bluuebunny/crossref_metadata_2025 huggingface dataset:
Blinded by the Light: A critique on the universality, normativity, and hegemony of paradox theory and research
Authors: Seidemann Iris
Published: October 2024

This paper intervenes in paradox theory and research by problematizing the taken-for-granted premises that currently dominate the field. Building on the “growing pains” of paradox theory, the paper offers three provocations for current paradox theory and research: it questions the conceptual universality of paradox, reveals the implicit normativity of some of its key assumptions, and problematizes the hegemony of the conception of both/and as core to responses to paradox. Deliberately stepping beyond the established guardrails of paradox theory, the paper critically assesses these premises and reflects on their potential risks and blind spots. Building on these three provocations, the paper offers in turn a set of distinct pathways for theoretical development, including interpreting presupposed features of paradox in light of ontological positions, integrating normative approaches into paradox management, and introducing much greater granularity to the study of paradox responses.
Innovative strategy for controlling resonant frequencies of syntactic polymer foams regulating by hollow microspheres
Authors: Li Rui , Xu Yang , Wu Zhoubin , Ma Ning , Ouyang Xiao
Published: October 2024

This study aims to precisely control the resonant frequency of synthetic composite foam materials with fixed dimensions. By incorporating rigid hollow glass microspheres XLD3000(XLD) and flexible hollow polymer microspheres MFL-81GCA(MFL) into the base resin (EP), we prepared synthetic composite foams containing different volume fractions of hollow microspheres (EP-XLD and EP-MFL). We conducted tests and analyses on the density, mechanical properties, resonant frequency, and microstructure of the EP-XLD and EP-MFL systems. Results indicate that as the volume fraction of hollow microspheres increases, the flexural specific modulus of the EP-XLD and EP-MFL systems, respectively, exhibits a linear increase and decrease, and the resonant frequency shifts linearly towards higher and lower frequencies. This trend aligns with theoretical predictions, affirming that the material’s resonant frequency is closely related to its flexural modulus. This research not only deepens the understanding of the control mechanisms for the resonant frequency of synthetic composite foams but also proposes an innovative material design strategy with broad application potential, particularly in the fields of acoustics, damping, and structural materials, where it promises to significantly enhance material performance and meet specific engineering needs.
Technical and economic assessment of hybrid PVT solar systems compared to independent solar thermal and photovoltaic collectors in high-temperature zones: A case study in Mexicali, Mexico
Authors: Aguilar-Jiménez J. A. , Velázquez-Limón N. , Islas-Pereda S. , Ríos-Arriola J. , Suástegui-Macias J. A. , Cásares-De la Torre C. A. , Gómez-Hernández J. A.
Published: October 2024

This study analyzes the technical and economic feasibility of hybrid photovoltaic/thermal (PVT) solar energy systems, comparing them with independent flat plate solar thermal collectors (FP) and photovoltaic (PV) modules. Using TRNSYS software, different configurations were simulated under the climatic conditions of Mexicali, Baja California, Mexico. The results indicate that, although independent FP and PV systems exhibit better energy performance in terms of energy production and solar fraction, PVT collectors offer higher specific global energy production (electrical + thermal). However, the economic feasibility of PVT systems is limited due to high investment and maintenance costs, coupled with the low cost of thermal and electrical energy in the study region. Independent FP and PV collectors also face similar economic challenges, with return on investment extending beyond the 20-year lifespan of the project. Additionally, the low thermal energy demand for domestic hot water in the studied region negatively impacts the efficient utilization of these systems. This analysis suggests that in contexts where available installation space is limited, PVT systems can be an efficient solution. However, in scenarios with sufficient space and high energy costs, energy generation with separate equipment remains more viable. Moreover, climatic conditions and DHW demand affect the efficiency of the systems. The discrepancy between solar energy generation and hourly DHW demand necessitates the implementation of TEST, which significantly increases costs and impacts the economic viability of the project.
Making a Case for Whole Person Health
Authors: Herman Patricia M. , Pitcher Mark H. , Langevin Helene M.
Published: October 2024

Background: Our conventional approach to health care tends to separate patients’ health by body system, treating each independently and “efficiently”—e.g., minimal time with a provider, reliance on medications, and little investment to support behavioral and lifestyle improvements. Meanwhile, the United States has the most expensive health care in the world, with some of the worse outcomes. Purpose In this paper, we make the case for transforming health care from a disease-centric approach to a “whole person” model.

Research Design: We provide detailed health and health care utilization assumptions for a hypothetical patient, Mrs. M, over her life from age 40 to 80 years under 2 care scenarios: the continuation of conventional care (Version A) and a whole person care approach (Version B). Analysis We developed a set of health care utilization assumptions for each scenario, applied 2023 U.S. dollar (USD) resource prices, and estimated cumulative total health care costs. The price and the health care utilization assumptions for the conventional care scenario were validated using Medical Expenditures Panel Survey (MEPS) data.

Results: At age 80, with conventional care, we find Mrs. M increasingly frail and living in a skilled nursing facility, with total cumulative health care costs of $353,155. With whole person care, we find her active and generally healthy at age 80, with total cumulative health care costs of $52,425.

Conclusions: Although based on an “imagined” case, the 2 versions of Mrs. M’s history illustrate how an investment beginning in early middle age to support a healthy diet, physical activity, and stress management can plausibly lead to improved health and well-being, as well as reduced health care spending.
Life without free will: Does it preclude possibilities?
Authors: Sapolsky Robert
Published: October 2024

In this partial precis of my recent book ( Determined: A Science of Life Without Free Will, 2023), I argue against the existence of free will, based on the clarity with which we are nothing more than the sum of the densely intertwined biology, over which we had no control, and its interactions with the environment over which we also had no control. Despite this, the vast majority people, including philosophers and psychologists, believe that free will is compatible with our materialist world. I suggest that this arises from, (a) the intense intuitive feeling of agency experienced when we form an intent and act upon it; (b) the examples of people who effortfully rise above their circumstances (or, conversely, who squander their opportunities) are so powerful and compelling that we decide that tenacity and willpower are not made of biology; (c) misinterpretation of the recent revolutions of chaoticism, emergent complexity, and quantum indeterminacy; and (d) difficulty in reconciling that the future is both deterministic and unpredictable. Finally, I suggest that a rejection of free will, rather than leading to an array of societal and existential ills, would be profoundly liberating.
Genetic predisposition and pathogenetic mechanisms of interstitial lung diseases of unknown origin
Authors: Verleden G.M. , du Bois R.M. , Bouros D. , Drent M. , Millar A. , Müller-Quernheim J. , Semenzato G. , Johnson S. , Sourvinos G. , Olivieri D. , Pietinalho A. , Xaubet A.
Published: October 2024

Understanding of the cellular and cytokine interactions associated with inflammation and fibrosis in interstitial lung diseases (ILDs) has increased substantially during the past few years. Presently, many agents are known to have the ability to induce ILDs, although only a small percentage of exposed individuals will develop the disease. In addition, the majority of ILDs are of unknown origin and many are labelled “idiopathic”. Therefore, host susceptibility, genetic factors and, possibly, environmental cofactors may be important for the clinical expression of ILDs.

The present review reports evidence of the genetic predisposition to develop ILDs of unknown origin, more specifically sarcoidosis, idiopathic pulmonary fibrosis (IPF), lymphangioleio-myomatosis and ILDs, in systemic sclerosis. For instance, for sarcoidosis and IPF several histocompatibility antigens have been associated with the development and/or the clinical presentation of the disease. Furthermore, there are also several types of ILD that are associated with inherited disorders, of which the tuberous sclerosis complex is only one example. This clearly indicates that pulmonary fibrosis can be influenced by genetic factors. Familial occurrence of sarcoidosis and IPF is also well known, although the exact modes of inheritance are debatable.

Several studies have shown that extrinsic factors, such as single or multiple fibrosing agents, probably contribute to the development of clinical ILDs of unknown origin. It is probable that some of these studies deal with patients who do not have classical IPF, as recently defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) consensus. Therefore, the true role of these extrinsic factors in the development of IPF, or even sarcoidosis, remains speculative.

With the help of animal studies and, more specifically, by using knock-out mice, it may be possible in the near future to unravel at least some of the genes that are responsible for the increased susceptibility of the development of interstitial lung diseases.
Hypersensitivity pneumonitis: current concepts
Authors: Bourke S.J. , Dalphin J.C. , Boyd G. , McSharry C. , Baldwin C.I. , Calvert J.E.
Published: October 2024

Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, is due to a hypersensitivity reaction after repeated inhalation of finely dispersed antigens, mainly organic particles or low molecular weight chemicals. The essence of this disease is an interaction between the host's immune system and external antigen, influenced by both genetic and environmental factors. In susceptible subjects, it leads to a combined type III allergic reaction of Gell and Coombs (with formation of precipitines) and a type IV lymphocytic reaction (with a granulomatous inflammation in the distal bronchioles and alveoli).

This review gives an update on epidemiology, antigens, pathogenesis, host susceptibility, environmental factors, clinical features, diagnosis and treatment in HP. The list of aetiological agents is long and new sources of antigens are constantly being identified. Host risk factors are poorly characterized, with the exception of those linked to exposure factors. Environmental factors and cofactors may be critical for the pathogenesis of the disease.

HP is not a uniform disease entity, but a complex dynamic clinical syndrome such that different patterns of disease emerge over time. The diagnosis is made from a combination of clinical features, radiographic abnormalities, lung function tests and immunological tests. The use of inhalation challenge tests for the diagnosis has been hampered by the lack of standardization.

Antigen avoidance is the key element in the treatment. There is often an apparent beneficial response to corticosteroids, but it may be difficult to distinguish between the effects of treatment, the natural course of the disease and the effect of antigen avoidance.
Genotype and phenotype in susceptibility to coal workers' pneumoconiosis. The use of cytokines in perspective
Authors: Borm P.J.A. , Schins R.P.F.
Published: October 2024

The readily available technique of screening for gene polymorphisms could be used to explain inter-individual variability in a classic occupational interstitial lung disease, such as coal workers' pneumoconiosis (CWP).

The objective of this paper is to describe candidate genes selected from the wide pool of cytokines and growth factors, and to discuss the applications and pitfalls when using them as biomarkers for susceptibility to CWP. The selection of candidate genes is mainly based on observed phenotypic changes in bronchoalveolar lavage (BAL) fluid or BAL cells of patients with CWP, or on animal experiments that use quartz as the fibrogenic agent.

This paper also reviews the studies that have been performed to validate tumour necrosis factor genotype and phenotype with respect to CWP.

Finally, it is proposed that a multiple marker approach to susceptibility to CWP should be used. This involves the measurement of two cytokines (tumour necrosis factor and transforming growth factor‐β) to improve denomination of high- and low-risk groups.
New perspectives on YTHDF2 O-GlcNAc modification in the pathogenesis of intervertebral disc degeneration
Authors: Lu Liangjie , Wang Lijun , Yang Minjie , Wang Huihan
Published: October 2024

This study investigates the potential molecular mechanisms by which O-GlcNAc modification of YTHDF2 regulates the cell cycle and participates in intervertebral disc degeneration (IDD). We employed transcriptome sequencing to identify genes involved in IDD and utilized bioinformatics analysis to predict key disease-related genes. In vitro mechanistic validation was performed using mouse nucleus pulposus (NP) cells. Changes in reactive oxygen species (ROS) and cell cycle were assessed through flow cytometry and CCK-8 assays. An IDD mouse model was also established for in vivo mechanistic validation, with changes in IDD severity measured using X-rays and immunohistochemical staining. Bioinformatics analysis revealed differential expression of YTHDF2 in NP cells of normal and IDD mice, suggesting its potential as a diagnostic gene for IDD. In vitro cell experiments demonstrated that YTHDF2 expression and O-GlcNAcylation were reduced in NP cells under H2O2 induction, leading to inhibition of the cell cycle through decreased stability of CCNE1 mRNA. Further, in vivo animal experiments confirmed a decrease in YTHDF2 expression and O-GlcNAcylation in IDD mice, while overexpression or increased O-GlcNAcylation of YTHDF2 promoted CCNE1 protein expression, thereby alleviating IDD pathology. YTHDF2 inhibits its degradation through O-GlcNAc modification, promoting the stability of CCNE1 mRNA and the cell cycle to prevent IDD formation.
Insomnia as a predictor of treatment outcomes in adolescents receiving concentrated exposure treatment for OCD
Authors: Skjold Solvei Harila , Hagen Kristen , Wheaton Michael G. , Kallestad Håvard , Hjelle Kay Morten , Björgvinsson Thröstur , Hansen Bjarne
Published: October 2024

Background

Research suggests that individuals with obsessive-compulsive disorder (OCD) frequently experience insomnia. Some previous studies have suggested that insomnia may predict treatment outcomes, but the evidence is limited, especially for adolescents. This study examined the prevalence of insomnia in an adolescent OCD patient sample, explored the correlation between OCD and insomnia, and tested whether levels of insomnia at baseline predict outcomes for adolescent patients receiving the Bergen 4-Day Treatment (B4DT) for OCD.

Methods

Forty-three adolescent OCD patients who received B4DT were selected for this study. Treatment outcome was quantified as change in Children Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores across time from pre- to posttreatment and 3-month follow-up. Insomnia symptoms were measured by the Bergen Insomnia Scale (BIS). Linear mixed models were used to examine the relationship between the BIS and changes in CY-BOCS scores. We controlled for symptoms of general anxiety disorder measured by the GAD-7 and depression symptoms measured by the PHQ-9.

Results

In this sample, 68.4% of the patients scored above the cutoff for insomnia on the BIS. There was a moderate correlation between baseline CY-BOCS and BIS that did not reach statistical significance (r = .32, p = .051). High BIS scores before treatment were significantly associated with poorer treatment outcomes, as measured by changes in CY-BOCS over time (p = .002). The association between baseline insomnia and change in OCD symptoms remained significant (p = .033) while controlling for GAD-7 and PHQ-9.

Conclusion

Insomnia is common among adolescents with OCD, and these data suggest that these patients may be at increased risk for poor treatment outcomes. Future research to explore mechanisms and adjunctive treatments is warranted.

Trial registration

The study was approved by the Regional Committee for Medical and Health Research Ethics of Northern Norway (REK Nord: 2023/606482).
The decriminalization of illicit drugs in British Columbia: a national evaluation protocol
Authors: Russell Cayley , Ali Farihah , Imtiaz Sameer , Butler Amanda , Greer Alissa , Rehm Jürgen ,   the Decriminalization Evaluation Research Group, Bardwell Geoff , Bonn Matthew , Boyd Jade , Bruneau Julie , Costello Jean , Crichlow Frank , Crépault Jean-François , Degenhardt Louisa , Elton-Marshall Tara , Ferencz Sarah , Gomes Tara , Goulão João Castel-Branco , Griffiths Paul N , Hickman Matthew , Hodgins David C. , Hodgson Kate , Hyshka Elaine , Le Foll Bernard , Linklater Rennie , Lock Kurt , Patenaude Sean , Mackinnon Laura M. , McLuckie Taija , Mitra Sanjana , Nurse Michael , Sedgemore Kali-olt , Shahin Rita , Smith Wayne M. , Stewart Sherry H. , Werb Dan , Xavier Jessica C.
Published: October 2024

Background

On January 31st, 2023, the province of British Columbia (BC), Canada, was granted a federal exemption allowing adults (aged 18 +) to possess up to 2.5 g of select illicit drugs. The exemption will be in place for three years (2023–2026), marking the first formal decriminalization of illicit drug policy reform in Canada. BC’s decriminalization initiative is premised on several goals. This project seeks to evaluate each of these goals and their individual and combined contributions to determine the overall success of this policy.

Methods

The following protocol paper provides a detailed outline of a five-year (2022-2027) national evaluation of BC’s decriminalization initiative, as well as the specific objectives, methodologies, and planned analyses for eight interrelated sub-studies that comprise the evaluation. These sub-studies fall under the following five topical areas of research: 1) people who use drugs (PWUD), 2) the police and the criminal justice system, 3) the general public, 4) the health services system, and 5) an economic analysis. Additional research activities may also be explored.

Results

The overall evaluation and specific sub-study designs were informed by intensive stakeholder engagement. The evaluation was developed in collaboration with an international expert committee who came together to undertake a nominal group technique to decide on the final evaluation design and corresponding logic model. The evaluation will also employ an advisory board and individual sub-study working groups comprised of experts and PWUD who will oversee the development and implementation of the overall evaluation as well as each sub-study.

Discussion

This evaluation will draw on implementation science research practices to evaluate and understand the full impacts of this novel drug policy experiment. Results will be widely disseminated through manuscripts, reports, presentations, and infographics, which will be adapted and tailored for specific audiences. The protocol identifies several anticipated challenges and limitations. This evaluation’s evidence-based findings will be poised to offer pivotal insights that can shape and refine the discourse on drug policy and will serve as a critical resource for understanding the multifaceted impacts of decriminalization.
General hospital patients’ attitude towards systematic health risk behavior screening and intervention
Authors: Timm Caroline , Krolo-Wicovsky Filipa , Tiede Anika , Spielmann Marie , Gaertner Beate , John Ulrich , Freyer-Adam Jennis
Published: October 2024

Background

Systematic counseling on behavioral health risk factors (HRFs) may be suitable to promote health among general hospital patients. This study aimed to investigate the openness of patients towards systematic screening and intervention of HRFs, its relation to actual participation in a multi-behavioral intervention, and whether socio-economic characteristics, HRFs and health indicators are related to approval.

Methods

All 18- to 64-year-old patients hospitalized in five medical departments at the University Medicine Hospital Greifswald in Germany were asked between May and July 2022 to participate in a survey and in a subsequent pre-post intervention study. Among all eligible patients, 225 (78.9%) participated in the survey. Patients’ approval of systematic screening and intervention of HRFs was assessed using five statements with a total sum score of 0–20 (i.e., scores of 0–6, 7–13, 14–20 referring to low, medium and high approval). Associations with intervention participation, socio-economic, behavioral and health-related patient characteristics were analyzed using logistic and multivariable linear regression analyses.

Results

The mean total approval of screening and intervention was 13.8 (SD = 4.8). Of the 125/ 73/ 16 patients with high/ medium/ low approval, 88.0%/ 78.1%/ 50.0% participated in the subsequent intervention, respectively. Approval was independent of socio-demographic and -economic characteristics and self-rated general health. Current tobacco smoking was the only HRF negatively (p = 0.02) and diabetes mellitus was the only disease positively (p = 0.01) associated with approval.

Conclusion

High approval of HRF screening, which was rather independent of socio-economic characteristics and worse self-rated general health, speaks in favor of proactively approaching and motivating all general hospital patients to participate in health behavior change intervention. Tobacco smokers might need higher efforts to motivate participation than non-smokers.

Trial registration

ClinicalTrials.gov Identifier NCT05365269 on May 9, 2022.
Aligning with the 3Rs: alternative models for research into muscle development and inherited myopathies
Authors: Mehmood Hashir , Kasher Paul R. , Barrett-Jolley Richard , Walmsley Gemma L.
Published: October 2024

Inherited and acquired muscle diseases are an important cause of morbidity and mortality in human medical and veterinary patients. Researchers use models to study skeletal muscle development and pathology, improve our understanding of disease pathogenesis and explore new treatment options. Experiments on laboratory animals, including murine and canine models, have led to huge advances in congenital myopathy and muscular dystrophy research that have translated into clinical treatment trials in human patients with these debilitating and often fatal conditions. Whilst animal experimentation has enabled many significant and impactful discoveries that otherwise may not have been possible, we have an ethical and moral, and in many countries also a legal, obligation to consider alternatives. This review discusses the models available as alternatives to mammals for muscle development, biology and disease research with a focus on inherited myopathies. Cell culture models can be used to replace animals for some applications: traditional monolayer cultures (for example, using the immortalised C2C12 cell line) are accessible, tractable and inexpensive but developmentally limited to immature myotube stages; more recently, developments in tissue engineering have led to three-dimensional cultures with improved differentiation capabilities. Advances in computer modelling and an improved understanding of pathogenetic mechanisms are likely to herald new models and opportunities for replacement. Where this is not possible, a 3Rs approach advocates partial replacement with the use of less sentient animals (including invertebrates (such as worms Caenorhabditis elegans and fruit flies Drosophila melanogaster) and embryonic stages of small vertebrates such as the zebrafish Danio rerio) alongside refinement of experimental design and improved research practices to reduce the numbers of animals used and the severity of their experience. An understanding of the advantages and disadvantages of potential models is essential for researchers to determine which can best facilitate answering a specific scientific question. Applying 3Rs principles to research not only improves animal welfare but generates high-quality, reproducible and reliable data with translational relevance to human and animal patients.
A gut check: understanding the interplay of the gastrointestinal microbiome and the developing immune system towards the goal of pediatric HIV remission
Authors: Soo Nicole , Farinre Omotayo , Chahroudi Ann , Boliar Saikat , Goswami Ria
Published: October 2024

Despite the efficacy of antiretroviral therapy (ART) in reducing the global incidence of vertical HIV transmissions, more than 120,000 children are still infected with the virus each year. Since ART cannot clear the HIV reservoir that is established soon after infection, children living with HIV (CLWH) are forced to rely on therapy for their lives and suffer from long-term drug-related complications. Pediatric HIV infection, like adult infection, is associated with gut microbial dysbiosis, loss of gut epithelial integrity, bacterial translocation, CD4 + T cell depletion, systemic immune activation, and viral reservoir establishment. However, unlike in adults, HIV that is vertically acquired by infants interacts with a gut microbiome that is continuously evolving while concomitantly shaping the infant’s immune ontogeny. Therefore, to determine whether there may be interventions that target the HIV reservoir through microbiome-directed approaches, understanding the complex tripartite interactions between the transmitted HIV, the maturing gut microbiome, and the developing immune system during early life is crucial. Importantly, early life is the time when the gut microbiome of an individual is highly dynamic, and this temporal development of the gut microbiome plays a crucial role in educating the maturing immune system of a child. Therefore, manipulation of the gut microbiome of CLWH to a phenotype that can reduce HIV persistence by fostering an antiviral immune system might be an opportune strategy to achieve ART-free viral suppression in CLWH. This review summarizes the current state of knowledge on the vertical transmission of HIV, the developing gut microbiome of CLWH, and the immune landscape of pediatric elite controllers, and explores the prospect of employing microbial modulation as a potential therapeutic approach to achieve ART-free viral suppression in the pediatric population.
A study on the digital restoration of an ancient city based on historic building information modeling of wooden architectural heritage: focusing on Suwon Hwaseong
Authors: Kim Sunghyun , Lee JiHyung
Published: October 2024

This study describes the process of digitally reconstructing the ancient Korean city of Suwon Hwaseong in 3D utilizing Historic Building Information Modeling (HBIM) resources to accurately represent its wooden architectural heritage. Previous 3D reconstructions of cultural heritage have often prioritized appearance or remained partially disassembled. However, our reconstruction method offers a comprehensive representation of the appearance and the internal structure of wooden architectural heritage, which can be suitable for restoration maintenance. To ensure accuracy in digital restoration, we collected and utilized administrative records and historical materials, including the geography, fortress walls, folk houses, and Haenggung (the temporary palace of the Joseon Dynasty)—drawing from the archive of the Korean Cultural Heritage Service’s management records and the 1796 manuscript “Uigwe: Royal Protocols of the Hwaseong Fortress” which documents the construction of the ancient city of Suwon Hwaseong. Extensive architectural records were used to generate HBIM data, which digitized historical records, documents, and drawings to accurately represent the complex layout of the wooden architectural heritage. For the folk houses that lacked design records and the fortress walls that retained their original shape, we performed a digital restoration-based façade modeling. These elements of the ancient city of Suwon Hwaseong were assembled into a 3D model using Unreal Engine (version 5.1.1) to digitally reconstruct the city and enhance its visual representation. The digital restoration content, which utilizes visual effects and precise rendering from a game engine, can be used for the restoration, repair, and maintenance of both appearance and internal structures.
Presence of Plasmodium falciparum strains with artemisinin-resistant K13 mutation C469Y in Busia County, Western Kenya
Authors: Makau Mark , Kanoi Bernard N. , Mgawe Calvin , Maina Michael , Bitshi Mimie , Too Edwin K. , Naruse Taeko K. , Abkallo Hussein M. , Waweru Harrison , Adung’o Ferdinand , Kaneko Osamu , Gitaka Jesse
Published: October 2024

Malaria remains a key health and economic problem, particularly in sub-Saharan Africa. The emergence of artemisinin drug resistance (ART-R) parasite strains poses a serious threat to the control and elimination of this scourge. This is because artemisinin-based combination therapies (ACTs) remain the first-line treatment in the majority of malaria-endemic regions in Sub-Saharan Africa. Certain single-nucleotide polymorphisms in the propeller domains of Plasmodium falciparum Kelch 13 protein (K13) have been associated with delayed parasite clearance in vivo and in vitro. These mutations serve as vital molecular markers for tracking the emergence and dispersion of resistance. Recently, there have been increasing reports of the emergence and spread of P. falciparum ART-R parasites in the Eastern Africa region. This necessitates continued surveillance to best inform mitigation efforts. This study investigated the presence of all reported mutations of K13 propeller domains in the parasite population in Busia County, Kenya, a known malaria-endemic region. Two hundred twenty-six participants with microscopically confirmed uncomplicated malaria were recruited for this study. They were treated with artemether–lumefantrine under observation for the first dose, and microscopic examination was repeated 1 day later after ensuring the participants had taken the second and third doses. P. falciparum DNA from all samples underwent targeted amplification of the K13 gene using a semi-nested PCR approach, followed by Sanger sequencing. The recently validated ART-R K13 mutation C469Y was identified in three samples. These three samples were among 63 samples with a low reduction in parasitemia on day 1, suggesting day 1 parasitemia reduction rate is a useful parameter to enrich the ART-R parasites for further analysis. Our findings highlight the need for continuous surveillance of ART-R in western Kenya and the region to determine the spread of ART-R and inform containment.
Design and development of a machine-learning-driven opioid overdose risk prediction tool integrated in electronic health records in primary care settings
Authors: Nguyen Khoa , Wilson Debbie L. , Diiulio Julie , Hall Bradley , Militello Laura , Gellad Walid F. , Harle Christopher A. , Lewis Motomori , Schmidt Siegfried , Rosenberg Eric I. , Nelson Danielle , He Xing , Wu Yonghui , Bian Jiang , Staras Stephanie A. S. , Gordon Adam J. , Cochran Jerry , Kuza Courtney , Yang Seonkyeong , Lo-Ciganic Weihsuan
Published: October 2024

Background

Integrating advanced machine-learning (ML) algorithms into clinical practice is challenging and requires interdisciplinary collaboration to develop transparent, interpretable, and ethically sound clinical decision support (CDS) tools. We aimed to design a ML-driven CDS tool to predict opioid overdose risk and gather feedback for its integration into the University of Florida Health (UFHealth) electronic health record (EHR) system.

Methods

We used user-centered design methods to integrate the ML algorithm into the EHR system. The backend and UI design sub-teams collaborated closely, both informed by user feedback sessions. We conducted seven user feedback sessions with five UF Health primary care physicians (PCPs) to explore aspects of CDS tools, including workflow, risk display, and risk mitigation strategies. After customizing the tool based on PCPs’ feedback, we held two rounds of one-on-one usability testing sessions with 8 additional PCPs to gather feedback on prototype alerts. These sessions informed iterative UI design and backend processes, including alert frequency and reappearance circumstances.

Results

The backend process development identified needs and requirements from our team, information technology, UFHealth, and PCPs. Thirteen PCPs (male = 62%, White = 85%) participated across 7 user feedback sessions and 8 usability testing sessions. During the user feedback sessions, PCPs (n = 5) identified flaws such as the term “high risk” of overdose potentially leading to unintended consequences (e.g., immediate addiction services referrals), offered suggestions, and expressed trust in the tool. In the first usability testing session, PCPs (n = 4) emphasized the need for natural risk presentation (e.g., 1 in 200) and suggested displaying the alert multiple times yearly for at-risk patients. Another 4 PCPs in the second usability testing session valued the UFHealth-specific alert for managing new or unfamiliar patients, expressed concerns about PCPs’ workload when prescribing to high-risk patients, and recommended incorporating the details page into training sessions to enhance usability.

Conclusions

The final backend process for our CDS alert aligns with PCP needs and UFHealth standards. Integrating feedback from PCPs in the early development phase of our ML-driven CDS tool helped identify barriers and facilitators in the CDS integration process. This collaborative approach yielded a refined prototype aimed at minimizing unintended consequences and enhancing usability.
Atezolizumab Plus Chemotherapy With or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial
Authors: Macarulla Teresa , Ren Zhenggang , Chon Hong Jae , Park Joon Oh , Kim Jin Won , Pressiani Tiziana , Li Daneng , Zhukova Lyudmila , Zhu Andrew X. , Chen Ming-Huang , Hack Stephen P. , Wu Stephanie , Liu Bo , Guan Xiangnan , Lu Shan , Wang Yulei , El-Khoueiry Anthony B.
Published: October 2024

PURPOSE

Biliary tract cancers (BTCs) harbor an immunosuppressed tumor microenvironment and respond poorly to PD-1/PD-L1 inhibitors. Bevacizumab (anti–vascular endothelial growth factor) plus chemotherapy can promote anticancer immunity, augmenting response to PD-L1 inhibition.

PATIENTS AND METHODS

This randomized, double-blind, proof-of-concept phase II study enrolled patients (n = 162) with previously untreated advanced BTC (IMbrave151; ClinicalTrials.gov identifier:
NCT04677504
). Patients were randomly assigned 1:1 to receive cycles of atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) or atezolizumab plus placebo once every 3 weeks until disease progression or unacceptable toxicity. All patients received cisplatin (25 mg/m
2
) plus gemcitabine (1,000 mg/m
2
; cisplatin plus gemcitabine [CisGem]) on days 1 and 8 once every 3 weeks for up to eight cycles. Stratification of patients was by disease status, geographic region, and primary tumor location. The primary end point was progression-free survival (PFS). No formal hypothesis testing was performed. Exploratory correlative biomarker analysis was undertaken using transcriptome analysis (n = 95) and mutation profiling (n = 102) on baseline tumor samples.

RESULTS

Between February and September 2021, 162 patients were enrolled. Median PFS was 8.3 months in the bevacizumab arm and 7.9 months in the placebo arm (stratified hazard ratio [HR], 0.67 [95% CI, 0.46 to 0.95]). Median overall survival (OS) was 14.9 and 14.6 months in the bevacizumab and placebo arms, respectively (stratified HR, 0.97 [95% CI, 0.64 to 1.47]). The incidence of grade 3 or 4 adverse events was 74% in both arms. High
VEGFA
gene expression was associated with improved PFS (HR, 0.44 [95% CI, 0.23 to 0.83]) in the bevacizumab arm versus placebo.

CONCLUSION

In unselected patients with advanced BTC, adding bevacizumab to atezolizumab plus CisGem modestly improves PFS but not OS. High
VEGFA
gene expression may represent a predictive biomarker of benefit from atezolizumab/bevacizumab, warranting further investigation.
From Mimeographs to Self-organization
Authors: Li Promise
Published: October 2024

This essay unpacks how Beijing-based workers’ handbills and posters during the 1989 democracy movement functioned as a counterinstitution that enabled everyday workers to translate economic demands into political self-organization through groups like the Workers’ Autonomous Federation. In contrast to liberal dissident writing at the time by the likes of Fang Lizhi and Liu Xiaobo, workers’ organizing strategies and political vision have seldom been analyzed. The author argues that these writings represent an important effort to create an inchoate civil society under authoritarian conditions, while going beyond these conditions by empowering workers to ground a broader struggle for democracy in reorganizing the control of society and productive industries through independent politics.
“Ka Aina No Ka Poe o Hawaii”
Authors: Katzeman Aaron , Broderick Drew Kahuʻāina
Published: October 2024

This article examines the independent newspaper Huli, published at the birth of the modern Hawaiian sovereignty movement from 1971 to 1973 by the grassroots political organization Kokua Hawaii. Reading through the surviving issues of Huli available in institutional archives, the article considers the variety of perspectives promoted within its pages to position Kokua Hawaii in relation to international understandings of anticolonial liberatory politics of the Global South. Revisiting prominent critiques of Kokua Hawaii, it argues that insights provided by Huli trouble lasting understandings of the organization and underscore the periodical’s relevance for navigating rising waves of political struggle in Hawaiʻi today. Moreover, the article contends that Huli—a timely revival of Hawaiʻi’s politically engaged print culture that flourished during the nineteenth century—offers one foundation for constructing a counterhegemonic lineage of socially concerned artists and cultural workers in Hawaiʻi. Through an analysis of Huli’s content, imagery, and context of production, the article uses the name of the periodical and its call to “huli” as a means of tracking the influence of Kokua Hawaii’s politics and aesthetics into the present, with Huli acting as a medium for insurgent inspiration.
The Periodical as Political Educator
Authors: Kazmi Sara
Published: October 2024

This essay discusses how forms like political magazines, cultural journals, and party newspapers produced by twentieth-century anticolonial, left, and oppositional movements instituted practices of alternative pedagogy and political education across the Global South. These “revolutionary papers” served as a pedagogical infrastructure encompassing a critical curriculum drawn from ongoing movements, alternative histories, and regional literary production, to be used for collective practices of debate and inquiry. The essay introduces a series of digital teaching tools featured in the issue that study revolutionary periodicals such as the Cairo-based Afro-Asian literary magazine Lotus and underground pamphlets from the Mau Mau movement in Kenya. These teaching tools are accessible, interactive resources that provide archival, literary, and historical insights on movements and associated print cultures and are designed as pedagogical aids for the classroom and for political education in community settings. Along the way, the essay reflects on anticolonial periodicals as a resource for ongoing debates around decolonizing the university, and the possibilities presented by digital humanities approaches for the study of anticolonialism and Global South cultures.
DRAK2 regulates myosin light chain phosphorylation in T cells
Authors: Wilander Benjamin A. , Harris Tarsha L. , Mandarano Alexandra H. , Guy Cliff S. , Prater Mollie S. , Pruett-Miller Shondra M. , Ogden Stacey K. , McGargill Maureen A.
Published: October 2024

Death-associated protein kinase-related apoptosis-inducing kinase-2 (DRAK2; also known as STK17B) is a serine/threonine kinase expressed in T cells. Drak2-deficient (Drak2−/−) mice respond effectively to tumors and pathogens while displaying resistance to T cell-mediated autoimmune disease. However, the molecular mechanisms by which DRAK2 impacts T cell function remain unclear. Gaining further insight into the function of DRAK2 in T cells will shed light on differentially regulated pathways in autoreactive and pathogen-specific T cells, which is crucial for improving autoimmune therapies. Here, we demonstrate that DRAK2 contributes to activation of myosin light chain (MLC2, encoded by Myl2) in both murine and human T cells. In the absence of Drak2, the amount of polymerized actin was decreased, suggesting that DRAK2 modulates actomyosin dynamics. We further show that myosin-dependent T cell functions, such as migration, T cell receptor microcluster accumulation, and conjugation to antigen presenting cells are decreased in the absence of Drak2. These findings reveal that DRAK2 plays an important role in regulating MLC activation within T cells.
Center of mass mechanics during locomotion in the arboreal squirrel monkey (Saimiri sciureus) as a function of speed and substrate
Authors: Miller Charlotte E. , Granatosky Michael C. , Schmitt Daniel
Published: October 2024

It is thought that the magnitude of center of mass (COM) oscillations can affect stability and locomotor costs in arboreal animals. Previous studies have suggested that minimizing collisional losses and maximizing pendular energy exchange are effective mechanisms to reduce muscular input and energy expenditure during terrestrial locomotion. However, few studies have explored whether these mechanisms are used in an arboreal context, where stability and efficiency often act as trade-offs. This study explores three-dimensional COM mechanics in an arboreal primate – the squirrel monkey (Saimiri sciureus) – moving quadrupedally at various speeds on instrumented arboreal and terrestrial supports. Using kinetic data, values of energy recovery, COM mechanical work and power, potential and kinetic energy congruity, and collision angle and fraction were calculated for each stride. Saimiri sciureus differed from many other mammals by having lower energy recovery. Although few differences were observed in COM mechanics between substrates at low or moderate speeds, as speed increased, COM work was done at a much greater range of rates on the pole. Collision angles were higher, whereas collision fractions and energy recovery values were lower on the pole, indicating less moderation of collisional losses during arboreal versus terrestrial locomotion. These data support the idea that the energetic demands of arboreal and terrestrial locomotion differ, suggesting that arboreal primates likely employ different locomotor strategies compared with their terrestrial counterparts – an important factor in the evolution of arboreal locomotion.
Glucocorticoid and glycemic responses to immune challenge in a viviparous snake afflicted with an emerging mycosis
Authors: Lind Craig M. , Agugliaro Joseph , Ortega Jason , Palmisano Jenna N. , Lorch Jeffrey M. , Truong Tran B. , Farrell Terence M.
Published: October 2024

Disease may be both a cause and a consequence of stress, and physiological responses to infectious disease may involve stress coping mechanisms that have important fitness consequences. For example, glucocorticoid and glycemic responses may affect host fitness by altering resource allocation and use in hosts, and these responses may be affected by competing stressors. To better understand the factors that affect host responses to infection, we challenged the immune system of field-acclimatized pygmy rattlesnakes, Sistrurus miliarius, with a sterile antigen, lipopolysaccharide (LPS), and measured the glucocorticoid and glycemic response in healthy non-reproductive snakes, snakes afflicted with an emerging mycosis (ophidiomycosis) and pregnant snakes. We hypothesized that LPS challenge would result in a glucocorticoid and glycemic response typical of the vertebrate acute phase response (APR), and therefore predicted that LPS challenge would result in an acute increase in plasma corticosterone (CORT) and a decline in plasma glucose in all individuals. Additionally, we hypothesized that the APR would be attenuated in individuals simultaneously coping with additional challenges to homeostasis (i.e. disease or reproduction). As predicted, the immune challenge elicited an acute increase in plasma CORT and a decrease in plasma glucose. Snakes coping with ophidiomycosis and pregnant snakes were able to mount a robust glucocorticoid and hypoglycemic response to LPS challenge, which was contrary to our hypothesis. Our findings clarify directions of causality linking infection, glucocorticoids and glucose, and emphasize the importance of future research examining the fitness consequences of interactions between stress and disease in wildlife threatened by emerging pathogens.
Patients’ & students’ perspectives on bedside teaching: A descriptive study
Authors: Malik Farhat Rehana , Khan Farzeen
Published: October 2024

Objective: To assess the student’s and patients’ perspectives about bedside teaching and to identify possible barriers that delay effective bedside teaching.
Methods: This cross-sectional study was conducted at two teaching hospitals in Peshawar with 153 participants through non-probability serial sampling from December 2017 to March 2018. Interview-based validated questionnaires were used and pilot tested as well. Ethical approval was taken with the participant’s consent. Data were analyzed using SPSS version 19.0 using descriptive statistics.
Results: Among the total 79 students, all of them completed the questionnaires with a 100% response rate. However, from the 76 patients only 74 responded with a response rate of 97%. The majority of the patients (n=58; 78%) were satisfied with bedside teaching with no problems faced. During the bedside teaching only (n= 13; 18.2%) felt anxious while others, enjoyed (n= 59; 80.5%) with satisfaction and only 13% (n= 10) thought their privacy was breached. The satisfied students with the time spent on bedside teaching were (n= 52; 65.5%) while (n= 30; 38.7%) thought thirty minutes time was not enough. The hurdles faced were lack of practice (37.3%), fear of embarrassment in front of peers (21.3%), and lack of confidence to approach the patient (16%).
Conclusion: The patients showed positive attitude and enjoyed bedside teaching. The students preferred it as a valuable tool for clinical experience. However, time constraints, lack of practice, lack of confidence, confidentiality, and anxiety must be overcome to make bedside teaching a useful method. Effective teaching still requires good teaching methodologies with confidence and competency.
doi: https://doi.org/10.12669/pjms.40.10.8743
How to cite this: Malik FR, Khan F. Patients’ & students’ perspectives on bedside teaching: A descriptive study. Pak J Med Sci. 2024;40(10):2384-2389. doi: https://doi.org/10.12669/pjms.40.10.8743
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.