bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study in the pseudocereal quinoa reveals selection pattern typical for crops with a short breeding history
Authors: Patiranage Dilan S. R. , Rey Elodie , Emrani Nazgol , Wellman Gordon , Schmid Karl , Schmöckel Sandra M. , Tester Mark , Jung Christian 
Published: December 2020

AbstractQuinoa germplasm preserves useful and substantial genetic variation, yet it remains untapped due to a lack of implementation of modern breeding tools. We have integrated field and sequence data to characterize a large diversity panel of quinoa. Whole-genome sequencing of 310 accessions revealed 2.9 million polymorphic high confidence SNP loci. Highland and Lowland quinoa were clustered into two main groups, withFSTdivergence of 0.36 and fast LD decay of 6.5 and 49.8 Kb, respectively. A genome-wide association study uncovered 600 SNPs stably associated with 17 agronomic traits. Two candidate genes are associated with thousand seed weight, and a resistance gene analog is associated with downy mildew resistance. We also identified pleiotropically acting loci for four agronomic traits that are highly responding to photoperiod hence important for the adaptation to different environments. This work demonstrates the use of re-sequencing data of an orphan crop, which is partially domesticated to rapidly identify marker-trait association and provides the underpinning elements for genomics-enabled quinoa breeding.
Augmented expansion of Treg cells from healthy and autoimmune subjects via adult progenitor cell co-culture
Authors: Reading JL , Roobrouck VD , Hull CM , Becker PD , Beyens J , Valentin-Torres A , Boardman D , Nova Lamperti E , Stubblefield S , Lombardi G , Deans R , Ting AE , Tree T 
Published: December 2020

AbstractRecent clinical experience has demonstrated that adoptive regulatory T cell therapy is a safe and feasible strategy to suppress immunopathology via induction of host tolerance to allo- and autoantigens. However, clinical trials continue to be compromised due to an inability to manufacture a sufficient Treg cell dose. Multipotent adult progenitor cells (MAPCⓇ) promote regulatory T cell differentiationin vitro, suggesting they may be repurposed to enhanceex vivoexpansion of Tregs for adoptive cellular therapy. Here, we use a GMP compatible Treg expansion platform to demonstrate that MAPC cell-co-cultured Tregs (MulTreg) exhibit a log-fold increase in yield across two independent cohorts, reducing time to target dose by an average of 30%. Enhanced expansion is linked with a distinct Treg cell-intrinsic transcriptional program, characterized by diminished levels of core exhaustion (BATF, ID2, PRDM1, LAYN, DUSP1), and quiescence (TOB1, TSC22D3) related genes, coupled to elevated expression of cell-cycle and proliferation loci (MKI67, CDK1, AURKA, AURKB). In addition, MulTreg display a unique gut homing (CCR7lo β7hi) phenotype and importantly, are more readily expanded from patients with autoimmune disease compared to matched Treg lines, suggesting clinical utility in gut and/or Th1-driven pathology associated with autoimmunity or transplantation. Relative to expanded Tregs, MulTreg retain equivalent and robust purity, FoxP3 TSDR demethylation, nominal effector cytokine production and potent suppression of Th1-driven antigen specific and polyclonal responsesin vitroand xeno graft vs host disease (xGvHD)in vivo. These data support the use of MAPC cell co-culture in adoptive Treg therapy platforms as a means to rescue expansion failure and reduce the time required to manufacture a stable, potently suppressive product.
The influence of the type of halogen substituent and its position on the molecular conformation, intermolecular interactions and crystal packing for a series of 1-benzoyl-3-(halogenophenyl)thioureas
Authors: Rosiak Damian , Okuniewski Andrzej , Chojnacki Jarosław 
Published: December 2020

By the reaction of benzoyl chloride, potassium isothiocyanate and the appropriate halogenoaniline, i.e. 2/3/4-(bromo/iodo)aniline, we have obtained five new 1-benzoyl-3-(halogenophenyl)thioureas, namely, 1-benzoyl-3-(2-bromophenyl)thiourea and 1-benzoyl-3-(3-bromophenyl)thiourea, C14H11BrN2OS, and 1-benzoyl-3-(2-iodophenyl)thiourea, 1-benzoyl-3-(3-iodophenyl)thiourea and 1-benzoyl-3-(4-iodophenyl)thiourea, C14H11IN2OS. Structural and conformational features of the compounds have been analyzed using X-ray diffraction and theoretical calculations. The novel compounds were characterized by solid-state IR and 1H/13C NMR spectroscopy. The conformations and intermolecular interactions, such as hydrogen bonds, π–π and S(6)...π stacking, and X...O (X = I or Br), I...S and I...π, have been examined and rationalized, together with four analogous compounds described previously in the literature. The set of nine compounds was chosen to examine how a change of the halogen atom and its position on the phenyl ring affects the molecular and crystal structures.
Mindful consumption of second-hand clothing: the role of eWOM, attitude and consumer engagement
Authors: Mohammad Jihad , Quoquab Farzana , Mohamed Sadom Nur Zulaikha 
Published: December 2020

PurposeThis study aims to examine the direct and indirect effects of electronic word of mouth (eWOM) on mindful consumption behaviour (MCB) in a sustainable clothing purchase context. In addition, it examines the mediating effect of “consumer engagement” and “attitude towards second-hand clothes”.Design/methodology/approachThe data were gathered through a self-administered questionnaire survey from Malaysian consumers who had experience in purchasing second-hand clothes. A total of 175 complete and useable questionnaires were obtained, which were then analysed by using the structural equation modelling-partial least square (SEM-PLS) technique.FindingsThe results of this study indicate support for the direct effect of eWOM on consumers' attitude towards second-hand clothes, consumer engagement and consumers’ MCB. The results also supported the relationship between consumer engagement and MCB, but the link between attitude and mindful consumption (MC) was not supported. Furthermore, the study confirmed the mediating effect of consumer engagement between eWOM and consumers’ MCB but did not support the mediating effect of attitude towards second-hand clothes.Originality/valueThis study is amongst the pioneers to elucidate MCB in the context of sustainable clothing. It examines the direct and indirect effects of eWOM on MCB, which has not been tested in the past literature. The mediating effects of consumer engagement and attitude towards second-hand clothes on the relationship between eWOM and MCB are also comparatively new links.
Manufacturer power over suppliers: scale development and validation
Authors: Jin Yan , Smith Joy Turnheim 
Published: December 2020

PurposeThis research empirically builds a manufacturing firm's power construct that can be used to assess the changes suppliers are willing to make in their operations decision areas, such as quality systems, product management, process management, material management systems and information systems. This approach has not been empirically explored in the operations and supply chain management literature. This research fills this gap with the new power definition method.Design/methodology/approachThis research conducted a two-stage scale development and validation process for a manufacturing firm's power over suppliers. A survey study collected 201 responses from the US manufacturing firms. The research used confirmatory factor analysis (CFA) to assess the validity and reliability of this construct.FindingsThe results confirmed the validity and reliability of a manufacturing firm's power over suppliers as a second-order variable, with five first-order constructs reflecting power in areas of quality, product, process, material and information systems.Practical implicationsManufacturing firms can use this instrument to assess the strengths and weaknesses of their power over suppliers in each decision area. From the results, companies can develop a power-competitiveness grid to guide their power enhancement efforts based on the competitive advantage being prioritized. Similarly, a resource-power grid can assist the manager in deciding whether to invest in a resource that benefits a particular power dimension.Originality/valueThis research contributes to supply chain power literature by taking a unique approach to defining a manufacturer's power regarding its suppliers' decision areas. This power structure opens the possibility to explore the relationship between a firm's resource, power and firm performance. As buyer–supplier power relationship building is increasingly important in the supply chain, knowing the parameters of the power relationship can help the manufacturing firm align its strategic focus to the areas that can be supported by the supply chain.
Representing Transgender in the 1970s Australian Media
Authors: Riseman Noah 
Published: December 2020

AbstractIn 1970s Australia, magazines and newspapers regularly featured stories about transgender women. The articles were often exploitative and depicted transgender people as freaks, with headlines designed to shock and mock. Digging deeper, there is another side to transgender people in the Australian media. Notwithstanding the exploitative nature of the coverage, the media was still a site of transgender visibility in an era where there otherwise was none. Oral histories with transgender Australians often mention the importance of a particular television show, article or magazine because they saw others ‘like them’, and they realised that they were not alone. Some transgender people even kept those articles for years because of the connections they felt to an otherwise uncertain identity. There were also features in the press that were empathetic to transgender Australians, whether that be on the Australian Broadcasting Commission (ABC), in magazines such as Cleo or in broadsheet newspapers. This article analyses the complex role that media played representing and relating to transgender Australians in the 1970s. Drawing on a mix of newspaper, magazine and television sources, as well as oral histories, the article opens new lines of inquiry about histories of transgender visibility, public discourse and understanding the self.
Review article: a treatment algorithm for patients with chronic liver disease and severe thrombocytopenia undergoing elective medical procedures in the United States
Authors: Dieterich Douglas T. , Bernstein David , Flamm Steven , Pockros Paul J. , Reau Nancy 
Published: December 2020

SummaryBackgroundThrombocytopenia is the most common haematological abnormality in patients with chronic liver disease in the United States. Severe thrombocytopenia (platelet count <50 × 109/L) can complicate the management of patients with chronic liver disease by significantly increasing the potential risk of bleeding during or after invasive procedures. The current standard‐of‐care treatment for severe thrombocytopenia is platelet transfusion. Novel agents that target the thrombopoietin pathway, including receptor agonists avatrombopag and lusutrombopag, have recently shown promise in clinical trials as alternatives to platelet transfusion.AimTo review treatment options for severe thrombocytopenia, including platelet transfusion and thrombopoietin‐receptor agonists, with the aim of producing a simplified treatment algorithm.MethodsFive liver disease specialists were assigned sections of the manuscript to research and present at a consensus meeting in April 2019, with the goal of creating an easy‐to‐use, effective treatment plan for severe thrombocytopenia in patients with chronic liver disease.ResultsThrough discussion and collaborative decision making, a simplified algorithm was developed to provide guidance to healthcare professionals on treating severe thrombocytopenia in patients with chronic liver disease undergoing elective medical procedures in the United States. As part of these guidelines, we outline the use of the US Food and Drug Administration‐approved thrombopoietin receptor agonists avatrombopag and lusutrombopag as well tolerated and effective alternatives to platelet transfusion.ConclusionsThis algorithm provides guidance for the management of severe thrombocytopenia to reduce bleeding risks in patients with chronic liver disease undergoing elective procedures, while reducing requirement for platelet transfusion.
Magnetic resonance imaging‐guided transurethral ultrasound ablation in patients with localised prostate cancer: 3‐year outcomes of a prospective Phase I study
Authors: Nair Shiva M. , Hatiboglu Gencay , Relle James , Hetou Khalil , Hafron Jason , Harle Christopher , Kassam Zahra , Staruch Robert , Burtnyk Mathieu , Bonekamp David , Schlemmer Heinz‐Peter , Roethke Matthias C. , Mueller‐Wolf Maya , Pahernik Sascha , Chin Joseph L. 
Published: December 2020

ObjectivesTo report the 3‐year follow‐up of a Phase I study of magnetic resonance imaging (MRI)‐guided transurethral ultrasound ablation (TULSA) in 30 men with localised prostate cancer. Favourable 12‐month safety and ablation precision were previously described.Patients and MethodsAs a mandated safety criterion, TULSA was delivered as near whole‐gland ablation, applying 3‐mm margins sparing 10% of peripheral prostate tissue in 30 men. After 12‐month biopsy and MRI, biannual follow‐up included prostate‐specific antigen (PSA), adverse events (AEs), and functional quality‐of‐life assessment, with repeat systematic biopsy at 3 years.ResultsA 3‐year follow‐up was completed by 22 patients. Between 1 and 3 years, there were no new serious or severe AEs. Urinary and bowel function remained stable. Erectile function recovered by 1 year and was stable at 3 years. The PSA level decreased 95% to a median (interquartile range) nadir of 0.33 (0.1–0.4) ng/mL, stable to 0.8 (0.4–1.6) ng/mL at 3 years. Serial biopsies identified clinically significant disease in 10/29 men (34%) and any cancer in 17/29 (59%). By 3 years, seven men had recurrence (four histological, three biochemical) and had undergone salvage therapy without complications (including six prostatectomies). At 3 years, three of 22 men refused biopsy, and two of the 22 (9%) had clinically significant disease (one new, one persistent). Predictors of salvage therapy requirement included less extensive ablation coverage and higher PSA nadir.ConclusionWith 3‐year Phase I follow‐up, TULSA demonstrates safe and precise ablation for men with localised prostate cancer, providing predictable PSA and biopsy outcomes, without affecting functional abilities or precluding salvage therapy.
Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma
Authors: Kroeze Stephanie G.C. , Fritz Corinna , Schaule Jana , Siva Shankar , Kahl Klaus H. , Sundahl Nora , Blanck Oliver , Kaul David , Adebahr Sonja , Verhoeff Joost J.C. , Skazikis Georgios , Roeder Falk , Geier Michael , Eckert Franziska , Guckenberger Matthias 
Published: December 2020

ObjectivesTo evaluate the safety and efficacy of stereotactic radiotherapy (SRT) in patients with metastatic renal cell carcinoma (mRCC) concurrently receiving targeted therapy (TT) or immunotherapy.Patients and MethodsData on patients with mRCC were extracted from a retrospective international multicentre register study (TOaSTT), investigating SRT concurrent (≤30 days) with TT/immune checkpoint inhibitor (ICI) therapy. Overall survival (OS), progression‐free survival (PFS), local metastasis control (LC) and time to systemic therapy switch were analysed using Kaplan–Meier curves and log‐rank testing. Clinical and treatment factors influencing survival were analysed using multivariate Cox regression. Acute and late SRT‐induced toxicity were defined according to the Common Terminology Criteria for Adverse Events v.4.03.ResultsFifty‐three patients who underwent 128 sessions of SRT were included, of whom 58% presented with oligometastatic disease (OMD). ICIs and TT were received by 32% and 68% of patients, respectively. Twenty patients (37%) paused TT for a median (range) of 14 (2–21) days. ICI therapy was not paused in any patient. A median (range) of 1 (1–5) metastatic tumour was treated per patient, with a median (range) SRT dose of 65 (40–129.4) Gy (biologically effective dose). The OS, LC and PFS rates at 1 year were 71%, 75% and 25%, respectively. The median OS and PFS were not significantly different among patients receiving TT vs those receiving ICIs (P = 0.329). New lesions were treated with a repeat radiotherapy course in 46% of patients. After 1 year, 62% of patients remained on the same systemic therapy as at the time of SRT; this was more frequent for ICI therapy compared to TT (83% vs 36%; P = 0.035). OMD was an independent prognostic factor for OS (P = 0.004, 95% confidence interval [CI] 0.035–0.528) and PFS (P = 0.004; 95% CI 0.165–0.717) in multivariate analysis. Eastern Cooperative Oncology Group performance status (ECOG‐PS) was the other independent prognostic factor for OS (P = 0.001, 95% CI 0.001–0.351). Acute grade 3 toxicity was observed in two patients, and late grade 3 toxicity in one patient. No grade 4 or 5 toxicity was observed.ConclusionCombined treatment with TT or immunotherapy and concurrent SRT was safe, without signals of increased severe toxicity. As we observed no signal of excess toxicity, full‐dose SRT should be considered to achieve optimal metastasis control in patients receiving TT or immunotherapy. Favourable PFS and OS were observed for patients with oligometastatic RCC with a good ECOG‐PS, which should form the basis for prospective testing of this treatment strategy in properly designed clinical trials.
Neoadjuvant chemotherapy plus radical cystectomy versus radical cystectomy alone in clinical T2 bladder cancer without hydronephrosis
Authors: Soria Francesco , Black Peter C. , Fairey Adrian S. , Cookson Michael S. , Yu Evan Y. , Kassouf Wassim , Dall'Era Marc A. , Sridhar Srikala S. , McGrath John S. , Wright Jonathan L. , Thorpe Andrew C. , Morgan Todd M. , Daneshmand Siamak , Holzbeierlein Jeff M. , Bivalacqua Trinity J. , North Scott , Barocas Daniel A. , Lotan Yair , Grivas Petros , Stephenson Andrew J. , Shah Jay B. , van Rhijn Bas W. , Spiess Philippe E. , Shariat Shahrokh F. , Gontero Paolo 
Published: December 2020

ObjectivesTo assess the efficacy of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in a retrospective multicentre cohort of patients with cT2N0M0 bladder cancer (BCa) without preoperative hydronephrosis.Patients and MethodsThis was a propensity‐based analysis of 619 patients. Of these, 316 were treated with NAC followed by RC and 303 with upfront RC. After multiple imputations, inverse probability of treatment weighting (IPTW) was used to account for potential selection bias. Multivariable logistic regression analysis was performed to evaluate the impact of NAC on pathological complete response and downstaging at RC, while IPTW‐adjusted Kaplan–Meier curves and Cox regression models were built to evaluate the impact of NAC on overall survival (OS).ResultsAfter IPTW‐adjusted analysis, standardised differences between groups were <15%. A complete response (pT0N0) at final pathology was achieved in 94 (30%) patients receiving NAC and nine (3%) undergoing upfront RC. Downstaging to non‐muscle‐invasive disease (<pT2N0M0) was observed in 174 (55%) patients after NAC and in 72 (24%) without NAC. On multivariable analysis, NAC was found to be an independent predictor of both pathological complete response and downstaging. No significant difference with respect to OS was observed between groups with a median follow‐up of 18 months.ConclusionsIn patients with cT2N0 BCa and no preoperative hydronephrosis, NAC increased the rate of pathological complete response and downstaging.
Activation of Wnt/β‐catenin signalling and HIF1α stabilisation alters pluripotency and differentiation/proliferation properties of human‐induced pluripotent stem cells
Authors: Wei Hua , Beeson Gyda C. , Ye Zhiwei , Zhang Jie , Yao Hai , Damon Brooke , Morad Martin 
Published: December 2020

Background InformationWnt/β‐catenin signalling, in the microenvironment of pluripotent stem cells (PSCs), plays a critical role in their differentiation and proliferation. Contradictory reports on the role of Wnt/β‐catenin signalling in PSCs self‐renewal and differentiation, however, render these mechanisms largely unclear.ResultsWnt/β‐catenin signalling pathway in human‐induced pluripotent stem cells (hiPSCs) was activated by inhibiting glycogen synthase kinase 3 (GSK3), driving the cells into a mesodermal/mesenchymal state, exhibiting proliferative, invasive and anchorage‐independent growth properties, where over 70% of cell population became CD 44 (+)/CD133 (+). Wnt/β‐catenin signalling activation also altered the metabolic state of hiPSCs from aerobic glycolysis to oxidative metabolism and changed their drug and oxidative stress sensitivities. These effects of GSK3 inhibition were suppressed in HIF1α‐stabilised cells.ConclusionsPersistent activation of Wnt/β‐catenin signalling endows hiPSCs with proliferative/invasive ‘teratoma‐like’ states, shifting their metabolic dependence and allowing HIF1α‐stabilisation to inhibit their proliferative/invasive properties.SignificanceThe hiPSC potential to differentiate into ‘teratoma‐like’ cells suggest that stem cells may exist in two states with differential metabolic and drug dependency.
Intestinal phenotype is maintained by Atoh1 in the cancer region of intraductal papillary mucinous neoplasm
Authors: Katsukura Nobuhiro , Watanabe Sho , Shirasaki Tomoaki , Hibiya Shuji , Kano Yoshihito , Akahoshi Keiichi , Tanabe Minoru , Kirimura Susumu , Akashi Takumi , Kitagawa Masanobu , Okamoto Ryuichi , Watanabe Mamoru , Tsuchiya Kiichiro 
Published: December 2020

AbstractIntraductal papillary mucinous neoplasm (IPMN) is a precancerous lesion of pancreatic cancer. Although there are 4 types of IPMN, among which intestinal‐type IPMN is likely to progress into invasive cancer known as colloid carcinoma, no information regarding the involvement of the intestinal phenotype in the carcinogenesis of IPMN exists. The present study was conducted to explore how the intestinal differentiation system is maintained during the tumor progression of intestinal‐type IPMN using surgical resection specimens. Results showed that Atoh1, a critical transcriptional factor for intestinal differentiation toward the secretory lineages of intestinal epithelial cells, was expressed in an invasive‐grade IPMN. To determine the function of Atoh1 in pancreatic cancer, we generated a pancreatic ductal adenocarcinoma (PDAC) cell line overexpressing Atoh1. In a xenograft model, we successfully induced an IPMN phenotype in PDAC cells via Atoh1 induction. Finally, for the first time, we discovered that GPA33 is expressed in intestinal‐type IPMN, thereby suggesting a novel target for cancer therapy. In conclusion, the intestinal differentiation system might be maintained during tumor progression of intestinal‐type IPMN. Further analysis of the function of Atoh1 in IPMN might be useful for understanding the molecular mechanism underlying the malignant potential during the tumor progression of IPMN.