bluuebunny/crossref_metadata_2025 huggingface dataset:
Fostering Inclusivity for Clients with Disabilities: Universal Design in Family Therapy
Authors: Scoresby Kristel , Norris Priscila , Autry-Cole Brittney , Lella Jessica
Published: August 2024

Over a quarter of adults in the United States live with a disability. Historically, disability was contextualized from the lens of a medical model, which identifies disability solely as impairment for the individual and should be treated or eradicated. Individuals with disabilities have been seen as abnormal and a threat to the family system. Critical Disability Theory challenges this thought by suggesting that disability is a social construct in which one's environment prioritizes able bodies. Although numerous accommodations have been mandated by the Americans with Disabilities Act, the environment of an individual living with disabilities frequently fails to meet their needs, including the family therapy office. Universal Design (UD) is a design strategy that increases access for individuals of all abilities, mental states, and learning types. Utilizing UD principles in family therapy settings can increase client engagement, representation, and learning in a in a safe, accessible environment.
Reduced Platelets Associated with All-Cause Mortality in the Pediatric Intensive Care Unit
Authors: Pang Yajing , Zhang Yong Hong , Yue Chaoyan , Wang Li
Published: August 2024

Platelets are crucial for maintaining physiological equilibrium, thrombosis formation, inflammation, bacterial defense, wound repair, angiogenesis, and tumorigenesis. In the Pediatric Intensive Care Unit (PICU), children frequently exhibit platelet reductions or functional alterations due to diverse pathological conditions, which significantly influence disease progression and therapeutic approaches. We analyzed the association between platelets count and its derived parameters and all-cause mortality. Adjusted smoothing spline plots, subgroup analysis and segmented multivariate logistic regression analysis were conducted to estimate the relative risk between proportional risk between platelets and all-cause mortality. Of the 11625 children, 677 (5.82%) died. After adjusting for confounders, there was a negative association between platelets and the risk of all-cause mortality in PICU. For every 100 × 10^9/L increase in platelets, the risk of death was reduced by 17% (adjusted OR = 0.83, 95% CI: 0.78, 0.89). The results of sensitivity analysis showed that in different stratified analyses (age, ICU category,WBC Count), the effect of platelets count on all-cause mortality remained stable. After adjusting for inflammation, nutrition, and liver function factors, platelets reduction is still an independent risk factor for PICU all-cause mortality.
Mosques and Public Health Promotion: A Scoping Review of Faith-Driven Health Interventions
Authors: Abu-Ras Wahiba , Aboul-Enein Basil H. , Almoayad Fatmah , Benajiba Nada , Dodge Elizabeth
Published: August 2024

Background

Religious institutions play a crucial role in health promotion and hold significant influence in the public health field.

Aim

The aim of this review is to examine outcomes of health-promoting interventions involving the use of mosques as the intervention venue, its role in promoting health behavior change, and the role of theory in each intervention.

Methods

A scoping review was conducted across 17 databases for relevant publications published up to and including August 2023 that involved the use of mosques as the intervention venue. Fourteen articles met inclusion criteria and were reviewed.

Results

The studies featured a wide range of interventions. However, only eight of these studies integrated theoretical frameworks into their approaches, indicating a need for more structured guidance in this field. These theoretical frameworks included Participatory Action Research (PAR), the theory of planned behavior, behavior-change constructs, the patient-centered outcomes research (PCOR) framework, and prolonged exposure techniques within Islamic principles. The review identified three main health-focused intervention categories: mental health, prevention, and communication, each providing valuable insights into initiatives within Muslim communities.

Conclusions

This review underscores the significance of inclusive and culturally sensitive health interventions, emphasizing the effectiveness of faith-based approaches in improving health outcomes, promoting positive health behaviors, and addressing communication and cultural barriers. The reviews findings stress the need for further research that incorporates theoretical frameworks and tailored interventions to meet the specific cultural needs of these communities, ultimately contributing to enhanced well-being within them.
Adverse events associated with robotic-assistance in total hip arthroplasty: an analysis based on the FDA MAUDE database
Authors: Graefe S Bradley , Kirchner Gregory J , Pahapill Natalie K , Nam Hannah H , Dunleavy Mark L , Haines Nikkole
Published: August 2024

Background:

The Food and Drug Administration (FDA) maintains the Manufacturer and User Facility Device Experience (MAUDE) database for reporting adverse events associated with medical devices, including emerging technologies, such as robotic-assisted total hip arthroplasty (THA). Aim of this study was to evaluate the variation of adverse events associated with robotics in THA.

Methods:

Medical device reports (MDRs) within the MAUDE database were identified between 2017 and 2021. For MDR identification the product class “orthopaedic stereotaxic equipment” and terms associated with THA were used. Individual adverse events were identified and organised by type and consequences, such as patient injury, surgical delay, or conversion to the manual technique.

Results:

521 MDRs constituting 546 discrete events were found. The most common reported complication was intraoperative hardware failure (304/546, 55.7%), among which the most common failure was a broken impaction handle/platform (110, 20.1%). Inaccurate cup placement was the second most common reported complication (63, 11.5%). Abandoning the robot occurred in 13.0% (71/521) of reports. A surgical delay was noted in 28% (146/521) of reports, with an average delay of 17.9 (range 1–60) minutes.

Conclusions:

Identifying complications that may occur with robotics in THA is an important first step in preventing adverse events and surgical delays. Database analysis provide an overview of the range of complications.
Post-COVID-19 Syndrome Associated With Multiple Autoimmune Diseases (DM I—LADA, Chronic Autoimmune Thyroiditis and Pernicious Anemia): Case Report
Authors: Milic Gordana , Ristic Masa , Milosevic Milica , Mitovic Nikola , Dimitrijevic Ljubica , Jesic Petrovic Tanja , Salovic Bojana
Published: August 2024

COVID-19, a global epidemic of infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), not only initially refers to acute manifestations but also chronic symptoms known as Long COVID-19. Long COVID-19 represents a significant burden to healthcare systems worldwide. This syndrome encompasses a wide range of continuing health problems with variable durations and consequences for patients’ everyday lives. A notable aspect of Long COVID-19 is the emergence of new-onset autoimmune diseases that could be triggered in predisposed patients with altered immune responses. Common autoimmune conditions that arise in post-COVID patients include autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune thyroid diseases, Kawasaki disease, Guillain-Barre syndrome, etc., but with unclear evidence of associated disease occurrence. We present a case of a female rheumatoid arthritis patient who developed autoimmune thyroid disease, latent autoimmune diabetes of adults (LADA), and pernicious anemia after SARS-CoV-2 infection.
Efficacy of Photodynamic Therapy in the Treatment of Actinic Keratosis: A Network Meta-Analysis
Authors: Wan Yuanyuan , Zeng Qinghai , Jiang Ling , Fu Chuhan , Mao Shunmin , Zhang Lan , Zhang Yushan , Zhang Xiaolin , Zhu Lu , Zhang Fan , Chen Jing , Lei Li
Published: August 2024

Background:

Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK) and uses different light sources as well as photosensitizers. In addition, PDT is often combined with other physical therapies or drugs.

Objectives:

This study was aimed to compare the efficacy of different PDTs against AK lesions based on Complete Response (CR) by conducting a network meta-analysis (NMA).

Methods:

Randomized controlled trials (RCTs) using PDT for AK were screened and a Bayesian model was developed to perform an NMA of CR at 3 months after the first treatment.

Results:

Twenty-six trials involving 2285 patients and 14 treatments were included. The treatments were broadly divided into mono-PDT and combination therapy. The photodynamic monotherapies included methyl 5-aminolevulinic acid (MAL)-daylight (DL)-PDT, MAL-light-emitting diode (LED)-PDT, 5-aminolevulinic acid (ALA)-LED-PDT, etc. Combination therapies included ablative fractional laser (AFL)-assisted MAL-LED-PDT, calcipotriol (CAL)-assisted MAL-LED-PDT, and 5-fluorouracil (5-Fu)-assisted MAL-DL-PDT. The results of the NMA showed that there is a high probability that AFL-MAL-LED-PDT is the most effective treatment option, followed by CAL-MAL-LED-PDT and ALA-LED-PDT. The subgroup analysis showed that MAL-based PDT had better efficacy when using LED versus other light sources, while LED-based PDT was likely to have better efficacy when using ALA versus other photosensitizers.

Conclusions:

The results of this NMA suggest that AFL-MAL-LED-PDT may be the superior choice for achieving complete clearance of AK lesions. PDT using LED as the light source and ALA as the photosensitizer may be more effective for the treatment of AK. However, more RCTs are needed to verify the results of this analysis.
Living my Latin American influencer dream: How racism and nationality shape Latin American influencers within the US
Authors: Arriagada Arturo , Craig David
Published: August 2024

This paper investigates the intersection of racism, nationality, and the global Latin American influencer dream. It examines the experiences of Latin American influencers in the United States, where pursuing commercial success intersects with cultural and economic aspirations. Additionally, it explores the role of content service organizations in shaping creator culture and the working experiences of Latin American influencers. Despite the global imagination, influencer economies largely remain national, constrained by socio-cultural, linguistic, and regional norms. Drawing from literature on influencer cultures, platform economies, and imaginaries, the study analyzes data from interviews with content service organization executives and influencers, alongside platform analytics and advertising campaigns. The findings elucidate how racial discourses shape and challenge creator cultures, highlighting barriers for Latin American influencers in the US. This research contributes to understanding the social dimensions of creator culture, revealing impediments faced by diasporic influencers.
Induction heating simulation for aircraft RTM toolings
Authors: Brieskorn L , Rahman M
Published: August 2024

Aircraft CFRP parts as sharklets are produced in resin transfer molding (RTM) tooling. The parts need to be heated up homogenously over the whole area with a constant temperature. The complex shape and accessibility of the tooling make it hard to introduce a common heating system. In addition, the heat must be transferred through the Invar metal tooling structure onto the CFRP. Infrared lamp, air fan and microwave heating are concepts in development. Electrical heating layer mats and cages are laborious in applying. Induction has the advantage of contact-less, efficient, and fast heating. Induction heating was tested for the structural bonding of CFRP frames and stringers showing high bonding strengths. To apply this technology for the RTM tooling, the placement and distance of the induction coils is important. Simulation can help to find the right adjustments and power needed for induction heating. With the program COMSOL the surface and the coils are modeled, and the numerically structured net is divided in small tetrahedron and quadratic sub elements. Since there is no magnetic streamline in the middle of the coil-section, a symmetric halving of the structure is applied as a boundary condition. The temperature-time development and the distance of the coils are simulated in 2D and 3D. Due to the material properties of the magnetic flux concentrator (MFC), higher flux concentration of the magnetic field occurred only in 2D. The results are validated by experiments and are in good agreement.
On the post-human political potential of puppets: a case study of Storm, an eco-activist
Authors: Thomas Rosa , Banfield Janet
Published: August 2024

With the confluence of interest in socio-natural or human-nonhuman entanglements and concern for the maintenance of a minimal humanism within such post-human ontologies, the puppet arises as a post-human artform that is well placed to address both simultaneously. To argue that the puppet is a post-human artform is not a new proposition, but what is new in this paper is its detailed account of how different features of puppet performance function in post-human fashion, both drawing the human spectator into the performance as part of its singularity and rendering accessible the enviro-political message behind the performance. Focusing on a giant (10 m tall) puppet – Storm – who attended COP26 in Glasgow in 2021 to promote protection of the world’s seas, we first address how the post-human puppet form was brought to performative life through identification of a series of constructional mechanisms, which function as spatial manoeuvres to reposition the spectator with respect to both the puppet character and her political message. Subsequently, we consider how these mechanisms differentially influence legibility, acuity and potency of the political message, explore potential risks to the effectiveness of those constructional mechanisms, and draw out three foundational tensions that must seemingly be navigated for optimal political effectiveness (relating to post-human, political and spatial concerns respectively). Ultimately, we hypothesise a bidirectional spatial and subjective transition on the part of the spectator, progressing from being one who becomes bound into the collective singularity of the puppet assemblage to one who funnels the agency of the collective singularity into their one-ness for optimum political potency. Thus, we present both a detailed empirical and critical reading of one specific puppet performance and provide a more abstracted account of the political potency of (giant) puppets.
Trace Toxins: The Key Component of a Healthful Diet
Authors: Stone Jonathan , Mason Rebecca , Mitrofanis John , Johnstone Daniel M.
Published: August 2024

Although it is well established that a vegetable-rich (Mediterranean) diet is associated with health benefits in later life, the mechanisms and biological origins of this benefit are not well established. This review seeks to identify the components a healthful diet that reduce the individual’s suffering from non-communicable disease and extend longevity. We note the difference between the claims made for an essential diet (that prevents deficiency syndromes) and those argued for a diet that also prevents or delays non-communicable diseases and ask: what chemicals in our food induce this added resilience, which is effective against cardiovascular and neurodegenerative diseases, diabetes and even cancer? Working in the framework of acquired resilience (tissue resilience induced by a range of stresses), we arguethat the toxins evolved by plants as part of allelopathy (the competition between plant species) are key in making the ‘healthful difference’. We further suggest the recognition of a category of micronutrients additional to the established ‘micro’ categories of vitamins and trace elements and suggest also that the new category be called ‘trace toxins’. Implications of these suggestions are discussed.
Principles of Interoperability of Diabetes Devices
Authors: Klonoff David C. , Aaron Rachel E. , Tian Tiffany , Espinoza Juan C.
Published: August 2024

Introduction:

Better interoperability is essential to derive maximum benefit from connected wireless diabetes devices. The need for this feature of diabetes devices is supported by trends in designing better performance for three types of devices: nonmedical devices, medical devices, and diabetes devices.

Framework:

First, interoperability is a standard attribute for the performance of nonmedical devices contained in smart systems that can sense and actuate. Second, interoperability is now mandated by the US Department of Health and Human Services as carried out by the Office of the National Coordinator for Health Information technology (ONC) and the US Food and Drug Administration (FDA) to improve the performance of all medical devices. Third, new guidance from the FDA and nongovernmental professional organizations are intended to promote interoperability because this feature will improve the performance of all diabetes devices.

Recommendations:

Wireless devices perform best when they are interoperable, and this is particularly true for diabetes devices.
Pre-pandemic preventable hospitalization is associated with increased telemedicine use in safety-net settings
Authors: Ojinnaka Chinedum O , Yuh Sandra , Nordstrom Lora , Adepoju Omolola E , Domino Marisa
Published: August 2024

Introduction

The COVID-19 pandemic necessitated a major expansion in telemedicine use. The continued use of telemedicine post-pandemic has the potential to enhance healthcare use for people at risk for sub-optimal healthcare access and utilization, such as patients with previous preventable hospitalization. This study analyzed the association between pre-pandemic preventable hospitalizations (PPHs) and telemedicine use during the pandemic.

Methods

This retrospective cohort study uses Medicaid administrative claims data (01/2018–06/2022) for patients of a large Federally Qualified Health Center in Arizona that implemented telemedicine in March 2020. Bivariate and multivariable generalized estimating equations were used to analyze the relationship between the outcome and predictor variables. We also analyze racial/ethnic and primary language disparities in telemedicine use among those with PPH and report the average predicted probability.

Results

There was a statistically significant relationship between telemedicine use and PPH even after adjusting for comorbidity severity (OR:1.85; CI: 1.74, 1.96). Analyses restricted to those who had PPHs showed an seven-percentage point difference in the predicted probability of telemedicine use between non-Hispanic White individuals and Asian/Pacific Islanders, the group with the lowest probability of telemedicine use among our study sample.

Conclusion

Telemedicine is a unique tool that can be leveraged by interventions that aim to optimize healthcare use among those with a history of preventable hospitalizations. However, the lack of targeted interventions to identify and address barriers to telemedicine use among minoritized groups could limit the impact of such interventions and widen disparities.
To Deliver or Not to Deliver: The Case For and Against Restaurant Delivery
Authors: Tabatabaei Farhad , Mensah Nyarko Yaa Pokua , Webb Timothy
Published: August 2024

Since the start of the COVID-19 pandemic, online food delivery has experienced significant growth. As consumer preferences continue to shift toward this new platform, it is crucial for restaurants to assess the benefits and risks associated with engaging in the delivery market. By synthesizing academic research and industry reports, this case highlights the associated benefits for restaurants including the extension of service capacity constraints, market growth, and ease of implementation. Additionally, risks are introduced including food quality control, profitability, production capacity constraints, and cannibalization. The topics are discussed and contrasted under the examples of a large service provider (Shake Shack) and smaller independent restaurant (EL Ideas). The case provides valuable insights regarding the opportunities and challenges of partnering with food delivery providers, enabling future restaurant managers to make informed decisions in this evolving market.
A Step Toward Precision Audiology: Individual Differences and Characteristic Profiles From Auditory Perceptual and Cognitive Abilities
Authors: Cherri Dana , Eddins David A. , Ozmeral Erol J.
Published: August 2024

Older adults with normal hearing or with age-related hearing loss face challenges when listening to speech in noisy environments. To better serve individuals with communication difficulties, precision diagnostics are needed to characterize individuals’ auditory perceptual and cognitive abilities beyond pure tone thresholds. These abilities can be heterogenous across individuals within the same population. The goal of the present study is to consider the suprathreshold variability and develop characteristic profiles for older adults with normal hearing (ONH) and with hearing loss (OHL). Auditory perceptual and cognitive abilities were tested on ONH ( n = 20) and OHL ( n = 20) on an abbreviated test battery using portable automated rapid testing. Using cluster analyses, three main profiles were revealed for each group, showing differences in auditory perceptual and cognitive abilities despite similar audiometric thresholds. Analysis of variance showed that ONH profiles differed in spatial release from masking, speech-in-babble testing, cognition, tone-in-noise, and binaural temporal processing abilities. The OHL profiles differed in spatial release from masking, speech-in-babble testing, cognition, and tolerance to background noise performance. Correlation analyses showed significant relationships between auditory and cognitive abilities in both groups. This study showed that auditory perceptual and cognitive deficits can be present to varying degrees in the presence of audiometrically normal hearing and among listeners with similar degrees of hearing loss. The results of this study inform the need for taking individual differences into consideration and developing targeted intervention options beyond pure tone thresholds and speech testing.
Ageism Harms Older People's Health, Cognition, and Well-Being: A Selective Review and Policy Recommendations
Authors: Barber Sarah J. , Shoemaker Katherine J. , Dotson Vonetta M.
Published: August 2024

Ageism refers to stereotypes, prejudice, and discrimination directed towards individuals based on their age, such as perceptions that someone is “too old” for certain activities. Ageism directed at older people is prevalent; over 90% of older people in the United States report that they regularly experience ageism, such as when others assume they are forgetful or need assistance because of their age. Experiencing ageism is associated with poorer health outcomes, reduced cognitive performance, and increased healthcare costs. Reducing ageism requires a multifaceted approach, including strengthening anti-ageism laws and reframing societal narratives about what it means to grow older. Growing older should not be presented as a problem but as a fundamental part of the human journey. Ageism can also be reduced through positive intergenerational interactions and educational initiatives. Reducing ageism can promote healthier aging trajectories.
Risk Management During the Transition From Hospital to Home: A Multiple Case Study Documenting the Experience of Patients Living With a Major Neurocognitive Disorder, Their Caregivers, and Healthcare Professionals
Authors: Provencher Véronique , Viscogliosi Chantal , Lacerte Julie , D’Amours Monia , Mailhot-Bisson Didier , Gagnon Lise , Lacombe Guy
Published: August 2024

Understanding the risks in the months following hospital discharge is crucial for healthcare professionals to ensure the need for assistance is met. However, this may be challenging in the case of patients living with a major neurocognitive disorder (PLMNCD). Thus, it is important to incorporate patients’ and caregivers’ experiences of the transition from hospital to home in the risk assessment. This multiple case study comprised 7 PLMNCD, their caregivers, and occupational therapists. Fifty-four interviews, conducted just before, as well as 3 weeks and 3 to 6 months after hospital discharge, were qualitatively analyzed. Results revealed that risk management during the hospital-to-home transition is a dynamic process aimed at establishing a satisfactory routine while avoiding adverse events. This risk management process, which identifies challenges over time and between stakeholders, involves (a) determining the seriousness and acceptability of risks, (b) reflecting on ways to manage risks, and (c) taking steps to manage risks. This knowledge will help to provide more appropriate care and services that strike a balance between safety and autonomy.
Educating Hematology-Oncology Fellows About How to Communicate with Patients About Clinical Trials: A Needs Assessment
Authors: Parker Naomi D. , Murphy Martina C. , Eggly Susan , Weiss Elisa S. , Amin Tithi B. , Wollney Easton N. , Wright Kevin B. , Friedman Daphne R. , Sae-Hau Maria , Sitlinger Andrea , Staras Stephanie A. S. , Szumita Leah , Cooks Eric , Bylund Carma L.
Published: August 2024

Objectives

Only 5–8% of adults with cancer participate in cancer clinical trials (CCTs), with even lower rates among underrepresented groups. Improving oncologists’ communication skills may enhance the frequency and quality of their discussions with patients about CCTs, consequently increasing participation. However, little is known about interest in or presence of CCT-related communication training during Hematology-Oncology (Hem-Onc) fellowships. This study aimed to describe, from the perspective of Hem-Onc fellowship program directors (PDs): (1) the current landscape of CCT education for Hem-Onc fellows; (2) the acceptability and feasibility of implementing a CCT communication skills workshop for Hem-Onc fellows.

Methods

We used an explanatory sequential mixed-methods approach. PDs were surveyed and interviewed about their graduate medical education (GME) programs’ current CCT curriculum, training challenges, fellows’ CCT knowledge and CCT communication skills, and preferences for a CCT communication workshop.

Results

PDs were surveyed (n = 40) and interviewed (n = 12). PDs reported that their institutions prioritize CCT accrual (M = 4.58, SD = .78; 1-5 scale, 5 = “Strongly Agree”) and clinical research training (M = 4.20, SD = .85). CCT skills that programs least often addressed were how to (1) discuss CCTs with newly diagnosed patients, (2) talk to patients about CCTs when none are available, and (3) help patients find CCTs at other institutions. PDs were interested in a CCT communication workshop for fellows (“yes” = 67.5%, “maybe” = 32.5%) and said training would be feasible (M = 4.28, SD = .78) and useful (M = 4.47, SD = .78). Qualitative results described programs’ current approaches to CCT education and insights about developing and implementing CCT communication training.

Conclusions

There is a clear need to improve CCT communication skills training in Hem-Onc fellowship programs and to implement and scale such training to increase CCT participation, especially among diverse patient populations. Furthermore, Hem-Onc GME PDs view such training as feasible and useful.
Quantifying the effects of Singapore’s street configurations on people’s activity spaces
Authors: Govind Anirudh , Poorthuis Ate , Derudder Ben
Published: August 2024

Although it is generally accepted that street configurations may influence people’s intra-urban travel, capturing the exact nature of that influence remains challenging. We frame this challenge as one of operationalization and measurement and attempt to quantify and analyze the impact of street configurations more precisely. We draw on geographic data science tools to suggest that street configurations may be captured using catchment area polygons. To illustrate our approach, we derive these polygons for every building in Singapore and show that catchment area sizes spatially cluster, thus acting as proxies for street configurations. Using a spatial error model, we demonstrate that these catchment area sizes partially explain people’s intra-urban travel, conceptualized as their activity spaces. That is, as street configurations lead to larger catchment areas, people’s activity spaces tend to shrink. We show that the explanatory power of catchment area sizes is distinct from, albeit correlated with, other built environment variables (such as amenity density and land use diversity) typically used to explain people’s travel. We conclude by considering the potential of our approach in broader urban geographical research agendas drawing on street configurations and other morphological influences in the study of socio-spatial processes.
CDK9 phosphorylates RUNX1 to promote megakaryocytic fate in megakaryocytic-erythroid progenitors
Authors: Kwon Nayoung , Lu Yi-Chien , Thompson Evrett N. , Mancuso Rubia Isler , Wang Lin , Zhang Ping-Xia , Krause Diane S.
Published: August 2024

The specification of megakaryocytic (Mk) or erythroid (E) lineages from primary human megakaryocytic-erythroid progenitors (MEPs) is crucial for hematopoietic homeostasis, yet the underlying mechanisms regulating fate specification remain elusive. In this study, we identify RUNX1 as a key modulator of gene expression during MEP fate specification. Overexpression of RUNX1 in primary human MEPs promotes Mk specification, whereas pan-RUNX inhibition favors E specification. Although total RUNX1 levels do not differ between Mk progenitors (MkPs) and E progenitors (ErPs), there are higher levels of serine-phosphorylated RUNX1 in MkPs than ErPs, and mutant RUNX1 with phosphorylated-serine/threonine mimetic mutations (RUNX1-4D) significantly enhances the functional efficacy of RUNX1. To model the effects of RUNX1 variants, we use human erythroleukemia (HEL) cell lines expressing wild-type (WT), phosphomimetic (RUNX1-4D), and nonphosphorylatable (RUNX1-4A) mutants showing that the 3 forms of RUNX1 differentially regulate expression of 2625 genes. Both WT and RUNX1-4D variants increase expression in 40%, and decrease expression in another 40%, with lesser effects of RUNX1-4A. We find a significant overlap between the upregulated genes in WT and RUNX1-4D–expressing HEL cells and those upregulated in primary human MkPs vs MEPs. Although inhibition of known RUNX1 serine/threonine kinases does not affect phosphoserine RUNX1 levels in primary MEPs, specific inhibition of cyclin dependent kinase 9 (CDK9) in MEPs leads to both decreased RUNX1 phosphorylation and increased E commitment. Collectively, our findings show that serine/threonine phosphorylation of RUNX1 promotes Mk fate specification and introduce a novel kinase for RUNX1 linking the fundamental transcriptional machinery with activation of a cell type–specific transcription factor.
JAK2-mutant clonal hematopoiesis is associated with venous thromboembolism
Authors: Zon Rebecca L. , Sekar Aswin , Clapham Katharine , Oren Ohad , Niroula Abhishek , Bick Alexander G. , Gibson Christopher J. , Griffin Gabriel , Uddin Md Mesbah , Neuberg Donna , Natarajan Pradeep , Ebert Benjamin L.
Published: August 2024

Venous thromboembolism (VTE) is common among older individuals, but provoking factors are not identified in many cases. Patients with myeloid malignancies, especially myeloproliferative neoplasms (MPNs), are at increased risk for venous thrombosis. Clonal hematopoiesis of indeterminate potential (CHIP), a precursor state to myeloid malignancies, is common among older individuals and may similarly predispose to venous thrombosis. We evaluated overall and genotype-specific associations between CHIP and prevalent and incident VTE in >400 000 samples from the UK Biobank. CHIP was modestly associated with incident VTE with a hazard ratio (HR) of 1.17 (95% confidence interval [CI], 1.09-1.3; P = .002) but was not significantly associated with prevalent VTE with an odds ratio (OR) of 1.02 (95% CI, 0.81-1.23; P = .81). TET2-mutant CHIP was associated with incident VTE with a HR of 1.33 (95% CI, 1.05-1.69; P = .02). JAK2 mutations were highly associated with both prevalent and incident VTE risk, with an OR of 6.58 (95% CI, 2.65-16.29; P = 4.7 × 10–5) and a HR of 4.2 (95% CI, 2.18-8.08; P = 1.7 × 10–5), respectively, consistent with the thrombophilia associated with JAK2-mutant MPN. The association between JAK2-mutant CHIP and VTE remained significant after excluding potential undiagnosed MPN based on laboratory parameters. JAK2-mutant CHIP was more strongly associated with VTE but was less common than heterozygous factor V Leiden and heterozygous prothrombin gene mutation. These results indicate that most individuals with CHIP do not have an altered risk of thrombosis, but individuals with JAK2-mutant CHIP have a significantly elevated risk of VTE.
The elasticity of silicone-stabilized liposomes has no impact on their in vivo behavior
Authors: Hinz Alicja , Lewandowska-Łańcucka Joanna , Werner Ewa , Cierniak Agnieszka , Stalińska Krystyna , Dyduch Grzegorz , Szuwarzyński Michał , Bzowska Monika
Published: August 2024

Background

The elastomechanical properties of nanocarriers have recently been discussed as important for the efficient delivery of various therapeutics. Some data indicate that optimal nanocarriers’ elasticity can modulate in vivo nanocarrier stability, interaction with phagocytes, and uptake by target cells. Here, we presented a study to extensively analyze the in vivo behavior of LIP-SS liposomes that were modified by forming the silicone network within the lipid bilayers to improve their elastomechanical properties. We verified liposome pharmacokinetic profiles and biodistribution, including retention in tumors on a mouse model of breast cancer, while biocompatibility was analyzed on healthy mice.

Results

We showed that fluorescently labeled LIP-SS and control LIP-CAT liposomes had similar pharmacokinetic profiles, biodistribution, and retention in tumors, indicating that modified elasticity did not improve nanocarrier in vivo performance. Interestingly, biocompatibility studies revealed no changes in blood morphology, liver, spleen, and kidney function but indicated prolonged activation of immune response manifesting in increased concentration of proinflammatory cytokines in sera of animals exposed to all tested liposomes.

Conclusion

Incorporating the silicone layer into the liposome structure did not change nanocarriers’ characteristics in vivo. Further modification of the LIP-SS surface, including decoration with hydrophilic stealth polymers, should be performed to improve their pharmacokinetics and retention in tumors significantly. Activation of the immune response by LIP-SS and LIP-CAT, resulting in elevated inflammatory cytokine production, requires detailed studies to elucidate its mechanism.

Graphical Abstract
Predictive ability of hypotension prediction index and machine learning methods in intraoperative hypotension: a systematic review and meta-analysis
Authors: Mohammadi Ida , Firouzabadi Shahryar Rajai , Hosseinpour Melika , Akhlaghpasand Mohammadhosein , Hajikarimloo Bardia , Tavanaei Roozbeh , Izadi Amirreza , Zeraatian-Nejad Sam , Eghbali Foolad
Published: August 2024

Introduction

Intraoperative Hypotension (IOH) poses a substantial risk during surgical procedures. The integration of Artificial Intelligence (AI) in predicting IOH holds promise for enhancing detection capabilities, providing an opportunity to improve patient outcomes. This systematic review and meta analysis explores the intersection of AI and IOH prediction, addressing the crucial need for effective monitoring in surgical settings.

Method

A search of Pubmed, Scopus, Web of Science, and Embase was conducted. Screening involved two-phase assessments by independent reviewers, ensuring adherence to predefined PICOS criteria. Included studies focused on AI models predicting IOH in any type of surgery. Due to the high number of studies evaluating the hypotension prediction index (HPI), we conducted two sets of meta-analyses: one involving the HPI studies and one including non-HPI studies. In the HPI studies the following outcomes were analyzed: cumulative duration of IOH per patient, time weighted average of mean arterial pressure < 65 (TWA-MAP < 65), area under the threshold of mean arterial pressure (AUT-MAP), and area under the receiver operating characteristics curve (AUROC). In the non-HPI studies, we examined the pooled AUROC of all AI models other than HPI.

Results

43 studies were included in this review. Studies showed significant reduction in IOH duration, TWA-MAP < 65 mmHg, and AUT-MAP < 65 mmHg in groups where HPI was used. AUROC for HPI algorithms demonstrated strong predictive performance (AUROC = 0.89, 95CI). Non-HPI models had a pooled AUROC of 0.79 (95CI: 0.74, 0.83).

Conclusion

HPI demonstrated excellent ability to predict hypotensive episodes and hence reduce the duration of hypotension. Other AI models, particularly those based on deep learning methods, also indicated a great ability to predict IOH, while their capacity to reduce IOH-related indices such as duration remains unclear.
Lycium barbarum glycopeptide promotes neuroprotection in ET-1 mediated retinal ganglion cell degeneration
Authors: Lakshmanan Yamunadevi , Wong Francisca Siu Yin , So Kwok-Fai , Chan Henry Ho-Lung
Published: August 2024

Background

Vascular dysregulation is one of the major risk factors of glaucoma, and endothelin-1 (ET-1) may have a role in the pathogenesis of vascular-related glaucoma. Fruit extract from Lycium Barbarum (LB) exhibits anti-ageing and multitarget mechanisms in protecting retinal ganglion cells (RGC) in various animal models. To investigate the therapeutic efficacy of LB glycoproteins (LbGP) in ET-1 induced RGC degeneration, LbGP was applied under pre- and posttreatment conditions to an ET-1 mouse model. Retina structural and functional outcomes were characterised using clinical-based techniques.

Methods

Adult C57BL/6 mice were randomly allocated into four experimental groups, namely vehicle control (n = 9), LbGP-Pretreatment (n = 8), LbGP-Posttreatment (day 1) (n = 8) and LbGP-Posttreatment (day 5) (n = 7). Oral administration of LbGP 1 mg/Kg or PBS for vehicle control was given once daily. Pre- and posttreatment (day 1 or 5) were commenced at 1 week before and 1 or 5 days after intravitreal injections, respectively, and were continued until postinjection day 28. Effects of treatment on retinal structure and functions were evaluated using optical coherence tomography (OCT), doppler OCT and electroretinogram measurements at baseline, post-injection days 10 and 28. RGC survival was evaluated by using RBPMS immunostaining on retinal wholemounts.

Results

ET-1 injection in vehicle control induced transient reductions in arterial flow and retinal functions, leading to significant RNFL thinning and RGC loss at day 28. Although ET-1 induced a transient loss in blood flow or retinal functions in all LbGP groups, LbGP treatments facilitated better restoration of retinal flow and retinal functions as compared with the vehicle control. Also, all three LbGP treatment groups (i.e. pre- and posttreatments from days 1 or 5) significantly preserved thRNFL thickness and RGC densities. No significant difference in protective effects was observed among the three LbGP treatment groups.

Conclusion

LbGP demonstrated neuroprotective effects in a mouse model of ET-1 induced RGC degeneration, with treatment applied either as a pretreatment, immediate or delayed posttreatment. LbGP treatment promoted a better restoration of retinal blood flow, and protected the RNFL, RGC density and retinal functions. This study showed the translational potential of LB as complementary treatment for glaucoma management.
Insights into gemcitabine resistance in pancreatic cancer: association with metabolic reprogramming and TP53 pathogenicity in patient derived xenografts
Authors: Konaté Mariam M. , Krushkal Julia , Li Ming-Chung , Chen Li , Kotliarov Yuri , Palmisano Alida , Pauly Rini , Xie Qian , Williams P. Mickey , McShane Lisa M. , Zhao Yingdong
Published: August 2024

Background

With poor prognosis and high mortality, pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Standard of care therapies for PDAC have included gemcitabine for the past three decades, although resistance often develops within weeks of chemotherapy initiation through an array of possible mechanisms.

Methods

We reanalyzed publicly available RNA-seq gene expression profiles of 28 PDAC patient-derived xenograft (PDX) models before and after a 21-day gemcitabine treatment using our validated analysis pipeline to identify molecular markers of intrinsic and acquired resistance.

Results

Using normalized RNA-seq quantification measurements, we first identified oxidative phosphorylation and interferon alpha pathways as the two most enriched cancer hallmark gene sets in the baseline gene expression profile associated with intrinsic gemcitabine resistance and sensitivity, respectively. Furthermore, we discovered strong correlations between drug-induced expression changes in glycolysis and oxidative phosphorylation genes and response to gemcitabine, which suggests that these pathways may be associated with acquired gemcitabine resistance mechanisms. Thus, we developed prediction models using baseline gene expression profiles in those pathways and validated them in another dataset of 12 PDAC models from Novartis. We also developed prediction models based on drug-induced expression changes in genes from the Molecular Signatures Database (MSigDB)’s curated 50 cancer hallmark gene sets. Finally, pathogenic TP53 mutations correlated with treatment resistance.

Conclusion

Our results demonstrate that concurrent upregulation of both glycolysis and oxidative phosphorylation pathways occurs in vivo in PDAC PDXs following gemcitabine treatment and that pathogenic TP53 status had association with gemcitabine resistance in these models. Our findings may elucidate the molecular basis for gemcitabine resistance and provide insights for effective drug combination in PDAC chemotherapy.
The physical and mental aspects of quality of life among patients with eye diseases: a cross-sectional survey study in Afghanistan
Authors: Neyazi Ahmad , Hosaini Farooq , Razaqi Nosaibah , Ahmadi Mahsa , Padhi Bijaya Kumar , Neyazi Mehrab , Noorzad Elhama , Rahmani Adina , NoorMohammadi Morteza , Afzali Habibah , Tabib Raz Mohmmad , Griffiths Mark D.
Published: August 2024

Background

The present study examined the quality of life and its relationship with socio-demographic characteristics among eye patients.

Methods

A cross-sectional survey was administered from January 2022 to April 2022. Data were collected from participants with eye diseases (N = 617) in the Herat province of Afghanistan.

Results

Of the 617 participants, 63.4% had poor physical quality of life and 14.9% had poor mental quality of life. Multiple regression analysis indicated that poor physical quality of life was significantly associated with being above 54 years old (adjusted odds ratio [AOR] = 1.15, p = .0048), being female (AOR = 3.58. p < 0.01), being illiterate (AOR = 3.31, p = 0.01), being unemployed (AOR = 1.93, p = 0.04), and experiencing a traumatic event during the past month (AOR = 2.06, p = 0.02). Poor mental quality of life was associated with occupational status (being unemployed) (AOR = 3.62, p = 0.05), and experiencing a traumatic event in the past month (AOR = 3.49, p < 0.01).

Conclusion

The present study provides a novel contribution to the field eye diseases and quality of life especially in relation to Afghanistan where there has been very little research in this area. The results indicate that public health authorities in Afghanistan should implement policies to improve mental and physical aspects of quality of life of patients with eye diseases as well as formulating strategies to help improve it.
High-risk human papillomavirus genotyping in cervical cancers in Tanzania
Authors: Murenzi Gad , Vuhahula Edda , Kimambo Asteria , Matiku Subira , Tuyishime Obed , Liwa Edwin , Habanabakize Thomas , Rugengamanzi Eulade , Malango Atuganile , Kubwimana Gallican , Anastos Kathryn , Castle Philip E.
Published: August 2024

Background

High-risk human papillomavirus (hrHPV) infection causes almost all cervical cancer. Women living with human immunodeficiency virus (Women living with HIV: WLWHIV) are at a six-fold increased risk of developing cervical cancer. This study assessed hrHPV types in cervical cancer by HIV status and histologic subtypes at Muhimbili National Hospital (MNH) in Tanzania.

Methods

This cross-sectional study used formalin-fixed paraffin-embedded (FFPE) archived tissue blocks of cervical carcinomas diagnosed in the Department of Anatomical Pathology at MNH from January to December 2020. Tissue sections were tested for 15 HPV genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, and 68) using the Ampfire assay. The distribution of HPV genotypes was assessed and compared by HIV status and histologic subtypes.

Results

The mean age ± standard deviation (N = 227, with valid HPV results) was 55 ± 12.9 years, 28.6% (n = 65) were WLWHIV, and squamous cell carcinoma (SCC) was the most common histologic subtype (91.2%). Most cervical carcinomas (81.1%, n = 184) tested positive for hrHPV with HPV16 (44.1%), HPV18 (15.9%), HPV35 (8.4%) and HPV45 (5.7%) being the most common HPV types. hrHPV was higher among older women with 64.5%, 85.1% and 81.3% among 30–40, 41–60 and ≥ 61-year-old women, respectively (p = 0.033). HPV16 was more commonly detected in SCC (47.8%) than in adenocarcinomas (5%) (p < 0.0001). There was no difference in hrHPV positivity by HIV status.

Conclusions

We found a high proportion of hrHPV among cervical carcinomas diagnosed in Tanzania. Rolling out HPV vaccines that target more hrHPV types than HPV16/18, especially HPV35 and HPV45, could optimize protection against cervical cancer in Tanzania.