bluuebunny/crossref_metadata_2025 huggingface dataset:
App-based assessment of patient-reported outcomes in the Molecular Tumor Board in the Center for Personalized Medicine—(TRACE)
Authors: Dörner Lorenz , Grosse Lucia , Stange Felix , Hille Hanni , Kurz Sylvia , Becker Hannes , Volkmer Sebastian , Hippler Melina , Rieger David , Bombach Paula , Rieger Johannes , Weinert Lina , Svensson Laura , Anders Carolin , Cekin Sila , Paulsen Frank , Öner Öznur , Ruhm Kristina , Malek Holly Sundberg , Möller Yonne , Tatagiba Marcos , Wallwiener Markus , Eckert Nils , Escher Pascal , Pfeifer Nico , Forschner Andrea , Bauer Armin , Zips Daniel , Bitzer Michael , Malek Nisar , Gani Cihan , Tabatabai Ghazaleh , Renovanz Mirjam
Published: January 2024

Background

Biomarker-based therapies are increasingly used in cancer patients outside clinical trials. Systematic assessment of patient-reported outcomes (PRO) is warranted to take patients’ perspectives during biomarker-based therapies into consideration. We assessed the feasibility of an electronic PRO assessment via a smartphone application.

Methods

An interdisciplinary expert panel developed a smartphone application based on symptom burden and health-related quality of life (HRQoL) metrics reported in a retrospective analysis of 292 neuro-oncological patients. The app included validated assessments of health-related quality of life (HRQoL), the burden of symptoms, and psychological stress. Feasibility and usability were tested in a pilot study. Semi-structured interviews with patients and health care professionals (HCP) were conducted, transcribed, and analyzed according to Mayring´s qualitative content analysis. Furthermore, we assessed compliance and descriptive data of ePROs.

Results

A total of 14 patients have been enrolled, (9 female, 5 male). A total of 4 HCPs, 9 patients, and 1 caregiver were interviewed regarding usability/feasibility. The main advantages were the possibility to complete questionnaires at home and comfortable implementation in daily life. Compliance was high, for example, 82% of the weekly distributed NCCN distress thermometer questionnaires were answered on time, however, with interindividual variability. We observed a median distress score of 5 (range 0–10, 197 results, n = 12, weekly assessed) and a median Global health score of 58.3 according to the EORTC QLQ-C30 instrument (range 16.7–100, 77 results, n = 12, monthly assessed).

Conclusions

This pilot study proved the feasibility and acceptance of the app. We will therefore expand its application during biomarker-guided therapies to enable systematic PRO assessments.
Application of Artificial Intelligence in Infant Movement Classification: A Reliability and Validity Study in Infants Who Were Full-Term and Preterm
Authors: Lin Shiang-Chin , Chandra Erick , Tsao Po Nien , Liao Wei-Chih , Chen Wei-J , Yen Ting-An , Hsu Jane Yung-Jen , Jeng Suh-Fang
Published: January 2024

Objective

Preterm infants are at high risk of neuromotor disorders. Recent advances in digital technology and machine learning algorithms have enabled the tracking and recognition of anatomical key points of the human body. It remains unclear whether the proposed pose estimation model and the skeleton-based action recognition model for adult movement classification are applicable and accurate for infant motor assessment. Therefore, this study aimed to develop and validate an artificial intelligence (AI) model framework for movement recognition in full-term and preterm infants.

Methods

This observational study prospectively assessed 30 full-term infants and 54 preterm infants using the Alberta Infant Motor Scale (58 movements) from 4 to 18 months of age with their movements recorded by 5 video cameras simultaneously in a standardized clinical setup. The movement videos were annotated for the start/end times and presence of movements by 3 pediatric physical therapists. The annotated videos were used for the development and testing of an AI algorithm that consisted of a 17-point human pose estimation model and a skeleton-based action recognition model.

Results

The infants contributed 153 sessions of Alberta Infant Motor Scale assessment that yielded 13,139 videos of movements for data processing. The intra and interrater reliabilities for movement annotation of videos by the therapists showed high agreements (88%–100%). Thirty-one of the 58 movements were selected for machine learning because of sufficient data samples and developmental significance. Using the annotated results as the standards, the AI algorithm showed satisfactory agreement in classifying the 31 movements (accuracy = 0.91, recall = 0.91, precision = 0.91, and F1 score = 0.91).

Conclusion

The AI algorithm was accurate in classifying 31 movements in full-term and preterm infants from 4 to 18 months of age in a standardized clinical setup.

Impact

The findings provide the basis for future refinement and validation of the algorithm on home videos to be a remote infant movement assessment.
Prognostic value of hypermetabolic bone sarcoidosis observed by 18F-fluorodeoxyglucose positron emission tomography
Authors: Bouchut Arthur , Lhote Raphael , Maksud Philippe , Ben Salem Thouraya , Fustier Anne , Moyon Quentin , Haroche Julien , Soussan Michael , Mathian Alexis , Hie Miguel , Amoura Zahir , Cohen Aubart Fleur
Published: January 2024

Objectives

Sarcoidosis is a multisystemic granulomatosis diagnosed mainly in young adults. 18F-fluorodeoxyglucose (18F-FDG) PET/CT is useful in sarcoidosis cases to search for a biopsiable site or assess disease activity.18F-FDG PET/CT can reveal bone hypermetabolism in sarcoidosis patients, even in the absence of osteoarticular symptoms. The aim of this study was to describe metabolic bone involvement in sarcoidosis patients and to evaluate its prognostic impact.

Methods

This was an observational, comparative, retrospective, monocentric study. Inclusion criteria were a confirmed diagnosis of sarcoidosis according to the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) criteria and at least one 18F-FDG PET/CT scan during follow-up. Metabolic bone involvement of sarcoidosis was defined as focal bone hypermetabolism with no argument for a differential diagnosis of bone 18F-FDG uptake. Patients with and without bone involvement were compared.

Results

Among the 175 included patients, 32 (18%) had metabolic bone involvement of sarcoidosis. The metabolic bone involvement was mainly axial and mostly without bone abnormalities on CT. Metabolic bone involvement was associated with intrathoracic and extrathoracic lymph node involvement and with a greater number of organs involved. Patients with metabolic bone involvement more frequently received corticosteroids, methotrexate and TNF-α inhibitors and a greater number of treatments. Relapse of sarcoidosis occurred sooner in patients with metabolic bone involvement.

Conclusion

These results suggest that metabolic bone involvement is associated with more diffuse and more severe sarcoidosis.
Detection of inflammation by whole-body MRI in young people with juvenile idiopathic arthritis
Authors: Choida Varvara , Bray Timothy J P , van Vucht Niels , Abbasi Maaz Ali , Bainbridge Alan , Parry Thomas , Sen Debajit , Mallett Sue , Ciurtin Coziana , Hall-Craggs Margaret A
Published: January 2024

Objectives

To assess the frequency of joint inflammation detected by whole-body MRI (WBMRI) in young people (YP) with JIA and controls, and to determine the relationship between WBMRI-detected inflammation and clinical findings.

Methods

YP aged 14–24 years, with JIA (patients) or arthralgia without JIA (controls), recruited from one centre, underwent a WBMRI scan after formal clinical assessment. Consensus between at least two of the three independent radiologists was required to define inflammation and damage on WBMRI, according to predefined criteria. YP with JIA were deemed clinically active as per accepted definitions. The proportions of YP with positive WBMRI scans for joint inflammation (one or more inflamed joint) as well as serum biomarkers were compared between active vs inactive JIA patients and controls.

Results

Forty-seven YP with JIA (25 active and 22 inactive patients) and 13 controls were included. WBMRI detected joint inflammation in 60% (28/47) of patients with JIA vs 15% (2/13) of controls (difference: 44%, 95% CI 20%, 68%). More active than inactive JIA patients had WBMRI-detected inflammation [76% (19/25) vs 41% (9/22), difference: 35% (95% CI 9%, 62%)], and this was associated with a specific biomarker signature. WBMRI identified inflammation in one or more clinically inactive joint in 23/47 (49%) patients (14/25 active vs 9/22 inactive JIA patients).

Conclusions

WBMRI’s validity in joint assessment was demonstrated by the higher frequency of inflammation in JIA patients vs controls, and in active vs inactive JIA patients. WBMRI found unsuspected joint inflammation in 49% YP with JIA, which needs further investigation of potential clinical implications.
“Normal vulva” based on the first national Labiagram design in adult Iranian women not seeking female genital cosmetic surgery: a pilot study
Authors: Ghanbari Zinat , Kazemi Maryam , Eshraghi Nasim , Shiri Hamedani Sina , Zafarbakhsh Azam
Published: January 2024

Background

Several studies have been published to present normal values of female genitalia in different age and racial groups.

Aim

The primary objective of our study was to measure the parameters of the external genitalia in adult Iranian women, record the data using the Labiagram system (the first national Labiagram design in Iran), and establish a preliminary database.

Methods

A descriptive study was conducted from March 2022 to December 2022, involving 220 nonpregnant adult women who presented to the gynecology clinic. Women who met the inclusion criteria for the study underwent a comprehensive examination of the external genitalia. The data collected during the examinations were recorded in electronic files and the Labiagram system.

Outcomes

The data showed the diversity of external genital parameters of nonpregnant adult Iranian women.

Results

In this descriptive study, the mean ± SD age of the participants was 51.5 ± 13.44 years, ranging from 15 to 84 years. A total of 192 women (87.3%) had a history of vaginal delivery. There was no statistically significant difference observed in the average measurements of the vulva among the 4 age groups (P < .05). The Pearson correlation coefficient test indicated a statistically weak correlation between body mass index and perineum length (r = 0.174, P = .010). Additionally, a weak correlation was found between body mass index and the width of the labia minora at the left-lower point (r = 0.143, P = .030) and the right-middle point (r = 0.146, P = .031). Furthermore, the results demonstrated that women with a history of vaginal delivery had a significantly longer introitus (49.3 vs 44.3 mm, P = .037), longer labia majora (91.3 vs 87.3 mm, P = .046), and longer labia minora (56.8 vs 50.9 mm, P = .008) when compared with women without prior labor experience.

Clinical Implications

The data will be used as a basis for future studies.

Strengths and Limitations

The use of simple tools for the measuring, data recording, and digital drawing of female external genital anatomy, along with privacy protection, is one of the strengths of this research. The weakness is the small sample size, which is the reason for piloting the Labiagram chart for more extensive studies.

Conclusion

Increasing age and the number of births had no statistically significant effect on the size of external genital parameters among Iranian women. Despite the considerable diversity in these parameters, it has not resulted in a significant demand among Iranian women for female cosmetic surgery.
Treating insomnia in people who are incarcerated: a feasibility study of a multicomponent treatment pathway
Authors: Dewa Lindsay H , Thibaut Bethan , Pattison Natalie , Campbell Sean James , Woodcock Thomas , Aylin Paul , Archer Stephanie
Published: January 2024

Around 60% of people who are incarcerated have insomnia; 6–10 times more prevalent than the general population. Yet, there is no standardized, evidence-based approach to insomnia treatment in prison. We assessed the feasibility of a treatment pathway for insomnia in a high-secure prison to inform a future randomized controlled trial (RCT) and initial efficacy data for sleep and mental health outcomes. We used a within-participants pre-post design. The stepped-care pathway included: self-management with peer support, environmental aids, and cognitive behavioral therapy for insomnia (CBTi). Assessment measures for insomnia, well-being, mood, anxiety, suicidality, overall health, sleepiness, fatigue, and cognitive functioning were administered at baseline and pathway exit. Feasibility criteria included eligibility to participate, CBTi uptake, and assessment completion. Forty-two adult males who are incarcerated were approached of which 95.2% were eligible. Of those deemed eligible, most participated (36/40, 90.0%). Most who completed baseline completed post-assessments (28/36, 77.8%) and of these, most showed improvements in their subjective sleep (27/28, 96.4%). Large reductions were found from pre- to posttreatment in insomnia severity (d = −1.81, 95% CI: 8.3 to 12.9) and 57.0% reported no clinically significant insomnia symptoms at post-assessment. There was no overall change in actigraphy-measured sleep. Large treatment benefits were found for depression, anxiety, well-being, and cognitive functioning, with a medium benefit on suicidal ideation. The treatment pathway for insomnia in prison was feasible and may be an effective treatment for insomnia in people who are incarcerated, with additional promising benefits for mental health. A pragmatic RCT across different prison populations is warranted. This paper is part of the Sleep and Circadian Health in the Justice System Collection.
Obstructive sleep apnea, nocturnal hypoxemia, and retinal microvasculature: The Atherosclerosis Risk in Communities Study
Authors: Hoeft Nathan , Full Kelsie M , Misialek Jeffrey R , Lakshminarayan Kamakshi , Shrestha Srishti , Deal Jennifer A , Lutsey Pamela L
Published: January 2024

Study Objectives

Retinal microvascular pathology (RMP) and obstructive sleep apnea (OSA) are both cardiovascular disease risk factors. Limited data exists on their interrelationship. We tested the hypotheses that OSA and nocturnal hypoxemia would be associated with RMP and vessel calibers.

Methods

We conducted a quasi-cross-sectional analysis of 1625 participants in the Atherosclerosis Risk in Communities Sleep Heart Health Study. Participants completed in-home polysomnography monitoring (1996–1998) and were categorized by OSA severity (apnea–hypopnea index: <5, 5–14.9, and ≥15) and proportion of total sleep time with oxygen saturation < 90% (T90). Retinal photography (1993–1995) was used to assess RMP and measure vascular diameters (central retinal arteriolar equivalent [CRAE] and central retinal venular equivalent [CRVE]). Logistic and linear models were adjusted for demographics, behaviors, and BMI.

Results

Of the participants, 19% had OSA (AHI > 15) and 4% had RMP. Severe OSA was not associated with RMP [OR (95% CI): 1.08 (0.49 to 2.38)] or CRAE in adjusted models. OSA severity showed a positive linear relationship with CRVE; adjusted mean CRVE for those with OSA was 195.8 μm compared to 193.2 μm for those without OSA (Ptrend = 0.03). T90 was strongly associated with CRVE, but not with RMP or CRAE. Adjusted mean CRVE for T90 ≥ 5% was 199.0 and 192.9 for T90 < 1% (ptrend < 0.0001).

Conclusions

OSA and T90 were not associated with RMP or CRAE. However, both OSA and T90 ≥ 5% were associated with wider venules, which may be early and indicative changes of increased inflammation and future risk of stroke and CHD.
Social norm change: drivers and consequences
Authors: Andrighetto Giulia , Gavrilets Sergey , Gelfand Michele , Mace Ruth , Vriens Eva
Published: January 2024

Social norms research is booming. In recent years, several experts have recommended using social norms (unwritten rules that prescribe what people ought or ought not to do) to confront the societal, environmental and health challenges our societies face. If we are to do so, a better understanding is required of how social norms themselves emerge, evolve and respond to these challenges. Social norms have long been used aspost hocexplanations of behaviour or are seen as stable social constructs. Yet norms evolve dynamically with the changing group processes (e.g. political polarization, kinship structures) and societal challenges (e.g. pandemics, climate change) for which they are presented as solutions. The Theme Issue ‘Social norm change: drivers and consequences' contains 14 contributions that present state-of-the-art approaches to understand what generates social norm change and how this impacts our societies. Contributions give insight into (i) the identification of norms, norm change and their effect on behaviour; (ii) drivers and consequences of spontaneous norm change; and (iii) how norm change can be engineered to promote desired behavioural change.

This article is part of the theme issue ‘Social norm change: drivers and consequences’.
Human and nonhuman norms: a dimensional framework
Authors: Andrews Kristin , Fitzpatrick Simon , Westra Evan
Published: January 2024

Human communities teem with a variety of social norms. In order to change unjust and harmful social norms, it is crucial to identify the psychological processes that give rise to them. Most researchers take it for granted that social norms are uniquely human. By contrast, we approach this matter from a comparative perspective, leveraging recent research on animal social behaviour. While there is currently only suggestive evidence for norms in nonhuman communities, we argue that human social norms are likely produced by a wide range of mechanisms, many of which we share with nonhuman animals. Approaching this variability from a comparative perspective can help norm researchers expand and reframe the range of hypotheses they test when attempting to understand the causes of socially normative behaviours in humans. First, we diagnose some of the theoretical obstacles to developing a comparative science of social norms, and offer a few basic constructs and distinctions to help norm researchers overcome these obstacles. Then we develop a six-dimensional model of the psychological and social factors that contribute to variability in both human and potential nonhuman norms.

This article is part of the theme issue ‘Social norm change: drivers and consequences’.
Modelling social norms: an integration of the norm-utility approach with beliefs dynamics
Authors: Gavrilets Sergey , Tverskoi Denis , Sánchez Angel
Published: January 2024

We review theoretical approaches for modelling the origin, persistence and change of social norms. The most comprehensive models describe the coevolution of behaviours, personal, descriptive and injunctive norms while considering influences of various authorities and accounting for cognitive processes and between-individual differences. Models show that social norms can improve individual and group well-being. Under some conditions though, deleterious norms can persist in the population through conformity, preference falsification and pluralistic ignorance. Polarization in behaviour and beliefs can be maintained, even when societal advantages of particular behaviours or belief systems over alternatives are clear. Attempts to change social norms can backfire through cognitive processes including cognitive dissonance and psychological reactance. Under some conditions social norms can change rapidly via tipping point dynamics. Norms can be highly susceptible to manipulation, and network structure influences their propagation. Future models should incorporate network structure more thoroughly, explicitly study online norms, consider cultural variations and be applied to real-world processes.

This article is part of the theme issue ‘Social norm change: drivers and consequences’.
Shaping new norms for AI
Authors: Baronchelli Andrea
Published: January 2024

As artificial intelligence (AI) becomes increasingly integrated into our lives, the need for new norms is urgent. However, AI evolves at a much faster pace than the characteristic time of norm formation, posing an unprecedented challenge to our societies. This paper examines possible criticalities of the processes of norm formation surrounding AI. It focuses on how new norms can be established, rather than on what these norms should be. It distinguishes different scenarios based on the centralization or decentralization of the norm formation process, analysing the cases where new norms are shaped by formal authorities or informal institutions, or emerge spontaneously in a bottom-up fashion. On the latter point, the paper reports a conversation with ChatGPT in which the LLM discusses some of the emerging norms it has observed. Far from seeking exhaustiveness, this article aims to offer readers interpretive tools to frame society’s response to the growing pervasiveness of AI. An outlook on how AI could influence the formation of future social norms emphasizes the importance for open societies to anchor their formal deliberation process in an open, inclusive and transparent public discourse.

This article is part of the theme issue ‘Social norm change: drivers and consequences’.
Signals of belonging: emergence of signalling norms as facilitators of trust and parochial cooperation
Authors: Macanovic Ana , Tsvetkova Milena , Przepiorka Wojtek , Buskens Vincent
Published: January 2024

Mechanisms of social control reinforce norms that appear harmful or wasteful, such as mutilation practises or extensive body tattoos. We suggest such norms arise to serve as signals that distinguish between ingroup ‘friends' and outgroup ‘foes', facilitating parochial cooperation. Combining insights from research on signalling and parochial cooperation, we incorporate a trust game with signalling in an agent-based model to study the dynamics of signalling norm emergence in groups with conflicting interests. Our results show that costly signalling norms emerge from random acts of signalling in minority groups that benefit most from parochial cooperation. Majority groups are less likely to develop costly signalling norms. Yet, norms that prescribe sending costless group identity signals can easily emerge in groups of all sizes—albeit, at times, at the expense of minority group members. Further, the dynamics of signalling norm emergence differ across signal costs, relative group sizes, and levels of ingroup assortment. Our findings provide theoretical insights into norm evolution in contexts where groups develop identity markers in response to environmental challenges that put their interests at odds with the interests of other groups. Such contexts arise in zones of ethnic conflict or during contestations of existing power relations.

This article is part of the theme issue ‘Social norm change: drivers and consequences’.
Jeans and language: kin networks and reproductive success are associated with the adoption of outgroup norms
Authors: He Qiao-Qiao , Yu Jie-Ru , Tang Song-Hua , Wang Ming-Yang , Wu Jia-Jia , Chen Yuan , Tao Yi , Ji Ting , Mace Ruth
Published: January 2024

Traditional norms of human societies in rural China may have changed owing to population expansion, rapid development of the tourism economy and globalization since the 1990s; people from different ethnic groups might adopt cultural traits from outside their group or lose their own culture at different rates. Human behavioural ecology can help to explain adoption of outgroup cultural values. We compared the adoption of four cultural values, specifically speaking outgroup languages/mother tongue and wearing jeans, in two co-residing ethnic groups, the Mosuo and Han. Both groups are learning outgroup traits, including each other's languages through contact in economic activities, education and kin networks, but only the Mosuo are starting to lose their own language. Males are more likely to adopt outgroup values than females in both groups. Females of the two groups are no different in speaking Mandarin and wearing jeans, whereas males do differ, with Mosuo males being keener to adopt them than Han males. The reason might be that Mosuo men experience more reproductive competition over mates, as Mosuo men have larger reproductive skew than others. Moreover, Mosuo men but not others gain fitness benefits from the adoption of Mandarin (they start reproducing earlier than non-speakers).

This article is part of the theme issue ‘Social norm change: drivers and consequences’.
When norm change hurts
Authors: Efferson Charles , Ehret Sönke , von Flüe Lukas , Vogt Sonja
Published: January 2024

Applied cultural evolution includes any effort to mobilize social learning and cultural evolution to promote behaviour change. Social tipping is one version of this idea based on conformity and coordination. Conformity and coordination can reinforce a harmful social norm, but they can also accelerate change from a harmful norm to a beneficial alternative. Perhaps unfortunately, the link between the size of an intervention and social tipping is complex in heterogeneous populations. A small intervention targeted at one segment of society can induce tipping better than a large intervention targeted at a different segment. We develop and examine two models showing that the link between social tipping and social welfare is also complex in heterogeneous populations. An intervention strategy that creates persistent miscoordination, exactly the opposite of tipping, can lead to higher social welfare than another strategy that leads to tipping. We show that the potential benefits of miscoordination often hinge specifically on the preferences of people most resistant to behaviour change. Altogether, ordinary forms of heterogeneity complicate applied cultural evolution considerably. Heterogeneity weakens both the link between the size of a social planner’s intervention and behaviour change and the link between behaviour change and the well-being of society.

This article is part of the theme issue ‘Social norm change: drivers and consequences’.
The
Misleading
count: an identity-based intervention to counter partisan misinformation sharing
Authors: Pretus Clara , Javeed Ali M. , Hughes Diána , Hackenburg Kobi , Tsakiris Manos , Vilarroya Oscar , Van Bavel Jay J.
Published: January 2024

Interventions to counter misinformation are often less effective for polarizing content on social media platforms. We sought to overcome this limitation by testing an identity-based intervention, which aims to promote accuracy by incorporating normative cues directly into the social media user interface. Across three pre-registered experiments in the US (
N
= 1709) and UK (
N
= 804), we found that crowdsourcing accuracy judgements by adding a
Misleading
count (next to the
Like
count) reduced participants' reported likelihood to share inaccurate information about partisan issues by 25% (compared with a control condition). The
Misleading
count was also more effective when it reflected in-group norms (from fellow Democrats/Republicans) compared with the norms of general users, though this effect was absent in a less politically polarized context (UK). Moreover, the normative intervention was roughly five times as effective as another popular misinformation intervention (i.e. the accuracy nudge reduced sharing misinformation by 5%). Extreme partisanship did not undermine the effectiveness of the intervention. Our results suggest that identity-based interventions based on the science of social norms can be more effective than identity-neutral alternatives to counter partisan misinformation in politically polarized contexts (e.g. the US).

This article is part of the theme issue ‘Social norm change: drivers and consequences’.
Effect of iris pigmentation of blue and brown eyed individuals with European ancestry on ability to see in low light conditions after a short-term dark adaption period
Authors: Cain Faith Erin , Yamaguchi Kyoko
Published: January 2024

The effect of iris depigmentation on ability to see in low light conditions has not been thoroughly investigated as an adaptive advantage that could have contributed to the evolution and persistence of blue eyes in Europe. In this study 40 participants took part in a simple eye test in increasing luminance to examine if there was a difference in capacity to see in low light conditions between blue and brown-eyed individuals after a brief adaptation period. Blue eyed individuals were identified to have significantly better ability to see in lower lighting after a short adaption period than brown eyed individuals making it likely depigmented irises provide an adaptive advantage (p=0.046). Superior ability to see in low light conditions could be the result of increased straylight in depigmented irises, which in light luminance is disadvantageous but in low light conditions may provide an advantage. More research is needed to determine the specific association between melanin content and low-light visual acuity. Furthermore, more research is needed to establish that the improved capacity of blue-eyed individuals to see in low light settings seen in this study is attributable to iris pigmentation rather than corresponding pigmentation elsewhere.
Inhibition of glioblastoma cell proliferation and invasion by the choline-kinase inhibitor JAS239 varies with cell type and hypoxia
Authors: Kelly Claire Louise , Wydrzynska Martyna , Phelan Marie M , Osharovich Sofya , Delikatny Edward J. , Sée Violaine , Poptani Harish
Published: January 2024

Background

Elevated choline kinase alpha (ChoK) is observed in most solid tumours including glioblastomas (GBM), yet until recently, inhibitors of ChoK have demonstrated limited efficacy in GBM models. Given that hypoxia is associated with GBM therapy resistance, we hypothesised that tumour hypoxia could be responsible for such limitations. We therefore evaluated in GBM cells, the effect of hypoxia on the function of JAS239, a potent ChoK inhibitor.

Methods

Rodent (F98 and 9L) and human (U-87 MG and U-251 MG) GBM cell lines were subjected to 72 hours of hypoxia conditioning and treated with JAS239 for 24 hours. NMR metabolomic measurements and analyses were performed to evaluate the signalling pathways involved. In addition, cell proliferation, cell cycle progression and cell invasion were measured in cell monolayers and 3D spheroids, with or without JAS239 treatment in normoxic or hypoxic cells to assess how hypoxia affects JAS239 function.

Results

Hypoxia and JAS239 treatment led to significant changes in the cellular metabolic pathways, specifically the phospholipid and glycolytic pathways associated with a reduction in cell proliferation via induced cell cycle arrest. Interestingly, JAS239 also impaired GBM invasion. However, JAS239 effects were variable depending on the cell line, reflecting the inherent heterogeneity observed in GBMs.

Conclusion

Our findings indicate that JAS239 and hypoxia can deregulate cellular metabolism, inhibit proliferation and alter cell invasion. These results may be useful for the design of new therapeutic strategies based on ChoK inhibition that can act on multiple pro-tumorigenic features.
Microbial diversity and ecological complexity emerging from environmental variation and horizontal gene transfer in a simple mathematical model
Authors: Babajanyan Sanasar G. , Garushyants Sofya K. , Wolf Yuri I. , Koonin Eugene V.
Published: January 2024

Microbiomes are generally characterized by high diversity of coexisting microbial species and strains that remains stable within a broad range of conditions. However, under fixed conditions, microbial ecology conforms with the exclusion principle under which two populations competing for the same resource within the same niche cannot coexist because the less fit population inevitably goes extinct. To explore the conditions for stabilization of microbial diversity, we developed a simple mathematical model consisting of two competing populations that could exchange a single gene allele via horizontal gene transfer (HGT). We found that, although in a fixed environment, with unbiased HGT, the system obeyed the exclusion principle, in an oscillating environment, within large regions of the phase space bounded by the rates of reproduction and HGT, the two populations coexist. Moreover, depending on the parameter combination, all three major types of symbiosis obtained, namely, pure competition, host-parasite relationship and mutualism. In each of these regimes, certain parameter combinations provided for synergy, that is, a greater total abundance of both populations compared to the abundance of the winning population in the fixed environments. These findings show that basic phenomena that are universal in microbial communities, environmental variation and HGT, provide for stabilization of microbial diversity and ecological complexity.
Genetic modification of the bee parasiteCrithidia bombifor improved visualization and protein localization
Authors: Bieber Blyssalyn V. , Lockett Sarah G. , Glasser Sonja K. , Clair Faith A. St. , Adler Lynn S. , Povelones Megan L.
Published: January 2024

Crithidia bombiis a trypanosomatid parasite that infects several species of bumble bees (Bombusspp.), by adhering to their intestinal tract.Crithidia bombiinfection impairs learning and reduces survival of workers and overwintering queens. Although there is extensive research on the ecology of this host-pathogen system, we understand far less about the mechanisms that mediate internal infection dynamics.Crithidia bombiinfects hosts by attaching to the hindgut via the flagellum, and one previous study found that a nectar secondary compound removed the flagellum, preventing attachment. However, approaches that allow more detailed observation of parasite attachment and growth would allow us to better understand factors mediating this host-pathogen relationship. We established techniques for genetic manipulation and visualization of culturedC. bombi. Using constructs established forCrithidia fasciculata, we successfully generatedC. bombicells expressing ectopic fluorescent transgenes using two different selectable markers. To our knowledge, this is the first genetic modification of this species. We also introduced constructs that label the mitochondrion and nucleus of the parasite, showing that subcellular targeting signals can function across parasite species to highlight specific organelles. Finally, we visualized fluorescently tagged parasitesin vitroin both their swimming and attached forms, andin vivoin bumble bee (Bombus impatiens) hosts. Expanding our cell and molecular toolkit forC. bombiwill help us better understand how factors such as host diet, immune system, and physiology mediate outcomes of infection by these common parasites.
Deep learning predicts DNA methylation regulatory variants in specific brain cell types and enhances fine mapping for brain disorders
Authors: Zhou Jiyun , Weinberger Daniel R. , Han Shizhong
Published: January 2024

DNA methylation (DNAm) is essential for brain development and function and potentially mediates the effects of genetic risk variants underlying brain disorders. We present INTERACT, a transformer-based deep learning model to predict regulatory variants impacting DNAm levels in specific brain cell types, leveraging existing single-nucleus DNAm data from the human brain. We show that INTERACT accurately predicts cell type-specific DNAm profiles, achieving an average area under the Receiver Operating Characteristic curve of 0.98 across cell types. Furthermore, INTERACT predicts cell type-specific DNAm regulatory variants, which reflect cellular context and enrich the heritability of brain-related traits in relevant cell types. Importantly, we demonstrate that incorporating predicted variant effects and DNAm levels of CpG sites enhances the fine mapping for three brain disorders—schizophrenia, depression, and Alzheimer’s disease—and facilitates mapping causal genes to particular cell types. Our study highlights the power of deep learning in identifying cell type-specific regulatory variants, which will enhance our understanding of the genetics of complex traits.

Teaser

Deep learning reveals genetic variations impacting brain cell type-specific DNA methylation and illuminates genetic bases of brain disorders
The FinnBrain Multimodal Neonatal Template and Atlas Collection: T1, T2, and DTI brain templates, and accompanying cortical and subcortical atlases
Authors: Tuulari Jetro J. , Rosberg Aylin , Pulli Elmo P. , Hashempour Niloofar , Ukharova Elena , Lidauer Kristian , Jolly Ashmeet , Luotonen Silja , Audah Hilyatushalihah K. , Vartiainen Elena , Bano Wajiha , Suuronen Ilkka , Mariani Wigley Isabella L.C. , Fonov Vladimir S. , Collins D. Louis , Merisaari Harri , Karlsson Linnea , Karlsson Hasse , Lewis John D.
Published: January 2024

The accurate processing of neonatal and infant brain MRI data is crucially important for developmental neuroscience, but presents challenges that child and adult data do not. Tissue segmentation and image coregistration accuracy can be improved by optimizing template images and / or related segmentation procedures. Here, we describe the construction of the FinnBrain Neonate (FBN-125) template; a multi-contrast template with T1- and T2-weighted as well as diffusion tensor imaging derived fractional anisotropy and mean diffusivity images. The template is symmetric and aligned to the Talairach-like MNI 152 template and has high spatial resolution (0.5 mm3). In addition, we provide atlas labels, constructed from manual segmentations, for cortical grey matter, white matter, cerebrospinal fluid, brainstem, and cerebellum as well as the bilateral hippocampi, amygdalae, caudate nuclei, putamina, globi pallidi, and thalami. We provide this multi-contrast template along with the labelled atlases for the use of the neuroscience community in the hope that it will prove useful in advancing developmental neuroscience, for example, by helping to achieve reliable means for spatial normalization and measures of neonate brain structure via automated computational methods. Additionally, we provide standard co-registration files that will enable investigators to reliably transform their statistical maps to the adult MNI space, which has the potential to improve the consistency and comparability of neonatal studies or the use of adult MNI space atlases in neonatal neuroimaging.
Drivers of Decision-Making for Adult Tracheostomy for Prolonged Mechanical Ventilation: A Qualitative Study
Authors: Mehta Anuj B , Lockhart Steven , Lange Allison V , Matlock Daniel D , Douglas Ivor S , Morris Megan A
Published: January 2024

Background

Decision-making about tracheostomy and prolonged mechanical ventilation (PMV) is emotionally complex. Expectations of surrogate decision-makers and physicians rarely align. Little is known about what surrogates need to make goal-concordant decisions. We sought to identify drivers of tracheostomy and PMV decision-making.

Methods

Using Grounded Theory, we performed a qualitative study with semi-structured interviews with surrogates of patients receiving mechanical ventilation (MV) being considered for tracheostomy and physicians routinely caring for patients receiving MV. Recruitment was stopped when thematic saturation was reached. Separate codebooks were created for surrogate and physician interviews. Themes and factors affecting decision-making were identified and a theoretical model tracheostomy decision-making was developed.

Results

43 participants (23 surrogates and 20 physicians) completed interviews. A theoretical model of themes and factors driving decision-making emerged for the data. Hope, Lack of Knowledge & Data, and Uncertainty emerged as the three main themes all which were interconnected with one another and, at times, opposed each other. Patient Wishes, Past Activity/Medical History, Short and Long-Term Outcomes, and Meaningful Recovery were key factors upon which surrogates and physicians based decision-making. The themes were the lens through which the factors were viewed and decision-making existed as a balance between surrogate emotions and understanding and physician recommendations.

Conclusions

Tracheostomy and prolonged MV decision-making is complex. Hope and Uncertainty were conceptual themes that often battled with one another. Lack of Knowledge & Data plagued both surrogates and physicians. Multiple tangible factors were identified that affected surrogate decision-making and physician recommendations.

Implications

Understanding this complex decision-making process has the potential to improve the information provided to surrogates and, potentially, increase the goal concordant care and alignment of surrogate and physician expectations.

Highlights

Decision-making for tracheostomy and prolonged mechanical ventilation is a complex interactive process between surrogate decision-makers and providers.

Using a Grounded Theory framework, a theoretical model emerged from the data with core themes of Hope, Uncertainty, and Lack of Knowledge & Data that was shared by both providers and surrogates.

The core themes were the lenses through which the key decision-making factors of Patient Wishes, Past Activity/Medical History, Short and Long-Term Outcomes, and Meaningful Recovery were viewed.

The theoretical model provides a roadmap to design a shared decision-making intervention to improve tracheostomy and prolonged mechanical ventilation decision-making.
Interrogating Changes in COVID-19 Vaccine Intent During the National Vaccine Rollout in the Philippines
Authors: Caple Alexandria , Dimaano Arnie , Sagolili Marc Martin , Uy April Anne , Aguirre Panjee Mariel , Alano Dean , Baul Kaila Andrine , Camaya Giselle Sophia , Carlos Angelo Raine , Ciriaco Brent John , Clavo Princess Jerah Mae , Cuyugan Dominic , Fermo Cleinne Florence Geeseler , Lanete Paul Jeremy , La Torre Ardwayne Jurel , Loteyro Thomas , Lua Raisa Mikaela , Manansala Nicole Gayle , Mosquito Raphael , Octaviano Alexa Marie , Orfanel Alexandra Erika , Papa Anne Elizabeth , Pascual Gheyanna Merly , Peralta Mark Nhel , Sale Aubrey Joy , Tendenilla Sophia Lorraine , Trinidad Maria Sofia Lauren , Trinidad Nicole Jan , Verano Daphne Louise , Austriaco Nicanor
Published: January 2024

To mitigate the unprecedented health, social, and economic damage of COVID-19, the Philippines implemented a nation-wide vaccine program to mitigate the effects of the global pandemic. In a previous study, we interrogated COVID-19 vaccine intent in the country by deploying a nationwide open-access online survey, two months before the initial rollout of the national vaccination program that began in March of 2021. In this follow-up study, we explored the influence of the ongoing vaccine rollout on vaccine intent by deploying a similar survey six months after the initial rollout of vaccines had begun throughout the archipelago. Our data suggests that the presence of vaccines and vaccinated individuals in a Filipino community predicts vaccination intent. When directly asked if they were more willing to receive a vaccination than six months prior, 92.26% agreed to some extent that they were indeed more willing. Finally, despite the changes in the numbers of respondents who were more open to the COVID-19 vaccines, there were no significant changes in the predictive power of our Health Belief Model (HBM) constructs. For the most part, the HBM factors that predicted vaccination intent in our earlier study also predicted vaccination intent in this current study.
Pre-operative Spine Tumor Embolization: Clinical Outcomes and Effect of Embolization Completeness
Authors: Omid-Fard Nima , Salameh Jean-Paul , McInnes Matthew DF , Fisher Charles G , Heran Manraj KS
Published: January 2024

Background and Purpose

To assess the association between the impact of the completeness of pre-operative spine tumour embolization and clinical outcomes including estimated blood loss (EBL), neurological status, and complications.

Materials and Methods

Retrospective chart review of all preoperative spine tumour embolization procedures performed over 11 years by a single operator (2007-2018) at Vancouver General Hospital, on 40 consecutive patients (mean age 58; 77.5% males) with 42 embolization procedures, of which surgery was done en bloc in 22 cases and intralesional in the remaining 20. A multivariable negative binomial regression model was fit to examine the association between EBL and surgery type, tumour characteristics, embolization completeness and operative duration.

Results

Among intralesional surgeries, complete versus incomplete embolization was associated with reduced blood loss (772 vs 1428 mL, P < 0.001). There was no statistically significant difference in neurological outcomes or complications between groups. Highly vascular tumours correlated with greater blood loss than their less vascular counterparts, but tumour location did not have a statistically significant effect.

Conclusion

This study provides early evidence in support of our hypothesis that complete as opposed to incomplete tumour embolization correlates with reduced blood loss in intralesional surgeries. Randomized control trials with larger samples are necessary to confirm this benefit and to ascertain other potential clinical benefits.
‘Involve those, who are managing these outbreaks’– Identifying barriers and facilitators to the implementation of clinical management guidelines for High-Consequence Infectious Diseases in Uganda
Authors: Kabajaasi Olive , Schilling Stefan , Akugizibwe Mathias , Horby Peter , Hart Peter , Sigfrid Louise , Jacob Shevin T.
Published: January 2024

Prior research highlighting the complexity of clinical management guidelines (CMG) implementation, has suggested that limited access to treatments and equipment [1] and substantial issues regarding availability, inclusivity, quality, and applicability [2–6] hinder the implementation of CMGs in Low- and Middle-Income Countries (LMICs). This in-depth case study of Uganda – coincidentally occurring during the 2022 Sudan Virus Disease outbreak – aimed to explore contextual and supplementary factors which hinder or facilitate CMG development and implementation. Using thematic network analysis [7–9] the research describes five thematic topics, that emerged from interviews with 43 healthcare personnel, as barriers to the implementation of CMGs in Uganda, namely: (1) deficient content and slow updates of CMGs; (2) limited pandemic preparedness and response infrastructure; (3) slow dissemination and lack of training; (4) scarce resources and healthcare disparities and (5) patient outcomes. The study displays how insufficient training, patchy dissemination and slow updating exacerbate many of the underlying difficulties in LMIC contexts, by illustrating how these issues are related to resource constraints, healthcare disparities, and limited surveillance and referral infrastructure. Key recommendations to enhance CMG implementation are provided, underscoring the necessity of integrating local stakeholders to ensure guidelines are reflective of the reality of the local health system, applicable and inclusive of resource-constrained settings, available as “living guidance” that is disseminated widely and supported by cascading hands-on training. Findings offer valuable insights for LMICs to improve high consequence infectious disease outbreak responses and for organizations involved in guideline development and funding.