bluuebunny/crossref_metadata_2025 huggingface dataset:
РЕТРОСПЕКТИВНИЙ АНАЛІЗ ПОКАЗНИКІВ ПРИМІСЬКИХ ПАСАЖИРСЬКИХ ПЕРЕВЕЗЕНЬ РЕГІОНАЛЬНОЇ ФІЛІЇ АТ «УКРЗАЛІЗНИЦЯ»
Authors: Чигрінов Вячеслав
Published: October 2024

В сучасних економічних умовах приміське залізничне сполучення має високу значимість у розвитку регіонів. Цей вид перевезень є ефективним і найдешевшим видом транспортного сполучення, який поєднує міста на відносно невеликій відстані і забезпечує мобільність трудових ресурсів. Основними проблемами приміських пасажирських перевезень, що виконуються залізничним транспортом є їх збитковість, яка обумовлюється значним рівнем зношеності рухомого складу, неповноцінним відшкодування місцевими бюджетами витрат на перевезення пасажирів, що користуються пільгами на безкоштовний проїзд залізничним транспортом, гостра конкуренція з боку автомобільного транспорту. АТ «Укрзалізниця» постійно розробляє заходи з підвищення ефективності та конкурентоспроможності приміських пасажирських перевезень. Одним з таких заходів може стати створення філії «Приміська пасажирська компанія». Для прогнозування тенденцій, з якими зіштовхнеться компанія необхідно провести ретроспективний аналіз особливостей приміських пасажирських перевезень за попередньою організаційною структурою управління. В статті надано результати ретроспективного аналізу показників приміських пасажирських перевезень Регіональної філії «Південна залізниця» АТ «Укрзалізниця».
ОСОБЛИВОСТІ ПРАКТИЧНОГО ЗАСТОСУВАННЯ СИСТЕМИ УПРАВЛІННЯ РИЗИКАМИ ДЛЯ ПРИЙНЯТТЯ РІШЕНЬ ЩОДО ПРОВЕДЕННЯ ПОСТ-МИТНОГО КОНТРОЛЮ
Authors: Руда Тетяна , Корчака Сергій , Неліпович Олена
Published: October 2024

У статті проаналізовано основні аспекти використання системи управління ризиками в процесі прийняття рішень щодо необхідності здійснення пост-митного контролю. Визначено випадки, в яких доцільно застосовувати пост-митний контроль та структуровано суб’єктів зовнішньоекономічної діяльності (ЗЕД), стосовно яких він може бути застосований. Окреслено фактори, які впливають на ефективність та визначають доцільність здійснення пост-митного контролю. Особливу увагу приділено аналізу результатів застосування суб’єктоорієнтованих критеріїв (тобто визначенню частки митних декларацій, до яких було застосовано коефіцієнт зменшення АСУР необхідності проведення митного огляду) в розрізі митних режимів за 2023 рік та дослідженню кон’юнктуру сучасного стану використання системи управління ризиками. Також у статті визначено перелік документальних митних формальностей, який може бути виконаний під час реалізації пост-митного контролю.
Leveraging ResNet-50 for Precision Toxicity Classification in Plants: A Vision-Based Approach to Safeguard Public Health
Authors: Makhija Aria
Published: October 2024

The classification of toxic and non-toxic plants plays an important role in ensuring public safety, especially in agriculture, food safety, and health. Correct identification of these plants can prevent accidental poisoning and promote ecological protection. In this paper, we investigate the application of the ResNet-50 model for the classification of toxic and non-toxic plants. Leveraging the powerful feature extraction techniques of the ResNet-50 architecture, the model achieved 89.6% accuracy, 87.4% precision, 91.1% recall, and an 89.2% F1 score, demonstrating the model’s effectiveness. Transfer learning proved effec-tive with limited data while maintaining high performance metrics in the classification task. Future research could focus on expanding the dataset to include more plant species and exploring other state-of-the-art models to improve classification accuracy. Addition-ally, integrating these models with mobile applications or monitoring systems could pro-vide solutions for business and public use, enhancing environmental protection and pub-lic safety.
Classification of Risks in the Aspect of Formation of Organizational and Economic Support for Energy Security Management of Enterprises
Authors:   Educational and Scientific Institute ", Prokhorova Viktoriia V. ,   Ukrainian Engineering and Pedagogical Academy",   of V. N. Karazin Kharkov National University, Mykhalchenko Hanna H. ,   Bakhmut Education Research and Professional Pedagogical Institute of V. N. Karazin Kharkiv National University, Budanov Mykola P. ,   Educational and Scientific Institute "Ukrainian Engineering and Pedagogical Academy" of V. N. Karazin Kharkov National University
Published: October 2024

The article considers the classification of risks in the context of the formation of organizational and economic support for energy security management of industrial enterprises of the electric power system. The study shows that risks arise at all stages of the energy cycle: from generation to transmission, transportation, distribution, and consumption of energy. The proposed classification of risks provides for their division into production, financial, economic, and informational risks, thus contributing to a detailed analysis and assessment of their impacts on the energy security of enterprises. The main aim of the article is to improve the classification of risks in order to increase the efficiency of organizational and economic support for energy security management. As result of researches, a ranking of risks by types, as well as specific threats inherent in each stage of energy production, was carried out. Energy security risks are classified at macro-, meso- and micro-levels, which made it possible to study in detail their impact at different levels of economic activity. This approach provides a comprehensive assessment of the state of energy security of enterprises in the face of both internal and external factors. Problematic issues of functioning of enterprises in an unstable economic environment are studied, a theoretical and practical analysis of risks and factors influencing their intensity is carried out. It is shown that efficient risk management is critically important for ensuring the stable operation of the enterprise, since the high dynamics of the external environment significantly increases the likelihood of threats that can have a negative impact on production processes. On the basis of the carried out study, an integrated approach to minimizing the impact of potential threats is proposed, in particular through the introduction of a system for early detection of risks and prompt response to them. It is concluded that one of the most important factors influencing the efficiency of enterprise and the level of its energy security is rapid adaptation to changes in the external environment. The proposed approaches can be used by managers of energy enterprises to optimize management decisions in the field of energy security.
Advancing Heart Disease Prediction through Machine Learning: Techniques and Insights for Improved Cardiovascular Health
Authors: Proshanta Kumar Bhowmik  , Mohammed Nazmul Islam Miah  , Md Kafil Uddin  , Mir Mohtasam Hossain Sizan  , Laxmi Pant  , Md Rafiqul Islam  , Nisha Gurung
Published: October 2024

Heart disease persists as one of the leading causes of death in the USA and worldwide, accounting for a substantial proportion of global mortality. The significance of early detection of heart disease lies in its capability to counter catastrophic events such as strokes and heart attacks, which are often irreversible and fatal. Machine learning algorithms are gradually revolutionizing heart disease prediction since they can handle complex, multi-dimensional data sets. This research project used the Cleveland dataset from the UCI Machine Learning Repository, containing 70,000 records of patients with 12 unique features. Three machining learning algorithms were trained: Logistic Regression, Random Forest, and Support Vector Machines. Each algorithm was evaluated for precision, accuracy, recall, F1-score, and ROC-AUC. Based on the proof of the evaluation metrics for Logistic Regression, Random Forest, and SVM. In that respect, Logistic Regression was the best overall model since it yielded the highest ROC-AUC score, balancing true positives and false positives better than the rest of the models. The Support Vector Machine had the best accuracy, although it performed similarly to Logistic Regression but slightly lower. In retrospect, the implications for heart disease prediction are evident with simple algorithms such as Logistic Regression affirmatively performing better in specific early heart detection tasks, especially when balancing precision and recall. Indisputably, Machine learning models will have a high clinical impact on heart disease prediction since they enable early detection of heart diseases, leading to timely interventions and better patient prognoses.
STAKEHOLDER-ORIENTED APPROACH TO THE FORMATION OF AN INTELLIGENT ECONOMIC SYSTEM OF CONSTRUCTION ENTERPRISES
Authors: Mamonov K. , Goi V. , Prunenko D. , Frolov V.
Published: October 2024

Forming modern systems of construction enterprises’ functioning requires rethinking approaches to using innovative tools that account for the features and level of stakeholder interaction. In this context, developing and implementing a stakeholder-oriented approach to forming an intelligent economic system of construction enterprises is particularly relevant.
The research aims to develop a stakeholder-oriented approach to forming an intelligent economic system of construction enterprises. To achieve the goal, the authors solve the following tasks: defining the intelligent economic system of construction enterprises, characterising the stakeholders influencing the formation of the intelligent economic system of construction enterprises, and justifying a stakeholder-oriented approach to the formation of an intelligent economic system of construction enterprises.
We propose to define the intelligent economic system of construction enterprises as a set of economic, geospatial, safety, and social components that are developed by applying modern mathematical methods and models, artificial intelligence, information, and analytical support and tools and form the basis for making management decisions in the context of the development of construction enterprises.
The research substantiated the theoretical propositions for defining the intelligent economic system of construction enterprises as an innovative complex toolkit affecting their development. In addition, it established that stakeholders and their level of interaction influence the formation of an intelligent economic system of construction enterprises.
As a result, we proposed a stakeholder-oriented approach to the formation of an intelligent economic system of construction enterprises, determined by a complex of interdependent stages based on a set of informational and analytical and regulatory and legal support, methods, and models, which is aimed at the formation of partner stakeholder relations to ensure the development of construction enterprises.
Keywords: construction enterprises, stakeholders, stakeholder-oriented approach, intelligent economic system, economic and mathematical modelling.
Knee Joint Injuries in the Structure of Injuries Among Elite Athletes of the Highest Achievements
Authors:   International Office, State Research Center – Burnasyan Federal Medical Biophysical Center  of Federal Medical Biological Agency, Moscow, Russiа, Petrova V.V. , Khan A.V. ,   International Office, State Research Center – Burnasyan Federal Medical Biophysical Center  of Federal Medical Biological Agency, Moscow, Russiа, Nazaryan S.E. ,   International Office, State Research Center – Burnasyan Federal Medical Biophysical Center  of Federal Medical Biological Agency, Moscow, Russiа, Shulepov P.A. ,   International Office, State Research Center – Burnasyan Federal Medical Biophysical Center  of Federal Medical Biological Agency, Moscow, Russiа, Petrov A.A. ,   International Office, State Research Center – Burnasyan Federal Medical Biophysical Center  of Federal Medical Biological Agency, Moscow, Russiа
Published: October 2024

The article carries out a statistical analysis of sports injuries, with the greatest attention paid to injuries of the knee joint, as the most common among athletes of a high level of professional skill in various sports. An analysis of the causes leading to injuries and operations on the knee joint was carried out, most often these are stress injuries. Risk factors for injury were analyzed.
Adoecimento decorrente de assédio moral pode ser caso de perícia complexa
Authors: Conceição Jemmis Karters Tomé da , Silva Anderson Lincoln Vital da , Heckmann Maria Izabel Ovellar
Published: October 2024

Embora exista desde os primórdios da humanidade, o assédio moral foi descrito na década de 90 e somente há cerca de 20 anos é que o assédio moral passou a ser estudado no Brasil, por meio de protocolos científicos próprios da psicologia. No Brasil a Convenção 190 da OIT que trata da eliminação da violência e do assédio no mundo do trabalho, encontrasse em debate por iniciativa do Governo Federal. Na mesma linha, o Conselho Federal de Psicologia emitiu a Resolução nº 14/2023 regulamentou o exercício profissional da psicologia na realização de avaliação de riscos psicossociais. O presente estudo analisou a formação dos profissionais que devem assistir os casos de assédio moral, enfatizando as dificuldades metodológica na produção probatória. Trata-se de uma pesquisa com coleção de julgados do TRT de 2009 a 2016 e legislação aplicada ao tema pesquisado. Os resultados revelam que adoecimento psíquico desencadeado por assédio moral deve ser assistido pelo médico Psiquiatra, para assistir às consequências (doença) da exposição aos fatores de risco psicossociais. E a avaliação dos fatores de riscos psicossociais do trabalho (entre eles, o assédio moral), os quais decorrem das interações entre os trabalhadores e condições de trabalho (conteúdo e contexto do trabalho), estrutura e organização do trabalho, é atribuição do profissional da Psicologia. Nitidamente são áreas que se complementam e necessárias para a apreciação eficiente que requer os casos de assédio moral, por tais razões podem ser tratadas como perícia complexa, nos termos dos art. 156, 465, 468 e 475 da Lei n° 13105/15 - CPC/15.
Analysis of Thermoelectric Properties of Hot-deformed Bismuth Telluride Sintered Materials
Authors: Joo Sung-Jae , Son Ji-Hee , Jang JeongIn , Min Bok-Ki , Kim Bong-Seo , Hong JongGan , Lee Dae-Keun , Kim Hyungmo
Published: October 2024

Bismuth telluride (Bi2Te3)-based alloys are widely used for thermoelectric cooling and power generation at low temperatures, and they are the only commercially available materials for thermoelectric applications below 500 K. The rhombohedral unit cell with a large c/a lattice constant ratio consisting of - Te-Bi-Te-Bi-Te- stacked layers inevitably brings about a large anisotropy in transport properties, which is why texturing is very important in polycrystalline Bi2Te3</sub alloys for maximum performance. In this report, p and n-type polycrystalline Bi2Te3</sub alloys were synthesized and hot-deformed to investigate the effects of texturing on thermoelectric properties. Hot deformation (HD) induces the strong alignment of (001) orientations along the compression direction, and a remarkable increase in the orientation factor F of (001) orientations is observed after HD in both p and n-type materials. All of the hot-deformed polycrystalline samples showed increased electrical conductivity (σ), power factor (PF), and thermal conductivity (k) in the in-plane (IP) direction, and vice versa in the out-of-plane (OOP) direction, which makes the IP direction of the hot-deformed bodies more favorable for module fabrication in terms of power factor, for both p and n-type Bi2Te3</sub-based alloys. However, due to the different degree of anisotropy of k and σ, the figures of merit (zT) were maximized in the OOP direction in the p-type materials after HD, whereas the zTs of the n-type materials were higher in the IP direction. This occurs because the anisotropy factor of electron conduction is higher than that of hole conduction, which more than offsets the advantage of the smaller k in the c-direction of n-type Bi2Te3</sub. The maximum zT of 1.33 (OOP) and 0.90 (IP) were obtained after HD from the p and n-type Bi2Te3 alloys, respectively, which were 9.3% and 18.4% higher than those of as-sintered materials.
The seven-dimensional universe
Authors: Kesanasetty Sasidhar
Published: October 2024

This paper elucidates the concept of dark energy and the acceleration of the universe through the quantization of space in hidden dimensions, which provides the foundation for gravitational force. Space-time is conceptualized as a four-dimensional elastic grid within a seven-dimensional universe, wherein matter expands concurrently with the universe. Each cube of the grid is considered a quantum of hidden three-dimensional space of Planck volume containing Planck charge, rendering the universe seven-dimensional. The phenomenon of dark energy is attributed to the electrostatic repulsion between Planck charges in each quantum of the hidden space, and the corresponding energy density is correlated with the Hubble parameter H(z), which accounts for the accelerated expansion of the universe and the increase in the relative cosmological potential energy/rest mass of matter. The expansion of space-time is posited to result not from the creation of new space but from the stretching of existing space-time, analogous to an elastic ruler where proper length and volume remain constant. The relative values of the Planck constant, gravitational constant, permittivity of free space, and Boltzmann constant are demonstrated to vary due to the expansion or contraction of space in cosmological and gravitational frameworks, but are compensated for by the proportional change in the relative rest mass. This theory also establishes a preliminary framework for the relativistic Newtonian theory of gravity, the respective MONDian (Modified Newtonian dynamics) gravity, identifies a rationale for the transition of Newtonian gravity to MOND at a0, and elucidates the dynamics of galaxy clusters without invoking dark matter.
Productivity of sorghum and millets under different in-field rainwater management options on soils of varying fertility status in Zimbabwe
Authors: Makuchete Layton , Hove Apollonia , Nezomba Hatirarami , Rurinda Jairos , Mbanyele Vengai , Mlambo Shaw , Nyakudya Elijah , Mtambanengwe Florence , Mapfumo Paul
Published: October 2024

Traditional cereal crops are important for food and nutrition security in rural communities of southern Africa, but their productivity is often constrained by low soil water largely linked to low seasonal rainfall and long intra-seasonal dry spells. Planting basins (PB), tied ridges (TR), and conventional ploughing (CP) were evaluated, over two cropping seasons (2020/2021 and 2021/2022), for their effects on sorghum [Sorghum bicolor (L.), Moench], pearl millet [Pennisetum glaucum (L.) R.Br.], and finger millet [Eleusine coracana (L.) Gaertn] productivity on degraded (<0.4% soil organic carbon) and productive (>0.6% soil organic carbon) fields under rainfed conditions in Mbire (<450 mm rainfall year−1) and Mutasa (>800 mm rainfall year−1) districts in Zimbabwe. Field trials were established on degraded and productive field sites in each district, with sorghum, pearl millet, and finger millet either sown as monocrops or intercropped with cowpea. The experiments were laid out in a 2 × 3 × 3 factorial in a randomized complete block design (RCBD). The highest sorghum grain yield response of 2100 kg ha−1 was attained under PB on productive soils. Overall, PB and TR increased sorghum, finger millet, and pearl millet grain yields by 43% to 58% compared with CP. Growing sorghum, finger millet, and pearl millet on productive soils increased grain yields by 64%, 33%, and 43%, respectively, compared with degraded soils. Intercropping sorghum, pearl millet, and finger millet with cowpea increased cereal yields by between 23% and 42% over the sole crops. Rainwater use efficiency averaged 1 kg grain mm−1 on productive fields and 0.4 kg grain mm−1 on degraded fields. PB produced the highest net profit of $US408 on a productive field. Overall, production of sorghum and millets on productive soils gave positive economic returns irrespective of rainwater management option and cropping system. Conversely, 63% of the treatments on degraded soils recorded negative economic returns in both districts. We conclude that in-field rainwater management technologies combined with other agronomic practices like intercropping increase the productivity of sorghum and millets under rainfed conditions. However, degraded soils remain a challenge for the increased productivity of traditional cereal crops.
Effects of Tanreqing injection on the gut microbiota in healthy volunteers
Authors: Li Shiyu , Zhang Wenxia , Liu Sijie , Zhou Yichen , Liu Wei , Yuan Weian , He Min
Published: October 2024

Objectives

Many studies have confirmed that antibacterial agents can disrupt the human gut microbiota. In China, Tanreqing injection (TRQ) is a drug with antibacterial activity that is widely used in the treatment of respiratory infections. However, its specific influence on gut microbiota remains unclear. This study aimed to investigate the effect of TRQ on the gut microbiota of healthy volunteers.

Methods

Twelve healthy adults received 20 ml of TRQ intravenously daily for 7 consecutive days. At six timepoints (Pre, on D1, D3, D5, D7 and follow-up visit) fecal samples were collected and analyzed using 16S rRNA gene sequencing.

Results

Eleven people were included in the analysis finally. TRQ did not significantly alter gut microbiota diversity or richness (Shannon and Simpson and Chao1 index) in healthy people during the intervention. Gut microbial structure was stable (weighted and unweighted Unifrac). Using a machine learning method based on PLS-DA analysis, the separation trend on D7 at the genus level was found, returning to baseline two days after discontinuation. The abundance of major genus fluctuated on D7 compared with that prior to treatment, including an increase of unclassified_f_Enterobacteriaceae (13.0611%), a decrease of Bifidobacterium and Escherichia-Shigella (6.887%, 10.487%). Functional prediction analysis did not reveal any significant difference.

Conclusions

Our study showed short-term use of TRQ at conventional doses may not cause perturbations to the gut microbiota in healthy adults. This finding provides some useful information for the safe use of TRQ in the treatment of respiratory infections.

Clinical trial registration

https://www.medicalresearch.org.cn/, identifier MR-31-24-014367.
Association of glycerolipid metabolism with gut microbiota disturbances in a hamster model of high-fat diet-induced hyperlipidemia
Authors: Han Lijie , Hu Chaowei , Du Zhiyong , Yu Huahui , Du Yunhui , Li Linyi , Li Fan , Wang Yu , Gao Xiaoqian , Sun Xuechun , Zhang Zihan , Qin Yanwen
Published: October 2024

Background

High-fat diet (HFD)-induced hyperlipidemia, which is associated with gut microbiota disturbances, remains a major public health challenge. Glycerolipid metabolism is responsible for lipid synthesis and is thus involved in the development of hyperlipidemia. However, possible association between the HFD-modulated gut microbiome and the glycerolipid metabolism pathway remains unclear.

Methods

Hamsters were fed a HFD for 4 weeks to establish a hyperlipidemia model. Fecal, plasma and liver samples collected from hamsters fed a HFD or a normal chow diet (NCD) were used for integrative metagenomic and untargeted metabolomic analyses to explore changes in the composition and functions of the gut microbiota, and relevant metabolites. Spearman rank correlation analysis was used to explore correlations between gut microbes and circulating glycerolipid metabolites, gut microbes and lipids, and circulating glycerolipid metabolites and lipids.

Results

The gut microbial composition of HFD hamsters showed significant alterations at the phylum, genus, and species levels that were skewed toward metabolic disorders compared with that of NCD hamsters. Functional characterization by KEGG analysis identified enrichment of the glycerolipid metabolism pathway in the gut microbiome of HFD hamsters. Plasma and liver metabolomics further indicated the upregulation and enrichment of glycerolipid metabolites in HFD hamsters. The Faecalibaculum, Allobaculum, and Eubacterium genera were positively correlated with plasma glycerolipid metabolites and lipid indices.

Conclusion

The findings of this study suggest an association between glycerolipid metabolism and the HFD-modulated gut microbiome that is involved in the development of hyperlipidemia.
Interleukin-26 expression in tuberculosis disease and its regulatory effect in macrophage polarization and intracellular elimination of Mycobacterium tuberculosis
Authors: Huang Kaisong , Zhou Haijin , Chen Mei , Chen Rui , Wang Xiaoping , Chen Qi , Shi Zhiyun , Liang Yanfang , Yu Luxin , Ouyang Ping , Li Li , Jiang Dan , Xu Guangxian
Published: October 2024

Tuberculosis(TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb) infections, remains the leading cause of mortality from a single infectious agent globally. The progression of tuberculosis disease is contingent upon the complex interplay between the host’s immune system and the pathogen Mtb. Interleukin-26 (IL-26), the most recently identified cytokine belonging to the IL-10 family, exhibits both extracellular antimicrobial properties and pro-inflammatory functions. However, the precise role of IL-26 in the host immune defense against Mtb infections and intracellular killing remains largely unexplored. In this study, we observed significantly elevated IL-26 mRNA expression in peripheral blood mononuclear cells of active-TB patients compared to healthy individuals. Conversely, circulating IL-26 levels in the plasma of adult TB patients were markedly lower than those of healthy cohorts. We purified recombinant IL-26 from an E. coli expression system using the Ni-NTA resin. Upon stimulations with the recombinant IL-26, human THP1 cells exhibited rapid morphological changes characterized by increased irregular spindle shape and formation of granular structures. Treating THP1 cells with IL-26 can also lead to heightened expressions of CD80, TNF-α, and iNOS but not CD206 and Arg1 in these cells, indicating an M1 macrophage differentiation phenotype. Furthermore, our investigations revealed a dose-dependent escalation of reactive oxygen species production, decreased mitochondrial membrane potential, and enhanced autophagy flux activity in THP1 macrophages following IL-26 treatment. Moreover, our results demonstrated that IL-26 contributed to the elimination of intracellular Mycobacterium tuberculosis via orchestrated ROS production. In conclusion, our findings elucidated the role of IL-26 in the development of tuberculosis and its contributions to intracellular bacilli killing by macrophages through the induction of M1-polarization and ROS production. These insights may have significant implications for understanding the pathogenesis of tuberculosis and developing novel therapeutic strategies.
Improvement science and school leadership: the precarious path to dynamic school improvement
Authors: Viano Samantha , Shahrokhi Farnoosh , Hunter Seth B.
Published: October 2024

School systems have increasingly turned to continuous improvement (CI) processes because traditional school improvement plans (SIPs) have resulted in neither reaching set goals nor maintaining performance in challenging times. Improvement science is one way of enacting CI that combines CI with networked improvement to encourage educational equity and build organizational resilience. This study examines the efforts of a school district in the United States to use improvement science to transition their static SIPs to a dynamic process in their underperforming schools. Using a case study design with observations and interviews, we find several sensemaking mechanisms acted as mediators between organizational learning and authentic improvement science implementation. The complexity of improvement science often inhibited sensemaking given time and resource constraints before and during the COVID-19 pandemic, leading to participants often reporting improvement science as too inefficient for their needs. Schools that more successfully integrated improvement science into SIPs saw the value of a systematic approach to SIPs, had interest in distributed leadership, and saw improvement science as advancing equity. This study provides insight into the utility of improvement science as a tool to build organizational resilience as part of school improvement while documenting the many difficulties school improvement teams have in shifting away from static school improvement practices.
Calorie restriction during gestation impacts maternal and offspring fecal microbiome in mice
Authors: Gilley Stephanie P. , Ruebel Meghan L. , Chintapalli Sree V. , Wright Clyde J. , Rozance Paul J. , Shankar Kartik
Published: October 2024

Background

Maternal undernutrition is the most common cause of fetal growth restriction (FGR) worldwide. FGR increases morbidity and mortality during infancy, as well as contributes to adult-onset diseases including obesity and type 2 diabetes. The role of the maternal or offspring microbiome in growth outcomes following FGR is not well understood.

Methods

FGR was induced by 30% maternal calorie restriction (CR) during the second half of gestation in C57BL/6 mice. Pup weights were obtained on day of life 0, 1, and 7 and ages 3, 4 and 16 weeks. Fecal pellets were collected from pregnant dams at gestational day 18.5 and from offspring at ages 3 and 4 weeks of age. Bacterial genomic DNA was used for amplification of the V4 variable region of the 16S rRNA gene. Multivariable associations between maternal CR and taxonomic abundance were assessed using the MaAsLin2 package. Associations between microbial taxa and offspring outcomes were performed using distance-based redundancy analysis and Pearson correlations.

Results

FGR pups weighed about 20% less than controls. Beta but not alpha diversity differed between control and CR dam microbiomes. CR dams had lower relative abundance of Turicibacter, Flexispira, and Rikenella, and increased relative abundance of Parabacteroides and Prevotella. Control and FGR offspring microbiota differed by beta diversity at ages 3 and 4 weeks. At 3 weeks, FGR offspring had decreased relative abundance of Akkermansia and Sutterella and increased relative abundance of Anaerostipes and Paraprevotella. At 4 weeks, FGR animals had decreased relative abundance of Allobaculum, Sutterella, Bifidobacterium, and Lactobacillus, among others, and increased relative abundance of Turcibacter, Dorea, and Roseburia. Maternal Helicobacter abundance was positively associated with offspring weight. Akkermansia abundance at age 3 and 4 weeks was negatively associated with adult weight.

Conclusions

We demonstrate gut microbial dysbiosis in pregnant dams and offspring at two timepoints following maternal calorie restriction. Additional research is needed to test for functional roles of the microbiome in offspring growth outcomes.
Causal association between thyroid function and the risk of infertility: a Mendelian randomization study
Authors: Liu Qinyu , Qiu Yingkun , Jiang Jialin , Long Shushu , Zhu Chengyu , Chen Gang , Wen Junping
Published: October 2024

Objectives

Thyroid dysfunction is commonly associated with the risk of infertility in both females and males. However, recent randomized controlled trials have demonstrated that thyroid function levels in females are not significantly related to infertility, and evidence on the association between male thyroid function and infertility is limited. We aim to investigate the association between thyroid function levels and infertility in both females and males.

Method

A two-sample Mendelian randomization study was conducted using four methods, with the inverse variance weighted method (IVW) as the primary approach. Data on thyroid function as the exposure were obtained from the ThyroidOmics Consortium and UK Biobank, including over 700,000 individuals from a large meta-analysis of genome-wide association studies for thyroid function and dysfunction. The outcome data for infertility in both sex encompassed more than 70,000 individuals from the FinnGen Consortium. All participants were adults of European ancestry. The MR Egger regression intercept and Cochran’s Q test were employed to evaluate directional pleiotropy and heterogeneity.

Results

The results indicated no causal effect of thyroid-stimulating hormone (TSH) and free tetraiodothyronine (fT4) on female and male infertility. Furthermore, no causal association between hypo- and hyperthyroidism and infertility were identified. Notably, we observed a causal relationship between high TSH and endometriosis-related infertility (OR=0.82, 95% CI: 0.74–0.91, P = 1.49E-04).

Conclusions

This study did not find evidence for casual relationship between thyroid function levels and risk of infertility. The findings suggest that overall thyroid function levels may not be a significant predictor of infertility risk.
Sex differences in the radiographic and symptomatic prevalence of knee and hip osteoarthritis
Authors: Faber Benjamin G. , Macrae Fiona , Jung Mijin , Zucker Benjamin E. , Beynon Rhona A. , Tobias Jonathan H.
Published: October 2024

Recognising sex differences in disease prevalence can lead to clues as to its pathogenesis, for example the role of hormonal factors and related influences such as body composition, as well as forming the basis for new treatments. However, if different methods are used to define the disorder it can be difficult to explore differences in prevalence, making it necessary to draw on multiple sources of evidence. This narrative review addresses sex differences in the prevalence of knee and hip osteoarthritis, which are the most common forms of large joint osteoarthritis. Females appear to have a higher prevalence of knee osteoarthritis across a wide range of disease definitions, while findings for the hip vary depending on how the disease is defined. Clinically or symptomatically defined hip osteoarthritis is more common in females, whereas radiographically defined hip osteoarthritis is more common in males. Therefore, understanding sex differences in large joint arthritis requires consideration that osteoarthritis, as defined structurally, more commonly affects females at the knee, whereas the opposite is true at the hip. Furthermore, despite structural changes in hip osteoarthritis being more common in males, symptomatic hip osteoarthritis is more common in females. The basis for these disparities is currently unclear, but may reflect a combination of hormonal, biomechanical and behavioural factors.
Predictive factors of response to liraglutide in patients with type 2 diabetes mellitus and metabolic syndrome
Authors: Song Jinfang , Li Na , Zhuang Yongru , Chen Ya , Zhang Chu , Zhu Jian
Published: October 2024

Background

Although liraglutide has established advantages in treating patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS), there are still some patients with lower responsiveness to liraglutide. The objective of the study was to identify the predictors of response to liraglutide in patients with T2DM and MS.

Methods

This retrospective cohort study included patients diagnosed with T2DM and MS who received liraglutide treatment as a part of their diabetes management for a minimum of six months. The participants were stratified into two groups: responders (HbA1c reduction≥1.0% and weight loss≥3%) and non-responders. The discrepancies in baseline data between the two groups were analyzed, containing comedications, test parameters, and basic profiles. The affecting factors of response to liraglutide by Logistic regression analysis were performed, and the predictive ability of the identified factors was evaluated by plotting a receiver operating characteristic (ROC) curve.

Results

A total of 417 patients with T2DM and MS were examined and followed up according to the inclusion criteria, and 206 patients completed the follow-up; 105 (50.97%) were responders and 101 (49.03%) were non-responders to liraglutide. The binary logistic regression analysis identified baseline HbA1c, baseline BMI, and the duration of T2DM as significant predictors of glycemic and weight responses to liraglutide (P <0.05). The area under the curve of the ROC for the three predictors of liraglutide response after 6 months of treatment was 0.851 (95% confidence interval: 0.793 - 0.910).

Conclusion

The baseline HbA1c, baseline BMI, and duration of T2DM were shown to be predictive factors of glycemic and weight improvements in patients with T2DM and MS treated with liraglutide, and had good predictive power.
A watch-and-wait approach for metachronous multiple colon cancer following neoadjuvant immunotherapy: a case report
Authors: Huang Wang , Zhang Shouru
Published: October 2024

The application of immunotherapy for treating colorectal cancer (CRC) is currently a research hotspot, and neoadjuvant immunotherapy has shown initial success in treating CRC. The watch-and-wait (W&W) approach is often used after achieving a clinical complete response (cCR) following preoperative treatment of low rectal cancer. However, thus far, the W&W approach has not been reported for patients with colon cancer. Here, we report the case of a 64-year-old patient with heterogeneous multigenic CRC who achieved cCR after five sessions of neoadjuvant immunotherapy before surgery. A W&W approach was used to spare the patient from surgery. A 64-year-old male presented with intermittent abdominal pain. A colonoscopy examination detected an irregular cauliflower-like mass near the hepatic flexure of the ascending colon. The biopsy results indicated adenocarcinoma of the ascending colon. The patient was administered pembrolizumab (200 mg, ivgtt, q3w). After one cycle of treatment, the intestinal obstruction symptoms disappeared, and the treatment was continued for additional three sessions. After complete clinical remission of the tumor was confirmed, the W&W approach was adopted. Follow-up CT scans and colonoscopy examinations confirmed no local tumor regeneration or metastasis. Neoadjuvant immunotherapy is effective for patients with DNA mismatch repair gene deficiency and/or microsatellite instability high with a high rate of cCR or pathologic complete response. The W&W approach may also be suitable for patients with colon cancer. The safety and feasibility of watch and wait in patients with colon cancer need to be verified by more clinical data.
Systemic increase in IL-26 is associated with severe COVID-19 and comorbid obstructive lung disease
Authors: Cardenas Eduardo I. , Robertson Josefina , Misaghian Salvia , Brown Jermaine , Wang Mingyue , Stengelin Martin , Sigal George , Wohlstadter Jacob , Gisslén Magnus , Lindén Anders
Published: October 2024

Background

IL-26 is a key mediator of pulmonary host defense given its abundant expression in human airways and its established antibacterial properties. Moreover, recent studies indicate that IL-26 can also inhibit viral replication. Along these lines, we have previously reported an increase in the plasma concentration of IL-26 among patients with acute COVID-19 that is linked to harmful hyperinflammation. Nevertheless, it is still unclear whether this systemic increase in IL-26 relates to disease severity, sex, comorbidities, viral load, or the innate immune response in acute COVID-19.

Methods

IL-26 was quantified using ELISA in plasma samples from a large cohort of well-characterized patients with acute COVID-19 (n=178) and healthy controls (n=30). The plasma concentrations of SARS-CoV-2 nucleocapsid and spike protein, as well as those of IFN-α2a, IFN-β, and IFN-γ, were determined using electrochemiluminescence immunoassay. The concentration of double-stranded DNA was determined using fluorometry.

Results

The plasma concentration of IL-26 was increased in patients with severe/critical COVID-19, particularly among males and patients with comorbid obstructive lung disease. Moreover, the concentration of IL-26 displayed positive correlations with length of hospital stay, as well as with systemic markers of viral load, antiviral immunity, and extracellular DNA.

Conclusions

Systemic IL-26 is involved in severe COVID-19, especially in males and patients with comorbid obstructive lung disease. These findings argue that systemic IL-26 has pathogenic and antiviral relevance, as well as biomarker potential.
Integrated transcriptome analysis of CSE1L regarding poor prognosis and immune infiltration in bladder urothelial carcinoma and experimental verification
Authors: Liu Runze , Ma Jiayi , Zhang Yong , Zhou Zhongbao
Published: October 2024

Background

Bladder urothelial carcinoma (BLCA) is one of the most prevalent tumors globally, with its incidence rising notably in developed countries, significantly affecting human health. CSE1L encodes a protein that is involved in various cellular processes and plays a critical role in cancer initiation and progression. However, its role in BLCA remains underexplored.

Methods

CSE1L expression in BLCA was analyzed using TCGA data and validated by qRT-PCR and Western blot in clinical samples. Survival analysis and Cox regression models were used to evaluate its prognostic value. Functional enrichment and protein interaction analyses were performed, and immune cell infiltration was assessed using CIBERSORT. Drug sensitivity was analyzed using GDSC data. In vitro assays evaluated the effects of CSE1L knockdown on cell proliferation, migration, and invasion.

Results

CSE1L was found to be significantly overexpressed in BLCA tissues compared to normal tissues. High CSE1L expression was associated with poor overall survival and unfavorable clinicopathological features. Functional enrichment analysis revealed that DEGs related to CSE1L were involved in cell cycle regulation and immune-related pathways. Immune infiltration analysis indicated a significant correlation between CSE1L expression and various immune cell types, particularly T cells and macrophages. Drug sensitivity analysis identified several chemotherapeutic agents, including MG-132, Palbociclib, and Nutlin-3a, which were more effective in the low-CSE1L expression group, while the high-CSE1L expression group showed sensitivity to drugs like S-Trityl-L-cysteine, Bleomycin, and Cisplatin. In vitro knockdown of CSE1L in BLCA cell lines inhibited cell proliferation, migration, and invasion.

Conclusions

The overexpression of CSE1L is associated with the progression and poor prognosis of bladder cancer, suggesting it could be a promising target for bladder cancer in the future.
FMNL1 and mDia1 promote efficient T cell migration through complex environments via distinct mechanisms
Authors: Sigler Ashton L. , Thompson Scott B. , Ellwood-Digel Logan , Kandasamy Adithan , Michaels Mary J. , Thumkeo Dean , Narumiya Shuh , Del Alamo Juan C. , Jacobelli Jordan
Published: October 2024

Lymphocyte trafficking and migration through tissues is critical for adaptive immune function and, to perform their roles, T cells must be able to navigate through diverse tissue environments that present a range of mechanical challenges. T cells predominantly express two members of the formin family of actin effectors, Formin-like 1 (FMNL1) and mammalian diaphanous-related formin 1 (mDia1). While both FMNL1 and mDia1 have been studied individually, they have not been directly compared to determine functional differences in promoting T cell migration. Through in vivo analysis and the use of in vitro 2D and 3D model environments, we demonstrate that FMNL1 and mDia1 are both required for effective T cell migration, but they have different localization and roles in T cells, with specific environment-dependent functions. We found that mDia1 promotes general motility in 3D environments in conjunction with Myosin-II activity. We also show that, while mDia1 is almost entirely in the cytoplasmic compartment, a portion of FMNL1 physically associates with the nucleus. Furthermore, FMNL1 localizes to the rear of migrating T cells and contributes to efficient migration by promoting deformation of the rigid T cell nucleus in confined environments. Overall, our data indicates that while FMNL1 and mDia1 have similar mechanisms of actin polymerization, they have distinct roles in promoting T cell migration. This suggests that differential modulation of FMNL1 and mDia1 can be an attractive therapeutic route to fine-tune T cell migration behavior.
Unraveling the ecological landscape of mast cells in esophageal cancer through single-cell RNA sequencing
Authors: Zhang Shengyi , Zhang Xinyi , Xiahou Zhikai , Zuo Shunqing , Xue Jialong , Zhang Yi
Published: October 2024

Background

Esophageal cancer (EC) is a major health issue, ranking seventh in incidence and sixth in mortality worldwide. Despite advancements in multidisciplinary treatment approaches, the 5-year survival rate for EC remains low at 21%. Challenges in EC treatment arise from late-stage diagnosis, high malignancy, and poor prognosis. Understanding the tumor microenvironment is critical, as it includes various cellular and extracellular components that influence tumor behavior and treatment response. Mast cells (MCs), as tissue-resident immune cells, play dual roles in tumor dynamics. High-throughput single-cell RNA sequencing offers a powerful tool for analyzing tumor heterogeneity and immune interactions, although its application in EC is limited.

Methods

In this study, we investigated the immune microenvironment of EC using single-cell RNA sequencing and established a comprehensive immune profile. We also performed analysis of upstream transcription factors and downstream pathway enrichment to further comprehensively decipher MCs in EC. Besides, we performed knockdown experiments to explore the role of epidermal growth factor receptor (EGFR) signaling pathway in MCs-tumor cell interactions, highlighting its potential as a prognostic marker. Finally, we constructed a prognostic model for EC, which provided valuable suggestions for the diagnosis and prognosis of EC.

Results

Our analysis identified 11 major cell types, of which MCs were particularly present in pericarcinoma tissues. Further grouping of the 5,001 MCs identified 8 distinct subtypes, including SRSF7-highly expressed MCs, which showed strong tumor preference and potential tumor-promoting properties. Moreover, we identified the key signaling receptor EGFR and validated it by in vitro knockdown experiments, demonstrating its cancer-promoting effects. In addition, we established an independent prognostic indicator, SRSF7+ MCs risk score (SMRS), which showed a correlation between high SMRS group and poor prognosis.

Conclusion

These findings illuminate the complex interactions within the tumor microenvironment of EC and suggest that targeting specific MCs subtypes, particularly via the EGFR signaling pathway, may present novel therapeutic strategies. This study establishes a comprehensive immune map of EC, offering insights for improved treatment approaches.