Miracle-dz/UniFAR-FTUs huggingface dataset:
Can Tenax Extraction Be Used as a Surrogate Exposure Metric for Laboratory‐Based Bioaccumulation Tests Using Marine Sediments?

The Tenax technique was used as an alternative exposure metric to assess the bioavailability of polychlorinated biphenyls (PCBs) from contaminated marine sediments. The sediments used were collected from 2 Superfund sites, New Bedford Harbor (MA, USA) and Gould Island (RI, USA). No sieving was conducted for either sediment after arrival, and sediments were stored in stainless steel drums at 2.8 to 4.0 °C in the dark until use. Exhaustive chemical extractions, single‐point 24‐h Tenax extractions, and 14‐d bioaccumulation tests using the amphipod Leptocheirus plumulosus were conducted for both sediments. The sum of 119 PCB congeners from total exhaustive chemical extraction in the New Bedford Harbor and Gould Island sediments were 1084 and 188.2 µg/g organic carbon, respectively. The PCB concentrations from the bioaccumulation tests and Tenax extractions showed that both exposure metrics followed a similar trend in amount and distribution of PCB congeners. The results from both exposure metrics were fit into a log–log linear regression, and then compared with a previously developed log–log linear model for freshwater organisms. The results showed that although the marine data fell within the prediction intervals of the freshwater linear model, the marine regression followed a lower trajectory due to the differences in both the slopes and intercepts between the marine and freshwater regressions. The present study showed a strong relationship between Tenax and marine invertebrate PCB concentrations. Environ Toxicol Chem 2019;38:1188–1197. © 2019 SETAC
Additivity of near work-induced transient myopia and its decay characteristics in different refractive groups.

PURPOSE To determine the additive effect, if any, of NITM after 1 and 2 hours of reading in different refractive groups. METHODS Fifteen early-onset myopes (EOMs), 14 late-onset myopes (LOMs), and 15 emmetropes (EMMs), as well as progressive myopes (PMs) and stable myopes (SMs), were tested. Subjects read binocularly for 2 hours at a distance of 35 to 40 cm. Distance refractive state of the right eye was assessed every 2 seconds for 30 seconds after the first hour of reading, and then every 2 seconds for 120 seconds after the second hour of reading. NITM was calculated as the difference in posttask distance refractive state compared with the pretask distance refractive state after each hour. RESULTS Initial NITM values (mean +/- SE) recorded at the end of the near work tasks were 0.22 +/- 0.03 D and 0.29 +/- 0.03 D for the EOMs, 0.14 +/- 0.02 D and 0.20 +/- 0.03 D for the LOMs, 0.14 +/- 0.02 D and 0.15 +/- 0.02 D for the EMMs, 0.20 +/- 0.03 D and 0.27 +/- 0.03 D for the PMs, and 0.09 +/- 0.04 D and 0.20 +/- 0.05 D for the SMs, after the first and second hours of reading, respectively. After the second hour, only in the EOMs and LOMs was NITM significantly greater than that found after the first hour. Seventy percent of the myopes (EOMs and LOMs) but only 47% of the EMMs exhibited increased NITM in the second hour compared with the first hour. Only EOMs exhibited longer decay duration after the second hour of reading. NITM was increased in progressive myopes (PMs), but not in stable myopes (SMs), after the first hour of reading only. Within the PMs, NITM was increased after the second hour compared with the first hour. The time constant for decay was greater in the PMs than in the SMs. Lastly, many myopes (up to 46%) did not experience decay to baseline after the near task over the 120-second posttask period. CONCLUSIONS EOMs and LOMs demonstrated larger NITM than the EMMs and exhibited NITM additivity, but the EOMs also exhibited prolonged decay of NITM compared with the EMMs and LOMs. PMs, but not SMs, exhibited additivity of NITM. These findings may be attributed to impaired sympathetic function in the subjects with myopia. It is speculated that with repeated cycles of near work, residual NITM may contribute to the progression of permanent myopia.
Cranial anatomy of the early cynodont Galesaurus planiceps and the origin of mammalian endocranial characters

The cranial anatomy of the early non‐mammalian cynodont Galesaurus planiceps from the South African Karoo Basin is redescribed on the basis of a computed tomographic reconstruction of the skull. Previously, little was known about internal skull morphology and the nervous and sensory system of this taxon. The endocranial anatomy of various cynodonts has been intensively studied in recent years to understand the origin of mammalian characters in the nasal capsule, brain and ear. However, these studies have focused on only a few taxa, the earliest of which is another Early Triassic cynodont, Thrinaxodon liorhinus. Galesaurus is phylogenetically stemward of Thrinaxodon and thus provides a useful test of whether the mammal‐like features observed in Thrinaxodon were present even more basally in cynodont evolution. The cranial anatomy of G. planiceps is characterized by an intriguing mosaic of primitive and derived features within cynodonts. In contrast to the very similar internal nasal and braincase morphology of Galesaurus and Thrinaxodon, parts of the skull that seem to be fairly conservative in non‐prozostrodont cynodonts, the morphology of the maxillary canal differs markedly between these taxa. Unusually, the maxillary canal of Galesaurus has relatively few ramifications, more similar to those of probainognathian cynodonts than that of Thrinaxodon. However, its caudal section is very short, a primitive feature shared with gorgonopsians and therocephalians. The otic labyrinth of Galesaurus is generally similar to that of Thrinaxodon, but differs in some notable features (e.g. proportional size of the anterior semicircular canal). An extremely large, protruding paraflocculus of the brain and a distinct medioventrally located notch on the anterior surface of the tabular, which forms the dorsal border of the large parafloccular lobe, are unique to Galesaurus among therapsids with reconstructed endocasts. These features may represent autapomorphies of Galesaurus, but additional sampling is needed at the base of Cynodontia to test this.
Influence of preparation designs on marginal adaptation and failure load of full-coverage occlusal veneers after thermomechanical aging simulation.

OBJECTIVES To evaluate the fracture resistance and marginal quality of maxillary molars restored using lithium disilicate glass-ceramic (LDG) occlusal veneers with two preparation designs. METHODS Sixteen extracted maxillary molars were assigned to two groups (n = 8). In group 1 (G1), the teeth received a preparation for a conservative full-coverage occlusal veneer restoration with a 90° rounded shoulder margin. In group 2 (G2), the teeth underwent a 1-mm cusp reduction with a marginal chamfer. LDG restorations (IPS e.max CAD) were obtained with the Cerec 3 CAD/CAM system and luted with Variolink II cement. After thermomechanical aging (1 250 000 cycles), the specimens were loaded to fracture. A semiquantitative marginal seal evaluation was performed observing resin replicas of the specimens at the scanning electron microscope. Cement thickness was assessed at the stereomicroscope on sectioned specimens. Collected data were statistically analyzed by parametric and nonparametric tests. RESULTS The maximum load to fracture was 2395.01 ± 150.96 N in G1 and 2408.39 ± 112.66 N in G2. Most of the observed specimens exhibited restorable fractures and continuous margins. Cement thickness was 132 ± 38 μm in G1 and 150 ± 41 μm in G2. No differences between the groups emerged. CONCLUSION This study demonstrated similar satisfactory performance of the two considered preparations designs for occlusal veneer with LDG. CLINICAL SIGNIFICANCE A new minimally invasive occlusal veneer preparation with marginal chamfer exhibited promising fracture resistance and marginal adaptation that were comparable to those of a standard conservative preparation for the restoration of molars with CAD/CAM lithium disilicate occlusal veneers.
The Phonographic Language Network: Using Network Science to Investigate the Phonological and Orthographic Similarity Structure of Language

Orthographic effects in spoken word recognition and phonological effects in visual word recognition have been observed in a variety of experimental tasks, strongly suggesting that a close interrelationship exists between phonology and orthography. However, the metrics used to investigate these effects, such as consistency and neighborhood size, fail to generalize to words of various lengths or syllable structures, and do not take into account the more global similarity structure that exists between phonological and orthographic representations in the language. To address these limitations, the tools of Network Science were used to simultaneously characterize the phonological as well as orthographic similarity structure of words in English. In the phonographic network of language, links are placed between words that are both phonologically and orthographically similar to each other (e.g., words such as pant (/pænt/) and punt (/p&U028C;nt/)). Conventional psycholinguistic experiments (auditory naming and auditory lexical decision) and an archival analysis of the English Lexicon Project (visual naming and visual lexical decision) were conducted to investigate the influence of 2 network science metrics derived from the phonographic network—phonographic degree and phonographic clustering coefficient—on spoken and visual word recognition. Results indicated a facilitatory effect of phonographic degree on visual word recognition, and a facilitatory effect of phonographic clustering coefficient on spoken word recognition. Implications of the present findings for theoretical models of spoken and visual word recognition are discussed.
Genetic Variants Associated with Immunosuppressant Pharmacokinetics and Adverse Effects in the DeKAF Genomics Genome Wide Association Studies.

BACKGROUND The immunosuppressants tacrolimus and mycophenolate are important components to the success of organ transplantation, but are also associated with adverse effects such as nephrotoxicity, anemia, leukopenia and new onset diabetes after transplant (NODAT). In this report, we attempted to identify genetic variants which are associated with these adverse outcomes. METHODS We performed a genome-wide association study (GWAS), using a genotyping array tailored specifically for transplantation outcomes containing 722,147 SNPs, and two cohorts of kidney allograft recipients, a discovery cohort and a confirmation cohort, to identify and then confirm genetic variants associated with immunosuppressant pharmacokinetics and adverse outcomes. RESULTS Several genetic variants were found to be associated with tacrolimus trough concentrations. We did not confirm variants associated with the other phenotypes tested although several suggestive variants were identified. DISCUSSION These results show that adverse effects associated with tacrolimus and mycophenolate are complex and recipient risk is not determined by a few genetic variants with large effects with but most likely are due to many variants, each with small effect sizes, and clinical factors.
Connexins and atrial fibrillation: filling in the gaps.

Atrial fibrillation (AF) is an extremely common arrhythmia with important consequences and presently suboptimal therapeutic options.1 A great deal of research has been performed to understand the detailed mechanisms of AF, with the hope that a better appreciation of the fundamental determinants of arrhythmogenesis will lead to the development of novel, more successful treatment possibilities.2 Article see p 216 One aspect of AF pathophysiology that has elicited great interest has been changes in gap junction/connexin physiology. An important role for altered gap junction function and the potential importance of gap junctions as a therapeutic target for AF were first emphasized by Spach and Starmer over 15 years ago.3 Since that time, our understanding of gap junction physiology, biophysics, and molecular biology has increased enormously,4,5 as have studies on their role in AF pathogenesis and management.2 Gap junctions contain transmembrane ion-channel proteins called connexins (Figure,panel A). Connexons (containing 6 connexin molecules each) in the gap junctions of adjacent cardiomyocytes line up and attach, transferring ions or molecules <1 kDa freely between cells, coupling them electrically (Figure, panel B). Cardiac tissues express a variety of connexins, including connexin (Cx)40, Cx43, Cx45, Cx30.2/31.9, and Cx37,5 with all but Cx37 present in cardiomyocytes and the most important connexins in atrial tissue being Cx40 and Cx43. There is evidence that posttranslational modification, particularly connexin phosphorylation, is important in governing connexin localization and function.6 Figure. A , Connexons contain 6 connexins each, arranged in a circle. Connexins …
Corneal Biomechanics Using a Scheimpflug‐Based Noncontact Device in Normal‐Tension Glaucoma and Healthy Controls

Purpose: To determine if a novel biomechanical parameter, corneal applanation velocity, as measured by the Corvis ST, is associated with a diagnosis of normal‐tension glaucoma (NTG). Design: Prospective, cross‐sectional study. Methods: Study and control subjects were recruited from the ophthalmology clinic of a university teaching hospital in Hong Kong over an 8‐week period in 2013. A total of 80 eyes with NTG diagnosis and 155 healthy eyes randomly selected to be in the control group were included in the final analysis. All subjects underwent corneal biomechanical testing with the Oculus Corvis ST non‐contact tonometer. Logistic regression analysis adjusted for age and central corneal thickness was conducted to assess the relationship between inward and outward applanation velocity and the risk of NTG. Secondary outcome variables included corneal applanation time, length, amplitude, and highest concavity. Results: Inward applanation velocity was faster in the NTG eyes (0.15 ± 0.02 m/s) than in the control eyes (0.14 ± 0.02 m/s) (P = 0.016). The odds ratio for a 0.01 m/s increase in inward applanation velocity when comparing NTG eyes with control eyes adjusted for age and central corneal thickness was 1.15 (95% confidence interval, 1.03‐1.30) (P = 0.016). There was no evidence that outward applanation velocity or any secondary corneal biomechanical variable differed between the NTG and control eyes. Conclusion: Normal‐tension glaucoma eyes demonstrated a small, statistically significant faster corneal inward applanation velocity than normal control eyes.
A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections

Importance In young febrile infants, serious bacterial infections (SBIs), including urinary tract infections, bacteremia, and meningitis, may lead to dangerous complications. However, lumbar punctures and hospitalizations involve risks and costs. Clinical prediction rules using biomarkers beyond the white blood cell count (WBC) may accurately identify febrile infants at low risk for SBIs. Objective To derive and validate a prediction rule to identify febrile infants 60 days and younger at low risk for SBIs. Design, Setting, and Participants Prospective, observational study between March 2011 and May 2013 at 26 emergency departments. Convenience sample of previously healthy febrile infants 60 days and younger who were evaluated for SBIs. Data were analyzed between April 2014 and April 2018. Exposures Clinical and laboratory data (blood and urine) including patient demographics, fever height and duration, clinical appearance, WBC, absolute neutrophil count (ANC), serum procalcitonin, and urinalysis. We derived and validated a prediction rule based on these variables using binary recursive partitioning analysis. Main Outcomes and Measures Serious bacterial infection, defined as urinary tract infection, bacteremia, or bacterial meningitis. Results We derived the prediction rule on a random sample of 908 infants and validated it on 913 infants (mean age was 36 days, 765 were girls [42%], 781 were white and non-Hispanic [43%], 366 were black [20%], and 535 were Hispanic [29%]). Serious bacterial infections were present in 170 of 1821 infants (9.3%), including 26 (1.4%) with bacteremia, 151 (8.3%) with urinary tract infections, and 10 (0.5%) with bacterial meningitis; 16 (0.9%) had concurrent SBIs. The prediction rule identified infants at low risk of SBI using a negative urinalysis result, an ANC of 4090/µL or less (to convert to ×109 per liter, multiply by 0.001), and serum procalcitonin of 1.71 ng/mL or less. In the validation cohort, the rule sensitivity was 97.7% (95% CI, 91.3-99.6), specificity was 60.0% (95% CI, 56.6-63.3), negative predictive value was 99.6% (95% CI, 98.4-99.9), and negative likelihood ratio was 0.04 (95% CI, 0.01-0.15). One infant with bacteremia and 2 infants with urinary tract infections were misclassified. No patients with bacterial meningitis were missed by the rule. The rule performance was nearly identical when the outcome was restricted to bacteremia and/or bacterial meningitis, missing the same infant with bacteremia. Conclusions and Relevance We derived and validated an accurate prediction rule to identify febrile infants 60 days and younger at low risk for SBIs using the urinalysis, ANC, and procalcitonin levels. Once further validated on an independent cohort, clinical application of the rule has the potential to decrease unnecessary lumbar punctures, antibiotic administration, and hospitalizations.
Pattern recognition scavenger receptor A/CD204 regulates airway inflammatory homeostasis following organic dust extract exposures

Abstract Exposure to agriculture organic dusts, comprised of a diversity of pathogen-associated molecular patterns, results in chronic airway diseases. The multi-functional class A macrophage scavenger receptor (SRA)/CD204 has emerged as an important class of pattern recognition receptors with broad ligand binding ability. The objective was to determine the role of SRA in mediating repetitive and post-inflammatory organic dust extract (ODE)-induced airway inflammation. Wild-type (WT) and SRA knockout (KO) mice were intra-nasally treated with ODE or saline daily for 3 weeks and immediately euthanized or allowed to recover for 1 week. Results show that lung histopathologic changes were increased in SRA KO mice as compared to WT following repetitive ODE exposures marked predominately by increased size and distribution of lymphoid aggregates. After a 1-week recovery from daily ODE treatments, there was significant resolution of lung injury in WT mice, but not SRA KO animals. The increased lung histopathology induced by ODE treatment was associated with decreased accumulation of neutrophils, but greater accumulation of CD4+ T-cells. The lung cytokine milieu induced by ODE was consistent with a TH1/TH17 polarization in both WT and SRA KO mice. Overall, the data demonstrate that SRA/CD204 plays an important role in the normative inflammatory lung response to ODE, as evidenced by the enhanced dust-mediated injury viewed in the absence of this receptor.
Effects of new dock-less bicycle-sharing programs on cycling: a retrospective study in Shanghai

Objectives To examine (1) the effect of new dock-less bicycle-sharing programmes on change in travel mode and (2) the correlates of change in travel mode. Design A retrospective natural experimental study. Setting 12 neighbourhoods in Shanghai. Participants 1265 respondents were recruited for a retrospective study in May 2017. Main outcome measures Prevalence of cycling before and after launch of dock-less bicycle-sharing programme. Results The proportion of participants cycling for transport increased from 33.3% prior to the launch of the bicycle-sharing programmes to 48.3% 1 year after the launch (p<0.001). Being in the age group of 30–49 years (OR 2.28; 95% CI 1.30 to 4.00), living within the inner ring of the city (OR 2.27; 95% CI 1.22 to 4.26), having dedicated bicycle lanes (OR 1.37, 95% CI 1.12 to 1.68) and perceiving riding shared bicycles as fashionable (OR 1.46, 95% CI 1.21 to 1.76) were positively associated with adopting cycling for transport. Access to a public transportation stop/station (OR 0.82, 95% CI 0.67 to 0.99) was inversely correlated with adopting cycling for transport. Conclusions Dock-less bicycle sharing may promote bicycle use in a metropolitan setting. Findings from this study also highlight the importance of cycling-friendly built environments and cultural norms as facilitators of adopting cycling.
Increased TGF-β and BMP Levels and Improved Chondrocyte-Specific Marker Expression In Vitro under Cartilage-Specific Physiological Osmolarity

During standard expansion culture (i.e., plasma osmolarity, 280 mOsm) human articular chondrocytes dedifferentiate, making them inappropriate for autologous chondrocyte implantation to treat cartilage defects. Increasing the osmolarity of culture media to physiological osmolarity levels of cartilage (i.e., 380 mOsm), increases collagen type II (COL2A1) expression of human articular chondrocytes in vitro, but the underlying molecular mechanism is not fully understood. We hypothesized that TGF-β superfamily signaling may drive expression of COL2A1 under physiological osmolarity culture conditions. Human articular chondrocytes were cultured in cytokine-free medium of 280 or 380 mOsm with or without siRNA mediated TGF-β2 knockdown (RNAi). Expression of TGF-β isoforms, and collagen type II was evaluated by RT-qPCR and immunoblotting. TGF-β2 protein secretion was evaluated using ELISA and TGF-β bioactivity was determined using an established reporter assay. Involvement of BMP signaling was investigated by culturing human articular chondrocytes in the presence or absence of BMP inhibitor dorsomorphin and BMP bioactivity was determined using an established reporter assay. Physiological cartilage osmolarity (i.e., physosmolarity) most prominently increased TGF-β2 mRNA expression and protein secretion as well as TGF-β bioactivity. Upon TGF-β2 isoform-specific knockdown, gene expression of chondrocyte marker COL2A1 was induced. TGF-β2 RNAi under physosmolarity enhanced TGF-β bioactivity. BMP bioactivity increased upon physosmotic treatment, but was not related to TGF-β2 RNAi. In contrast, dorsomorphin inhibited COL2A1 mRNA expression in human articular chondrocytes independent of the osmotic condition. Our data suggest a role for TGF-β superfamily member signaling in physosmolarity-induced mRNA expression of collagen type II. As physosmotic conditions favor the expression of COL2A1 independent of our manipulations, contribution of other metabolic, post-transcriptional or epigenetic factors cannot be excluded in the underlying complex and interdependent regulation of marker gene expression. Dissecting these molecular mechanisms holds potential to further improve future cell-based chondral repair strategies.