bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased FNDC5/IRISIN protein expression in breast cancer tissue is associated with obesity in postmenopausal women
Authors: Tejeda María Elena , Canto Patricia , Tenorio-Torres Alberto , Orozco-Arguelles Letica , Coral-Vázquez Ramón Mauricio , Zentella-Dehesa Alejandro , Leal-García Marcela , Vega-García Claudia Cecilia , Bautista-Piña Verónica , Méndez Juan Pablo 
Published: June 2021

AimTo analyse the fibronectin type III domain containing 5 (FNDC5)/irisin expression in tumour tissue of postmenopausal women presenting breast cancer and different body mass indexes (BMIs), proposing that obesity deregulates the expression of FNDC5/irisin at the breast tumour level. In addition, we investigated if different breast cancer cell lines are capable to synthesise this protein.MethodsA total of 150 postmenopausal women (50 with a normal BMI, 50 presenting overweight and 50 having obesity) diagnosed with operable breast cancer were included. FNDC5/irisin expression was determined by immunohistochemistry or by immunocytochemistry. Qualitative analysis of protein expression was performed by the H-Score method, through ImageJ’s IHC Profiler software. Statistical analyses were carried out using STATA V.14.0 (Texas, USA); p value<0.05 was accepted as statistically significant. Statistical power of the study was >80% with a p<0.05.ResultsFNDC5/irisin expression in breast cancer tissue of postmenopausal women with obesity was significantly increased when compared with FNDC5/irisin expression in women with a normal BMI (p=0.001). Furthermore, three breast cancer cell lines studied were capable to synthesise and express FNDC5/irisin, being the BT-474 cell line the one that exhibited the highest intensity of expression.ConclusionsOur results confirm that women with breast cancer and obesity exhibit an increased irisin expression in their tumorous tissue compared with women with breast cancer and normal BMI. Likewise, in vitro breast cancer cell lines have the capacity to synthesise and express FNDC5/irisin, without any extracellular stimuli, however the microenvironment surrounding these cells in vivo participates in its regulation.
Abnormal umbilical cord insertions in singleton deliveries: placental histology and neonatal outcomes
Authors: Visentin Sivlia , Londero Ambrogio P , Santoro Luisa , Pizzi Sara , Andolfatto Matteo , Venturini Maria , Saraggi Deborah , Coati Irene , Sacchi Diana , Rugge Massimo , Cosmi Erich 
Published: June 2021

AimsThis study aimed to identify any microscopic features associated with abnormal (membranous/velamentous or marginal) placental cord insertions and to analyse their adverse neonatal outcomes.MethodsWe retrospectively analysed the records—including pathological findings, clinical information and pregnancy outcomes—for 1060 singleton pregnancies, involving newborn delivered after 24 weeks of gestation.ResultsMarginal cord insertions were identified in 26.60% of cases and membranous cord insertions in 2.64%. Subchorionic vessel thrombus was more prevalent in marginal or membranous insertions (0.97%) than in normal cord insertions (0.27%) (p=0.129). Intervillous thrombi (13.73% vs 8.41%, p<0.05) and chorioamnionitis (8.53% vs 5.48%, p=0.089) were more prevalent in normal cord insertions. Premature rupture of membranes was significantly more commonly associated with abnormal (marginal 15.25% and membranous 17.86%) than with normal (9.87%) insertions (p<0.05). Pre-eclampsia was more common in the group with membranous cord insertions (7.14%) than in the other groups (marginal 0.35%; normal 0.80%) (p<0.05). Marginal and membranous placental cord insertions were associated with earlier gestational age at delivery and smaller fetuses than in the group with normal insertions. Intrauterine fetal demise, cardiac malformations and pregestational diabetes were also more common among cases of abnormal cord insertions.ConclusionsSubchorionic vessel thrombus and adverse pregnancy-related outcomes were more prevalent in cases of marginal/membranous cord insertion than for normal insertions.
Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma
Authors: Simonds Erin F , Lu Edbert D , Badillo Oscar , Karimi Shokoufeh , Liu Eric V , Tamaki Whitney , Rancan Chiara , Downey Kira M , Stultz Jacob , Sinha Meenal , McHenry Lauren K , Nasholm Nicole M , Chuntova Pavlina , Sundström Anders , Genoud Vassilis , Shahani Shilpa A , Wang Leo D , Brown Christine E , Walker Paul R , Swartling Fredrik J , Fong Lawrence , Okada Hideho , Weiss William A , Hellström Mats 
Published: June 2021

BackgroundGlioblastoma (GBM) is refractory to immune checkpoint inhibitor (ICI) therapy. We sought to determine to what extent this immune evasion is due to intrinsic properties of the tumor cells versus the specialized immune context of the brain, and if it can be reversed.MethodsWe used CyTOF mass cytometry to compare the tumor immune microenvironments (TIME) of human tumors that are generally ICI-refractory (GBM and sarcoma) or ICI-responsive (renal cell carcinoma), as well as mouse models of GBM that are ICI-responsive (GL261) or ICI-refractory (SB28). We further compared SB28 tumors grown intracerebrally versus subcutaneously to determine how tumor site affects TIME and responsiveness to dual CTLA-4/PD-1 blockade. Informed by these data, we explored rational immunotherapeutic combinations.ResultsICI-sensitivity in human and mouse tumors was associated with increased T cells and dendritic cells (DCs), and fewer myeloid cells, in particular PD-L1+ tumor-associated macrophages. The SB28 mouse model of GBM responded to ICI when grown subcutaneously but not intracerebrally, providing a system to explore mechanisms underlying ICI resistance in GBM. The response to ICI in the subcutaneous SB28 model required CD4 T cells and NK cells, but not CD8 T cells. Recombinant FLT3L expanded DCs, improved antigen-specific T cell priming, and prolonged survival of mice with intracerebral SB28 tumors, but at the cost of increased Tregs. Targeting PD-L1 also prolonged survival, especially when combined with stereotactic radiation.ConclusionsOur data suggest that a major obstacle for effective immunotherapy of GBM is poor antigen presentation in the brain, rather than intrinsic immunosuppressive properties of GBM tumor cells. Deep immune profiling identified DCs and PD-L1+ tumor-associated macrophages as promising targetable cell populations, which was confirmed using therapeutic interventions in vivo.
Global effect of COVID-19 pandemic on the rate of acute coronary syndrome admissions: a comprehensive review of published literature
Authors: Helal Ayman , Shahin Lamis , Abdelsalam Mahmoud , Ibrahim Mokhtar 
Published: June 2021

BackgroundThe COVID-19 pandemic has disrupted healthcare systems across the world. The rate of acute coronary syndrome (ACS) admissions during the pandemic has varied significantly.ObjectivesThe purpose of this study is to investigate the effect of the pandemic on ACS hospital admissions and to determine whether this is related to the number of COVID-19 cases in each country.MethodSearch engines including PubMed, Embase, Ovid and Google Scholar were searched from December 2019 to the 15 September 2020 to identify studies reporting ACS admission data during COVID-19 pandemic months in 2020 compared with 2019 admissions.ResultsA total of 40 studies were included in this multistudy analysis. They demonstrated a 28.1% reduction in the rate of admission with ACS during the COVID-19 pandemic period compared with the same period in 2019 (total of 28 613 patients in 2020 vs 39 225 in 2019). There was a significant correlation between the absolute risk reduction in the total number of ACS cases and the number of COVID-19 cases per 100 000 population (Pearson correlation=0.361 (p=0.028)). However, the correlation was not significant for each of the ACS subgroups: non-ST-elevation myocardial infarction (STEMI) (p=0.508), STEMI (p=0883) and unstable angina (p=0.175).ConclusionThere was a significant reduction in the rate of ACS admission during the COVID-19 pandemic period compared with the same period in 2019 with a significant correlation with COVID-19 prevalence.
Concise genetic profile of lung carcinoma
Authors: Umakanthan Srikanth , Bukelo Maryann M 
Published: June 2021

Abstract
The WHO classification of lung cancer (2015) is based on immunohistochemistry and molecular evaluation. This also includes microscopic analysis of morphological patterns that aids in the pathological diagnosis and classification of lung cancers. Lung cancers are the leading cause of cancer deaths worldwide. Recent advancements in identifying the etiopathogenesis are majorly driven by gene mutation studies. This has been explained by The Cancer Genome Atlas, next-generation sequencer and TRAcking non-small cell lung cancer evolution through therapy [Rx]. This article reviews the genetic profile of adenocarcinoma, squamous cell carcinoma, small cell carcinoma, large cell neuroendocrine carcinoma and pulmonary carcinoids. This includes the prolific genetic alterations and novel molecular changes seen in these tumours. In addition, target- specific drugs that have shown promising effects in clinical use and trials are also briefly discussed.
Gender bias in reference letters for residency and academic medicine: a systematic review
Authors: Khan Shawn , Kirubarajan Abirami , Shamsheri Tahmina , Clayton Adam , Mehta Geeta 
Published: June 2021

Abstract
Reference letters play an important role for both postgraduate residency applications and medical faculty hiring processes. This study seeks to characterise the ways in which gender bias may manifest in the language of reference letters in academic medicine. In particular, we conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched Embase, MEDLINE and PsycINFO from database inception to July 2020 for original studies that assessed gendered language in medical reference letters for residency applications and medical faculty hiring. A total of 16 studies, involving 12 738 letters of recommendation written for 7074 applicants, were included. A total of 32% of applicants were women. There were significant differences in how women were described in reference letters. A total of 64% (7/11) studies found a significant difference in gendered adjectives between men and women. Among the 7 studies, a total of 86% (6/7) noted that women applicants were more likely to be described using communal adjectives, such as “delightful” or “compassionate”, while men applicants were more likely to be described using agentic adjectives, such as “leader” or “exceptional”. Several studies noted that reference letters for women applicants had more frequent use of doubt raisers and mentions of applicant personal life and/or physical appearance. Only one study assessed the outcome of gendered language on application success, noting a higher residency match rate for men applicants. Reference letters within medicine and medical education exhibit language discrepancies between men and women applicants, which may contribute to gender bias against women in medicine.
Effects of angiotensin receptor neprilysin inhibitor on renal function in patients with heart failure: a systematic review and meta-analysis
Authors: Shi Yuwu , Wang Yiwen , Chen Junhong , Lu Chi , Xuan Haochen , Wang Chaofan , Li Dongye , Xu Tongda 
Published: June 2021

Abstract
The angiotensin receptor neprilysin inhibitor (ARNI) has been recommended as a first-line treatment in patients with heart failure (HF). However, the effects of ARNI on renal function remain controversial.
The PubMed, Embase, the Cochrane Library of Trials and Web of Science were searched in the period from inception to 31 January 2021. Randomised controlled trial, cohort studies and observational studies reporting at least one of renal function indicators were included.
In patients with HF with reduced ejection fraction (HFrEF), ARNI did not lead to a significant decrease in estimated glomerular filtration rate (eGFR, p=0.87), and the risk of worsening renal function (WRF) dropped by 11% compared with control group. Though the level of serum creatinine (SCr) and serum potassium had a slight increase (p=0.01; p=0.02), in contrast to the baseline level, but without clinical significance. In patients with HF with preserved ejection fraction (HFpEF), the level of SCr and serum potassium did not have a significant change, and patients with HFpEF assigned to ARNI had a much lower rate of WRF (p=0.0007). In contrast to control group, both patients with HFrEF and HFpEF had a less decrease in eGFR and a lower rate of hyperkalaemia in ARNI group.
ARNI did not lead to a significant decrease in eGFR in HFrEF. Compared with control group, ARNI could delay the progression of decrease in eGFR and result in less events of hyperkalaemia in patients with HF. Besides, patients with HFpEF had a lower rate in the events of WRF.
Primary care-based smoking cessation treatment and subsequent healthcare service utilisation: a matched cohort study of smokers using linked administrative healthcare data
Authors: Baliunas Dolly , Selby Peter , de Oliveira Claire , Kurdyak Paul , Rosella Laura , Zawertailo Laurie , Fu Longdi , Sutradhar Rinku 
Published: June 2021

BackgroundNo research has assessed the individual-level impact of smoking cessation treatment delivered within a general primary care patient population on multiple forms of subsequent healthcare service use.ObjectiveWe aimed to compare the rate of outpatient visits, emergency department (ED) visits and hospitalisations during a 5-year follow-up period among smokers who had and had not accessed a smoking cessation treatment programme.MethodsThe study was a retrospective matched cohort study using linked demographic and administrative healthcare databases in Ontario, Canada. 9951 patients who accessed smoking cessation services between July 2011 and December 2012 were matched to a smoker who did not access services, obtained from the Canadian Community Health Survey, using a combination of hard matching and propensity score matching. Outcomes were rates of healthcare service use from index date (programme enrolment or survey response) to March 2017.ResultsAfter controlling for potential confounders, patients in the overall treatment cohort had modestly greater rates of the outcomes: outpatient visits (rate ratio (RR) 1.10, 95% CI: 1.06 to 1.14), ED visits (RR 1.08, 95% CI: 1.03 to 1.13) and hospitalisations (RR 1.09, 95% CI: 1.02 to 1.18). Effect modification of the association between smoking cessation treatment and healthcare service use by prevalent comorbidity was found for outpatient visits (p=0.006), and hospitalisations (p=0.050), but not ED visits.ConclusionsPatients who enrolled in smoking cessation treatment offered through primary care clinics in Ontario displayed a modest but significantly greater rate of outpatient visits, ED visits and hospitalisations over a 5-year follow-up period.
Prognostic Value and Relation with Adjuvant Treatment Duration of ctDNA in Stage III Colon Cancer: aPost HocAnalysis of the PRODIGE-GERCOR IDEA-France Trial
Authors: Taieb Julien , Taly Valérie , Henriques Julie , Bourreau Camille , Mineur Laurent , Bennouna Jaafar , Desrame Jérôme , Louvet Christophe , Lepere Céline , Mabro May , Egreteau Joëlle , Bouche Olivier , Mulot Claire , Hormigos Katia , Chaba Kariman , Mazard Thibault , de Gramont Aimery , Vernerey Dewi , André Thierry , Laurent-Puig Pierre 
Published: June 2021

AbstractPurpose:Circulating tumor DNA (ctDNA) has been suggested as a major prognostic factor in resected stage-III colon cancer. We analyzed ctDNA of patients randomized in the phase III IDEA-France trial.Experimental Design:ctDNA was tested for WIF1 and NPY by droplet digital PCR with method developed and validated for colorectal cancer. Disease-free survival (DFS) and overall survival (OS) were analyzed via multivariable analysis in patients with ctDNA samples and in sub-groups according to treatment duration (3/6 months) and disease stage (high/low-risk stage III).Results:Of 2,010 randomized patients, 1,345 had available ctDNA samples (1,017 collected both post-surgery and pre-chemotherapy). More Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 (78% versus 69%) and T4 and/or N2 (40% versus 36%) were observed in patients studied (n = 1017) versus not analyzed (n = 993). There were 877 ctDNA-negative (86.2%) and 140 ctDNA-positive (13.8%) patients; their baseline characteristics were similar. With a median follow-up of 6.6 years, the 3-year DFS rate was 66.39% for ctDNA-positive patients and 76.71% for ctDNA-negative patients (P = 0.015). ctDNA was confirmed as an independent prognostic marker for DFS (adjusted HR = 1.55, 95% CI 1.13–2.12, P = 0.006) and OS (HR = 1.65, 95% CI 1.12–2.43, P = 0.011). ctDNA was prognostic in patients treated for 3 months and with T4 and/or N2 tumors, but not in those treated for 6 months and with T1–3/N1 tumors.Conclusions:In this first ctDNA assessment of a large series of patients with stage III colon cancer enrolled in phase III trial, post-surgery ctDNA was found in 13.8% of them and was confirmed as an independent prognostic marker.See related commentary by Bent and Kopetz, p. 5449
Evolution of Castration-Resistant Prostate Cancer in ctDNA during Sequential Androgen Receptor Pathway Inhibition
Authors: Annala Matti , Taavitsainen Sinja , Khalaf Daniel J. , Vandekerkhove Gillian , Beja Kevin , Sipola Joonatan , Warner Evan W. , Herberts Cameron , Wong Amanda , Fu Simon , Finch Daygen L. , Oja Conrad D. , Vergidis Joanna , Zulfiqar Muhammad , Eigl Bernhard J. , Kollmansberger Christian K. , Nykter Matti , Gleave Martin E. , Chi Kim N. , Wyatt Alexander W. 
Published: June 2021

AbstractPurpose:Cross-resistance renders multiple lines of androgen receptor (AR) signaling inhibitors increasingly futile in metastatic castration-resistant prostate cancer (mCRPC). We sought to determine acquired genomic contributors to cross-resistance.Experimental Design:We collected 458 serial plasma cell-free DNA samples at baseline and progression timepoints from 202 patients with mCRPC receiving sequential AR signaling inhibitors (abiraterone and enzalutamide) in a randomized phase II clinical trial (NCT02125357). We utilized deep targeted and whole-exome sequencing to compare baseline and posttreatment somatic genomic profiles in circulating tumor DNA (ctDNA).Results:Patient ctDNA abundance was correlated across plasma collections and independently prognostic for sequential therapy response and overall survival. Most driver alterations in established prostate cancer genes were consistently detected in ctDNA over time. However, shifts in somatic populations after treatment were identified in 53% of patients, particularly after strong treatment responses. Treatment-associated changes converged upon the AR gene, with an average 50% increase in AR copy number, changes in AR mutation frequencies, and a 2.5-fold increase in the proportion of patients carrying AR ligand binding domain truncating rearrangements.Conclusions:Our data show that the dominant AR genotype continues to evolve during sequential lines of AR inhibition and drives acquired resistance in patients with mCRPC.
A γδ T–cell Imprint in a Rare Skin Tumor
Authors: Jaeger Natalia , Colonna Marco 
Published: June 2021

Abstract
In-depth immune profiling can guide the development and targeting of cancer immunotherapies. In this issue, Gherardin and colleagues find a strong signature of γδ T cells in the immune infiltrate of Merkel cell carcinoma that correlates with a more favorable prognosis and heightened responsiveness to checkpoint inhibitors. This may lead to future γδ T cell–targeted immunotherapies.
See article by Gherardin et al., p. 612
Artificial intelligence based handover decision and network selection in heterogeneous internet of vehicles
Authors: Hussain Shaik Mazhar , Yusof Kamaludin Mohamad , Asuncion Rolito , Hussain Shaik Ashfaq 
Published: June 2021

Internet of vehicles (IoV) is an emerging area that gives support for vehicles via internet assisted communication. IoV with 5G provides ubiquitous connectivity due to the participation of more than one radio access network. The mobility of vehicles demands to make handover in such heterogeneous network. The vehicles at short range uses dedicated short range communication (DSRC), while it has to use better technology for long range and any type of traffic. Usually, the previous work will directly select the network for handover or it connects with available radio access. Due to this, the occurrence of handover takes place frequently. In this paper, the integration of DSRC, LTE and mmWave 5G on IoV is incorporated with novel handover decision making, network selection and routing. The handover decision is to ensure whether there is a need for vertical handover by using Dynamic Q-learning algorithm that uses entropy function for threshold prediction as per the current characteristics of the environment. Then the network selection is based on fuzzy-convolution neural network (F-CNN) that creates fuzzy rules from signal strength, distance, vehicle density, data type and line of sight. V2V chain routing is proposed to select V2V pairs using jellyfish optimization algorithm (JOA) that takes in account of channel, vehicle and transmission metrics. This system is developed in OMNeT++ simulator and the performances are evaluated in terms of success probability, handover failure, unnecessary handover, mean throughput, delay and packet loss.
Age at Menopause and Risk of Ischemic and Hemorrhagic Stroke
Authors: Welten Sabrina J.G.C. , Onland-Moret N. Charlotte , Boer Jolanda M.A. , Verschuren W.M. Monique , van der Schouw Yvonne T. 
Published: June 2021

Background and Purpose:
The few epidemiological studies that addressed the association between age at menopause and ischemic and hemorrhagic stroke risk in women had conflicting findings. We aimed to investigate whether age at (natural and surgical) menopause is a risk factor for total, ischemic, and hemorrhagic stroke in women.

Methods:
We analyzed data from 16 244 postmenopausal women, aged 26 to 70 years at recruitment who were enrolled in the European Prospective Investigation into Cancer and Nutrition–Netherlands cohort between 1993 and 1997. Participants were followed for the occurrence of stroke until January 1, 2011. At baseline, participants filled in questionnaires about health, reproductive history including age at menopause, diet, and lifestyle. Cox regression was used to investigate the association between age at menopause and stroke. All analyses were adjusted for age, smoking, systolic blood pressure, and body mass index.

Results:
Mean age of menopause was 46.4 (7.0) years. A total of 830 strokes (571 ischemic, 162 hemorrhagic, 97 unclassified) were identified. Earlier menopause was associated with an increased risk of total stroke. Compared with women who experienced menopause between 50 and 54 years old, women who underwent menopause before age 40 years had 1.48× higher risk (95% CI, 1.19–1.85) of total stroke. In continuous analyses, we observed a 2% lower total stroke risk for each year menopause was delayed (hazard ratio, 0.98 [95% CI, 0.97–0.99]). The risk between earlier menopause and stroke was confined to ischemic stroke, earlier menopause was not associated with hemorrhagic stroke. The association with age at menopause was stronger for natural menopause (hazard ratio <40 versus 50–54 years, 1.74 [95% CI, 1.12–2.70]) than for surgical menopause (hazard ratio <40 versus 50–54 years, 1.26 [95% CI, 0.84–1.89]).

Conclusions:
The risk of total and ischemic stroke decreased with an increase in age at menopause. Whether this should have clinical consequences such as intensified risk factor control should be subject of further studies.