bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Adolescence 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

The 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

The 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

Ravulizumab 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

Objective and Method

Adult 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.

Result

As 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.

Conclusion

Higher 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

Epilepsy 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

This 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.
Roles of type IIa receptor protein tyrosine phosphatases as synaptic organizers
Authors: Fukai Shuya , Yoshida Tomoyuki
Published: December 2020

Neurons establish circuits for brain functions such as cognition, emotion, learning, and memory. Their connections are mediated by synapses, which are specialized cell‐cell adhesions responsible for neuronal signal transmission. During neurodevelopment, synapse formation is triggered by interactions of cell adhesion molecules termed synaptic organizers or synapse organizers. Type IIa receptor protein tyrosine phosphatases (IIa RPTPs; also known as leukocyte common antigen‐related receptor tyrosine phosphatases or LAR‐RPTPs) play important roles in axon guidance and neurite extension, and also serve as presynaptic organizers. IIa RPTPs transsynaptically interact with multiple sets of postsynaptic organizers, mostly in a splicing‐dependent fashion. Here, we review and update research progress on IIa RPTPs, particularly regarding their functional roles in vivo demonstrated using conditional knockout approach and structural insights into their extracellular and intracellular molecular interactions revealed by crystallography and other biophysical techniques. Future directions in the research field of IIa RPTPs are also discussed, including recent findings of the molecular assembly mechanism underlying the formation of synapse‐specific nanostructures essential for synaptic functions.
Putting local on the MAP: A model for engaging foreign language students with local cultures
Authors: Klimanova Liudmila , Hellmich Emily A.
Published: December 2020

Culture 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

The 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

A 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.
Jekyll or Hyde? The genome (and more) of Nesidiocoris tenuis, a zoophytophagous predatory bug that is both a biological control agent and a pest
Authors: Ferguson K. B. , Visser S. , Dalíková M. , Provazníková I. , Urbaneja A. , Pérez‐Hedo M. , Marec F. , Werren J. H. , Zwaan B. J. , Pannebakker B. A. , Verhulst E. C.
Published: December 2020

Nesidiocoris tenuis (Reuter) is an efficient predatory biological control agent used throughout the Mediterranean Basin in tomato crops but regarded as a pest in northern European countries. From the family Miridae, it is an economically important insect yet very little is known in terms of genetic information and no genomic or transcriptomic studies have been published. Here, we use a linked‐read sequencing strategy on a single female N. tenuis. From this, we assembled the 355 Mbp genome and delivered an ab initio, homology‐based and evidence‐based annotation. Along the way, the bacterial “contamination” was removed from the assembly. In addition, bacterial lateral gene transfer (LGT) candidates were detected in the N. tenuis genome. The complete gene set is composed of 24 688 genes; the associated proteins were compared to other hemipterans (Cimex lectularis, Halyomorpha halys and Acyrthosiphon pisum). We visualized the genome using various cytogenetic techniques, such as karyotyping, CGH and GISH, indicating a karyotype of 2n = 32. Additional analyses include the localization of 18S rDNA and unique satellite probes as well as pooled sequencing to assess nucleotide diversity and neutrality of the commercial population. This is one of the first mirid genomes to be released and the first of a mirid biological control agent.
Respiratory syncytial virus seasonality in three epidemiological zones of Kenya
Authors: Rose Erica Billig , Nyawanda Bryan O. , Munywoki Patrick K. , Murunga Nickson , Bigogo Godfrey M. , Otieno Nancy A. , Onyango Clayton , Chaves Sandra S. , Verani Jennifer R. , Emukule Gideon O. , Widdowson Marc‐Alain , Nokes D. James , Gerber Susan I. , Langley Gayle E.
Published: December 2020

Understanding respiratory syncytial virus (RSV) circulation patterns is necessary to guide the timing of limited‐duration interventions such as vaccines. We describe RSV circulation over multiple seasons in three distinct counties of Kenya during 2006‐2018. Kilifi and Siaya counties each had consistent but distinct RSV seasonality, lasting on average 18‐22 weeks. Based on data from available years, RSV did not have a clear pattern of circulation in Nairobi. This information can help guide the timing of vaccines and immunoprophylaxis products that are under development.
Association between Chlamydial Infections and Pelvic Lesions
Authors: Nakamura Kouichi , Ishimaru Tadayuki , Kurata Suwako , Fujishita Akira , Samejima Teturo , Masuzaki Hideaki , Yamabe Tooru
Published: December 2020

Abstract

Chlamydia trachomatis usually causes asymptomatic cervicitis, but it sometimes ascends into the uterine cavity, fallopian tubes, or peritoneal cavity, causing pelvic inflammatory disease and infertility. In this study, we examined endocervical chlamydial antigens and serum chlamydial antibodies in infertile women and laparoscopically evaluated pelvic lesions according to our pelvic scoring system. In patients testing positive for a chlamydial infection, the total pelvic score was significantly higher than in patients testing negative. When each area examined was assessed separately, however, only the tubal score was significantly higher in the chlamydia infected patients. These findings may indicate that tubal lesions are the major cause of infertility in women with chlamydial infections.
Restriction Enzyme Analysis of Norrie Disease Pedigrees
Authors: Chung Sung‐Ro , Katayama Susumu , Lebo Roger , Golbus Mitchell S.
Published: December 2020

Abstract

Carrier detection and prenatal diagnosis of Norrie disease (ND) were performed using the polymorphic L1.28, OTC, and 58–1 probes. L1.28 was polymorphic in 3 of the 5 ND families tested and informative in 2 families (40%). Probe 58–1 and OTC were informative in one of 3 families (33%) and in both of the 2 families (100%) tested, respectively. The major allele frequency was 73% in L1.28 (DXS7), 89% in 58–1 (DXS14), and 50% in OTC in our patient population. One of 5 families studies showed a recombination between probes (L1.28 and OTC) and the ND gene locus placing the ND locus proximal to L1.28 and OTC.
Menopause Related Changes of Adrenocortical Steroid Production
Authors: Akamatsu Tatsuya , Chiba Hiroshi , Kamiyama Hiroshi , Hirose Kazuhiro , Saito Hiroshi , Yanaihara Takumi
Published: December 2020

Abstract

To elucidate changes of adrenocortical steroid production with age, reproductive age (n=14), peri‐menopausal (n=12) and post‐menopausal (n=13) women were studied using basal hormone levels and the results of a rapid ACTH stimulation test. Peripheral serum levels of pregnenolone, 17α‐hydroxypregnenolone, 17α‐hydroxyprogesterone, dehydroepiandrosterone and androstenedione were measured by RIA. The basal levels of all steroids except pregnenolone decreased with age. A significant increase in the levels of all steroids after ACTH stimulation was observed in all subjects. Although, there was an age related decrease in the response of C19‐steroids to ACTH, the response of pregnenolone and 17α‐hydroxyprogesterone to ACTH did not alter with age. The preserved response of 17α‐hydroxyprogesterone to ACTH in post‐menopausal women suggests that 17α‐hydroxyprogesterone production plays a role in the age independency of cortisol.

In the present paper, the changes in the capacity of the post‐menopausal adrenal cortex to produce androgens and C21‐steroids were demonstrated.
The Adverse Effects of l‐Methamphetamine on the Development of Explanted Rat Embryos
Authors: Ozaki Takashi , Nakamura Yukio , Saito Yoshiharu
Published: December 2020

Abstract

The adverse effects of l‐methamphetamine on the development of rat embryos were studied by means of a whole culture system. The embryos explanted at 12.5th days of gestational age were cultured for a total of 24 hours. After pre‐culturing for 6 hours, 4 groups of embryos received additional culturing for 18 hours with saline or various concentrations of l‐methamphetamine; 0.5, 2.0 and 5.0 μmol/dl. There was no significant difference in the survival rate among 4 groups. The groups over 2.0 μmol/dl of l‐methamphetamine showed significant reduction of crown‐rump length, somite number, protein content, DNA content, and protein/DNA ratio. It is suggested that over 2.0 μmol/dl of l‐methamphetamine reduces the development but not the survival of rat embryos under whole culture system.
Detection of Human Papillomavirus DNA in the Normal Cervices of Japanese Women by the Dot‐Blot (Vira Pap™) Method
Authors: Saito Junko , Fukuda Takehiko , Nakatani Hiroshi , Sumiyoshi Michiyoshi , Kinoshita Moritoshi , Ikeda Masanori , Noda Kiichiro
Published: December 2020

Abstract

Exfoliated cervical cells obtained from 9 patients with cervical intraepithelial neoplasia (CIN) I and II, 11 with CIN III, 22 with cervical carcinoma, and 599 with cytologically normal cervices (including 63 pregnant women) were evaluated for the presence of human papillomavirus (HPV) by the dot‐blot (Vira Pap™) method. HPV infection was detected in 33.3% of the CIN I and II cases, in 54.5% of the CIN III cases, in 68.2% of invasive cervical carcinoma cases, and in 4.2% of the normal group. The rate of detectable HPV infection increased in exfoliated cervical cells during pregnancy. These results suggested that a few Japanese women with cytologically normal cervices were infected with HPV.
Mapping Oral Disease Impact with a Common Metric (MOM)—Project summary and recommendations
Authors: John Mike T. , Häggman‐Henrikson Birgitta , Sekulic Stella , Stamm Tanja , Oghli Ibrahim , Schierz Oliver , List Thomas , Baba Kazuyoshi , Bekes Katrin , van Wijk Arjen , Su Naichuan , Reissmann Daniel R. , Fueki Kenji , Larsson Pernilla , Theis‐Mahon Nicole , Omara Maisa , Bondemark Lars , Visscher Corine M.
Published: December 2020

Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact—the dimensions of oral health‐related quality of life—capture dental patients’ oral health problems worldwide and regardless of whether the patient currently suffers from oral diseases or intends to prevent them in the future. Using scores for these dimensions, the project Mapping Oral Disease Impact with a Common Metric (MOM) aims to provide four‐dimensional oral health impact information across oral diseases and settings. In this article, project authors summarize MOM’s findings and provide recommendations about how to improve standardized oral health impact assessment. Project MOM’s systematic reviews identified four‐dimensional impact information for 189 adult and 22 pediatric patient populations that were contained in 170 publications. A typical functional, pain‐related, aesthetical, and psychosocial impact (on a 0‐8 impact metric based on two items with a response format 0 = never, 1 = hardly ever, 2 = occasionally, 3 = fairly often, 4 = very often) was about 2 to 3 units. Project MOM provides five recommendations to improve standardized oral health impact assessment for all oral diseases in all settings.
Preference Sorting as a tool for Dulce de Leches' drivers of liking determination
Authors: Rodrigues Jéssica Ferreira , de Souza Vanessa Rios , de Sousa Amorim Isabel , Lima Renato Ribeiro , Freitas Mônica Queiroz , Esmerino Erick Almeida , da Cruz Adriano Gomes , Pinheiro Ana Carla Marques
Published: December 2020

Sensory descriptive methods are useful tools for quality control and product development. In recent years, faster methods (such as Sorting task), which do not require trained sensory panels, have been increasingly implemented to save time and consumption. Sorting task is a simple procedure for collecting similarity data, in which each assessor groups stimuli based on their perceived similarities, following or not by the samples description. Several variations of this method have been developed and presented. However, none of these approaches focused mainly on determining attributes that drive product acceptance. Thus, it is important to evaluate some tasks variations to establish recommendations about procedures useful for screening numerous samples, considering their characteristics that most contribute to their acceptance. Therefore, this study assessed three sorting task variations, varying the sorting criteria—based on similarities or based on acceptance, to assess Dulce de leche drivers of liking. Sorting criteria and the sensory description task influenced sensory results. Focusing on drivers of liking determination, grouping criteria based on preference (suggested name as Preference Sorting), following the description of the characteristics that most contribute to product acceptance, seems to be interesting.

Practical application

The findings of this study show practical utility for consumer‐based methodologies, focusing on sorting task and drivers of liking determination. In addition, they are useful for Brazilian Dulce de leche producers as it enables understanding the consumer preferences to plan production, marketing, and commercialization strategies.
Atypical bartonellosis in children: What do we know?
Authors: Lemos Ana P , Domingues Rui , Gouveia Catarina , de Sousa Rita , Brito Maria J
Published: December 2020

Aim

To characterise Bartonella infections in a paediatric population requiring hospital admission and review its treatment.

Methods

Longitudinal observational retrospective data analysis of children and adolescents admitted with Bartonella infection at a paediatric tertiary hospital from 2010 to 2019.

Results

We identified 16 cases of bartonellosis, with a mean age of 8.0 ± 4.5 years old, no sex predominance and 14 had contact with cats. Most of the cases occurred in fall and winter. Clinical presentations included osteomyelitis/arthritis (n = 9), hepatosplenic disease (n = 2), lymphadenitis (n = 2), neuroretinitis (n = 2) and encephalitis (n = 1). Clinical diagnosis was confirmed by serology (n = 16) and Bartonella DNA detection in patient's lymph nodes/hepatic lesion (n = 3). Therapeutic approach varied according to the clinical presentation: azithromycin in lymphadenitis, rifampicin plus ciprofloxacin in hepatosplenic disease, rifampicin and doxycycline in neuroretinitis, ceftriaxone in encephalitis and azithromycin, cotrimoxazole or rifampicin plus azithromycin, cefuroxime, ciprofloxacin or doxycycline in osteomyelitis/arthritis. Immunodeficiency was excluded in seven patients. Seven patients' cats were screened by veterinarians and treated when infected (n = 5).

Conclusions

In these clinical presentations, where other infections may be involved, a high index of suspicion is necessary, with emphasis on the epidemiological context. The association of systemic forms with immunodeficiency did not occur in our study. The lack of recommendations for treatment of atypical infection makes the approach of these cases a challenge. Randomised control studies are essential to define the best approach in each case.
Achieving health equity through oral health value‐based care: a funder's perspective
Authors: Ravelli Parrish , Hakuta Katinka , Simpson Trenae
Published: December 2020

Because dental caries is one of the most preventable diseases in the world, poor oral health and inequitable outcomes are not just a failing of our current system of care and financing, but the result of decades of unjust and oppressive systems that were not designed to serve all patients equitably. Reducing these disparities will take deep and intentional work to focus on value, outcomes, and each patient as a whole person. In this article, we describe some of the unique opportunities funders have to listen, learn, and leverage strategies to redesign the oral health system in a way that prioritizes historically marginalized people and communities and transforms the way oral health care is accessed, delivered, and received.
Interprofessional value‐based health care: Nurse practitioner‐dentist model
Authors: Dolce Maria C. , Barrow Jane , Jivraj Ashiana , Pham Dalton , Da Silva John D.
Published: December 2020

Objectives

The United States health system is challenged to improve patient and population health, enhance patients' experience of care, and reduce health care costs. Value‐based health care (VBHC) models are proposed to address these issues. Medical health systems are making strides toward VBHC, whereas dental care systems lag behind. The aims of this paper are to a) present study findings of an interprofessional practice model integrating oral health and primary care in a dental practice setting, and b) discuss practice and research implications for advancing VBHC approaches in oral health.

Methods

A nonexperimental research method was employed to evaluate the Nurse Practitioner‐Dentist Model for Primary Care (NPD Model) at the Harvard Dental Center. Pretest/post‐test design was used to assess clinical patient outcomes for a convenience cohort of Medicare beneficiaries (n = 31) with a reported diagnosis of hypertension and/or type 2 diabetes. Clinical outcome measures included: blood pressure, weight, body mass index (BMI), and Hemoglobin A1c.

Results

Positive and significant improvements in biometrics (blood pressure, body weight, BMI, HbA1c) were found.

Conclusions

The NPD Model is an early prototype for interprofessional VBHC in oral health and holds promise for improving patient and population health outcomes. Integration of interprofessional VBHC in oral health is an imperative for achieving the Triple Aim to improve the overall health of our nation.
Risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis B virus (HBV) infection: a systematic review and meta‐analysis
Authors: Campbell Cori , Wang Tingyan , McNaughton Anna L. , Barnes Eleanor , Matthews Philippa C.
Published: December 2020

Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide and is a leading cause of death in individuals with chronic hepatitis B virus (HBV) infection. It is uncertain how the presence of other metabolic factors and comorbidities influences HCC risk in HBV. Therefore, we performed a systematic literature review and meta‐analysis to seek evidence for significant associations. MEDLINE, EMBASE and Web of Science databases were searched from 1 January 2000 to 24 June 2020 for studies investigating associations of metabolic factors and comorbidities with HCC risk in individuals with chronic HBV infection, written in English. We extracted data for meta‐analysis and generated pooled effect estimates from a fixed‐effects model. Pooled estimates from a random‐effects model were also generated if significant heterogeneity was present. We identified 40 observational studies reporting on associations of diabetes mellitus (DM), hypertension, dyslipidaemia and obesity with HCC risk. Only DM had a sufficient number of studies for meta‐analysis. DM was associated with >25% increase in hazards of HCC (fixed‐effects hazards ratio [HR] 1.26, 95% confidence interval (CI) 1.20–1.32, random‐effects HR 1.36, 95% CI 1.23–1.49). This association was attenuated towards the null in a sensitivity analysis restricted to studies adjusted for metformin use. In conclusion, in adults with chronic HBV infection, DM is a significant risk factor for HCC, but further investigation of the influence of antidiabetic drug use and glycaemic control on this association is needed. Enhanced screening of individuals with HBV and diabetes may be warranted.
Machine‐learning radiomics to predict early recurrence in perihilar cholangiocarcinoma after curative resection
Authors: Qin Huan , Hu Xianling , Zhang Junfeng , Dai Haisu , He Yonggang , Zhao Zhiping , Yang Jiali , Xu Zhengrong , Hu Xiaofei , Chen Zhiyu
Published: December 2020

Background and aims

Up to 40%‐65% of patients with perihilar cholangiocarcinoma (PHC) rapidly progress to early recurrence (ER) even after curative resection. Quantification of ER risk is difficult and a reliable prognostic prediction tool is absent. We developed and validated a multilevel model, integrating clinicopathology, molecular pathology and radiology, especially radiomics coupled with machine‐learning algorithms, to predict the ER of patients after curative resection in PHC.

Methods

In total, 274 patients who underwent contrast‐enhanced CT (CECT) and curative resection at 2 institutions were retrospectively identified and randomly divided into training (n = 167), internal validation (n = 70) and external validation (n = 37) sets. A machine‐learning analysis of 18,120 radiomic features based on multiphase CECT and 48 clinico‐radiologic characteristics was performed for the multilevel model.

Results

Comprehensively, 7 independent factors (tumour differentiation, lymph node metastasis, pre‐operative CA19‐9 level, enhancement pattern, A‐Shrink score, V‐Shrink score and P‐Shrink score) were built to the multilevel model and quantified the risk of ER. We benchmarked the gain in discrimination with the area under the curve (AUC) of 0.883, superior to the rival clinical and radiomic models (AUCs 0.792‐0.805). The accuracy (ACC) of the multilevel model was 0.826, which was significantly higher than those of the conventional staging systems (AJCC 8th (0.641), MSKCC (0.617) and Gazzaniga (0.581)).

Conclusion

The radiomics‐based multilevel model demonstrated superior performance to rival models and conventional staging systems, and could serve as a visual prognostic tool to plan surveillance of ER and guide post‐operative individualized management in PHC.
Historical Acknowledgment as an Early Conflict Negotiation Strategy: A Feasibility Study of Israel/Palestine
Authors: Ben‐Josef Hirsch Michal
Published: December 2020

This article proposes that historical acknowledgment strategies are not only useful if and when they lead to coexistence and reconciliation in the post‐conflict stages, but also as an early conflict negotiation strategy. To develop this proposition the article integrates literature on conflict resolution and conflict transformation with models of negotiation and underscores the potential utility of historical acknowledgment strategies in early stages of official negotiations. The article proposes that historical acknowledgment strategies address the lack of long‐term trust, which is often a significant impediment during negotiations. Such strategies signal a commitment to changing the public space as well as the education of future generations in ways that acknowledge the adversary’s history and identity. This action is likely to provide assurances to the other side that peaceful coexistence is a long‐term goal of the leadership and the public. Furthermore, the article proposes that the current international normative environment—that is, existing human rights norms and strengthening international norms of “dealing with the past”—places expectations and demands on states’ leadership. These expectations and demands are part of the constraints and pressures within which a conflict operates and within which any peace process is negotiated. Therefore, the current international normative environment makes the positive effects of incorporating historical acknowledgment strategies into early peace negotiations more likely. To illustrate the feasibility of the rationale developed here and its practical implications, the article considers the application of historical acknowledgment strategies to the case of Israel/Palestine and specifically to the 1948 Palestinian refugees issue.
Astrocytes release glutamate via cystine/glutamate antiporter upregulated in response to increased oxidative stress related to sporadic amyotrophic lateral sclerosis
Authors: Kazama Miku , Kato Yoichiro , Kakita Akiyoshi , Noguchi Noriko , Urano Yasuomi , Masui Kenta , Niida‐Kawaguchi Motoko , Yamamoto Tomoko , Watabe Kazuhiko , Kitagawa Kazuo , Shibata Noriyuki
Published: December 2020

A vast body of evidence implicates increased oxidative stress and extracellular glutamate accumulation in the pathomechanism of sporadic amyotrophic lateral sclerosis (ALS). Cystine/glutamate antiporter (xCT) carries extracellular cystine uptake and intracellular glutamate release (cystine/glutamate exchange) in the presence of oxidative stress. The aim of the present study was to determine the involvement of xCT in ALS. Immunohistochemical observations in the spinal cord sections demonstrated that xCT was mainly expressed in astrocytes, with staining more intense in 12 sporadic ALS patients as compared to 12 age‐matched control individuals. Western blot and densitometric analyses of the spinal cord samples revealed that the relative value of xCT/β‐actin optical density ratio was significantly higher in the ALS group as compared to the control group. Next, we conducted cell culture experiments using a human astrocytoma‐derived cell line (1321N1) and a mouse motor neuron/neuroblastoma hybrid cell line (NSC34). In 1321N1 cells, the normalized xCT expression levels in cell lysates were significantly increased by H2O2 treatment. Glutamate concentrations in 1321 N1 cell culture‐conditioned media were significantly elevated by H2O2 treatment, and the H2O2‐driven elevations were completely canceled by the xCT inhibitor erastin pretreatment. In motor neuron‐differentiated NSC34 cells (NSC34d cells), both the normalized xCT expression levels in the cell lysates and glutamate concentrations in the cell‐conditioned media were constant with or without H2O2 treatment. The present results provide in vivo and in vitro evidence that astrocytes upregulate xCT expression to release glutamate in response to increased oxidative stress associated with ALS, contributing to extracellular glutamate accumulation.
High‐resolution manometry reveals different effect of polyethylene glycol, bisacodyl, and prucalopride on colonic motility in healthy subjects: An acute, open label, randomized, crossover, reader‐blinded study with potential clinical implications
Authors: Corsetti Maura , Thys Alexander , Harris Alexander , Pagliaro Giuseppe , Deloose Eveline , Demedts Ingrid , Tack Jan
Published: December 2020

Background

Polyethylene glycol (PEG), bisacodyl, and prucalopride have been reported to be more effective than placebo in treating patients with constipation but about 50% of the patients still do not respond to these medications. Only bisacodyl and prucalopride are expected to directly stimulate the colonic motility in humans in vivo. As no previous study has done this, the aim of the study was to investigate the effect of PEG, bisacodyl, and prucalopride as compared to placebo on colonic motility assessed by means of the high‐resolution manometry (HRM) in healthy subjects.

Methods

Ten healthy subjects have been enrolled in an acute, open label, randomized, reader‐blinded, crossover study and requested to undergo a colonoscopy‐assisted HRM measuring their colonic motility before and after oral administration of 13.8 g (two doses) PEG, 10 mg bisacodyl, 2 mg prucalopride, and placebo.

Key Results

In the human prepared colon, oral administration of PEG significantly increases the number of low‐amplitude long distance propagating contractions (p = 0.007 vs placebo) while bisacodyl significantly increases the number of high‐amplitude propagating contractions (HAPCs) (all p < 0.01 vs PEG, prucalopride, and placebo). Prucalopride has no major effect on the number of propagating contractions but increases HAPCs amplitude (p = 0.01).

Conclusions & Inferences

In humans, PEG, prucalopride, and bisacodyl have distinct effects on colonic motility. This information has clinical implication, as it indicates that the combination of prucalopride and bisacodyl, normally not considered in clinical practice, could be effective in treating patients with constipation refractory to single medications.
Insect egg‐killing: a new front on the evolutionary arms‐race between brassicaceous plants and pierid butterflies
Authors: Griese Eddie , Caarls Lotte , Bassetti Niccolò , Mohammadin Setareh , Verbaarschot Patrick , Bukovinszkine’Kiss Gabriella , Poelman Erik H. , Gols Rieta , Schranz M. Eric , Fatouros Nina E.
Published: December 2020

Evolutionary arms‐races between plants and insect herbivores have long been proposed to generate key innovations such as plant toxins and detoxification mechanisms that can drive diversification of the interacting species. A novel front‐line of plant defence is the killing of herbivorous insect eggs.

We test whether an egg‐killing plant trait has an evolutionary basis in such a plant–insect arms‐race. Within the crucifer family (Brassicaceae), some species express a hypersensitive response (HR)‐like necrosis underneath butterfly eggs (Pieridae) that leads to eggs desiccating or falling off the plant. We studied the phylogenetic distribution of this trait, its egg‐killing effect on and elicitation by butterflies, by screening 31 Brassicales species, and nine Pieridae species.

We show a clade‐specific induction of strong, egg‐killing HR‐like necrosis mainly in species of the Brassiceae tribe including Brassica crops and close relatives. The necrosis is strongly elicited by pierid butterflies that are specialists of crucifers. Furthermore, HR‐like necrosis is linked to PR1 defence gene expression, accumulation of reactive oxygen species and cell death, eventually leading to egg‐killing.

Our findings suggest that the plants’ egg‐killing trait is a new front on the evolutionary arms‐race between Brassicaceae and pierid butterflies beyond the well‐studied plant toxins that have evolved against their caterpillars.
On tree longevity
Authors: Piovesan Gianluca , Biondi Franco
Published: December 2020

Large, majestic trees are iconic symbols of great age among living organisms. Published evidence suggests that trees do not die because of genetically programmed senescence in their meristems, but rather are killed by an external agent or a disturbance event. Long tree lifespans are therefore allowed by specific combinations of life history traits within realized niches that support resistance to, or avoidance of, extrinsic mortality. Another requirement for trees to achieve their maximum longevity is either sustained growth over extended periods of time or at least the capacity to increase their growth rates when conditions allow it. The growth plasticity and modularity of trees can then be viewed as an evolutionary advantage that allows them to survive and reproduce for centuries and millennia. As more and more scientific information is systematically collected on tree ages under various ecological settings, it is becoming clear that tree longevity is a key trait for global syntheses of life history strategies, especially in connection with disturbance regimes and their possible future modifications. In addition, we challenge the long‐held notion that shade‐tolerant, late‐successional species have longer lifespans than early‐successional species by pointing out that tree species with extreme longevity do not fit this paradigm. Identifying extremely old trees is therefore the groundwork not only for protecting and/or restoring entire landscapes, but also to revisit and update classic ecological theories that shape our understanding of environmental change.