bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lineage-specific early complete donor chimerism and risk of relapse after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia
Authors: Lindahl Hannes , Vonlanthen Sofie , Valentini Davide , Björklund Andreas T. , Sundin Mikael , Mielke Stephan , Hauzenberger Dan 
Published: February 2022

AbstractRecipient–donor chimerism is routinely analyzed after allogeneic hematopoietic stem cell transplantation (HSCT) to monitor engraftment and graft rejection. For malignancies, chimerism can also be used to screen for disease relapse post-HSCT but methodology and interpretation of results are not standardized and likely depend on underlying diagnosis. We have implemented highly sensitive and accurate methodologies for chimerism analysis for the purpose of improving relapse prediction. Here, we report an exploratory retrospective analysis of clinical routine chimerism results from all 154 HSCTs for acute myeloid leukemia (AML) performed at our center during the years 2015–2020 with the aim of suggesting a clinically useful threshold at which risk of relapse is high. Relapse was not reliably predicted based on single elevated chimerism values obtained before time of overt relapse. However, early complete donor chimerism, here defined as recipient DNA < 0.2% in CD33+ cells in any blood or bone marrow sample taken during the first 60 days after HSCT, correlated inversely with relapse during the observation time (log-rank test P = 0.033). We propose that achievement of complete chimerism determined early after HSCT using sensitive methods can be used for risk-stratification of AML patients.
SUMOylation of PDPK1 Is required to maintain glycolysis-dependent CD4 T-cell homeostasis
Authors: Sun Fei , Wang Fa-Xi , Zhu He , Yue Tian-Tian , Yang Chun-Liang , Luo Jia-Hui , Luo Xi , Zhou Hai-Feng , Rong Shan-Jie , Lu Wan-Ying , Zhou Qing , Yang Ping , Xiong Fei , Liu Yan-Jun , Yan Tong , Liao Yun-Fei , Zhang Shu , Wang Cong-Yi 
Published: February 2022

AbstractThe immune system is finely tuned to fight against infections, eradicate neoplasms, and prevent autoimmunity. Protein posttranslational modification (PTM) constitutes a molecular layer of regulation to guarantee the proper intensity of immune response. Herein, we report that UBC9-mediated protein SUMOylation plays an essential role in peripheral CD4 T-cell proliferation, but without a perceptible impact on T-cell polarization. Both conventional T-cell (Tcon) and regulatory T-cell (Treg) maintenance are differentially affected, which was likely caused by a shared deficit in cell glycolytic metabolism. Mechanistically, PDPK1 (3-phosphoinositide-dependent protein-kinase 1) was identified as a novel SUMOylation substrate, which occurred predominantly at lysine 299 (K299) located within the protein-kinase domain. Loss of PDPK1 SUMOylation impeded its autophosphorylation at serine 241 (S241), thereby leading to hypoactivation of downstream mTORC1 signaling coupled with incompetence of cell proliferation. Altogether, our results revealed a novel regulatory mechanism in peripheral CD4 T-cell homeostatic proliferation, which involves SUMOylation regulation of PDPK1–mTORC1 signaling-mediated glycolytic process.
Single-cell analysis of skin immune cells reveals an Angptl4-ifi20b axis that regulates monocyte differentiation during wound healing
Authors: Wee Wei Kiat Jonathan , Low Zun Siong , Ooi Chin Kiat , Henategala Benjamin Patrana , Lim Zhi Guang Ridley , Yip Yun Sheng , Vos Marcus Ivan Gerard , Tan William Wei Ren , Cheng Hong Sheng , Tan Nguan Soon 
Published: February 2022

AbstractThe persistent inflammatory response at the wound site is a cardinal feature of nonhealing wounds. Prolonged neutrophil presence in the wound site due to failed clearance by reduced monocyte-derived macrophages delays the transition from the inflammatory to the proliferative phase of wound healing. Angiopoietin-like 4 protein (Angptl4) is a matricellular protein that has been implicated in many inflammatory diseases. However, its precise role in the immune cell response during wound healing remains unclear. Therefore, we performed flow cytometry and single-cell RNA sequencing to examine the immune cell landscape of excisional wounds from Angptl4+/+ and Angptl4−/− mice. Chemotactic immune cell recruitment and infiltration were not compromised due to Angptl4 deficiency. However, as wound healing progresses, Angptl4−/− wounds have a prolonged neutrophil presence and fewer monocyte-derived macrophages than Angptl4+/+ and Angptl4LysM−/− wounds. The underlying mechanism involves a novel Angptl4-interferon activated gene 202B (ifi202b) axis that regulates monocyte differentiation to macrophages, coordinating neutrophil removal and inflammation resolution. An unbiased kinase inhibitor screen revealed an Angptl4-mediated kinome signaling network involving S6K, JAK, and CDK, among others, that modulates the expression of ifi202b. Silencing ifi202b in Angptl4−/− monocytes, whose endogenous expression was elevated, rescued the impaired monocyte-to-macrophage transition in the in vitro reconstituted wound microenvironment using wound exudate. GSEA and IPA functional analyses revealed that ifi202b-associated canonical pathways and functions involved in the inflammatory response and monocyte cell fate were enriched. Together, we identified ifi202b as a key gatekeeper of monocyte differentiation. By modulating ifi202b expression, Angptl4 orchestrates the inflammatory state, innate immune landscape, and wound healing process.
Identification of distinct cytotoxic granules as the origin of supramolecular attack particles in T lymphocytes
Authors: Chang Hsin-Fang , Schirra Claudia , Ninov Momchil , Hahn Ulrike , Ravichandran Keerthana , Krause Elmar , Becherer Ute , Bálint Štefan , Harkiolaki Maria , Urlaub Henning , Valitutti Salvatore , Baldari Cosima T. , Dustin Michael L. , Jahn Reinhard , Rettig Jens 
Published: February 2022

AbstractCytotoxic T lymphocytes (CTL) kill malignant and infected cells through the directed release of cytotoxic proteins into the immunological synapse (IS). The cytotoxic protein granzyme B (GzmB) is released in its soluble form or in supramolecular attack particles (SMAP). We utilize synaptobrevin2-mRFP knock-in mice to isolate fusogenic cytotoxic granules in an unbiased manner and visualize them alone or in degranulating CTLs. We identified two classes of fusion-competent granules, single core granules (SCG) and multi core granules (MCG), with different diameter, morphology and protein composition. Functional analyses demonstrate that both classes of granules fuse with the plasma membrane at the IS. SCG fusion releases soluble GzmB. MCGs can be labelled with the SMAP marker thrombospondin-1 and their fusion releases intact SMAPs. We propose that CTLs use SCG fusion to fill the synaptic cleft with active cytotoxic proteins instantly and parallel MCG fusion to deliver latent SMAPs for delayed killing of refractory targets.
Sequential metamaterials with alternating Poisson’s ratios
Authors: Farzaneh Amin , Pawar Nikhil , Portela Carlos M. , Hopkins Jonathan B. 
Published: February 2022

AbstractMechanical metamaterials have been designed to achieve custom Poisson’s ratios via the deformation of their microarchitecture. These designs, however, have yet to achieve the capability of exhibiting Poisson’s ratios that alternate by design both temporally and spatially according to deformation. This capability would enable dynamic shape-morphing applications including smart materials that process mechanical information according to multiple time-ordered output signals without requiring active control or power. Herein, both periodic and graded metamaterials are introduced that leverage principles of differential stiffness and self-contact to passively achieve sequential deformations, which manifest as user-specified alternating Poisson’s ratios. An analytical approach is provided with a complementary software tool that enables the design of such materials in two- and three-dimensions. This advance in design capability is due to the fact that the tool computes sequential deformations more than an order of magnitude faster than contemporary finite-element packages. Experiments on macro- and micro-scale designs validate their predicted alternating Poisson’s ratios.
Space-efficient optical computing with an integrated chip diffractive neural network
Authors: Zhu H. H. , Zou J. , Zhang H. , Shi Y. Z. , Luo S. B. , Wang N. , Cai H. , Wan L. X. , Wang B. , Jiang X. D. , Thompson J. , Luo X. S. , Zhou X. H. , Xiao L. M. , Huang W. , Patrick L. , Gu M. , Kwek L. C. , Liu A. Q. 
Published: February 2022

AbstractLarge-scale, highly integrated and low-power-consuming hardware is becoming progressively more important for realizing optical neural networks (ONNs) capable of advanced optical computing. Traditional experimental implementations needN2units such as Mach-Zehnder interferometers (MZIs) for an input dimensionNto realize typical computing operations (convolutions and matrix multiplication), resulting in limited scalability and consuming excessive power. Here, we propose the integrated diffractive optical network for implementing parallel Fourier transforms, convolution operations and application-specific optical computing using two ultracompact diffractive cells (Fourier transform operation) and onlyNMZIs. The footprint and energy consumption scales linearly with the input data dimension, instead of the quadratic scaling in the traditional ONN framework. A ~10-fold reduction in both footprint and energy consumption, as well as equal high accuracy with previous MZI-based ONNs was experimentally achieved for computations performed on theMNISTandFashion-MNISTdatasets. The integrated diffractive optical network (IDNN) chip demonstrates a promising avenue towards scalable and low-power-consumption optical computational chips for optical-artificial-intelligence.
Fast custom wavelet analysis technique for single molecule detection and identification
Authors: Ganjalizadeh Vahid , Meena Gopikrishnan G. , Wall Thomas A. , Stott Matthew A. , Hawkins Aaron R. , Schmidt Holger 
Published: February 2022

AbstractMany sensors operate by detecting and identifying individual events in a time-dependent signal which is challenging if signals are weak and background noise is present. We introduce a powerful, fast, and robust signal analysis technique based on a massively parallel continuous wavelet transform (CWT) algorithm. The superiority of this approach is demonstrated with fluorescence signals from a chip-based, optofluidic single particle sensor. The technique is more accurate than simple peak-finding algorithms and several orders of magnitude faster than existing CWT methods, allowing for real-time data analysis during sensing for the first time. Performance is further increased by applying a custom wavelet to multi-peak signals as demonstrated using amplification-free detection of single bacterial DNAs. A 4x increase in detection rate, a 6x improved error rate, and the ability for extraction of experimental parameters are demonstrated. This cluster-based CWT analysis will enable high-performance, real-time sensing when signal-to-noise is hardware limited, for instance with low-cost sensors in point of care environments.
Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis
Authors: Sattar Naveed , McGuire Darren K. , Pavo Imre , Weerakkody Govinda J. , Nishiyama Hiroshi , Wiese Russell J. , Zoungas Sophia 
Published: February 2022

AbstractTirzepatide is a novel, once weekly, dual GIP/GLP-1 receptor agonist and is under development for the treatment of type 2 diabetes (T2D) and obesity. Its association with cardiovascular outcomes requires evaluation. This pre-specified cardiovascular meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks from the tirzepatide T2D clinical development program, SURPASS. The pre-specified primary objective of this meta-analysis was the comparison of the time to first occurrence of confirmed four-component major adverse cardiovascular events (MACE-4; cardiovascular death, myocardial infarction, stroke and hospitalized unstable angina) between pooled tirzepatide groups and control groups. A stratified Cox proportional hazards model, with treatment as a fixed effect and trial-level cardiovascular risk as the stratification factor, was used for the estimation of hazard ratios (HRs) and confidence intervals (CIs) comparing tirzepatide to control. Data from 4,887 participants treated with tirzepatide and 2,328 control participants were analyzed. Overall, 142 participants, 109 from the trial with high cardiovascular risk and 33 from the six trials with lower cardiovascular risk, had at least one MACE-4 event. The HRs comparing tirzepatide versus controls were 0.80 (95% CI, 0.57–1.11) for MACE-4; 0.90 (95% CI, 0.50–1.61) for cardiovascular death; and 0.80 (95% CI, 0.51–1.25) for all-cause death. No evidence of effect modifications was observed for any subgroups, although the evidence was stronger for participants with high cardiovascular risk. Tirzepatide did not increase the risk of major cardiovascular events in participants with T2D versus controls.
18β-Glycyrrhetinic acid suppresses allergic airway inflammation through NF-κB and Nrf2/HO-1 signaling pathways in asthma mice
Authors: Liu Jianming , Xu Yanqi , Yan Minyu , Yu Yingjie , Guo Yongmei 
Published: February 2022

Abstract18β-Glycyrrhetinic acid (18β-GA), the main bioactive component of Glycyrrhizae Radix, is considered a promising anti-inflammatory and antioxidant agent. Here, we evaluated the anti-inflammatory and antioxidant effects of 18β-GA in an ovalbumin (OVA)-induced asthma mouse model, and examined the role of NF-κB and Nrf2/HO-1 signaling pathways. The histopathological changes of lung tissue in mouse were assessed by histochemical staining and counting of inflammatory cells. The levels of IgE and inflammatory cytokines in the bronchoalveolar lavage fluid of mice were detected by ELISA. In OVA-induced asthmatic mice, 18β-GA treatment can significantly improve lung function and reduce lung inflammation including infiltration of inflammatory cells. In addition, 18β-GA reduced the OVA-induced NF-κB phosphorylation in lungs of mice while increasing the expression of Nrf2 and HO-1. These results indicate that 18β-GA protects OVA-induced allergic inflammation of airway by inhibiting phosphorylation of NF-κB and enhancing the Nrf2/HO-1 pathway, and serves as a potential treatment option for allergic inflammation of airway.
Unpacking the complexity of longitudinal movement and recruitment patterns of facultative amphidromous fish
Authors: Ramírez-Álvarez Rodrigo , Contreras Sergio , Vivancos Aurélien , Reid Malcolm , López-Rodríguez Ruby , Górski Konrad 
Published: February 2022

AbstractLongitudinal movement plays fundamental role in habitat colonization and population establishment of many riverine fish species. Movement patterns of amphidromous fish species at fine-scales that would allow characterizing the direction of movement and factors associated with the establishment of specific life-history strategies (resident or amphidromous) in rivers are still poorly understood. We assess fine-scale longitudinal movement variability patterns of facultative amphidromous fish species Galaxias maculatus in order to unfold its life-history variation and associated recruitment habitats. Specifically, we analyzed multi-elemental composition along core to edge transects in ear-bones (otoliths) of each fish using recursive partitions that divides the transect along signal discontinuities. Fine-scale movement assessment in five free-flowing river systems allowed us to identify movement direction and potential recruitment habitats. As such, resident recruitment of G. maculatus in freshwater (71%) and estuarine (24%) habitats was more frequent than amphidromous recruitment (5%), and was linked to availability of slow-flowing lotic or lentic habitats that produce or retain small-bodied prey consumed by their larvae. We postulate that life-history variation and successful recruitment of facultative amphidromous fish such as G. maculatus in river systems is driven by availability of suitable recruitment habitats and natural hydrologic connectivity that allows fish movement to these habitats.
Local inhibition of TGF-β1 signaling improves Th17/Treg balance but not joint pathology during experimental arthritis
Authors: Aarts Joyce , van Caam Arjan , Chen Xinlai , Marijnissen Renoud J. , Helsen Monique M. , Walgreen Birgitte , Vitters Elly L. , van de Loo Fons A. , van Lent Peter L. , van der Kraan Peter M. , Koenders Marije I. 
Published: February 2022

AbstractTGF-β1 is an important growth factor to promote the differentiation of T helper 17 (Th17) and regulatory T cells (Treg). The potential of TGF-β1 as therapeutic target in T cell-mediated diseases like rheumatoid arthritis (RA) is unclear. We investigated the effect of TGF-β1 inhibition on murine Th17 differentiation in vitro, on human RA synovial explants ex vivo, and on the development of experimental arthritis in vivo. Murine splenocytes were differentiated into Th17 cells, and the effect of the TGF-βRI inhibitor SB-505124 was studied. Synovial biopsies were cultured in the presence or absence of SB-505124. Experimental arthritis was induced in C57Bl6 mice and treated daily with SB-505124. Flow cytometry analysis was performed to measure different T cell subsets. Histological sections were analysed to determine joint inflammation and destruction. SB-505124 potently reduced murine Th17 differentiation by decreasing Il17a and Rorc gene expression and IL-17 protein production. SB-505124 significantly suppressed IL-6 production by synovial explants. In vivo, SB-505124 reduced Th17 numbers, while increased numbers of Tregs were observed. Despite this skewed Th17/Treg balance, SB-505124 treatment did not result in suppression of joint inflammation and destruction. Blocking TGF-β1 signalling suppresses Th17 differentiation and improves the Th17/Treg balance. However, local SB-505124 treatment does not suppress experimental arthritis.
Effect of single session receptive music therapy on anxiety and vital parameters in hospitalized Covid-19 patients: a randomized controlled trial
Authors: Giordano Filippo , Losurdo Antonia , Quaranta Vitaliano Nicola , Campobasso Nicla , Daleno Antonio , Carpagnano Elisiana , Gesualdo Loreto , Moschetta Antonio , Brienza Nicola 
Published: February 2022

AbstractHospitalized COVID-19 patients are vulnerable to different degrees of stress disorders as well as depression, anxiety and fear. The aim of this study was to evaluate the feasibility of introducing Music therapy on site with Covid-19 patients and investigating the immediate effects a single session has on anxiety, heart rate (HR), oxygen saturation (O2Sat) and satisfaction compared to standard care. A randomized controlled trial of 40 patients was conducted. Participants were assigned to control group (CG) or the treatment group (MG). MG received an individual single session of music therapy in presence. CG received standard care. MG and CG were subjected to identical measurements (pre-during-post) of the parameters STAI-Y, HR and O2Sat. Participants in MG were asked to fill in an optional open-ended question concerning their experience with music therapy. Significant difference in anxiety levels between scores in MG and CG (34.50 (23.25–40.00) vs 45.00(38, 25–54.00); p = 0.000) was observed. MG compared to CG had statistically significantly higher values of O2Sat (97.50 (96.25–99.00) versus 96.00 (96.00–98.00); p = 0.026). Results show the feasibility of introducing music therapy as a supporting complementary/non-pharmacological intervention on site in Covid-19 patients. A single session of music therapy improves O2Sat and can significantly reduce anxiety.Trial registration: 14/10/2021 No. NCT05077306. https://www.clinicaltrials.cov.
Incidence and risk factors for early postoperative stiffness after arthroscopic rotator cuff repair in patients without preoperative stiffness
Authors: Cho Chul-Hyun , Bae Ki-Choer , Kim Du-Han 
Published: February 2022

AbstractThe purpose of this study was to investigate the incidence and risk factors of early postoperative stiffness in patients without preoperative stiffness undergoing isolated arthroscopic rotator cuff repair (ARCR). Two hundred seventy-four patients who underwent primary ARCR were included. At 3 months after surgery, criteria for shoulder stiffness was set as follows: (1) passive forward flexion < 120˚, or (2) external rotation at side < 30˚. Patients with preoperative stiffness or who underwent additional procedures were excluded. Patients-related, radiological (muscle atrophy and fatty infiltration), and intraoperative (tear size, repair techniques, number of anchors used, and synovitis scores) risk factors were analyzed. Univariate and multivariate analyses were used to identify risk factors for postoperative stiffness. Thirty-nine of 274 patients (14.2%) who underwent ARCR developed postoperative stiffness. Univariate analyses revealed that early postoperative stiffness was significantly associated with diabetes mellitus (p = 0.030). However, radiological and intraoperative factors did not affect postoperative shoulder stiffness (all p > 0.05). Multivariate analyses revealed early postoperative stiffness was significantly associated with diabetes mellitus and timing of rehabilitation (p = 0.024, p = 0.033, respectively). The overall incidence of early postoperative stiffness following isolated ARCR in patients without preoperative stiffness was 14.2%. Diabetes mellitus and timing of rehabilitation were independent risk factors for early postoperative stiffness following ARCR.
Deep learning-based quantitative analyses of spontaneous movements and their association with early neurological development in preterm infants
Authors: Shin Hyun Iee , Shin Hyung-Ik , Bang Moon Suk , Kim Don-Kyu , Shin Seung Han , Kim Ee-Kyung , Kim Yoo-Jin , Lee Eun Sun , Park Seul Gi , Ji Hye Min , Lee Woo Hyung 
Published: February 2022

AbstractThis study aimed to develop quantitative assessments of spontaneous movements in high-risk preterm infants based on a deep learning algorithm. Video images of spontaneous movements were recorded in very preterm infants at the term-equivalent age. The Hammersmith Infant Neurological Examination (HINE) was performed in infants at 4 months of corrected age. Joint positional data were extracted using a pretrained pose-estimation model. Complexity and similarity indices of joint angle and angular velocity in terms of sample entropy and Pearson correlation coefficient were compared between the infants with HINE < 60 and ≥ 60. Video images of spontaneous movements were recorded in 65 preterm infants at term-equivalent age. Complexity indices of joint angles and angular velocities differed between the infants with HINE < 60 and ≥ 60 and correlated positively with HINE scores in most of the joints at the upper and lower extremities (p < 0.05). Similarity indices between each joint angle or joint angular velocity did not differ between the two groups in most of the joints at the upper and lower extremities. Quantitative assessments of spontaneous movements in preterm infants are feasible using a deep learning algorithm and sample entropy. The results indicated that complexity indices of joint movements at both the upper and lower extremities can be potential candidates for detecting developmental outcomes in preterm infants.