bluuebunny/crossref_metadata_2025 huggingface dataset:
Future-proofing quality education using integrated assessment systems
Authors: Chamba Lucy Tambudzai , Chikusvura Namatirai
Published: August 2024

Purpose

Current assessment models in education have focused solely on measuring knowledge and fail to address the goals of Sustainable Development Goal 4 (SDG4) for a well-rounded, future-proof education. While SDG4 emphasizes quality education, traditional assessments do not account for the diverse skills and intelligence learners possess. This gap between assessment and the needs of SDG4 presents a conundrum for educators: How can we develop assessment strategies that encompass multiple intelligences and prepare learners for the future while ensuring the delivery of quality education as outlined by SDG4? This paper aims to propose integrated assessment strategies as a solution, examining their effectiveness in assessing multiple intelligences and supporting the future-proofing agenda within quality education.

Design/methodology/approach

The study used a qualitative research design. Interviews were held up to saturation point with 60 teachers and students purposively selected from schools in ten provinces across the country. Data from interviews were analysed using thematic network analysis. The data were complemented by documentary analysis from the Ministry of Primary and Secondary Education, Zimbabwe documents which included Curriculum Frameworks and policy documents as well as a systematic literature review.

Findings

Results indicated that integrated assessment systems provide an avenue for testing deeper learning and help students acquire competencies needed in the world of work, such as problem-solving and teamwork. However, certain conditions mitigate against the effective implementation of integrated assessment in schools.

Research limitations/implications

This study uses the use of a qualitative research methodology, hence the generalizability of results in other settings may not be possible. The data collected from the research findings was manually coded and analysed. However, coding the data manually allowed the researchers to be fully immersed in the emerging themes enriching the study with additional data. This means that in-depth data engagement was ensured.

Practical implications

The paper concludes that integrated assessment provides authentic assessment which prepares learners for the future. The study recommends that the government should redress the teaching-learning environment in schools for effective implementation of integrated assessment systems so that not only one regime of intelligence is tested and future-proofing of quality is guaranteed.

Originality/value

The research contributes to increasing the motivation to deliver quality education by investing in integrated evaluation systems.
Valency‐Conditioned Allomorphy in the Verbal Agreement of the Takestani Dialect of Southern Tati
Authors: Taherkhani Neda , Dolatian Hossep
Published: August 2024

This paper studies the morphological structure of verbs in Takestani, an endangered Iranian dialect of Southern Tati. We analyse the effects of various morphological conditions on subject agreement allomorphy. The agreement suffix exhibits a large range of allomorphs in the past tense. We show that the primary factor for the agreement allomorphy is the valency of the root, and secondary factors are the presence of auxiliaries or perfective aspect. We also propose that the agreement allomorphy is a long‐distance process. The agreement allomorphy is conditioned by the voice or transitivity of the verb stem even though the stem is not directly adjacent to the agreement suffix. Alternative formulations in terms of clitics vs. suffixes do not negate the long‐distance nature of this allomorphy. We also find morphomic patterns of behaviour, such that the verbal agreement suffixes are mobile and can alternatively surface as possessive suffixes on nouns.
Issue congruence in international organizations: A study of World Bank spending
Authors: Heinzel Mirko , Reinsberg Bernhard , Zaccaria Giuseppe
Published: August 2024

International organizations (IOs) are often criticized for insulated decision‐making processes that do not react to the preferences of key stakeholders that are directly affected by them. However, empirical studies probing the degree to which IOs’ policies are aligned with the preferences of such key constituencies are scarce. This paper tackles the gap by studying the case of the World Bank. We argue that congruence with stakeholder preferences increases when recipients have institutional means of participation and decreases when donors restrict the purposes of their funds. We utilize survey data from 269 stakeholder surveys conducted in 114 countries between 2012 and 2022 for our empirical analysis. Our findings carry important implications for the responsiveness of IOs to stakeholders in low‐ and middle‐income countries.
Impact of device variability and protocol differences on kidney function during normothermic machine perfusion: A comparative study using porcine and human kidneys
Authors: Lantinga Veerle A. , Arykbaeva Asel S. , Spraakman Nora A. , Blom Elwin W. P. , Huijink Tobias M. , de Vries Dorottya K. , Ploeg Rutger J. , Alwayn Ian P. J. , Leuvenink Henri G. D. , Moers Cyril , van Leeuwen L. Leonie
Published: August 2024

Introduction

A growing interest in renal normothermic machine perfusion (NMP) has resulted in more clinically available perfusion devices. While all perfusion systems have the same aim, there are significant differences in their circuits, pumps, sensors, and software. Therefore, our objective was to assess the impact of different perfusion protocols and devices on kidney function and perfusion parameters during NMP.

Methods

Porcine kidneys were subjected to 30 min of warm ischemia, 24 h of static cold storage, and subsequently perfused for 6 h using (1) the Kidney Assist (KA) machine with a pressure of 75 mm Hg, (2) the KA device incorporating several adjustments and a pressure of 85 mm Hg (modified KA), or (3) the Perlife (PL) perfusion device (n = 4). Consecutively, discarded human kidneys were perfused using the KA or modified KA (n = 3) protocol.

Results

The PL group quickly reached the device’s upper flow limit and consequently received a significantly lower pressure compared to the KA groups. The arterial pO2 was significantly lower in the PL group. Yet, hemoglobin concentration increased over time, and oxygen consumption was significantly higher compared to the KA groups. Fractional sodium excretion was significantly lower in the PL group. Tissue ATP levels, urine production, and creatinine clearance rates did not differ between groups. In human kidneys, the modified KA group showed significantly lower vascular resistance, higher oxygen delivery, and lower levels of lactate in the perfusate compared to the KA group.

Conclusions

This study shows that perfusion characteristics and kidney function are significantly influenced by the perfusion protocol and the device and its settings during normothermic machine perfusion and therefore should be interpreted with caution.
A novel thrombocytopenia‐4‐causing CYCS gene variant decreases caspase activity: Three‐generation study
Authors: Štika Jiří , Pešová Michaela , Kozubík Kateřina Staňo , Skalníková Magdalena , Dostálová Lenka , Loja Tomáš , Radová Lenka , Palušová Veronika , Réblová Kamila , Vrzalová Zuzana , Blaháková Ivona , Trizuljak Jakub , Uldrijan Stjepan , Blatný Jan , Šmída Michal , Pospíšilová Šárka , Doubek Michael
Published: August 2024

The CYCS gene is highly evolutionarily conserved, with only a few pathogenic variants that cause thrombocytopenia‐4 (THC4). Here, we report a novel CYCS variant NM_018947.6: c.59C>T [NP_061820.1:p.(Thr20Ile)] segregating with thrombocytopenia in three generations of a Czech family. The phenotype of the patients corresponds to THC4 with platelets of normal size and morphology and dominant inheritance. Intriguingly, a gradual decline in platelet counts was observed across generations. CRISPR/Cas9‐mediated gene editing was used to introduce the new CYCS gene variant into a megakaryoblast cell line (MEG‐01). Subsequently, the adhesion, shape, size, ploidy, viability, mitochondrial respiration, cytochrome c protein (CYCS) expression, cell surface antigen expression and caspase activity were analysed in cells carrying the studied variant. Interestingly, the variant decreases the expression of CYCS while increasing mitochondrial respiration and the expression of CD9 cell surface antigen. Surprisingly, the variant abates caspase activation, contrasting with previously known effects of other CYCS variants. Some reports indicate that caspases may be involved in thrombopoiesis; thus, the observed dysregulation of caspase activity might contribute to thrombocytopenia. The findings significantly enhance our understanding of the molecular mechanisms underlying inherited thrombocytopenia and may have implications for diagnosis, prognosis and future targeted therapies.
Incorporation mutational profile might reduce the importance of blast count in prognostication of low‐risk myelodysplastic syndromes
Authors: García‐Culebras Marta , Alcalde Patricia , Márquez‐Malaver Francisco J. , Carrillo Estrella , Soria Elena , Prats Concepción , Morales Rosario , Vargas María T. , Pérez‐Simón Jose Antonio , Falantes Jose F.
Published: August 2024

Addition of molecular data to prognostic models has improved risk stratification of myelodysplastic neoplasms (MDS). However, the role of molecular lesions, particularly in the group of low‐risk disease (LR‐MDS), is uncertain. We evaluated a set of 227 patients with LR‐MDS. Overall survival (OS) and probability of leukaemic progression were the main endpoints. RUNX1 was associated with lower OS and SF3B1 with a reduced risk of death (HR: 1.7, 95% CI, 1.1–2.9; p = 0.05; and HR: 0.23, 95% CI 0.1–0.5; p < 0.001; respectively). TP53 and RUNX1 mutations were predictive covariates for the probability of leukaemic progression (p < 0.001). Blast percentage, neither analysed as categorical (<5% vs. 5%–9%; HR: 1.3, 95% CI, 0.7–2.9; p = 0.2) nor as a continuous variable (HR: 1.07, 95% CI, 0.9–1.1; p = 0.07), had impact on survival or probability of progression (sHR: 1.05, 95% CI, 0.9–1.1; p = 0.2). These results retained statistical significance when analysis was restricted to the definition of LR‐MDS according to the WHO 2022 and ICC classifications (<5% blasts). Thus, with the incorporation of molecular data, blast percentage happens to lose clinical significance both for survival and probability of progression in the group of patients with LR‐MDS.
WT1 together with RUNX1::RUNX1T1 targets DUSP6 to dampen ERK activity in acute myeloid leukaemia
Authors: Xu Nan , Dao Feng‐Ting , Shi Zong‐Yan , Sun Kai , Qin Ya‐Zhen
Published: August 2024

Wilms' tumour 1 (WT1) can function as an oncogene or a tumour suppressor. Our previous clinical cohort studies showed that low WT1 expression at diagnosis independently predicted poor outcomes in acute myeloid leukaemia (AML) with RUNX1::RUNX1T1, whereas it had an opposite role in AML with non‐favourable cytogenetic risk (RUNX1::RUNX1T1‐deficient). The molecular mechanism by which RUNX1::RUNX1T1 affects the prognostic significance of WT1 in AML remains unknown. In the present study, first we validated the prognostic significance of WT1 expression in AML. Then by using the established transfected cell lines and xenograft tumour model, we found that WT1 suppresses proliferation and enhances effect of cytarabine in RUNX1::RUNX1T1(+) AML but has opposite functions in AML cells without RUNX1::RUNX1T1. Furthermore, as a transcription factor, WT1 physically interacts with RUNX1::RUNX1T1 and acts as a co‐factor together with RUNX1::RUNX1T1 to activate the expression of its target gene DUSP6 to dampen extracellular signal‐regulated kinase (ERK) activity. When RUNX1::RUNX1T1‐deficient, WT1 can activate the mitogen‐activated extracellular signal‐regulated kinase/ERK axis but not through targeting DUSP6. These results provide a mechanism by which WT1 together with RUNX1::RUNX1T1 suppresses cell proliferation through WT1/DUSP6/ERK axis in AML. The current study provides an explanation for the controversial prognostic significance of WT1 expression in AML patients.
Palaeogeography and 3D variability of a dynamically uplifted shelf: Observations from seismic stratigraphy of the Palaeocene East Shetland Platform
Authors: Valore Lucas Albanese , Sømme Tor Oftedal , Patruno Stefano , Robin Cécile , Guillocheau François , Eide Christian Haug
Published: August 2024

In the Palaeocene North Sea, pulses in turbidite fan deposition and shelfal progradation have been correlated with episodes of regional uplift caused by a precursor of the Icelandic Plume. In the East Shetland Platform, the specific impacts of dynamic uplift on the regional palaeogeographic evolution are less understood. Using new, high‐resolution 3D seismic data from an underexplored proximal area, we investigate the palaeogeography of the East Shetland Platform in terms of the extent and timing of erosion versus deposition, focusing on how these can be used to reconstruct changes in relative sea‐level along strike. Using a combination of well data, clinoform‐based seismic stratigraphy and seismic attribute analysis of >60,000 km2 of 3D data, we have obtained palaeogeographic maps of multiple Palaeocene to Early Eocene units, with high temporal resolution for the Late Palaeocene–Early Eocene Moray Group. This includes six unconformity‐bounded units marked by prograding clinoforms of the Dornoch Formation, which are covered by backstepping sequences of the Beauly Member (Balder Formation). Temporal and spatial changes in the distribution of downdip depocentres and updip unconformities indicate strong lateral variability in patterns of shelf accommodation/erosion and local sediment supply. This results from a complex interplay among laterally uneven relative sea‐level fall, inherited topography, time‐varied sediment entry point distribution and along‐shore sediment transport regimes. Unconformities and palaeogeographic maps suggest a first‐order control on erosion and sediment distribution promoted by the transiently and differentially uplifted topography of Shetland, which is characterized by an anomalous erosive history in the Bressay High, in the centre of our study area, where the Lower Dornoch Formation has been eroded and marked fluvial incision is observed. Ultimately, results indicate shorter‐wavelength and shorter‐period variations in uplift than what is typically assumed for dynamic topography, perhaps as a result of additional modulation by lithospheric structures or influence of previous rift‐related faults.
Non‐immune hydrops fetalis is associated with bi‐allelic pathogenic variants in the MYB Binding Protein 1a (MYBBP1A) gene
Authors: Tenorio‐Castano Jair , Mansilla Aparicio Elena , García Santiago Fe Amalia , Klotz Cherise M. , Regojo Rita María , Anguita Estefanía , Ryan Erin , Juusola Jane , Herrero Beatriz , Arias Pedro , Parra Alejandro , Pascual Patricia , Gallego Natalia , Cazalla Mario , Rodriguez‐González Roberto , Antolín Eugenia , Nevado Julián , Ruiz‐Perez Víctor L. , Lapunzina Pablo
Published: August 2024

Non‐immune hydrops fetalis (NIHF) is a rare entity characterized by excessive accumulation of fluid within the fetal extravascular compartments and body cavities. Here we present two intrauterine fetal demises with NIHF presenting with oligohydramnios, cystic hygroma, pleural effusion, and generalized hydrops with predominance of subcutaneous edema. The fetuses also presented with ascites, severe and precocious IUGR and skeletal anomalies. Whole exome sequencing was applied in order to screen for a possible genetic cause. The results identified biallelic variants in MYBBP1A in both fetuses. A previous report described another case with a similar phenotype having compound heterozygous variants in the same gene. The protein encoded by MYBBP1A is involved in several cellular processes including the synthesis of ribosomal DNA, the response to nucleolar stress, and tumor suppression. Our functional protein analysis through immunohistochemistry indicates that MYBBP1A is a gene expressed during fetal stages. Altogether, we concluded that MYBBP1A is associated with the development of hydrops fetalis. More cases and further studies are necessary to understand the role of this gene and the mechanism associated with NIHF.
Endoscopic ultrasound‐guided rendezvous techniques for difficult biliary cannulation: Technical review
Authors: Iwashita Takuji , Uemura Shinya , Tezuka Ryuichi , Senju Akihiko , Iwata Shota , Ohashi Yosuke , Shimizu Masahito
Published: August 2024

Endoscopic retrograde cholangiopancreatography (ERCP) is the standard procedure for the diagnosis and treatment of biliary diseases. However, selective biliary cannulation, the essential first step in ERCP, can sometimes fail due to anatomical variations or technical limitations. In these cases, the endoscopic ultrasound‐guided rendezvous technique (EUS‐RV) offers a valuable salvage option. Nevertheless, it is crucial to be aware of potential adverse events associated with bile duct puncture. To optimize the success rate and safety of EUS‐RV, understanding the basic techniques, technical tips for each procedural step, and troubleshooting strategies for potential difficulties is essential. This review article summarizes the clinical outcomes and technical considerations of EUS‐RV, including a comprehensive analysis of the current evidence.
Fish oil supplementation in relation to the risk of chronic kidney disease among patients with diabetes
Authors: Ao Yang , Ye Hao , Liu Xiaohui , Li Yin , Liu Haoyin , Ye Shu , Hu Yepeng , Zhuang Pan , Zhang Yu , Zheng Chao , Jiao Jingjing
Published: August 2024

Aim

To investigate the association between fish oil supplementation and subsequent risk of chronic kidney disease (CKD) among patients with diabetes, and further evaluate the mediation effect of typical glycolipid and inflammatory biomarkers.

Methods

In total, 24 497 patients with diabetes from the UK Biobank were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD risk, and the rate advancement period was calculated to quantify and communicate the impact of fish oil upon that risk. In addition, we also used mediation analysis to assess the mediating role of plasma biomarkers.

Results

Overall, 7122 patients reported taking fish oil supplements. During a mean of 11.3 years of follow‐up, 3533 CKD cases occurred. In the fully adjusted model, fish oil use was inversely associated with the incidence of CKD (HR 0.90; 95% CI: 0.83, 0.97), which was mediated by serum levels of HbA1c (4.7%), C‐reactive protein (CRP) (3.4%) and high‐density lipoprotein cholesterol (HDL‐C) (2.3%). Participants who took fish oil supplements displayed the same risk of CKD events, but that risk was delayed by approximately 2.79 years compared with non‐users of fish oil.

Conclusions

Our findings advocate the beneficial role of fish oil use in preventing CKD among patients with diabetes, which may be mediated by serum levels of HbA1c, CRP and HDL‐C, and support public health policies aiming to promote fish oil supplementation for the prevention of diabetes complications.
Use of continuous glucose monitoring when initiating glucagon‐like peptide‐1 receptor agonist therapy in insulin‐treated diabetes
Authors: Hirsch Irl B. , Parkin Christopher G. , Cavaiola Tricia Santos , Bergenstal Richard M.
Published: August 2024

Glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) medications have been shown to be effective in achieving optimal glucose control and reducing all‐cause death, cardiovascular death, nonfatal myocardial infarction, hospitalization for heart failure, and end‐stage kidney disease in individuals with type 1 (T1D) and type 2 diabetes (T2D). However, use of these medications has been associated with increased hypoglycaemia risk in patients treated with concomitant antihyperglycaemic medications. The risk is particularly high in patients with T1D due to their loss of glucagon counter‐regulatory response. This article reviews the effect of GLP‐1RA formulations on the development of hypoglycaemia in individuals with T1D and T2D treated with insulin therapy, discusses the benefits of continuous glucose monitoring with GLP‐1RA treatment, and presents strategies for safely initiating GLP‐1RA therapy in these individuals.
Health‐related quality of life of people with type 1 diabetes: An IMI2 SOPHIA post hoc analysis of FUTURE and ADJUNCT‐ONE
Authors: Steenackers Nele , Sparsø Thomas , Charleer Sara , De Block Christophe , De Cock Diederik , Delfin Carl , Mathieu Chantal , Nobels Frank , Pazmino Sofia , Rosen Jonathan , del Pozo Carmen Hurtado , Gillard Pieter , Van der Schueren Bart
Published: August 2024

Aim

To characterize and stratify health‐related quality of life in individuals with type 1 diabetes (T1D) using body mass index (BMI) and clustering analysis.

Material and Methods

Baseline data on individuals with T1D were pooled from two studies. A post hoc analysis of health‐related quality of life, measured using the 36‐item Short‐Form questionnaire, was performed, referenced to the 2010 US general population. Descriptive statistics were presented for the pooled cohort and per BMI category. K‐means clustering was performed. One‐way analysis of variance was conducted to examine differences in clinical characteristics between clusters.

Results

The pooled cohort consisted of 2256 individuals with T1D (age: 45.4 ± 15.0 years, BMI: 26.2 ± 4.6 kg/m2, diabetes duration: 22.7 ± 13.5 years). All quality‐of‐life domains were slightly lower than 50(the general population's mean), except for vitality. Individuals with a BMI ≥30 kg/m2 reported lower scores for bodily pain, physical functioning, general health, and vitality. A first cluster with a high and a second cluster with a low quality of life were identified, with significant differences in the mental (Cluster 1: 53.8 ± 6.8 vs. Cluster 2: 39.5 ± 10.7; p < 0.001) and physical component summary scores (Cluster 1: 49.6 ± 6.3 vs. Cluster 2: 35.2 ± 12.0; p < 0.001), which exceeded differences found between BMI categories.

Conclusions

In our population of people living with T1D, higher BMI may have adversely impacted physical domains of quality of life, but larger differences between the high‐ and low‐quality‐of‐life cluster indicate that more factors play a role.
Achieving normoglycaemia with tirzepatide: Post hoc exploratory analysis of the SURPASS J‐mono and J‐combo studies
Authors: Fujihara Kazuya , Matsubayashi Yasuhiro , Kitazawa Masaru , Sato Takaaki , Takeuchi Masakazu , Oura Tomonori , Sone Hirohito
Published: August 2024

Aim

Normoglycaemia was achieved in a significant proportion of Japanese participants with type 2 diabetes in two phase 3 studies of tirzepatide. This post hoc exploratory analysis aimed to identify predictive factors associated with normoglycaemia achievement.

Materials and Methods

SURPASS J‐mono and SURPASS J‐combo study data were pooled for this analysis. Characteristics of participants in whom normoglycaemia [glycated haemoglobin (HbA1c) <5.7%] was achieved were summarized. Logistic regression analyses were performed with HbA1c <5.7% achievement as the target variable.

Results

Of 912 participants, normoglycaemia was achieved in 553 (60.6%) following 52 weeks of tirzepatide treatment. Overall, the mean (SD) age was 56.7 (10.6) years and mean diabetes duration was 7.7 (6.0) years, and 76% of participants were men. Mean (SD) change from baseline in HbA1c and bodyweight was −2.87% (0.95) versus −2.47% (1.1) and −10.30 (5.8) kg versus −3.75 (4.3) kg for participants in whom normoglycaemia was and was not reached, respectively. Multivariate regression analyses showed that lower baseline body mass index, shorter disease duration and lower baseline HbA1c were significantly associated with higher rates of normoglycaemia achievement (p = 0.009, p = 0.008, p < 0.001, respectively) as was a tirzepatide dose of 10 or 15 mg compared with 5 mg (p < 0.001). The highest percentage of participants in whom normoglycaemia (94%) was achieved were those with lower baseline HbA1c (<8%) and the greatest weight reduction (≥15%).

Conclusions

Baseline HbA1c and body mass index, disease duration and the tirzepatide treatment group were shown to be predictive factors for achieving normoglycaemia. A lower baseline HbA1c was most strongly associated with normoglycaemia achievement.
Elucidating the role of weight loss and glycaemic control in patients with type 2 diabetes
Authors: Sharma Anukriti , Mariam Arshiya , Zacherle Emily , Milinovich Alex , Bauman Janine , Sugano David S. , Noone Josh , Rajpura Jigar R. , Zimmerman Robert S. , Burguera Bartolome , Kattan Michael W. , Misra‐Hebert Anita D. , Pantalone Kevin M. , Rotroff Daniel M.
Published: August 2024

Aims

To investigate the independent contributions of glycated haemoglobin (HbA1c) reduction and weight loss to clinical outcomes in patients with type 2 diabetes (T2D) treated with antidiabetic drugs, including glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs).

Materials and Methods

This observational, retrospective cohort study used deidentified electronic health record‐derived data from patients evaluated at the Cleveland Clinic (1 January 2000–31 December 2020). Cohort A included 8876 patients with newly diagnosed T2D treated with any of six antidiabetic drug classes. Cohort B included 4161 patients with T2D initiating GLP‐1RA treatment. The effects of body mass index (BMI) and HbA1c reduction, variability, and durability on clinical outcomes were investigated.

Results

In Cohort A, each 1% BMI reduction was associated with 3%, 1%, and 4% reduced risk of heart failure (p = 0.017), hypertension (p = 0.006), and insulin initiation (p = 0.001), respectively. Each 1% (~11 mmol/mol) HbA1c reduction was associated with 4% and 29% reduced risk of hypertension (p = 0.041) and insulin initiation (p = 0.001), respectively. In Cohort B, each 1% BMI reduction was associated with 4% and 3% reduced risk of cardiovascular disease (p = 0.008) and insulin initiation (p = 0.002), respectively. Each 1% (~11 mmol/mol) HbA1c reduction was associated with 4% and 16% reduced risk of chronic kidney disease (p = 0.014) and insulin initiation (p = 1 × 10−4), respectively. Lower BMI variability and greater BMI durability were associated with decreased risk of clinical outcomes in both cohorts.

Conclusions

Antidiabetic medication‐associated, and specifically GLP‐1RA‐associated, weight loss and HbA1c reductions independently reduce real‐world clinical outcome risk.
Real‐time fMRI neurofeedback of the anterior insula using arterial spin labelling
Authors: Grössinger Doris , Spann Stefan M. , Stollberger Rudolf , Pfeuffer Josef , Koten Jan Willem , Wood Guilherme
Published: August 2024

Arterial spin labelling (ASL) is the only non‐invasive technique that allows absolute quantification of perfusion and is increasingly used in brain activation studies. Contrary to the blood oxygen level‐dependent (BOLD) effect ASL measures the cerebral blood flow (CBF) directly. However, the ASL signal has a lower signal‐to‐noise ratio (SNR), than the BOLD signal, which constrains its utilization in neurofeedback studies. If successful, ASL neurofeedback can be used to aid in the rehabilitation of health conditions with impaired blood flow, for example, stroke. We provide the first ASL‐based neurofeedback study incorporating a double‐blind, sham‐controlled design. A pseudo‐continuous ASL (pCASL) approach with background suppression and 3D GRASE readout was combined with a real‐time post‐processing pipeline. The real‐time pipeline allows to monitor the ASL signal and provides real‐time feedback on the neural activity to the subject. In total 41 healthy adults (19–56 years) divided into three groups underwent a neurofeedback‐based emotion imagery training of the left anterior insula. Two groups differing only in the explicitness level of instruction received real training and a third group received sham feedback. Only those participants receiving real feedback with explicit instruction showed significantly higher absolute CBF values in the trained region during neurofeedback than participants receiving sham feedback. However, responder analyses of percent signal change values show no differences in activation between the three groups. Persisting limitations, such as the lower SNR, confounding effects of arterial transit time and partial volume effects still impact negatively the implementation of ASL neurofeedback.
Conditioning‐ and reward‐related dendritic and presynaptic plasticity of nucleus accumbens neurons in male and female sign‐tracker rats
Authors: Colom Morgane , Kraev Igor , Stramek Agata K. , Loza Iwona B. , Rostron Claire L. , Heath Christopher J. , Dommett Eleanor J. , Singer Bryan F.
Published: August 2024

For a subset of individuals known as sign‐trackers, discrete Pavlovian cues associated with rewarding stimuli can acquire incentive properties and exert control over behaviour. Because responsiveness to cues is a feature of various neuropsychiatric conditions, rodent models of sign‐tracking may prove useful for exploring the neurobiology of individual variation in psychiatric vulnerabilities. Converging evidence points towards the involvement of dopaminergic neurotransmission in the nucleus accumbens core (NAc) in the development of sign‐tracking, yet whether this phenotype is associated with specific accumbal postsynaptic properties is unknown. Here, we examined dendritic spine structural organisation, as well as presynaptic and postsynaptic markers of activity, in the NAc core of male and female rats following a Pavlovian‐conditioned approach procedure. In contrast to our prediction that cue re‐exposure would increase spine density, experiencing the discrete lever‐cue without reward delivery resulted in lower spine density than control rats for which the lever was unpaired with reward during training; this effect was tempered in the most robust sign‐trackers. Interestingly, this same behavioural test (lever presentation without reward) resulted in increased levels of a marker of presynaptic activity (synaptophysin), and this effect was greatest in female rats. Whilst some behavioural differences were observed in females during initial Pavlovian training, final conditioning scores did not differ from males and were unaffected by the oestrous cycle. This work provides novel insights into how conditioning impacts the neuronal plasticity of the NAc core, whilst highlighting the importance of studying the behaviour and neurobiology of both male and female rats.
The combined impact of migraine and gestational diabetes on long‐term risk of premature myocardial infarction and stroke: A population‐based cohort study
Authors: Fuglsang Cecilia H. , Pedersen Lars , Schmidt Morten , Vandenbroucke Jan P. , Bøtker Hans Erik , Sørensen Henrik Toft
Published: August 2024

Objective

To examine the combined impact of migraine and gestational diabetes mellitus (GDM) on the risks of premature (persons aged ≤60 years) major adverse cardiovascular and cerebrovascular events (MACCE) based on a composite endpoint of fatal and non‐fatal myocardial infarction (MI) and stroke.

Background

Migraine and GDM are risk factors for cardiovascular disease. It is unknown how the combination of migraine and GDM may affect cardiovascular disease risk.

Methods

In a Danish population‐based cohort longitudinal study, we established four cohorts among women with at least one pregnancy during 1996–2018: women with migraine, women with GDM, women with both migraine and GDM, and women free of migraine and free of GDM. Risks of premature MACCE and component endpoints were assessed for each cohort.

Results

We included 1,307,456 women free of migraine and free of GDM, 56,811 women with migraine, 24,700 women with GDM, and 1484 women with migraine and GDM. The 20‐year absolute risk of MACCE was 1.3% (MI: 0.4%, ischemic stroke: 0.6%, hemorrhagic stroke: 0.3%) among women free of migraine and free of GDM, 2.3% (MI: 0.8%, ischemic stroke: 1.2%, hemorrhagic stroke: 0.5%) among women with migraine, 2.2% (MI: 1.0%, ischemic stroke: 1.0%, hemorrhagic stroke: 0.4%) among women with GDM, and 3.7% (MI: 1.7%, ischemic stroke: 1.7%, hemorrhagic stroke: 0.3%) among women with both migraine and GDM. The 20‐year adjusted hazard ratio of premature MACCE was 1.65 (95% confidence interval [CI] 1.49–1.82) for women with migraine; 1.64 (95% CI 1.37–1.96) for women with GDM; and 2.35 (95% CI 1.03–5.36) for women with both GDM and migraine when compared with women free of migraine and free of GDM.

Conclusions

Migraine and GDM were each independently associated with an increased risk of MACCE. Risk of premature MACCE was greatest among women with both migraine and GDM, although this risk estimate was imprecise.
Exploring Chinese as a second language learners’ motivational factors: Influence of selves and contexts
Authors: Li Junzhe , Tsung Linda
Published: August 2024

The past decades have witnessed a significant increase in the number of global Chinese as a second language (L2) learners. Accompanying the surge is the growing body of research on their motivational factors. This mixed‐methods study was primarily informed by Dörnyei's L2 motivational self system (L2MSS), aiming to scrutinize Chinese as a second language (CSL) learners’ motivational factors from the perspectives of selves and contexts. Leveraging the concepts of the ideal L2 self and ought‐to L2 self from L2MSS, the anti‐ought‐to‐L2 self was incorporated into the framework. The L2 learning experience was reframed into three contextual dimensions, including attitudes toward the L2 community, cultural interest and pedagogical influence. Data were collected from 231 international students from a Chinese comprehensive university. Factor analyses confirmed seven motivational factors. Findings revealed that the ideal L2 self, ought‐to L2 self, pedagogical influence and cultural interest were effective in predicting individuals’ intended learning effort. Significant differences were identified in the motivational selves based on demographic variables of employment status, gender and student type. The novelty of this study lies in its focus on the motivations of languages other than English learners and the refinement of the L2MSS framework. It also offers CSL instructors pedagogical implications for developing targeted teaching strategies and promoting motivations among students from distinct educational and socio‐economic backgrounds.
La sombra alargada del patrón: Gamonalismo y hábitos hacendatarios en Chimborazo tras la reforma agraria
Authors: Bretón Víctor
Published: August 2024

This paper explores selective aspects of the historical processes of organization of the kichwa peasantry in the Andes of Ecuador. Based on the analysis of two representative cases of confrontation between peasants and landowners over access to land in the province of Chimborazo, it discusses the relevance of the concept of “gamonalismo” as both a category with which to interpret the system of peasant subjugation until the 1960s, and as significant social system conceived by Mariátegui in 1927. The paper identifies perceptions of social space that suggest the symbolic presence of the gamonal order among the generations who inherited the processes of struggle. It has an exploratory nature as it probes the interconnections between topics such as the ecological characteristics of the territory, the historical construction of a long‐standing system of domination and, after its dissolution, the persistence of its symbolic universe in Andean communities.
Misprogramming of glucose metabolism impairs recovery of hippocampal slices from neuronal GLT‐1 knockout mice and contributes to excitotoxic injury through mitochondrial superoxide production
Authors: Li S. , Wang J. , Andersen J. V. , Aldana B. I. , Zhang B. , Prochownik E. V. , Rosenberg P. A.
Published: August 2024

We have previously reported a failure of recovery of synaptic function in the CA1 region of acute hippocampal slices from mice with a conditional neuronal knockout (KO) of GLT‐1 (EAAT2, Slc1A2) driven by synapsin‐Cre (synGLT‐1 KO). The failure of recovery of synaptic function is due to excitotoxic injury. We hypothesized that changes in mitochondrial metabolism contribute to the heightened vulnerability to excitotoxicity in the synGLT‐1 KO mice. We found impaired flux of carbon from 13C‐glucose into the tricarboxylic acid cycle in synGLT‐1 KO cortical and hippocampal slices compared with wild‐type (WT) slices. In addition, we found downregulation of the neuronal glucose transporter GLUT3 in both genotypes. Flux of carbon from [1,2‐13C]acetate, thought to be astrocyte‐specific, was increased in the synGLT‐KO hippocampal slices but not cortical slices. Glycogen stores, predominantly localized to astrocytes, are rapidly depleted in slices after cutting, and are replenished during ex vivo incubation. In the synGLT‐1 KO, replenishment of glycogen stores during ex vivo incubation was compromised. These results suggest both neuronal and astrocytic metabolic perturbations in the synGLT‐1 KO slices. Supplementing incubation medium during recovery with 20 mM D‐glucose normalized glycogen replenishment but had no effect on recovery of synaptic function. In contrast, 20 mM non‐metabolizable L‐glucose substantially improved recovery of synaptic function, suggesting that D‐glucose metabolism contributes to the excitotoxic injury in the synGLT‐1 KO slices. L‐lactate substitution for D‐glucose did not promote recovery of synaptic function, implicating mitochondrial metabolism. Consistent with this hypothesis, phosphorylation of pyruvate dehydrogenase, which decreases enzyme activity, was increased in WT slices during the recovery period, but not in synGLT‐1 KO slices. Since metabolism of glucose by the mitochondrial electron transport chain is associated with superoxide production, we tested the effect of drugs that scavenge and prevent superoxide production. The superoxide dismutase/catalase mimic EUK‐134 conferred complete protection and full recovery of synaptic function. A site‐specific inhibitor of complex III superoxide production, S3QEL‐2, was also protective, but inhibitors of NADPH oxidase were not. In summary, we find that the failure of recovery of synaptic function in hippocampal slices from the synGLT‐1 KO mouse, previously shown to be due to excitotoxic injury, is caused by production of superoxide by mitochondrial metabolism.

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Capital Commitment
Authors: GOURIER ELISE , PHALIPPOU LUDOVIC , WESTERFIELD MARK M.
Published: August 2024

Twelve trillion dollars are allocated to private market funds that require outside investors to commit to transferring capital on demand. We show within a novel dynamic portfolio allocation model that ex‐ante commitment has large effects on investors' portfolios and welfare, and we quantify those effects. Investors are underallocated to private market funds and are willing to pay a larger premium to adjust the quantity committed than to eliminate other frictions, like timing uncertainty and limited tradability. Perhaps counterintuitively, commitment risk premiums increase with secondary market liquidity, and they do not disappear when investments are spread over many funds.
Hospitalization after hydroxychloroquine initiation in patients with heart failure with preserved ejection fraction and autoimmune disease
Authors: Riaz Munaza , Park Haesuk , Pepine Carl J. , Shukla Ashutosh M.
Published: August 2024

Background

Hydroxychloroquine (HCQ) reduces cardiovascular events among patients with autoimmune disorders and is being evaluated as a therapeutic option for populations with high‐risk cardiovascular disease. However, recent studies have raised concerns about HCQ use and cardiovascular events.

Objective

To assess the association of HCQ initiation with heart failure–related and all‐cause hospitalizations among patients with heart failure and preserved ejection fraction (HFpEF).

Methods

We conducted a cohort study of patients aged ≥18 years with diagnosed HFpEF and autoimmune disease using MarketScan Commercial and Medicare Supplemental databases (2007–2019). Patients were required to initiate HCQ after their first HFpEF diagnosis (HCQ users) or not (HCQ nonusers). For the patients in the HCQ users group, the first HCQ prescription date was assigned as the index date. Index date for the HCQ nonuser group was assigned by prescription‐time distribution matching HCQ users, by utilizing the number of days from HFpEF diagnosis to the first HCQ prescription. After 1:≥3 propensity score (PS) matching, Cox proportional hazards regression models were used to compare HF‐related and all‐cause hospitalizations between users and nonusers.

Results

After PS matching, 2229 patients (592 HCQ users and 1637 HCQ nonusers) were included. After controlling for covariates, patients who received HCQ had lower risks of HF‐related hospitalization (adjusted hazard ratio, 0.44; 95% CI, 0.24–0.82) and all‐cause hospitalization (adjusted hazard ratio, 0.69; 95% CI, 0.57–0.83) compared with patients not using HCQ.

Conclusions

Among patients with HFpEF and autoimmune disease, initiation of HCQ use was associated with a decreased risk of HF‐related and all‐cause hospitalizations.
Genetic susceptibility to temporomandibular joint involvement in juvenile idiopathic arthritis
Authors: Niibo P. , Nikopensius T. , Jagomägi T. , Voog Ü. , Haller T. , Tõnisson N. , Metspalu A. , Saag M. , Pruunsild C.
Published: August 2024

Background

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Temporomandibular joint (TMJ) is among the most commonly affected joints in JIA patients. When JIA involves the TMJ, it may affect condylar growth in the joint; therefore, JIA patients are at risk of unfavourable long‐term outcomes from associated joint damage. If undetected, TMJ involvement can lead to various functional disabilities such as reduced mandibular mobility and disorders of the mastication muscles. Limitations in sagittal and vertical mandibular growth can result in micrognathia and anterior open bite with aesthetic and functional restrictions.

Objective

Genetic factors may play a role in determining which individuals are more prone to develop TMJ disorders or in predicting the severity of the disease process. Therefore, we applied a GWAS approach to identify loci associated with TMJ involvement in a sample of Estonian patients with JIA. Our aim was to address the potential role of genetic susceptibility factors in TMJ‐JIA, a condition not previously studied in this context.

Methods

The case group consisted of 55 JIA patients with TMJ involvement and 208 patients without TMJ involvement comprised the control group. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. Imputation was performed using a nationwide reference panel obtained of 2240 individuals whose data were obtained from the Estonian Biobank.

Results

We identified six loci as being associated with the risk of TMJ‐JIA in Estonian JIA patients. The strongest associations were identified at CD6 rs3019551 (P = 3.80 × 10−6), SLC26A8/MAPK14 rs9470191 (P = 6.15 × 10−6), NLRP3 rs2056795 (P = 8.91 × 10−6) and MAP2K4 rs7225328 (P = 1.64 × 10−5).

Conclusion

This study provides first insights into the risk‐associated loci between JIA and its manifestation in the TMJ. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that render the TMJ susceptible to involvement by JIA in Estonian patients.
Fish production, water quality, and the role of nitrification as an ammonia removal process in intensively aerated hybrid catfish ponds
Authors: Ott Brian D. , Torrans Eugene L. , Tucker Craig S.
Published: August 2024

Six 0.1‐ha earthen ponds with 45 kW/ha of aeration capacity were stocked with hybrid catfish (Ictalurus punctatus x I. furcatus) ranging from 15,000 to 90,000 fish ha−1 in 15,000 fish ha−1 increments to analyze the effect of nitrogen loading on ammonia accumulation and fish production. Minimum dissolved oxygen (DO) concentration was maintained above 3.0 mg O2 L−1 to prevent hypoxia‐induced appetite reduction. Stocking density did not impact survival but decreased average fish harvest weight and increased food conversion ratio (FCR). Gross production increased with stocking density and ranged from 7249 to 35,674 kg ha−1. Average total (TAN) and un‐ionized ammonia (NH3) were not different among stocking densities despite greater nitrogen inputs in ponds with higher feeding rates. Nitrite () and nitrate () concentrations were significantly higher in ponds with higher stocking densities, suggesting that nitrification increased with nitrogen loading. Phytoplankton assimilation of ammonia is the primary ammonia removal process in traditional catfish ponds with modest fish densities and feeding rates. However, in intensively aerated ponds with high feeding rates, nitrification can become an important process for ammonia removal. These data indicate that small earthen hybrid catfish ponds with high aeration capacities can increase catfish production without ammonia accumulating.
Social costs and policy preferences: Evidence from territorial strategies in Catalonia
Authors: Balcells Laia , Kuo Alexander
Published: August 2024

Research on territorial preferences in self‐determination disputes has traditionally focused on economic and identity‐related factors. However, the impact of social costs—encompassing overall societal comfort and conviviality—on specific preferences for territorial strategies remains understudied. This paper presents a novel perspective by investigating how social costs affect such policy preferences in Catalonia, a region in Spain where secession has become a politically salient and defining feature of the political debate in recent decades. Through embedded experiments conducted within regionally representative online surveys over two time periods, we examine the relationship between social costs and preferences for territorial strategies. Our theoretical framework and empirical findings underscore the importance of considering social costs as a determinant of policy preferences, warranting further cross‐national exploration—beyond territorial debates.