bluuebunny/crossref_metadata_2025 huggingface dataset:
TRENDS AND PROSPECTS FOR THE DEVELOPMENT OF THE GLOBAL ADVERTISING MARKET
Authors:   Uzhhorod Brenzovych National University, Riabak Victoriya , Brenzovych Kateryna ,   Uzhhorod National University
Published: December 2023

The article is devoted to the analysis of trends and prospects for the development of the global advertising market under the influence of changing conditions of the market environment and scientific and technological progress. Advertising is seen as a market research tool that allows advertisers to increase the effectiveness of their market. It is substantiated that the global advertising market, integrating into the socio-economic processes of society's development, has become an integral ele- ment of the global economy. It was determined that the informatization of the world economy and the development of modern media markets led to the diversification of advertising, the emergence of new, more effective types of advertising, and the con- ceptuality of advertising and the establishment of feedback from the consumer are the key to the success of the marketing activi- ties of a modern enterprise. The main trends in the development of advertising in modern society are highlighted, including the creation of a new format of communication with the consumer, the use of non-standard media carriers for advertising messages, the globalization of advertising campaigns, and others. Emphasis is placed on such features of the development of the advertis- ing market as increasing the social coloring of advertising and the social responsibility of advertisers. The transformations of the structure of the world advertising market and the role of the main types of advertising in the market, the peculiarities of the geographical structure of the advertising market are studied. A detailed analysis of statistical data on the volume of advertising by such types as advertising on television, advertising in print media and on the radio, Internet advertising was carried out, as a result of which a significant dynamic of the development of network advertising and a significant decrease in the contribution to the value volume of the advertising market of traditional types of advertising were revealed. The prerequisites, trends and prospects for the development of Internet advertising are analyzed. It is concluded that the redistribution of the advertising market and the growth of the share of Internet advertising is a global trend.
MANAGEMENT OF THE COMPANY'S DISTRIBUTION ACTIVITIES IN INTERNATIONAL BUSINESS
Authors:   Uzhhorod National University, Steblak Diana , Bakhtyn Ivanna ,   Uzhhorod National University
Published: December 2023

The issue of managing a company's distribution activities in international business is examined in this article. With the growth of trade and increasing competition, it is necessary to implement effective strategies for expanding company's products and services to the global market. It is evident that companies are establishing international partnerships with local distributors and partners to access new markets, highlighting the necessity of developing a strategically sound system for managing distribution activities. Furthermore, facing economic challenges and market volatility, it becomes imperative for businesses to regulate their distribution management strategies. Effective distribution management ensures that not only products and services reach their intended international markets efficiently but it also plays a crucial role in maintaining a competitive edge in the global arena. It is importent to emphasize the significance of cultivating strong relationships with local distributors and partners. The collaboration within local entities who possess an in-depth knowledge of the regional market dynamics, consumer preferences, and legal frameworks can be instrumental in navigating the complication of international business. Such partnerships enable companies to tap into local knowledge and resources, adapt their offerings accordingly, and establish a stronger presence in new territories. Moreover, the implementation of a well-thought-out distribution management system aids in optimizing supply chains, reducing operational costs, and enhancing the overall customer experience. It helps in streamlining inventory management, minimizing lead times, and ensuring timely deliveries. These factors, in turn, can contribute to customer satisfaction and loyalty, ultimately gaining business success on a global scale. Additionally, the evolving landscape of international business is increasingly dependent on technology and data-driven insights. The use of modern tools and technologies is paramount for efficient distribution management. Automation, data analytics, and digital platforms enable companies to monitor inventory in real-time, track sales performance, and adapt their strategies promptly in response to market changes. Companies that successfully master these aspects are well-positioned to thrive in the global marketplace, expand their reach, and remain competitive amidst the challenges and opportunities that international business presents.
STABILISATION OF THE COUNTRY'S ECONOMY IN TIMES OF CRISIS
Authors:   Academy of Applied Sciences (WSHIU), Trzonkowski Konrad , Ushenko Natalya ,   Borys Grinchenko Kyiv University
Published: December 2023

Ukraine is currently facing difficult economic conditions caused by Russia's military expansion. At the same time, despite the negative consequences caused by the Russian aggression, the country's economy is showing positive dynamics towards structural changes. In such circumstances, it is important to analyse the methodology for stabilising the country's economy and to find effective forms of attracting international financial assistance, which is a significant factor of supporting the country in times of crisis. The article examines the issues of stabilisation of the country's economy in the context of the crisis. The article analyses forms and methods of stabilisation of the country's economy in crisis conditions. An empirical study of financial measures at the macro and micro levels that had a positive effect on the recovery of the economic situation in the country has been carried out. It is established that under the conditions of martial law, the country's economy has begun to gradually recover since the beginning of 2023. Despite the low production volumes, the overall financial performance is tending to improve. The expected growth in economic forecasts is explained by the fact that Ukraine's energy sector has withstood the air attacks of the aggressor country. Due to this, the economic performance of enterprises, primarily in the retail and service sectors, has improved. The improvement of households' expectations and the growth of state budget expenditures, thanks to international assistance, will support consumer demand. However, the destruction of production facilities and infrastructure, including energy infrastructure, will continue to limit economic activity, and its recovery will require significant resources. It is specified that inflation is decreasing faster than expected, which is facilitated by an adequate supply of food and fuel, a lower electricity shortage, and a favourable situation on the foreign exchange market. An analysis of the activity of other countries in providing assistance to Ukraine made it possible to note that international aid covers the balance of payments gap and helps to build up financial reserves. It has been found that, in general, the National Bank of Ukraine forms positive theses on improving the economic situation in the country for future periods. In conclusion, the main source of financing of the country's budget is international aid and a minor percentage of its own GDP. Due to the stable inflow of international aid, the economy's liquidity has improved. The created liquidity buffer creates the conditions for increasing internal expenditures and paying expenses and fulfilling external obligations in a timely manner.
СТАЛИЙ ТА БЕЗПЕЧНИЙ РОЗВИТОК ТУРИЗМУ ЯК ОДИН З КРИТЕРІЇВ ТРАНСФОРМАЦІЇ КОНКУРЕНТНОГО ПОТЕНЦІАЛУ СУБ’ЄКТІВ ТУРИСТИЧНОЇ ІНДУСТРІЇ
Authors: Єрко І.В.
Published: December 2023

У статті досліджено сталий та безпечний розвиток туризму як один з критеріїв трансформації конкурентного потенціалу суб’єктів туристичної індустрії. Проведено огляд літератури щодо дослідження сталого та безпечного розвитку туризму. Встановлено одностайність в думці, що сталий розвиток туризму передбачає оптимальне співвідношення між екологічним навантаженням туристів на довкілля, соціальними потребами (або соціальною відповідальністю) та економічним розвитком. Цілі статті полягають у дослідженні сталого та безпечного розвитку туризму як одного з критеріїв трансформації конкурентного потенціалу суб’єктів туристичної індустрії. Запропоновано тири види співвідношень в системі сталого розвитку туристичної індустрії: охорона довкілля – соціальні потреби; соціальні потреби – економічний розвиток; економічний розвиток – охорона довкілля. Дотримання таких співвідношень дозволить забезпечити збалансований розвиток туристичної індустрії через задоволення потреб споживачів у якісних послугах, збереження довкілля та туристичного потенціалу дестинацій, отримання економічної вигоди від діяльності суб’єктів туристичної індустрії. Встановлено, що безпека є важливим індикатором розвитку туристичної індустрії. Дійшли до висновку, туристична привабливість дестинації обов’язково супроводжується забезпеченням безпеки туристів, дотриманням нормативів та стандартів якості туристичного обслуговування. Тому, важливим завданням у повоєнний період є зміна стереотипів сприйняття України у міжнародному туристичному просторі як країни воєнних дій на безпечну дестинацію, відкриту для туристів.
ОБҐРУНТУВАННЯ ІЄРАРХІЧНОСТІ СТРУКТУРИ КОМПЕТЕНТНОСТІ ОРГАНІЗАЦІЇ
Authors: Грузіна І.А.
Published: December 2023

Компетенції організації, вдало поєднуючись із супутніми компетенціями співробітників формують загальну організаційну компетентність. З огляду на те, що жодна з компетенцій не в змозі відігравати ключову роль для досягнення цілей організацій, виникає необхідність їх оптимального поєднання для вирішення управлінських завдань кожного етапу життєвого циклу організації. У статті визначено перелік компетенцій, що формують структуру організаційної компетентності, та обґрунтовано необхідність їх ієрархічного розташування за рівнями піраміди. Співвіднесення рівнів організаційних компетенцій із завданнями на кожній стадії життєвого циклу організації, доповнене постійним моніторингом їх стану, дозволить керівникам визначати необхідність їх оновлення, а також можливості трансформації та розвитку.
ІННОВАЦІЙНИЙ ПОТЕНЦІАЛ ЕКОНОМІЧНОГО РОЗВИТКУ ПІДПРИЄМСТВ
Authors: Гаврильченко О.В.
Published: December 2023

Обґрунтовано концептуальні підходи до оцінки інноваційного потенціалу підприємства, що базуються на: розмежуванні сукупності ресурсів, що формують інноваційний потенціал, на два типи (наскрізні й специфічні); позиціонуванні персоналу організації в якості домінантної наскрізної ресурсної складової інноваційного потенціалу; виділенні чотирьох етапів діагностики рівня розвитку інноваційного потенціалу, структурованих по типах ресурсних складових (ревізія ресурсів, первісна оцінка ресурсів, інкубація ресурсів, констатація готовності ресурсів). Розглянуто стратегії інноваційного розвитку: стратегія виробничо- інноваційного прориву та стратегія інтелектуального прориву, які передбачають побудову виробничої моделі за типом Кобба- Дугласа на основі аналізу впливу факторів фондовіддачі й продуктивності праці на обсяг реалізації інноваційної продукції.
ПРОЦЕС МОДЕЛЮВАННЯ РИЗИКІВ ФІНАНСОВИХ ІНВЕСТИЦІЙ
Authors: Олешко Тамара , Попик Наталія , Турченюк Денис
Published: December 2023

У статті досліджується проблема моделювання ризиків фінансових інвестицій. Авторами було проаналізовано основні методи та інструменти, які використовуються для оцінки та управління ризиками в інвестиційній сфері. В результаті проведених досліджень були ідентифіковані ключові фактори, які впливають на ризиковість інвестиційних проектів. На основі цих факторів можуть були розроблені моделі, які допомагають інвесторам приймати обґрунтовані рішення та зменшувати можливі втрати. В ході дослідження було проведено аналіз основних підходів до моделювання ризиків, а також запропоновано практичні приклади застосування моделей в реальних інвестиційних ситуаціях. Результати досліджень можуть бути використаними фахівцями в галузі фінансів та інвестицій, а також для всіх, хто цікавиться ризиками та ефективним керуванням ними у фінансовому секторі.
ГЕОІНФОРМАЦІЙНІ СИСТЕМИ ЯК ІНСТРУМЕНТ АНАЛІЗУ РОЗСЕЛЕННЯ В КОНТЕКСТІ ВПЛИВУ НА ТУРИСТИЧНУ СФЕРУ СУСПІЛЬНО-ГЕОГРАФІЧНОГО РАЙОНУ
Authors: Сологуб Юрiй , Безпала Ольга , Харченко Олена
Published: December 2023

Стаття присвячена аналізу диференціації рівнів сформованості міської системи розселення Столичного суспільно-географічного району як фактора розвитку туристичної сфери. Розкрито сутність міської розселенської мережі Столичного суспільно-географічного району та проведено її структурний аналіз. Виявлено особливості функціонування міської системи розселення суспільно-географічного району, окреслено шляхи її подальшого розвитку. Дослідження системи розселення району проводилося на основі аналізу статистичних індикаторів її функціонування та розвитку з використанням інструментальних можливостей сучасних геоінформаційних систем. Розвиток столиці й Столичного суспільно-географічного району характеризується більш швидкими темпами, що зумовлено наявністю своєрідного каталізатора соціально-економічного життя району, а саме, центрального міста з особливим статусом – Києва.
Exilic-Diasporic Life Writing and Human Rights: A Diasporic Iranian Perspective
Authors: Naghibi Nima
Published: December 2023

[para. 1]: "This special issue of a/b: Auto/Biography Studies provides us with an opportunity to think through the transformation and the future direction of auto|biographical studies as a field of scholarly inquiry. It allows us to consider what the stakes are in the aademic study of auto|biographical writing, to reflect on the popularity of life writing resulting in the "memoir boom" about which life-writing scholars have written, and leads us to ask: what kind of intellectual (and political) engagement does the study of life narrative make possible?"
Diva Worship and the Sonic Search for Queer Utopia
Authors: Jennex Craig
Published: December 2023

Pragmatic and assimilationist ideals permeate contemporary gay culture: Michael Joseph Gross in The Atlantic, for instance, argues that gay male participation in music culture still fetishizes normativity. According to Gross, the current generation of gay men is indifferent to the veneration of female icons, an important aspect of gay male identity of the past. In this article I challenge these assertions. Using ethnographic research with fans of Lady Gaga, the article shows that for many gay men the continuing veneration of female icons remains an integral aspect of gay identity. I explore gay male music fandom of the past and of the present to imagine a potential queer future.

 
Affective Interruptions: Political Collectivity in Halftime
Authors: Jennex Craig
Published: December 2023

In this article, I analyze a rhythmic device in musical theater performance that is often used but rarely discussed: The sudden break into halftime. Breaking into halftime—a rhythmic shift that is performed and perceived as occurring at half the tempo (or speed) of the groove in preceding and subsequent sections—has the effect of abruptly stretching out and slowing down musical temporality. With a break into halftime, a song's groove is suddenly broader, more open, and expansive. When accompanied by lyrics, the move suggests deliberateness, calls attention to the lyrical address, and invites a considered response from the listener. It is a musical device akin to drastically slowing down a spoken cadence to ensure that the listener is fully grasping the significance of one's words. With or without lyrics, this temporal disruption has a powerful effect on listeners’ bodies as, suddenly, the established timing of one's musical experience is disrupted and immediately set to half the speed of the previous pace. By analyzing the use of halftime in three filmed musicals—Newsies, Rent, and the Rocky Horror Picture Show—I show how the rhythmic device carries with it social coding of solidarity and collective power among queer, marginalized, and/or otherwise outcast individuals and ultimately alters the broader narrative of the shows. Ultimately, I articulate how halftime serves to queer time and forge collective action, allowing us to reimagine what sort of politics, formations, collectives, and futures are possible.
Topographically channeled ocean-atmosphere coupling in the southern Caribbean and summer climate variability
Authors: Jury MR
Published: December 2023

This research links global climate to regional weather by considering Caribbean trade wind strength in the context of the large-scale Walker circulation across the Pacific-Atlantic basins, and localized processes involving air-sea interactions between freshwater flux, the ocean mixed-layer depth, and topographic channeling of airflow north of Colombia. Trade wind driven coastal upwelling in the southern Caribbean is enhanced by the Andes Mountains, and creates a focal point for summer climate variability. This emerges in empirical orthogonal function (EOF) analysis of June-July surface zonal winds in the period 1979-2022. Highest EOF loading occurs at 12° N, 75° W northwest of Colombia. Point-to-field correlations with the EOF time score reflect a Pacific-Atlantic thermal dipole and Walker circulation linked with the El Niño-Southern Oscillation (ENSO). As southern Caribbean trade winds weaken, run-off increases, the upper ocean becomes buoyant, and westward currents slacken. Composite differences show that slow trade-wind conditions in June-July induce a counter-current that spreads warm fresh water northeastward from Colombia. This plume disperses toward the Antilles Islands with sufficient memory to triple the number of tropical cyclones in August-September. A slow trade-wind case study in June 2011 emphasizes key air-sea interactions. Channeling of the large-scale airflow north of the Andes Mountains creates a narrow atmospheric bridge for transmission of ENSO signals.
Comparative Study of Several Lymphocyte Functions in Two Strains of Mice with Different Models of Endotoxic Shock.
Authors: Víctor VM , Rubio D , De la Fuente M
Published: December 2023

Previously, the changes in phagocyte functions such as adherence, chemotaxis or TNFa production were found to be associated with oxidative stress in endotoxin-induced septic shock. However, in this type of oxidative stress the lymphocyte involvement has rarely been studied. In the present report, we analyzed the above functions in peritoneal lymphocytes from male and female BALB/c mice with a lethal endotoxic shock caused by intraperitoneal injection of E. coli lipopolysaccharide (LPS) (100 mg/kg), male and female Swiss mice with lethal endotoxic shock caused by intraperitoneal injection of LPS (150 and 250 mg/kg, respectively) or non-lethal endotoxic shock (100 mg/kg). In peritoneal lymphocytes obtained at 0, 2, 4, 12 or 24 h after LPS injection, the first two functions of these cells in the immune response, i.e. adherence to tissues and directed migration (chemotaxis), were studied. At 0, 0.5, 1, 1.5, 2, 4, 12 and 24 h after LPS injection, TNFa released by lymphocytes was also analyzed. The results show that endotoxic shock increases the adherence and TNFa release, and decreases the chemotaxis of peritoneal lymphocytes. These changes were more significant in mice with lethal than with non-lethal endotoxic shock, a fact that confirms the important role of lymphocytes during endotoxic shock.
Gender in the disclosure of loneliness on Twitter during COVID-19 lockdowns
Authors: Mejova Yelena , Hommadova Lu Anya
Published: December 2023

Introduction

Loneliness has been shown to affect both mental and physical health, and was a major concern even before the COVID-19 pandemic. During the COVID-19 distancing measures, millions of people took to social media to express their feelings and seek social support.

Methods

In this mixed-methods study, we examine the self-disclosure of loneliness by users identifying as male or female (via self-disclosed naming conventions) on Twitter before and during the COVID-19 “lockdowns.”

Results

We show that in the first two months of COVID-19 restrictions, self-disclosure of loneliness on this platform rose dramatically, and also have changed qualitatively. We find that female accounts tend to post more loneliness self-disclosures compared to male ones, even before COVID. Female disclosures more often center around pregnancy, family, and close relationships, whereas those posted by the male ones are more related to leadership, video gaming and sex. During COVID lockdowns, female accounts turn to online messaging apps and hobbies, and male become increasingly vocal in seeking partners.

Discussion

The insights of this study have important implications for the design of interventions for lessening the burden of loneliness in the current digitized world.
Championing awareness of the opioid epidemic through a service-learning module for non-STEM biology majors
Authors: Fleming Ryleigh , Adkins Sarah J. , Esteban Marco , Cross Cinnamin , Chatham Amy Hutson , Raut Samiksha A.
Published: December 2023

Over 50,000 people die annually from opioid overdoses in the United States leading to what has become known as the “opioid epidemic.” This is of heightened concern in states like Alabama that experience higher rates of overall drug use and overdose deaths. Thus, it is increasingly important for college students in Alabama to learn about how the opioid epidemic is affecting their communities. Previous studies have demonstrated that engaging non-majors in innovative active-learning oriented pedagogies like service-learning can enhance their understanding and awareness about contemporary societal issues. Despite its pedagogical potential, the impact of opioid-related service-learning, particularly for non-majors, continues to remain unexplored. In this study, we describe the implementation of a service-learning module centered on opioid addiction. Students in a non-major biology course learned the science behind opioids, had Naloxone training, and engaged in active discussions with an opioid researcher, physician, and former illicit opioid user. Our assessment of the thematic analysis of pre- and post-reflection free-write data from 87 consenting students revealed 10 categories that students reported in the post- but not pre-reflections (essay gain), pre- and post-reflections (neutral), and pre- but not post-reflections (essay loss). We found essay gains in students humanizing addiction and awareness of the cultural context of opioid addiction and essay losses from students indicating that non-major students had a low level of awareness related to these issues. Eight one-on-one, semi-structured interviews revealed that students were personally impacted by the epidemic and valued its curricular inclusion. Our data supports that service-learning can increase non-major biology student’s awareness and contextual understanding about the opioid epidemic, enabling much-needed advocacy to further enhance its awareness among the public.
Topography and structural diversity regulate ecosystem multifunctionality in a subtropical evergreen broad-leaved forest
Authors: Wang Jiaming , Liu Heming , Yang Qingsong , Shen Guochun , Zhu Xuyang , Xu Yue , Wang Xihua
Published: December 2023

Forest functionality is generally considered a byproduct of forest diversity. Perhaps unsurprisingly, many researchers associate increasing multi-functionality with increasing diversity. Diversity, however, is an often-overused word that may describe a host of features, including the diversity of species, functional trait and structure. Furthermore, variable environmental features (such as topography) influence the interaction between forest plants and their function. Incorporating complex topography (like that associated with tropical and subtropical forests) into estimates of forest functionality is challenging and highly uncertain. In this paper, we applied structural equation models to disentangle the relative importance of topography and different components of what might be considered “plant diversity” to forest multifunctionality using repeated census of a 20-ha subtropical forest plot. We found that multifunctionality was principally influenced by structural diversity more so than either species composition or functional trait diversity. In our SEM model approach, we observed variations in topography could account for about 30% of variation in multifunctionality. Furthermore, variations in topography could indirectly influence forest multifunctionality by changing species composition, functional trait diversity, and structural diversity. Our work highlights the importance of topography and forest structure in regulating subtropical forest multifunctionality on the local scale. This suggests future subtropical forest management should focus on regulating forest structure. Namely, our results suggest land managers must take topography (and the complex interaction between topography and plant diversity) into account in order to build robust and multifunctional forests.
A data management plan for the NESHIE observational study
Authors: Strydom Adéle , Van Rensburg Jeanne , Pepper Michael S.
Published: December 2023

With regard to the use and transfer of research participants’ personal information, samples and other data nationally and internationally, it is necessary to construct a data management plan. One of the key objectives of a data management plan is to explain the governance of clinical, biochemical, laboratory, molecular and other sources of data according to the regulations and policies of all relevant stakeholders. It also seeks to describe the processes involved in protecting the personal information of research participants, especially those from vulnerable populations. In most data management plans, the framework therefore consists of describing the collection, organization, use, storage, contextualization, preservation, sharing and access of/to research data and/or samples. It may also include a description of data management resources, including those associated with analyzed samples, and identifies responsible parties for the establishment, implementation and overall management of the data management strategy. Importantly, the data management plan serves to highlight potential problems with the collection, sharing, and preservation of research data. However, there are different forms of data management plans and requirements may vary due to funder guidelines and the nature of the study under consideration. This paper leverages the detailed data management plans constructed for the ‘NESHIE study’ and is a first attempt at providing a comprehensive template applicable to research focused on vulnerable populations, particularly those within LMICs, that includes a multi-omics approach to achieve the study aims. More particularly, this template, available for download as a supplementary document, provides a modifiable outline for future projects that involve similar sensitivities, whether in clinical research or clinical trials. It includes a description of the management not only of the data generated through standard clinical practice, but also that which is generated through the analysis of a variety of samples being collected from research participants and analyzed using multi-omics approaches.
Case Report: Telitacicept in severe myasthenia gravis: a case study with multiple autoantibodies
Authors: Guo Qian , Huang Yusen , Wang Fangruyue , Fang Le
Published: December 2023

Multi-antibody-positive myasthenia gravis (MG) presentations are relatively rare, often found in older patients, and generally predict a poor prognosis. We report a case of a female patient with generalized MG, testing positive for Titin antibodies (Titin-Ab), ryanodine receptor antibodies (RyR-Ab), and acetylcholine receptor antibodies (AChR-Ab), and resistant to acetylcholinesterase inhibitors. Following unsuccessful traditional therapies, she received Telitacicept, leading to significant improvements. This case underscores Telitacicept’s potential efficacy for similar patients and offers insights into the clinical characteristics of multi-antibody MG.
Clinical markers predict the efficacy of several immune checkpoint inhibitors in patients with non-small cell lung cancer in China
Authors: Wang Yuxin , Lu Jiahui , Wu Chenxi , Fei Fei , Chu Zhuze , Lu Peihua
Published: December 2023

Objectives

Immune checkpoint inhibitors (ICIs) are one of the most significant oncological treatment modalities as a result of the rapid advancement of immunotherapy. Programmed Cell Death-Ligand 1 (PD-L1) and tumor mutational burden (TMB) have emerged as key markers for predicting the efficacy and prognosis of ICIs in non-small cell lung cancer (NSCLC), and the predictive role of tumor-infiltrating lymphocytes (TILs) has also received significant attention. However, the prognosis of some individuals cannot be determined by these indicators; for instance, some patients with low PD-L1 expression also benefit from longer survival. Therefore, the purpose of this research was to investigate the connection between new haematological and pathological markers and clinical outcomes in NSCLC patients receiving ICIs.

Methods

Seventy-six patients with stage III-IV NSCLC treated with ICIs were included in this study. We used the Mann-Whitney test, COX regression and Kaplan-Meier analysis to retrospectively analyze peripheral blood indicators and survival prognostic data of 76 patients in order to investigate the relationship between baseline neutrophil-to-lymphocyte ratio (NLR) and the efficacy of ICIs. To investigate the correlation between CXCL13, CXCR5, CD8 and the efficacy of ICIs, we assessed the expression levels of aforementioned indicators in biopsied tissues of 10 non-small cell lung tumors by immunohistochemistry (IHC) and immunofluorescence (IF) and performed statistical analysis.

Results

Disease control rate (DCR) was higher in patients with baseline NLR <3.4 (p=0.016) and neutrophil percentage <71% (P=0.015). Baseline NLR (HR=2.364, P=0.003) and neutrophil percentage (HR=2.824, P=0.013) had the greatest influence on patients’ survival prognosis, with baseline NLR exhibiting a stronger predictive value (AUC=0.717), according to univariate and multifactorial COX regression analyses of progression-free survival (PFS) and overall survival (OS). In NSCLC tissues, higher expression of CXCL13 was associated with better clinical outcomes (P=0.032) and higher expression of CD8 was associated with prolonged survival (P=0.022).

Conclusion

Low baseline NLR in peripheral blood and high expression of CD8 in tissues are associated with longer PFS and may have a potential predictive value for patients with stage III-IV NSCLC using ICIs.
Sutterella and its metabolic pathways positively correlate with vaccine-elicited antibody responses in infant rhesus macaques
Authors: Jiang Danting , Goswami Ria , Dennis Maria , Heimsath Holly , Kozlowski Pamela A. , Ardeshir Amir , Van Rompay Koen K. A. , De Paris Kristina , Permar Sallie R. , Surana Neeraj K.
Published: December 2023

Introduction

It is becoming clearer that the microbiota helps drive responses to vaccines; however, little is known about the underlying mechanism. In this study, we aimed to identify microbial features that are associated with vaccine immunogenicity in infant rhesus macaques.

Methods

We analyzed 16S rRNA gene sequencing data of 215 fecal samples collected at multiple timepoints from 64 nursery-reared infant macaques that received various HIV vaccine regimens. PERMANOVA tests were performed to determine factors affecting composition of the gut microbiota throughout the first eight months of life in these monkeys. We used DESeq2 to identify differentially abundant bacterial taxa, PICRUSt2 to impute metagenomic information, and mass spectrophotometry to determine levels of fecal short-chain fatty acids and bile acids.

Results

Composition of the early-life gut microbial communities in nursery-reared rhesus macaques from the same animal care facility was driven by age, birth year, and vaccination status. We identified a Sutterella and a Rodentibacter species that positively correlated with vaccine-elicited antibody responses, with the Sutterella species exhibiting more robust findings. Analysis of Sutterella-related metagenomic data revealed five metabolic pathways that significantly correlated with improved antibody responses following HIV vaccination. Given these pathways have been associated with short-chain fatty acids and bile acids, we quantified the fecal concentration of these metabolites and found several that correlated with higher levels of HIV immunogen-elicited plasma IgG.

Discussion

Our findings highlight an intricate bidirectional relationship between the microbiota and vaccines, where multiple aspects of the vaccination regimen modulate the microbiota and specific microbial features facilitate vaccine responses. An improved understanding of this microbiota–vaccine interplay will help develop more effective vaccines, particularly those that are tailored for early life.
Akkermansia muciniphila - friend or foe in colorectal cancer?
Authors: Gubernatorova Ekaterina O. , Gorshkova Ekaterina A. , Bondareva Marina A. , Podosokorskaya Olga A. , Sheynova Anna D. , Yakovleva Anastasia S. , Bonch-Osmolovskaya Elizaveta A. , Nedospasov Sergei A. , Kruglov Andrey A. , Drutskaya Marina S.
Published: December 2023

Akkermansia muciniphila is a gram-negative anaerobic bacterium, which represents a part of the commensal human microbiota. Decline in the abundance of A. muciniphila among other microbial species in the gut correlates with severe systemic diseases such as diabetes, obesity, intestinal inflammation and colorectal cancer. Due to its mucin-reducing and immunomodulatory properties, the use of probiotics containing Akkermansia sp. appears as a promising approach to the treatment of metabolic and inflammatory diseases. In particular, a number of studies have focused on the role of A. muciniphila in colorectal cancer. Of note, the results of these studies in mice are contradictory: some reported a protective role of A. muciniphila in colorectal cancer, while others demonstrated that administration of A. muciniphila could aggravate the course of the disease resulting in increased tumor burden. More recent studies suggested the immunomodulatory effect of certain unique surface antigens of A. muciniphila on the intestinal immune system. In this Perspective, we attempt to explain how A. muciniphila contributes to protection against colorectal cancer in some models, while being pathogenic in others. We argue that differences in the experimental protocols of administration of A. muciniphila, as well as viability of bacteria, may significantly affect the results. In addition, we hypothesize that antigens presented by pasteurized bacteria or live A. muciniphila may exert distinct effects on the barrier functions of the gut. Finally, A. muciniphila may reduce the mucin barrier and exerts combined effects with other bacterial species in either promoting or inhibiting cancer development.
Nanoplanktonic diatom rapidly alters sinking velocity via regulating lipid content and composition in response to changing nutrient concentrations
Authors: Zhang Wei , Hao Qiang , Zhu Jie , Deng Yangjie , Xi Maonian , Cai Yuming , Liu Chenggang , Zhai Hongchang , Le Fengfeng
Published: December 2023

Diatom sinking plays a crucial role in the global carbon cycle, accounting for approximately 40% of marine particulate organic carbon export. While oceanic models typically represent diatoms as microphytoplankton (> 20 μm), it is important to recognize that many diatoms fall into the categories of nanophytoplankton (2-20 μm) and picophytoplankton (< 2 μm). These smaller diatoms have also been found to significantly contribute to carbon export. However, our understanding of their sinking behavior and buoyancy regulation mechanisms remains limited. In this study, we investigate the sinking behavior of a nanoplanktonic diatom, Phaeodactylum tricornutum (P. tricornutum), which exhibits rapid changes in sinking behavior in response to varying nutrient concentrations. Our results demonstrate that a higher sinking rate is observed under phosphate limitation and depletion. Notably, in phosphate depletion, the sinking rate of P. tricornutum was 0.79 ± 0.03 m d-1, nearly three times that of the previously reported sinking rates for Skeletonema costatum, Ditylum brightwellii, and Chaetoceros gracile. Furthermore, during the first 6 h of phosphate spike, the sinking rate of P. tricornutum remained consistently high. After 12 h of phosphate spike, the sinking rate decreased to match that of the phosphate repletion phase, only to increase again over the next 12 hours due to phosphate depletion. This rapid sinking behavior contributes to carbon export and potentially allows diatoms to exploit nutrient-rich patches when encountering increased nutrient concentrations. We also observed a significant positive correlation (P< 0.001) between sinking rate and lipid content (R = 0.91) during the phosphate depletion and spike experiment. It appears that P. tricornutum regulates its sinking rate by increasing intracellular lipid content, particularly digalactosyldiacylglycerol, hexosyl ceramide, monogalactosyldiacylglycerol, and triglycerides. Additionally, P. tricornutum replaces phospholipids with more dense membrane sulfolipids, such as sulfoquinovosyldiacylglycerol under phosphate shortage. These findings shed light on the intricate relationship between nutrient availability, sinking behavior, and lipid composition in diatoms, providing insights into their adaptive strategies for carbon export and nutrient utilization.
Endothelial cell clonality, heterogeneity and dysfunction in pulmonary arterial hypertension
Authors: Newcomb Geoffrey , Farkas Laszlo
Published: December 2023

Our understanding of the pathophysiology of pulmonary arterial hypertension (PAH) has evolved over recent years, with the recognition that endothelial cell (EC) dysfunction and inflammation play an integral role in the development of this disease. ECs within the pulmonary vasculature play a unique role in maintaining vascular integrity and barrier function, regulating gas exchange, and contributing to vascular tone. Using single-cell transcriptomics, research has shown that there are multiple, unique EC subpopulations with different phenotypes. In response to injury or certain stressors such as hypoxia, there can be a dysregulated response with aberrant endothelial injury repair involving other pulmonary vascular cells and even immune cells. This aberrant signaling cascade is potentially a primary driver of pulmonary arterial remodeling in PAH. Recent studies have examined the role of EC clonal expansion, immune dysregulation, and genetic mutations in the pathogenesis of PAH. This review summarizes the existing literature on EC subpopulations and the intricate mechanisms through which ECs develop aberrant physiologic phenotypes and contribute to PAH. Our goal is to provide a framework for understanding the unique pulmonary EC biology and pathophysiology that is involved in the development of PAH.
Jeongeuplla avenae gen. nov., sp. nov., a novel β-carotene-producing bacterium that alleviates salinity stress in Arabidopsis
Authors: Jiang Lingmin , Peng Yuxin , Kim Ki-Hyun , Jeon Doeun , Choe Hanna , Han Ah-Reum , Kim Cha Young , Lee Jiyoung
Published: December 2023

A novel endophytic bacterium, designated DY-R2A-6T, was isolated from oat (Avena sativa L.) seeds and found to produces β-carotene. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain DY-R2A-6T had 96.3% similarity with Jiella aquimaris LZB041T, 96.0% similarity with Aurantimonas aggregate R14M6T and Aureimonas frigidaquae JCM 14755T, and less than 95.8% similarity with other genera in the family Aurantimonadaceae. The complete genome of strain DY-R2A-6T comprised 5,929,370 base pairs, consisting of one full chromosome (5,909,198 bp) and one plasmid (20,172 bp), with a G + C content was 69.1%. The overall genome-related index (OGRI), including digital DNA–DNA hybridization (<20.5%), ANI (<79.2%), and AAI (<64.2%) values, all fell below the thresholds set for novel genera. The major cellular fatty acids (>10%) of strain DY-R2A-6T were C16:0, C19:0 cyclo ω8c, and summed feature 8 (C18:1ω7c and/or C18:1ω6c). Ubiquinone-10 was the main respiratory quinone. We identified the gene cluster responsible for carotenoid biosynthesis in the genome and found that the pink-pigment produced by strain DY-R2A-6T is β-carotene. In experiment with Arabidopsis seedlings, co-cultivation with strain DY-R2A-6T led to a 1.4-fold increase in plant biomass and chlorophyll content under salt stress conditions, demonstrating its capacity to enhance salt stress tolerance in plants. Moreover, external application of β-carotene to Arabidopsis seedlings under salt stress conditions also mitigated the stress significantly. Based on these findings, strain DY-R2A-6T is proposed to represent a novel genus and species in the family Aurantimonadaceae, named Jeongeuplla avenae gen. nov., sp. nov. The type strain is DY-R2A-6T (= KCTC 82985T = GDMCC 1.3014T). This study not only identified a new taxon but also utilized genome analysis to predict and confirm the production of β-carotene by strain DY-R2A-6T. It also demonstrated the ability of this strain to enhance salt stress tolerance in plants, suggesting potential application in agriculture to mitigate environmental stress in crops.
Phenotypic and metabolic adaptations of Rhodococcus cerastii strain IEGM 1243 to separate and combined effects of diclofenac and ibuprofen
Authors: Tyumina Elena , Bazhutin Grigory , Kostrikina Nadezhda , Sorokin Vladimir , Mulyukin Andrey , Ivshina Irina
Published: December 2023

Introduction

The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) has raised concerns regarding their environmental impact. To address this, understanding the effects of NSAIDs on bacteria is crucial for bioremediation efforts in pharmaceutical-contaminated environments. The primary challenge in breaking down persistent compounds lies not in the biochemical pathways but in capacity of bacteria to surmount stressors.

Methods

In this study, we examined the biodegradative activity, morphological and physiological changes, and ultrastructural adaptations of Rhodococcus cerastii strain IEGM 1243 when exposed to ibuprofen, diclofenac, and their mixture.

Results and Discussion

Our findings revealed that R. cerastii IEGM 1243 exhibited moderate biodegradative activity towards the tested NSAIDs. Cellular respiration assay showed higher metabolic activity in the presence of NSAIDs, indicating their influence on bacterial metabolism. Furthermore, catalase activity in R. cerastii IEGM 1243 exposed to NSAIDs showed an initial decrease followed by fluctuations, with the most significant changes observed in the presence of DCF and the NSAID mixture, likely influenced by bacterial growth phases, active NSAID degradation, and the formation of multicellular aggregates, suggesting potential intercellular synergy and task distribution within the bacterial community. Morphometric analysis demonstrated alterations in size, shape, and surface roughness of cells exposed to NSAIDs, with a decrease in surface area and volume, and an increase in surface area-to-volume ratio (SA/V). Moreover, for the first time, transmission electron microscopy confirmed the presence of lipid inclusions, polyphosphates, and intracellular membrane-like structures in the ibuprofen-treated cells.

Conclusion

These results provide valuable insights into the adaptive responses of R. cerastii IEGM 1243 to NSAIDs, shedding light on the possible interaction between bacteria and pharmaceutical compounds in the environment.
Diversity and correlation analysis of different root exudates on the regulation of microbial structure and function in soil planted with Panax notoginseng
Authors: Shi Huineng , Yang Jianli , Li Qi , PinChu Cier , Song Zhanhua , Yang Honglei , Luo Yu , Liu Chunlan , Fan Wei
Published: December 2023

Introduction

Specific interactions between root exudates and soil microorganisms has been proposed as one of the reasons accounting for the continuous cropping obstacle (CCO) of Panax notoginseng. However, rotation of other crops on soils planted with P. notoginseng (SPP) did not show CCO, suggesting that root exudates of different crops differentially regulate soil microorganisms in SPP.

Methods

Here, we investigated the microbial community structure and specific interaction mechanisms of the root exudates of the four plant species, P. notoginseng (Pn), Zea mays (Zm), Nicotiana tabacum (Nt) and Perilla frutescens (Pf), in SPP by static soil culture experiment.

Results

The results showed that the chemical diversity of root exudates varied significantly among the four plant species. Pn had the highest number of unique root exudates, followed by Nt, Zm and Pf. Terpenoids, flavonoids, alkaloids and phenolic acids were the most abundant differentially accumulated metabolites (DAMs) in Pn, Nt, Zm and Pf, respectively. However, lipids were the most abundant common DAMs among Zm Nt and Pf. Pn root exudates decreased the relative abundance of bacteria, but increased that of fungi. While specific DAMs in Pn enriched Phenylobacterium_zucineum, Sphingobium_yanoikuyae, Ophiostoma_ulmi and functional pathways of Nucleotide excision repair, Streptomycin biosynthesis, Cell cycle-Caulobacter and Glycolysis/Gluconeogenesis, it inhibited Paraburkholderia _caledonica and Ralstonia_pickettii. However, common DAMs in Zm, Nt and Pf had opposite effects. Moreover, common DAMs in Zm, Nt and Pf enriched Ralstonia_pseudosolanacearum and functional pathway of Xylene degradation; unique DAMs in Zm enriched Talaromyces_purcureogeneus, while inhibiting Fusarium_tricinctum and functional pathways of Nucleotide excision repair and Alanine, aspartate and glutamate metabolism; unique DAMs in Pf enriched Synchytrium_taraxaci.

Discussion

The core strains identified that interact with different root exudates will provide key clues for regulation of soil microorganisms in P. notoginseng cultivation to alleviate CCO.
Gut microbe and hepatic macrophage polarization in non-alcoholic fatty liver disease
Authors: Chen Yao , Gan Yumeng , Zhong Huijie , Liu Yincong , Huang Jingdi , Wang Wenxue , Geng Jiawei
Published: December 2023

Non-alcoholic fatty liver disease (NAFLD) is a common chronic hepatic disorder with the potential to progress to hepatic fibrosis, hepatic cirrhosis, and even hepatocellular carcinoma. Activation of hepatic macrophages, important innate immune cells predominantly composed of Kupffer cells, plays a pivotal role in NAFLD initiation and progression. Recent findings have underscored the regulatory role of microbes in both local and distal immune responses, including in the liver, emphasizing their contribution to NAFLD initiation and progression. Key studies have further revealed that gut microbes can penetrate the intestinal mucosa and translocate to the liver, thereby directly influencing hepatic macrophage polarization and NAFLD progression. In this review, we discuss recent evidence regarding the translocation of intestinal microbes into the liver, as well as their impact on hepatic macrophage polarization and associated cellular and molecular signaling pathways. Additionally, we summarize the potential mechanisms by which translocated microbes may activate hepatic macrophages and accelerate NAFLD progression.