bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of pannexin 1-regulated genes, interactome, and pathways in rhabdomyosarcoma and its tumor inhibitory interaction with AHNAK
Authors: Xiang Xiao , Langlois Stéphanie , St-Pierre Marie-Eve , Blinder Anna , Charron Philippe , Graber Tyson E. , Fowler Stephanie L. , Baird Stephen D. , Bennett Steffany A. L. , Alain Tommy , Cowan Kyle N. 
Published: February 2021

AbstractRhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, is an aggressive cancer with a poor prognosis. Despite current management, the 5-year survival rate for patients with metastatic RMS is ∼30%; underscoring the need to develop better treatment strategies. We have recently reported that pannexin 1 (PANX1) levels are downregulated in RMS and that restoring its expression inhibits RMS progression. Here, we have surveyed and characterized the molecular changes induced by PANX1 re-expression in RMS. We cataloged transcriptomic changes in this context by RNA sequencing. At the protein level, we unveiled PANX1 interactors using BioID, complemented by co-immunoprecipitation coupled to high-performance liquid chromatography/electrospray ionization tandem mass spectrometry performed in PANX1-enriched fractions. Using these data, we generated searchable public databases for the PANX1 interactome and changes to the RMS transcriptome occurring when PANX1 expression is restored. STRING network analyses revealed a PANX1 interactome involving plasma membrane and cytoskeleton-associated proteins including the previously undescribed interactor AHNAK. Indeed, AHNAK knockdown abrogated the PANX1-mediated reduction in RMS cell viability and migration. Using these unbiased approaches, we bring insight to the mechanisms by which PANX1 inhibits RMS progression, identifying the cell migration protein AHNAK as a key modifier of PANX1-mediated changes in RMS malignant properties.
MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma
Authors: Ke Xin-Yu , Chen Ye , Tham Valarie Yu-Yan , Lin Ruby Yu-Tong , Dakle Pushkar , Nacro Kassoum , Puhaindran Mark Edward , Houghton Peter , Pang Angela , Lee Victor Kwanmin , Ding Ling-Wen , Gery Sigal , Hill Jeffrey , Chen Leilei , Xu Liang , Koeffler H. Phillip 
Published: February 2021

AbstractSoft tissue sarcoma (STS) is a heterogeneous disease that arises from connective tissues. Clinical outcome of patients with advanced tumors especially de-differentiated liposarcoma and uterine leiomyosarcoma remains unsatisfactory, despite intensive treatment regimens including maximal surgical resection, radiation, and chemotherapy. MAP kinase-interacting serine/threonine-protein kinase 1 and 2 (MNK1/2) have been shown to contribute to oncogenic translation via phosphorylation of eukaryotic translation initiation factor 4E (eIF4E). However, little is known about the role of MNK1/2 and their downstream targets in STS. In this study, we show that depletion of either MNK1 or MNK2 suppresses cell viability, anchorage-independent growth, and tumorigenicity of STS cells. We also identify a compelling antiproliferative efficacy of a novel, selective MNK inhibitor ETC-168. Cellular responsiveness of STS cells to ETC-168 correlates positively with that of phosphorylated ribosomal protein S6 (RPS6). Mirroring MNK1/2 silencing, ETC-168 treatment strongly blocks eIF4E phosphorylation and represses expression of sarcoma-driving onco-proteins including E2F1, FOXM1, and WEE1. Moreover, combination of ETC-168 and MCL1 inhibitor S63845 exerts a synergistic antiproliferative activity against STS cells. In summary, our study reveals crucial roles of MNK1/2 and their downstream targets in STS tumorigenesis. Our data encourage further clinical translation of MNK inhibitors for STS treatment.
Classification of node-positive melanomas into prognostic subgroups using keratin, immune, and melanogenesis expression patterns
Authors: Netanely Dvir , Leibou Stav , Parikh Roma , Stern Neta , Vaknine Hananya , Brenner Ronen , Amar Sarah , Factor Rivi Haiat , Perluk Tomer , Frand Jacob , Nizri Eran , Hershkovitz Dov , Zemser-Werner Valentina , Levy Carmit , Shamir Ron 
Published: February 2021

AbstractCutaneous melanoma tumors are heterogeneous and show diverse responses to treatment. Identification of robust molecular biomarkers for classifying melanoma tumors into clinically distinct and homogenous subtypes is crucial for improving the diagnosis and treatment of the disease. In this study, we present a classification of melanoma tumors into four subtypes with different survival profiles based on three distinct gene expression signatures: keratin, immune, and melanogenesis. The melanogenesis expression pattern includes several genes that are characteristic of the melanosome organelle and correlates with worse survival, suggesting the involvement of melanosomes in melanoma aggression. We experimentally validated the secretion of melanosomes into surrounding tissues by melanoma tumors, which potentially affects the lethality of metastasis. We propose a simple molecular decision tree classifier for predicting a tumor’s subtype based on representative genes from the three identified signatures. Key predictor genes were experimentally validated on melanoma samples taken from patients with varying survival outcomes. Our three-pattern approach for classifying melanoma tumors can contribute to advancing the understanding of melanoma variability and promote accurate diagnosis, prognostication, and treatment.
RBMX suppresses tumorigenicity and progression of bladder cancer by interacting with the hnRNP A1 protein to regulate PKM alternative splicing
Authors: Yan Qiuxia , Zeng Peng , Zhou Xiuqin , Zhao Xiaoying , Chen Runqiang , Qiao Jing , Feng Ling , Zhu Zhenjie , Zhang Guozhi , Chen Cairong 
Published: February 2021

AbstractThe prognosis for patients with metastatic bladder cancer (BCa) is poor, and it is not improved by current treatments. RNA-binding motif protein X-linked (RBMX) are involved in the regulation of the malignant progression of various tumors. However, the role of RBMX in BCa tumorigenicity and progression remains unclear. In this study, we found that RBMX was significantly downregulated in BCa tissues, especially in muscle-invasive BCa tissues. RBMX expression was negatively correlated with tumor stage, histological grade and poor patient prognosis. Functional assays demonstrated that RBMX inhibited BCa cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth and metastasis in vivo. Mechanistic investigations revealed that hnRNP A1 was an RBMX-binding protein. RBMX competitively inhibited the combination of the RGG motif in hnRNP A1 and the sequences flanking PKM exon 9, leading to the formation of lower PKM2 and higher PKM1 levels, which attenuated the tumorigenicity and progression of BCa. Moreover, RBMX inhibited aerobic glycolysis through hnRNP A1-dependent PKM alternative splicing and counteracted the PKM2 overexpression-induced aggressive phenotype of the BCa cells. In conclusion, our findings indicate that RBMX suppresses BCa tumorigenicity and progression via an hnRNP A1-mediated PKM alternative splicing mechanism. RBMX may serve as a novel prognostic biomarker for clinical intervention in BCa.
The microRNA-195 - BDNF pathway and cognitive deficits in schizophrenia patients with minimal antipsychotic medication exposure
Authors: Pan Shujuan , Feng Wei , Li Yanli , Huang Junchao , Chen Song , Cui Yimin , Tian Baopeng , Tan Shuping , Wang Zhiren , Yao Shangwu , Chiappelli Joshua , Kochunov Peter , Chen Shuo , Yang Fude , Li Chiang-Shan R. , Tian Li , Tan Yunlong , Elliot Hong L. 
Published: February 2021

AbstractCognitive impairment is a core characteristic of schizophrenia, but its underlying neural mechanisms remain poorly understood. Reduced brain-derived neurotrophic factor (BDNF), a protein critical for neural plasticity and synaptic signaling, is one of the few molecules consistently associated with cognitive deficits in schizophrenia although the etiological pathway leading to BDNF reduction in schizophrenia is unclear. We examined microRNA-195 (miR-195), a known modulator of BDNF protein expression, as a potential mechanistic component. One-hundred and eighteen first-episode patients with schizophrenia either antipsychotic medication-naïve or within two weeks of antipsychotic medication exposure and forty-seven age- and sex-matched healthy controls were enrolled. MiR-195 and BDNF mRNA and BDNF protein levels in peripheral blood were tested. Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB). MiR-195 was significantly higher (p = 0.01) whereas BDNF mRNA (p < 0.001) and protein (p = 0.016) levels were significantly lower in patients compared with controls. Higher miR-195 expression was significantly correlated to lower BDNF protein levels in patients (partial r = −0.28, p = 0.003) and lower BDNF protein levels were significantly associated with poorer overall cognitive performance by MCCB and also in speed of processing, working memory, and attention/vigilance domains composite score (p = 0.002–0.004). The subgroup of patients with high miR-195 and low BDNF protein showed the lowest level of cognitive functions, and miR-195 showed significant mediation effects on cognitive functions through BDNF protein. Elevated miR-195 may play a role in regulating BDNF protein expression thereby influencing cognitive impairments in schizophrenia, suggesting that development of cognition enhancing treatment for schizophrenia may consider a micro-RNA based strategy.
Prognosis of young patients with monoclonal gammopathy of undetermined significance (MGUS)
Authors: Pang Li , Rajkumar S. Vincent , Kapoor Prashant , Buadi Francis , Dispenzieri Angela , Gertz Morie , Lacy Martha , Kyle Robert , Kumar Shaji 
Published: February 2021

AbstractMonoclonal gammopathy of undetermined significance (MGUS) is rare in young patients (age <40 years at diagnosis), with a prevalence of <0.3%, representing ~2% of all patients with MGUS. We hypothesized that MGUS detected in young patients may be associated with a higher risk of progression. We examined 249 patients with MGUS < 40 years old. Among these, 135 patients had immune-related conditions, including infections, autoimmune and inflammatory disorders at the time of diagnosis of MGUS. The risk of progression to multiple myeloma or a related disorder at 5 years and 10 years was 6.0% and 13.8%, respectively. The size of M protein was a significant risk factor for progression (HR 4.2, 95% CI 2.2–7.9). There was a trend that the risk of progression was higher in patients without immune-related conditions (HR 2.36, 95% CI 0.85–6.52, p = 0.088). The M protein resolved in 36 (14%) patients, with a greater likelihood of resolution in patients with immune-related conditions (RR 1.9, 95% CI 1.02–3.6). Young patients with MGUS have a similar risk of progression as older patients, 1.4% per year. Over 50% are diagnosed in the setting of immune-related disorders. Patients with immune-related disorders may have a lower risk of progression.
Mass spectrometry for the evaluation of monoclonal proteins in multiple myeloma and related disorders: an International Myeloma Working Group Mass Spectrometry Committee Report
Authors: Murray David L. , Puig Noemi , Kristinsson Sigurdur , Usmani Saad Z. , Dispenzieri Angela , Bianchi Giada , Kumar Shaji , Chng Wee Joo , Hajek Roman , Paiva Bruno , Waage Anders , Rajkumar S. Vincent , Durie Brian 
Published: February 2021

AbstractPlasma cell disorders (PCDs) are identified in the clinical lab by detecting the monoclonal immunoglobulin (M-protein) which they produce. Traditionally, serum protein electrophoresis methods have been utilized to detect and isotype M-proteins. Increasing demands to detect low-level disease and new therapeutic monoclonal immunoglobulin treatments have stretched the electrophoretic methods to their analytical limits. Newer techniques based on mass spectrometry (MS) are emerging which have improved clinical and analytical performance. MS is gaining traction into clinical laboratories, and has replaced immunofixation electrophoresis (IFE) in routine practice at one institution. The International Myeloma Working Group (IMWG) Mass Spectrometry Committee reviewed the literature in order to summarize current data and to make recommendations regarding the role of mass spectrometric methods in diagnosing and monitoring patients with myeloma and related disorders. Current literature demonstrates that immune-enrichment of immunoglobulins coupled to intact light chain MALDI-TOF MS has clinical characteristics equivalent in performance to IFE with added benefits of detecting additional risk factors for PCDs, differentiating M-protein from therapeutic antibodies, and is a suitable replacement for IFE for diagnosing and monitoring multiple myeloma and related PCDs. In this paper we discuss the IMWG recommendations for the use of MS in PCDs.
Among classic myeloproliferative neoplasms, essential thrombocythemia is associated with the greatest risk of venous thromboembolism during COVID-19
Authors: Barbui Tiziano , De Stefano Valerio , Alvarez-Larran Alberto , Iurlo Alessandra , Masciulli Arianna , Carobbio Alessandra , Ghirardi Arianna , Ferrari Alberto , Cancelli Valeria , Elli Elena Maria , Andrade-Campos Marcio Miguel , Kabat Mercedes Gasior , Kiladjian Jean-Jaques , Palandri Francesca , Benevolo Giulia , Garcia-Gutierrez Valentin , Fox Maria Laura , Foncillas Maria Angeles , Morcillo Carmen Montoya , Rumi Elisa , Osorio Santiago , Papadopoulos Petros , Bonifacio Massimiliano , Cervantes Keina Susana Quiroz , Serrano Miguel Sagues , Carreno-Tarragona Gonzalo , Sobas Marta Anna , Lunghi Francesca , Patriarca Andrea , Elorza Begoña Navas , Angona Anna , Mazo Elena Magro , Koschmieder Steffen , Carli Giuseppe , Cuevas Beatriz , Hernandez-Boluda Juan Carlos , Abadia Emma Lopez , Cirici Blanca Xicoy , Guglielmelli Paola , Garrote Marta , Cattaneo Daniele , Daffini Rosa , Cavalca Fabrizio , Bellosillo Beatriz , Benajiba Lina , Curto-Garcia Natalia , Bellini Marta , Betti Silvia , Harrison Claire , Rambaldi Alessandro , Vannucchi Alessandro Maria 
Published: February 2021

AbstractIn a multicenter European retrospective study including 162 patients with COVID-19 occurring in essential thrombocythemia (ET, n = 48), polycythemia vera (PV, n = 42), myelofibrosis (MF, n = 56), and prefibrotic myelofibrosis (pre-PMF, n = 16), 15 major thromboses (3 arterial and 12 venous) were registered in 14 patients, of whom all, but one, were receiving LMW-heparin prophylaxis. After adjustment for the competing risk of death, the cumulative incidence of arterial and venous thromboembolic events (VTE) reached 8.5% after 60 days follow-up. Of note, 8 of 12 VTE were seen in ET. Interestingly, at COVID-19 diagnosis, MPN patients had significantly lower platelet count (p < 0.0001) than in the pre-COVID last follow-up.This decline was remarkably higher in ET (−23.3%, p < 0.0001) than in PV (−16.4%, p = 0.1730) and was associated with higher mortality rate (p = 0.0010) for pneumonia. The effects of possible predictors of thrombosis, selected from those clinically relevant and statistically significant in univariate analysis, were examined in a multivariate model. Independent risk factors were transfer to ICU (SHR = 3.73, p = 0.029), neutrophil/lymphocyte ratio (SHR = 1.1, p = 0.001) and ET phenotype (SHR = 4.37, p = 0.006). The enhanced susceptibility to ET-associated VTE and the associated higher mortality for pneumonia may recognize a common biological plausibility and deserve to be delved to tailor new antithrombotic regimens including antiplatelet drugs.
Transforming the landscape of early cancer detection using blood tests—Commentary on current methodologies and future prospects
Authors: Liu Minetta C. 
Published: February 2021

SummaryEarly cancer detection should lead to an overall stage shift, less-intensive treatments and better patient outcomes. Current recommended screening programmes are limited to a handful of individual cancers. A multi-cancer early detection test that simultaneously detects and localises multiple cancers could reduce the morbidity and mortality associated with cancer.
The tele-transition of toxicity management in routine oncology care during the severe acute respiratory syndrome (SARS-CoV-2) pandemic
Authors: Rasschaert Marika , Vanclooster Pieterjan , Mertens Tim , Roelant Ella , Lesage Katrien , Prenen Hans , Verlinden Anke , van Brussel Ilse , Ravelingien Jo , Janssens Annelies , Van Dam Peter , Peeters Marc 
Published: February 2021

Abstract
Background
Telehealth modalities were introduced during the SARS-CoV-2 pandemic to assure continuation of cancer care and maintain social distance.

Methods
This is a retrospective cohort analysis of our telehealth expansion programme. We adapted two existing patient-reported outcome (PRO) telemonitoring tools that register and (self-)manage toxicities to therapy, while screening for SARS-CoV-2-related symptoms. Outpatients from a tertiary cancer centre were enrolled. The adapted PRO interface allowed for uniform registration of SARS-CoV-2-related symptoms and effective triage of patients at home where we also implemented systematic throat washings, when available.

Results
Three hundred and sixty patients registered to the telemonitoring systems from March 13 to May 15, 2020. Four prespecified SARS-CoV-2 alarms resulted in three patients with positive PCR testing. Other Covid-19 symptoms (fever 5× and cough 2×) led to pretreatment triage resulting in 1 seroconversion after initial negative testing. One of the 477 throat washings proved positive.

Conclusions
The rapid adoption of an amended PRO (self-)registrations and toxicity management system was feasible and coordinated screening for Covid-19. Continued clinical cancer care was maintained, with significant decreased waiting time. The systemic screening with throat washings offered no real improvement.
Determination of breast cancer prognosis after neoadjuvant chemotherapy: comparison of Residual Cancer Burden (RCB) and Neo-Bioscore
Authors: Laas Enora , Labrosse Julie , Hamy Anne-Sophie , Benchimol Gabriel , de Croze Diane , Feron Jean-Guillaume , Coussy Florence , Balezeau Thomas , Guerin Julien , Lae Marick , Pierga Jean-Yves , Reyal Fabien 
Published: February 2021

Abstract
Background
To compare RCB (Residual Cancer Burden) and Neo-Bioscore in terms of prognostic performance and see if adding pathological variables improve these scores.

Methods
We analysed 750 female patients with invasive breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) at Institut Curie between 2002 and 2012. Scores were compared in global population and by BC subtype using Akaike information criterion (AIC), C-Index (concordance index), calibration curves and after adding lymphovascular invasion (LVI) and pre-/post-NAC TILs levels.

Results
RCB and Neo-Bioscore were significantly associated to disease-free and overall survival in global population and for triple-negative BC. RCB had the lowest AICs in every BC subtype, corresponding to a better prognostic performance. In global population, C-Index values were poor for RCB (0.66; CI [0.61–0.71]) and fair for Neo-Bioscore (0.70; CI [0.65–0.75]). Scores were well calibrated in global population, but RCB yielded better prognostic performances in each BC subtype. Concordance between the two scores was poor. Adding LVI and TILs improved the performance of both scores.

Conclusions
Although RCB and Neo-Bioscore had similar prognostic performances, RCB showed better performance in BC subtypes, especially in luminal and TNBC. By generating fewer prognostic categories, RCB enables an easier use in everyday clinical practice.
Early cancer diagnosis: reaching targets across whole populations amidst setbacks
Authors: McCormack Valerie , Aggarwal Ajay 
Published: February 2021

SummaryEarly diagnosis of cancer, followed by timely and appropriate therapy, are the cornerstones of the secondary prevention of cancer, thus the NHS has set a 2028 target to achieve 75% early stage (TNM I/II) at cancer diagnosis. In this context, Barclay et al. evaluated overall, sex, age and deprivation-group-specific progress towards this target based on 202,000 cancer patients diagnosis in 2015. Herein, we discuss their findings which form a valuable pre-COVID-19 pandemic status. We discuss the impact of the pandemic and the efforts being made in innovative early detection and diagnosis research.
Socio-demographic variation in stage at diagnosis of breast, bladder, colon, endometrial, lung, melanoma, prostate, rectal, renal and ovarian cancer in England and its population impact
Authors: Barclay M. E. , Abel G. A. , Greenberg David. C. , Rous B. , Lyratzopoulos G. 
Published: February 2021

Abstract
Background
Stage at diagnosis strongly predicts cancer survival and understanding related inequalities could guide interventions.

Methods
We analysed incident cases diagnosed with 10 solid tumours included in the UK government target of 75% of patients diagnosed in TNM stage I/II by 2028. We examined socio-demographic differences in diagnosis at stage III/IV vs. I/II. Multiple imputation was used for missing stage at diagnosis (9% of tumours).

Results
Of the 202,001 cases, 57% were diagnosed in stage I/II (an absolute 18% ‘gap’ from the 75% target). The likelihood of diagnosis at stage III/IV increased in older age, though variably by cancer site, being strongest for prostate and endometrial cancer. Increasing level of deprivation was associated with advanced stage at diagnosis for all sites except lung and renal cancer. There were, inconsistent in direction, sex inequalities for four cancers. Eliminating socio-demographic inequalities would translate to 61% of patients with the 10 studied cancers being diagnosed at stage I/II, reducing the gap from target to 14%.

Conclusions
Potential elimination of socio-demographic inequalities in stage at diagnosis would make a substantial, though partial, contribution to achieving stage shift targets. Earlier diagnosis strategies should additionally focus on the whole population and not only the high-risk socio-demographic groups.
Eye fluke infection changes diet composition in juvenile European perch (Perca fluviatilis)
Authors: Vivas Muñoz Jenny C. , Feld Christian K. , Hilt Sabine , Manfrin Alessandro , Nachev Milen , Köster Daniel , Jochmann Maik A. , Schmidt Torsten C. , Sures Bernd , Ziková Andrea , Knopf Klaus 
Published: February 2021

AbstractIntraspecific diet specialization, usually driven by resource availability, competition and predation, is common in natural populations. However, the role of parasites on diet specialization of their hosts has rarely been studied. Eye flukes can impair vision ability of their hosts and have been associated with alterations of fish feeding behavior. Here it was assessed whether European perch (Perca fluviatilis) alter their diet composition as a consequence of infection with eye flukes. Young-of-the-year (YOY) perch from temperate Lake Müggelsee (Berlin, Germany) were sampled in two years, eye flukes counted and fish diet was evaluated using both stomach content and stable isotope analyses. Perch diet was dominated by zooplankton and benthic macroinvertebrates. Both methods indicated that with increasing eye fluke infection intensity fish had a more selective diet, feeding mainly on the benthic macroinvertebrateDikerogammarus villosus, while less intensively infected fish appeared to be generalist feeders showing no preference for any particular prey type. Our results show that infection with eye flukes can indirectly affect interaction of the host with lower trophic levels by altering the diet composition and highlight the underestimated role of parasites in food web studies.