bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secular trends and sociodemographic disparities in physical activity among adults in eleven African countries: WHO STEPS 2003–2020
Authors: Oyeyemi Adewale L. , Araujo Raphael H.O. , Hassan Umar A. , Ofori Edward , Stetcher Chad , Werneck André O. 
Published: October 2024

Abstract
Background
Mortality from physical inactivity-related non-communicable diseases (NCDs) is projected to surpass deaths from communicable diseases by 2030 in Africa. Monitoring physical activity (PA) is important for planning public health interventions addressing NCDS and planetary health, but there is a dearth of evidence on PA trends in Africa. This study explored the secular trends in overall and domains of PA (leisure, occupation, and transport), and examined the gender, age, and education disparities in PA trends across African countries.

Methods
We utilized data from the STEPwise approach to NCDs risk factor surveillance in eleven African countries (Algeria, Benin, Botswana, Cabo Verde, Eritrea, Eswatini, Malawi, Mali, Central Africa Republic, Sao Tome and Principe, and Zambia) with at least two surveys conducted between 2003/2010 (first-wave) and 2010/2020 (second-waves). A total of 29,282 and 40,147 adults (18–69 years) in the first and second waves, respectively, completed PA interviews using the Global Physical Activity Questionnaire. Gender, age, and education status were self-reported. Weighted individual-country PA prevalence and 95% confidence interval (95%CI) were obtained. Random-effect meta-analysis was conducted to assess pooled estimates of PA trends across countries. Gender, age, and education disparities in PA trends were also investigated.

Results
Country-specific results showed significant upward trends in total PA in eight countries. Seven countries showed significant increasing trends in some leisure-time PA (2.0% − 13.9% increase) and ≥ 150 min/week transport PA (4.0% − 24.5% increase), while five countries recorded significant increasing trends in occupational PA (6.6% − 56.9% increase). Gender, age and education disparities in meeting the WHO PA guidelines remained relatively stable over time, but disparities in leisure, transport and occupational PA increased in most countries.

Conclusions
The prevalence of overall PA among African adults has marginally increased over 17 years. There are still many adults, especially women and people with lower education, not doing well in domain specific PA. Policy and environmental interventions are needed to improve PA and to reduce gender, age, and education disparities in leisure, transport, and occupational PA in African countries.
Winsorization greatly reduces false positives by popular differential expression methods when analyzing human population samples
Authors: Yang Lu , Zhang Xianyang , Chen Jun 
Published: October 2024

AbstractA recent study found severely inflated type I error rates for DESeq2 and edgeR, two dominant tools used for differential expression analysis of RNA-seq data. Here, we show that by properly addressing the outliers in the RNA-Seq data using winsorization, the type I error rate of DESeq2 and edgeR can be substantially reduced, and the power is comparable to Wilcoxon rank-sum test for large datasets. Therefore, as an alternative to Wilcoxon rank-sum test, they may still be applied for differential expression analysis of large RNA-Seq datasets.
Low-dose dobutamine in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (the DOBERMANN-D trial): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial
Authors: Holle Sarah Louise Duus , Kunkel Joakim Bo , Hassager Christian , Pecini Redi , Wiberg Sebastian , Palm Pernille , Holmvang Lene , Bang Lia Evi , Kjærgaard Jesper , Thomsen Jakob Hartvig , Engstrøm Thomas , Møller Jacob Eifer , Lønborg Jacob Thomsen , Søholm Helle , Frydland Martin 
Published: October 2024

Abstract
Background
Cardiogenic shock (CS) occurs in 5–10% of patients with acute myocardial infarction (AMI), and the condition is associated with a 30-day mortality rate of up to 50%. Most of the AMI patients are in SCAI SHOCK stage B upon hospital arrival, but some of these patients will progression through the stages to overt shock (SCAI C-E). Around one third of patients who develop CS are not in shock at the time of hospital admission. Pro-B-type natriuretic peptide (proband) is a biomarker closely related to CS development. The aim of this study is to investigate the potential for preventing progression of hemodynamic instability by early inotropic support with low-dose dobutamine infusion administrated after revascularization in AMI patients with intermediate to high risk of in-hospital CS development.

Methods
This investigator-initiated, double-blinded, placebo-controlled, randomized, single-center, clinical trial will include 100 AMI patients (≥ 18 years) without CS at hospital admission and at intermediate-high risk of in-hospital CS development (ORBI risk score ≥ 10). Patients will be randomized in a 1:1 ratio to a 24 h intravenous (IV) infusion of dobutamine (5 μg/kg/min) or placebo (NaCl) administrated after acute percutaneous coronary intervention (PCI) (< 24 h from symptom onset). Blood samples are drawn at time points from study inclusion (before infusion, 12, 24, 36, and 48 h).

The primary outcome is peak plasma proBNP within 48 h after infusion as a surrogate-measure for the hemodynamic status. Hemodynamic function will be assessed pulse rate, blood pressure, and lactate within 48 h after infusion and by transthoracic echocardiography (TTE) performed after 24–48 h and at follow-up after 3 months. Markers of cardiac injury (troponin T and creatine kinase MB (CK-MB)) will be assessed.

Discussion
Early inotropic support with low-dose dobutamine infusion in patients with AMI, treated with acute PCI, and at intermediate-high risk of in-hospital CS may serve as an intervention promoting hemodynamic stability and facilitating patient recovery. The effect will be assessed using proBNP as a surrogate marker of CS development, hemodynamic measurements, and TTE within the initial 48 h and repeated at a 3-month follow-up.

Trial registration
The Regional Ethics Committee
: H-21045751. EudraCT: 2021–002028-19. ClinicalTrials.gov: NCT05350592, Registration date: 2022-03-08. WHO Universal Trial Number: U1111-1277–8523.
Starch granules in algal cells play an inherent role to shape the popular SSC signal in flow cytometry
Authors: Sandmann Michael , Rading Michael 
Published: October 2024

Abstract
Objective
Flow cytometry (FC) is probably the most important technique for single-cell analysis. It’s precisely, rapid, and suitable for multidimensional single-cell analysis. The commonly used side scatter (SSC) intensity determined by FC is often interpreted as a measure of the internal cellular complexity of cells. In simple terms, the more structured a cell is, the higher the SSC intensity quantified by FC. Nevertheless, most of the studies that support this interpretation are based on data derived from animal or human cell lines and while it is assumed that the results can also be transferred to plant or algal cell lines, the details remain unclear. The objective of the recent work is to clarify the interpretation of the SSC signal from algal cells.

Results
Algal lipid droplets and their starch play an inherent role to shape the popular SSC signal derived from FC. This was shown by a theoretical approach based on Lorenz–Mie theory. These results were supported by experiments with different model cultures of Chlamydomonas reinhardtii in which a high linear correlation was observed between the SSC signal and the ‘physical’ starch quantity.
Prospective phase II trial of [68Ga]Ga-NOTA-AE105 uPAR-PET/MRI in patients with primary gliomas: Prognostic value and Implications for uPAR-targeted Radionuclide Therapy
Authors: Azam Aleena , Kurbegovic Sorel , Carlsen Esben Andreas , Andersen Thomas Lund , Larsen Vibeke André , Law Ian , Skjøth-Rasmussen Jane , Kjaer Andreas 
Published: October 2024

Abstract
Background
Treatment of patients with low-grade and high-grade gliomas is highly variable due to the large difference in survival expectancy. New non-invasive tools are needed for risk stratification prior to treatment. The urokinase plasminogen activator receptor (uPAR) is expressed in several cancers, associated with poor prognosis and may be non-invasively imaged using uPAR-PET. We aimed to investigate the uptake of the uPAR-PET tracer [68Ga]Ga-NOTA-AE105 in primary gliomas and establish its prognostic value regarding overall survival (OS), and progression-free survival (PFS). Additionally, we analyzed the proportion of uPAR-PET positive tumors to estimate the potential number of candidates for future uPAR-PRRT.

Methods
In a prospective phase II clinical trial, 24 patients suspected of primary glioma underwent a dynamic 60-min PET/MRI following the administration of approximately 200 MBq (range: 83–222 MBq) [68Ga]Ga-NOTA-AE105. Lesions were considered uPAR positive if the tumor-to-background ratio, calculated as the ratio of TumorSUVmax-to-Normal-BrainSUVmean tumor-SUVmax-to-background-SUVmean, was ≥ 2.0. The patients were followed over time to assess OS and PFS and stratified into high and low uPAR expression groups based on TumorSUVmax.

Results
Of the 24 patients, 16 (67%) were diagnosed with WHO grade 4 gliomas, 6 (25%) with grade 3, and 2 (8%) with grade 2. Two-thirds of all patients (67%) presented with uPAR positive lesions and 94% grade 4 gliomas. At median follow up of 18.8 (2.1–45.6) months, 19 patients had disease progression and 14 had died. uPAR expression dichotomized into high and low, revealed significant worse prognosis for the high uPAR group for OS and PFS with HR of 14.3 (95% CI, 1.8-112.3; P = 0.011), and HR of 26.5 (95% CI, 3.3–214.0; P = 0.0021), respectively. uPAR expression as a continuous variable was associated with worse prognosis for OS and PFS with HR of 2.7 (95% CI, 1.5–4.8; P = 0.0012), and HR of 2.5 (95% CI, 1.5–4.2; P = 0.00073), respectively.

Conclusions
The majority of glioma patients and almost all with grade 4 gliomas displayed uPAR positive lesions underlining the feasibility of 68Ga-NOTA-AE105 PET/MRI in gliomas. High uPAR expression is significantly correlated with worse survival outcomes for patients. Additionally, the high proportion of uPAR positive gliomas underscores the potential of uPAR-targeted radionuclide therapy in these patients.

Trail Registration
EudraCT No: 2016-002417-21; the Scientific Ethics Committee: H-16,035,303; the Danish Data Protection Agency: 2012-58-0004; clinical trials registry: NCT02945826, 26Oct2016, URL: https://classic.clinicaltrials.gov/ct2/show/NCT02945826.
Amide proton transfer-weighted CEST MRI for radiotherapy target delineation of glioblastoma: a prospective pilot study
Authors: Tang Patrick L. Y. , Romero Alejandra Méndez , Nout Remi A. , van Rij Caroline , Slagter Cleo , Swaak-Kragten Annemarie T. , Smits Marion , Warnert Esther A. H. 
Published: October 2024

Abstract
Background
Extensive glioblastoma infiltration justifies a 15-mm margin around the gross tumor volume (GTV) to define the radiotherapy clinical target volume (CTV). Amide proton transfer (APT)-weighted imaging could enable visualization of tumor infiltration, allowing more accurate GTV delineation. We quantified the impact of integrating APT-weighted imaging into GTV delineation of glioblastoma and compared two APT-weighted quantification methods—magnetization transfer ratio asymmetry (MTRasym) and Lorentzian difference (LD) analysis—for target delineation.

Methods
Nine glioblastoma patients underwent an extended imaging protocol prior to radiotherapy, yielding APT-weighted MTRasym and LD maps. From both maps, biological tumor volumes were generated (BTVMTRasym and BTVLD) and added to the conventional GTV to generate biological GTVs (GTVbio,MTRasym and GTVbio,LD). Wilcoxon signed-rank tests were performed for comparisons.

Results
The GTVbio,MTRasym and GTVbio,LD were significantly larger than the conventional GTV (p ≤ 0.022), with a median volume increase of 9.3% and 2.1%, respectively. The GTVbio,MTRasym and GTVbio,LD were significantly smaller than the CTV (p = 0.004), with a median volume reduction of 72.1% and 70.9%, respectively. There was no significant volume difference between the BTVMTRasym and BTVLD (p = 0.074). In three patients, BTVMTRasym delineation was affected by elevated signals at the brain periphery due to residual motion artifacts; this elevation was absent on the APT-weighted LD maps.

Conclusion
Larger biological GTVs compared to the conventional GTV highlight the potential of APT-weighted imaging for radiotherapy target delineation of glioblastoma. APT-weighted LD mapping may be advantageous for target delineation as it may be more robust against motion artifacts.

Relevance statement
The introduction of APT-weighted imaging may, ultimately, enhance visualization of tumor infiltration and eliminate the need for the substantial 15-mm safety margin for target delineation of glioblastoma. This could reduce the risk of radiation toxicity while still effectively irradiating the tumor.

Trial registration
NCT05970757 (ClinicalTrials.gov).

Key Points

Integration of APT-weighted imaging into target delineation for radiotherapy is feasible.

The integration of APT-weighted imaging yields larger GTVs in glioblastoma.

APT-weighted LD mapping may be more robust against motion artifacts than APT-weighted MTRasym.

Graphical Abstract
Hypoxia-inducible factor-1α-deficient adipose-tissue macrophages produce the heat to mediate lipolysis of white adipose tissue through uncoupling protein-1
Authors: Kang Gi-Sue , Kim Young-Eun , Oh Ho Rim , Jo Hye-Ju , Bok Seoyeon , Jeon Yoon Kyung , Cheon Gi Jeong , Roh Tae-Young , Chang Young-Tae , Park Do Joong , Ahn G-One 
Published: October 2024

Abstract
Background
Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane generally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming 'beige’ adipocytes.

Results
In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking functional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased glycolysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of co-cultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals.

Conclusions
UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.
Autistic psychiatrists’ experiences of recognising themselves and others as autistic: a qualitative study
Authors: Doherty Mary , Chown Nick , Martin Nicola , Shaw Sebastian C. K. 
Published: October 2024

Background
Diagnosis of autism falls under the remit of psychiatry. Recognition that psychiatrists could be autistic is recent. Psychiatrists are the second largest specialty group in Autistic Doctors International, a peer support group for autistic doctors.

Aims
To explore the experiences of autistic psychiatrists in relation to recognising themselves and others as autistic.

Method
This was a qualitative study using loosely structured interviews and an interpretive phenomenological analysis.

Results
Eight autistic senior psychiatrists based in the UK participated. One had a childhood diagnosis, two had been diagnosed in adulthood and the remainder self-identified as autistic as adults. Recognition of autism followed diagnosis of their children or encounters with autistic patients. Barriers to self-recognition included lack of autism training, the deficit-based diagnostic criteria and stereotypical views of autism. Recognising that they were autistic led to the realisation that many colleagues were also likely to be autistic, particularly in neurodevelopmental psychiatry. All participants reported the ability to quickly recognise autistic patients and to develop a good rapport easily, once they were aware of their own autistic identity. Difficulties recognising patients as autistic occurred before self-recognition when they shared autistic characteristics and experiences. ‘If we don't recognise ourselves as autistic how on earth can we diagnose patients accurately?’

Conclusions
Autistic psychiatrists face multiple barriers to recognising that they are autistic. Lack of self-recognition may impede diagnostic accuracy with autistic patients. Self-recognition and disclosure by autistic psychiatrists may be facilitated by reframing the traditional deficit-based view of autism towards a neurodiversity-affirmative approach, with consequent benefits for autistic patients.
Associations of psychotic symptom dimensions with clinical and developmental variables in twin and general clinical samples
Authors: Cardno Alastair G. , Allardyce Judith , Bakker Steven C. , Toulopoulou Timothea , Kravariti Eugenia , Picchioni Marco M. , Kane Fergus , Rijsdijk Frühling V. , Mahmood Tariq , Nasser el din Soumaya , du Toit Deline , Jones Lisa A. , Quattrone Diego , Walters James T. R. , Legge Sophie E. , Holmans Peter A. , Murray Robin M. , Vassos Evangelos 
Published: October 2024

BackgroundPositive, negative and disorganised psychotic symptom dimensions are associated with clinical and developmental variables, but differing definitions complicate interpretation. Additionally, some variables have had little investigation.AimsTo investigate associations of psychotic symptom dimensions with clinical and developmental variables, and familial aggregation of symptom dimensions, in multiple samples employing the same definitions.MethodWe investigated associations between lifetime symptom dimensions and clinical and developmental variables in two twin and two general psychosis samples. Dimension symptom scores and most other variables were from the Operational Criteria Checklist. We used logistic regression in generalised linear mixed models for combined sample analysis (n = 875 probands). We also investigated correlations of dimensions within monozygotic (MZ) twin pairs concordant for psychosis (n = 96 pairs).ResultsHigher symptom scores on all three dimensions were associated with poor premorbid social adjustment, never marrying/cohabiting and earlier age at onset, and with a chronic course, most strongly for the negative dimension. The positive dimension was also associated with Black and minority ethnicity and lifetime cannabis use; the negative dimension with male gender; and the disorganised dimension with gradual onset, lower premorbid IQ and substantial within twin-pair correlation. In secondary analysis, disorganised symptoms in MZ twin probands were associated with lower premorbid IQ in their co-twins.ConclusionsThese results confirm associations that dimensions share in common and strengthen the evidence for distinct associations of co-occurring positive symptoms with ethnic minority status, negative symptoms with male gender and disorganised symptoms with substantial familial influences, which may overlap with influences on premorbid IQ.
Soluble Immune Checkpoints Associated With Disease Activity and Treatment Response in GD and TED
Authors: Yin Qinglei , Zhu Tianyi , Song Dalong , Fang Sijie , Zhou Huifang , Guan Haixia 
Published: October 2024

Abstract

Context
Soluble immune checkpoints play an important role in peripheral tolerance that has seldom been investigated in Graves' disease (GD) and thyroid eye disease (TED).

Objective
The objective of this work is to examine the alteration of soluble immune checkpoints in GD and TED.

Methods
We performed a quantitative multiplex analysis of 17 immune checkpoint proteins in serum from 50 GD patients without TED, 28 GD patients with TED, and 40 healthy controls. The association with demographic, serologic, clinical features and 27 cytokines was analyzed. A follow-up was conducted in GD patients without TED. Functional outcomes of sLAG-3 and sGITR were assessed in cell cultures using rh-LAG3, rh-GITR, an antagonistic LAG-3 antibody, and an antagonistic GITR antibody.

Results
GD Patients with TED had distinct sICP and cytokine profiles compared with GD patients without TED. Active patients with TED exhibited elevation in the levels of sBTLA, sLAG-3, sGITR, sCD80, sCD86, and sPD-L1. Further, GD patients without TED with high sBTLA, sCD27, and sCD40 levels at baseline showed a better improvement in thyrotropin receptor antibody titers after antithyroid drug treatment. Adding recombinant human GITR and LAG-3 to peripheral blood mononuclear cell cultures resulted in increased inflammatory cytokine secretion and decreased anti-inflammatory cytokine secretion.

Conclusion
The present study uncovers disturbed soluble immune checkpoints and cytokines in GD patients with and without TED and may pave the way for novel immunological screening, allowing for identification of patients with TED at higher risk of developing active disease and patients with GD a better treatment response after antithyroid drug treatment.