bluuebunny/crossref_metadata_2025_split huggingface dataset:
ASXL1 and STAG2 are common mutations in GATA2 deficiency patients with bone marrow disease and myelodysplastic syndrome
Authors: West Robert R. , Calvo Katherine R. , Embree Lisa J. , Wang Weixin , Tuschong Laura M. , Bauer Thomas R. , Tillo Desiree , Lack Justin , Droll Stephenie , Hsu Amy P. , Holland Steven M. , Hickstein Dennis D. 
Published: September 2021

Abstract
Patients with GATA2 deficiencyharbor de novo or inherited germline mutations in the GATA2 transcription factor gene, predisposing them to myeloid malignancies. There is considerable variation in disease progression, even among family members with the same mutation in GATA2. We investigated somatic mutations in 106 patients with GATA2 deficiency to identify acquired mutations that are associated with myeloid malignancies. Myelodysplastic syndrome (MDS) was the most common diagnosis (∼44%), followed by GATA2 bone marrow immunodeficiency disorder (G2BMID; ∼37%). Thirteen percent of the cohort had GATA2 mutations but displayed no disease manifestations. There were no correlations between age or sex with disease progression or survival. Cytogenetic analyses showed a high incidence of abnormalities (∼43%), notably trisomy 8 (∼23%) and monosomy 7 (∼12%), but the changes did not correlate with lower survival. Somatic mutations in ASXL1 and STAG2 were detected in ∼25% of patients, although the mutations were rarely concomitant. Mutations in DNMT3A were found in ∼10% of patients. These somatic mutations were found similarly in G2BMID and MDS, suggesting clonal hematopoiesis in early stages of disease, before the onset of MDS. ASXL1 mutations conferred a lower survival probability and were more prevalent in female patients. STAG2 mutations also conferred a lower survival probability, but did not show a statistically significant sex bias. There was a conspicuous absence of many commonly mutated genes associated with myeloid malignancies, including TET2, IDH1/2, and the splicing factor genes. Notably, somatic mutations in chromatin-related genes and cohesin genes characterized disease progression in GATA2 deficiency.
Cardiac sarcoidosis: systematic review of the literature on corticosteroid and immunosuppressive therapies
Authors: Stievenart Julien , Le Guenno Guillaume , Ruivard Marc , Rieu Virginie , André Marc , Grobost Vincent 
Published: September 2021

BackgroundCardiac sarcoidosis (CS) is a life-threatening condition in which clear recommendations are lacking. We aimed to systematically review the literature on cardiac sarcoidosis treated by corticosteroids and/or immunosuppressive agents in order to update the management of CS.MethodsUsing PubMed, Embase and Cochrane Library databases, we found original articles on corticosteroid and standard immunosuppressive therapies for CS that provided at least a fair Scottish Intercollegiate Guidelines Network (SIGN) overall assessment of quality and we analysed the relapse rate, major cardiac adverse events (MACEs) and adverse events. We based our methods on the PRISMA statement and checklist.ResultsWe retrieved 21 studies. Mean quality provided by SIGN assessment was 6.8 out of 14 (range 5–9). Corticosteroids appeared to have a positive impact on left ventricular function, atrioventricular block and ventricular arrhythmias. For corticosteroids alone, nine studies (45%, n=351) provided data on relapses, representing an incidence of 34% (n=119). Three studies (14%, n=73) provided data on MACEs (n=33), representing 45% of MACEs in patients treated by corticosteroid alone. Nine studies provided data on adjunctive immunosuppressive therapy, of which four studies (n=78) provided data on CS relapse, representing an incidence of 33% (n=26). Limitations consisted of no randomised control trial retrieved and unclear data on MACEs in patients treated by combined immunosuppressive agents and corticosteroids.ConclusionCorticosteroids should be started early after diagnosis but the exact scheme is still unclear. Studies concerning adjunctive conventional immunosuppressive therapies are lacking and benefits of adjunctive immunosuppressive therapies are unclear. Homogenous data on CS long-term outcomes under corticosteroids, immunosuppressive therapies and other adjunctive therapies are lacking.
Is asthma associated with COVID-19 infection? A UK Biobank analysis
Authors: Lodge Caroline J. , Doherty Alice , Bui Dinh S. , Cassim Raisa , Lowe Adrian J. , Agusti Alvar , Russell Melissa A. , Dharmage Shyamali C. 
Published: September 2021

Background
The relationship between asthma and coronavirus disease 2019 (COVID-19) risk is not clear and may be influenced by level of airway obstruction, asthma medication and known COVID-19 risk factors. We aimed to investigate COVID-19 risk in people with asthma.

Methods

We used UK Biobank data from all participants tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n=107 412; 17 979 test positive). Questions at baseline defined ever asthma and asthma medications. Baseline forced expiratory volume in 1 s (FEV
1
) was categorised into quartiles. Logistic regression modelled relationships between asthma, and asthma categories (age at onset, medications, FEV
1
quartiles), and risk of SARS-CoV-2 positive test. We investigated modification by sex, ethnic group, smoking and body mass index.

Results
There was a reduced risk of a positive test associated with early-onset asthma (<13 years) (OR 0.91, 95% CI 0.84–0.99). This was found for participants with early-onset asthma who were male (OR 0.87, 95% CI 0.78–0.98), nonsmokers (OR 0.87, 95% CI 0.78–0.98), overweight/obese (OR 0.85, 95% CI 0.77–0.93) and non-Black (OR 0.90, 95% CI 0.82–0.98). There was increased risk amongst early-onset individuals with asthma in the highest compared to lowest quartile of lung function (1.44, 1.05–1.72).

Conclusion
Amongst male, nonsmoking, overweight/obese and non-Black participants, having early-onset asthma was associated with lower risk of a SARS-CoV-2 positive test. We found no evidence of a protective effect from asthma medication. Individuals with early-onset asthma of normal weight and with better lung function may have lifestyle differences placing them at higher risk. Further research is needed to elucidate the contribution of asthma pathophysiology and different health-related behaviour, across population groups, to the observed risks.
MicroRNA-214 promotes alveolarization in neonatal rat models of bronchopulmonary dysplasia via the PlGF-dependent STAT3 pathway
Authors: Zhang Zhi-Qun , Hong Hui , Li Jing , Li Xiao-Xia , Huang Xian-Mei 
Published: September 2021

Abstract
Background
Recently, the role of several microRNAs (miRNAs or miRs) in pulmonary diseases has been described. The molecular mechanisms by which miR-214 is possibly implicated in bronchopulmonary dysplasia (BPD) have not yet been addressed. Hence, this study aimed to investigate a putative role of miR-214 in alveolarization among preterm neonates with BPD.

Methods
Microarray-based gene expression profiling data from BPD was employed to identify differentially expressed genes. A BPD neonatal rat model was induced by hyperoxia. Pulmonary epithelial cells were isolated from rats and exposed to hyperoxia to establish cell injury models. Gain- and loss-of-function experiments were performed in BPD neonatal rats and hyperoxic pulmonary epithelial cells. MiR-214 and PlGF expression in BPD neonatal rats, and eNOS, Bcl-2, c-myc, Survivin, α-SMA and E-cadherin expression in hyperoxic pulmonary epithelial cells were measured using RT-qPCR and Western blot analysis. The interaction between PlGF and miR-214 was identified using dual luciferase reporter gene and RIP assays. IL-1β, TNF-a, IL-6, ICAM-1 and Flt-1 expression in the rat models was measured using ELISA.

Results
The lung tissues of neonatal rats with BPD showed decreased miR-214 expression with elevated PlGF expression. PlGF was found to be a target of miR-214, whereby miR-214 downregulated PlGF to inactivate the STAT3 pathway. miR-214 overexpression or PlGF silencing decreased the apoptosis of hyperoxic pulmonary epithelial cells in vitro and restored alveolarization in BPD neonatal rats.

Conclusion
Overall, the results demonstrated that miR-214 could facilitate alveolarization in preterm neonates with BPD by suppressing the PlGF-dependent STAT3 pathway.
TFTenricher: a python toolbox for annotation enrichment analysis of transcription factor target genes
Authors: Magnusson Rasmus , Lubovac-Pilav Zelmina 
Published: September 2021

Abstract
Background
Transcription factors (TFs) are the upstream regulators that orchestrate gene expression, and therefore a centrepiece in bioinformatics studies. While a core strategy to understand the biological context of genes and proteins includes annotation enrichment analysis, such as Gene Ontology term enrichment, these methods are not well suited for analysing groups of TFs. This is particularly true since such methods do not aim to include downstream processes, and given a set of TFs, the expected top ontologies would revolve around transcription processes.

Results
We present the TFTenricher, a Python toolbox that focuses specifically at identifying gene ontology terms, cellular pathways, and diseases that are over-represented among genes downstream of user-defined sets of human TFs. We evaluated the inference of downstream gene targets with respect to false positive annotations, and found an inference based on co-expression to best predict downstream processes. Based on these downstream genes, the TFTenricher uses some of the most common databases for gene functionalities, including GO, KEGG and Reactome, to calculate functional enrichments. By applying the TFTenricher to differential expression of TFs in 21 diseases, we found significant terms associated with disease mechanism, while the gene set enrichment analysis on the same dataset predominantly identified processes related to transcription.

Conclusions and availability
The TFTenricher package enables users to search for biological context in any set of TFs and their downstream genes. The TFTenricher is available as a Python 3 toolbox at https://github.com/rasma774/Tftenricher, under a GNU GPL license and with minimal dependencies.
Characteristics of nursing home units with high versus low levels of person-centred care in relation to leadership, staff- resident- and facility factors: findings from SWENIS, a cross-sectional study in Sweden
Authors: Backman Annica , Sandman Per-Olof , Sköldunger Anders 
Published: September 2021

Abstract
Background
The context of care consists of factors that determines the extent to which staff can offer person-centred care. However, few studies have investigated factors that can explain variation in levels of person-centred care among nursing home units. The aim of this study was to explore factors characterizing nursing home units with high and low degree of person-centred care, with focus on leadership, staff, resident and facility factors.

Methods
Cross-sectional data from residents, staff, and managers in 172 randomly selected nursing homes in Sweden were collected in 2014. Activities of Daily Living Index, Gottfries’ cognitive scale, Person-centred Care Assessment Tool together with demographic information and estimations of leadership engagement was used. Independent samples t-test and Chi2 test were conducted.

Results
Highly person-centred units were characterised by leaders engaging in staff knowledge, professional development, team support and care quality. In highly person-centred units’ staff also received supervision of a nurse to a larger extent. Highly person-centred units were also characterised as dementia specific units, units with fewer beds and with a larger proportion of enrolled nurses. No differences in degree of person-centred care were seen between public or private providers.

Conclusions
This study provides guidance for practitioners when designing, developing and adapting person-centred units in aged care contexts. Managers and leaders have an important role to promote the movement towards a person-centred practice of care, by supporting their staff in daily care, and engaging in staff knowledge and professional development. Targeting and adjusting environmental factors, such as provide small and dementia adapted environments to match the residents’ personal preferences and capacity are also important when striving towards person-centredness.
Do prescription rates of psychotropic drugs change over three years from nursing home admission?
Authors: Callegari Enrico , Šaltytė Benth Jūratė , Selbæk Geir , Grønnerød Cato , Bergh Sverre 
Published: September 2021

Abstract
Background
In this longitudinal study, we describe how psychotropic drugs (PTDs) are prescribed in nursing home (NH) patients from admission and over a 3-year period, to understand which clinical and environmental factors are associated with PTD prescription.

Methods
We used data from the Resource Use and Disease Course in Dementia – Nursing Home (REDIC-NH) study, examining physical and mental health, dementia, and PTD prescription during a 3-year period from admission to a NH. Data were collected every six months. At baseline, we included 696 participants from 47 Norwegian NHs. We presented prevalence, incidence, and deprescribing rates of PTD prescriptions for each assessment point. We calculated the odds of receiving PTDs and used a generalized linear mixed model to analyze the variables associated with a change in odds throughout the 3-year period.

Results
PTD prescriptions were frequent throughout the 3-year period. Antidepressants had the highest prescription rates (28.4%–42.2%). Every PTD category had the highest incidence rate between admission and six months, and antidepressants had the highest values (18.9%). Deprescribing rates were generally highest between baseline and 6-months follow-up, except for sedatives and hypnotics. The odds of antipsychotic prescriptions were lower for older people (OR = 0.96, 95%CI:0.92–0.99, p = 0.023). People with more severe dementia had lower odds of being prescribed sedatives/hypnotics (OR = 0.89, 95%CI:0.85–0.94, p < 0.001).

Conclusions
PTDs, particularly antidepressants, are widely prescribed over time to NH patients. Older patients are less likely to receive antipsychotics. A higher severity of dementia decreases the odds of being prescribed sedatives/hypnotics. Close attention should be paid to PTD prescriptions during long-term NH stay to avoid prolonged and excessive treatment with these types of drugs.

Trial registration
ClinicalTrials.gov Identifier: NCT01920100.
Association between low-density cholesterol change and outcomes in acute ischemic stroke patients who underwent reperfusion therapy
Authors: Cui Ting , Wang Changyi , Zhu Qiange , Wang Anmo , Zhang Xuening , Li Shucheng , Yang Yuan , Shang Wenzuo , Peng Rong , Wu Bo 
Published: September 2021

AbstractBackgroundLow-density lipoprotein cholesterol (LDL-C) can increase cardiovascular risk. However, the association between LDL-C change and functional outcomes in acute ischemic stroke (AIS) patients who underwent reperfusion therapy remains unclear.MethodsPatients who received reperfusion therapy were consecutively enrolled. LDL-C measurement was conducted at the emergency department immediately after admission and during hospitalization. The change of LDL-C level (ΔLDL-C) was calculated by subtracting the lowest LDL-C among all measurements during hospitalization from the admission LDL-C. Poor functional outcome was defined as modified Rankin Scale (mRS) > 2 at 90 days.ResultsA total of 432 patients were enrolled (mean age 69.2 ± 13.5 years, 54.6 % males). The mean LDL-C level at admission was 2.55 ± 0.93 mmol/L. The median ΔLDL-C level was 0.43 mmol/L (IQR 0.08–0.94 mmol/L). A total of 263 (60.9 %) patients had poor functional outcomes at 90 days. There was no significant association between admission LDL-C level and functional outcome (OR 0.99, 95 % CI 0.77–1.27,p = 0.904). ΔLDL-C level was positively associated with poor functional outcome (OR 1.80, 95 % CI 1,12-2.91,p = 0.016). When patients were divided into tertiles according to ΔLDL-C, those in the upper tertile (T3, 0.80–3.98 mmol/L) were positively associated with poor functional outcomes compared to patients in the lower tertile (T1, -0.91-0.13 mmol/L) (OR 2.56, 95 % CI 1.22–5.36,p = 0.013). The risk of poor functional outcome increased significantly with ΔLDL-C tertile (P-trend = 0.010).ConclusionsIn AIS patients who underwent reperfusion therapy, the decrease in LDL-C level during hospitalization was significantly associated with poor functional outcomes at 90 days.
Pregnancy after liver transplant: maternal and perinatal outcomes
Authors: Marzec Izabela , Słowakiewicz Aleksandra , Gozdowska Jolanta , Tronina Olga , Pacholczyk Marek , Lisik Wojciech , Fleming Agata , Durlik Magdalena 
Published: September 2021

Abstract
Background
Liver transplantation is a life-saving and successful therapeutic procedure which is more and more frequent worldwide, also among women of reproductive age. Consequently, there is an increasing number of reports of pregnancy following liver transplantation, but doubts still exist regarding preconception counseling and the optimal method of managing pregnancy. The aim of this study was to report and evaluate pregnancy outcomes in women who had undergone liver transplantation.

Methods
We retrospectively analyzed female patients after orthotopic liver transplantation who reported pregnancy and were under medical care of a single transplant center.

Results
We identified 14 pregnancies in 10 women who had undergone liver transplantation (12 childbirths, one induced abortion due to fetal death in the first trimester, one pregnancy is still ongoing). Causes of transplantation include congenital or acquired disorders and the most common indication was autoimmune hepatitis (50%).
The mean age at the point of transplantation was 28.5 (range 21–36), mean maternal age at pregnancy was 32 (range 26–43), and transplant-to-pregnancy interval was 4.07 years (range 1.5–7). The mean gestational week was 36.67 (range 31–40). Immunosuppression was maintained with combinations of prednisone (n = 11), tacrolimus (n = 13), and azathioprine (n = 8) prior to and during pregnancy. Two pregnancies were unintended, so women took mycophenolate mofetil in the first weeks of gestation. Another two women stopped taking azathioprine due to increasing anemia. Maternal complications included increase of aspartate transaminase and alanine transaminase (n = 2), anemia (n = 4) and hyperthyroidism (n = 2). Among the 12 childbirths, five (41.67%) were preterm. Only five women entered labor spontaneously, while seven (58,33%) had cesarean delivery.

Conclusions
Pregnancy after liver transplantation can achieve relatively favorable outcomes. Liver transplantation does not influence women’s fertility and, during pregnancy, we report low rates of minor graft complications. A multidisciplinary team should be involved in contraceptive, fertility and consequently pregnancy counseling of female transplant recipients.
Prediction of serosal invasion in gastric cancer: development and validation of multivariate models integrating preoperative clinicopathological features and radiographic findings based on late arterial phase CT images
Authors: Liu Song , Xu Mengying , Qiao Xiangmei , Ji Changfeng , Li Lin , Zhou Zhengyang 
Published: September 2021

AbstractBackgroundTo develop and validate multivariate models integrating endoscopic biopsy, tumor markers, and CT findings based on late arterial phase (LAP) to predict serosal invasion in gastric cancer (GC).MethodsThe preoperative differentiation degree, tumor markers, CT morphological characteristics, and CT value-related and texture parameters of 154 patients with GC were analyzed retrospectively. Multivariate models based on regression analysis and machine learning algorithms were performed to improve the diagnostic efficacy.ResultsThe differentiation degree, carbohydrate antigen (CA) 199, CA724, CA242, and multiple CT findings based on LAP differed significantly between T1–3 and T4 GCs in the primary cohort (allP < 0.05). Multivariate models based on regression analysis and random forest achieved AUCs of 0.849 and 0.865 in the primary cohort, respectively.ConclusionWe developed and validated multivariate models integrating endoscopic biopsy, tumor markers, CT morphological characteristics, and CT value-related and texture parameters to predict serosal invasion in GCs and achieved favorable performance.
Heterogeneity in major depression and its melancholic and atypical specifiers: a secondary analysis of STAR*D
Authors: Lorenzo-Luaces Lorenzo , Buss John F. , Fried Eiko I. 
Published: September 2021

AbstractObjectivesThe melancholic and atypical specifiers for a major depressive episode (MDE) are supposed to reduce heterogeneity in symptom presentation by requiring additional, specific features. Fried et al. (2020) recently showed that the melancholic specifier may increase the potential heterogeneity in presenting symptoms. In a large sample of outpatients with depression, our objective was to explore whether the melancholic and atypical specifiers reduced observed heterogeneity in symptoms.MethodsWe used baseline data from the Inventory of Depression Symptoms (IDS), which was available for 3,717 patients, from the Sequenced Alternatives to Relieve Depression (STAR*D) trial. A subsample met criteria for MDE on the IDS (“IDS-MDE”; N =2,496). For patients with IDS-MDE, we differentiated between those with melancholic, non-melancholic, atypical, and non-atypical depression. We quantified the observed heterogeneity between groups by counting the number of unique symptom combinations pertaining to their given diagnostic group (e.g., counting the melancholic symptoms for melancholic and non-melancholic groups), as well as the profiles of DSM-MDE symptoms (i.e., ignoring the specifier symptoms).ResultsWhen considering the specifier and depressive symptoms, there was more observed heterogeneity within the melancholic and atypical subgroups than in the IDS-MDE sample (i.e., ignoring the specifier subgroups). The differences in number of profiles between the melancholic and non-melancholic groups were not statistically significant, irrespective of whether focusing on the specifier symptoms or only the DSM-MDE symptoms. The differences between the atypical and non-atypical subgroups were smaller than what would be expected by chance. We found no evidence that the specifier groups reduce heterogeneity, as can be quantified by unique symptom profiles. Most symptom profiles, even in the specifier subgroups, had five or fewer individuals.ConclusionWe found no evidence that the atypical and melancholic specifiers create more symptomatically homogeneous groups. Indeed, the melancholic and atypical specifiers introduce heterogeneity by adding symptoms to the DSM diagnosis of MDE.