bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blunt duct adenosis: a separate entity from columnar cell lesions?
Authors: de Boer Mirthe , van Diest Paul J 
Published: April 2021

Blunt duct adenosis (BDA) is a breast lesion first described by Foote and Stewart in 1945 as a proliferative benign lesion of the terminal duct lobular unit. Throughout recent decades, further literature descriptions of BDA have been confusing. Some consider BDA to be a separate entity, some a growth pattern of columnar cell changes. The WHO 2012 considered BDA and columnar cell changes to be synonyms, while columnar cell lesions, especially those with atypia, are part of a spectrum of early precursors of the low nuclear grade breast neoplasia family. In the updated WHO 2019 version, BDA is mentioned as ‘not recommended’ terminology for columnar cell lesions without further discussing it, leaving the question open if BDA should be considered a separate entity.Good diagnostic criteria for BDA have however largely been lacking, and its biological background has not yet been unravelled. In this paper, we point out that BDA is mainly associated with benign breast lesions and not with other recognised precursor lesions. Further, 16q loss, which is the hallmark molecular event in the low nuclear grade breast neoplasia family, is lacking in BDA. We therefore hypothesise that BDA may not be a true precursor lesion but a benign polyclonal lesion, and propose morphological diagnostic criteria to better differentiate it from columnar cell lesions.
Fibrotic extracellular matrix induces release of extracellular vesicles with pro-fibrotic miRNA from fibrocytes
Authors: Sato Seidai , Chong Sy Giin , Upagupta Chandak , Yanagihara Toyoshi , Saito Takuya , Shimbori Chiko , Bellaye Pierre-Simon , Nishioka Yasuhiko , Kolb Martin RJ 
Published: April 2021

Rationale
Extracellular vesicles (EVs) are small lipid vesicles, and EV-coupled microRNAs (miRNAs) are important modulators of biological processes. Fibrocytes are circulating bone marrow-derived cells that migrate into the injured lungs and contribute to fibrogenesis. The question of whether EV-coupled miRNAs derived from fibrocytes are able to regulate pulmonary fibrosis has not been addressed yet.

Methods
Pulmonary fibrosis was induced in rats by intratracheal administration of an adenoviral gene vector encoding active transforming growth factor-β1 (TGF-β1) or control vector. Primary fibrocytes and fibroblasts were cultured from rat lungs and were sorted by anti-CD45 magnetic beads. Human circulating fibrocytes and fibrocytes in bronchoalveolar lavage fluid (BALF) were isolated by fibronectin-coated dishes. Fibrocytes were cultured on different stiffness plates or decellularised lung scaffolds. We also determined the effects of extracellular matrix (ECM) and recombinant TGF-β1 on the cellular and EV-coupled miRNA expression of fibrocytes.

Results

The EVs of fibrocytes derived from fibrotic lungs significantly upregulated the expression of
col1a1
of fibroblasts. Culturing on rigid plates or fibrotic decellularised lung scaffolds increased miR-21-5 p expression compared with soft plates or normal lung scaffolds. Dissolved ECM collected from fibrotic lungs and recombinant TGF-β1 increased miR-21-5 p expression on fibrocytes, and these effects were attenuated on soft plates. Fibrocytes from BALF collected from fibrotic interstitial pneumonia patients showed higher miR-21-5 p expression than those from other patients.

Conclusions
Our results indicate that ECM contributes to fibrogenesis through biomechanical and biochemical effects on miRNA expression in fibrocytes.
Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19
Authors: Saris Anno , Reijnders Tom D Y , Nossent Esther J , Schuurman Alex R , Verhoeff Jan , Asten Saskia van , Bontkes Hetty , Blok Siebe , Duitman Janwillem , Bogaard Harm-Jan , Heunks Leo , Lutter Rene , van der Poll Tom , Garcia Vallejo Juan J 
Published: April 2021

BackgroundKnowledge of the pathophysiology of COVID-19 is almost exclusively derived from studies that examined the immune response in blood. We here aimed to analyse the pulmonary immune response during severe COVID-19 and to compare this with blood responses.MethodsThis was an observational study in patients with COVID-19 admitted to the intensive care unit (ICU). Mononuclear cells were purified from bronchoalveolar lavage fluid (BALF) and blood, and analysed by spectral flow cytometry; inflammatory mediators were measured in BALF and plasma.FindingsPaired blood and BALF samples were obtained from 17 patients, four of whom died in the ICU. Macrophages and T cells were the most abundant cells in BALF, with a high percentage of T cells expressing the ƴδ T cell receptor. In the lungs, both CD4 and CD8 T cells were predominantly effector memory cells (87·3% and 83·8%, respectively), and these cells expressed higher levels of the exhaustion marker programmad death-1 than in peripheral blood. Prolonged ICU stay (>14 days) was associated with a reduced proportion of activated T cells in peripheral blood and even more so in BALF. T cell activation in blood, but not in BALF, was higher in fatal COVID-19 cases. Increased levels of inflammatory mediators were more pronounced in BALF than in plasma.InterpretationThe bronchoalveolar immune response in COVID-19 has a unique local profile that strongly differs from the immune profile in peripheral blood. Fully elucidating COVID-19 pathophysiology will require investigation of the pulmonary immune response.
Illicit cigarette trade in the cities of Pakistan: comparing findings between the consumer and waste recycle store surveys
Authors: Khan Amina , Dobbie Fiona , Siddiqi Kamran , Ansaari Saeed , Abdullah S M , Iqbal Romaina , Khan Zohaib , Sohail Salman , Kanaan Mona , Huque Rumana , Islam Ziauddin , Boeckmann Melanie , Ross Hana 
Published: April 2021

BackgroundConcerns about the magnitude of illicit cigarette trade have prevented the Government of Pakistan from increasing tobacco taxes. We estimated the proportion of illicit cigarettes sold in Pakistani cities. Moreover, we compared two methods for collecting cigarette packs and investigated if the illicit cigarette trade equates to tax evasion.MethodWe analysed cigarette packs collected from 10 cities of Pakistan using two methods: consumer survey based on a two-stage random sampling strategy to recruit adult smokers and photograph their cigarette packs and waste recycle store survey to purchase used cigarette packs. Cigarettes were considered illicit if any one of the following was absent from their packs: text and pictorial health warning, underage sale prohibition warning, retail price and manufacturer’s name. From the consumer survey, we also estimated the proportion of smokers who purchased loose cigarettes (illegal) and packs below the minimum retail price. Taxation officers (n=4) were consulted to assess their level of confidence in judging tax evasion using the above criteria.ResultsOut of 2416 cigarette packs in the consumer survey, 454 (17.8%; 95% CI 15.4% to 20.2%) were illicit. Similarly, out of 6213 packs from waste recycle shops, 1046 (16.8%; 95% CI 15.9% to 17.7%) were illicit; the difference was not statistically significant (p=0.473). Among consumers, 29.5% bought loose cigarettes and 13.8% paid less than the minimum retail price. The taxation officers considered the manufacturer’s name and retail price on cigarette packs as the most relevant criteria to detect tax evasion.ConclusionsOne in six cigarette packs consumed in Pakistan could be illicit. These figures are far less than those propagated by the tobacco industry. Collecting packs from waste recycle stores is an efficient and valid method to estimate illicit cigarette trade.
Efficient synthetic generation of ecological data with preset spatial association of individuals
Authors: Strimbu Bogdan M. , Paun Andrei , Amarioarei Alexandru , Paun Mihaela , Strimbu Victor F. 
Published: April 2021

Many experiments cannot feasibly be conducted as factorials. Simulations using synthetically generated data are viable alternatives to such factorial experiments. The main objective of the present research is to develop a methodology and platform to synthetically generate spatially explicit forest ecosystems represented by points with a predefined spatial pattern. Using algorithms with polynomial complexity and parameters that control the number of clusters, the degree of clusterization, and the proportion of nonrandom trees, we show that spatially explicit forest ecosystems can be generated time efficiently, which enables large factorial simulations. The proposed method was tested on 1200 synthetically generated forest stands, each of 25 ha, using 10 spatial indices: Clark–Evans aggregation index; Ripley’s K; Besag’s L; Morisita’s dispersion index; Greig–Smith index; the size dominance index of Hui; index of nonrandomness of Pielou; directional index and mean directional index of Corral–Rivas; and size differentiation index of Von Gadow. The size of individual trees was randomly generated aiming at variograms such as real forests. We obtained forest stands with the expected spatial arrangement and distribution of sizes in less than 1 h. To ensure replicability of the study, we have provided free, fully functional software that executes the stated tasks.
The neuromuscular system in flatworms: serotonin and FMRFamide immunoreactivities and musculature in Prodistomum alaskense (Digenea: Lepocreadiidae), an endemic fish parasite of the northwestern Pacific
Authors: Nefedova D.A. , Terenina N.B. , Mochalova N.V. , Poddubnaya L.G. , Movsesyan S.O. , Gordeev I.I. , Kuchin A.V. , Kreshchenko N.D. 
Published: April 2021

Using the immunocytochemical method and confocal scanning laser microscopy, we obtained pioneering data on the muscle system organization and presence and localization of biogenic amine serotonin and FMRFamide-related peptides in the nervous system of the trematode Prodistomum alaskense (Ward and Fillingham, 1934) Bray and Merrett 1998 (family Lepocreadiidae). This flatworm is an intestinal parasite of endemic representatives of the marine fauna of the northwestern Pacific Ocean — the prowfish (Zaprora silenus Jordan, 1896) and the lumpfish (Aptocyclus ventricosus (Pallas, 1769)). We provide data of scanning electron microscopy on the tegumental topography of P. alaskense. The body wall musculature of P. alaskense has three layers of muscle fibres — the outer circular, intermediate longitudinal, and inner diagonal. The muscle system elements are well developed in the attachment organs, digestive and reproductive systems, and in the excretory sphincter. Serotonin– and FMRFamide–immunopositive neurons and neurites are found in the head ganglia, circular commissure, longitudinal nerve cords, and in the transversal connective commissures. The innervation of the oral and ventral suckers, pharynx, and the reproductive system compartments by the serotonergic and FMRFamide–immunopositive neurites is revealed. The results discus connection with the published data on the presence and functional roles of the serotonin and FMRFamide-related peptides in Platyhelminthes.
Quantum criticality in dimerised anisotropic spin-1 chains
Authors: Ejima Satoshi , Lange Florian , Fehske Holger 
Published: April 2021

AbstractApplying the (infinite) density-matrix renormalisation group technique, we explore the effect of an explicit dimerisation on the ground-state phase diagram of the spin-1 XXZ chain with single-ion anisotropy D. We demonstrate that the Haldane phase between large-D and antiferromagnetic phases survives up to a critical dimerisation only. As a further new characteristic the dimerisation induces a direct continuous Ising quantum phase transition between the large-D and antiferromagnetic phases with central charge $$c=1/2$$

c
=
1
/
2

, which terminates at a critical end-point where $$c=7/10$$

c
=
7
/
10

. Calculating the critical exponents of the order parameter, neutral gap and spin–spin-correlation function, we find $$\beta =1/8$$

β
=
1
/
8

(1/24), $$\nu =1$$

ν
=
1

(5/9), and $$\eta =1/4$$

η
=
1
/
4

(3/20), respectively, which proves the Ising (tricritical Ising) universality class in accordance with field-theoretical predictions.
Non-Markovian quantum Otto refrigerator
Authors: Wiedmann Michael , Stockburger Jürgen T. , Ankerhold Joachim 
Published: April 2021

AbstractBased on a recently developed non-perturbative platform designed to simulate the full quantum dynamics of quantum thermal machines, the situation of a quantum refrigerator operating according to an Otto cycle is studied. The periodic steady-state dynamics is discussed in detail as well as the key thermodynamic quantities work, heat, and entropy. A particular benefit of the formulation is that it allows to access explicitly the work required for switching on and off the interaction with the respective thermal reservoirs in a consistent way. The domains in which the device operates in refrigerator mode are characterized.
Soft Drink and Juice Consumption and Renal Cell Carcinoma Incidence and Mortality in the European Prospective Investigation into Cancer and Nutrition
Authors: Heath Alicia K. , Clasen Joanna L. , Jayanth Nick P. , Jenab Mazda , Tjønneland Anne , Petersen Kristina Elin Nielsen , Overvad Kim , Srour Bernard , Katzke Verena , Bergmann Manuela M. , Schulze Matthias B. , Masala Giovanna , Krogh Vittorio , Tumino Rosario , Catalano Alberto , Pasanisi Fabrizio , Brustad Magritt , Olsen Karina Standahl , Skeie Guri , Luján-Barroso Leila , Rodríguez-Barranco Miguel , Amiano Pilar , Santiuste Carmen , Barricarte Gurrea Aurelio , Axelson Håkan , Ramne Stina , Ljungberg Börje , Watts Eleanor L. , Huybrechts Inge , Weiderpass Elisabete , Riboli Elio , Muller David C. 
Published: April 2021

Abstract

Background:
Renal cell carcinoma (RCC) accounts for more than 80% of kidney cancers in adults, and obesity is a known risk factor. Regular consumption of sweetened beverages has been linked to obesity and several chronic diseases, including some types of cancer. It is uncertain whether soft drink and juice consumption is associated with risk of RCC. We investigated the associations of soft drink and juice consumption with RCC incidence and mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods:
A total of 389,220 EPIC participants with median age of 52 years at recruitment (1991–2000) were included. Cox regression yielded adjusted HRs and 95% confidence intervals (CI) for RCC incidence and mortality in relation to intakes of juices and total, sugar-sweetened, and artificially sweetened soft drinks.

Results:
A total of 888 incident RCCs and 356 RCC deaths were identified. In models including adjustment for body mass index and energy intake, there was no higher risk of incident RCC associated with consumption of juices (HR per 100 g/day increment = 1.03; 95% CI, 0.97–1.09), total soft drinks (HR = 1.01; 95% CI, 0.98–1.05), sugar-sweetened soft drinks (HR = 0.99; 95% CI, 0.94–1.05), or artificially sweetened soft drinks (HR = 1.02; 95% CI, 0.96–1.08). In these fully adjusted models, none of the beverages was associated with RCC mortality (HR, 95% CI per 100 g/day increment 1.06, 0.97–1.16; 1.03, 0.98–1.09; 0.97, 0.89–1.07; and 1.06, 0.99–1.14, respectively).

Conclusions:
Consumption of juices or soft drinks was not associated with RCC incidence or mortality after adjusting for obesity.

Impact:
Soft drink and juice intakes are unlikely to play an independent role in RCC development or mortality.
Risk Factors for Breast Cancer, Overall and by Tumor Subtype, among Women from Mozambique, Sub-Saharan Africa
Authors: Brandão Mariana , Guisseve Assucena , Damasceno Albertino , Bata Genoveva , Silva-Matos Carla , Alberto Matos , Ferro Josefo , Garcia Carlos , Zaqueu Clésio , Lorenzoni Cesaltina , Leitão Dina , Soares Otília , Gudo-Morais Alberto , Schmitt Fernando , Morais Samantha , Tulsidás Satish , Carrilho Carla , Lunet Nuno 
Published: April 2021

AbstractBackground:Breast cancer incidence is rising in Africa, but there are scare data regarding risk factors in this region. We assessed the relation between risk factors and the occurrence of breast cancer, overall and by tumor subtype in women from Mozambique.Methods:The associations between education, number of births, height, weight, body mass index (BMI), and breast cancer risk among 138 cases (participants from the Moza-BC cohort) and 638 controls from the general population (from a World Health Organization stepwise approach to surveillance survey), recruited during 2014 to 2017, were investigated. Adjusted ORs (aOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression.Results:Multiparity (≥6 vs. 0–1 live births) was a protective factor for the development of hormone receptor (HR)–positive (aOR = 0.22; 95% CI, 0.08–0.64) and HR-positive/HER2-negative tumors (aOR = 0.20; 95% CI, 0.06–0.68), whereas a higher educational level (≥8 vs. 0 schooling years) increased breast cancer risk across all subtypes (overall aOR = 1.98; 95% CI, 1.04–3.80). Higher weight and BMI were associated with a higher breast cancer risk among postmenopausal women (per 1-kg increase: aOR = 1.05; 95% CI, 1.02–1.08; per 1-kg/m2 increase: aOR = 1.11; 95% CI, 1.04–1.18, respectively), but were protective in premenopausal women (aOR = 0.98; 95% CI, 0.96–0.99; aOR = 0.95; 95% CI, 0.91–0.99, respectively), regardless of subtype. Higher height increased the risk of HR-negative tumors in postmenopause (per 10-cm increase: aOR = 2.81; 95% CI, 1.41–6.03).Conclusion:These results demonstrate the etiological heterogeneity of breast cancer among native African women, namely regarding the differential effect of multiparity, education, and body parameters in breast cancer risk.Impact:As the prevalence of obesity grows, these findings are important to inform public health policies on cancer prevention, by highlighting obesity as a modifiable risk factor for breast cancer among African women.
Development and Validation of a Novel Nomogram for Individualized Prediction of Survival in Cancer of Unknown Primary
Authors: Raghav Kanwal , Hwang Hyunsoo , Jácome Alexandre A. , Bhang Eric , Willett Anneleis , Huey Ryan W. , Dhillon Nishat P. , Modha Jignesh , Smaglo Brandon , Matamoros Aurelio , Estrella Jeannelyn S. , Jao Justin , Overman Michael J. , Wang Xuemei , Greco F. Anthony , Loree Jonathan M. , Varadhachary Gauri R. 
Published: April 2021

Abstract

Purpose:
Prognostic uncertainty is a major challenge for cancer of unknown primary (CUP). Current models limit a meaningful patient-provider dialogue. We aimed to establish a nomogram for predicting overall survival (OS) in CUP based on robust clinicopathologic prognostic factors.

Experimental Design:
We evaluated 521 patients with CUP at MD Anderson Cancer Center (MDACC; Houston, TX; 2012–2016). Baseline variables were analyzed using Cox regression and nomogram developed using significant predictors. Predictive accuracy and discriminatory performance were assessed by calibration curves, concordance probability estimate (CPE ± SE), and concordance statistic (C-index). The model was subjected to bootstrapping and multi-institutional external validations using two independent CUP cohorts: V1 [MDACC (2017), N = 103] and V2 (BC Cancer, Vancouver, Canada and Sarah Cannon Cancer Center/Tennessee Oncology, Nashville, TN; N = 302).

Results:
Baseline characteristics of entire cohort (N = 926) included: median age (63 years), women (51%), Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 (64%), adenocarcinomas (52%), ≥3 sites of metastases (30%), and median follow-up duration and OS of 40.1 and 14.7 months, respectively. Five independent prognostic factors were identified: gender, ECOG PS, histology, number of metastatic sites, and neutrophil-lymphocyte ratio. The resulting model predicted OS with CPE of 0.69 [SE: ± 0.01; C-index: 0.71 (95% confidence interval: 0.68–0.74)] outperforming Culine/Seve prognostic models (CPE: 0.59 ± 0.01). CPE for external validation cohorts V1 and V2 were 0.67 (± 0.02) and 0.70 (± 0.01), respectively. Calibration curves for 1-year OS showed strong agreement between nomogram prediction and actual observations in all cohorts.

Conclusions:
Our user-friendly CUP nomogram integrating commonly available baseline factors provides robust personalized prognostication which can aid clinical decision making and selection/stratification for clinical trials.
Phase II Multicenter Study of Enzalutamide in Metastatic Castration-Resistant Prostate Cancer to Identify Mechanisms Driving Resistance
Authors: McKay Rana R. , Kwak Lucia , Crowdis Jett P. , Sperger Jamie M. , Zhao Shuang G. , Xie Wanling , Werner Lillian , Lis Rosina T. , Zhang Zhenwei , Wei Xiao X. , Lang Joshua M. , Van Allen Eliezer M. , Bhatt Rupal S. , Yu Evan Y. , Nelson Peter S. , Bubley Glenn J. , Montgomery R. Bruce , Taplin Mary-Ellen 
Published: April 2021

Abstract

Purpose:
Enzalutamide is a second-generation androgen receptor (AR) inhibitor that has improved overall survival (OS) in metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients develop resistance. We designed a phase II multicenter study of enzalutamide in metastatic CRPC incorporating tissue and blood biomarkers to dissect mechanisms driving resistance.

Patients and Methods:
Eligible patients with metastatic CRPC underwent a baseline metastasis biopsy and then initiated enzalutamide 160 mg daily. A repeat metastasis biopsy was obtained at radiographic progression from the same site when possible. Blood for circulating tumor cell (CTC) analysis was collected at baseline and progression. The primary objective was to analyze mechanisms of resistance in serial biopsies. Whole-exome sequencing was performed on tissue biopsies. CTC samples underwent RNA sequencing.

Results:
A total of 65 patients initiated treatment, of whom 22 (33.8%) had received prior abiraterone. Baseline biopsies were enriched for alterations in AR (mutations, amplifications) and tumor suppression genes (PTEN, RB1, and TP53), which were observed in 73.1% and 92.3% of baseline biopsies, respectively. Progression biopsies revealed increased AR amplifications (64.7% at progression vs. 53.9% at baseline) and BRCA2 alterations (64.7% at progression vs. 38.5% at baseline). Genomic analysis of baseline and progression CTC samples demonstrated increased AR splice variants, AR-regulated genes, and neuroendocrine markers at progression.

Conclusions:
Our results demonstrate that a large proportion of enzalutamide-treated patients have baseline and progression alterations in the AR pathway and tumor suppressor genes. We demonstrate an increased number of BRCA2 alterations post-enzalutamide, highlighting the importance of serial tumor sampling in CRPC.