bluuebunny/crossref_metadata_2025 huggingface dataset:
TANGGGUNG JAWAB HUKUM PROVIDER TERHADAP KERUGIAN NASABAH
Authors: Wulansari Febilita , Sukmawati Ita
Published: January 2024

Indonesia is experiencing very rapid technological developments that are changing the order of human life to become more innovative. The existence of an electronic payment system is one way that people can make cashless transactions. With the emergence of electronic wallets such as DANA, people can carry out many transactions practically, such as paying bills, purchasing goods and services, transferring funds and much more. This research aims to determine the provider's legal responsibility for customer losses on e-wallets. With this research, it is hoped that Bank Indonesia can be more assertive towards providers so that they can take responsibility for losses experienced by customers. This research uses a normative juridical approach. The results state that the provider's responsibility is to provide compensation to customers based on statutory regulations. When making transactions with electronic money, users must feel safe and comfortable so that one of the rights of saving customers is only the right to collect and get the funds back. Other responsibilities are contained in the Electronic Money PBI, Articles 74 and 75 are part of the regulations that regulate sanctions or penalties that can be imposed by Bank Indonesia or other authorities if there is a violation of these regulations. With legal protection, it is hoped that electronic money service providers will better comply with applicable regulations, and consumers will have legal means to protect their rights when using these services.
Analysis of Deviant Behavior that Occurs at SMA 1 Bukit Sundi
Authors: Lisa Rahmawati  , Afrahamiryano
Published: January 2024

Deviant behavior carried out by teenagers generally occurs when they are in middle school (SMP) and high school (SMA). This is because during this period, adolescents are in a phase that is vulnerable to external influences, and the adolescent's psyche is still in an unstable state. At this school age, teenagers can receive various influences, both positive and negative, which can influence their behavior. The aim of this research is to determine the influence of deviant behavior in high school children in the learning process at school. Deviant behavior is behavior that is not in accordance with the stages of improvement and is not always in accordance with relevant norms. Deviant behavior here is also called negative behavior. The results of the research show that forms of deviant behavior among students who enter counseling at SMA 1 Bukit Sundi include frequently missing school, not being polite in talking to teachers, and also not participating in lessons at school, fighting with their friends. There are quite a lot and varied behavioral deviations that have been carried out by students, therefore students must be given sufficient provisions so that they do not fall into the wrong company.
Efforts to Prevent Violence in Dating
Authors: Karimah Darojat  , Elok Halimatus Sa’diyah  , Rifa Hidayah
Published: January 2024

Dating violence includes physical, emotional, verbal, social and sexual aggressive behavior aimed at controlling and hurting a parter. Dating violence is in second place in cases of violence against women. This makes it necessary to conduct studies regarding preventing cases of dating violence. The method used in this research is literature study, data was obtained from previous research articles which were then analyzed critically using the content analysis method. The aim of this research is to discuss efforts to prevent violence in dating. The results obtained are that prevention of dating violence can be done by victims and perpetrators. From the victim’s side, prevention can be done in the form of changing the meaning of love, then changing the belief from love is having to love is a process of becoming. Furthermore, by improving assertive attitudes, self-images, self-esteem and perceptions about gender which can be done by educational institutions  and related agencies. Meanwhile, efforts to prevent violence in dating from the perpetrator’s side can be carried out by the family. Families can provide education about healthy relationships and provide direct examples.
The Influence of Parenting Patterns on Early Childhood Social Development
Authors: Anggi Nursahara  , Haliatun Nisa  , Risnaeni Ainunsyah
Published: January 2024

Social emotional aspects in early childhood are very important to develop from an early age. The importance of parenting patterns to introduce social-emotional influences greatly influences children's ability to interact with their environment. The aim of this research is to study literature and libraries regarding the influence of parenting styles on the social emotional development of early childhood. As well as being a reference for parents and prospective parents to find out the best parenting style in providing child care. This research uses a literature study type of research by collecting data through various theoretical references that are relevant to the cases or problems found. Based on the results of this research, it shows that the parenting style that best suits children's social and emotional development is a democratic parenting style where children have the freedom to do things but are still responsible. Because democratic parenting gives children the opportunity and freedom to choose.
Kaum Muda dan Industri Kreatif Kriya Tenun “Songke” Manggarai-Flores, NTT
Authors: Haryatno Yulius Rudi
Published: January 2024

Sejak Labuan Bajo, Manggarai Barat, NTT ditetapkan sebagai salah satu destinasi super prioritas pada 2019 lalu, ada banyak industri kreatif yang juga berkembang di sana. Salah satu industri kreatif yang berkembang adalah kain tenun songke. Industri kreatif bidang kriya ini dianggap memberikan pengaruh positif pada sektor lapangan kerja, kesejahteraan ekonomi, dan bisnis. Ironisnya, walaupun berpotensi berkontribusi terhadap kesejahteraan (ekonomi), kreativitas menenun masih digandrungi oleh perajin dari kalangan usia tertentu (kisaran umur 35-60 thn). Anak-anak muda produktif (generasi Y) seakan kurang berminat pada kreativitas menenun ini. Karena itu, penelitian ini bertujuan untuk mengeksplorasi secara kualitatif-analitis alasan di balik minimnya minat kaum muda dalam industri kreatif menenun. Hasil penelitian analitis ini menunjukkan bahwa pola produksi yang masih tradisional, pola kerja informal, dan kuatnya budaya patriarki menjadi dasar bagi kaum muda Manggarai untuk tidak terlibat dalam industri kreatif menenun.
Sichere und Datenschutz konforme Messaging-Strategien für das Gesundheitswesen;
Authors: Meier Pierre-Michael , Hülsken Gregor , Flynn Herbst
Published: January 2024

Im digitalen Zeitalter hat sich die Kommunikation im Gesundheitswesen grundlegend gewandelt, wobei sich sichere Messaging-Strategien als entscheidende Faktoren für eine effektive Zusammenarbeit und den Datenschutz herauskristallisiert haben. Vor dem Hintergrund einer zunehmenden Vernetzung von medizinischem Personal, Patienten und externen Partnern ist der Bedarf an schnellen, vertraulichen und zuverlässigen Kommunikationslösungen stetig gewachsen. Secure-Messenger-Dienste spielen daher eine zentrale Rolle, um die Qualität der Patientenversorgung sicherzustellen und gleichzeitig den Schutz sensibler Informationen zu gewährleisten.
Studi Tingkat Keramahan Lingkungan dan Finansial Belat di Perairan Sungai Siak Kampung Benayah Kecamatan Pusako Kabupaten Siak Provinsi Riau
Authors: Setiawan Arief , Bustari Bustari , Brown Arthur
Published: January 2024

Perairan Sungai Siak Kampung Benayah terdapat beberapa alat tangkap yang digunakan dalam aktivitas penangkapan ikan, salah satunya adalah belat. Belat termasuk jenis perangkap dalam klasifikasi termasuk alat perangkap yang lain (other traps). Tujuan penelitian adalah untuk mengetahui kontruksi alat tangkap secara umum, operasional penangkapan, tingkat keramahan lingkungan dan kelayakan usaha perikanan belat. Penelitian ini akan dilaksanakan pada Desember 2022 yang belokasi di perairan Sungai Siak. Metode yang digunakan adalah survey. Dari hasil penelitian menunjukkan belat di Kampung Benayah tergolong teknologi penangkapan yang sangat ramah lingkungan. Dari hasil analisis usaha perikanan alat tangkap belat diketahui (NPV) dengan prediksi 10 tahun menunjukkan usaha kembali modal pada tahun pertama sebesar Rp 1.995.283.
Look before you LEP: English Cluster Policy from RDAs to LEPs
Authors: De Propris Lisa , Bailey David
Published: January 2024

Soumission à Epi-revel

International audience

The policy and academic debate on industrial clusters has developed in a context dominated by ‘industry champions’ which are not necessarily national. Despite the fact that indust ial dist icts first emerged and indeed were first studied in England by Alfred Marshall over 100 years ago, the spatial dimension of economic activities has in fact been marginal to much of the economic and policy debate in the UK. The idea that industrial clusters could be engines of regional growth was only seriously taken on board in the late 1990s by the newly created Regional Development Agencies (RDAs) in England, and by development agencies in Scotland and Wales. Regional and cluster policies were subsequently used as a key part of UK regions’ economic strategies over the late 1990s and 2000s; despite some successes, question marks now remain over their future in England at least given the abolition of RDAs there from 2012. Favouring a supposedly ‘localist’ rather than regional agenda, the coalition Government elected in 2010 has replaced RDAs with smaller-scale Local Enterprise Partnership (LEPs) at the sub-regional level. With more limited powers than RDAs and much less funding, time will tell how these LEPs will perform in economic development terms generally and in terms of cluster policies specifically.
Kepemimpinan Efektif pada Aparatur Sipil Negara “Generasi Z”
Authors: Ayuningtyas Atika
Published: January 2024

Pembangunan sumber daya manusia merupakan proses holistik yang melibatkan sistem, tata kelola manajemen dan hubungan kerja. Salah satu faktor penting untuk mendukung tercapainya tujuan organisasi pemerintah ialah gaya kepemimpinan yang dibutuhkan untuk mempengaruhi dan menggerakkan sumber daya aparatur. Transformasi digital yang telah berkembang sedemikian rupa tentunya memberikan pengaruh pada gaya, pola pikir dan cara kerja pegawai khususnya kelompok generasi “Z”. Tujuan penelitian untuk mengetahui tentang Kepemimpinan Efektif pada Aparatur Sipil Negara Generasi “Z”. Penelitian menggunakan metode kualitatif dengan analisis deskriptif melalui studi kasus dan studi literatur sebagai bahan analisa kepemimpinan efektif pada Aparatur Sipil Negara Generasi “Z”, dengan responden Aparatur Sipil Negara alumni Pelatihan Dasar CPNS Tahun 2021 di wilayah kerja Pusat Pengembangan Sumber Daya Manusia Regional Yogyakarta menggunakan instrumen berupa kuesioner. Sedangkan referensi literatur diperoleh dari karya tulis yang relevan dengan tema pokok tulisan. Kesimpulan berdasarkan hasil penelitian dan pembahasan ialah bahwa generasi “Z” yang praktis, kompetitif, spontan dan memiliki kecakapan teknologi digital berpendapat bahwa kepemimpinan efektif terwujud melalui pemimpin yang demokratis, terbuka, terpercaya dan dapat diandalkan. Generasi “Z” menyukai pimpinan yang memiliki kualitas kepemimpinan yang proaktif, partisipatif dan suportif sehingga mereka merasa dihargai saat dilibatkan dalam penyelesaian pekerjaan dan pengambilan keputusan.
Penerapan Sistem Akuntansi Berbasis Komputer Dalam Penyusunan Laporan Keuangan Menggunakan ABSS (Asian Bussiness Software Solution) Accounting V.25 (Studi Kasus Pada UD Los Kayu Ayu Mon)
Authors: Mulyadi  , Melli Herfina
Published: January 2024

Dalam sistem akuntansi, pemakaian apikasi akuntansi akan meningkatkan efisiensi dengan cara mempersingkat alur kerja sistem, membagi penyimpanan dan kerja kolaboratif serta dirancang untuk mempermudah pekerjaan dalam pencatatan transaksi sampai dengan membuat laporan keuangan. ABSS Accounting V.25 merupakan salah satu aplikasi akuntansi yang banyak digunakan dalam proses pekerjaan akuntansi yang mudah dioperasikan (user friendly) dan memliki sistem otomatisasi yang dapat mengintegrasikan secara lengkap seluruh fungsi akuntansi dalam satu program sehingga pengguna dapat meggunakan dengan mudah dan cepat dalam pembuatan dan penyajian laporan keuangan. Tujuan penelitian ini adalah untuk menyususn dan menyajikan laporan keuangan pada UD Los Kayu Ayu Mon degan menggunakan ABSS Accounting V.25.Metode yang digunakan penulis dalam penelitian ini yaitu deskriptif kuantitatif. Hasil dari penelitian ini yaitu penulis dapat menyusun dan menyajikan laporan keuangan pada UD Los Kayu Ayu Mon. kesimpulan yang dapat diambil bahwa ABSS Accounting V. merupakan aplikasi akuntansi yang mudah dalam pengoperasiaannya sehingga bisa menghemat waktu, tenaga dan biaya serta dapat mengatasi human error dalam mengontrol dan mengendalikan keuangan perusahaan.
Nilai-Nilai Pendidikan Akhlak Dalam Novel Children Of Heaven Karya Enang Rokajat Asura
Authors: Rahmad Hulbat
Published: January 2024

This research is a qualitative research (library research). This study examines the values ​​of moral education in the novel children of heaven by Enang Rokajat Asura. The purpose of this study is to describe the values ​​of moral education in the novel children of heaven, including the value of moral education to Allah SWT and the value of moral education to fellow humans. The data sources of this research are the novel children of heaven by Enang Rokajat Asura and various literatures related to the object of research. The data collection technique used the library research method, namely in the form of data collection techniques that were not directly aimed at the research subject, but through several books, magazines, journals, pamphlets, and other relevant documentary materials in the research. The results showed that several values ​​of moral education were found in the novel children of heaven by Enang Rokajat Asura which include; 1) The values ​​of moral education to Allah SWT are obedience, trustworthiness, gratitude, and patience. 2) The values ​​of moral education to fellow human beings are love, responsibility, and help.
Pembelajaran Kitab Al-Mabadi Al-Fiqhiyyah Dalam Membentuk Karakter Religius Santri Di Pondok Pesantren Al-Munawwir Sangatta Selatan
Authors: Mega Ayu utamima  , M. Abdul Rozak  , Maratul Latifah  , Sinta Silvia Melia  , Ramlah Harniati hapsah  , Eko Nursalim
Published: January 2024

The goal of this research was to illuminate how students at Al-munawwir Islamic Boarding School, located in Sangatta Selatan, were affected by studying Al-Mabadi AlFiqhiyyah. This approach to research employs qualitative, descriptive methods. Purposeful sampling will be used to select research participants, and observation, interviews, and documentation will be used to collect data. Reducing and summarizing data, presenting findings, and drawing conclusions are all part of the data analysis process. Visualization and summarization of data. Using data triangulation and source triangulation to confirm the veracity of the collected information. Religious affiliation among students is supported by the results of this study. Congregational prayer and reading the wirid (prayer) afterward are clear signs of this. study of Salaf books and reading the Qur'an, the entire religious series is carried out in accordance with Islamic principles.
Analysis of modern SOTA-architectures of artificial neural networks for solving problems of image classification and object detection
Authors: Korchagin Valeriy Dmitrievich
Published: January 2024

The scientific research is focused on conducting a study of current artificial neural network architectures in order to highlight the advantages and disadvantages of current approaches. The relevance of the research relies on the growing interest in machine learning technologies and regular improvement of computer vision algorithms.Within the scope of this paper, an analytical study of the advantages and disadvantages of existing solutions has been conducted and advanced SOTA architectures have been reviewed. The most effective approaches to improve the accuracy of basic models have been studied. The number of parameters used, the size of the training sample, the accuracy of the model, its size, adaptability, complexity and the required computational resources for training a single architecture were determined.Prospects for further research in the field of hybridization of convolutional neural networks and visual transformers are revealed, and a new solution for building a complex neural network architecture is proposed.In the framework of the present research work, a detailed analysis of the internal structure of the most effective neural network architectures.Plots of the accuracy dependence on the number of parameters used in the model and the size of the training sample are plotted. The conducted comparative analysis of the efficiency of the considered solutions allowed to single out the most effective methods and technologies for designing artificial neural network architectures. A novel method focused on creating a complex adaptive model architecture that can be dynamically tuned depending on an input set of parameters is proposed, representing a potentially significant contribution to the field of adaptive neural network design.
Resource availability as a condition for the effectiveness of professional activity of the senior staff of departments and faculties of educational organizations of the Ministry of Internal Affairs of Russia
Authors: Tikhonova Elena Aleksandrovna
Published: January 2024

The subject of the study is the psychological resources of the senior staff of departments and faculties of educational organizations of the Ministry of Internal Affairs of Russia. The purpose of the research is to study the relationship between subjective representations of the success and effectiveness of the professional activities of managers and their resource availability. It was suggested that a large number of requirements imposed on the leadership of departments and faculties will actualize the psychological resources of the personality of managers with high efficiency of professional activity and lead to depletion of resources with low efficiency of professional activity. The study involved 376 heads and deputy heads of departments and faculties of educational organizations of the Ministry of Internal Affairs of Russia with service experience in the internal affairs bodies from 2 to 38 years, in office from several months to 29 years.  In order to collect empirical data, the following methods were used: author's questionnaire; questionnaire "Strategies for overcoming stressful situations" by S. E. Hobfoll; "Questionnaire of proactive coping behavior" by E. Greenglas, R. Schwarzer and S. Taubert; questionnaire of "Psychological capital" by A. Bakker; "Test of resilience" by S. Maddi; "Test of life orientations" by J. Crambo and L. Maholika. The results of the study indicate that the self-assessment of the professional effectiveness and success of the management of educational organizations of the Ministry of Internal Affairs of Russia reflects the level of its resource availability. In general, the results of the study indicate a high resource availability of the senior staff of departments and faculties of educational organizations of the Ministry of Internal Affairs of Russia. In addition, based on subjective representations of the professional effectiveness and success of the leaders of this group, it is possible to predict the choice of constructive and proactive coping strategies that act as psychological resources of the individual: the higher the head evaluates the effectiveness of his professional activity, the more often he implements constructive and proactive coping strategies. The most significant contribution of the study is that its results can be used for an operational assessment of the actual resource availability of the head when conducting group and/or individual psychological support work by a psychologist.
About the Miscellany of Charms from the Collection of V. M. Undolsky
Authors: Alekseeva Alina
Published: January 2024

The article deals with a collection of handwritten charms of the second half of the 17th century from the collection of V. M. Undolsky (Russian State Library. F. 310. No. 1179). The manuscript was published twice by L. I. Sazonova and A. L. Toporkov (in 2000 and 2002) with a commentary, but it has not yet been the subject of textual and linguistic investigations, which are necessary in the study of texts circulating in the handwritten sphere. These purposes make possible to draw conclusions about the origin of the collection, the pecularities of its creation and sources. The article presents the results of the study manuscript de visu. The special attention is paid to the peculiarities of handwriting, scribe’s mistakes and reflections of live pronunciation which is considered in the context of the handwritten culture of Old Rus’. In present article the observations is based on the textual, linguistic and comparative research methods that are relevant in the study of medieval manuscripts. The investigation allowed to propose several commented refinements to the edition based on a detailed study of paleography, textual features, and language, as well as the involvement of other manuscript and printed texts, historical and dialect dictionaries. The scribe’s errors in the manuscript from the collection of V. M. Undolsky are related to the existence of the antigraph, which does not allow us to agree with the publishers’ assumption that the collection was recorded from an oral source. The dialectal features of the charms leads to the conclusion about the Central or Middle Russian dialect of the scribe. It is possible that the owner of the manuscript, Vasily Volotsky, is the podyachy Vasily Volotsky, who is mentioned in the documents of 1699 and 1701 years of the Arzamas clerk’s izba.
Coordinated regulation of gene expression in Plasmodium female gametocytes by two transcription factors
Authors: Murata Yuho , Nishi Tsubasa , Kaneko Izumi , Iwanaga Shiroh , Yuda Masao
Published: January 2024

Gametocytes play key roles in the
Plasmodium
lifecycle. They are essential for sexual reproduction as precursors of the gametes. They also play an essential role in parasite transmission to mosquitoes. Elucidation of the gene regulation at this stage is essential for understanding these two processes at the molecular level and for developing new strategies to break the parasite life cycle. We identified a novel
Plasmodium
transcription factor (TF), designated as a partner of AP2-FG or PFG. In this paper, we report that this TF regulates the gene expression in female gametocytes in concert with another female-specific TF AP2-FG. Upon the disruption of
PFG
, majority of female-specific genes were significantly downregulated, and female gametocyte lost the ability to produce ookinetes. ChIP-seq analysis showed that it was located in the same position as AP2-FG, indicating that these two TFs form a complex. ChIP-seq analysis of PFG in
AP2-FG
-disrupted parasites and ChIP-seq analysis of AP2-FG in
PFG
-disrupted parasites demonstrated that PFG mediates the binding of AP2-FG to the ten-base motif and that AP2-FG binds another motif, GCTCA, in the absence of PFG. In promoter assays, this five-base motif was identified as another female-specific cis-acting element. Genes under the control of the two forms of AP2-FG, with or without PFG, partly overlapped; however, each form had target preferences. These results suggested that combinations of these two forms generate various expression patterns among the extensive genes expressed in female gametocytes.
circHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA
Authors: Okholm Trine Line Hauge , Kamstrup Andreas Bjerregaard , Nielsen Morten Muhlig , Hollensen Anne Kruse , Graversgaard Mette Laugesen , Sørensen Matilde Helbo , Kristensen Lasse Sommer , Vang Søren , Park Samuel S , Yeo Eugene , Dyrskjøt Lars , Kjems Jørgen , Pedersen Jakob Skou , Damgaard Christian Kroun
Published: January 2024

Circular RNAs represent a class of endogenous RNAs that regulate gene expression and influence cell biological decisions with implications for the pathogenesis of several diseases. Here, we disclose a novel gene-regulatory role of circHIPK3 by combining analyses of large genomics datasets and mechanistic cell biological follow-up experiments. Using time-course depletion of circHIPK3 and specific candidate RNA-binding proteins, we identify several perturbed genes by RNA sequencing analyses. Expression-coupled motif analyses identify an 11-mer motif within circHIPK3, which also becomes enriched in genes that are downregulated upon circHIPK3 depletion. By mining eCLIP datasets and combined with RNA immunoprecipitation assays, we demonstrate that the 11-mer motif constitutes a strong binding site for IGF2BP2 in bladder cancer cell lines. Our results suggest that circHIPK3 can sequester IGF2BP2 as a competing endogenous RNA (ceRNA), leading to target mRNA stabilization. As an example of a circHIPK3-regulated gene, we focus on the STAT3 mRNA as a specific substrate of IGF2BP2 and validate that manipulation of circHIPK3 regulates IGF2BP2-STAT3 mRNA binding and, thereby, STAT3 mRNA levels. Surprisingly, absolute copy number quantifications demonstrate that IGF2BP2 outnumbers circHIPK3 by orders of magnitude, which is inconsistent with a simple 1:1 ceRNA hypothesis. Instead, we show that circHIPK3 can nucleate multiple copies of IGF2BP2, potentially via phase separation, to produce IGF2BP2 condensates. Our results support a model where a few cellular circHIPK3 molecules can induce IGF2BP2 condensation, thereby regulating key factors for cell proliferation.
circHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA
Authors: Okholm Trine Line Hauge , Kamstrup Andreas Bjerregaard , Nielsen Morten Muhlig , Hollensen Anne Kruse , Graversgaard Mette Laugesen , Kristensen Lasse Sommer , Vang Søren , Park Samuel S. , Yeo Gene W. , Dyrskjøt Lars , Kjems Jørgen , Pedersen Jakob Skou , Damgaard Christian Kroun
Published: January 2024

Circular RNAs (circRNAs) represent a class of widespread endogenous RNAs that regulate gene expression and thereby influence cell biological decisions with implications for the pathogenesis of several diseases. Here, we disclose a novel gene-regulatory role of circHIPK3 by combining analyses of large genomics datasets and mechanistic cell biological follow-up experiments. Specifically, we use temporal depletion of circHIPK3 or specific RNA binding proteins (RBPs) and identify several perturbed genes by RNA sequencing analyses. Using expression-coupled motif analyses of mRNA expression data from various knockdown experiments, we identify an 11-mer motif within circHIPK3, which is also enriched in genes that become downregulated upon circHIPK3 depletion. By mining eCLIP datasets, we find that the 11-mer motif constitutes a strong binding site for IGF2BP2 and validate this circHIPK3-IGF2BP2 interaction experimentally using RNA-immunoprecipitation and competition assays in bladder cancer cell lines. Our results suggest that circHIPK3 and IGF2BP2 mRNA targets compete for binding. Since the identified 11-mer motif found in circHIPK3 is enriched in upregulated genes following IGF2BP2 knockdown, and since IGF2BP2 depletion conversely globally antagonizes the effect of circHIPK3 knockdown on target genes, our results suggest that circHIPK3 can sequester IGF2BP2 as a competing endogenous RNA (ceRNA), leading to target mRNA stabilization. As an example of a circHIPK3-regulated gene, we focus on the
STAT3
mRNA as a specific substrate of IGF2BP2 and validate that manipulation of circHIPK3 regulates IGF2BP2-
STAT3
mRNA binding and thereby
STAT3
mRNA levels. However, absolute copy number quantifications demonstrate that IGF2BP2 outnumbers circHIPK3 by orders of magnitude, which is inconsistent with a simple 1:1 ceRNA hypothesis. Instead, we show that circHIPK3 can nucleate multiple copies of IGF2BP2, potentially via phase separation, to produce IGF2BP2 condensates. Finally, we show that circHIPK3 expression correlates with overall survival of patients with bladder cancer. Our results are consistent with a model where relatively few cellular circHIPK3 molecules function as inducers of IGF2BP2 condensation thereby regulating STAT3 and other key factors for cell proliferation and potentially cancer progression.
Mutant mice lacking alternatively spliced p53 isoforms unveil Ackr4 as a male-specific prognostic factor in Myc-driven B-cell lymphomas
Authors: Fajac Anne , Simeonova Iva , Leemput Julia , Gabriel Marc , Morin Aurélie , Lejour Vincent , Hamon Annaïg , Rakotopare Jeanne , Vaysse-Zinkhöfer Wilhelm , Eldawra Eliana , Pinskaya Marina , Morillon Antonin , Bourdon Jean-Christophe , Bardot Boris , Toledo Franck
Published: January 2024

The Trp53 gene encodes several isoforms of elusive biological significance. Here, we show that mice lacking the Trp53 alternatively spliced (AS) exon, thereby expressing the canonical p53 protein but not isoforms with the AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in Trp53+/+Eμ-Myc males compared to Trp53ΔAS/ΔAS Eμ-Myc males, but also compared to Trp53+/+Eμ-Myc and Trp53ΔAS/ΔAS Eμ-Myc females. Pre-tumoral splenic cells from Trp53+/+Eμ-Myc males exhibited a higher expression of Ackr4, encoding an atypical chemokine receptor with tumor suppressive effects. We identified Ackr4 as a p53 target gene whose p53-mediated transactivation is inhibited by estrogens, and as a male-specific factor of good prognosis relevant for murine Eμ-Myc-induced and human Burkitt lymphomas. Furthermore, the knockout of ACKR4 increased the chemokine-guided migration of Burkitt lymphoma cells. These data demonstrate the functional relevance of alternatively spliced p53 isoforms and reveal sex disparities in Myc-driven lymphomagenesis.
A syngeneic spontaneous zebrafish model of tp53-deficient, EGFRviii, and PI3KCAH1047R-driven glioblastoma reveals inhibitory roles for inflammation during tumor initiation and relapse in vivo
Authors: Weiss Alex , D’Amata Cassandra , Pearson Bret J. , Hayes Madeline N.
Published: January 2024

To build a patient-relevant
in vivo
model of human glioblastoma, we expressed common oncogenic variants including activated human EGFR
viii
and PI3KCA
H1047R
under the control of the radial glial-specific promoter
her4.1
in syngeneic
tp53
loss-of-function mutant zebrafish. Robust tumor formation was observed prior to 45 days of life, with a gene expression signature similar to human glioblastoma of the mesenchymal subtype, along with a strong inflammatory component. Within early stage tumor lesions, and in an intact and endogenous tumor microenvironment, we visualized infiltration of phagocytic cells, as well as internalization of tumor cells by
mpeg1.1
:GFP+ microglia/macrophages, suggesting negative regulatory pressure by pro-inflammatory cell types on tumor growth at early stages of glioblastoma initiation
in vivo
. Furthermore, CRISPR/Cas9-mediated gene targeting of master inflammatory transcription factors
irf7
and
irf8
led to increased tumor formation in the primary context, while suppression of microglial/macrophage activity led to enhanced tumor cell engraftment following transplantation into otherwise immune competent zebrafish hosts. Altogether, we developed a genetically-relevant model of aggressive human glioblastoma and harnessed the unique advantages of zebrafish including live imaging, high-throughput genetic and chemical manipulations to highlight important tumor suppressive roles for the innate immune system on glioblastoma initiation, with important future significance for therapeutic discovery and optimizations.
Lesions in a songbird vocal circuit increase variability in song syntax
Authors: Koparkar Avani , Warren Timothy L , Charlesworth Jonathan D , Shin Sooyoon , Brainard Michael S , Veit Lena
Published: January 2024

Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered syllables, controlled in part by the songbird premotor nucleus HVC (proper name). Here, we test whether one of HVC’s recurrent inputs, mMAN (medial magnocellular nucleus of the anterior nidopallium), contributes to sequencing in adult male Bengalese finches (Lonchura striata domestica). Bengalese finch song includes several patterns: (1) chunks, comprising stereotyped syllable sequences; (2) branch points, where a given syllable can be followed probabilistically by multiple syllables; and (3) repeat phrases, where individual syllables are repeated variable numbers of times. We found that following bilateral lesions of mMAN, acoustic structure of syllables remained largely intact, but sequencing became more variable, as evidenced by ‘breaks’ in previously stereotyped chunks, increased uncertainty at branch points, and increased variability in repeat numbers. Our results show that mMAN contributes to the variable sequencing of vocal elements in Bengalese finch song and demonstrate the influence of recurrent projections to HVC. Furthermore, they highlight the utility of species with complex syntax in investigating neuronal control of ordered sequences.
Germline cis variant determines epigenetic regulation of the anti-cancer drug metabolism gene dihydropyrimidine dehydrogenase (DPYD)
Authors: Zhang Ting , Ambrodji Alisa , Huang Huixing , Bouchonville Kelly J. , Etheridge Amy S. , Schmidt Remington E. , Bembenek Brianna M. , Temesgen Zoey B. , Wang Zhiquan , Innocenti Federico , Stroka Deborah , Diasio Robert B. , Largiadèr Carlo R. , Offer Steven M.
Published: January 2024

Enhancers are critical for regulating tissue-specific gene expression, and genetic variants within enhancer regions have been suggested to contribute to various cancer-related processes, including therapeutic resistance. However, the precise mechanisms remain elusive. Using a well-defined drug-gene pair, we identified an enhancer region for dihydropyrimidine dehydrogenase (DPD,
DPYD
gene) expression that is relevant to the metabolism of the anti-cancer drug 5-fluorouracil (5-FU). Using reporter systems, CRISPR genome edited cell models, and human liver specimens, we demonstrated
in vitro
and
vivo
that genotype status for the common germline variant (rs4294451; 27% global minor allele frequency) located within this novel enhancer controls
DPYD
transcription and alters resistance to 5-FU. The variant genotype increases recruitment of the transcription factor CEBPB to the enhancer and alters the level of direct interactions between the enhancer and
DPYD
promoter. Our data provide insight into the regulatory mechanisms controlling sensitivity and resistance to 5-FU.
Progressively shifting patterns of co-modulation among premotor cortex neurons carry dynamically similar signals during action execution and observation
Authors: Zhao Zhonghao , Schieber Marc H.
Published: January 2024

Many neurons in the premotor cortex show firing rate modulation whether the subject performs an action or observes another individual performing the same action. Although such “mirror neurons” have been thought to have highly congruent discharge during execution and observation, many if not most show non-congruent activity. Studies of such neuronal populations have shown that the most prevalent patterns of co-modulation—captured as neural trajectories—pass through subspaces which are shared in part, but in part are visited exclusively during either execution or observation. These studies focused on reaching movements for which the neural trajectories show comparatively simple dynamical motifs. But the neural dynamics of hand movements are more complex. We developed a novel approach to examine prevalent patterns of co-modulation during execution and observation of a task that involved reaching, grasping and manipulation. Rather than following neural trajectories in subspaces that contain their entire time course, we identified time series of instantaneous subspaces, sampled trajectory segments at the times of selected behavioral events, and projected each segment into the series of instantaneous subspaces. We found that instantaneous neural subspaces were partially shared between execution and observation in only one of three monkeys and were otherwise exclusive to one context or the other. Nevertheless, the patterns during execution and observation could be aligned with canonical correlation, indicating that though distinct, neural representations during execution and observation show dynamical similarity that may enable the nervous system to recognize particular actions whether performed by the subject or by another individual.
Research insights into the chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM): their roles in various tumors
Authors: Duan Sai-Li , Jiang Yingke , Li Guo-Qing , Fu Weijie , Song Zewen , Li Li-Nan , Li Jia
Published: January 2024

The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family includes CMTM1–8 and CKLF, and they play key roles in the hematopoietic, immune, cardiovascular, and male reproductive systems, participating in the physiological functions, cancer, and other diseases associated with these systems. CMTM family members activate and chemoattract immune cells to affect the proliferation and invasion of tumor cells through a similar mechanism, the structural characteristics typical of chemokines and transmembrane 4 superfamily (TM4SF). In this review, we discuss each CMTM family member’s chromosomal location, involved signaling pathways, expression patterns, and potential roles, and mechanisms of action in pancreatic, breast, gastric and liver cancers. Furthermore, we discuss several clinically applied tumor therapies targeted at the CMTM family, indicating that CMTM family members could be novel immune checkpoints and potential targets effective in tumor treatment.
Elementos del Contexto Interno que Facilitan y Obstaculizan la Implementación de un Programa en Salud Mental Escolar
Authors: Leiva Loreto , Barría Daniela , Zavala-Villalón Gloria
Published: January 2024

El propósito de esta investigación fue identificar aquellas dimensiones del Contexto Interno de Implementación que facilitaban u obstaculizaban la ejecución de un programa público de salud mental escolar (SME) basado en la comunidad. Se entrevistaron a 51 miembros de las comunidades educativas en las cuales se ejecuta el programa. Las entrevistas semiestructuradas fueron analizadas mediante el análisis de contenido cuantitativo y cualitativo. Los resultados permitieron (1) identificar tres categorías principales: escenario organizacional, gestión de información y receptividad organizacional, las que daban cuenta de los principales contenidos destacados por quienes participaban en el programa y (2) establecer, según la valoración positiva o negativa otorgada, aquellas dimensiones que operaban como facilitadoras u obstaculizadoras en la implementación del programa, las cuales fueron señaladas como aspectos centrales y críticos para comprender el desempeño y efectividad del programa estudiado. Se discuten las implicancias, limitaciones y proyecciones de lo encontrado.
Salud Mental en Mujeres Embarazadas y COVID-19: Un Estudio Comparativo
Authors: Legarra Leire , Gómez-Gutiérrez Mar , Valverde Natalia , Mollejo Encarnación
Published: January 2024

La depresión y la ansiedad son problemas psicológicos que presentan una alta prevalencia en el periodo perinatal. Además, durante la pandemia del COVID-19, la vulnerabilidad de las mujeres embarazadas ha sido aún mayor, por lo que se hace más necesario el estudio de los principales factores de riesgo asociados. El presente estudio pretende evaluar el impacto de la pandemia sobre la salud mental en una muestra de mujeres embarazadas a través de la comparación de mujeres que gestaron antes de la pandemia y aquellas que vivieron su embarazo durante esta, así como evaluar la relación con los principales factores de riesgo y protección, siendo uno de ellos el apoyo social. Con este objetivo, se administró una batería de instrumentos de evaluación psicológica a mujeres de la población general que se encontraban en el tercer trimestre de embarazo (N=59), con la que se evaluaron los siguientes factores: variables sociodemográficas, situaciones de estrés vividas el último año e historial previo de depresión, depresión perinatal (EPDS), ansiedad (STAI) y apoyo social (MOS). Los resultados apoyan parcialmente las hipótesis planteadas, puesto que, a pesar de no haber hallado diferencias significativas entre los grupos evaluados antes y después de la pandemia, las puntuaciones de ansiedad y depresión mostraron correlaciones negativas con el apoyo social. Estos resultados tienen implicaciones clínicas en tanto que el apoyo social, especialmente por parte de la pareja, puede ser una variable determinante a la hora de realizar una detección precoz efectiva y desarrollar programas de prevención.
The Impact of Genexpert MTB/RIF Technology on the Minimization of Tuberculosis: A Review of Literature
Authors: Sorvor Felix Kodzo Besah , Ewusie Ebenezer Ato
Published: January 2024

The molecular revolution in tuberculosis (TB) diagnosis has ushered in a new era of patient treatment that is quicker, more accurate, and clinically appropriate. In cases where treatment resistance is suspected or if tuberculosis (TB) is present, the most cutting-edge molecular diagnostic tool available is the Xpert test developed by Cepheid in Sunnyvale, California. In December 2010, it was swiftly recognized as the main technique for TB diagnosis by the World Health Organization. This comprehensive review provides an in-depth understanding of TB and GeneXpert technology and its impact on the minimization of TB. The leading infectious disease killer in 2019 was tuberculosis (TB). Worldwide, tuberculosis (TB) killed an estimated 1.2 million people in 2019, with an additional 208,000 lost to the disease among HIV-positive individuals. almost the world, the sickness affected almost 10.0 million people. Of all tuberculosis cases, 88% were in adults, while 12% were in children less than 15 years old. The 2019 tuberculosis case rates were lower in the East Mediterranean (8.2%), the Americas (2.9%), and Europe (2.5%), compared to the World Health Organization (WHO) zones of South-East Asia (44%), Africa (25%), and the Western Pacific (18%). This study will provide an in-depth understanding of GeneXpert technology and its impact on the healthcare system.
Assessment of Protective Roles of Aqueous Seed Extract of Sour-Sop (Annona muricata) in Cerebellum Following Cadmium-induced Neurotoxicity of Adult Wistar Rats
Authors: Fakunle P. B.  , Samuel Ehiremen , Kayode Odubela , Kehinde Bamgbose
Published: January 2024

Cadmium, a deleterious heavy metal that pervades the environment, has the potential to accumulate in the body and cause health complications. In the domain of traditional medicine, medicinal plants have been employed to combat the toxicity of heavy metals and treating of many diseases in traditional medicine.

Aim: To access the protective impact of Annona muricata seed extract on cadmium-triggered neurotoxicity in the cerebellum of albino wistarrat.

Place of Study: Department of Anatomy, Faculty of Basic Medical Sciences Olabisi Onabanjo University, Ogun State between June 2022 and June 2023

METHODOLOGY: After a period of 14 days of acclimatization, 40 healthy male wistar rats were randomly allocated to four groups, group1(2ml/kg of distilled water), group2 cadmium only(2g/kg SC), group3 (2g/kg cadmium + 100mg/kg extract of Annona muricata) and group4(2g/kg cadmium + 200mg/kg extract of Annona muricata) The rats were subjected to cadmium subcutaneously followed by the oral administration of aqueous seed extract of Annona Muricata for fifteen consecutive days.

Results: The impact of the extract on antioxidant enzymes activities of the cerebellum, cerebellar weight, as well as the histology of the cerebellum were scrutinized. The data revealed that the aqueous seed extract of Annona muricata, in a dose-dependent manner, augmented the levels of superoxide dismutase (SOD) (P=0.005) and catalase (CAT) (P=0.027) in contrast to the cadmium-only group. The relative weight of the cerebellum exhibited a significant increasein the treated groups compared to the cadmium-only group.

The histology of the cerebellum delineated pathological changes arising from the exposure to cadmium, while Annona muricata brought about regenerative changes.

Conclusion:  In summary, the study posits that owing to the presence of phytochemicals in Annona muricata aqueous seed extract, it was efficacious in mitigating the neurotoxicity induced by cadmium in the cerebellum of male rats.
Microbial Melanin: Recent Developments and Challenges in the Production, Extraction, Purification and Application of Microbial Melanin
Authors: Fatima Meraj
Published: January 2024

A class of biopolymers known by the common name melanin has several potential uses in the medicinal sciences, bioelectronics, cosmeceutical and bioremediation. These pigments wide distribution indicates that they help a variety of life forms- fight biotic and abiotic stressors. Different types of melanin, such as eumelanin, pheomelanin, allomelanin, pyomelanin, and neuromelanin, are produced by the oxidative polymerization of phenolic compounds in fungi and bacteria, primarily via the 1,8-dihydroxynaphthalene [DHN] or 3,4-dihydroxyphenylalanine [DOPA] pathways. The tyrosinase, laccase, and polyketide synthase are the groups of enzymes that are primarily responsible for the production of melanin in many microorganisms. Research has indicated that utilising recombinant technologies in conjunction with culture parameter manipulation can enhance melanin yield for industrial production. Its low solubility has hindered the development of extraction techniques despite tremendous efforts, and its heterogeneous structural complexity has hindered structural elucidation, which limits the full potential of its biotechnological applications. The process of extraction may differ slightly depending on the kind of tissue and where the melanin is located. Melanin pigments from various taxa of life (like Sepia, bacteria, fungi) have been the subject of countless investigations to expand our understanding of them and enable their effective use in a wide range of applications. Due to these studies, there is an immediate need for a thorough review of melanin pigments that have been isolated from microorganisms. A review that covers biosynthesis, bioproduction, characterization, and possible applications will aid researchers from a variety of backgrounds in appreciating the significance of microbial melanins and in organizing their own melanin-related research projects. In order to achieve this, the current study contrasts traditional and cutting-edge concepts for environmentally sustainable melanin extraction processes.