bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of a Lay Health Worker–Led Intervention on Goals of Care, Quality of Life, and Clinical Trial Participation Among Low-Income and Minority Adults With Cancer
Authors: Patel Manali I. , Khateeb Sana , Coker Tumaini 
Published: May 2021

PURPOSE: New approaches are needed to overcome low supportive care and clinical trial participation among low-income and minority adults with cancer. The objective of this project was to determine whether a lay health worker intervention was associated with improvements in supportive care and trial participation. METHODS: We conducted a quality improvement initiative in collaboration with a union organization. We enrolled union members newly diagnosed with cancer into a 6-month lay health worker–led intervention from October 15, 2016, to February 28, 2017. The primary outcome was goals of care. Secondary outcomes were health-related quality of life (HRQOL), health care use, and trial participation. All outcomes except HRQOL were compared with a cohort of union members diagnosed within the 6-month preintervention period. RESULTS: Sixty-six adults participated in the intervention group, and we identified 72 adults in the control group. Demographic characteristics were similar between groups. The mean age was 56.0 years; 47 (34%) were male, and 22 were White (16%). Within 6 months enrollment, more intervention group participants, as compared with the control, had clinician-documented goals of care (94% v 26%; P < .001) and participated in cancer clinical trials (72% v 22%; P < .001). At 4 months postenrollment, as compared with baseline, intervention participants experienced HRQOL improvements (mean difference, 3.98 points; standard deviation, 2.83; P < .001). Before death, more intervention group participants used palliative care and hospice than the control group. CONCLUSION: Lay health worker–led interventions may improve supportive care and clinical trial participation among low-income and minority populations with cancer.
Room temperature superconductivity dome at a Fano resonance in superlattices of wires
Authors: Vittoria Mazziotti Maria , Jarlborg Thomas , Bianconi Antonio , Valletta Antonio 
Published: May 2021

Abstract
Recently room temperature superconductivity with

degrees Celsius has been discovered in a pressurized complex ternary hydride, CSH
x
, which is a carbon- and hydrogen-doped H3S alloy. The nanoscale structure of H3S is a particular realization of the 1993 patent claim of superlattice of quantum wires for room temperature superconductors and the maximum T

C
occurs at the top of a superconducting dome. Here we focus on the electronic structure of materials showing nanoscale heterostructures at the atomic limit made of a superlattice of quantum wires like hole-doped cuprate perovskites, and organics focusing on A15 intermetallics and pressurized hydrides. We provide a perspective of the theory of room temperature multigap superconductivity in heterogeneous materials tuned at a shape resonance or Fano resonance in the superconducting gaps near a Lifshitz transition focusing on H3S where the maximum T

C
occurs where the multiband metal is tuned by pressure near a Lifshitz transition. Here the superconductivity dome of T

C
vs. pressure is driven by both electron-phonon coupling and contact exchange interaction. We show that the T

C
amplification up to room temperature is driven by the Fano resonance between a superconducting gap in the anti-adiabatic regime and other gaps in the adiabatic regime. In these cases the T

C
amplification via contact exchange interaction is the missing term in conventional multiband BCS and anisotropic Migdal-Eliashberg theories including only Cooper pairing.
A Life Course Approach to the Relationship Between Fetal Growth and Hypothalamic-Pituitary-Adrenal Axis Function
Authors: Martin Wrivu N , Wang Carol A , Lye Stephen J , Matthews Stephen G , Reynolds Rebecca M , McLaughlin Carly E , Smith Roger , Pennell Craig E 
Published: May 2021

Abstract

Context
Human and animal studies suggest that hypothalamic-pituitary-adrenal axis (HPA-A) function may be programmed in utero; however, these findings are inconsistent. Given the powerful metabolic actions of cortisol, it is important to clarify the influence of early life on adult HPA-A function.

Objective
To determine the relationship between fetal growth and HPA-A stress response to a psychosocial stressor in young adults.

Design
Multigenerational, prospective cohort study (the Raine Study) conducted between 1989 and 1991.

Setting
King Edward Memorial Hospital, Perth, Western Australia, Australia.

Participants
A total of 917 participants aged 18 years from Gen2 of the Raine Study.

Main Outcome Measures
Measures of hypothalamic-pituitary-adrenal axis function before and after exposure to the Trier Social Stress Test.

Results
In fully adjusted models, an inverse linear relationship was observed between birthweight and plasma measures of (1) baseline cortisol (β = -0.90%, 95% CI: -1.73 to -0.07; P = 0.03); (2) peak cortisol (β = -0.78%, 95% CI -1.51 to -0.06; P = 0.03); (3) area under the curve with respect to ground (β = -0.89%, 95% CI -1.60 to -0.18; P = 0.01); and (4) adrenal sensitivity (β = -1.02, 95% CI: -1.85 to -0.18; P = 0.02). Similar results were demonstrated for percent optimal birthweight. No consistent quadratic relationships were identified. No associations were found between measures of fetal adiposity and HPA-A function at age 18 years, or fetal growth and HPA-A response pattern. Removal of anticipatory responders from the models substantially attenuated the observed relationships.

Conclusion
We observed an inverse linear relationship between fetal growth and HPA-A function at age 18 years. This differs from the inverse parabolic relationship (inverted U curve) reported in adults of advanced age. Altered adrenal sensitivity may underlie this relationship.
MRI-based Texture Analysis of Trabecular Bone for Opportunistic Screening of Skeletal Fragility
Authors: Zaworski Caroline , Cheah Jonathan , Koff Matthew F , Breighner Ryan , Lin Bin , Harrison Jonathan , Donnelly Eve , Stein Emily M 
Published: May 2021

Abstract

Context
Many individuals at high risk for osteoporosis and fragility fracture are never screened by traditional methods. Opportunistic use of imaging obtained for other clinical purposes is required to foster identification of these patients.

Objective
The aim of this pilot study was to evaluate texture features as a measure of bone fragility, by comparing clinically acquired magnetic resonance imaging (MRI) scans from individuals with and without a history of fragility fracture.

Methods
This study retrospectively investigated 100 subjects who had lumbar spine MRI performed at our institution. Cases (n = 50) were postmenopausal women with osteoporosis and a confirmed history of fragility fracture. Controls (n = 50) were age- and race-matched postmenopausal women with no known fracture history. Trabecular bone from the lumbar vertebrae was segmented to create regions of interest within which a gray level co-occurrence matrix was used to quantify the distribution and spatial organization of voxel intensity. Heterogeneity in the trabecular bone texture was assessed by several features, including contrast (variability), entropy (disorder), and angular second moment (homogeneity).

Results
Texture analysis revealed that trabecular bone was more heterogeneous in fracture patients. Specifically, fracture patients had greater texture variability (+76% contrast; P = 0.005), greater disorder (+10% entropy; P = 0.005), and less homogeneity (−50% angular second moment; P = 0.005) compared with controls.

Conclusions
MRI-based textural analysis of trabecular bone discriminated between patients with known osteoporotic fractures and controls. Further investigation is required to validate this promising methodology, which could greatly expand the number of patients screened for skeletal fragility.
G Protein–coupled Receptors in Radioiodine-refractory Thyroid Cancer in the Era of Precision Medicine
Authors: Suteau Valentine , Seegers Valérie , Munier Mathilde , Ben Boubaker Rym , Reyes Cécile , Gentien David , Wery Méline , Croué Anne , Illouz Frédéric , Hamy Antoine , Rodien Patrice , Briet Claire 
Published: May 2021

Abstract

Context
Radioiodine-refractory thyroid cancers have poor outcomes and limited therapeutic options (tyrosine kinase inhibitors) due to transient efficacy and toxicity of treatments. Therefore, combinatorial treatments with new therapeutic approaches are needed. Many studies link G protein–coupled receptors (GPCRs) to cancer cell biology.

Objective
To perform a specific atlas of GPCR expression in progressive and refractory thyroid cancer to identify potential targets among GPCRs aiming at drug repositioning.

Methods
We analyzed samples from tumor and normal thyroid tissues from 17 patients with refractory thyroid cancer (12 papillary thyroid cancers [PTCs] and 5 follicular thyroid cancers [FTCs]). We assessed GPCR mRNA expression using NanoString technology with a custom panel of 371 GPCRs. The data were compared with public repositories and pharmacological databases to identify eligible drugs. The analysis of prognostic value of genes was also performed with TCGA datasets.

Results
With our transcriptomic analysis, 4 receptors were found to be downregulated in FTC (VIPR1, ADGRL2/LPHN2, ADGRA3, and ADGRV1). In PTC, 24 receptors were deregulated, 7 of which were also identified by bioinformatics analyses of publicly available datasets on primary thyroid cancers (VIPR1, ADORA1, GPRC5B, P2RY8, GABBR2, CYSLTR2, and LPAR5). Among all the differentially expressed genes, 22 GPCRs are the target of approved drugs and some GPCRs are also associated with prognostic factors.

Discussion
For the first time, we performed GPCR mRNA expression profiling in progressive and refractory thyroid cancers. These findings provide an opportunity to identify potential therapeutic targets for drug repositioning and precision medicine in radioiodine-refractory thyroid cancer.
Early Impairment of Insulin Sensitivity, β-Cell Responsiveness, and Insulin Clearance in Youth with Stage 1 Type 1 Diabetes
Authors: Galderisi Alfonso , Moran Antoinette , Evans-Molina Carmella , Martino Mariangela , Santoro Nicola , Caprio Sonia , Cobelli Claudio 
Published: May 2021

Abstract

Context
Clinical onset of type 1 diabetes (Stage 3 T1D) is preceded by a presymptomatic phase characterized by multiple islet autoantibodies with normal glucose tolerance (Stage 1 T1D).

Objective
The aim was to explore the metabolic phenotypes of β-cell function and insulin sensitivity and clearance in normoglycemic youth with Stage 1 T1D and compare them with healthy nonrelated peers during a 3-hour oral glucose tolerance test (OGTT).

Methods
Twenty-eight lean youth, 14 with ≥2 islet autoantibodies (cases) and 14 healthy controls underwent a 3-hour 9-point OGTT with measurement of glucose, C-peptide, and insulin. The oral minimal model was used to quantitate β-cell responsiveness (φtotal) and insulin sensitivity (SI), allowing assessment of β-cell function by the disposition index (DI=φtotal×SI). Fasting insulin clearance (CL0) was calculated as the ratio between the fasting insulin secretion rate (ISR) and plasma insulin levels (ISR0/I0), while postload clearance (CL180) was estimated by the ratio of AUC of ISR over the plasma insulin AUC for the 3-hour OGTT (ISRAUC/IAUC). Participants with impaired fasting glucose, impaired glucose tolerance, or any OGTT glucose concentration ≥200 mg/dL were excluded.

Results
Cases (10.5 years [8, 15]) exhibited reduced DI (P &lt; .001) due to a simultaneous reduction in both φtotal (P &lt; 0.001) and SI (P = .008) compared with controls (11.5 years [10.4, 14.9]). CL0 and CL180 were lower in cases than in controls (P = .005 and P = .019).

Conclusion
Presymptomatic Stage 1 T1D in youth is associated with reduced insulin sensitivity and lower β-cell responsiveness, and the presence of blunted insulin clearance.
Dysgenesis and Dysfunction of the Pancreas and Pituitary Due toFOXA2Gene Defects
Authors: Kaygusuz Sare Betul , Arslan Ates Esra , Vignola Maria Lillina , Volkan Burcu , Geckinli Bilgen Bilge , Turan Serap , Bereket Abdullah , Gaston-Massuet Carles , Guran Tulay 
Published: May 2021

AbstractContextDevelopmental disorders of the pituitary gland leading to congenital hypopituitarism can either be isolated or associated with extrapituitary abnormalities (syndromic hypopituitarism). A large number of syndromic hypopituitarism cases are linked to mutations in transcription factors. The forkhead box A2 (FOXA2) is a transcription factor that plays a key role in the central nervous system, foregut, and pancreatic development.ObjectiveThis work aims to characterize 2 patients with syndromic hypopituitarism due to FOXA2 gene defects.ResultsWe report a novel heterozygous nonsense c.616C &gt; T(p.Q206X) variant that leads to a truncated protein that lacks part of the DNA-binding domain of FOXA2, resulting in impaired transcriptional activation of the glucose transporter type 2 (GLUT2)-luciferase reporter. The patient is the sixth patient described in the literature with a FOXA2 mutation, and the first patient exhibiting pancreatic hypoplasia. We also report a second patient with a novel de novo 8.53 Mb deletion of 20p11.2 that encompasses FOXA2, who developed diabetes mellitus that responded to sulfonylurea treatment.ConclusionOur 2 cases broaden the molecular and clinical spectrum of FOXA2-related disease, reporting the first nonsense mutation and the first case of pancreatic dysgenesis.
Noncanonical Thyroid Hormone Receptor α Action Mediates Arterial Vasodilation
Authors: Geist Daniela , Hönes G Sebastian , Gassen Janina , Kerp Helena , Kleinbongard Petra , Heusch Gerd , Führer Dagmar , Moeller Lars C 
Published: May 2021

Abstract

Context
Hypothyroidism impairs cardiovascular health and contributes to endothelial dysfunction with reduced vasodilation. How 3,5,3′-triiodothyronine (T3) and its receptors are involved in the regulation of vasomotion is not yet fully understood. In general, thyroid hormone receptors (TRs) either influence gene expression (canonical action) or rapidly activate intracellular signaling pathways (noncanonical action).

Objective
Here we aimed to characterize the T3 action underlying the mechanism of arterial vasodilation and blood pressure (BP) regulation.

Methods
Mesenteric arteries were isolated from male rats, wild-type (WT) mice, TRα knockout (TRα 0) mice, and from knockin mice with a mutation in the DNA-binding domain (TRα GS). In this mutant, DNA binding and thus canonical action is abrogated while noncanonical signaling is preserved. In a wire myograph system, the isolated vessels were preconstricted with norepinephrine. The response to T3 was measured, and the resulting vasodilation (Δ force [mN]) was normalized to maximum contraction with norepinephrine and expressed as percentage vasodilation after maximal preconstriction with norepinephrine (%NE). Isolated vessels were treated with T3 (1 × 10–15 to 1 × 10–5 mol/L) alone and in combination with the endothelial nitric oxide–synthase (eNOS) inhibitor L-NG-nitroarginine methyl ester (L-NAME) or the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin. The endothelium was removed to determine the contribution of T3 to endothelium-dependent vasodilation. The physiological relevance of T3-induced vasodilation was determined by in vivo arterial BP measurements in male and female mice.

Results
T3 treatment induced vasodilation of mesenteric arteries from WT mice within 2 minutes (by 21.5 ± 1.7%NE). This effect was absent in arteries from TRα 0 mice (by 5.3 ± 0.6%NE, P &lt; .001 vs WT) but preserved in TRα GS arteries (by 17.2 ± 1.1%NE, not significant vs WT). Inhibition of either eNOS or PI3K reduced T3-mediated vasodilation from 52.7 ± 4.5%NE to 28.5 ± 4.1%NE and 22.7 ± 2.9%NE, respectively. Removal of the endothelium abolished the T3-mediated vasodilation in rat mesenteric arteries (by 36.7 ± 5.4%NE vs 3.5 ± 6.2%NE). In vivo, T3 injection led to a rapid decrease of arterial BP in WT (by 13.9 ± 1.9 mm Hg) and TRα GS mice (by 12.4 ± 1.9 mm Hg), but not in TRα 0 mice (by 4.1 ± 1.9 mm Hg).

Conclusion
These results demonstrate that T3 acting through noncanonical TRα action affects cardiovascular physiology by inducing endothelium-dependent vasodilation within minutes via PI3K and eNOS activation.
Stable establishment of organ polarity occurs several plastochrons before primordium outgrowth in Arabidopsis
Authors: Zhao Feng , Traas Jan 
Published: May 2021

ABSTRACT
In many species, leaves are initiated at the flanks of shoot meristems. Subsequent growth usually occurs mainly in the plane of the leaf blade, which leads to the formation of a bifacial leaf with dorsoventral identities. In a classical set of surgical experiments in potato meristems, Sussex provided evidence that dorsoventrality depends on a signal emanating from the meristem center. Although these results could be reproduced in tomato, this concept has been debated. We revisited these experiments in Arabidopsis, in which a range of markers are available to target the precise site of ablation. Using specific markers for organ founder cells and dorsoventral identity, we were unable to perturb the polarity of leaves and sepals long before organ outgrowth. Although results in Solanaceae suggested that dorsoventral patterning was unstable during early development, we found that, in Arabidopsis, the local information contained within and around the primordium is able to withstand major invasive perturbations, long before polarity is fully established.
Visual perception and camouflage response to 3D backgrounds and cast shadows in the European cuttlefish, Sepia officinalis
Authors: El Nagar Aliya , Osorio Daniel , Zylinski Sarah , Sait Steven M. 
Published: May 2021

ABSTRACT
To conceal themselves on the seafloor, European cuttlefish, Sepia officinalis, express a large repertoire of body patterns. Scenes with 3D relief are especially challenging because it is not possible either to directly recover visual depth from the 2D retinal image or for the cuttlefish to alter its body shape to resemble nearby objects. Here, we characterised cuttlefish camouflage responses to 3D relief, and to cast shadows, which are complementary depth cues. Animals were recorded in the presence of cylindrical objects of fixed (15 mm) diameter, but varying in height, greyscale and strength of cast shadows, and to corresponding 2D pictorial images. With the cylinders, the cuttlefish expressed a ‘3D’ body pattern, which is distinct from previously described Uniform, Mottle and Disruptive camouflage patterns. This pattern was insensitive to variation in object height, contrast and cast shadow, except when shadows were most pronounced, in which case the body patterns resembled those used on the 2D backgrounds. This suggests that stationary cast shadows are not used as visual depth cues by cuttlefish, and that rather than directly matching the 2D retinal image, the camouflage response is a two-stage process whereby the animal first classifies the physical environment and then selects an appropriate pattern. Each type of pattern is triggered by specific cues that may compete, allowing the animal to select the most suitable camouflage, so the camouflage response is categorical rather than continuously variable. These findings give unique insight into how an invertebrate senses its visual environment to generate the body pattern response.
How head shape and substrate particle size affect fossorial locomotion in lizards
Authors: Bergmann Philip J. , Berry David S. 
Published: May 2021

ABSTRACTGranular substrates ranging from silt to gravel cover much of the Earth's land area, providing an important habitat for fossorial animals. Many of these animals use their heads to penetrate the substrate. Although there is considerable variation in head shape, how head shape affects fossorial locomotor performance in different granular substrates is poorly understood. Here, head shape variation for 152 species of fossorial lizards was quantified for head diameter, slope and pointiness of the snout. The force needed to penetrate different substrates was measured using 28 physical models spanning this evolved variation. Ten substrates were considered, ranging in particle size from 0.025 to 4 mm in diameter and consisting of spherical or angular particles. Head shape evolved in a weakly correlated manner, with snouts that were gently sloped being blunter. There were also significant clade differences in head shape among fossorial lizards. Experiments with physical models showed that as head diameter increased, absolute penetration force increased but force normalized by cross-sectional area decreased. Penetration force decreased for snouts that tapered more gradually and were pointier. Larger and angular particles required higher penetration forces, although intermediate size spherical particles, consistent with coarse sand, required the lowest force. Particle size and head diameter effect were largest, indicating that fossorial burrowers should evolve narrow heads and bodies, and select relatively fine particles. However, variation in evolved head shapes and recorded penetration forces suggests that kinematics of fossorial movement are likely an important factor in explaining evolved diversity.
Description and comparison of physical activity from self-reports and accelerometry among primary school children in Kilimanjaro, Tanzania: a pilot study
Authors: Mosha Mary Vincent , Kasagama Elizabeth , Ayieko Philip , Todd Jim , Msuya Sia E. , Grosskurth Heiner , Filteau Suzanne 
Published: May 2021

Background: Self-reports are commonly used to assess physical activity in children. Existing self-reports for physical activity have not been validated for primary school children in Tanzania. To understand if primary school children can accurately report their physical activity, we examined the validity of self-reported physical activity against accelerometer measured physical activity. Methods: A community-based cross-sectional study was conducted from May to July 2018. We conveniently selected four primary schools in Moshi municipal and Moshi rural districts in Kilimanjaro, Tanzania. From these districts, 51 children aged 9 – 11 years were randomly selected. A self-reported questionnaire was used to collect physical activity-related variables. Children wore accelerometers for seven consecutive days to capture physical activity movements. Spearman’s rank test and Bland Altman plots were used for assessing validity and agreement between self-reports and accelerometer moderate to vigorous physical activity (MVPA). Results: The study participants' mean age was 10 (SD=0.8) years, and 32 (63%) were girls. A significant positive correlation was found between self-reports and accelerometer MVPA (rho=0.36, p=0.009). The mean total of weekday minutes in MVPA from accelerometers was higher than from self-reports, 408 (SD = 66) versus 261 (SD = 179). Conclusions: This study found a significant positive correlation between self-reports and accelerometers. Self-reports are prone to errors due to recall bias, which interferes with their validity. More research is needed to develop better self-reported measures with specific activities that children can easily remember. Also, researchers should carefully consider the inherent limitations in the validity of self-reports.