bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting Automated Vehicle Takeover Decision During the Nighttime
Authors: Liang Nade , Lim Chiho , Yu Denny , Prakah-Asante Kwaku O. , Pitts Brandon J.
Published: October 2023

Conditionally automated vehicles require drivers to take over control occasionally. To date, takeover performance has been mostly evaluated using only re-engagement time and quality metrics. However, the appropriateness of takeover decisions, which has not been considered by previous research, should also be included as a performance indicator as it reflects one’s situation awareness of the takeover scenario. The goal of this study was to use eye-tracking, demographic factors, workload, and non-driving-related task (NDRT) conditions to predict takeover decisions. Forty-three participants drove a simulated conditionally automated vehicle while performing visual NDRTs and needed to decide the most appropriate maneuver around a roadway obstacle. Six classifiers were used to predict takeover decisions. The Random Forest model achieved the best performance, and driving experience and perceived workload were the most influential features. Findings may be used to assist in the design of adaptive algorithms that support drivers taking over from automated vehicles.
Impacts of AI-Generated Confidence and Explanations on Task Performance and Trust in Human-autonomy Teaming
Authors: Ling Shihong , Zhang Yutong , Du Na
Published: October 2023

In human-autonomy teaming (HAT), human operators and intelligent agents cooperate and coordinate together to achieve shared goals. This study aimed to enhance autonomy transparency by proposing the automatic generation of confidence and explanations (bounding boxes, and bounding boxes and keypoints) and investigating their impacts in HAT. A total of 36 participants engaged in a simulated surveillance task, during which they were assisted by the intelligent agents we designed using Keypoint Faster R-CNN. As a result, we found that visual explanations using bounding boxes and keypoints improved detection task performance only when confidence was not visualized. Moreover, participants had higher trust in and preference for autonomy when visual explanations were provided but whether confidence was visualized did not influence their trust and preference. These findings have implications for the design of autonomy and can facilitate human-machine interactions in HAT.
Sharing Vehicle Situation Awareness Reduces Driver-Initiated Overrides in Urban Environments
Authors: Lee Joonbum , Rheem Hansol , Lee John D. , Szczerba Joseph F. , Rajavenkatanarayanan Akilesh , Mathieu Roy
Published: October 2023

Driver assistance technologies have rapidly advanced. However, using partially automated driving systems in urban environments is still challenging. The potential disuse of driving automation is one of the challenges that prevents users from taking full advantage of the system. To address this issue, we investigated whether sharing the vehicle’s situation awareness (SA) information could increase the proper use of driving automation in urban contexts. An Augmented Reality Head-Up Display (AR HUD) was developed to present the vehicle’s SA information, and its effect was tested using a driving simulator. We used a two-part mixed model to analyze driver reliance behavior. The results showed that sharing the vehicle’s SA information decreased override responses when the automation could handle the situation but had no significant effect on the override time. These findings suggest that providing drivers with the vehicle SA information can increase the appropriate use of driving automation in complex urban driving situations.
Promises and Trust Repair in UGVs
Authors: Esterwood Connor , Ali Arsha , George Zariq , Dubrow Samantha , Smereka Jonathon , Riegner Kayla , Tilbury Dawn , Robert Lionel P.
Published: October 2023

Unmanned ground vehicles (UGVs) are autonomous robots capable of performing tasks through self- navigation and decision-making. They have the potential to replace humans in dangerous driving scenarios. However, UGVs must be viewed as trustworthy to be accepted, and like any automation, they can make mistakes that decrease human trust in them. Trust repair strategies can mitigate the consequences of trust violations, but they are not always effective. To better understand their effectiveness on UGVs, we designed a between-subjects study examining promises on a UGV’s trustworthiness. Preliminary results showed that promises had a marginal impact on overall trustworthiness but were influential in repairing benevolence but not ability or integrity. These findings have implications for the design of UGV’s and trust repair theory.
Effects of Back-support Exoskeletons on Task Performance and Perceived Exertion During Construction-related Tasks: Differences related to Experience
Authors: Ojelade Aanuoluwapo , Kim Sunwook , Morris Wallace , Harris-Adamson Carisa , Barr Alan , Nussbaum Maury A.
Published: October 2023

The effects of three Back-support Exoskeletons (BSEs) on task performance (completion time) and perceived exertion were examined during simulated construction tasks. Forty participants (20 novices) completed the tasks using no BSE and three BSEs, each with two support settings (On and Off). There were significant main and interaction effects of Experience level on both outcome measures. Using BSEs negatively affected task performance for some tasks, though these effects were smaller among experienced participants. Interestingly, using BSEs inconsistently affected perceived physical effort, possibly due to the characteristics of the tasks, BSE designs, and experience levels. These results indicate that the effects of BSE on task performance and perceived physical effort are specific to experience level, BSE designs, and task demands. Further study is needed to better understand how to generalize these results to the actual work population.
Effect of a Simultaneous Mental Arithmetic Task to a MMH Lifting Task on Muscle Activity in the Trunk and Shoulders
Authors: Kachlan Anas , Lavender Steven A. , Sommerich Carolyn M.
Published: October 2023

Introduction: This study investigated the effects of concurrent mental demands on material handling tasks. Methods: Eleven subjects performed a material handling task with and without cognitive loads while lifting a 5 kg box to three different destination heights. The cognitive load was created by having participants perform a concurrent math task while lifting the box. The study measured the muscle activity in trunk and shoulder muscles. Results: The study found that, in select muscles, the cognitive load conditions led to longer lift times and increased cumulative muscle activity, but lower peak muscle activity. Conclusion: These findings suggest that lifting tasks with a concurrent cognitive load could lead to greater cumulative muscle activity, increasing the risk of muscular fatigue during manual material handling tasks.
Look Before You Leap: Insights On The Implementation Of Ai Across Healthcare Settings
Authors: Anders Shilo , Militello Laura G. , Bitan Yuval , Salwei Megan E. , Ratwani Raj , Papautsky Elizabeth Lerner
Published: October 2023

The prevalence of artificial intelligence (AI) is rapidly growing across industries including in health care. AI has the potential to improve patient safety (e.g., diagnostic error) and reduce clinician workload (e.g., documentation burden) and healthcare costs. Yet, many questions remain about how clinicians will interact with and use AI to support their work and how these technologies will impact clinician workflow, decision-making, and teamwork. It is also uncertain how patients will interact with AI, with a recent report suggesting 60 percent of US adults are uncomfortable with their health care providers using AI. In this panel, we will discuss AI applications across differing health care contexts and describe how AI influences clinician (and patient) workflows. We will outline considerations for the design and implementation of AI-based technologies in health care and needed areas of future research.
Learning data science methods through a mobile device and full body motion data
Authors: Jung SeHee , Wang Hanwen , Su Bingyi , Lu Lu , Qing Liwei , Xu Xu
Published: October 2023

This study presents a mobile app that facilitates undergraduate students to learn data science through their own full body motions. Leveraging the built-in camera of a mobile device, the proposed app captures the user and feeds their images into an open-source computer-vision algorithm that localizes the key joint points of human body. As students can participate in the entire data collection process, the obtained motion data is context-rich and personally relevant to them. The app utilizes the collected motion data to explain various concepts and methods in data science under the context of human movements. The app also visualizes the geometric interpretation of data through various visual aids, such as interactive graphs and figures. In this study, we use principal component analysis, a commonly used dimensionality reduction method, as an example to demonstrate the proposed learning framework. Strategies to encompass other learning modules are also discussed for further improvement.
Waking Up to the Challenge of Fatigue Management in Transportation
Authors: Rudin-Brown Christina M. , Filtness Ashleigh J. , Gauthier Michelle , Kirkley Crystal , Luisi Daria , Jaber Muataz , Price Jana , Thiffault Pierre
Published: October 2023

While a vehicle operator falling asleep at the controls is the most obvious symptom of fatigue in transportation operations, less extreme and apparent fatigue levels are reliably associated with performance impairments in, for example, attention, information processing, memory, and situation awareness. Compared to in other industries, fatigue in transportation is made more likely by challenges to the body's circadian rhythm caused by shiftwork and travel across time zones. While experiencing fatigue is a normal physiological and behavioral state, for drivers, pilots, mariners, and other vehicle operators, experiencing fatigue while operating a vehicle can have catastrophic consequences. Fatigue can also contribute to heightened, though less-direct, risk for those who support transport operations, such as shift schedulers, supervisors, and managers. This discussion panel will explore high risk and important human factors challenges to fatigue management facing transportation workers and their industries today, and some practical, and proven, ways to manage them.
Biochemical and Physiological Dynamics in Ligament Injury & Healing
Authors: Ramahi Amjad A , Fathallah Fadi , Jue Thomas
Published: October 2023

Ligaments play a crucial role in the musculoskeletal system. When maximal and sub-maximal ligamentous injury occur, a cascading response is initiated, starting with platelet plug formation and ending with remodeling. A rodent model was used to examine the role of modulating the initial recruitment of platelets and their impact on biochemical, histological, functional, and mechanical material properties. Functional gait testing, Enzyme Linked Immunosorbent Assay (ELISA), histological evaluations, and material property testing were performed. Animals (n=150) were randomized to a no-treatment group, a platelet rich fibrin treatment group and, a Nonsteroidal Anti-inflammatory Drug (NSIAD) treatment group. Initial results show that antiinflammatory drugs slow gait functional recovery; whereas, PRF shows faster functional recovery. PRF shows a faster increase in VEGF, and NSAIDs slows down VEGF and reduced its intensity. Evaluating injury recovery and impact of treatment methods, in both occupational and sports settings, provides insights about the healing response.
Control Task Analysis of the Deprescription Process: A Pilot Study
Authors: Wurst Connor , Chen Huei-Yen Winnie , Wahler Robert , Tenzek Kelly , Singh Ranjit , Cosmai Matthew , Wahler Alexandria , Monte Scott
Published: October 2023

Deprescription is the process by which a physician supervises a patient’s withdrawal or dose reduction of a given medication due to side effects or diminishing efficacy. Prior studies on the process of deprescription have resulted in a number of models, two of which are used in this pilot study alongside the decision ladder to construct a novel analytic method. Initial findings indicate that this approach can offer unique insight into the deprescription process, particularly regarding the paths physicians take through the decision making process and when certain factors are most important. These early results are limited but lay the foundation for a rich variety of future work.
Effects of Demographic and Socio-Economic Factors on Investigation Time of Lung Cancer Patients in Denmark: A Retrospective Cohort Study
Authors: Iachina Maria , Anru Pavithra Laxsen , Jakobsen Erik
Published: October 2023

Background

Lung cancer is one of the most common cancer types worldwide. The significance of the individual socio-economic position on the delay in lung cancer diagnosis has not been properly investigated. The purpose of this nationwide population-based study is to examine the association between position and the length of the primary investigation for lung cancer.

Materials and Methods

This register study was based on all lung cancer patients in Denmark who were diagnosed in 2012 to 2017, in total 28,431 patients. We used a multivariate logistic regression model and multivariate zero-inflated negative binomial model to estimate the effect of education level, family income, difficulty of transport, and cohabitation status on the length of the primary investigation.

Results

We found that the patients’ income, difficulty of transport, and cohabitation status were associated with the length of the primary investigation. The chance of carrying out the investigation process within 24 days is higher for patients with a high income (adjusted OR = 0.86 with 95% CI (0.81; 0.91)), lower for patients with troublesome transport (adjusted OR = 0.67 with 95% CI (0.61; 0.72)), and lower for patients living alone (adjusted OR = 0.93 with 95% CI (0.88; 0.99)).

Conclusion

Several socio-economic factors are associated with the length of the primary lung cancer investigation. To ensure that all patients receive the most appropriate health care and to avoid extra investigation time, clinicians may pay extra attention to patients who are less fortunate due to low income, troublesome transport to the hospital, or living alone.
Predictors of Survival Among the Oldest Old Following Acute Hospital Admission: Insights From Clinical and Biochemical Factors
Authors: Painkra Bhawana , Anwar Masroor , Singh Abhinay Kumar , Singh Vishwajeet , Rao Abhijith Rajaram , Rao Akshata , Thakral Meenal , Chakrawarty Avinash , Chatterjee Prasun , Dey Aparajit Ballav
Published: October 2023

Understanding the factors influencing survival in oldest old population is crucial for providing appropriate care and improving outcomes. This prospective observational study aimed to investigate the determinants of survival in acutely ill oldest old patients during acute hospitalization and 1-month follow-up. Various geriatric domains and biochemical markers were assessed. Among the 70 included patients with a median age of 87 (Inter quartile range: 85–90), the presence of diabetes, delirium, tachypnea, and high sirtuin-5 levels were associated with reduced in-hospital survival. Non-survivors had raised levels of Sirtuin 1 and Sirtuin 5, with an increase of 43% and 70%, respectively. At 1 month, delirium and diabetes were still associated with reduced survival. These findings suggest that type-2 diabetes, delirium, tachypnea, and high sirtuin-5 levels could serve as predictors of reduced survival in acutely ill, hospitalized oldest old patients.
Death world economy: Race, meat-processing plants, and COVID-19
Authors: Fukushima Annie Isabel , Gaytán Marie Sarita , Alvarez Gutiérrez Leticia
Published: October 2023

As COVID-19 outbreaks and deaths ravaged US meat-processing facilities, companies and officials supported production instead of people. Analyzing the content of newspaper articles, court records, press releases, and company websites, we argue that (1) despite their “essential” status, meat factory workers are a disposable labor force; and (2) factory worker dispensability is the result of a racialized historical process. The expendability of primarily immigrant and people of color laborers takes place in what we call a “death world economy”—a system through which corporations, together with the state, normalize the relegation of bodies to disease, injury, and death across time and space. Responding to the intensification of this violence during COVID-19, plant employees and their families advocate for their communities’ safety needs, highlight industry inaction, and demand accountability from companies and state officials.
Evolution of an Independent Research Institution: A Reflective Analysis
Authors: Jha Jyotsna
Published: October 2023

This article examines the idea of institutions and the elements of the process of institutionalisation, using the features of and experiences in an independent research organisation, which was established in 1998, in India. The author, using her experience of heading this organisation for nearly 13 years, and drawing from the Scott’s three pillar approach, reflects on the aspects of why and how an organisation becomes an institution, and what the joys and challenges of leading the process of institution building are. She argues that institution-building is a continuous process where Scott’s three pillars support each other, and change over time and space. The real test of an organisation in becoming an institution is in the capacity to respond to the emergent needs both inside the organisation, and to the external environment, while managing to work as per the vision and perceived mandate, maintain order and stability, within given resources and legal frameworks that guide the functioning of the organisation. Using her own experiences, she identifies plurality as the most important principle that helped in the process of institutionalisation in this case.
Surgical Setting in Achilles Tendon Repair: How Does It Relate to Costs and Complications?
Authors: Bronheim Rachel S. , Shu Henry T. , Jami Meghana , Hsu Nigel N. , Aiyer Amiethab A.
Published: October 2023

Background:

Primary Achilles tendon repair (ATR) can be performed in ambulatory surgery centers (ASCs) or hospitals. We compared costs and complication rates of ATR performed in these settings.

Methods:

We retrospectively queried the electronic medical record of our academic health system and identified 97 adults who underwent primary ATR from 2015 to 2021. Variables were compared between patients treated at ASCs vs those treated in hospitals. We compared continuous variables with Wilcoxon rank-sum tests and categorical variables with χ2 tests. We used an α of 0.05. Multivariable logistic regression was performed to determine associations between surgical setting and costs. Linear regression was performed between each charge subtype and total cost to identify which charge subtypes were most associated with total cost.

Results:

Patients who underwent ATR in hospitals had a higher rate of unanticipated postoperative hospital admission (13%) than those treated in ASCs (0%) ( P = .01). We found no differences with regard to postoperative complications, emergency department visits, readmission, rerupture, reoperation/revision, or death. Patients treated in hospitals had a higher mean (±SD) implant cost ($664 ± $810) than those treated in ASCs ($175 ± $585) ( P < .01). We found no differences between settings with regard to total cost, supply costs, operating room charges, or anesthesia charges. Higher implant cost was associated with hospital setting (odds ratio = 16 [95% CI: 1.7-157]) and body mass index > 25 (odds ratio = 1.2 [95% CI: 1.0-1.5]). Operating room costs were strongly correlated with total costs ( R2 = .94).

Conclusion:

The overall cost and complication rate of ATRs were not significantly different between ASCs and hospitals. ATRs performed in hospitals had higher implant costs and higher rates of postoperative admission than those performed in ASCs.

Level of Evidence:

Level III, retrospective comparative study.
Transabdominal Fetal Ultrasound Before Early-Term Planned Delivery for Norrie Disease
Authors: Justin Grant A. , Boyd Brita K. , Vajzovic Lejla
Published: October 2023

Purpose: To describe a case of early-term planned delivery of a fetus with Norrie disease. Methods: A retrospective chart review was performed. Results: A fetus with an older sibling with bilateral blindness from Norrie disease had positive NPD genetic testing on chorionic villus sampling. Transabdominal fetal ophthalmic ultrasound found bilateral total retinal detachments (RDs) at 32 weeks gestational age. The fetus was delivered at 37 weeks and had an examination under anesthesia, which showed bilateral inoperable RDs. Conclusions: Transabdominal fetal ophthalmic ultrasound was able to identity bilateral total RDs in utero. Further study is warranted on preterm or early-term delivery if a fetus has evidence of RD in utero.
Bayesian Analysis of Cross-Sectional Networks: A Tutorial in R and JASP
Authors: Huth Karoline B. S. , de Ron Jill , Goudriaan Anneke E. , Luigjes Judy , Mohammadi Reza , van Holst Ruth J. , Wagenmakers Eric-Jan , Marsman Maarten
Published: October 2023

Network psychometrics is a new direction in psychological research that conceptualizes psychological constructs as systems of interacting variables. In network analysis, variables are represented as nodes, and their interactions yield (partial) associations. Current estimation methods mostly use a frequentist approach, which does not allow for proper uncertainty quantification of the model and its parameters. Here, we outline a Bayesian approach to network analysis that offers three main benefits. In particular, applied researchers can use Bayesian methods to (1) determine structure uncertainty, (2) obtain evidence for edge inclusion and exclusion (i.e., distinguish conditional dependence or independence between variables), and (3) quantify parameter precision. In this article, we provide a conceptual introduction to Bayesian inference, describe how researchers can facilitate the three benefits for networks, and review the available R packages. In addition, we present two user-friendly software solutions: a new R package, easybgm, for fitting, extracting, and visualizing the Bayesian analysis of networks and a graphical user interface implementation in JASP. The methodology is illustrated with a worked-out example of a network of personality traits and mental health.
A Tai Chi Class Collaboratively Developed for Persons With Interstitial and Other Lung Diseases: An Ethnographic Investigation
Authors: Kilgore Karen , Leinfelder Jesse , Campbell Joan , Wayne Peter M. , Hallowell Robert W. , Barakat Aliaa
Published: October 2023

Background

Participating in physical activity (PA) can be challenging for persons with chronic and significant lung disease due to the multifaceted disruptive effects of their symptoms and variable disease course.

Objectives

Our study investigates a novel approach to increasing PA by collaboratively and adaptively developing a Tai Chi (TC) class for and by persons with lung diseases and explores participants’ perceptions of their experiences in the co-developed TC class.

Methods

We initiated a collaboration between the Interstitial Lung Disease (ILD) Collaborative and the Tai Chi Foundation to develop a TC class appropriate for persons with ILD and other lung diseases. The TC class was offered online, during the early phases of the COVID-19 pandemic, when pulmonary patients were isolated socially. TC class sessions were held twice weekly for 12 weeks with 12 participants. Ethnographic field methods were used to collect observations and conduct interviews with teachers and students. The Social Ecological Model (SEM) for understanding factors in intrapersonal, interpersonal, social, and organizational contexts was used to explore ways in which wellness practices, particularly those involving changes in health behaviors, can be collaboratively conceived, and developed by persons with the lived experience of illness and community organizations that are sensitive to their personal and social contexts. The constant comparative method was used for data analysis.

Results

Our findings include the importance of (1) creating a supportive class environment, characterized by interactive and reciprocal relationships among students and teachers; (2) alternating segments of movement and meditation to avoid fatigue and breathlessness; (3) cultivating sensory awareness and body trust, resting when needed and rejoining the movements when ready; (4) increasing the capacity to meditate through deepening presence and renewing the vital connection with inner and outer sources of energy; (5) reducing, through meditative movement, the persistent anxiety, isolation, and sense of loss that accompany chronic disease diagnosis and progression.

Conclusion

We documented a collaboration between the TC and pulmonary communities to design a TC class for persons with chronic and significant lung disease. We employed the SEM to provide insights into how teachers, informed by their students, can use effective pedagogical skills to create core curricula with modifications appropriate for a specific population.
Urban inequality – methods, flows and state processes
Authors: Jupp Eleanor
Published: October 2023

As DeVerteuil asserts, urban studies should engage anew with matters of inequality and social justice. In this commentary piece, additional perspectives on this task are offered, drawing on research on community action and austerity. These include the importance of paying attention to the importance of ‘small’ practices, feelings and affects as constitutive of urban politics, which can be accessed via ethnography; attending to the digital as it remakes city fabrics and communities; and new explorations of state processes drawing on feminist and psycho-social approaches.
Engineering validation of BB-SPEEDset, a data set of near-source physics-based simulated accelerograms
Authors: Smerzini Chiara , Amendola Chiara , Paolucci Roberto , Bazrafshan Arsalan
Published: October 2023

Physics-based numerical simulations (PBS) have progressed to the level of providing a realistic description of earthquake ground motion and of its variability, both in time and space, thus enabling to fill the knowledge gaps due to the sparsity of recordings (especially in the near-source region of strong earthquakes). Nevertheless, to build confidence in the utilization of the PBS by the engineering community, simulated accelerograms need to be validated against recorded data from both seismological and engineering perspectives. This article aims at extending the validation of BB-SPEEDset, a data set of near-source broadband simulated accelerograms from multiple regions and faulting styles, obtained by the spectral element computer code SPEED. In addition to seismological checks of BB-SPEEDset proving the absence of systematic biases with respect to a near-source records data set, in this work, the validation is addressed in terms of engineering demand parameters (EDPs) of elastoplastic single-degree-of-freedom systems, taking advantage of a ground motion selection tool including simulated accelerograms. It is found that, when simulated and recorded accelerograms are selected according to the same spectral compatibility criteria, consistent statistical distributions of EDPs are obtained from the two sets. To highlight the potentialities of BB-SPEEDset for near-source analyses, an example of utilization of spectrum-compatible pulse-like motions for structural inelastic analyses is also given, resulting in a good agreement with literature solutions in terms of inelastic displacement demands.
Considerations for Remote and Hybrid Service Delivery for Students With Visual Impairments
Authors: Liu Yichen , Anne Schles Rachel
Published: October 2023

The Individuals with Disabilities Education Act (IDEA) mandates high-quality special education services for U.S. students with visual impairments (VI) in their least restrictive environment. Due to shortages of teachers of students with visual impairments (TVIs) and other resources, however, many students with VI, especially those in rural or remote areas, receive limited Individualized Education Program (IEP) services from TVIs and may not consistently receive appropriately adapted materials for accessing the class content in a timely manner. One possible solution is hybrid service modality, consisting of in-person and remote instruction. This article discusses considerations for conducting high-quality hybrid services and practical strategies that TVIs can implement during the preparation and instruction of students with VI.
The bone marrow is the primary site of thrombopoiesis
Authors: Asquith Nathan L. , Carminita Estelle , Camacho Virginia , Rodriguez-Romera Antonio , Stegner David , Freire Daniela , Becker Isabelle C. , Machlus Kellie R. , Khan Abdullah O. , Italiano Joseph E.
Published: October 2023

Megakaryocytes (MKs) generate thousands of platelets over their lifespan. The roles of platelets in infection and inflammation has guided an interest to the study of extramedullary thrombopoiesis and therefore MKs have been increasingly reported within the spleen and lung. However, the relative abundance of MKs in these organs compared to the bone marrow and the scale of their contribution to the platelet pool in a steady state remain controversial. We investigated the relative abundance of MKs in the adult murine bone marrow, spleen, and lung using whole-mount light-sheet and quantitative histological imaging, flow cytometry, intravital imaging, and an assessment of single-cell RNA sequencing (scRNA-seq) repositories. Flow cytometry revealed significantly higher numbers of hematopoietic stem and progenitor cells and MKs in the murine bone marrow than in spleens or perfused lungs. Two-photon intravital and light-sheet microscopy, as well as quantitative histological imaging, confirmed these findings. Moreover, ex vivo cultured MKs from the bone marrow subjected to static or microfluidic platelet production assays had a higher capacity for proplatelet formation than MKs from other organs. Analysis of previously published murine and human scRNA-seq data sets revealed that only a marginal fraction of MK-like cells can be found within the lung and most likely only marginally contribute to platelet production in the steady state.
Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5)
Authors: Neelapu Sattva S. , Chavez Julio C. , Sehgal Alison R. , Epperla Narendranath , Ulrickson Matthew , Bachy Emmanuel , Munshi Pashna N. , Casulo Carla , Maloney David G. , de Vos Sven , Reshef Ran , Leslie Lori A. , Oluwole Olalekan O. , Yakoub-Agha Ibrahim , Khanal Rashmi , Rosenblatt Joseph , Korn Ronald , Peng Weixin , Lui Christine , Wulff Jacob , Shen Rhine , Poddar Soumya , Jung A. Scott , Miao Harry , Beygi Sara , Jacobson Caron A.
Published: October 2023

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel for patients with R/R indolent non-Hodgkin lymphoma (iNHL; N = 104), including FL and marginal zone lymphoma (MZL). In the primary analysis (median follow-up, 17.5 months), the overall response rate (ORR) was 92% (complete response rate, 74%). Here, we report long-term outcomes from ZUMA-5. Eligible patients with R/R iNHL after ≥2 lines of therapy underwent leukapheresis, followed by lymphodepleting chemotherapy and axi-cel infusion (2 × 106 CAR T cells per kg). The primary end point was ORR, assessed in this analysis by investigators in all enrolled patients (intent-to-treat). After median follow-up of 41.7 months in FL (n = 127) and 31.8 months in MZL (n = 31), ORR was comparable with that of the primary analysis (FL, 94%; MZL, 77%). Median progression-free survival was 40.2 months in FL and not reached in MZL. Medians of overall survival were not reached in either disease type. Grade ≥3 adverse events of interest that occurred after the prior analyses were largely in recently treated patients. Clinical and pharmacokinetic outcomes correlated negatively with recent exposure to bendamustine and high metabolic tumor volume. After 3 years of follow-up in ZUMA-5, axi-cel demonstrated continued durable responses, with very few relapses beyond 2 years, and manageable safety in patients with R/R iNHL. The ZUMA-5 study was registered at www.clinicaltrials.gov as #NCT03105336.
B-vitamins, related vitamers, and metabolites in patients with quiescent inflammatory bowel disease and chronic fatigue treated with high dose oral thiamine
Authors: Bager Palle , Hvas Christian Lodberg , Hansen Mette Mejlby , Ueland Per , Dahlerup Jens Frederik
Published: October 2023

Background

High doses of oral thiamine improve clinical fatigue scores in patients with quiescent inflammatory bowel disease (IBD) and chronic fatigue. In this study we analysed plasma samples obtained in a randomised clinical trial and aimed compare levels of vitamins B1, B2, B3 and B6, and their related vitamers and metabolites in patients with IBD, with or without chronic fatigue and with or without effect of high dose oral thiamine for chronic fatigue.

Methods

Blood samples from patients with fatigue were drawn prior and after thiamine exposure and only once for patients without fatigue. A wide panel of analysis were done at Bevital AS Lab.

Results

Concentration of flavin mononucleotide (FMN) was lower in patients with chronic fatigue compared to patients without fatigue (p = 0.02). Patients with chronic fatigue who reported a positive effect on fatigue after 4 weeks of high dose thiamine treatment had a statistically significantly lower level of riboflavin after thiamine treatment (p = 0.01).

Conclusion

FMN and Riboflavin were associated with chronic fatigue in patients with quiescent IBD. Levels of other B vitamins and metabolites were not significantly different between the investigated groups or related to effect of the thiamine intervention.

Clinical trial registration: ClinicalTrials.gov study identifier NCT036347359. Registered 15 August 2018, https://clinicaltrials.gov/study/NCT03634735?cond=Inflammatory%20Bowel%20Diseases&intr=Thiamine&rank=1
EFR3A: a new raft domain organizing protein?
Authors: Trybus Magdalena , Hryniewicz-Jankowska Anita , Wójtowicz Karolina , Trombik Tomasz , Czogalla Aleksander , Sikorski Aleksander F.
Published: October 2023

Background

Membrane rafts play a crucial role in the regulation of many important biological processes. Our previous data suggest that specific interactions of flotillins with MPP1 are responsible for membrane raft domain organization and regulation in erythroid cells. Interaction of the flotillin-based protein network with specific membrane components underlies the mechanism of raft domain formation and regulation, including in cells with low expression of MPP1.

Methods

We sought to identify other flotillin partners via the immobilized recombinant flotillin-2-based affinity approach and mass spectrometry technique. The results were further confirmed via immunoblotting and via co-immunoprecipitation. In order to study the effect of the candidate protein on the physicochemical properties of the plasma membrane, the gene was knocked down via siRNA, and fluorescence lifetime imaging microscopy and spot-variation fluorescence correlation spectroscopy was employed.

Results

EFR3A was identified as a candidate protein that interacts with flotillin-2. Moreover, this newly discovered interaction was demonstrated via overlay assay using recombinant EFR3A and flotillin-2. EFR3A is a stable component of the detergent-resistant membrane fraction of HeLa cells, and its presence was sensitive to the removal of cholesterol. While silencing the EFR3A gene, we observed decreased order of the plasma membrane of living cells or giant plasma membrane vesicles derived from knocked down cells and altered mobility of the raft probe, as indicated via fluorescence lifetime imaging microscopy and spot-variation fluorescence correlation spectroscopy. Moreover, silencing of EFR3A expression was found to disturb epidermal growth factor receptor and phospholipase C gamma phosphorylation and affect epidermal growth factor-dependent cytosolic Ca2+ concentration.

Conclusions

Altogether, our results suggest hitherto unreported flotillin-2-EFR3A interaction, which might be responsible for membrane raft organization and regulation. This implies participation of this interaction in the regulation of multiple cellular processes, including those connected with cell signaling which points to the possible role in human health, in particular human cancer biology.
Effects of dietary PUFA patterns and FADS genotype on breast milk PUFAs in Chinese lactating mothers
Authors: Xu Wen-Hui , Chen Yi-Ru , Tian Hui-Min , Chen Yi-Fei , Gong Jia-Yu , Yu Hai-Tao , Liu Guo-Liang , Xie Lin
Published: October 2023

Background

Breastfeeding affects the growth and development of infants, and polyunsaturated fatty acids (PUFAs) play a crucial role in this process. To explore the factors influencing the PUFA concentration in breast milk, we conducted research on two aspects: dietary fatty acid patterns and single nucleotide polymorphisms (SNPs) in maternal fatty acid desaturase genes.

Methods

Three hundred seventy Chinese Han lactating mothers were recruited. A dietary semi-quantitative food frequency questionnaire (FFQ) was used to investigate the dietary intake of lactating mothers from 22 to 25 days postpartum for 1 year. Meanwhile, breast milk samples were collected from the participants and tested for the concentrations of 8 PUFAs and 10 SNP genotypes. We sought to determine the effect of dietary PUFA patterns and SNPs on breast milk PUFAs. We used SPSS 24.0 statistical software for data analysis. Statistical tests were all bilateral tests, with P < 0.05 as statistically significant.

Results

Under the same dietary background, PUFA contents in breast milk expressed by most major allele homozygote mothers tended to be higher than that expressed by their counterparts who carried minor allele genes. Moreover, under the same gene background, PUFA contents in breast milk expressed by the mother’s intake of essential PUFA pattern tended to be higher than that expressed by their counterparts who took the other two kinds of dietary.

Conclusions

Our study suggests that different genotypes and dietary PUFA patterns affect PUFA levels in breast milk. We recommend that lactating mothers consume enough essential fatty acids to ensure that their infants ingest sufficient PUFAs.
TreeKernel: interpretable kernel machine tests for interactions between -omics and clinical predictors with applications to metabolomics and COPD phenotypes
Authors: Carpenter Charlie M. , Gillenwater Lucas , Bowler Russell , Kechris Katerina , Ghosh Debashis
Published: October 2023

Background

In this paper, we are interested in interactions between a high-dimensional -omics dataset and clinical covariates. The goal is to evaluate the relationship between a phenotype of interest and a high-dimensional omics pathway, where the effect of the omics data depends on subjects’ clinical covariates (age, sex, smoking status, etc.). For instance, metabolic pathways can vary greatly between sexes which may also change the relationship between certain metabolic pathways and a clinical phenotype of interest. We propose partitioning the clinical covariate space and performing a kernel association test within those partitions. To illustrate this idea, we focus on hierarchical partitions of the clinical covariate space and kernel tests on metabolic pathways.

Results

We see that our proposed method outperforms competing methods in most simulation scenarios. It can identify different relationships among clinical groups with higher power in most scenarios while maintaining a proper Type I error rate. The simulation studies also show a robustness to the grouping structure within the clinical space. We also apply the method to the COPDGene study and find several clinically meaningful interactions between metabolic pathways, the clinical space, and lung function.

Conclusion

TreeKernel provides a simple and interpretable process for testing for relationships between high-dimensional omics data and clinical outcomes in the presence of interactions within clinical cohorts. The method is broadly applicable to many studies.
Xpert MTB/RIF assay for the differential diagnosis between sarcoidosis and tuberculosis intrathoracic lymphadenopathy
Authors: He Xian , Zhang Yuan , Zhou Ying , Li Li , Li Qiuhong
Published: October 2023

Background

The aim of this study was to evaluate the role of Xpert MTB/RIF assay in the detection of Mycobacterium tuberculosis for differentiating tuberculosis intrathoracic lymphadenopathy from sarcoidosis intrathoracic lymphadenopathy.

Methods

The patients who were suspected to having sarcoidosis or tuberculosis intrathoracic lymphadenopathy at the Shanghai Pulmonary Hospital between October 1, 2020 and June 30, 2021 were retrospectively evaluated in this study. All patients underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and Xpert analysis. Differences in clinical and radiological features were recorded. The diagnostic performances of EBUS-TBNA Xpert, acid-fast bacilli, culture, and peripheral blood QuantiFERON-TB Gold (QFT) for differentiating sarcoidosis from tuberculosis intrathoracic lymphadenopathy were analyzed.

Results

A total of 119 patients were included in this analysis. Of those, 83 patients were finally diagnosed with sarcoidosis (N = 50) and tuberculosis (N = 33) intrathoracic lymphadenopathy. Young individuals were more likely to have tuberculosis versus sarcoidosis intrathoracic lymphadenopathy (P = 0.006). Markers of inflammation, including fever, leukocytes, and serum ferritin levels, were significantly higher in tuberculosis versus sarcoidosis intrathoracic lymphadenopathy (P < 0.01). Bilateral lung involvement and symmetry intrathoracic lymphadenopathy were more common in sarcoidosis intrathoracic lymphadenopathy (P < 0.01). In addition, the longest diameter of intrathoracic lymphadenopathy (in cm) was significantly larger in sarcoidosis intrathoracic lymphadenopathy (P = 0.001). However, the largest diameter of lung lesions was significantly shorter (P = 0.005). The sensitivity and specificity values of Xpert and QFT for differentiating these two diseases were 69.70% and 100%, and 96.43% and 91.84%, respectively.

Conclusion

Xpert MTB/RIF is recommended for the diagnosis of tuberculosis intrathoracic lymphadenopathy using EBUS-TBNA samples. A negative QFT suggests the exclusion of the diagnosis of tuberculosis intrathoracic lymphadenopathy.
Characteristics of sodium and water retention in rats with nephrotic syndrome induced by puromycin aminonucleoside
Authors: Xu Zaiping , Wang Yunlai , Feng Ye , Yang Mo , Shi Gaoxiang , Xuan Zihua , Xu Fan
Published: October 2023

Introduction

Nephrotic syndrome (NS) is characterized by renal sodium and water retention. The mechanisms are not fully elucidated.

Methods

The NS rat model was established by single intraperitoneal injection of 100 mg/kg puromycin aminonucleoside (PAN). The plasma electrolyte level and urinary sodium excretion were monitored dynamically. The changes of some sodium transporters, including epithelial Na+ channel (ENaC), Na+/H+ exchanger 3 (NHE3), Na+-K+-2Cl− cotransporter 2 (NKCC2) and Na+-Cl− cotransporter (NCC) in renal cortex at different time points and the level of peripheral circulation factors were detected.

Results

The urinary sodium excretion of the model group increased significantly on the first day, then decreased compared with the control group, and there was no significant difference between the model group and the control group on the 12th day. The changes of peripheral circulation factors were not obvious. Some sodium transporters in renal cortex increased in varying degrees, while NKCC2 decreased significantly compared with the control group.

Conclusions

The occurrence of NS edema may not be related to the angiotensin system. The decrease of urinary sodium excretion is independent of the development of albuminuria. During the 18 days of observation, it can be divided into three stages: sodium retention, sodium compensation, and simple water retention. The mechanism is related to the increased expression of α-ENaC, γ-ENaC, NHE3 and NCC in a certain period of time, the compensatory decrease of NKCC2 expression and the continuous increase of aquaporin 2 (AQP2) expression.
Relationship between lead concentration in maternal and umbilical cord blood and some neonatal outcomes in primiparous opium-dependent mothers in Zahedan, Southeast of Iran in 2022
Authors: Khayat Samira , Fanaei Hamed
Published: October 2023

Background

There are limited studies on maternal and umbilical cord blood lead levels and their relationship with each other and with pregnancy outcomes in women addicted to opium. The present study was conducted with the aim of investigating the relationship between lead concentrations in maternal blood and umbilical cord blood with some neonatal outcomes in primiparous opium-dependent mothers.

Method

The present study is a cross-sectional and analytical research. A total of 35 mothers addicted to opium and 35 women without addiction from Zahedan city of Iran participated in this study in 2022. Convenience sampling was done, lead levels were measured and pregnancy outcomes checked by a checklist to collect information. Data analysis was done by independent t-tests, Pearson’s correlation coefficient, Point-Biserial Correlation Coefficient, multivariate linear regression and multivariate logistic regression using SPSS version 26 software.

Results

There was a significant difference in maternal blood lead levels (24.97 ± 8.45 in addicted mothers and 7.5 ± 4.25 in healthy mothers) and in umbilical cord blood lead concentrations (18.68 ± 6.95 in the addicted group and 5.7 ± 2.84 in the healthy group) between the two groups (P < 0.0001 and P < 0.0001, respectively).The lead concentration of all the samples in the addicted group was higher than the high-risk levels. Birth weight, Apgar score, admission to NICU and need for resuscitation were significantly different between the two groups (P < 0.0001, P < 0.0001, p = 0.03 and p = 0.04, respectively). Based on the results of multivariate linear regression test, only addiction can reversely predict the birth weight (Beta= -0.74, P < 0.0001), 1-minute Apgar score (Beta = -0.47, P = 0.004) and 5th minute (Beta= -0.62, P = 0.001). According to multivariate logistic regression test, OR of none of the predictor variables was significant with the outcomes. Maternal and umbilical cord blood lead concentrations were not predictors of pregnancy outcomes.

Conclusion

The use of opium during pregnancy leads to an increase in the level of lead in maternal blood and umbilical cord blood. Addiction increased adverse pregnancy outcomes but lead concentration did not predict pregnancy complications. It is recommended that the addiction treatment program be included in pre-pregnancy and pregnancy care plans.