq databases, including their limitations and assumptions, is crucial for effectively utilizing this data to make robust discoveries and identify novel biological insights. Such platforms can help bridge the gap between computational and wet lab scientists through user-friendly web-based interfaces needed for democratizing access to single-cell data. These platforms would facilitate interdisciplinary research, enabling researchers from various disciplines to collaborate effectively. This review underscores the importance of leveraging computational approaches to unravel the complexities of single-cell data and offers a promising direction for future research in the field.
Exploring the central region of amylin and its analogs aggregation: the influence of metal ions and residue substitutions
Authors: Alghrably Mawadda , Bennici Giulia , Szczupaj Gabriela , Alasmael Noura , Qutub Somayah , Maatouk Batoul , Chandra Kousik , Nowakowski Michal , Emwas Abdul-Hamid , Jaremko Mariusz
Published: July 2024

Human amylin (hIAPP) is found in the form of amyloid deposits within the pancreatic cells of nearly all patients diagnosed with type 2 diabetes mellitus (T2DM). However, rat amylin (rIAPP) and pramlintide - hIAPP analogs - are both non-toxic and non-amyloidogenic. Their primary sequences exhibit only slight variations in a few amino acid residues, primarily concentrated in the central region, spanning residues 20 to 29. This inspired us to study this fragment and investigate the impact on the aggregation properties of substituting residues within the central region of amylin and its analogs. Six fragments derived from amylin have undergone comprehensive testing against various metal ions by implementing a range of analytical techniques, including Nuclear Magnetic Resonance (NMR) spectroscopy, Thioflavin T (ThT) assays, Atomic Force Microscopy (AFM), and cytotoxicity assays. These methodologies serve to provide a thorough understanding of how the substitutions and interactions with metal ions impact the aggregation behavior of amylin and its analogs.
An insight into the vaginal microbiome of infertile women in Bangladesh using metagenomic approach
Authors: Hasan Zahid , Netherland Michael , Hasan Nur A. , Begum Nurjahan , Yasmin Mahmuda , Ahmed Sangita
Published: July 2024

Introduction

The dysbiosis of vaginal microbiota is recognized as a potential underlying factor contributing to infertility in women. This study aimed to compare the vaginal microbiomes of infertile and fertile women to investigate their relationship with infertility.

Methods

Metagenomic analysis was conducted on samples from 5 infertile and 5 fertile individuals using both amplicon 16S and metagenomics shotgun sequencing methods.

Results and discussion

In the infertile group, the bacterial community was primarily represented by three major bacterial genera: Lactobacillus (79.42%), Gardnerella (12.56%) and Prevotella (3.33%), whereas, the fertile group exhibited a more diverse composition with over 8 major bacterial genera, accompanied by significantly reduced abundance of Lactobacillus (48.79%) and Gardnerella (6.98%). At the species level, higher abundances of L. iners, L. gasseri and G. vaginalis were observed in the infertile group. Regarding the microbiome composition, only one fertile and two infertile subjects exhibited the healthiest Community State Types, CST-1, while CST-3 was observed among two infertile and one fertile subject, and CST-4 in three other fertile and one infertile subject. Overall, alpha diversity metrics indicated greater diversity and lower species richness in the control (fertile) group, while the infertile group displayed the opposite trend. However, beta-diversity analysis did not show distinct clustering of samples associated with any specific group; instead, it demonstrated CST-type specific clustering. Shotgun metagenomics further confirmed the dominance of Firmicutes, with a greater abundance of Lactobacillus species in the infertile group. Specifically, L. iners and G. vaginalis were identified as the most dominant and highly abundant in the infertile group. Fungi were only identified in the control group, dominated by Penicillium citrinum (62.5%). Metagenome-assembled genomes (MAGs) corroborated read-based taxonomic profiling, with the taxon L. johnsonii identified exclusively in disease samples. MAG identities shared by both groups include Shamonda orthobunyavirus, L. crispatus, Human endogenous retrovirus K113, L. iners, and G. vaginalis. Interestingly, the healthy microbiomes sequenced in this study contained two clusters, Penicillium and Staphylococcus haemolyticus, not found in the public dataset. In conclusion, this study suggests that lower species diversity with a higher abundance of L. iners, L. gasseri and G. vaginalis, may contribute to female infertility in our study datasets. However, larger sample sizes are necessary to further evaluate such association.
A systematic literature review on contemporary and future trends in virtual machine scheduling techniques in cloud and multi-access computing
Authors: Rana Nadim , Jeribi Fathe , Khan Zeba , Alrawagfeh Wagdi , Ben Dhaou Imed , Haseebuddin Mohammad , Uddin Mueen
Published: July 2024

Introduction

The migration of business and scientific operations to the cloud and the surge in data from IoT devices have intensified the complexity of cloud resource scheduling. Ensuring efficient resource distribution in line with user-specified SLA and QoS demands novel scheduling solutions. This study scrutinizes contemporary Virtual Machine (VM) scheduling strategies, shedding light on the complexities and future prospects of VM design and aims to propel further research by highlighting existing obstacles and untapped potential in the ever-evolving realm of cloud and multi-access edge computing (MEC).

Method

Implementing a Systematic Literature Review (SLR), this research dissects VM scheduling techniques. A meticulous selection process distilled 67 seminal studies from an initial corpus of 722, spanning from 2008 to 2022. This critical filtration has been pivotal for grasping the developmental trajectory and current tendencies in VM scheduling practices.

Result

The in-depth examination of 67 studies on VM scheduling has produced a taxonomic breakdown into three principal methodologies: traditional, heuristic, and meta-heuristic. The review underscores a marked shift toward heuristic and meta-heuristic methods, reflecting their growing significance in the advancement of VM scheduling.

Conclusion

Although VM scheduling has progressed markedly, the focus remains predominantly on metaheuristic and heuristic approaches. The analysis enlightens ongoing challenges and the direction of future developments, highlighting the necessity for persistent research and innovation in this sector.
PCSK9 inhibitors and inclisiran with or without statin therapy on incident muscle symptoms and creatine kinase: a systematic review and network meta-analysis
Authors: Li Wenshu , Sun Lichaoyue , Yan Sichao
Published: July 2024

Background

Atherosclerotic cardiovascular disease (ASCVD), a leading cause of global fatalities, has inconsistent findings regarding the impact of muscle symptoms despite promising clinical trials involving PCSK9 inhibitors (PCSK9i) and siRNA as potential therapeutic options.

Methods

The databases EMBASE, PubMed, Web of Science, Cochrane, and ClinicalTrials.gov were thoroughly searched without any restrictions on language. Review Manager 5.3 software was utilized to calculate relative risks with 95% confidence intervals (CIs) for dichotomous data and mean differences or standardized mean differences with 95%CIs for continuous data. To evaluate publication bias, Egger's test was employed using Stata/SE software.

Results

This analysis included 26 studies comprising 28 randomized controlled trials (RCTs) involving a total of 100,193 patients, and 4 different lipid-lowering therapy combinations. For events with creatine kinase >3ULN, evolocumab and alirocumab demonstrated significant advantages compared to inclisiran. Evolocumab showed the best results in terms of both new muscle symptom events and creatine kinase >3ULN.

Conclusions

Based on this network meta-analysis (NMA) results, evolocumab has emerged as a promising treatment option for patients with hyperlipidemia and muscle disorders compared to other PCSK9 inhibitors and inclisiran.

Systematic Review Registration

PROSPERO [CRD42023459558].
Classification of rock types of porous limestone reservoirs: case study of the A oilfield
Authors: Huang Tingting , Chen Mingjiang , Wang Xia , Duan Guanghui , Fu Meiyan
Published: July 2024

Rock types with similar lithological components and pore structures form the basic units of porous limestone reservoirs; this influences the reservoir evaluation efficiency and water injection development. As the main oil and gas pay zone in central Iraq, the Cretaceous Khasib Formation reservoirs are influenced by deposition, dissolution, and cementation. There is strong vertical heterogeneity in the most important zone of the Kh2 layer, with diverse rock types and complex pore structures. Based on core observation and casting thin-section identification, the Kh2 layer in the study area was divided into eight lithofacies types as argillaceous bioclastic wackestone, planktic foraminiferium wackestone, lamellar bioclastic wackestone, intraclastic–bioclastic packstone, patchy green algae packstone, green algae and pelletoid packstone, benthic foraminiferium–bioclastic packstone, and intraclastic grainstone. Along with the reservoir void space types of the lithofacies, capillary pressure curves are used to quantitatively analyze the throat and pore features of the different lithofacies. From the porosity–permeability cross-plot characteristics and distribution of pore types, 14 petrophysical facies are obtained. Finally, based on the differences between the lithofacies and petrophysical facies, the Kh2 member is divided into 13 rock types with different geological origins and petrophysical characteristics. Among these, the rock type RT1-8-14 has the best and rock type RT1-1-1 has the worst physical properties among the reservoir rock types. This study provides an optimization method for carbonate reservoir evaluation and is expected to be beneficial for efficient development of similar carbonate reservoirs.
Unraveling teacher stressors in Bhutan: a qualitative exploration of contributing elements
Authors: Dorji Tenzin
Published: July 2024

School teaching is widely acknowledged to be a highly demanding profession. Consequentially, an emerging academic literature deals with the stress levels teachers face. While existing studies predominantly focus on quantifying relevant stressors, this study investigates the subjective perceptions and interpretations of stressors by teachers. Data comes from Bhutan, a country with a high teacher resignation rate primarily due to teacher stress, despite being one of the highest-paid occupations. The results show that teacher stress in Bhutan predominantly emanates from heightened job demands. These demands are perceived differently in terms of how individuals view teaching responsibilities and non-academic obligations (e.g., Class Teacher). The pervasive impact of inadequate leadership and management exacerbates stress levels, directly encroaching upon psycho-social wellbeing. Ten teachers in Bhutan were interviewed using a semi-structured format. The interview data was recorded, transcribed, and coded using MAXQDA. Thematic analysis was then conducted based on the generated codes. By adopting a qualitative lens, this research enriches our understanding of teacher stress by unraveling how stressors are interconnected and how different teachers perceive the same stressor differently, providing insights on targeted interventions and support mechanisms. The results also show that supportive leadership can sometimes be viewed as a source of stress as opposed to the popular notion of perceiving it entirely as a stress-mitigating factor.
The causal relationship between human brain morphometry and knee osteoarthritis: a two-sample Mendelian randomization study
Authors: Liu Yongming , Huang Chao , Xiong Yizhe , Wang Xiang , Shen Zhibi , Zhang Mingcai , Gao Ningyang , Wang Nan , Du Guoqing , Zhan Hongsheng
Published: July 2024

Background

Knee Osteoarthritis (KOA) is a prevalent and debilitating condition affecting millions worldwide, yet its underlying etiology remains poorly understood. Recent advances in neuroimaging and genetic methodologies offer new avenues to explore the potential neuropsychological contributions to KOA. This study aims to investigate the causal relationships between brain-wide morphometric variations and KOA using a genetic epidemiology approach.

Method

Leveraging data from 36,778 UK Biobank participants for human brain morphometry and 487,411 UK Biobank participants for KOA, this research employed a two-sample Mendelian Randomization (TSMR) approach to explore the causal effects of 83 brain-wide volumes on KOA. The primary method of analysis was the Inverse Variance Weighted (IVW) and Wald Ratio (WR) method, complemented by MR Egger and IVW methods for heterogeneity and pleiotropy assessments. A significance threshold of p < 0.05 was set to determine causality. The analysis results were assessed for heterogeneity using the MR Egger and IVW methods. Brain-wide volumes with Q_pval < 0.05 were considered indicative of heterogeneity. The MR Egger method was employed to evaluate the pleiotropy of the analysis results, with brain-wide volumes having a p-value < 0.05 considered suggestive of pleiotropy.

Results

Our findings revealed significant causal associations between KOA and eight brain-wide volumes: Left parahippocampal volume, Right posterior cingulate volume, Left transverse temporal volume, Left caudal anterior cingulate volume, Right paracentral volume, Left paracentral volume, Right lateral orbitofrontal volume, and Left superior temporal volume. These associations remained robust after tests for heterogeneity and pleiotropy, underscoring their potential role in the pathogenesis of KOA.

Conclusion

This study provides novel evidence of the causal relationships between specific brain morphometries and KOA, suggesting that neuroanatomical variations might contribute to the risk and development of KOA. These findings pave the way for further research into the neurobiological mechanisms underlying KOA and may eventually lead to the development of new intervention strategies targeting these neuropsychological pathways.
DSB profiles in human spermatozoa highlight the role of TMEJ in the male germline
Authors: Scheuren Maurice , Möhner Jonas , Müller Max , Zischler Hans
Published: July 2024

The male mammalian germline is characterized by substantial chromatin remodeling associated with the transition from histones to protamines during spermatogenesis, followed by the reversal to nucleohistones in the male pronucleus preceding the zygotic genome activation. Both transitions are associated with the extensive formation of DNA double-strand breaks (DSBs), requiring an estimated 5 to 10 million transient DSBs per spermatozoa. Additionally, the high transcription rate in early stages of spermatogenesis leads to transcription-coupled damage preceding meiotic homologous recombination, potentially further contributing to the DSB landscape in mature spermatozoa. Once meiosis is completed, spermatozoa remain haploid and therefore cannot rely on error-free homologous recombination, but instead depend on error-prone classical non-homologous end joining (cNHEJ). This DNA damage/repair-scenario is proposed to be one of the main causes of the observed paternal mutation propensity in human evolution. Recent studies have shown that DSBs in the male pronucleus are repaired by maternally provided Polθ in Caenorhabditis elegans through Polθ-mediated end joining (TMEJ). Additionally, population genetic datasets have revealed a preponderance of TMEJ signatures associated with human variation. Since these signatures are the result of the combined effect of TMEJ and DSB formation in spermatozoa and male pronuclei, we used a BLISS-based protocol to analyze recurrent DSBs in mature human sperm heads as a proxy of the male pronucleus before zygotic chromatin remodeling. The DSBs were found to be enriched in (YR)n short tandem repeats and in evolutionarily young SINEs, reminiscent to patterns observed in murine spermatids, indicating evolutionary hotspots of recurrent DSB formation in mammalian spermatozoa. Additionally, we detected a similar DSB pattern in diploid human IMR90 cells when cNHEJ was selectively inhibited, indicating the significant impact of absent cNHEJ on the sperm DSB landscape. Strikingly, regions associated with most retained histones, and therefore less condensed chromatin, were not strongly enriched with recurrent DSBs. In contrast, the fraction of retained H3K27me3 in the mature spermatozoa displayed a strong association with recurrent DSBs. DSBs in H3K27me3 are associated with a preference for TMEJ over cNHEJ during repair. We hypothesize that the retained H3K27me3 may trigger transgenerational DNA repair by priming maternal Polθ to these regions.
Dual roles of CD11b+CD33+HLA-DR-/lowCD14- myeloid-derived suppressor cells with a granulocytic morphology following allogeneic hematopoietic stem cell transplantation: from inflammation promoters to immune suppressors within 90 days
Authors: Ni Ming , Cui Jing , Yang Xin , Ding Yuntian , Zhao Peng , Hu Tianzhen , Zhan Yun , Kang Qian , Hu Xiuying , Zhao Jiangyuan , Xu Yao , Chen Lu , Liu Min , Zhao Mei , Zhang Fengqi , Huang Shisi , Li Ya , Yang Xueying , Zhang Luxin , Zhang Tianzhuo , Deng Bo , Yang Bing , Lu Deqin , Wang Jishi
Published: July 2024

Introduction

Granulocytic myeloid-derived suppressor cells (G-MDSCs) show fast recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) constituting the major part of peripheral blood in the early phase. Although G-MDSCs mediate immune suppression through multiple mechanisms, they may also promote inflammation under specific conditions.

Methods

G-MDSCs were isolated from 82 patients following allo-HSCT within 90 days after allo-HSCT, and their interactions with autologous CD3+ T-cells were examined. T-cell proliferation was assessed by flow cytometry following CFSE staining, while differentiation and interferon-γ secretion were characterized using chemokine receptor profiling and ELISpot assays, respectively. NK cell cytotoxicity was evaluated through co-culture with K562 cells. An aGVHD xenogeneic model in humanized mice was employed to study the in vivo effects of human leukocytes. Furthermore, transcriptional alterations in G-MDSCs were analyzed via RNA sequencing to investigate functional transitions.

Results

G-MDSCs promoted inflammation in the early-stage, by facilitating cytokine secretion and proliferation of T cells, as well as their differentiation into pro-inflammatory T helper subsets. At day 28, patients with a higher number of G-MDSCs exhibited an increased risk of developing grades II-IV aGvHD. Besides, adoptive transfer of G-MDSCs from patients at day 28 into humanized mice exacerbated aGvHD. However, at day 90, G-MDSCs led to immunosuppression, characterized by upregulated expression of indoleamine 2,3-dioxygenase gene and interleukin-10 secretion, coupled with the inhibition of T cell proliferation. Furthermore, transcriptional analysis of G-MDSCs at day 28 and day 90 revealed that 1445 genes were differentially expressed. These genes were associated with various pathways, revealing the molecular signatures of early post-transplant differentiation in G-MDSCs. In addition, genes linked to the endoplasmic reticulum stress were upregulated in patients without aGvHD. The acquisition of immunosuppressive function by G-MDSCs may depend on the activation of CXCL2 and DERL1 genes.

Conclusion

Our findings revealed the alteration in the immune characteristics of G-MDSCs within the first 90 days post-allo-HSCT. Moreover, the quantity of G-MDSCs at day 28 may serve as a predictive indicator for the development of aGvHD.
A novel NKp80-based strategy for universal identification of normal, reactive and tumor/clonal natural killer-cells in blood
Authors: Morán-Plata F. Javier , Muñoz-García Noemí , González-González María , Pozo Julio , Carretero-Domínguez Sonia , Mateos Sheila , Barrena Susana , Belhassen-García Moncef , Lau Catarina , Teixeira Maria Dos Anjos , Santos Ana Helena , Yeguas Ana , Balanzategui Ana , García-Sancho Alejandro Martín , Orfao Alberto , Almeida Julia
Published: July 2024

Purpose

Natural killer (NK) cells are traditionally identified by flow cytometry using a combination of markers (CD16/CD56/CD3), because a specific NK-cell marker is still missing. Here we investigated the utility of CD314, CD335 and NKp80, compared to CD16/CD56/CD3, for more robust identification of NK-cells in human blood, for diagnostic purposes.

Methods

A total of 156 peripheral blood (PB) samples collected from healthy donors (HD) and patients with diseases frequently associated with loss/downregulation of classical NK-cell markers were immunophenotyped following EuroFlow protocols, aimed at comparing the staining profile of total blood NK-cells for CD314, CD335 and NKp80, and the performance of distinct marker combinations for their accurate identification.

Results

NKp80 showed a superior performance (vs. CD314 and CD335) for the identification of NK-cells in HD blood. Besides, NKp80 improved the conventional CD16/CD56/CD3-based strategy to identify PB NK-cells in HD and reactive processes, particularly when combined with CD16 for further accurate NK-cell-subsetting. Although NKp80+CD16 improved the identification of clonal/tumor NK-cells, particularly among CD56- cases (53%), aberrant downregulation of NKp80 was observed in 25% of patients, in whom CD56 was useful as a complementary NK-cell marker. As NKp80 is also expressed on T-cells, we noted increased numbers of NKp80+ cytotoxic T-cells at the more advanced maturation stages, mostly in adults.

Conclusion

Here we propose a new robust approach for the identification of PB NK-cells, based on the combination of NKp80 plus CD16. However, in chronic lymphoproliferative disorders of NK-cells, addition of CD56 is recommended to identify clonal NK-cells, due to their frequent aberrant NKp80- phenotype.
Mutual regulations between Toxoplasma gondii and type I interferon
Authors: Song Lingling , Wang Ruoyu , Cao Yuanyuan , Yu Li
Published: July 2024

In the decades since the discovery, Type I interferon (IFN-I) has been intensively studied for their antiviral activity. However, increasing evidences suggest that it may also play an important role in the infection of Toxoplasma gondii, a model organism for intracellular parasites. Recent studies demonstrated that the induction of IFN-I by the parasite depends on cell type, strain genotype, and mouse strain. IFN-I can inhibit the proliferation of T. gondii, but few studies showed that it is beneficial to the growth of the parasite. Meanwhile, T. gondii also can secrete proteins that impact the pathway of IFN-I production and downstream induced interferon-stimulated genes (ISGs) regulation, thereby escaping immune destruction by the host. This article reviews the major findings and progress in the production, function, and regulation of IFN-I during T. gondii infection, to thoroughly understand the innate immune mechanism of T. gondii infection, which provides a new target for subsequent intervention and treatment.
A framework for assessing the blue equity of social-ocean systems in marine governance transformation
Authors: Chen Mingbao , Wang Yuhao , Xu Zhibin
Published: July 2024

The equitable utilization of marine resources and the maintenance of healthy and sustainable marine ecosystems are essential to advancing the United Nations Sustainable Development Goals (SDGs) and promoting the well-being of all humanity. In this paper, we propose a Blue Equity Assessment Framework, which is based on a systematic literature review approach and takes into account the characteristics of Social-Ocean Systems (SOSs). The framework consists of Distributional Equity, Procedural Equity, Recognitional Equity, and Contextual Equity. The aim of this framework is to conduct equity analyses of policies or behaviors within SOSs in order to assess whether blue equity is explicitly implemented and practiced in these societal norms and policy mechanisms. The assessment framework reveals that blue equity has a positive synergy for the majority of the SDGs. This synergy is analyzed in terms of its influence on the assessment dimensions of distributional justice, procedural justice, recognitional justice, and contextual justice. The findings aim to enhance societal understanding of blue equity issues, thereby guiding policymakers in the prioritization of blue equity in the development and utilization of marine resources and in the transformation of global ocean governance.
Discrimination of different forms and oceanic regions of purpleback flying squid (Sthenoteuthis oualaniensis) based on stable isotopes and fatty acid composition
Authors: Zhu Kai , Xu Kaida , Zhu Wenbin
Published: July 2024

Introduction

Pelagic cephalopods play a key role in the Chinese food supply. The market value of seafood frequently fluctuates based on its geographical origin and species, making it imperative to trace the origin and distinguish forms to guarantee food quality and accurate information.

Methods

In this study, we used biochemical tracers, including stable isotope analysis and fatty acid composition profiling, to trace the origin of purpleback flying squid (Sthenoteuthis oualaniensis) from the Indian Ocean and South China Sea. We measured the δ13C and δ15N values and fatty acid (FA) contents in samples from different forms of S. oualaniensis obtained from these two oceanic regions. We analyzed the feeding and nutritional differences among these populations and conducted discriminant analysis.

Results and discussion

Significant regional and form differences were observed in both isotopic values and FA profiles in the muscle tissues of S. oualaniensis. Forms with larger sizes exhibited higher δ13C and δ15N values, potentially resulting from different feeding preferences and geographical environments. The discriminant analysis revealed that isotopic composition could effectively distinguish individuals from different oceanic regions, whereas FA composition was more effective in distinguishing different forms within the same oceanic region. The combination of isotopes and FAs could accurately discriminate S. oualaniensis of different forms and from different oceanic regions, achieving a discrimination accuracy of 100%. This study provides a reference for tracing the origin of pelagic cephalopods with complex form structures.
Outcome after decompressive craniectomy in older adults after traumatic brain injury
Authors: Kapapa Thomas , Jesuthasan Stefanie , Schiller Franziska , Schiller Frederike , Woischneck Dieter , Gräve Stefanie , Barth Eberhard , Mayer Benjamin , Oehmichen Marcel , Pala Andrej
Published: July 2024

Objective

Globally, many societies are experiencing an increase in the number of older adults (>65 years). However, there has been a widening gap between the chronological and biological age of older adults which trend to a more active and social participating part of the society. Concurrently, the incidence of traumatic brain injury (TBI) is increasing globally. The aim of this study was to investigate the outcome after TBI and decompressive craniectomy (DC) in older adults compared with younger patients.

Methods

A retrospective, multi-centre, descriptive, observational study was conducted, including severe TBI patients who were treated with DC between 2005 and 2022. Outcome after discharge and 12 months was evaluated according to the Glasgow Outcome Scale (Sliding dichotomy based on three prognostic bands). Significance was established as p ≤ 0.05.

Results

A total of 223 patients were included. The majority (N = 158, 70.9%) survived TBI and DC at discharge. However, unfavourable outcome was predominant at discharge (88%) and after 12 months (67%). There was a difference in favour of younger patients (≤65 years) between the age groups at discharge (p = 0.006) and at 12 months (p < 0.001). A subgroup analysis of the older patients (66 to ≤74 vs. ≥75 years) did not reveal any significant differences. After 12 months, 64% of the older patients had a fatal outcome. Only 10% of those >65 years old had a good or very good outcome. 25% were depending on support in everyday activities. After 12 months, the age (OR 0.937, p = 0.007, CI 95%: 0.894–0.981; univariate) and performed cranioplasty (univariate and multivariate results) were influential factors for the dichotomized GOS. For unfavourable outcome after 12 months, the thresholds were calculated for age = 55.5 years (p < 0.001), time between trauma and surgery = 8.25 h (p = 0.671) and Glasgow Coma Scale (GCS) = 4 (p = 0.429).

Conclusion

Even under the current modern conditions of neuro-critical care, with significant advances in intensive care and rehabilitation medicine, the majority of patients >65 years of age following severe TBI and DC died or were dependent and usually required extensive support. This aspect should also be taken into account during decision making and counselling (inter-, intradisciplinary or with relatives) for a very mobile and active older section of society, together with the patient’s will.
Changes in the ocular surface microbiome of patients with coronavirus disease 2019 (COVID-19)
Authors: Lin Jia , Wang Jingrao , Feng Jiaoyang , Zhu Rui , Guo Yu , Dong Yueyan , Zhang Hong , Jin Xin
Published: July 2024

Purpose

To elucidate the reasons behind the increased incidence of ocular disease in patients with coronavirus disease 2019 (COVID-19), this study delved deeper into the specific effects of COVID-19 on patients’ ocular surface microbiome (OSM) and investigated its relationship with the increased incidence of ocular disease.

Methods

In this study, conjunctival sac swabs were collected from 43 participants for 16S rRNA amplicon sequencing. The participants were categorized into three groups based on their COVID-19 status: the control group (C group) consisted of 15 participants who showed no evidence of COVID-19, the experimental group (E group) included 15 participants who tested positive for COVID-19, and the COVID-19 recovery period group (R group) comprised 13 participants.

Results

In the comparison of alpha diversity, group E had a higher Shannon, Chao1 and Goods coverage index. When comparing beta diversity, groups E and R were more similar to each other. At the phylum level, although the OSM of the three groups was dominated by Proteobacteria, Actinobacteriota, Bacteroidota and Firmicutes, the compositional proportions were significantly different. At the genus level, the dominant species in the three OSM groups were significantly different, with Pseudomonas becoming the dominant genus in groups E and R compared to group C, and the abundance of Ralstonia decreasing significantly.

Conclusion

This study provides additional evidence supporting the association between the OSM and COVID-19, which contributes to our understanding of the potential mechanisms underlying ocular symptoms and complications associated with COVID-19 in the future.
Impact of veterinary pharmaceuticals on environment and their mitigation through microbial bioremediation
Authors: Saeed Humaira , Padmesh Sudhakar , Singh Aditi , Nandy Abhishek , Singh Sujit Pratap , Deshwal Ravi K.
Published: July 2024

Veterinary medications are constantly being used for the diagnosis, treatment, and prevention of diseases in livestock. However, untreated veterinary drug active compounds are interminably discharged into numerous water bodies and terrestrial ecosystems, during production procedures, improper disposal of empty containers, unused medication or animal feed, and treatment procedures. This exhaustive review describes the different pathways through which veterinary medications enter the environment, discussing the role of agricultural practices and improper disposal methods. The detrimental effects of veterinary drug compounds on aquatic and terrestrial ecosystems are elaborated with examples of specific veterinary drugs and their known impacts. This review also aims to detail the mechanisms by which microbes degrade veterinary drug compounds as well as highlighting successful case studies and recent advancements in microbe-based bioremediation. It also elaborates on microbial electrochemical technologies as an eco-friendly solution for removing pharmaceutical pollutants from wastewater. Lastly, we have summarized potential innovations and challenges in implementing bioremediation on a large scale under the section prospects and advancements in this field.
Pheromone cCF10 inhibits the antibiotic persistence of Enterococcus faecalis by modulating energy metabolism
Authors: Zhu Li , Yang Xiaobo , Fu Xinyue , Yang Panpan , Lin Xiaoli , Wang Feng , Shen Zhiqiang , Wang Jingfeng , Sun Feilong , Qiu Zhigang
Published: July 2024

Introduction

Bacterial resistance presents a major challenge to both the ecological environment and human well-being, with persistence playing a key role. Multiple studies were recently undertaken to examine the factors influencing the formation of persisters and the underlying process, with a primary focus on Gram-negative bacteria and Staphylococcus aureus (Gram-positive bacteria). Enterococcus faecalis (E. faecalis) is capable of causing a variety of infectious diseases, but there have been few studies of E. faecalis persisters. Previous studies have shown that the sex pheromone cCF10 secreted by E. faecalis induces conjugative plasmid transfer. However, whether the pheromone cCF10 regulates the persistence of E. faecalis has not been investigated.

Methods

As a result, we investigated the effect and potential molecular mechanism of pheromone cCF10 in regulating the formation of persisters in E. faecalis OG1RF using a persistent bacteria model.

Results and discussion

The metabolically active E. faecalis OG1RF reached a persistence state and temporarily tolerated lethal antibiotic concentrations after 8  h of levofloxacin hydrochloride (20 mg/mL) exposure, exhibiting a persistence rate of 0.109 %. During the growth of E. faecalis OG1RF, biofilm formation was a critical factor contributing to antibiotic persistence, whereas 10 ng/mL cCF10 blocked persister cell formation. Notably, cCF10 mediated the antibiotic persistence of E. faecalis OG1RF via regulating metabolic activity rather than suppressing biofilm formation. The addition of cCF10 stimulated the Opp system and entered bacterial cells, inhibiting (p)ppGpp accumulation, thus maintaining the metabolically active state of bacteria and reducing persister cell generation. These findings offer valuable insights into the formation, as well as the control mechanism of E. faecalis persisters.