bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy and safety of tofacitinib in anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis associated interstitial lung disease: a systematic review and meta-analysis
Authors: Wang Yanhong , Zou Ruyi , Wei Jie , Tang Cheng , Wang Junjie , Lin Minjie 
Published: October 2024

Background: The presence of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies in dermatomyositis (DM) is associated with an increased risk of developing rapidly progressive interstitial lung disease (RP-ILD) and a poor prognosis. Objectives: We aimed to explore whether tofacitinib could improve the prognosis of Anti-MDA5 antibody positive DM-interstitial lung disease (ILD). Design: Systematic review and meta-analysis. Data Sources and Methods: Studies were included if they compared mortality rate and infection events in patients with anti-MDA5 antibody positive DM-associated ILD who were treated with or without tofacitinib. Results: The systematic review and meta-analysis included a total of 148 patients from four cohort studies. Fifty-eight patients with anti-MDA5 antibody positive DM-ILD who received combined treatment-containing tofacitinib were enrolled in the experimental group. Additionally, 90 DM-ILD patients who did not receive tofacitinib-based therapy were included in the control group. The pooled risk ratio (RR) for all-cause mortality was 0.61 (95% CI, 0.41–0.91, p = 0.02) with I2 = 0 indicating no heterogeneity among the included studies. For virus infection risk, the pooled RR was 1.92 (95% CI, 0.90–4.10, p = 0.09), while bacterial and fungal infection-associated RRs were found to be 1.29 (95% CI, 0.65–2.55, p = 0.47) and 1.15 (95% CI, 0.46–2.89, p = 0.77), respectively. There was no statistically significant difference in infection risk between the two groups, and no heterogeneity was observed. Conclusion: Our findings suggest that tofacitinib may reduce the risk of all-cause mortality in patients with anti-MDA5 antibody-positive DM-ILD without an increased risk of additional infections. Trial registration: PROSPERO: CRD42023445427; https://www.crd.york.ac.uk/prospero/
Optical coherence tomography angiography to assess for retinal vascular changes in Neuro-Sjögren
Authors: Haar Melanie , Konen Franz Felix , Gehlhaar Marten A. , Oluwatoba-Popoola Irene , Donicova Emilia , Wachsmann Marija , Lubbad Ahmed , Hufendiek Katerina , Pielen Amelie , Hohberger Bettina , Mardin Christian , Gingele Stefan , Prenzler Nils K. , Ernst Diana , Witte Torsten , Framme Carsten , Skripuletz Thomas , Seeliger Tabea , Bajor Anna 
Published: October 2024

Background: Sjögren’s syndrome is an autoimmune disease characterized by sicca symptoms and various extraglandular manifestations including vasculitis. Neurological involvement occurs frequently (Neuro-Sjögren) and often mimics immune neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP). Objectives: We aim to assess relevant differences in vessel density (VD) in Optical Coherence Tomography Angiography (OCTA) in those diseases to use it as an easily available diagnostic tool. Design: Prospective, monocentric pilot-study. Methods: OCTA (Heidelberg Engineering OCT SPECTRALIS) of the superficial vascular plexus, intermediate capillary plexus (ICP) and deep capillary plexus (DCP) of the retina was prospectively performed in Neuro-Sjögren, age-matched CIDP patients ( n = 31, each), and healthy controls ( n = 30). Vessel density (VD) and foveal avascular zone (FAZ) was measured with Erlangen Angio Tool. Results: Significantly lower VD were found for the DCP and ICP in Neuro-Sjögren and CIDP patients compared to healthy controls ( p = 0.0002 and <0.0001). When group comparison was age-adjusted, these differences were not found anymore. Different frequencies of “low” retinal blood flow in each layer comparing Neuro-Sjögren and CIDP patients were not found. FAZ revealed no significant differences between patients with Neuro-Sjögren, CIDP and healthy controls. Conclusion: This study found no significant differences in VD or the foveal avascular zone between Neuro-Sjögren and CIDP patients using OCTA, suggesting that inflammatory vascular changes in the retina are uncommon in Neuro-Sjögren patients.
Experience or perception: What healthcare providers need when using the Utrecht Symptom Diary—4 Dimensional, a mixed-methods study
Authors: Lormans Tom , de Graaf Everlien , Leget Carlo , Teunissen Saskia 
Published: October 2024

Background: The Utrecht Symptom Diary—4 Dimensional (USD-4D), an adaptation of the Edmonton Symptom Assessment System, supports healthcare providers (HCPs) in identifying, monitoring, and exploring multidimensional symptoms and needs of patients in the palliative phase. For the USD-4D to be optimally implemented in clinical palliative care, it is essential to know and understand the needs of HCPs when using it. Objective: To identify and interpret the needs of HCPs when using the USD-4D in clinical palliative care, operationalized as perceived facilitators and barriers. Design: An explanatory mixed-methods study with a sequential design. Methods: Data were collected between October 2019 and September 2020. In phase I, quantitative data were collected through a survey targeting Dutch HCPs working in palliative care. Facilitators were identified as items answered positively by ⩾80% of participants, while barriers were identified as items answered negatively by ⩾20% of participants. In phase II, these identified facilitators and barriers were explored in depth through mixed composition focus groups. The Capability-Opportunity-Motivation-Behavior (COM-B) model was utilized to contextualize and interpret the perceived facilitators and barriers. Results: A total of 122 HCPs completed the survey, with 95% of the respondents being women with a mean age of 48 years and 72% being nurses. Additionally, 53% of the respondents had no prior experience with the USD-4D. In phase II, 21 HCPs participated in focus groups. 95% of the participants were women with a mean age of 49 years and 67% being nurses. HCPs pinpointed facilitators primarily related to the potential benefits of the USD-4D for daily patient care. Conversely, the identified barriers included issues related to HCPs’ behavior, knowledge gaps, uncertainty regarding their abilities and attitudes toward the USD-4D, and technical obstacles. Conclusion: Facilitators and barriers across all facets of the COM-B model were recognized, with a notable emphasis on motivational barriers. It should be acknowledged that facilitators and barriers can evolve throughout the implementation process, underscoring the importance of viewing implementation and integration as fluid and continuous endeavors. Facilitators and barriers are closely linked to HCPs’ reflective capacities, emphasizing the need for tailored intervention strategies that align with different stages of USD-4D implementation.
Neutrophilic inflammation in sputum or blood does not define a clinically distinct asthma phenotype in ATLANTIS
Authors: Kuks Pauline J.M. , Kole Tessa M. , Kraft Monica , Siddiqui Salman , Fabbri Leonardo M. , Rabe Klaus F. , Papi Alberto , Brightling Chris , Singh Dave , van der Molen Thys , Kocks Jan Willem W.H. , Chung Kian Fan , Adcock Ian M. , Bhavsar Pankaj K. , Kermani Nazanin Zounemat , Heijink Irene H. , Pouwels Simon D. , Kerstjens Huib A.M. , Slebos Dirk-Jan , van den Berge Maarten 
Published: October 2024

IntroductionNeutrophilic asthma has been suggested to be a clinically distinct phenotype characterised by more severe airflow obstruction and higher exacerbation risk. However, this has only been assessed in few and smaller studies, using different cut-offs to define neutrophilia, and with conflicting results. We used data from ATLANTIS, an observational longitudinal study including a large number of patients with asthma and healthy controls. The aim of the present study was to examine whether neutrophilic inflammation, either in sputum or blood, is more prevalent in asthma and whether it correlates with disease severity.MethodsATLANTIS included 773 asthma patients, with blood collected from 767 (99%) and sputum from 228 patients (30%). Data were available from 244 healthy controls, all providing blood and 126 (52%) providing sputum. Asthma patients were characterised, including parameters of large and small airways disease at baseline and after 6 and 12 months of follow-up. Sputum and blood neutrophilia were defined as values exceeding the upper quartile in asthma patients.ResultsThe prevalence of sputum neutrophilia did not differ between asthma patients and healthy controls. Asthma patients with sputum neutrophilia did not display more severe symptoms, large or small airways disease or more frequent exacerbations. Blood neutrophilia was more common in asthma and was associated with higher body mass index, female sex, current smoking and systemic corticosteroid use. Patients with blood neutrophilia had a statistically significant, but small, increase in residual volume/total lung capacity. Blood neutrophilia was not associated with large or small airways disease or exacerbation risk.ConclusionSputum and blood neutrophilia do not define a distinct clinical phenotype in asthma.
Cardiovascular effects of obstructive sleep apnoea and effects of continuous positive airway pressure therapy: evidence from different study models
Authors: Bradicich Matteo , Pengo Martino F , Steier Joerg , Schwarz Esther Irene 
Published: October 2024

INTRODUCTIONCardiovascular consequences of obstructive sleep apnoea (OSA) and the effects of continuous positive airway pressure (CPAP) therapy on blood pressure, endothelial dysfunction, and MACE (major adverse cardiovascular events) have been studied over decades using different study designs. However, clinical findings from different study models on cardiovascular outcomes are sometimes contradictory.METHODSA literature search was conducted in PubMed for randomised controlled trials, meta-analyses, population-based epidemiological studies and OSA cohort studies up to September 2023 investigating the cardiovascular effect of OSA and CPAP in adults with OSA on the following cardiovascular endpoints: blood pressure, arterial hypertension, endothelial function, and MACE (myocardial infarction, stroke, transient ischemic attack, cardiovascular death). The level of evidence for these outcomes was discussed on the basis of different study models.RESULTS AND CONCLUSIONSThere is high-level evidence of a causal relationship between OSA and arterial hypertension and endothelial dysfunction, as well as on higher MACE incidence among subgroups of patients with untreated OSA. The cardiovascular effects of OSA depend on the severity of OSA, symptoms, phenotype, and comorbidities. The blood pressure-lowering effect of CPAP is mainly observed in uncontrolled and treatment-resistant hypertension. The MACE risk reduction in OSA depends on good long-term CPAP adherence. Younger, sleepy patients with more severe OSA, higher hypoxaemic burden and without overt cardiovascular end-organ disease may particularly benefit from CPAP treatment in terms of cardiovascular risk reduction. Randomised controlled trials of CPAP or other effective OSA treatments in primary cardiovascular prevention and in patients at highest risk are lacking.
Anti-inflammatory effects of tiotropium in copd: a randomized double-blind trial
Authors: van Smoorenburg Lisa H. , Karp Tatiana , Ditz B. , van Geffen W.H. , Guryev Victor , Almusa Ali , Kistemaker L. , Gosens R. , van den Berge Maarten , Kerstjens Huib A.M. 
Published: October 2024

IntroductionChronic Obstructive Pulmonary Disease (COPD) is a major global health issue characterized by respiratory symptoms and exacerbations, significantly impacting mortality and quality of life. Muscarinic antagonists are known to prevent exacerbations, possibly by mitigating airway inflammation. This study evaluated the anti-inflammatory effects of tiotropium in patients with COPD by examining inflammatory protein profiles in sputum and blood, and genome-wide expression in sputum.MethodsWe conducted the prospective, double-blind, randomized-controlled ANTIOFLAM trial. Patients with COPD GOLD II and worse, aged≥40 years and with≥10 smoking pack years were included. After a 4-week wash-out period of inhaled corticosteroids (ICS) and anticholinergics, participants were randomized to 6 weeks of treatment with placebo or tiotropium (soft mist inhaler, 5 µg daily). Our primary endpoint was a decrease of sputum interleukin-6 and interleukin-8 levels in the tiotropium group when compared to the placebo group.ResultsWe evaluated samples of 33 participants (n=17 placebo and n=16 tiotropium). Changes in sputum proteins interleukin-6 and interleukin-8 were significantly higher after treatment with tiotropium when compared to placebo (p<0.05). Differential expression analysis did not reveal gene expression differences including interleukin-6 and −8.ConclusionWe did not find tiotropium to have anti-inflammatory effects in sputum or blood of patients with COPD. In contrast, we found 6 weeks of treatment with tiotropium to increase the concentration of almost all tested sputum inflammatory proteins when compared to placebo, while RNA expression levels did not change.
Sequencing the orthologs of human autosomal forensic short tandem repeats provides individual- and species-level identification in African great apes
Authors: Fedele Ettore , Wetton Jon H. , Jobling Mark A. 
Published: October 2024

Abstract
Background
Great apes are a global conservation concern, with anthropogenic pressures threatening their survival. Genetic analysis can be used to assess the effects of reduced population sizes and the effectiveness of conservation measures. In humans, autosomal short tandem repeats (aSTRs) are widely used in population genetics and for forensic individual identification and kinship testing. Traditionally, genotyping is length-based via capillary electrophoresis (CE), but there is an increasing move to direct analysis by massively parallel sequencing (MPS). An example is the ForenSeq DNA Signature Prep Kit, which amplifies multiple loci including 27 aSTRs, prior to sequencing via Illumina technology. Here we assess the applicability of this human-based kit in African great apes. We ask whether cross-species genotyping of the orthologs of these loci can provide both individual and (sub)species identification.

Results
The ForenSeq kit was used to amplify and sequence aSTRs in 52 individuals (14 chimpanzees; 4 bonobos; 16 western lowland, 6 eastern lowland, and 12 mountain gorillas). The orthologs of 24/27 human aSTRs amplified across species, and a core set of thirteen loci could be genotyped in all individuals. Genotypes were individually and (sub)species identifying. Both allelic diversity and the power to discriminate (sub)species were greater when considering STR sequences rather than allele lengths. Comparing human and African great-ape STR sequences with an orangutan outgroup showed general conservation of repeat types and allele size ranges. Variation in repeat array structures and a weak relationship with the known phylogeny suggests stochastic origins of mutations giving rise to diverse imperfect repeat arrays. Interruptions within long repeat arrays in African great apes do not appear to reduce allelic diversity.

Conclusions
Orthologs of most human aSTRs in the ForenSeq DNA Signature Prep Kit can be analysed in African great apes. Primer redesign would reduce observed variability in amplification across some loci. MPS of the orthologs of human loci provides better resolution for both individual and (sub)species identification in great apes than standard CE-based approaches, and has the further advantage that there is no need to limit the number and size ranges of analysed loci.
Body posture can modulate liver stiffness measured by transient elastography: a prospective observational study
Authors: Huang Zi-Hao , Deng Miao-Qin , Lin Yangmin , Ye Chen-Hui , Zheng Ming-Hua , Zheng Yong-Ping 
Published: October 2024

Abstract
Background
Non-invasive measurement of liver stiffness (LS), traditionally performed in the supine position, has been established to assess liver fibrosis. However, fibrosis degree is not the sole determinant of LS, necessitating the identification of relevant confounders. One often-overlooked factor is body posture, and it remains unclear whether normal daily postures interfere with LS irrespective of fibrosis. A prospective two-group comparison study was conducted to investigate the relationship between posture and LS.

Methods
Sixty-two adults participated, divided into two groups: patients with chronic liver disease and healthy controls. Both groups were assessed using transient elastography (TE) under the supine, seated, and standing postures. Randomization was applied to the order of the two upright postures. A two-way mixed ANOVA was conducted to assess the posture-dependence of LS and its variations between two groups.

Results
Results showed that posture differentially affected LS depending on the presence of liver fibrosis. In 31 healthy individuals (baseline LS range: 3.5–6.8 kPa), a transition from the supine (5.0 ± 1.0 kPa) to seated (5.7 ± 1.4 kPa; p = 0.036) or standing (6.2 ± 1.7 kPa; p = 0.002) positions increased LS, indicating liver stiffening. Conversely, in 31 patients with varying fibrosis stages (baseline LS range: 8.8–38.2 kPa), posture decreased LS from the supine (15.9 ± 7.3 kPa) to seated (13.8 ± 6.2 kPa; p < 0.001) or standing (13.9 ± 6.2 kPa; p = 0.001) positions. No significant difference in LS was observed between the seated and standing positions in both groups (control group: 5.7 vs. 6.2 kPa, p = 0.305; patient group: 13.8 vs. 13.9 kPa, p = 1). Additionally, different postures did not elicit significant changes in the success rate (supine, 98.6 ± 4%; seated, 97.6 ± 6%; standing, 99.1 ± 3%; p = 0.258) and IQR/median value (supine, 25 ± 8%; seated, 29 ± 15%; standing, 29 ± 12%; p = 0.117), implying no impact on both measurement feasibility and reliability.

Conclusions
We demonstrated, for the first time, the feasibility of utilizing upright postures as an alternative measurement protocol for TE. We further unravel a previously unrecognized role of transitioning between different postures to assist the diagnosis of cirrhosis. The findings suggested that daily physiological activity of postural changes suffices to alter LS. Therefore, body positioning should be standardized and carefully considered when interpreting LS.
Elevated expression levels of the protein kinase DYRK1B induce mesenchymal features in A549 lung cancer cells
Authors: Sester Soraya , Wilms Gerrit , Ahlburg Joana , Babendreyer Aaron , Becker Walter 
Published: October 2024

Abstract
Background
The protein kinase DYRK1B is a negative regulator of cell proliferation but has been found to be overexpressed in diverse human solid cancers. While DYRK1B is recognized to promote cell survival and adaption to stressful conditions, the consequences of elevated DYRK1B levels in cancer cells are largely uncharted.

Methods
To elucidate the role of DYRK1B in cancer cells, we established a A549 lung adenocarcinoma cell model featuring conditional overexpression of DYRK1B. This system was used to characterize the impact of heightened DYRK1B levels on gene expression and to monitor phenotypic and functional changes.

Results
A549 cells with induced overexpression of wild type DYRK1B acquired a mesenchymal cell morphology with diminished cell-cell contacts and a reorganization of the pericellular actin cytoskeleton into stress fibers. This transition was not observed in cells overexpressing a catalytically impaired DYRK1B variant. The phenotypic changes were associated with increased expression of the transcription factors SNAIL and SLUG, which are core regulators of epithelial mesenchymal transition (EMT). Further profiling of DYRK1B-overexpressing cells revealed transcriptional changes that are characteristic for the mesenchymal conversion of epithelial cells, including the upregulation of genes that are related to cancer cell invasion and metastasis. Functionally, DYRK1B overexpression enhanced the migratory capacity of A549 cells in a wound healing assay.

Conclusions
The present data identify DYRK1B as a regulator of phenotypic plasticity in A549 cells. Increased expression of DYRK1B induces mesenchymal traits in A549 lung adenocarcinoma cells.
Weight status and psychosomatic complaints in Swedish adolescent boys and girls: does family support play a buffering role?
Authors: Venäläinen Jasmin , Låftman Sara Brolin , Landberg Jonas 
Published: October 2024

Abstract
Background
Psychosomatic complaints have increased among adolescents in recent decades, as have overweight and obesity rates. Both of these trends are regarded as public health concerns. However, the associations between weight status and psychosomatic complaints are not yet clear, necessitating further research. The aim of the present study was to investigate the associations between weight status and psychosomatic complaints in Swedish adolescent boys and girls, as well as to explore the potential buffering effect of family support.

Methods
The data was obtained from the cross-sectional Swedish Health Behaviour in School-aged Children (HBSC) study conducted in 2017/18, which involved 3,135 students aged 11, 13, and 15 years. Weight status was based on self-reported information on weight and height, which allowed for the calculation of body mass index (BMI) and the categorisation of participants into three groups: non-overweight, overweight, and obese. Psychosomatic complaints were assessed based on information regarding the frequency of eight different complaints, which were summed into an index. Family support was measured using three items describing the level of perceived emotional support, and an index was created, which was dichotomised into low and high family support. Gender stratified linear regression models were run to examine the associations between weight status and psychosomatic complaints. Age and family affluence were included as covariates. Interaction terms were included to evaluate whether family support moderated the main association.

Results
Obesity was associated with higher levels of psychosomatic complaints in both boys and girls when compared to being non-overweight (boys: b = 2.56, 95% CI 0.32, 4.79; girls: b = 3.35, 95% CI 0.77, 5.94), while being overweight did not show any statistically significant associations with the outcome (boys: b = 0.21, 95% CI -0.72, 1.15; girls: b = 0.78, 95% CI -0.42, 1.98). In girls, a statistically significant interaction effect between family support and weight status was observed (p = 0.031), indicating that family support buffered against psychosomatic complaints in girls with obesity. No statistically significant interaction was found for boys (p = 0.642).

Conclusions
The findings of this study highlight the importance of public health initiatives aimed at preventing childhood obesity. They also underscore the significant role of family support in reducing psychosomatic complaints among adolescents with obesity. Further research is necessary to gain a deeper understanding of these relationships.