bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Formants Analysis of English Vowels Using PRAAT
Authors: Azzahra Sekar , Syarfina Tengku , Br Sembiring Franinta Egia D. R
Published: July 2024

This research focuses on the comparative formant analysis of English vowels between native and non-native speakers using PRAAT software. The study aims to investigate the comparison of the acoustic properties of English vowels to understand the pronunciation differences encountered by non-native speakers. By analyzing the formant frequencies of monophthongs in English vowels, specifically the first formant (F1), this research seeks to identify any significant differences between English native speaker and five non-native speakers, whose first language is Indonesia. The data collected from speech samples will be descriptively analyzed to determine variations in formant patterns. The finding shows that the F1 values of the vowels show variations among the non-native speakers compared to the native speaker. There are still monophthongs that these participants mispronounce, indicating that the learner's understanding is an obstacle to their fluency in speaking and pronouncing the sounds correctly. The research findings imply that these mispronunciations are linked to differences in tongue height, vowel backness, and vowel quality between native and non-native speakers. The results underscore the analysis of F1 values for 12 words containing vowel monophthongs, highlighting these variations. This suggests that the learner's understanding of these phonetic aspects is crucial for achieving fluency in vowel production and pronunciation.
The Use of Board Games for EFL Learning
Authors: Lailia Magfirotul , Suwarso Pratnyawati Nuridi , Iswahyuni Iswahyuni
Published: July 2024

Nowadays, digital-based media-integrated is needed in the learning context. This study aims to find out the teacher's perspective on the use of board games as a for EFL learning. This research used a descriptive qualitative approach with an in-depth interview instrument. The participant was one English teacher in a private Junior High School in Malang Regency. The data was displayed descriptively. With the advent of digital technology, the result showed that board game still have various benefits. By using board games, teacher motivate students and make the learning process understandable. Board games are also an effective teaching media for improving motivation in learning English. Board games increase student participation, motivation, and enjoyment, making learning more efficient and fun. It is showed that board games improve students' scores in English class. The board game showed that students were more active during English learning. It is concluded that board games improve students' ability to learn English. Thus, it is recommended that board games be used as a learning media for EFL learning.
Denominal conversion verbs and the ‘verb + it’ construction in English
Authors: Baeskow Heike
Published: July 2024

In English, a number of verbs enter a noteworthy, though understudied, combination with a morpheme it, which evidently lacks a referential function. Among these verbs, there are quite a few which were formed from nouns by means of conversion (e.g. to bus it, to au pair it, to verse it, to newspaper it). While some authors assume that the expletive morpheme it in direct-object position functions to enhance a verb’s transitivity, the most recent diachronic study has shown that its influence on transitivity is rather marginal. If transitivization is not the driving force behind the use of the ‘verb +  it’ construction, the question as to other functions arises. The aim of this article is to present a new proposal according to which the expletive element is primarily (though not exclusively) an aspectual marker, which, in contrast to the bare verb, expresses telicity (e.g. to bus vs. to bus it). In this function, this element provides the verb it complements with a temporal endpoint. Proceeding from a distinction between (a)telicity and (un)boundedness drawn in the pertinent literature, it will be shown that this endpoint may or may not actually be reached. The aspectual function of the expletive element it is assumed here to co-exist with other functions identified in the few previous works and in the present study. These functions, which are independent of telicity, comprise the expression of necessity, the intensification of activities, the preservation of the verse metre especially in literary texts, and the support of the verbal status of innovative or weakly established denominal conversion verbs.
Generative Artificial Intelligence in Education and its Governance: Perspective of Copyright Law
Authors: Mayana Ranti Fauza , Santika Tisni
Published: July 2024

As a domain of science and technology, Artificial Intelligence (AI) opened new horizons for education. Technologies change the ways we teach and learn. While Generative AI tools create new prospects for learning, several concerns also arise. Educators are worried that they cannot differentiate between the output of students' work and the output from AI and this will impact the discipline, originality, integrity, and ethics in such cases. In addition, the problem also potentially arises in the matter of the authorship of the works regarding Copyright Law.  This paper examines several legal issues of the utilization of Generative AI through the perspective of Copyright Law. This paper concludes several important points; First, although the framework of Indonesia’s copyright law is based on the principle of human authorship, the rapid development of Generative AI must be balanced with an accommodative legal framework, Second, it is particularly important to formulate a special provisions to guide the implementation concerning the utilization of copyrighted works as the input material for generative AI so that it will not harm the "legitimate interest of the author" in the limit of "normal exploitation of the work" and classified as fair use, Third, academics and administrators need to gain a better understanding of the promise and perils of generative AI, how it will likely impact education, and how it might best govern by encourage the school and universities to develop institutional policies and/or formal guidance concerning the use of digital technology and Generative AI for the future of education.
Comparison of modulation efficiency between normal and degenerated primate retina
Authors: Yoo Yongseok , Cha Seongkwang , Goo Yong Sook
Published: July 2024

With electrical stimulation, retinal prostheses bypass dysfunctional photoreceptors and activate the surviving bipolar or retinal ganglion cells (RGCs). Therefore, the effective modulation of RGCs is crucial for developing retinal prostheses. Substantial research has been performed on the ability of an electrical stimulus to generate a reliable RGC response. However, different experimental conditions show varying levels of how well the electrical stimulation evokes RGC spikes. Therefore, in this study, we attempted to extract an indicator to understand how the electrical stimulation effectively evokes RGC spikes. Six cynomolgus monkeys were used: three as controls and three as an N-methyl-N-nitrosourea (MNU)-induced retinal degeneration model. The retinal recordings were performed using 8 × 8 multi-electrode arrays (MEAs). Electrical stimulation consisted of symmetrical biphasic pulses of varying amplitudes and durations. The number of stimulation conditions that resulted in significantly higher post-stimulation firing rates than pre-stimulus firing rates was defined as the modulation efficiency ratio (MER). The MER was significantly lower in degenerated retinas than in normal retinas. We investigated the relationship between the variables and the MER in normal and degenerated primate RGCs. External variables, such as duration and inter-electrode distance, and internal variables, such as average firing rates and statistics (mean, standard deviation, and coefficient of variation [CV]) of inter-spike intervals (ISIs) of spontaneous spikes, were used. External variables had similar effects on MER in normal and degenerated RGCs. In contrast, internal variables affected MER differently in normal and degenerated RGCs. While in normal RGCs, they were not related to MER, in degenerated RGCs, the mean ISIs were positively correlated with MER, and the CV of ISIs was negatively correlated with MER. The most important variable affecting MER was the mean ISI. A shorter ISI indicates hyperactive firing in the degenerated retina, which prevents electrical stimulation from evoking more RGCs. We believe that this hyperactivity in degenerated retinas results in a lower MER than that in the normal retina. Our findings can be used to optimize the selection of stimulation channels for in vitro MEA experiments and practical calibration methods to achieve higher efficiency when testing retinal prostheses.
Programmed cell death in Helicobacter pylori infection and related gastric cancer
Authors: Lin Yukun , Liu Kunjing , Lu Fang , Zhai Changming , Cheng Fafeng
Published: July 2024

Programmed cell death (PCD) plays a crucial role in maintaining the normal structure and function of the digestive tract in the body. Infection with Helicobacter pylori (H. pylori) is an important factor leading to gastric damage, promoting the Correa cascade and accelerating the transition from gastritis to gastric cancer. Recent research has shown that several PCD signaling pathways are abnormally activated during H. pylori infection, and the dysfunction of PCD is thought to contribute to the development of gastric cancer and interfere with treatment. With the deepening of studies on H. pylori infection in terms of PCD, exploring the interaction mechanisms between H. pylori and the body in different PCD pathways may become an important research direction for the future treatment of H. pylori infection and H. pylori-related gastric cancer. In addition, biologically active compounds that can inhibit or induce PCD may serve as key elements for the treatment of this disease. In this review, we briefly describe the process of PCD, discuss the interaction between different PCD signaling pathways and the mechanisms of H. pylori infection or H. pylori-related gastric cancer, and summarize the active molecules that may play a therapeutic role in each PCD pathway during this process, with the expectation of providing a more comprehensive understanding of the role of PCD in H. pylori infection.
Tad pili contribute to the virulence and biofilm formation of virulent Aeromonas hydrophila
Authors: Tekedar Hasan C. , Patel Fenny , Blom Jochen , Griffin Matt J. , Waldbieser Geoffrey C. , Kumru Salih , Abdelhamed Hossam , Dharan Vandana , Hanson Larry A. , Lawrence Mark L.
Published: July 2024

Type IV pili (T4P) are versatile proteinaceous protrusions that mediate diverse bacterial processes, including adhesion, motility, and biofilm formation. Aeromonas hydrophila, a Gram-negative facultative anaerobe, causes disease in a wide range of hosts. Previously, we reported the presence of a unique Type IV class C pilus, known as tight adherence (Tad), in virulent Aeromonas hydrophila (vAh). In the present study, we sought to functionalize the role of Tad pili in the pathogenicity of A. hydrophila ML09-119. Through a comprehensive comparative genomics analysis of 170 A. hydrophila genomes, the conserved presence of the Tad operon in vAh isolates was confirmed, suggesting its potential contribution to pathogenicity. Herein, the entire Tad operon was knocked out from A. hydrophila ML09-119 to elucidate its specific role in A. hydrophila virulence. The absence of the Tad operon did not affect growth kinetics but significantly reduced virulence in catfish fingerlings, highlighting the essential role of the Tad operon during infection. Biofilm formation of A. hydrophila ML09-119 was significantly decreased in the Tad operon deletant. Absence of the Tad operon had no effect on sensitivity to other environmental stressors, including hydrogen peroxide, osmolarity, alkalinity, and temperature; however, it was more sensitive to low pH conditions. Scanning electron microscopy revealed that the Tad mutant had a rougher surface structure during log phase growth than the wildtype strain, indicating the absence of Tad impacts the outer surface of vAh during cell division, of which the biological consequences are unknown. These findings highlight the role of Tad in vAh pathogenesis and biofilm formation, signifying the importance of T4P in bacterial infections.
The development and application of a novel E-commerce recommendation system used in electric power B2B sector
Authors: Meng Wenjun , Chen Lili , Dong Zhaomin
Published: July 2024

The advent of the digital era has transformed E-commerce platforms into critical tools for industry, yet traditional recommendation systems often fall short in the specialized context of the electric power industry. These systems typically struggle with the industry's unique challenges, such as infrequent and high-stakes transactions, prolonged decision-making processes, and sparse data. This research has developed a novel recommendation engine tailored to these specific conditions, such as to handle the low frequency and long cycle nature of Business-to-Business (B2B) transactions. This approach includes algorithmic enhancements to better process and interpret the limited data available, and data pre-processing techniques designed to enrich the sparse datasets characteristic of this industry. This research also introduces a methodological innovation that integrates multi-dimensional data, combining user E-commerce activities, product specifics, and essential non-tendering information. The proposed engine employs advanced machine learning techniques to provide more accurate and relevant recommendations. The results demonstrate a marked improvement over traditional models, offering a more robust and effective tool for facilitating B2B transactions in the electric power industry. This research not only addresses the sector's unique challenges but also provides a blueprint for adapting recommendation systems to other industries with similar B2B characteristics.
Interest and motivation of disadvantaged students toward online learning during the COVID-19 pandemic in Nepal
Authors: Nepal Ratna Mani , Khadka Bimal , Guragain Shyam , Ghimire Jiwnath
Published: July 2024

Online learning and teaching during the COVID-19 pandemic had mixed impacts on students’ accessibility and performance. It benefited the concerned stakeholders, including management, teachers, and the students, to retain in the system, but it reinforced pre-existing discrimination among students from various disadvantaged groups. Studies reveal that the online learning system created an environment that facilitated students’ motive and interest in learning who disengaged themselves from classrooms due to various socioeconomic reasons during the pandemic. The present study explored students’ experience and perception of online learning in Nepal and analyzed the predictors of their interest in participating in the new learning environments. More specifically, it studied how the online modes of learning were associated with the interests of disadvantaged higher education students in their academic pursuits during the COVID-19 pandemic and how online learning impacted the pre-existing discrimination among them. The study generated concepts and variables drawing from the technology acceptance model (TAM) and a review of existing literature. A survey among 324 higher education students and a follow-up interview among nine selected respondents were conducted in Nepal between April and June 2021. The sample represented students from all social classes, genders, financial status, and geographies. Using a logistic regression model of the survey data and thematic analysis of interviews, this study found that compared to others, students from disadvantaged groups were significantly motivated by the online learning system. Their perception of online learning was positive despite the shortcomings of the system, such as the lack of internet infrastructure and the continuous flow of electricity. Students’ motivation toward the online learning system was triggered by their perception, which helped them to retain and continue in the higher education system. Based on the findings, this study concludes that in a developing country like Nepal, where students face social, economic, and geographical challenges in accessing higher education, the online learning system could be an effective alternative to traditional face-to-face learning to minimize pre-existing discrimination.
Impacts of dietary animal and plant protein on weight and glycemic control in health, obesity and type 2 diabetes: friend or foe?
Authors: Anjom-Shoae Javad , Feinle-Bisset Christine , Horowitz Michael
Published: July 2024

It is well established that high-protein diets (i.e. ~25–30% of energy intake from protein) provide benefits for achieving weight loss, and subsequent weight maintenance, in individuals with obesity, and improve glycemic control in type 2 diabetes (T2D). These effects may be attributable to the superior satiating property of protein, at least in part, through stimulation of both gastrointestinal (GI) mechanisms by protein, involving GI hormone release and slowing of gastric emptying, as well as post-absorptive mechanisms facilitated by circulating amino acids. In contrast, there is evidence that the beneficial effects of greater protein intake on body weight and glycemia may only be sustained for 6–12 months. While both suboptimal dietary compliance and metabolic adaptation, as well as substantial limitations in the design of longer-term studies are all likely to contribute to this contradiction, the source of dietary protein (i.e. animal vs. plant) has received inappropriately little attention. This issue has been highlighted by outcomes of recent epidemiological studies indicating that long-term consumption of animal-based protein may have adverse effects in relation to the development of obesity and T2D, while plant-based protein showed either protective or neutral effects. This review examines information relating to the effects of dietary protein on appetite, energy intake and postprandial glycemia, and the relevant GI functions, as reported in acute, intermediate- and long-term studies in humans. We also evaluate knowledge relating to the relevance of the dietary protein source, specifically animal or plant, to the prevention, and management, of obesity and T2D.
Factors influencing accelerated aging in patients with type 2 diabetes mellitus and coronary heart disease
Authors: Huang Zehua , Liu Nana , Chen Shiyi , Chen Zhiren , Wang Peian
Published: July 2024

Objective

To investigate the factors influencing accelerated aging in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD).

Methods

A total of 216 patients diagnosed with T2DM and CHD between August 2019 and August 2023 at Xuzhou Central Hospital were selected. Patients were divided into an aging group and a non-aging group, based on the positive or negative values of phenotypic age acceleration (PhenoAgeAccel). Logistic regression analysis was conducted. Variables that had a univariate analysis P< 0.05 were included in the multivariate analysis to identify factors influencing aging in patients with T2DM and CHD, and the area under the curve of the model was reported.

Results

This study included 216 patients, with 89 in the accelerated aging group, and 127 in the non-accelerated aging group. The average age of patients was 70.40 (95% CI: 69.10-71.69) years, with 137 males (63.4%). Compared with the non-accelerated aging group, patients in the accelerated aging group were older, with a higher proportion of males, and a higher prevalence of hypertension, stable angina pectoris, and unstable angina pectoris. Multivariate Logistic regression analysis indicated that the absolute value of neutrophils (NEUT#), urea (UREA), adenosine deaminase (ADA), and the triglyceride-glucose index (TyG) were risk factors for accelerated aging, while cholinesterase (CHE) was a protective factor. For each unit increase in NEUT#, UREA, ADA, and TyG, the risk of aging increased by 64%, 48%, 10%, and 789%, respectively. The overall area under the receiver operating characteristic (ROC) curve of the model in the training set was 0.894, with a 95% confidence interval (CI) of 0.851-0.938.

Conclusion

NEUT#, CHE, UREA, ADA, and TyG are predictors of accelerated aging in patients with T2DM and CHD, with the model showing favorable overall predictive performance.
Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of oxytocin-elicited reductions of body weight and adiposity in male diet-induced obese mice
Authors: Edwards Melise M. , Nguyen Ha K. , Dodson Andrew D. , Herbertson Adam J. , Wolden-Hanson Tami , Wietecha Tomasz A. , Honeycutt Mackenzie K. , Slattery Jared D. , O’Brien Kevin D. , Graham James L. , Havel Peter J. , Mundinger Thomas O. , Sikkema Carl L. , Peskind Elaine R. , Ryu Vitaly , Taborsky Gerald J. , Blevins James E.
Published: July 2024

Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (TIBAT, a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase TIBAT and elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9 ± 2.0, 77.4 ± 12.7 and 93.6 ± 4.6% (P<0.05), respectively and was unchanged in inguinal white adipose tissue, pancreas or liver. We subsequently measured the effects of acute 4V OT (1, 5 µg ≈ 0.99, 4.96 nmol) on TIBAT in DIO mice following sham or bilateral surgical SNS denervation to IBAT. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) elevated TIBAT similarly in sham mice as in denervated mice. We subsequently measured the effects of chronic 4V OT (16 nmol/day over 29 days) or vehicle infusions on body weight, adiposity and food intake in DIO mice following sham or bilateral surgical denervation of IBAT. Chronic 4V OT reduced body weight by 5.7 ± 2.23% and 6.6 ± 1.4% in sham and denervated mice (P<0.05), respectively, and this effect was similar between groups (P=NS). OT produced corresponding reductions in whole body fat mass (P<0.05). Together, these findings support the hypothesis that sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and reductions of body weight and adiposity in male DIO mice.
Effect modification by sex of genetic associations of vitamin C related metabolites in the Canadian Longitudinal study on aging
Authors: Lelievre Rebecca , Rakesh Mohan , Hysi Pirro G. , Little Julian , Freeman Ellen E. , Roy-Gagnon Marie-Hélène
Published: July 2024

Introduction: Vitamin C is an essential nutrient. Sex differences in serum vitamin C concentrations have been observed but are not fully known. Investigation of levels of metabolites may help shed light on how dietary and other environmental exposures interact with molecular processes. O-methylascorbate and ascorbic acid 2-sulfate are two metabolites in the vitamin C metabolic pathway. Past research has found genetic factors that influence the levels of these two metabolites. Therefore, we investigated possible effect modification by sex of genetic variant-metabolite associations and characterized the biological function of these interactions.

Methods: We included individuals of European descent from the Canadian Longitudinal Study on Aging with available genetic and metabolic data (n = 9004). We used linear mixed models to tests for genome-wide associations with O-methylascorbate and ascorbic acid 2-sulfate, with and without a sex interaction. We also investigated the biological function of the important genetic variant-sex interactions found for each metabolite.

Results: Two genome-wide statistically significant (p value < 5 × 10−8) interaction effects and several suggestive (p value < 10–5) interaction effects were found. These suggestive interaction effects were mapped to several genes including HSD11B2, associated with sex hormones, and AGRP, associated with hunger drive. The genes mapped to O-methylascorbate were differently expressed in the testis tissues, and the genes mapped to ascorbic acid 2-sulfate were differently expressed in stomach tissues.

Discussion: By understanding the genetic factors that impact metabolites associated with vitamin C, we can better understand its function in disease risk and the mechanisms behind sex differences in vitamin C concentrations.
Targeted multiplex validation of CSF proteomic biomarkers: implications for differentiation of PCNSL from tumor-free controls and other brain tumors
Authors: Ma Jingjing , Lin Zhiguang , Zhang Yaqi , Ding Yun , Tang Qiming , Qian Yufeng , Jin Bo , Luo Ruben Y. , Liao Wei-Li , Thyparambil Sheeno , Han Zhi , Chou C. James , Schilling James , Li Qing , Zhang Mengxue , Lin Yunan , Ma Yan , Sylvester Karl G. , Nagpal Seema , McElhinney Doff B. , Ling Xuefeng B. , Chen Bobin
Published: July 2024

Introduction

Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin’s lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation.

Methods

CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels.

Results

Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features.

Discussion

This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.
Research advances on signaling pathways regulating the polarization of tumor-associated macrophages in lung cancer microenvironment
Authors: Li Wenqiang , Yuan Quan , Li Mei , He Xiaoyu , Shen Chen , Luo Yurui , Tai Yunze , Li Yi , Deng Zhiping , Luo Yao
Published: July 2024

Lung cancer (LC) is one of the most common cancer worldwide. Tumor-associated macrophages (TAMs) are important component of the tumor microenvironment (TME) and are closely related to the stages of tumor occurrence, development, and metastasis. Macrophages are plastic and can differentiate into different phenotypes and functions under the influence of different signaling pathways in TME. The classically activated (M1-like) and alternatively activated (M2-like) represent the two polarization states of macrophages. M1 macrophages exhibit anti-tumor functions, while M2 macrophages are considered to support tumor cell survival and metastasis. Macrophage polarization involves complex signaling pathways, and blocking or regulating these signaling pathways to enhance macrophages’ anti-tumor effects has become a research hotspot in recent years. At the same time, there have been new discoveries regarding the modulation of TAMs towards an anti-tumor phenotype by synthetic and natural drug components. Nanotechnology can better achieve combination therapy and targeted delivery of drugs, maximizing the efficacy of the drugs while minimizing side effects. Up to now, nanomedicines targeting the delivery of various active substances for reprogramming TAMs have made significant progress. In this review, we primarily provided a comprehensive overview of the signaling crosstalk between TAMs and various cells in the LC microenvironment. Additionally, the latest advancements in novel drugs and nano-based drug delivery systems (NDDSs) that target macrophages were also reviewed. Finally, we discussed the prospects of macrophages as therapeutic targets and the barriers to clinical translation.
Viewpoint of multi-omics potential in tuberculosis research: identifying biomarkers for biomanufacturing of efficient control tools
Authors: Otchere Isaac Darko , Aboagye Sammy Yaw , Arthur Patrick Kobina , Asante-Poku Adwoa
Published: July 2024

Tuberculosis (TB), caused by Mycobacterium tuberculosis complex (MTBC), remains a global health burden, claiming millions of lives annually. Despite the availability of a vaccine (the Bacillus Calmette-Guérin; BCG), diagnostics (smear microscopy and DNA-based diagnostics) and drugs for treatment, challenges like drug resistance, lower diagnostic sensitivity such as microscopy, instrumentation and high-level operational expertise requirement and poor vaccine efficacy pose a greater hinderance to TB monitoring and control. The inability of the BCG vaccine to protect against TB other than disseminated disease in neonates call for innovative approaches to provide improved interventions. This review highlights the potential of multi-omics as a powerful emerging tool offering a holistic insight into the intricate interplay between pathogens and the host immune response. It discusses the potential of multi-omics for discovering biomarkers as targets for rational drug design, production of more effective vaccines and as stable targets for production of universally applicable rapid diagnostics for early and accurate TB detection as well as monitoring treatment.
The effect of postpartum nursing guidance on early pelvic floor dysfunction recovery in women of advanced maternal age: a randomized controlled trial
Authors: Huang Qingyu , Tang Junfang , Zeng Dingyuan , Zhang Yu , Ying Ting
Published: July 2024

Objective

This study aimed to investigate the efficacy of postpartum nursing guidance in the treatment of early pelvic floor dysfunction (PFD) in women of advanced maternal age.

Methods

A total of 146 patients of advanced maternal age admitted to our hospital between January and December 2021 were enrolled in this study and randomly divided into two groups: the control group and the experimental group, with 73 patients in each group. Parturients in the control group received routine pelvic floor rehabilitation treatment, whereas those in the experimental group were given individualized postpartum nursing guidance alongside routine pelvic floor rehabilitation treatment. The recovery of pelvic floor muscle (PFM) strength, the incidence of PFD diseases and nursing satisfaction were compared between the two groups after 3 months of treatment.

Results

The enhancement of PFM strength in the experimental group significantly surpassed that in the control group. Furthermore, the experimental group exhibited a notably lower overall occurrence of PFD and significantly greater maternal satisfaction compared with the control group, and the difference was statistically significant (p < 0.05).

Conclusion

Combining postpartum nursing guidance with pelvic floor rehabilitation for women of advanced maternal age represents a treatment regimen deserving of clinical endorsement, as it offers numerous advantages, including substantial improvement in PFM strength, decreased incidence of PFD and enhanced patient satisfaction.
More than red tape: exploring complexity in medical device regulatory affairs
Authors: Han Yu , Ceross Aaron , Bergmann Jeroen
Published: July 2024

Introduction

This study investigates the complexity of regulatory affairs in the medical device industry, a critical factor influencing market access and patient care.

Methods

Through qualitative research, we sought expert insights to understand the factors contributing to this complexity. The study involved semi-structured interviews with 28 professionals from medical device companies, specializing in various aspects of regulatory affairs. These interviews were analyzed using a mix of qualitative coding and natural language processing (NLP) techniques.

Results

The findings reveal key sources of complexity within the regulatory landscape, divided into five domains: (1) regulatory language complexity, (2) intricacies within the regulatory process, (3) global-level complexities, (4) database-related considerations, and (5) product-level issues.

Discussion

The participants highlighted the need for strategies to streamline regulatory compliance, enhance interactions between regulatory bodies and industry players, and develop adaptable frameworks for rapid technological advancements. Emphasizing interdisciplinary collaboration and increased transparency, the study concludes that these elements are vital for establishing coherent and effective regulatory procedures in the medical device sector.
Genetic and causal relationship between chronic gastrointestinal diseases and erectile dysfunction: a Mendelian randomization study
Authors: Zeng Xiaoyan , Tong Li
Published: July 2024

Background

Studies based on observations have indicated potential associations between chronic gastrointestinal diseases and an increased risk of erectile dysfunction (ED). However, the causality of these connections remains ambiguous.

Methods

Summary data for chronic gastrointestinal diseases were extracted from public data. Summary data on ED were extracted from three distinct sources. The genetic correlations between chronic gastrointestinal diseases and ED were explored using linkage disequilibrium score regression (LDSC). The causal associations between chronic gastrointestinal diseases and ED were evaluated using Mendelian randomization (MR) analysis, followed by a meta-analysis to determine the ultimate causal effect.

Results

The LDSC results suggested significant genetic correlations between Crohn's disease (CD) and ED. Inflammatory bowel disease (IBD), ulcerative colitis (UC), and liver cirrhosis (LC) were found to have potential genetic correlations with ED. The combined multiple MR results indicate that IBD and CD have significant causal relationships with ED, while colorectal cancer (CRC) may have a potential causal effect on ED.

Conclusion

This research provided evidence supporting a causal association between IBD, CD, CRC, and ED. The impact of chronic gastrointestinal diseases on ED warrants greater attention in clinical practice.
Pain, obesity, adenosine salvage disruption, and smoking behavior mediate the effect of gut microbiota on sleep disorders: results from network Mendelian randomization and 16S rDNA sequencing
Authors: Li Fu-Jia , Zhang Ru-Yu , Li Jin-Yu , Liu Yu-Ning , Zhang Zi-Xuan , Du Li , Li Yang-Dan-Yu , Liu Xu , Zhang Wei , Cui Gui-Yun , Xu Chuan-Ying
Published: July 2024

Objectives

The objective of this study is to investigate the indirect causalities between gut microbiota and sleep disorders.

Methods

In stage 1, we utilized 196 gut microbiota as the exposure factor and conducted a two-sample univariable Mendelian randomization (MR) analysis on five sleep disorders: insomnia, excessive daytime sleepiness (EDS), sleep-wake rhythm disorders (SWRD), obstructive sleep apnea (OSA), and isolated REM sleep behavior disorder (iRBD). In stage 2, we validated the MR findings by comparing fecal microbiota abundance between patients and healthy controls through 16S rDNA sequencing. In stage 3, we explored the indirect pathways by which the microbiota affects sleep, using 205 gut microbiota metabolic pathways and 9 common risk factors for sleep disorders as candidate mediators in a network MR analysis.

Results

In stage 1, the univariable MR analysis identified 14 microbiota potentially influencing five different sleep disorders. In stage 2, the results from our observational study validated four of these associations. In stage 3, the network MR analysis revealed that the Negativicutes class and Selenomonadales order might worsen insomnia by increasing pain [mediation: 12.43% (95% CI: 0.47, 24.39%)]. Oxalobacter could raise EDS by disrupting adenosine reuptake [25.39% (1.84, 48.95%)]. Allisonella may elevate OSA risk via obesity promotion [36.88% (17.23, 56.54%)], while the Eubacterium xylanophilum group may lower OSA risk by decreasing smoking behavior [7.70% (0.66, 14.74%)].

Conclusion

Triangulation of evidence from the MR and observational study revealed indirect causal relationships between the microbiota and sleep disorders, offering fresh perspectives on how gut microbiota modulate sleep.
Spartina alterniflora invasion reduces soil microbial diversity and weakens soil microbial inter-species relationships in coastal wetlands
Authors: Zhang Tao , Song Bing , Wang Luwen , Li Yong , Wang Yi , Yuan Min
Published: July 2024

Soil microorganisms play a crucial role in the plant invasion process, acting as both drivers of and responders to plant invasion. However, the effects of plant invasion on the complexity and stability of co-occurrence networks of soil microbial communities remain unclear. Here, we investigated how the invasion of Spartina alterniflora affected the diversity, composition, and co-occurrence networks of soil bacterial and fungal communities in the Yellow River Delta, China. Compared to the native plant (Suaeda salsa), S. alterniflora invasion decreased the α-diversity of soil bacterial communities but did not affect that of fungal communities. The β-diversity of soil bacterial and fungal communities under S. salsa and S. alterniflora habitats also differed dramatically. S. alterniflora invasion increased the relative abundance of the copiotrophic phylum Bacteroidota, whereas decreased the relative abundances of the oligotrophic phyla Acidobacteriota and Gemmatimonadota. Additionally, the relative abundance of Chytridiomycota, known for its role in degrading recalcitrant organic matter, increased substantially within the soil fungal community. Functional predictions revealed that S. alterniflora invasion increased the relative abundance of certain soil bacteria involved in carbon and nitrogen cycling, including aerobic chemoheterotrophy, nitrate reduction, and nitrate respiration. More importantly, S. alterniflora invasion reduced the complexity and stability of both soil bacterial and fungal community networks. The shifts in soil microbial community structure and diversity were mainly induced by soil available nutrients and soil salinity. Overall, our study highlights the profound impacts of S. alterniflora invasion on soil microbial communities, which could further indicate the modification of ecosystem functioning by invasive species.
Detection of foot-and-mouth disease virus RNA using a closed loop-mediated isothermal amplification system
Authors: Edwards Natasha , Reboud Julien , Yan Xiaoxiang , Guo Xin , Cooper Jonathan M. , Wadsworth Jemma , Waters Ryan , Mioulet Valerie , King Donald P. , Shaw Andrew E.
Published: July 2024

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals responsible for economic losses that amount to >$20 billion annually. Rapid recognition of FMD cases provides vital information to guide control programmes. A range of point-of-need amplification technologies have been developed which allow sensitive detection of the causative virus (FMDV) in the field at locations remote from laboratories. Here we describe a novel system to detect FMDV RNA using loop-mediated isothermal amplification (LAMP). This test was evaluated using a panel of FMDV isolates (n = 79) and RNA standards demonstrating capability to amplify viral genome directly from clinical material in the absence of nucleic acid extraction. This extraction-free RT-LAMP assay was transferred to a bespoke closed-system lateral flow test (LFT) that was used in combination with a low-cost hand-held heater. Our results show that the RT-LAMP-LFT assay retains a high level of diagnostic and analytical sensitivity when using direct clinical material, with a limit of detection under 80 copies per reaction. Together, our data support the potential for the use of this assay at the point-of-need to facilitate rapid feedback on the status of suspect cases.
A computational model for potential microbe–disease association detection based on improved graph convolutional networks and multi-channel autoencoders
Authors: Zhang Chuyi , Zhang Zhen , Zhang Feng , Zeng Bin , Liu Xin , Wang Lei
Published: July 2024

Introduction

Accumulating evidence shows that human health and disease are closely related to the microbes in the human body.

Methods

In this manuscript, a new computational model based on graph attention networks and sparse autoencoders, called GCANCAE, was proposed for inferring possible microbe–disease associations. In GCANCAE, we first constructed a heterogeneous network by combining known microbe–disease relationships, disease similarity, and microbial similarity. Then, we adopted the improved GCN and the CSAE to extract neighbor relations in the adjacency matrix and novel feature representations in heterogeneous networks. After that, in order to estimate the likelihood of a potential microbe associated with a disease, we integrated these two types of representations to create unique eigenmatrices for diseases and microbes, respectively, and obtained predicted scores for potential microbe–disease associations by calculating the inner product of these two types of eigenmatrices.

Results and discussion

Based on the baseline databases such as the HMDAD and the Disbiome, intensive experiments were conducted to evaluate the prediction ability of GCANCAE, and the experimental results demonstrated that GCANCAE achieved better performance than state-of-the-art competitive methods under the frameworks of both 2-fold and 5-fold CV. Furthermore, case studies of three categories of common diseases, such as asthma, irritable bowel syndrome (IBS), and type 2 diabetes (T2D), confirmed the efficiency of GCANCAE.
Characterization and transmission of plasmid-mediated multidrug resistance in foodborne Vibrio parahaemolyticus
Authors: Zhou Haibo , Lu Zhaoxin , Liu Xinmei , Bie Xiaomei , Cui Xinping , Wang Zuwei , Sun Xiaojie , Yang Jun
Published: July 2024

Objectives

The purpose of this study was to determine the structural features and transferability of the multidrug-resistance (MDR) plasmid, and resistance phenotypes for the tested antimicrobials in foodborne Vibrio parahaemolyticus.

Methods

Plasmids were isolated from a V. parahaemolyticus strain of seafood origin, then sequenced using the Illumina NovaSeq 6000 and PacBio Sequel II sequencing platforms to obtain the complete genome data. Characterization of the MDR plasmid pVP52-1, including determination of antimicrobial resistance genes (ARGs), plasmid incompatibility groups, and transferability, was carried out.

Results

V. parahaemolyticus strain NJIFDCVp52 contained two circular chromosomes and two circular plasmids (pVP52-1 and pVP52-2). Plasmid typing indicated that pVP52-1 belonged to the incompatibility group IncA/C2 and the sequence type pST3. pVP52-1 carried 12 different ARGs, an IS110-composite transposon consisting of aac(6′)-Ib-cr, qnrVC1, aac(6′)-Ib, dfrA14, and the IS26-mphA-IS6100 unit flanked by inverted sequences of IS5075 and IS4321. pVP52-2 carried no ARGs. A plasmid elimination assay showed that only pVP52-1 and its ARGs were lost, the loss of resistance to several antimicrobials, causing a change from the ampicillin-ampicillin/sulbactam-cefazolin-cefoxitin-ceftazidime-cefotaxime-imipenem-trimethoprim/sulfamethoxazole resistance pattern to the ampicillin resistance pattern. In accordance, a conjugation transfer assay showed that only pVP52-1 and its ARGs were horizontally transferred, leading to increased antimicrobial resistance in Escherichia coli strain EC600, causing a change from the ampicillin-nalidixic acid resistance pattern to the ampicillin-ampicillin/sulbactam-cefazolin-cefoxitin-ceftazidime-cefotaxime-imipenem-nalidixic acid-chloramphenicol-tetracycline-trimethoprim/sulfamethoxazole-azithromycin resistance pattern. Further transferability experiments revealed that pVP52-1 could be transferred to other enterobacterial strains of E. coli and Salmonella.

Discussion

This study emphasizes the urgent need for continued surveillance of resistance plasmids and changes in antimicrobial resistance profiles among the V. parahaemolyticus population.
Curing of chronic hepatitis C combined with coronavirus disease 2019 in a couple over 85 years old: a case series study
Authors: Zeng Qing-Lei , Lv Xue-Yan , Chen Ru-Yue , Pan Ya-Jie
Published: July 2024

Introduction

Data on the management of patients aged more than 85 years with chronic hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequential infections are lacking.

Methods

The current study described the management of an older couple aged more than 85 years with these above-mentioned two diseases treated with 12 weeks of sofosbuvir/velpatasvir (Epclusa®) and 5 days of nirmatrelvir/ritonavir (Paxlovid®) sequentially. The effectiveness and safety profiles were closely monitored during therapy and till 9 months posttreatment.

Results

In late March 2023, the husband with the main complaint of repeated gingival bleeding and asymptomatic wife were 86 and 85 years old, and had HCV RNA levels of 91,800 and 6,630,000 IU/mL, respectively. On the fourth day of sofosbuvir/velpatasvir treatment, the husband had a moderate headache, and the wife had severe headache and moderate fever and dizziness. We then found that their SARS-CoV-2 test results were positive. After careful consideration, the expert panel decided to treat the couple with oral nirmatrelvir/ritonavir (300 mg/100 mg, twice daily) beginning on the fifth day of sofosbuvir/velpatasvir treatment for 5 days. During the 5 days of nirmatrelvir/ritonavir treatment, the patient’s symptoms and signs gradually improved, and the patient was negative for SARS-CoV-2 RNA on the fifth day of nirmatrelvir/ritonavir therapy. Meanwhile, the husband’s HCV RNA was not detectable after one week of sofosbuvir/velpatasvir treatment till posttreatment month 9, and his ALT level was normal beginning at week 1 of sofosbuvir/velpatasvir treatment. Moreover, the wife’s HCV RNA was not detectable after week 4 of sofosbuvir/velpatasvir treatment till posttreatment month 9. Notably, no other symptoms or signs occurred during the treatment or follow-up period, and other serum biochemical parameters remained stable until 9 months after the discontinuation of sofosbuvir/velpatasvir treatment.

Conclusion

The older couple aged more than 85 years with chronic HCV and SARS-CoV-2 sequential infection were safely cured by the sofosbuvir/velpatasvir and nirmatrelvir/ritonavir sequential treatment.

Discussion

This study suggested that old age should not be a barrier to HCV/SARS-CoV-2 treatment. Given that the proportion of older HCV-infected patients is increasing, clinical trials of direct-acting antiviral agents should include older HCV-infected individuals.