bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics of axonal β‐actin mRNA in live hippocampal neurons
Authors: Lee Byung Hun , Bang Seokyoung , Lee Seung‐Ryeol , Jeon Noo Li , Park Hye Yoon 
Published: August 2022

AbstractLocalization of mRNA facilitates spatiotemporally controlled protein expression in neurons. In axons, mRNA transport followed by local protein synthesis plays a critical role in axonal growth and guidance. However, it is not yet clearly understood how mRNA is transported to axonal subcellular sites and what regulates axonal mRNA localization. Using a transgenic mouse model in which endogenous β‐actin mRNA is fluorescently labeled, we investigated β‐actin mRNA movement in axons of hippocampal neurons. We cultured neurons in microfluidic devices to separate axons from dendrites and performed single‐particle tracking of axonal β‐actin mRNA. Compared with dendritic β‐actin mRNA, axonal β‐actin mRNA showed less directed motion and exhibited mostly subdiffusive motion, especially near filopodia and boutons in mature dissociated hippocampal neurons. We found that axonal β‐actin mRNA was likely to colocalize with actin patches (APs), regions that have a high density of filamentous actin (F‐actin) and are known to have a role in branch initiation. Moreover, simultaneous imaging of F‐actin and axonal β‐actin mRNA in live neurons revealed that moving β‐actin mRNA tended to be docked in the APs. Our findings reveal that axonal β‐actin mRNA localization is facilitated by actin networks and suggest that localized β‐actin mRNA plays a potential role in axon branch formation.
The Effects of Blackcurrant and Caffeine Combinations on Performance and Physiology During Repeated High-Intensity Cycling
Authors: Paton Carl D. , Morton Lillian C. , Bomal Benoit , Braakhuis Andrea J. 
Published: August 2022

Blackcurrant juices and extracts containing anthocyanin may provide ergogenic benefits to sports performance. However, there are no studies examining the effects of coingestion of blackcurrant and caffeine. This investigation examined the effects of acute supplementation with a proprietary blackcurrant beverage administered in isolation or in combination with caffeine on repeated high-intensity cycling. Twelve well-trained male cyclists (mean ± SD: age, 39.5 ± 11.4 years; height, 177.9 ± 5.7 cm; weight, 78.2 ± 8.9 kg; and peak oxygen consumption, 4.71 ± 0.61 L/min) completed experimental sessions consisting of repeated (8 × 5 min) maximal intensity efforts. Four experimental treatments were administered in a double-blind, balanced Latin square design: blackcurrant + caffeine, blackcurrant + placebo, caffeine + placebo and placebo + placebo. Differences in power output, heart rate, oxygen consumption, muscle oxygen saturation, rate of perceived exertion, and cognitive function (Stroop) were compared between treatments using two-way repeated-measures analysis of variance and effect size analysis. There were no significant differences (p > .05) in either physiological or cognitive variables with any supplement treatment (blackcurrant + caffeine, blackcurrant + placebo, and caffeine + placebo) relative to placebo + placebo. Moreover, any observed differences were deemed trivial (d < 0.2) in magnitude. However, power output was lower (p < .05) in blackcurrant + placebo compared with blackcurrant + caffeine. A blackcurrant extract beverage administered in isolation or combination with caffeine provided no beneficial effect on cycling performance or physiological measures relative to a placebo control.
Temporal trends and rural–urban disparities in cerebrovascular risk factors, in-hospital management and outcomes in ischaemic strokes in China from 2005 to 2015: a nationwide serial cross-sectional survey
Authors: Wang Chun-Juan , Gu Hong-Qiu , Zhang Xin-Miao , Jiang Yong , Li Hao , Bettger Janet Prvu , Meng Xia , Dong Ke-Hui , Wangqin Run-Qi , Yang Xin , Wang Meng , Liu Chelsea , Liu Li-Ping , Tang Bei-Sha , Li Guo-Zhong , Xu Yu-Ming , He Zhi-Yi , Yang Yi , Yip Winnie , Fonarow Gregg C , Schwamm Lee H , Xian Ying , Zhao Xing-Quan , Wang Yi-Long , Wang Yongjun , Li Zixiao 
Published: August 2022

BackgroundStroke is the leading cause of mortality in China, with limited evidence of in-hospital burden obtained from nationwide surveys. We aimed to monitor and track the temporal trends and rural–urban disparities in cerebrovascular risk factors, management and outcomes from 2005 to 2015.MethodsWe used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005, 2010 and 2015. We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach. We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015.ResultsWe analysed 28 277 ischaemic stroke admissions from 189 participating hospitals. From 2005 to 2015, the estimated national hospital admission rate for ischaemic stroke per 100 000 people increased (from 75.9 to 402.7, Ptrend<0.001), and the prevalence of risk factors, including hypertension, diabetes, dyslipidaemia and current smoking, increased. The composite score of diagnostic tests for stroke aetiology assessment (from 0.22 to 0.36, Ptrend<0.001) and secondary prevention treatments (from 0.46 to 0.70, Ptrend<0.001) were improved. A temporal decrease was found in discharge against medical advice (DAMA) (from 15.2% (95% CI 13.7% to 16.7%) to 8.6% (8.1% to 9.0%); adjusted Ptrend=0.046), and decreases in in-hospital mortality (0.7% in 2015 vs 1.8% in 2005; adjusted OR (aOR) 0.52; 95% CI 0.32 to 0.85) and the composite outcome of in-hospital mortality or DAMA (8.4% in 2015 vs 13.9% in 2005; aOR 0.65; 95% CI 0.47 to 0.89) were observed. Disparities between rural and urban hospitals narrowed; however, disparities persisted in in-hospital management (brain MRI: rural–urban difference from −14.4% to −11.2%; cerebrovascular assessment: from −20.3% to −16.7%; clopidogrel: from −2.1% to −10.3%; anticoagulant for atrial fibrillation: from −10.9% to −8.2%) and in-hospital outcomes (DAMA: from 2.7% to 5.0%; composite outcome of in-hospital mortality or DAMA: from 2.4% to 4.6%).ConclusionsFrom 2005 to 2015, improvements in hospital admission and in-hospital management for ischaemic stroke in China were found. A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed. Disparities between rural and urban hospitals generally narrowed but persisted.
Compositeness of S-wave weakly-bound states from next-to-leading order Weinberg’s relations
Authors: Albaladejo M. , Nieves J. 
Published: August 2022

AbstractWe discuss a model-independent estimator of the likelihood of the compositeness of a shallow S-wave bound or virtual state. The approach is based on an extension of Weinberg’s relations in Weinberg (Phys Rev 137:B672, 1965) and it relies only on the proximity of the energy of the state to the two-hadron threshold to which it significantly couples. The scheme only makes use of the experimental scattering length and the effective range low energy parameters, and it is shown to be fully consistent for predominantly molecular hadrons. As explicit applications, we analyse the case of the deuteron, the $$^1\mathrm{S}_0$$

1

S
0

nucleon-nucleon virtual state and the exotic $$D^{*}_{s0}(2317)^\pm $$

D

s
0

∗

(
2317
)

±

, and find strong support to the molecular interpretation in all cases. Results are less conclusive for the $$D^{*}_{s0}(2317)^\pm $$

D

s
0

∗

(
2317
)

±

, since the binding energy of this state would be significantly higher than that of the deuteron, and the approach employed here is at the limit of its applicability. We also qualitatively address the case of the recently discovered $$T_{cc}^+$$

T

cc

+

state, within the isospin limit to avoid the complexity of the very close thresholds $$D^0D^{*+}$$

D
0

D

∗
+

and $$D^+D^{*0}$$

D
+

D

∗
0

, which could mask the ingredients of the approach proposed in this work.
Changing the nature of AI research
Authors: Kambhampati Subbarao 
Published: August 2022

The
Communications
website, https://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

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Follow us on Twitter at http://twitter.com/blogCACM
https://cacm.acm.org/blogs/blog-cacm
Subbarao Kambhampati considers how artificial intelligence may be straying from its roots.
Predictive Polygenic Score for Outcome after First-Line Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients Using Supervised Principal Component Analysis
Authors: Park Hanla A. , Edelmann Dominic , Canzian Federico , Harrison Tabitha A. , Hua Xinwei , Shi Qian , Silverman Allison , Schneider Martin , Goldberg Richard M. , Alberts Steven R. , Hoffmeister Michael , Brenner Hermann , Chan Andrew T. , Peters Ulrike , Newcomb Polly A. , Chang-Claude Jenny 
Published: August 2022

Abstract

Background:
Associations between candidate germline genetic variants and treatment outcome of oxaliplatin, a drug commonly used for patients with colorectal cancer, have been reported but not robustly established. This study aimed to construct polygenic hazard scores (PHSs) as predictive markers for oxaliplatin treatment outcome by using a supervised principal component approach (PCA).

Methods:
Genome-wide association analysis for overall survival, including interaction terms (SNP*treatment type) was carried out using two phase III trials, 3,098 resected stage III colon cancer (rCC) patients of NCCTG N0147 and 506 metastatic colorectal cancer (mCRC) patients of NCCTG N9741, separately. SNPs showing interaction with genome-wide significance (P &lt; 5 × 10–8) were selected for PCA to derive a PHS. PHS interaction with treatment was included in Cox regression models to predict outcome. Replication of prediction models was performed in an independent cohort, DACHS.

Results:
The two PHSs based on the first two principal components of selected SNPs (15SNPs for rCC and 13SNPs for mCRC) were used to construct interaction terms with treatment type and included in models adjusted for clinical covariables. However, in the DACHS study, the addition of the two PHS terms to clinical models did not improve the prediction error in either patients with rCC or mCRC. PHS interaction was also not replicated.

Conclusions:
The PHSs derived using principal components efficiently combined multiple predictive SNPs for estimating likelihood of benefit from oxaliplatin versus other treatment but could not be replicated.

Impact:
These results highlight the potential but also challenges in generating evidence for a predictive polygenic score for oxaliplatin efficacy.
XL-ing at Induction of Apoptosis in Kidney Cancer through Inhibition of BCL-XL
Authors: Wang Naitao , Hakimi A. Ari , Chen Yu 
Published: August 2022

Through analysis of the cancer dependency map of CRISPR and short hairpin RNA datasets, the antiapoptotic BCL-XL was found to be a selective dependency in kidney cancer. Among kidney cancers, BCL-XL inhibition is most active in those with a mesenchymal gene signature, which portends a poor prognosis and response to current therapies.See related article by Grubb et al., p. 4689
Cinema at a Standstill
Authors: McDonough Tom 
Published: August 2022

Abstract
“Cinema at a Standstill” examines the theory and practice of film within the Situationist International, circa 1968. Questioning Guy Debord's refusal to document the group's participation in the abortive revolution of May-June ‘68, the essay explores the Situationists' ambivalence to the image as mnemonic device. Their refusal of film's iconicity did not, however, mean a complete refusal of its logic: The austere, text-based posters produced by the SI during the uprising are here read as a species of revolutionary intertitle for a film running in real time along the streets. Sharing the aniconic quality found at the same moment in the work of Daniel Buren and Jean-Luc Godard, this Situationist imageless cinema is read through the dialectic of repetition and stoppage first developed by Giorgio Agamben.
Angelica Mesiti's World Citizens
Authors: Rodowick D. N. 
Published: August 2022

Abstract
In this essay, I review a 2019 exhibition at the Palais de Tokyo entitled When Saying Is Doing, which featured work by Angelica Mesiti, a contemporary Australian artist who works on questions of performance, immigration, and non-verbal communication in multi-screen moving image installations. On the contemporary global stage, if we do not share the same linguistic community or communities, how is human interrelatedness expressed through other forms of ordinary language, where “language” is now considered not as speech but rather as human expressiveness in its most diverse and complex manifestations? What happens when shared language is neither “speech” nor conversation in the linguistic sense? Needed here is a newly imagined vision of the communicability of human community that I refer to as “neighboring.” Putting Mesiti's work in productive dialogue with Stanley Cavell and other critics, I examine how skeptical problems of isolation, privacy, and unknownness are potentially addressed and responded to in contemporary art.
Chloroquine Attenuates Oxidative Stress in Gentamicin-Induced Nephrotoxicity in Rats
Authors: Brkić Branislava Medić , Rovčanin Branislav , Stojanović Marko , Srebro Dragana , Vučković Sonja , Savić Vujović Katarina 
Published: August 2022

The wider application of gentamicin is limited by potential adverse effects (nephrotoxicity and ototoxicity). The goal of our study was to investigate the effects of chloroquine on biochemical and oxidative stress parameters in gentamicin-induced nephrotoxicity in rats. Animals were randomly divided into 1 of 5 groups. First was Sham group (0.9% NaCl) (n = 8); second group received gentamicin (n = 8); while third (n = 8), fourth (n = 8) and fifth group (n = 8) received gentamicin and chloroquine in a dose of 0.3, 1 and 3 mg/kg, respectively. The urea and creatinine levels were significantly lower in chloroquine treated groups in doses of 0.3 mg/kg and 1 mg/kg ( P < 0.001). Total oxidant status and the oxidative stress index showed significantly lower values in all chloroquine treated groups ( P < 0.001; P < 0.005). Malondialdehyde was lower in chloroquine treatment in doses of 0.3 mg/kg ( P < 0.005) and 3 mg/kg ( P < 0.05). Chloroquine treatment markedly reduced the level of superoxide dismutase in doses of 1 mg/kg ( P < 0.01) and 3 mg/kg ( P < 0.05). Our study showed that chloroquine attenuates gentamicin-induced nephrotoxicity in rats regarding biochemical and oxidative stress parameters.
Donor natural killer cells trigger production of β-2-microglobulin to enhance post–bone marrow transplant immunity
Authors: Ruggeri Loredana , Urbani Elena , Chiasserini Davide , Susta Federica , Orvietani Pier Luigi , Burchielli Emanuela , Ciardelli Sara , Sola Rosaria , Bruscoli Stefano , Cardinale Antonella , Pierini Antonio , Piersma Sander R. , Pasquino Stefano , Locatelli Franco , Ramarli Dunia , Velardi Enrico , Binaglia Luciano , Jimenez Connie R. , Holländer Georg A. , Velardi Andrea 
Published: August 2022

Abstract
Allogeneic hematopoietic transplantation is a powerful treatment for hematologic malignancies. Posttransplant immune incompetence exposes patients to disease relapse and infections. We previously demonstrated that donor alloreactive natural killer (NK) cells ablate recipient hematopoietic targets, including leukemia. Here, in murine models, we show that infusion of donor alloreactive NK cells triggers recipient dendritic cells (DCs) to synthesize β-2-microglobulin (B2M) that elicits the release of c-KIT ligand and interleukin-7 that greatly accelerate posttransplant immune reconstitution. An identical chain of events was reproduced by infusing supernatants of alloreactive NK/DC cocultures. Similarly, human alloreactive NK cells triggered human DCs to synthesize B2M that induced interleukin-7 production by thymic epithelial cells and thereby supported thymocyte cellularity in vitro. Chromatography fractionation of murine and human alloreactive NK/DC coculture supernatants identified a protein with molecular weight and isoelectric point of B2M, and mass spectrometry identified amino acid sequences specific of B2M. Anti-B2M antibody depletion of NK/DC coculture supernatants abrogated their immune-rebuilding effect. B2M knock-out mice were unable to undergo accelerated immune reconstitution, but infusion of (wild-type) NK/DC coculture supernatants restored their ability to undergo accelerated immune reconstitution. Similarly, silencing the B2M gene in human DCs, before coculture with alloreactive NK cells, prevented the increase in thymocyte cellularity in vitro. Finally, human recombinant B2M increased thymocyte cellularity in a thymic epithelial cells/thymocyte culture system. Our studies uncover a novel therapeutic principle for treating posttransplant immune incompetence and suggest that, upon its translation to the clinic, patients may benefit from adoptive transfer of large numbers of cytokine-activated, ex vivo–expanded donor alloreactive NK cells.
Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation
Authors: Vallet Nicolas , Le Grand Sophie , Bondeelle Louise , Hoareau Bénédicte , Corneau Aurélien , Bouteiller Delphine , Tournier Simon , Derivry Lucille , Bohineust Armelle , Tourret Marie , Gibert Delphine , Mayeur Ethan , Itzykson Raphael , Pacchiardi Kim , Ingram Brian , Cassonnet Stéphane , Lepage Patricia , Peffault de Latour Régis , Socié Gérard , Bergeron Anne , Michonneau David 
Published: August 2022

Abstract
Administration of azithromycin after allogeneic hematopoietic stem cell transplantation for hematologic malignancies has been associated with relapse in a randomized phase 3 controlled clinical trial. Studying 240 samples from patients randomized in this trial is a unique opportunity to better understand the mechanisms underlying relapse, the first cause of mortality after transplantation. We used multi-omics on patients’ samples to decipher immune alterations associated with azithromycin intake and post-transplantation relapsed malignancies. Azithromycin was associated with a network of altered energy metabolism pathways and immune subsets, including T cells biased toward immunomodulatory and exhausted profiles. In vitro, azithromycin exposure inhibited T-cell cytotoxicity against tumor cells and impaired T-cell metabolism through glycolysis inhibition, down-regulation of mitochondrial genes, and up-regulation of immunomodulatory genes, notably SOCS1. These results highlight that azithromycin directly affects immune cells that favor relapse, which raises caution about long-term use of azithromycin treatment in patients at high risk of malignancies. The ALLOZITHRO trial was registered at www.clinicaltrials.gov as #NCT01959100.
Dietary methionine starvation impairs acute myeloid leukemia progression
Authors: Cunningham Alan , Erdem Ayşegül , Alshamleh Islam , Geugien Marjan , Pruis Maurien , Pereira-Martins Diego Antonio , van den Heuvel Fiona A. J. , Wierenga Albertus T. J. , ten Berge Hilde , Dennebos Robin , van den Boom Vincent , Hogeling Shanna M. , Weinhäuser Isabel , Knops Ruth , de Blaauw Pim , Heiner-Fokkema M. Rebecca , Woolthuis Carolien , Günther Ulrich L. , Rego Eduardo M. , Martens Joost H. A. , Jansen Joop H. , Schwalbe Harald , Huls Gerwin , Schuringa Jan Jacob 
Published: August 2022

Abstract
Targeting altered tumor cell metabolism might provide an attractive opportunity for patients with acute myeloid leukemia (AML). An amino acid dropout screen on primary leukemic stem cells and progenitor populations revealed a number of amino acid dependencies, of which methionine was one of the strongest. By using various metabolite rescue experiments, nuclear magnetic resonance−based metabolite quantifications and 13C-tracing, polysomal profiling, and chromatin immunoprecipitation sequencing, we identified that methionine is used predominantly for protein translation and to provide methyl groups to histones via S-adenosylmethionine for epigenetic marking. H3K36me3 was consistently the most heavily impacted mark following loss of methionine. Methionine depletion also reduced total RNA levels, enhanced apoptosis, and induced a cell cycle block. Reactive oxygen species levels were not increased following methionine depletion, and replacement of methionine with glutathione or N-acetylcysteine could not rescue phenotypes, excluding a role for methionine in controlling redox balance control in AML. Although considered to be an essential amino acid, methionine can be recycled from homocysteine. We uncovered that this is primarily performed by the enzyme methionine synthase and only when methionine availability becomes limiting. In vivo, dietary methionine starvation was not only tolerated by mice, but also significantly delayed both cell line and patient-derived AML progression. Finally, we show that inhibition of the H3K36-specific methyltransferase SETD2 phenocopies much of the cytotoxic effects of methionine depletion, providing a more targeted therapeutic approach. In conclusion, we show that methionine depletion is a vulnerability in AML that can be exploited therapeutically, and we provide mechanistic insight into how cells metabolize and recycle methionine.
Low serum insulin-like growth factor-1 in patients with erectile dysfunction
Authors: Otunctemur Alper , Ozbek Emin , Sahin Suleyman , Ozcan Levent , Dursun Murat , Polat Emre Can , Cekmen Mustafa , Ozsoy Ozgur Doga , Erkoc Mustafa , Danis Eyup , Bozkurt Muammer 
Published: August 2022

Abstract
Objective
Endothelial dysfunction and microvascular damage play a crurical role in the pathogenesis of erectile dysfunction (ED). Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. IGF-1 is an important mediator of cell growth, differentiation and transformation in various tissues. The purpose of the current study was to determine the association between IGF-1 levels and ED.

Materials and methods
All men were evaluated for ED and divided into two groups: 80 patients suffering from ED for > 1 year and 80 subjects without ED were enrolled as a control group in this study. Diagnosis of ED was based on the International Index of Erectile Function Score-5. IGF-1 levels were measured in serum by an automated chemiluminescence immunoassay. The relationship between IGF-1 levels and ED scores in patients was statistically evaluated.

Results
The mean age of patients in ED group was 60.4 ± 11.3 years and 55.4 ± 9.6 in control group. The plasma IGF-1 levels were significantly lower in ED than in control group (96.5 ± 38.3 and 132.5 ± 53.3 ng/ mL, respectively, P < 0.001). The IGF-1 levels were positively correlated with ED score (r = 0.623, P < 0.01).

Conclusion
In this study serum IGF-1 levels were found to be associated with endothelial dysfunction that predicts ED. Serum IGF-1 level appears to be a specific predictor of ED, and it might be used in early prediction of ED in male population.