bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opposition or Acquiescence to Neoliberal Hegemony? A Sociological Analysis of the Use of Human Rights Frames in UK Social Movements
Authors: Duncan John 
Published: December 2024

Abstract
Building on recent work in the field of sociology of rights which emphasizes the ‘social life of rights’ and the interaction between micro-level social constructions via social movement action, and macro-level systemic forces, this paper constructs a counter-hegemonic theory of human rights. By drawing on both Gramscian theories and a Social Reproduction Theory framework, a novel view of neoliberal hegemony is described. The role of human rights as part of this hegemony is then clarified as an essential element of the production of consent to hegemony. This hegemonic form of human rights is contrasted against a counter-hegemonic construction which is grounded in data generated from 10 in-depth qualitative interviews conducted with social movement activists in the UK. Three findings generated from the data are described. The activists interviewed 1) consistently rejected hegemonic, legal/non-governmental organization human rights structures; 2) used human rights as an introduction to their activism and a base upon which further critiques are built; and 3) frequently used human rights to contest the commodification of socially reproductive goods. Considering these findings, the role of contesting hegemonic constructions of human rights in resisting wider neoliberal hegemony is considered. While counter-hegemonic rights are not considered to have produced the level of social movement action required to overcome deeply embedded neoliberalism, counter-hegemonic human rights hold the potential to contribute to challenging the production of both consent and coercion to neoliberalism in the UK.
Intestinal stem cells in intestinal homeostasis and colorectal tumorigenesis
Authors: Shi Gaoli , Li Yang , Shen Haihong , He Qiankun , Zhu Pingping 
Published: December 2024

Abstract
Colorectal cancer (CRC), one of the most common tumors in the world, is generally proposed to be generated from intestinal stem cells (ISCs). Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5)-positive ISCs are located at the bottom of the crypt and harbor self-renewal and differentiation capacities, serving as the resource of all intestinal epithelial cells and CRC cells as well. Here we review recent progress in ISCs both in non-tumoral and tumoral contexts. We summarize the molecular mechanisms of ISC self-renewal, differentiation, and plasticity for intestinal homeostasis and regeneration. We also discuss the function of ISCs in colorectal tumorigenesis as cancer stem cells and summarize fate dynamic, competition, niche regulation, and remote environmental regulation of ISCs for CRC initiation and propagation.
A phase II trial of larotrectinib in tumors with NTRK fusions or extremes of NTRK mRNA overexpression identified by comprehensive genomic profiling
Authors: Thavaneswaran Subotheni , Sim Hao-Wen , Grady John , Espinoza David , Huang Min Li , Lin Frank , McGrath Margaret , Desai Jayesh , Charakidis Michail , Brown Michael , Kansara Maya , Simes John , Thomas David 
Published: December 2024

Abstract

Background
TRK-inhibitors have demonstrated efficacy across several cancers with NTRK fusions. Their activity in cancers with NTRK overexpression remains unclear.

Methods
This trial enrolled patients with advanced cancers harboring NTRK fusions or extreme mRNA overexpression, defined as NTRK1/2/3 expression by RNA profiling &gt;5 SDs for a given cancer type. The primary endpoint was objective response rate (ORR), with secondary endpoints including time-to-progression (TTP) ratio [TTP on study to TTP on previous systemic therapy (TTP1)], progression-free survival (PFS), and overall survival (OS). Initially planned for 2 non-comparator groups: primary central nervous system (CNS) and non-CNS tumours with NTRK fusions, the protocol was amended to permit NTRK overexpression.

Results
Seventeen patients were treated with larotrectinib: one glioblastoma with a SPECC1L::NTRK2 fusion (group 1), and a peripheral nerve sheath tumor with a TPM3::NTRK1 fusion and 15 patients with overexpression (group 2). The ORR was 6%. An additional 3 of 12 (25%) TTP1-evaluable patients achieved a TTP ratio ≥1.3 and 2 of 5 without an evaluable TTP1 had a PFS &gt;6 months. Median PFS and OS were 3.5 (95% CI, 1.4-6.0) and 15.9 months (95% CI, 6.4-NR), respectively.

Conclusion
Unlike its efficacy in NTRK-fusion positive cancers, larotrectinib did not demonstrate a signal of efficacy among tumors with NTRK overexpression.
Making responsible research and innovation meaningful in citizen science
Authors: Tauginienė Loreta , Butkevičienė Eglė , Heinisch Barbara , Massetti Luciano , Ugolini Francesca , Popov Snežana 
Published: December 2024

Abstract
This study aims to explore what aspects of citizen science (CS) make the involvement of researchers (implementing CS projects) meaningful in terms of Responsible Research and Innovation (RRI) principles. Using constructivist grounded theory, we analysed semi-structured interviews conducted with 20 CS projects in terms of sensemaking and sensegiving. In terms of sensemaking, researchers of CS projects tend to implicitly self-incorporate RRI principles into work and among these principles, public engagement and inclusion are key aspects motivating researchers into CS projects. In terms of sensegiving, researchers prioritize open access and science education over other RRI principles. The lack of acknowledgment of RRI’s importance in the current research culture proves to be a significant barrier to implementing these principles in a sustained manner. Likewise, experiential learning was widely practised; however, CS projects encountered different concerns and dilemmas. Therefore, tailored training on RRI is necessary for researchers involved in CS projects.
Cardiovascular diseases in patients with cancer: A comprehensive review of epidemiological trends, cardiac complications, and prognostic implications
Authors: Alshahrani Ali A. , Kontopantelis Evangelos , Morgan Catharine , Ravindrarajah Rathi , Martin Glen P. , Mamas Mamas A. 
Published: December 2024

Abstract
This article provides an overview of the current evidence on the epidemiology, overlapping risk factors, and pathophysiology of cardiovascular disease (CVD) in patients with cancer. It explores the cardiotoxic effects of anticancer therapy and their impact on prognosis. Although cancer survival rates have improved over the last two decades, the risk of CVD has risen over time in patients with cancer. CVD and cancer share similar risk factors and a common pathophysiology involving inflammation. Many chemotherapeutic agents used to treat cancer are associated with cardiovascular complications (such as heart failure, myocardial infarction, and thrombosis). Current evidence indicates a significant burden of CVD in patients with cancer, particularly in the first year following cancer diagnosis, with elevated risk persisting beyond this period. This short- and long-term risk of CVD may vary depending on the cancer type and treatment regimen. Early identification of potential cardiovascular risk in patients with cancer, can lead to more favorable clinical and survival outcomes. Given the acute and long-term consequences, patients with cancer require increased cardiovascular care and lifestyle optimization. This article offers valuable insights into the cardiovascular burden and needs of patients with cancer. It is intended for a general medical research readership interested in the intersection of cardiology and oncology.
Design of semi-open prosthetic socket with constant force for lower limb
Authors: Wang Minghui , Song Jianguo , Nong Qingjun , Qian Yu , Yan Xianbo , Yu Hongliu 
Published: December 2024

Background:
Prosthetic socket is a key component of the prosthesis for clinical application; its performance directly affects the adaptation of the residual limb to the prosthetic socket. There are long-term and short-term volume fluctuation of the residual limb. The volume fluctuation of the residual limb will lead to the pressure mismatch at the interface of the residual limb and the prosthetic socket, which will cause a series of skin and fit problems. The volume fluctuation of the residual limb is considered a key factor for the successful application of the prosthetic socket; its solution is imminent. The purpose of this paper is to design a prosthetic socket with a constant force unit to solve the problem of volume fluctuation of the residual limb.

Methods:
Constant force extrusion for the residual limb is proposed to solve the problem in this paper. A constant force unit is designed based on the superelasticity of shape memory alloy, and a semi-open prosthetic socket embedded in the constant force unit is designed. The constant force property of prosthetic socket is optimized and verified by finite element analysis.

Results:
The constant force unit obtains a maximum constant force region of 9.36 mm at 13 mm applied displacement, and the minimum stress amplitude is 0.0264%.

Conclusions:
The semi-open prosthetic socket may achieve constant pressure at the interface between the residual limb and prosthetic socket within a certain range of the residual limb volume change, and it has a lightweight, good heat dissipation, size adjustability, and constant interface pressure.
Validity and reliability of Glittre activities of daily living test in lower-limb prosthetic users
Authors: Çiftçi Özge , Yurt Yasin , Koltak Cansu , Eker Levent 
Published: December 2024

Background:
Functional capacity assessments have an important role in determining the level of mobility in lower-limb prosthetic users.

Objectives:
Our aim was to investigate the reliability and validity of the Glittre activities of daily living (ADL) test in lower-limb prosthetic users.

Study design:
A cross-sectional study.

Methods:
The study included 66 people over the age of 18 years who had used a lower-limb prosthesis for at least 6 months and could walk at least 30 m independently. For construct validity, the correlation of the Glittre ADL test with the 2-min walk test, timed up and go test, and functional reach test was examined, and Bland-Altman agreement analysis was performed. Intra-rater reliability was examined with 2 tests performed by the same physiotherapist on different days, and inter-rater reliability was examined with a test performed by a second physiotherapist on a different day.

Results:
The reliability of the Glittre ADL test was found to be excellent for intra-rater (intraclass correlation coefficient = 0.940, 95% confidence interval = 0.903–0.963, standard error of measurement = 26.03, minimal detectable change = 72.31) and good for inter-rater (intraclass correlation coefficient = 0.890, 95% confidence interval = 0.806–0.936, standard error of measurement = 36.80, minimal detectable change = 102.06, p < 0.001). There was a strong negative correlation between Glittre ADL test and 2-min walk test (r = −0.785), a strong positive correlation with timed up and go (r = 0.805), and a weak negative correlation with functional reach test (r = −0.266, p < 0.05). Bland-Altman plots showed 95% agreement for both validity and reliability measurements.

Conclusions:
The Glittre ADL test is a valid and reliable test that can be used in the assessment of functional capacity in lower extremity prosthesis users.
Effects of dynamic elastomeric fabric orthoses in children with cerebral palsy: A single-blind randomized controlled trial
Authors: Bezgin Sabiha , Novak Iona , Çobanoğlu Gamze , Elbasan Bülent 
Published: December 2024

Background:
The dynamic elastomeric fabric orthoses (DEFOs) are made of neoprene material, providing the right biomechanical alignment and afferent input in the trunk, pelvis, and extremities, potentially allowing individuals to actively participate in daily life.

Objective:
The aim of this study was to investigate the effects of DEFOs applied to the lower trunk and pelvis, on balance, gait parameters, and pelvic symmetry in children with cerebral palsy (CP).

Study Design:
An evaluator-blinded randomized controlled trial.

Methods:
Twenty-two children (7 girls, 15 boys) aged 4–10 years, with spastic CP, Gross Motor Function Classification System levels 1 and 2 were included. Thirteen children were randomly assigned to the control group (group 1) and 13 to the orthosis group (group 2), but 4 withdrew before treatment commenced. There were 10 children in group 1 and 12 in group 2. Both groups received a physiotherapy and rehabilitation program twice a week for 8 weeks. Children in group 2 received lower body and pelvis DEFOs in addition to physiotherapy and rehabilitation sessions. Dynamic elastomeric fabric orthoses wearing tolerance was gradually built up over the first week, until the child was wearing the DEFO 8 h per day. The pediatric balance scale and timed up and go test were used to assess balance, while gait parameters and pelvic kinematic values were evaluated using the BTS G-Walk, a wireless mini digital gait analysis system. All of the measurement tools used were validated for CP.

Results:
Only stride length among the gait parameters changed in the group using DEFO compared with the group not using it (p = 0.035). There was no change in gait speed and cadence nor were there any differences in the balance scores between the groups. However, the pelvic tilt in the frontal plane of the pelvis improved significantly in the group using DEFOs compared with the group not using it (p = 0.014).

Conclusions:
Dynamic elastomeric fabric orthoses used in the lower body and pelvis conferred superior stride length and the pelvic tilt in the frontal plane to conventional physiotherapy. All other outcomes were equally effective between groups.
demres: An R package to study time-varying demographic resilience
Authors: Louvrier Julie , Courtiol Alexandre , White Ella W. , Clark Adam T. , Benhaiem Sarah , Radchuk Viktoriia 
Published: December 2024

AbstractQuantifying the resilience of populations to disturbances is essential to assess how threatened populations are. Demographic resilience has been defined as the ability of populations to resist and recover from alterations in their demographic structures. Resilience metrics are typically obtained by applying transient analyses to matrix population models. Until now, the questions of how demographic resilience can change over time, how to quantify such temporal variation and when it is important to account for it have not yet been studied. However, since demographic rates fluctuate over time, it is essential to evaluate whether and under what conditions the assumption of time-constant demographic resilience remains appropriate.In this study we introduce demres - an R package that offers functions to quantify time- varying and time-constant demographic resilience metrics, including time to convergence, damping ratio, inertia, maximum amplification, maximum attenuation and reactivity. The package also allows the comparison of these two approaches, both visually and by means of distance metrics.We use a case study to illustrate the versatility of demres and demonstrate how this tool can be readily used by conservation biologists, managers and others to assess the time- varying resilience of wildlife populations using long-term demographic data. Our framework facilitates standardised comparisons of demographic resilience metrics, for example by means of comparative studies across populations and species.
A multiscale electro-metabolic model of a rat neocortical circuit reveals the impact of ageing on central cortical layers
Authors: Farina Sofia , Cattabiani Alessandro , Mandge Darshan , Shichkova Polina , Isbister James B. , Jacquemier Jean , King James G. , Markram Henry , Keller Daniel 
Published: December 2024

AbstractThe high energetic demands of the brain arise primarily from neuronal activity. Neurons consume substantial energy to transmit information as electrical signals and maintain their resting membrane potential. These energetic requirements are met by the neuro-glial-vascular (NGV) ensemble, which generates energy in a coupled metabolic process. In ageing, metabolic function becomes impaired, producing less energy and, consequently, the system is unable to sustain the neuronal energetic needs. We propose a multiscale model of electro-metabolic coupling in a reconstructed rat neocortex. This combines an electro-morphologically reconstructed electrophysiological model with a detailed NGV metabolic model. Our results demonstrate that the large-scale model effectively captures electro-metabolic processes at the circuit level, highlighting the importance of heterogeneity within the circuit, where energetic demands vary according to neuronal characteristics. Finally, in metabolic ageing, our model indicates that the middle cortical layers are particularly vulnerable to energy impairment.
When does sexual selection through mate choice deplete versus exaggerate genetic variation: is there a lek paradox?
Authors: Xu Kuangyi , Servedio Maria R. 
Published: December 2024

AbstractThe evolution of female preferences for male display traits relies on females receiving indirect benefits from their choice of mate. This requires substantial genetic variation in display traits or male quality. Nevertheless, sexual selection through mate choice has been assumed to deplete this genetic variation and thus ultimately diminish strong preferences. In fact, sexual traits often have higher genetic variation than non-sexual traits. The puzzle presented by this pattern, and, relatedly, how costly preferences and display traits are maintained, is known as the “lek paradox”. Using infinitesimal models, we show that, contrary to prior suppositions, sexual selection through mate choice may exaggerate genetic variance in male display traits and female preferences, provided that the variance of female preferences relative to the male trait at the stage of mate choice is not too small and preferences are not too weak. In fact, even if preference variation is substantially smaller than trait variation, trait variation can still increase over the case of random mating, as long as selection on the trait is sufficiently strong compared to that on preferences. When trait variation does decrease, we find this reduction to be generally slight. It is under situations such as lekking, in which females can simultaneously choose from many males so that mate discrimination tends to be effectively strong and the cost of choice weak, that sexual selection through mate choice should be expected to be the most powerful in exaggerating genetic variance in male displays.Significance statementThe “lek paradox” – how variation in sexual display traits can be maintained, and mating preferences persist, over evolutionary time – has been one of the most enduring mysteries of the sexual selection literature. We clarify the multiple pathways by which sexual selection via mate preferences alters the genetic variance in display traits and female preferences. Using a mathematical model, we show that the lek paradox is built upon a false premise. We find a wide range of realistic conditions under which sexual selection will increase or minimally reduce variation in display traits, allowing mating preferences to be maintained in a population.
Mu-opioid receptor activation potentiates excitatory transmission at the habenulo-peduncular synapse
Authors: Singhal Sarthak M. , Szlaga Agata , Chen Yen-Chu , Conrad William S. , Hnasko Thomas S. 
Published: December 2024

AbstractThe continuing opioid epidemic poses a huge burden on public health. Identifying the neurocircuitry involved and how opioids modulate their signaling is essential for developing new therapeutic strategies. The medial habenula (MHb) is a small epithalamic structure that projects predominantly to the interpeduncular nucleus (IPN) and represents a mu-opioid receptor (MOR) hotspot. This habenulo-peduncular (HP) circuit can regulate nicotine and opioid withdrawal; however, little is known about the physiological impact of MOR on its function. Using MOR-reporter mice, we observed that MORs are expressed in a subset of MHb and IPN cells. Patch-clamp recordings revealed that MOR activation inhibited action potential firing in MOR+MHb neurons and induced an inhibitory outward current in IPN neurons, consistent with canonical inhibitory effects of MOR. We next used optogenetics to stimulate MOR+MHb axons to investigate the effects of MOR activation on excitatory transmission at the HP synapse. In contrast to its inhibitory effects elsewhere, MOR activation significantly potentiated evoked glutamatergic transmission to IPN. The facilitatory effects of MOR activation on glutamate co-release was also observed from cholinergic-defined HP synapses. The potentiation of excitatory transmission mediated by MOR activation persisted in the presence of blockers of GABA receptors or voltage-gated sodium channels, suggesting a monosynaptic mechanism. Finally, disruption of MOR in the MHb abolished the faciliatory action of DAMGO, indicating that this non-canonical effect of MOR activation on excitatory neurotransmission at the HP synapse is dependent on pre-synaptic MOR expression. Our study demonstrates canonical inhibitory effects of MOR activation in somatodendritic compartments, but non-canonical faciliatory effects on evoked glutamate transmission at the HP synapse, establishing a new mode by which MOR can modulate neuronal function.
Combined deletion of ZFP36L1 and ZFP36L2 drives superior cytokine production in T cells at the cost of cell fitness
Authors: Zandhuis Nordin D. , Bradarić Antonia , van der Zwaan Carmen , Hoogendijk Arie J. , Popović Branka , Wolkers Monika C. 
Published: December 2024

ABSTRACTA key feature of cytotoxic CD8+T cells for eliminating pathogens and malignant cells is their capacity to produce pro-inflammatory cytokines, which includes TNF and IFNγ. Provided that these cytokines are highly toxic, a tight control of their production is imperative. RNA-binding proteins (RBPs) are essential for the fine-tuning of cytokine production. The role of the RBP ZFP36L1 and its sister protein ZFP36L2 herein has been established, however, their relative contribution to cytokine production is not well known. We here compared the effect of ZFP36L1 and ZFP36L2 single and double deficiency in murine effector CD8+T cells. Whereas single deficient T cells significantly increased cytokine production, double deficiency completely unleashed the cytokine production. Not only the TNF production was substantially prolonged in double-deficient T cells. Also, the production of IFNγ reached unprecedented levels with >90% IFNγ–producing T cells compared to 3% in WT T cells, even after 3 days of continuous activation. This continuous cytokine production by double-deficient T cells was also observed in tumor-infiltrating lymphocytes in vivo, however, with no effect on tumor growth. Rather, ZFP36L1 and ZFP36L2 double deficiency resulted in decreased cell viability, impaired STAT5 signaling, and dysregulated cell cycle progression. In conclusion, while combined deletion in ZFP36L1 and ZFP36L2 can drive continuous cytokine production even under chronic activation, safeguards are in place to counteract such super-cytokine producers.