bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative analysis of structural valve deterioration after bioprosthetic tricuspid valve replacement: Bovine pericardial versus porcine valves
Authors: Kang Yoonjin , Hwang Ho Young , Sohn Suk Ho , Choi Jae Woong , Kim Kyung Hwan , Kim Ki‐Bong
Published: January 2021

This study was conducted to compare the occurrence and the risk factors of structural valve deterioration (SVD) after bioprosthetic tricuspid valve replacement (TVR) between bovine pericardial valves and porcine valves. One‐hundred and thirty‐four TVR patients were enrolled; 108 patients underwent TVR with bovine pericardial bioprostheses (BTVR group) and 26 underwent TVR with porcine bioprostheses (PTVR group). The early results and long‐term clinical outcomes were compared. The median follow‐up duration was 90 (interquartile range: 33‐135) months. Propensity score (PS) adjusted Cox regression and competing risk analyses were performed. The mean ages of the BTVR and PTVR groups were 62.2 ± 10.7 and 57.3 ± 13.9 years, respectively. The overall survival and cumulative incidence of cardiac death in the BTVR group were similar to those in the PTVR group (hazard ratio [95% confidence interval] = 1.399 [0.500‐3.922] and 0.742 [0.249‐2.212], respectively). SVD was significantly more frequent in the BTVR group (17.544 [1.070‐243.902], P = .045). The tricuspid valve reoperation rate was significantly higher in the BTVR group (38.462 [2.591‐476.190], P = .008). The cumulative incidence of SVD after bioprosthetic TVR was higher when using bovine pericardial valves than when using porcine valves.
Silicone microbubbles after anti‐vascular endothelial growth factor injections in patients with wet age‐related macular degeneration: incidence, quantification and secondary optical coherence tomography artfacts
Authors: Sanabria Maria R. , Alonso‐Tarancón Ana M. , Calles‐Monar Paola S. , Ibañez Patricia , García de Arriba Santiago , Alvarez Nuria , Piñuel Jesús A. , Coco Rosa M. , Fernández Itziar
Published: January 2021

Purpose

To report the incidence and quantity of silicone oil microbubbles and the relationship with the number of intravitreal anti‐vascular endothelial growth factor (VEGF) injections and evaluate if microbubbles induce artefacts on optical coherence tomography (OCT) images.

Methods

Observational, descriptive, cross‐sectional study. Patients with wet age‐related macular degeneration were included who had been treated for 1 year minimally with anti‐VEGF injections repackaged in the hospital pharmacy. Detection and quantification of silicone microbubbles by mydriatic biomicroscopic examination were conducted 1 month after the last injection. The numbers of microbubbles were quantified on a scale of 0–3: 0, none; 1 scarce (1–10 microbubbles); 2 moderate (10–30); or 3 numerous (>30). Shadowing on OCT images was classified as 0–3: 0, none; 1 obscuring some retinal layers; 2 obscuring all retinal layers; or 3 obscuring the retinal thickness.

Results

The study included 142 eyes of 98 patients (mean age, 82.4 years + 7.3; range, 65–97) treated with 2377 injections. Microbubbles were detected in 127 (89.4%) eyes, 62 (43.6%) with numerous microbubbles and 36 (25.4%) and 29 (20.4%), respectively, with scarce and moderate numbers. A positive correlation was found between the numbers of injections and intravitreal silicone (rho, 0.7). Optical coherence tomography (OCT) artefacts were detected in 11 eyes; the artefacts obscured all retinal layers in three eyes. No significant relationship could be established between the appearance of floaters and the microbubbles.

Conclusion

The presence and number of silicone microbubbles were correlated with the number of intravitreal injections. Microbubbles can produce OCT artefacts, which can hinder the treatment decision.
Retinal oximetry does not predict 12‐month visual outcome after anti‐VEGF treatment for central retinal vein occlusion: A multicentre study
Authors: Krejberg Jeppesen Signe , Sín Martin , Hakon Hardarson Sveinn , Bek Toke
Published: January 2021

Purpose

Central retinal vein occlusion (CRVO) entails retinal hypoxia that often causes visual impairment. It has been shown that oxygen saturation in larger retinal vessels correlates with the visual acuity at the time of diagnosis of CRVO but has no predictive value for the visual outcome in patients treated with anti‐VEGF medication after 3 months. However, assessing the predictive value of retinal oxygen saturation after 12 months is essential because this is when the main restitution after CRVO occurs.

Methods

Retinal oximetry was performed in 117 patients referred with CRVO to three European centres. The correlation between oxygen saturation and visual acuity at baseline and the predictive value of oxygen saturation in larger retinal vessels for the 12‐month visual outcome after treatment with anti‐VEGF medication were studied.

Results

In the affected eye, the oxygen saturation was significantly higher in the arterioles, significantly lower in the venules, and the arterio‐venous (A‐V) significantly higher than in the unaffected eye (p < 0.001 for all comparisons). Correlations between best‐corrected visual acuity (BCVA) and oxygen saturations were moderate and negative for arterioles (p < 0.001), positive for venules (p = 0.03) and negative for the A‐V difference (p = 0.001). Best‐corrected visual acuity (BCVA), but not oxygen saturation or the other explanatory variables at baseline, contributed significantly to predicting BCVA after 12 months.

Conclusion

Retinal vessel oxygen saturation is affected in CRVO, and saturation correlates with BCVA. However, retinal oximetry cannot replace measures of visual function as a predictor of visual outcome after 12 months of anti‐VEGF treatment for CRVO.
The prevalence of vitreomacular adhesion in eyes with macular oedema secondary to retinal vein occlusion selected for intravitreal injections
Authors: Maggio Emilia , Maraone Giorgia , Mete Maurizio , Vingolo Enzo Maria , Grenga Pier Luigi , Guerriero Massimo , Pertile Grazia
Published: January 2021

Purpose

To assess the prevalence of vitreomacular adhesion (VMA) in consecutive naïve eyes diagnosed with macular oedema (ME) secondary to retinal vein occlusion (RVO) and to longitudinally evaluate the incidence of vitreomacular interface changes over time and the influence on response to treatment.

Design

Retrospective cross‐sectional analysis and longitudinal cohort study conducted at two Italian tertiary referral centres.

Methods

A total of 295 eyes, treated with intravitreal ranibizumab and/or dexamethasone for ME secondary to RVO between June 2008 and May 2018, were enrolled in the study. 280 fellow eyes met the inclusion criteria and were included as control group. The vitreomacular interface status was evaluated by spectral domain optical coherence tomography (OCT) and graded according to the OCT‐based International Classification System developed by the International Vitreomacular Traction Study (IVTS) group.

Results

At baseline, VMA was present in 130 (44.07%) RVO eyes and 142 (50.7%) control eyes (no statistically significant difference was found; p = 0.455). Mean follow‐up (FU) was 35.98 months (min 6 – max 112). Throughout the FU, the incidence of spontaneous release of VMA (RVMA) in RVO eyes was significantly higher in comparison with that of the control group [59 (41.84%) RVO eyes versus 18 (12.33%) control eyes; p < 0.0001]. The number of injections in VMA+ eyes was significantly higher when compared with VMA− eyes. No significant difference was found between VMA+ and VMA− eyes regarding their mean best‐corrected visual acuity (BCVA) at baseline and at each annual time point (p = 0.2). Differences in central macular thickness (CMT) were significant only at the baseline evaluation (p = 0.0303).

Conclusions

Vitreomacular adhesion (VMA) was not found to be more prevalent in eyes with RVO compared to healthy fellow eyes, and RVO, in turn, did not result in a higher persistence of VMA over time. This suggests that VMA and RVO might be two independent retinal phenomena, with no mutual pathogenetic influence. Vitreomacular adhesion (VMA) might have an impact on the response to treatment, since it was found to result in a more intensive treatment regimen; however, it did not affect visual and anatomic outcomes. These results do not support vitrectomy or PVD induction in the prevention, nor the treatment, of RVO.
Effects of feeding high volumes of milk replacer on reproductive performance and on concentrations of metabolites and hormones in blood of Japanese black heifer calves
Authors: Taguchi Yutaka , Inabu Yudai , Hayasaki Koki , Maeda Noriyuki , Kanmera Yoshiro , Yamasaki Seiji , Ota Noboru , Mukawa Kenji , Tsuboi Arisa , Miyamoto Hirokuni , Etoh Tetsuji , Shiotsuka Yuji , Fujino Ryoichi , McMahon Christopher D. , Takahashi Hideyuki
Published: January 2021

We evaluated the effects of feeding high volumes of milk replacer on growth and reproductive performances in Japanese black heifers. Fifty‐one heifers were fed milk replacer at 9 L/day for 60 days (9 L × 60 days; n = 18) or 41 days (9 L × 41 days; n = 15), or at 7 L/day for 40 days (7 L × 40 days; n = 18). Artificial insemination (AI) was performed on heifers with ≥270 kg body weight and ≥116 cm body height at 300 days of age. The age at the first AI was 0.35 month later for 7 L × 40 days than the other groups (p < .01). However, age at calving did not differ among treatments (22.1 months). The interval from the first AI to pregnancy tended to be ~2 months longer for the 9 L × 60 days than the other groups (p = .07). Our results showed that feeding high volumes of milk replacer may reduce the age at calving via an improved rate of growth. In addition, we propose that feeding a maximum of 7 L milk replacer for 40 days may be the most appropriate rearing regime because the success of pregnancy per AI may be reduced in calves fed a maximum of 9 L for 41 and 60 days.
Clinical usefulness of a urine dipstick to detect ethyl glucuronide (EtG): A quantitative clinical study in healthy young female volunteers
Authors: Rausgaard Nete Lundager Klokker , Ravn Pernille , Ibsen Inge Olga , Fruekilde Palle Bach Nielsen , Nohr Ellen Aagaard , Damkier Per
Published: January 2021

The metabolite of ethanol, ethyl glucuronide (EtG), reflects alcohol intake longer than ethanol and is used as a biomarker in clinical settings to detect alcohol use. We aimed to assess the clinical usefulness in a low‐to‐moderate alcohol intake setting and validate a new urine EtG dipstick. A three‐way, open, cross‐over trial was conducted. Data were collected from January to June 2019. Among 12 healthy female volunteers, we quantified urine EtG and used a dipstick following intake of either one, two or four units of alcohol. Main outcomes were concentrations of EtG in urine and serum, and creatinine and ethanol in serum. EtG in urine was determined dichotomously by dipsticks at two different thresholds and by mass spectrometry used as gold standard. EtG in urine was quantifiable up to 24 hours after alcohol intake. In some individual cases, EtG was quantifiable up to 72 hours at low concentrations. The dipstick detected EtG in urine up to 24 hours. At thresholds of 1000 and 1500 ng/mL, the dipsticks had a specificity of 100% (both), while sensitivity was 84% and 69%, respectively. The sensitivity of the dipsticks was insufficient to support a screening purpose in this setting of low‐to‐moderate alcohol intake.
Culture, convention, and continuity: Islam and family firm ethical behavior
Authors: Alrubaishi Dalal , McAdam Maura , Harrison Richard
Published: January 2021

Although some scholarly attention has been devoted to the role of religion in entrepreneurship, there is a scarcity of research that focuses on the influence of Islam in the family business domain in general and the impact of Islamic concepts on the ethical behavior of Muslim family firms in particular. In addressing this, we reveal how the founder's ethical behavior which is informed by the Islamic conceptstawakkul, taqwa,honesty, and dignity is imprinted as values onto next‐generation leaders through mentoring, role modeling, and job shadowing, and thus embedded at the family firm level. We conceptualize these insights through the development of a formal framework for the analysis of the imprinting of Islamic influences on family firm ethical behavior. In addressing the roots of ethical behavior, we make contributions to the family business, Islamic entrepreneurship, and imprinting literatures. In practical terms, we highlight the importance of informal practices in endorsing the ethical behavior of the next‐generation family members.
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

Precision 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

We 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 Purpose

The 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 Approach

Co‐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 Results

CPT1C 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 Implications

Our 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

The 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

Intentional 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

Despite 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.
After the downturn: Perceptions of crime and policing in the southeastern Saskatchewan oil patch
Authors: O'Connor Christopher D. , Ruddell Rick
Published: January 2021

The relationship between crime and the rapid growth and industrialization associated with resource‐based booms in large boomtowns is well‐documented. This study focuses on changes in police‐reported crime and perceptions of crime and disorder in a region experiencing a mini‐boom after the boom subsides. Analyses of survey results of 1,336 respondents living in oil‐impacted and non‐impacted communities in southeastern Saskatchewan reveal several noteworthy differences between these two groups. Inconsistent with prior research, respondents in the oil‐impacted region were less fearful of being victimized than their counterparts in non‐impacted communities and did not believe that a lack of law enforcement was a problem. Our analyses also revealed that the economic downturn after oil prices and production plunged was associated with significant decreases in rates of reported crime, crime severity, and traffic collisions. Implications for establishing a more comprehensive theory of the boom‐crime relationship and future research are discussed.
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

Genetic 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

Background

Interleukin (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.

Objective

To 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.

Methods

We 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.

Results

In 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 relevance

Inhibition 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

Objective

Ultrasound (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.

Design

Retrospective single‐centre case series with chart review.

Patients

Patients diagnosed with thyroid cancer during 2017‐2019 that had cUS followed by hqUS pre‐operative counselling were included in this retrospective analysis.

Measurements

The 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.

Results

Among 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%.

Conclusions

Community 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

Deep 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

Objectives

To introduce a standardized and less invasive clinical model that provides histological information on the abutment–mucosa interface in humans.

Materials and methods

New 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.

Results

None 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.

Conclusions

The presented model is a promising approach to reduce invasiveness during the sampling process for human non‐separated abutment biopsies.
Linguistic diversity and conservation opportunities at UNESCO World Heritage Sites in Africa
Authors: Gorenflo L. J. , Romaine Suzanne
Published: January 2021

Africa contains much of Earth's biological and cultural–linguistic diversity, but conserving this diversity is enormously challenging amid widespread poverty, expanding development, social unrest, and rapidly growing human population. We examined UNESCO (United Nations Educational, Scientific and Cultural Organization) Natural World Heritage Sites (WHSs) on continental Africa and nearby islands—48 protected areas containing globally important natural or combined natural and cultural resources—to gauge the potential for enlisting Indigenous peoples in their conservation. We used geographic information system technology to identify instances where Natural WHSs co‐occur with Indigenous languages, a key indicator of cultural diversity. And, we compared the geographic ranges for 4 taxa and selected freshwater species with occurrence of all Indigenous languages within Natural WHSs and subsections of WHSs covered by the geographic extent of Indigenous languages to measure the correlation between linguistic and biological diversity. Results indicated that 147 languages shared at least part of their geographic extent with Natural WHSs. Instances of co‐occurrence where a WHS, a language, or both were endangered marked localities particularly deserving conservation attention. We examined co‐occurrence of all languages and all species, all languages and endangered species, and endangered languages and endangered species and found a correlation between linguistic and biological diversity that may indicate fundamental links between these very different measures of diversity. Considering only endangered species or endangered languages and species reduced that correlation, although considerable co‐occurrence persisted. Shared governance of government‐designated reserves is applicable for natural WHSs because it capitalizes on the apparent connection between culture and nature. Natural WHSs in Africa containing speakers of Indigenous languages present opportunities to conserve both nature and culture in highly visible settings where maintaining natural systems may rely on functioning Indigenous cultural systems and vice versa.
Changes in adhesive ingredients in continuous glucose monitoring systems may induce new contact allergy pattern
Authors: Svedman Cecilia , Ulriksdotter Josefin , Lejding Tina , Bruze Magnus , Mowitz Martin
Published: January 2021

Background

Medical devices (MD) in close skin‐contact for a prolonged time, such as glucose monitoring (CGM) systems, are a risk factor for contact allergy, and there has been an increase in patients using these. Correct diagnosis demands targetted testing.

Objectives

We report a new allergen in a continuous CGM system in which the adhesive was changed. The allergy pattern of the patients diagnosed is reported.

Methods

The three patients reported were patch tested with an MD series, own material, and possible allergens found through analysis with gas chromatography‐mass spectrometry, comparing analysis from the CGM system before and after change.

Results

The patients were sensitized to isobornyl acrylate (IBOA), found in previously used devices and the present CGM. Apart from IBOA, the culprit allergen was found to be 2,2′‐methylenebis(6‐tert‐butyl‐4‐methylphenol) monoacrylate.

Conclusion

Allergic contact dermatitis due to CGM systems and insulin pumps are difficult to investigate and require chemical analysis. Because of the lack of information on substances used in the production, and when changes with MDs are initiated, it is difficult to advise patients, especially since they risk sensitization to several allergens. The use of MDs has increased and, thus, the need for collaboration between manufacturers, clinicians, and patient organizations.
The relationship between in‐person voting and COVID‐19: Evidence from the Wisconsin primary
Authors: Cotti Chad , Engelhardt Bryan , Foster Joshua , Nesson Erik , Niekamp Paul
Published: January 2021

On April 7, 2020, Wisconsin held its presidential primary election, and news reports showed long lines of voters due to fewer polling locations. We use county‐level variation in voting patterns and weekly county‐level COVID test data to examine whether in‐person voting increased COVID‐19 cases. We find a statistically significant association between in‐person voting density and the spread of COVID‐19 2–3 weeks after the election. In our main results, a 10% increase in in‐person voters per polling location is associated with an 18.4% increase in the COVID‐19 positive test rate 2–3 weeks later.
Measuring the intensity of conflicts in conservation
Authors: Cusack Jeremy J. , Bradfer‐Lawrence Tom , Baynham‐Herd Zachary , Castelló y Tickell Sofia , Duporge Isla , Hegre Håvard , Moreno Zárate Lara , Naude Vincent , Nijhawan Sahil , Wilson John , Zambrano Cortes Dario Gerardo , Bunnefeld Nils
Published: January 2021

Conflicts between the interests of biodiversity conservation and other human activities pose a major threat to natural ecosystems and human well‐being, yet few methods exist to quantify their intensity and model their dynamics. We develop a categorization of conflict intensity based on the curve of conflict, a model originally used to track the escalation and deescalation of armed conflicts. Our categorization assigns six intensity levels reflecting the discourse and actions of stakeholders involved in a given conflict, from coexistence or collaboration to physical violence. Using a range of case studies, we demonstrate the value of our approach in quantifying conflict trends, estimating transition probabilities between conflict stages, and modeling conflict intensity as a function of relevant covariates. By taking an evidence‐based approach to quantifying stakeholder behavior, the proposed framework allows for a better understanding of the drivers of conservation conflict development across a diverse range of socioecological scenarios.
Leveraging innovative technology to generate drug response phenotypes for the advancement of biomarker‐driven precision dosing
Authors: Oni‐Orisan Akinyemi , Srinivas Nithya , Mehta Krina , Das Jesmin Lohy , Nguyen Thu T. , Tison Geoffrey H. , Bauer Scott R. , Burian Maria , Funk Ryan S. , Graham Richard A. ,   Biomarkers and Translational Tools Community Working Group of the American Society for Clinical Pharmacology and Therapeutics
Published: January 2021

Although traditional approaches to biomarker discovery have elucidated key molecular markers that have improved drug selection (precision medicine), the discovery of biomarkers that inform optimal dose selection (precision dosing) continues to be a challenge in many therapeutic areas. Larger and more diverse study populations are necessary to discover additional biomarkers that provide the resolution needed for a more tailored dose. To generate and accommodate large datasets of drug response phenotypes, time‐ and cost‐efficient strategies are necessary. In particular, a multitude of technological advances that originated for purposes outside of biomedical research (electronic health records, direct‐to‐consumer genetic testing, social media, mobile devices, and machine learning) have made it easier to communicate, connect, and gather information from consumers. Although these technologies have been used with success in the health sciences for an array of purposes, these resources have not been fully capitalized on for precision dosing. This perspective will touch on how these innovations can be used as data sources, data collection tools, and data processing tools for drug‐response phenotypes with a unique focus on advancing biomarker‐driven precision dosing.
Interstitial granuloma after interferon‐gamma and narrowbandUVBtherapy in a patient with mycosis fungoides: Immunological and histopathological considerations
Authors: Goto Hiroyuki , Sugita Kazunari , Yamamoto Osamu
Published: January 2021

In mycosis fungoides (MF), cutaneous granuloma formation is unusual. Furthermore, MF showing interstitial granuloma, a rare type, after combination therapy with interferon‐gamma (IFN‐γ) and narrowband UVB (nbUVB) has not been previously reported. A 77‐year‐old man was referred to our hospital with a 2‐month history of erythroderma. Biopsied specimens revealed infiltration of atypical lymphocytes and eosinophils. A diagnosis of an erythrodermic variant of MF was made. He was treated with combination therapy of IFN‐γ and nbUVB. After the therapy, papules newly appeared and a histopathological specimen revealed interstitial granuloma. There were several CXCR3‐positive cells around the granuloma. We speculated that the combination therapy made T‐helper 1 cells migrate to the cutaneous lesion and resulted in the granuloma formation. Furthermore, judging from the disappearance of elastic fibers around the interstitial granuloma, we considered that IFN‐γ may induce the infiltration of histiocytes interstitially after damage of elastic fibers caused by nbUVB therapy, and both IFN‐γ and nbUVB may thus play an important role in the histogenesis. Not only histopathology but also immunological observations are needed to elucidate the mechanisms underlying the development of different types of granuloma in MF.
Endoscopic retrieval of a migrated biliary stent into intrahepatic bile duct by using fine‐gauge biliary balloon dilation catheter
Authors: Ito Takashi , Shimatani Masaaki , Naganuma Makoto
Published: January 2021

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