bluuebunny/crossref_metadata_2025 huggingface dataset:
PENENTUAN NILAI ERODIBILITAS TANAH PADA KEMIRINGAN LERENG DI ATAS 15% PADA DAS JENELATA KABUPATEN GOWA PROVINSI SULAWESI SELATAN
Authors: Al Muamalah A. Syawal , Tjoneng Amir , Syarif Muhammad Munawir
Published: June 2024

This research was conducted from February 2022 to March 2022. This research uses the Wischmeier Method (1978) to calculate the Erodibility Value of Soil on Slope Slopes above 15%. Research conducted in the Jenelata watershed in determining the value of K shows that there are variations in the level of soil erodibility in the study area and it is known that the level of soil erodibility consists of high, rather high, medium and low levels. The low value of soil erodibility on rather steep and very steep slopes on land units U13, U2, and U6 with soil types Typic Eutrudepts, Fluvaquentic Endoaquepts then followed by soil types Typic Haplustepts having values of 0.12; 0.15 and 0.22; The influence of the low value of soil erodibility on slopes above 15% is caused by the high content of soil permeability with an average of 31.37 cm/hour with a fast rating, and the low content of fine sand which is an average of 7.43, dust on average with an average of 62.72 and an average high clay content of 124.25 , so erodibility which is the ability of the soil to withstand erosion that occurs and has a low soil erodibility value but is on a rather steep, steep to very steep slope but still has a possibility of erosion. It is known that land units U1 and U11 have the highest K values with Inceptisol soil types on steep to very steep slopes of 42% to 62%. Based on the results, it can be concluded that, the erodibility value of the soil in the Jenelata watershed, Gowa Regency with several land units on the Slope Slope above 15%, namely slightly steep, steep to very steep, varying from low to high level with a value of 0.12 – 0, 53. The influence of slope is not the main factor of the magnitude of the erodibility value that occurs but there is a role or influence of the physical properties of the soil, including: texture, organic matter, structure and permeability.
Effect of the Large Magellanic Cloud on the kinematics of Milky Way satellites and virial mass estimate
Authors: Kravtsov Andrey , Winney Sophia
Published: June 2024

We present a study illustrating the effects of the passage of a Large Magellanic Cloud (LMC) mass satellite on the distance and velocity distributions of satellites in Λ+Cold Dark Matter simulations of Milky Way (MW) sized halos. In agreement with previous studies, we find that during such a passage the velocity distribution develops a high-velocity tail, which can bias velocity-based virial halo mass estimates. When the velocity distribution of MW satellites is corrected for effects of the LMC passage, it is consistent with the distributions in halos of masses as low as and as high as 1.5×1012M⊙. We present a new halo mass estimator , where c is the coefficient calibrated using satellite systems in the simulated MW-sized halos, is the variance of 3D velocities taken with the sign of the radial velocity of each satellite, and is the median halocentric distance of the satellites. We show that the estimator has only s=8% scatter around the median relation of the estimated and true halo masses and deviates by <2s from the median during the pericentric passage of an LMC-like subhalo. This is because and deviate in the opposite directions during such passages. We apply the estimator to the MW satellite system and estimate the virial mass of the Milky Way of , in good agreement with several recent estimates using other methods.
Semantic Segmentation of Solar Radio Spikes at Low Frequencies
Authors: Murphy Pearse C , Aicardi Stéphane , Cecconi Baptiste , Briand Carine , Peccoux Thibault
Published: June 2024

Solar radio spikes are short lived, narrow bandwidth features in low frequency solar radio observations. The timing of their occurrence and the number of spikes in a given observation is often unpredictable. The high temporal and frequency of resolution of modern radio telescopes such as NenuFAR mean that manually identifying radio spikes is an arduous task. Machine learning approaches to data exploration in solar radio data is on the rise. Here we describe a convolutional neural network to identify the per pixel location of radio spikes as well as determine some simple characteristics of duration, spectral width and drift rate. The model, which we call SpikeNet, was trained using an Nvidia Tesla T4 16GB GPU with ~100000 sample spikes in a total time of 2.2 hours. The segmentation performs well with an intersection over union in the test set of ~0.85. The root mean squared error for predicted spike properties is of the order of 23%. Applying the algorithm to unlabelled data successfully generates segmentation masks although the accuracy of the predicted properties is less reliable, particularly when more than one spike is present in the same 64 X 64 pixel time-frequency range. We have successfully demonstrated that our convolutional neural network can locate and characterise solar radio spikes in a number of seconds compared to the weeks it would take for manual identification.
Comparative analysis of Eastern and Western European investment activity models
Authors: Sazanova Svetlana L.
Published: June 2024

Investments and investment activities play a leading role in the development of modern countries. The outflow of capital from the country and the decline in investment activity are the factors hindering its development in the short and long term. The influx of capital and expansion of investment activity, on the contrary, is a stimulus for economic development. Investment activity is influenced by many factors, the least studied of which are historical prerequisites, motives, incentives, goals, sources of financing and other aspects of investment activity. The analysis of investment activity as a modern economic phenomenon needs to be supplemented with historical and economic analysis for identifying the characteristics of investment activity in different regions of the world. This, in turn, will make possible to establish the historically established features of investment activity in Russia, understand the relationship of motives and incentives for investing in Russia, and formulate recommendations for improving investment activity in Russia. The purpose of the study is to identify patterns of investment activity formed during the period of Antiquity and the Middle Ages in three regions of the world: the East (using the example of Ancient Egypt, Ancient Babylon, Ancient China and Ancient India), Western Europe (using the example of Ancient Greece, Ancient Rome and Medieval Europe) and Russia. To achieve this goal, the following tasks were solved: the historical and economic prerequisites for the formation and development of investment activity in the states of the Ancient East, Antiquity, European countries and Russia were identified during the Middle Ages, modern and contemporary times. Differences were established in goals, sources of financing, actors, objects and other aspects of investment activity. The research methodology includes the method of historical and economic research, the historical and retrospective method, the method of historical and economic reconstruction, the method of comparative analysis, elements of a system method and others. The novelty of the research results lies in the substantiation of the historically established Eastern, Western European and Russian models of investment activity.
Strategic automotive alliance of Russia and China: opportunities and risks
Authors: Lebedev Kirill K.
Published: June 2024

The period of active development of the Russian automotive industry from the late 1990s to 2021 ended with the complete shutdown of all assembly plants of automakers from the USA, Japan, South Korea and the countries Europe. As part of the sanctions regime, all Western companies stopped investment projects, sold all assets and withdrew from all joint projects with Russian producers. Uncertainty in the timing of the lifting of sanctions has also given rise to uncertainty in the timing, conditions and opportunities for further development of the Russian automotive industry. Moreover, the very development of the automotive industry in Russia without a new strategic partner, which many of the world's best companies previously acted as, is in question. But thanks to the experience gained from the implementation of the industrial assembly regime and modern infrastructure, a new strategy for the development of the industry until 2035, geographical location and extent, the unique task of finding such a partner can be considered solved by definition. However, the risks for potential cooperation are already being realized. In these unique conditions of new opportunities and unprecedented limitations, the most appropriate time is for the formation of a strategic alliance of Russian and Chinese automakers, because Russia has no alternatives, and China so needs support for its expansion into the global car market.
Education Management in the Development of Contextual Problems Using Mobile Augmented Reality to Support Mechanical Engineering Students Creativity in Learning Mathematics
Authors: Umam Khoerul , Fatayan Arum , Irdalisa . , Sari Yessy Yanita , Awang Isha
Published: June 2024

There are still many mechanical engineering students who are passive in learning activities. The aim of this research is to create Mobile Augmented Reality to provide contextual problems to mechanical engineering students. So, students can imagine and be active in learning. The method used is 4D development (Define, Design, Develop, and Disseminate). Apart from that, it uses quantitative research to influence the use of mobile augmented reality. Next is qualitative research to analyze the use of mobile augmented reality. The conclusion of this research states that there is a significant influence on the activeness and creativity of mechanical engineering students after developing and using mobile augmented reality in mathematics learning activities.
Pseudoexfoliation Syndrome Post COVID Vaccination
Authors: Russell-Jones Gregory
Published: June 2024

In an attempt to rapidly control of the unprecedented effects of the COVID-19 pandemic, a series of vaccination programmes were rapidly rolled out across the world, with a paucity of studies on their side-effects or efficacy. Lack of testing may be the reason for why there have been an increasing number of reports of new-onset autoimmune phenomena following COVID-19 vaccination. These conditions include immune thrombotic thrombocytopenia, autoimmune liver diseases, Guillain-Barre syndrome, IgA nephropathy, rheumatoid arthritis and systemic lupus erythematosus). It has been postulated that production of autoantibodies may have been due the use of certain vaccine adjuvants such as PEG, used by Pfizer [1]. These side-effects are somewhat more serious than the systemic side effects seen following 2 injections of the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccine (58.75%), or BNT162b2 (68.5%) [2]. We report evidence of an extensive and prolonged inflammatory response to a combination of 2 injections of ChAdOx1 nCoV-19, followed by 1 injection of BNT162b2, which subsequently lead to the development of irreversible eye damage typical of Pseudoexfoliation syndrome, in a 71 year old man, of excellent health with no predisposing sequelae apart from his age.
Help Seeking Among Male Farmers and their Female Partners: A Qualitative Exploration
Authors: Carswell Emma , McLaughlin Marian , Cassidy Tony
Published: June 2024

This study explored help-seeking among male farmers and their female partners, using data collected via 16 face-to-face semi-structured interviews. Eight male farmers and eight female partners aged 26-56 years were recruited. Data were analysed using thematic analysis. Seven main themes were identified, healthcare, self-protection, costs, support, roles, accessibility, and community. Both partners valued healthcare but identified barriers to enacting help seeking. Stigma and fear of embarrassment and disclosure led to self protection through avoidance of help seeking. A community culture of masculinity mitigated against disclosure and help seeking though females were more open to change. Males were more reluctant to discuss mental health and focused mainly on physical healthcare. Time and cost were also restrictive but support enabled help seeking. It is suggested that a social ecological model should be applied and there is a need to provide a more farming friendly primary care. What is known: • Males are reluctant to talk about mental health. • Males are reluctant to seek help. • There are high levels of suicide among farmers. What this paper adds: • Male farmers and their female partners value help-seeking • Male farmers and their female partners avoid help-seeking for reasons on self-protection. The farming community culture mitigates against help-seeking.
Anthropogenic and environmental drivers of Acanthurus achilles presence in Hawai‘i
Authors: Layko RB , Donovan MK
Published: June 2024

Despite the ecological and social importance of reef fishes, data on their populations, habitat use, and other drivers are often scarce, which creates challenges for effective management. These challenges are particularly acute for rare or at-risk species such as Acanthurus achilles, a reef fish with a documented population decline in recent years in Hawai‘i, USA. We used a data set of in situ fish surveys from across the main Hawaiian Islands combined from multiple survey programs to quantify A. achilles presence and absence and applied generalized linear mixed-effects models to examine the relationships between presence of (1) all individuals, (2) juveniles, and (3) adults with 27 spatially continuous environmental and anthropogenic drivers to understand the main drivers of presence. Using the modeled relationships between presence and all drivers, we predicted the probability of A. achilles presence at a 100 m scale within the 30 m depth contour of the main Hawaiian Islands. Environmental drivers, especially habitat drivers such as depth and rugosity, emerged as significant drivers of A. achilles presence, while anthropogenic drivers like land-based pollution and fishing had fewer significant relationships with A. achilles presence. The predicted probability of presence varied both between islands as well as within islands, with the highest probability of presence around Kaho‘olawe and Hawai‘i and the lowest around O‘ahu. Our modeling approach and high-resolution spatial predictions provide empirical evidence of the importance of environmental drivers in explaining A. achilles presence and identify preferred habitat at relevant scales for fisheries management.
Conceptual Design of an Industrial Manipulator for the Prevention of Musculoskeletal Disorders: a Participatory Approach
Authors: Ron Misael , Escalona Evelin , Hernández-Runque Estela , Gonzalez-Argote Javier
Published: June 2024

Background. This study outlines the conceptual design process of an innovative load manipulator adapted to the brewing industry, to mitigate ergonomic risk factors associated with manual handling of heavy loads, stacking, and manual palletizing.
The aim. To design a load manipulator for the function of “low-pressure table assistant” within a brewery.
Methods. A descriptive non-experimental study was accomplished, using an ergonomic and participatory approach, that is divided into three phases. Anthropometric adaptability and worker dimensions were assessed to determine the selected design. Finally, the given concept was thoroughly documented by creating drawings and technical data.
Results. The mean measured height was 173.4 centimeters, with a standard deviation of 4.6 centimeters, spanning a range of 165.8 centimeters (5th percentile) to 178.5 centimeters (95th percentile). This range suggests a moderate adequacy of the evaluated workforce in terms of height. Four main functions were identified: transporting boxes within the workspace, providing load support, allowing operator control, and ensuring safety. In addition, with this lifting device, the operator can handle 2, 4, or even 6 boxes simultaneously, with speed, flexibility, and functionality.
Conclusions. In particular, the developed concept introduces significant innovations, such as the ability to, simultaneously handle several heavy loads and the integration of double-jointed pivots, which extends its operational range. These innovations contribute to the prevention of forced postures and manual lifting of heavy loads.
Keywords: ergonomics, equipment design, industrial manipulator, prevention, musculoskeletal disorders.
Ahşap malzemede kerf kesim tekniği üzerine bir değerlendirme
Authors: Kırkpınar Gökçe , Akgün Yenal , Pedergnana Matthieu Joseph
Published: June 2024

Ahşap, geleneksel endüstriyel yapı malzemelerine kıyasla sağladığı hafiflik ve çevresel avantajlar ile mimarlar, iç mimarlar ve mobilya tasarımcıları için her zaman ilham kaynağı olmuştur. Ahşap, uygun kalınlıklarda doğru kesim ve üretim teknikleri uygulandığında esnek bir yapıya dönüştürülebilmektedir. Bu esnekliği kazandırma yöntemlerinden birisi de kerf kesim tekniğidir. Kerf kesim tekniği, bir panel üzerinde belirli bir desen veya şekil oluşturmak için kesimler yaparak sert bir malzemeyi esnek hale getirmeye dayanır. Bu sayede karmaşık fabrikasyon yöntemlerine ve ileri teknoloji malzemelere ihtiyaç duymadan, esnek ve şekil değiştirme özelliğine sahip mimari elemanlar ve mobilya ürünleri tasarlanabilir. Bu çalışmada, kerf kesim tekniğinin ahşap ürünlerdeki kullanım alanları incelenerek kesim teknolojileri, üretim teknikleri, kesim tipleri ve desen türleri üzerinden bir sınıflandırma yapılmaktadır. Kerf kesim tekniğinin ahşap işleri alanında önemini ve son yıllarda artan ilgiyi vurgulayan bu çalışma, tasarımcılar ve üreticiler için yenilikçi bir üretim yöntemi sunmaktadır. Bu teknik, esnek ve estetik açıdan özgün tasarımların geliştirilmesine katkıda bulunarak ahşap ürünlerin kullanım alanlarını genişletme potansiyeline sahiptir.
Sleep disturbances and their link with cardiac alterations in patients with implantable automatic cardioverter defibrillators.
Authors: Guarin Karen , Dulcey Luis , Gómez Jaime , Guevara Ana , Hernández Salomé , Herrera Nathalia , León María , López Malieth , Martínez Deivid , Hernández Jorge , Gómez Juan , Theran Juan
Published: June 2024

Sleep-related breathing disorders are common in patients with cardiovascular disease, yet their impact on ventricular tachycardia VT and ventricular fibrillation VF remains unclear. In this study we evaluate the incidence, severity and pattern of SVRTs in patients with implantable cardioverter-defibrillator ICDs and their role in recurrent VT and VF episodes. Data from 50 patients aged 65 to 85 years, predominantly male, with ICDs implanted for primary prevention 20 patients and secondary prevention 30 patients of cardiac events were analyzed. SRBD was diagnosed in 58 of the patients, with 20 mild, 16 moderate and 22 severe forms. The results indicate that moderate to severe DSRBs are frequent in patients with ICDs, however they do not increase the risk of VT and VF recurrence.
Culturas transnacionais: cinema, migração e identidade no Vale do Itajaí nas primeiras décadas do século XX
Authors: Pozzo Renata Rogowski , Müller Yasmin Lopes
Published: June 2024

Nas análises sobre a Deutschtum (germanidade) do Vale do Itajaí (Santa Catarina), o binômio lar-língua é destacado como base para a criação e manutenção da identidade étnica teuto-brasileira. Assim, dentre as instituições criadas para valorização da língua comum alemã, cita-se as escolas, os jornais e as associações recreativas. O presente escrito busca analisar o papel do cinema nesse sistema cultural, tendo em vista que, entre 1900 e 1930, era comum justamente tais espaços culturais, criados para manutenção da germanidade, abrigarem também sessões de cinema, notadamente, projetadas no idioma alemão. Argumenta-se que, no Vale do Itajaí, na transição do século XIX para o XX, o cinema participou da construção da Alemanha como uma comunidade imaginada, que permitiu o estabelecimento de uma ponte de sentidos entre a origem destes imigrantes e o novo território ocupado, configurando uma identidade transnacional baseada na germanidade: a comunidade étnica dos deutschbrasilianer (teuto-brasileiros).
Projetos desenvolvidos em 2006/2007
Authors: Pátaro Cristina Satiê de Oliveira
Published: June 2024

Projetos desenvolvidos em 2006/2007
Examining the influence of body fat distribution on standing balance and functional performance in overweight female patients with degenerative lumbar disease
Authors: Chen Jung-Hsuan , Chen Po-Jung , Kantha Phunsuk , Tsai Yi-Ching , Lai Dar-Ming , Hsu Wei-Li
Published: June 2024

Introduction:Degenerative lumbar disease (DLD) is a prevalent disorder that predominantly affects the elderly population, especially female. Extensive research has demonstrated that overweight individuals (categorized by body fat distribution) have a higher susceptibility to developing DLD and an increased risk of falling. However, there is limited research available on the standing balance and functional performance of overweight females with DLD.

Aims:To determine the impact of body fat distribution on standing balance and functional performance in overweight females with DLD.

Methods:This cross-sectional study evaluated thirty females with DLD were categorized into three types of body fat distribution based on body mass index (BMI) and waist-hip ratio, specifically as android-type, gynoid-type, and normal weight groups. In addition, a control group of ten age-matched females with normal weight was recruited. The Visual Analogue Scale, Roland Morris Disability Questionnaire, Cobb angle (Determined using x-ray), and body composition (Determined using the InBody S10), were conducted only on the DLD groups. All participants were assessed standing balance in the anteroposterior and mediolateral directions. The functional assessments included timed-up-and-go and 5-times-sit-to-stand tests.

Results:There were 10 people in each group. Android-type (Age = 65.00 ± 6.34 years; BMI = 26.87 ± 2.05 kg/m2), Gynoid-type (Age = 65.60 ± 4.99 years; BMI = 26.60 ± 1.75 kg/m2), Normal weight (Age = 65.70 ± 5.92 years; BMI = 22.35 ± 1.26 kg/m2), and Control (Age = 65.00 ± 5.23 years; BMI = 22.60 ± 1.12 kg/m2). The android-type group had higher body fat, visceral fat, and lower muscle mass (p< 0.05), along with an increased Cobb angle (p< 0.05). They showed greater ellipse area, total excursion, and mean distance in the anteroposterior direction (p< 0.05). During the functional performance assessments, the android-type group had longer durations in both the 5-times-sit-to-stand and timed-up-and-go tasks (p< 0.05).

Conclusion:Our study found that android-type overweight individuals showed postural instability, reduced functional performance, and insufficient lower limb muscle strength and mass. These findings might help physical therapists in planning interventions, as they imply that patients with DLD may require specific types of standing balance training and lower extremities muscle-strengthening based on their body fat distribution.

Clinical Trial Registration:ClinicalTrials.gov, identifier NCT05375201
Acute activation of hemichannels by ethanol leads to Ca2+-dependent gliotransmitter release in astrocytes
Authors: Gómez Gonzalo I. , García-Rodríguez Claudia , Marillán Jesús E. , Vergara Sergio A. , Alvear Tanhia F. , Farias-Pasten Arantza , Sáez Juan C. , Retamal Mauricio A. , Rovegno Maximiliano , Ortiz Fernando C. , Orellana Juan A.
Published: June 2024

Multiple studies have demonstrated that acute ethanol consumption alters brain function and cognition. Nevertheless, the mechanisms underlying this phenomenon remain poorly understood. Astrocyte-mediated gliotransmission is crucial for hippocampal plasticity, and recently, the opening of hemichannels has been found to play a relevant role in this process. Hemichannels are plasma membrane channels composed of six connexins or seven pannexins, respectively, that oligomerize around a central pore. They serve as ionic and molecular exchange conduits between the cytoplasm and extracellular milieu, allowing the release of various paracrine substances, such as ATP, D-serine, and glutamate, and the entry of ions and other substances, such as Ca2+ and glucose. The persistent and exacerbated opening of hemichannels has been associated with the pathogenesis and progression of several brain diseases for at least three mechanisms. The uncontrolled activity of these channels could favor the collapse of ionic gradients and osmotic balance, the release of toxic levels of ATP or glutamate, cell swelling and plasma membrane breakdown and intracellular Ca2+ overload. Here, we evaluated whether acute ethanol exposure affects the activity of astrocyte hemichannels and the possible repercussions of this phenomenon on cytoplasmatic Ca2+ signaling and gliotransmitter release. Acute ethanol exposure triggered the rapid activation of connexin43 and pannexin1 hemichannels in astrocytes, as measured by time-lapse recordings of ethidium uptake. This heightened activity derived from a rapid rise in [Ca2+]i linked to extracellular Ca2+ influx and IP3-evoked Ca2+ release from intracellular Ca2+ stores. Relevantly, the acute ethanol-induced activation of hemichannels contributed to a persistent secondary increase in [Ca2+]i. The [Ca2+]i-dependent activation of hemichannels elicited by ethanol caused the increased release of ATP and glutamate in astroglial cultures and brain slices. Our findings offer fresh perspectives on the potential mechanisms behind acute alcohol-induced brain abnormalities and propose targeting connexin43 and pannexin1 hemichannels in astrocytes as a promising avenue to prevent deleterious consequences of alcohol consumption.
Characterization of the somatostatin system in tilapia: implications for growth and reproduction
Authors: Mizrahi Naama , Hollander-Cohen Lian , Atre Ishwar , Shulman Miriam , Campo Aurora , Levavi-Sivan Berta
Published: June 2024

Somatostatin (SST) plays diverse physiological roles in vertebrates, particularly in regulating growth hormone secretion from the pituitary. While the function of SST as a neuromodulator has been studied extensively, its role in fish and mammalian reproduction remains poorly understood. To address this gap, we investigated the involvement of the somatostatin system in the regulation of growth and reproductive hormones in tilapia. RNA sequencing of mature tilapia brain tissue revealed the presence of three SST peptides: SST6, SST3, and low levels of SST1. Four different isoforms of the somatostatin receptor (SSTR) subfamily were also identified in the tilapia genome. Phylogenetic and synteny analysis identified tiSSTR2-like as the root of the tree, forming two mega clades, with SSTR1 and SSTR4 in one and SSTR2a, SSTR3a, and SSTR5b in the other. Interestingly, the tiSSTR-5 isoforms 5x1, 5x2, and 5x3 were encoded in the sstr3b gene and were an artifact of misperception in the nomenclature in the database. RNA-seq of separated pituitary cell populations showed that SSTRs were expressed in gonadotrophs, with sstr3a enriched in luteinizing hormone (LH) cells and sstr3b significantly enriched in follicle-stimulating hormone (FSH) cells. Notably, cyclosomatostatin, an SSTR antagonist, induced cAMP activity in all SSTRs, with SSTR3a displaying the highest response, whereas octreotide, an SSTR agonist, showed a binding profile like that observed in human receptors. Binding site analysis of tiSSTRs from tilapia pituitary cells revealed the presence of canonical binding sites characteristic of peptide-binding class A G-protein-coupled receptors. Based on these findings, we explored the effect of somatostatin on gonadotropin release from the pituitary in vivo. Whereas cyclosomatostatin increased LH and FSH plasma levels at 2 h post-injection, octreotide decreased FSH levels after 2 h, but the LH levels remained unaffected. Overall, our findings provide important insights into the somatostatin system and its mechanisms of action, indicating a potential role in regulating growth and reproductive hormones. Further studies of the complex interplay between SST, its receptors, and reproductive hormones may advance reproductive control and management in cultured populations.
Case report: Nerve fiber regeneration in children with melanocortin 4 receptor gene mutation related obesity treated with semaglutide
Authors: Gad Hoda , Mohammed Idris , Dauleh Hajar , Pasha Maheen , Al-Barazenji Tara , Hussain Khalid , Malik Rayaz A.
Published: June 2024

Melanocortin 4 receptor (MC4R) mutations are the commonest cause of monogenic obesity through dysregulation of neuronal pathways in the hypothalamus and prefrontal cortex that regulate hunger and satiety. MC4R also regulates neuropathic pain pathways via JNK signaling after nerve injury. We show evidence of corneal small fiber degeneration in 2 siblings carrying a heterozygous missense variant c.508A>G, p.Ille170Val in the MC4R gene. Both children were treated with once weekly semaglutide for 6 months with no change in weight, and only a minor improvement in HbA1c and lipid profile. However, there was evidence of nerve regeneration with an increase in corneal nerve fiber density (CNFD) [child A (13.9%), child B (14.7%)], corneal nerve branch density (CNBD) [child A (110.2%), child B (58.7%)] and corneal nerve fiber length (CNFL) [child A (21.5%), child B (44.0%)].
Pro-inflammatory diets promote the formation of hyperuricemia
Authors: Liu Xin , Chen Ting-Yu , Gao Teng-Yu , Shi Ke-Qin , Yin Fu-Qiang , Yu Yun-Xiang , Zhang Chao
Published: June 2024

Background

Hyperuricemia, as a very prevalent chronic metabolic disease with increasing prevalence year by year, poses a significant burden on individual patients as well as on the global health care and disease burden, and there is growing evidence that it is associated with other underlying diseases such as hypertension and cardiovascular disease. The association between hyperuricemia and dietary inflammatory index (DII) scores was investigated in this study.

Methods

This study enrolled 13, 040 adult subjects (aged ≥ 20 years) from the US National Health and Nutrition Survey from 2003 to 2018. The inflammatory potential of the diet was assessed by the DII score, and logistic regression was performed to evaluate the relationship between the DII score and the development of hyperuricemia; subgroup analyses were used to discuss the influence of other factors on the relationship.

Results

Participants in the other quartiles had an increased risk of hyperuricemia compared to those in the lowest quartile of DII scores. Stratification analyses stratified by body mass index (BMI), sex, hypertension, drinking, diabetes, education level and albumin-creatinine-ratio (ACR) revealed that the DII score was also associated with the risk of hyperuricemia (P<0.05). There was an interaction in subgroup analysis stratified by sex, age, and hypertension (P for interaction <0.05). The results showed a linear-like relationship between DII and hyperuricemia, with a relatively low risk of developing hyperuricemia at lower DII scores and an increased risk of developing hyperuricemia as DII scores increased.

Conclusions

This study showed that the risk of hyperuricemia increased at slightly higher DII scores (i.e., with pro-inflammatory diets), but not significantly at lower levels (i.e., with anti-inflammatory diets). The contribution of the DII score to the development of hyperuricemia increased with higher scores. The relationship between inflammatory diets and hyperuricemia requires more research on inflammation, and this study alerts the public that pro-inflammatory diets may increase the risk of developing hyperuricemia.
Evolution of regulatory mechanisms underlying nutrition-responsive plasticity in insects
Authors: Casasa Sofia
Published: June 2024

Phenotypic plasticity is a fundamental property of developing organisms and is thought to play an important role in diversification. Plastic responses themselves are remarkably diverse and respond to a wide range of environmental factors. Here I focus on plasticity in response to variation in nutrition in insects since 1) nutrition is a widespread factor that impacts most organisms, and 2) insects are important models to study phenotypic plasticity. First, I provide a brief overview of our current mechanistic understanding of the regulation of nutritionally cued plasticity in insects, in both traditional as well as emerging model systems. Then, I explore evolutionary mechanisms enabling the diversification of regulation across taxa, emphasizing the role of gene duplication and gene regulatory network co-option. Furthermore, I examine nutrition-responsive phenotypes as suites of multiple traits that develop in a coordinated manner. I argue that understanding how these traits are integrated at the molecular level can shed light on the evolution of complex phenotypes. Finally, I discuss potential challenges and opportunities to further our understanding of nutrition-responsive plasticity, its regulation, and its evolution.
A novel variation in DEPDC5 causing familial focal epilepsy with variable foci
Authors: Wang Yanchi , Niu Wenbin , Shi Hao , Bao Xiao , Liu Yidong , Lu Manman , Sun Yingpu
Published: June 2024

Background

Disheveled, EGL-10, and pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a component of GTPase-activating protein (GAP) activity toward the RAG complex 1 (GATOR1) protein, which is an inhibitor of the amino acid-sensing branch of the mammalian target of rapamycin complex 1 (mTORC1) pathway. GATOR1 complex variations were reported to correlate with familial focal epilepsy with variable foci (FFEVF). With the wide application of whole exome sequencing (WES), more and more variations in DEPDC5 were uncovered in FFEVF families.

Methods

A family with a proband diagnosed with familial focal epilepsy with variable foci (FFEVF) was involved in this study. Whole exome sequencing (WES) was performed in the proband, and Sanger sequencing was used to confirm the variation carrying status of the family members. Mini-gene splicing assay was performed to validate the effect on the alternative splicing of the variation.

Results

A novel variant, c.1217 + 2T>A, in DEPDC5 was identified by WES in the proband. This splicing variant that occurred at the 5′ end of intron 17 was confirmed by mini-gene splicing assays, which impacted alternative splicing and led to the inclusion of an intron fragment. The analysis of the transcribed mRNA sequence indicates that the translation of the protein is terminated prematurely, which is very likely to result in the loss of function of the protein and lead to the occurrence of FFEVF.

Conclusion

The results suggest that c.1217 + 2T>A variations in DEPDC5 might be the genetic etiology for FFEVF in this pedigree. This finding expands the genotype spectrum of FFEVF and provides new etiological information for FFEVF.
SOCS1 and SOCS3 as key checkpoint molecules in the immune responses associated to skin inflammation and malignant transformation
Authors: Morelli Martina , Madonna Stefania , Albanesi Cristina
Published: June 2024

SOCS are a family of negative inhibitors of the molecular cascades induced by cytokines, growth factors and hormones. At molecular level, SOCS proteins inhibit the kinase activity of specific sets of receptor-associated Janus Activated Kinases (JAKs), thereby suppressing the propagation of intracellular signals. Of the eight known members, SOCS1 and SOCS3 inhibit activity of JAKs mainly induced by cytokines and can play key roles in regulation of inflammatory and immune responses. SOCS1 and SOCS3 are the most well-characterized SOCS members in skin inflammatory diseases, where their inhibitory activity on cytokine activated JAKs and consequent anti-inflammatory action has been widely investigated in epidermal keratinocytes. Structurally, SOCS1 and SOCS3 share the presence of a N-terminal domain containing a kinase inhibitory region (KIR) motif able to act as a pseudo-substrate for JAK and to inhibit its activity. During the last decades, the design and employment of SOCS1 and SOCS3-derived peptides mimicking KIR domains in experimental models of dermatoses definitively established a strong anti-inflammatory and ameliorative impact of JAK inhibition on skin inflammatory responses. Herein, we discuss the importance of the findings collected in the past on SOCS1 and SOCS3 function in the inflammatory responses associated to skin immune-mediated diseases and malignancies, for the development of the JAK inhibitor drugs. Among them, different JAK inhibitors have been introduced in the clinical practice for treatment of atopic dermatitis and psoriasis, and others are being investigated for skin diseases like alopecia areata and vitiligo.
CHI3L1 on fibrinolytic system imbalance in chronic rhinosinusitis with nasal polyp
Authors: Yang Hyun-Woo , Park Joo-Hoo , Shin Jae-Min , Son Hyeong-Guk , Kim Tae-Hoon , Lee Seung-Hoon , Park Il-Ho
Published: June 2024

Background

Chronic rhinosinusitis (CRS) is an inflammatory disease affecting more than 10% of the global adult population. It is classified into Th1, Th2, and Th17 endotypes and eosinophilic and non-eosinophilic types. Th2-based inflammation and eosinophilic CRS (ECRS) are associated with tissue remodeling and fibrinolytic system impairment.

Objective

To elucidate the role of eosinophils in inducing fibrin deposition in CRS nasal polyp tissues and explore potential regulatory mechanisms.

Methods

We analyzed the expression of genes related to the serpin family and fibrinolytic system using Gene Expression Omnibus and Next-generation sequencing data. Differentially expression genes (DEGs) analysis was used to compare control and nasal polyp tissues, followed by KEGG and Gene ontology (GO) analysis. We measured the expression and correlation of plasminogen activator-1 (PAI-1), tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and urokinase plasminogen activator surface receptor (u-PAR) in CRS tissues, and evaluated the effect of eosinophils on the fibrinolytic system using a cytokine array and co-culture.

Results

Nasal polyp tissues showed upregulated PAI-1, u-PA, and u-PAR expression and downregulated t-PA expression. Fibrinolytic system-related genes positively correlated with Th2 cytokines, except for t-PA. Eosinophil-derived Chitinase-3-like protein 1 (CHI3L1) increased PAI-1 expression and decreased t-PA levels in fibroblasts and epithelial cells. The inhibition of CHI3L1 suppresses these alterations.

Conclusion

CHI3L1 contributes to fibrin deposition by impairing the fibrinolytic system during nasal polyp formation. The regulation of CHI3L1 expression may inhibit fibrin deposition and edema in ECRS, presenting a potential treatment for this condition.
Integrating single-cell and spatial transcriptomic analysis to unveil heterogeneity in high-grade serous ovarian cancer
Authors: Luo Haixia , Wang Kunyu , Li Bin
Published: June 2024

High-grade serous ovarian cancer (HGSOC) presents significant challenges due to its heterogeneity and late-stage diagnoses. Using single-cell and spatial transcriptomics to elucidate the complex landscape of HGSOC to understand its underlying mechanism. Our analysis reveals significant inter- and intra-tumoral diversity, manifested through distinct cellular subpopulations and varied microenvironmental niches. Notably, our findings highlight a widespread immunosuppressive environment, marked by complex networks of cell-cell interactions, particularly evident in areas of elevated tumor cell density within metastatic samples. We identify the exclusive presence of COL14A1+ neoplastic cells in metastatic specimens, alongside a strong correlation between CD8A+ NKT cells and poor prognosis, and elevated CHODL expression in HGSOC metastasis tissues. Furthermore, knockdown experiments targeting CHODL demonstrate its role in reducing migration and invasion abilities in HGSOC cells. A pivotal discovery of our study is the delineation of specific cellular signatures correlated with adverse outcomes, notably a subset of CHODL+ neoplastic cells characterized by a distinct metabolic phenotype with a predilection for lipid metabolism. The therapeutic targeting of this metabolic pathway with existing inhibitors appears promising in curbing tumor proliferation. These findings enhance our understanding of HGSOC heterogeneity and reveal potential therapeutic targets, promising more effective management strategies for this aggressive cancer subtype.
Contribution of coastal seiches to sediment transport in a microtidal semi-enclosed bay
Authors: Seo Jun Young , Choi Byoung-Ju , Choi Sun Min , Ryu Jongseong , Ha Ho Kyung
Published: June 2024

Moorings and axial surveys using acoustic Doppler current profilers in microtidal Masan Bay were conducted to reveal impacts of coastal seiches on sediment behaviors. The hydrodynamic circulation in the bay was dominated by sluggish tidal and residual currents, with which the coastal seiches with a 1-h period were detected. The coastal seiches velocity (useiche) accounted for approximately 30% of the total velocities, causing back-and-forth water motions along the channel. This was insufficient to resuspend bed sediments without external forcings. Nevertheless, it influenced the suspended sediment concentration (SSC) of turbidity maximum (~40 mg l−1) at the central part of bay, showing SSC anomaly of 8 mg l−1. Although the seiche-induced sediment fluxes were only 1% of the total fluxes due to offsetting effect of bidirectional flows, they reached up to 0.040×10−3 kg m−2 s−1 at each pulse of coastal seiches. Repetitive coastal seiches lifted the sediment particles to the upper layer where they would not have risen if not for seiche vertical motion. However, the distance that the coastal seiches can transport the suspended sediments was too short compared to their transportable amounts. Even if sediment particles within turbidity maximum were advected by coastal seiches, they could not leave the region. This process was intensified toward the land because the useiche slowed down the further as it moved away from the node. As long as the bed sediments were resuspended, the coastal seiches were expected to enhance the potential for water pollution by causing repetitive sediment redistribution.
Investigating Propionibacterium acnes antibiotic susceptibility and response to bacteriophage in vitro and in vivo
Authors: Yu Ruixing , Yu Lingyun , Ning Xiaoli , Cui Yong
Published: June 2024

Introduction

A total of 94 Propionibacterium acnes (P. acnes) isolates were obtained from a hospital in Beijing to evaluate their susceptibility to erythromycin, clarithromycin, doxycycline, and minocycline. As well as the determination of the effectiveness of P. acnes phages in vitro and in P. acnes-induced lesions mouse model.

Methods

Patients with acne vulgaris (AV) were enrolled from August 2021 to October 2022. Standard methods were employed for specimen collection, culture, and identification of P. acnes. Susceptibility testing was conducted using E-strips for erythromycin, clarithromycin, minocycline, and doxycycline. Phage culture and identification followed standard procedures. A mouse model with P. acnes-induced skin lesions was established, and data was analyzed using χ2 test.

Results

The results showed that all isolates were susceptible to minocycline and doxycycline, while 53 (56.4%) and 52 (55.3%) isolates were susceptible to erythromycin and clarithromycin, respectively. Interestingly, younger patients and those with lower acne severity exhibited reduced resistance. Phage cleavage rates ranged from 88.30 to 93.60%. Multilocus sequence typing (MLST) analysis was conducted on eight randomly selected P. acnes isolates, and the IA-2 subtype was used in experiments to address P. acnes-induced lesions in mice. Phage therapy proved effective in this model.

Discussion

This study highlights the high susceptibility of P. acnes to doxycycline and tetracycline, while erythromycin and clarithromycin exhibited elevated resistance. Additionally, P. acnes phages demonstrated high cleavage rates and potential effectiveness in treating P. acnes-induced lesions. These findings suggest promising avenues for further exploration of phage therapy in acne treatment.
Longitudinal evaluation of laboratory results and method precision in worldwide erythropoietin external quality assessments
Authors: Toll Luisa , Weiss Nathalie , Vierbaum Laura , Schellenberg Ingo , Thevis Mario , Wenzel Folker
Published: June 2024

Introduction: This study presents a longitudinal analysis of external quality assessment (EQA) results for erythropoietin (EPO) determinations conducted between 2017 and 2022 with a continuously increasing number of participating laboratories. The aim of this work was to evaluate participant performance and methodological aspects.

Methods: In each of the eleven EQA surveys, a blinded sample set of lyophilized human serum containing one sample with lower EPO concentrations (L) and one with higher EPO concentrations (H) was sent to the participating laboratories.

Results: A total of 1,256 measurements were included. The median (interquartile range) fraction of participants not meeting the criteria of acceptance set at 20% around the robust mean of the respective survey was 9.5% (6.1%–10.7%) (sample L) and 9.1% (5.8%–11.8%) (sample H) but lacked a clear trend in the observed period. Some surveys exhibited unusually high interlaboratory variation, suggesting interfering components in the EQA samples. Different immunological methods and reagent manufacturers also showed variability in measurement outcomes to some extent.

Conclusion: These findings highlight the need for continuous quality assessment in EPO measurements to ensure patient safety and identify areas for further research and investigation.
A pangenome analysis of ESKAPE bacteriophages: the underrepresentation may impact machine learning models
Authors: Lee Jeesu , Hunter Branden , Shim Hyunjin
Published: June 2024

Bacteriophages are the most prevalent biological entities in the biosphere. However, limitations in both medical relevance and sequencing technologies have led to a systematic underestimation of the genetic diversity within phages. This underrepresentation not only creates a significant gap in our understanding of phage roles across diverse biosystems but also introduces biases in computational models reliant on these data for training and testing. In this study, we focused on publicly available genomes of bacteriophages infecting high-priority ESKAPE pathogens to show the extent and impact of this underrepresentation. First, we demonstrate a stark underrepresentation of ESKAPE phage genomes within the public genome and protein databases. Next, a pangenome analysis of these ESKAPE phages reveals extensive sharing of core genes among phages infecting the same host. Furthermore, genome analyses and clustering highlight close nucleotide-level relationships among the ESKAPE phages, raising concerns about the limited diversity within current public databases. Lastly, we uncover a scarcity of unique lytic phages and phage proteins with antimicrobial activities against ESKAPE pathogens. This comprehensive analysis of the ESKAPE phages underscores the severity of underrepresentation and its potential implications. This lack of diversity in phage genomes may restrict the resurgence of phage therapy and cause biased outcomes in data-driven computational models due to incomplete and unbalanced biological datasets.