bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian group sequential enrichment designs based on adaptive regression of response and survival time on baseline biomarkers
Authors: Park Yeonhee , Liu Suyu , Thall Peter F. , Yuan Ying 
Published: January 2021

AbstractPrecision medicine relies on the idea that, for a particular targeted agent, only a subpopulation of patients is sensitive to it and thus may benefit from it therapeutically. In practice, it is often assumed based on preclinical data that a treatment‐sensitive subpopulation is known, and moreover that the agent is substantively efficacious in that subpopulation. Due to important differences between preclinical settings and human biology, however, data from patients treated with a new targeted agent often show that one or both of these assumptions are false. This paper provides a Bayesian randomized group sequential enrichment design that compares an experimental treatment to a control based on survival time and uses early response as an ancillary outcome to assist with adaptive variable selection and enrichment. Initially, the design enrolls patients under broad eligibility criteria. At each interim decision, submodels for regression of response and survival time on a baseline covariate vector and treatment are fit; variable selection is used to identify a covariate subvector that characterizes treatment‐sensitive patients and determines a personalized benefit index, and comparative superiority and futility decisions are made. Enrollment of each cohort is restricted to the most recent adaptively identified treatment‐sensitive patients. Group sequential decision cutoffs are calibrated to control overall type I error and account for the adaptive enrollment restriction. The design provides a basis for precision medicine by identifying a treatment‐sensitive subpopulation, if it exists, and determining whether the experimental treatment is superior to the control in that subpopulation. A simulation study shows that the proposed design reliably identifies a sensitive subpopulation, yields much higher generalized power compared to several existing enrichment designs and a conventional all‐comers group sequential design, and is robust.
Optimal intervention in a random‐matching model of money
Authors: Nozawa Wataru , Yang Hoonsik 
Published: January 2021

AbstractWe numerically find optimal transfer scheme in the Shi–Trejos–Wright model with extended upper bounds on money holdings. The choice of upper bound matters for the optimal policy as some potentially beneficial transfer schemes cannot be studied under small upper bounds. Money creation (and accompanying inflation) becomes optimal in more examples when the upper bound on money holdings is larger, and the type of optimal transfer depends on the parameters in utility function. This result is in line with the conjecture of Wallace, which says that there generically exists an inflation‐financed transfer scheme that improves welfare over no intervention in pure‐currency economies.
Carnitine palmitoyltransferase 1C negatively regulates the endocannabinoid hydrolase ABHD6 in mice, depending on nutritional status
Authors: Miralpeix Cristina , Reguera Ana Cristina , Fosch Anna , Casas Maria , Lillo Jaume , Navarro Gemma , Franco Rafael , Casas Josefina , Alexander Stephen P.H. , Casals Núria , Rodríguez‐Rodríguez Rosalía 
Published: January 2021

Background and PurposeThe enzyme α/β‐hydrolase domain containing 6 (ABHD6), a new member of the endocannabinoid system, is a promising therapeutic target against neuronal‐related diseases. However, how ABHD6 activity is regulated is not known. ABHD6 coexists in protein complexes with the brain‐specific carnitine palmitoyltransferase 1C (CPT1C). CPT1C is involved in neuro‐metabolic functions, depending on brain malonyl–CoA levels. Our aim was to study CPT1C–ABHD6 interaction and determine whether CPT1C is a key regulator of ABHD6 activity depending on nutritional status.Experimental ApproachCo‐immunoprecipitation and FRET assays were used to explore ABHD6 interaction with CPT1C or modified malonyl–CoA‐insensitive or C‐terminal truncated CPT1C forms. Cannabinoid CB1 receptor‐mediated signalling was investigated by determining cAMP levels. A novel highly sensitive fluorescent method was optimized to measure ABHD6 activity in non‐neuronal and neuronal cells and in brain tissues from wild‐type (WT) and CPT1C–KO mice.Key ResultsCPT1C interacted with ABHD6 and negatively regulated its hydrolase activity, thereby regulating 2‐AG downstream signalling. Accordingly, brain tissues of CPT1C–KO mice showed increased ABHD6 activity. CPT1C malonyl–CoA sensing was key to the regulatory role on ABHD6 activity and CB1 receptor signalling. Fasting, which attenuates brain malonyl–CoA, significantly increased ABHD6 activity in hypothalamus from WT, but not CPT1C–KO, mice.Conclusions and ImplicationsOur finding that negative regulation of ABHD6 activity, particularly in the hypothalamus, is sensitive to nutritional status throws new light on the characterization and the importance of the proteins involved as potential targets against diseases affecting the CNS.
Basement geology and its controls on the nucleation and growth of rift faults in the northern Campos Basin, offshore Brazil
Authors: Strugale Michael , Schmitt Renata da Silva , Cartwright Joe 
Published: January 2021

AbstractThe rift phase of the Campos Basin developed during the Early Cretaceous on a heterogeneous crust comprising structures inherited from the Brasiliano‐Pan African tectonic events, mostly generated during the Neoproterozoic‐Cambrian amalgamation of western Gondwana blocks. The main rifting episode took place from the Hauterivian to the Barremian, then was succeeded by the transition and post‐rift (SAG) phases during the Aptian. Rift faults developed as a result of a progressive rotation of extension from E‐W to NW‐SE. The role of pre‐existing intra‐basement structures on the style and evolution of the rift faults was investigated using 3D high‐resolution seismic data, borehole logs and sidewall samples. Three seismic facies (SF1, SF2 and SF3) and three types of intra‐basement structures (Surfaces, Geobodies and Internal Reflections) were identified and mapped. They represent, respectively, contrasting levels of seismic anisotropy, interpreted as metamorphic foliation, and ductile shear zones that bound rock units with particular seismic facies signatures. Sidewall cores show that banded biotite‐gneiss is the predominant rock type in the eastern half of the study area, while more homogeneous granitoid is the dominant lithology on the west. Such a binary division of lithotypes is consistent with the distribution of mapped intra‐basement seismic facies and features. The contrasting basement heterogeneity across the study area is the major control in the strain distribution during rifting. Where the basement is highly heterogeneous, the pre‐existing fabric was selectively reactivated whenever its orientation was favourable, resulting in faults forming progressively as the extension direction rotates, whilst shallower low to very low angle basement fabric were cross‐cut by rift faults. Where the basement is homogeneous, only early formed faults remain active throughout the rifting.
Intentional communication: solving methodological issues to assigning first‐order intentional signalling
Authors: Ben Mocha Yitzchak , Burkart Judith M. 
Published: January 2021

ABSTRACTIntentional signalling plays a fundamental role in human communication. Mapping the taxonomic distribution of comparable capacities may thus shed light on the selective pressures that enabled the evolution of human communication. Nonetheless, severe methodological issues undermine comparisons among studies, species and communicative modalities. Here, we discuss three main obstacles that hinder comparative research of ‘first‐order’ intentional signalling (i.e. voluntary signalling in pursuit of a cognitively represented goal): (i) inconsistency in how behavioural hallmarks are defined and operationalised, (ii) testing of behavioural hallmarks without statistical comparison to control conditions, and (iii) bias against the publication of negative results. To address these obstacles, we present a four‐step scheme with 20 statistical operational criteria to distinguish between non‐intentional and first‐order intentional signalling. Our unified scheme applies to visual and audible signals, thereby validating comparison across communicative modalities and species. This, in turn, promotes the generation and testing of hypotheses about the evolution of intentional communication.
Leaf trait co‐variation and trade‐offs in gallery forest C3 and CAM epiphytes
Authors: de Paula Oliveira Rodolfo , Zotz Gerhard , Wanek Wolfgang , Franco Augusto Cesar 
Published: January 2021

AbstractDespite their unique adaptations to thrive in canopy environments without access to soil resources, epiphytes are underrepresented in studies of functional traits and of functional composition of tropical plant communities. We investigated functional traits of spermatophytic (seed‐bearing) C3 and CAM epiphyte communities in flooded and non‐flooded gallery forests in Central Brazil. The two forest types differ in floristic, structure, microclimate, and edaphic conditions. We studied plant size, leaf thickness, leaf dry matter content (LDMC), leaf water content, leaf area (LA), specific leaf area (SLA), leaf C, N, P, K, Mg, and Ca, and stable isotope ratios (δ13C and δ15N). Because photosynthetic pathway (C3 or CAM) is an important aspect of ecological differentiation for spermatophytic epiphytes, we expected that functional trait syndromes in a multivariate space would be more associated with photosynthetic pathway than forest type, and changes in abundance of C3 and CAM epiphytes would drive functional trait composition at the community level. C3 and CAM epiphytes segregated in the multivariate trait space; however, more complex functional typologies were also evident. Despite lower light levels, CAM epiphytes were more abundant in the flooded gallery forest. There, they accounted for 80% of all individuals, whereas C3 epiphytes dominated in the non‐flooded forest. These large differences in the proportion of CAM and C3 epiphytes strongly affected functional trait values at the community level, despite very little intraspecific variation in trait values between forest types for species that occurred in both forests.Abstract in Portuguese is available with online material.
Genetic profile of adult T‐cell leukemia/lymphoma in Okinawa: Association with prognosis, ethnicity, and HTLV‐1 strains
Authors: Sakihama Shugo , Morichika Kazuho , Saito Rumiko , Miyara Megumi , Miyagi Takashi , Hayashi Masaki , Uchihara Junnosuke , Tomoyose Takeaki , Ohshiro Kazuiku , Nakayama Shingo , Nakachi Sawako , Morishima Satoko , Sakai Kazuko , Nishio Kazuto , Masuzaki Hiroaki , Fukushima Takuya , Karube Kennosuke 
Published: January 2021

AbstractGenetic alterations in adult T‐cell leukemia/lymphoma (ATLL), a T‐cell malignancy associated with HTLV‐1, and their clinical impacts, especially from the perspective of viral strains, are not fully elucidated. We employed targeted next‐generation sequencing and single nucleotide polymorphism array for 89 patients with ATLL in Okinawa, the southernmost islands in Japan, where the frequency of HTLV‐1 tax subgroup‐A (HTLV‐1‐taxA) is notably higher than that in mainland Japan, where most ATLL cases have HTLV‐1‐taxB, and compared the results with previously reported genomic landscapes of ATLL in mainland Japan and the USA. Okinawan patients exhibited similar mutation profiles to mainland Japanese patients, with frequent alterations in TCR/NF‐ĸB (eg, PRKCB, PLCG1, and CARD11) and T‐cell trafficking pathways (CCR4 and CCR7), in contrast with North American patients who exhibited a predominance of epigenome‐associated gene mutations. Some mutations, especially GATA3 and RHOA, were detected more frequently in Okinawan patients than in mainland Japanese patients. Compared to HTLV‐1‐taxB, HTLV‐1‐taxA was significantly dominant in Okinawan patients with these mutations (GATA3, 34.1% vs 14.6%, P = .044; RHOA, 24.4% vs 6.3%, P = .032), suggesting the contribution of viral strains to these mutation frequencies. From a clinical viewpoint, we identified a significant negative impact of biallelic inactivation of PRDM1 (P = .027) in addition to the previously reported PRKCB mutations, indicating the importance of integrated genetic analysis. This study suggests that heterogeneous genetic abnormalities in ATLL depend on the viral strain as well as on the ethnic background. This warrants the need to develop therapeutic interventions considering regional characteristics.
Comparing Automatic and Manual Measures of Parent–Infant Conversational Turns: A Word of Caution
Authors: Ferjan Ramírez Naja , Hippe Daniel S. , Kuhl Patricia K. 
Published: January 2021

The Language ENvironment Analysis system (LENA) records children’s language environment and provides an automatic estimate of adult–child conversational turn count (CTC). The present study compares LENA’s CTC estimate to manually coded CTC on a sample of 70 English‐speaking infants recorded longitudinally at 6, 10, 14, 18, and 24 months of age. At each age, LENA’s CTC was significantly higher than manually coded CTC (all ps < .001, Cohen’s ds: 0.9–2.05), with the largest discrepancies between the two methods observed at younger ages. The Limits of Agreement Analyses confirm wide disagreements between the two methods, highlighting potential problems with automatic measurement of parent–infant verbal interaction. These findings suggest that future studies should validate LENA’s CTC estimates with manual coding.
Effects of Reinforcement Learning on Gaze Following of Gaze and Head Direction in Early Infancy: An Interactive Eye‐Tracking Study
Authors: Michel Christine , Kayhan Ezgi , Pauen Sabina , Hoehl Stefanie 
Published: January 2021

The current four experiments investigated gaze following behavior in response to gaze and head turns in 4‐month‐olds and how reinforcement learning influences this behavior (N = 99). Using interactive eye tracking, infants’ gaze elicited an animation whenever infants followed a person’s head or gaze orientation (Experiment 1.1, 2.1 and 2.2) or looked at the opposite side (Experiment 1.2). Infants spontaneously followed the direction of a turning head with and without simultaneously shifted gaze direction (Cohen’sd: 0.93–1.05) but not the direction of isolated gaze shifts. We only found a weak effect of reinforcement on gaze following in one of the four experiments. Results will be discussed with regard to the impact of reinforcement on the maintenance of already existing gaze following behavior.
Is Skill Type the Key to the PreK Fadeout Puzzle? Differential Associations Between Enrollment in PreK and Constrained and Unconstrained Skills Across Kindergarten
Authors: McCormick Meghan , Weiland Christina , Hsueh JoAnn , Pralica Mirjana , Weissman Amanda K. , Moffett Lillie , Snow Catherine , Sachs Jason 
Published: January 2021

This study examines whether associations between enrollment in public and non‐public PreK and children’s (N = 508; Mage = 5.60 years in fall of kindergarten) math and language and literacy outcomes were more likely to be sustained through the spring of kindergarten for unconstrained versus constrained skills. Associations between public PreK and language, literacy, and math outcomes were more strongly sustained through the spring of kindergarten for unconstrained skills, relative to constrained skills. Only associations between non‐public PreK and unconstrained language skills were sustained through the spring of kindergarten. Associations in the fall of kindergarten differed by family income and dual language learner (DLL) status but there was no subgroup variation by the spring of kindergarten. Implications for policy and practice are discussed.
Role of autophagy in regulating interleukin‐10 and the responses to corticosteroids and statins in asthma
Authors: Maneechotesuwan Kittipong , Kasetsinsombat Kanda , Wongkajornsilp Adisak , Barnes Peter J 
Published: January 2021

AbstractBackgroundInterleukin (IL)‐10 is a key anti‐inflammatory cytokine that may be reduced in asthma but is enhanced by corticosteroids, especially when combined with a statin, although the mechanisms of these effects are uncertain.ObjectiveTo study the role of autophagy in macrophages in promoting inflammation in asthma through reducing IL‐10 secretion and how corticosteroids and statins may reverse this process.MethodsWe conducted a randomised double‐blind placebo‐controlled study in moderate to severe asthmatic patients (n = 44) to investigate the effect of an inhaled corticosteroid (budesonide 400 μg/day) and the combination of budesonide with an oral statin (simvastatin 10 mg/day) given for 8 weeks on autophagy protein expression in sputum cells by using immunocytochemistry and measurement of IL‐10 release. In in vitro experiments, we studied cross‐regulation between autophagy and IL‐10 release by measuring the expression of autophagy proteins in M2‐like macrophages and the effects of budesonide and simvastatin on these mechanisms.ResultsIn asthmatic patients, inhaled budesonide inhibited airway macrophage autophagy (beclin‐1, LC3) as well as autophagic flux (p62), which was enhanced by simvastatin and was correlated with increased sputum IL‐10 and reduced IL‐4 concentrations. In macrophages in vitro, budesonide and simvastatin inhibited rapamycin‐induced autophagy as well as autophagic flux, with reduced expression of beclin‐1 and LC3, but enhanced the accumulation of p62 and increased expression of IL‐10, which itself further inhibited autophagy in macrophages. With siRNA‐mediated silencing, LC3‐deficient macrophages also showed a maximal induction of IL‐10 transcription. Neutralisation of IL‐10 with recombinant specific blocking antibody and silencing IL‐10 transcription reversed the inhibitory effects of budesonide and simvastatin on macrophage autophagy.Conclusion and clinical relevanceInhibition by corticosteroids and a statin of macrophage autophagy enhances IL‐10 production, resulting in the control of asthmatic inflammation.
Impact of high‐quality ultrasound following community ultrasound on surgical planning and active surveillance in patients with thyroid cancer
Authors: Cohen Oded , Blank Annat , Meiersdorf Shmuel , Hod Keren , Gabay Shiran , Guindy Michal , Khafif Avi 
Published: January 2021

AbstractObjectiveUltrasound (US) has gained a critical role in thyroid cancer treatment planning, yet it is limited by its user‐dependent nature. The aim of this study was to compare the impact of US performed by radiologists specializing in thyroid imaging (hqUS) and US performed by radiographers in the community (cUS) on treatment plans of patients diagnosed with well‐differentiated thyroid malignancies.DesignRetrospective single‐centre case series with chart review.PatientsPatients diagnosed with thyroid cancer during 2017‐2019 that had cUS followed by hqUS pre‐operative counselling were included in this retrospective analysis.MeasurementsThe main outcome was management alternations based on one of two sonographic measures: (1) extrathyroid extension (ETE); (2) The presence of central or lateral lymph nodes suspicious for metastases (LNM), which were compared with the final pathology.ResultsAmong those with non‐recurrent tumour (n = 76), ETE was reported 22 times more by hqUS compared with cUS (28.9% vs 1.3%, P < .001). Central and lateral LNM were reported approximately 6.5 and 1.5 times more by hqUS, respectively (25.0% vs 3.9%, P < .001 and 15.8% vs., 9.2%, P = .227, respectively). Overall, hqUS altered the initial treatment plan of 35.5% of patients. In 27.6% of patients, hqUS and its subsequent surgery resulted in a change to the patients' 2015 ATA risk stratification system. In 40% of patients with microcarcinomas, hqUS findings mandated surgery according to findings that were not reported by cUS. False‐positive rate was 5.2%.ConclusionsCommunity US may under‐diagnose important features such as ETE and LNM, leading to potential under‐treatment in many patients. High‐quality US of the neck should be considered in patients with differentiated thyroid carcinoma before making any treatment decisions.
TopoAct: Visually Exploring the Shape of Activations in Deep Learning
Authors: Rathore Archit , Chalapathi Nithin , Palande Sourabh , Wang Bei 
Published: January 2021

AbstractDeep neural networks such as GoogLeNet, ResNet, and BERT have achieved impressive performance in tasks such as image and text classification. To understand how such performance is achieved, we probe a trained deep neural network by studying neuron activations, i.e.combinations of neuron firings, at various layers of the network in response to a particular input. With a large number of inputs, we aim to obtain a global view of what neurons detect by studying their activations. In particular, we develop visualizations that show the shape of the activation space, the organizational principle behind neuron activations, and the relationships of these activations within a layer. Applying tools from topological data analysis, we presentTopoAct, a visual exploration system to study topological summaries of activation vectors. We present exploration scenarios usingTopoActthat provide valuable insights into learned representations of neural networks. We expectTopoActto give a topological perspective that enriches the current toolbox of neural network analysis, and to provide a basis for network architecture diagnosis and data anomaly detection.
Novel method to obtain human non‐separated histological samples for the assessment of peri‐implant soft tissue response: A feasibility study
Authors: Kraus Dominik , Götz Werner , Bayer Stefan , Frentzen Matthias , Marder Michael , Albrecht Dominic , Enkling Norbert 
Published: January 2021

AbstractObjectivesTo introduce a standardized and less invasive clinical model that provides histological information on the abutment–mucosa interface in humans.Materials and methodsNew experimental healing abutments were left in an open healing position on bone‐level implants in the interforaminal region of the mandibles in six edentulous patients. The one‐piece abutments were hollow cylinder‐shaped with two lateral openings that allow for ingrowth of the peri‐implant mucosa into the central abutment cavity. After three months of healing, abutments and ingrown mucosa were sampled and processed for histological analysis in a non‐separated resin‐embedding technique. To test the validity of the new model, the ingrown tissue was compared to the peri‐implant mucosa around the same samples.ResultsNone of the experimental abutments exhibited signs of failure, and all samples showed mucosal ingrowth to the inner‐abutment cavity. Comparison of ingrown tissue and peri‐implant mucosa revealed no significant differences regarding the traits: tissue morphology, quality of collagen fibers, and adherence to the abutment. Ingrown mucosa exhibited a tendency for higher leukocyte infiltration.ConclusionsThe presented model is a promising approach to reduce invasiveness during the sampling process for human non‐separated abutment biopsies.