bluuebunny/crossref_metadata_2025 huggingface dataset:
Mâverâünnehirli Muhaddis Heysem b. Küleyb eş-Şâşî ve el-Müsned Adlı Eserinin Hadis Tarihindeki Yayılımı
Authors: Yamanus Ayşe Nur
Published: July 2024

Mâverâünnehir havzası gerek yetiştirdiği muhaddisler gerekse onların telif ettiği musannefât dolayısıyla hadis ilmi açısından son derece önemli bir coğrafyadır. Bünyesinde barındırdığı Semerkant, Buhârâ, Şâş ve Tirmiz gibi ilim merkezlerindeki hadis faaliyetleriyle erken dönemden itibaren dikkati çeken bir bölge olan Mâverâünnehir’e mensup hadis hafızı Ebû Saîd el-Heysem b. Küleyb eş-Şâşî (ö. 335/946), bölgedeki hadisçilik faaliyetleriyle öne çıkan bir alimdir. Kaynaklarda “Mâverâünnehir muhaddisi” diye tavsif edilen Heysem b. Küleyb eş-Şâşî’nin ilmî hayatı, hicrî üçüncü ve dördüncü asırda Mâverâünnehir ilim havzasındaki hadis çalışmalarının seyrine dair kesitler sunması bakımından güzel bir örnektir. Bölge dışına rihle yapması, meşhur hadis alimlerine talebelik etmesi, bazı önemli eserlerin râvîsi olması, Mâverâünnehirli muhaddislerden pek çoğunun yetişmesine katkıda bulunması, farklı beldelerden Mâverâünnehir’e rihle gerçekleştiren talebeler için adeta bir çekim merkezi oluşturması ve bir Müsned tasnif etmesi gibi yönleriyle Şâşî, hadis tarihinde mühim bir konuma sahiptir. Onun hadis mirası olan Müsned, asırlar boyu muhaddisler tarafından aktarılmak suretiyle farklı coğrafyalara intikal etmiştir. Şâşî’nin ilmî hayatının mercek altına alındığı ve onun telif ettiği Müsned’in hadis tarihindeki izinin sürüldüğü bu çalışmanın amacı, hicrî dördüncü asra ait Mâverâünnehir rivâyet birikiminin hadis tarihindeki yayılımına Şâşî ve eseri özelinde ışık tutmaktır.
KEDUDUKAN FATWA ULAMA DALAM SISITEM HUKUM NASIONAL DI INDONESIA
Authors: Rahmad Rahmad
Published: July 2024

Islamic economics was born simultaneously with the birth of the teachings of Islam itself starting from the Prophet Muhammad SAW became an apostle. Economic activity in Islam is also considered as an activity that aims to serve oneself to Allah SWT. Therefore, its principles and characteristics are in line with the main guidelines of Muslims, namely the Qur'an and Hadith. The principles and characteristics of Islamic economics are formulated in such a way that the realization of happiness, peace, comfort and justice for economic actors without neglecting the right to develop themselves. The main goal of Islamic economics is to achieve Falah or the fulfillment of needs and the creation of prosperity so as to give birth to happiness in the world and happiness in the Hereafter.
Public service performance in the distribution of cash assistance for female heads of poor households in Semarang City
Authors: Auliansyah Rahadian
Published: July 2024

Background: This paper discusses the performance of public services in the distribution of direct cash assistance (BLT) for female heads of poor households in Semarang City, focusing on the aspects of planning, implementation, and program impact. Methods: The research aims to analyze the effectiveness of the BLT program, evaluate solutions to challenges faced, and formulate recommendations for sustainable improvement. Findings: The research results show that thorough and responsive planning, transparent implementation, and innovative solutions can enhance public service performance. The BLT program has a positive impact on empowering female heads of households through economic strengthening and active participation. Semarang City has successfully created a model of successful public service, providing hope for a higher quality future for female heads of households. Conclusion: Recommendations include increasing digital literacy and evaluating gender-responsive policies to support inclusive and sustainable development. Novelty/Originality of this Study: The study uniquely highlights the specific challenges and successes in the distribution of Direct Cash Assistance (BLT) to female heads of poor households in Semarang City, emphasizing the importance of gender-responsive policies and the empowerment of women. Its originality lies in its detailed focus on planning, implementation, and impact analysis, providing a model for improving public service performance in similar urban settings.
Dynamics of Social Interaction, Social Support, and Psychological Well-Being in Urban Communities: Social Support Theory Perspective
Authors: . Suaib
Published: July 2024

This study aims to investigate the effect of Quality of Social Relationships on Social Welfare and Urban Community Quality of Life, using the Structural Equation Modeling (SEM) quantitative analysis method with the SMARTPLS tool.  This research method involves collecting data from 600 samples representing various backgrounds and characteristics of individuals in an urban environment.  The results showed that Quality of Social Relationships has a positive and significant influence on Social Welfare and Urban Community Quality of Life. The quality of strong and supportive social relationships is shown to play an important role in enhancing individual social welfare and improving the overall quality of life in urban communities. From the analysis using the SEM method with SMARTPLS, the findings suggest that social interaction, life satisfaction, social support, and the ability to adapt to environmental changes contribute positively to the quality of social relationships which in turn influence Social Welfare and Urban Community Quality of Life.  The implication of these findings is the need to consider the importance of strengthening the quality of social relationships in developing social policies and programs aimed at improving social welfare and quality of life in urban environments.
Becoming a Victim of Domestic Abuse and Partner’s Lack of Knowledge of Marriage Laws
Authors: Susanti Vinita , Riyadi Bambang Slamet
Published: July 2024

Domestic abuse with husbands as the offenders and wives as the victims shows that there is an imbalance of rights and obligations in living a married life, despite the rights and obligations of husband and wife are strictly regulated in Law Number 1 of 1974 concerning Marriage. As the offender of domestic abuse, a husband cannot escape from criminal sanctions that have been determined in Law Number 23 of 2004 concerning the Elimination of Domestic abuse. In response to domestic abuse, the author argued, using feminist research and a qualitative methodology, that women (wives) who killed their partners were also victims. Therefore, they shouldn't be imprisoned. This article discusses the public perspective of women who have homicidal as a response to domestic abuse by looking at the motivations behind their actions, rehabilitation tactics, forgiveness policies and protection programs for these women. After careful consideration, the author concludes that the Indonesian government should enact legislation to regulate alternative intervention programs for victims of domestic abuse who have killed their abusers.
Peningkatan Pengetahuan Tentang Komplikasi Hipertensi Beserta Pencegahannya
Authors: Suciana Fitri , Hidayati Istianna Nur , Daryani Daryani
Published: July 2024

Hipertensi merupakan masalah kesehatan Masyarakat yang sampai saat ini menduduki peringkat tertinggi karena telah terjadi pergeseran pola penyakit di Masyarakat yang awalnya penyakit infeksi menjadi penyakit degeneratif. Tingginya prevalensi penyakit degeneratif salah satunya adalah hipertensi. Hipertensi dapat disebabkan oleh beberapa faktor seperti gaya hidup, makanan siap saji, obesitas, merokok dan alkohol. Hipertensi yang tidak terkendali dapat menyebabkan ketidakmampuan fisik, gangguan psikososial, dan fungsi kognisi serta meningkatnya layanan kesehatan. Dan pada akhirnya dapat mengakibatkan komplikasi yang dapat mempengaruhi kualitas hidup penderita. Desa Manjung, Kecamatan Ngawen merupakan desa industri yang berada di Kabupaten Klaten dan merupakan desa penghasil soun terbesar di Jawa Tengah. Hal tersebut menjadi salah satu penyebab banyaknya kasus hipertensi di di desa tersebut. Banyak warga di desa Manjung yang tidak mengetahui komplikasi akibat hipertensi dan pencegahannya. Sehingga diperlukan pendidikan kesehatan tentang pengenalan komplikasi akibat hipertensi beserta pencegahannya. Luaran yang diharapkan dari kegiatan ini adalah pemahaman dan peningkatan pengetahuan serta perilaku warga dalam mengenal komplikasi akibat hipertensi serta mencegah terjadinya komplikasi tersebut.
Soczewkowanie grawitacyjne gwiazd bozonowych i fermionowych
Authors: Osarczuk Janusz
Published: July 2024

Boson stars and fermion stars may have formed in the early universe during a first-order gravitational phase transition. Perhaps some of them have survived till now.The search for them covers mainly the central parts of galaxies. Gravitational lensing is one of the observational methods that can help find them.
Effect of Soil Fertility on the Growth Characteristics of Two Young Trees of the Neem Family
Authors: Wang Wenyi , Ma Cong , Wang Yanhong
Published: July 2024

To select tree species suitable for growth under Chinese ephedra forests, this study set up three soil fertility treatments: pure sandy soil, V (sand): V (fertilizer) = 3:1, and V (sand): V (fertilizer) = 1:1, to investigate the effects of different soil fertility levels on the growth characteristics of two tree species, Azadirachta indica A. Juss (neem) and Melia azedarach (chinaberry). The results show that: (1) Under low light conditions and pure sandy soil, the height and basal diameter of neem significantly increased, while chinaberry showed a significant increase in height and basal diameter under the V (sand): V (fertilizer) = 1:1 condition. (2) Under the V (sand): V (fertilizer) = 1:1 condition, both neem and chinaberry exhibited maximum leaf growth characteristics, while there was a decreasing trend under the V (sand): V (fertilizer) = 3:1 condition. These results indicate that neem is more suitable for growth in pure sandy soil and is more tolerant to poor soil conditions, while chinaberry thrives under the V (sand): V (fertilizer) = 1:1 condition. This preliminary selection provides a theoretical basis for the initial screening of tree species for coastal defense forests.
The Construction Path of Service System for Special Groups in Grass-roots Cultural Center
Authors: Wei Zuojun
Published: July 2024

In the digital age, as an important institution to promote the popularization of social culture and enhance public cultural services, grass-roots cultural centers are facing new challenges in effectively serving special groups and promoting cultural inclusiveness and social equity. Based on the significance of the service system for special groups in the construction of grass-roots cultural centers, this paper puts forward some strategies, such as increasing capital investment, introducing new digital technologies, and actively cultivating and introducing cultural professionals, to solve the problems of limited capital investment, imperfect barrier-free facilities and shortage of cultural professionals in the service of special groups in grass-roots cultural centers. It provides theoretical guidance for the construction of the service system of grass-roots cultural libraries, and also provides a useful reference for promoting the diversity and inclusiveness of social culture.
Critical Notes - A USEFUL, HAPPY BENTHAM: WHO SAVED HIM FROM MILL? WHEN FREEDOM IS MORE THAN JUST A MATTER OF TASTE
Authors: ȘERBAN Oana ,   University of Bucharest, Faculty of Philosophy,   CCIIF – The Research Center for the History and Circulation of Philosophical Ideas
Published: July 2024

When it comes to Bentham, both pro- and anti-utilitarianists are profoundly challenged by the hedonist inheritance that has been deeply criticized, undermined, and somewhat overshadowed by the Millian perspective, which confined the presuppositions of a higher and clearer moral purism within the logical framework of satisfaction and happiness. Since the real test of Bentham’s philosophy lies in the requirements of asceticism, which are, at least at first glance, incompatible with hedonism, the major difficulty seems to be that of using both his moral writings and aesthetic considerations on pleasure and taste to face such a challenge. Would a Romantic Bentham still be valuable for the legacy of modern political philosophy? To what extent might literary figures rely on Bentham to save and protect free speech, and how much do theologians find the Benthamite perspectives on sympathies and antipathies, love and hate, acceptable? Should anyone save Bentham from being just an architect of the panopticon, by refashioning his philosophy as a pragmatic, more human, or even more altruistic utilitarianism than that of Mill, which invariably conquered the liberals? Could we defy reality for a moment, projecting a possible world in which a visit to a museum with Bentham would convince us that there is no such thing as good or bad taste, only a higher or lower amount of pleasure that we feel contemplating art and consuming culture? Finally, who could imagine Bentham happy?
Diálogos colaborativos para a formação na eja O contexto das relações de gênero
Authors: Rosa Naiara de Oliveira
Published: July 2024

O estudo correlaciona as relações de gênero com a Educação de Jovens e Adultos. Tivemos o objetivo de analisar as possibilidades de construção da temática gênero em conjunto com a EJA. O lócus do estudo foi uma escola municipal com a colaboração dos discentes e o docente da turma de EJA. E com a finalidade de compartilharmos espaços dialógicos da temática, optamos por uma pesquisa de metodologia colaborativa. Como estratégia para produção de dados, realizamos sessão coletiva de diálogo com os princípios da colaboração e da pesquisa-formação. Logo, o estudo demonstra possibilidades formativas da temática na escola; dialógicos estabelecidos viabilizaram desvelar nos dizeres dos/as partícipes, suas relações familiares, domésticas e profissionais literalmente conectadas a temática. Concluímos que, em colaboração com os sujeitos da EJA, foram provocadas sensações que fazem refletir sobre a pertinência e a essência formativa da temática.
REFLECTION OF THE PROBLEM OF COMPETENT APPROACH AND DIGITALIZATION IN WORK I. BEKBOEVA IN THE 70s OF THE XX CENTURY
Authors: Isakov T. E.
Published: July 2024

In the modern education system, the main core of education is the Bologna process, credit technology of education, competency-based approach, competence and digitalization. It is known that back in the second half of the 20th century these issues were implemented in the education of our country. It's just that most of the terms were used under different names. This article analyzes and explores the representation of the competency-based method and issues of digitalization in the works of Isak Bekboev, Doctor of Pedagogical Sciences, professor, corresponding member of the National Academy of the Kyrgyz Republic, people's teacher of the Kyrgyz Republic in the 70s of the XX century. For this purpose, some of the works of I. Bekboev dating back to that time were analyzed, their meaning was compared with modern issues, and proposals were developed. We believe that the results of these studyies will not leave a wide range of readers indifferent.
THE POLITICS OF FEAR: FABRICATING THE ENDANGERMENT OF THE SERBIAN MINORITY IN KOSOVO AS AN EXPANSIONIST STRATEGY FOR SERBIA
Authors: Elshani Taulant
Published: July 2024

This study investigates the methods used by Serbia to maintain influence over the Serbian minority in Kosovo, exploring the potential use of these strategies to further Serbia's regional ambitions in the Western Balkans. The research focuses on various tactics such as media narratives and political maneuvers, aiming to understand their role in Serbia's strategic goals. By analyzing contemporary practices alongside historical cases, such as Serbia's narratives during the early 1990s conflicts in Bosnia and Herzegovina and Croatia, this study draws parallels to discern behavioral patterns. Additionally, comparative case studies of Nazi Germany's use of propaganda about the Sudeten Germans and Russia in the Crimea provide a broader context of state-led ethnic manipulation. This research contributes to understanding how ethnic dynamics are used for political gain in volatile regions.
Analýza objemu zákonov - odhalenie spiaceho potenciálu
Authors: Zeman Jakub , Škoda Jakub
Published: July 2024

Zložitosť administratívnych procesov a rýchlo sa meniaca legislatíva sú na Slovensku najvýznamnejšími problémami pri podnikaní. Tieto dve oblasti sa viac ako 10 rokov v meraniach Eurobarometra umiestňujú na prvých 2 priečkach, pred problémami s vymáhaním dlhov, daňovými sadzbami, infraštruktúrou, či korupciou. Podnikatelia na Slovensku zároveň oveľa negatívnejšie vnímajú obe tieto oblasti ako podnikatelia v ostatných členských štátoch EÚ. Posledných sedem slovenských vlád, vrátane súčasnej, vo svojich Programových vyhláseniach deklarovali úsilie o „stabilizáciu podnikateľského prostredia“ založenú najmä na „odstraňovaní neprimeranej administratívnej záťaže.“ Zaväzovali sa reformovať byrokraciu, znížiť počet regulácií, zlepšiť podnikateľské prostredie či tvoriť zákony pre ľudí. INESS vo svojej štúdii pripravil kvantitatívnu analýzu časti slovenskej legislatívy. V oblastiach podnikateľské prostredie, zdravotníctvo a školstvo sme celkovo analyzovali 10 najvýznamnejších zákonov. Sledovali sme dva kľúčové ukazovatele: počet slov a priemernú dĺžku viet. Zistili sme, že dochádza k systematickému znižovaniu zrozumiteľnosti legislatívy v oblasti podnikateľského prostredia, zdravotníctva a školstva. Výsledky si môžete pozrieť v publikácii Analýza objemu zákonov - odhalenie spiaceho potenciálu.
Collaborative Strategies for Enhancing Child Protection Practices in Pre-Primary Schools: A Case Study of Kira Municipality, Uganda
Authors:   Kyambogo University, Mutumba Safina , Busingye Sr Evangelista , Samson Maani John
Published: July 2024

Child protection practices are measures and interventions intended to safeguard children against violence in school. These practices create safe environments that enable children to thrive. Some of these include the prevention of child abuse and neglect. Child protection agencies’ collaboration is a partnership that supports children’s well-being. This study investigated the contribution of child protection agencies’ collaboration on protection practices in Pre-primary schools in Kira Municipality, which has continued to be challenging. This study was informed by the social capital theory emphasizing the significance of social relationships, trust, and mutuality. The study used a descriptive cross-sectional survey design, and data was collected using quantitative and qualitative tools. These included document analysis checklists, interview guides, observation checklists, and questionnaires. The respondents included headteachers, Centre Management Committee members, parents, Local Council members, and Probation officers. The results indicated that schools rarely collaborated with child protection agencies to ensure that protection practices were implemented in pre-primary schools. In contrast, the probation officers reported that the schools didn’t involve them during the planning, though it was when they would know the areas for collaboration. Four significant recommendations for improving child protection practices are given. Child protection workers need to jointly develop plans that promote child safety and protection, train and build the capacity of educators on issues of child protection, increase resources and financial support to promote child safety and protection, and finally, advocate for laws and policies that promote children’s rights.
Burnout, stress traumatique secondaire et détresse psychologique chez les intervenant(e)s et les gestionnaires dans le milieu communautaire au Québec. Portrait de la situation pendant la pandémie de la COVID-19
Authors: Truong Alexis H , Le Pain Isabelle , Malone Anthony , Larose-Hébert Katharine , Gauthier Véronique , Deblois Dominique
Published: July 2024

Objectifs Cet article s’intéresse aux difficultés émotionnelles (DÉ) vécues par les intervenant(e)s et les gestionnaires oeuvrant dans 3 regroupements d’organisations communautaires (santé mentale, itinérance et pour personnes handicapées) durant la pandémie de la COVID-19 au Québec. Plus spécifiquement, nous documentons les manifestions, parfois concomitantes, de burnout (BO), de stress traumatique secondaire (STS) et de détresse psychologique (DP) rapportées par les participant(e)s. Une comparaison est aussi effectuée entre les participant(e)s qui ont rapporté jouer un rôle de gestion ou non.

Méthode Les analyses reposent sur les réponses de près de 300 personnes à un questionnaire en ligne qui comportait 140 items, incluant des échelles sur les risques psychosociaux, la qualité de vie professionnelle et la DP.

Résultats Nos résultats montrent qu’une majorité de participant(e)s souffrent de DÉ, vivant parfois un niveau de BO, de STS moyen ou de DP élevé, ou une combinaison de 2 ou 3 difficultés de façon concomitante. Les chances d’obtenir un résultat plus élevé pour le BO et la DP étaient plus élevées chez les personnes qui avaient un rôle de gestion que celles qui n’en avaient pas.

Conclusion Contrairement à la tendance qui se concentre sur l’amélioration des capacités d’adaptation individuelle au stress, les DÉ vécues par les intervenant(e)s constituent des enjeux collectifs qui requièrent à cet effet des solutions collectives. Deux limites sont la question de la représentativité de l’échantillon, ainsi que la façon dont celui-ci pourrait aussi refléter ou non la réalité des intervenant(e)s travaillant dans le réseau public au Québec ou dans ce champ ailleurs au Canada.
Reconciling the Ledger: The Rupert’s Land Purchase, Settler Capitalism, and Indigenous Dispossession on the Prairies
Authors: McKenzie Elizabeth , Mosby Ian
Published: July 2024

This article examines one of the greatest land grabs in history and what may represent one of the single greatest transfers of wealth from Indigenous peoples to a private company: the so-called Rupert’s Land Purchase of 1870. By comparing the lands and money given to the Hudson’s Bay Company following Confederation for the transfer of Rupert’s Land to Canada with the lands and money set aside for First Nations signatories of Treaties 1–7 (1871–77) and the Métis Nation under the Manitoba Act of 1870, we attempt to establish what this looked like in material terms. In addition to highlighting the scale of wealth dispossession that occurred in both quantitative and qualitative terms, this article is primarily concerned with Canada’s actual implementation of these agreements. In recognizing the treaties beyond their written documents, this article seeks to challenge some of the popular narratives surrounding the Rupert’s Land Purchase and its significance in histories of stolen Indigenous land and wealth.
Resistances, Relationships, and True Community: Sikhs (Asian-Canadians?) in BC’s Lower Mainland
Authors: Kaur Sandhra Sharanjit
Published: July 2024

This article looks at the experience of Sikh Canadians in British Columbia’s lower mainland. First, I offer a critique of how and where their stories and histories fit within broader academic explorations of “Asian Canadian” themes. I then examine erasures in the archive connected to the building of the oldest still-standing gurdwara in the western hemisphere, the Gur Sikh Temple. The building of this Sikh sacred space offers several markers of resistance, including those that focus on relationships between different Asian Canadian communities as opposed to seeing resistance in relationship to whiteness only.
GABA-immunoreactivity in Neuroepithelial Bodies of Spontaneously Hypertensive Rats
Authors: Stamenov Nikola , Atanasova Dimitrinka , Dandov Angel , Jelev Lazar , Lazarov Nikolai
Published: July 2024

Neuroepithelial bodies (NEBs) are complex sensory receptors dispersed throughout the intrapulmonary airways. They are composed of pulmonary neuroendocrine cells (PNECs) which have a large amount of dense-core vesicles containing calcitonin gene-related peptide (CGRP), serotonin (5HT), substance P (SP) and δ-aminobutyric acid (GABA). NEBs are densely innervated by vagal sensory terminals, dorsal root afferents and intrinsic motor fibres. Their location, neurochemical composition and dense innervation make NEBs a key component for the regulation of lung homeostasis.
Pulmonary arterial hypertension is a rare disease characterized by morphological alterations in the microcirculation of the lungs causing a wide array of complications and high mortality. Spontaneously hypertensive rats (SHRs) are a common model for essential hypertension, that may develop secondary pulmonary hypertension and thus can be used as an animal model to study pulmonary pressure changes.
The present study focuses on the immunohistochemical demonstration of GABA in the NEBs and its potential role in the regulation of the pulmonary pressure. Two groups of SHRs were used and age-matched normotensive Wistar Kyoto (WKY) rats served as controls. We found single PNECs and clusters of GABA-immunoreactive cells protruding into the lumen of the intrapulmonary airways in all examined groups of SHRs and in the normotensive WKY rats. However, the expressional levels statistically differed within the two age groups of SHRs and the controls. Specifically, the NEBs and PNECs in 1-month-old SHRs and particularly in 3-month-old SHRs showed more intense GABA-immunostaining compared to the WKY rats.
In conclusion, NEBs and PNECs react to the alterations of the pulmonary pressure homeostasis by an increased GABA expression as a preventive or reactive regulation mechanism against developing pulmonary hypertension.
MotorNet, a Python toolbox for controlling differentiable biomechanical effectors with artificial neural networks
Authors: Codol Olivier , Michaels Jonathan A , Kashefi Mehrdad , Pruszynski J Andrew , Gribble Paul L
Published: July 2024

Artificial neural networks (ANNs) are a powerful class of computational models for unravelling neural mechanisms of brain function. However, for neural control of movement, they currently must be integrated with software simulating biomechanical effectors, leading to limiting impracticalities: (1) researchers must rely on two different platforms and (2) biomechanical effectors are not generally differentiable, constraining researchers to reinforcement learning algorithms despite the existence and potential biological relevance of faster training methods. To address these limitations, we developed MotorNet, an open-source Python toolbox for creating arbitrarily complex, differentiable, and biomechanically realistic effectors that can be trained on user-defined motor tasks using ANNs. MotorNet is designed to meet several goals: ease of installation, ease of use, a high-level user-friendly application programming interface, and a modular architecture to allow for flexibility in model building. MotorNet requires no dependencies outside Python, making it easy to get started with. For instance, it allows training ANNs on typically used motor control models such as a two joint, six muscle, planar arm within minutes on a typical desktop computer. MotorNet is built on PyTorch and therefore can implement any network architecture that is possible using the PyTorch framework. Consequently, it will immediately benefit from advances in artificial intelligence through PyTorch updates. Finally, it is open source, enabling users to create and share their own improvements, such as new effector and network architectures or custom task designs. MotorNet’s focus on higher-order model and task design will alleviate overhead cost to initiate computational projects for new researchers by providing a standalone, ready-to-go framework, and speed up efforts of established computational teams by enabling a focus on concepts and ideas over implementation.
A robust method for measuring aminoacylation through tRNA-Seq
Authors: Davidsen Kristian , Sullivan Lucas B
Published: July 2024

Current methods to quantify the fraction of aminoacylated tRNAs, also known as the tRNA charge, are limited by issues with either low throughput, precision, and/or accuracy. Here, we present an optimized charge transfer RNA sequencing (tRNA-Seq) method that combines previous developments with newly described approaches to establish a protocol for precise and accurate tRNA charge measurements. We verify that this protocol provides robust quantification of tRNA aminoacylation and we provide an end-to-end method that scales to hundreds of samples including software for data processing. Additionally, we show that this method supports measurements of relative tRNA expression levels and can be used to infer tRNA modifications through reverse transcription misincorporations, thereby supporting multipurpose applications in tRNA biology.
Divergent folding-mediated epistasis among unstable membrane protein variants
Authors: Chamness Laura M , Kuntz Charles P , McKee Andrew G , Penn Wesley D , Hemmerich Christopher M , Rusch Douglas B , Woods Hope , Dyotima  , Meiler Jens , Schlebach Jonathan P
Published: July 2024

Many membrane proteins are prone to misfolding, which compromises their functional expression at the plasma membrane. This is particularly true for the mammalian gonadotropin-releasing hormone receptor GPCRs (GnRHR). We recently demonstrated that evolutionary GnRHR modifications appear to have coincided with adaptive changes in cotranslational folding efficiency. Though protein stability is known to shape evolution, it is unclear how cotranslational folding constraints modulate the synergistic, epistatic interactions between mutations. We therefore compared the pairwise interactions formed by mutations that disrupt the membrane topology (V276T) or tertiary structure (W107A) of GnRHR. Using deep mutational scanning, we evaluated how the plasma membrane expression of these variants is modified by hundreds of secondary mutations. An analysis of 251 mutants in three genetic backgrounds reveals that V276T and W107A form distinct epistatic interactions that depend on both the severity and the mechanism of destabilization. V276T forms predominantly negative epistatic interactions with destabilizing mutations in soluble loops. In contrast, W107A forms positive interactions with mutations in both loops and transmembrane domains that reflect the diminishing impacts of the destabilizing mutations in variants that are already unstable. These findings reveal how epistasis is remodeled by conformational defects in membrane proteins and in unstable proteins more generally.
The Bacterial Quorum-Sensing Signal 2-Aminoacetophenone Rewires Immune Cell Bioenergetics through the PGC-1α/ERRα Axis to Mediate Tolerance to Infection
Authors: Chakraborty Arijit , Bandyopadhaya Arunava , Singh Vijay K , Kovacic Filip , Cha Sujin , Oldham William M , Tzika A Aria , Rahme Laurence G
Published: July 2024

How bacterial pathogens exploit host metabolism to promote immune tolerance and persist in infected hosts remains elusive. To achieve this, we show that
Pseudomonas aeruginosa (PA),
a recalcitrant pathogen, utilizes the quorum sensing (QS) signal 2-aminoacetophenone (2-AA). Here, we unveil how 2-AA-driven immune tolerization causes distinct metabolic perturbations in macrophages’ mitochondrial respiration and bioenergetics. We present evidence indicating that these effects stem from decreased pyruvate transport into mitochondria. This reduction is attributed to decreased expression of the mitochondrial pyruvate carrier (MPC1), which is mediated by diminished expression and nuclear presence of its transcriptional regulator, estrogen-related nuclear receptor alpha (ERRα). Consequently, ERRα exhibits weakened binding to the MPC1 promoter. This outcome arises from the impaired interaction between ERRα and the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Ultimately, this cascade results in diminished pyruvate influx into mitochondria and, consequently reduced ATP production in tolerized macrophages. Exogenously added ATP in infected macrophages restores the transcript levels of
MPC1
and
ERR-
α
and
enhances cytokine production and intracellular bacterial clearance. Consistent with the
in vitro
findings, murine infection studies corroborate the 2-AA-mediated long-lasting decrease in ATP and acetyl-CoA and its association with
PA
persistence, further supporting this QS signaling molecule as the culprit of the host bioenergetic alterations and
PA
persistence. These findings unveil 2-AA as a modulator of cellular immunometabolism and reveal an unprecedented mechanism of host tolerance to infection involving the PGC-1α/ERRα axis in its influence on MPC1/OXPHOS-dependent energy production and
PA
clearance. These paradigmatic findings pave the way for developing treatments to bolster host resilience to pathogen-induced damage. Given that QS is a common characteristic of prokaryotes, it is likely that 2-AA-like molecules with similar functions may be present in other pathogens.
A split-GAL4 driver line resource for Drosophila neuron types
Authors: Meissner Geoffrey W , Vannan Allison , Jeter Jennifer , Close Kari , DePasquale Gina M , Dorman Zachary , Forster Kaitlyn , Beringer Jaye Anne , Gibney Theresa , Hausenfluck Joanna H , He Yisheng , Henderson Kristin , Johnson Lauren , Johnston Rebecca M , Ihrke Gudrun , Iyer Nirmala A , Lazarus Rachel , Lee Kelley , Li Hsing-Hsi , Liaw Hua-Peng , Melton Brian , Miller Scott , Motaher Reeham , Novak Alexandra , Ogundeyi Omotara , Petruncio Alyson , Price Jacquelyn , Protopapas Sophia , Tae Susana , Taylor Jennifer , Vorimo Rebecca , Yarbrough Brianna , Zeng Kevin Xiankun , Zugates Christopher T , Dionne Heather , Angstadt Claire , Ashley Kelly , Cavallaro Amanda , Dang Tam , Gonzalez Guillermo A , Hibbard Karen L , Huang Cuizhen , Kao Jui-Chun , Laverty Todd , Mercer Monti , Perez Brenda , Pitts Scarlett Rose , Ruiz Danielle , Vallanadu Viruthika , Zheng Grace Zhiyu , Goina Cristian , Otsuna Hideo , Rokicki Konrad , Svirskas Robert R , Cheong Han SJ , Dolan Michael-John , Ehrhardt Erica , Feng Kai , Galfi Basel EI , Goldammer Jens , Huston Stephen J , Hu Nan , Ito Masayoshi , McKellar Claire , Minegishi Ryo , Namiki Shigehiro , Nern Aljoscha , Schretter Catherine E , Sterne Gabriella R , Venkatasubramanian Lalanti , Wang Kaiyu , Wolff Tanya , Wu Ming , George Reed , Malkesman Oz , Aso Yoshinori , Card Gwyneth M , Dickson Barry J , Korff Wyatt , Ito Kei , Truman James W , Zlatic Marta , Rubin Gerald M ,   FlyLight Project Team
Published: July 2024

Techniques that enable precise manipulations of subsets of neurons in the fly central nervous system (CNS) have greatly facilitated our understanding of the neural basis of behavior. Split-GAL4 driver lines allow specific targeting of cell types in Drosophila melanogaster and other species. We describe here a collection of 3060 lines targeting a range of cell types in the adult Drosophila CNS and 1373 lines characterized in third-instar larvae. These tools enable functional, transcriptomic, and proteomic studies based on precise anatomical targeting. NeuronBridge and other search tools relate light microscopy images of these split-GAL4 lines to connectomes reconstructed from electron microscopy images. The collections are the result of screening over 77,000 split hemidriver combinations. Previously published and new lines are included, all validated for driver expression and curated for optimal cell-type specificity across diverse cell types. In addition to images and fly stocks for these well-characterized lines, we make available 300,000 new 3D images of other split-GAL4 lines.
Untangling stability and gain modulation in cortical circuits with multiple interneuron classes
Authors: Bos Hannah , Miehl Christoph , Oswald Anne-Marie , Doiron Brent
Published: July 2024

Synaptic inhibition is the mechanistic backbone of a suite of cortical functions, not the least of which are maintaining network stability and modulating neuronal gain. In cortical models with a single inhibitory neuron class, network stabilization and gain control work in opposition to one another – meaning high gain coincides with low stability and vice versa. It is now clear that cortical inhibition is diverse, with molecularly distinguished cell classes having distinct positions within the cortical circuit. We analyze circuit models with pyramidal neurons (E) as well as parvalbumin (PV) and somatostatin (SOM) expressing interneurons. We show when E – PV networks recurrently connect with SOM neurons then an SOM mediated modulation that leads to increased neuronal gain can also yield increased network stability. Our work exposes how the impact of an inhibition mediated modulation depends critically on how inhibition is recruited from within the circuit.
Control glucémico y estudio del metabolismo lipídico y del óseo en niños con diabetes de tipo 1
Authors: Calmarza Pilar , Pérez-Ajami Rasha Isabel , Prieto-López Carlos , Gallego-Rojo Alba , García-Carro Celia , Lou-Francés Graciela María
Published: July 2024

Introducción. La diabetes mellitus de tipo 1 se considera una de las enfermedades crónicas más frecuentes de la infancia. Es un factor de gran riesgo de desarrollar enfermedad cardiovascular temprana y afecta también la salud ósea.Objetivo. Describir las características demográficas y los parámetros bioquímicos de una población de niños con diabetes de tipo 1, supervisados en la unidad pediátrica de diabetes de un hospital español de tercer nivel.Materiales y métodos. En este estudio retrospectivo, se determinaron los parámetros de control metabólico, lipídico y óseo en 124 niños con diabetes de tipo 1, a los que se hizo seguimiento en la Unidad Pediátrica de Diabetes del Hospital Universitario Miguel Servet de Zaragoza, desde mayo del 2020 hasta julio del 2021.Resultados. Los niños con diabetes de tipo 1 presentan peor control metabólico de la enfermedad en la pubertad, pero su control lipídico se puede considerar aceptable. Existe una correlación inversa de los marcadores de formación ósea con el tiempo de evolución de la enfermedad, así como con el control metabólico.Conclusión. Los marcadores de formación ósea se encuentran correlacionados de forma inversa con el porcentaje de hemoglobina glicosilada y con el tiempo de evolución de la diabetes. En estos pacientes, el perfil lipídico y el óseo son más favorables cuando existe un buen control metabólico de la enfermedad.
Factores relacionados con la mortalidad en pacientes con enfermedad pulmonar obstructiva crónica en población colombiana
Authors: Tuta-Quintero Eduardo , Bastidas Alirio R. , Giraldo-Cadavid Luis F. , Echeverri Juliana , Botero Juan D. , Villarreal Valentina , Zambrano Camila , Rabe Valeria , Hernández Juan , Tavera Daniel , Acosta Juan , Martínez Ángela , Granados Carlos , Nieto María , Román Sergio E. , Achry William A. , Guezguan-Pérez Jonathan , Prieto Paula , Parra-Cárdenas Diana
Published: July 2024

Introducción. En los países de medianos y bajos ingresos, los datos sobre la mortalidad y los factores de riesgo en pacientes con enfermedad pulmonar obstructiva crónica son limitados.Objetivo. Identificar la incidencia de muerte y sus variables relacionadas en una población colombiana durante 12 meses de seguimiento.Materiales y métodos. Se llevó a cabo un estudio retrospectivo de sujetos con diagnóstico de enfermedad pulmonar obstructiva crónica en una clínica de tercer nivel en Colombia. Los cocientes de probabilidades se calcularon mediante un análisis de regresión logística multivariable con la variable de resultado “mortalidad a los 12 meses”.Resultados. Ingresaron 524 pacientes, de los cuales el 18,1 % (95 / 524) murió. La edad promedio fue de 69,7 (DE = 8,92) y el 59,2 % (310 / 524) eran mujeres. Las variables asociadas con la mortalidad fueron la edad (OR = 6,54; IC95%: 3,65-11,36; p < 0,001), años de exposición al humo de leña (OR = 4,59; IC95%: 1,64-12,82; p = 0,002), insuficiencia cardiaca crónica (OR = 1,81; IC95%: 1,13-2,91; p = 0,014), enfermedad cerebrovascular (OR = 3,35; IC95%: 1,04-10,75; p = 0,032) y enfermedad renal crónica (OR=6,96; IC 95%:1,15-41,67; p = 0,015). Al ajustar las variables en el análisis multivariado únicamente se mostró asociación entre el sexo (OR = 1,55; IC95%: 0,95-2,54; p = 0,008) y la edad (OR = 5,94; IC95%: 3,3-10,69; p < 0,001).Conclusión. La edad, los años de exposición al humo de leña, la insuficiencia cardiaca crónica, la enfermedad cerebrovascular y la renal crónica fueron variables clínicas asociadas a un desenlace fatal. Sin embargo, la edad y el sexo fueron las únicas relacionadas con la mortalidad al ajustarlas por factores de confusión.
Development of a web application to evaluate spirometric curve and clinical variables to support COPD diagnosis in primary care
Authors: Maldonado-Franco Adriana , Giraldo-Cadavid Luis F. , Tuta-Quintero Eduardo , Bastidas Alirio R. , Moreno-Giraldo Angélica , Botero-Rosas Daniel A.
Published: July 2024

Introduction. Choric obstructive pulmonary disease (COPD) is the third mortality cause in the world, and the development of useful diagnostic tools is necessary to improve timely diagnostic rates in primary care settings.Objective. To develop a web application displaying spirometric and clinical information – including respiratory symptoms and risk factors– to facilitate a COPD diagnosis.Materials and methods. In this cross-sectional study, an expert consensus was carried out with three specialists using the Delphi method to choose the relevant variables for COPD diagnosis. We developed a Python-based web application to diagnose COPD, displaying the clinical variables deemed relevant by the experts along the spirometric curve. Results. Twenty-six clinical variables were included in the web application for the diagnosis of COPD. A fourth expert used the web application to classify a cohort of 695 patients who had undergone spirometry in a third-level centre and had answered at least one of five questionnaires for COPD screening. Out of the 695 subjects, 34% had COPD, according to the expert that diagnosed them using the web application. Only 42% of the patients in the COPD group had received a previous COPD diagnosis and 19% of the patients in the no COPD group had been misdiagnosed with the disease.Conclusion. We developed a web application that displays demographic and clinical information, as well as spirometric data, to facilitate the process of diagnosing COPD in primary care settings.
La soledad como predictor de mortalidad en pacientes con cáncer, un estudio de cohorte
Authors: Valdelamar Adriana , De La Hoz Fernando , Sánchez Ricardo
Published: July 2024

Introducción. Algunos estudios han señalado que la soledad podría estar relacionada con un aumento en el riesgo de mortalidad en pacientes con cáncer ya que puede debilitar la respuesta al tratamiento y del sistema inmunológico y promover comportamientos perjudiciales, lo que puede empeorar el pronóstico y aumentar la probabilidad de muerte en estos pacientes. El abordar la soledad en la salud pública es esencial para brindar apoyo social y mejorar los resultados en los pacientes con cáncer.Objetivo. Obtener un estimador de la asociación soledad no deseada – mortalidad en pacientes con cáncer.Materiales y métodos. Se le hizo el seguimiento durante dos años a una cohorte prospectiva de 400 pacientes (exposición=niveles de soledad; desenlace=tiempo hasta la muerte). Se incluyeron variables de control sociodemográficas y clínicas. Se utilizó un modelo de supervivencia paramétrico (log normal).Resultados. En la cohorte se encontró una mediana de supervivencia de 20,2 meses y una tasa de mortalidad de 3,2 muertes por 100 pacientes-mes (IC95 %: 2,8 a 3,7). En el modelo de supervivencia se encontraron las siguientes razones de tiempo (RT): nivel moderado-nivel bajo: RT=0,55; IC95 %: 0,39 a 0,77; nivel moderadamente alto-nivel bajo: RT=0,62; IC95 %: 0.41 a 0.93; nivel alto-nivel bajo: RT=1,17; IC95 %: 0,31 a 4,42. Conclusión. En comparación con los pacientes con niveles bajos de soledad, los pacientes con niveles moderados o moderadamente altos llegan más rápidamente a la muerte (RT estadísticamente significativas, habiendo ajustado por el efecto de las demás variables del modelo). Esto sugiere la utilidad de las intervenciones para mitigar la soledad y promover el apoyo social en los pacientes con cáncer.
Síndrome de feocromocitoma-paraganglioma de tipo 5 como causa de hipertensión arterial en una paciente colombiana: reporte de caso
Authors: Morales Juan , Arturo Daniela , Folleco Miguel
Published: July 2024

El feocromocitoma es un tumor derivado de las células de la cresta neural con la capacidad de producir sustancias simpaticomiméticas y, por ende, un cuadro clínico particular. Causa menos del 1 % de los casos de hipertensión arterial sistémica y su incidencia se estima entre 0,4 y 0,6 casos por 100.000 personas cada año, con una supervivencia media de siete años. De todos los tumores sólidos, el feocromocitoma tiene un mayor componente genético, que puede heredarse hasta en el 40 % de los casos. Una vez diagnosticada la enfermedad, se debe definir el tratamiento y el pronóstico, en parte condicionados por las variantes genéticas asociadas, en especial RET, SDHx, VHL y NF1.Se presenta el caso de una mujer joven con dolor abdominal e hipertensión arterial sistémica, a quien se le diagnosticó feocromocitoma. Al secuenciar el exoma, se identificó una variante patogénica extremadamente rara y de reciente descubrimiento: SDHA: c.1A>C (p.Met1Leu). La paciente respondió adecuadamente al tratamiento quirúrgico y continuó en seguimiento sin recurrencias.El abordaje diagnóstico de los pacientes con feocromocitoma comienza con la sospecha clínica, seguida de la medición de determinados metabolitos en sangre y orina, y, finalmente, los estudios de imagenología. Los desarrollos tecnológicos actuales permiten la aplicación de la medicina de precisión en este campo. En este caso de feocromocitoma, se identificó un componente genético importante que no solo afecta al paciente, sino también, a sus familiares. La tamización adecuada del caso índice permite identificar mutaciones y caracterizar mejor la enfermedad.