bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for the PRIMARY clinical trial, a prospective, multicentre, cross‐sectional study of the additive diagnostic value of gallium‐68 prostate‐specific membrane antigen positron‐emission tomography/computed tomography to multiparametric magnetic resonance imaging in the diagnostic setting for men being investigated for prostate cancer
Authors: Amin Amer , Blazevski Alexandar , Thompson James , Scheltema Matthijs J. , Hofman Michael S. , Murphy Declan , Lawrentschuk Nathan , Sathianathen Niranjan , Kapoor Jada , Woo Henry H. , Chalasani Venu , Rasiah Krishan , van Leeuwen Pim J. , Tang Reuben , Cusick Thomas , Stricker Phillip , Emmett Louise 
Published: January 2020

ObjectivesPrimary objectives: To determine the additive value of gallium‐68 prostate‐specific membrane antigen (PSMA) positron emission topography (PET)/computed tomography (CT) when combined with multiparametric magnetic resonance imaging (mpMRI) detecting clinically significant prostate cancer (csPCa) in men undergoing initial biopsy for suspicion of PCa, and to determine the proportion of men who could have avoided prostate biopsy with positive mpMRI (PI‐RADS ≥3) but negative PSMA‐PET/CT. Secondary objectives: To determine the proportion of men who had csPCa detected only by PSMA‐PET/CT or only by systematic prostate biopsy; to compare index lesions by template biopsies vs targeted lesions identified on mpMRI or PSMA‐PET/CT; to assess whether there may be health economic benefit or harm if PSMA‐PET/CT is incorporated into the diagnostic algorithm; and to develop a nomogram which combines clinical, imaging and biomarker data to predict the likelihood of csPCa. Patients and MethodsThe PRIMARY trial is a multicentre, prospective, cross‐sectional study that meets the criteria for level 1 evidence in diagnostic test evaluation. PRIMARY will investigate if a limited (pelvic‐only) PSMA‐PET/CT in combination with routine mpMRI can reliably discriminate men with csPCa from those without csPCa. We conducted a power calculation based on pilot data and will recruit up to 600 men who will undergo PSMA‐PET/CT (the index test), mpMRI (standard test) and transperineal template + targeted (PSMA‐PET/CT and/or mpMRI) biopsies (reference test). The conduct and reporting of the mpMRI and PSMA‐PET/CT will be blinded to each other.ResultsThe PRIMARY trial will measure and compare sensitivity, specificity, positive predictive value and negative predictive value of both mpMRI and PSMA‐PET/CT vs targeted prostrate biopsy. The results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of csPCa. Furthermore, we will assess whether there is a health economic benefit in incorporating PSMA‐PET/CT into the diagnostic algorithm.ConclusionsThis trial will provide robust prospective data to determine the diagnostic ability of PSMA‐PET/CT used in addition to mpMRI. It will establish if certain patients can avoid biopsy in the investigation of PCa.
Using next‐generation sequencing to redefineBRCAnessin triple‐negative breast cancer
Authors: Lin Po‐Han , Chen Ming , Tsai Li‐Wei , Lo Chiao , Yen Tzu‐Chun , Huang Thomas Yoyan , Chen Chih‐Kai , Fan Sheng‐Chih , Kuo Sung‐Hsin , Huang Chiun‐Sheng 
Published: January 2020

AbstractBRCAnessis considered a predictive biomarker to platinum and poly(ADP‐ribose) polymerase (PARP) inhibitors. However, recent trials showed that its predictive value was limited in triple‐negative breast cancer (TNBC) treated with platinum. Moreover, tumors with mutations of DNA damage response (DDR) genes, such as homologous recombination (HR) genes, could be sensitive to platinum and PARP inhibitors. Thus, we aim to explore the relationship between mutation status of DDR genes andBRCAnessin TNBC. We sequenced 56 DDR genes in 120 TNBC and identifiedBRCAnessby array comparative genomic hybridization. The sequencing results showed that 13, 14, and 14 patients hadBRCA, non‐BRCAHR, and non‐HR DDR gene mutations, respectively. Array comparative genomic hybridization revealed thatBRCA‐mutated and HR gene‐mutated TNBC shared similarBRCAnessfeatures, both having higher numbers and longer length of large‐scale structural aberration (LSA, >10 Mb) and similar altered chromosomal regions of LSA. These suggested non‐BRCAHR gene‐mutated TNBC shared similar characteristics withBRCA‐mutated TNBC, indicating non‐BRCAHR gene‐mutated TNBC sensitive to platinum and PARP inhibitors. Among tumors with mutation of non‐HR DDR genes, 3PTENand 1MSH6mutation also contained significant LSAs (BRCAness); however, they had different regions of genomic alteration toBRCAand HR gene‐mutated tumors, might explain prior findings thatPTEN‐andMSH6‐mutated cancer cells not sensitive to PARP inhibitors. Therefore, we hypothesize that the heterogeneous genomic background ofBRCAnessindicates different responsiveness to platinum and PARP inhibitors. Direct sequencing DDR genes in TNBC should be applied to predict their sensitivity toward platinum and PARP inhibitors.
Genome organization in proximity to the BAP1 locus appears to play a pivotal role in a variety of cancers
Authors: Sharma Amit , Liu Hongde , Tobar‐Tosse Fabian , Noll Angela , Chand Dakal Tikam , Li Huamei , Holz Frank G. , Loeffler Karin U. , Herwig‐Carl Martina C. 
Published: January 2020

AbstractCancer studies primarily focus on the characterization of the key driver genes and the underlying pathways. However, the contribution of other cancer‐associated genes located in the genomic neighborhood of the driver genes could help to understand further aspects of cancer progression. Given the frequent involvement of chromosome 3 in multiple human cancers, in particular in the form of the prognostically highly relevant monosomy 3 in uveal melanoma (UM), we investigated the cumulative impact of cancer‐associated genes on chromosome 3. Our analysis showed that these genes are enriched with repetitive elements with genes surrounded by distinctive repeats (MIR, hAT‐Charlie, ERVL‐MaLR, LINE‐2, and simple/low complexity) in the promoter being more precisely associated with cancer‐related pathways than the ones with major transposable elements (SINE/Alu and LINE‐1). Additionally, these genes showed strong intrachromosomal chromatin interactions in 3D nuclear organization. Further investigations revealed a genomic hotspot in the vicinity of BAP1 locus, which is affected in 27 types of different cancers and contains abundant noncoding RNAs that are often expressed in a tissue‐specific manner. The cross‐species comparison of these cancer‐associated genes revealed mostly a shared synteny in closer primates. However, near to the BAP1 locus signs of chromosomal inversions were observed during the course of evolution. To our knowledge, this is the first study to characterize the entire genomic neighborhood of cancer‐associated genes located on any single chromosome. Based on our results, we hypothesize that monosomy of chromosome 3 will have important clinical and molecular consequences in the respective diseases and in particular in UM.
Evolution of macroprolactinomas during pregnancy: A cohort study of 85 pregnancies
Authors: Barraud Sara , Guédra Lucile , Delemer Brigitte , Raverot Gérald , Ancelle Déborah , Fèvre Anne , Jouanneau Emmanuel , Litré Claude‐Fabien , Wolak‐Thierry Aurore , Borson‐Chazot Françoise , Decoudier Bénédicte 
Published: January 2020

AbstractObjectivePregnancy in patients with macroprolactinomas has been associated with a higher risk of pituitary tumour growth. However, the incidence and risk factors remain unclear. We aimed to evaluate the evolution of macroprolactinomas during pregnancy and to identify potential risk factors.Design, patients and measurementsThis is a two‐centre, retrospective, observational study. All patients with macroprolactinomas, treated with a dopamine receptor agonist (DA), and who had at least one pregnancy were included.ResultsThere were a total of 85 viable pregnancies in 46 patients with macroprolactinomas. At diagnosis, mean size of pituitary adenomas was 17.9 ± 8.2 mm (10‐43 mm) and mean plasma prolactin level was 1012.2 ± 1606.1 µg/L (60‐7804 µg/L). Tumour growth‐related symptoms were identified 12 times in 9 patients (19.6%) including 3 cases of apoplexy. Restarting, changing and/or increasing DA treatment was effective in 10 cases. Emergency surgery had to be performed twice (due to pituitary apoplexy). Patients with tumour progression tended to present with larger tumours after initial treatment and before pregnancy (9.9 vs 5.9 mm; P = .0504 and 11.5 vs 7.3 mm; P = .0671, respectively), whereas adenoma size at diagnosis did not seem to be a significant factor. The obstetrical outcomes were comparable to the general population.ConclusionsSymptomatic growth of macroprolactinoma during pregnancy occurred in 19.6% of medically treated patients. This risk seems higher for patients with poor initial tumour response to the DA treatment. Tumour progression is generally well controlled with medical treatment during pregnancy.
Implications of zero‐deforestation commitments: Forest quality and hunting pressure limit mammal persistence in fragmented tropical landscapes
Authors: Deere Nicolas J. , Guillera‐Arroita Gurutzeta , Platts Philip J. , Mitchell Simon L. , Baking Esther L. , Bernard Henry , Haysom Jessica K. , Reynolds Glen , Seaman Dave J. I. , Davies Zoe G. , Struebig Matthew J. 
Published: January 2020

AbstractZero‐deforestation commitments seek to decouple agricultural production and forest loss to improve prospects for biodiversity. However, the effectiveness of methods designed to meet these commitments is poorly understood. In a highly fragmented tropical landscape dominated by oil palm, we tested the capacity for the High Carbon Stock (HCS) Approach to prioritize forest remnants that sustain mammal diversity. Patches afforded high priority by HCS protocols (100 ha core area) provided important refuges for IUCN‐threatened species and megafauna. However, patch‐scale HCS area recommendations conserved only 35% of the mammal community. At least 3,000 ha would be required to retain intact mammal assemblages, with nearly 10 times this area needed if hunting pressure was high. While current HCS protocols will safeguard patches capable of sustaining biodiversity, highly fragmented tropical landscapes typical of zero‐deforestation pledges will require thinking beyond the patch toward strategically configured forest remnants at the landscape level and enforcing strict controls on hunting.
Human monocytes subjected to ischaemia/reperfusion inhibit angiogenesis and wound healing in vitro
Authors: Hummitzsch Lars , Albrecht Martin , Zitta Karina , Hess Katharina , Parczany Kerstin , Rusch René , Cremer Jochen , Steinfath Markus , Haneya Assad , Faendrich Fred , Berndt Rouven 
Published: January 2020

AbstractObjectivesThe sequence of initial tissue ischaemia and consecutive blood flow restoration leads to ischaemia/reperfusion (I/R) injury, which is typically characterized by a specific inflammatory response. Migrating monocytes seem to mediate the immune response in ischaemic tissues and influence detrimental as well as regenerative effects during I/R injury.Materials and MethodsTo clarify the role of classical monocytes in I/R injury, isolated human monocytes were subjected to I/R in vitro (3 hours ischaemia followed by 24 hours of reperfusion). Cellular resilience, monocyte differentiation, cytokine secretion, as well as influence on endothelial tube formation, migration and cell recovery were investigated.ResultsWe show that I/R supported an enhanced resilience of monocytes and induced intracellular phosphorylation of the prosurvival molecules Erk1/2 and Akt. FACS analysis showed no major alteration in monocyte subtype differentiation and surface marker expression under I/R. Further, our experiments revealed that I/R changes the cytokine secretion pattern, release of angiogenesis associated proteins and MMP‐9 activity in supernatants of monocytes exposed to I/R. Supernatants from monocytes subjected to I/R attenuated endothelial tube formation as indicator for angiogenesis as well as endothelial cell migration and recovery.ConclusionIn summary, monocytes showed no significant change in cellular integrity and monocyte subtype after I/R. Functionally, monocytes might have a rather detrimental influence during the initial phase of I/R, suppressing endothelial cell migration and neoangiogenesis.
Active interfacial dynamic transport of fluid in a network of fibrous connective tissues throughout the whole body
Authors: Li Hongyi , Yin Yajun , Yang Chongqing , Chen Min , Wang Fang , Ma Chao , Li Hua , Kong Yiya , Ji Fusui , Hu Jun 
Published: January 2020

AbstractFluid in interstitial spaces accounts for ~20% of an adult body weight and flows diffusively for a short range. Does it circulate around the body like vascular circulations? This bold conjecture has been debated for decades. As a conventional physiological concept, interstitial space is a micron‐sized space between cells and vasculature. Fluid in interstitial spaces is thought to be entrapped within interstitial matrix. However, our serial data have further defined a second space in interstitium that is a nanosized interfacial transport zone on a solid surface. Within this fine space, fluid along a solid fibre can be transported under a driving power and identically, interstitial fluid transport can be visualized by tracking the oriented fibres. Since 2006, our data from volunteers and cadavers have revealed a long‐distance extravascular pathway for interstitial fluid flow, comprising at least four types of anatomic distributions. The framework of each extravascular pathway contains the longitudinally assembled and oriented fibres, working as a fibrorail for fluid flow. Interestingly, our data showed that the movement of fluid in a fibrous pathway is in response to a dynamic driving source and named as dynamotaxis. By analysis of previous studies and our experimental results, a hypothesis of interstitial fluid circulatory system is proposed.
Identification and characterization of chronic lung allograft dysfunction patients with mixed phenotype: A single‐center study
Authors: Verleden Stijn E. , Von Der Thüsen Jan , Van Herck Anke , Weynand Birgit , Verbeken Erik , Verschakelen Johny , Dubbeldam Adriana , Vanaudenaerde Bart M. , Vos Robin , Verleden Geert M. ,   the Leuven Lung Transplant Group
Published: January 2020

AbstractRationalePatients can change chronic lung allograft dysfunction (CLAD) phenotype, especially from BOS to mixed phenotype. Our aim was to further characterize these patients.MethodMixed CLAD was defined as a restrictive physiology with persistent CT opacities, after initial bronchiolitis obliterans syndrome (BOS) diagnosis. The incidence, prognosis, pulmonary function, radiology, pathology, and airway inflammation were compared between patients with restrictive allograft syndrome (RAS) and mixed CLAD.ResultA total of 268 (44%) patients developed CLAD of which 47 (18%) were diagnosed with RAS “ab initio,” 215 (80%) with BOS, and 6 (2%) an undefined phenotype. Twenty‐five patients developed a mixed CLAD phenotype (24 BOS to mixed and 1 RAS to mixed). Survival after mixed phenotype diagnosis was comparable (P = .39) to RAS. More emphysema patients developed a mixed phenotype (P = .020) compared to RAS ab initio, while mixed CLAD patients had a lower FEV1 (P < .0001) and FEV1/FVC (P = .0002) at diagnosis compared to RAS ab initio. CT scans in patients with the mixed phenotype demonstrated apical predominance of the opacities (P = .0034) with pleuroparenchymal fibroelastosis on histopathology.ConclusionWe further characterized patients with a mixed phenotype of CLAD. Although the survival after diagnosis was comparable to RAS ab initio patients, there was a difference in demography, pulmonary function, radiology, and pathology.
Development of an objective, standardized tool for surgical assessment of deceased donor kidneys: The Cambridge Kidney Assessment Tool
Authors: Ayorinde John O. O. , Hamed Mazin , Goh Mingzheng Aaron , Summers Dominic M. , Dare Anna , Chen Yining , Saeb‐Parsy Kourosh 
Published: January 2020

AbstractQuality assessment in kidney transplantation involves inspection to identify negative markers of organ quality. However, there is a paucity of evidence guiding surgical appraisal, and currently there is no evidence to differentiate important features from those that can be safely ignored. We propose a method to standardize surgical assessment and derived a simple rule to rapidly identify kidneys suitable for transplantation. Donor and recipient data were recorded alongside clinical outcomes in a prospectively maintained database. We developed a proforma (Cambridge Kidney Assessment Tool, CKAT) and used it to assess deceased donor kidney transplants. Factors predictive of utilization were identified by multivariate and univariate logistic regression analysis of CKAT‐assessment scores, and test performance was evaluated using standard 2 × 2 contingency tables. Ninety‐seven kidneys were included at a single center (2013‐2014), and 184 CKAT assessments were performed. A CKAT threshold of “Carrell + Perfusion >3” was highly specific (99%) and performed favorably to consultant opinion (specificity 95%). 96% of the kidneys implanted in accordance with the rule survived to 1 year (mean eGFR 45.3 mL/min/1.73 m2). To our knowledge, this is the first attempt to objectively define macroscopic features that are relevant to kidney utilization. Common language could support training in organ assessment and ultimately help address unnecessary discard of donor kidneys.
Role of pretransplant anti‐thymocyte globulin in matched sibling donor stem cell transplantation after reduced intensity conditioning for myelodysplastic syndrome
Authors: Yahng Seung‐Ah , Min Gi‐June , Park Sung‐Soo , Park Silvia , Jeon Young‐Woo , Yoon Jae‐Ho , Shin Seung‐Hwan , Lee Sung‐Eun , Cho Byung‐Sik , Eom Ki‐Seong , Lee Seok , Min Chang‐Ki , Kim Hee‐Je , Lee Jong‐Wook , Kim Yoo‐Jin 
Published: January 2020

AbstractObjectiveWe investigated the role of anti‐thymocyte globulin (ATG; Thymoglobulin) in matched sibling donor hematopoietic stem cell transplantation (MSD‐HSCT) after reduced intensity conditioning (RIC) in myelodysplastic syndrome (MDS).MethodsForty‐seven patients with 10 mg/kg ATG (ATG group; median age 53 years) and 33 without ATG (no‐ATG group; median age 43, P < .0001) were compared.ResultsMedian time to engraftment was similar. Two‐year cumulative incidence of moderate‐to‐severe chronic graft‐versus‐host disease (GVHD) was significantly lower in the ATG group (15% vs 55%, P < .0001), while that of acute GVHD was similar compared with the no‐ATG group. After a median follow‐up of 60 months (range, 14‐184), the 3‐year cumulative incidences of non‐relapse mortality and relapse were 9% and 21% for ATG group and 15% and 19% for no‐ATG group (P = .408 and P = .717), respectively, leading to a significantly better 3‐year GVHD‐free and relapse‐free survival (GRFS) in the ATG group (55% vs 19%, P = .006): The 3‐year overall and disease‐free survival were similar. Infectious complication occurred with similar frequencies in both groups.ConclusionThese findings suggest that ATG can be safely used to decrease moderate‐to‐severe chronic GVHD with improved GRFS for patients with MDS receiving MSD‐HSCT in RIC setting.
Surgical osteochondral defect repair in the horse—a matter of form or function?
Authors: Fugazzola Maria C. , van Weeren Paul R. 
Published: January 2020

AbstractFocal cartilaginous and osteochondral lesions can have traumatic or chondropathic degenerative origin. The fibrocartilaginous repair tissue that forms naturally, eventually undergoes fibrillation and degeneration leading to further disruption of joint homeostasis. Both types of lesion will therefore eventually lead to activity‐related pain, swelling and decreased mobility and will frequently progress to osteoarthritis. Most attempts at realising cartilage regeneration have so far resulted in cartilage repair (and not regeneration). The aim of this article was to review experimental research on surgical cartilage restoration techniques performed so far in equine models. Currently available surgical options for treatment of osteochondral lesions in the horse are summarised. The experimental validity of equine experimental models is addressed and finally possible avenues for further research are discussed.
Going public through mergers with special purpose acquisition companies
Authors: Kim Hyunseok , Ko Jayoung , Jun Chulhee , Song Kyojik “Roy” 
Published: January 2020

AbstractIn this study, we find that private operating firms with larger controlling shareholders' ownership merge with special purpose acquisition companies (SPACs) rather than take the conventional initial public offering (IPO) route to go public in Korea. This finding indicates that compared to U.S. SPACs, the controlling shareholders' motive to avoid their ownership dilution makes SPAC mergers popular in Korea. In addition, we document that the merged firms do not reveal difference in stock and operating performance over the long run compared to conventional IPO firms. However, SPAC mergers incur higher direct cost and do not generate marketing benefits for the listing firms.
Critical role of cationic local stresses on the stabilization of entropy‐stabilized transition metal oxides
Authors: Bhaskar Lalith K. , Nallathambi Varatharaja , Kumar Ravi 
Published: January 2020

AbstractEntropy‐stabilized transition metal oxides ([MgNiCoCuZn]O) (ESO) in recent years have received considerable attention owing to their unique functional properties. Solution combustion and solid state syntheses resulted in crystallites varying from 5‐15 nm to 3‐5 μm respectively. Phase stability studies showed that all the systems containing Cu2+ions in the ESO lattice segregated upon slow cooling in the furnace. It was only when ESO was quenched in air from 1000°C the lattice stabilized to a single phase. Experiments concomitant with molecular dynamics (MD) simulations demonstrated that the local stress fields around the cations played a critical role in stabilizing the single phase. The local stress fields are a result of Jahn‐Teller distortion induced by the Cu2+ions in the lattice. It is clearly established that in the absence of the minimization of the local stress fields around the Cu2+ions, segregation leading to the formation of a multi‐phase material is imminent for this particular composition.
Pioglitazone attenuates advanced glycation end products‐induced apoptosis and calcification by modulating autophagy in tendon‐derived stem cells
Authors: Xu Langhai , Xu Kai , Wu Zhipeng , Chen Zhonggai , He Yuzhe , Ma Chiyuan , Moqbel Safwat A. A. , Ran Jisheng , Zhang Caihua , Wu Lidong , Xiong Yan 
Published: January 2020

AbstractDiabetes mellitus (DM) is one of the prominent risk factors for pathological development and progression of tendinopathy. One feature of DM‐related changes in tendinopathy is accumulation of advanced glycation end products (AGEs) in affected tendons. Pioglitazone (Pio), a peroxisome proliferator‐activated receptor γ agonist, performs a protective effect against AGEs. The present study aimed to investigate the pathogenetic role of AGEs on tendon‐derived stem cells (TDSCs) and to determine the effect of Pio on AGEs‐induced TDSC dysfunctions. Results indicated that AGEs induced TDSC apoptosis as well as compensatory activation of autophagy. Pharmacologic activation/inhibition of autophagy leaded to alleviate/exacerbate apoptosis induced by AGEs. We further confirmed the effect of Pio on autophagy, which ameliorated apoptosis and abnormal calcification caused by AGEs both in vitro and in vivo. Thus, we suggest that Pio ameliorates the dysfunctions of TDSCs against AGEs by promoting autophagy, and we also reveal that Pio is a potential pharmacological choice for tendinopathy.