bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are the recommendations of paediatricians about complementary feeding aligned with current guidelines in Uruguay?
Authors: Vidal Leticia , Bove Isabel , Brunet Gerónimo , Girona Alejandra , Alcaire Florencia , Antúnez Lucía , Ares Gastón 
Published: January 2021

AbstractObjective:To explore Uruguayan paediatricians’ personal recommendations about complementary feeding and to assess if they are aligned with current guidelines and scientific evidence.Design:A questionnaire composed of open-ended questions was used to explore foods recommended to start complementary feeding, foods regarded as the most important during the first meals, recommendations for delayed introduction of foods and foods that should be avoided. Reasons underlying the recommendations were also explored.Setting:Montevideo, the capital city of Uruguay (Latin America).Participants:A total of 212 paediatricians were recruited during a National Pediatrics Conference, organised by the Uruguayan Society of Pediatrics.Results:The recommendations about complementary feeding provided by paediatricians to parents and caregivers in Uruguay seemed not to be fully aligned with the guidelines provided by the Ministry of Health. Paediatricians recommend a rigid food introduction sequence, characterised by the early introduction of soft pureed vegetables and fruits, followed by meat and the delayed introduction of allergenic foods. Food diversity and the concept of ultra-processed were not frequently identified in the responses.Conclusions:Results stress the importance of developing educational and communication approaches targeted at paediatricians to contribute to the uptake of updated recommendations regarding complementary feeding.
Advice to use infant formula and free samples are common in both urban and rural areas in China: a cross-sectional survey
Authors: Li Jia , Nguyen Tuan T , Duan Yifan , Mathisen Roger , Yang Zhenyu 
Published: January 2021

AbstractObjective:To examine the association between the place of residence and receiving free samples and advice to feed the baby with infant formula.Design:A cross-sectional study.Setting:The current study covered twelve counties/districts in China.Participants:5112 mothers with infants aged 0–5·9 months.Results:About 16 % of the mothers received free samples of infant formula. During pregnancy, this likelihood was higher among mothers in small and medium cities (OR: 1·96; 95 % CI 1·14, 3·38) and non-poor rural counties (OR: 4·65; 95 % CI 1·65, 13·14) compared with mothers in big cities. During the hospital stay, it was lower in big cities. After discharge, it was lower in poor rural counties (OR: 0·14; 95 % CI 0·05, 0·41). About 26 % of the mothers were advised to feed their infants with infant formula. The likelihood of receiving advice to feed the baby with infant formula from hospitals was lower in non-poor (OR: 0·37; 95 % CI 0·21, 0·66) and poor rural counties (OR: 0·35; 95 % CI 0·13, 0·91) than in big cities. Mothers in non-poor rural counties were less likely to receive advice from traditional mass media (OR: 0·17; 95 % CI 0·06, 0·48), while mothers in small and medium cities were more likely to receive advice from modern mass media (OR: 1·84; 95 % CI 1·20, 2·80) compared with mothers in big cities.Conclusions:The promotion strategy of infant formula varies from different places of residence in China. The study suggests the need to strengthen enforcement of relevant regulations, especially within health facilities and through modern mass media.
RECURSION FOR MASUR-VEECH VOLUMES OF MODULI SPACES OF QUADRATIC DIFFERENTIALS
Authors: Kazarian Maxim 
Published: January 2021

AbstractWe derive a quadratic recursion relation for the linear Hodge integrals of the form

$\langle \tau _{2}^{n}\lambda _{k}\rangle $
. These numbers are used in a formula for Masur-Veech volumes of moduli spaces of quadratic differentials discovered by Chen, Möller and Sauvaget. Therefore, our recursion provides an efficient way of computing these volumes.
VARIATION ON A THEME BY KISELEV AND NAZAROV: HÖLDER ESTIMATES FOR NONLOCAL TRANSPORT-DIFFUSION, ALONG A NON-DIVERGENCE-FREE BMO FIELD
Authors: Vasilyev Ioann , Vigneron François 
Published: January 2021

AbstractWe prove uniform Hölder regularity estimates for a transport-diffusion equation with a fractional diffusion operator and a general advection field in of bounded mean oscillation, as long as the order of the diffusion dominates the transport term at small scales; our only requirement is the smallness of the negative part of the divergence in some critical Lebesgue space. In comparison to a celebrated result by Silvestre, our advection field does not need to be bounded. A similar result can be obtained in the supercritical case if the advection field is Hölder continuous. Our proof is inspired by Kiselev and Nazarov and is based on the dual evolution technique. The idea is to propagate an atom property (i.e., localisation and integrability in Lebesgue spaces) under the dual conservation law, when it is coupled with the fractional diffusion operator.
A call for greater conceptual clarity in the field of mental health and psychosocial support in humanitarian settings
Authors: Miller K. E. , Jordans M. J. D. , Tol W. A. , Galappatti A. 
Published: January 2021

AbstractAimsWhen the Interagency Standing Committee (IASC) adopted the composite term mental health and psychosocial support (MHPSS) and published its guidelines for MHPSS in emergency settings in 2007, it aimed to build consensus and strengthen coordination among relevant humanitarian actors. The term MHPSS offered an inclusive tent by welcoming the different terminologies, explanatory models and intervention methods of diverse actors across several humanitarian sectors (e.g., health, protection, education, nutrition). Since its introduction, the term has become well-established within the global humanitarian system. However, it has also been critiqued for papering over substantive differences in the intervention priorities and conceptual frameworks that inform the wide range of interventions described as MHPSS. Our aims are to clarify those conceptual frameworks, to argue for their essential complementarity and to illustrate the perils of failing to adequately consider the causal models and theories of change that underlie our interventions.MethodsWe describe the historical backdrop against which the term MHPSS and the IASC guidelines were developed, as well as their impact on improving relations and coordination among different aid sectors. We consider the conceptual fuzziness in the field of MHPSS and the lack of clear articulation of the different conceptual frameworks that guide interventions. We describe the explanatory models and intervention approaches of two primary frameworks within MHPSS, which we labelclinicalandsocial-environmental. Using the examples of intimate partner violence and compromised parenting in humanitarian settings, we illustrate the complementarity of these two frameworks, as well as the challenges that can arise when either framework is inappropriately applied.ResultsClinical interventions prioritise the role of intrapersonal variables, biological and/or psychological, as mediators of change in the treatment of distress. Social-environmental interventions emphasise the role of social determinants of distress and target factors in the social and material environments in order to lower distress and increase resilience in the face of adversity. Both approaches play a critical role in humanitarian settings; however, the rationale for adopting one or the other approach is commonly insufficiently articulated and should be based on a thorough assessment of causal processes at multiple levels of the social ecology.ConclusionsGreater attention to the ‘why’ of our intervention choices and more explicit articulation of the causal models and theories of change that underlie those decisions (i.e., the ‘how’), may strengthen intervention effects and minimise the risk of applying the inappropriate framework and actions to a particular problem.
C1GALT1 high expression is associated with poor survival of patients with pancreatic ductal adenocarcinoma and promotes cell invasiveness through integrin αv
Authors: Kuo Ting-Chun , Wu Ming-Hsun , Yang Shih-Hung , Chen Syue-Ting , Hsu Tzu-Wen , Jhuang Jie-Yang , Liao Ying-Yu , Tien Yu-Wen , Huang Min-Chuan 
Published: January 2021

AbstractPancreatic adenocarcinoma (PDAC) is a leading cause of cancer-related death. Altered glycosylation contributes to tumor progression and chemoresistance in many cancers. C1GALT1 is the key enzyme controlling the elongation of GalNAc-type O-glycosylation. Here we showed that C1GALT1 was overexpressed in 85% (107/126) of PDAC tumors compared with adjacent non-tumor tissues. High expression of C1GALT1 was associated with poor disease-free and overall survival (n = 99). C1GALT1 knockdown using siRNA suppressed cell viability, migration, and invasion as well as increased gemcitabine sensitivity in PDAC cells. In contrast, C1GALT1 overexpression enhanced cell migration and invasion. In subcutaneous and pancreatic orthotopic injection models, C1GALT1 knockdown decreased tumor growth and metastasis of PDAC cells in NOD/SCID mice. Mechanistically, C1GALT1 knockdown dramatically suppressed cell-extracellular matrix (ECM) adhesion, which was associated with decreased phosphorylation of FAK at Y397/Y925 and changes in O-glycans on integrins including the β1, αv, and α5 subunits. Using functional blocking antibodies, we identified integrin αv as a critical factor in C1GALT1-mediated invasiveness of PDAC cells. In conclusion, this study not only reveals that C1GALT1 could be a potential therapeutic target for PDAC but also provides novel insights into the role of O-glycosylation in the α subunits of integrins.
A feed-forward loop between SorLA and HER3 determines heregulin response and neratinib resistance
Authors: Al-Akhrass Hussein , Conway James R. W. , Poulsen Annemarie Svane Aavild , Paatero Ilkka , Kaivola Jasmin , Padzik Artur , Andersen Olav M. , Ivaska Johanna 
Published: January 2021

AbstractCurrent evidence indicates that resistance to the tyrosine kinase-type cell surface receptor (HER2)-targeted therapies is frequently associated with HER3 and active signaling via HER2-HER3 dimers, particularly in the context of breast cancer. Thus, understanding the response to HER2-HER3 signaling and the regulation of the dimer is essential to decipher therapy relapse mechanisms. Here, we investigate a bidirectional relationship between HER2-HER3 signaling and a type-1 transmembrane sorting receptor, sortilin-related receptor (SorLA; SORL1). We demonstrate that heregulin-mediated signaling supports SorLA transcription downstream of the mitogen-activated protein kinase pathway. In addition, we demonstrate that SorLA interacts directly with HER3, forming a trimeric complex with HER2 and HER3 to attenuate lysosomal degradation of the dimer in a Ras-related protein Rab4-dependent manner. In line with a role for SorLA in supporting the stability of the HER2 and HER3 receptors, loss of SorLA compromised heregulin-induced cell proliferation and sensitized metastatic anti-HER2 therapy-resistant breast cancer cells to neratinib in cancer spheroids in vitro and in vivo in a zebrafish brain xenograft model.
Comprehensive characterisation of intronic mis-splicing mutations in human cancers
Authors: Jung Hyunchul , Lee Kang Seon , Choi Jung Kyoon 
Published: January 2021

AbstractPrevious studies studying mis-splicing mutations were based on exome data and thus our current knowledge is largely limited to exons and the canonical splice sites. To comprehensively characterise intronic mis-splicing mutations, we analysed 1134 pan-cancer whole genomes and transcriptomes together with 3022 normal control samples. The ratio-based splicing analysis resulted in 678 somatic intronic mutations, with 46% residing in deep introns. Among the 309 deep intronic single nucleotide variants, 245 altered core splicing codes, with 38% activating cryptic splice sites, 12% activating cryptic polypyrimidine tracts, and 36% and 12% disrupting authentic polypyrimidine tracts and branchpoints, respectively. All the intronic cryptic splice sites were created at pre-existing GT/AG dinucleotides or by GC-to-GT conversion. Notably, 85 deep intronic mutations indicated gain of splicing enhancers or loss of splicing silencers. We found that 64 tumour suppressors were affected by intronic mutations and blood cancers showed higher proportion of deep intronic mutations. In particular, a telomere maintenance gene, POT1, was recurrently mis-spliced by deep intronic mutations in blood cancers. We validated a pseudoexon activation involving a splicing silencer in POT1 by CRISPR/Cas9. Our results shed light on previously unappreciated mechanisms by which noncoding mutations acting on splicing codes in deep introns contribute to tumourigenesis.
Inhibition of PFKFB3 induces cell death and synergistically enhances chemosensitivity in endometrial cancer
Authors: Xiao Yinan , Jin Ling , Deng Chaolin , Guan Ye , Kalogera Eleftheria , Ray Upasana , Thirusangu Prabhu , Staub Julie , Sarkar Bhattacharya Sayantani , Xu Haotian , Fang Xiaoling , Shridhar Viji 
Published: January 2021

AbstractThe advanced or recurrent endometrial cancer (EC) has a poor prognosis because of chemoresistance. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a glycolytic enzyme, is overexpressed in a variety of human cancers and plays important roles in promoting tumor cell growth. Here, we showed that high expression of PFKFB3 in EC cell lines is associated with chemoresistance. Pharmacological inhibition of PFKFB3 with PFK158 and or genetic downregulation of PFKFB3 dramatically suppressed cell proliferation and enhanced the sensitivity of EC cells to carboplatin (CBPt) and cisplatin (Cis). Moreover, PFKFB3 inhibition resulted in reduced glucose uptake, ATP production, and lactate release. Notably, we found that PFK158 with CBPt or Cis exerted strong synergistic antitumor activity in chemoresistant EC cell lines, HEC-1B and ARK-2 cells. We also found that the combination of PFK158 and CBPt/Cis induced apoptosis- and autophagy-mediated cell death through inhibition of the Akt/mTOR signaling pathway. Mechanistically, we found that PFK158 downregulated the CBPt/Cis-induced upregulation of RAD51 expression and enhanced CBPt/Cis-induced DNA damage as demonstrated by an increase in γ-H2AX levels in HEC-1B and ARK-2 cells, potentially revealing a means to enhance PFK158-induced chemosensitivity. More importantly, PFK158 treatment, either as monotherapy or in combination with CBPt, led to a marked reduction in tumor growth in two chemoresistant EC mouse xenograft models. These data suggest that PFKFB3 inhibition alone or in combination with standard chemotherapy may be used as a novel therapeutic strategy for improved therapeutic efficacy and outcomes of advanced and recurrent EC patients.
Loss of COPZ1 induces NCOA4 mediated autophagy and ferroptosis in glioblastoma cell lines
Authors: Zhang Yulin , Kong Yang , Ma Yuan , Ni Shilei , Wikerholmen Tobias , Xi Kaiyan , Zhao Feihu , Zhao Zhimin , Wang Junpeng , Huang Bin , Chen Anjing , Yao Zhong , Han Mingzhi , Feng Zichao , Hu Yaotian , Thorsen Frits , Wang Jian , Li Xingang 
Published: January 2021

AbstractDysregulated iron metabolism is a hallmark of many cancers, including glioblastoma (GBM). However, its role in tumor progression remains unclear. Herein, we identified coatomer protein complex subunit zeta 1 (COPZ1) as a therapeutic target candidate which significantly dysregulated iron metabolism in GBM cells. Overexpression of COPZ1 was associated with increasing tumor grade and poor prognosis in glioma patients based on analysis of expression data from the publicly available database The Cancer Genome Atlas (P < 0.001). Protein levels of COPZ1 were significantly increased in GBM compared to non-neoplastic brain tissue samples in immunohistochemistry and western blot analysis. SiRNA knockdown of COPZ1 suppressed proliferation of U87MG, U251 and P3#GBM in vitro. Stable expression of a COPZ1 shRNA construct in U87MG inhibited tumor growth in vivo by ~60% relative to controls at day 21 after implantation (P < 0.001). Kaplan–Meier analysis of the survival data demonstrated that the overall survival of tumor bearing animals increased from 20.8 days (control) to 27.8 days (knockdown, P < 0.05). COPZ1 knockdown also led to the increase in nuclear receptor coactivator 4 (NCOA4), resulting in the degradation of ferritin, and a subsequent increase in the intracellular levels of ferrous iron and ultimately ferroptosis. These data demonstrate that COPZ1 is a critical mediator in iron metabolism. The COPZ1/NCOA4/FTH1 axis is therefore a novel therapeutic target for the treatment of human GBM.
Targeting STAT3 by a small molecule suppresses pancreatic cancer progression
Authors: Chen Huang , Bian Aiwu , Yang Lian-fang , Yin Xuan , Wang Jie , Ti Chaowen , Miao Ying , Peng Shihong , Xu Shifen , Liu Mingyao , Qiu Wen-Wei , Yi Zhengfang 
Published: January 2021

AbstractPancreatic cancer is lethal in over 90% of cases since it is resistant to current therapeutic strategies. The key role of STAT3 in promoting pancreatic cancer progression has been proven, but effective interventions that suppress STAT3 activities are limited. The development of novel anticancer agents that directly target STAT3 may have potential clinical benefits for pancreatic cancer treatment. Here, we report a new small-molecule inhibitor (N4) with potent antitumor bioactivity, which inhibits multiple oncogenic processes in pancreatic cancer. N4 blocked STAT3 and phospho-tyrosine (pTyr) peptide interactions in fluorescence polarization (FP) assay, specifically abolished phosphor-STAT3 (Tyr705), and suppressed expression of STAT3 downstream genes. The mechanism involved the direct binding of N4 to the STAT3 SH2 domain, thereby, the STAT3 dimerization, STAT3-EGFR, and STAT3-NF-κB cross-talk were efficiently inhibited. In animal models of pancreatic cancer, N4 was well tolerated, suppressed tumor growth and metastasis, and significantly prolonged survival of tumor-bearing mice. Our results offer a preclinical proof of concept for N4 as a candidate therapeutic compound for pancreatic cancer.
YAP/TAZ inhibition reduces metastatic potential of Ewing sarcoma cells
Authors: Bierbaumer Lisa , Katschnig Anna M. , Radic-Sarikas Branka , Kauer Maximilian O. , Petro Jeffrey A. , Högler Sandra , Gurnhofer Elisabeth , Pedot Gloria , Schäfer Beat W. , Schwentner Raphaela , Mühlbacher Karin , Kromp Florian , Aryee Dave N. T. , Kenner Lukas , Uren Aykut , Kovar Heinrich 
Published: January 2021

AbstractEwing sarcoma (EwS) is a highly metastatic bone cancer characterized by the ETS fusion oncoprotein EWS-FLI1. EwS cells are phenotypically highly plastic and switch between functionally distinct cell states dependent on EWS-FLI1 fluctuations. Whereas EWS-FLI1high cells proliferate, EWS-FLI1low cells are migratory and invasive. Recently, we reported activation of MRTFB and TEAD, effectors of RhoA and Hippo signalling, upon low EWS-FLI1, orchestrating key steps of the EwS migratory gene expression program. TEAD and its co-activators YAP and TAZ are commonly overexpressed in cancer, providing attractive therapeutic targets. We find TAZ levels to increase in the migratory EWS-FLI1low state and to associate with adverse prognosis in EwS patients. We tested the effects of the potent YAP/TAZ/TEAD complex inhibitor verteporfin on EwS cell migration in vitro and on metastasis in vivo. Verteporfin suppressed expression of EWS-FLI1 regulated cytoskeletal genes involved in actin signalling to the extracellular matrix, effectively blocked F-actin and focal-adhesion assembly and inhibited EwS cell migration at submicromolar concentrations. In a mouse EwS xenograft model, verteporfin treatment reduced relapses at the surgical site and delayed lung metastasis. These data suggest that YAP/TAZ pathway inhibition may prevent EwS cell dissemination and metastasis, justifying further preclinical development of YAP/TAZ inhibitors for EwS treatment.
G protein-coupled receptors: structure- and function-based drug discovery
Authors: Yang Dehua , Zhou Qingtong , Labroska Viktorija , Qin Shanshan , Darbalaei Sanaz , Wu Yiran , Yuliantie Elita , Xie Linshan , Tao Houchao , Cheng Jianjun , Liu Qing , Zhao Suwen , Shui Wenqing , Jiang Yi , Wang Ming-Wei 
Published: January 2021

AbstractAs one of the most successful therapeutic target families, G protein-coupled receptors (GPCRs) have experienced a transformation from random ligand screening to knowledge-driven drug design. We are eye-witnessing tremendous progresses made recently in the understanding of their structure–function relationships that facilitated drug development at an unprecedented pace. This article intends to provide a comprehensive overview of this important field to a broader readership that shares some common interests in drug discovery.
Potentiation of NETs release is novel characteristic of TREM-1 activation and the pharmacological inhibition of TREM-1 could prevent from the deleterious consequences of NETs release in sepsis
Authors: Boufenzer Amir , Carrasco Kevin , Jolly Lucie , Brustolin Benjamin , Di-Pillo Elisa , Derive Marc , Gibot Sébastien 
Published: January 2021

AbstractDuring sepsis, neutrophil activation induces endothelial cell (EC) dysfunction partly through neutrophil extracellular trap (NET) release. The triggering receptor expressed on myeloid cell-1 (TREM-1) is an orphan immune receptor that amplifies the inflammatory response mediated by Toll-like receptor-4 (TLR4) engagement. Although the key role of TLR4 signaling in NETosis is known, the role of TREM-1 in this process has not yet been investigated. Here, we report that TREM-1 potentiates NET release by human and murine neutrophils and is a component of the NET structure. In contrast, pharmacologic inhibition or genetic ablation of TREM-1 decreased NETosis in vitro and during experimental septic shock in vivo. Moreover, isolated NETs were able to activate ECs and impair vascular reactivity, and these deleterious effects were dampened by TREM-1 inhibition. TREM-1 may, therefore, constitute a new therapeutic target to prevent NETosis and associated endothelial dysfunction.
Artificial synapses with a sponge-like double-layer porous oxide memristor
Authors: Gao Qin , Huang Anping , Zhang Jing , Ji Yuhang , Zhang Jingjing , Chen Xueliang , Geng Xueli , Hu Qi , Wang Mei , Xiao Zhisong , Chu Paul K. 
Published: January 2021

AbstractClosely following the rapid development of artificial intelligence, studies of the human brain and neurobiology are focusing on the biological mechanisms of neurons and synapses. Herein, a memory system employing a nanoporous double-layer structure for simulation of synaptic functions is described. The sponge-like double-layer porous (SLDLP) oxide stack of Pt/porous LiCoO2/porous SiO2/Si is designed as presynaptic and postsynaptic membranes. This bionic structure exhibits high ON–OFF ratios up to 108 during the stability test, and data can be maintained for 105 s despite a small read voltage of 0.5 V. Typical synaptic functions, such as nonlinear transmission characteristics, spike-timing-dependent plasticity, and learning-experience behaviors, are achieved simultaneously with this device. Based on the hydrodynamic transport mechanism of water molecules in porous sponges and the principle of water storage, the synaptic behavior of the device is discussed. The SLDLP oxide memristor is very promising due to its excellent synaptic performance and potential in neuromorphic computing.