bluuebunny/crossref_metadata_2025 huggingface dataset:
Why do Songs get “Stuck in our Heads”? Towards a Theory for Explaining Earworms
Authors: Arthur Claire
Published: April 2023

This paper offers a critical reflection on the paucity of theories for the phenomenon of “earworms,” also known as involuntary musical imagery (INMI), and poses some as-yet unanswered questions relating to the unique nature of the phenomenon, the optimal conditions for earworm induction, as well the underlying mechanisms that may drive the behavior. While numerous earworm studies have focused on analyzing the symptoms of the phenomenon, few studies have attempted to focus on investigating the underlying cause. In addition, common explanations are typically tied to proximal rather than distal causes (e.g., recent exposure). In particular, the question of “why music” (as opposed to other time-based auditory stimuli such as language/poetry), or, perhaps “what about music” is raised, and some conjectures and starting places for future studies are offered. Possible theoretical avenues and testable hypotheses are suggested, based on synthesizing informal observations and existing empirical research across multiple disciplines.
Researching Forms of Shadow Education: Methodological Challenges and Complexities of Private Supplementary Tutoring in Myanmar
Authors: Suante Peter Kamtungtuang , Bray Mark
Published: April 2023

Purpose

The growing literature on private supplementary tutoring, widely known as shadow education, addresses multiple dimensions and roles. However, many studies inadequately capture the diversity and implications of different forms of tutoring. This paper examines these matters in Myanmar, highlighting complexities and ambiguities in descriptors and in the nature of provision.

Design/Approach/Methods

Using a mixed-methods design, this study was conducted in Mandalay Region and Chin State. The data were obtained from interviews with 110 Grade 11 students, 34 high school teachers, 30 parents, 29 private tutoring providers, and two private school owners.

Findings

The article categorizes tutoring forms based on their styles and orientations, particularly lecture-type teaching and homework supervision by guides, class sizes, durations of fee-charging (e.g., annually), the number of subjects taught per tutor, and tutoring locations. The study brings the topic out of the shadows for clearer analysis of the phenomenon and thus for assessment of its implications.

Originality/Value

The study makes a methodological contribution to the wider picture by demonstrating the need for greater clarity and precision in the national and international comparative literatures. It also underscores shortcomings of predetermined categories in questionnaires and the value of qualitative interviews.
On the Trail of Self-Directed Online Learners
Authors: Bonk Curtis J. , Zhu (朱美娜) Meina
Published: April 2023

Purpose

We describe a series of more than a dozen studies on self-directed online learning spanning over a decade.

Design/Approach/Methods

We incorporated surveys, interviews, focus groups, and content analyses into these research studies, which initially targeted the goals, motivations, and challenges of learners using open educational resources and OpenCourseWare and then focused on learning from massive open online courses (MOOCs). This research accelerated after creating a database of over 3,000 MOOC instructors, through which we explored cultural sensitivity and personalization practices in MOOCs as well as instructional design considerations and challenges, MOOC instructor professional development and career development, instructor motivation and engagement, and student and instructor perceptions of self-directed learning.

Findings

This study reveals that self-directed online learners (SDOLs) seek learning environments offering freedom, choice, control, and a sense of autonomy and that both learners and instructors have intrinsic motivation for engaging in open online learning environments.

Originality/Value

Based on this research with both MOOC instructors and MOOC learners, we offer instructional design guidelines to address SDOLs’ needs and assist in efforts to foster a new generation of SDOLs.
America’s Racial Reckoning Within Perinatal Communication: A Rapid Review Using Sociotechnical Systems Theory to Compare Publications Before and After 2020
Authors: Henderson Maren S.G. , JaKa Meghan M. , Dinh Jennifer M. , Olson-Bullis Barbara A. , Brown-Robinson Corinne , Kottke Thomas E. , Ziegenfuss Jeanette Y.
Published: April 2023

Perinatal communication is one factor driving racial disparities in maternal and infant morbidity. The murder of George Floyd in May 2020, in addition to the disproportionate impacts of the Covid-19 pandemic on communities of color, was a catalyst for American society to address racial injustices with a renewed sense of urgency. Drawing upon sociotechnical systems (STS) theory, this rapid review describes changes in the literature regarding the organizational, social, technical, and external subsystems that affect communication between perinatal providers and their Black patients. The goal of this work is to support health system optimization of health communication initiatives and, as a result, improve patient experience and parent and child outcomes. As part of a multi-year project designed to improve health communications about safe fish consumption during pregnancy, and in response to racial disparities among our health system’s patient population related to receipt of nutrition messages during prenatal visits, we conducted a rapid review of literature on Black parents’ experience of all communication while receiving perinatal care. A search of PubMed identified relevant articles published in English since 2000. Articles were screened to include articles that focused on Black people receiving perinatal care. Article content was then coded using deductive content analysis guided by STS theory to inform healthcare system improvement efforts. Differences in the prevalence of codes pre- and post-2020 are compared using chi-square statistics. The search in PubMed yielded 2419 articles. After screening, 172 articles were included in the rapid review. There was an increased recognition of communication as a key component of quality perinatal care after 2020 ( P = .012) and of the limitations of standardized technical communication ( P = .002) after 2020. Emerging literature suggests improving perinatal health communication and relationships with Black parents would address disparities in perinatal patient and baby outcomes. Healthcare systems must address the racial disparities in maternal and child outcomes. Since 2020, public attention and published research on this issue has increased. Understanding perinatal communication using STS theory aligns subsystems in service of racial justice.
Odds of Achieving Target Serum Uric Acid Levels Among Gout Patients: The Role of Rurality in Outcomes and Treatment Adherence
Authors: Sutton S. Scott , Magagnoli Joseph , Cummings Tammy H. , Hardin James W.
Published: April 2023

Objective:

The goal of this paper was to analyze patient outcomes related to gout treatment including, serum uric acid (sUA) measures and treatment adherence across patients in metropolitan, micropolitan or rural counties.

Methods:

We conducted a drug-disease cohort study among patients with gout initiating urate lowering therapy. The proportion of patients with sUA < 6 mg/dL at 1 year of follow-up is compared over the cohort groups using a chi-square test and adjusted logistic regression. Adherence to urate lowering therapy was calculated using the proportion of days covered (PDC). A T-test was used to compare the average PDC and an adjusted logistic regression model was used to estimate the odds of a PDC greater than 80%.

Results:

A total of 9922 patients were included in the study. Most patients were in a metropolitan (77.4%) area, followed by micropolitan (11.8%) and finally, (10.8%) in a rural area. We found no statistically significant difference among the proportion of patients achieving target sUA of <6 mg/dL, 37.17% among metropolitan patients, 38.9% among micropolitan patients, and 37.7% for those in a rural area, P-value = .502. The proportion of patients achieving 80% treatment adherence was 49.92% in the metropolitan, 51.78% in the micropolitan, and 55.05% in the rural areas, P-value = .005. Adjusted regression models showed no statistically significant difference in proportions achieving target sUA levels or 80% adherence.

Conclusions:

Urban patients treated for gout did not have better gout outcomes compared to rural patients. Future research should consider provider-based interventions to improve outcomes.
Exploring Factors of HR Climate and Their Influence on Faculty Retention: Unfolding HRM in Indian Higher Educational Settings
Authors: Verma Sahil , Kaur Gurvinder
Published: April 2023

Human resource climate plays an important role in associating people with their organizations. However, there is a lack of empirical evidence about how faculty perceives components of the HR system, particularly in higher educational institutions. The aim of this paper is to explore the factors of HR climate and study their association with faculty retention in different Indian universities. The data for this study was collected through structured questionnaire administered to 306 faculty members of universities and their responses were analyzed using SPSS and AMOS. The results revealed that mentoring, professional development and compensation were perceived as major components of the HR climate. Of these three, mentoring and professional development played a significant role in predicting faculty retention. The post-hoc results showed that the factors varied in their significance according to the university type. These findings suggest that Indian universities lack a formal HR system and the need to integrate HR departments in the university environment is strongly recommended.
From Supportive to Strained: A Mixed Methods Exploration of Emerging Adults’ Characterizations of Past and Present Grandparent-Grandchild Roles and Relationships
Authors: Stephan Abigail T. , Hochstetter Nora D. , Clark Virginia E. , Jamil Faiza M.
Published: April 2023

Though many emerging adults now have the opportunity to engage meaningfully with their grandparents, few studies have examined emerging adults’ perceptions of grandparent relationships and the roles taken on by grandparents and grandchildren. Informed by theories of psychosocial development, intergenerational solidarity, and sociocultural learning, this mixed methods study draws on closed- and open-ended survey items to explore emerging adults’ ( N=52) characterizations of their relationships with grandparents in the United States. Results highlight the roles assumed by grandparents and emerging adult grandchildren often mirror each other, taking on instrumental, relational, and guiding qualities. The relationship itself was often described as a bond that is simultaneously punctuated by obstacles limiting close connections (e.g., geographic distance, challenging family dynamics). These findings suggest grandparent-grandchild relationships, both past and present, hold salience for emerging adults; researchers and practitioners should consider broader family systems when considering grandparent-grandchild relationships and their impact on individual development.
Accuracy of Self-Reported Physical Capacities as a Clinical Screening Test for Older Adults With Mobility Disability
Authors: Sciamanna Christopher N. , Lemaster Kent A. , Danilovich Margaret K. , Conroy David E. , Schmitz Kathryn H. , Silvis Matthew , Ladwig Matthew , Ballentine Noel
Published: April 2023

Background: Screening for poor physical performance has the potential to identify older adults at risk for loss of future independence, yet clinically feasible measures have yet to be identified. Methods: Using data from the National Health and Aging Trends Study, we evaluated the diagnostic utility of self-reported physical capacities of older adults (walking three blocks or six blocks, climbing 10 stairs or 20 stairs) compared to the objectively measured Short Physical Performance Battery (SPPB). Sensitivity, specificity, and likelihood ratio (LR) were calculated across three SPPB cut-points (≤8, ≤9, ≤10). Results: Sensitivity of single item-measures for detecting a low SBBP averaged 0.39 (range: 0.26–0.52), specific averaged 0.97 (range: 0.94–0.99) and likelihood ratio averaged 20.0 (range: 9.0–35.5). Among age and gender subgroups, all measures maintained clinically applicable LRs (minimum = 4.59). Conclusion: Single-item self-reported physical capacities are accurate for screening older adults with physical limitations, making them potentially useful in healthcare settings.
The Effect of Chewing Sugar-Free Gum to Improve Bowel Movement After Colorectal Surgeries in Patients With Colorectal Cancer
Authors: Al-kharabsheh Mohammad , Alwahedi Huda , Elhamshary Jaber , Younis Lina , Al Masri Mahmoud
Published: April 2023

Introduction

Colorectal cancer is classified as the second most prevalent type of cancer among males and females in Jordan; approximately 1260 (10.9%) out of 11559 cases were diagnosed with colorectal cancer in 2020. According to American statistics, colorectal cancer is the third leading cause of cancer-related deaths among both males and females, as well as the second leading cause when combining both numbers .

Objective

The current study aimed to assess the effectiveness of chewing gum in reducing postoperative ileus in patients with cancer after colorectal surgeries and evaluate the length of hospital stay (LOS) after colorectal resection, complications, and costs.

Methods

One-hundred twenty-nine patients who underwent colorectal surgeries at a specialized cancer center in Jordan from April 2019 to May 2020 were recruited. After colorectal surgeries, patients were randomized into two groups. The control group (69 patients) received conventional postoperative care; the experimental group (60 patients) was asked to chew free sugar gum over one hour in the morning, noon, and evening until the first flatus.

Result

The passage of the first flatus was significantly shorter in the experimental group (mean 48.02 h) than in the control group (116.45); p = .001. Also, there was a significant difference between both groups according to gender and age.

Conclusion

Chewing free sugar gum after colorectal surgeries can significantly improve the recovery of bowel motion by accelerating the time to first auscultation to bowel sounds, the first passage of flatus, and reduction in the LOS, which went in agreement with many studies. However, chewing gum is considered a safe, cheap, and practical method to reduce ileus.
Assessment of Alarm Fatigue Risk Among Oncology Nurses in Jordan
Authors: Ali Al-Quraan Hamza , Eid Amjad , Alloubani Aladeen
Published: April 2023

Introduction

Using technology in the clinical setting where clinical alarms frequently occur, resulting in many false alarms, which is called alarm fatigue, alarm fatigue may increase nurses’ distraction, and that might negatively affect patient safety.

Objective

This study aimed to assess alarm fatigue among oncology nurses in Jordan.

Methods

A descriptive cross-sectional design was used in a non-profit specialized cancer center. A self-reported questionnaire was answered by nurses who participated in the study.

Results

A total of 222 questionnaires were analyzed with a more than 95% response rate. More than half of the sample (60.4%) were females. The participants were young nurses with a mean age of 25.18 ± 3.33 years. The total mean score of alarm fatigue was 31.62 ± 7.14 on a scale ranging from zero to 52. Post-hoc analysis showed that the palliative unit (25.73 ± 7.22) and emergency room (28.73 ± 6.62) had low scores of total mean alarm fatigue than remaining area of practice, such as the ICU (33.92 ± 6.99); p-value: .004.

Conclusion

Alarm fatigue is a global issue affecting many practice areas. An educational program is recommended for nurses to learn how to deal with alarm fatigue. In order to effectively manage alarms, nurses’ education and individual training are crucial.
Examining heat inequity in a Brazilian metropolitan region
Authors: Jung Meen Wook , Haddad Mônica A , Gelder Brian K
Published: April 2023

Urban heat islands (UHIs) are one of the major global issues that need to be addressed because of the negative effects that higher temperatures can cause to people and the environment, such as health issues and higher energy consumption. Within the literature on climate justice, specifically heat inequity, there are very few studies about Global South urban areas. Our study examines the spatial relationships between heat risk, urban form composition, and vulnerable social groups in Belo Horizonte Metropolitan Region (BHMR), in Brazil. We evaluated the spatial pattern of heat risk and concluded that the study area was experiencing UHIs in 2015. We estimated spatial regressions and found that the non-White population, low-income residents, and the elderly population were statistically significantly associated with heat risk. This case study indicates that even though Global South urban areas have the opposite spatial distribution of social groups (i.e., high-income residents living in the center and low-income living in the periphery) when compared to the Global North, areas where vulnerable social groups reside are experiencing similar inequities concerning the UHI effects in both South and North. Our case study exemplifies that climate justice is not taking place in BHMR, and specifically, heat inequity is being experienced by vulnerable social groups.
Modeling the spatial dynamics of income in cities
Authors: Verbavatz Vincent , Barthelemy Marc
Published: April 2023

Urban inequality is a major challenge for cities in the 21st century. This inequality is reflected in the spatial income structure of cities which evolves in time through various processes. Gentrification is a well-known illustration of these dynamics in which the population of a low-income area changes as wealthier residents arrive and old-settled residents are expelled. Less understood but very important is the reverse process of gentrification through which areas of cities get impoverished. Gentrification has been widely studied among social sciences, especially in case studies, but there have been fewer quantitative analyses of this phenomenon, and more generally about the spatial dynamics of income in cities. Here, we first propose a quantitative analysis of these income dynamics in cities based on household incomes in 45 American and nine French Functional Urban Areas (FUA). We found that an important ingredient that determines the evolution of the income level of an area is the income level of its immediate neighboring areas. This empirical finding leads to the idea that these dynamics can be modeled by the voter model of statistical physics. We show that such a model constitutes an interesting tool for both describing and predicting evolution scenarios of urban areas with a very limited number of parameters (two for the United States and one for France). We illustrate our results by computing the probability that areas will change their income status in the case of Boston and Paris at the horizon of 2030.
Rotator Cuff Repair With a Novel Interpositional Allograft Augmentation
Authors: Forsythe Brian , Gamsarian Vahram , Mirle Vikranth , Berlinberg Elyse J. , Patel Harsh H. , Swindell Hasani , Yanke Adam B. , Garrigues Grant E. , Brusalis Christopher M.
Published: April 2023

Background:

Nearly half a million rotator cuff repairs are performed annually in the United States. Rotator cuff healing occurs at the interface between the tendon and greater tuberosity, known as the enthesis. Given that a significant number of rotator cuff tears do not heal following surgical repair, multiple adjunctive strategies have been devised to improve the structural integrity of the repaired construct. Recently, a biphasic, demineralized allograft bone implant has been developed to improve enthesis healing.

Indications:

Relative indications for use of tissue augmentation include greater tuberosity osteopenia, revision rotator cuff surgery, attenuated rotator cuff tissue quality, and massive rotator cuff tears. Relative contraindications include a history of infection and recent immunosuppression.

Technique Description:

Following preparation of the footprint with an arthroscopic burr, two triple-loaded PEEK suture anchors were placed along the medial aspect of the greater tuberosity. Sutures were then passed through the rotator cuff tendon in a horizontal mattress configuration, and each pair of suture limbs were tied along the medial row. To aid in arthroscopic passage, the biphasic graft is folded longitudinally and clamped with a curved hemostat. The graft is loaded into an arthroscopic cannula and both are delivered simultaneously through a lateral arthroscopic portal. Two 18-gauge spinal needles are placed percutaneously to fix the allograft in the desired position. Subsequently, double-row transosseous-equivalent rotator cuff repair with standard techniques is done, which provides sufficient stability to the graft.

Discussion:

In a series of 192 patients who underwent arthroscopic rotator cuff repair augmented with a similar bioinductive collagen implant, patients demonstrated significant improvement in patient-reported outcomes at 1 year postoperatively. Moreover, a meta analysis published in 2022 demonstrated a significantly reduced retear rate among patch-augmented rotator cuff repairs as compared to isolated rotator cuff repairs.

Conclusion:

Tissue augmentation can be performed efficiently and reproducibly to promote biologic healing of arthroscopic rotator cuff repairs. The specific biphasic cancellous allograft presented in this video may be a viable treatment adjunct in the setting of deficient greater tuberosity bone stock, revision cases, or impaired native enthesis healing; however, further research is needed to assess clinical outcomes associated with its use.

Patient Consent Disclosure Statement:

The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
What are the ways in which a culturally responsive school leader influences the learning environment of historically marginalized students in an urban high school?
Authors: Kandjanga Fabrice Kabele
Published: April 2023

This qualitative case study describes one urban school leader’s behaviors in the process of implementing culturally responsive school practices. Through deductive and inductive analysis, this study identifies key behaviors of urban culturally responsive school leaders that promote sustainable culturally responsive practices in their schools. Evidence from interviews, observations, and documents shows the unique actions that culturally responsive school leaders embody and how they respond to culturally unique school contexts. Further research is recommended to expand the understanding and knowledge of culturally responsive school practices and strategies used by school leaders in relation to community contexts and influence.
Challenges and suggestions regarding the aesthetic experience of mathematics when teaching and learning fully online
Authors: Trenholm Sven
Published: April 2023

Growth in fully online mathematics education has been steady for decades. This is where essentially all interactions associated with the teaching and learning process are mediated via the online medium. Initially spurred on by technological innovation and a variety of socio-cultural forces, growth has more recently rapidly accelerated due to pandemic restrictions. Many suggest we are on the precipice of profound transformation in mathematics education, the outlines of which remain unknown. In leveraging online education possibilities and advancing online mathematics education, this paper considers aesthetic experiences associated with learning mathematics fully online. First, three assumptions are made to highlight the importance of these experiences. Second, three challenges are identified regarding the current state of fully online mathematics education. Finally, specific instructional design and online teaching strategies are outlined that potentiate experiences of wonder and beauty often associated with mathematical discovery. As its central theme, the paper seeks to answer how we may take advantage of this technology in delivering quality mathematics education without allowing it to diminish our human essence.
Orelabrutinib for the treatment of relapsed or refractory MCL: a phase 1/2, open-label, multicenter, single-arm study
Authors: Deng Li-Juan , Zhou Ke-Shu , Liu Li-Hong , Zhang Ming-Zhi , Li Zhi-Ming , Ji Chun-Yan , Xu Wei , Liu Ting , Xu Bing , Wang Xin , Gao Su-Jun , Zhang Hui-Lai , Hu Yu , Li Yan , Cheng Ying , Yang Hai-Yan , Cao Jun-Ning , Zhu Zun-Min , Hu Jian-Da , Zhang Wei , Jing Hong-Mei , Ding Kai-Yang , Zhang Xiang-Yang , Zhao Ren-Bin , Zhang Bin , Tian Ya-Min , Song Yong-Ping , Song Yu-Qin , Zhu Jun
Published: April 2023

Relapsed or refractory (r/r) mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a poor prognosis. Bruton tyrosine kinase (BTK) is a mediator of B-cell receptor signaling and is associated with the development of B-cell lymphomas. Patients with r/r MCL were enrolled in this phase 1/2 study and treated with orelabrutinib, a novel, highly selective BTK inhibitor. The median number of prior regimens was 2 (range, 1-4). The median age was 62 years (range, 37-73 years). Eligible patients received oral orelabrutinib 150 mg once daily (n = 86) or 100 mg twice daily (n = 20) until disease progression or unacceptable toxicity. A dose of 150 mg once daily was chosen as the preferred recommended phase 2 dose. After a median follow-up duration of 23.8 months, the overall response rate was 81.1%, with 27.4% achieving a complete response and 53.8% achieving a partial response. The median duration of response and progression-free survival were 22.9 and 22.0 months, respectively. The median overall survival (OS) was not reached, and the rate of OS at 24 months was 74.3%. Adverse events (AEs) occurring in >20% of patients were thrombocytopenia (34.0%), upper respiratory tract infection (27.4%), and neutropenia (24.5%). Grade ≥3 AEs were infrequent and most commonly included thrombocytopenia (13.2%), neutropenia (8.5%), and anemia (7.5%). Three patients discontinued treatment because of treatment-related adverse events (TRAEs), but no fatal TRAEs were reported. Orelabrutinib showed substantial efficacy and was well tolerated in patients with r/r MCL. This trial was registered at www.clinicaltrials.gov as #NCT03494179.
TP53mutations identify high-risk events for peripheral T-cell lymphoma treated with CHOP-based chemotherapy
Authors: Johnson William T. , Ganesan Nivetha , Epstein-Peterson Zachary D. , Moskowitz Alison J. , Stuver Robert N. , Maccaro Catherine R. , Galasso Natasha , Chang Tiffany , Khan Niloufer , Aypar Umut , Lewis Natasha E. , Zelenetz Andrew D. , Palomba M. Lia , Matasar Matthew J. , Noy Ariela , Hamilton Audrey M. , Hamlin Paul , Caron Philip C. , Straus David J. , Intlekofer Andrew M. , Lee Batlevi Connie , Kumar Anita , Owens Colette N. , Sauter Craig S. , Falchi Lorenzo , Lue Jennifer K. , Vardhana Santosha A. , Salles Gilles , Dogan Ahmet , Schultz Nikolaus D. , Arcila Maria E. , Horwitz Steven M.
Published: April 2023

Nodal peripheral T-cell lymphomas (PTCL), the most common PTCLs, are generally treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based curative-intent chemotherapy. Recent molecular data have assisted in prognosticating these PTCLs, but most reports lack detailed baseline clinical characteristics and treatment courses. We retrospectively evaluated cases of PTCL treated with CHOP-based chemotherapy that had tumors sequenced by the Memorial Sloan Kettering Integrated Mutational Profiling of Actionable Cancer Targets next-generation sequencing panel to identify variables correlating with inferior survival. We identified 132 patients who met these criteria. Clinical factors correlating with an increased risk of progression (by multivariate analysis) included advanced-stage disease and bone marrow involvement. The only somatic genetic aberrancies correlating with inferior progression-free survival (PFS) were TP53 mutations and TP53/17p deletions. PFS remained inferior when stratifying by TP53 mutation status, with a median PFS of 4.5 months for PTCL with a TP53 mutation (n = 21) vs 10.5 months for PTCL without a TP53 mutation (n = 111). No TP53 aberrancy correlated with inferior overall survival (OS). Although rare (n = 9), CDKN2A-deleted PTCL correlated with inferior OS, with a median of 17.6 months vs 56.7 months for patients without CDKN2A deletions. This retrospective study suggests that patients with PTCL with TP53 mutations experience inferior PFS when treated with curative-intent chemotherapy, warranting prospective confirmation.
Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation
Authors: Das Nilakash , Happaerts Sofie , Gyselinck Iwein , Staes Michael , Derom Eric , Brusselle Guy , Burgos Felip , Contoli Marco , Dinh-Xuan Anh Tuan , Franssen Frits M.E. , Gonem Sherif , Greening Neil , Haenebalcke Christel , Man William D-C. , Moisés Jorge , Peché Rudi , Poberezhets Vitalii , Quint Jennifer K. , Steiner Michael C. , Vanderhelst Eef , Abdo Mustafa , Topalovic Marko , Janssens Wim
Published: April 2023

Background

Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.

Methods

The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists’ decisions.

Results

In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.

Conclusion

A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.
A novel thiol-saccharide mucolytic for the treatment of muco-obstructive lung diseases
Authors: Addante Annalisa , Raymond Wilfred , Gitlin Irina , Charbit Annabelle , Orain Xavier , Scheffler Aaron Wolfe , Kuppe Aditi , Duerr Julia , Daniltchenko Maria , Drescher Marika , Graeber Simon Y. , Healy Anne-Marie , Oscarson Stefan , Fahy John V. , Mall Marcus A.
Published: April 2023

Background

Mucin disulfide cross-links mediate pathologic mucus formation in muco-obstructive lung diseases. MUC-031, a novel thiol-modified carbohydrate compound, cleaves disulfides to cause mucolysis. The aim of this study was to determine the mucolytic and therapeutic effects of MUC-031 in sputum from patients with cystic fibrosis (CF) and mice with muco-obstructive lung disease (βENaC-Tg mice).

Methods

We compared the mucolytic efficacy of MUC-031 and existing mucolytics (N-acetylcysteine (NAC) and recombinant human deoxyribonuclease I (rhDNase)) using rheology to measure the elastic modulus (G′) of CF sputum, and we tested effects of MUC-031 on airway mucus plugging, inflammation and survival in βENaC-Tg mice to determine its mucolytic efficacyin vivo.

Results

In CF sputum, compared to the effects of rhDNase and NAC, MUC-031 caused a larger decrease in sputum G′, was faster in decreasing sputum G′ by 50% and caused mucolysis of a larger proportion of sputum samples within 15 min of drug addition. Compared to vehicle control, three treatments with MUC-031 in 1 day in adult βENaC-Tg mice decreased airway mucus content (16.8±3.2versus7.5±1.2 nL·mm−2, p<0.01) and bronchoalveolar lavage cells (73 833±6930versus47 679±7736 cells·mL−1, p<0.05). Twice-daily treatment with MUC-031 for 2 weeks also caused decreases in these outcomes in adult and neonatal βENaC-Tg mice and reduced mortality from 37% in vehicle-treated βENaC-Tg neonates to 21% in those treated with MUC-031 (p<0.05).

Conclusion

MUC-031 is a potent and fast-acting mucolytic that decreases airway mucus plugging, lessens airway inflammation and improves survival in βENaC-Tg mice. These data provide rationale for human trials of MUC-031 in muco-obstructive lung diseases.
Long-term inhaled treprostinil for pulmonary hypertension due to interstitial lung disease: INCREASE open-label extension study
Authors: Waxman Aaron , Restrepo-Jaramillo Ricardo , Thenappan Thenappan , Engel Peter , Bajwa Abubakr , Ravichandran Ashwin , Feldman Jeremy , Hajari Case Amy , Argula Rahul G. , Tapson Victor , Smith Peter , Deng Chunqin , Shen Eric , Nathan Steven D.
Published: April 2023

Introduction

The 16-week randomised, placebo-controlled INCREASE trial (RCT) met its primary end-point by improving 6-min walk distance (6MWD) in patients receiving inhaled treprostinil for pulmonary hypertension due to interstitial lung disease (PH-ILD). The open-label extension (OLE) evaluated long-term effects of inhaled treprostinil in PH-ILD.

Methods

Of 258 eligible patients, 242 enrolled in the INCREASE OLE and received inhaled treprostinil. Assessments included 6MWD, pulmonary function testing, N-terminal pro-brain natriuretic peptide (NT-proBNP), quality of life and adverse events. Hospitalisations, exacerbations of underlying lung disease and death were recorded.

Results

At INCREASE OLE baseline, patients had a median age of 70 years and a mean 6MWD of 274.2 m; 52.1% were male. For the overall population, the mean 6MWD at week 52 was 279.1 m and the mean change from INCREASE RCT baseline was 3.5 m (22.1 m for the prior inhaled treprostinil arm and −19.5 m for the prior placebo arm); the median NT-proBNP decreased from 389 pg·mL−1at RCT baseline to 359 pg·mL−1at week 64; and the absolute (% predicted) mean forced vital capacity change from RCT baseline to week 64 was 51 mL (2.8%). Patients who received inhaled treprostinilversusplacebo in the RCT had a 31% lower relative risk of exacerbation of underlying lung disease in the OLE (hazard ratio 0.69 (95% CI 0.49–0.97); p=0.03). Adverse events leading to drug discontinuation occurred in 54 (22.3%) patients.

Conclusions

These results support the long-term safety and efficacy of inhaled treprostinil in patients with PH-ILD, and are consistent with the results observed in the INCREASE RCT.
Computed tomography measure of lung injury and future interstitial features: the CARDIA Lung Study
Authors: Liu Gabrielle Y. , Colangelo Laura A. , Ash Samuel Y. , San Jose Estepar Raul , Jacobs David R. , Thyagarajan Bharat , Wells J. Michael , Putman Rachel K. , Choi Bina , Stevenson Christopher S. , Carnethon Mercedes , Washko George R. , Kalhan Ravi
Published: April 2023

Introduction

Visually normal areas of the lung with high attenuation on computed tomography (CT) imaging, termed CT lung injury, may represent injured but not yet remodelled lung parenchyma. This prospective cohort study examined if CT lung injury is associated with future interstitial features on CT and restrictive spirometry abnormality among participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Methods

CARDIA is a population-based cohort study. CT scans obtained at two time points were assessed objectively for amount of lung tissue characterised as CT lung injury and interstitial features. Restrictive spirometry was defined as having a forced vital capacity (FVC) <80% predicted with forced expiratory volume in 1 s/FVC ratio >70%.

Results

Among 2213 participants, the median percentage of lung tissue characterised as CT lung injury at a mean age of 40 years was 3.4% (interquartile range 0.8–18.0%). After adjustment for covariates, a 10% higher amount of CT lung injury at mean age 40 years was associated with a 4.37% (95% CI 3.99–4.74%) higher amount of lung tissue characterised as interstitial features at mean age 50 years. Compared to those with the lowest quartile of CT lung injury at mean age 40 years, there were higher odds of incident restrictive spirometry at mean age 55 years in quartile 2 (OR 2.05, 95% CI 1.20–3.48), quartile 3 (OR 2.80, 95% CI 1.66–4.72) and quartile 4 (OR 3.77, 95% CI 2.24–6.33).

Conclusions

CT lung injury is an early objective measure that indicates risk of future lung impairment.
ERS International Congress 2022: highlights from the Airway Diseases Assembly
Authors: Beech Augusta , Portacci Andrea , Herrero-Cortina Beatrice , Mathioudakis Alexander G. , Gotera Carolina , Uller Lena , Ricciardolo Fabio Luigi Massimo , Pobeha Pavol , Snelgrove Robert J. , Braunstahl Gert-Jan , Bossios Apostolos , Usmani Omar , Ananth Sachin
Published: April 2023

The European Respiratory Society (ERS) celebrated the return of an in-person meeting in Barcelona, Spain, after 2 years of virtual congresses. The ERS Congress 2022 programme was replete with symposia, skills workshops and abstract presentations from all 14 assemblies, encompassing over 3000 abstracts presented in the form of thematic poster discussion and oral presentations. In this article, highlights from the ERS Congress 2022 (including from thematic poster sessions, oral presentations and symposia from keynote speakers), presented by Assembly 5 (Airway diseases, asthma, COPD and chronic cough), are reviewed by Early Career Members and experts in the field, with the aim of presenting key recent findings in the field.
Efficacy of interventions to alter measures of fat-free mass in people with COPD: a systematic review and meta-analysis
Authors: Jenkins Alex R. , Gaynor-Sodeifi Kaveh , Lewthwaite Hayley , Triandafilou Jaycie , Belo Letícia F. , de Oliveira Mayron Faria , Jensen Dennis
Published: April 2023

Introduction

Low fat-free mass (FFM) is linked to poor health outcomes in COPD, including impaired exercise tolerance and premature death. The aim of this systematic review was to synthesise evidence on the effectiveness of interventions for increasing FFM in COPD.

Methods

Searches of electronic databases (MEDLINE, Cochrane Library, Embase, Web of Science, Scopus) and trial registers (ClinicalTrials.gov) were undertaken from inception to August 2022 for randomised studies of interventions assessing measures of FFM in COPD. The primary outcome was change in FFM (including derivatives). Secondary outcomes were adverse events, compliance and attrition.

Results

99 studies (n=5138 people with COPD) of 11 intervention components, used alone or in combination, were included. Exercise training increased mid-thigh cross-sectional area (k=3, standardised mean difference (SMD) 1.04, 95% CI 0.02–2.06; p=0.04), but not FFM (k=4, SMD 0.03, 95% CI −0.18–0.24; p=0.75). Nutritional supplementation significantly increased FFM index (k=11, SMD 0.31, 95% CI 0.13–0.50; p<0.001), but not FFM (k=19, SMD 0.16, 95% CI −0.06–0.39; p=0.16). Combined exercise training and nutritional supplementation increased measures related to FFM in 67% of studies. Anabolic steroids increased FFM (k=4, SMD 0.98, 95% CI 0.24–1.72; p=0.009). Neuromuscular electrical stimulation increased measures related to FFM in 50% of studies. No interventions were more at risk of serious adverse events, low compliance or attrition.

Discussion

Exercise training and nutritional supplementation were not effective in isolation to increase FFM, but were for localised muscle and index measures, respectively. Combined, exercise and nutritional supplementation shows promise as a strategy to increase FFM in COPD. Anabolic steroids are efficacious for increasing FFM in COPD.
Effects of pH alteration on respiratory syncytial virus in human airway epithelial cells
Authors: Saunders Jessica L. , Daniels Ivana A. , Edwards Taiya L. , Relich Ryan F. , Zhao Yi , Smith Laura A. , Gaston Benjamin M. , Davis Michael D.
Published: April 2023

Background

Respiratory syncytial virus (RSV) is a leading cause of respiratory distress and hospitalisation in the paediatric population. Low airway surface pH impairs antimicrobial host defence and worsens airway inflammation. Inhaled Optate safely raises airway surface pH in humans and raises intracellular pH in primary human airway epithelial cells (HAECs)in vitro. We aimed to determine whether raising intracellular pH with Optate would decrease infection and replication of RSV in primary HAECs.

Methods

We cultured HAECs from healthy subjects in both air–liquid interface and submerged conditions. We infected HAECs with green fluorescent protein-labelled RSV (GFP-RSV; multiplicity of infection=1) and treated them with Optate or PBS control. We collected supernatant after a 4-h incubation and then every 24 h. We used fluorescence intensity, fluorescent particle counts, plaque assays, Western blots and ELISA to quantitate infection.

Results

In submerged culture, fluorescence intensity decreased in Optate-treated cells (48 h p=0.0174, 72 h p≤0.001). Similarly, Optate treatment resulted in decreased fluorescent particle count (48 h p=0.0178, 72 h p=0.0019) and plaque-forming units (48 h p=0.0011, 72 h p=0.0148) from cell culture supernatant. In differentiated HAECs cultured at ALI, Optate treatment decreased fluorescence intensity (p≤0.01), GFPviaWestern blot and ELISA (p<0.0001), and RSV-fusion proteinviaELISA (p=0.001). Additionally, RSV infection decreased as Optate concentration increased in a dose-dependent manner (p<0.001).

Conclusions

Optate inhibits RSV infection in primary HAECs in a dose-dependent manner. These findings suggest that Optate may have potential as an inhaled therapeutic for patients with RSV.
Acute health effects of heated tobacco products: comparative analysis with traditional cigarettes and electronic cigarettes in young adults
Authors: Majek Paulina , Jankowski Mateusz , Brożek Grzegorz Marek
Published: April 2023

Background

Heated tobacco products (HTPs) were designed to deliver nicotine by heating the tobacco instead of burning it. This study aimed to examine the acute health effects on the respiratory and cardiovascular systems during the use of HTPs and compare these effects with acute health effects evoked by cigarette smoking or electronic cigarettes (e-cigarettes).

Methods

The study group comprised 160 healthy young adults (age 23 years; quartile 1 (Q1) 21 years; quartile 3 (Q3) 26 years) with both sexes divided into groups according to their smoking status: 40 HTP users (H group), 40 traditional cigarette smokers (T group), 40 e-cigarette users (E group) and 40 non-smokers (C group). Heart rate, blood pressure, oxygen saturation, exhaled nitric oxide fraction (FENO), carbon monoxide concentration, temperature of exhaled air and spirometry were measured three times: initially, immediately after the exposure, and after 30 min. The exposure differed depending on smoking status: heating HTP, smoking a cigarette, using an e-cigarette and simulation of smoking.

Results

After 5 min of exposure, a significant decrease inFENOwas observed in the H and E groups, from 12.8±5.5 ppb to 11.2±5.3 ppb in the H group and from 16.9±6.5 ppb to 14.2±6.8 ppb in the E group (p<0.01). A slight but statistically significant increase in the temperature of exhaled air after 30 min was observed in groups T and E, from 34.1°C (Q1 33.6°C; Q3 34.4°C) to 34.4°C (Q1 34.1°C; Q3 34.6°C) (p=0.02) in the T group and from 34.2°C (Q1 33.9°C; Q3 34.5°C) to 34.4°C (Q1 33.8°C; Q3 34.6°C) (p<0.01) in the E group. A significant increase in heart rate and blood pressure was observed in the T, E and H groups. Only cigarette smoking increased carbon monoxide levels (p<0.01).

Conclusions

The use of HTPs elicits acute respiratory and cardiovascular health effects.
Treatment with prophylactic oral anticoagulants and the risk of mortality in COVID-19 patients: a nationwide cohort study
Authors: Altaraihi Sarah , Kamstrup Peter , Eklöf Josefin , Dyrby Johansen Niklas , Biering-Sørensen Tor , Sivapalan Pradeesh , Jensen Jens-Ulrik
Published: April 2023

Background

Venous thromboembolism has been reported in patients with coronavirus disease 2019 (COVID-19). It remains unclear if premorbid use of prophylactic oral anticoagulation, for reasons other than COVID-19, protects against death in patients with COVID-19. The aim of this study was to estimate if the risk of all-cause mortality, hospital admission or intensive care unit (ICU) admission for individuals with verified SARS-CoV-2 was lower if patients used oral anticoagulant (OAC) therapy prior to a positive COVID-19 status.

Methods

Data were obtained using national health registries. Cohort entry was the day of a positive SARS-CoV-2 test, and individuals were followed for 14 days or until death or hospital admission. Adjusted Cox proportional hazard regressions and competing risk analyses were used to estimate the risk of all-cause mortality, hospital admission and ICU admission in OAC users compared with patients with no use of OAC.

Results

In this nationwide cohort study a total of 244 522 individuals were included (median age 35 years (interquartile range 21–52); 124 095 (51%) female), among whom 3710 (1.5%) were OAC users. In the adjusted Cox regression cohort, there was no difference in risk of all-cause mortality in OAC
versus
non-OAC users. (hazard ratio (HR) 1.13, 95% CI 0.99–1.30). Hospital admission risk (HR 1.11, 95% CI 1.02–1.20) was slightly increased in OAC users, and there was no difference between the groups regarding the risk of ICU admission (HR 0.96, 95% CI 0.74–1.24).

Conclusions

In individuals with confirmed SARS-CoV-2, pre-existing treatment with OAC was not associated with prophylactic benefits in the prevention of hospital admission, ICU admissions or death. Prescription patterns should remain unchanged.