bluuebunny/crossref_metadata_2025 huggingface dataset:
ОСОБЛИВОСТІ ОСВІТНІХ ПРОГРАМ ІЗ ПУБЛІЧНОГО УПРАВЛІННЯ ТА АДМІНІСТРУВАННЯ ГАЛУЗЕВОЇ СПРЯМОВАНОСТІ (НА ПРИКЛАДІ МАГІСТЕРСЬКОЇ ПРОГРАМИ «ДЕРЖАВНЕ УПРАВЛІННЯ У СФЕРІ МІСТОБУДІВНОЇ ДІЯЛЬНОСТІ»)
Authors: Андреєв Сергій
Published: August 2023

У статті порушено актуальне питання щодо доцільності започаткування в Україні професійної підготовки кадрів для органів державної влади та органів місцевого самоврядування з питань галузевого та міжгалузевого державного управління, а також стосовно необхідності поширення відповідних освітніх програм зі спеціальності 281 «Публічне управління та адміністрування». За результатами аналізу інформаційних даних ЄДЕБО (Вступ 2022) щодо магістерських програм із вказаної спеціальності станом на січень цього року, в Україні нині існує дефіцит програм з державного управління галузевої та міжгалузевої спрямованості. Однією з причин зазначеного є наявність недоліків у чинному стандарті вищої освіти зі спеціальності 281  «Публічне управління та адміністрування» для другого (магістерського) рівня. На прикладі магістерської програми «Державне управління у сфері містобудівної діяльності» Київського національного університету будівництва і архітектури визначено особливості та переваги освітніх програм із публічного управління та адміністрування галузевої спрямованості, сформульовано висновки стосовно подальшого поширення галузевого підходу до структури і змісту освітніх програм із зазначеної спеціальності. Зокрема, серед особливостей відповідних програм відзначено їхній комплексний і міждисциплінарний характер, цільову орієнтацію на професійну підготовку управлінських кадрів для конкретної сфери (галузі) державного управління, формування у здобувачів вищої освіти додаткових фахових компетентностей, необхідних для належного виконання управлінських функцій у відповідній галузі. Обґрунтовано думку про те, що поширенню в освітньому просторі України програм із державного управління галузевої спрямованості сприяло б відновлення в установленому законодавством порядку галузі знань і освітньої спеціальності «Державне управління» з подальшим розробленням та запровадженням якісного стандарту вищої освіти за цією спеціальністю.
СУЧАСНІ ЗАРУБІЖНІ ПРАКТИКИ УПРАВЛІННЯ РОЗВИТКОМ КАДРОВОГО ПОТЕНЦІАЛУ СФЕРИ ОХОРОНИ ЗДОРОВ’Я
Authors: Колісніченко Наталя
Published: August 2023

Досліджено сучасні зарубіжні практики розвитку кадрового потенціалу сфери охорони здоров’я та окреслено перспективи реалізації відповідних заходів в Україні. Доведено, що розвиток потенціалу персоналу пов’язаний насамперед із його навчанням, яке охоплює формальну орієнтаційну програму, міжфункціональне навчання, підтримку професійних навичок, коучинг, розвиток кар’єри та особистий розвиток. Окреслено вигоди різних форм навчання для сфери охорони здоров’я, що пов’язуються з утриманням медпрацівників; підтриманням їхнього морального духу; ефективністю практики; розвитком посадової компетентності; рівнем задоволеності пацієнтів. Розглянуто різні методики, що спрямовані на зростання кадрового потенціалу і застосовуються у зарубіжній практиці, зокрема тренінг з управління чи менеджменту для керівників першої ланки сфери охорони здоров’я, орієнтаційні практики для нових медпрацівників, ефективне професійне навчання тощо. Надано опис зарубіжних практик, які можуть бути корисними для персоналу і є безкоштовними, – журнальні клуби; просвітницькі програми для медпрацівників; програми, що підтримуються урядом; навчальні програми внутрішньої підготовки тощо. Проаналізовано роль та значення інших чинників у розвитку кадрового потенціалу сфери охорони здоров’я, зокрема переваги від членства у професійній асоціації, коучинг та наставництво. Наведено рекомендації із реалізації перевірених західною практикою заходів у вітчизняній системі охорони здоров’я щодо: трансформування системи безперервного професійного розвитку працівників охорони здоров’я відповідно до міжнародних стандартів поліпшення якості безперервної медичної освіти на накопичувальний принцип діяльності; впровадження у практику уніфікованих модульних програм післядипломної освіти працівників із найбільш актуальних проблем теорії та практики охорони здоров’я; включення до структури модулів післядипломної освіти фахівців обов’язкової клінічної практики, спрямованої на навчання сучасним методикам та технологіям надання медичної допомоги.
ДЕЯКІ ПІДХОДИ ЩОДО КРИТЕРІЇВ ВИЗНАЧЕННЯ ЧИСЕЛЬНОСТІ ПІДРОЗДІЛІВ ЦИВІЛЬНОГО ЗАХИСТУ, ЯКІ УТВОРЮЮТЬСЯ У СКЛАДІ ВИКОНАВЧИХ ОРГАНІВ МІСЬКИХ, СЕЛИЩНИХ ТА СІЛЬСЬКИХ РАД
Authors: Коробкін Валерій
Published: August 2023

Запропоновано алгоритм дій щодо створення в структурі виконавчого органу підрозділу з питань цивільного захисту. На підставі проведення аналізу стану техногенно-екологічної безпеки громади, паспортизації території громади щодо ризику виникнення надзвичайних ситуацій та визначення обсягу робіт щодо запобігання надзвичайним ситуаціям на території громади надано критерії стосовно встановлення чисельності структурного підрозділу з питань цивільного захисту. Наголошено на доцільності виявлення рівня впливу кожного критерію на можливий обсяг робіт щодо запобігання надзвичайним ситуаціям, який мають виконувати працівники структурного підрозділу цивільного захисту під час розрахунків чисельності структурного підрозділу цивільного захисту органу місцевої влади.
Approximations of Time-Dependent Nonlinear Partial Differential Equations using Galerkin Optimal Auxiliary Function Method
Authors: Trisha Nilormy Gupta , Islam Md Shafiqul
Published: August 2023

The purpose of this research work is to employ the Optimal Auxiliary Function Method (OAFM) for obtaining numerical approximations of time-dependent nonlinear partial differential equations (PDEs) that arise in many disciplines of science and engineering. The initial and first approximations of parabolic nonlinear PDEs associated with initial conditions have been generated by utilizing this method. Then the Galerkin method is applied to estimate the coefficients that remain unknown. Finally, the values of the coefficients generated by the Galerkin method have been inserted into the first approximation. In each example, all numerical computations and corresponding absolute errors are provided in schematic representations. The rate of convergence attained by the proposed method is depicted in tabular form.

GANIT J. Bangladesh Math. Soc. 43.1 (2023) 001- 016
Manual operativo para la inclusión de niños y niñas de 3 a 5 años: Con necesidades educativas especiales derivadas de la discapacidad auditiva
Authors:   Universidad del Azuay, León-Pesántez Adriana
Published: August 2023

Esta propuesta operativa inclusiva tiene como objetivo fundamental brindar información teórica y práctica pertinente, que permita a los docentes, equipos de apoyo, padres de familia y comunidad llevar a cabo procesos inclusivos con calidad y calidez . El manual operativo consta de dos capítulos: el primero aborda la discapacidad auditiva su concepto, causas, prevalencia y clasificación que permitirá al lector conocer aspectos fundamentales sobre esta condición. El segundo capítulo incorpora el componente práctico con aportaciones necesarias para crear un ambiente humano y físico adecuado para la inclusión, se abordan los procesos para la realización de la planificación con sus adaptaciones curriculares y se provee información sobre los recursos que se utilizan en las aulas inclusivas. Incluye además direcciones y teléfonos de las instituciones, equipos y centros de educación que trabajan en favor de la inclusión. En la parte final, se ofrecen diversos anexos que constan de: planes de desarrollo, fichas para registrar el historial del niño, fichas para el registro de las adaptaciones curriculares, etcétera que facilitarán la labor del docente al momento de realizar un verdadero proceso inclusivo. 176 páginas ISBN: 978-9978-325-32-2
VARVO: a Novel Method for the Fast Detection of Vehicle Crash Events from Video Only Data
Authors: Moreno Pallares Mario , Yoo Sang Guun , Aguilar Wilbert G.
Published: August 2023

Around 1,35 million people worldwide die each year because of traffic incidents, and it is estimated that another 50 million suffers serious injuries. This picture is particularly dramatic in the Andean Region where the death toll due to traffic accidents is as high as 127 deaths per million inhabitants. In recent years the deployment of the so-called Intelligent Transport Systems (ITS) across several developed countries has helped to reduce the number of deaths due to traffic accidents. An integral part of an ITS is the automatic detection of traffic incidents from video and sensor data. However, the scarcity of curated datasets, especially those that contained a reasonable number of positive instances of traffic incidents is hampering the development of artificial intelligence applications for the domain of traffic research. Given this scenario, we pursued answering the following research question: is it possible to detect car crashes through supervised machine learning based on the estimated speeds of cars from video only-data? Here we present VARVO, a novel algorithm for the detection of traffic incidents that does not rely on sensors for cars speed detection. VARVO performs a supervised classification task based on the sequential use of convolutional network-based object detection and bi-directional tracking. We also describe how the models implemented in VARVO improved their classification accuracy by applying an oversampling algorithm to deal with class imbalance. We believe that the deployment of VARVO could be linked to static traffic video cameras and could be part of the Intelligent Transport Systems foundations in other Andean countries.
A DIGNIDADE UNIVERSAL: UMA ANÁLISE DA DECLARAÇÃO DE PUNTA DEL ESTE
Authors: Klaus Júnior Cláudio Antônio , Hülse Levi , Mattos Martins Anderson Antônio
Published: August 2023

Este artigo analisa a Declaração de Punta del Este, adotada no 70º aniversário da Declaração Universal dos Direitos Humanos (DUDH), que celebra e reafirma o compromisso com a proteção da dignidade humana como núcleo dos direitos humanos. Os principais temas da Declaração são discutidos, incluindo a educação em direitos humanos, a busca por consenso, a delimitação e especificação dos direitos humanos, e as obrigações e responsabilidades. O artigo destaca a importância da cooperação entre diversos atores e a promoção do diálogo e compreensão mútua para enfrentar os desafios no campo dos direitos humanos e garantir a igualdade e dignidade para todos.
PALAVRAS CHAVE: Declaração de Punta del Este. Declaração Universal dos Direitos Humanos. Dignidade humana. Educação em direitos humanos Cooperação. Liberdade religiosa.
 
ABSTRACT
This article examines the Punta del Este Declaration, adopted on the 70th anniversary of the Universal Declaration of Human Rights (UDHR), which celebrates and reaffirms the commitment to protect human dignity as the core of human rights. The main themes of the Declaration are discussed, including human rights education, the search for consensus, the delimitation and specification of human rights, and obligations and responsibilities. The article highlights the importance of cooperation among diverse actors and the promotion of dialogue and mutual understanding to address the challenges in the field of human rights and ensure equality and dignity for all.
Keywords: Punta del Este Declaration. Universal Declaration of Human Rights. Human dignity. Human rights education. Cooperation. Religious freedom.
Biskuit Balita Tepung Sagu yang Disubstitusi Tepung Ikan Gabus (Channa striata)
Authors: Dara Widia , Yensasnidar Yensasnidar , Pandeni Asni , Mailinda Roza
Published: August 2023

meningkatkan kandungan gizi biskuit sagu.Tujuan penelitian menganalisis substitusi tepung ikan gabus terhadap karakteristik sensorik dan kandungan gizi biskuit. Penelitian ini merupakan eksperimen. Biskuit B0 tidak disubstitusi tepung ikan gabus. Biskuit B1, B2 dan B3 adalah biskuit yang disubstitusi tepung ikan  gabus masing masing 10%, 20% dan 30 % .  Uji  organoleptik dilakukan pada 25 panelis agak terlatih. Uji daya terima dilakukan kepada 15 orang balita berumur 12-24 bulan di posyandu Balita Puskesmas Kinali.  Analisis uji sensori  uji Kruskal Wallis, bila terdapat perbedaan dilanjutkan dengan uji Mann-Whitney. Hasil uji sensori pada warna biskuit yang paling disukai adalah  (B0) 4,12= suka ) dan warna biskuit B1 (4,08= suka). Aroma biskuit yang paling disukai adalah B0 (4,20 = suka) dan biskuit B1 (3,20 = agak suka). Tekstur biskuit yang paling disukai adalah B0 (4,08= suka) dan B1 (3,68 = suka). Rasa biskuit yang paling disukai adalah B0 (4,40 = suka) dan B1 (3,28= biasa). Hasil analisis statistik tidak terdapat perbedaan yang nyata antara biskuit B0 dan B1 terhadap warna dan tekstur biskuit. Berdasarkan hasil uji daya terima biskuit B1di habiskan baik sekali sebanyak 53,3 %. Kandungan gizi biskuit B0 adalah kadar air: 3,95%, abu: 0,66%, protein: 2,48%, lemak: 16,42%, serat:  3,58%, karbohidrat: 76,49% dan betakaroten: 131,75 mg/100 gram. Biskuit B1 kadar air: 4,43%, abu: 0,95%, protein: 11,75%, lemak: 15,04%, serat: 3,05%,  karbohidrat: 64,76% dan β-karoten: 1.304,75 mg/100 gram. Disarankan  substitusi tepung ikan gabus sebanyak 10 % pada  biskuit Balita.
Asupan Zinc dan Magnesium terhadap Tekanan Darah Lansia
Authors: Jelmila Sri Nani , Hasni Dita , Nindra Yhofa
Published: August 2023

Hipertensi merupakan faktor utama untuk penyakit kardiovaskuler yang dipengaruhi oleh faktor usia dan asupan mikronutrien seperti zinc dan magnesium. Lanjut usia beresiko mengalami hipertensi karena faktor penuaan dan kurangnya asupan mikronutrien. Penelitian ini bertujuan untuk melihat hubungan asupan zinc dan magnesium dengan tekanan darah lansia. Jenis penelitian ini adalah analitik observasional dengan design cross sectional. Sampel pada penelitian ini berjumlah 38 orang lanjut usia di Panti Sosial Tresna Werdha Sabai Nan Aluih Sicincin Kabupaten Padang Pariaman. Analisis data menggunakan korelasi Pearson. Hasil penelitian menunjukkan bahwa rerata asupan zinc responden adalah 3,91±0,93 mg, rerata asupan magnesium 148,48±33,50 mg. Uji statistik hubungan asupan zinc dengan tekanan darah sistolik  didapatkan nilai p=0,38, r=-0,14, hubungan asupan zinc dengan tekanan darah diastolik didapatkan nilai p=0,19, r=-0,21. Asupan magnesium dengan tekanan darah sistolik didapatkan nilai p=0,23, r=-0,19. Hubungan asupan magnesium dengan tekanan darah diastolik didapatkan nilai p=0,16, r=-0,22. Kesimpulan penelitian ini Tidak terdapat hubungan asupan zinc dan magnesium dengan tekanan darah sistolik dan diastolik lansia di Panti Sosial Sabai Nan Aluih Sicincin.
Kejadian Stunting Pada Anak Batita Berdasarkan Pemberian Riwayat ASI Ekslusif, Riwayat Bayi Berat Lahir Rendah (BBLR)
Authors: Migang Yena Wineini , Utama Nang Randu , Astutik Linda Puji , Mgang Evan Kristianus
Published: August 2023

Stunting merupakan masalah yang dapat mengganggu perkembangan balita ASI eksklusif menjadi salah satu faktor yang dapat mempengaruhi kejadian stunting karena zat gizi yang terkandung dalam ASI merupakan salah satu faktor penting yang menentukan masa tumbuh kembang anak. Penelitian ini tujuannya untuk mengetahui hubungan kejadian stunting pada batita umur 24-36 bulan berdasarkan riwayat pemberian ASI ekslusif dan variabel lainnya seperti, umur ibu, status Pendidikan ibu, status pekerjaan ibu, penghasilan keluarga, Riwayat BBLR, jenis kelamin balita. Jenis penelitian ini merupakan penelitian deskriptif korelasioanal yang bersifat kuantitatif dengan pendekatan cross sectional. Pengambilan responden menggunakan teknik purposive sampling dengan rumus slovin, jumlah 141 responden. Instrumen penelitian ini menggunakan kuesioner dan microtoise/pita meteran, serta bantuan aplikasi Anthro WHO.  Analisis data menggunakan Chi square dengan alternatif fisher exact test. Ada hubungan riwayat pemberian ASI Eksklusif dengan kejadian stunting pada anak batita dengan hubungan keeratan yang lemah. Ada hubungan riwayat BBLR dengan kejadian stunting pada anak batita, dengan hubungan positif tetapi keeratan lemah. Variabel lain yang memiliki hubungan penghasilan keluarga dan riwayat BBLR. Keluarga dipersiapkan untuk dapat memberikan ASI ekslusif, pemantauan berat badan janin saat hamil dan manajemen keuangan keluarga untuk mencukupi kebutuhan gizi keluarga.
Pengembangan E-Work Arsos (e-worksheet aritmetika sosial) berbasis android dalam pembelajaran matematika
Authors: Suryadi Sarah Jevo , Setyadi Danang
Published: August 2023

Tujuan penelitian ini adalah menjelaskan apakah media “E-Work Arsos” (E-Worksheet Aritmatika Sosial) valid, praktis, serta efektif untuk digunakan oleh peserta didik. Media “E-Work Arsos” dibuat agar menarik motivasi serta minat belajar peserta didik untuk digunakan dalam pembelajaran mandiri maupun berkelompok. Penelitian pengembangan atau Research and Development (R & D) adalah jenis yang digunakan dalam penelitian ini. Prosedur dalam penelitian “E-Work Arsos” menggunakan model ADDIE, dalam model ADDIE terdapat lima tahap diantaranya tahap Analyze, tahap Design, tahap Development, tahap Implementation, serta tahap Evaluation. Teknik pengumpulan data yang digunakan meliputi dokumentasi, tes, dan angket serta digunakan untuk penilaian kevalidan, kepraktisan, dan keefektifan media “E-Work Arsos”. Media “E-Work Arsos” (E-Worksheet Aritmatika Sosial) diuji oleh validator yaitu dosen pendidikan matematika dengan hasil akhir dari analisis data pada kevalidan media adalah 94,87%, dan kepraktisan media yaitu 100% yang artinya media “E-Work Arsos” dapat dikatakan valid untuk digunakan sebagai media pembelajaran peserta didik pada materi aritmetika sosial. Berdasarkan hasil dari keefektifan diperoleh nilai signifikan sebesar 0,000 atau kurang dari 0,05 yang artinya media “E-Work Arsos” dapat dikatakan valid, praktis dan efektif untuk digunakan sebagai media pembelajaran oleh peserta didik.
Revisable A Priori as a Political Problem: Critique of Constitution in Critical Theory
Authors: Säynäjoki Sakari , Tiisala Tuomo
Published: August 2023

According to the received view, Marxian (ideology) critique and Foucaultian (genealogical) critique constitute two divergent approaches of critical theory that have remarkably different goals and little in common. In this article, however, we identify a guiding thread that connects the Marxian and Foucaultian traditions and motivates a distinctive approach within critical theory we call the ‘critique of constitution’. The problem of restricted consciousness, we show, is the core problem in common between Michel Foucault's critical history of thought and Georg Lukács's theory of reification which underlies the tradition of Western Marxism and Frankfurt School critical theory. The problem concerns the limits of intelligibility and, by the same token, the apparent inevitability of the given social ontology. Our sense of what is possible depends on what we are able to think. But we know from the history of sciences that the limits of intelligibility change, thereby also altering our sense of what is possible. This becomes a political problem in connection with the intelligibility of social reality, because our restricted consciousness limits the alternatives we can so much as consider and seek to bring about. The critique of constitution, then, aims to expand the scope of possibility by revealing the contingent formation of the given limits of intelligibility. We argue that this is the paramount political task for Foucault and Lukács alike, other important differences notwithstanding.
EasyChain: an IoT-friendly blockchain for robust and energy-efficient authentication
Authors: Bapatla Anand K. , Puthal Deepak , Mohanty Saraju P. , Yanambaka Venkata P. , Kougianos Elias
Published: August 2023

The Internet of Everything (IoE) is a bigger picture that tries to fit the Internet of Things (IoT) that is widely deployed in smart applications. IoE brings people, data, processes, and things to form a network that is more connected and increases overall system intelligence. A further investigation of the IoE can really mean creating a distributed network focusing on edge computing instead of relying on the cloud. Blockchain is one of the recently distributed network technologies which by structure and operations provide data integrity and security in trust-less P2P networks such as IoE. Blockchain can also remove the need for central entities which is the main hurdle for the wide adoption of IoT in large networks. IoT “things” are resource-constrained both in power and computation to adopt the conventional blockchain consensus algorithms that are power and compute-hungry. To solve that problem, this paper proposes EasyChain, a blockchain that is robust along with running on a lightweight authentication-based consensus protocol that is known as Proof-of-Authentication (PoAh). This blockchain based on the lightweight consensus protocol replaces the power-hungry transaction, blocks validation steps, and provides ease of usage in resource-constrained environments such as IoE. The proposed blockchain is designed using the Python language for an easy understanding of the functions and increased ease of integration into IoE applications. The designed blockchain system is also deployed on a single-board computer to analyze its feasibility and scalability. The latency observed in the simulated and experimental evaluations is 148.89 ms which is very fast compared to the existing algorithms.
In vitro cross-talk between metastasis-competent circulating tumor cells and platelets in colon cancer: a malicious association during the harsh journey in the blood
Authors: Eslami-S Zahra , Cortés-Hernández Luis Enrique , Glogovitis Ilias , Antunes-Ferreira Mafalda , D’Ambrosi Silvia , Kurma Keerthi , Garima Françoise , Cayrefourcq Laure , Best Myron G. , Koppers-Lalic Danijela , Wurdinger Thomas , Alix-Panabières Catherine
Published: August 2023

Background: Platelets are active players in hemostasis, coagulation and also tumorigenesis. The cross-talk between platelets and circulating tumor cells (CTCs) may have various pro-cancer effects, including promoting tumor growth, epithelial-mesenchymal transition (EMT), metastatic cell survival, adhesion, arrest and also pre-metastatic niche and metastasis formation. Interaction with CTCs might alter the platelet transcriptome. However, as CTCs are rare events, the cross-talk between CTCs and platelets is poorly understood. Here, we used our established colon CTC lines to investigate the colon CTC-platelet cross-talk in vitro and its impact on the behavior/phenotype of both cell types.

Methods: We exposed platelets isolated from healthy donors to thrombin (positive control) or to conditioned medium from three CTC lines from one patient with colon cancer and then we monitored the morphological and protein expression changes by microscopy and flow cytometry. We then analyzed the transcriptome by RNA-sequencing of platelets indirectly (presence of a Transwell insert) co-cultured with the three CTC lines. We also quantified by reverse transcription-quantitative PCR the expression of genes related to EMT and cancer development in CTCs after direct co-culture (no Transwell insert) with platelets.

Results: We observed morphological and transcriptomic changes in platelets upon exposure to CTC conditioned medium and indirect co-culture (secretome). Moreover, the expression levels of genes involved in EMT (p < 0.05) were decreased in CTCs co-cultured with platelets, but not of genes encoding mesenchymal markers (FN1 and SNAI2). The expression levels of genes involved in cancer invasiveness (MYC, VEGFB, IL33, PTGS2, and PTGER2) were increased.

Conclusion: For the first time, we studied the CTC-platelet cross-talk using our unique colon CTC lines. Incubation with CTC conditioned medium led to platelet aggregation and activation, supporting the hypothesis that their interaction may contribute to preserve CTC integrity during their journey in the bloodstream. Moreover, co-culture with platelets influenced the expression of several genes involved in invasiveness and EMT maintenance in CTCs.
Prediction accuracy of regulatory elements from sequence varies by functional sequencing technique
Authors: Nowling Ronald J. , Njoya Kimani , Peters John G. , Riehle Michelle M.
Published: August 2023

Introduction

Various sequencing based approaches are used to identify and characterize the activities of cis-regulatory elements in a genome-wide fashion. Some of these techniques rely on indirect markers such as histone modifications (ChIP-seq with histone antibodies) or chromatin accessibility (ATAC-seq, DNase-seq, FAIRE-seq), while other techniques use direct measures such as episomal assays measuring the enhancer properties of DNA sequences (STARR-seq) and direct measurement of the binding of transcription factors (ChIP-seq with transcription factor-specific antibodies). The activities of cis-regulatory elements such as enhancers, promoters, and repressors are determined by their sequence and secondary processes such as chromatin accessibility, DNA methylation, and bound histone markers.

Methods

Here, machine learning models are employed to evaluate the accuracy with which cis-regulatory elements identified by various commonly used sequencing techniques can be predicted by their underlying sequence alone to distinguish between cis-regulatory activity that is reflective of sequence content versus secondary processes.

Results and discussion

Models trained and evaluated on D. melanogaster sequences identified through DNase-seq and STARR-seq are significantly more accurate than models trained on sequences identified by H3K4me1, H3K4me3, and H3K27ac ChIP-seq, FAIRE-seq, and ATAC-seq. These results suggest that the activity detected by DNase-seq and STARR-seq can be largely explained by underlying DNA sequence, independent of secondary processes. Experimentally, a subset of DNase-seq and H3K4me1 ChIP-seq sequences were tested for enhancer activity using luciferase assays and compared with previous tests performed on STARR-seq sequences. The experimental data indicated that STARR-seq sequences are substantially enriched for enhancer-specific activity, while the DNase-seq and H3K4me1 ChIP-seq sequences are not. Taken together, these results indicate that the DNase-seq approach identifies a broad class of regulatory elements of which enhancers are a subset and the associated data are appropriate for training models for detecting regulatory activity from sequence alone, STARR-seq data are best for training enhancer-specific sequence models, and H3K4me1 ChIP-seq data are not well suited for training and evaluating sequence-based models for cis-regulatory element prediction.
COVID-19 alters human microbiomes: a meta-analysis
Authors: Reuben Rine Christopher , Beugnon Rémy , Jurburg Stephanie D.
Published: August 2023

Introduction

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected a substantial portion of the world’s population, and novel consequences of COVID-19 on the human body are continuously being uncovered. The human microbiome plays an essential role in host health and well-being, and multiple studies targeting specific populations have reported altered microbiomes in patients infected with SARS-CoV-2. Given the global scale and massive incidence of COVID on the global population, determining whether the effects of COVID-19 on the human microbiome are consistent and generalizable across populations is essential.

Methods

We performed a synthesis of human microbiome responses to COVID-19. We collected 16S rRNA gene amplicon sequence data from 11 studies sampling the oral and nasopharyngeal or gut microbiome of COVID-19-infected and uninfected subjects. Our synthesis included 1,159 respiratory (oral and nasopharyngeal) microbiome samples and 267 gut microbiome samples from patients in 11 cities across four countries.

Results

Our reanalyses revealed communitywide alterations in the respiratory and gut microbiomes across human populations. We found significant overall reductions in the gut microbial diversity of COVID-19-infected patients, but not in the respiratory microbiome. Furthermore, we found more consistent community shifts in the gut microbiomes of infected patients than in the respiratory microbiomes, although the microbiomes in both sites exhibited higher host-to-host variation in infected patients. In respiratory microbiomes, COVID-19 infection resulted in an increase in the relative abundance of potentially pathogenic bacteria, including Mycoplasma.

Discussion

Our findings shed light on the impact of COVID-19 on the human-associated microbiome across populations, and highlight the need for further research into the relationship between long-term effects of COVID-19 and altered microbiota.
Prognostic value of soluble ST2 in AL and TTR cardiac amyloidosis: a multicenter study
Authors: Nicol Martin , Vergaro Giuseppe , Damy Thibaud , Kharoubi Mounira , Baudet Mathilde , Canuti Elena Sofia , Aimo Alberto , Castiglione Vincenzo , Emdin Michele , Royer Bruno , Harel Stephanie , Cohen-Solal Alain , Arnulf Bertrand , Logeart Damien
Published: August 2023

Background

Both light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis are types of cardiac amyloidosis (CA) that require accurate prognostic stratification to plan therapeutic strategies and follow-ups. Cardiac biomarkers, e.g., N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (Hs-cTnT), remain the cornerstone of the prognostic assessment. An increased level of soluble suppression of tumorigenesis-2 (sST2) is predictive of adverse events [all-cause death and heart failure (HF) hospitalizations] in patients with HF. This study aimed to evaluate the prognostic value of circulating sST2 levels in AL-CA and ATTR-CA.

Methods

We carried out a multicenter study including 133 patients with AL-CA and 152 patients with ATTR-CA. During an elective outpatient visit for the diagnosis of CA, Mayo Clinic staging [NT-proBNP, Hs-cTnT, differential of free light chains (DFLCs)] and sST2 were assessed for all AL patients. Gillmore staging [including estimated glomerular filtration rate (eGFR), NT-proBNP] and Grogan staging (including NT-proBNP and Hs-cTnT) were assessed for TTR-CA patients.

Results

The median age was 73 years [interquartile range (IQR) 61–81], and 53% were men. The endpoint was the composite of all-cause death or first HF-related hospitalization. The median follow-up was 20 months (IQR 3–34) in AL amyloidosis and 33 months (6–45) in TTR amyloidosis. The primary outcome occurred in 70 (53%) and 99 (65%) of AL and TTR patients, respectively. sST2 levels were higher in patients with AL-CA than in patients with ATTR-CA: 39 ng/L (26–80) vs. 32 ng/L (21–46), p < 0.001. In AL-CA, sST2 levels predicted the outcome regardless of the Mayo Clinic score (HR: 2.16, 95% CI: 1.17–3.99, p < 0.001). In TTR-CA, sST2 was not predictive of the outcome in multivariate models, including Gillmore staging and Grogan staging (HR: 1.17, CI: 95% 0.77–1.89, p = 0.55).

Conclusion

sST2 level is a relevant predictor of death and HF hospitalization in AL cardiac amyloidosis and adds prognostic stratification on top of NT-proBNP, Hs cTnT, and DFLC.
Cardiac mechanics and reverse remodelling under mechanical support from left ventricular assist devices
Authors: Pamias-Lopez Blanca , Ibrahim Michael E. , Pitoulis Fotios G.
Published: August 2023

In recent years, development of mechanical circulatory support devices has proved to be a new treatment modality, in addition to standard pharmacological therapy, for patients with heart failure or acutely depressed cardiac function. These include left ventricular assist devices, which mechanically unload the heart when implanted. As a result, they profoundly affect the acute cardiac mechanics, which in turn, carry long-term consequences on myocardial function and structural function. Multiple studies have shown that, when implanted, mechanical circulatory assist devices lead to reverse remodelling, a process whereby the diseased myocardium reverts to a healthier-like state. Here, we start by first providing the reader with an overview of cardiac mechanics and important hemodynamic parameters. We then introduce left ventricular assist devices and describe their mode of operation as well as their impact on the hemodynamics. Changes in cardiac mechanics caused by device implantation are then extrapolated in time, and the long-term consequences on myocardial phenotype, as well as the physiological basis for these, is investigated.
Anterior diaphyseal curvature of the femur and tibia has biomechanical consequences during unloaded uphill locomotion
Authors: Murray Alison A. , MacKinnon Marla , Carswell Tess M. R. , Giles Joshua W.
Published: August 2023

The biomechanics of limb bone curvature are complex, and though anterior curvature clearly exhibits some relationship with behavior, the mechanisms shaping it and its biomechanical purpose remain unclear. Among both Neanderthals and humans, anterior limb bone curvature correlates strongly with other limb bone adaptations known to reflect high mobility, particularly in steep variable terrain. We developed a computational musculoskeletal model to test the impact of opposing patterns of human femoral and tibial anterior curvature on muscle kinetics during a proxy for uphill walking: stair-climbing. Femoral and tibial laser scans were used from two archaeological individuals matched for estimated body mass, bi-iliac breadth, and crural index but with reverse patterns of anterior diaphyseal curvature. A default OpenSim musculoskeletal model was modified twice – once to each individual’s anatomy – and the resulting models performed stair-climbing gait simulations with experimentally-collected motion capture data. Both custom MSk models followed the general gait kinematics expected based on stair-climbing gait studies, but differed in muscle kinetics in key areas. When a curved femur was paired with a straight tibia, the opposite pattern of recruitment of bi-articular superficial hamstring muscles was observed compared to the pairing of a straight femur with a curved tibia. Pairing a curved femur with a straight tibia was also associated with reduced soleal recruitment and an increased reliance on secondary ankle plantarflexors. These effects are attributed to variation in muscle moment arms about the knee and the relationships that curvature likely has with other three-dimensional morphological variation within the bone/limb. While the tissue-level mechanisms shaping anterior limb bone curvature remain poorly understood, results of the current study suggest that opposing patterns of variation in long bone curvature within the leg do elicit different kinetic solutions to the problem of achieving the same gait kinematics during uphill locomotion. This is an important first step not just in better understanding the biomechanical impact of anatomical variation in bone curvature on locomotion, but also contributes more broadly to the recognition in biological anthropology of variability in the relationship between locomotor function and underlying skeletal structure.
The pursuit of genetic gain in agricultural crops through the application of machine-learning to genomic prediction
Authors: Jones Darcy , Fornarelli Roberta , Derbyshire Mark , Gibberd Mark , Barker Kathryn , Hane James
Published: August 2023

Current practice in agriculture applies genomic prediction to assist crop breeding in the analysis of genetic marker data. Genomic selection methods typically use linear mixed models, but using machine-learning may provide further potential for improved selection accuracy, or may provide additional information. Here we describe SelectML, an automated pipeline for testing and comparing the performance of a range of linear mixed model and machine-learning-based genomic selection methods. We demonstrate the use of SelectML on an in silico-generated marker dataset which simulated a randomly-sampled (mixed) and an unevenly-sampled (unbalanced) population, comparing the relative performance of various methods included in SelectML on the two datasets. Although machine-learning based methods performed similarly overall to linear mixed models, they performed worse on the mixed dataset and marginally better on the unbalanced dataset, being more affected than linear mixed models by the imposed sampling bias. SelectML can assist in the training, comparison, and selection of genomic selection models, and is available from https://github.com/darcyabjones/selectml.
When NIPT meets WES, prenatal diagnosticians face the dilemma: genetic etiological analysis of 2,328 cases of NT thickening and follow-up of pregnancy outcomes
Authors: Ji Xueqi , Li Qiongmei , Qi Yiming , Wang Xingwang , Ding Hongke , Lu Jian , Zhang Yan , Yin Aihua
Published: August 2023

Objective: To assess the performance of diverse prenatal diagnostic approaches for nuchal translucency (NT) thickening and to investigate the optimal prenatal screening or diagnostic action with a NT thickening of 95th percentile-3.50 mm.

Methods: A retrospective analysis of 2,328 pregnancies with NT ≥ 95th percentile through ultrasound-guided transabdominal chorionic villus sampling (CVS), amniocentesis, or cordocentesis obtained clinical samples (chorionic villi, amniotic fluid, and cord blood), and real-time quantitative fluorescent PCR (QF-PCR), chromosome karyotyping (CS), chromosome microarray analysis (CMA), or whole exome sequencing (WES) were provided to identify genetic etiologies.

Results: In this study, the incidence of chromosomal defects increased with NT thickness. When NT ≥ 6.5 mm, 71.43% were attributed to genetic abnormalities. The 994 gravidas with fetal NT thickening underwent short tandem repeat (STR), CS, and CMA. In 804 fetuses with normal karyotypes, CMA detected 16 (1.99%) extra pathogenic or likely pathogenic copy number variations (CNVs). The incremental yield of CMA was only 1.16% (3/229) and 3.37% (10/297) in the group with NT 95th percentile-2.99 mm and NT 3.0–3.49 mm, separately. Among the 525 gravidas with fetal NT thickening who underwent STR, CMA, and WES, the incremental yield of WES was 4.09% (21/513). In the group of NT 95th percentile-2.99 mm, there were no additional single-nucleotide variations (SNVs) detected in WES, while in 143 cases with NT of 3.0–3.49 mm, the incremental yield of WES was 5.59% (8/143).

Conclusion: In the group of NT 95th percentile-3.0 mm, since chromosomal aneuploidy and chromosomal copy number variation were the primary causes and the additional contribution of CMA and WES was not significant, we recommend NIPT-Plus for pregnant women with a NT thickening of 95th percentile-3.0 mm first. In addition, comprehensive prenatal genetic testing involving CMA and WES can benefit pregnancies with NT thickening of 3.0–3.49 mm.
Menstrual hygiene management in flood-affected Pakistan: Addressing challenges and ensuring women's health and dignity
Authors: Tufail Zarnab , Ahmer Wania , Gulzar Shanza , Hasanain Muhammad , Shah Hussain Haider
Published: August 2023

Pakistan's recent floods have worsened women's and girls' menstrual hygiene problems, compromising their health, dignity, and well-being. Supply chain issues, poor facilities, and cultural stigma limit menstrual products and hygiene management. Gender-sensitive disaster management and menstrual health education programmes can help. The Minimum Initial Service Package (MISP) can provide emergency reproductive health services. Involving men, working with religious leaders, and pre-disaster planning for menstrual hygiene management can help break the taboo and increase access to resources. Meeting ongoing needs requires timely menstrual hygiene product distribution, restocking, and renewal. By addressing these issues, Pakistan can empower post-flood women and girls through economic opportunities and legal protection.
Suppression of neutrophils by sodium exacerbates oxidative stress and arthritis
Authors: Zlatar Leticija , Mahajan Aparna , Muñoz-Becerra Marco , Weidner Daniela , Bila Galyna , Bilyy Rostyslav , Titze Jens , Hoffmann Markus H. , Schett Georg , Herrmann Martin , Steffen Ulrike , Muñoz Luis E. , Knopf Jasmin
Published: August 2023

Introduction

Typical Western diet, rich in salt, contributes to autoimmune disease development. However, conflicting reports exist about the effect of salt on neutrophil effector functions, also in the context of arthritis.

Methods

We investigated the effect of sodium chloride (NaCl) on neutrophil viability and functions in vitro, and in vivo employing the murine K/BxN-serum transfer arthritis (STA) model.

Results and discussion

The effects of NaCl and external reactive oxygen species (H2O2) were further examined on osteoclasts in vitro. Hypertonic sodium-rich media caused primary/secondary cell necrosis, altered the nuclear morphology, inhibited phagocytosis, degranulation, myeloperoxidase (MPO) peroxidation activity and neutrophil extracellular trap (NET) formation, while increasing total ROS production, mitochondrial ROS production, and neutrophil elastase (NE) activity. High salt diet (HSD) aggravated arthritis by increasing inflammation, bone erosion, and osteoclast differentiation, accompanied by increased NE expression and activity. Osteoclast differentiation was decreased with 25 mM NaCl or 100 nM H2O2 addition to isotonic media. In contrast to NaCl, external H2O2 had pro-resorptive effects in vitro. We postulate that in arthritis under HSD, increased bone erosion can be attributed to an enhanced oxidative milieu maintained by infiltrating neutrophils, rather than a direct effect of NaCl.
Risk factors and outcome of Chimeric Antigen Receptor T-Cell patients admitted to Pediatric Intensive Care Unit: CART-PICU study
Authors: Caballero-Bellón Marina , Alonso-Saladrigues Anna , Bobillo-Perez Sara , Faura Anna , Arqués Laura , Rivera Cristina , Català Albert , Dapena Jose Luis , Rives Susana , Jordan Iolanda
Published: August 2023

Introduction

Chimeric antigen receptor (CAR)T-cell CD19 therapy is an effective treatment for relapsed/refractory B-cell acute lymphoblastic leukemia. It can be associated with life-threatening toxicities which often require PICU admission. Purpose: to describe clinical characteristics, treatment and outcome of these patients.

Methods

Prospective observational cohort study conducted in a tertiary pediatric hospital from 2016-2021. Children who received CAR-T admitted to PICU were included. We collected epidemiological, clinical characteristics, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), treatment, length of stay and mortality.

Results

CAR T-cells (4-1BB constructs) were infused in 59 patients. Twenty-four (40.7%) required PICU admission, length of stay was 4 days (IQR 3-6). Median age was 8.3 years (range 4-24). Patients admitted to PICU presented higher disease burden before infusion: 24% blasts in bone marrow (IQR 5-72) vs. 0 (0-6.9), p<0.001. No patients with <5% blasts were admitted to PICU. Main reasons for admissions were CRS (n=20, 83.3%) and ICANS (n=3, 12.5%). Fourteen patients (58.3%) required inotropic support, 14(58.3%) respiratory. Sixteen patients (66.6%) received tocilizumab, 10(41.6%) steroids, 6(25.0%) anakinra, and 5(20.8%) siltuximab. Ten patients (41.6%) presented neurotoxicity, six of them severe (ICANS 3-4). Two patients died at PICU (8.3%) because of refractory CRS-hemophagocytic lymphohistyocitosis (carHLH) syndrome. There were no significant differences in relapse rate after CAR-T in patients requiring PICU, it was more frequently CD19 negative (p=0.344).

Discussion

PICU admission after CAR-T therapy was mainly due to CRS. Supportive treatment allowed effective management and high survival. Some patients presenting with carHLH, can suffer a fulminant course.
Deformed wing virus of honey bees is inactivated by cold plasma ionized hydrogen peroxide
Authors: Cook Steven C. , Ryabov Eugene V. , Becker Christian , Rogers Curtis W. , Posada-Florez Francisco , Evans Jay D. , Chen Yan Ping
Published: August 2023

Deformed wing virus (DWV) is a widespread pathogen of Apis mellifera honey bees, and is considered a major causative factor for the collapse of infected honey bee colonies. DWV can be horizontally transmitted among bees through various oral routes, including via food sharing and by interactions of bees with viral-contaminated solid hive substrates. Cold plasma ionized hydrogen peroxide (iHP) is used extensively by the food production, processing and medical industries to clean surfaces of microbial contaminants. In this study, we investigated the use of iHP to inactivate DWV particles in situ on a solid substrate. iHP-treated DWV sources were ~105-fold less infectious when injected into naïve honey bee pupae compared to DWV receiving no iHP treatment, matching injected controls containing no DWV. iHP treatment also greatly reduced the incidence of overt DWV infections (i.e., pupae having >109 copies of DWV). The level of DWV inactivation achieved with iHP treatment was higher than other means of viral inactivation such as gamma irradiation, and iHP treatment is likely simpler and safer. Treatment of DWV contaminated hive substrates with iHP, even with honey bees present, may be an effective way to decrease the impacts of DWV infection on honey bees.
Decision trees for early prediction of inadequate immune response to coronavirus infections: a pilot study on COVID-19
Authors: Pisano Fabio , Cannas Barbara , Fanni Alessandra , Pasella Manuela , Canetto Beatrice , Giglio Sabrina Rita , Mocci Stefano , Chessa Luchino , Perra Andrea , Littera Roberto
Published: August 2023

Introduction

Few artificial intelligence models exist to predict severe forms of COVID-19. Most rely on post-infection laboratory data, hindering early treatment for high-risk individuals.

Methods

This study developed a machine learning model to predict inherent risk of severe symptoms after contracting SARS-CoV-2. Using a Decision Tree trained on 153 Alpha variant patients, demographic, clinical and immunogenetic markers were considered. Model performance was assessed on Alpha and Delta variant datasets. Key risk factors included age, gender, absence of KIR2DS2 gene (alone or with HLA-C C1 group alleles), presence of 14-bp polymorphism in HLA-G gene, presence of KIR2DS5 gene, and presence of KIR telomeric region A/A.

Results

The model achieved 83.01% accuracy for Alpha variant and 78.57% for Delta variant, with True Positive Rates of 80.82 and 77.78%, and True Negative Rates of 85.00% and 79.17%, respectively. The model showed high sensitivity in identifying individuals at risk.

Discussion

The present study demonstrates the potential of AI algorithms, combined with demographic, epidemiologic, and immunogenetic data, in identifying individuals at high risk of severe COVID-19 and facilitating early treatment. Further studies are required for routine clinical integration.