bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex differences in acromegaly at diagnosis: A nationwide cohort study and meta‐analysis of the literature
Authors: Dal Jakob , Skov Benedikte G. , Andersen Marianne , Feldt‐Rasmussen Ulla , Feltoft Claus L. , Karmisholt Jesper , Nielsen Eigil H. , Dekkers Olaf M. , Jørgensen Jens Otto L. 
Published: December 2020

AbstractObjectiveData on sex differences in acromegaly at the time of diagnosis vary considerably between studies.DesignA nationwide cohort study including all incident cases of acromegaly (1978–2010, n = 596) and a meta‐analysis on sex differences in active acromegaly (40 studies) were performed.MethodSex‐dependent differences in prevalence, age at diagnosis, diagnostic delay, pituitary adenoma size, insulin‐like growth factor 1 (IGF‐I) and growth hormone (GH) concentrations were estimated.ResultsThe cohort study identified a balanced gender distribution (49.6% females) and a comparable age (years) at diagnosis (48.2 CI95% 46.5–49.8 (males) vs. 47.2 CI95% 45.5–48.9 (females), p = 0.4). The incidence rate significantly increased during the study period (R2 = 0.42, p < 0.01) and the gender ratio (F/M) changed from female predominance to an even ratio (SR: 1.4 vs. 0.9, p = 0.03). IGF‐ISDS was significantly lower in females compared to males, whereas neither nadir GH nor pituitary adenoma size differed between males and females.In the meta‐analysis, the weighted percentage female was 53.3% (CI95% 51.5–55.2) with considerable heterogeneity (I2 = 85%) among the studies. The mean age difference at diagnosis between genders was 3.1 years (CI95% 1.9–4.4), and the diagnostic delay was longer in females by 0.9 years (CI95% −0.4 to 2.1). Serum IGF‐I levels were significantly lower in female patients, whereas nadir GH, and pituitary adenoma size were comparable.ConclusionThere are only a minor sex differences in the epidemiology of acromegaly at the time of diagnosis except that female patients are slightly older and exhibit lower IGF‐I concentrations and a longer diagnostic delay.
Male erectile function after treatment for colorectal cancer: a population‐based cross‐sectional study
Authors: Laurberg Jens Reumert , Laurberg Viktoria Reumert , Elfeki Hossam , Jensen Jørgen Bjerggaard , Emmertsen Katrine J. 
Published: December 2020

AbstractAimThe aim of this work was to determine the knowledge gap in the field of erectile function (EF) after colorectal cancer surgery and investigate and compare long‐term male EF in colon and rectal cancer survivors in a national population.MethodDanish male patients alive without evidence of recurrence who were treated for colon or rectal cancer between May 2001 and December 2014 were invited to participate. Using the International Index of Erectile Function (IIEF) score the derived dichotomized erectile dysfunction (ED) was defined as moderate/severe or no/mild. Patients were grouped based on type of surgery [colon resection, rectal resection (RR) or local resection] and stratified for stoma, preoperative radiotherapy (RT), age and American Society of Anesthesiologists (ASA) score.ResultsOf 10 037 eligible patients, 4334 responded (43.18%). The EF score was significantly lower for RR (mean 12.14) compared with both colon resection (mean 15.82) and local resection (mean 14.81) (p < 0.0001). No significant difference between colon resection and local resection was found (p = 0.29). Both a stoma and the use of RT were independent risk factors for ED. After excluding patients with stoma and RT and adjusting for age and ASA score, RR still had a higher risk of ED (OR 1.42, CI 1.20–1.67) compared with colon resection.ConclusionRR has a negative affect on EF. No difference between patients who underwent colon resection and local resection was found. RT and stoma were independent risk factors for ED.
Oesophageal squamous cell carcinoma–associated IL‐33 rewires macrophage polarization towards M2 via activating ornithine decarboxylase
Authors: Mai Shijie , Liu Le , Jiang Jianjun , Ren Pengfei , Diao Dingwei , Wang Haofei , Cai Kaican 
Published: December 2020

AbstractBackgroundThe tumour microenvironment primarily constitutes macrophages in the form of an immunosuppressive M2 phenotype, which promotes tumour growth. Thus, the development of methodologies to rewire M2‐like tumour‐associated macrophages (TAMs) into the M1 phenotype, which inhibits tumour growth, might be a critical advancement in cancer immunotherapy research.MethodsThe expressions of IL‐33 and indicators related to macrophage polarization in oesophageal squamous cell carcinoma (ESCC) tissues and peripheral blood mononuclear cell (PBMC)–derived macrophages were determined. Inhibition of ornithine decarboxylase (ODC) with small interfering RNA was used to analyse the phenotype of macrophage polarization and polyamine secretory signals. CCK‐8, wound‐healing and Transwell assays were used to detect the proliferation and migration of ECA109 cells in vitro. The tumour xenograft assay in nude mice was used to examine the role of IL‐33 in ESCC development in vivo.ResultsThis study showed the substantially elevated IL‐33 expression in ESCC tissues compared with the normal tissues. Additionally, enhanced infiltration of M2‐like macrophages into the ESCC tumour tissue was also observed. We observed a strong correlation between the IL‐33 levels and the infiltration of M2‐like macrophages in ESCC tumours locally. Mechanistically, IL‐33 induces M2‐like macrophage polarization by activating ODC, a key enzyme that catalyses the synthesis of polyamines. Inhibition of ODC suppressed M2‐like macrophage polarization. Finally, in vivo, we confirmed that IL‐33 promotes tumour progression.ConclusionsThis study revealed an oncogenic role of IL‐33 by actively inducing M2‐like macrophage differentiation; thus, contributing to the formation of an immunosuppressive ESCC tumour microenvironment. Thus, IL‐33 could act as a novel target for cancer immunotherapies.
Population Pharmacokinetic Analysis of the BTK Inhibitor Zanubrutinib in Healthy Volunteers and Patients With B‐Cell Malignancies
Authors: Ou Ying C. , Liu Lucy , Tariq Bilal , Wang Kun , Jindal Ashutosh , Tang Zhiyu , Gao Yuying , Sahasranaman Srikumar 
Published: December 2020

Zanubrutinib is a potent, second‐generation Bruton’s tyrosine kinase inhibitor that is currently being investigated in patients with B‐cell malignancies and recently received accelerated approval in the United States for treatment of relapsed/refractory mantle cell lymphoma. The objective of this analysis was to develop a population pharmacokinetic (PK) model to characterize the PKs of zanubrutinib and identify the potential impact of intrinsic and extrinsic covariates on zanubrutinib PK. Data across nine clinical studies of patients with B‐cell malignancies and data of healthy volunteers (HVs) were included in this analysis, at total daily doses ranging from 20 to 320 mg. In total, 4,925 zanubrutinib plasma samples from 632 subjects were analyzed using nonlinear mixed‐effects modeling. Zanubrutinib PKs were adequately described by a two‐compartment model with sequential zero‐order then first‐order absorption, and first‐order elimination. A time‐dependent residual error model was implemented in order to better capture the observed maximum concentration variability in subjects. Baseline alanine aminotransferase and health status (HVs or patients with B‐cell malignancies) were identified as statistically significant covariates on the PKs of zanubrutinib. These factors are unlikely to be clinically meaningful based on a sensitivity analysis. No statistically significant differences in the PKs of zanubrutinib were observed based on age, sex, race (Asian, white, and other), body weight, mild or moderate renal impairment (creatinine clearance ≥ 30 mL/minute as estimated by Cockcroft‐Gault), baseline aspartate aminotransferase, bilirubin, tumor type, or use of acid‐reducing agents (including proton pump inhibitors). These results support that no dose adjustment is considered necessary based on the aforementioned factors.
Are adolescents more optimal decision‐makers in novel environments? Examining the benefits of heightened exploration in a patch foraging paradigm
Authors: Lloyd Alex , McKay Ryan , Sebastian Catherine L. , Balsters Joshua H. 
Published: December 2020

AbstractAdolescence is a period of heightened exploration relative to adulthood and childhood. This predisposition has been linked with negative behaviours related to risk‐taking, including dangerous driving, substance misuse and risky sexual practices. However, recent models have argued that adolescents’ heightened exploration serves a functional purpose within the lifespan, allowing adolescents to develop experiential knowledge of their surroundings. Yet, there is limited evidence that heightened exploration in adolescence is associated with positive outcomes. To address this, the present pre‐registered study utilised a foraging paradigm with a sample of adolescents aged 16–17 (N = 68) and of adults aged 21 and above (N = 69). Participants completed a patch foraging task, which required them to choose between exploiting a known resource which gradually yields fewer rewards, and exploring a novel, unknown resource with a fresh distribution of rewards. Findings demonstrated that adolescents explored more than adults, which – in the context of the current task—represented more optimal patch foraging behaviour. These findings indicate that adolescents’ heightened exploration can be beneficial, as they were able to effectively navigate unknown environments and accrue rewards more successfully than adults. This provides evidence that heightened exploration in adolescence, relative to adulthood, can lead to positive outcomes and contributes to our understanding of the role increased novelty‐seeking plays at this point in the lifespan.
Resource partitioning across a trophic gradient between a freshwater fish and an intraguild exotic
Authors: Kraus Richard T. , Schmitt Joseph D. , Keretz Kevin R. 
Published: December 2020

AbstractThe introduction of exotic species has the potential to cause resource competition with native species and may lead to competitive exclusion when resources are limiting. On the other hand, information is lacking to predict under what alternate trophic conditions coexistence may occur. Comparing diets of native yellow perch Perca flavescens and nonindigenous white perch Morone americana, we examined variation in resource partitioning and body condition across a prominent longitudinal nutrient gradient in Lake Erie (north‐eastern United States, Canada). As measured with Analysis of Similarity and Schoener's index, diet similarity declined monotonically from west to east tracking declines in nutrients, productivity and relative abundance of both species. Additionally, diet similarity increased from spring through fall, following seasonal development of stratification and hypolimnetic hypoxia—phenomena which tend to increase spatial overlap between these species. Finally, relative weights of both species peaked in the Central Basin (relative weights > 0.85), which, on average, had intermediate values of prey diversity, ecosystem trophic status and water clarity. Our results highlight that native yellow perch coexist with invasive white perch under a wide range of trophic conditions. Of importance to fishery managers, mesotrophy in the Central Basin correlated with the highest body conditions and intermediate prey resource partitioning, although the effect size was small and variable. While competitive exclusion appears unlikely, the goal of reducing nutrient inputs in Lake Erie could affect not only the distributions of both species but also stakeholder decisions about where to fish.
The Polish interbella puzzle: the biological standard of living in the Second Polish Republic, 1918–39 †
Authors: Kopczyński Michał , Rodak Mateusz 
Published: December 2020

AbstractThe article aims to assess the importance of the timing of exposure to nutritional stress for adult stature. We test the hypothesis that exposure in adolescence (12 to 20 years of age) may have a more detrimental effect than exposure in infancy. To substantiate this, we analyse a sample of male prison inmates incarcerated in central Poland in the interwar period. We find that the secular trend in stature that had started in Poland in the 1860s was reversed in cohorts born between 1896 and 1904, who were exposed to nutritional stress during the First World War between the ages of 12 and 25 years. In comparison, wartime infants and toddlers did much better. In the improving economic conditions of the 1920s, they were able to undo the scars of war during their adolescence. The conclusion is corroborated by data concerning soldiers and conscripts to the Polish army. With regard to body mass index (BMI), we found that the trends among convicts and conscripts differ. This is caused by changes in the composition of the prison sample, related to the impact of the Great Depression. In summary, it seems that stature is a more robust proxy of well‐being than BMI.
One‐year outcomes from a phase 3 randomized trial of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria who received prior eculizumab
Authors: Kulasekararaj Austin G. , Hill Anita , Langemeijer Saskia , Wells Richard , González Fernández F. Ataúlfo , Gaya Anna , Ojeda Gutierrez Emilio , Piatek Caroline I. , Mitchell Lindsay , Usuki Kensuke , Bosi Alberto , Brodsky Robert A. , Ogawa Masayo , Yu Ji , Ortiz Stephan , Röth Alexander , Lee Jong Wook , Peffault de Latour Régis 
Published: December 2020

AbstractRavulizumab every 8 weeks showed non‐inferiority to eculizumab every 2 weeks in a 26‐week, phase 3, randomized controlled trial in adults with paroxysmal nocturnal hemoglobinuria (PNH) who were clinically stable on eculizumab (NCT03056040). We report results from the first 26 weeks of the extension period in which patients continued ravulizumab (n = 96) or switched from eculizumab to ravulizumab (n = 95). At week 52, mean (SD) lactate dehydrogenase levels increased 8.8% (29%) with ravulizumab‐ravulizumab and 5.8% (27%) with eculizumab‐ravulizumab from primary evaluation period baseline. During the extension period, four patients (ravulizumab‐ravulizumab, n = 3; eculizumab‐ravulizumab, n = 1) experienced breakthrough hemolysis, but none associated with serum free C5 ≥ 0.5 μg/mL. Mean Functional Assessment of Chronic Illness Therapy (FACIT)‐Fatigue scores remained stable through week 52. During the extension period, proportions of patients avoiding transfusion remained stable (ravulizumab‐ravulizumab, 86.5%; eculizumab‐ravulizumab, 83.2%); 81.2% and 81.1%, respectively, had stabilized hemoglobin. All patients maintained serum free C5 levels < 0.5 μg/mL. Adverse events were generally similar between groups, and rates were lower in the extension period. Adults with PNH on stable eculizumab therapy who received ravulizumab over 52 weeks experienced durable efficacy, with consistent efficacy in patients who received eculizumab during the primary evaluation period and then switched to ravulizumab. Ravulizumab was well tolerated.
Higher average chemotherapy dose intensity improves prognosis in patients with aggressive adult T‐cell leukemia/lymphoma
Authors: Sekine Masaaki , Kameda Takuro , Shide Kotaro , Maeda Kouichi , Toyama Takanori , Kawano Noriaki , Takeuchi Masanori , Kawano Hiroshi , Sato Seiichi , Ishizaki Junzo , Kukita Toshimasa , Kamiunten Ayako , Akizuki Keiichi , Tahira Yuki , Shimoda Haruko , Hidaka Tomonori , Yamashita Kiyoshi , Matsuoka Hitoshi , Kitanaka Akira , Kubuki Yoko , Shimoda Kazuya 
Published: December 2020

AbstractObjective and MethodAdult T‐cell leukemia/lymphoma (ATL) is an aggressive peripheral T‐cell lymphoma with poor prognosis. We retrospectively reviewed the medical records of 312 patients with aggressive ATL and analyzed the effect of chemotherapy dose intensity on prognosis in clinical practice.ResultAs first‐line therapy, 62 patients underwent best supportive care (BSC) or single‐agent chemotherapy, and 235 underwent intensive chemotherapy. The median survival time (MST) was 0.58 years in the 312 total patients, and 0.13 years and 0.75 years in the BSC/single‐agent chemotherapy group and intensive chemotherapy group, respectively. The median average relative dose intensity (ARDI) of patients who received intensive chemotherapy was 60%. We divided patients into 3 groups according to ARDI. Those in the top tertile of ARDI (ARDI ≥ 75%, n = 82) had better overall survival compared with those in the intermediate tertile (45% ≤ ARDI < 75%, n = 79) (P < .0001), with MSTs of 4.69 and 0.75 years, respectively. The occurrence of organ dysfunction and infectious complications was comparable between the two ARDI groups.ConclusionHigher ARDI improves prognosis in patients with aggressive ATL in clinical practice.
Possible interplay between the theories of pharmacoresistant epilepsy
Authors: Juvale Iman Imtiyaz Ahmed , Che Has Ahmad Tarmizi 
Published: December 2020

AbstractEpilepsy is one of the oldest known neurological disorders and is characterized by recurrent seizure activity. It has a high incidence rate, affecting a broad demographic in both developed and developing countries. Comorbid conditions are frequent in patients with epilepsy and have detrimental effects on their quality of life. Current management options for epilepsy include the use of anti‐epileptic drugs, surgery, or a ketogenic diet. However, more than 30% of patients diagnosed with epilepsy exhibit drug resistance to anti‐epileptic drugs. Further, surgery and ketogenic diets do little to alleviate the symptoms of patients with pharmacoresistant epilepsy. Thus, there is an urgent need to understand the underlying mechanisms of pharmacoresistant epilepsy to design newer and more effective anti‐epileptic drugs. Several theories of pharmacoresistant epilepsy have been suggested over the years, the most common being the gene variant hypothesis, network hypothesis, multidrug transporter hypothesis, and target hypothesis. In our review, we discuss the main theories of pharmacoresistant epilepsy and highlight a possible interconnection between their mechanisms that could lead to the development of novel therapies for pharmacoresistant epilepsy.
Taxes
Authors: Fama Eugene F. 
Published: December 2020

AbstractThis is a compendium of notes on taxes. Section 2 presents a general tax scheme. It is a tax on value added by labour and capital that does not favour one or the other. Section 3 contrasts taxation of business income for pass‐through entities and corporations. Section 4 discusses property taxes as taxes on housing services and so a form of income tax. Section 5 turns to wealth taxes. The closing Section 6 attempts to explain why people donate to nonprofits but minimise tax payments to governments, even though governments and nonprofits engage in many of the same activities.
Putting local on the MAP: A model for engaging foreign language students with local cultures
Authors: Klimanova Liudmila , Hellmich Emily A. 
Published: December 2020

AbstractCulture in the teaching and learning of foreign languages tends to be stereotypical and monolithic, marginalizing the diversity of local cultures and practices and resulting in a monocultural and monolingual bias. Expanding on the ACTFL Cultures and Comparisons Standards, the current article presents the MAPS model for Exploring Local Cultures aimed at engaging students with local products, practices, and perspectives through the creation, exchange, and analysis of digital artifacts of local cultures. The article demonstrates how a complex pedagogical model can be constructed from existing research and theory as well as how to implement it: in addition to presenting the model and its underlying literature, the article details its implementation in two classes.
Biomass and methane yield of giant reed (Arundo donaxL.) as affected by single and double annual harvest
Authors: Ceotto Enrico , Vasmara Ciro , Marchetti Rosa , Cianchetta Stefano , Galletti Stefania 
Published: December 2020

AbstractThe replacement of silage maize with giant reed as energy crop has been proposed as a mean for reducing the need of irrigation water as well as monetary and environmental costs of cultivation. Little is known about giant reed response to within‐season harvesting, and its effect on the methane production in anaerobic digestion. The effect of three harvest schedules on yield, biomass composition and methane production of giant reed was evaluated at one site of the Po Valley, northern Italy, for three consecutive years. In a completely randomized block design with four replicates the treatments applied annually were: (i) double harvest 1: first cut at the end of June + second cut at the beginning of October (DH1); (ii) double harvest 2: first cut at the end of July + second cut at the beginning of October (DH2); (iii) single harvest at the beginning of October (SH). The crop stand was established in the year 2015 and treatments were repeatedly applied in the years 2016, 2017 and 2018. The SH treatment determined the highest average annual dry matter (DM) yield (59.0 Mg DM ha−1). The DM yield for treatments with double harvest was significantly lower, that is, −30% for DH1 and −15% for DH2. In terms of specific methane yield there was little advantage in harvesting biomass twice during the growing season. The average specific methane yield varied substantially between years (i.e. from 144 to 233 ml CH4 g−1 VS), and in every year the values tended to decrease with the ageing of harvested biomass. Methane yield per hectare, however, was driven by DM yield, thus SH also determined the highest average value (9110 m3 CH4‐STP ha−1). In conclusion, the single annual harvest at the end of the growing season is an ideal strategy for maximizing methane production from giant reed.
Labour market flexibility in Indian manufacturing: A critical survey of the literature
Authors: BHATTACHARJEA Aditya 
Published: December 2020

AbstractA growing literature seeks to establish a relationship between India's supposedly “restrictive” labour laws and its poor performance on a range of industrial and social indicators. After providing an overview of this literature, this article shows that multiple errors were made in the foundational papers that constructed indices measuring interstate differences in labour regulation. These indices were then misinterpreted as measures of labour market flexibility. The literature is also marred by econometric problems and by difficulties involved in replicating the analysis with corrected and updated indices. The author concludes by summarizing evidence of deteriorating labour market outcomes for workers in Indian manufacturing.