bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of temperature on the chemical evolution and desorption of pure CO ices irradiated by cosmic-rays analogues
Authors: Pilling S , Mateus M S , Ojeda-González A , Ferrão L F A , Galvão B R L , Boduch P , Rothard H 
Published: February 2024

ABSTRACT
Carbon monoxide (CO) plays a vital role in interstellar chemistry, existing abundantly in both gaseous and frozen environments. Understanding the radiation-driven chemistry of CO-rich ices is crucial for comprehending the formation and desorption of C-bearing molecules in the interstellar medium (ISM), particularly considering the potential impact of temperature on these processes. We report experimental data on irradiation processing of pure CO ice by cosmic ray analogues (95.2 MeV 136Xe23+ ions) at temperatures of 10, 15, and 20 K, in the IGLIAS set-up coupled to the IRRSUD beamline at GANIL (Caen, France). The evolution of the irradiated frozen samples was monitored by infrared spectroscopy. The computational PROCODA code allows us to quantify the chemical evolution of the samples, determining effective reaction rates coefficients (ERCs), molecular abundances at the chemical equilibrium (CE) phase, and desorption processes. The model integrated 18 chemical species – 8 observed (CO, CO2, C3, O3, C2O, C3O, C3O2, and C5O3) and 10 non-observed but predicted (C, O, C2, O2, CO3, C4O, C5O, C2O2, C2O3, C4O2) – linked via 156 reactions. Our findings reveal temperature-driven influences on molecular abundances at chemical equilibrium, desorption yields and rates, and ERC values. Certain reaction routes exhibit distinct thermochemical behaviours of gas- and ice-phase reactions which may be attributed to the presence of neighbouring molecules within the ice matrix. This study provides pivotal insights into the chemical evolution of CO-enriched ice under irradiation, impacting solid-state astrochemistry, clarifying molecular abundances, and advancing our understanding of ISM chemistry and temperature effects on ionized radiation-processed frozen ices.
Left ventricular recovery after total arterial coronary artery bypass grafting versus conventional coronary artery bypass grafting in patients with multivessel coronary artery disease and reduced left ventricular ejection fraction
Authors: Lin Zhi-qin , Chen Xiujun , Xu Zheng , Chen Liang-wan , Dai Xiao-fu 
Published: February 2024

Abstract

Background
We compared total arterial revascularization (TAR) versus conventional revascularization (CR) in terms of left ventricular function recovery in patients with multivessel coronary artery disease (CAD) and reduced left ventricular ejection fraction (LVEF).

Methods
We conducted a retrospective cohort study of 162 consecutive patients with multivessel CAD and reduced LVEF who underwent isolated coronary artery bypass grafting at our institution between January 2013 and July 2022. We assessed left ventricular function by transthoracic echocardiography at admission, before discharge, and at follow-up of 3, 6, and 12 months, using LVEF, global longitudinal peak strain, end-diastolic volume index, and end-systolic volume index. We also evaluated mitral valve regurgitation and graft patency rate at 1 year.

Results
The TAR group had a significantly higher increase in LVEF and global longitudinal peak strain, and a significantly lower decrease in end-diastolic volume index and end-systolic volume index than the CR group at 6 and 12 months after surgery. The TAR group also had a significantly lower degree of mitral valve regurgitation than the CR group at all-time points within 12 months after surgery. The TAR group had a significantly higher graft patency rate than the CR group at 12 months. There was no significant difference in hospital mortality or repeat revascularization between the groups.

Conclusions
TAR was associated with better recovery of left ventricular function than CR in patients with multivessel CAD and reduced LVEF. Further studies are needed to confirm these findings in this high-risk population.
Activation of the p62‐Keap1‐Nrf2 pathway improves pulmonary arterial hypertension in MCT‐induced rats by inhibiting autophagy
Authors: Jiang Gang , Shi Li‐Fang , Li Ling‐Jiao , Duan Xiao‐Ju , Zheng Zhao‐Fen 
Published: February 2024

AbstractAutophagy is implicated in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to investigate whether the p62‐Keap1‐Nrf2 pathway affects the development of PAH by mediating autophagy. A PAH rat model was established using monocrotaline (MCT). Pulmonary artery smooth muscle cells (PASMCs) were extracted, and the changes in proliferation, migration, autophagy, and oxidative stress were analyzed following overexpression or knockdown of p62. The impact of p62 on the symptoms of PAH rats was assessed by the injection of an adenovirus overexpressing p62. We found that the knockdown of p62 increased the proliferation and migration of PASMCs, elevating the oxidative stress of PASMCs and upregulating gene expression of NADPH oxidases. Co‐IP assay results demonstrated that p62 interacted with Keap1. p62 knockdown enhanced Keap1 protein stability and Nrf2 ubiquitination. LC3II/I and ATG5 were expressed more often when p62 was knocked down. Treating with an inhibitor of autophagy reversed the impact of p62 knockdown on PASMCs. Nrf2 inhibitor treatment reduced the expression of Nrf2 and p62, while increasing the expression of Keap1, LC3II/I, and ATG5 in PASMCs. However, overexpressing p62 diminished mRVP, SPAP, and Fulton index in PAH rats and attenuated pulmonary vascular wall thickening. Overexpression of p62 also decreased the expression of Keap1, LC3II/I, and ATG5 and increased the nuclear expression of Nrf2 in PAH rats. Importantly, overexpression of p62 reduced oxidative stress and the NADPH oxidase expression in PAH rats. Overall, activation of the p62‐Keap1‐Nrf2 positive feedback signaling axis reduces the proliferation and migration of PASMCs and alleviates PAH by inhibiting autophagy and oxidative stress.
Ruxolitinib, IV Immunoglobulin, and High-Dose Glucocorticoids for Critically Ill Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-Center Observational Pilot Study
Authors: Scholz Laura , Posch Florian , Schulz Eduard , Gornicec Max , Wölfler Albert , Reisinger Alexander C. , Reinisch Andreas , Eller Philipp , Eisner Florian , Kreuzer Philipp , Stradner Martin , Rosenkranz Alexander R. , Krammer Florian , Schilcher Gernot , Krause Robert , Hatzl Stefan 
Published: February 2024

OBJECTIVES:
Secondary hemophagocytic lymphohistiocytosis (sHLH) is a cytokine-driven inflammatory syndrome that is associated with substantial morbidity and mortality and frequently leads to ICU admission. Overall survival in adults with sHLH remains poor, especially in those requiring intensive care. Classical chemotherapeutic treatment exhibits myelosuppression and toxicity. Recently, inhibition of Janus kinase signaling by ruxolitinib has shown efficacy in pediatric HLH. We therefore aimed to determine the activity and safety of a ruxolitinib-based regimen, in critically ill adults with sHLH.

DESIGN:
Observational pilot study.

SETTING:
Single-center tertiary academic ICU.

PATIENTS:
Nine adults (≥ 18 yr) who fulfilled at least five of the eight HLH-2004 criteria.

INTERVENTION:
Triplet regimen combining: 1) ruxolitinib, 2) polyvalent human IV immunoglobulins (IVIG) at a dose of 1 g/kg bodyweight for 5 days, and 3) high-dose corticosteroids (CSs, dexamethasone 10 mg/m² body surface area, or methylprednisolone equivalent) with subsequent tapering according to the HLH-2004 protocol.

MEASUREMENT AND MAIN RESULTS:
Nine patients (median age: 42 yr [25th-75th percentile: 32–54]; male: n = 6 males, median H-score: 299 [255–304]) were treated with the triplet regimen. The median Sequential Organ Failure Assessment score at HLH diagnosis was 9 (median; 25th–75th percentile: 7–12), indicating multiple-organ dysfunction in all patients. Within 10 days a significant decrease of the inflammatory parameters soluble interleukin-2 receptor and ferritin as well as a stabilization of the blood count could be shown. All patients were alive at ICU discharge (100% ICU survival), 1 patient died after ICU discharge because of traumatic intracerebral hemorrhage that might be related to HLH or treatment, corresponding to an overall survival of 86% in a 6 months follow-up period.

CONCLUSION:
In this small case series, a triplet regimen of ruxolitinib in combination with IVIG and CS was highly effective and save for treating critically ill adults with sHLH.
Atypical perforated appendicitis secondary to schistosomiasis: a rare case report
Authors: Osoble Osman Faisal Abdi , Mohamed Yahye Garad , Salad Najib Mohamed , Yahye Nuh Mohamed 
Published: February 2024

Introduction:
Schistosomiasis is the second most common parasite disease after malaria and a rare cause of appendicitis. It has been well-documented in the literature that schistosomiasis infection can have several multisystem effects. The unusual condition known as schistosomal appendicitis was initially described by Turner.

Case presentation:
We present a 48-year-old man with perforated appendicitis and schistosomiasis-like radiological findings. An appendectomy was performed, and schistosomiasis was confirmed by a histological study of the excised appendix. Praziquantel was administered in a single dosage.

Conclusion:
Although schistosomiasis is a rare cause of appendicitis and is very prevalent in developing nations, it should be considered when managing the condition. Anti-shistosoma drugs, which are not frequently used in post-appendectomy cases, should also be considered in the management.
Comparison of the effect of open-box versus closed-box prostheses on blood loss following total knee arthroplasty: a meta-analysis
Authors: Elhalag Rowan H. , Dean Yomna E. , Hamdy Anas , Hadhoud Abdalla Mohamed , Chébl Pensée , Shah Jaffer , Gawad Mohamed , Motawea Karam R. 
Published: February 2024

Purpose:
Postoperative blood loss is a common complication following total knee arthroplasty (TKA). The authors aimed to analyze the significance of open versus closed-box prostheses in reducing blood loss after TKA.

Methods:
PubMed, Cochrane, Scopus, and Web of Science were searched. Observational studies and clinical trials comparing the effect of open-box versus closed-box prostheses on blood loss following TKA were included. The primary outcome was total blood loss following TKA. Secondary outcomes included average transfused units and total operation time. Continuous data were represented as mean difference (MD) and CI, while dichotomous data were presented as odds ratio (OR) and CI. RevMan software version 5.4 was used to conduct the analysis.

Results:
Four studies with a total number of 687 patients were included. The pooled analysis showed a statistically significant association between closed-box and decreased total blood loss following TKA compared with open-box (MD=173.19, 95% CI=88.77–257.61, P value <0.0001). Similar findings were reported in unilateral TKA (MD=190.63, 95% CI=70.91–310.35, P value=0.002), and bilateral TKA (MD=160.79, 95% CI=61.70–359.86, P value=0.001). There was no significant difference between open and closed-box regarding average transfused units (MD=0.02, 95% CI=−0.07–0.11, P value=0.68), blood transfusion rate (OR=1.38, 95% CI=0.85–2.26, P value=0.20), length of stay (MD=0.06, 95% CI=−0.27 to 0.38, P value=0.74), and total operation time (MD=1.08, 95% CI=−4.62 to 6.79, P value=0.71).

Conclusion:
Closed-box reduces the total blood loss following unilateral and bilateral TKA. More studies are warranted to explore the benefits of Closed-box in patients with high bleeding susceptibility.
Dissecting reprogramming heterogeneity at single-cell resolution using scTF-seq
Authors: Liu Wangjie , Saelens Wouter , Rainer Pernille , Biočanin Marjan , Gardeux Vincent , Gralak Antoni , van Mierlo Guido , Russeil Julie , Liu Tingdang , Chen Wanze , Deplancke Bart 
Published: February 2024

AbstractReprogramming approaches often produce heterogeneous cell fates and the mechanisms behind this heterogeneity are not well-understood. To address this gap, we developed scTF-seq, a technique inducing single-cell barcoded and doxycycline-inducible TF overexpression while quantifying TF dose-dependent transcriptomic changes. Applied to mouse embryonic multipotent stromal cells (MSCs), scTF-seq produced a gain-of-function atlas for 384 murine TFs. This atlas offers a valuable resource for gene regulation and reprogramming research, identifying key TFs governing MSC lineage differentiation, cell cycle control, and their interplay. Leveraging the single-cell resolution, we dissected reprogramming heterogeneity along dose and pseudotime. We thereby revealed TF dose-dependent and stochastic cell fate branching, unveiling gene expression signatures that enhance our understanding and prediction of reprogramming efficiency. scTF-seq also allowed us to classify TFs into four sensitivity classes based on dose response and determining features. Finally, in combinatorial scTF-seq, we observed that the same TF can exhibit both synergistic and antagonistic effects on another TF depending on its dose. In summary, scTF-seq provides a powerful tool for gaining mechanistic insights into how TFs determine cell states, while offering novel perspectives for cellular engineering strategies.
TBX3 is essential to establish the posterior boundary of anterior genes and up-regulate posterior genes with HAND2 during onset of limb bud development
Authors: Soussi Geoffrey , Girdziusaite Ausra , Jhanwar Shalu , Palacio Victorio , Sheth Rushikesh , Zeller Rolf , Zuniga Aimée 
Published: February 2024

ABSTRACTDuring limb bud formation, axes polarities are established as evidenced by the spatially restricted expression of key regulator genes. In particular, the mutually antagonistic interaction between the GLI3 repressor and HAND2 results in the distinct and non-overlapping anterior-distalGli3and posteriorHand2expression domains. This hallmarks establishment of antero-posterior (AP) limb axis polarity together with spatially restricted expression of homeodomain and other transcriptional regulators. Here, we identify TBX3 as the transcription factor to initiate AP axis polarity in mouse limb buds. ChIP-seq and differential gene expression analysis of wildtype and mutant limb buds identifies the TBX3-specific and shared TBX3-HAND2 target genes. High sensitivity fluorescent whole mountin situhybridisation shows that the posterior expression boundaries of anterior genes are positioned by TBX3-mediated repression, which excludes anterior genes such asGli3,Alx4,Hand1andIrx3/5from the posterior limb bud mesenchyme. This exclusion delineates the posterior mesenchymal territory competent to establish theShh-expressing limb bud organiser. In turn, HAND2 is required forShhactivation and cooperates with TBX3 to up-regulate shared posterior identity target genes in early limb buds.
Meta-analyses of mouse and human prostate single-cell transcriptomes reveal widespread epithelial plasticity in tissue regression, regeneration, and cancer
Authors: Aparicio Luis , Crowley Laura , Christin John R. , Laplaca Caroline J. , Hibshoosh Hanina , Rabadan Raul , Shen Michael M. 
Published: February 2024

AbstractRecent advances in single-cell RNA-sequencing (scRNA-seq) technology have facilitated studies of cell states and plasticity in tissue maintenance and cancer, including in the prostate. Here we present meta-analyses of multiple new and published scRNA-seq datasets to establish reference cell type classifications for the normal mouse and human prostate. Our analyses demonstrate transcriptomic similarities between epithelial cell states in the normal prostate, in the regressed prostate after androgen-deprivation, and in primary prostate tumors. During regression in the mouse prostate, all epithelial cells shift their expression profiles towards a proximal periurethral (PrU) state, demonstrating an androgen-dependent plasticity that is restored to normal during androgen restoration and regeneration. In the human prostate, we find progressive rewiring of transcriptional programs across epithelial cell types in benign prostate hyperplasia and treatment-naïve prostate cancer. Notably, we detect copy number variants predominantly within Luminal Acinar cells in prostate tumors, suggesting a bias in their cell type of origin, as well as a larger field of transcriptomic alterations in non-tumor cells. Finally, we observe that Luminal Acinar tumor cells in treatment-naïve prostate cancer display heterogeneous androgen receptor (AR) signaling activity, including a split between high-AR and low-AR profiles with similarity to PrU-like states. Taken together, our analyses of cellular heterogeneity and plasticity provide important translational insights into the origin and treatment response of prostate cancer.
Towards Equitable MHC Binding Predictions: Computational Strategies to Assess and Reduce Data Bias
Authors: Glynn Eric , Ghersi Dario , Singh Mona 
Published: February 2024

AbstractDeep learning tools that predict peptide binding by major histocompatibility complex (MHC) proteins play an essential role in developing personalized cancer immunotherapies and vaccines. In order to ensure equitable health outcomes from their application, MHC binding prediction methods must work well across the vast landscape of MHC alleles. Here we show that there are alarming differences across individuals in different racial and ethnic groups in how much binding data are associated with their MHC alleles. We introduce a machine learning framework to assess the impact of this data disparity for predicting binding for any given MHC allele, and apply it to develop a state-of-the-art MHC binding prediction model that additionally provides per-allele performance estimates. We demonstrate that our MHC binding model successfully mitigates much of the data disparities observed across racial groups. To address remaining inequities, we devise an algorithmic strategy for targeted data collection. Our work lays the foundation for further development of equitable MHC binding models for use in personalized immunotherapies.
NOTCH1 fusions in pediatric T-cell lymphoblastic lymphoma: a high-risk subgroup with CCL17 (TARC) levels as diagnostic biomarker
Authors: Kroeze Emma , Kleisman Michelle M , Kester Lennart A , Scheijde-Vermeulen Marijn A , Sonneveld Edwin , Buijs-Gladdines Jessica GC , Hagleitner Melanie M , Meyer-Wentrup Friederike AG , Veening Margreet A , Beishuizen Auke , Meijerink Jules PP , Loeffen Jan LC , Kuiper Roland P 
Published: February 2024

AbstractTwenty percent of children with T-cell lymphoblastic lymphoma (T-LBL) will relapse and have an extremely poor outcome. Currently, we can identify a genetically low-risk subgroup in pediatric T-LBL, yet these high-risk patients who need intensified or alternative treatment options remain undetected. Therefore, there is an urgent need to recognize these high-risk T-LBL patients through identification of molecular characteristics and biomarkers. By using RNA sequencing which was performed in 29/49 T-LBL patients who were diagnosed in the Princess Maxima Center for Pediatric Oncology between 2018-2023, we discovered a previously unknown high-risk biological subgroup of children with T-LBL. This subgroup is characterized byNOTCH1gene fusions, found in 21% of our T-LBL cohort (6/29). All patients presented with a large mediastinal mass, pleural/pericardial effusions, and absence of blasts in the bone marrow, blood, and central nervous system. Blood CCL17 (C-C Motif Chemokine Ligand 17, TARC) levels were measured at diagnosis in 26/29 patients, and all six patients withNOTCH1gene fusions patients exclusively expressed highly elevated blood CCL17 levels, defining a novel and previously not known clinically relevant biomarker for T-cell lymphoblastic lymphoma. Four out of these six patients relapsed during therapy, a fifth developed a therapy related acute myeloid leukemia during maintenance therapy. These data indicate that T-LBL patients with aNOTCH1fusion have a high risk of relapse which can be easily identified using a blood CCL17 screening at diagnosis. Further molecular characterization throughNOTCH1gene fusion analysis offers these patients the opportunity for treatment intensification or new treatment strategies.
High-throughput neural stem cell-based drug screening identifies S6K1 inhibition as a selective vulnerability in SHH-medulloblastoma
Authors: Zhou Leilei , van Bree Niek , Boutin Lola , Moussaud Simon , Otrocka Magdalena , Falk Anna , Wilhelm Margareta 
Published: February 2024

AbstractBackgroundMedulloblastoma (MB) is one of the most common malignant brain tumors in children. Current treatments have increased overall survival but can lead to devastating side effects and late complications in survivors, emphasizing the need for new, improved targeted therapies that specifically eliminate tumor cells while sparing the normally developing brain.MethodsHere, we used a SHH-MB model based on a patient-derived neuroepithelial stem (NES) cell system for an unbiased high-throughput screen with a library of 172 compounds with known targets. Compounds were evaluated in both healthy neural stem cells and tumor cells derived from the same patient. Based on the difference of cell viability and drug sensitivity score between normal cells and tumor cells, hit compounds were selected and further validatedin vitroandin vivo.ResultsWe identified PF4708671 (S6K1 inhibitor) as a potential agent that selectively targets Sonic Hedgehog (SHH) driven MB tumor cells while sparing neural stem cells and differentiated neurons. Subsequent validation studies confirmed that PF4708671 inhibited the growth of SHH-MB tumor cells bothin vitroandin vivo, and that knockdown of S6K1 resulted in reduced tumor formation.ConclusionOverall, our results suggest that inhibition of S6K1 specifically affects tumor growth, whereas it has less effect on non-tumor cells. Our data also show that the NES cell platform can be used to identify potentially effective new therapies and targets for SHH-MB.Key pointsHigh-throughput screening system using the NES model identifies efficient compounds and targets against SHH-MB.S6K1 inhibition shows selectivity toward tumor cells while having less effect on normal neural stem cells and neurons.Importance of the studyCurrent treatment modalities for medulloblastoma have improved overall survival but also come with detrimental side effects for survivors. Therefore, novel treatment options need to be developed which will specifically target the tumor cells while sparing the healthy brain. In this study, we tested a library of compounds targeting commonly dysregulated oncogenic pathways on both normal neural stem cells and SHH-MB tumor cells derived from the same patients. Interestingly, we found that most compounds including commonly used targeted therapy such as PI3K or mTOR inhibition, albeit effective, affected tumor cells and normal cells similarly. However, inhibition of the downstream effector S6K1 preferentially targeted tumor cells bothin vitroandin vivo. These results thus reveal potential targets for translational studies of novel therapies that specifically target medulloblastoma tumor cells.