bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro blood sample assessment: investigating correlation of laboratory hemoglobin and spectral properties of dual-energy CT measurements (ρ/Z)
Authors: Schulz Bastian , Euler André , Schmid Hans-Ruedi , Kubik-Huch Rahel A. , Thali Michael , Niemann Tilo
Published: June 2024

Objectives

Our study comprised a single-center retrospective in vitro correlation between spectral properties, namely ρ/Z values, derived from scanning blood samples using dual-energy computed tomography (DECT) with the corresponding laboratory hemoglobin/hematocrit (Hb/Hct) levels and assessed the potential in anemia-detection.

Methods

DECT of 813 patient blood samples from 465 women and 348 men was conducted using a standardized scan protocol. Electron density relative to water (ρ or rho), effective atomic number (Zeff), and CT attenuation (Hounsfield unit) were measured.

Results

Positive correlation with the Hb/Hct was shown for ρ (r-values 0.37–0.49) and attenuation (r-values 0.59–0.83) while no correlation was observed for Zeff (r-values −0.04 to 0.08). Significant differences in attenuation and ρ values were detected for blood samples with and without anemia in both genders (p value < 0.001) with area under the curve ranging from 0.7 to 0.95. Depending on the respective CT parameters, various cutoff values for CT-based anemia detection could be determined.

Conclusion

In summary, our study investigated the correlation between DECT measurements and Hb/Hct levels, emphasizing novel aspects of ρ and Zeff values. Assuming that quantitative changes in the number of hemoglobin proteins might alter the mean Zeff values, the results of our study show that there is no measurable correlation on the atomic level using DECT. We established a positive in vitro correlation between Hb/Hct values and ρ. Nevertheless, attenuation emerged as the most strongly correlated parameter with identifiable cutoff values, highlighting its preference for CT-based anemia detection.

Clinical relevance statement

By scanning multiple blood samples with dual-energy CT scans and comparing the measurements with standard laboratory blood tests, we were able to underscore the potential of CT-based anemia detection and its advantages in clinical practice.

Key Points

Prior in vivo studies have found a correlation between aortic blood pool and measured hemoglobin and hematocrit.

Hemoglobin and hematocrit correlated with electron density relative to water and attenuation but not Zeff.

Dual-energy CT has the potential for additional clinical benefits, such as CT-based anemia detection.

Graphical Abstract
Introduction and reflections on the comparative physiology of sleep and circadian rhythms
Authors: Foster Russell G.
Published: June 2024

Circadian rhythms and the sleep/wake cycle allows us, and most life on Earth, to function optimally in a dynamic world, adjusting all aspects of biology to the varied and complex demands imposed by the 24-hour rotation of the Earth upon its axis. A key element in understanding these rhythms, and the success of the field in general, has been because researchers have adopted a comparative approach. Across all taxa, fundamental questions relating to the generation and regulation of sleep and circadian rhythms have been address using biochemical, molecular, cellular, system and computer modelling techniques. Furthermore, findings have been placed into an ecological and evolutionary context. By addressing both the “How” – mechanistic, and “Why” – evolutionary questions in parallel, the field has achieved remarkable successes, including how circadian rhythms are generated and regulated by light. Yet many key questions remain. In this special issue on the Comparative Physiology of Sleep and Circadian Rhythms, celebrating the 100th anniversary of the Journal of Comparative Physiology, important new discoveries are detailed. These findings illustrate the power of comparative physiology to address novel questions and demonstrate that sleep and circadian physiology are embedded within the biological framework of an organism.
Inflammatory diseases causing joint and bone destruction: rheumatoid arthritis and hemophilic arthropathy
Authors: Terashima Asuka , Ono Kumiko , Omata Yasunori , Tanaka Sakae , Saito Taku
Published: June 2024

Various diseases and conditions cause joint disorders. Osteoarthritis (OA) is characterized by the degeneration of articular cartilage, synovitis, and anabolic changes in surrounding bone tissues. In contrast, rheumatoid arthritis (RA) and hemophilic arthropathy (HA) display marked destruction of bone tissues caused by synovitis. RA is a representative autoimmune disease. The primary tissue of RA pathogenesis is the synovial membrane and involves various immune cells that produce catabolic cytokines and enzymes. Hemophilia is a genetic disorder caused by a deficiency in blood clotting factors. Recurrent intra-articular bleeding leads to chronic synovitis through excessive iron deposition and results in the destruction of affected joints. Although the triggers for these two joint diseases are completely different, many cytokines and enzymes are common in the pathogenesis of both RA and HA. This review focuses on the similarities between joint and bone destruction in RA and HA. The insights may be useful in developing better treatments for hemophilia patients with arthropathy and osteoporosis by leveraging advanced therapeutics for RA.
Report of the HIMSS-SIIM Enterprise Imaging Community Data Standards Evaluation Workgroup: Anatomic Ontology Assessment
Authors: Cram Dawn , Eid Monief , Goldburgh Mitchell M. , Nagels Jason , Yudkovitch Lawrence , Towbin Alexander J.
Published: June 2024

Previously, the lack of a standard body part ontology has been identified as a critical deficiency needed to enable enterprise imaging. This whitepaper aims to provide a comprehensive assessment of anatomical ontologies with the aim of facilitating enterprise imaging. It offers an overview of the process undertaken by the Health Information Management Systems Society (HIMSS) and Society for Imaging Informatics in medicine (SIIM) Enterprise Imaging Community Data Standards Evaluation workgroup to assess the viability of existing ontologies for supporting cross-disciplinary medical imaging workflows. The report analyzes the responses received from representatives of three significant ontologies: SNOMED CT, LOINC, and ICD, and delves into their suitability for the complex landscape of enterprise imaging. It highlights the strengths and limitations of each ontology, ultimately concluding that SNOMED CT is the most viable solution for standardizing anatomy terminology across the medical imaging community.
Genetics and genetic diagnosis of focal childhood epilepsy
Authors: Krey Ilona , Lemke Johannes R. , von Spiczak Sarah
Published: June 2024

Self-limiting focal epilepsies are among the most common forms of epilepsy in children. Based on family studies, a genetic basis is assumed for the epilepsy as well as the typical electroencephalographic (EEG) feature of centrotemporal spikes, although complex inheritance and possibly additional influencing factors must be considered. Variants in GRIN2A, encoding the GluN2A subunit of the N‑methyl-D-aspartate (NMDA) glutamate receptor, represent the most important genetic risk factor to date. With memantine for variants with a gain-of-function effect and L‑serine for loss-of-function variants, two personalized therapeutic approaches are potentially available. Their effectiveness and significance need to be clarified in further investigations and clinical trials.
Telehealth Models for PrEP Delivery: A Systematic Review of Acceptability, Implementation, and Impact on the PrEP Care Continuum in the United States
Authors: Bonett Stephen , Li Qian , Sweeney Anna , Gaither-Hardy Denise , Safa Hussein
Published: June 2024

Pre-exposure prophylaxis (PrEP) is pivotal in curbing HIV transmission and is integral to the national plan to end the HIV epidemic in the United States (US). Nonetheless, widespread PrEP adoption faces barriers. Telehealth delivery models for PrEP, or telePrEP, can enhance PrEP access and adherence by providing flexible care remotely. This study presents a systematic review of telePrEP programs in the US, aiming to describe model characteristics and summarize clinical, implementation, and equity outcomes. We reviewed studies published from 2012 to 2023. We included articles that described telePrEP systems in the US and measured PrEP care continuum outcomes (awareness, initiation, uptake, adherence) or acceptability of the intervention by program users. Eight articles describing six distinct telePrEP initiatives met our inclusion criteria. Studies described models implemented in community-based, academic, and commercial settings, with most programs using a direct-to-client telePrEP model. Across studies, clients reported high acceptability of the telePrEP programs, finding them easy to use, convenient, and helpful as a tool for accessing HIV prevention services. No programs were offering injectable PrEP at the time these studies were conducted. Data was limited in measuring PrEP retention rates and the reach of services to underserved populations, including Black and Latinx communities, transgender individuals, and cis-gender women. Findings underscore the potential of telePrEP to bolster the reach of PrEP care and address structural barriers to access. As telehealth models for PrEP care gain prominence, future research should concentrate on refining implementation strategies, enhancing equity outcomes, and expanding services to include injectable PrEP.
The Impact of COVID-19 on the HIV Cascade of Care in Botswana – An Interrupted Time Series
Authors: Sehurutshi Alice , Farooqui Habib , Chivese Tawanda
Published: June 2024

Globally, Botswana has one of the highest burdens of HIV. This study estimated the impact of the COVID-19 pandemic on the HIV cascade of care in Sub-Saharan Africa. We conducted an interrupted time series analysis on national-level data to estimate the effect of COVID-19 on the numbers of HIV tests, positive HIV tests and ART initiations from April 2019 until March 2021. In multivariable Poisson interrupted time series regression, the COVID-19 lockdown was associated with a 27% decrease in the monthly numbers of HIV tests (IRR 0.73, 95%CI 0.72–0.73), a 25% decrease in HIV positive tests (IRR 0.75, 95%CI 0.71–0.79), and a 43% reduction in ART initiations (IRR 0.57, 95%CI 0.55–0.60). The impact of the pandemic on all three outcomes was worse in males and those aged ≥ 50 years. In conclusion, COVID-19 had a strong negative impact on HIV screening, diagnosis and ART initiation in Botswana.
The Role of the Multidisciplinary HIV Care Center in Mitigating Social Isolation Among Patients with HIV During the Early COVID-19 Pandemic
Authors: Mgbako Ofole , Loughran Claire , Vaughn Michael P. , Felder Jason , Augustin Ashley , Gordon Peter , Remien Robert H. , Olender Susan
Published: June 2024

As the COVID-19 pandemic began in 2020, significant public health mitigation efforts were vital to combat an unprecedented health crisis. These efforts, which involved social distancing and self-quarantine, likely worsened a public health crisis of social isolation and loneliness in the U.S., particularly among people with HIV (PWH). Multidisciplinary HIV care centers, which served as the main source of clinical care for PWH and in some cases the only point of social contact, faced evolving dynamics of in-person visits during the COVID-19 pandemic, as well as a shift to telehealth services. Using in-depth interviews, we explored the role that multidisciplinary HIV care centers and providers played in the experience of social isolation among PWH in New York City. We recruited participants (n = 30) from a multidisciplinary HIV care center in NYC between October 2020 and June 2021. We conducted semi-structured interviews to understand the specific domains of social isolation that were mitigated. In this cohort, the major theme that drove both in-person and telehealth care continuity was the strength of the patient-provider relationship. We found that participants saw members of the HIV care center as part of their social network, and providers served both as a source of emotional support and provided important social resources and benefits. Thus, in times of heightened social isolation, HIV care centers can play a critical role in providing social support in addition to clinical care.
Unlocking the capabilities of explainable few-shot learning in remote sensing
Authors: Lee Gao Yu , Dam Tanmoy , Ferdaus Md. Meftahul , Poenar Daniel Puiu , Duong Vu N.
Published: June 2024

Recent advancements have significantly improved the efficiency and effectiveness of deep learning methods for image-based remote sensing tasks. However, the requirement for large amounts of labeled data can limit the applicability of deep neural networks to existing remote sensing datasets. To overcome this challenge, few-shot learning has emerged as a valuable approach for enabling learning with limited data. While previous research has evaluated the effectiveness of few-shot learning methods on satellite-based datasets, little attention has been paid to exploring the applications of these methods to datasets obtained from Unmanned Aerial Vehicles (UAVs), which are increasingly used in remote sensing studies. In this review, we provide an up-to-date overview of both existing and newly proposed few-shot classification techniques, along with appropriate datasets that are used for both satellite-based and UAV-based data. We demonstrate few-shot learning can effectively handle the diverse perspectives in remote sensing data. As an example application, we evaluate state-of-the-art approaches on a UAV disaster scene dataset, yielding promising results. Furthermore, we highlight the significance of incorporating explainable AI (XAI) techniques into few-shot models. In remote sensing, where decisions based on model predictions can have significant consequences, such as in natural disaster response or environmental monitoring, the transparency provided by XAI is crucial. Techniques like attention maps and prototype analysis can help clarify the decision-making processes of these complex models, enhancing their reliability. We identify key challenges including developing flexible few-shot methods to handle diverse remote sensing data effectively. This review aims to equip researchers with an improved understanding of few-shot learning’s capabilities and limitations in remote sensing, while pointing out open issues to guide progress in efficient, reliable and interpretable data-efficient techniques.
Determinants of Intention to Use HIV Pre-exposure Prophylaxis and Condom Use Among a Sample of Cisgender Female Sex Workers Working Mostly Outdoors in Madrid, Spain
Authors: Vazquez Guillamet Laia J. , Valencia Jorge , Ryan Pablo , Cuevas-Tascón Guillermo , del-Olmo-Morales Miguel Angel , Cobo Ines , Lazarus Jeffrey V. , Chevance Guillaume
Published: June 2024

There is scant knowledge regarding pre-exposure prophylaxis (PrEP) use among female sex workers (FSWs) in Europe. Spain recognized FSWs as a population at high risk of acquiring HIV and granted them subsidized access to PrEP when the medication first became nationally available in 2019. Nevertheless, FSWs represented just 0.2% of PrEP users in 2022. A total of 102 HIV-negative FSWs reached through field activities of local NGOs located in Madrid were interviewed between January and March 2022. Participants were selected through convenience sampling over a fixed recruitment period. FSWs completed a 73-item survey with questions about individual, occupational, social, and structural determinants. The objective of this study was to identify (1) the prevalence of intention to use oral PrEP and its determinants, and (2) the prevalence of inconsistent condom use, which is the risk factor that qualifies FSWs for subsidized PrEP in the national health system, and its determinants. Importantly, the study sample overrepresented street-based FSWs (71.6%). A quarter (25.5%) of the study participants used condoms inconsistently. PrEP awareness was low (9.8%), but intention to use PrEP was high (72.5%). Intention to use oral PrEP was significantly associated with feeling protected against HIV by taking PrEP and perceiving insufficient protection by condom use alone. Inconsistent condom use was significantly associated with frequent heroin/cocaine use, having clients who inject drugs, and willingness to take PrEP despite it not protecting 100% against HIV infection. FSWs, in this specific sample, are likely to benefit from targeted PrEP awareness campaigns and implementation projects that prioritize those who use drugs and are more likely to engage in condomless sex.
A randomized controlled trial of shared decision-making treatment planning process to enhance shared decision-making in patients with MBC
Authors: Rocque Gabrielle B. , Eltoum Noon , Caston Nicole E. , Williams Courtney P. , Oliver Marian M. , Moradi Lauren , Ingram Stacey , Azuero Andres , Pisu Maria , Bhatia Smita
Published: June 2024

Purpose

Opportunities exist for patients with metastatic breast cancer (MBC) to engage in shared decision-making (SDM). Presenting patient-reported data, including patient treatment preferences, to oncologists before or during a treatment plan decision may improve patient engagement in treatment decisions.

Methods

This randomized controlled trial evaluated the standard-of-care treatment planning process vs. a novel treatment planning process focused on SDM, which included oncologist review of patient-reported treatment preferences, prior to or during treatment decisions among women with MBC. The primary outcome was patient perception of shared decision-making. Secondary outcomes included patient activation, treatment satisfaction, physician perception of treatment decision-making, and use of treatment plans.

Results

Among the 109 evaluable patients from December 2018 to June 2022, 28% were Black and 12% lived in a highly disadvantaged neighborhood. Although not reaching statistical significance, patients in the intervention arm perceived SDM more often than patients in the control arm (63% vs. 59%; Cramer’s V = 0.05; OR 1.19; 95% CI 0.55–2.57). Among patients in the intervention arm, 31% were at the highest level of patient activation compared to 19% of those in the control arm (V = 0.18). In 82% of decisions, the oncologist agreed that the patient-reported data helped them engage in SDM. In 45% of decision, they reported changing management due to patient-reported data.

Conclusions

Oncologist engagement in the treatment planning process, with oncologist review of patient-reported data, is a promising approach to improve patient participation in treatment decisions which should be tested in larger studies.

Trial registration

NCT03806738.
External codes for multiple unicast networks via interference alignment
Authors: Kschischang F. R. , Manganiello F. , Ravagnani A. , Savary K.
Published: June 2024

We introduce a formal framework to study the multiple unicast problem for a coded network in which the network code is linear over a finite field and fixed. We show that the problem corresponds to an interference alignment problem over a finite field. In this context, we establish an outer bound for the achievable rate region and provide examples of networks where the bound is sharp. We finally give evidence of the crucial role played by the field characteristic in the problem.
Demystifying Lesotho, Rwandan and Nigerian educators’ viewpoints on smart technologies supporting AI in higher education
Authors: Theodorio Adedayo Olayinka , Waghid Zayd , Mataka Tawanda Wallace , Adegoke Oyebimpe
Published: June 2024

Given the deluge of technology flowing into African countries from the global north, it is not a hyperbole to make a point that developed nations are better equipped to practically integrate Smart Technologies supporting Artificial Intelligence (STAI) into higher education teaching methodologies. However, conversations regarding the application of AI in higher education have been spurred by attempts at its practical implementation in developing countries such as Lesotho, Rwanda, and Nigeria. Furthermore, a dearth of literature exists regarding STAI in higher education within the contexts of higher education in Lesotho, Rwanda, and Nigeria. This dearth points to a necessity for research to be conducted to include the three countries’ higher education contexts in order for researchers to be able to comprehend the perspectives of educators in these countries on their use of STAI in teaching and learning, as well as to identify the challenges associated with integrating STAI into higher education instructional practices. This study examines these three countries as case studies to gain insights into the perspectives of these educators on smart technologies which support AI in their higher education sectors. Vygotsky’s (1978) emphasis on ‘cultural tools’ and social interaction remains crucial in the knowledge-building process, and his social constructivist learning theory underpins the study. An online, semi-structured questionnaire was designed to address the question: What are e the viewpoints of a sampled group of higher education educators from Rwanda, Nigeria and Lesotho on Smart Technologies which support AI in Higher Education? The findings revealed participant from these countries to possess varied technological knowledge of the use of STAI to facilitate content comprehension and achievement of their teaching objectives. However, we argue in this paper that the participating educators’ varied understandings of the use of STAI in higher education needs to expand and to be swiftly accommodated if the three countries are to be on par with developed countries.
Procedural efficiency is enhanced combining the pentaspline pulsed field ablation catheter with three-dimensional electroanatomical mapping system for pulmonary vein isolation
Authors: Falasca Zamponi Alessio , Olson Jens , Scheel Sergej , Englund Anders , Scorza Raffaele , Tabrizi Fariborz
Published: June 2024

Background

Pulsed field ablation (PFA) offers a safe, non-thermal alternative for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Currently, the pentaspline PFA-system relies heavily on fluoroscopy for catheter manipulation, which poses challenges due to the complexity of left atrium anatomy. Incorporating three-dimensional electroanatomical mapping (3D-EAM) could improve procedural efficiency reducing dependency on fluoroscopy guidance. This study aims to evaluate the effects of integration of 3D-EAM with PFA during PVI.

Methods

Between September 2022 and December 2023, we retrospectively enrolled 248 patients with paroxysmal or persistent AF undergoing PVI at our center using the pentaspline PFA catheter. The control group (n = 104) received conventional PFA with fluoroscopic guidance alone, while the intervention group (n = 144) underwent PVI with PFA with 3D-EAM integration. Primary outcomes were procedural time, fluoroscopy time (FT), and dose area product (DAP). Secondary endpoints included acute procedural success and incidence of periprocedural complications.

Results

In the 3D-EAM-PFA group, procedural time was 63.3 ± 14.3 min, compared to 65.6 ± 14.9 min in the control group (p = 0.22). The 3D-EAM group experienced significantly reduced FT (9.7 ± 4.4 min vs. 16.7 ± 5.2 min) and DAP (119.2 ± 121.7 cGycm2 vs. 338.7 ± 229.9 cGycm2) compared to the control group, respectively (p < 0.001). Acute procedural success was achieved in all cases. No major complications were observed in either group.

Conclusion

Integration of 3D-EAM with the pentaspline PFA catheter for PVI in AF treatment offers a promising approach, with significantly reduced fluoroscopy exposure without compromising procedural time and efficacy.

Graphical abstract
Lower Humoral and Cellular Immunity Following Asymptomatic SARS-CoV-2 Infection Compared to Symptomatic Infection in Education (The ACE Cohort)
Authors: Hopkins Georgina , Gomez Nancy , Tucis Davis , Bartlett Laura , Steers Graham , Burns Ellie , Brown Michaela , Harvey-Cowlishaw Tyler , Santos Rute , Lauder Sarah N , Scurr Martin , Capitani Lorenzo , Burnell Stephanie , Rees Tara , Smart Kathryn , Somerville Michelle , Gallimore Awen , Perera Marianne , Potts Martin , Metaxaki Marina , Krishna Benjamin , Jackson Hannah , Tighe Paddy , Onion David , Godkin Andrew , Wills Mark , Fairclough Lucy
Published: June 2024

Purpose

Asymptomatic SARS-CoV-2 infections were widely reported during the COVID-19 pandemic, acting as a hidden source of infection. Many existing studies investigating asymptomatic immunity failed to recruit true asymptomatic individuals. Thus, we conducted a longitudinal cohort study to evaluate humoral- and cell-mediated responses to infection and vaccination in well-defined asymptomatic young adults (the Asymptomatic COVID-19 in Education [ACE] cohort).

Methods

Asymptomatic testing services located at three UK universities identified asymptomatic young adults who were subsequently recruited with age- and sex-matched symptomatic and uninfected controls. Blood and saliva samples were collected after SARS-CoV-2 Wuhan infection, and again after vaccination. 51 participant’s anti-spike antibody titres, neutralizing antibodies, and spike-specific T-cell responses were measured, against both Wuhan and Omicron B.1.1.529.1.

Results

Asymptomatic participants exhibited reduced Wuhan-specific neutralization antibodies pre- and post-vaccination, as well as fewer Omicron-specific neutralization antibodies post-vaccination, compared to symptomatic participants. Lower Wuhan and Omicron-specific IgG titres in asymptomatic individuals were also observed pre- and post-vaccination, compared to symptomatic participants. There were no differences in salivary IgA levels. Conventional flow cytometry analysis and multi-dimensional clustering analysis indicated unvaccinated asymptomatic participants had significantly fewer Wuhan-specific IL-2 secreting CD4+ CD45RA+ T cells and activated CD8+ T cells than symptomatic participants, though these differences dissipated after vaccination.

Conclusions

Asymptomatic infection results in decreased antibody and T cell responses to further exposure to SARS-CoV-2 variants, compared to symptomatic infection. Post-vaccination, antibody responses are still inferior, but T cell immunity increases to match symptomatic subjects, emphasising the importance of vaccination to help protect asymptomatic individuals against future variants.
The Chemistry of the Defensive Secretions of Three Species of Millipedes in the Genus Brachycybe
Authors: Banks Paige , Funkhouser Emma M. , Macias Angie M. , Lovett Brian , Meador Shelby , Hatch Arden , Garraffo H. Martin , Cartwright Kaitie C. , Kasson Matt T. , Marek Paul E. , Jones Tappey H. , Mevers Emily
Published: June 2024

Millipedes have long been known to produce a diverse array of chemical defense agents that deter predation. These compounds, or their precursors, are stored in high concentration within glands (ozadenes) and are released upon disturbance. The subterclass Colobognatha contains four orders of millipedes, all of which are known to produce terpenoid alkaloids—spare the Siphonophorida that produce terpenes. Although these compounds represent some of the most structurally-intriguing millipede-derived natural products, they are the least studied class of millipede defensive secretions. Here, we describe the chemistry of millipede defensive secretions from three species of Brachycybe: Brachycybe producta, Brachycybe petasata, and Brachycybe rosea. Chemical investigations using mass spectrometry-based metabolomics, chemical synthesis, and 2D NMR led to the identification of five alkaloids, three of which are new to the literature. All identified compounds are monoterpene alkaloids with the new compounds representing indolizidine (i.e. hydrogosodesmine) and quinolizidine alkaloids (i.e. homogosodesmine and homo-hydrogosodesmine). The chemical diversity of these compounds tracks the known species phylogeny of this genus, rather than the geographical proximity of the species. The indolizidines and quinolizidines are produced by non-sympatric sister species, B. producta and B. petasata, while deoxybuzonamine is produced by another set of non-sympatric sister species, B. rosea and Brachycybe lecontii. The fidelity between the chemical diversity and phylogeny strongly suggests that millipedes generate these complex defensive agents de novo and begins to provide insights into the evolution of their biochemical pathways.
Virtual clinical trials via a QSP immuno-oncology model to simulate the response to a conditionally activated PD-L1 targeting antibody in NSCLC
Authors: Ippolito Alberto , Wang Hanwen , Zhang Yu , Vakil Vahideh , Popel Aleksander S.
Published: June 2024

Recently, immunotherapies for antitumoral response have adopted conditionally activated molecules with the objective of reducing systemic toxicity. Amongst these are conditionally activated antibodies, such as PROBODY® activatable therapeutics (Pb-Tx), engineered to be proteolytically activated by proteases found locally in the tumor microenvironment (TME). These PROBODY® therapeutics molecules have shown potential as PD-L1 checkpoint inhibitors in several cancer types, including both effectiveness and locality of action of the molecule as shown by several clinical trials and imaging studies. Here, we perform an exploratory study using our recently published quantitative systems pharmacology model, previously validated for triple-negative breast cancer (TNBC), to computationally predict the effectiveness and targeting specificity of a PROBODY® therapeutics drug compared to the non-modified antibody. We begin with the analysis of anti-PD-L1 immunotherapy in non-small cell lung cancer (NSCLC). As a first contribution, we have improved previous virtual patient selection methods using the omics data provided by the iAtlas database portal compared to methods previously published in literature. Furthermore, our results suggest that masking an antibody maintains its efficacy while improving the localization of active therapeutic in the TME. Additionally, we generalize the model by evaluating the dependence of the response to the tumor mutational burden, independently of cancer type, as well as to other key biomarkers, such as CD8/Treg Tcell and M1/M2 macrophage ratio. While our results are obtained from simulations on NSCLC, our findings are generalizable to other cancer types and suggest that an effective and highly selective conditionally activated PROBODY® therapeutics molecule is a feasible option.
Mechanisms and clinical landscape of N6-methyladenosine (m6A) RNA modification in gastrointestinal tract cancers
Authors: Zhu Dan-Hua , Su Kun-Kai , Ou-Yang Xiao-Xi , Zhang Yan-Hong , Yu Xiao-Peng , Li Zu-Hong , Ahmadi-Nishaboori Seyedeh-Sara , Li Lan-Juan
Published: June 2024

Epigenetics encompasses reversible and heritable chemical modifications of non-nuclear DNA sequences, including DNA and RNA methylation, histone modifications, non-coding RNA modifications, and chromatin rearrangements. In addition to well-studied DNA and histone methylation, RNA methylation has emerged as a hot topic in biological sciences over the past decade. N6-methyladenosine (m6A) is the most common and abundant modification in eukaryotic mRNA, affecting all RNA stages, including transcription, translation, and degradation. Advances in high-throughput sequencing technologies made it feasible to identify the chemical basis and biological functions of m6A RNA. Dysregulation of m6A levels and associated modifying proteins can both inhibit and promote cancer, highlighting the importance of the tumor microenvironment in diverse biological processes. Gastrointestinal tract cancers, including gastric, colorectal, and pancreatic cancers, are among the most common and deadly malignancies in humans. Growing evidence suggests a close association between m6A levels and the progression of gastrointestinal tumors. Global m6A modification levels are substantially modified in gastrointestinal tumor tissues and cell lines compared to healthy tissues and cells, possibly influencing various biological behaviors such as tumor cell proliferation, invasion, metastasis, and drug resistance. Exploring the diagnostic and therapeutic potential of m6A-related proteins is critical from a clinical standpoint. Developing more specific and effective m6A modulators offers new options for treating these tumors and deeper insights into gastrointestinal tract cancers.
An investigation of the longitudinal trajectory patterns of health-related quality of life among Australians with disabilities: explaining disability types and properties
Authors: Hashmi Rubayyat , Keating Byron W. , Ali Mohammad Afshar , Keramat Syed Afroz
Published: June 2024

Background

Research on health-related quality of life (HRQoL) trajectory patterns for people with disabilities (PwD) is scant. Understanding the HRQoL trajectory patterns for PwDs and investigating their relationship with disability types and socioeconomic factors can have important implications for Australia’s welfare policy.

Methods

We analysed data from waves 11 to 21 of the Household, Income and Labour Dynamics in Australia (HILDA) survey of respondents aged 15 + years of the PwDs. The analytic sample consists of 3724 self-reported disabled individuals and 34,539 observations in total. The SF-6D utility score is our HRQoL measure. Group-based trajectory modelling was utilised to identify trajectory groups, and multinomial logistic regression was employed to determine the baseline factors associated with trajectory group membership.

Results

The study identified four distinct types of HRQoL trajectories (high, moderate improving, moderate deteriorating and low HRQoL trajectories). Psychosocial disability types followed by physical disability types had a high Relative Risk Ratio (RRR) in the low group compared with high trajectory group membership of PwDs (psychosocial: 6.090, physical: 3.524). Similar, results followed for the moderate improving group albeit with lower RRR (psychosocial: 2.868, Physical: 1.820). In the moderate deteriorating group, the disability types were not significant as this group has a similar profile to high group at the baseline. Compared with males, females had a higher RRR in low and moderate versus high improving HRQoL trajectories (low: 1.532, moderate improving: 1.237). Comparing the richest class to the poorest class, socioeconomic factors (income and education) predicted significantly lower exposure for the richer class to the low and medium HRQoL trajectories groups (RRR < 1).

Conclusion

Different forms of disability, demographic and socioeconomic factors have distinct effects on the HRQoL trajectories of disabled individuals. Healthcare and economic resource efficiency might be improved with targeted government policy interventions based on disability trajectories.
The impacts of inter- and intra-seasonal burns on the terrestrial orchid Pterostylis curta
Authors: Thomsen Alexandria M. , Davies Richard J. P. , Ooi Mark K. J.
Published: June 2024

Prescribed burning is a management tool used for both management of fuel loads and for ecological purposes across fire prone areas. While in temperate areas wildfires usually occur during the hottest summer months, prescribed burns are generally conducted in autumn and spring, when conditions are more suitable for controlling fire. Orchids maintain avoidance mechanisms, such as persisting as dormant tubers during the predominant fire season, and therefore may be at risk from prescribed burns occurring during their active life cycle period. Using a glasshouse experiment, we investigated the impacts of fire season on the Australian orchid species Pterostylis curta. This approach allowed us to i) implement seasonal burns and relate impacts to quantifiable above and belowground life cycle stages of the study species, ii) isolate and assess the role of smoke, and iii) control for fire intensity and life stage of the study species at each of the treatment levels to enable robust comparison focused on fire season effects. We found that late autumn burns caused complete failure of a cohort in our glasshouse study. Heat alone was not the driver of tuber mortality, because soil heating was similar across all burn seasons, and plants burnt in the three other seasons were able to re-emerge strongly in the growing season after fire. Furthermore, a lack of post-fire emergence was due to tuber mortality, not dormancy. Our results highlight that there is likely an interaction between fire-related heat and the life cycle stage at which burning occurs, especially replacement tuber initiation, that drives post-fire demography. We show that orchids like P. curta had the lowest risk of negative impacts when burnt in the later stages of their growing season, and that an understanding of finer-scale phenological cycles can inform more robust fire management of orchid species.
High temperature and solar radiation in the Red Sea enhance the dissolution of crude oil from surface films
Authors: Kottuparambil Sreejith , Ashok Ananya , López Patricia , Amad Maan H. , Duarte Carlos M. , Agusti Susana
Published: June 2024

The Red Sea is a hotspot of biodiversity susceptible to oil pollution. Besides, it is one of the warmest seas on the Earth with highly transparent waters. In this study, we estimated the oil dissolution rates under natural sunlight spectra and temperature conditions using coastal oil slicks collected after the 2019 Sabiti oil spill in the Red Sea. Optical analyses revealed the significant interactive effect of sunlight and temperature in enhancing the dissolution of oil into dissolved organic matter (DOM). The highest oil dissolution rate (38.68 g C m−3 d−1) was observed in full-spectrum sunlight. Oil dissolution significantly enhanced total organic carbon (TOC) and polycyclic aromatic hydrocarbons (PAHs) in seawater. High nucleic acid (HNA) bacteria, likely the oil degraders, proliferated from 30 to 70 – 90% after 4 days. The heavier stable carbon isotopic composition of methane (δ13C-CH4) and lighter stable carbon isotopic composition of carbon dioxide (δ13C-CO2) indicate the putative role of bacterial processes in the natural degradation of crude oil. The results indicated that the combined effect of temperature and solar radiation enhanced the biological and photochemical dissolution of oil on the Red Sea surface.
Measuring financial divide in the rural environment. The potential role of the digital transformation of finance
Authors: Gallego-Losada María-Jesús , Montero-Navarro Antonio , Gallego-Losada Rocío , Rodríguez-Sánchez José-Luis
Published: June 2024

Financial inclusion, which means the promotion of an affordable, timely and adequate access to a wide range of regulated financial products and services, as well as its use by all the segments of the society, is a high potential tool that may contribute to the development of the rural environment, while its absence could in turn cause a major harm. The availability of a sufficient level of financial literacy, which can be defined as the ability to understand financial concepts and risks, as well as the motivation and trust to use it when making financial decisions, is frequently deemed to be a need to reach financial inclusion by the academic literature. Financial literacy is, in turn, influenced by different variables, such as the degree of rural or urban predominance, the level of education and the available income in the household. This paper analyses the impact of such factors on financial literacy. The degree of financial literacy tends to be lower in rural environments, with limited incomes and poorer educational backgrounds, which creates a vicious circle that potentially worsens the situation of what has been called the empty Spain. Considering the importance of financial literacy to reach financial inclusion, we remark the potential of digital transformation as a valuable tool to break this negative trend in the less populated Spanish regions, and so, a cornerstone for the regenerative development of the Spanish rural areas.
Problematic Gaming and Students’ Academic Performance: A Systematic Review
Authors: Alzahrani Alanood Khalid D , Griffiths Mark D.
Published: June 2024

Introduction

Research indicates that videogames can have many benefits. However, gaming can be problematic for some individuals. Consequently, over the past two decades, researchers have actively studied the risk factors and consequences of problematic gaming and gaming disorder which may affect many aspects of individuals’ lives, including their academic performance.

Method

The present study is the first ever systematic review of studies examining the relationship between problematic gaming and student academic performance utilising the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of 27 empirical studies met the inclusion criteria and were eligible for review.

Results

Most of the studies (n = 24) reported a negative relationship between problematic gaming and academic performance. Moreover, older studies (conducted before 2015) suggest that problematic gaming was a significant factor in predicting poor academic performance. However, most of the recent studies have found the opposite, showing that problematic gaming is not a significant predictor for academic performance and/or that academic performance is a significant factor in predicting problematic gaming. Overall, the findings suggest that poor academic performance is more likely to be a cause for problematic gaming rather than a consequence based on more recent studies.

Conclusion

Although most of the reviewed studies showed a negative relationship between problematic gaming and academic performance, research is still limited in this area because most the reviewed studies had a cross-sectional design that are unable to establish the direction of the effect. Therefore, more studies with methodological approaches that can determine the causality between problematic gaming and poor academic performance are needed.
Health technology assessment in musculoskeletal radiology: the case study of EOSedge™
Authors: Tomaiuolo Rossella , Banfi Giuseppe , Messina Carmelo , Albano Domenico , Gitto Salvatore , Sconfienza Luca Maria
Published: June 2024

Objectives

Health technology assessment (HTA) is a systematic process used to evaluate the properties and effects of healthcare technologies within their intended use context. This paper describes the adoption of HTA process to assess the adoption of the EOSedge™ system in clinical practice.

Methods

The EOSedge™ system is a digital radiography system that delivers whole-body, high-quality 2D/3D biplanar images covering the complete set of musculoskeletal and orthopedic exams. Full HTA model was chosen using the EUnetHTA Core Model® version 3.0. The HTA Core Model organizes the information into nine domains. Information was researched and obtained by consulting the manufacturers’ user manuals, scientific literature, and institutional sites for regulatory aspects.

Results

All nine domains of the EUnetHTA Core Model® helped conduct the HTA of the EOSedge, including (1) description and technical characteristics of the technology; (2) health problem and current clinical practice; (3) safety; (4) clinical effectiveness; (5) organizational aspects; (6) economic evaluation; (7) impact on the patient; (8) ethical aspects; and (9) legal aspects.

Conclusions

EOS technologies may be a viable alternative to conventional radiographs. EOSedge has the same intended use and similar indications for use, technological characteristics, and operation principles as the EOS System and provides significant dose reduction factors for whole spine imaging compared to the EOS System without compromising image quality. Regarding the impact of EOS imaging on patient outcomes, most studies aim to establish technical ability without evaluating their ability to improve patient outcomes; thus, more studies on this aspect are warranted.
The usefulness of combined analysis using CIScore and VSRAD parameters for differentiating between dementia with Lewy body and Alzheimer’s disease
Authors: Honda Gaku , Nagamachi Shigeki , Takahashi Mai , Higuma Yukie , Tani Tomonobu , Hida Kosuke , Yoshimitsu Kengo , Ogomori Koji , Tsuboi Yoshio
Published: June 2024

Purpose

The Cingulate Island score (CIScore) is useful index for differentiating between dementia with Lewy body (DLB) and Alzheimer’s disease (AD) using regional cerebral blood flow (rCBF) SPECT. The Z score standing for medial temporal lobe (MTL) atrophy and the ratio of Z score between dorsal brain stem (DBS) to MTL are useful indices for differentiating between DLB and AD using MRI with VSRAD. The current study investigated the diagnostic ability by the combined use of rCBF SPECT and MRI in the differentiation between AD and DLB.

Materials and methods

In cases with 42 AD and 28 DLB undertaken Tc-99m-ECD SPECT and MRI, we analyzed differential diagnostic ability between AD and DLB among following conditions by single or combined settings. Namely, they were (1) the CIScore as a parameter of rCBF SPECT (DLB ≦ 0.25), (2) Z score value of MTL atrophy (DLB ≦ 2.05), (3) the ratio of Z score of DBS to medial temporal gray matter as a parameter of brain atrophy using VSRAD (DLB ≧ 0.38). Also, we analyzed them both including and omitting the elderly (over 75 years old).

Results

The accuracy of differential diagnosis in this condition was 74% for (1), 69% for (2), and 67% for (3). The accuracy by combination condition was 84% for (1) and (2), 81% for (1) and (3), and 67% for (2) and (3), respectively. The combination method by CIScore and the Z score of MTL showed the best accuracy. When we confined condition to ages younger than 75 years, the accuracy improved to 94% in the combination method.

Conclusion

The combined use of CIScore and Z score of MTL was suggested to be useful in the differential diagnosis between DLB and AD particularly in younger than 75 years old.