bluuebunny/crossref_metadata_2025 huggingface dataset:
Wisdom, Political Expertise and the Unity of Virtues in Aristotle
Authors: Chong I Xuan
Published: October 2024

‘Unity of virtues’ (UV) in Aristotle is the claim that the ethical virtues are mutually entailing. But commentators typically focus on the fact that wisdom implies all the ethical virtues, without explaining how the ethical virtues themselves are mutually entailing. I argue that the so-called ‘Grand End’ view, understood as applying to both wisdom (φρόνησις) and political expertise (πολιτική), allows us to give an account of UV at the level of the ethical virtues. By discussing the ethical virtues individually, I show how all the ethical virtues can be seen as different aspects of the philosopher-statesman’s multifaceted character.
Rootism, Modernity, and the Jew: Antisemitism and the Reactionary Imaginary, 1789–1945
Authors: Landa Ishay
Published: October 2024

The far-right identification of Jews with modernity has been noted by many scholars, yet most analyses have fallen short of offering a properly dialectical account of antisemitism, one that will scrutinise the antinomies at the heart of the antisemitic discourse and trace their relations to the contradictions of modernity itself. In this paper, I will make modernity as movement the focus of the analysis.

Modernity, philosophically underpinned by the Enlightenment, and politically ushered in by the French Revolution of 1789, was seen by its reactionary and fascist opponents both as a time of great upheaval, constant change and social disruption, but also as the setting-up of an era of stasis and degeneration. It was paradoxically decried, sometimes simultaneously, as both helplessly nomadic and incurably sedentary. And in both respects ‘the Jew’ and ‘the Jewish spirit’ were often placed, no matter how spuriously, at the very centre of attacks. Qua ‘wandering’ or ‘eternal’, the Jews were seen as embodying the spirit of restlessness and lack of roots, undermining tradition and fixed national and racial identities; their dynamic role as revolutionaries, conspirators and rabble rousers was ritually denounced.

Jews were also condemned, however, as a major obstacle to movement and expansion, the arch-enemies of imperialism, seeking to establish a realm of universal brotherhood, peace and egalitarianism. By attacking the Jews, reactionaries and fascists thus attempted to settle their scores with a modernity that they feared and loathed in equal measure.
Negotiating the Climate Long-Term Global Goal
Authors: Beaudoin Simon
Published: October 2024

Global goals play a catalyzing role in orienting efforts to address climate change. Yet, the negotiation of the main goal in climate governance is understudied. This article aims to fill this gap by examining the negotiation, adoption, and refinement of the United Nations Framework Convention on Climate Change’s (unfccc) Long-Term Global Goal (ltgg), from the late 1970s to date. I gather insights from semi-structured interviews with climate governance experts, the scientific literature, and official documentation to highlight the developments that shaped the ltgg over time. The study shows that agential, ideational, normative, structural, and contextual factors co-interacted in negotiating, adopting, and refining the ltgg. Drawing lessons from the ltgg experience, the manuscript contributes to knowledge on the politics of global goals, international negotiations, climate governance, and, more broadly, international relations, diplomacy, and global environmental politics.
Development of an automated radial scanning microscopy-based imaging system and its use for measuring resin canal size and frequency in Pinus taeda
Authors: Pokhrel Nawa Raj , Dahlen Joseph , Eberhardt Thomas L. , Gandhi Kamal J.K.
Published: October 2024

Resin canals produce and transport oleoresins that are important for tree defenses within the Pinaceae family. Rapid measurement techniques are needed to better understand how resin canal characteristics vary due to genetic and environmental effects. Here we describe a semi-automated microscopy imaging system that was built for quantifying longitudinal resin canals. Tree increment cores from 210 loblolly pine (Pinus taeda L.) trees were prepared into radial strips and the transverse surface of the samples polished with 400 and then 600 grit sandpaper. Each sample was imaged along its entire length (pith to bark) with the images collected from a monochrome camera connected to a Plan Fluorite 4× objective lens. The samples were imaged on the transverse surface via transmitted 850 nm near-infrared light directed at the radial surfaces of the samples. A total of 24 153 images were collected and then processed offline in Python using the Open Computer Vision Library (OpenCV) using a series of algorithms including contrast correction, noise removal, thresholding, contour identification, erosion, and dilation. A total of 24 491 resin canals were identified and their size quantified. The resin canals were assigned into annual rings and positioned within the earlywood or latewood of a ring using cross-correlation whereby a pseudo-density value was derived from the images and matched with density values measured by X-ray densitometry. Of the total resin canals identified, 51.5% were in the earlywood and 48.5% in the latewood, with the majority being detected in the earlywood in the first six years and the latewood in years 7 and above. This study represents the most information collected on the resin canals of loblolly pine. The detailed description of the hardware and image analysis methods should serve as a useful guide to others interested in imaging resin canals as well as other anatomical features.
Natation et perfection : un marqueur de la civilisation arabo-islamique
Authors: Chraïbi Aboubakr , Mezeghrane Samira
Published: October 2024

Swimming (sibāḥa / ʿawm) enjoyed a very positive image in the premodern Arab world and, according to several classical authors, its practice was highly recommended by the caliph ʿUmar b. al-Ḫaṭṭāb. Pioneering work has shown that Greek traditions are at the root of such a phenomenon. It remains to be understood, however, why Arab scholars had recourse especially to the caliph ʿUmar as the most suitable authority to promote Swimming, and why, specifically in the Arab area, the importance of swimming was stressed to such an extent that, combined with knowledge of Arabic writing and archery, it became a means of achieving perfection, disregarding, thus, any constraints, such as religion or kinship.
Insights into the genus Xeromphalina, X. tenuipes (Schwein.) A.H. Sm. complex and discovery of a novel species, X. pseudotenuipes from Thailand
Authors: BERA ISHIKA , SYSOUPHANTHONG PHONGEUN , KHYAJU SABIN , HYDE KEVIN D. , THONGKLANG NARITSADA
Published: October 2024

Xeromphalina belonging to the family Xeromphalinaceae and characterized as a saprobe thriving on fallen, decayed logs, has undergone taxonomic revisionary study predominantly in the Northern Hemisphere. Despite approximately 36 documented species, studies on complex groups with similar-looking species within this genus are quite fragmentary and have led to misnaming and misidentification. Recent observations have revealed one interesting species from Thailand belonging to the X. tenuipes species complex. Morphological features along phylogenetic analysis (nrITS, nrLSU, and rpb2) inferred that this species is new to science. This novel species, namely X. pseudotenuipes can be distinguished from X. tenuipes by its pileocystidia appearing brownish in 5% KOH, and hyphae of pileipellis and stipitipellis turning orangish brown in 5% KOH. Moreover, this study is the first attempt to undertake a comprehensive phylogenetic analysis encompassing all potential species of Xeromphalina for which sequences are available, aiming to identify which sequence accurately represents each species.
Miliusa longicarpa (Annonaceae): a new species from Yunnan, China
Authors: SHI ZHIYUAN , HOU XUELIANG
Published: October 2024

N/A
2. A Cycle of Rāgs
Authors: Clarke David
Published: October 2024

This part of the book curates the fourteen rāgs of the Rāg samay cakra album, providing supporting materials of practical utility to students and also of interest to listeners and scholars. Of the five sections in this part, the first four are essentially prefatory. Section 2.1 includes background information about the album and summarises the conventions of the khayāl style. Section 2.2 considers the song texts: their poetics, and issues of their translation and transliteration—in short, the problematics of producing a written edition of material passed down orally through tradition. In similar vein, section 2.3 discusses the written representation of the music, and how musicians might deploy the notations supplied here within the orally transmitted conventions of extemporised performance. Section 2.4 is in effect a glossary of technical terms used to specify the rāgs of the collection. Finally, section 2.5 presents the rāgs themselves. For each, we provide a technical specification; a thumbnail description of both the rāg and of the bandiś (song) chosen to represent it; a presentation and translation of the song text; and a notation of the bandiś.
4. Explorations and Analyses (II)
Authors: Clarke David
Published: October 2024

In this part of the book, I offer a detailed commentary on the companion album Twilight Rāgs from North India. In section 4.2, the subject under the spotlight is Vijay Rajput’s performance of Rāg Bhairav on the Twilight Rāgs album. One priority in this essay is to provide details of the texts and notations of the bandiśes, in the interests not least of students who want to learn them. A further aim is to consider issues raised by these songs. I first examine the mutable identity of the baṛā khayāl bandiś ‘Balamavā more saīyā̃’, alongside alternative versions sung by doyens of the Kirana gharānā. I then analyse the subtleties of the bandiś ‘Suno to sakhī batiyā’, and the ways in which VR works it into an extended drut khayāl. With this last analysis, I conjecture further about the possibility of an underlying performance grammar, as first raised in section 3.3. In section 4.3, I turn to the question, ‘How do you sing a baṛā khayāl?’ Also known as vilambit [slow] khayāl, a baṛā khayāl is where an artist is able most fully to display not only their technical prowess, but also their ability to explore the deeper reaches of a rāg. In this essay, I focus on the subtle tension between non-metrical and metrical principles (anibaddh and nibaddh) that permeates, and arguably defines, a baṛā khayāl. My case study here is Vijay Rajput’s performance of the baṛā khayāl ‘Kahe sakhī kaise ke karīe’, in Rāg Yaman, the second rāg featured on the album Twilight Rāgs from North India. In this analysis, I seek not only to illustrate what happens and in what order (under the wider principles of baṛhat and laykārī), but also to convey the various ways in which a baṛā khayāl’s ambiguous temporality, and its related interplay between the fixed and the free, permeate the performance ethos and contribute to the experience of musical depth. This also relates to the question of how a baṛā khayāl gets taught; as elsewhere in Rāgs Around the Clock, my account here includes insights gleaned directly from learning with my own guruji, VR.
Semi-Quantitative Assessment of Surgical Navigation Accuracy During Endoscopic Sinus Surgery in a Real-World Environment
Authors: Allen David Z. , Talmadge Jason , Citardi Martin J.
Published: October 2024

Introduction:

Although surgical navigation is commonly used in rhinologic surgery, data on real world performance are sparse because of difficulties in collecting measurements for target registration error (TRE). Despite publications showing submillimeter TRE, surgeons do report TRE of >3 mm. We describe a novel method for assessing TRE during surgery and report findings with this technique.

Methods:

The TruDi navigation system (Acclarent, Irving, CA) was registered using a contour-based protocol. The surgeon estimated target registration error (e-TRE) at up to 8 points (anatomic regions of interest [ROI]) during endoscopic sinus surgery (ESS). System logs were used to simulate the localization for quantitative assessment of TRE (q-TRE).

Results:

We performed 98 localizations in 20 patients. The ROI in the sinuses were ethmoid (33 sites), maxillary (28 sites), frontal (17 sites), and sphenoid (22 sites). For localizations, mean qTRE and eTRE were 0.93 and 0.84 mm ( P = .56). Notably, 80% of qTRE and 81% of eTRE were 1 mm or less. Mean qTRE and eTRE were less for attending-performed registrations at the maxillary, frontal and sphenoid.

Conclusion:

Surgical navigation accuracy, as measured by qTRE and eTRE, approaches 1 mm or better at all sinus sites in a real-world setting for 80% of localizations. The qTRE method provides a unique approach for assessing TRE. Surgeons underestimate TRE (overstate navigation accuracy), but this difference does not seem to be statistically significant. Registration performed by trainees yields higher TRE than registration performed by attendings. These data may be used to guide navigation optimization.
Endonasal Thermal Imaging Before and After Nasal Airway Surgery
Authors: Seresirikachorn Kachorn , Png Lu Hui , Do Timothy Quy-Phong , Kalish Larry , Campbell Raewyn G. , Rimmer Janet , Alvarado Raquel , Raji Nelufer , Choy Christine , Snidvongs Kornkiat , Sacks Raymond , Harvey Richard J.
Published: October 2024

Objective

Nasal airway surgery is often applied when treatment fails to relieve nasal obstruction. However, surgery that improves airflow does not always alleviate the symptoms of nasal obstruction. The perception of nasal breathing is likely more related to changes in mucosal temperature than the mechanical sensation of flow or pressure. This study aims to measure intranasal mucosal temperature pre-and post-surgery using endonasal thermal imaging, exploring its correlation with subjective nasal breathing and objective airflow measurements.

Methods

A prospective study of adult patients with nasal obstruction managed with nasal airway surgery was performed. Intranasal mucosal temperatures were determined using the thermal endonasal image of the nasal passage produced by the infrared radiometric thermal camera (FILR VS290). A comparison was made between the mean values of mid-expiration (ExT) and mid-inspiration (InT) temperature data (internal nasal valve, nasal cavity, inferior turbinate, and overall airway [mean value]) and visual analog scale (VAS), Nasal Obstruction Symptom Evaluation (NOSE) scale and nasal airway resistance (NAR) before and after surgery.

Results

Seven patients (35.14 ± 16.45 years, 57.14% female) were included. All NOSE, VAS, and NAR improved after surgery (59.29 ± 10.89 vs 17.14 ± 14.64; P < .001, 64.50 ± 26.79 vs 18.57 ± 19.99; P < .001, 0.82 ± 0.48 vs 0.34 ± 0.11 Pa/cm3/s; P = .002, respectively). ExT, InT, and the difference between ExT and InT of three areas and overall airway were similar between pre-and post-surgery. No statistically significant correlations were found between intranasal mucosal temperature, VAS, NOSE, and NAR at pre-and post-surgery except for the difference between ExT and InT of overall airway and NOSE pre-operative (Pearson r = 0.57; 95% CI 0.06-1.09; P = .03).

Conclusion

Endonasal thermal imaging can assess the intranasal mucosal temperature of a patient. However, more precise imaging of the nasal passages and data acquisition are required to establish mucosal temperature as an objective measure of nasal obstruction before and after nasal airway surgery in a clinical setting.
Effect of Gestational Diabetes Mellitus on Newborn Hearing: A Systematic Review
Authors: Aggarwal Komal , Ravi Rohit
Published: October 2024

Objective:

Gestational diabetes mellitus (GDM) is associated with several adverse health conditions in newborns such as preterm birth, hyperbilirubinemia, macrosomia, respiratory distress. However, the effect of GDM on the hearing sensitivity of newborns is still unclear. The study aimed to explore the effect of GDM on newborn hearing. The study aimed to explore the effect of GDM on newborn hearing.

Method:

A systematic search was conducted using PubMed, Scopus, and CHINAL databases. Keywords like “gestational diabetes,” “diabetic pregnancies,” “hearing loss,” “hearing impairment,” and “hearing disorder” were used to form a search string. The Rayyan software was used for screening procedure. The full-length articles were shortlisted, extracted, and appraised.

Results:

The 7 articles were included in the review. Findings suggest that hearing loss is more prevalent in newborns with GDM pregnancies than in non-GDM pregnancies. In addition, OAE findings were “referred during the first hearing screening of newborns with GDM pregnancies.” The refer rate of the first bilateral hearing screening was higher for newborns with GDM pregnancies. Furthermore, children of diabetic pregnancies were found to be at risk of bilateral hearing loss, particularly sensorineural in nature.

Conclusion:

The present systematic review suggests an association between GDM and a higher refer rate in hearing screening. A multidisciplinary collaboration between gynecologists, pediatricians, and audiologists can smoothen the early detection of hearing loss in newborns with GDM pregnancies, leading to early intervention and better clinical outcomes to improve the quality of life of affected newborns.
Addressing Registered Nurse Retention and Attrition in Thailand Hospitals: An Integrative Review
Authors: Phakdeechanuan Kirana , Kellett Ursula , Henderson Saras , Corones-Watkins Katina , Saito Amornrat , Thiangchanya Pratyanan
Published: October 2024

Thailand is one of the Southeast Asia countries that has been significantly impacted by Registered Nurse (RN) workforce shortages. This integrative review aimed to critically analyze factors influencing the attrition and retention of RNs practicing in Thailand’s hospital sector. The databases searched included CINAHL (via EBSCOhost), EMBASE, Nursing Allied (via ProQuest), Ovid, Scopus, Web of Science, and Medline. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were utilized to record the search strategy findings in compliance with the review standards, while the Mixed-Methods Appraisal Tool (MMAT) was used to appraise quality. Sources for review totaled 35, using quantitative methods (n = 30), qualitative methods (n = 3), and mixed methods (n = 2). Thematic analysis revealed factors that challenge RNs’ job motivation fueled by a lack of autonomy, a loss of confidence and sense of competence, and negative workplace relations with co-workers, resulting in poor job satisfaction. Future research is needed to elicit an understanding of “how” Thai RNs sense of autonomy, competence, and relatedness in their workplace practice provides insight into “why” they choose to remain employed or leave the nursing workforce.
Educating Dora: Teaching a conversational agent to talk
Authors: Brandt Adam , Hazel Spencer , McKinnon Rory , Sideridou Kleopatra , Tindale Joe , Ventoura Nikoletta
Published: October 2024

Many organisations are witnessing the introduction of automated systems to mediate between them and their clients, often designed as dialogic user interfaces which are conversational in nature. Despite calls for the design of AI-powered conversational agents to draw on Ethnomethodological Conversation Analysis (EMCA), how an EMCA-informed conversation design can improve interactions between humans and conversational agents is yet to be empirically examined. This paper reports on a collaboration between EMCA researchers and AI conversation designers at digital health company Ufonia to develop Dora, a pre-existing ‘automated clinical assistant’ that provides telephone consultations for patients of the UK’s National Health Service. Our analysis identified differences between the conversation design of the product and conversational practices found in equivalent activities involving human clinicians, relevant to implementing changes to improve user experience. We demonstrate that users are prompted to recalibrate their practices (such as for turn-taking) in situ as they engage with a system which does not match their prior experiences of this activity type. Such insights can be leveraged to adapt system design so that it more closely approximates users’ prior experiences of such engagements.
Does industry co-location improve corporate information environment?
Authors: Boone Jeff P , Kang Tae G , Park Sung-Jin
Published: October 2024

This study examines how the co-location of firms within the same industry enhances their information environments. We hypothesize that benefits arise from two effects: the industry peer effect, involving intra-industry information spillovers, and the geographic peer effect, related to shared local economic conditions with nearby non-industry peers. Our analysis evaluates how these effects, both separately and jointly, impact analysts’ forecast properties and stock price informativeness regarding future earnings. We find that the industry peer effect is negatively related to forecast dispersion and positively related to forecast accuracy, while the geographic peer effect shows no significant correlation. In addition, stock price informativeness about future earnings is positively associated with the industry peer effect but not with the geographic peer effect. We also find that greater proximity to industry or local peers enables analysts to incorporate more private (relative to public) information into their earnings forecasts, thereby enhancing the firm’s information environment.

JEL CLASSIFICATION: M41, D80, G10
How I treat sickle cell disease with gene therapy
Authors: Sharma Akshay
Published: October 2024

In 2023, 2 different gene therapies were approved for individuals with severe sickle cell disease (SCD). The small number of patients treated on the pivotal clinical trials that led to these approvals have experienced dramatic short-term reductions in the occurrence of painful vaso-occlusive crises, but the long-term safety and efficacy of these genetic therapies are yet to be ascertained. Several challenges and treatment-related concerns have emerged in regard to administering these therapies in clinical practice. This article discusses the selection and preparation of individuals with SCD who wish to receive autologous gene therapy, as well as the salient features of the care needed to support them through a long and arduous treatment process. I specifically focus on postinfusion care, as it relates to immune monitoring and infection prevention. Compared with allogeneic hematopoietic cell transplantation, delivering autologous gene therapy to an individual with SCD has distinct nuances that require awareness and special interventions. Using clinical vignettes derived from real-life patients, I provide perspectives on the complex decision-making process for gene therapy for SCD based on currently available data and make recommendations for evaluating and supporting these patients.
How I treat older patients with relapsed/refractory diffuse large B-cell lymphoma
Authors: Wallace Danielle S. , Loh Kah Poh , Casulo Carla
Published: October 2024

Diffuse large B-cell lymphoma (DLBCL) is an aggressive, yet curable, malignancy, but older patients are at higher risk of relapsed disease because they may not be eligible for full-intensity frontline chemoimmunotherapy or have comorbidities that limit standard treatments. Recent years have brought more treatment options than ever for this patient population, but it remains challenging to determine which can be safely and effectively offered to older patients. Formal determinations of fitness including geriatric assessments remain critical, but there is less guidance on how to best use this tool in the relapsed setting. Chimeric antigen receptor T-cell therapy is accessible to older patients, provided they can be supported through the intensive road to this treatment. If relapse occurs despite this or alternative therapies are preferred, many novel therapeutic options and combinations exist with some potential modifications for older adults, such as bispecific antibodies, tafasitamab and lenalidomide, polatuzumab-containing regimens, or loncastuximab tesirine. This article provides a summary of our approach to the management of this diverse population of older patients with relapsed or refractory DLBCL.
Ex vivo venetoclax sensitivity predicts clinical response in acute myeloid leukemia in the prospective VenEx trial
Authors: Kytölä Sari , Vänttinen Ida , Ruokoranta Tanja , Partanen Anu , Holopainen Annasofia , Saad Joseph , Kuusisto Milla E. L. , Koskela Sirpa , Räty Riikka , Itälä-Remes Maija , Västrik Imre , Suvela Minna , Parsons Alun , Porkka Kimmo , Wennerberg Krister , Heckman Caroline A. , Jalkanen Tero , Huttunen Teppo , Ettala Pia , Rimpiläinen Johanna , Siitonen Timo , Pyörälä Marja , Kuusanmäki Heikki , Kontro Mika
Published: October 2024

The B-cell lymphoma 2 inhibitor venetoclax has shown promise for treating acute myeloid leukemia (AML). However, identifying patients likely to respond remains a challenge, especially for those with relapsed/refractory (R/R) disease. We evaluated the utility of ex vivo venetoclax sensitivity testing to predict treatment responses to venetoclax-azacitidine in a prospective, multicenter, phase 2 trial. The trial recruited 104 participants with previously untreated (n = 48), R/R (n = 39), or previously treated secondary AML (sAML) (n = 17). The primary end point was complete remission or complete remission with incomplete hematologic recovery (CR/CRi) rate in ex vivo sensitive trial participants during the first 3 therapy cycles. The key secondary end points included the correlations between ex vivo drug sensitivity, responses, and survival. Venetoclax sensitivity was successfully assessed in 102 of 104 participants, with results available within a median of 3 days from sampling. In previously untreated AML, ex vivo sensitivity corresponded to an 85% (34/40) CR/CRi rate, with a median overall survival (OS) of 28.7 months, compared with 5.5 months for ex vivo resistant patients (P = .002). For R/R/sAML, ex vivo sensitivity resulted in a 62% CR/CRi rate (21/34) and median OS of 9.7 vs 3.3 months for ex vivo resistant patients (P < .001). In univariate and multivariate analysis, ex vivo venetoclax sensitivity was the strongest predictor for a favorable treatment response and survival. This trial demonstrates the feasibility of integrating ex vivo drug testing into clinical practice to identify patients with AML, particularly in the R/R setting, who benefit from venetoclax. This trial was registered at www.clinicaltrials.gov as #NCT04267081.
Time to STEP UP: methods and findings from the development of guidance to help researchers design inclusive clinical trials
Authors: Biggs K. , Hullock K. , Dix C. , Lane JA. , Green H. , Treweek S. , Shiely F. , Shepherd V. , Willis A. , Isaacs T. , Cooper C.
Published: October 2024

Background

It is important to design clinical trials to include all those who may benefit from the intervention being tested. Several frameworks have been developed to help researchers think about the barriers to inclusion of particular under-served groups when designing a trial, but there is a lack of practical guidance on how to implement these frameworks. This paper describes the ACCESS project, the findings from each phase of the project and the guidance we developed (STEP UP) on how to design more inclusive trials.

Methods

Development of the STEP UP guidance had five phases: (1) Scoping literature review, (2) ‘roundtable’ discussion meetings, (3) redesign of trials, (4) interviews and (5) guidance document development, with input from public contributors and the ACCESS team.

Results

Over 40 experts contributed to the ACCESS project—patients and the public, clinicians, NHS research staff, trialists and other academics. The scoping review identified several strategies being used to improve inclusion, mostly around recruitment settings, but there was little evaluation of these strategies. The ‘roundtable’ discussions identified additional strategies being used across the UK and Ireland to improve inclusion, which were grouped into: Communication, Community engagement, Recruitment sites, Patient information, Flexibility, Recruitment settings, Consent process, Monitoring, Training for researchers and Incentives. These strategies were used to redesign three existing trials by applying one of the three INCLUDE frameworks (ethnicity, socioeconomic disadvantage, impaired capacity to consent) to one trial each, to produce the key recommendations for the guidance. Issues around implementation were explored in stakeholder interviews and key facilitators were identified: funders requesting information on inclusion, having the time and funding to implement strategies, dedicated staff, flexibility in trial protocols, and considering inclusion of under-served groups at the design stages. The STEP UP guidance is freely available at http://step-up-clinical-trials.co.uk.

Conclusion

Researchers should consider inclusivity to shape initial trial design decisions. Trial teams and funders need to ensure that trials are given both the resources and time needed to implement the STEP UP guidance and increase the opportunities to recruit a diverse population.
Three-outcome designs for external pilot trials with progression criteria
Authors: Wilson Duncan T. , Hudson Eleanor , Brown Sarah
Published: October 2024

Background

Whether or not to progress from a pilot study to a definitive trial is often guided by pre-specified quantitative progression criteria with three possible outcomes. Although the choice of these progression criteria will help to determine the statistical properties of the pilot trial, there is a lack of research examining how they, or the pilot sample size, should be determined.

Methods

We review three-outcome trial designs originally proposed in the phase II oncology setting and extend these to the case of external pilots, proposing a unified framework based on univariate hypothesis tests and the control of frequentist error rates. We apply this framework to an example and compare against a simple two-outcome alternative.

Results

We find that three-outcome designs can be used in the pilot setting, although they are not generally more efficient than simpler two-outcome alternatives. We show that three-outcome designs can help allow for other sources of information or other stakeholders to feed into progression decisions in the event of a borderline result, but this will come at the cost of a larger pilot sample size than the two-outcome case. We also show that three-outcome designs can be used to allow adjustments to be made to the intervention or trial design before commencing the definitive trial, providing the effect of the adjustment can be accurately predicted at the pilot design stage. An package, , is provided to optimise progression criteria and pilot sample size.

Conclusions

The proposed three-outcome framework provides a way to optimise pilot trial progression criteria and sample size in a way that leads to desired operating characteristics. It can be applied whether or not an adjustment following the pilot trial is anticipated, but will generally lead to larger sample size requirements than simpler two-outcome alternatives.
Expanding horizons: lung transplantation for non-IPF interstitial lung diseases
Authors: Citak Sevinc , Saribas Ertan , Halis Ayse Nigar , Alkilic Fatma Feyza , Cardak Murat Ersin , Vayvada Mustafa , Tasci Ahmet Erdal
Published: October 2024

Objective

Interstitial lung diseases (ILDs) are diverse pulmonary disorders marked by diffuse lung inflammation and fibrosis. The variability in characteristics and treatment approaches complicates diagnosis and management. In advanced cases requiring transplantation, determining indications and selecting suitable candidates presents additional challenges.

Methods

Of all patients with non-IPF ILD between December 2016 to December 2022 were analyzed retrospectively. Patients were categorized into two groups: transplanted patients and deceased patients on the waiting list. Clinical data and survival outcomes were compared between groups.

Results

Of the 43 patients, 20 underwent lung transplantation while 23 died awaiting transplantation. Waiting list mortality was 53.4%, with median waiting times similar between groups (3 months for transplant patients and 6 months for those on the waiting list). There were no significant differences between groups in age, gender, height, BMI, 6-minute walk test (6MWT), or forced vital capacity (FVC). The prevalence of pulmonary hypertension (PH) was 76.7% in right heart catheterizations, similar in both groups. One single and 19 bilateral lung transplants were performed. Overall, 13 of the 20 patients survived to discharge from the hospital. One-year mortality was 7/20 (35%). The median follow-up was 34 months, with a 1-year conditional survival of 90.9% at 3 years and 70.7% at 5 years.

Conclusions

This study underscores the importance of further research into non-IPF ILDs. Lung transplantation remains a viable option that can significantly enhance both the quality and longevity of life for patients with advanced ILD.
Marketing mental health services: a mixed-methods analysis of racially and ethnically diverse college students’ engagement with and perspectives on U.S. university mental health clinics’ websites
Authors: Aguilar Silvan Yesenia , Hamza Sarah , Fardeheb Sara , Bird Christine , Ng Lauren C.
Published: October 2024

Background

The United States (U.S.) faces a significant mental health crisis, with around 52.9 million adults experiencing mental health disorders, with young adults (18–25 years old), such as college students, having the highest prevalence and lowest service utilization rates. While efforts to expand mental health services through “push” strategies are in place (e.g., training therapists in evidence-based therapies), limited initial engagement suggests a need for “pull strategies” and targeted marketing that make services attractive to college students and increase demand. This mixed-methods study identifies U.S. university mental health clinic websites and website characteristics that are attractive and engaging to college students interested in seeking mental health services (i.e., students were considering or actively looking for mental health support).

Methods

Eleven U.S. university websites were chosen (10 randomly and one from the university where students were attending) from a pool of 44 Psychological Clinical Science Accreditation System training clinics websites. Fifty-seven college students (Mage = 20.95, SD = 2.97; 81% female; 68% racial/ethnic minority) were videorecorded engaging with two U.S. university mental health clinic websites, completed self-report engagement measures, and gave detailed feedback about websites through semi-structured interviews.

Results

Likert scale scores revealed moderate engagement with all websites (e.g., they were interesting and helpful). Qualitative results indicated that websites that provided important and easily understood information about key features of services (e.g., types, evidence-base, and cost), therapist backgrounds, psychoeducation, used lay language, and had an appealing website layout (e.g., color, font, images, organization, and interactive components) generated greater consumer interest and trust in their mental health services.

Conclusions

This study emphasizes the importance of using marketing strategies to enhance college students’ engagement through mental health service websites. Salient features, psychoeducation, and effective promotional strategies (e.g., how information is presented) were identified as crucial for website engagement and subsequent mental health service uptake. Using marketing strategies, such as tailoring language to consumer literacy levels, describing the evidence-base of services, and improving website design may address college students’ needs and enhance initial mental health service engagement.
Ionizing radiation effects on blood-derived extracellular vesicles: insights into miR-34a-5p-mediated cellular responses and biomarker potential
Authors: Huber Chiara , Elsaeed Omar , Lahmer Pia , Moertl Simone
Published: October 2024

Adverse effects of ionizing radiation on normal tissues limit the radiation dose in cancer treatment, thereby compromising treatment efficiency. Among the consistently affected non-cancer cells, peripheral blood mononuclear cells (PBMCs) exhibit high radiosensitivity and have the potential to induce systemic effects. PBMC-released extracellular vesicles (EVs), contribute to the communication of such systemic effects. This study aimed to investigate the effects of ionizing radiation on EVs as part of the systemic response of PBMCs in terms of microRNA cargo and biological functions.

Therefore, whole blood samples from healthy donors were irradiated ex-vivo (0 Gy, 1 Gy, 2 Gy, 4 Gy) and EVs from PBMCs were isolated after 96 h by PEG precipitation or ultracentrifugation. Candidate microRNAs were examined in PBMC-derived EVs from individual donors. The uptake of membrane-stained fluorescent EVs by different recipient cells was quantified by fluorescence-activated cell sorting analysis. The biological effects of increased miR-34a-5p and of total EVs on recipient cells were assessed.

Irradiation of PBMCs induced a dose-dependent upregulation of miR-34a-5p within EVs and PBMCs. However, interindividual differences between donors were noticed in the extent of upregulation, and small EVs displayed more pronounced changes in microRNA levels in comparison to large EVs. Irradiation in presence of the small molecule inhibitor KU-60019 demonstrated that this upregulation is dependent on ATM (Ataxia telangiectasia mutated) activation. Moreover, fibroblasts and keratinocytes were identified as preferred EV recipients. Increased miR-34a-5p levels led to a significant reduction in viability and induction of senescence in keratinocytes but not in fibroblasts, indicating a cell type-specific response.

In conclusion, this study further elucidated the complex cellular response of normal tissue after radiation exposure. It confirmed radiation-induced modifications of microRNA expression levels in EVs from PBMCs and identified a robust upregulation of miR-34a-5p in the small EV subfraction, suggesting this microRNA as a potential novel candidate for the development of biomarkers for radiation exposure. Moreover, the different uptake efficiencies observed among specific cell types suggested that EVs induce cell type-specific responses in the intercellular communication of systemic radiation effects.
Impact of a short-term pharmacy study abroad Program: student outcomes and program evaluation
Authors: Elmokadem Eman Mohamed , Mahmoud Azza A. , Bennett-Lenane Harriet , Murphy Kevin D. , Khalil Noha
Published: October 2024

Objective

This study examined the impact of a short-term study abroad program, focusing on program evaluation, attendee satisfaction, and acquired knowledge and skills. A questionnaire survey was conducted covering various aspects including demographics, program evaluation, and feedback.

Results

Results indicated higher female participation due to gender imbalances in pharmacy students in Egypt, with senior students recognizing the value of international experience. Attendee satisfaction was high, with positive feedback on accommodation, tours, and workshop materials. Field visits and workshops provided valuable experiential learning, with attendees suggesting extending the program’s duration. The program equipped attendees with knowledge and skills relevant to pharmaceutical products and services, leading to improved competences and perceptions. The study concludes that such study abroad experiences profoundly impact personal growth and recommends integrating them into educational curricula for valuable experiences.
The feasibility and acceptability of using EMA and physiological data to measure day-to-day occupational stress, musculoskeletal pain and mental health
Authors: Weale Victoria , Love Jasmine , Clays Els , Oakman Jodi
Published: October 2024

Objectives

This study aimed to assess the feasibility and acceptability of using EMA questionnaires and physiological data via wristbands to measure day-to-day occupational stress, musculoskeletal pain, and mental health among university employees (N = 23), across 10 work days. Adherence to the study protocol as well as participant experiences (via semi-structured interviews) with the protocol were used to assess feasibility and acceptability of the method.

Results

Adherence to the study protocol was excellent. Participants wore the wristband for a mean of 9.7 days. Participants completed a mean of 24.5 EMAs (out of 30). Semi-structured interviews with participants revealed that a small number of participants had difficulties uploading data from the wristband. The timing of EMAs was challenging for some participants, resulting in missed EMAs, raising questions about whether EMA frequency and timing could be changed to improve adherence. Some EMA items were difficult to answer due to the nature of participants’ roles and the work undertaken. Overall, the protocol was feasible and acceptable but highlighted future potential changes including using a different physiological data collection tool, reducing the number of EMAs, adjusting EMA timings, and reviewing EMA items.
Targeting senescent cells in aging and COVID-19: from cellular mechanisms to therapeutic opportunities
Authors: Yu Yuan , Lin Kaixuan , Wu Haoyu , Hu Mingli , Yang Xuejie , Wang Jie , Grillari Johannes , Chen Jiekai
Published: October 2024

The COVID-19 pandemic has caused a global health crisis and significant social economic burden. While most individuals experience mild or non-specific symptoms, elderly individuals are at a higher risk of developing severe symptoms and life-threatening complications. Exploring the key factors associated with clinical severity highlights that key characteristics of aging, such as cellular senescence, immune dysregulation, metabolic alterations, and impaired regenerative potential, contribute to disruption of tissue homeostasis of the lung and worse clinical outcome. Senolytic and senomorphic drugs, which are anti-aging treatments designed to eliminate senescent cells or decrease the associated phenotypes, have shown promise in alleviating age-related dysfunctions and offer a novel approach to treating diseases that share certain aspects of underlying mechanisms with aging, including COVID-19. This review summarizes the current understanding of aging in COVID-19 progression, and highlights recent findings on anti-aging drugs that could be repurposed for COVID-19 treatment to complement existing therapies.
Development of Bacillus stratosphericus Lysate Concentrate to Control Sebum Secretion through In vitro Studies and Clinical Trial
Authors: Ki Hosam , Yoon Sung Geon , Han Jeung Hi , Shin Byeongmin , Kim Young Soo , Choi Yang Gyu , Hwang Kwang Yeon
Published: October 2024

The sebum on human skin is generated for various causes. The composition of the formed sebum increases the proliferation of Cutibacterium acnes (C. acnes) residing on the skin. As C. acnes proliferates, it produces skin irritants that stimulate the sebaceous glands, increasing sebum production. Skin troubles such as acne may occur. The lysate concentrates of Bacillus stratosphericus (B. stratosphericus), first discovered in the stratosphere, confirmed a 66.35% inhibition of Nitric Oxide (NO) production at 0.50 mg/ml concentration in vitro. Additionally, the growth inhibition efficacy of B. stratosphericus lysate concentrate (BSLC) against C. acnes was confirmed, showing a 95.1% inhibition of growth proliferation at a consistency of 0.50 mg/ml. Based on the in vitro results, the efficacy of BSLC in degrading and reducing sebum was confirmed by reacting it with artificial sebum to various concentrations. The results showed a concentration-dependent decrease in artificial sebum ccording to the efficacy results confirmed in vitro, a clinical trial was conducted to evaluate the daily sebum reduction efficacy of a serum formulation containing 50 mg/ml of BSLC. After a 4-week application, the test group containing BSLC determined a significant 28.68% reduction in sebum levels, demonstrating the practical implications of the research. In conclusion, BSLC is considered to have sufficient industrial value as a valuable ingredient for the cosmetics industry aimed at sebum improvement.
Evaluation of ten plant-derived biocides for the inhibition of photosynthetic organisms on the karst surfaces of heritage buildings
Authors: Long Mingzhong , Xiong Kangning , Lin Jiayu , Tang Boyan , Ao Ziqiang , Chen Yingqiu , Xu Zhiyi
Published: October 2024

Biodeterioration is a significant problem in the conservation of stone heritage buildings. In this study, 10 plant essential oils were assessed for their effectiveness in biofilm inhibition on stone heritage building surfaces under laboratory and in situ conditions, and were compared with traditional biocides such as benzalkonium chloride. The plant extracts were tested against algae and mosses. The effect on algae removal was evaluated by measuring the color of the surface before treatment, after 24 h and after 1 month of treatment. The effect on mosses was assessed by measuring the photosynthetic pigment content of mosses after 24 h of treatment. The results showed that the different plant extracts exhibited different levels of antibiotic activity. Benzalkonium chloride, S. aromaticum and C. cassia extracts showed strong antibiotic activity against all algae and mosses tested. T. mongolicus extracts showed antibiotic activity against only some of the algae and mosses, while the application of P. cablin extracts increased chlorophyll b content in the mosses. The other plant extracts were less effective at inhibiting the growth of algae and mosses. GC–MS compositional analysis further indicated that the higher antibiotic activity of S. aromaticum and C. cassia extracts was related to the high content of eugenol and cinnamaldehyde.
Dietary partitioning in sympatric Paradoxurinae civets in Borneo suggested by compound-specific nitrogen isotope analysis of amino acids
Authors: Nakabayashi Miyabi , Tsutaya Takumi , Ahmad Abdul Hamid , Sasaki Yoko , Ogawa Nanako O. , Ishikawa Naoto F. , Ohkouchi Naohiko
Published: October 2024

We applied stable carbon and nitrogen isotopic analyses to understand the faunivory of the four sympatric wild Paradoxurinae civet species in Borneo, which share similar ecological characteristics. We also employed compound-specific nitrogen isotope analysis of amino acids to estimate these species’ trophic positions (TPs). The bulk stable isotope analysis revealed distinctly lower nitrogen isotope ratios in binturongs than in the other three species. This suggests that binturongs exhibit the lowest degree of faunivory among the four species. Binturongs had the lowest TP estimated from the nitrogen isotope ratios of amino acids (2.0–2.1), followed by small-toothed palm civets (2.4–2.5), masked palm civets (2.7), and common palm civets (2.9). These results suggest that there is little faunivory in binturong and variations in faunivory in the other species. Although the number of samples measured for the nitrogen isotope ratios of amino acids is small (n = 2 for each species), our results suggest that the varying degree of consumption of animal food sources, such as insects, is the key mechanism of niche partitioning in these four Paradoxurinae civet species in Borneo. Such subtle but essential differences in closely related sympatric species would maintain high biodiversity in tropical regions.