bluuebunny/crossref_metadata_2025_split huggingface dataset:
A blind benchmark of analysis tools to infer kinetic rate constants from single-molecule FRET trajectories
Authors: Götz Markus , Barth Anders , Bohr Søren S.-R. , Börner Richard , Chen Jixin , Cordes Thorben , Erie Dorothy A. , Gebhardt Christian , Hadzic Mélodie C. A. S. , Hamilton George L. , Hatzakis Nikos S. , Hugel Thorsten , Kisley Lydia , Lamb Don C. , de Lannoy Carlos , Mahn Chelsea , Dunukara Dushani , de Ridder Dick , Sanabria Hugo , Schimpf Julia , Seidel Claus A. M. , Sigel Roland K. O. , Sletfjerding Magnus Berg , Thomsen Johannes , Vollmar Leonie , Wanninger Simon , Weninger Keith R. , Xu Pengning , Schmid Sonja 
Published: September 2022

AbstractSingle-molecule FRET (smFRET) is a versatile technique to study the dynamics and function of biomolecules since it makes nanoscale movements detectable as fluorescence signals. The powerful ability to infer quantitative kinetic information from smFRET data is, however, complicated by experimental limitations. Diverse analysis tools have been developed to overcome these hurdles but a systematic comparison is lacking. Here, we report the results of a blind benchmark study assessing eleven analysis tools used to infer kinetic rate constants from smFRET trajectories. We test them against simulated and experimental data containing the most prominent difficulties encountered in analyzing smFRET experiments: different noise levels, varied model complexity, non-equilibrium dynamics, and kinetic heterogeneity. Our results highlight the current strengths and limitations in inferring kinetic information from smFRET trajectories. In addition, we formulate concrete recommendations and identify key targets for future developments, aimed to advance our understanding of biomolecular dynamics through quantitative experiment-derived models.
Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6Chi monocytes and differentiation to pro-angiogenic myeloid cells
Authors: Tran Thi , Lavillegrand Jean-Remi , Lereverend Cedric , Esposito Bruno , Cartier Lucille , Montabord Melanie , Tran-Rajau Jaouen , Diedisheim Marc , Gruel Nadège , Ouguerram Khadija , Paolini Lea , Lenoir Olivia , Pinteaux Emmanuel , Brabencova Eva , Tanchot Corinne , Urquia Pauline , Lehmann-Che Jacqueline , Le Naour Richard , Merrouche Yacine , Stockmann Christian , Mallat Ziad , Tedgui Alain , Ait-Oufella Hafid , Tartour Eric , Potteaux Stephane 
Published: September 2022

AbstractCancer and cardiovascular disease (CVD) share common risk factors such as dyslipidemia, obesity and inflammation. However, the role of pro-atherogenic environment and its associated low-grade inflammation in tumor progression remains underexplored. Here we show that feeding C57BL/6J mice with a non-obesogenic high fat high cholesterol diet (HFHCD) for two weeks to induce mild dyslipidemia, increases the pool of circulating Ly6Chi monocytes available for initial melanoma development, in an IL-1β-dependent manner. Descendants of circulating myeloid cells, which accumulate in the tumor microenvironment of mice under HFHCD, heighten pro-angiogenic and immunosuppressive activities locally. Limiting myeloid cell accumulation or targeting VEGF-A production by myeloid cells decrease HFHCD-induced tumor growth acceleration. Reverting the HFHCD to a chow diet at the time of tumor implantation protects against tumor growth. Together, these data shed light on cross-disease communication between cardiovascular pathologies and cancer.
In situ analysis of nanoparticle soft corona and dynamic evolution
Authors: Baimanov Didar , Wang Jing , Zhang Jun , Liu Ke , Cong Yalin , Shi Xiaomeng , Zhang Xiaohui , Li Yufeng , Li Xiumin , Qiao Rongrong , Zhao Yuliang , Zhou Yunlong , Wang Liming , Chen Chunying 
Published: September 2022

AbstractHow soft corona, the protein corona’s outer layer, contributes to biological identity of nanomaterials is largely because capturing protein composition of the soft corona in situ remains challenging. We herein develop an in situ Fishing method that can monitor the dynamic formation of protein corona on ultra-small chiral Cu2S nanoparticles (NPs) allowing us to directly separate and identify the corona protein composition. Our method detects spatiotemporal processes in the evolution of hard and soft coronas on chiral NPs, revealing subtle differences in NP − protein interactions even within several minutes. This study highlights the importance of in situ and dynamic analysis of soft/hard corona, provides insights into the role of soft corona in mediating biological responses of NPs, and offers a universal strategy to characterize soft corona to guide the rational design of biomedical nanomaterials.
A pilot study of neoadjuvant combination of anti-PD-1 camrelizumab and VEGFR2 inhibitor apatinib for locally advanced resectable oral squamous cell carcinoma
Authors: Ju Wu-tong , Xia Rong-hui , Zhu Dong-wang , Dou Sheng-jin , Zhu Guo-pei , Dong Min-jun , Wang Li-zhen , Sun Qi , Zhao Tong-chao , Zhou Zhi-hang , Liang Si-yuan , Huang Ying-ying , Tang Yong , Wu Si-cheng , Xia Jing , Chen Shi-qing , Bai Yue-zong , Li Jiang , Zhu Qi , Zhong Lai-ping 
Published: September 2022

AbstractNovel neoadjuvant therapy regimens are warranted for oral squamous cell carcinoma (OSCC). In this phase I trial (NCT04393506), 20 patients with locally advanced resectable OSCC receive three cycles of camrelizumab (200 mg, q2w) and apatinib (250 mg, once daily) before surgery. The primary endpoints are safety and major pathological response (MPR, defined as ≤10% residual viable tumour cells). Secondary endpoints include 2-year survival rate and local recurrence rate (not reported due to inadequate follow-up). Exploratory endpoints are the relationships between PD-L1 combined positive score (CPS, defined as the number of PD-L1-stained cells divided by the total number of viable tumour cells, multiplied by 100) and other immunological and genomic biomarkers and response. Neoadjuvant treatment is well-tolerated, and the MPR rate is 40% (8/20), meeting the primary endpoint. All five patients with CPS ˃10 achieve MPR. Post-hoc analysis show 18-month locoregional recurrence and survival rates of 10.5% (95% CI: 0%–24.3%) and 95% (95% CI: 85.4%–100.0%), respectively. Patients achieving MPR show more CD4+ T-cell infiltration than those without MPR (P = 0.02), and decreased CD31 and ɑ-SMA expression levels are observed after neoadjuvant therapy. In conclusion, neoadjuvant camrelizumab and apatinib is safe and yields a promising MPR rate for OSCC.
Mettl3-dependent m6A modification attenuates the brain stress response in Drosophila
Authors: Perlegos Alexandra E. , Shields Emily J. , Shen Hui , Liu Kathy Fange , Bonini Nancy M. 
Published: September 2022

AbstractN6-methyladenosine (m6A), the most prevalent internal modification on eukaryotic mRNA, plays an essential role in various stress responses. The brain is uniquely vulnerable to cellular stress, thus defining how m6A sculpts the brain’s susceptibility may provide insight to brain aging and disease-related stress. Here we investigate the impact of m6A mRNA methylation in the adult Drosophila brain with stress. We show that m6A is enriched in the adult brain and increases with heat stress. Through m6A-immunoprecipitation sequencing, we show 5′UTR Mettl3-dependent m6A is enriched in transcripts of neuronal processes and signaling pathways that increase upon stress. Mettl3 knockdown results in increased levels of m6A targets and confers resilience to stress. We find loss of Mettl3 results in decreased levels of nuclear m6A reader Ythdc1, and knockdown of Ythdc1 also leads to stress resilience. Overall, our data suggest that m6A modification in Drosophila dampens the brain’s biological response to stress.
Biochemical and structural insights of multifunctional flavin-dependent monooxygenase FlsO1-catalyzed unexpected xanthone formation
Authors: Yang Chunfang , Zhang Liping , Zhang Wenjun , Huang Chunshuai , Zhu Yiguang , Jiang Xiaodong , Liu Wei , Zhao Mengran , De Bidhan Chandra , Zhang Changsheng 
Published: September 2022

AbstractXanthone-containing natural products display diverse pharmacological properties. The biosynthetic mechanisms of the xanthone formation have not been well documented. Here we show that the flavoprotein monooxygenase FlsO1 in the biosynthesis of fluostatins not only functionally compensates for the monooxygenase FlsO2 in converting prejadomycin to dehydrorabelomycin, but also unexpectedly converts prejadomycin to xanthone-containing products by catalyzing three successive oxidations including hydroxylation, epoxidation and Baeyer-Villiger oxidation. We also provide biochemical evidence to support the physiological role of FlsO1 as the benzo[b]-fluorene C5-hydrolase by using nenestatin C as a substrate mimic. Finally, we resolve the crystal structure of FlsO1 in complex with the cofactor flavin adenine dinucleotide close to the “in” conformation to enable the construction of reactive substrate-docking models to understand the basis of a single enzyme-catalyzed multiple oxidations. This study highlights a mechanistic perspective for the enzymatic xanthone formation in actinomycetes and sets an example for the versatile functions of flavoproteins.
Effects of biological sex mismatch on neural progenitor cell transplantation for spinal cord injury in mice
Authors: Pitonak Michael , Aceves Miriam , Kumar Prakruthi Amar , Dampf Gabrielle , Green Peyton , Tucker Ashley , Dietz Valerie , Miranda Diego , Letchuman Sunjay , Jonika Michelle M. , Bautista David , Blackmon Heath , Dulin Jennifer N. 
Published: September 2022

AbstractDespite advancement of neural progenitor cell transplantation to spinal cord injury clinical trials, there remains a lack of understanding of how biological sex of transplanted cells influences outcomes after transplantation. To address this, we transplanted GFP-expressing sex-matched, sex-mismatched, or mixed donor cells into sites of spinal cord injury in adult male and female mice. Biological sex of the donor cells does not influence graft neuron density, glial differentiation, formation of the reactive glial cell border, or graft axon outgrowth. However, male grafts in female hosts feature extensive hypervascularization accompanied by increased vascular diameter and perivascular cell density. We show greater T-cell infiltration within male-to-female grafts than other graft types. Together, these findings indicate a biological sex-specific immune response of female mice to male donor cells. Our work suggests that biological sex should be considered in the design of future clinical trials for cell transplantation in human injury.
Epigenetic activation of the FLT3 gene by ZNF384 fusion confers a therapeutic susceptibility in acute lymphoblastic leukemia
Authors: Zhao Xujie , Wang Ping , Diedrich Jonathan D. , Smart Brandon , Reyes Noemi , Yoshimura Satoshi , Zhang Jingliao , Yang Wentao , Barnett Kelly , Xu Beisi , Li Zhenhua , Huang Xin , Yu Jiyang , Crews Kristine , Yeoh Allen Eng Juh , Konopleva Marina , Wei Chia-Lin , Pui Ching-Hon , Savic Daniel , Yang Jun J. 
Published: September 2022

AbstractFLT3is an attractive therapeutic target in acute lymphoblastic leukemia (ALL) but the mechanism for its activation in this cancer is incompletely understood. Profiling global gene expression in large ALL cohorts, we identify over-expression ofFLT3inZNF384-rearranged ALL, consistently across cases harboring different fusion partners withZNF384. Mechanistically, we discover an intergenic enhancer element at theFLT3locus that is exclusively activated inZNF384-rearranged ALL, with the enhancer-promoter looping directly mediated by the fusion protein. There is also a global enrichment of active enhancers within ZNF384 binding sites across the genome inZNF384-rearranged ALL cells. Downregulation ofZNF384bluntsFLT3activation and decreases ALL cell sensitivity to FLT3 inhibitor gilteritinib in vitro. In patient-derived xenograft models ofZNF384-rearranged ALL, gilteritinib exhibits significant anti-leukemia efficacy as a monotherapy in vivo. Collectively, our results provide insights into FLT3 regulation in ALL and point to potential genomics-guided targeted therapy for this patient population.
Machine learning-based detection of immune-mediated diseases from genome-wide cell-free DNA sequencing datasets
Authors: Che Huiwen , Jatsenko Tatjana , Lannoo Lore , Stanley Kate , Dehaspe Luc , Vancoillie Leen , Brison Nathalie , Parijs Ilse , Van Den Bogaert Kris , Devriendt Koenraad , Severi Sabien , De Langhe Ellen , Vermeire Severine , Verstockt Bram , Van Calsteren Kristel , Vermeesch Joris Robert 
Published: September 2022

AbstractThe early detection of tissue and organ damage associated with autoimmune diseases (AID) has been identified as key to improve long-term survival, but non-invasive biomarkers are lacking. Elevated cell-free DNA (cfDNA) levels have been observed in AID and inflammatory bowel disease (IBD), prompting interest to use cfDNA as a potential non-invasive diagnostic and prognostic biomarker. Despite these known disease-related changes in concentration, it remains impossible to identify AID and IBD patients through cfDNA analysis alone. By using unsupervised clustering on large sets of shallow whole-genome sequencing (sWGS) cfDNA data, we uncover AID- and IBD-specific genome-wide patterns in plasma cfDNA in both the obstetric and general AID and IBD populations. We demonstrate that pregnant women with AID and IBD have higher odds of receiving inconclusive non-invasive prenatal screening (NIPS) results. Supervised learning of the genome-wide patterns allows AID prediction with 50% sensitivity at 95% specificity. Importantly, the method has the potential to identify pregnant women with AID during routine NIPS. Since AID pregnancies have an increased risk of severe complications, early recognition or detection of new-onset AID can redirect pregnancy management and limit potential adverse events. This method opens up new avenues for screening, diagnosis and monitoring of AID and IBD.
A dataset of hourly sea surface temperature from drifting buoys
Authors: Elipot Shane , Sykulski Adam , Lumpkin Rick , Centurioni Luca , Pazos Mayra 
Published: September 2022

AbstractA dataset of sea surface temperature (SST) estimates is generated from the temperature observations of surface drifting buoys of NOAA’s Global Drifter Program. Estimates of SST at regular hourly time steps along drifter trajectories are obtained by fitting to observations a mathematical model representing simultaneously SST diurnal variability with three harmonics of the daily frequency, and SST low-frequency variability with a first degree polynomial. Subsequent estimates of non-diurnal SST, diurnal SST anomalies, and total SST as their sum, are provided with their respective standard uncertainties. This Lagrangian SST dataset has been developed to match the existing and on-going hourly dataset of position and velocity from the Global Drifter Program.
Agreement between two photoplethysmography-based wearable devices for monitoring heart rate during different physical activity situations: a new analysis methodology
Authors: Alfonso Carla , Garcia-Gonzalez Miguel A. , Parrado Eva , Gil-Rojas Jessyca , Ramos-Castro Juan , Capdevila Lluis 
Published: September 2022

AbstractWearables are being increasingly used to monitor heart rate (HR). However, their usefulness for analyzing continuous HR in research or at clinical level is questionable. The aim of this study is to analyze the level of agreement between different wearables in the measurement of HR based on photoplethysmography, according to different body positions and physical activity levels, and compared to a gold-standard ECG. The proposed method measures agreement among several time scales since different wearables obtain HR at different sampling rates. Eighteen university students (10 men, 8 women; 22 ± 2.45 years old) participated in a laboratory study. Participants simultaneously wore an Apple Watch and a Polar Vantage watch. ECG was measured using a BIOPAC system. HR was recorded continuously and simultaneously by the three devices, for consecutive 5-min periods in 4 different situations: lying supine, sitting, standing and walking at 4 km/h on a treadmill. HR estimations were obtained with the maximum precision offered by the software of each device and compared by averaging in several time scales, since the wearables obtained HR at different sampling rates, although results are more detailed for 5 s and 30 s epochs. Bland–Altman (B-A) plots show that there is no noticeable difference between data from the ECG and any of the smartwatches while participants were lying down. In this position, the bias is low when averaging in both 5 s and 30 s. Differently, B-A plots show that there are differences when the situation involves some level of physical activity, especially for shorter epochs. That is, the discrepancy between devices and the ECG was greater when walking on the treadmill and during short time scales. The device showing the biggest discrepancy was the Polar Watch, and the one with the best results was the Apple Watch. We conclude that photoplethysmography-based wearable devices are suitable for monitoring HR averages at regular intervals, especially at rest, but their feasibility is debatable for a continuous analysis of HR for research or clinical purposes, especially when involving some level of physical activity. An important contribution of this work is a new methodology to synchronize and measure the agreement against a gold standard of two or more devices measuring HR at different and not necessarily even paces.
SMAD3 contributes to ascending aortic dilatation independent of transforming growth factor-beta in bicuspid and unicuspid aortic valve disease
Authors: Balint Brittany , Federspiel Jan , Kollmann Catherine , Teping Paul , Schwab Tanja , Schäfers Hans-Joachim 
Published: September 2022

AbstractWe sought to determine whether there are differences in transforming growth factor-beta (TGFß) signaling in aneurysms associated with bicuspid (BAV) and unicuspid (UAV) aortic valves versus normal aortic valves. Ascending aortic aneurysms are frequently associated with BAV and UAV. The mechanisms are not yet clearly defined, but similarities to transforming growth factor-beta TGFß vasculopathies (i.e. Marfan, Loeys-Dietz syndromes) are reported. Non-dilated (ND) and aneurysmal (D) ascending aortic tissue was collected intra-operatively from individuals with a TAV (N = 10ND, 10D), BAV (N = 7ND, 8D) or UAV (N = 7ND, 8D). TGFß signaling and aortic remodeling were assessed through immuno-assays and histological analyses. TGFß1 was increased in BAV/UAV-ND aortas versus TAV (P = 0.02 and 0.04, respectively). Interestingly, TGFß1 increased with dilatation in TAV (P = 0.03) and decreased in BAV/UAV (P = 0.001). In TAV, SMAD2 and SMAD3 phosphorylation (pSMAD2, pSMAD3) increased with dilatation (all P = 0.04) and with TGFß1 concentration (P = 0.04 and 0.03). No relationship between TGFß1 and pSMAD2 or pSMAD3 was observed for BAV/UAV (all P > 0.05). pSMAD3 increased with dilatation in BAV/UAV aortas (P = 0.01), whereas no relationship with pSMAD2 was observed (P = 0.56). Elastin breaks increased with dilatation in all groups (all P < 0.05). In TAV, elastin degradation correlated with TGFß1, pSMAD2 and pSMAD3 (all P < 0.05), whereas in BAV and UAV aortas, elastin degradation correlated only with pSMAD3 (P = 0.0007). TGFß signaling through SMAD2/SMAD3 contributes to aortic remodeling in TAV, whereas TGFß-independent activation of SMAD3 may underlie aneurysm formation in BAV/UAV aortas. Therefore, SMAD3 should be further investigated as a therapeutic target against ascending aortic dilatation in general, and particularly in BAV/UAV patients.
Friction control of elastic materials on glass by means of textured surfaces
Authors: Fujita Naoki , Kinoshita Takumi , Iwao Masaru , Masuda Noriaki , Nakanishi Yoshitaka 
Published: September 2022

AbstractTo investigate the friction behaviors of elastomer and polyacetal writing tips sliding on various textured glass surfaces, the influences of the pitch size and height of sub-millimeter to millimeter sized texture on friction were examined via reciprocating friction tests. The friction coefficients of each writing tip could be systematically varied by changing the pitch and height of the texture. These changes in friction were based on the relationship between the convex-concave shapes and the contact parts of the writing tip, and hence, influence the adhesive, abrasive, and deformation frictions. By inducing a surface texture with a pitch smaller than the contact area of the writing tip, the friction coefficient could be reduced effectively. By inducing a surface texture with a larger height, the friction coefficient of the elastomer could be increased due to deformation friction. These behaviors indicate the possibility of controlling the friction by changing the parameters such as the pitch and height of the textured glass surfaces.
Effects of luseogliflozin and voglibose on high-risk lipid profiles and inflammatory markers in diabetes patients with heart failure
Authors: Ejiri Kentaro , Miyoshi Toru , Kihara Hajime , Hata Yoshiki , Nagano Toshihiko , Takaishi Atsushi , Toda Hironobu , Namba Seiji , Nakamura Yoichi , Akagi Satoshi , Sakuragi Satoru , Minagawa Taro , Kawai Yusuke , Nishii Nobuhiro , Fuke Soichiro , Yoshikawa Masaki , Nakamura Kazufumi , Ito Hiroshi ,   The MUSCAT-HF Study Investigators, Ejiri Kentaro , Miyoshi Toru , Nakamura Kazufumi , Ito Hiroshi , Kihara Hajime , Hata Yoshiki , Nagano Toshihiko , Takaishi Atsushi , Toda Hironobu , Namba Seiji , Nakamura Yoichi , Akagi Satoshi , Sakuragi Satoru , Minagawa Taro , Kawai Yusuke , Nishii Nobuhiro , Sato Tetsuya , Fuke Soichiro , Yoshikawa Masaki , Sugiyama Hiroyasu , Imai Michio , Gotoh Naoki , Segawa Tomonori , Noda Toshiyuki , Koshiji Masatoshi 
Published: September 2022

AbstractSodium-glucose cotransporter 2 inhibitors could reduce cardiovascular events in patients with heart failure irrespective of diabetes status. In this prespecified sub-analysis of randomised-controlled trial, we investigated the efficacy of luseogliflozin (2.5 mg daily), a sodium–glucose cotransporter 2 inhibitor, with that of voglibose (0.6 mg daily), an alpha-glucosidase inhibitor, on high-risk lipid profile and inflammatory markers in patients with type-2 diabetes and heart failure. Among the 157 patients studied, there were no significant differences in the mean malondialdehyde LDL or small-dense LDL cholesterol levels between the luseogliflozin and voglibose groups (percent change: 0.2% vs. − 0.6%, p = 0.93; − 1.7% vs. − 8.6%, p = 0.21) after 12 weeks in comparison to levels at the baseline. No significant difference was observed between the two groups in the adiponectin and high-sensitivity C-reactive protein levels after 12 weeks compared to the baseline levels (percent change, − 1.6% vs. − 4.0% and 22.5% vs. 10.0%; p = 0.52 and p = 0.55, respectively). In conclusion, in patients with type-2 diabetes and heart failure, compared to voglibose, luseogliflozin did not significantly improve the high-risk lipoprotein profile including malondialdehyde LDL and small-dense LDL cholesterol or the levels of inflammatory markers, including adiponectin and high-sensitivity C-reactive protein.Trial registration:Trial number: UMIN-CTR, UMIN000018395; Registered 23 July 2015; URL:https://www.umin.ac.jp/ctr/index.htm.