bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of probiotics plus zinc supplementation on clinical outcomes of infants and children with acute infectious diarrhea: a randomized controlled trial
Authors: Abdulah Deldar Morad , Sulaiman Saad Jbraeil , Ahmed Zaid Waad
Published: February 2024

Background: Findings are conflicting regarding the effect of zinc supplementation on disease severity in children with acute gastroenteritis.Purpose: To examine the effects of probiotics and zinc on the clinical outcomes of infants and children with acute infectious diarrhea.Methods: In this randomized controlled trial, children with mild or moderate to severe acute gastroenteritis in the Kurdistan Region from November 2021 to June 2022 were diagnosed clinically and randomly assigned to the experimental or control group. The experimental group (n=50) received probiotics and zinc, whereas the control group (n=51) received probiotics alone for 1 week. The product contained live Bifidobacterium infantis, Lactobacillus paracasei, and Lactobacillus rhamnosus (10×106 colony-forming units/day for 7 days). Zinc syrup was administered to the probiotic plus zinc group. Each 5 mL of syrup contained 15 mg of zinc sulfate. Dehydration and disease severity in both groups were measured using the Clinical Dehydration Scale and the Modified Vesikari Scale, respectively. An illness episode was defined as an episode of gastroenteritis with a total score of ≥9 on the Modified Vesikari Scale (range, 0–20).Results: The probiotic and probiotic plus zinc groups were similar in age (1.79 years vs. 1.69 years, respectively; P= 0.645), sex (male/female ratio: 1.43 and 1.0, respectively; P=0.373), and medical characteristics. The groups had similar mean dehydration and disease severity scores and a similar incidence of dehydration recovery (some dehydration, 3.92% and 4.00%, respectively; P=1.000), and recovery from mild gastroenteritis (0.0% and 2.0%, respectively; P=0.495) at 2 weeks. Significant decreases in mean dehydration severity and disease severity score (1.80 to 0 and 6.66 to 0, respectively; P<0.001) and the development of dehydration (some dehydration, from 94.0% to 4.0%; P<0.001) from baseline to 2 weeks were noted in the probiotics plus zinc group. The probiotics group responded similarly. The development of mild gastroenteritis was significantly reduced from baseline to 2 weeks (90.2% to 0% and 78.0% to 2.0% in the probiotics and probiotics plus zinc groups, respectively; P<0.0001). The probiotics plus zinc group had a shorter mean recovery time (1.34 days vs. 2.00 days, respectively; P<0.001).Conclusion: Taking probiotics plus zinc did not significantly affect disease severity in children with gastroenteritis at 2 weeks. However, the probiotics plus zinc group recovered more quickly than the probiotics group.
Community-Based Participatory Research and Fat Studies: Tensions and Alignments
Authors: Haney Carly-Ann , Walsh Christine
Published: February 2024

Community-based participatory research (CBPR) is an overarching methodology taken up across various disciplines. Rather than a specific approach, CBPR encompasses varied action-based methodologies. While many disciplines use CBPR methodologies in their work, Fat Studies has yet to broadly create research that uses CBPR methodologies. Fat Studies counters many dominant fields that examine and pathologize the body. Rather than viewing Fat as a site of moral panic and concern, Fat Studies values the subjectivity, fluidity, and embodied experience of what it means to be Fat. As CBPR methodologies share a commitment towards critical, emancipatory, and social action research, the potential intersection with Fat Studies is noteworthy, however limited literature at this intersection exists. In this article, we highlight the alignments and tensions between CBPR and Fat Studies while offering future directions for scholars at this intersection.
Suburbs of Medieval Košice: Origin, Topography and Population
Authors:   Pavol Jozef Šafárik University in Košice, Magdoško Drahoslav
Published: February 2024

A particularly understudied topic concerning the medieval city of Košice in the Hungarian kingdom is the development and size of its suburbs. Only a few historians have dealt with this issue so far, as most of the research attention has focused on the walled area. In the course of the current preparatory work on the Historical Atlas of Košice, it has therefore become necessary to explore this issue much more comprehensively than hitherto. The author of this study re-identifi es the location of individual suburban streets and adjacent religious buildings and defi nes their legal relationship to the city. Based on fragmentary tax registers, he also attempts to determine the number of taxpayers and inhabitants outside the city walls.v
Episcopal Power and Authority in Communication with the City of Bardejov in the Late Middle Ages
Authors:   Pavol Jozef Šafárik University in Košice, Fedorčáková Mária
Published: February 2024

This study deals with communications between the town of Bardejov and bishops in the Middle Ages. The author examines how the ecclesiastical power and authority of the bishops was demonstrated in their communications with the royal city of Bardejov. The bishops’ power toward medieval towns in the Kingdom of Hungary was primarily manifested in the tithes and exemptions granted in the rights of archdeacons. In the case of Bardejov, there can be found some areas where the power of bishops of Eger (frequently represented by episcopal vicars) was demonstrated. First of all, the episcopal tithe collection caused permanent disputes between the parish priest, town representatives and the bishop. The author describes how the problems were solved and the machinery of episcopal powers in these cases. Another area of communication and the manifestation of episcopal authority was that of judicial cases between burghers, which were occasionally brought before ecclesiastical court contrary to town law. A further, greatly signifi cant manifestation of episcopal power in the area of the city was that of ecclesiastical rituals and symbolic communication. The study mentions various examples of episcopal presence in the consecration of churches, chapels, altars and liturgical dress.
Analysis of Power Interventions into Public Space as a Tool for Research into Cities in Non-Democratic Regimes (Sociological-Historical Approach)
Authors:   Pavol Jozef Šafárik University in Košice, Pekár Martin , Fogelová Patrícia ,   Pavol Jozef Šafárik University in Košice
Published: February 2024

According to the prominent sociologist Henri Lefebvre, space is an instrument of power. Every state regime strives to use space for social control through various interventions. While in democratic regimes the use of public space is the result of by majority-accepted interventions, in non-democratic regimes these are power interventions usually based on ideological starting points, not generally accepted by society. On the contrary, interventions into public space are becoming one of the tools for implementing state ideology into the consciousness of society. In their research on public space, German sociologists Walter Siebel and Jan Wehrheim defi ned its four basic dimensions – legal, functional, social and material-symbolic. Interdisciplinary sociological-historical research of interventions into each of these dimensions seems to be a suitable analytical tool in understanding the relationship between public space and the state regime, the conclusions of which allow a detailed understanding of the nature of individual non-democratic (authoritarian or totalitarian) regimes typical for twentiethcentury Europe, as well as transnational ideological connections. In the article we introduce our interdisciplinary socio-historical approach on the example of the authoritarian para-fascist regime of the Slovak state (1939–1945).
‘blotted into the unreadable darkness’: Feminist Solidarity as Feminist Utopia in Michel Faber's The Crimson Petal and the White (2002)
Authors: Ntola Georgia
Published: February 2024

This article investigates the representation of feminist solidarity as feminist utopia through the relationship between Sugar and Agnes, the female protagonists of Michel Faber's neo-Victorian novel The Crimson Petal and the White (2002). The article argues that the two women's relationship serves as a metaphor for the feminist debate on difference, negotiated in neo-Victorian fiction, and dramatises the process whereby support is consciously and actively offered in order to defy oppression and alleviate suffering, despite their different positionalities. A key aspect of this process is the (literal and metaphorical) journey which Sugar undertakes to the sites of Agnes's lived experience, which provides her with an insight into the kind of oppression Agnes experiences and enables her to offer the latter woman the assistance she needs. Feminist solidarity, the article asserts, is ultimately conceptualised as a feminist utopia, as Agnes's desired mode of aid entails that she chase her own utopia once Sugar liberates her. In this way, the text asserts the necessity of thinking about feminist solidarity as feasible within the context of late-twentieth and early-twenty-first-century feminist controversies on that issue.
La complejidad de lo complejo (otro modo de neurosis obsesiva)
Authors: Ordóñez-García José
Published: February 2024

Lo complejo es la imposibilidad de un reduccionismo metodológico que conozca de una manera definitiva a la cosa, lo cual requeriría de una actitud dogmática y escolar, donde lo dicho en un momento histórico sobre la cosa adquiera el carácter de definitivo y atemporal. Partiendo de esta convicción, se traza en este texto una deriva de la obra de Edgar Morin Introducción al pensamiento complejo, teniendo en cuenta una serie de consideraciones críticas en torno a algunas de sus ideas fundamentales desde el psicoanálisis, la fenomenología y otras tradiciones teóricas.
Educação especial e inclusiva no Brasil: desafios e contribuições
Authors: Reis Otávio Yukio Onozato , Beraldo Mylena Mikaellen
Published: February 2024

O presente artigo de cunho qualitativo, bibliográfico visa analisar os desafios e contribuições da formação docente para a atuação na modalidade da Educação Especial. O trabalho apresentará um resumo sobre a história da Educação Especial brasileira, a fim de destacar os principais acontecimentos e analisar as leis vigentes sobre a temática, especialmente a partir da década de 1990 até os dias atuais, buscando compreender como a atual legislação sobre a Educação Especial tem contribuído ou não para favorecer a inclusão dos alunos com necessidades especiais.
Laboratory investigation and core flood demonstration of enhanced biogenic methane generation from lignite
Authors: Basera Priyanka , Lavania Meeta , Singh Nimmi , Lal Banwari
Published: February 2024

Over the last several decades, coalbed methane (CBM) has emerged as an important energy source in developing nations like India as well as worldwide and is expected to play a significant role in the energy portfolio of the future. The current scenario of rapid exhaustion of fossil fuels is leading to the need to explore alternative and efficient fuel resources. The present study demonstrates enhanced methane production per gram of lignite (lowest-rank coal). Optimization of the bioconversion of lignite to methane revealed 55°C temperature and 1.5 g/L NaCl concentration as ambient conditions for the process. A scale-up study in the optimized condition showed 2,800 mM methane production per 25 g of lignite in anaerobic conditions. Further, Fourier transform Infrared (FTIR) and Gas Chromatography Mass Spectrometry (GCMS) analysis showed bioconversion of lignite into simpler intermediate substrates required for methane production. The results highlighted that the bacterial action first converts lignite into volatile fatty acids, which subsequently get converted into methane. Further, the exploration of indigenous microbial consortia in Tharad well (THAA) mainly comprises the order Methanosarcinales and Methanomicrobiales. The pathogenicity of the microbial consortium THAA was declared safe for use in mice via the oral route by The Energy and Resources Institute (TERI), India. The study demonstrated the development of indigenous consortia (TERI THAA), which can potentially enhance methane production from the lowest coal grade under extreme conditions in Indian coal beds.
Melatonin alleviates oxidative stress damage in mouse testes induced by bisphenol A
Authors: Qi Qi , Yang Jiaxin , Li Shuang , Liu Jingjing , Xu Da , Wang Guoqing , Feng Lei , Pan Xiaoyan
Published: February 2024

We investigated the effect of melatonin on bisphenol A (BPA)-induced oxidative stress damage in testicular tissue and Leydig cells. Mice were gavaged with 50 mg/kg BPA for 30 days, and concurrently, were injected with melatonin (10 mg/kg and 20 mg/kg). Leydig cells were treated with 10 μmol/L of BPA and melatonin. The morphology and organ index of the testis and epididymis were observed and calculated. The sperm viability and density were determined. The expressions of melatonin receptor 1A and luteinizing hormone receptor, and the levels of malonaldehyde, antioxidant enzymes, glutathione, steroid hormone synthases, aromatase, luteinizing hormone, testosterone, and estradiol were measured. TUNEL assay was utilized to detect testicular cell apoptosis. The administration of melatonin at 20 mg/kg significantly improved the testicular index and epididymis index in mice treated with BPA. Additionally, melatonin promoted the development of seminiferous tubules in the testes. Furthermore, the treatment with 20 mg/kg melatonin significantly increased sperm viability and sperm density in mice, while also promoting the expressions of melatonin receptor 1A and luteinizing hormone receptor in Leydig cells of BPA-treated mice. Significantly, melatonin reduced the level of malonaldehyde in testicular tissue and increased the expression of antioxidant enzymes (superoxide dismutase 1, superoxide dismutase 2, and catalase) as well as the content of glutathione. Moreover, melatonin also reduced the number of apoptotic Leydig cells and spermatogonia, aromatase expression, and estradiol level, while increasing the expression of steroid hormone synthases (steroidogenic acute regulatory protein, cytochrome P450 family 17a1, cytochrome P450 17α-hydroxylase/20-lyase, and, 17β-hydroxysteroid dehydrogenase) and the level of testosterone. Melatonin exhibited significant potential in alleviating testicular oxidative stress damage caused by BPA. These beneficial effects may be attributed to melatonin’s ability to enhance the antioxidant capacity of testicular tissue, promote testosterone synthesis, and reduce testicular cell apoptosis.
What makes a multimodal construction? Evidence for a prosodic mode in spoken English
Authors: Lehmann Claudia
Published: February 2024

Traditionally, grammar deals with morphosyntax, and so does Construction Grammar. Prosody, in contrast, is deemedparalinguistic. Testifying to the “multimodal turn,” the past decade has witnessed a rise in interest in multimodal Construction Grammar, i.e., an interest in grammatic constructions other than exclusively morphosyntactic ones. Part of the debate in this recent area of interest is the question of what defines a multimodal construction and, more specifically, which role prosody plays. This paper will show that morphosyntax and prosody are two different semiotic modes and, therefore, can combine to form a multimodal construction. To this end, studies showing the independence of prosody for meaning-making will be reviewed and a small-scale experimental study on the ambiguous utteranceTell me about itwill be reported on.
What kind of a problem is loneliness? Representations of connectedness and participation from a study of telepresence technologies in the UK
Authors: Hughes Gemma , Moore Lucy , Hennessy Megan , Sandset Tony , Jentoft Elian E. , Haldar Marit
Published: February 2024

Loneliness is represented in UK policy as a public health problem with consequences in terms of individual suffering, population burden and service use. However, loneliness is historically and culturally produced; manifestations of loneliness and social isolation also require social and cultural analysis. We explored meanings of loneliness and social isolation in the UK 2020–2022 and considered what the solutions of telepresence technologies reveal about the problems they are used to address. Through qualitative methods we traced the introduction and use of two telepresence technologies and representations of these, and other technologies, in policy and UK media. Our dataset comprises interviews, fieldnotes, policy documents, grey literature and newspaper articles. We found loneliness was represented as a problem of individual human connection and of collective participation in social life, with technology understood as having the potential to enhance and inhibit connections and participation. Technologically-mediated connections were frequently perceived as inferior to in-person contact, particularly in light of the enforced social isolation of the COVID-19 pandemic. We argue that addressing loneliness requires attending to other, related, health and social problems and introducing technological solutions requires integration into the complex social and organisational dynamics that shape technology adoption. We conclude that loneliness is primarily understood as a painful lack of co-presence, no longer regarded as simply a subjective experience, but as a social and policy problem demanding resolution.
Building knowledge from the epistemology of the South: the importance of training researchers in initial teacher training
Authors: Parada Ulloa Marcos , Lárez Hernández José Humberto , Vega-Gutiérrez Óscar
Published: February 2024

This study aims to reflect on the importance of considering epistemologies of the South and research training as benchmarks in the initial teacher of educators in the Latin American context. In recent years, there has been a growing recognition of the need to diversify and decolonize knowledge production in education, especially in the Global South. The epistemology of the South provides a conceptual framework that challenges traditional Eurocentric perspectives and promotes alternative ways of knowing and understanding education. To achieve the research objective, a literature review was conducted focusing on key concepts such as Southern epistemology, researcher training, and initial teacher education. The review encompassed academic articles, books and relevant theoretical frameworks. Content analysis techniques were employed to critically examine the literature, identifying themes, theoretical perspectives, and implications for research training in Initial Teacher Education (ITE). The findings of this study suggest that the incorporation of the epistemology of the South into researcher training can have a transformative impact on the educational sector. By adopting ways of knowing and understanding, future researchers can develop a more nuanced and contextualized understanding of educational phenomena. This approach promotes critical thinking skills and encourages researchers to question dominant narratives and power structures in education. Additionally, the study highlights the importance of integrating research training into initial teacher education. By fostering the development and consolidation of research skills and a critical mindset in future teachers, it promotes their transformation into change agents within the Latin American educational system in which they operate. From this perspective, research-oriented teacher training programs empower educators to engage in evidence-based practices, contribute to educational research, and advocate for pedagogical approaches that respond to local contexts and social realities in which they act. This study underscores the need to integrate Southern epistemologies and research training within into initial teacher education. By doing so, we can nurture a new generation of educators with critical thinking skills capable of effecting significant societal changes. This research contributes to the ongoing dialogue on the decolonization of education and promotes the development of inclusive and contextually relevant educational practices.
Efficacy and safety of Mazdutide on weight loss among diabetic and non-diabetic patients: a systematic review and meta-analysis of randomized controlled trials
Authors: Nalisa David Lubasi , Cuboia Nelson , Dyab Eman , Jackson Idongesit Linus , Felix Habimana Jean , Shoki Pantaleon , Mubiana Mary , Oyedeji-Amusa Mariam , Azevedo Luís , Jiang Hongwei
Published: February 2024

Background

Overweight and obesity are increasing global public health problems. Mazdutide is a new dual agonist drug that can potentially reduce weight and blood glucose levels simultaneously. However, the synthesis of evidence on the efficacy and safety of this drug is scarce. Therefore, this study aimed to synthesize evidence on the efficacy and safety of Mazdutide compared to placebo on weight reduction among adults with and without diabetes.

Methods

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Data were retrieved from six electronic databases: PubMed, Web of Science, Scopus, Cochrane Library, ClinicalTrial.gov, and Google Scholar, and manually searched from the included references. The data were synthesized using a random effect model. This analysis was performed in the R programming language using the Meta package.

Results

A total of seven RCTs involving 680 participants were included in this study. Mazdutide was more effective in reducing body weight (mean difference [MD]= -6.22%, 95% confidence interval [CI]: -8.02% to -4.41%, I2 = 90.0%), systolic blood pressure (MD = -7.57 mmHg, 95% CI: -11.17 to -3.98 mmHg, I2 = 46%), diastolic blood pressure (MD = -2.98 mmHg, 95% CI: -5.74 to -0.22 mmHg, I2 = 56%), total cholesterol (MD = -16.82%, 95% CI: -24.52 to -9.13%, I2 = 61%), triglycerides (MD = -43.29%, 95% CI: -61.57 to -25.01%, I2 = 68%), low-density lipoprotein (MD= -17.07%, 95% CI: -25.54 to -8.60%, I2 = 53%), and high-density lipoprotein (MD = -7.54%, 95% CI: -11.26 to -3.83%, I2 = 0%) than placebo. Mazdutide was associated with reduced hemoglobin A1c (HbA1c) and fasting plasma glucose in participants with type 2 diabetes. In the subgroup and meta-regression analyses, weight reduction was more significant in non-diabetics compared to diabetics, and in those who received a longer treatment duration (24 weeks) than in those on shorter durations (12-20 weeks). Participants who received Mazdutide had a higher risk of transient mild or moderate gastrointestinal side effects.

Conclusion

Mazdutite appears to be effective in weight reduction among patients with and without diabetes, and it has an advantage over other associated comorbidities. However, it was associated with mild or moderate gastrointestinal side effects.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=403859, identifier CRD42023403859.
Green energy-sourced AI-controlled multilevel UPQC parameter selection using football game optimization
Authors: Srilakshmi Koganti , Rao Gummadi Srinivasa , Balachandran Praveen Kumar , Senjyu Tomonobu
Published: February 2024

The power quality (PQ) has been significantly affected by the integration of intermittent non-conventional sources (NCS) into the local distribution system in addition to the adoption of power electronic technologies to regulate non-linear loads. This article combines the H-bridge cascade five-level unified power quality conditioner (5L-UPQC) with the wind power generation system (WPGS), solar photovoltaic power generation system (SPVGS), and battery storage system (BSS) as an effective approach to address PQ problems. The utilization of the Levenberg–Marquardt backpropagation (LMBP)-trained Artificial neural network controller (ANNC) in the UPQC is recommended for generating appropriate reference signals for the converters. This eliminates the requirement for conventional complex conversions, such as abc, dq0, and αβ. Moreover, the artificial neuro-fuzzy interface system (ANFIS) is recommended for achieving a DC-link balance. Football game optimization (FBGO) is utilized to determine the optimal shunt and series filter characteristics. The major objectives of the proposed system are to reduce the current waveform irregularities, resulting in a decrease in the total harmonic distortion (THD), an enhancement in the power factor (PF), the mitigation of supply voltage imbalances and disturbances, and the maintenance of a steady direct-current link capacitor voltage (DLCV), despite the variations in the load, solar irradiation, and wind velocity. The efficiency of the suggested strategy is assessed using four case studies that involve different loads, variable wind velocities, and source voltage balancing conditions. Based on the simulation studies and obtained results, the suggested method significantly decreases the THD to values of 2.91%, 3.63%, 3.75%, and 3.50%. Additionally, it achieves a power factor of unity, which is considerably lower compared to other multilevel schemes that use the traditional symmetrical reference frame (SRF) and instantaneous reactive power (pq) methods. This design has been executed using the MATLAB/Simulink program.
Typological thinking in human genomics research contributes to the production and prominence of scientific racism
Authors: Bird Kevin A. , Carlson Jedidiah
Published: February 2024

Public genomic datasets like the 1000 Genomes project (1KGP), Human Genome Diversity Project (HGDP), and the Adolescent Brain Cognitive Development (ABCD) study are valuable public resources that facilitate scientific advancements in biology and enhance the scientific and economic impact of federally funded research projects. Regrettably, these datasets have often been developed and studied in ways that propagate outdated racialized and typological thinking, leading to fallacious reasoning among some readers that social and health disparities among the so-called races are due in part to innate biological differences between them. We highlight how this framing has set the stage for the racist exploitation of these datasets in two ways: First, we discuss the use of public biomedical datasets in studies that claim support for innate genetic differences in intelligence and other social outcomes between the groups identified as races. We further highlight recent instances of this which involve unauthorized access, use, and dissemination of public datasets. Second, we discuss the memification, use of simple figures meant for quick dissemination among lay audiences, of population genetic data to argue for a biological basis for purported human racial groups. We close with recommendations for scientists, to preempt the exploitation and misuse of their data, and for funding agencies, to better enforce violations of data use agreements.
Neisseria gonorrhoeae lipooligosaccharide glycan epitopes recognized by bactericidal IgG antibodies elicited by the meningococcal group B-directed vaccine, MenB-4C
Authors: Tzeng Yih-Ling , Sannigrahi Soma , Borrow Ray , Stephens David S.
Published: February 2024

Introduction

Outer membrane vesicles (OMVs) of Neisseria meningitidis in the group B-directed vaccine MenB-4C (BexseroR) protect against infections with Neisseria gonorrhoeae. The immunological basis for protection remains unclear. N. meningitidis OMV vaccines generate human antibodies to N. meningitidis and N. gonorrhoeae lipooligosaccharide (LOS/endotoxin), but the structural specificity of these LOS antibodies is not defined.

Methods

Ten paired human sera obtained pre- and post-MenB-4C immunization were used in Western blots to probe N. meningitidis and N. gonorrhoeae LOS. Post-MenB-4C sera (7v5, 19v5, and 17v5), representing individual human variability in LOS recognition, were then used to interrogate structurally defined LOSs of N. meningitidis and N. gonorrhoeae strains and mutants and studied in bactericidal assays.

Results and discussion

Post-MenB-4C sera recognized both N. meningitidis and N. gonorrhoeae LOS species, ~10% of total IgG to gonococcal OMV antigens. N. meningitidis and N. gonorrhoeae LOSs were broadly recognized by post-IgG antibodies, but with individual variability for LOS structures. Deep truncation of LOS, specifically a rfaK mutant without α-, β-, or γ-chain glycosylation, eliminated LOS recognition by all post-vaccine sera. Serum 7v5 IgG antibodies recognized the unsialyated L1 α-chain, and a 3-PEA-HepII or 6-PEA-HepII was part of the conformational epitope. Replacing the 3-PEA on HepII with a 3-Glc blocked 7v5 IgG antibody recognition of N. meningitidis and N. gonorrhoeae LOSs. Serum 19v5 recognized lactoneotetrose (LNT) or L1 LOS-expressing N. meningitidis or N. gonorrhoeae with a minimal α-chain structure of Gal-Glc-HepI (L8), a 3-PEA-HepII or 6-PEA-HepII was again part of the conformational epitope and a 3-Glc-HepII blocked 19v5 antibody binding. Serum 17v5 LOS antibodies recognized LNT or L1 α-chains with a minimal HepI structure of three sugars and no requirement for HepII modifications. These LOS antibodies contributed to the serum bactericidal activity against N. gonorrhoeae. The MenB-4C vaccination elicits bactericidal IgG antibodies to N. gonorrhoeae conformational epitopes involving HepI and HepII glycosylated LOS structures shared between N. meningitidis and N. gonorrhoeae. LOS structures should be considered in next-generation gonococcal vaccine design.
Engaging stimulatory immune checkpoint interactions in the tumour immune microenvironment of primary liver cancers – how to push the gas after having released the brake
Authors: Rakké Yannick S. , Buschow Sonja I. , IJzermans Jan N. M. , Sprengers Dave
Published: February 2024

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the first and second most common primary liver cancer (PLC). For decades, systemic therapies consisting of tyrosine kinase inhibitors (TKIs) or chemotherapy have formed the cornerstone of treating advanced-stage HCC and CCA, respectively. More recently, immunotherapy using immune checkpoint inhibition (ICI) has shown anti-tumour reactivity in some patients. The combination regimen of anti-PD-L1 and anti-VEGF antibodies has been approved as new first-line treatment of advanced-stage HCC. Furthermore, gemcibatine plus cisplatin (GEMCIS) with an anti-PD-L1 antibody is awaiting global approval for the treatment of advanced-stage CCA. As effective anti-tumour reactivity using ICI is achieved in a minor subset of both HCC and CCA patients only, alternative immune strategies to sensitise the tumour microenvironment of PLC are waited for. Here we discuss immune checkpoint stimulation (ICS) as additional tool to enhance anti-tumour reactivity. Up-to-date information on the clinical application of ICS in onco-immunology is provided. This review provides a rationale of the application of next-generation ICS either alone or in combination regimen to potentially enhance anti-tumour reactivity in PLC patients.
Knowledge, attitude, and practice of medication and its influencing factors among residents in western China: a large-scale cross-sectional study
Authors: Shi Hong-xia , Tan Xue , Shu Jian-qin , Zhou Jun , Dan Si-yuan , Yang Lin , Chen Ze-lian
Published: February 2024

Background

This study aimed to understand the knowledge, attitude, and practice (KAP) of drug use among residents in western China and its influencing factors for accurately designing the knowledge, contents, and methods of popular science activities for safe drug use among residents to provide a reference for conducting rational drug use educational activities and improving residents’ level of safe drug use.

Methods

A cross-sectional questionnaire survey was conducted to investigate the KAP of medication among western China residents and its influencing factors from March to April 2023. Each question option was assigned a score according to logic, and the risk factors for resident medication safety KAP were explored through univariate and logistic regression analyses.

Results

A total of 7,557 valid questionnaires were collected, with an effective recovery rate of 96.7%. The average scores of KAP were 72.77 ± 22.91, 32.89 ± 10.64, and 71.27 ± 19.09, respectively. In the evaluation criteria of the questionnaire, the score of medication knowledge reached “good,” and the score of attitude and practice was “average.” Multiple linear regression analysis indicated that male sex and low education level were significant factors affecting the lack of drug knowledge among residents. Old age and low education level were the factors of poor attitude toward medication. The low condition of medical security was a factor in residents’ irregular drug use behavior.

Conclusion

The overall level of rational drug use among residents in western China is good, but there are still some inconsistencies. Rational drug use education should be conducted according to the risk points of residents in drug safety KAP to further improve the level of rational drug use of residents.
Forecasting the potential impact of cell and gene therapies in France: projecting product launches and patients treated
Authors: Lee Ming Kei , Seyedmousavi Sama , Auvity Sylvain , Pourroy Bertrand , Elleboode Vincent , Kachaner Isabelle , Jansen Christel , Lilliu Herve
Published: February 2024

Objective

To evaluate the potential impact of cell and gene therapies (CGTs) in France by forecasting the number of patients that will be treated with CGTs over the period 2023–2030 by therapeutic area and region.

Methods

A review of CGTs in clinical development and related disease epidemiology was conducted to forecast the number of CGT launches and patient population between 2023 and 2030. The number of expected launches was identified by filtering the clinical development pipeline with estimated time to launch and probability of success values from Project ALPHA. Disease prevalence and incidence in France were combined with projected adoption rates derived from historical data to forecast the patient population to be treated.

Results

Up to 44 new CGTs are forecasted to launch in France in the period 2023–2030, which translates into more than 69,400 newly treated patients in 2030. Leading indications in terms of newly treated patients per year include cardiovascular disease, hematological cancers and solid tumors with 27,300, 15,200 and 13,000 newly treated patients in 2030, respectively.

Discussion

The forecast suggests that the future landscape of CGTs will undergo a shift, moving from CGTs targeting (ultra) rare diseases to more prevalent diseases. In France, this will likely pose organizational challenges hindering patient access to these transformative therapies. Further research and planning around network organization and patient distribution are needed to assess and improve the readiness of the French healthcare system for ensuring access for this growing number of patients to be treated with CGTs.
Iliopsoas fibrosis after revision of total hip arthroplasty revealed by 68Ga-FAPI PET/CT: a case report
Authors: Wang Yiqun , Sun Yabing , Song Junlei , Zhang Xiaojun , Li La , Shen Zhihui , Tian Jiahe , Ao Yingfang
Published: February 2024

Background

Total hip arthroplasty (THA) is a well-established surgical procedure that has been extensively validated to alleviate pain, enhance joint function, improve the ability to perform daily activities, and enhance overall quality of life. However, this procedure is associated with certain complications, among which skeletal muscle fibrosis is a frequently overlooked but significant complication that can lead to persistent pain. Currently, there is no effective method for diagnosing skeletal muscle fibrosis following total hip arthroplasty.

Case report

We report a 75-year-old male patient who complained of left groin pain after revision total hip arthroplasty. Serological examinations, X-rays, and bone scan results were all normal. However, during the 68Ga-FAPI PET/CT examination, we observed significant radiotracer uptake along the iliopsoas muscle. This abnormal uptake pattern suggested potential biological activity in this specific area. Combined with physical examination, the patient was diagnosed with iliopsoas fibrosis.

Conclusions

The presented images indicated that the uptake pattern was an important indicator for diagnosis, and the prospect of fibroblast activation protein in the diagnosis of skeletal muscle fibrosis has shown certain application value.
Christensenella minuta interacts with multiple gut bacteria
Authors: Xu Chang , Jiang He , Feng Li-Juan , Jiang Min-Zhi , Wang Yu-Lin , Liu Shuang-Jiang
Published: February 2024

Introduction

Gut microbes form complex networks that significantly influence host health and disease treatment. Interventions with the probiotic bacteria on the gut microbiota have been demonstrated to improve host well-being. As a representative of next-generation probiotics, Christensenella minuta (C. minuta) plays a critical role in regulating energy balance and metabolic homeostasis in human bodies, showing potential in treating metabolic disorders and reducing inflammation. However, interactions of C. minuta with the members of the networked gut microbiota have rarely been explored.

Methods

In this study, we investigated the impact of C. minuta on fecal microbiota via metagenomic sequencing, focusing on retrieving bacterial strains and coculture assays of C. minuta with associated microbial partners.

Results

Our results showed that C. minuta intervention significantly reduced the diversity of fecal microorganisms, but specifically enhanced some groups of bacteria, such as Lactobacillaceae. C. minuta selectively enriched bacterial pathways that compensated for its metabolic defects on vitamin B1, B12, serine, and glutamate synthesis. Meanwhile, C. minuta cross-feeds Faecalibacterium prausnitzii and other bacteria via the production of arginine, branched-chain amino acids, fumaric acids and short-chain fatty acids (SCFAs), such as acetic. Both metagenomic data analysis and culture experiments revealed that C. minuta negatively correlated with Klebsiella pneumoniae and 14 other bacterial taxa, while positively correlated with F. prausnitzii. Our results advance our comprehension of C. minuta’s in modulating the gut microbial network.

Conclusions

C. minuta disrupts the composition of the fecal microbiota. This disturbance is manifested through cross-feeding, nutritional competition, and supplementation of its own metabolic deficiencies, resulting in the specific enrichment or inhibition of the growth of certain bacteria. This study will shed light on the application of C. minuta as a probiotic for effective interventions on gut microbiomes and improvement of host health.
Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease
Authors: Collu Roberto , Yin Zheng , Giunti Elisa , Daley Sarah , Chen Mei , Morin Peter , Killick Richard , Wong Stephen T. C. , Xia Weiming
Published: February 2024

Introduction

The goal of this study is to explore the pharmacological potential of the amyloid-reducing vasodilator fasudil, a selective Ras homolog (Rho)-associated kinases (ROCK) inhibitor, in the P301S tau transgenic mouse model (Line PS19) of neurodegenerative tauopathy and Alzheimer's disease (AD).

Methods

We used LC-MS/MS, ELISA and bioinformatic approaches to investigate the effect of treatment with fasudil on the brain proteomic profile in PS19 tau transgenic mice. We also explored the efficacy of fasudil in reducing tau phosphorylation, and the potential beneficial and/or toxic effects of its administration in mice.

Results

Proteomic profiling of mice brains exposed to fasudil revealed the activation of the mitochondrial tricarboxylic acid (TCA) cycle and blood-brain barrier (BBB) gap junction metabolic pathways. We also observed a significant negative correlation between the brain levels of phosphorylated tau (pTau) at residue 396 and both fasudil and its metabolite hydroxyfasudil.

Conclusions

Our results provide evidence on the activation of proteins and pathways related to mitochondria and BBB functions by fasudil treatment and support its further development and therapeutic potential for AD.
Football referee gesture recognition algorithm based on YOLOv8s
Authors: Yang Zhiyuan , Shen Yuanyuan , Shen Yanfei
Published: February 2024

Gesture serves as a crucial means of communication between individuals and between humans and machines. In football matches, referees communicate judgment information through gestures. Due to the diversity and complexity of referees’ gestures and interference factors, such as the players, spectators, and camera angles, automated football referee gesture recognition (FRGR) has become a challenging task. The existing methods based on visual sensors often cannot provide a satisfactory performance. To tackle FRGR problems, we develop a deep learning model based on YOLOv8s. Three improving and optimizing strategies are integrated to solve these problems. First, a Global Attention Mechanism (GAM) is employed to direct the model’s attention to the hand gestures and minimize the background interference. Second, a P2 detection head structure is integrated into the YOLOv8s model to enhance the accuracy of detecting smaller objects at a distance. Third, a new loss function based on the Minimum Point Distance Intersection over Union (MPDIoU) is used to effectively utilize anchor boxes with the same shape, but different sizes. Finally, experiments are executed on a dataset of six hand gestures among 1,200 images. The proposed method was compared with seven different existing models and 10 different optimization models. The proposed method achieves a precision rate of 89.3%, a recall rate of 88.9%, a mAP@0.5 rate of 89.9%, and a mAP@0.5:0.95 rate of 77.3%. These rates are approximately 1.4%, 2.0%, 1.1%, and 5.4% better than those of the newest YOLOv8s, respectively. The proposed method has right prospect in automated gesture recognition for football matches.
Harmonizing multisite data with the ComBat method for enhanced Parkinson’s disease diagnosis via DAT-SPECT
Authors: Wakasugi Noritaka , Takano Harumasa , Abe Mitsunari , Sawamoto Nobukatsu , Murai Toshiya , Mizuno Toshiki , Matsuoka Teruyuki , Yamakuni Ryo , Yabe Hirooki , Matsuda Hiroshi , Hanakawa Takashi ,   Parkinson’s and Alzheimer’s disease Dimensional Neuroimaging Initiative (PADNI)
Published: February 2024

Background

Dopamine transporter single-photon emission computed tomography (DAT-SPECT) is a crucial tool for evaluating patients with Parkinson’s disease (PD). However, its implication is limited by inter-site variability in large multisite clinical trials. To overcome the limitation, a conventional prospective correction method employs linear regression with phantom scanning, which is effective yet available only in a prospective manner. An alternative, although relatively underexplored, involves retrospective modeling using a statistical method known as “combatting batch effects when combining batches of gene expression microarray data” (ComBat).

Methods

We analyzed DAT-SPECT-specific binding ratios (SBRs) derived from 72 healthy older adults and 81 patients with PD registered in four clinical sites. We applied both the prospective correction and the retrospective ComBat correction to the original SBRs. Next, we compared the performance of the original and two corrected SBRs to differentiate the PD patients from the healthy controls. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC).

Results

The original SBRs were 6.13 ± 1.54 (mean ± standard deviation) and 2.03 ± 1.41 in the control and PD groups, respectively. After the prospective correction, the mean SBRs were 6.52 ± 1.06 and 2.40 ± 0.99 in the control and PD groups, respectively. After the retrospective ComBat correction, the SBRs were 5.25 ± 0.89 and 2.01 ± 0.73 in the control and PD groups, respectively, resulting in substantial changes in mean values with fewer variances. The original SBRs demonstrated fair performance in differentiating PD from controls (Hedges’s g = 2.76; AUC-ROC = 0.936). Both correction methods improved discrimination performance. The ComBat-corrected SBR demonstrated comparable performance (g = 3.99 and AUC-ROC = 0.987) to the prospectively corrected SBR (g = 4.32 and AUC-ROC = 0.992) for discrimination.

Conclusion

Although we confirmed that SBRs fairly discriminated PD from healthy older adults without any correction, the correction methods improved their discrimination performance in a multisite setting. Our results support the utility of harmonization methods with ComBat for consolidating SBR-based diagnosis or stratification of PD in multisite studies. Nonetheless, given the substantial changes in the mean values of ComBat-corrected SBRs, caution is advised when interpreting them.
Application of LightGBM hybrid model based on TPE algorithm optimization in sleep apnea detection
Authors: Xiong Xin , Wang Aikun , He Jianfeng , Wang Chunwu , Liu Ruixiang , Sun Zhiran , Zhang Jiancong , Zhang Jing
Published: February 2024

Introduction

Sleep apnoea syndrome (SAS) is a serious sleep disorder and early detection of sleep apnoea not only reduces treatment costs but also saves lives. Conventional polysomnography (PSG) is widely regarded as the gold standard diagnostic tool for sleep apnoea. However, this method is expensive, time-consuming and inherently disruptive to sleep. Recent studies have pointed out that ECG analysis is a simple and effective diagnostic method for sleep apnea, which can effectively provide physicians with an aid to diagnosis and reduce patients’ suffering.

Methods

To this end, in this paper proposes a LightGBM hybrid model based on ECG signals for efficient detection of sleep apnea. Firstly, the improved Isolated Forest algorithm is introduced to remove abnormal data and solve the data sample imbalance problem. Secondly, the parameters of LightGBM algorithm are optimised by the improved TPE (Tree-structured Parzen Estimator) algorithm to determine the best parameter configuration of the model. Finally, the fusion model TPE_OptGBM is used to detect sleep apnoea. In the experimental phase, we validated the model based on the sleep apnoea ECG database provided by Phillips-University of Marburg, Germany.

Results

The experimental results show that the model proposed in this paper achieves an accuracy of 95.08%, a precision of 94.80%, a recall of 97.51%, and an F1 value of 96.14%.

Discussion

All of these evaluation indicators are better than the current mainstream models, which is expected to assist the doctor’s diagnostic process and provide a better medical experience for patients.