Miracle-dz/UniFAR-FTUs huggingface dataset:
In vivo measurement of trabecular meshwork stiffness in a corticosteroid-induced ocular hypertensive mouse model

Significance Glaucoma is the leading cause of irreversible blindness worldwide. The primary and only modifiable risk factor for the development of glaucoma is elevated intraocular pressure (IOP), and lowering IOP effectively slows glaucomatous disease progression. Unfortunately, the majority of available treatments do not target, or intentionally bypass, the diseased and stiffened glaucomatous outflow tissues responsible for IOP elevation. We recently established that conventional outflow tissue stiffness reflects tissue function. Therefore, detection of outflow tissue stiffness using noncontact, noninvasive optical coherence tomography, as we here demonstrate in an animal model of glaucoma, represents a valuable tool for assessing outflow tissue functional status. Such technology has the potential to monitor recently approved treatments targeting the outflow tissues, and to inform glaucoma surgery decisions. Ocular corticosteroids are commonly used clinically. Unfortunately, their administration frequently leads to ocular hypertension, i.e., elevated intraocular pressure (IOP), which, in turn, can progress to a form of glaucoma known as steroid-induced glaucoma. The pathophysiology of this condition is poorly understood yet shares similarities with the most common form of glaucoma. Using nanotechnology, we created a mouse model of corticosteroid-induced ocular hypertension. This model functionally and morphologically resembles human ocular hypertension, having titratable, robust, and sustained IOPs caused by increased resistance to aqueous humor outflow. Using this model, we then interrogated the biomechanical properties of the trabecular meshwork (TM), including the inner wall of Schlemm’s canal (SC), tissues known to strongly influence IOP and to be altered in other forms of glaucoma. Specifically, using spectral domain optical coherence tomography, we observed that SC in corticosteroid-treated mice was more resistant to collapse at elevated IOPs, reflecting increased TM stiffness determined by inverse finite element modeling. Our noninvasive approach to monitoring TM stiffness in vivo is applicable to other forms of glaucoma and has significant potential to monitor TM function and thus positively affect the clinical care of glaucoma, the leading cause of irreversible blindness worldwide.
Social Cognitive Predictors of Engineering Students’ Academic Persistence Intentions, Satisfaction, and Engagement

The demand for high quality engineers is of particular importance as engineering jobs are projected to grow in the next 10 years (United States Bureau of Labor Statistics, 2018). More work is needed to understand factors related to academic engagement, satisfaction, and persistence intentions of Latino/as and women in engineering: 2 underrepresented groups in the engineering pipeline. We present findings that explored the role of social-cognitive, environmental, and personality variables in engineering persistence intentions, engagement and satisfaction of a diverse sample of 1,335 engineering students using an extension of the integrative social cognitive career theory model (SCCT; Lent et al., 2013). Results indicated that (a) the hypothesized model fit the data well for the full sample and across 8 subsamples based on gender-ethnicity (i.e., Latinas, Latinos, White women, and White men) and ethnicity-school type (i.e., Latina/os at Hispanic-serving institutions [HSIs], Latina/os at predominantly White institutions [PWIs], Whites at HSIs, and Whites at PWIs), (b) all but 5 model parameters were significant and positive for the full sample, (c) a subset of model parameters differed by the interactions of race/ethnicity-gender and race/ethnicity-school type groups, and (d) the relations within the model explained a significant amount of variance in engineering academic engagement, satisfaction, and persistence intentions for the full sample and 8 subsamples. Implications of the findings for educational and career interventions aimed at retaining Latina/os and women in engineering are discussed in relation to building on social cognitions in engineering academic engagement, satisfaction, and persistence intentions.
Beneficial Effects of an Aged Black Garlic Extract in the Metabolic and Vascular Alterations Induced by a High Fat/Sucrose Diet in Male Rats

Aged black garlic (ABG) is a functional food with antioxidant and anti-inflammatory properties. Recent studies also report its beneficial metabolic effects in a context of obesity or diabetes, although the mechanisms involved are poorly understood. The aim of this work was to analyze the effects of an ABG extract in the vascular and metabolic alterations induced by a high-fat/sucrose diet in rats. For this purpose, male Sprague–Dawley rats were fed either a standard chow (controls; n = 12) or a high-fat/sucrose diet (HFD; n = 24) for 16 weeks. From week 8 on, half of the HFD rats were treated with a commercial ABG extract concentrated in S-allyl cysteine and melanoidins (ABG10+®; 250 mg/kg daily by gavage; 5 mL/kg). ABG10+®-treated rats showed lower mean caloric intake, body weight, triglycerides, low density lipoprotein cholesterol (LDL-c), insulin and leptin serum concentrations and higher high density lipoprotein cholesterol (HDL-c) and adiponectin serum concentrations than non-treated rats. In the hypothalamus, ABG10+® treatment induced an increase in the gene expression of proopiomelanocortin (POMC) and a decrease in leptin receptor (ObR) mRNA levels. No significant changes were found in visceral adipose tissue except for an overexpression of β3-adrenergic receptor (β3-ADR) in ABG-treated rats. In subcutaneous adipose tissue, ABG10+® treatment decreased adipose weight and downregulated the gene expression of PPAR-γ, LPL, ObR and HSL. In brown adipose tissue, an overexpression of InsR, GLUT-4, UCP-1 and β3-ADR in ABG10+®-treated rats was found, whereas PPAR-γ mRNA levels were significantly decreased. Regarding vascular function, ABG10+® treatment attenuated the obesity-induced vasoconstriction in response to potassium chloride both in presence/absence of perivascular adipose tissue (PVAT). On the contrary, aorta segments from ABG-treated rats showed and improved relaxation in response to acetylcholine only when PVAT was present, with this fact possible being related to the decreased gene expression of proinflammatory cytokines in this tissue. In conclusion, ABG10+® administration partially improves the metabolic and vascular alterations induced by a high-fat/high-sucrose diet in rats through modifications in the gene expression of proteins and neuropeptides involved in inflammation, fat metabolism and food intake regulation. Further studies are required to assess the bioavailability of ABG between rats and humans.
Conducting gene set tests in meta‐analyses of transcriptome expression data

Research synthesis, eg, by meta‐analysis, is more and more considered in the area of high‐dimensional data from molecular research such as gene and protein expression data, especially because most studies and experiments are performed with very small sample sizes. In contrast to most clinical and epidemiological trials, raw data are often available for high‐dimensional expression data. Therefore, direct data merging followed by a joint analysis of selected studies can be an alternative to meta‐analysis by P value or effect‐size merging or, more generally spoken, the merging of results.
Sand Dollar Larvae Show Within-Population Variation in Their Settlement Induction by Turbulence

Settlement—the generally irreversible transition from a planktonic phase to a benthic phase—is a critical stage in the life history of many shoreline organisms. It is reasonable to expect that larvae are under intense selection pressure to identify appropriate settlement habitat. Several decades of studies have focused mainly on local indicators that larvae use to identify suitable habitat, such as olfactory cues that indicate the presence of conspecifics or a favored food source. Our recent work has shown that the larvae of seashore-dwelling echinoids (sea urchins, sand dollars, and kin) can be primed to settle following a brief exposure to a broader-scale indicator of their approach to shore: an increase in fluid turbulence. Here we demonstrate that this priming shows within-population variation: the offspring of certain Pacific sand dollar (Dendraster excentricus) parents—both specific fathers and specific mothers, regardless of the other parent—are more responsive to turbulence than others. In particular, the observation of the effect correlating, in some cases, with specific fathers leads us to conclude that these behavioral differences are likely genetic and thus heritable. We also report that turbulence exposure causes larvae to temporarily sink to the bottom of a container of seawater and that larvae that respond in this way are also more likely to subsequently settle. We hypothesize a two-step scenario for the evolution of turbulence responsiveness at settlement and suggest that the evolutionary origin of these behaviors could be a driving force for population differentiation and speciation.
Efficacy of the ketamine metabolite (2R,6R)-hydroxynorketamine in mice models of pain

Background and objectives Ketamine has been shown to reduce chronic pain; however, the adverse events associated with ketamine makes it challenging for use outside of the perioperative setting. The ketamine metabolite (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) has a therapeutic effect in mice models of depression, with minimal side effects. The objective of this study is to determine if (2R,6R)-HNK has efficacy in both acute and chronic mouse pain models. Methods Mice were tested in three pain models: nerve-injury neuropathic pain, tibia fracture complex regional pain syndrome type-1 (CRPS1) pain, and plantar incision postoperative pain. Once mechanical allodynia had developed, systemic (2R,6R)-HNK or ketamine was administered as a bolus injection and compared with saline control in relieving allodynia. Results In all three models, 10 mg/kg ketamine failed to produce sustained analgesia. In the neuropathic pain model, a single intraperitoneal injection of 10 mg/kg (2R,6R)-HNK elevated von Frey thresholds over a time period of 1–24hours compared with saline (F=121.6, p<0.0001), and three daily (2R,6R)-HNK injections elevated von Frey thresholds for 3 days compared with saline (F=33.4, p=0.0002). In the CRPS1 model, three (2R,6R)-HNK injections elevated von Frey thresholds for 3 days and then an additional 4 days compared with saline (F=116.1, p<0.0001). In the postoperative pain model, three (2R,6R)-HNK injections elevated von Frey thresholds for 3 days and then an additional 5 days compared with saline (F=60.6, p<0.0001). Conclusions This study demonstrates that (2R,6R)-HNK is superior to ketamine in reducing mechanical allodynia in acute and chronic pain models and suggests it may be a new non-opioid drug for future therapeutic studies.
Oxidation of methionine residues in human apolipoprotein A-I generates a potent pro-inflammatory molecule

Amyloid deposits of apolipoprotein A-I (apoA-I) and inflammation are common in atherosclerotic arteries. In this study, we investigated the interplay between oxidation of apoA-I methionine residues (Met(O)-ApoA-I), a known amyloidogenic modification of apoA-I, and the inflammatory response of immune cells. Soluble pre-fibrillar Met(O)-ApoA-I, but not apoA-I, induced intracellular accumulation of pro-interleukin (IL)-1β and secretion of the pro-inflammatory cytokines tumor necrosis factor α (TNFα) and IL-6 in mouse bone marrow–derived macrophages (BMDMs) and human primary monocytes. Additionally, secretion of mature IL-1β was also activated in human monocytes. The pro-inflammatory activity of Met(O)-ApoA-I was Toll-like receptor 4 (TLR4)-dependent and CD36-independent and was solely determined by oxidation of apoA-I methionine residues, in particular Met-86 and Met-148. In contrast, amyloid fibrils or reconstituted high-density lipoproteins (HDLs) generated from Met(O)-ApoA-I did not induce cytokine production in BMDMs. Although lipid-free Met(O)-ApoA-I remained functional in extracting lipids from cells and generating HDL, it gained strong pro-inflammatory properties that may aggravate local inflammation in the arteries and atherosclerosis. Our study indicates that oxidation of apoA-I methionine residues produces a potent danger-associated molecular pattern capable of stimulating pro-inflammatory cytokine secretion at levels similar to those induced by known pathogen-associated molecular patterns, such as lipopolysaccharide.
Association of obesity with colonic findings in screening colonoscopy in a large population-based study

Background and aims Obesity is associated with an increased incidence of and mortality from colorectal cancer (CRC). Screening colonoscopy seems particularly important for individuals with obesity. The aim of this study is to analyse the characteristics of screening colonoscopy in individuals with obesity. Methods We performed a cross-sectional analysis of records of 75,278 patients from a national colonoscopy screening programme in Poland. The database contained demographic data, colonoscopy results, self-reported data on weight and height, a standardized screenees’ experience questionnaire and colorectal findings. Results Adenoma detection rate and advanced neoplasia detection rate increased significantly in groups of increasing body mass index (BMI). In subjects with morbid obesity, odds ratios for proximal adenoma and proximal advanced neoplasia were 1.69 (95% confidence interval (CI) 1.28–2.21) and 1.66 (95% CI 1.01–2.72), respectively, despite the fact that with BMI increasing over 30 the preparation for colonoscopy was worse. Moreover, caecal intubation increased with increasing BMI. Tolerance of colonoscopy was better and preparation for colonoscopy was less inconvenient in individuals with obesity. Conclusions Obesity and morbid obesity are associated with increased detection of colorectal precursor lesions and better performance of screening colonoscopy. Participation in screening colonoscopy should be emphasized among individuals with obesity, taking into account the burden of CRC in this population.
Association of Germline Genetic Test Type and Results With Patient Cancer Worry After Diagnosis of Breast Cancer.

Background There are concerns that multigene panel testing compared with BRCA1/ 2-only testing after diagnosis of breast cancer may lead to unnecessary patient worry about cancer because of more ambiguous results. Methods Patients with breast cancer diagnosed from 2013 to 2015 and accrued from SEER registries in Georgia and Los Angeles were surveyed (n = 5,080; response rate, 70%), and responses were merged with SEER data and germline genetic testing and results. We examined patient reports of cancer worry by test type and results in 1,063 women who linked to a genetic test and reported undergoing testing. Results More than half of the sample (n = 640; 60.2%) received BRCA1/2-only testing versus 423 patients (39.8%) who had a multigene panel. A minority of tested patients reported substantial cancer worry after treatment: 11.1% (n = 130) reported higher impact of cancer worry, and 15.1% (n = 162) reported a high frequency of cancer worry (worrying often or almost always) in the past month. Impact of cancer worry did not substantively differ by test type, test result outcomes, or clinical or treatment factors. The odds ratio for higher impact of cancer worry was 0.81 (95% CI, 0.51 to 1.28) for multigene versus BRCA1/2-only testing. In a separate model, the odds ratios were 1.21 (95% CI, 0.54 to 2.68) and 0.90 (95% CI, 0.50 to 1.62) for pathogenic variant and variant of uncertain significance, respectively, versus a negative test (the reference group). Conclusion Compared with BRCA1/2 testing alone, multigene panel testing was not associated with increased cancer worry after diagnosis of breast cancer.
Being limited by Parkinson’s disease and struggling to keep up exercising; is the group the glue?

Abstract Background: People with Parkinson’s disease find that exercise helps to improve their physical performance. However, when performed in a group, they also tend to appreciate each other’s company. Purpose: After people with Parkinson’s disease participated in a community-based group balance exercise program, our aims were to explore the participants’ general attitude to their balance ability and exercise, and specifically their experiences of participating in a group exercise. Materials and Methods: Informants were people living with Parkinson’s disease at an early stage (n = 15) who had participated in a community-based “Somatosensory Focused Balance Training without Cues. ” Each informant took part in one face-to-face interview. The interviews were transcribed, according to content analysis, coded independently by two researchers and triangulated together with a third experienced researcher. Categories and themes were derived in consensus. Results: The participants felt limited by their body. They agreed that the group balance exercise program did help with their balance control. Moreover, the vast majority found that the group context implied a positive social contribution to their lives and to their ability to cope with living with the disease. Conclusion: Group balance exercise might constitute a context with potential to improve quality of life for people with Parkinson’s disease, not only by improving balance control, but also contributing to social connections, fellowship and the exchange of mutual experiences. Implications for rehabilitation Group-based exercise in early Parkinson seems to add more than just the physical effects of training, since it also gives a platform for meeting social and emotional needs, as well as addressing physical ability. The group dynamics and the support of peers seem to promote a positive attitude to life and enable people to learn coping strategies from each other. Community-based exercise groups for people with early Parkinson seem to be a way to get out in society and regain a feeling of being part of society. Due to body limits, people with Parkinson’s disease must struggle daily, already at an early stage of their disease; this stresses the need to begin rehabilitation early.
Rn7SK small nuclear RNA is involved in cellular senescence

Rn7SK is a conserved small nuclear noncoding RNA which its function in aging has not been studied. Recently, we have demonstrated that Rn7SK overexpression reduces cell viability and is significantly downregulated in stem cells, human tumor tissues, and cell lines. In this study, we analyzed the role of Rn7SK on senescence in adipose tissue‐derived mesenchymal stem cells (AD‐MSCs). For this purpose, Rn7SK expression was downregulated and upregulated via transfection and transduction, respectively, in AD‐MSCs and subsequently, various distinct characteristics of senescence including cell viability, proliferation, colony formation, senescence‐associated β galactosidase activity, and differentiation potency was analyzed. Our results demonstrated the transient knockdown of Rn7SK in MSCs leads to delayed senescence, while its overexpressions shows opposite effects. When osteogenic differentiation was started, however, they exhibited a greater differentiation potential than the original MSCs, suggesting a potential tool for stem cell‐based regenerative medicine.
The BDNF rs6265 variant may interact with overweight and obesity to influence obesity-related physical, metabolic and behavioural traits in Pakistani individuals

Abstract Background: The association of the variant rs6265 (G>A) in the brain-derived neurotrophic factor (BDNF) gene with obesity and other obesity-related parameters is not known for the Pakistani population. Moreover, the effects of interaction between BDNF rs6265 and overweight/obesity on obesity-related traits have never been investigated before. Aim: To find the association of the BDNF rs6265 with obesity and related traits and to explore the effect of rs6265 × obesity interaction on obesity-related traits in Pakistanis. Subjects and methods: The study involved a total of 606 subjects, including 306 overweight and obese (OW/OB) cases and 300 normal weight (NW) controls. The genotyping of the BDNF rs6265 was done and obesity-related anthropometric, physical, behavioural and metabolic parameters were determined. Statistical analyses using SPSS software were performed to find the associations. Results: The study revealed a lack of association of the BDNF rs6265 with obesity and obesity-related traits. On the other hand, the interaction between the BDNF rs6265 and overweight/obesity was found to be significantly associated with some of the obesity-related anomalous traits. However, no association between rs6265 and these anomalous traits was seen in either group when the association test was performed in NW and OW/OB groups separately. Conclusion: The BDNF rs6265, in the presence of obesity, may be associated with elevated risk of anomalous metabolic, behavioural and physical traits and obesity-related co-morbidities, but it needs to be validated in a significantly larger Pakistani sample population.
Favorable Cardiovascular Health at Young and Middle Ages and Dementia in Older Age—The CHA Study

Background Data are sparse on the association of cardiovascular health ( CVH ) in younger/middle age with the incidence of dementia later in life. Methods and Results We linked the CHA (Chicago Heart Association Detection Project in Industry) study data, assessed in 1967 to 1973, with 1991 to 2010 Medicare and National Death Index data. Favorable CVH was defined as untreated systolic blood pressure/diastolic blood pressure ≤120/≤80 mm Hg, untreated serum total cholesterol <5.18 mmol/L, not smoking, bone mass index <25 kg/m2, and no diabetes mellitus. International Classification of Diseases, Ninth Revision (ICD-9) codes and claims dates were used to identify the first dementia diagnosis. Cox models were used to estimate hazard ratios of incident dementia after age 65 years by baseline CVH status. Among 10 119 participants baseline aged 23 to 47 years, 32.4% were women, 9.2% were black, and 7.3% had favorable baseline CVH . The incidence rate of dementia during follow-up after age 65 was 13.9%. After adjustment, the hazard ratio for incident dementia was lowest in those with favorable baseline CVH and increased with higher risk factor burden ( P-trend<0.001). The hazards of dementia in those with baseline favorable, moderate, and 1-only high-risk factor were lower by 31%, 26%, and 20%, respectively, compared with those with ≥2 high-risk factors. The association was attenuated but remained significant ( P-trend<0.01) when the model was further adjusted for competing risk of death. Patterns of associations were similar for men and women, and for those with a higher and lower baseline education level. Conclusions In this large population-based study, a favorable CVH profile at younger age is associated with a lower risk of dementia in older age.