Miracle-dz/UniFAR-FTUs huggingface dataset:
Leptin stimulates migration and invasion and maintains cancer stem-like properties in gastric cancer cells

Obesity is a risk factor for various types of cancer. Leptin, an adipocyte-derived hormone, may stimulate the proliferation of gastric cancer cells. However, the effect of leptin and underlying mechanism in gastric cancer remain unclear. In the present study, the role of leptin in gastric cancer was evaluated. The effect of leptin on the JAK-STAT and MEK signaling pathways was investigated in gastric cancer cells using wound-healing and cell invasion assays, immunoblotting and inhibition studies. Cancer-initiating cells derived from gastric cancer cells were used to investigate the effect of leptin on the maintenance of stemness and epithelial-mesenchymal transition (EMT) by immunoblotting. Clinicopathological characteristics including the serum leptin level and overall survival (OS) were analyzed in patients with (n=23) and without (n=23) obesity. Leptin induced the migration and invasion of gastric cancer cells by activating AKT and ERK and upregulating vascular endothelial growth factor (VEGF). Leptin increased the mRNA and protein levels of markers of stemness (CD44) and the EMT (Snail and N-cadherin). Pharmacological inhibitors of the JAK-STAT and MEK signaling pathways decreased leptin-induced migration and invasion, and the expression of VEGF. Obesity was associated with an elevated leptin level and body mass index was positively correlated with the leptin level (P=0.001 for both). The 5-year OS rate was not significantly different between the two groups (P=0.098). Leptin stimulates the migration and invasion of gastric cancer cells by activating the JAK-STAT and MEK pathways, and contributes to the maintenance of cancer stemness and metastatic potential. The present findings support an adverse effect of obesity in gastric cancer. Consequently, targeting of leptin-associated signaling pathways may have therapeutic potential for gastric cancer.
Pharmacogenetic and drug interaction aspects on ketamine safety in its use as antidepressant ‐ implications for precision dosing in a global perspective

Ketamine and its enantiomer S‐ketamine (esketamine) are known to produce rapid‐onset antidepressant effects in major depression. Intranasal esketamine has recently come onto the market as an antidepressant. Besides experience from short‐term use in anaesthesia and analgesia, the experience with ketamine as long‐term medication is rather low. The use of ketamine and esketamine is limited due to potential neurotoxicity, psychotomimetic side effects, potential abuse and interindividual variability in treatment response including cessation of therapy. Therefore, taking a look at individual patient risks and potential underlying variability in pharmacokinetics may improve safety and dosing of these new antidepressant drugs in clinical practice.
Global trends in the incidence of psoriasis from 1990 to 2019

The global, regional, and national burden of psoriasis was investigated based on the Global Burden of Disease (GBD) study. To report the incidence of psoriasis in 204 countries and territories from 21 regions according to age, sex, region, country, and social-demographic index (SDI) between 1990 and 2019. Estimates from the GBD 2019 study were used to analyse the incidence of psoriasis at the global, regional, and national levels. The estimated annual percentage changes (EAPCs) in the age-standardized incidence rate (ASIR) were calculated to quantify trends between 1990 and 2019. From 1990 to 2019, the global incidence of psoriasis increased by 26.53%, but the ASIR of psoriasis decreased, with an EAPC of −0.77 (95% confidence interval [CI]: −0.78 to −0.76). In 2019, the highest ASIRs of psoriasis (112.58 per 100,000 population; 95% uncertainty interval, 108.89 to 116.07) were observed in high-SDI regions. The male-to-female ratio for psoriasis incidence peaked globally in the 50–54-year-old age group and peaked in the 75–79-year-old age group in high-SDI regions. Regionally, Central Sub-Saharan Africa (EAPC, −0.57; 95% CI: −0.67 to −0.48) and Eastern Sub-Saharan Africa (EAPC, −0.36; 95% CI, −0.38 to −0.34) had the largest decrease in ASIR of psoriasis from 1990 to 2019. Nationally, increases in the ASIR of psoriasis was observed only in Japan (EAPC, 0.04; 95% CI: 0.02 to 0.05). Globally, the incidence of psoriasis showed an increasing trend, but the ASIR of psoriasis decreased significantly from 1990 to 2019. Only Japan showed an unfavourable increasing trend.
The multisystemic effects of oral appliance therapy for obstructive sleep apnea: A narrative review

Obstructive sleep apnea (OSA) is a chronic condition accompanied by repeated obstruction of the upper airway during sleep despite respiratory efforts, resulting in intermittent hypoxemia, altered sleep structure, and sympathetic activation. Previous studies have shown a significant association between OSA and general health issues such as cardiovascular diseases, endocrine disorders, neurocognitive function decline, and poor quality of life. Continuous positive airway pressure (CPAP) has been considered as the first line treatment for OSA. However, accumulating evidence supports the role of oral appliance (OA) therapy, including mandibular advancement devices, as an alternative option for snoring and OSA patients who do not comply with or refuse CPAP usage. Despite a generally favorable outcome of OA therapy for OSA related respiratory indices, studies focusing on the impact of systemic effects of OA therapy in OSA patients are relatively scarce compared with the extensive literature focusing on the systemic effects of CPAP. Therefore, this article aimed to provide an overview of the current evidence regarding the multisystemic effects of OA therapy for OSA.
Improvement in linear depressed atrophic scar using 755-nm picosecond alexandrite laser vs. ablative fractional carbon dioxide laser

ABSTRACT Ablative Fractional laser (AFL), which has been widely used, but non-ablative and less invasive techniques such as picosecond laser with fewer side effects are available. To objectively determine the degree of scar improvement with picosecond laser compared with ablative fractional carbon dioxide laser in depressed facial scar. This prospective, evaluator-blinded trial enrolled patients with linear depressed atrophic scar. There were 26 patients in the picosecond laser group and 38 patients in the AFL patient group. Standardized images were acquired by the same person using the same device in the same place. Five physicians compared the scar improvement effect using modified Vancouver Scar Scale (mVSS) and Stony Brook Scar Evaluation Scale. No statistically significant demographic differences existed between the two laser groups. On the Stony Brook Scar Rating Scale, the improvement of depression and hatch marks was significantly greater with the picosecond laser group. The picosecond laser resulted in a better score improvement in the overall scar scale on both mVSS and Stony Brook Scar Evaluation Scale. In conclusion, the 755-nm picosecond laser is a safe and effective non-ablative modality for wide and depressed facial scar, with significantly superior scar improvement when compared with the AFL. Abbreviations AFL = ablative fractional laser, CO2= carbon dioxide, LiOB = laser-induced optical breakdown, PIH = postinflammatory hyperpigmentation, mVSS = Modified Vancouver scar scale.
Association of compassion and empathy with prosocial health behaviors and attitudes in a pandemic

This investigation examined how dispositional compassion and empathy were associated with prosocial behaviors and attitudes in the SARS-CoV-2 pandemic. Every two weeks from March 22 to June 15, 2020, we fielded a survey to a new cohort of adults in the U.S. Compassion related to whether one stayed home to protect others, more hours spent staying home and distancing from others, and more frequent mask wearing in public, in the past two weeks. Compassion also related to greater perceived ability to help others who were negatively affected. Empathy related to more endorsement of understanding others’ fear of COVID-19, and less endorsement of the view that others were overreacting to COVID-19. There was an interaction between empathy and political ideology, suggesting that empathy may matter for understanding others’ fear among those with more conservative-leaning beliefs. Empathy also related to greater understanding that sheltering-in-place helps prevent the spread of COVID-19. Findings suggest that messaging and interventions to increase compassion and empathy may promote public health behaviors during a pandemic regardless of political orientation. Targeting empathy may be one way to reach individuals with more conservative political beliefs, and it is important to use an evidence-based approach accounting for political party differences in motivated reasoning.
The Pain Clinic for Older People.

OBJECTIVE Multidisciplinary Pain Clinics have an established role in the management of persistent pain, however there is little evidence to support this approach in an older population. This study describes the characteristics and pain outcomes of patients attending a pain clinic designed exclusively for older people. METHODS Retrospective audit of outcomes of the Pain Clinic for Older People (PCOP) from 2015-2019. Response to treatment was determined by change in Brief Pain Inventory scores (BPI) at initial attendance and following a treatment program. Clinically meaningful improvement was defined using the Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT) consensus criteria of ≥ 30% improvement in average pain and 1-point improvement in pain interference. Results were compared to the national benchmark collated by the electronic Persistent Pain Outcomes Collaboration (ePPOC), which reports the combined results from 67 participating Australian and New Zealand (AU/NZ) pain services. RESULTS PCOP patients had a mean age of 80.5 years and had high rates of frailty (84%), cognitive impairment (30%) and multimorbidity. Significant reductions in BPI average pain and BPI pain interference scores were achieved. Clinically meaningful improvement in BPI average pain was achieved in 63% attending the PCOP aged 65-74 years, and 46% in patients aged ≥ 75 years, which met the national benchmark set by ePPOC of 40% for both age groups. Clinically meaningful improvement in BPI pain interference was achieved in 69% in 65-74 year-olds attending PCOP and 66% of those ≥ 75 years, comparable to the ePPOC benchmark of 71% and 65% for the respective age groups. CONCLUSION . PCOP clients achieved significant and meaningful improvements in their pain outcomes that satisfied the national benchmark. Advanced age, cognitive impairment, frailty and multimorbidity should not be regarded as barriers to benefit from a pain clinic specifically designed for older people.
Reasons for living, positive psychological constructs and their relationship with suicide ideation in people with moderate to severe traumatic brain injury: A cross-sectional study

ABSTRACT Positive psychological constructs such as reasons for living, self-esteem and resilience have previously been shown to act as protective psychological barriers against negative psychological outcomes, including suicide ideation in both clinical populations and the general population. This study aims to explore the positive psychological constructs of reasons for living, self-esteem, resilience and their relationship with suicide ideation and predictors of suicide ideation (depression, hopelessness) for N = 50 people who have a severe TBI and are currently receiving community rehabilitation at Liverpool Brain Injury Rehabilitation Unit (LBIRU), NSW. Results indicated good reliability for the use of the RFLI with people who have TBI, with the most frequently endorsed subscale (range 0–5) being “survival and coping beliefs” (4.7 ± 1.0) and the least frequently being “fear of suicide” (2.2 ± 1.1). The shortened version of the RFLI (BRFLI) also displayed good reliability. Positive psychological constructs (reasons for living, resilience, self-esteem) were all significantly inversely associated with suicide and suicide predictors (depression, hopelessness). This study suggests that positive psychological constructs can act as a buffer against suicide ideation after moderate to severe TBI.
Efficient proton shuttle makes SazCA an excellent CO2 hydration enzyme

Abstract The fastest member of the carbonic anhydrase family catalysing the reversible hydration of carbon dioxide to bicarbonate ions has been recently reported to be SazCA. While thermostable, this enzyme shows exceptional activity at 353 K for the reaction. This study explores the molecular basis for the exceptional activity of SazCA, in contrast to SspCA, probed using molecular dynamics simulations. Our simulations, carried out at different temperatures, indicate the presence of efficient proton shuttle between the active zinc centre and His64 residue in the two enzymes. The proton accepting His64 residue was identified to have in and out conformations with the in conformations being supportive to proton acceptance. Our simulations show a large population of in conformations in SazCA making the enzyme exhibit an exceptional activity. The RMSF and H-bonds analysis confirmed the role of His2 and His207 in supporting the attainment of in conformations in SazCA resulting in exceptional activity. Communicated by Ramaswamy H. Sarma
D‐pinitol attenuates isoproterenol‐induced myocardial infarction by alleviating cardiac inflammation, oxidative stress and ultrastructural changes in Swiss albino mice

Cardiovascular diseases are the most disturbing problems throughout the world. The side effects of existing drugs are continuously compelling the scientist to look for better options in terms of safety, efficacy and cost‐effectiveness. Our study is also a move in this direction. We have chosen D‐pinitol to see its cardioprotective role in isoproterenol‐induced myocardial infarction in Swiss albino mice. Grouping was made by dividing mice into eight groups (n = 6). Group I, control; Group II, isoproterenol (ISO) (150 mg/kg, i.p.); Group III, D‐pinitol (PIN) (25 mg); Group IV, PIN (50 mg); Group V, PIN (100 mg) per kg per oral, respectively with ISO; Group VI, PIN per se (100 mg D‐pinitol only); Group VII, Propranolol (PRO) (20 mg/kg/oral) with ISO; and Group VIII, PRO per se (20 mg/kg, p.o.). After 24 h of the last dose, the blood sample was collected for biochemical parameters, then mice were, killed through cervical dislocation under anaesthesia and cardiac tissue was collected for biochemical, histopathological and ultrastructural evaluation. Administration of ISO in mice altered the level of antioxidant markers, cardiac injury markers and inflammatory markers, which were significantly restored towards normal by D‐pinitol at the dose of 50 and 100 mg. 25 mg of D‐pinitol dosage, did not produce significant cardio protection. The histopathological and ultrastructural analysis further confirmed these findings. Our study showed that D‐pinitol significantly protected myocardial damage which was induced by ISO and reverted oxidative stress and inflammation considerably.
Association of free thyroxine with obstructive lung pattern in euthyroid middle-aged subjects: A population-based study

Background The association between thyroid hormone levels and pulmonary function in euthyroid population is still unclear. We aimed to examine the relationship between thyroid function and lung function in a large cohort study of euthyroid subjects. Methods We analyzed biochemical and spirometry data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 1,261 middle-aged participants aged 45–65 years with spirometry tests and normal thyroid function were included in this study. The subjects were grouped according to free thyroxine (fT4) (ng/dL) quartiles (Q1, 0.89–1.09; Q2, 1.10–1.19; Q3, 1.20–1.30; Q4, 1.31–1.76). Obstructive lung pattern was defined as forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) <0.7. The probability of obstructive lung patterns according to fT4 quartiles was assessed using logistic regression models, adjusted for potential confounders. Results Overall, 10.9% of the subjects had an obstructive lung pattern. The mean fT4 levels were significantly higher in those with obstructive lung pattern than in those with normal lung function (1.26 vs. 1.20 ng/dL, p<0.001). The proportion of participants with obstructive lung pattern increased across the fT4 quartile categories (p<0.001). With the Q1 group as reference, the multivariate-adjusted odds ratios (95% confidence intervals) for obstructive lung pattern in the Q3 and Q4 groups were 2.875 (1.265–6.535) and 2.970 (1.287–6.854), respectively, even after adjusting for confounding variables. Conclusion High fT4 levels are an independent predictor of obstructive lung pattern in euthyroid middle-aged subjects. Further prospective studies are needed to confirm these findings.
Evaluation of SS-31 as a Potential Strategy for Tendinopathy Treatment: An In Vitro Model

Background: Studies in our laboratory have demonstrated mitochondrial dysfunction in human and animal models of supraspinatus tendinopathy. SS-31 (elamipretide) has been reported to improve mitochondrial function and to be effective in clinical trials for several diseases. The potential of SS-31 in treating tendinopathy has not been explored. Hypothesis: SS-31 would improve mitochondrial function in human tenocytes sampled from patients with tendinopathy. Study Design: Controlled laboratory study. Methods: Healthy tenocytes were obtained from normal hamstring tendon biopsy specimens in 9 patients undergoing anterior cruciate ligament reconstruction, and tenocytes were collected from degenerative supraspinatus tendon biopsy specimens in 9 patients undergoing rotator cuff repair. Tenocytes were cultured, used at passage 1, and assigned to 4 groups: healthy tenocytes, healthy tenocytes with 1μM SS-31 treatment for 72 hours, degenerative tenocytes, and degenerative tenocytes with 1μM SS-31 treatment for 72 hours. The outcomes included measurements of mitochondrial potential, mitochondrial morphology by transmission electron microscopy imaging, reactive oxygen species and superoxidative dismutase activity, gene expression, and cell viability. Results: An increase in the cell fraction with depolarized mitochondria was found in degenerative tenocytes (P = .014), followed by a decrease after SS-31 treatment (P = .018). Transmission electron microscopy images demonstrated morphological changes with a decreased number and size of mitochondria per cell in the degenerative tenocytes (P = .018) and with improvement after SS-31 treatment. There was no significant difference in the level of reactive oxygen species between healthy and degenerative tenocytes in culture, but superoxidative dismutase activity was significantly decreased in the degenerative group (P = .006), which then increased after SS-31 treatment (P = .012). These findings suggested that mitochondrial dysfunction may be reversed by SS-31 treatment. The gene expression of matrix metalloproteinase-1 (matrix remodeling, P = .029) and fatty acid–binding protein 4 (fatty infiltration, P = .046) was significantly upregulated in the degenerative tenocytes and reduced by SS-31 treatment (P = .048; P = .007). Gene expression for hypoxia-inducible factor1 α and the proapoptotic regulator Bcl-2–associated X protein was increased in the degenerative tenocytes. There was a significant decrease in cell viability in degenerative tenocytes as compared with the healthy tenocytes, with small improvement after treatment with SS-31. Conclusion: There are changes in mitochondrial structure and function in tenocytes derived from degenerative tendons, and SS-31, as a mitochondrial protectant, could improve mitochondrial function and promote the healing of tendinopathy. Clinical Relevance: Mitochondrial dysfunction appears to play a role in the development of tendinopathy, and SS-31, as a mitochondrial protective agent, may be a therapeutic agent in the treatment of tendinopathy.
Bioaccumulation of Mercury and Radiocesium in Waterfowl Introduced to a Site with Legacy Contamination

Despite the propensity of waterfowl species to readily accumulate anthropogenic contaminants within polluted environments, few studies have examined bioaccumulation rates over time when entering such a contaminated site. We examined mercury (Hg) and radiocesium (137Cs) bioaccumulation over time in two waterfowl species released into a wetland system containing legacy contamination on the US Department of Energy's Savannah River Site in South Carolina. Released birds were collected at select time intervals over an exposure period of 94 days. We quantified total Hg concentrations in blood, muscle, and liver tissues, and 137Cs activity in whole‐body and muscle tissues. The relationship between the contaminant burdens of different body tissue types was examined over time. Likely a result of microhabitat selection, mallards in our study readily accumulated both Hg and 137Cs at consistent rates over time within our study system, while ring‐neck ducks did not. The findings demonstrated that whole blood can be used as a robust, nondestructive sampling alternative to estimate Hg burdens within muscle and liver, and whole‐body 137Cs activity is a good predictor of muscle burdens. Understanding such bioaccumulation information in waterfowl is useful for the assessment of the potential health risk in wildlife, as well as being important for human risk assessment toward the consumption of popular game species. Environ Toxicol Chem 2022;41:2479–2487. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Antheridiogen controls spatial dynamics of sex expression in naturally occurring gametophytes of the tree fern Cyathea multiflora

Abstract Premise Antheridiogen systems are a set of pheromonal mechanisms that control sex expression in fern gametophytes. However, antheridiogen has rarely been studied outside of the laboratory, and little is known about its function in natural settings. Combining predictions based on field and laboratory study, we tested whether the sexual structure of gametophytic colonies of a tree fern were attributable to antheridiogen. Methods Gametophytic colonies of the antheridiogen‐producing tree fern Cyathea multiflora were collected at La Selva Biological Station in Costa Rica in January 2019. The sex of each gametophyte was determined, mapped, and spatial statistic approaches were used to examine the distribution of sex in each colony. Results In all gametophytic colonies, males were most common, representing 62–68% of individuals. No hermaphroditic gametophytes were identified in any colony. A quadrat‐based method showed female gametophytes were not clustered in each colony, while male gametophytes were clustered. In two of the colonies, the K(r) test statistic for males was greater than expected compared to random simulations of sex expression, indicating male sex expression was spatially associated with females. Conclusions This study provides the first documentation of spatial sex expression in natural settings of gametophytes of an antheridiogen‐producing tree fern species. The profound impact of antheridiogen on gametophytic sex expression in field settings suggests this system is intimately tied to mating system, fitness, and genetic diversity in Cyathea multiflora.