bluuebunny/crossref_metadata_2025 huggingface dataset:
Insurance coverage change and survivorship care among young adult survivors of childhood cancer
Authors: Mobley Erin M. , Kim Sue E. , Cousineau Michael , Tsui Jennifer , Miller Kimberly A. , Tobin Jessica , Freyer David R. , Milam Joel E.
Published: August 2021

Objective

To (1) characterize change in type of insurance coverage among childhood cancer survivors from diagnosis to survivorship and (2) examine whether insurance change is associated with cancer‐related follow‐up care utilization.

Data Sources

Participants in this study were derived from the Project Forward study, a population‐based, observational study of childhood cancer survivors in Los Angeles County that used California Cancer Registry data to identify participants.

Study Design

Multivariable logistic regression models incorporating survey nonresponse weights estimated the change in the marginal predicted probabilities of insurance change and survivorship care, adjusting for demographic, socioeconomic, and clinical covariates and clustering by treating hospital.

Data Collection/Extraction Methods

Study participants were diagnosed with cancer who were younger than age 20 years while living in Los Angeles County from 1996 to 2010 and were older than the age 18 years at the time of survey participation, from 2015 to 2017 (N = 1106).

Principal Findings

Most participants were 18–26 years of age, male, diagnosed before 2004, Hispanic/Latino race/ethnicity, single, without children, highly educated, not employed full time, and lived with their parents at survey. Almost half (N = 529) of participants experienced insurance change from diagnosis to survivorship. Insurance change was associated with insurance coverage at diagnosis, as those who were uninsured were most likely to experience change and gain coverage during survivorship (by 51 percentage points [ppt], standard error [SE] of 0.05). Survivors who experienced any change had decreased probability of reporting a recent cancer‐related follow‐up care visit, a disparity that was magnified for those who lost insurance coverage (−5 ppt, SE 0.02 for those who gained coverage; −15 ppt, SE 0.04 for those who lost coverage).

Conclusions

Insurance coverage change was associated with lower cancer‐related follow‐up care utilization. Indeed, survivors who experienced any insurance coverage change had decreased probability of having a cancer‐related follow‐up care visit, and this was magnified for those who lost their insurance coverage.
Future trends of processed meat products concerning perceived healthiness: A review
Authors: Badar Iftikhar Hussain , Liu Haotian , Chen Qian , Xia Xiufang , Kong Baohua
Published: August 2021

The 21st‐century consumer is highly demanding when it comes to the health benefits of food and food products. In the pursuit of attracting these consumers and easing the rise in demand for high‐quality meat products, the processed meat sector is intensely focused on developing reformulated, low‐fat, healthy meat products. Meat and meat products are considered the primary sources of saturated fatty acids in the human diet. Therefore, these reformulation strategies aim to improve the fatty acid profile and reduce total fat and cholesterol, which can be achieved by replacing animal fat with plant‐based oils; it could be performed as direct inclusion of these oils or pre‐emulsified oils. However, emulsions offer a viable option for incorporating vegetable oils while avoiding the multiple issues of direct inclusion of these oils in meat products. Processed meat products are popular worldwide and showing a gradually increasing trend of consumption. Various types of plant‐based oils have been studied as fat replacers in meat products. This review will focus on possible methods to reduce the saturated fatty acid content in meat products.
The factors influencing the identification of the chronological intersecting sequence between ink and toner
Authors: Chai Tianruomei , Li Biao
Published: August 2021

Identifying the formation time of a document is a problem forensic document examiners often face. It is understood that intersections with different intersecting sequences made by the same laser printer and the same gel pen are distinct from each other under coaxial light, and the appearance of an oil film or bright metallic marks in the regions of interest can be used as the basis to identify that the ink is above the toner. However, the characteristics of intersections may be influenced by a number of factors. Studying the characteristics of the intersections formed by laser‐printed graphics and handwriting strokes made with a gel pen in different intersecting sequences can help us determine the formation sequence of each part on a questioned document. In this manuscript, samples were made using three pen types and two laser printers. A Leica stereo microscope M205A was used to capture the apparent morphology of the intersections. Microspectrophotometry spectra of all intersections were collected in reflectance mode using a video spectral comparator 6000 (VSC6000), and the resultant data were measured and analyzed in Statistical Product and Service Solutions 26.0 (SPSS). The results showed that 92.5% absolute accuracy was achieved from blind tests, and the intersecting sequence can be determined using the optical data of the intersections with an accuracy of up to 97.5% through discriminant analysis under ideal conditions.
Rising inequalities, deepening divides: Urban citizenship in the time of COVID‐19
Authors: Recio Redento B. , Lata Lutfun Nahar , Chatterjee Ishita
Published: August 2021

As governments around the globe navigate the effects of COVID‐19 crisis, the urban poor endure the unevenly distributed socio‐economic impacts of the pandemic. This burden is more pronounced in Global South megacities, where millions of people engage in precarious informal employment. We examine how the urban poor in Delhi (India), Dhaka (Bangladesh), and Manila (Philippines) have been disproportionately affected by the crisis. A cross‐case analysis was undertaken to determine how the realities and relations of one context can enrich our understanding of the other. We argue that the current COVID‐19 pandemic has exposed the unequal urban citizenship in these three metropolises. Drawing on research reports, news articles, and interviews with urban poor leaders, we explain how limited government assistance has forced some to retreat to their rural hometowns or rely on self‐help and mutual aid practices to survive. We consider the patterns both in governments’ treatment of impoverished citizens and in the unjust effects of lockdown enforcement on marginalised populations. We also discuss the roles that women and non‐government organisations (NGOs) have played in facilitating solidarity‐based practices to help urban poor communities cope with COVID‐19 vulnerabilities.
Profiling the physiological pitfalls of anti‐hepatitis C direct‐acting agents in budding yeast
Authors: Yahya Galal , Hashem Mohamed Nashwa , Pijuan Jordi , Seleem Noura M. , Mosbah Rasha , Hess Steffen , Abdelmoaty Ahmed A. , Almeer Rafa , Abdel‐Daim Mohamed M. , Shulaywih Alshaman Hamoud , Juraiby Ibrahim , Metwally Kamel , Storchova Zuzana
Published: August 2021

Sofosbuvir and Daclatasvir are among the direct‐acting antiviral (DAA) medications prescribed for the treatment of chronic hepatitis C (CHC) virus infection as combination therapy with other antiviral medications. DAA‐based therapy achieves high cure rates, reaching up to 97% depending on the genotype of the causative hepatitis C virus (HCV). While DAAs have been approved as an efficient and well‐tolerated therapy for CHC, emerging concerns about adverse cardiac side effects, higher risk of recurrence and occurrence of hepatocellular carcinoma (HCC) and doubts of genotoxicity have been reported. In our study, we investigated in detail physiological off‐targets of DAAs and dissected the effects of these drugs on cellular organelles using budding yeast, a unicellular eukaryotic organism. DAAs were found to disturb the architecture of the endoplasmic reticulum (ER) and the mitochondria, while showing no apparent genotoxicity or DNA damaging effect. Our study provides evidence that DAAs are not associated with genotoxicity and highlights the necessity for adjunctive antioxidant therapy to mitigate the adverse effects of DAAs on ER and mitochondria.
Geothermal Model of the Fore‐Yenisey Sedimentary Basin—Transitional Structure between the Ancient Siberian Platform and the Young West Siberian Plate
Authors: NOVIKOV Dmitriy , DULTSEV Fedor , FILIPPOV Yuriy
Published: August 2021

Results of the investigation into the geothermal regime of the Fore‐Yenisey sedimentary basin, formed during the collision and subsidence of the Kas‐Turukhan microcontinent and the western margin of the Siberian craton in the late Neoproterozoic and early Paleozoic are reported. It was established that the structural and geothermal conditions of the upper Precambrian–Paleozoic sections are similar to those in the western regions of the Siberian platform and are characterized by rather low geothermal gradients (12.5–25.5 °C/km). In the western parts of the basin, formation temperatures in the uppermost pre‐Jurassic sediments are 50°C–85°C, decreasing eastward to 30°C–55°C. For the first time, the detailed geothermal model of the basin sedimentary fill was developed. This model allows predictions of the geothermal conditions of Earth's interior.
Advances and highlights in allergic rhinitis
Authors: Zhang Yuan , Lan Feng , Zhang Luo
Published: August 2021

Allergic rhinitis (AR) is a growing public health, medical and economic problem worldwide. The current review describes the major discoveries related to AR during the past 2 years, including risk factors for the prevalence of AR, the corresponding diagnostic strategy, precise underlying immunological mechanisms, and efficient therapies for AR during the ongoing global “coronavirus disease 2019” (COVID‐19) pandemic. The review further attempts to highlight future research perspectives. Increasing evidence suggests that environmental exposures, climate changes, and lifestyle are important risk factors for AR. Consequently, detailed investigation of the exposome and the connection between environmental exposures and health in the future should provide better risk profiles instead of single predictors, and also help mitigate adverse health outcomes in allergic diseases. Although patients with dual AR, a newly defined AR phenotype, display perennial and seasonal allergens‐related nasal symptoms, they are only allergic to seasonal allergens, indicating the importance of measuring inflammation at the local sites. Herein, we suggest that a combination of precise diagnosis in local sites and traditional diagnostic methods may enhance the precision medicine‐based approach for management of AR; however, this awaits further investigations. Apart from traditional treatments, social distancing, washing hands, and disinfection are also required to better manage AR patients in the ongoing global COVID‐19 pandemic. Despite recent advances in understanding the immune mechanisms underlying the effects of allergen immunotherapy (AIT), further understanding changes of cell profiles after AIT and accurately evaluate the efficacy of AIT are required.
Do you get what you pay for? Preventing insufficient effort responding in MTurk and student samples
Authors: Toich Margaret J. , Schutt Elizabeth , Fisher David M.
Published: August 2021

Previous research has developed multiple indices to detect instances of insufficient effort responding (IER; Huang et al., 2015, 0.1037/a0038510). Although these techniques are largely successful, conflation between effort and insufficient effort leads to unnecessary data removal, thus warranting investigation into IER prevention strategies such as warning statements. For example, Brühlmann et al. (2020, 10.1016/j.metip.2020.100022) reported that close to 60% of participants were flagged for IER on at least one IER detection index. The current study used positive, negative, and no warning statements in two samples (MTurk and university participant pool) to examine their impact on two types of IER. Results do not support the use of warning statements to reduce IER covertly, overtly, or overall. Although slightly more university participants were flagged for IER for two of five IER indices, the remaining three indices did not differ between samples. This finding represents an important contribution to survey research literature by directly comparing samples on a variety of IER indices. Implications for survey research necessitate the examination of additional prevention strategies and sample differences in IER.
Neonatal outcomes after neuraminidase inhibitor use during pregnancy: A meta‐analysis of cohort studies
Authors: Lian Jiangshan , Adilijiang Munire , Chang Caihua , Jiang Haiyin , Zhang Yongping
Published: August 2021

Aim

Influenza infection poses a severe threat to pregnant mothers, and antiviral treatment is recommended. However, the safety of neuraminidase‐inhibitor antiviral medications during pregnancy has not been well described.

Methods

A systematic review and meta‐analysis were performed to evaluate the adverse neonatal outcomes associated with exposure to neuraminidase inhibitors during pregnancy. The PubMed, Embase and Cochrane Library databases were searched to identify potential studies for inclusion.

Results

Nine cohort studies that estimated adverse neonatal outcomes associated with exposure to neuraminidase‐inhibitor medication during pregnancy were included. Exposure to a neuraminidase inhibitor during pregnancy was not associated with an increased risk of congenital malformation (odds ratio [OR] 0.9, 95% confidence interval [CI] 0.72‐1.12, P = .341), low Apgar score (OR 0.96, 95% CI 0.77‐1.2, P = .733) or preterm birth (OR 0.99, 95% CI 0.89‐1.09, P = .771) compared with no exposure. However, exposure to a neuraminidase inhibitor was associated with a reduced risk of low birth weight (OR 0.79, 95% CI 0.68‐0.92, P = .002) and giving birth to a small‐for‐gestational‐age infant (OR 0.78, 95% CI 0.69‐0.88, P < .001). Further analyses limited to oseltamivir exposure were consistent with the overall results.

Conclusion

Exposure to neuraminidase‐inhibitor medication during pregnancy does not appear to be associated with adverse neonatal outcomes. We recommend further studies to investigate this association, which will help clinicians determine whether to prescribe a neuraminidase inhibitor during pregnancy.
A randomized, open‐label, two‐period crossover bridging study on fuzuloparib capsules of different specifications in healthy Chinese volunteers
Authors: Jiang Xin , Tao Ye , Liu Yanping , Shi Ping , Li Ting , Sun Feifei , Cao Yu , Wang Chenjing
Published: August 2021

Aims

Fuzuloparib, also known as fluzoparib or SHR3162, is a poly ADP‐ribose polymerase (PARP) inhibitor developed for the treatment of malignant tumours. Three specifications of fuzuloparib capsules (10 mg, 40 mg and 100 mg) were originally developed for clinical trials. After the recommended dose was determined, a new specification of fuzuloparib capsule (50 mg) was produced for clinical use. This bridging study was conducted to determine the bioequivalence of the new specification to the three other specifications at the recommended dose.

Methods

A single‐centre, randomized, open‐label, two‐period, crossover bridging study was conducted in 40 healthy Chinese subjects under fed conditions. Enrolled subjects received a single oral dose of test or reference preparations according to a randomization list in the first period and crossed over to receive the other preparations in the second period after a 6‐day washout interval. Blood samples were collected pre‐dose and post‐dose at specified time intervals. Plasma fuzuloparib concentrations were analysed by liquid chromatography‐mass spectroscopy (LC‐MS). A non‐compartment model was adopted to calculate pharmacokinetic parameters of investigational preparations. Primary PK parameters including area under the concentration–time curve (AUC) from administration to the last sampling time (AUC0‐t), AUC extrapolated to infinity (AUC0‐∞) and Cmax of test and reference preparations were compared to evaluate their bioequivalence.

Results

The 90% confidence intervals (CIs) of geometric mean ratios of AUC0‐t, AUC0‐∞ and Cmax were 96.99–104.95%, 97.03–104.93% and 96.53–108.98%, respectively, all of which were within the bioequivalence range of 80–125%. No serious adverse events were observed in this study and no subjects withdrew from the study due to adverse events.

Conclusions

The test preparations were bioequivalent to the reference preparations. All investigational products were well tolerated.
Alpha haemoglobin‐stabilising protein concentration in the red blood cells of patients with sickle cell anaemia with and without hydroxycarbamide treatment
Authors: Vasseur Corinne , Domingues‐Hamdi Elisa , Pakdaman Sadaf , Galactéros Frédéric , Baudin‐Creuza Véronique
Published: August 2021

Alpha haemoglobin‐stabilising protein (AHSP) is a key chaperone synthesised in red blood cell (RBC) precursors. Many studies have reported AHSP as a potential biomarker of various diseases. AHSP gene expression has been studied in detail, but little is known about AHSP protein levels in RBCs. We investigated the AHSP concentration of RBC lysates from control subjects (n = 10) and patients with sickle cell anaemia (SCA) with (n = 10) and without (n = 12) hydroxycarbamide (HC) treatment, to evaluate the clinical relevance of AHSP in SCA. We developed a sandwich enzyme‐linked immunosorbent assay method, with which we were able, for the first time, to determine the mean AHSP concentration in control RBC lysates (0·82 µg/ml). The AHSP concentration (2·23 µg/ml) was significantly higher in untreated patients with the SS genotype than in controls. The AHSP concentration decreased significantly on HC treatment (1·50 µg/ml) but remained significantly higher than that in controls. A strong positive correlation was observed between the AHSP concentration and the α‐haemoglobin pool with the three groups of subjects pooled into a single group. Our present findings indicate that AHSP concentration can be considered a candidate biomarker for monitoring HC responses in patients with SCA and suggest a role for AHSP in various RBC diseases.
Presence of ethanol‐sensitive and ethanol‐insensitive glycine receptors in the ventral tegmental area and prefrontal cortex in mice
Authors: Araya Anibal , Gallegos Scarlet , Viveros Rodrigo , San Martin Loreto , Muñoz Braulio , Harvey Robert J. , Zeilhofer Hanns U. , Aguayo Luis G.
Published: August 2021

Background and Purpose

Glycine receptors composed of α1 and β subunits are primarily found in the spinal cord and brainstem and are potentiated by ethanol (10–100 mM). However, much less is known about the presence, composition and ethanol sensitivity of these receptors in higher CNS regions. Here, we examined two regions of the brain reward system, the ventral tegmental area (VTA) and the prefrontal cortex (PFC), to determine their glycine receptor subunit composition and sensitivity to ethanol.

Experimental Approach

We used Western blot, immunohistochemistry and electrophysiological techniques in three different models: wild‐type C57BL/6, glycine receptor subunit α1 knock‐in and glycine receptor subunit α2 knockout mice.

Key Results

Similar levels of α and β receptor subunits were detected in both brain regions, and electrophysiological recordings demonstrated the presence of glycine‐activated currents in both areas. Sensitivity of glycine receptors to glycine was lower in the PFC compared with VTA. Picrotoxin only partly blocked the glycine‐activated current in the PFC and VTA, indicating that both regions express heteromeric αβ receptors. Glycine receptors in VTA neurons, but not in PFC neurons, were potentiated by ethanol.

Conclusion and Implications

Glycine receptors in VTA neurons from WT and α2 KO mice were potentiated by ethanol, but not in neurons from the α1 KI mice, supporting the conclusion that α1 glycine receptors are predominantly expressed in the VTA. By contrast, glycine receptors in PFC neurons were not potentiated in any of the mouse models studied, suggesting the presence of α2/α3/α4, rather than α1 glycine receptor subunits.
Targeting lipid metabolism in multiple myeloma cells: Rational development of a synergistic strategy with proteasome inhibitors
Authors: Xu Gaojie , Huang Sheng , Peng Jian , Gao Xiaofang , Li Minhui , Yu Sisi , Liu Zuofeng , Qie Pengfan , Wang Yu , Yu Siqi , Liu Siyuan , Wen Hu , Su Lijuan , Li Ping , Guang Bin , Dong Renhan , Liu Jin , Yang Tai
Published: August 2021

Background and Purpose

Aberrant lipid metabolism is recognized as a key feature of cancer cells. Our initial research on MS‐based analysis of lipids in a multiple myeloma (MM) cell line showed a significant accumulation of lipids in multiple myeloma cells after proteasome inhibition. This finding prompted us to hypothesize that multiple myeloma cell survival depends on the maximal utilization of abnormally accumulated lipids. Therefore, we explored whether lipid metabolism‐modulating agents would synergize with proteasome inhibitors.

Experimental Approach

Lipid accumulation in multiple myeloma cells was measured by MS. Synergism between lipid regulators and proteasome inhibitors was assessed by cell viability and apoptosis. A novel stable derivative of fenofibrate (FCE) was synthesized and used to treat multiple myeloma cells in vitro and in vivo along with the proteasome inhibitor ixazomib. ChIP‐seq, western blotting and RT‐qPCR were performed to explore the potential mechanism(s) underlying the increase in lipid levels in multiple myeloma cells after proteasome inhibition.

Key Results

Accumulation of lipids in multiple myeloma cells was induced by proteasome inhibition. Lipid‐lowering drugs and MG‐132 exerted a synergistic effect to kill multiple myeloma cells. FCE showed significant synergistic activity in vitro and in vivo with ixazomib. The abnormal lipid accumulation in multiple myeloma cells that was enhanced by proteasome inhibitors might be due to the elevated SREBP1/2 expression induced by ATF4.

Conclusions and Implications

Our results provide a proof of principle and support for the further clinical evaluation of the combination of lipid‐modulating drugs with proteasome inhibitors in the treatment of multiple myeloma.
The inhibition of enkephalin catabolism by dual enkephalinase inhibitor: A novel possible therapeutic approach for opioid use disorders
Authors: Alvarez‐Perez Beltran , Poras Hervé , Maldonado Rafael
Published: August 2021

Despite the increasing impact of opioid use disorders on society, there is a disturbing lack of effective medications for their clinical management. An interesting innovative strategy to treat these disorders consists in the protection of endogenous opioid peptides to activate opioid receptors, avoiding the classical opioid‐like side effects. Dual enkephalinase inhibitors (DENKIs) physiologically activate the endogenous opioid system by inhibiting the enzymes responsible for the breakdown of enkephalins, protecting endogenous enkephalins and increasing their half‐lives and physiological actions. The activation of opioid receptors by the increased enkephalin levels, and their well‐demonstrated safety, suggests that DENKIs could represent a novel analgesic therapy and a possible effective treatment for acute opioid withdrawal, as well as a promising alternative to opioid substitution therapy minimizing side effects. This new pharmacological class of compounds could bring effective and safe medications avoiding the major limitations of exogenous opioids, representing a novel approach to overcome the problem of opioid use disorders.

LINKED ARTICLES

This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc
Education: Optimal choice and efficient policy
Authors: Richter Wolfram F. , Schneider Kerstin
Published: August 2021

This paper argues that it suffices to assume distortionary wage taxation to prove the efficiency of effective subsidization of education. The paper does not rely on considerations of equity and market failure to justify subsidies. Instead, the optimal subsidy reduces the social cost of distortive wage taxation. The theoretical approach assumes a Mincer‐type earnings function, analyzes corner solutions of optimal schooling choice and derives the result of efficient subsidization in a Ramsey‐type framework. Second‐best policy is confronted with empirical evidence from OECD countries. The majority of countries are shown to subsidize tertiary education in effective terms.
Four‐implant‐supported overdenture treatment in the maxilla. Part II: Speech‐ and oral health‐related quality of life in patients with implant‐supported overdentures in the maxilla—A prospective 3‐year follow‐up
Authors: Fonteyne Ester , Burms Eline , Matthys Carine , Van Lierde Kristiane , De Bruyn Hugo
Published: August 2021

Background

Implant‐supported overdentures (IOD) are becoming a more commonly used treatment in the dental practice and it risks causing speech problems.

Purpose

The aim of this study was investigating the changes in speech, satisfaction with speech, and overall oral health‐related quality of life (OHRQoL) in edentulous patients during and after treatment with maxillary IODs.

Materials and methods

Twenty‐one patients receiving an IOD participated in speech assessment. They were examined preoperatively with their conventional denture (CD) with full palatal coverage, after connection of the implant‐bar connected denture, without palatal coverage, and 3 years thereafter. The examination included assessment of articulation in speech, OHRQoL based on total OHIP‐14, and satisfaction with overall oral health and speech (visual analogue scale).

Results

There was a reduction in mean number of articulation disorders from 1.00 at baseline to 0.55 at connection, although statistically insignificant (p = 0.059). Especially the /s/ sound is vulnerable. At 3 years follow‐up, still 6/16 (37.5%) of the patients suffered from this speech problem. Overall satisfaction improved from 64.05/100 at baseline to 82.95/100 at connection (p = 0.008) and remained unchanged with 81.69/100 after 3 years follow‐up. Patients' satisfaction with speech increased from 70.62/100 with CD to 82.63/100, 3 years follow‐up (p = 0.009). Total OHIP‐14 decreased from 21.45/56 with CD to 8.00/56 (p < 0.001) with IOD and 6.13/56 3 years after connection (p = 0.001). Significant improvement of all seven domains in OHRQoL was observed with IOD compared to CD.

Conclusions

Patients treated with maxillary IODs show improved OHRQoL 3 years after connection of the IOD compared to the CD. Even though patients reported improvement of satisfaction and OHRQoL, articulation disorders were still present, suggesting that patients should be informed about possible speech issues.
A panel analysis of income inequality and energy use
Authors: Sonora Robert J.
Published: August 2021

This paper investigates the relationship between energy consumption and income inequality in an unbalanced panel of 144 countries over the period 1990–2018. Using fixed effect and instrumental variable panel methods and controlling for other determinants of inequality, I find a large and strong negative relationship between energy use and income inequality. The paper also demonstrates that results hold for models which divide the total sample into subsamples of economic blocs and regions. In addition, greater energy use reduces the income share of the top 10% and increases the share of the bottom 40%.
Emergent Goal‐Anticipatory Gaze in Infants via Event‐Predictive Learning and Inference
Authors: Gumbsch Christian , Adam Maurits , Elsner Birgit , Butz Martin V.
Published: August 2021

From about 7 months of age onward, infants start to reliably fixate the goal of an observed action, such as a grasp, before the action is complete. The available research has identified a variety of factors that influence such goal‐anticipatory gaze shifts, including the experience with the shown action events and familiarity with the observed agents. However, the underlying cognitive processes are still heavily debated. We propose that our minds (i) tend to structure sensorimotor dynamics into probabilistic, generative event‐predictive, and event boundary predictive models, and, meanwhile, (ii) choose actions with the objective to minimize predicted uncertainty. We implement this proposition by means of event‐predictive learning and active inference. The implemented learning mechanism induces an inductive, event‐predictive bias, thus developing schematic encodings of experienced events and event boundaries. The implemented active inference principle chooses actions by aiming at minimizing expected future uncertainty. We train our system on multiple object‐manipulation events. As a result, the generation of goal‐anticipatory gaze shifts emerges while learning about object manipulations: the model starts fixating the inferred goal already at the start of an observed event after having sampled some experience with possible events and when a familiar agent (i.e., a hand) is involved. Meanwhile, the model keeps reactively tracking an unfamiliar agent (i.e., a mechanical claw) that is performing the same movement. We qualitatively compare these modeling results to behavioral data of infants and conclude that event‐predictive learning combined with active inference may be critical for eliciting goal‐anticipatory gaze behavior in infants.
Motivated Reasoning in an Explore‐Exploit Task
Authors: Caddick Zachary A. , Rottman Benjamin M.
Published: August 2021

The current research investigates how prior preferences affect causal learning. Participants were tasked with repeatedly choosing policies (e.g., increase vs. decrease border security funding) in order to maximize the economic output of an imaginary country and inferred the influence of the policies on the economy. The task was challenging and ambiguous, allowing participants to interpret the relations between the policies and the economy in multiple ways. In three studies, we found evidence of motivated reasoning despite financial incentives for accuracy. For example, participants who believed that border security funding should be increased were more likely to conclude that increasing border security funding actually caused a better economy in the task. In Study 2, we hypothesized that having neutral preferences (e.g., preferring neither increased nor decreased spending on border security) would lead to more accurate assessments overall, compared to having a strong initial preference; however, we did not find evidence for such an effect. In Study 3, we tested whether providing participants with possible functional forms of the policies (e.g., the policy takes some time to work or initially has a negative influence but eventually a positive influence) would lead to a smaller influence of motivated reasoning but found little evidence for this effect. This research advances the field of causal learning by studying the role of prior preferences, and in doing so, integrates the fields of causal learning and motivated reasoning using a novel explore‐exploit task.
Parsing as a Cue‐Based Retrieval Model
Authors: Dotlačil Jakub
Published: August 2021

This paper develops a novel psycholinguistic parser and tests it against experimental and corpus reading data. The parser builds on the recent research into memory structures, which argues that memory retrieval is content‐addressable and cue‐based. It is shown that the theory of cue‐based memory systems can be combined with transition‐based parsing to produce a parser that, when combined with the cognitive architecture ACT‐R, can model reading and predict online behavioral measures (reading times and regressions). The parser's modeling capacities are tested against self‐paced reading experimental data (Grodner & Gibson, 2005), eye‐tracking experimental data (Staub, 2011), and a self‐paced reading corpus (Futrell et al., 2018).
Distorting Face Representations in Newborn Brains
Authors: Wood Samantha M. W. , Wood Justin N.
Published: August 2021

What role does experience play in the development of face recognition? A growing body of evidence indicates that newborn brains need slowly changing visual experiences to develop accurate visual recognition abilities. All of the work supporting this “slowness constraint” on visual development comes from studies testing basic‐level object recognition. Here, we present the results of controlled‐rearing experiments that provide evidence for a slowness constraint on the development of face recognition, a prototypical subordinate‐level object recognition task. We found that (1) newborn chicks can rapidly develop view‐invariant face recognition and (2) the development of this ability relies on experience with slowly moving faces. When chicks were reared with quickly moving faces, they built distorted face representations that largely lacked invariance to viewpoint changes, effectively “breaking” their face recognition abilities. These results provide causal evidence that slowly changing visual experiences play a critical role in the development of face recognition, akin to basic‐level object recognition. Thus, face recognition is not a hardwired property of vision but is learned rapidly as the visual system adapts to the temporal structure of the animal's visual environment.
A new composite abundance metric detects stream fish declines and community homogenization during six decades of invasions
Authors: Sleezer Logan J. , Angermeier Paul L. , Frimpong Emmanuel A. , Brown Bryan L.
Published: August 2021

Aim

We developed a new technique, utilizing species‐specific counts of individuals from historical fish community samples, to examine landscape‐level, spatio‐temporal trends in relative abundance distributions. Abundance‐based historical distribution analyses are often plagued by data comparability issues, but provide critical information about community composition trends inaccessible to those using analyses based only on species presence–absence. We established trends in native and non‐native fish abundance and community homogenization, uniqueness and diversity to help local conservation managers prioritize targets and motivate similar studies globally to support fish conservation.

Location

Upper and middle New River (UMNR) basin, Appalachian Mountains, USA.

Methods

We compiled catch data from 61 years of fish community surveys (1958–2019) and tested for community homogenization by comparing data from repeatedly sampled sites (1900s versus 2000s samples) using dispersion analyses. We measured community uniqueness (site contributions to beta diversity) and species diversity (Shannon index) at sampled streams to identify potential conservation hotspots. We then used regression analyses and Wilcoxon signed‐rank tests to examine species‐specific basin‐wide and local abundance trends and identify species of potential conservation concern.

Results

Dispersion of sites in species abundance space was significantly greater in the 1900s compared with the 2000s, indicating homogenization had occurred. Of 36 native species analysed, 44.4% (16) showed basin‐wide declines. Non‐native species exhibited mixed patterns; site‐level abundance increased in 2 of 15 species analysed (13%).

Main conclusions

Our results indicate basin‐wide community homogenization has occurred within the UMNR, but many unique and diverse communities persist. If conserved, these could help maintain regional fish diversity. We found basin‐wide declines in four endemic species, as well as spread patterns of non‐native and native species that were not detected by a presence–absence analysis applied within the same study area. This finding illustrates the importance of considering both species’ abundance and occurrence patterns as separate dimensions of biodiversity to inform conservation planning.
Community engagement in genomic research: Proposing a strategic model for effective participation of indigenous communities
Authors: Ogunrin Olubunmi , Gabbay Mark , Woolfall Kerry , Frith Lucy
Published: August 2021

Community engagement (CE) contributes to successful research. There is, however, a lack of literature on the effectiveness of different models of CE and, specifically, on CE strategies for the conduct of genomic research in sub‐Saharan Africa. There is also a need for models of CE that transcend the recruitment stage of engaging prospective individuals and communities and embed CE throughout the research process and after the research has concluded. The qualitative study reported here was designed to address these knowledge gaps and comprised of 36 key informant semi‐structured interviews and fifteen focus groups with 50 participants. We interviewed selected stakeholders in genomic research in Nigeria: biomedical researchers, community rulers, opinion leaders, community health workers, and prospective research participants. We explored these stakeholders’ views on their understanding of community engagement, their expectations, experiences, and their opinions on acceptable processes of community consultation in genomic research. The methodological design, adapted from grounded theory, used the constant comparative method of data analysis; while normative conclusions were made using the symbiotic empirical ethics approach. Data analysis revealed five main themes important for successfully engaging communities in genomic research: effective communication, diversity of community gatekeeping, trust, cultural integration of research, and conservation of the research setting. From these themes, we have developed a four‐stage model of community engagement that covers all stages of the research process; namely, the Community Approach, Intermediate phase, Collaboration and Post‐research Cordiality model (CICP). This model could be used to improve the integration of CE in genomic research among local communities.
Leibniz and Bolzano on conceptual containment
Authors: Claas Jan
Published: August 2021

Philosophers often rely on the notion of conceptual containment and apply mereological terminology when they talk about the parts or constituents of a complex concept. In this paper, I explore two historical approaches to this general notion. In particular, I reconstruct objections Bernard Bolzano puts forward against a criterion that played a prominent role in the history of philosophy and that was endorsed, among others, by Leibniz. According to this criterion, a concept that represents objects contains all and only the concepts that represent properties the objects must have in order to be represented by the former concept. Bolzano offers several counterexamples and arguments against the criterion. I argue that while some of them presuppose a strongly mereological understanding of containment, which Leibniz is not committed to, one of them also succeeds without relying on demanding mereological principles.
Efficacy of erlotinib and its effects on the quality of life of older patients with epidermal growth factor receptor‐mutant non‐small cell lung cancer: A prospective, multicenter, dose‐modification study
Authors: Tsubata Yukari , Masuda Takeshi , Hamai Kosuke , Taniwaki Masaya , Tanino Akari , Hotta Takamasa , Hamaguchi Megumi , Hamaguchi Shunichi , Yamasaki Masahiro , Ishikawa Nobuhisa , Fujitaka Kazunori , Sutani Akihisa , Isobe Takeshi
Published: August 2021

Aim

Gefitinib and erlotinib are efficacious and safe for older patients with epidermal growth factor receptor‐mutant non‐small cell lung cancer. However, prolonged use of epidermal growth factor receptor‐tyrosine kinase inhibitors in older patients is difficult, owing to potential adverse events. Hence, dose reduction or treatment discontinuation is often required. We investigated the efficacy of low‐dose first‐line erlotinib and its effects on the quality of life of older patients with lung cancer.

Methods

A prospective, multicenter, phase II clinical trial was carried out in patients aged ≥75 years with epidermal growth factor receptor‐mutant non‐small cell lung cancer. Initially, 100 mg/day erlotinib was administered orally; if well tolerated, it was increased to 150 mg/day. The primary end‐point was progression‐free survival, and secondary end‐points were the response rate, overall survival and change in quality of life (“Care Notebook” questionnaire).

Results

The median progression‐free survival was 17.8 months, response rate was 63.6% and median overall survival was 27.8 months. The change in the quality of life after 6 weeks was assessed in 72.7% of the patients. Fatigue, pain, anxiety and deterioration in daily activities were found in at least 40% of the patients. Despite the therapeutic effect of 100 mg/day erlotinib, many patients required dose reduction, and in some, the quality of life could not be maintained.

Conclusions

Many older patients with epidermal growth factor receptor‐mutant non‐small cell lung cancer might require treatment dose reduction. Further studies are required to develop individualized treatments for older patients with lung cancer. Geriatr Gerontol Int 2021; 21: 881–886.
Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A
Authors: Pasi K John , Laffan Michael , Rangarajan Savita , Robinson Tara M , Mitchell Nina , Lester Will , Symington Emily , Madan Bella , Yang Xinqun , Kim Benjamin , Pierce Glenn F , Wong Wing Yen
Published: August 2021

Introduction

Valoctocogene roxaparvovec is an investigational AAV5‐based factor VIII (FVIII) gene therapy that has demonstrated sustained clinical benefit in people with severe haemophilia A.

Aim

To report safety, tolerability, efficacy, and quality of life (QOL) among participants who received valoctocogene roxaparvovec in a phase 1/2 clinical study (NCT02576795).

Methods

Men ≥18 years of age with severe haemophilia A (FVIII ≤1 IU/dl) without history of FVIII inhibitors or anti‐AAV5 antibodies received a single infusion of valoctocogene roxaparvovec and were followed for 5 years (6 × 1013 vg/kg dose, n = 7) and 4 years (4 × 1013 vg/kg dose, n = 6).

Results

Over the past 2 years, few adverse events and no FVIII inhibitors were reported. Per chromogenic substrate (CSA) assay at years 5 and 4, four of seven and three of six participants in the 6 × 1013 and 4 × 1013 vg/kg cohorts, respectively, maintained median FVIII levels >5 IU/dl, corresponding to mild haemophilia. By regression analysis, rate of change in FVIII activity was ‐0.14 (95% confidence interval [CI]: ‐.32 to .03) IU/dl/wk in the 6 × 1013 vg/kg cohort in year 5 and ‐.06 (95% CI: ‐.14 to .01) IU/dl/wk in the 4 × 1013 vg/kg cohort in year 4. No participants resumed FVIII prophylaxis, and eight of 13 participants reported zero bleeds in the past 2 years. Improved QOL from baseline persisted in the 6 × 1013 vg/kg cohort; all six Haemo‐QOL‐A domain scores increased. For the 4 × 1013 vg/kg cohort, high baseline Haemo‐QOL‐A scores persisted.

Conclusion

These results demonstrate transgene expression and haemostatic response for up to 5 years in individuals with haemophilia A.
End‐stage kidney disease patients from ethnic minorities and mortality in coronavirus disease 2019
Authors: Tabinor Matthew , Crowley Lisa Emma , Godlee Alexandra , Flanagan Daisy , Rashid Raja Muhammad , Baharani Jyoti , Ferro Charles Joseph , Eddington Helen
Published: August 2021

Introduction

Coronavirus disease 2019 (COVID‐19) adversely affects patients who are older, multimorbid, and from Black, Asian or minority ethnicities (BAME). We assessed whether being from BAME is independently associated with mortality in end‐stage kidney disease (ESKD) patients with COVID‐19.

Methods

Prospective observational study in a single UK renal center. A study was conducted between March 10, 2020 and April 30, 2020. Demographics, socioeconomic deprivation (index of multiple deprivation), co‐morbidities (Charlson comorbidity index [CCI]), and frailty data (clinical frailty score) were collected. The primary outcome was all‐cause mortality. Data were censored on the 1st June 2020.

Findings

Overall, 191 of our 3379 ESKD patients contracted COVID‐19 in the 8‐week observation period; 84% hemodialysis, 5% peritoneal dialysis, and 11% kidney transplant recipients (KTR). Of these, 57% were male and 67% were from BAME groups (43% Asian, 17% Black, 2% mixed race, and 5% other). Mean CCI was 7.45 (SD 2.11) and 3.90 (SD 2.10) for dialysis patients and KTR, respectively. In our cohort, 60% of patients lived in areas classified as being in the most deprived 20% in the United Kingdom, and of these, 77% of patients were from BAME groups. The case fatality rate was 29%. Multivariable cox regression demonstrated that BAME (hazard ratio [HR]: 2.37, 95% CI: 1.22–4.61) was associated with all‐cause mortality after adjustment for age, deprivation, co‐morbidities, and frailty. Associations with all‐cause mortality persisted in sensitivity analyses in patients from South Asian (HR: 2.52, 95% CI: 1.24–5.12) and Black (HR: 2.43, 95% CI: 1.04–5.67) ethnic backgrounds.

Discussion

BAME ESKD patients with COVID‐19 are just over twice as likely to die compared to White patients, despite adjustment for age, deprivation, comorbidity, and frailty. This study highlights the need to develop strategies to improve BAME patient outcomes in future outbreaks of COVID‐19.
Trajectories of clinical and laboratory characteristics associated with COVID‐19 in hemodialysis patients by survival
Authors: Chaudhuri Sheetal , Lasky Rachel , Jiao Yue , Larkin John , Monaghan Caitlin , Winter Anke , Neri Luca , Kotanko Peter , Hymes Jeffrey , Lee Sangho , Wang Yuedong , Kooman Jeroen P. , Maddux Franklin , Usvyat Len
Published: August 2021

Introduction

The clinical impact of COVID‐19 has not been established in the dialysis population. We evaluated the trajectories of clinical and laboratory parameters in hemodialysis (HD) patients.

Methods

We used data from adult HD patients treated at an integrated kidney disease company who received a reverse transcription polymerase chain reaction (RT‐PCR) test to investigate suspicion of a severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection between May 1 and September 1, 2020. Nonparametric smoothing splines were used to fit data for individual trajectories and estimate the mean change over time in patients testing positive or negative for SARS‐CoV‐2 and those who survived or died within 30 days of first suspicion or positive test date. For each clinical parameter of interest, the difference in average daily changes between COVID‐19 positive versus negative group and COVID‐19 survivor versus nonsurvivor group was estimated by fitting a linear mixed effects model based on measurements in the 14 days before (i.e., Day −14 to Day 0) Day 0.

Results

There were 12,836 HD patients with a suspicion of COVID‐19 who received RT‐PCR testing (8895 SARS‐CoV‐2 positive). We observed significantly different trends (p < 0.05) in pre‐HD systolic blood pressure (SBP), pre‐HD pulse rate, body temperature, ferritin, neutrophils, lymphocytes, albumin, and interdialytic weight gain (IDWG) between COVID‐19 positive and negative patients. For COVID‐19 positive group, we observed significantly different clinical trends (p < 0.05) in pre‐HD pulse rate, lymphocytes, neutrophils, and albumin between survivors and nonsurvivors. We also observed that, in the group of survivors, most clinical parameters returned to pre‐COVID‐19 levels within 60–90 days.

Conclusion

We observed unique temporal trends in various clinical and laboratory parameters among HD patients who tested positive versus negative for SARS‐CoV‐2 infection and those who survived the infection versus those who died. These trends can help to define the physiological disturbances that characterize the onset and course of COVID‐19 in HD patients.