bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Many Tunings of Balinese Gamelan
Authors: Sethares William , Vitale Wayne
Published: September 2024

The study of gamelan tunings has a long history, both within Indonesia and among the many foreign researchers who have sought to reconcile those tuning systems with ideas and practices of Western music. Challenges arise because Indonesian gamelan and Western tuning systems are based on fundamentally different concepts and principles. This article introduces and describes the Gamelan Tuning Explorer (GTE), a Max patch intended to help facilitate, through visualization and adjustable parameters, greater understanding of certain core aspects of Balinese gamelan tuning—specifically, the nonstandardized tunings used for gamelan gong kebyar, a large orchestra of bronze-keyed metallophones, tuned gongs, and other instruments. The GTE incorporates measured tuning data from 47 complete gamelan gong kebyar; each encompasses about 150 keys and tuned gong chimes. Forty-two of these tuning data sets were collected in the mid 1970s by American ethnomusicologist Andrew Toth, who spent decades in Bali engrossed in research on this topic; five were remeasured by the authors in 2019 to document how they had changed over the ensuing decades. In addition to collecting this treasure trove of data, Toth identified several key conceptual ideas of Balinese gamelan tunings. These include the consistent use of ombak (the prominent beating of two paired notes played in “unison”); the relationship of paired-tuning ombak to octave treatment; the stretching and compression of octaves, both by register and by note; the Begbeg versus Tirus models of intervallic formation; and more. Toth's data and each of these tuning concepts have been analyzed in two previous articles (Vitale and Sethares 2021; Sethares and Vitale 2022). We seek to make these concepts more immediate and accessible with GTE by using a graphical, interactive interface. Each of these parameters can be explored by the simple manipulation of a slider or other interface element. The corresponding changes in the sound can be readily heard, and visualized with interactive Toth plots—graphic representations of gamelan tuning profiles developed by Toth and named in his honor. This article describes a series of observations enabled by GTE.
‘To Adopt the Principles of Freedom’: Christianity, Women’s Education, and Progress in U.S. Press Coverage of the Iwakura Mission
Authors: Henning Joseph M. , Makalsky Leo
Published: September 2024

In U.S. press reports, the visit of Meiji Japan’s Iwakura Mission in 1872 presented both an opportunity for Americans to facilitate progress in Japan and evidence of social reform already underway there. As an opportunity, the mission served as a potential medium for American efforts to improve the Meiji government’s treatment of Japanese Christians. Many American political and religious leaders hoped to convince the mission ambassadors that freedom of religion was an essential component of civilization and a prerequisite for engaging with the treaty powers on equal terms. As evidence of social reform, the five Japanese girls who came with the mission to study in the United States embodied Japan’s new commitment to expanding educational opportunities for women. Focusing on the themes of religion and gender in U.S. newspaper coverage, this article shows how Americans projected onto the Iwakura Mission their own images of the United States as an inspiration and model for reform in Japan. Treating the mission as both an opportunity and evidence, the U.S. press depicted it in a self-congratulatory fashion to embellish Americans’ national identity as a people committed to progress.
Iwakura Mission and the Network of Japanese Students in the United States
Authors: Wakabayashi Haruko
Published: September 2024

One notable characteristic of the Iwakura Mission was, in Tanaka Akira’s words, its historical and cultural “continuity in discontinuity.” While its leaders were mostly from the aristocracy and the powerful Satsuma and Chōshū domains with little experience in the West, the secretaries who assisted them were former Tokugawa retainers that were experts in foreign affairs. The ryūgakusei, or overseas students, who were in the United States or Europe prior to the mission’s arrival and joined them on site, were another group that exemplified the “continuity.” Reform-minded daimyo and the progressive members of the Tokugawa regime had dispatched many to the West during the Tokugawa period with the very purpose to become useful servants to assist Japan’s quick and successful modernization. Once recruited to the mission, these ryūgakusei served as guides, interpreters, and investigators, collecting and compiling information on various institutions and policies in the respective countries. The knowledge, experience, and linguistic skills they had acquired and the network they created while abroad were vital in facilitating the Iwakura Mission and the new Meiji government’s subsequent effort of modernization.
Free vibration analysis of an O-pattern graphene reinforced axial functionally graded polymer matrix nano-composite non-uniform beam
Authors: Gantayat Amit Kumar , Sutar Mihir Kumar , Mohanty Jyoti Ranjan , Pattnaik Sarojrani
Published: September 2024

Recently, the demand for nanocomposites in the form of functionally graded materials (FGM) has increased because of their improved weight-to-stiffness ratios, less delamination effects, and ability to have desired qualities at the right location. Additionally, compared to typical composites, static qualities like strength and elasticity are superior. In this research work, a model for an axially graphene-reinforced functionally graded polymer matrix nanocomposite non-uniform beam is prepared, to obtain the dynamic behavior of the beam in form of its Natural Frequencies. Along the length of the beam, the graphene Nano reinforcement is dispersed in an epoxy polymer matrix as “O” pattern using a function. Material modulus at each location of the beam is modelled using Halpin-Tsai micromechanics theory, the mass density and Poisson’s Ratio of the beam are determined using rule of mixture. The geometry non-uniformity of the beam is modelled using an exponential function. Using MATLAB software code, simulation and parametric analysis of the beam are performed for various slenderness ratios and varied boundary conditions. The non-uniform beam result is obtained after the result for a uniform beam is used to validate it. In result it is analyzed that for the particular geometric and reinforcement configuration of the beam, as the non-uniformity in the beam geometry is increases, the fundamental frequency decreases, and the slenderness ratio has also the same effect on its fundamental frequency.
African Migration at a Crossroads: The Social and Theoretical Implications of Emerging International Migration Trends
Authors: Thomas Kevin J. A. , Mara Miracle
Published: September 2024

This study examines international migration trends in Africa since the mid-1960s. It argues that African international migration trends are at a turning point that could significantly affect the future of migration studies. New African immigrant communities are emerging in Asia, South America, and other world regions, while the influence of state and non-state institutions is increasing. Moreover, interstate migration in Africa is now more disconnected from the legacies of the continent's colonial labor migration systems. By 2050, Africa is also expected to have the world's largest population in the age-groups that typically have the highest probabilities of migration, while per-capita incomes will increase in ways that could reduce the costs of migration. Although Africa's influence on future migration research is likely to increase, progress in developing theories to examine its emerging trends has been limited. With few exceptions, studies on migration in Africa focus on theory application rather than theory building. New theoretical approaches are therefore needed to adequately situate Africa's emerging migration trends within the larger context of migration studies. The building blocks for developing these theories include decolonial approaches that highlight African perspectives and the integration of the substantive influences of future migration trends into theory-building processes.
Core problems in information systems implementation: An analytical review and implications for AI systems
Authors: Yi Sangyoon , Choi Jungtae , Kim Gayoung
Published: September 2024

Research on information systems (IS) has identified diverse problems encountered in system implementation and organizational change. We reviewed and analyzed the implementation problems explored in prior research to determine the core problems and the important causal relations between the problems. The causal mechanism behind the relations was articulated with illustrating examples. This analytical review provides a deeper understanding of the fundamental aspects of IS implementation processes, which are conducive to preparing for the implementation of artificial intelligence (AI) systems. AI systems are an information system as well. However, by embedding machine learning elements and necessary data flows, the implementation of AI systems would be much more complicated and challenging. We derived useful implications for AI systems implementation by advancing the understanding of the core problems of IS implementation and connecting them with the fundamental problems inherent in AI systems. The analyses and discussions motivate further studies on implementing IS with or without AI.
Fluvial encounters: Experimenting with a ‘River’s voice’ amidst light-based datafication
Authors: Lantto Klein Mirjami , Dixon Deborah P , Williams Richard
Published: September 2024

Fluvial geomorphologists’ advocacy for a culture of care towards rivers is increasingly animated by the potentialities of hyperscale environmental data. Championing catchment-specific responses, it has been argued that intensified datafication of rivers can help them express their own voice. Motivated by this provocation, this paper discusses prosthetic research encounters with the River Feshie in Scotland to tentatively approach the question ‘what is a river’s voice’ in a moment of increasing digitisation and automation of geomorphological fieldwork via technologies of light. Exploring the allowances and excesses of illumination in the scientific imaging of the Feshie, it draws on ‘critical physical geography’ and ‘feminist new materialism’ to conceptualise the geovisualisation of riverscapes as a partial practice of envisioning, rather than a process of total illumination. By highlighting the multiplicity of riverine voices that become co-produced through differently configured sensing ensembles, the paper advocates for a critical fluvial geomorphology that interrogates its assumptions about access to the ‘real’.
Wear particles image enhancement using long short-term memory 3D recurrent reconstruction neural network (LSTM 3D-R2N2)
Authors: Xi Yinhu , Zhang Haohao , Li Bo
Published: September 2024

3D modeling of wear particles has proven to be a useful tool for monitoring mechanical failure conditions. In this work, a new method for 3D reconstruction of wear particles in uncontaminated oil (healthy oil) and contaminated oil (used oil) was proposed. The image acquisition device can capture multi-view images of moving wear particles in both healthy and used oil by using the reflected light. The images were pretreated first, and the image color inversion was conducted using the Pillow library. The pretreated wear particle images were used for 3D reconstruction using long short-term memory 3D recurrent reconstruction neural network. The current results were verified against existing results, and good agreement can be found. It can be concluded that we can reconstruct the similar 3D wear particle results with fewer images by comparison with other methods. Specifically, only 4–6 image samples were used for the 3D reconstruction of wear particles, and at least 8 image samples were needed for other existing reports.
From Me-Search to We-Search: (Re)Imagining Mentorship and Intergenerational Relationships for Black Women in Leadership
Authors: Gardner Paige J. , Cowan Pitre Charisse , Dillard Cynthia B.
Published: September 2024

This article examines the process of forming an intergenerational mentoring relationship among three Black women scholars at different levels of academic leadership in higher education. Over the course of a summer, we came together to critically examine how our collective journey as leaders shifted from “me-search” to “we-search.” In the spirit of Ubuntu or “I am because we are,” our we-search centers Black indigenous knowledge that honors a communal destiny and legacy where leadership and mentorship must be done in a collective. Thus, we used Black Feminist Action Research as a critical methodology that disrupts hegemony in inquiry, mentoring, and leadership. In a four-phased approach, we analyzed personal artifacts and narratives, grounded in radical Black feminist honesty. By conducting such qualitative “we-search,” we co-construct sites of healing and sanctuary and provide valuable insights and strategies for Black scholars and leaders.
Exploring the Impact of COVID-19 on Cervical Cancer Screening Services: A Qualitative Study of Healthcare Providers’ and Women’s Perspectives and Experiences
Authors: Mantula Fennie , Toefy Yoesrie
Published: September 2024

A qualitative exploration was conducted to analyse the reasons behind the low utilisation of cervical cancer screening services in Gwanda district, Zimbabwe, focusing on the impact of the COVID-19 pandemic. The study involved 5 focus group discussions with 36 women, utilising maximum variation sampling to explore the effects of COVID-19 on screening coverage. Additionally, in-depth interviews were conducted with 25 health-care providers from primary health facilities and the provincial hospital offering screening services. The results suggest a decline in the progress of the cervical cancer screening programme due to the disruptions caused by COVID-19 which subsequently reduced women’s access to screening and treatment services. It was anticipated that restoring women’s confidence in adherence to screening would require time post-pandemic. Moreover, findings highlighted the potential progression of undetected precursor lesions to advanced cancer stages during non-screening periods, which may increase future cervical cancer morbidity and mortality. The findings underscore the importance of integrating cervical cancer screening messaging within broader health communication strategies to emphasise the significance of health interventions for overall well-being. This study recommends the adoption of more efficient screening methods, such as Human-Papillomavirus self-sampling to mitigate future disruptions in screening services, thereby guiding policymakers towards implementing best screening approaches.
Missed opportunities to provide sexually transmitted and blood-borne infections testing in British Columbia: An interpretive description of users’ experiences of Get Checked Online's design and implementation
Authors: Iyamu Ihoghosa , Kassam Rosemin , Worthington Catherine , Grace Daniel , Pedersen Heather , Haag Devon , Bondyra Mark , Salmon Amy , Koehoorn Mieke , Gilbert Mark
Published: September 2024

Background

Digital testing services for sexually transmitted and blood-borne infections (STBBIs), such as GetCheckedOnline, experience significant user drop-offs. For example, 32% of GetCheckedOnline users needing testing at account creation do not test, constituting missed opportunities. We explored the influence of users’ expectations and experiences of GetCheckedOnline's web design and implementation on missed opportunities.

Methods

This interpretive description purposively sampled 14 GetCheckedOnline users who created accounts between April 2022 and February 2023, indicated needed testing at account creation but did not test. We conducted semi-structured interviews and cognitive walkthroughs of GetCheckedOnline on Zoom, exploring participants’ expectations and experiences, including problems using the service. Interviews were audio recorded, transcribed verbatim, and analyzed using reflexive thematic analyses.

Results

Three themes were identified: (a) transitioning between GetCheckedOnline and laboratory services is a major testing barrier; (b) users’ appraisal of their health and social contexts is a determinant of testing through GetCheckedOnline; and (c) tailoring GetCheckedOnline's design and implementation to accommodate varying user needs can promote equitable testing. Health equity issues occurred along sociodemographic gradients as the GetCheckedOnline-laboratory transition was more onerous for older users. Users’ appraisal of their testing needs which varied by age and gender, and their assessment of time, and travel requirements for testing in remote communities influenced testing. Learning about GetCheckedOnline from healthcare providers improved testing compared with learning about the service through Google search which raised trust concerns regarding GetCheckedOnline's authenticity. Suggested improvements to promote health equity include personalized education, mail-in testing options, and simpler seamless web experiences.

Conclusions

To promote equitable access to digital STBBI testing services such as GetCheckedOnline, we can adapt web-design and implementation to suit user needs and contexts, ensuring simplicity and options for testing that reduce user burdens.
Clinical features, pathophysiology, and management of acute myelopathy following CAR T-cell therapy
Authors: Deschênes-Simard Xavier , Santomasso Bianca D. , Dahi Parastoo B.
Published: September 2024

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of patients with relapsed or refractory hematologic malignancies, but it comes with unique toxicities, notably cytokine release syndrome and ICANS (immune effector cell–associated neurotoxicity syndrome). As experience with CAR T-cell therapy grows, distinct and infrequent neurologic complications are becoming increasingly evident. Recently, reports of acute myelopathy after the administration of CAR T-cell therapies have been accumulating. Despite the establishment of consensus guidelines for managing ICANS, there remains limited guidance on the appropriate investigations and treatments for this rare complication. In this manuscript, we delve into the clinical features, pathophysiology, and strategies for the optimal management of acute myelitis after CAR T-cell therapy and draw insights from reported cases in the literature.
Regulation of KLRC and Ceacam gene expression by miR-141 supports cell proliferation and metastasis in cervical cancer cells
Authors: Dabous Emad , Alalem Mai , Awad Ahmed M. , Elawdan Khaled A. , Tabl Ahmed M. , Elsaka Shorouk , Said Walid , Guirgis Adel A. , Khalil Hany
Published: September 2024

Introduction

MicroRNAs (miRNAs) are single RNA molecules that act as global regulators of gene expression in mammalian cells and thus constitute attractive targets in treating cancer. Here we aimed to investigate the possible involvement of miRNA-141 (miR-141) in cervical cancer and to identify its potential targets in cervical cancer cell lines.

Methods

The level of miR-141 in HeLa and C-33A cells has been assessed using the quantitative real-time PCR (qRT-PCR). A new miR-141 construct has been performed in a CMV promoter vector tagged with GFP. Using microarray analysis, we identified the potentially regulated genes by miR-141 in transfected HeLa cells. The protein profile of killer-like receptor C1 (KLRC1), KLRC3, carcinoembryonic antigen‐related cell adhesion molecule 3 (CAM3), and CAM6 was investigated in HeLa cells transfected with either an inhibitor, antagonist miR-141, or miR-141 overexpression vector using immunoblotting and flow cytometry assay. Finally, ELISA assay has been used to monitor the produced cytokines from transfected HeLa cells.

Results

The expression of miR-141 significantly increased in HeLa and C-33A cells compared to the normal cervical HCK1T cell line. Transfection of HeLa cells with an inhibitor, antagonist miR-141, showed a potent effect on cancer cell viability, unlike the transfection of miR-141 overexpression vector. The microarray data of HeLa cells overexpressed miR-141 provided a hundred of downregulated genes, including KLRC1, KLRC3, CAM3, and CAM6. KLRC1 and KLRC3 expression profiles markedly depleted in HeLa cells transfected with miR-141 overexpression accompanied by decreasing interleukin 8 (IL-8), indicating the role of miR-141 in avoiding programmed cells death in HeLa cells. Likewise, CAM3 and CAM6 expression reduced markedly in miR-141 transduced cells accompanied by an increasing level of transforming growth factor beta (TGF-β), indicating the impact of miR-141 in cancer cell migration. The IntaRNA program and miRWalk were used to check the direct interaction and potential binding sites between miR-141 and identified genes. Based on this, the seeding regions of each potential target was cloned upstream of the luciferase reporter gene in the pGL3 control vector. Interestingly, the luciferase activities of constructed vectors were significantly decreased in HeLa cells pre-transfected with miR-141 overexpression vector, while increasing enormously in cells pre-transfected with miR-141 specific inhibitor.

Conclusion

Together, these data uncover an efficient miR-141-based mechanism that supports cervical cancer progression and identifies miR-141 as a credible therapeutic target.
How does the role of complementary and alternative medicine in general practice differ between countries? Interviews with doctors who have worked both in Germany and elsewhere in Europe
Authors: Linde Klaus , Bayer Robert , Gehrmann Jan , Jansky Bianca
Published: September 2024

Background

Available data suggest that general practitioners (GPs) in Germany use complementary and alternative medicine (CAM) modalities more frequently than GPs in many other countries. We investigated the country differences perceived by general practitioners who have worked in Germany and in one of four other European countries with regard to the role of complementary and alternative treatments in primary care.

Methods

In this qualitative study we conducted semi-structured interviews with 12 GPs who had worked both in Germany and Italy, the Netherlands, Norway or the United Kingdom (UK; n = 3 for each of the four countries). Participants were asked how they perceived and experienced country differences regarding health system, relevance of CAM modalities, the role of evidence-based medicine (EBM) and science, and how they handle so-called indeterminate situations. For the analysis, we followed a thematic analysis approach according to Braun and Clarke with focus on themes that cover CAM.

Results

Participants unanimously reported that they perceived CAM to be more relevant in general practice in Germany compared to the other countries. We identified four overarching themes in relation to the perceived reasons for these differences. Firstly, physicians with experiences in countries with a strong EBM and science orientation (Netherlands, Norway and the UK) considered the deeply ingrained view in national healthcare systems and GP communities that CAM modalities are not evidence-based as the main reason for the lower use of CAM by GPs. Secondly, extensive training of communication skills was cited as a reason that reduced the need for CAM in the Netherlands, Norway and the UK. Thirdly, differences in patient expectations and demands were perceived as a factor contributing to greater utilisation of CAM by German GPs compared to the other countries. Finally, country-specific reimbursement mechanisms were considered as a factor influencing the role of CAM in general practice.

Conclusions

The study results point to major differences between countries with regard to the role of CAM in GP care. Differences in basic attitudes in the discipline of general practice, patient expectations and system conditions appear to play an important role here.
Fenofibrate to prevent amputation and reduce vascular complications in patients with diabetes: FENO-PREVENT
Authors: Ku Eu Jeong , Kim Bongseong , Han Kyungdo , Lee Seung-Hwan , Kwon Hyuk-Sang
Published: September 2024

Background

The potential preventive effect of fenofibrate on lower extremity amputation (LEA) and peripheral arterial disease (PAD) in patients with type 2 diabetes (T2D) is not fully elucidated.

Methods

We selected adult patients ≥ 20 years of age with T2D from the Korean National Health Insurance Service Database (2009–2012). The fenofibrate users were matched in a 1:4 ratio with non-users using propensity scores (PS). The outcome variables were a composite of LEA and PAD and the individual components. The risks of outcomes were implemented as hazard ratio (HR) with 95% confidence intervals (CI). For safety issues, the risks of acute kidney injury, rhabdomyolysis and resulting hospitalization were analyzed.

Results

A total of 114,920 patients was included in the analysis with a median follow-up duration of 7.6 years (22,984 and 91,936 patients for the fenofibrate user and non-user groups, respectively). After PS matching, both groups were well balanced. The fenofibrate group was associated with significantly lower risks of composite outcome of LEA and PAD (HR 0.81; 95% CI 0.70–0.94), LEA (HR 0.76; 95% CI 0.60–0.96), and PAD (HR 0.81; 95% CI 0.68–0.96). The risk of acute kidney injury, rhabdomyolysis, or hospitalization for these events showed no significant difference between the two groups. Subgroup analyses revealed consistent benefits across age groups, genders, and baseline lipid profiles.

Conclusions

This nationwide population-based retrospective observational study suggests that fenofibrate can prevent LEA and PAD in patients with T2D who are on statin therapy.
Prevalence of child maltreatment in a nationwide sample of 18 to 31 year-olds in Germany
Authors: Kasinger Christoph , Schlack Robert , Brähler Elmar , Fegert Jörg M. , Clemens Vera
Published: September 2024

Background

Child maltreatment (CM) can have devastating and potentially lifelong effects for those affected and is a major contributor to mental health problems. To tackle public health problems it is crucial to have reliable data on CM. The aim of this study is to assess the prevalence and predictors of CM in a nationwide sample of the German population of young adults.

Methods

The study population (young adults aged 18 to 31 years) stems from the KiGGS Cohort study, the longitudinal branch of the German Health Interview and Examination Survey for children and adolescents. This sample meets the criteria of the United Nations Sustainable Development Goals (SDG) indicator 16.2.3. The data was collected between 2014 and 2017. CM were assessed with the Childhood Trauma Questionnaire (CTQ) in. In addition, socio-demographic variables and other known risk factors for CM were assessed. A total of 6433 (47.8% female) participants were included in the analyses. Binary logistic regression analyses were used to investigate predictors of maltreatment subtypes. Ordinal regression was used to examine their association with experience of multiple forms of CM.

Results

Overall, 18.4% (f: 20.9%, m: 16.1%) of the participants reported having experienced at least one type of CM; 6.7% (f: 8.8%, m: 4.8%) reported experiences of emotional abuse, 3.7% (f: 3.9%, m: 3.5%) physical abuse, 3.5% (f: 5.3%, m: 1.7%) sexual abuse, 9.0% (f: 9.9%, m: 8.2%) emotional neglect and 8.6% (f: 8.5%, m: 8.7%) physical neglect. Gender, subjective social status, education and household dysfunction (e.g. living with an individual who is using substances) emerged as significant predictors for different types of CM. Additionally, all these factors were significant risk factors for experiencing cumulative CM.

Conclusions

CM is common in the German population, with almost one in five people experiencing at least one type of CM. The results reveal important risk factors for the occurrence of CM. In particular, people with lower social status and those who grew up in dysfunctional households are at higher risk of CM. Greater support for this vulnerable population may reduce the prevalence of CM.
Simulated weightlessness procedure, head-down bed rest has reversible effects on the metabolism of rhesus macaque
Authors: Li Yuting , Zhang Xu , Xu Zhen , Chu Xixia , Hu Zhiqiang , Ye Zhengyang , Li Caiqin , Wang Zhenbo , Zeng Bin , Pan Jingyu , Zhao Qian , Zhou Chengbin , Lan Zhaohui , Kan Guanghan , He Guang , Xu Xiaodan , Li Weidong
Published: September 2024

It is a consensus in the international manned space field that factors such as microgravity during the space flight can cause anxiety, depression and other important brain function abnormalities in astronauts. However, the neural mechanism at the molecular level is still unclear. Due to the limitations of research conditions, studies of biological changes in the primate brain have been comparatively few. We took advantage of -6° head-down bed rest (HDBR), one of the most implemented space analogues on the ground, to investigate the effects of simulated weightlessness on non-human primate brain metabolites. The Rhesus Macaque monkeys in the experiment were divided into three groups: the control group, the 42-day simulated weightlessness group with HDBR, and the recovery group, which had 28 days of free activity in the home cage after the HDBR. Liquid chromatography-mass spectrometry (LC-MS) was used to perform metabolomics analysis on specific brain areas of the monkeys under three experimental conditions. Our results show that simulated weightlessness can cause neurotransmitter imbalances, the amino acid and energy metabolism disorders, and hormone disturbances. But these metabolomics changes are reversible after recovery. Our study suggests that long-term brain damage in space flight might be reversible at the metabolic level. This lays a technical foundation for ensuring brain health and enhancing the brain function in future space studies.
Repurposing of a library for high-content screening of inhibitors against Echinococcus granulosus
Authors: Zheng Weinan , Lv Gaofei , Li Jun , Zhang Yao , Qi Wenjing , Yan Mingzhi , Wu Jinzhi , Chan Chikin , Pan Xiaoben , Zhang Wenbao
Published: September 2024

Background

Cystic echinococcosis (CE) is a zoonotic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus sensu lato (E. granulosus), with a worldwide distribution. The current treatment strategy for CE is insufficient. Limited drug screening models severely hamper the discovery of effective anti-echinococcosis drugs.

Methods

In the present study, using high-content screening technology, we developed a novel high-throughput screening (HTS) assay by counting the ratio of propidium iodide-stained dead protoscoleces (PSCs) to the total number of PSCs. In vitro and ex vivo cyst viability assays were utilized to determine the effect of drugs on cyst viability.

Results

Using the newly established HTS assay, we screened approximately 12,000 clinical-stage or The Food and Drug Administration (FDA)-approved small molecules from the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library, as well as the LOPAC1280 and SelleckChem libraries, as a strategic approach to facilitate the drug discovery process. Initial screening yielded 173 compounds with anti-echinococcal properties, 52 of which demonstrated dose–response efficacy against E. granulosus PSCs in vitro. Notably, two agents, omaveloxolone and niclosamide, showed complete inhibition upon further validation in cyst and microcyst viability assays in vitro after incubation for 3 days, and in an ex vivo cyst viability assay using cysts isolated from the livers of mice infected with E. granulosus, as determined by morphological assessment.

Conclusions

Through the development of a novel HTS assay and by repurposing libraries, we identified omaveloxolone and niclosamide as potent inhibitors against E. granulosus. These compounds show promise as potential anti-echinococcal drugs, and our strategic approach has the potential to promote drug discovery for parasitic infections.

Graphical Abstract
Role of extracellular vesicle-associated proteins in the progression, diagnosis, and treatment of hepatocellular carcinoma
Authors: Liu Yao-Ge , Jiang Shi-Tao , Zhang Jun-Wei , Zheng Han , Zhang Lei , Zhao Hai-Tao , Sang Xin-Ting , Xu Yi-Yao , Lu Xin
Published: September 2024

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, characterized by difficulties in early diagnosis, prone to distant metastasis, and high recurrence rates following surgery. Extracellular vesicles (EVs) are a class of cell-derived particles, including exosomes, characterized by a phospholipid bilayer. They serve as effective carriers for intercellular communication cargo, including proteins and nucleic acids, and are widely involved in tumor progression. They are being explored as potential tumor biomarkers and novel therapeutic avenues. We provide a brief overview of the biogenesis and characteristics of EVs to better understand their classification standards. The focus of this review is on the research progress of EV-associated proteins in the field of HCC. EV-associated proteins are involved in tumor growth and regulation in HCC, participate in intercellular communication within the tumor microenvironment (TME), and are implicated in events including angiogenesis and epithelial-mesenchymal transition (EMT) during tumor metastasis. In addition, EV-associated proteins show promising diagnostic efficacy for HCC. For the treatment of HCC, they also demonstrate significant potential including enhancing the efficacy of tumor vaccines, and as targeting cargo anchors. Facing current challenges, we propose the future directions of research in this field. Above all, research on EV-associated proteins offers the potential to enhance our comprehension of HCC and offer novel insights for developing new treatment strategies.
Implementation of a rural emergency department-initiated buprenorphine program in the mountain west: a study protocol
Authors: Seliski Natasha , Madsen Troy , Eley Savannah , Colosimo Jennifer , Engar Travis , Gordon Adam , Barnett Christinna , Humiston Grace , Morsillo Taylor , Stolebarger Laura , Smid Marcela C , Cochran Gerald
Published: September 2024

Background

Opioid related overdose morbidity and mortality continue to significantly impact rural communities. Nationwide, emergency departments (EDs) have seen an increase in opioid use disorder (OUD)-related visits compared to other substance use disorders (SUD). ED-initiated buprenorphine is associated with increased treatment engagement at 30 days. However, few studies assess rural ED-initiated buprenorphine implementation, which has unique implementation barriers. This protocol outlines the rationale and methods of a rural ED-initiated buprenorphine program implementation study.

Methods

This is a two-year longitudinal implementation design with repeated qualitative and quantitative measures of an ED-initiated buprenorphine program in the rural Mountain West. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework outlines intervention assessments. The primary outcome is implementation measured by ED-initiated buprenorphine protocol core components. Reach, adoption, and maintenance are secondary outcomes. External facilitators from an academic institution with addiction medicine and prior program implementation expertise partnered with community hospital internal facilitators to form an implementation team. External facilitators provide ongoing support, recommendations, education, and academic detailing. The implementation team designed and implemented the rural ED-initiated buprenorphine program. The program includes OUD screening, low-threshold buprenorphine initiation, naloxone distribution and administration training, and patient navigator incorporation to provide warm hand off referrals for outpatient OUD management. To address rural based implementation barriers, we organized implementation strategies based on Expert Recommendations for Implementing Change (ERIC). Implementation strategies include ED workflow redesign, local needs assessments, ED staff education, hospital leadership and clinical champion involvement, as well as patient and community resources engagement.

Discussion

Most ED-initiated buprenorphine implementation studies have been conducted in urban settings, with few involving rural areas and none have been done in the rural Mountain West. Rural EDs face unique barriers, but tailored implementation strategies with external facilitation support may help address these. This protocol could help identify effective rural ED-initiated buprenorphine implementation strategies to integrate more accessible OUD treatment within rural communities to prevent further morbidity and mortality.

Trial Registration

ClinicalTrials.gov National Clinical Trials, NCT06087991. Registered 11 October 2023 – Retrospectively registered, https://clinicaltrials.gov/study/NCT06087991.
Modeling regional occupancy of fishes using acoustic telemetry: a model comparison framework applied to lake trout
Authors: Futia Matthew H. , Binder Thomas R. , Henderson Mark , Marsden J. Ellen
Published: September 2024

Acoustic telemetry is a common tool used in fisheries management to estimate fish space use (i.e., occupancy) from a local habitat scale to entire systems. Numerous analytical models have been developed to estimate different aspects of fish movement from telemetry datasets, yet evaluations of model performance and comparisons among models are limited. Here, we develop a framework to evaluate model estimates of regional occupancy in large and fragmented systems using an acoustic receiver array in Lake Champlain. We simulated the tracks of 100 acoustically tagged fish using a random walk function and created detection events based on receiver positions and distance-based detection probability. Regional occupancy for the simulated data was estimated by six movement models that ranged in analytical complexity, and results were compared to the true distributions for each simulated track to evaluate model error. The six movement models included: (1) a basic residency index using detections alone; (2) a residency index using last-observation-carried-forward; (3) a centers of activity model; (4) linear and non-linear interpolations (i.e., least-cost paths); and (5 and 6) two dynamic Brownian bridge movement models generated using separate packages in R. We developed a model selection process to compare model performance and select the optimal analysis based on simulation error. This process showed significant differences in model performance among the six movement models based on model error. Overall, the model generating least-cost paths using linear and non-linear interpolations consistently provided the most accurate regional occupancy estimates. Based on these simulation results, we applied this model to a case study that evaluated patterns in the regional distribution of stocked lake trout (Salvelinus namaycush) in Lake Champlain, which demonstrated distinct regional occupancy of two stocked lake trout groups. These results demonstrate potential for large variability in interpretation of acoustic telemetry data for describing regional fish distribution dependent on the analytical method used.
Evaluation of the drug-drug interactions management system for appropriate use of nirmatrelvir/ritonavir: a retrospective observational study
Authors: Tomida Takeshi , Kimura Takeshi , Yamamoto Kazuhiro , Uda Atsushi , Matsumoto Yuki , Tamura Naoki , Iida Masashi , Tanifuji Akiko , Matsumoto Kumiko , Mizuta Naomi , Ebisawa Kei , Ohji Goh , Omura Tomohiro , Iwata Kentaro , Yano Ikuko
Published: September 2024

Purpose

While nirmatrelvir/ritonavir (NMV-r) has been positioned as a first-line treatment for mild to moderate COVID-19, it has multiple and significant drug-drug interactions (DDIs). The use of NMV-r in Japan has been limited compared to the United States. This study aimed to describe the distribution of DDIs with NMV-r and their management in patients with COVID-19 under the control of a management system for the appropriate use of NMV-r.

Methods

A retrospective observational study was conducted at a Japanese university hospital. The management system included a flowchart for selecting antivirals and a list for reviewing DDI management, based on the National Institutes of Health guidelines and the guidance of the Japanese Society of Pharmaceutical Health Care and Sciences. Patients with mild to moderate COVID-19 and prescribed NMV-r or molnupiravir (MOV) were included. The primary outcome was DDI management practices, including the selected COVID-19 medications. The secondary outcome included the distribution of DDI classification and the 30-day all-cause mortality.

Results

This study included 241 patients (median age of 60 years, 112 [46.5%] females), of whom 126 and 115 received NMV-r and MOV, respectively. Of the 241 patients, 145 (60.2%) received concomitant medications that have DDIs with NMV-r. All 30 patients with severe renal impairment or insufficient details on concomitant medications received MOV. Forty-nine patients with concomitant medications required alternative COVID-19 therapy consideration due to DDIs, of whom 42 (85.7%) patients received MOV. Eighty-one patients had concomitant medications requiring temporary adjustment, of whom 44 (54.3%) patients received NMV-r, and 42 of these patients temporarily adjusted these concomitant medications. Five patients with concomitant medications that can continued by monitoring the effects/adverse effects, of whom 4 (80.0%) patients received NMV-r. Seventy-six patients without concomitant medications requiring DDI management, of whom 71 (93.4%) patients received NMV-r. The 30-day all-cause mortality for eligible patients was 0.9% [95% confidence interval, 0.1–3.1].

Conclusions

Most patients received appropriate antivirals according to the classification of DDIs, and most patients with concomitant medications requiring temporary adjustment received the recommended DDI management. Our management system is effective in promoting the use of NMV-r in the appropriate patients and managing problematic DDIs.
Emerging technological developments to address pest resistance in Bt cotton
Authors: Nagaraj Selvarani , Rajasekaran Ravikesavan , Palaniappan Jayamani , Rangasamy Selvakumar , Narayanasamy Chitra , Narayanan Manikanda Booapathi
Published: September 2024

Cotton plays a crucial role in shaping Indian economy and rural livelihoods. The cotton crop is prone to numerous insect pests, necessitating insecticidal application, which increases production costs. The advent of the expression of Bacillus thuringiensis (Bt) insecticidal protein in cotton has significantly reduced the burden of pest without compromising environmental or human health. After the introduction of transgenic cotton, the cultivated area expanded to 22 million hectares, with a 64% increase in adoption by farmers worldwide. Currently, Bt cotton accounts for 93% of the cultivated cotton area in India. However, extensive use of Bt cotton has accelerated resistance development in pests like the pink bollworm. Furthermore, the overreliance on Bt cotton has reduced the use of broad-spectrum pesticides, favouring the emergence of secondary pests with significant challenges. This emphasizes the urgent necessity for developing novel pest management strategies. The high-dose and refuge strategy was initially effective for managing pest resistance in Bt cotton, but its implementation in India faced challenges due to misunderstandings about the use of non-Bt refuge crops. Although gene pyramiding was introduced as a solution, combining mono toxin also led to instances of cross-resistance. Therefore, there is a need for further exploration of biotechnological approaches to manage insect resistance in Bt cotton. Advanced biotechnological strategies, such as sterile insect release, RNA interference (RNAi)-mediated gene silencing, stacking Bt with RNAi, and genome editing using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR-Cas), offer promising tools for identifying and managing resistance genes in insects. Additionally, CRISPR-mediated gene drives and the development of novel biopesticides present potential avenues for effective pest management in cotton cultivation. These innovative approaches could significantly enhance the sustainability and efficacy of pest resistance management in Bt cotton.
Unlocking the Nile Delta subsurface via advanced processing and imaging
Authors: Davies Daniel , Brown Peter , Agnisola Piero , Valler Victoria , Romanenko Matvey , Fruehn Juergen , Raffle James , Nicholson Matthew , Pan Sophie
Published: September 2024

The subsurface of the Nile Delta is infamous for challenges that are caused by a variety of geologic features that need to be resolved to unlock the full potential of the basin. The primary cause for many of the issues is the Messinian interval. This is a well-studied regional salt body with significant variation in composition, ranging from mobile shales to sand bodies over contaminated salt to anhydrite. The layer locally shows a hard top and base, which sets up mode conversions and complex multiples. The Messinian is also highly variable in terms of its geometry, thickness, faulting, and rugosity, which results in significant scattering of the seismic wavefield. The problem is further complicated by the presence of mud volcanoes that are scattered throughout the basin. Some of the mud volcanoes are currently active, and others are buried beneath more recent deposits. Free gas is often associated with these structures, and a high degree of lateral and vertical rock property variation is present, leading to complexities in seismic velocity and attenuation. The water depth varies considerably within the basin. Some producing assets exist that straddle the coastline, while others are located in water depths in excess of 1000 m. The transition is not simple due to erosional features on the seabed, leading to complex free-surface multiples. While many discoveries and developments have already been made in the post-Messinian, prospectivity in the basin is now located in the pre-Messinian, with targets ranging in depth from 2 to 10 km. When all of these features are combined, it results in a truly complex geophysical challenge.
Geophysics Bright Spots
Authors: Behura Jyoti
Published: September 2024

Geophysics Bright Spots reviews a number of interesting research articles from recent issues of the journal Geophysics.
Pinning synchronization of a complex network: Nodes, edges and higher-order edges
Authors: Jiang QiShu , Zhou Jin , Li Bo , Liu HaoRan , Lu Jun-an
Published: September 2024

In recent years, the interdisciplinary study of complex networks has become increasingly important in fields ranging from biology and physics to sociology and mathematics. This paper focuses on pinning control, an approach essential for achieving coordinated behavior in dynamic networks. We explore recent advancements in pinning control strategies, explaining theoretical frameworks and simulation techniques. Additionally, we discuss the significance of certain structures within networks across different orders. Finally, we conclude with a summary of key insights and propose our outlook on future research.