bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic impact ofDDX41germline mutations in intensively treated acute myeloid leukemia patients: an ALFA-FILO study
Authors: Duployez Nicolas , Largeaud Laëtitia , Duchmann Matthieu , Kim Rathana , Rieunier Julie , Lambert Juliette , Bidet Audrey , Larcher Lise , Lemoine Jean , Delhommeau François , Hirsch Pierre , Fenwarth Laurène , Kosmider Olivier , Decroocq Justine , Bouvier Anne , Le Bris Yannick , Ochmann Marlène , Santagostino Alberto , Adès Lionel , Fenaux Pierre , Thomas Xavier , Micol Jean-Baptiste , Gardin Claude , Itzykson Raphael , Soulier Jean , Clappier Emmanuelle , Recher Christian , Preudhomme Claude , Pigneux Arnaud , Dombret Hervé , Delabesse Eric , Sébert Marie 
Published: April 2022

AbstractDDX41 germline mutations (DDX41MutGL) are the most common genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia (AML). Recent reports suggest that DDX41MutGL myeloid malignancies could be considered as a distinct entity, even if their specific presentation and outcome remain to be defined. We describe here the clinical and biological features of 191 patients with DDX41MutGL AML. Baseline characteristics and outcome of 86 of these patients, treated with intensive chemotherapy in 5 prospective Acute Leukemia French Association/French Innovative Leukemia Organization trials, were compared with those of 1604 patients with DDX41 wild-type (DDX41WT) AML, representing a prevalence of 5%. Patients with DDX41MutGL AML were mostly male (75%), in their seventh decade, and with low leukocyte count (median, 2 × 109/L), low bone marrow blast infiltration (median, 33%), normal cytogenetics (75%), and few additional somatic mutations (median, 2). A second somatic DDX41 mutation (DDX41MutSom) was found in 82% of patients, and clonal architecture inference suggested that it could be the main driver for AML progression. DDX41MutGL patients displayed higher complete remission rates (94% vs 69%; P &lt; .0001) and longer restricted mean overall survival censored at hematopoietic stem cell transplantation (HSCT) than 2017 European LeukemiaNet intermediate/adverse (Int/Adv) DDX41WT patients (5-year difference in restricted mean survival times, 13.6 months; P &lt; .001). Relapse rates censored at HSCT were lower at 1 year in DDX41MutGL patients (15% vs 44%) but later increased to be similar to Int/Adv DDX41WT patients at 3 years (82% vs 75%). HSCT in first complete remission was associated with prolonged relapse-free survival (hazard ratio, 0.43; 95% confidence interval, 0.21-0.88; P = .02) but not with longer overall survival (hazard ratio, 0.77; 95% confidence interval, 0.35-1.68; P = .5).
Determinants of long-term outcomes of splenectomy in pediatric autoimmune cytopenias
Authors: Pincez Thomas , Aladjidi Nathalie , Héritier Sébastien , Garnier Nathalie , Fahd Mony , Abou Chahla Wadih , Fernandes Helder , Dichamp Claire , Ducassou Stéphane , Pasquet Marlène , Bayart Sophie , Moshous Despina , Cheikh Nathalie , Paillard Catherine , Plantaz Dominique , Jeziorski Eric , Thomas Caroline , Guitton Corinne , Deparis Marianna , Marie Cardine Aude , Stephan Jean-Louis , Pellier Isabelle , Doré Eric , Benadiba Joy , Pluchart Claire , Briandet Claire , Barlogis Vincent , Leverger Guy , Leblanc Thierry 
Published: April 2022

Abstract
Splenectomy is effective in ∼70% to 80% of pediatric chronic immune thrombocytopenia (cITP) cases, and few data exist about it in autoimmune hemolytic anemia (AIHA) and Evans syndrome (ES). Because of the irreversibility of the procedure and the lack of predictions regarding long-term outcomes, the decision to undertake splenectomy is difficult in children. We report here factors associated with splenectomy outcomes from the OBS’CEREVANCE cohort, which prospectively includes French children with autoimmune cytopenia (AIC) since 2004. The primary outcome was failure-free survival (FFS), defined as the time from splenectomy to the initiation of a second-line treatment (other than steroids and intravenous immunoglobulins) or death. We included 161 patients (cITP, n = 120; AIHA, n = 19; ES, n = 22) with a median (minimum-maximum) follow-up of 6.8 years (1.0-33.3) after splenectomy. AIC subtype was not associated with FFS. We found that immunopathological manifestations (IMs) were strongly associated with unfavorable outcomes. Diagnosis of an IM before splenectomy was associated with a lower FFS (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.21-0.72, P = .003, adjusted for AIC subtype). Diagnosis of an IM at any timepoint during follow-up was associated with an even lower FFS (HR, 0.22; 95% CI, 0.12-0.39; P = 2.8 × 10−7, adjusted for AIC subtype) as well as with higher risk of recurrent or severe bacterial infections and thrombosis. In conclusion, our results support the search for associated IMs when considering a splenectomy to refine the risk-benefit ratio. After the procedure, monitoring IMs helps to identify patients with higher risk of unfavorable outcomes.
Platelet activation by SARS-CoV-2 implicates the release of active tissue factor by infected cells
Authors: Puhm Florian , Allaeys Isabelle , Lacasse Emile , Dubuc Isabelle , Galipeau Yannick , Zaid Younes , Khalki Loubna , Belleannée Clemence , Durocher Yves , Brisson Alain R. , Wolberg Alisa S. , Langlois Marc-André , Flamand Louis , Boilard Eric 
Published: April 2022

Abstract
Platelets are hyperactivated in coronavirus disease 2019 (COVID-19). However, the mechanisms promoting platelet activation by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not well understood. This may be due to inherent challenges in discriminating the contribution of viral vs host components produced by infected cells. This is particularly true for enveloped viruses and extracellular vesicles (EVs), as they are concomitantly released during infection and share biophysical properties. To study this, we evaluated whether SARS-CoV-2 itself or components derived from SARS-CoV-2-infected human lung epithelial cells could activate isolated platelets from healthy donors. Activation was measured by the surface expression of P-selectin and the activated conformation of integrin αIIbβ3, degranulation, aggregation under flow conditions, and the release of EVs. We find that neither SARS-CoV-2 nor purified spike activates platelets. In contrast, tissue factor (TF) produced by infected cells was highly potent at activating platelets. This required trace amounts of plasma containing the coagulation factors FX, FII, and FVII. Robust platelet activation involved thrombin and the activation of protease-activated receptor (PAR)-1 and -4 expressed by platelets. Virions and EVs were identified by electron microscopy. Through size-exclusion chromatography, TF activity was found to be associated with a virus or EVs, which were indistinguishable. Increased TF messenger RNA (mRNA) expression and activity were also found in lungs in a murine model of COVID-19 and plasma of severe COVID-19 patients, respectively. In summary, TF activity from SARS-CoV-2–infected cells activates thrombin, which signals to PARs on platelets. Blockade of molecules in this pathway may interfere with platelet activation and the coagulation characteristic of COVID-19.
RODAN: a fully convolutional architecture for basecalling nanopore RNA sequencing data
Authors: Neumann Don , Reddy Anireddy S. N. , Ben-Hur Asa 
Published: April 2022

Abstract
Background
Despite recent progress in basecalling of Oxford nanopore DNA sequencing data, its wide adoption is still being hampered by its relatively low accuracy compared to short read technologies. Furthermore, very little of the recent research was focused on basecalling of RNA data, which has different characteristics than its DNA counterpart.

Results
We fill this gap by benchmarking a fully convolutional deep learning basecalling architecture with improved performance compared to Oxford nanopore’s RNA basecallers.

Availability
The source code for our basecaller is available at: https://github.com/biodlab/RODAN.
Identification of novel PHD-finger genes in pepper by genomic re-annotation and comparative analyses
Authors: Guk Ji-Yoon , Jang Min-Jeong , Kim Seungill 
Published: April 2022

Abstract
Background
The plant homeodomain (PHD)-finger gene family that belongs to zinc-finger genes, plays an important role in epigenetics by regulating gene expression in eukaryotes. However, inaccurate annotation of PHD-finger genes hinders further downstream comparative, evolutionary, and functional studies.

Results
We performed genome-wide re-annotation in Arabidopsis thaliana (Arabidopsis), Oryza sativa (rice), Capsicum annuum (pepper), Solanum tuberosum (potato), and Solanum lycopersicum (tomato) to better understand the role of PHD-finger genes in these species. Our investigation identified 875 PHD-finger genes, of which 225 (26% of total) were newly identified, including 57 (54%) novel PHD-finger genes in pepper. The PHD-finger genes of the five plant species have various integrated domains that may be responsible for the diversification of structures and functions of these genes. Evolutionary analyses suggest that PHD-finger genes were expanded recently by lineage-specific duplication, especially in pepper and potato, resulting in diverse repertoires of PHD-finger genes among the species. We validated the expression of six newly identified PHD-finger genes in pepper with qRT-PCR. Transcriptome analyses suggest potential functions of PHD-finger genes in response to various abiotic stresses in pepper.

Conclusions
Our data, including the updated annotation of PHD-finger genes, provide useful information for further evolutionary and functional analyses to better understand the roles of the PHD-finger gene family in pepper.
Genome-wide analysis and functional characterization of CHYR gene family associated with abiotic stress tolerance in bread wheat (Triticum aestivum L.)
Authors: Liu Hao , Yang Wenbo , Zhao Xingli , Kang Guozhang , Li Na , Xu Huawei 
Published: April 2022

Abstract
Background
CHY zinc-finger and RING finger (CHYR) proteins have been functionally characterized in plant growth, development and various stress responses. However, the genome-wide analysis was not performed in wheat.

Results
In this study, a total of 18 TaCHYR genes were identified in wheat and classified into three groups. All TaCHYR genes contained CHY-zinc finger, C3H2C3-type RING finger and zinc ribbon domains, and group III members included 1–3 hemerythrin domains in the N-terminus regions. TaCHYR genes in each group shared similar conserved domains distribution. Chromosomal location, synteny and cis-elements analysis of TaCHYRs were also analyzed. Real-time PCR results indicated that most of selected 9 TaCHYR genes exhibited higher expression levels in leaves during wheat seedling stage. All these TaCHYR genes were up-regulated after PEG treatment, and these TaCHYRs exhibited differential expression patterns in response to salt, cold and heat stress in seedling leaves. The growth of yeast cells expressing TaCHYR2.1, TaCHYR9.2 and TaCHYR11.1 were inhibited under salt and dehydration stress. Moreover, gene ontology (GO) annotation, protein interaction and miRNA regulatory network of TaCHYR genes were analyzed.

Conclusions
These results increase our understanding of CHYR genes and provide robust candidate genes for further functional investigations aimed at crop improvement.
Higher chronic stress and less satisfaction with GP communication in migrants with unemployment experience: data from the representative German DEGS1 and the GPCare-1 study
Authors: Offenberg Luisa K. , Sommer Samira T. , Schmidt Manuela , Kasten Stefanie , Bockheim Florian , Gavrilov Boris , Hunzelar Carmen , Ikar Nur , Oberholz Maja P. S. , Paños-Willuhn Joana L. , Weltermann Birgitta 
Published: April 2022

Abstract
Background
The impact of unemployment on health is well studied. However, information on associations of unemployment, migration background and general practitioner-patient communication is scarce.

Methods
Data from the representative German Health Interview and Examination Survey for Adults (DEGS1) of individuals in working age (n = 5938) were analysed stratified by unemployment and migration background. Using official weighting factors, the prevalence of chronic stress, having ≥1 chronic disease, having a GP and GP visits in the last 12 months was determined. Multivariate regression models were analysed for associations between unemployment, migration background, and other socio-demographic characteristics with GP visits and chronic stress. Data from the General Practice Care-1 (GPCare-1) study (n = 813 patients) were analysed for differences in patient-physician communication between unemployed with and without migration background. Reverse proportional odds models were estimated for associations of unemployment and migration background with physician-patient communication.

Results
In the DEGS1, 21.5% had experienced unemployment (n = 1170). Of these, 31.6% had a migration background (n = 248). Compared to unemployed natives, unemployed with migration background had higher chronic stress (mean: 14.32 vs. 13.13, p = 0.02), while the prevalence of chronic disease was lower (21.7% vs. 30.2%, p = 0.03). They were less likely to have a GP (83.6% vs. 90%, p = 0.02), while GP visits were similar (mean: 3.7 vs. 3.3, p = 0.26). Migration background and unemployment experience were not associated with GP visits, while both factors were significantly associated with higher chronic stress (both: p < 0.01). In GPCare-1, 28.8% had ever experienced unemployment (n = 215). Of these, 60 had a migration background (28.6%). The unemployed with migration background reported less frequently that the GP gives them enough space to describe personal strains (46.5% vs. 58.2%; p = 0.03), and that their problems are taken very seriously by their GP (50.8% vs. 73.8%; p = 0.04). In multivariate analyses, migration background showed a lower probability of having enough space to describe personal strains and feeling that problems were taken very seriously.

Conclusion
Unemployment experience and migration background were associated with higher chronic stress. Only migration background was associated with less satisfaction regarding physician-patient communication.
Low serum free triiodothyronineis level predicts worse outcome of patients with severe fever with thrombocytopenia syndrome
Authors: Wang Li , Liu Youde , Yu Haifeng , Ding Kun , Zou Zhiqiang 
Published: April 2022

Abstract
Background
Severe fever with thrombocytopenia syndrome (SFTS) caused by phlebovirus results in neuropsychiatric symptoms, multiorgan dysfunction and significant mortality. We aimed to evaluate the thyroid function in SFTS patients, elucidate its association with neuropsychiatric manifestations, disease severity, and prognosis, retrospectively.

Methods
Serum levels of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were compared between survivors and non-survivors, between those with and without nervous symptoms at baseline, and at baseline and remission. Logistic regression analysis was utilized to determine independent risk factors for mortality. A risk model based on risk factors was constructed and its prognostic value was evaluated by receiver operating characteristic (ROC) curve.

Results
A total of 207 SFTS cases with thyroid function data enrolled from January 2016 to January 2020 were included with 34 patients (16.4%) died. Baseline serum levels of FT3, TSH (p < 0.001), and FT3/FT4 ratio (p < 0.05) were significantly decreased in nonsurvivors than in survivors. Prevalence of low serum FT3 in nonsurvivors (81.8%) was greater than in survivors (41.3%). FT3 level (p < 0.001) was markedly reduced in patients with central neurological symptoms than those without. FT3 and FT4 levels were increased in remission than at baseline (p < 0.001). Logistic regression analysis showed that age (OR 0.92, 95% CI 0.868–0.958) and serum FT3 level (OR 3.055, 95% CI 1.494–6.248) were the independent risk factors for mortality. A risk model based on age and FT3 had a high predictive value for mortality (AUC = 0.818, 95% CI 0.795–0.868) at a cutoff value of > 3.39.

Conclusions
Low serum FT3 level was associated with a worse outcome of SFTS patients.
Preconception leisure-time physical activity and family history of stroke and myocardial infarction associate with preterm delivery: findings from a Norwegian cohort
Authors: Engen Tone , Owe Katrine Mari , Horn Julie , Sulo Gerhard , Næss Øyvind Erik , Juliusson Petur Benedikt , Morken Nils-Halvdan , Egeland Grace Margrethe 
Published: April 2022

Abstract
Background
Preterm birth poses short and long-term health consequences for mothers and offspring including cardiovascular disease sequelae. However, studies evaluating preexisting family history of cardiovascular disease and risk factors, such as physical activity, as they relate prospectively to risk of delivering preterm are lacking.

Objectives
To evaluate whether preconception past-year weekly leisure-time physical activity or a family history of stroke or of myocardical infarction prior to age 60 years in first degree relatives associated, prospectively, with preterm delivery.

Design
Cohort study. Baseline data from Cohort Norway (1994–2003) health surveys were linked to the Medical Birth Registry of Norway for identification of all subsequent births (1994–2012). Logistic regression models provided odds ratios (OR) and 95% confidence intervals (CI) for preterm delivery (< 37 weeks gestation); multinomial logistic regression provided OR for early preterm (< 34 weeks) and late preterm (34 through to end of 36 weeks gestation) relative to term deliveries.

Results
Mean (SD) length of time from baseline health survey participation to delivery was 5.6 (3.5) years. A family history of stroke associated with a 62% greater risk for late preterm deliveries (OR 1.62; CI 1.07–2.47), while a family history of myocardial infarction associated with a 66% greater risk of early preterm deliveries (OR 1.66; CI 1.11–2.49). Sensitivity analyses, removing pregnancies complicated by hypertensive disorders of pregnancy, diabetes mellitus, and stillbirth deliveries, gave similar results. Preconception vigorous physical activity of three or more hours relative to less than 1 h per week associated with increased risk of early preterm delivery (OR 1.52; 95% CI 1.01–2.30), but not late or total preterm deliveries. Light physical activity of three or more hours per week relative to less activity prior to pregnancy was not associated with early, late, or total preterm deliveries.

Conclusions
Results suggest that family history of cardiovascular disease may help identify women at risk for preterm delivery. Further, research is needed regarding preconception and very early pregnancy vigorous physical activity and associated risks.
Survival outcomes in endometrial cancer patients according to diabetes: a systematic review and meta-analysis
Authors: McVicker Lauren , Cardwell Christopher R. , Edge Lauren , McCluggage W Glenn , Quinn Declan , Wylie James , McMenamin Úna C. 
Published: April 2022

Abstract
Background
Diabetes is an established risk factor for endometrial cancer development but its impact on prognosis is unclear and epidemiological studies to date have produced inconsistent results. We aimed to conduct the first systematic review and meta-analysis to compare survival outcomes in endometrial cancer patients with and without pre-existing diabetes.

Methods
We conducted a systematic search of MEDLINE, EMBASE and Web of Science databases up to February 2022 for observational studies that investigated the association between pre-existing diabetes and cancer-specific survival in endometrial cancer patients. Secondary outcomes included overall survival and progression or recurrence-free survival. Quality assessment of included studies was undertaken using the Newcastle–Ottawa Scale and a random-effects model was used to produce pooled hazard ratios (HRs) and 95% confidence intervals (CIs). (PROSPERO 2020 CRD42020196088).

Results
In total, 31 studies were identified comprising 55,475 endometrial cancer patients. Pooled results suggested a worse cancer-specific survival in patients with compared to patients without diabetes (n = 17 studies, HR 1.15, 95% CI 1.00–1.32, I2 = 62%). Similar results were observed for progression or recurrence-free survival (n = 6 studies, HR 1.23, 95% CI 1.02–1.47, I2 = 0%) and for overall survival (n = 24 studies, HR 1.42, 95% CI 1.31–1.54, I2 = 46%).

Conclusion
In this systematic review and meta-analysis, we show that diabetes is associated with a worse cancer-specific and overall survival in endometrial cancer patients.
Baseline soluble MICA levels act as a predictive biomarker for the efficacy of regorafenib treatment in colorectal cancer
Authors: Arai Jun , Otoyama Yumi , Fujita Ken-ichi , Goto Kaku , Tojo Masayuki , Katagiri Atsushi , Nozawa Hisako , Kubota Yutaro , Takahashi Takehiro , Ishida Hiroo , Tsunoda Takuya , Matsumoto Natsumi , Ogawa Keita , Nakagawa Ryo , Muroyama Ryosuke , Kato Naoya , Yoshida Hitoshi 
Published: April 2022

Abstract
Background
To evaluate the effect of regorafenib on soluble MHC class I polypeptide-related sequence A (MICA) (sMICA) level in vitro. In addition, we clinically examined whether its plasma levels were associated with regorafenib activity in terms of progression-free survival (PFS) in patients with CRC.

Methods
Human CRC cell line HCT116 and HT29 cells were treated with regorafenib and its pharmacologically active metabolites, M2 or M5 at the same concentrations as those in sera of patients. We also examined the sMICA levels and the area under the plasma concentration–time curve of regorafenib, M2 and M5.

Results
Regorafenib, M2, and M5 significantly suppressed shedding of MICA in human CRC cells without toxicity. This resulted in the reduced production of sMICA. In the clinical examination, patients with CRC who showed long median PFS (3.7 months) had significantly lower sMICA levels than those with shorter median PFS (1.2 months) (p = 0.045).

Conclusions
MICA is an attractive agent for manipulating the immunological control of CRC and baseline sMICA levels could be a predictive biomarker for the efficacy of regorafenib treatment.