bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic activity of GARP:TGF-β1 blockade in murine primary myelofibrosis
Authors: Lecomte Sara , Devreux Julien , de Streel Grégoire , van Baren Nicolas , Havelange Violaine , Schröder David , Vaherto Noora , Vanhaver Christophe , Vanderaa Christophe , Dupuis Noémie , Pecquet Christian , Coulie Pierre G. , Constantinescu Stefan N. , Lucas Sophie 
Published: November 2022

Abstract
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by the clonal expansion of myeloid cells, notably megakaryocytes (MKs), and an aberrant cytokine production leading to bone marrow (BM) fibrosis and insufficiency. Current treatment options are limited. TGF-β1, a profibrotic and immunosuppressive cytokine, is involved in PMF pathogenesis. While all cell types secrete inactive, latent TGF-β1, only a few activate the cytokine via cell type–specific mechanisms. The cellular source of the active TGF-β1 implicated in PMF is not known. Transmembrane protein GARP binds and activates latent TGF-β1 on the surface of regulatory T lymphocytes (Tregs) and MKs or platelets. Here, we found an increased expression of GARP in the BM and spleen of mice with PMF and tested the therapeutic potential of a monoclonal antibody (mAb) that blocks TGF-β1 activation by GARP-expressing cells. GARP:TGF-β1 blockade reduced not only fibrosis but also the clonal expansion of transformed cells. Using mice carrying a genetic deletion of Garp in either Tregs or MKs, we found that the therapeutic effects of GARP:TGF-β1 blockade in PMF imply targeting GARP on Tregs. These therapeutic effects, accompanied by increased IFN-γ signals in the spleen, were lost upon CD8 T-cell depletion. Our results suggest that the selective blockade of TGF-β1 activation by GARP-expressing Tregs increases a CD8 T-cell-mediated immune reaction that limits transformed cell expansion, providing a novel approach that could be tested to treat patients with myeloproliferative neoplasms.
Regulation of iron homeostasis by hepatocyte TfR1 requires HFE and contributes to hepcidin suppression in β-thalassemia
Authors: Xiao Xia , Moschetta Gillian A. , Xu Yang , Fisher Allison L. , Alfaro-Magallanes Víctor M. , Dev Som , Wang Chia-Yu , Babitt Jodie L. 
Published: November 2022

Abstract
Transferrin receptor 1 (TfR1) performs a critical role in cellular iron uptake. Hepatocyte TfR1 is also proposed to influence systemic iron homeostasis by interacting with the hemochromatosis protein HFE to regulate hepcidin production. Here, we generated hepatocyte Tfrc knockout mice (Tfrcfl/fl;Alb-Cre+), either alone or together with Hfe knockout or β-thalassemia, to investigate the extent to which hepatocyte TfR1 function depends on HFE, whether hepatocyte TfR1 impacts hepcidin regulation by serum iron and erythropoietic signals, and its contribution to hepcidin suppression and iron overload in β-thalassemia. Compared with Tfrcfl/fl;Alb-Cre− controls, Tfrcfl/fl;Alb-Cre+ mice displayed reduced serum and liver iron; mildly reduced hematocrit, mean cell hemoglobin, and mean cell volume; increased erythropoietin and erythroferrone; and unchanged hepcidin levels that were inappropriately high relative to serum iron, liver iron, and erythroferrone levels. However, ablation of hepatocyte Tfrc had no impact on iron phenotype in Hfe knockout mice. Tfrcfl/fl;Alb-Cre+ mice also displayed a greater induction of hepcidin by serum iron compared with Tfrcfl/fl;Alb-Cre− controls. Finally, although acute erythropoietin injection similarly reduced hepcidin in Tfrcfl/fl;Alb-Cre+ and Tfrcfl/fl;Alb-Cre− mice, ablation of hepatocyte Tfrc in a mouse model of β-thalassemia intermedia ameliorated hepcidin deficiency and liver iron loading. Together, our data suggest that the major nonredundant function of hepatocyte TfR1 in iron homeostasis is to interact with HFE to regulate hepcidin. This regulatory pathway is modulated by serum iron and contributes to hepcidin suppression and iron overload in murine β-thalassemia.
Dasatinib/prednisone induction followed by blinatumomab/dasatinib in Ph+ acute lymphoblastic leukemia
Authors: Advani Anjali S. , Moseley Anna , O’Dwyer Kristen M. , Wood Brent L. , Park Jae , Wieduwilt Matthew , Jeyakumar Deepa , Yaghmour George , Atallah Ehab L. , Gerds Aaron T. , O'Brien Susan M. , Liesveld Jane L. , Othus Megan , Litzow Mark , Stone Richard M. , Sharon Elad , Erba Harry P. 
Published: November 2022

Abstract
Novel treatment strategies are needed for the treatment of Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) in older patients. This trial evaluated the feasibility and outcomes with the anti-CD19 bispecific T-cell–engaging antibody, blinatumomab, in combination with dasatinib and steroids. Patients 65 years of age or older with Ph+ or Ph-like ALL (with dasatinib-sensitive fusions/mutations) were eligible and could be newly diagnosed or relapsed/refractory. Induction therapy consisted of dasatinib/prednisone. Patients not achieving response by day 56 proceeded to blinatumomab reinduction therapy. Patients achieving response with induction or reinduction therapy proceeded to blinatumomab/dasatinib postremission therapy for 3 cycles followed by dasatinib/prednisone maintenance. All patients received central nervous system prophylaxis with intrathecal methotrexate for a total of 8 doses. Response was assessed at days 28, 56, and 84 and at additional time points based on response parameters. Measurable residual disease was assessed centrally by 8-color flow cytometry at day 28. A total of 24 eligible patients with newly diagnosed Ph+ ALL were enrolled with a median age of 73 years (range, 65-87 years). This combination was safe and feasible. With a median of 2.7 years of follow-up, 3-year overall survival and disease-free survival were 87% (95% confidence interval [CI], 64-96) and 77% (95% CI, 54-90), respectively. Although longer follow-up is needed, these results are encouraging, and future trials are building on this backbone regimen. This trial was registered at www.clinicaltrials.gov as #NCT02143414.
Clinical outcomes associated with NPM1 mutations in patients with relapsed or refractory AML
Authors: Issa Ghayas C. , Bidikian Aram , Venugopal Sangeetha , Konopleva Marina , DiNardo Courtney D. , Kadia Tapan M. , Borthakur Gautam , Jabbour Elias , Pemmaraju Naveen , Yilmaz Musa , Short Nicholas J. , Maiti Abhishek , Sasaki Koji , Masarova Lucia , Pierce Sherry , Takahashi Koichi , Tang Guilin , Loghavi Sanam , Patel Keyur , Andreeff Michael , Bhalla Kapil , Garcia-Manero Guillermo , Ravandi Farhad , Kantarjian Hagop , Daver Naval 
Published: November 2022

Abstract
Mutations in Nucleophosmin 1 (NPM1) are associated with a favorable prognosis in newly diagnosed acute myeloid leukemia (AML), however, their prognostic impact in relapsed/refractory (R/R) settings are unknown. In a retrospective analysis, we identified 206 patients (12%) with mutated NPM1 (NPM1c) and compared their outcomes to 1516 patients (88%) with NPM1 wild-type (NPM1wt). NPM1c was associated with higher rates of complete remission or complete remission with incomplete count recovery compared with NPM1wt following each line of salvage therapy (first salvage, 56% vs 37%; P &lt; .0001; second salvage, 33% vs 22%; P = .02; third salvage, 24% vs 14%; P = .02). However, NPM1 mutations had no impact on relapse-free survival (RFS) and overall survival (OS) with each salvage therapy with a median OS following salvage 1, 2 or 3 therapies in NPM1c vs NPM1wt of 7.8 vs 6.0; 5.3 vs 4.1; and 3.5 vs 3.6 months, respectively. Notably, the addition of venetoclax to salvage regimens in patients with NPM1c improved RFS and OS (median RFS, 15.8 vs 4.6 months; P = .05; median OS, 14.7 vs 5.9 months; P = .02). In conclusion, NPM1 mutational status has a minimal impact on prognosis in relapsed or refractory AML; therefore, novel treatment strategies are required to improve outcomes in this entity.
Onset of the COVID-19 pandemic reduced active time in patients with implanted cardiac devices
Authors: Sommers Nicholas , Berger Marcie , Rubenstein Jason C. , Roth James , Pan Amy , Thompson Colton , Widlansky Michael E. 
Published: November 2022

Abstract
Background
Physical inactivity and sedentary behavior are modifiable risk factors for chronic disease and all-cause mortality that may have been negatively impacted by the COVID-19 shutdowns.

Methods
Accelerometry data was retrospectively collected from 332 permanent pacemaker (PPM) and 244 implantable cardiac defibrillation (ICD) patients for 6 time points: March 15-May 15, 2020 (pandemic period), January 1-March 14, 2020, October 1-December 31, 2019, March 15-May 15, 2019, January 1-March 14, 2019, and October 1-December 31, 2018. Paired t-tests, with Bonferroni correction, were used to compare time periods.

Results
Activity significantly decreased during the pandemic period compared to one year prior by an average of 0.53 ± 1.18h/day (P < 0.001) for PPM patients and 0.51 ± 1.2h/day (P < 0.001) for ICD patients. Stratification of subjects by active time (< 2 versus ≥ 2h/day) showed patients with < 2h, particularly those with ICDs, had modestly greater activity reductions with the pandemic onset. Logistical regression analyses suggest a trend toward a greater reduction in active time at the onset of the pandemic and an increased risk of hospital or emergency department (ED) admission for PPM patients, but not ICD patients.

Conclusion
The onset of the pandemic in the United States was associated with a significant drop in PPM and ICD patient active hours that was modestly more pronounced in less active patients and cannot be explained by one year of aging or seasonal variation. If sustained, these populations may experience excess cardiovascular morbidity.
Comparative transcriptome analysis of resistant and susceptible Kentucky bluegrass varieties in response to powdery mildew infection
Authors: Zhang Yujuan , Dong Wenke , Zhao Chunxu , Ma Huiling 
Published: November 2022

Abstract
Background
Poa pratensis is one of the most common cold-season turfgrasses used for urban turf building, and it is also widely used in ecological environment management worldwide. Powdery mildew is a common disease of P. pratensis. To scientifically and ecologically control lawn powdery mildew, the molecular mechanism underlying the response of P. pratensis to powdery mildew infection must better understood.

Results
To explore molecular mechanism underlying the response of P. pratensis to powdery mildew infection, this study compared physiological changes and transcriptomic level differences between the highly resistant variety ‘BlackJack’ and the extremely susceptible variety ‘EverGlade’ under powdery mildew infection conditions. We analyzed DEGs using reference canonical pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the results showed that “starch and sucrose metabolism”, “photosynthesis” and “fatty acid metabolism”pathways were only enriched in ‘BlackJack’, and the expression of DEGs such as HXK, INV, GS, SS, AGpase and β-amylase in “starch and sucrose metabolism” pathway of ‘BlackJack’ were closely related to powdery mildew resistance. Meanwhile, compared with ‘EverGlade’, powdery mildew infection promoted synthesis of sucrose, expression of photosynthesis parameters and photosynthesis-related enzymes in leaves of ‘BlackJack’ and decreased accumulation of monosaccharides such as glucose and fructose.

Conclusions
This study identified the key metabolic pathways of a P. pratensis variety with high resistance to powdery mildew infection and explored the differences in physiological characteristics and key genes related to sugar metabolism pathways under powdery mildew stress. These findings provide important insights for studying underlying molecular response mechanism.
Plastome phylogenomic analysis reveals evolutionary divergences of Polypodiales suborder Dennstaedtiineae
Authors: Lu Jin-Mei , Du Xin-Yu , Kuo Li-Yaung , Ebihara Atsushi , Perrie Leon R. , Zuo Zheng-Yu , Shang Hui , Chang Yi-Han , Li De-Zhu 
Published: November 2022

Abstract
Background
Polypodiales suborder Dennstaedtiineae contain a single family Dennstaedtiaceae, eleven genera, and about 270 species, and include some groups that were previously placed in Dennstaedtiaceae, Hypolepidaceae, Monachosoraceae, and Pteridaceae. The classification and phylogenetic relationships among these eleven genera have been poorly understood. To explore the deep relationships within suborder Dennstaedtiineae and estimate the early diversification of this morphologically heterogeneous group, we analyzed complete plastomes of 57 samples representing all eleven genera of suborder Dennstaedtiineae using maximum likelihood and Bayesian inference.

Results
The phylogenetic relationships of all the lineages in the bracken fern family Dennstaedtiaceae were well resolved with strong support values. All six genera of Hypolepidoideae were recovered as forming a monophyletic group with full support, and Pteridium was fully supported as sister to all the other genera in Hypolepidoideae. Dennstaedtioideae (Dennstaedtia s.l.) fell into four clades with full support: the Microlepia clade, the northern Dennstaedtia clade, the Dennstaedtia globulifera clade, and the Dennstaedtia s.s. clade. Monachosorum was strongly resolved as sister to all the remaining genera of suborder Dennstaedtiineae. Based on the well resolved relationships among genera, the divergence between Monachosorum and other groups of suborder Dennstaedtiineae was estimated to have occurred in the Early Cretaceous, and all extant genera (and clades) in Dennstaedtiineae, were inferred to have diversified since the Late Oligocene.

Conclusion
This study supports reinstating a previously published family Monachosoraceae as a segregate from Dennstaedtiaceae, based on unique morphological evidence, the shady habitat, and the deep evolutionary divergence from its closest relatives.
The effect of varying inhaled oxygen concentrations of high-flow nasal cannula oxygen therapy during gastroscopy with propofol sedation in elderly patients: a randomized controlled study
Authors: Zhang Wenwen , Yin Hailing , Xu Yajie , Fang Zhaojing , Wang Wanling , Zhang Chen , Shi Hongwei , Wang Xiaoliang 
Published: November 2022

Abstract
Background
Despite evidence that high-flow nasal cannula oxygen therapy (HFNC) promotes oxygenation, its application in sedated gastroscopy in elderly patients has received little attention. This study investigated the effect of different inhaled oxygen concentrations (FiO2) of HFNC during sedated gastroscopy in elderly patients.

Methods
In a prospective randomized single-blinded study, 369 outpatients undergoing regular gastroscopy with propofol sedation delivered by an anesthesiologist were randomly divided into three groups (n = 123): nasal cannula oxygen group (Group C), 100% FiO2 of HFNC group (Group H100), and 50% FiO2 of HFNC (Group H50). The primary endpoint in this study was the incidence of hypoxia events with pulse oxygen saturation (SpO2) ≤ 92%. The secondary endpoints included the incidence of other varying degrees of hypoxia and adverse events associated with ventilation and hypoxia.

Results
The incidence of hypoxia, paradoxical response, choking, jaw lift, and mask ventilation was lower in both Group H100 and Group H50 than in Group C (P < 0.05). Compared with Group H100, Group H50 showed no significant differences in the incidence of hypoxia, jaw lift and mask ventilation, paradoxical response, or choking (P > 0.05). No patients were mechanically ventilated with endotracheal intubation or found to have complications from HFNC.

Conclusion
HFNC prevented hypoxia during gastroscopy with propofol in elderly patients, and there was no significant difference in the incidence of hypoxia when FiO2 was 50% or 100%.

Trial registration
This single-blind, prospective, randomized controlled trial was approved by the Ethics Committee of Nanjing First Hospital (KY20201102-04) and registered in the China Clinical Trial Center (20/10/2021, ChiCTR2100052144) before patients enrollment. All patients signed an informed consent form.
The relationship of genetic risk score with cardiometabolic risk factors: a cross-sectional study
Authors: Gholami Fatemeh , Rasaei Niloufar , Samadi Mahsa , Yekaninejad Mir Saeid , Keshavarz Seyed Ali , Javdan Gholamali , Karimi Zahra , Mirzaei Khadijeh 
Published: November 2022

Abstract
Background & aims
For more than eight decades, cardiovascular disease (CVD) has remained the leading cause of death in the world. CVD risk factors are multifaceted, with genetics and lifestyle both playing a role. The aim of this study was to investigate the association between a genetic profile risk score for obesity GRS and cardio-metabolic risk factors in overweight and obese women.

Methods
The current cross-sectional study was conducted on 391 overweight and obese women. The genetic risk score was created by combining three single nucleotide polymorphisms [MC4R (rs17782313), CAV-1 (rs3807992), and Cry-1 (rs2287161)]. Anthropometric measurements, blood pressure, and some blood parameters were measured by standard protocols.

Results
A significant association between the GRS and some of cardiometabolic risk factors variables such as body mass index (β = 0. 49, 95%CI = 0.22 to 0.76, p < 0.001), waist circumference (β = 0. 86, 95%CI = 0.18 to 1.54, p = 0.01), body fat mass (β = 0. 82, 95%CI = 0.25 to 1.39, p = 0.005), %body fat (β = 0. 44, 95%CI = 0.06 to 0.82, p = 0.02), and hs-CRP (β = 0.46, 95% CI = 0.14 to 0.78, p = 0.005) was observed in crude model. After adjustment for confounding factors (age, BMI, and physical activity), a significant positive association was observed between BMI (p = 0.004), WC (p = 0.02), body fat mass (p = 0.01), %BF (p = 0.01), hs-CRP (p = 0.009), and GRS. In addition, we discovered a significant negative association between the GRS and BMC (= -0.02, 95%CI = -0.05 to -0.001, p = 0.04). But other variables did not show any significant association with GRS among obese and overweight women.

Conclusion
We found a significant positive association between GRS, including MC4R (rs17782313), CAV-1 (rs3807992), and Cry-1 (rs2287161) and cardiometabolic risk factors among overweight and obese Iranian women.
Dementia risk prediction in individuals with mild cognitive impairment: a comparison of Cox regression and machine learning models
Authors: Wang Meng , Greenberg Matthew , Forkert Nils D. , Chekouo Thierry , Afriyie Gabriel , Ismail Zahinoor , Smith Eric E. , Sajobi Tolulope T. 
Published: November 2022

Abstract
Background
Cox proportional hazards regression models and machine learning models are widely used for predicting the risk of dementia. Existing comparisons of these models have mostly been based on empirical datasets and have yielded mixed results. This study examines the accuracy of various machine learning and of the Cox regression models for predicting time-to-event outcomes using Monte Carlo simulation in people with mild cognitive impairment (MCI).

Methods
The predictive accuracy of nine time-to-event regression and machine learning models were investigated. These models include Cox regression, penalized Cox regression (with Ridge, LASSO, and elastic net penalties), survival trees, random survival forests, survival support vector machines, artificial neural networks, and extreme gradient boosting. Simulation data were generated using study design and data characteristics of a clinical registry and a large community-based registry of patients with MCI. The predictive performance of these models was evaluated based on three-fold cross-validation via Harrell’s concordance index (c-index), integrated calibration index (ICI), and integrated brier score (IBS).

Results
Cox regression and machine learning model had comparable predictive accuracy across three different performance metrics and data-analytic conditions. The estimated c-index values for Cox regression, random survival forests, and extreme gradient boosting were 0.70, 0.69 and 0.70, respectively, when the data were generated from a Cox regression model in a large sample-size conditions. In contrast, the estimated c-index values for these models were 0.64, 0.64, and 0.65 when the data were generated from a random survival forest in a large sample size conditions. Both Cox regression and random survival forest had the lowest ICI values (0.12 for a large sample size and 0.18 for a small sample size) among all the investigated models regardless of sample size and data generating model.

Conclusion
Cox regression models have comparable, and sometimes better predictive performance, than more complex machine learning models. We recommend that the choice among these models should be guided by important considerations for research hypotheses, model interpretability, and type of data.
Histogram-based analysis of diffusion-weighted imaging for predicting aggressiveness in papillary thyroid carcinoma
Authors: Wei Ran , Zhuang Yuzhong , Wang Lanyun , Sun Xilin , Dai Zedong , Ge Yaqiong , Wang Hao , Song Bin 
Published: November 2022

Abstract
Background
To assess the potential of apparent diffusion coefficient (ADC) map in predicting aggressiveness of papillary thyroid carcinoma (PTC) based on whole-tumor histogram-based analysis.

Methods
A total of 88 patients with PTC confirmed by pathology, who underwent neck magnetic resonance imaging, were enrolled in this retrospective study. Whole-lesion histogram features were extracted from ADC maps and compared between the aggressive and non-aggressive groups. Multivariable logistic regression analysis was performed for identifying independent predictive factors. Receiver operating characteristic curve analysis was used to evaluate the performances of significant factors, and an optimal predictive model for aggressiveness of PTC was developed.

Results
The aggressive and non-aggressive groups comprised 67 (mean age, 44.03 ± 13.99 years) and 21 (mean age, 43.86 ± 12.16 years) patients, respectively. Five histogram features were included into the final predictive model. ADC_firstorder_TotalEnergy had the best performance (area under the curve [AUC] = 0.77). The final combined model showed an optimal performance, with AUC and accuracy of 0.88 and 0.75, respectively.

Conclusions
Whole-lesion histogram analysis based on ADC maps could be utilized for evaluating aggressiveness in PTC.