bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rising drug cost impacts on cost‐effectiveness of 2 chemotherapy regimens for intermediate‐risk rhabdomyosarcoma: A report from the Children's Oncology Group
Authors: Russell Heidi V. , Chi Yueh‐Yun , Okcu M. Fatih , Bernhardt M. Brooke , Rodriguez‐Galindo Carlos , Gupta Abha A. , Hawkins Douglas S. 
Published: October 2021

BackgroundThe Children's Oncology Group clinical trial for intermediate risk rhabdomyosarcoma randomized participants to a combination of vincristine, dactinomycin, and cyclophosphamide (VAC) alone or VAC alternating with vincristine plus irinotecan (VAC/VI). Clinical outcomes were similar, but toxicity profiles differed. This study estimates the cost differences between arms from the health care system's perspective.MethodsA decision‐analytic model was used to estimate the incremental cost‐effectiveness ratio (ICER) of VAC versus VAC/VI. Protocol‐required or recommended medications and laboratory studies were included. Costs were obtained from national databases or supporting literature and inflated to 2019 US dollars. Demographic and outcome data were obtained from the clinical trial and directed chart reviews. Life‐years (LY) were estimated from life‐expectancy tables and discounted by 3% annually. Probabilistic sensitivity analyses and alternative clinical scenarios identified factors driving costs.ResultsMean direct medical costs of VAC and VAC/VI were $164,757 and $102,303, respectively. VAC was associated with an additional 0.97 LY and an ICER of $64,386/LY compared with VAC/VI. The ICER was sensitive to survival estimations and to alternative clinical scenarios including outpatient cyclophosphamide delivery (ICER $49,037/LY) or substitution of alternative hematopoietic growth factor schedules (ICER $73,191‐$91,579/LY). Applying drug prices from 2012 decreased the total costs of VAC by 20% and VAC/VI by 15% because of changes in dactinomycin and pegfilgrastim prices.ConclusionsNeither arm was clearly more cost‐effective. Pharmaceutical pricing and location of treatment drove costs and may inform future treatment decisions. Rising pharmaceutical costs added $30,000 per patient, a finding important for future drug‐pricing policy decisions.Lay Summary

Two chemotherapy regimens recently tested side‐by‐side for rhabdomyosarcoma had similar tumor outcomes, but different side effects.

The health care costs of each regimen were compared; neither was clearly more cost‐effective.

However, the costs of each treatment changed dramatically with choices of supportive medicines and location of treatment.

Costs of treatment rose by 15% to 20% because of rising US drug costs not associated with the clinical trial.
Impact of including second and later cancers in cause‐specific survival estimates using population‐based registry data
Authors: Forjaz Gonçalo , Howlader Nadia , Scoppa Steve , Johnson Christopher J. , Mariotto Angela B. 
Published: October 2021

BackgroundSecond or later primary cancers account for approximately 20% of incident cases in the United States. Currently, cause‐specific survival (CSS) analyses exclude these cancers because the cause of death (COD) classification algorithm was available only for first cancers. The authors added rules for later cancers to the Surveillance, Epidemiology, and End Results cause‐specific death classification algorithm and evaluated CSS to include individuals with prior tumors.MethodsThe authors constructed 2 cohorts: 1) the first ever primary cohort, including patients whose first cancer was diagnosed during 2000 through 2016) and 2) the earliest matching primary cohort, including patients with any cancer who matched the selection criteria irrespective of whether it was the first or a later cancer diagnosed during 2000 through 2016. The cohorts' CSS estimates were compared using follow‐up through December 31, 2017. The new rules were used in the second cohort for patients whose first cancers during 2000 through 2016 were their second or later cancers.ResultsOverall, there were no statistically significant differences in CSS estimates between the 2 cohorts. Estimates were similar by age, stage, race, and time since diagnosis, except for patients with leukemia and those aged 65 to 74 years (3.4 percentage point absolute difference).ConclusionsThe absolute difference in CSS estimates for the first cancer ever cohort versus earliest of any cancers cohort in the study period was small for most cancer types. As the number of newly diagnosed patients with prior cancers increases, the algorithm will make CSS more inclusive and enable estimating survival for a group of patients with cancer for whom life tables are not available or life tables are available but do not capture other‐cause mortality appropriately.
ESL curriculum with a heuristic anchorage: Tokenist discourses and the epistemology of community service education
Authors: Chandrasoma Ranamukalage 
Published: October 2021

AbstractCommunity service education (CSE) in developing countries still remains under‐represented in research. Addressing this gap, this article reports a study that investigated a CSE activity at a secondary school in Sri Lanka. The participants of this study comprised 10 English as a second language (ESL) teachers from four secondary schools, 68 Grade 10 students from a secondary school located in a semi‐urban area and the author as participant observer. Based on this qualitative case study in the context of ESL writing pedagogy, the article conceptualises the epistemology of CSE in terms of four dimensions: experiential learning, knowledge/skills application, community participation and critical judgement. It also emphasises the futility of tokenist discourses and suggests that an ESL curriculum needs to have a heuristic orientation in CSE not as a mere extra‐curricular exercise but as a mandatory component of social interaction where mutually constitutive benefits for students, teachers and the community are foregrounded. This article highlights how the student writer participants in this study were disadvantaged as a result of tokenist discourses and their teachers demoralised due to an inadequate grasp of the epistemology of CSE, curricular deficiencies, politically driven constraints and poorly resourced classrooms.
Behavioral reinforcement of pathological exercise in anorexia nervosa
Authors: Coniglio Kathryn A. , Cooper Marita , Selby Edward A. 
Published: October 2021

AbstractPathological exercise in anorexia nervosa (AN) is a harmful behavior associated with a chronic course and poor prognosis. To date, no comprehensive theoretical model exists to describe pathological exercise in the context of AN, and as such, few treatments are effective at promoting direct and sustained pathological exercise extinction. Using a framework put forth by Wise & Koob (2014), debating the relative importance of positive and negative reinforcement in substance use, we present three hypotheses of behavioral reinforcement of exercise, encompassing biological, psychological, and environmental influences. Specifically, we argue that exercise is positively reinforced through receipt of biological and behavioral rewards, negatively reinforced through avoidance of aversive emotions, and that these two systems work in tandem over time to engrain pathological exercise as a habit. We then present suggestions for testing each of these hypotheses as future directions for the field.
Relatedness and the evolution of mechanisms to divide labor in microorganisms
Authors: Liu Ming , West Stuart Andrew , Cooper Guy Alexander 
Published: October 2021

AbstractDivision of labor occurs when cooperating individuals specialize to perform different tasks. In bacteria and other microorganisms, some species divide labor by random specialization, where an individual's role is determined by random fluctuations in biochemical reactions within the cell. Other species divide labor by coordinating across individuals to determine which cells will perform which task, using mechanisms such as between‐cell signaling. However, previous theory, examining the evolution of mechanisms to divide labor between reproductives and sterile helpers, has only considered clonal populations, where there is no potential for conflict between individuals. We used a mixture of analytical and simulation models to examine nonclonal populations and found that: (a) intermediate levels of coordination can be favored, between the extreme of no coordination (random) and full coordination; (b) as relatedness decreases, coordinated division of labor is less likely to be favored. Our results can help explain why coordinated division of labor is relatively rare in bacteria, where groups may frequently be nonclonal.
Evaluating otter reintroduction outcomes using genetic spatial capture–recapture modified for dendritic networks
Authors: Murphy Sean M. , Adams Jennifer R. , Waits Lisette P. , Cox John J. 
Published: October 2021

AbstractMonitoring the demographics and genetics of reintroduced populations is critical to evaluating reintroduction success, but species ecology and the landscapes that they inhabit often present challenges for accurate assessments. If suitable habitats are restricted to hierarchical dendritic networks, such as river systems, animal movements are typically constrained and may violate assumptions of methods commonly used to estimate demographic parameters. Using genetic detection data collected via fecal sampling at latrines, we demonstrate applicability of the spatial capture–recapture (SCR) network distance function for estimating the size and density of a recently reintroduced North American river otter (Lontra canadensis) population in the Upper Rio Grande River dendritic network in the southwestern United States, and we also evaluated the genetic outcomes of using a small founder group (n = 33 otters) for reintroduction. Estimated population density was 0.23–0.28 otter/km, or 1 otter/3.57–4.35 km, with weak evidence of density increasing with northerly latitude (β = 0.33). Estimated population size was 83–104 total otters in 359 km of riverine dendritic network, which corresponded to average annual exponential population growth of 1.12–1.15/year since reintroduction. Growth was ≥40% lower than most reintroduced river otter populations and strong evidence of a founder effect existed 8–10 years post‐reintroduction, including 13–21% genetic diversity loss, 84%–87% genetic effective population size decline, and rapid divergence from the source population (FSTaccumulation = 0.06/generation). Consequently, genetic restoration via translocation of additional otters from other populations may be necessary to mitigate deleterious genetic effects in this small, isolated population. Combined with non‐invasive genetic sampling, the SCR network distance approach is likely widely applicable to demogenetic assessments of both reintroduced and established populations of multiple mustelid species that inhabit aquatic dendritic networks, many of which are regionally or globally imperiled and may warrant reintroduction or augmentation efforts.
African manatee (Trichechus senegalensis) habitat suitability at Lake Ossa, Cameroon, using trophic state models and predictions of submerged aquatic vegetation
Authors: Takoukam Aristide K. , Gomes Dylan G. E. , Hoyer Mark V. , Keith‐Diagne Lucy W. , Bonde Robert K. , Francis‐Floyd Ruth 
Published: October 2021

AbstractThe present study aims at investigating the past and current trophic status of Lake Ossa and evaluating its potential impact on African manatee health. Lake Ossa is known as a refuge for the threatened African manatees in Cameroon. Little information exists on the water quality and health of the ecosystem as reflected by its chemical and biological characteristics. Aquatic biotic and abiotic parameters including water clarity, nitrogen, phosphorous, and chlorophyll concentrations were measured monthly during four months at each of 18 water sampling stations evenly distributed across the lake. These parameters were then compared with historical values obtained from the literature to examine the dynamic trophic state of Lake Ossa. Results indicate that Lake Ossa's trophic state parameters doubled in only three decades (from 1985 to 2016), moving from a mesotrophic to a eutrophic state. The decreasing nutrient gradient moving from the mouth of the lake (in the south) to the north indicates that the flow of the adjacent Sanaga River is the primary source of nutrient input. Further analysis suggests that the poor transparency of the lake is not associated with chlorophyll concentrations but rather with the suspended sediments brought‐in by the Sanaga River. Consequently, our model demonstrated that despite nutrient enrichment, less than 5% of the lake bottom surface sustained submerged aquatic vegetation. Thus, shoreline emergent vegetation is the primary food available for the local manatee population. During the dry season, water recedes drastically and disconnects from the dominant shoreline emergent vegetation, decreasing accessibility for manatees. The current study revealed major environmental concerns (eutrophication and sedimentation) that may negatively impact habitat quality for manatees. The information from the results will be key for the development of the management plan of the lake and its manatee population. Efficient land use and water management across the entire watershed may be necessary to mitigate such issues.
Physical effects of motion sickness for comfortable VR viewing
Authors: Ono Rentaro , Matsuura Yasuyuki , Nakane Kohki , Takada Hiroki 
Published: October 2021

AbstractIn accordance with developments in the image technology over recent years, it has become easier to watch 3D video clips. As the viewing of 3D video has become more commonplace, symptoms such as visually induced motion sickness (VIMS) and eye fatigue have been reported. Although various theories regarding the underlying causes of the VIMS have been proposed, these causes have yet to be fully investigated. In a previous study, the background of an image was shown to influence the equilibrium function of a subject viewing a 3D video clip. In this study, the authors investigated the influence of image elements such as the size of the visual field especially in the backgrounds of the projected image and velocity of the visual target speed on the body of a subject viewing a 3D video clips by measuring their body sway, the electrocardiogram signals, and the cerebral blood flow using functional near‐infrared spectroscopy (fNIRS). Our results has indicated that the value of the total locus length is significantly higher while viewing a video clip whose visual fields of backgrounds is not narrowed than that with narrower backgrounds. This suggests that stability in the system to control their posture can be enhanced by reducing the amount of visual information.
Magnetohydrodynamic numerical simulation of bubble‐bubble interaction in alkaline water electrolysis with magnetic field
Authors: Kodama Manabu , Matsumae Hikaru , Kiuchi Takeshi , Murakami Naoki , Hirai Shuichiro 
Published: October 2021

AbstractThree‐dimensional large scale magnetohydrodynamic, two‐phase flow, and electrochemical reaction coupling numerical simulations of alkaline water electrolysis with magnetic field were conducted to elucidate the bubble‐bubble interaction and the influence of that on the overpotential. Numerical results show that the magnetic field enhances the coalesce of bubbles and the bubble size was increased with the increase in the magnetic flux density. Moreover, the magnetic field suppressed the cell overpotential by suppressing the anode overpotential and ohmic overpotential. This is because KOH concentration around the anode is increased by mixing of the electrolyte, and the reduction of the shielding effect by coalescing of the bubbles.
Early and short‐term intensive management after discharge for patients hospitalized with acute heart failure: a randomized study (ECAD‐HF)
Authors: Logeart Damien , Berthelot Emmannuelle , Bihry Nicolas , Eschalier Romain , Salvat Muriel , Garcon Philippe , Eicher Jean‐Christophe , Cohen Ariel , Tartiere Jean‐Michel , Samadi Alireza , Donal Erwan , deGroote Pascal , Mewton Nathan , Mansencal Nicolas , Raphael Pierre , Ghanem Nachwan , Seronde Marie‐France , Chavelas Christophe , Rosamel Yann , Beauvais Florence , Kevorkian Jean‐Philippe , Diallo Abdourahmane , Vicaut Eric , Isnard Richard 
Published: October 2021

AbstractAimsHospitalization for acute heart failure (HF) is followed by a vulnerable time with increased risk of readmission or death, thus requiring particular attention after discharge. In this study, we examined the impact of intensive, early follow‐up among patients at high readmission risk at discharge after treatment for acute HF.Methods and resultsHospitalized acute HF patients were included with at least one of the following: previous acute HF < 6 months, systolic blood pressure ≤ 110 mmHg, creatininaemia ≥ 180 µmol/L, or B‐type natriuretic peptide ≥ 350 pg/mL or N‐terminal pro B‐type natriuretic peptide ≥ 2200 pg/mL. Patients were randomized to either optimized care and education with serial consultations with HF specialist and dietician during the first 2–3 weeks, or to standard post‐discharge care according to guidelines. The primary endpoint was all‐cause death or first unplanned hospitalization during 6‐month follow‐up. Among 482 randomized patients (median age 77 and median left ventricular ejection fraction 35%), 224 were hospitalized or died. In the intensive group, loop diuretics (46%), beta‐blockers (49%), angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers (39%) and mineralocorticoid receptor antagonists (47%) were titrated. No difference was observed between groups for the primary endpoint (hazard ratio 0.97; 95% confidence interval 0.74–1.26), nor for mortality at 6 or 12 months or unplanned HF rehospitalization. Additionally, no difference between groups according to age, previous HF and left ventricular ejection fraction was found.ConclusionsIn high‐risk HF, intensive follow‐up early post‐discharge did not improve outcomes. This vulnerable post‐discharge time requires further studies to clarify useful transitional care services.
Feasibility and efficacy of transcatheter interatrial shunt devices for chronic heart failure: a systematic review and meta‐analysis
Authors: Lauder Lucas , Pereira Tiago V. , Degenhardt Markus C. , Ewen Sebastian , Kulenthiran Saarraaken , Coats Andrew J.S. , Böhm Michael , Anker Stefan D. , da Costa Bruno R. , Mahfoud Felix 
Published: October 2021

AbstractAimsTo assess the feasibility and efficacy of interatrial shunt devices (IASD) for the treatment of chronic heart failure (CHF).Methods and resultsMEDLINE and the Cochrane Central Register of Controlled Trials from inception until April 2021 were searched for prospective studies investigating dedicated transcatheter IASD for the treatment of CHF. Standardised mean differences were calculated for the within‐group changes before and after implantation of the IASD. The pre‐defined primary outcome was change in 6‐min walking distance (6MWD) from baseline to 12 months. Other outcomes were change in New York Heart Association class, health‐related quality of life (HRQoL), echocardiographic and haemodynamic data, device performance and safety. Subgroup analyses were crude univariable meta‐regression analyses. Six studies (five single‐arm open‐label studies, one sham‐controlled trial) were included. In these, 226 patients underwent IASD implantation using four different devices. From baseline to 12 months, 6MWD increased by 28.1 m [95% confidence interval (CI) 10.9–45.3] with no evidence for a difference between devices (P for interaction = 0.66) and patients with left ventricular ejection fraction (LVEF) >40% or ≤40% (P for interaction = 0.21). At 12 months, HRQoL improved by 17.7 points (95% CI 10.8–24.6) and pulmonary capillary wedge pressure (PCWP) decreased by 2.0 mmHg (95% CI −3.6 to −0.4). There were no changes in LVEF or N‐terminal pro brain natriuretic peptide during follow‐up. Shunt patency ranged from 50% for the first‐generation v‐Wave to 100% for the Corvia IASD II and the second‐generation v‐Wave system, respectively. The summary risk of serious adverse device‐related effects was 8% (95% CI 1–20) at 12 months.ConclusionsInteratrial shunt device implantation in CHF is feasible and associates with improved submaximal exercise capacity (measured by 6MWD) and HRQoL, and reductions in PCWP.
Cover Image, Volume 69, Issue 12
Authors: Pirnat Samo , Božić Mićo , Dolanc Dorian , Horvat Anemari , Tavčar Petra , Vardjan Nina , Verkhratsky Alexei , Zorec Robert , Stenovec Matjaž 
Published: October 2021

Cover Illustration: Live arborized astrocyte in culture (NB+), containing numerous dextran‐laden endocytotic vesicles (green), revealed by confocal microscopy. Arborized astrocytes display increased resting levels of intracellular Ca2+ concentration ([Ca2+]i) and [cAMP]i, increased subcellular heterogeneity in [Ca2+]i, but not in [cAMP]i, and attenuated vesicle mobility. (See Pirnat, S., et al, https://doi.org/10.1002/glia.24076.)image
Pupillometry tracks cognitive load and salience network activity in a working memory functional magnetic resonance imaging task
Authors: Fietz Julia , Pöhlchen Dorothee , Binder Florian P. ,   BeCOME Working Group, Czisch Michael , Sämann Philipp G. , Spoormaker Victor I. 
Published: October 2021

AbstractThe diameter of the human pupil tracks working memory processing and is associated with activity in the frontoparietal network. At the same time, recent neuroimaging research has linked human pupil fluctuations to activity in the salience network. In this combined functional magnetic resonance imaging (fMRI)/pupillometry study, we recorded the pupil size of healthy human participants while they performed a blockwise organized working memory task (N‐back) inside an MRI scanner in order to monitor the pupil fluctuations associated neural activity during working memory processing. We first confirmed that mean pupil size closely followed working memory load. Combining this with fMRI data, we focused on blood oxygen level dependent (BOLD) correlates of mean pupil size modeled onto the task blocks as a parametric modulation. Interrogating this modulated task regressor, we were able to retrieve the frontoparietal network. Next, to fully exploit the within‐block dynamics, we divided the blocks into 1 s time bins and filled these with corresponding pupil change values (first‐order derivative of pupil size). We found that pupil change within N‐back blocks was positively correlated with BOLD amplitudes in the areas of the salience network (namely bilateral insula, and anterior cingulate cortex). Taken together, fMRI with simultaneous measurement of pupil parameters constitutes a valuable tool to dissect working memory subprocesses related to both working memory load and salience of the presented stimuli.
Mental health effects of same‐sex marriage legalization
Authors: Chen Shuai , van Ours Jan C. 
Published: October 2021

AbstractSame‐sex marriage legalization (SSML) is a typical anti‐discrimination policy to remove institutional discrimination against sexual minorities by providing them with marriage equality. We examine how this legalization in the Netherlands affected mental health. Conducting a difference‐in‐differences analysis with heterosexual individuals as a reference group, we find that SSML significantly improved mental health of sexual minorities and substantially reduced the sexual orientation gap of mental health. The beneficial effects were present for both married and non‐married sexual minorities. This phenomenon suggests that part of the health gains were related to mechanisms beyond marriage itself.