bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of KFC company marketing activities: aspects of sustainable development
Authors: S. Ya Kasian , K. Ye Zozula , V. B Buniak
Published: February 2024

Methods. A number of general scientific and specific research methods were used in the research of the marketing activity of the international company Kentucky Fastfood Center (KFC), which is represented on the territory of Ukraine by a chain of fast food restaurants. In particular, statistical methods were applied – when analyzing the dynamics of financial indicators of the company’s activity; analysis and synthesis – when forming an assessment of the product range; methods of expert evaluations in the form of IFAS analysis – when conducting a study of the internal environment of KFC. Results. The article describes the economic activity of the KFC company and highlights its specifics as an institution belonging to fast food restaurants. The specifics of the consumer behavior of the company’s customers were identified, and a forecast of its possible change due to the establishment of the principles of a healthy lifestyle in public consciousness was made. The financial and economic indicators of the institution’s activity for 2020–2022 were analyzed, and a number of problems were identified that could disrupt its stability in the future. Based on the marketing mix model, the company’s marketing product and price policy, as well as its target segment, are characterized. The analysis of internal factors of KFC’s development was carried out based on the IFAS analysis. The components of sustainable development marketing within the strategy of the KFC enterprise are described. The use of steam ovens instead of traditional fryers is proposed, which can reduce electricity consumption and switch to technologies in line with sustainable development goals. Novelty. Based on the results of the analysis, the width of the KFC assortment and the KFC company logo were determined. The marketing promotion of products in the area of sustainable development has been specified, in particular, raising the awareness of consumers regarding the problems of sustainable development and the impact of their consumption habits on the environment. Practical valur. The performed analysis allows to improve the planning and organization of marketing activities of the KFC company, taking into account the aspects of sustainable development.
Theoretical and methodological basis of the concept of sustainable development of an enterprise
Authors: V. Ye Komandrovska
Published: February 2024

Methods. The theoretical, scientific and methodological basis is the system approach, which allows to consider an enterprise as a system that functions in a changing external environment and is influenced by external and internal factors that affect the system’s sustainability, and makes the basis for understanding the essence and prerequisites for sustainable and resilient development of an enterprise. The process approach is the basis for developing a structural and logical scheme of the process of enterprise development as an economic system. The methods of analysis and synthesis allowed to identify possible levels of development of economic systems for the study of sustainable development of enterprises. Factor analysis was used to identify the problems associated with ensuring the sustainable development of enterprises in the conditions of Economy 5.0. Results. The article examines the theoretical and methodological foundations of the concept of sustainable development of an enterprise. Different approaches to the definition of the concept of development are distinguished, in particular evolutionary, synergistic, genetic, and conflictological. The essence and features of enterprise development as an economic system are considered. The author’s view on the development process in the form of a structural and logical scheme is proposed. Such components as the state of the economic entity, internal and external determinants, results, sources and causes of development are allocated. The differences between the concepts of stability and sustainability of systems are investigated. The specifics of sustainable development of an enterprise in comparison with sustainable development, which is, in particular, a broader concept with an emphasis on economic, social and environmental aspects, are determined. Conclusions are drawn regarding the multidimensional nature of approaches to understanding enterprise development and the growing role of the concept of sustainable development in the context of Economy 5.0. Novelty. Different approaches to defining the concept of sustainable development are pointed out, in particular, evolutionary, synergistic, genetic, and conflictological. The author’s view on the development process is proposed. Practical value. The results of the study are of theoretical and practical importance for developing the models of innovation-oriented transformation of domestic enterprises on the basis of sustainable development, taking into account global technological trends.
Phase I Pharmacokinetics Study of Oral Administration of Esperavir® (INN: Molnupiravir) (LLC "PROMOMED RUS", Russia)
Authors: Komarov T. N. , Bagaeva N. S. , Karnakova K. K. , Zaslavskaya K. Ya. , Bely P. A. , Shohin I. E.
Published: February 2024

Introduction. The pandemic of the new coronavirus infection COVID-19 (Coronavirus Disease 2019) was caused by a single-stranded RNA virus SARS-CoV-2 (Severe acute respiratory syndrome-related coronavirus 2). Molnupiravir is an antiviral drug with activity against RNA viruses including SARS-CoV-2. Molnupiravir exerts the antiviral effect by introducing copy errors during viral RNA replication – by that the replication of SARS-CoV-2 inhibits. For oral administration of molnupiravir the drug Esperavir® has been registered in Russia.

Aim. The aim is pharmacokinetics study of Esperavir®, capsules 200 mg (the manufacturer is JSC "Biokhimic", LLC "PROMOMED RUS", Russia, as registration certificate holder) by a single dose (800 mg) and multiple doses oral administration (800 mg twice a day with a gap of 12 hours between doses) in healthy volunteers in a phase I pharmacokinetics study, comparison the obtained data of pharmacokinetic parameters with the literature data.

Materials and methods. The clinical and analytical phases of the pharmacokinetic study as well as pharmacokinetic analyses have been performed as a part of a clinical trial of the drug Esperavir®, capsules 200 mg (the manufacturer is JSC "Biokhimic", LLC "PROMOMED RUS", Russia, as registration certificate holder). Chromatographic separation and detection by Nexera XR high-performance liquid chromatograph with triple quadrupole tandem mass spectrometry LCMS-8040 (Shimadzu Corporation, Japan). The pharmacokinetic parameters were calculated with the Boomer pharmacokinetic analysis add-in for Microsoft Excel (Department of Pharmacokinetics and Drug Metabolism, Allergan, Irvine, CA 92606, USA). Descriptive pharmacokinetic statistics were calculated with Microsoft Excel (Microsoft Corporation, USA).

Results and discussion. Pharmacokinetic parameters for cohort 1 (800 mg single dose of Esperavir®) and for cohort 2 (800 mg of Esperavir® twice a day with a gap of 12 hours between doses) were calculated. Averaged pharmacokinetic profiles of mean NHC concentrations over time in linear and log-linear scales were plotted. The geometric mean of Cmax and T1/2, the median, minimum and maximum of Tmax showed the comparability of the obtained data after a single dose administration of 800 mg of Esperavir® and the available literature data.

Conclusion. According to the concentrations from the analytical phase of the pharmacokinetic study the pharmacokinetic parameters were calculated, averaged pharmacokinetic profiles in linear and log-linear scales were plotted after a single dose and multiple doses of the drug Esperavir®, capsules (the manufacturer is JSC "Biokhimic", LLC "PROMOMED RUS", Russia, as registration certificate holder). The comparability of the obtained data and the available literature data was shown. The results justified the study of the subsequent phases of clinical trials of Esperavir®.
Oral administration of bone marrow-derived mesenchymal stem cells attenuates intestinal injury in necrotizing enterocolitis
Authors: Lee Yeong Seok , Jun Yong Hoon , Lee Juyoung
Published: February 2024

Background: Necrotizing enterocolitis (NEC) is a major cause of morbidity in premature infants. However, effective treatment options for NEC are currently lacking. Purpose: This study aimed to determine the optimal dose of intraperitoneally administered bone marrow-derived mesenchymal stem cells (BM-MSCs) and investigate the therapeutic potential of orally administered BM-MSCs in NEC.Methods: Neonatal mice were fed maternal breast milk for the first 2 days of life. On day 3, the neonatal mice were randomly divided into control, negative control, and BM-MSC-treated groups. Lipopolysaccharide (LPS) was administered for 3 days, and cold stress (4°C, 10 minutes) was applied 3 times a day to induce NEC. High-dose (1×106 cells) or low-dose (1×105 cells) BM-MSCs were administered intraperitoneally 1 or 3 times between days 6 and 8 to treat the NEC. The orally administered group received a low dose of BM-MSCs on day 6. Furthermore, except for the control group, intraepithelial cells (IECs) of the small intestine of neonatal mice were treated with LPS and exposed to 5% O2/95% N2 hypoxic stress for 2 hours. Thereafter, each was treated with BM-MSCs.Results: Tissue injury, apoptosis, and inflammatory marker levels were significantly reduced after BM-MSC administration. Oral administration was as effective as intraperitoneal administration, even at a low dose (1×105 cells) of BM-MSCs. The efficacy of high (1×106 cells) or multiple divided doses of BM-MSCs did not differ from that of low-dose treatment. Significantly improved wound healing was observed after BM-MSC administration to injured IECs.Conclusion: The oral administration of BM-MSCs is a promising treatment option for NEC in infants. Further human studies of BM-MSCs are necessary to determine the optimal dose required to achieve safe and effective outcomes.
Resource partitioning in hammerhead shark species out-migrating from coastal ecosystems in the Gulf of California
Authors: Besnard L , Le Croizier G , Galván-Magaña F , Mathieu-Resuge M , Kraffe E , Martínez-Rincón RO , Le Grand F , Bideau A , Schaal G
Published: February 2024

Juveniles of large hammerhead shark species occupy coastal nurseries before migrating offshore to reproduce. In the central Gulf of California, artisanal elasmobranch fisheries have reported catches of juvenile scalloped Sphyrna lewini and smooth S. zygaena hammerhead sharks, but their local foraging habits are yet to be fully understood. In this study, the trophic niches of both hammerhead species as well as of sympatric Pacific sharpnose sharks Rhizoprionodon longurio were investigated using stable isotope values (δ13C, δ34S and δ15N) and fatty acid compositions in whole blood and muscle tissues. Despite interspecific similarities among trophic niches, smooth hammerheads were characterized by lower δ13C, higher δ34S and greater proportion of docosahexaenoic acid (DHA) in both tissues, suggesting they were already partly relying on offshore pelagic resources. For scalloped hammerheads, muscle reflected coastal dietary resources, while offshore trophic markers were detected in blood integrating prey signal over shorter time periods, indicating their more recent initiation of ontogenetic migration. Multidimensional niche calculation revealed low overlap between hammerhead shark trophic niches, implying that potential fine-scale differences in habitat use could reduce competition between these morphologically and ecologically similar species. In the meantime, the isotopic niches of juvenile scalloped and smooth hammerheads were smaller than that of Pacific sharpnose sharks, suggesting they could be more specialized consumers. Overall, the identification of foraging grounds for juvenile hammerhead sharks calls for a future characterization of their residency time in coastal ecosystems to further understand their interactions with fishing pressure in the Gulf of California.
Speed, Adventure, Politics: Leisure Motoring in Interwar Slovakia with Regard to the Activities of the Autoclub Košice
Authors:   Pavol Jozef Šafárik University in Košice, Jančura Mikuláš
Published: February 2024

The text concentrates on the interpretation of “free time” during the initial years of the twentieth century, and the role of motor vehicles as a “means of its consumption” within leisure activities is signifi cant. However, the use of cars and motorcycles in leisure time was strictly determined by the specifi c economic and cultural conditions of interwar Czechoslovakia, particularly in the territory of Slovakia. Socio-economic barriers limited such activities to the upper and, in the case of motorcycles, middle classes. At the same time, leisure motoring was strongly linked with a novel form of tourism that was highly organized in interwar Czechoslovakia (particularly in Slovakia). Within this context, the association emerges as a recreational entity, fostering distinct connections and a collective identity. However, the process was signifi cantly infl uenced by the politicization of organised free-time activities. Examining the role of cars and motorcycles in leisure activities during the researched period, the analysis will consider the defi nitions of free time and how these vehicles were utilized in their social and cultural context, specifi cally through the example of the activities of the Autoclub Košice. The presented text draws on previously published studies and the author’s monograph, as well as recent works and additional sources. Positioning this within the context of the historical-sociological discourse on leisure activities alongside the “consumption” of goods and experiences off ers novel insights into the functioning of motoring associations in Slovakia, particularly in Košice. The Autoclub Košice is identifi ed as a prominent organization that signifi cantly impacted the local rise of motor tourism, sports and general recreational tourism in the observed period.
‘We Fall Asleep and Never Wake Again’: Lucretius in James Thomson’s The City of Dreadful Night
Authors: Matić Andrija
Published: February 2024

The influence of Lucretius’ De Rerum Natura ( On the Nature of Things) on Victorian poetry was considerable. Various poets from Matthew Arnold to Alfred Tennyson praised or criticised Lucretius’ ideas, especially during the debate on religion and the origin of humanity sparked off by Darwin’s theory of evolution. However, no poet of the Victorian era was impacted by Lucretius’ poetry more than James Thomson (‘B. V.’), whose The City of Dreadful Night (1874) has striking parallels with De Rerum Natura. Even though Thomson acknowledged such similarities, scholars have not analysed the intertextual relations between De Rerum Natura and The City of Dreadful Night. My article demonstrates that Thomson shared not only Lucretius’ ideas on religion, death, and the impossibility of the afterlife, but also his concept of a goddess as a symbol of creativity. My analysis also indicates that Thomson borrowed certain images from Lucretius and shared his belief in the power of poetry to convey controversial ideas.
Presentación
Authors: Rey Castelao Ofelia , Sixto Barcia Ana M.
Published: February 2024

Introducción al monográfico "Mujeres en conflicto, Mujeres ante la justicia (siglos XV-XIX)"
Sexualidad extramatrimonial y control de poderes locales: los procesos de espontáneas en Galicia (ss. XVIII-XIX)
Authors: González López Tamara
Published: February 2024

Los procesos de espontánea, habituales en Galicia, era un procedimiento legal por el que una mujer embarazada fuera del matrimonio acudía ante la justicia a dar cuenta de él. Las características y la información aportada en estos documentos permiten acercarse al papel y a la perspectiva que las justicias locales tuvieron sobre las mujeres encintas fuera del matrimonio, así como a la procedencia socioeconómica de estas y al contexto de las relaciones sexuales. En el presente texto tratamos de analizar el recurso real a esta fórmula legal y dilucidar el impacto de espontanearse y el perfil de las mujeres afectadas que muestran un reducido recurso a esta fórmula, a pesar de la benevolencia dada y de la protección y beneficios que implicaba. Aunque buena parte de las relaciones estaban supeditadas a promesas de matrimonio, también se muestra una vivencia del sexo alejada de la normativa eclesiástica.
El delito de adulterio y las penas impuestas a las mujeres a través de la legislación castellana (ss. XV-XIX)
Authors: Tovar Pulido Raquel
Published: February 2024

Se profundiza en la desigualdad jurídica en materia matrimonial entre mujeres y hombres durante el Antiguo Régimen, teniendo en cuenta la influencia de la legislación medieval en las cuestiones relativas a las mujeres casadas adúlteras. Se analiza la tipificación del delito y el procedimiento de acusación, así como las penas corporales y pecuniarias a las que tenían que hacer frente las casadas y los amantes de estas. Asimismo, se tienen en consideración las leyes que prohibían otros delitos sexuales que conllevaban la infidelidad entre los esposos, por lo que se analiza también la bigamia y el amancebamiento de mujeres y hombres casados, junto con la prostitución por parte de mujeres casadas. Se hace hincapié en una mayor impunidad para los varones infieles y el castigo a las mujeres adúlteras por parte de la justicia.
La influencia de la misoginia escolástica en la legislación castellana de Antiguo Régimen
Authors: F. Armesto Mónica
Published: February 2024

En este artículo se abordan las ideas heredadas de la tradición romanística y patrística que contribuyeron a la formulación medieval de la infirmitas o fragilidad de las mujeres. Se presenta un análisis de larga duración en que se explora cómo los discursos de la infirmitas se plasmaron en las compilaciones legales de Castilla en forma de restricciones a la capacidad de obrar de las mujeres, prohibiciones de ejercicio y disfrute de cargos u oficios públicos y articulación de figuras jurídicas tendentes a la protección de la supuesta fragilidad de cuerpo y mente, tanto en el ámbito civil como en lo criminal. Cierra esta perspectiva formal, teórica, un acercamiento crítico a los datos de participación de las mujeres ante los tribunales de Antiguo Régimen.
Effect of pineapple waste biochar and compost application on the growth and yield of pineapple varieties in Ghana
Authors: Hanyabui Emmanuel , Frimpong Kwame Agyei , Annor-Frempong Festus , Atiah Kofi
Published: February 2024

Introduction

Biochar is one of the commonly used soil amendments for sustainable agriculture. The effect of biochar on crop yields depends on the quality of the biochar, which is influenced by feedstock type and pyrolysis conditions. Sole application of pineapple waste biochar and compost, and their combination has not been rigorously investigated. In this study, we investigated the effects of pineapple waste biochar and compost applied solely or in combination on growth and yield of pineapple on a coastal savanna Acrisol in Ghana.

Methods

The split-plot design with three replications was used, with pineapple varieties as the main plot and fertilizer application rates as the sub-plots.

Results and discussion

The results showed that sole application of biochar and compost or their combination as a soil amendment increased pineapple growth and yield as compared to the unamended soil. Biochar applied in combination with compost/or inorganic NPK (nitrogen, phosphorus, and potassium) fertilizer significantly increased plant height and the number of leaves of pineapple plant, which resulted in improved fruits yield of the three (sugar loaf, MD2 and smooth cayenne) pineapple varieties at maturity over control, sole application of biochar, compost and inorganic NPK fertilizer. The Smooth cayenne variety outperformed MD2 and Sugar loaf variety.

Conclusion

In conclusion, the results revealed that biochar applied solely or in addition to compost or inorganic NPK fertilizer has the capability to enhance soil quality and improve pineapple yield. Application of biochar in combination with compost/or inorganic NPK improves pineapple growth and yield.
Identification of potential novel proteomic markers of Leishmania spp.-derived exosomes
Authors: da Silva Lira Filho Alonso , Lafleur Andrea , Marcet-Palacios Marcelo , Olivier Martin
Published: February 2024

Introduction

Extracellular vesicles (EVs) are heterogenous cell-derived membrane-bound structures which can be subdivided into three distinct classes according to distinct morphological characteristics, cellular origins, and functions. Small EVs, or exosomes, can be produced by the protozoan parasite Leishmania through the evolutionarily conserved ESCRT pathway, and act as effectors of virulence and drivers of pathogenesis within mammalian hosts. Techniques for the identification of EVs of non-mammalian origin, however, remain inaccurate in comparison to their well-characterized mammalian counterparts. Thus, we still lack reliable and specific markers for Leishmania-derived exosomes, which poses a significant challenge to the field.

Methods

Herein, we utilized serial differential ultracentrifugation to separate Leishmania-derived EV populations into three distinct fractions. Nanoparticle tracking analysis and transmission electron microscopy were used to validate their morphological characteristics, and bioinformatic analysis of LC-MS/MS proteomics corroborated cellular origins and function.

Discussion

Proteomic data indicated potential novel proteic markers of Leishmania-derived exosomes, including proteins involved in endosomal machinery and the ESCRT pathway, as well as the parasitic phosphatase PRL-1. Further investigation is required to determine the specificity and sensitivity of these markers.
Case Report: Sudden very late-onset near fatal PD1 inhibitor-associated myocarditis with out-of-hospital cardiac arrest after >2.5 years of pembrolizumab treatment
Authors: Lewis Richard I. , Seuthe Katharina , Lennartz Simon , Weber Jan-Phillip , Kreuzberg Nicole , Klingel Karin , Bröckelmann Paul J.
Published: February 2024

Introduction

Immune checkpoint inhibitors have advanced the outcomes of many different types of cancer. A rare but extraordinarily severe complication of these agents resembles immune checkpoint inhibitor-related myocarditis, which typically occurs within the first few weeks after treatment initiation with a mortality of 25%–50%.

Case report

A 57-year-old woman had uneventfully received pembrolizumab for metastatic non-small cell lung cancer for over 2.5 years and was admitted after an out-of-hospital cardiac arrest due to ventricular fibrillation. After successful cardiopulmonary resuscitation, the initial diagnostic work-up showed elevated cardiac enzymes and a limited left-ventricular ejection fraction, while coronary angiography did not show relevant stenosis. Despite cardiac MRI being unsuggestive of myocarditis, myocardial biopsies were obtained and histologically confirmed anti-PD-1 antibody-associated myocarditis. After the initiation of prednisone at 1 mg/kg body weight, the patient gradually recovered and was discharged three weeks later with markedly improved cardiac function.

Conclusion

This case resembles the first description of a very late onset irMyocarditis, occurring over 2.5 years after the start of treatment. It demonstrates the importance of contemplating that severe immune-related toxicities with a sudden onset clinical presentation may occur even after long uneventful periods of anti-PD-1 immune checkpoint inhibitor treatment. Furthermore, it underlines the critical importance of myocardial biopsies in this setting, especially when cardiac MRI remains inconclusive. Moreover, it demonstrates the necessity and benefits of early immunosuppressive treatment if immune-related myocarditis is considered a differential diagnosis.
Experiences, barriers and expectations regarding current patient monitoring systems among ICU nurses in a University Hospital in Lebanon: a qualitative study
Authors: Rayan Ahmad , Al-Ghabeesh Suhair H. , Fawaz Mirna , Behar Amal , Toumi Amina
Published: February 2024

Purpose

The aim of the study is to assess the experiences, barriers, and expectations regarding current patient monitoring systems among intensive care unit nurses at one university hospital.

Methods

A qualitative exploratory study approach was adopted to test the research questions.

Results

Intensive care unit personnel placed a high value on practical criteria such as user friendliness and visualization while assessing the present monitoring system. Poor alarm handling was recognized as possible patient safety hazards. The necessity of high accessibility was highlighted once again for a prospective system; wireless, noninvasive, and interoperability of monitoring devices were requested; and smart phones for distant patient monitoring and alert management improvement were required.

Conclusion

Core comments from ICU personnel are included in this qualitative research on patient monitoring. All national healthcare involved parties must focus more on user-derived insights to ensure a speedy and effective introduction of digital health technologies in the ICU. The findings from the alarm control or mobile device studies might be utilized to train ICU personnel to use new technology, minimize alarm fatigue, increase medical device accessibility, and develop interoperability standards in critical care practice.
Safe long-term therapy of Cushing’s syndrome over 37 years with mitotane
Authors: Seibold Jonas , Hönemann Mario , Tönjes Anke , Sandner Benjamin
Published: February 2024

While suggested, surgery is not always possible as a first-line treatment of Cushing’s Disease (CD). In such cases, patients require medical therapy in order to prevent complications resulting from hypercortisolism. Although there has been a wide expansion in pharmacological options in recent years, mitotane was the agent of choice for treating hypercortisolism decades ago. Due to the introduction of other therapies, long-term experience with mitotane remains limited. Here, we report the case of a woman with CD who was treated with mitotane for 37 years. During the treatment period, biochemical and clinical disease control was achieved and the patient had two uncomplicated pregnancies. Drug-related side effects remained moderate and could be controlled by several dose adjustments. Our case highlights the ability of mitotane to allow an effective control of hypercortisolism and to represent a safe treatment option in special situations where CD requires an alternative therapeutic approach. Furthermore, we provide a literature review of the long-term use of mitotane and reported cases of pregnancy in the context of mitotane therapy.
Exercise training modalities in prediabetes: a systematic review and network meta-analysis
Authors: Zhang Hang , Guo Yuting , Hua Guangshun , Guo Chenyang , Gong Simiao , Li Min , Yang Yan
Published: February 2024

Background

Lifestyle modification based on exercise intervention is still the primary way to delay or reverse the development of diabetes in patients with prediabetes. However, there are still challenges in setting up a detailed exercise prescription for people with prediabetes. This study mainly ranks exercise prescriptions by comparing the improvement of glucose and lipid metabolism and the level of weight loss in patients.

Method

All studies on exercise intervention in prediabetes were identified by searching five electronic databases. Risk assessment and meta-analysis were performed on eligible studies.

Results

Twenty-four studies involving 1946 patients with prediabetes and seven exercise intervention models were included in the final analysis. The meta-analysis showed that exercise of any type was more effective for glycemic control in prediabetes than no exercise. However, the changes in blood glucose were moderate. In prediabetes, combining moderate-intensity aerobic exercise with low-to moderate-load resistance training showed the most significant improvements in glycosylated hemoglobin (HbA1c), body mass index (BMI), body weight (BW), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL) (P-score=0.82; 0.70; 0.87; 1; 0.99), low-to moderate-load resistance training showed the most significant improvements in fasting blood glucose (FBG) (P-score=0.98), the vigorous-intensity aerobic exercise showed the most significant improvements in 2-hour post-meal blood glucose (2hPG) and systolic blood pressure (SBP) (P-score=0.79; 0.78), and moderate-intensity aerobic exercise showed the most significant improvements in diastolic blood pressure (DBP) (P-score=0.78).

Conclusion

In summary, moderate-intensity aerobic exercise, low-to moderate-load resistance training and the combination of both have beneficial effects on glycemic control, weight loss, and cardiovascular health in patients with prediabetes. These findings provide valuable guidance for rehabilitation clinicians and patients alike to follow.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD 42021284922.
An integrated connectivity risk ranking for phosphorus and nitrogen along agricultural open ditches to inform targeted and specific mitigation management
Authors: Opoku D. G. , Healy M. G. , Fenton O. , Daly K. , Condon T. , Tuohy P.
Published: February 2024

Introduction: On dairy farms with poorly drained soils and high rainfall, open ditches receive nutrients from different sources along different pathways which are delivered to surface water. Recently, open ditches were ranked in terms of their hydrologic connectivity risk for phosphorus (P) along the open ditch network. However, the connectivity risk for nitrogen (N) was not considered in that analysis, and there remains a knowledge gap. In addition, the P connectivity classification system assumes all source–pathway interactions within open ditches are active, but this may not be the case for N. The objective of the current study, conducted across seven dairy farms, was to create an integrated connectivity risk ranking for P and N simultaneously to better inform where and which potential mitigation management strategies could be considered.

Methods: First, a conceptual figure of known N open ditch source–pathway connections, developed using both the literature and observations in the field, was used to identify water grab sampling locations on the farms. During fieldwork, all open ditch networks were digitally mapped, divided into ditch sections, and classified in terms of the existing P connectivity classification system.

Results and Discussion: The results showed that not all source–pathway connections were present across ditch categories for all species of N. This information was used to develop an improved open ditch connectivity classification system. Farmyard-connected ditches were the riskiest for potential point source losses, and outlet ditches had the highest connectivity risk among the other ditch categories associated with diffuse sources. Tailored mitigation options for P and N speciation were identified for these locations to intercept nutrients before reaching receiving waters. In ditches associated with diffuse sources, nitrate was introduced by subsurface sources (i.e., in-field drains and groundwater interactions from springs, seepage, and upwelling) and ammonium was introduced through surface connectivity pathways (i.e., runoff from internal roadways). On similar dairy farms where open ditches are prevalent, the integrated classification system and mapping procedure presented herein will enable a targeted and nutrient-specific mitigation plan to be developed. The same methodology may be applied to develop a bespoke integrated connectivity risk ranking for P and N along agricultural open ditches in other areas.
The impact of ESG performance on firms’ technological innovation: evidence from China
Authors: Zhang Xiaoyun , Li Wenjun , Ji Tonghui , Xie Huimin
Published: February 2024

Technological innovation is crucial for creating sustainable corporate value and shaping competitive advantage in the market. ESG, as an indicator of corporate value practices, plays a significant role in enterprise technological innovation. However, there is little empirical evidence to support this claim. This study analyzes the relationship between ESG performance and technological innovation in Chinese A-share listed enterprises from 2011 to 2021. The statistical data shows that strong ESG performance has a significant positive impact on corporate technological innovation. ESG performance can promote corporate technological innovation through external mechanisms, such as enhancing corporate network location and increasing institutional shareholding. Additionally, internal mechanisms, such as reducing labor costs and easing financing constraints, can also promote corporate technological innovation. The impact of ESG performance on corporations exhibits heterogeneity, with ESG performance promoting innovation more strongly among labor-intensive firms, non-state-owned firms, highly competitive industries, and mature firms. Based on the study results, it is recommended that enterprises actively practice ESG development concepts, optimize their equity structure, strengthen information communication with stakeholders, and alleviate problems such as information asymmetry to improve their technological innovation. The government should focus on enterprise characteristics, improve ESG development policies, and promote enterprise innovation through ESG performance.
Intraspecific variation of early Cambrian (stage 3) arthropod Retifacies abnormalis revealed by morphometric analyses
Authors: Lin Weiliang , Pates Stephen , Losso Sarah R. , Fu Dongjing
Published: February 2024

Retifacies abnormalis is a large artiopodan euarthropod known only from the famous fossil deposits of the Chengjiang biota, China (Cambrian Series 2, Stage 3). It is well known for its pronounced reticulated ornamentation that covers the entire dorsal surface of the exoskeleton. Here 109 new specimens of R. abnormalis from multiple deposits are reported. Some larger specimens display a distinct carapace ornamentation to what was previously known. By qualitatively separating specimens into two groups (‘Morph A’, ‘Morph B’) and analyzing the shape of the body, pygidium, and shape of the polygons in the reticulation, using linear and geometric morphometrics and elliptical Fourier analysis, the two morphs are shown to overlap in morphospace and display similar length:width ratios of body parts, rather than form two distinct clusters. The differences are interpreted as intraspecific rather than as diagnosing two species. As Morph B are only found in larger size classes, R. abnormalis ornamentation differences are interpreted to have developed during ontogeny, but are not thought to represent sexual dimorphs.
Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies
Authors: Heil Martin
Published: February 2024

The coronavirus disease 2019 (COVID-19) pandemic triggered an unprecedented concentration of economic and research efforts to generate knowledge at unequalled speed on deregulated interferon type I signalling and nuclear factor kappa light chain enhancer in B-cells (NF-κB)-driven interleukin (IL)-1β, IL-6, IL-18 secretion causing cytokine storms. The translation of the knowledge on how the resulting systemic inflammation can lead to life-threatening complications into novel treatments and vaccine technologies is underway. Nevertheless, previously existing knowledge on the role of cytoplasmatic or circulating self-DNA as a pro-inflammatory damage-associated molecular pattern (DAMP) was largely ignored. Pathologies reported ‘de novo’ for patients infected with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 to be outcomes of self-DNA-driven inflammation in fact had been linked earlier to self-DNA in different contexts, e.g., the infection with Human Immunodeficiency Virus (HIV)-1, sterile inflammation, and autoimmune diseases. I highlight particularly how synergies with other DAMPs can render immunogenic properties to normally non-immunogenic extracellular self-DNA, and I discuss the shared features of the gp41 unit of the HIV-1 envelope protein and the SARS-CoV 2 Spike protein that enable HIV-1 and SARS-CoV-2 to interact with cell or nuclear membranes, trigger syncytia formation, inflict damage to their host’s DNA, and trigger inflammation – likely for their own benefit. These similarities motivate speculations that similar mechanisms to those driven by gp41 can explain how inflammatory self-DNA contributes to some of most frequent adverse events after vaccination with the BNT162b2 mRNA (Pfizer/BioNTech) or the mRNA-1273 (Moderna) vaccine, i.e., myocarditis, herpes zoster, rheumatoid arthritis, autoimmune nephritis or hepatitis, new-onset systemic lupus erythematosus, and flare-ups of psoriasis or lupus. The hope is to motivate a wider application of the lessons learned from the experiences with COVID-19 and the new mRNA vaccines to combat future non-COVID-19 diseases.
Single-cell RNA sequencing reveals cell type-specific immune regulation associated with human neuromyelitis optica spectrum disorder
Authors: Jiang Yushu , Dai Shuhua , Pang Rui , Qin Lingzhi , Zhang Milan , Liu Huiqin , Wang Xiaojuan , Zhang Jiewen , Peng Gongxin , Wang Yongchao , Li Wei
Published: February 2024

Introduction

One rare type of autoimmune disease is called neuromyelitis optica spectrum disorder (NMOSD) and the peripheral immune characteristics of NMOSD remain unclear.

Methods

Here, single-cell RNA sequencing (scRNA-seq) is used to characterize peripheral blood mononuclear cells from individuals with NMOSD.

Results

The differentiation and activation of lymphocytes, expansion of myeloid cells, and an excessive inflammatory response in innate immunity are observed. Flow cytometry analyses confirm a significant increase in the percentage of plasma cells among B cells in NMOSD. NMOSD patients exhibit an elevated percentage of CD8+ T cells within the T cell population. Oligoclonal expansions of B cell receptors are observed after therapy. Additionally, individuals with NMOSD exhibit elevated expression of CXCL8, IL7, IL18, TNFSF13, IFNG, and NLRP3.

Discussion

Peripheral immune response high-dimensional single-cell profiling identifies immune cell subsets specific to a certain disease and identifies possible new targets for NMOSD.
Impacts of systemic inflammation response index on the prognosis of patients with ischemic heart failure after percutaneous coronary intervention
Authors: Ma Meishi , Wu Kang , Sun Tienan , Huang Xin , Zhang Biyang , Chen Zheng , Zhao Zehao , Zhao Jiajian , Zhou Yujie
Published: February 2024

Background

Atherosclerosis and cardiovascular diseases are significantly affected by low-grade chronic inflammation. As a new inflammatory marker, the systemic inflammation response index (SIRI) has been demonstrated to be associated with several cardiovascular disease prognoses. This study aimed to investigate the prognostic impact of SIRI in individuals having ischemic heart failure (IHF) following percutaneous coronary intervention (PCI).

Methods

This observational, retrospective cohort study was conducted at a single site. Finally, the research involved 1,963 individuals with IHF who underwent PCI, with a 36-month follow-up duration. Based on the SIRI quartiles, all patients were classified into four groups. Major adverse cardiovascular events (MACEs) were the primary outcomes. Every element of the main endpoint appeared in the secondary endpoints: all-cause mortality, non-fatal myocardial infarction (MI), and any revascularization. Kaplan–Meier survival analysis was conducted to assess the incidence of endpoints across the four groups. Multivariate Cox proportional hazards analysis confirmed the independent impact of SIRI on both the primary and secondary endpoints. The restricted cubic spline (RCS) was used to assess the nonlinear association between the SIRI and endpoints. Subgroup analysis was performed to confirm the implications of SIRI on MACE in the different subgroups.

Results

The main outcome was much more common in patients with a higher SIRI. The Kaplan–Meier curve was another tool that was used to confirm the favorable connection between SIRI and MACE. SIRI was individually connected to a higher chance of the main outcome according to multivariate analyses, whether or not SIRI was a constant [SIRI, per one−unit increase, hazard ratio (HR) 1.04, 95% confidence interval (95% CI) 1.01–1.07, p = 0.003] or categorical variable [quartile of SIRI, the HR (95% CI) values for quartile 4 were 1.88 (1.47–2.42), p <0.001, with quartile 1 as a reference]. RCS demonstrated that the hazard of the primary and secondary endpoints generally increased as SIRI increased. A non-linear association of SIRI with the risk of MACE and any revascularization (Non-linear P <0.001) was observed. Subgroup analysis confirmed the increased risk of MACE with elevated SIRI in New York Heart Association (NYHA) class III–IV (P for interaction = 0.005).

Conclusion

In patients with IHF undergoing PCI, increased SIRI was a risk factor for MACE independent of other factors. SIRI may represent a novel, promising, and low-grade inflammatory marker for the prognosis of patients with IHF undergoing PCI.
T cell senescence: a new perspective on immunotherapy in lung cancer
Authors: Huang Mengge , Wang Yuetong , Fang Liguang , Liu Cun , Feng Fubin , Liu Lijuan , Sun Changgang
Published: February 2024

T cell senescence is an indication of T cell dysfunction. The ability of senescent T cells to respond to cognate antigens is reduced and they are in the late stage of differentiation and proliferation; therefore, they cannot recognize and eliminate tumor cells in a timely and effective manner, leading to the formation of the suppressive tumor microenvironment. Establishing methods to reverse T cell senescence is particularly important for immunotherapy. Aging exacerbates profound changes in the immune system, leading to increased susceptibility to chronic, infectious, and autoimmune diseases. Patients with malignant lung tumors have impaired immune function with a high risk of recurrence, metastasis, and mortality. Immunotherapy based on PD-1, PD-L1, CTLA-4, and other immune checkpoints is promising for treating lung malignancies. However, T cell senescence can lead to low efficacy or unsuccessful treatment results in some immunotherapies. Efficiently blocking and reversing T cell senescence is a key goal of the enhancement of tumor immunotherapy. This study discusses the characteristics, mechanism, and expression of T cell senescence in malignant lung tumors and the treatment strategies.
CD274 (PD-L1) negatively regulates M1 macrophage polarization in ALI/ARDS
Authors: Tang Nana , Yang Yang , Xie Yifei , Yang Guohui , Wang Qin , Li Chang , Liu Zeyi , Huang Jian-an
Published: February 2024

Background

Acute lung injury (ALI)/severe acute respiratory distress syndrome (ARDS) is a serious clinical syndrome characterized by a high mortality rate. The pathophysiological mechanisms underlying ALI/ARDS remain incompletely understood. Considering the crucial role of immune infiltration and macrophage polarization in the pathogenesis of ALI/ARDS, this study aims to identify key genes associated with both ALI/ARDS and M1 macrophage polarization, employing a combination of bioinformatics and experimental approaches. The findings could potentially reveal novel biomarkers for the diagnosis and management of ALI/ARDS.

Methods

Gene expression profiles relevant to ALI were retrieved from the GEO database to identify co-upregulated differentially expressed genes (DEGs). GO and KEGG analyses facilitated functional annotation and pathway elucidation. PPI networks were constructed to identify hub genes, and differences in immune cell infiltration were subsequently examined. The expression of hub genes in M1 versus M2 macrophages was evaluated using macrophage polarization datasets. The diagnostic utility of CD274 (PD-L1) for ARDS was assessed by receiver operating characteristic (ROC) analysis in a validation dataset. Experimental confirmation was conducted using two LPS-induced M1 macrophage models and an ALI mouse model. The role of CD274 (PD-L1) in M1 macrophage polarization and associated proinflammatory cytokine production was further investigated by siRNA-mediated silencing.

Results

A total of 99 co-upregulated DEGs were identified in two ALI-linked datasets. Enrichment analysis revealed that these DEGs were mainly involved in immune-inflammatory pathways. The following top 10 hub genes were identified from the PPI network: IL-6, IL-1β, CXCL10, CD274, CCL2, TLR2, CXCL1, CCL3, IFIT1, and IFIT3. Immune infiltration analysis revealed a significantly increased abundance of M1 and M2 macrophages in lung tissue from the ALI group compared to the control group. Subsequent analysis confirmed that CD274 (PD-L1), a key immunological checkpoint molecule, was highly expressed within M1 macrophages. ROC analysis validated CD274 (PD-L1) as a promising biomarker for the diagnosis of ARDS. Both in vitro and in vivo experiments supported the bioinformatics analysis and confirmed that the JAK-STAT3 pathway promotes CD274 (PD-L1) expression on M1 macrophages. Importantly, knockdown of CD274 (PD-L1) expression potentiated M1 macrophage polarization and enhanced proinflammatory cytokines production.

Conclusion

This study demonstrates a significant correlation between CD274 (PD-L1) and M1 macrophages in ALI/ARDS. CD274 (PD-L1) functions as a negative regulator of M1 polarization and the secretion of proinflammatory cytokines in macrophages. These findings suggest potential new targets for the diagnosis and treatment of ALI/ARDS.
Neoadjuvant Immune Checkpoint Inhibitors in hepatocellular carcinoma: a meta-analysis and systematic review
Authors: Tian Chunhong , Yu Yifan , Wang Yuqing , Yang Lunwei , Tang Ying , Yu Chengyang , Feng Gaofei , Zheng Dayong , Wang Xiongwen
Published: February 2024

Background

Neoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular carcinoma (HCC) are currently lacking. This systematic review and meta-analysis aims to investigate the reliability of neoadjuvant immunotherapy’s efficacy and safety in the context of HCC.

Methods

A systematic search was conducted across PubMed (MEDLINE), EMBASE, the Web of Science, the Cochrane Library, and conference proceedings to identify clinical trials involving resectable HCC and neoadjuvant immunotherapy. Single-arm meta-analyses were employed to compute odds ratios and 95% confidence intervals (CIs). Heterogeneity analysis, data quality assessment, and subgroup analyses based on the type of immunotherapy drugs and combination therapies were performed. This meta-analysis is registered in PROSPERO (identifier CRD42023474276).

Results

This meta-analysis included 255 patients from 11 studies. Among resectable HCC patients, neoadjuvant immunotherapy exhibited an overall major pathological response (MPR) rate of 0.47 (95% CI 0.31-0.70) and a pathological complete response (pCR) rate of 0.22 (95% CI 0.14-0.36). The overall objective response rate (ORR) was 0.37 (95% CI 0.20-0.69), with a grade 3-4 treatment-related adverse event (TRAE) incidence rate of 0.35 (95% CI 0.24-0.51). Furthermore, the combined surgical resection rate was 3.08 (95% CI 1.66-5.72). Subgroup analysis shows no significant differences in the efficacy and safety of different single-agent immunotherapies; the efficacy of dual ICIs (Immune Checkpoint Inhibitors) combination therapy is superior to targeted combined immunotherapy and monotherapy, while the reverse is observed in terms of safety.

Discussion

Neoadjuvant immunotherapy presents beneficial outcomes in the treatment of resectable HCC. However, large-scale, high-quality experiments are warranted in the future to provide robust data support.