bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time from image acquisition to endovascular team notification: a new target for enhancing acute stroke workflow
Authors: Yaeger Kurt A , Rossitto Christina P , Marayati Naoum Fares , Lara-Reyna Jacques , Ladner Travis , Hardigan Trevor , Shoirah Hazem , Mocco J , Fifi Johanna T 
Published: April 2021

ObjectiveTo quantify the time between initial image acquisition (CT angiography (CTA)) and notification of the neuroendovascular surgery (NES) team, a potentially high yield time window to target for optimization of endovascular thrombectomy (ET) treatment times.MethodsWe reviewed our multihospital database for all patients with a stroke with emergent large vessel occlusion treated with ET between January 1, 2017 and August 5, 2020. We dichotomized patients into rapid (≤20 min) and delayed (>20 min) notification times and analyzed treatment characteristics and outcomes.ResultsOf 367 patients with ELVO undergoing ET for whom notification data were available, the median time from CTA to NES team notification was 24 min (IQR 12–47). The median total treatment time was 180 min (IQR 129–252). The median times from CTA to NES team notification for rapid (n=163) and delayed (n=204) cohorts were 11 (IQR 6–15) and 43 (IQR 30–80) min, respectively (p<0.001). The median overall times to reperfusion were 134 min (IQR 103–179) and 213 min (IQR 172–291), respectively (p<0.001). The delayed patients had a significantly lower National Institutes of Health Stroke Scale (NIHSS) score on presentation (15 (IQR 9–20) vs 16 (IQR 11–22), p=0.03), were younger (70 (IQR 60–79) vs 77 (IQR 64–85), p<0.001), and more often presented with posterior circulation occlusion (16.7% vs 7.4%, p<0.01). The group with rapid notification time had a statistically larger median improvement in NIHSS score from admission to discharge (6 (IQR 0.5–14) vs 5 (IQR 0.5–10), p=0.04).ConclusionsTime delays from initial CTA acquisition to NES team notification can prevent expedient treatment with ET. Process improvements and automated stroke detection on imaging with automated notification of the NES team may ultimately improve time to reperfusion.
Sexual consent and chemsex: a quantitative study on sexualised drug use and non-consensual sex among men who have sex with men in Amsterdam, the Netherlands
Authors: Drückler Susanne , Speulman Jilke , van Rooijen Martijn , De Vries Henry J C 
Published: April 2021

BackgroundChemsex (drug use to enhance sex) has emerged among men who have sex with men (MSM). Non-consensual sex (NCS) is hypothesised to occur frequently under the influence of chemsex, however data are scarce. In this cross-sectional study, it was aimed to assess whether NCS is associated with chemsex.MethodsWe offered a survey about chemsex in the past 6 months (crystal methamphetamine, mephedrone and/or gamma-hydroxybutyrate/gamma-butyrolacton use) and NCS (sexual experiences beyond one’s limits or unpleasant sexual experiences) in the past 5 years to Amsterdam-located gay dating platform users. Associations were assessed using χ² test, Fisher’s exact test and multivariable logistic regression.ResultsOf 891 participants, 30.6% (273 of 891) engaged in chemsex; 21.2% engaging and 16.7% not engaging in chemsex reported any NCS experiences (p=0.109).Among MSM who reported any NCS experiences, chemsex engagers reported being touched against one’s will less often compared with non-engagers (22.4% vs 39.8%; p=0.036). Yet, chemsex engagers reported passing out and not remembering what happened during drug use more often (41.4% vs 8.7%; p<0.001). The level of suffering from NCS experiences did not differ between chemsex engagers and non-engagers (p=0.539); and was rated by most participants with no suffering at all or low suffering (77.1%). In the multivariable regression analyses, chemsex engagement in the past 6 months was associated with NCS (adjusted OR 1.46; 95% CI 1.01 to 2.11).ConclusionsA substantial proportion of MSM (regardless of chemsex engagement) reported NCS in the past 5 years. In multivariate logistic regression analysis, chemsex engagement was associated with an NCS experience. Among participants who reported NCS, suffering related to NCS however, did not differ between chemsex engagers and non-engagers. Sexual healthcare professionals need to address chemsex and NCS during consultations involving MSM and refer men for specialised help if deemed necessary.
Effects of mulching with crushed wheat straw padding and plastic film on sunflower emergence, yield, and yield components under different irrigation intensity in the northwest arid regions, China
Authors: Zhang Jinxia , Zhang Fu , Xing Zisheng , Guo Xiaolong , Hui Shijia , Du Liangliang , Ding Lin 
Published: April 2021

Crops in the northwest arid region of China frequently suffer from low emergence and poor yield due to high water deficit. Mulching is an important approach to reduce irrigation amount while increasing productivity but faces the challenge of ecological adaptability in this region. A field experiment was carried out in the three growing seasons from 2011 to 2013 to study the effects of mulching with crushed wheat straw padding and plastic film on sunflower seed emergence and yield under different irrigation intensities. A two-factor (mulching and irrigation intensity) completely randomized block design was applied, resulting in a total of 12 treatments repeated three times. Mulching treatments include zero mulch (N), straw mulching at the beginning of the experiment (S), plastic film mulching when sowing (F; a commonly used mulching by local farmers), and double mulching with plastic film on the crushed wheat straw layer (SF). Irrigation intensity includes high (H = 900 m3·ha−1), medium (M = 750 m3·ha−1), and low (L = 600 m3·ha−1). Results showed that all mulching treatments promoted the early emergence of seedlings compared with N, with SF and F performing better than the rest. SF was the best-performing mulching approach in this study, and it had significantly improved sunflower yield and yield components compared with other treatments. In SF, medium irrigation level had significantly increased sunflower 100-seed weight. Therefore, SF with M irrigation level showed the most positive effect on sunflower production, and it is now the recommended agronomic solution for sunflower production in the northwest arid regions and, potentially, other irrigated areas with similar ecological conditions.
Effects of induced water deficit and biofertilization on growth dynamics and bulb yield of onion (Allium cepaL.) in a neotropical semi-arid environment
Authors: Blanco Erika Lorena , Rada Fermín , Paolini Jorge , Guerrero José Argenis 
Published: April 2021

In a scenario of world population increase and climate change, an efficient use of water is key for agricultural production. Onion is one of the most profitable crops and can adapt to particular conditions of water stress. The objective of this research was to determine growing degree-days and accumulated radiation under non-stress conditions and yield of an F1 2000 hybrid of onion (Allium cepa L.) under water deficit (WD) and biofertilization in a semi-arid environment. An established nutrient requirement of 247 kg N, 240 kg P2O5(105 kg P), 240 kg K2O (199 kg K), and two irrigation factors were applied: normal irrigation with a daily and WD with a 3 d interval irrigation frequencies. The effect of biofertilization was evaluated through the inoculation of a microbial consortium (MC) in combination with four NPK fertilizer treatments. The crop accumulated 1334 degree-days and 1188 MJ m−2·d−1at the time of harvest at 71 d after transplanting. The yield was 36 t·ha−1, similar under both irrigation conditions; and the WD treatment resulted in a 35% water savings, a 47% and 65% increase in water use efficiency and modulus of elasticity, respectively. The MC resulted in a 50% NPK savings under non-limiting water conditions and produced a similar yield compared with the 100% NPK non-inoculated control. The lower irrigation frequency together with the 100% NPK fertilization dose without the MC and the use of the microorganisms and the 50% NPK treatment without water stress are recommended as agrosustainable practices for onion production.
A model-independent test of the evolution of gas depletion factor for SPT-SZ and Planck ESZ clusters
Authors: Bora Kamal , Desai Shantanu 
Published: April 2021

AbstractThe gas mass fraction in galaxy clusters has been widely used to determine cosmological parameters. This method assumes that the ratio of the cluster gas mass fraction to the cosmic baryon fraction ($$\gamma (z)$$

γ
(
z
)

) is constant as a function of redshift. In this work, we look for a time evolution of $$\gamma (z)$$

γ
(
z
)

at $$R_{500}$$

R
500

by using both the SPT-SZ and Planck Early SZ (ESZ) cluster data, in a model-independent fashion without any explicit dependence on the underlying cosmology. For this calculation, we use a non-parametric functional form for the Hubble parameter obtained from Gaussian Process regression using cosmic chronometers. We parameterize $$\gamma (z)$$

γ
(
z
)

as: $$\gamma (z)= \gamma _0(1+\gamma _1 z)$$

γ

(
z
)

=

γ
0

(
1
+

γ
1

z
)

to constrain the redshift evolution. We find contradictory results between both the samples. For SPT-SZ, $$\gamma (z)$$

γ
(
z
)

decreases as a function of redshift (at more than 5$$\sigma $$
σ
), whereas a positive trend with redshift is found for Planck ESZ data (at more than 4$$\sigma $$
σ
). We however find that the $$\gamma _1$$

γ
1

values for a subset of SPT-SZ and Planck ESZ clusters between the same redshift interval agree to within $$1\sigma $$

1
σ

. When we allow for a dependence on the halo mass in the evolution of the gas depletion factor, the $$4-5\sigma $$

4
-
5
σ

discrepancy reduces to $$2\sigma $$

2
σ

.
Lagrangian mechanics of active systems
Authors: Solovev Anton , Friedrich Benjamin M. 
Published: April 2021

Abstract
We present a multi-scale modeling and simulation framework for low-Reynolds number hydrodynamics of shape-changing immersed objects, e.g., biological microswimmers and active surfaces. The key idea is to consider principal shape changes as generalized coordinates and define conjugate generalized hydrodynamic friction forces. Conveniently, the corresponding generalized friction coefficients can be pre-computed and subsequently reused to solve dynamic equations of motion fast. This framework extends Lagrangian mechanics of dissipative systems to active surfaces and active microswimmers, whose shape dynamics is driven by internal forces. As an application case, we predict in-phase and anti-phase synchronization in pairs of cilia for an experimentally measured cilia beat pattern.

Graphic Abstract
On alternating closed braids
Authors: de los Angeles Guevara-Hernández María , Kawauchi Akio 
Published: April 2021

We introduce a numerical invariant called the braid alternation number that measures how far a link is from being an alternating closed braid. This invariant resembles the alternation number, which was previously introduced by the second author. However, these invariants are not equal, even for alternating links. We study the relation of this invariant with others and calculate this invariant for some infinite knot families. In particular, we show arbitrarily large gaps between the braid alternation number and the alternation and unknotting numbers. Furthermore, we estimate the braid alternation number for prime knots with nine crossings or less.
OnionMHC: A deep learning model for peptide — HLA-A*02:01 binding predictions using both structure and sequence feature sets
Authors: Saxena Shikhar , Animesh Sambhavi , Fullwood Melissa J. , Mu Yuguang 
Published: April 2021

The peptide binding to Major Histocompatibility Complex (MHC) proteins is an important step in the antigen-presentation pathway. Thus, predicting the binding potential of peptides with MHC is essential for the design of peptide-based therapeutics. Most of the available machine learning-based models predict the peptide-MHC binding based on the sequence of amino acids alone. Given the importance of structural information in determining the stability of the complex, here we have utilized both the complex structure and the peptide sequence features to predict the binding affinity of peptides to human receptor HLA-A*02:01. To our knowledge, no such model has been developed for the human HLA receptor before that incorporates both structure and sequence-based features. Results: We have applied machine learning techniques through the natural language processing (NLP) and convolutional neural network to design a model that performs comparably with the existing state-of-the-art models. Our model shows that the information from both sequence and structure domains results in enhanced performance in the binding prediction compared to the information from one domain alone. The testing results in 18 weekly benchmark datasets provided by the Immune Epitope Database (IEDB) as well as experimentally validated peptides from the whole-exome sequencing analysis of the breast cancer patients indicate that our model has achieved state-of-the-art performance. Conclusion: We have developed a deep-learning model (OnionMHC) that incorporates both structure as well as sequence-based features to predict the binding affinity of peptides with human receptor HLA-A*02:01. The model demonstrates state-of-the-art performance on the IEDB benchmark dataset as well as the experimentally validated peptides. The model can be used in the screening of potential neo-epitopes for the development of cancer vaccines or designing peptides for peptide-based therapeutics. OnionMHC is freely available at https://github.com/shikhar249/OnionMHC .
Anlotinib in Locally Advanced or Metastatic Medullary Thyroid Carcinoma: A Randomized, Double-Blind Phase IIB Trial
Authors: Li Dapeng , Chi Yihebali , Chen Xiaohong , Ge Minghua , Zhang Yuan , Guo Zhuming , Wang Jun , Chen Jie , Zhang Jiewu , Cheng Ying , Li Zhendong , Liu Hui , Qin Jianwu , Zhu Jingqiang , Cheng Ruochuan , Xu Zhengang , Zheng Xiangqian , Tang Pingzhang , Gao Ming 
Published: April 2021

Abstract

Purpose:
Medullary thyroid cancer (MTC) accounts for about 2% of all thyroid cancer, but has a relatively poor prognosis compared with differentiated thyroid cancer. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This multicenter, randomized, double-blind, placebo-controlled phase IIB study (ALTER 01031 and NCT02586350) was conducted to investigate the efficacy and safety of anlotinib in MTC.

Patients and Methods:
Patients with histopathologically confirmed, unresectable locally advanced or metastatic MTC were enrolled and randomly assigned in a 2:1 ratio to receive anlotinib (12 mg once daily from day 1 to 14 every 3 weeks) or placebo. Patients in placebo group were allowed to receive open-label anlotinib after disease progression. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS).

Results:
Ninety-one patients were enrolled. At data cutoff date, the median PFS was significantly prolonged in the anlotinib group than in the placebo group (20.7 months vs. 11.1 months, P = 0.029; HR, 0.53; 95% confidence interval, 0.30–0.95). The ORR of anlotinib treatment was 48.4%. The incidence of treatment-related adverse events (TRAE) was 100% and 89.7% in the anlotinib and placebo groups, respectively. The most common TRAEs of all grades in the anlotinib group were palmar–plantar erythrodysesthesia syndrome (62.9%), proteinuria (61.3%), and hypertriglyceridemia (48.4%).

Conclusions:
Anlotinib demonstrates its efficacy and safety in this phase IIB trial for the treatment of MTC and may become a new choice for this rare disease, especially for Chinese patients.
Anti-CLL1 Chimeric Antigen Receptor T-Cell Therapy in Children with Relapsed/Refractory Acute Myeloid Leukemia
Authors: Zhang Hui , Wang Pengfei , Li Zhuoyan , He Yingyi , Gan Wenting , Jiang Hua 
Published: April 2021

Abstract

Purpose:
The survival rate of children with refractory/relapsed acute myeloid leukemia (R/R-AML) by salvage chemotherapy is minimal. Treatment with chimeric antigen receptor T cells (CAR T) has emerged as a novel therapy to improve malignancies treatment. C-type lectin-like molecule 1 (CLL1) is highly expressed on AML stem cells, blast cells, and monocytes, but not on normal hematopoietic stem cells, indicating the therapeutic potential of anti-CLL1 CAR T in AML treatment. This study aimed to test the safety and efficacy of CAR T-cell therapy in R/R-AML.

Patients and Methods:
Four pediatric patients with R/R-AML were enrolled in the ongoing phase I/II anti-CLL1 CAR T-cell therapy trial. The CAR design was based on an apoptosis-inducing gene, FKBP-caspase 9, to establish a safer CAR (4SCAR) application. Anti-CLL1 CAR was transduced into peripheral blood mononuclear cells of the patients via lentivector 4SCAR, followed by infusion into the recipients after lymphodepletion chemotherapy. Cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and other adverse events were documented. Treatment response was evaluated by morphology and flow cytometry–based minimal residual disease assays.

Results:
Three patients with R/R-AML achieved complete remission and minimal residual disease negativity, while the other patient remained alive for 5 months. All these patients experienced low-grade and manageable adverse events.

Conclusions:
On the basis of our single-institution experience, autologous anti-CLL1 CAR T-cell therapy has the potential to be a safe and efficient alternative treatment for children with R/R-AML, and therefore requires further investigation.
Exercise Training Improves Tumor Control by Increasing CD8+ T-cell Infiltration via CXCR3 Signaling and Sensitizes Breast Cancer to Immune Checkpoint Blockade
Authors: Gomes-Santos Igor L. , Amoozgar Zohreh , Kumar Ashwin S. , Ho William W. , Roh Kangsan , Talele Nilesh P. , Curtis Hannah , Kawaguchi Kosuke , Jain Rakesh K. , Fukumura Dai 
Published: April 2021

AbstractThe mechanisms behind the antitumor effects of exercise training (ExTr) are not fully understood. Using mouse models of established breast cancer, we examined here the causal role of CD8+ T cells in the benefit acquired from ExTr in tumor control, as well as the ability of ExTr to improve immunotherapy responses. We implanted E0771, EMT6, MMTV-PyMT, and MCa-M3C breast cancer cells orthotopically in wild-type or Cxcr3−/− female mice and initiated intensity-controlled ExTr sessions when tumors reached approximately 100 mm3. We characterized the tumor microenvironment (TME) using flow cytometry, transcriptome analysis, proteome array, ELISA, and immunohistochemistry. We used antibodies against CD8+ T cells for cell depletion. Treatment with immune checkpoint blockade (ICB) consisted of anti–PD-1 alone or in combination with anti–CTLA-4. ExTr delayed tumor growth and induced vessel normalization, demonstrated by increased pericyte coverage and perfusion and by decreased hypoxia. ExTr boosted CD8+ T-cell infiltration, with enhanced effector function. CD8+ T-cell depletion prevented the antitumor effect of ExTr. The recruitment of CD8+ T cells and the antitumor effects of ExTr were abrogated in Cxcr3−/− mice, supporting the causal role of the CXCL9/CXCL11–CXCR3 pathway. ExTr also sensitized ICB-refractory breast cancers to treatment. Our results indicate that ExTr can normalize the tumor vasculature, reprogram the immune TME, and enhance the antitumor activity mediated by CD8+ T cells via CXCR3, boosting ICB responses. Our findings and mechanistic insights provide a rationale for the clinical translation of ExTr to improve immunotherapy of breast cancer.
Chemotherapy Induces Tumor-Associated Macrophages that Aid Adaptive Immune Responses in Ovarian Cancer
Authors: Heath Owen , Berlato Chiara , Maniati Eleni , Lakhani Anissa , Pegrum Colin , Kotantaki Panoraia , Elorbany Samar , Böhm Steffen , Barry Simon T. , Annibaldi Alessandro , Barton Desmond P. , Balkwill Frances R. 
Published: April 2021

Abstract

Neoadjuvant chemotherapy (NACT) may stimulate anticancer adaptive immune responses in high-grade serous ovarian cancer (HGSOC), but little is known about effects on innate immunity. Using omental biopsies from HGSOC, and omental tumors from orthotopic mouse HGSOC models that replicate the human tumor microenvironment, we studied the impact of platinum-based NACT on tumor-associated macrophages (TAM). We found that chemotherapy reduces markers associated with alternative macrophage activation while increasing expression of proinflammatory pathways, with evidence of inflammasome activation. Further evidence of a shift in TAM functions came from macrophage depletion via CSF1R inhibitors (CSF1Ri) in the mouse models. Although macrophage depletion in established disease had no impact on tumor weight or survival, CSF1Ri treatment after chemotherapy significantly decreased disease-free and overall survival. This decrease in survival was accompanied by significant inhibition of adaptive immune response pathways in the tumors. We conclude that chemotherapy skews the TAM population in HSGOC toward an antitumor phenotype that may aid adaptive immune responses, and therapies that enhance or sustain this during remission may delay relapse.
Fetal Programming by Methyl Donor Deficiency Produces Pathological Remodeling of the Ascending Aorta
Authors: Balint Brittany , Hergalant Sébastien , Camadro Jean-Michel , Blaise Sébastien , Vanalderwiert Laetitia , Lignières Laurent , Guéant-Rodriguez Rosa-Maria , Guéant Jean-Louis 
Published: April 2021

Objective:
Deficiency in vitamin B12/folate (methyl donor deficiency [MDD]) produces cardiovascular outcomes during aging and fetal programming effects in newborns of MDD mothers. Whether fetal programming provokes long-term effects on aorta remains largely unknown.

Approach and Results:

We investigated the impact of fetal programming on ascending aorta of aged rats born from mothers subjected to MDD during gestation/lactation. We performed morphological and molecular examinations of ascending aortas in 21 days- and 400 days-aged rats with initial MDD fetal programming (iMDD) compared with control matched rats. iMDD induces remodeling of the ascending aorta in aged rats, with collagen deposition (
P
=0.0008), decreased thickness of elastin (
P
<0.0001), and 8.7-fold increase of elastin breaks (
P
=0.0002). Proteomic analyses, Western blotting, and immunohistochemical examination revealed decreased expression of α-smooth muscle actin, vinculin, SM22α (smooth muscle 22α), and N-cadherin and increased expression of TGF (transforming growth factor) β1. Elastin breaks were correlated to increased neutrophil elastase (
P
=0.0002), cathepsin-K (
P
=0.0002), cathepsin-S (
P
<0.0001), MMP (matrix metalloproteinase) 9, and MMP2 (
P
<0.0001 and
P
=0.02). Proximity Duolink ligation assay showed homocysteinylation of actin-associated and extracellular matrix proteins, including SM22α (
P
=0.01), N-cadherin (
P
=0.0008), and vinculin (
P
=0.001), which was associated with elastin breaks (
P
=0.002) and increased expression of MARS (methionyl-tRNA synthetase; involved in irreversible protein homocysteinylation). Furthermore, we observed an inverse relationship between elastin breaks and blood pressure (systolic,
P
=0.004 and diastolic,
P
=0.0007).

Conclusions:
MDD fetal programming produced altered integrity and remodeling of ascending aorta during aging and irreversible MARS-associated homocysteinylation of key proteins of extracellular matrix and elastin homeostasis. This contributes to understanding why homocysteine-lowering vitamin B supplementation fails to relieve vascular complications in adulthood.