bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of effectiveness and safety between ticagrelor and clopidogrel in patients with acute coronary syndrome and on dialysis in Taiwan
Authors: Li Yun‐Syuan , Wang Shih‐Han , Hwang Shang‐Jyh , Yang Yi‐Hsin , Hsieh Kun‐Pin 
Published: June 2021

AimsThis study aimed to evaluate and compare the effectiveness and safety between clopidogrel and ticagrelor in acute coronary syndrome (ACS) with renal dysfunction.MethodsWe conducted a retrospective cohort study on patients on chronic dialysis and whose admission diagnosis between 1 July 2013 and 31 December 2016 included ACS. The primary effectiveness endpoint was a major adverse cardiovascular event (MACE), and the primary safety endpoint was a major bleeding event. The application of propensity scores through the inverse probability of treatment weighting (IPTW) was applied to the study groups. Cox regression was used to estimate hazard ratios (aHRs) of study endpoints. In addition, the competing risk was adjusted using the Fine and Gray competing risk model.ResultsThere were 1915 patients in the clopidogrel group and 270 patients in the ticagrelor group. At 12 months, the ticagrelor group had higher risks for MACE (aHR with IPTW: 1.29; 95% CI 1.16–1.44); death (aHR with IPTW: 1.65; 95% CI 1.47–1.86) and cardiac death (subdistribution HR [SHR] with IPTW: 1.64; 95% CI 1.41–1.91), compared with those in the clopidogrel group. For major bleeding event, the risk was significantly higher with ticagrelor than with clopidogrel (SHR with IPTW: 1.49; 95% CI 1.34–1.65). In terms of the risk for any bleeding event, there was no significant difference between the two groups (SHR with IPTW: 1.05; 95% CI 0.95–1.17).ConclusionsCompared with clopidogrel, ticagrelor was associated with higher MACE, death, cardiac death and major bleeding risk within 12 months in patients with ACS and on dialysis.
Functional analysis of LAT3 in prostate cancer: Its downstream target and relationship with androgen receptor
Authors: Rii Junryo , Sakamoto Shinichi , Sugiura Masahiro , Kanesaka Manato , Fujimoto Ayumu , Yamada Yasutaka , Maimaiti Maihulan , Ando Keisuke , Wakai Ken , Xu Minhui , Imamura Yusuke , Shindo Norihisa , Hirota Toru , Kaneda Atsushi , Kanai Yoshikatsu , Ikehara Yuzuru , Anzai Naohiko , Ichikawa Tomohiko 
Published: June 2021

AbstractL‐type amino acid transporter 3 (LAT3, SLC43A1) is abundantly expressed in prostate cancer (PC) and is thought to play an essential role in PC progression through the cellular uptake of essential amino acids. Here, we analyzed the expression, function, and downstream target of LAT3 in PC. LAT3 was highly expressed in PC cells expressing androgen receptor (AR), and its expression was increased by dihydrotestosterone treatment and decreased by bicalutamide treatment. In chromatin immunoprecipitation sequencing of AR, binding of AR to the SLC43A1 region was increased by dihydrotestosterone stimulation. Knockdown of LAT3 inhibited cell proliferation, migration, and invasion, and the phosphorylation of p70S6K and 4EBP‐1. Separase (ESPL1) was identified as a downstream target of LAT3 by RNA sequencing analysis. In addition, immunostaining of prostatectomy specimens was performed. In the multivariate analysis, high expression of LAT3 was an independent prognostic factor for recurrence‐free survival (hazard ratio: 3.24; P = .0018). High LAT3 expression was correlated with the pathological T stage and a high International Society of Urological Pathology grade. In summary, our results suggest that LAT3 plays an important role in the progression of PC.
CCL23 suppresses liver cancer progression through the CCR1/AKT/ESR1 feedback loop
Authors: Meng Jin , Wang Lianghai , Hou Jun , Yang Xiaofeng , Lin Ke , Nan Hongxing , Li Man , Wu Xiangwei , Chen Xueling 
Published: June 2021

AbstractWith the ability to activate certain signaling pathways, chemokines and their receptors may facilitate tumor progression at key steps, including proliferation, immunomodulation, and metastasis. Nevertheless, their prognostic value and regulatory mechanism warrant thorough studies in liver cancer. Here, by screening the expression profiles of all known chemokines in independent liver cancer cohorts, we found that CCL23 was frequently downregulated at mRNA and protein levels in liver cancer. Decreased CCL23 correlated with shortened patient survival, enrichment of signatures related to cancer stem cell property, and metastatic potential. In addition to serving as a tumor suppressor through recruiting CD8+ T cell infiltration in liver cancer, CCL23 could repress cancer cell proliferation, stemness, and mobility. Mechanistically, the expression of CCL23 was transcriptionally regulated by ESR1. On the other hand, CCL23 could suppress the activation of AKT signaling and thus promote the expression of ESR1, forming a feedback loop in liver cancer cells. Collectively, these findings reveal that loss of CCL23 drives liver cancer progression by coordinating immune evasion and metastasis initiation. Targeting the ESR1/CCL23/CCR1/AKT regulatory axis could be an effective therapeutic strategy.
Exceeding 30 ELNs is strongly recommended for pT3‐4N0 patients with gastric cancer: A multicenter study of survival, recurrence, and prediction model
Authors: Zhao Lulu , Han Weili , Yang Xisheng , Zhao Dongbing , Niu Penghui , Gao Xianchun , Wu Zhenkun , Zhang Xiaojie , Li Zefeng , Ji Gang , Chen Yingtai 
Published: June 2021

AbstractThe argument concerning the exact minimum number of examined lymph nodes (ELNs) has continued for a long time among various regions, and no consensus has been reached for stratified pathological T stages for data to date. Data from 4607 pN0 patients with gastric cancer were analyzed. Kaplan‐Meier analysis showed the similar overall survival (OS) outcomes among the 3 groups (ELNs ≤ 15, 16 ≤ ELNs ≤ 29 and ELNs ≥ 30, P = .171). However, the ELNs ≥ 30 group had a better disease‐free survival (DFS) outcome compared with the others (all P < .05). An increased ELN group (ELNs ≥ 30) showed an improved OS only for pT3 patients (hazard ratio [HR] = 0.397, 95% confidence interval (CI): 0.182‐0.866, P = .020), while an improved DFS for pT3 patients (HR = 0.362, 95%CI: 0.152‐0.860, P = .021) and pT4 patients (HR = 0.484, 95%CI: 0.277‐0.844, P = .011) in the multivariate analysis. A well discriminated and calibrated nomogram was constructed to predict the probability of the OS and DFS, with the C‐index for OS and DFS prediction of 0.782 (95%CI: 0.735 to 0.829) and 0.738 (95%CI: 0.685 to 0.791), respectively. This study provides new and useful insights into the impact of ELN count on reducing stage migration and postoperative recurrence of pN0 patients with gastric cancer in 2000‐2017. In conclusion, a larger number of ELNs is suggested for surgeons to prolong the prognosis of pN0 gastric cancer, especially for pT3 patients.
Magnetic resonance imaging in neuromyelitis optica spectrum disorder
Authors: Clarke Laura , Arnett Simon , Lilley Kate , Liao Jacky , Bhuta Sandeep , Broadley Simon A 
Published: June 2021

Abstract
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system (CNS) associated with antibodies to aquaporin-4 (AQP4), which has distinct clinical, radiological and pathological features, but also has some overlap with multiple sclerosis and myelin oligodendrocyte glycoprotein (MOG) antibody associated disease. Early recognition of NMOSD is important because of differing responses to both acute and preventive therapy. Magnetic resonance (MR) imaging has proved essential in this process. Key MR imaging clues to the diagnosis of NMOSD are longitudinally extensive lesions of the optic nerve (more than half the length) and spinal cord (three or more vertebral segments), bilateral optic nerve lesions and lesions of the optic chiasm, area postrema, floor of the IV ventricle, periaqueductal grey matter, hypothalamus and walls of the III ventricle. Other NMOSD-specific lesions are denoted by their unique morphology: heterogeneous lesions of the corpus callosum, ‘cloud-like’ gadolinium (Gd)-enhancing white matter lesions and ‘bright spotty’ lesions of the spinal cord. Other lesions described in NMOSD, including linear periventricular peri-ependymal lesions and patch subcortical white matter lesions, may be less specific. The use of advanced MR imaging techniques is yielding further useful information regarding focal degeneration of the thalamus and optic radiation in NMOSD and suggests that paramagnetic rim patterns and changes in normal appearing white matter are specific to MS. MR imaging is crucial in the early recognition of NMOSD and in directing testing for AQP4 antibodies and guiding immediate acute treatment decisions. Increasingly, MR imaging is playing a role in diagnosing seronegative cases of NMOSD.
Immunosuppression practices during the COVID‐19 pandemic: A multinational survey study of transplant programs
Authors: Sandal Shaifali , Boyarsky Brian J. , Massie Allan , Chiang Teresa Po‐Yu , Segev Dorry L. , Cantarovich Marcelo 
Published: June 2021

AbstractDuring the COVID‐19 pandemic, there has been wide heterogeneity in the medical management of transplant recipients. We aimed to pragmatically capture immunosuppression practices globally following the early months of the pandemic. From June to September 2020, we surveyed 1267 physicians; 40.5% from 71 countries participated. Management decisions were made on a case‐by‐case basis by the majority (69.6%) of the programs. Overall, 76.8% performed ≥1 transplantation and many commented on avoiding high‐risk transplantations. For induction, 26.5% were less likely to give T‐cell depletion and 14.8% were more likely to give non‐depleting agents. These practices varied by program‐level factors more so than the COVID‐19 burden. In patients with mild, moderate and severe COVID‐19 symptoms 59.7%, 76.0%, and 79.5% decreased/stopped anti‐metabolites, 23.2%, 45.4%, and 68.2% decreased/stopped calcineurin inhibitors, and 25.7%, 43.9%, and 57.7% decreased/stopped mTOR inhibitors, respectively. Also, 2.1%, 30.6%, and 46.0% increased steroids in patients with mild, moderate, and severe COVID‐19 symptoms. For prevalent transplant recipients, some programs also reported decreasing/stopping steroids (1.8%), anti‐metabolites (10.3%), calcineurin inhibitors (4.1%), and mTOR inhibitors (5.5%). Transplant programs changed immunosuppression practices but also avoided high‐risk transplants and increased maintenance steroids. The long‐term ramifications of these practices remain to be seen as programs face the aftermath of the pandemic.
Heat shock cognate 70 genes contribute to Drosophila spermatocyte growth progression possibly through the insulin signaling pathway
Authors: Azuma Maho , Ogata Tsubasa , Yamazoe Kanta , Tanaka Yuri , Inoue Yoshihiro H. 
Published: June 2021

AbstractDrosophila spermatocytes grow up to 25 times their original volume before the onset of male meiosis. Several insulin‐like peptides and their cognate receptors (InR) are essential for the cell growth process in Drosophila. Here, we aimed to identify additional signaling pathways and other regulatory factors required for germline cell growth in Drosophila males. Spermatocyte‐specific expression of the dominant‐negative form of InR inhibits cell growth. Conversely, constitutively active forms of signaling factors downstream of InR suppress growth inhibition. Furthermore, hypomorphic mutations in the target of rapamycin (Tor) inhibit spermatocyte growth. These data indicate that the insulin/TOR pathway is essential for the growth of premeiotic spermatocytes. RNA interference (RNAi) screening for the identification of other novel genes associated with cell growth showed that the silencing of each of the five members of heat shock cognate 70 (Hsc70) genes significantly inhibited the process. Hsc70‐silenced spermatocytes showed Akt inhibition downstream of the insulin signaling pathway. Our pleckstrin homology domain‐​green fluorescent protein (PH‐GFP) reporter studies indicated that PI3K remained activated in Hsc70‐4‐silenced cells, suggesting that the Hsc70‐4 protein possibly targets Akt or Pdk1 acting downstream of PI3K. Moreover, each of the Hsc70 proteins showed different subcellular localizations. Hsc70‐2 exhibited cytoplasmic colocalization with Akt in spermatocytes before nuclear entry of the kinase during the growth phase. These results indicated the involvement of Hsc70 proteins in the activation of various steps in the insulin signaling pathway, which is essential for spermatocyte growth. Our findings provide insights into the mechanism(s) that enhance signal transduction to stimulate the growth of Drosophila spermatocytes.
Efficient and safe glycaemic control with basal‐bolus insulin therapy during fasting periods in hospitalized patients with type 2 diabetes using decision support technology: A post hoc analysis
Authors: Hochfellner Daniel A. , Rainer Raphael , Ziko Haris , Aberer Felix , Simic Amra , Lichtenegger Katharina M. , Beck Peter , Donsa Klaus , Pieber Thomas R. , Fruhwald Friedrich M. , Rosenkranz Alexander R. , Kamolz Lars‐Peter , Baumann Petra M. , Mader Julia K. , Plank Johannes 
Published: June 2021

AbstractAimTo evaluate the efficacy and safety of basal‐bolus insulin therapy in managing glycaemia during fasting periods in hospitalized patients with type 2 diabetes.Materials and MethodsWe performed a post hoc analysis of two prospective, uncontrolled interventional trials that applied electronic decision support system‐guided basal‐bolus (meal‐related and correction) insulin therapy. We searched for fasting periods (invasive or diagnostic procedures, medical condition) during inpatient stays. In a mixed model analysis, patientsʼ glucose levels and insulin doses on days with regular food intake were compared with days with fasting periods.ResultsOut of 249 patients, 115 patients (33.9% female, age 68.3 ± 10.3 years, diabetes duration 15.1 ± 10.9 years, body mass index 30.1 ± 5.4 kg/m2, HbA1c 69 ± 20 mmol/mol) had 194 days with fasting periods. Mean daily blood glucose (BG) was lower (modelled difference [ModDiff]: −0.5 ± 0.2 mmol/L, P = .006), and the proportion of glucose values within the target range (3.9‐10.0 mmol/L) increased on days with fasting periods compared with days with regular food intake (ModDiff: +0.06 ± 0.02, P = .005). Glycaemic control on fasting days was driven by a reduction in daily bolus insulin doses (ModDiff: −11.0 ± 0.9 IU, P < .001), while basal insulin was similar (ModDiff: −1.1 ± 0.6 IU, P = .082) compared with non‐fasting days. Regarding hypoglycaemic events (BG < 3.9 mmol/L), there was no difference between fasting and non‐fasting days (χ2 0.9% vs. 1.7%, P = .174).ConclusionsWhen using well‐titrated basal‐bolus insulin therapy in hospitalized patients with type 2 diabetes, the basal insulin dose does not require adjustment during fasting periods to achieve safe glycaemic control, provided meal‐related bolus insulin is omitted and correction bolus insulin is tailored to glucose levels.
CAREER CONCERNS, BEIJING STYLE
Authors: Che Jiahua , Chung Kim‐Sau , Qiao Xue 
Published: June 2021

AbstractThe China model is increasingly viewed by developing countries as a viable alternative to democracy. China's allegedly merit‐based promotion system is lauded as a secret ingredient of the China model. However, once being promoted to the top, Chinese leaders are as unconstrained as other autocrats. If there are fundamental reasons why other autocrats cannot commit to such a promotion system, why are Chinese leaders any different? We provide a unified theory that accommodates both China and other autocracies by postulating that they coordinate on different equilibria. Both the presence and the absence of political career concerns can arise in equilibrium.
CAN THE OPTIMAL TARIFF BE ZERO FOR A GROWING LARGE COUNTRY?
Authors: Naito Takumi 
Published: June 2021

AbstractCan the optimal tariff be zero for a growing large country? To pursue the possibility, we extend the Rivera‐Batiz–Romer lab‐equipment model of endogenous technological change to include asymmetric countries, import tariffs, and either homogeneous or heterogeneous firms. Each country's domestic revenue share is a sufficient statistic for its long‐run growth rate, but it is not for its long‐run welfare. A unilateral tariff reduction by either country always increases the balanced growth rate. A zero tariff is locally optimal for a country under a mild condition, which is automatically satisfied at a symmetric balanced growth path with the zero tariff.
Female reproductive mode shapes allometric scaling of male traits in live‐bearing fishes (family Poeciliidae)
Authors: Furness Andrew I. , Hagmayer Andres , Pollux Bart J. A. 
Published: June 2021

AbstractReproductive mode is predicted to influence the form of sexual selection. The viviparity‐driven conflict hypothesis posits that a shift from lecithotrophic (yolk‐nourished) to matrotrophic (mother‐nourished or placental) viviparity drives a shift from precopulatory towards post‐copulatory sexual selection. In lecithotrophic species, we predict that precopulatory sexual selection will manifest as males exhibiting a broad distribution of sizes, and small and large males exhibiting contrasting phenotypes (morphology and coloration); conversely, in matrotrophic species, an emphasis on post‐copulatory sexual selection will preclude these patterns. We test these predictions by gathering data on male size, morphology and coloration for five sympatric Costa Rican poeciliid species that differ in reproductive mode (i.e. lecithotrophy vs. matrotrophy). We find tentative support for these predictions of the viviparity‐driven conflict hypothesis, with some interesting caveats and subtleties. In particular, we find that the three lecithotrophic species tend to show a broader distribution of male sizes than matrotrophic species. Furthermore, large males of such species tend to exhibit proportionately large dorsal and caudal fins and short gonopodia relative to small males, while these patterns are expressed to a lesser extent in the two matrotrophic species. Finally, large males in some of the lecithotrophic species exhibit darker fins relative to small males, a pattern not evident in either matrotrophic species. One unexpected finding was that even in the matrotrophic species Poeciliopsis retropinna and Poeciliopsis paucimaculata, which lack courtship and dichromatic coloration, some morphological traits exhibit significant allometric relationships, suggesting that even in these species precopulatory sexual selection may be present and shaping size‐specific male phenotypes in subtle ways.
Practical segmentation of nuclei in brightfield cell images with neural networks trained on fluorescently labelled samples
Authors: Fishman Dmytro , Salumaa Sten‐Oliver , Majoral Daniel , Laasfeld Tõnis , Peel Samantha , Wildenhain Jan , Schreiner Alexander , Palo Kaupo , Parts Leopold 
Published: June 2021

AbstractIdentifying nuclei is a standard first step when analysing cells in microscopy images. The traditional approach relies on signal from a DNA stain, or fluorescent transgene expression localised to the nucleus. However, imaging techniques that do not use fluorescence can also carry useful information. Here, we used brightfield and fluorescence images of fixed cells with fluorescently labelled DNA, and confirmed that three convolutional neural network architectures can be adapted to segment nuclei from the brightfield channel, relying on fluorescence signal to extract the ground truth for training. We found that U‐Net achieved the best overall performance, Mask R‐CNN provided an additional benefit of instance segmentation, and that DeepCell proved too slow for practical application. We trained the U‐Net architecture on over 200 dataset variations, established that accurate segmentation is possible using as few as 16 training images, and that models trained on images from similar cell lines can extrapolate well. Acquiring data from multiple focal planes further helps distinguish nuclei in the samples. Overall, our work helps to liberate a fluorescence channel reserved for nuclear staining, thus providing more information from the specimen, and reducing reagents and time required for preparing imaging experiments.
The gravitostat protects diet‐induced obese rats against fat accumulation and weight gain
Authors: Bake Tina , Peris‐Sampedro Fiona , Wáczek Zita , Ohlsson Claes , Pálsdóttir Vilborg , Jansson John‐Olov , Dickson Suzanne L. 
Published: June 2021

AbstractThe gravitostat is a novel homeostatic body weight‐regulating mechanism, mostly studied in mice, and recently confirmed in obese humans. In the present study, we explored the effect of weight loading on metabolic outcomes, meal patterns and parameters linked to energy expenditure in both obese and lean rats. Diet‐induced obese (DIO) and lean rats were implanted with capsules weighing either 15% of biological body weight (load) or empty capsules (1.3% of body weight; controls). Loading protected against fat accumulation more markedly in the DIO group. In line with this, the obesity‐related impairment in insulin sensitivity was notably ameliorated in DIO rats upon loading, as revealed by the reduction in serum insulin levels and homeostatic model assessment for insulin resistance index scores. Although 24‐hour caloric intake was reduced in both groups, this effect was greater in loaded DIO rats than in loaded lean peers. During days 10‐16, after recovery from surgery, loading: (i) decreased meal size in both groups (only during the light phase in DIO rats) but this was compensated in lean rats by an increase in meal frequency; (ii) reduced dark phase locomotor activity only in lean rats; and (iii) reduced mean caloric efficiency in DIO rats. Muscle weight was unaffected by loading in either group. Dietary‐obese rats are therefore more responsive than lean rats to loading.
Prevalence and risk factors of striae gravidarum in a cohort of multiracial postpartum Nepalese population
Authors: Punj Pragya , Agrawal Sudha , Regmi Mohan Chandra , Pandey Prajwal 
Published: June 2021

AbstractBackgroundStriae gravidarum (SG), popularly called as stretch marks, is a common pregnancy‐related asymptomatic skin condition, but is a cosmetic concern for females. A few epidemiological studies have been reported from Asian countries. However, no such study has been done in Nepal.AimsThis study was aimed to know the prevalence and risk factors associated with SG in a cohort of multi‐ethnic postpartum Nepalese women who had delivered after completion of 36 weeks.Patients/methodA cross‐sectional comparative study was conducted among 420 postpartum females who had delivered after completion of 36 weeks of gestation. Data were collected in the form of a questionnaire and relevant physical examination was done. The severity of SG was assessed by using Davey's scoring.ResultOut of 420 females, 260 (62%) had SG while 160 (38%) did not. According to the results of logistic regression analysis, young age (<25 years), large abdominal circumference (>100 cm), increased weight gain during pregnancy (>15 kg), presence of family history of SG, gestational diabetes mellitus, altered bowel movement, and presence of striae on the breasts, thighs, and buttocks were found to be independent risk factors for SG.ConclusionsFuture expectant mothers must be informed about the risk factors of SG development. They need to be made aware that SG can be prevented by considering the modifiable risk factors, such as excessive weight gain. They should also be informed that SG is permanent and currently there is no definite treatment.