Miracle-dz/UniFAR-FTUs huggingface dataset:
LPIN1 downregulation enhances anticancer activity of the novel HDAC/PI3K dual inhibitor FK‐A11

Phosphatidylinositol‐3 kinase (PI3K) inhibitor and histone deacetylase (HDAC) inhibitor have been developed as potential anticancer drugs. However, the cytotoxicity of PI3K inhibitor or HDAC inhibitor alone is relatively weak. We recently developed a novel HDAC/PI3K dual inhibitor FK‐A11 and confirmed its enhanced cytotoxicity when compared to that of PI3K inhibitor or HDAC inhibitor alone on several cancer cell lines. However, the in vivo antitumor activity of FK‐A11 was insufficient. We conducted high‐throughput RNA interfering screening and identified gene LPIN1 which enhances the cytotoxicity of FK‐A11. Downregulation of LPIN1 enhanced simultaneous inhibition of HDAC and PI3K by FK‐A11 and enhanced the cytotoxicity of FK‐A11. Propranolol, a beta‐adrenoreceptor which is also a LPIN1 inhibitor, enhanced the in vitro and in vivo cytotoxicity and antitumor effect of FK‐A11. These findings should help in the development of FK‐A11 as a novel HDAC/PI3K dual inhibitor.
In vitro and computational studies of the antioxidant and anti-diabetic properties of Bridelia ferruginea

Abstract The leaves, stem and root bark of Bridelia ferruginea were sequentially extracted with solvents of increasing polarity to yield the hexane, ethyl acetate, ethanol and aqueous extracts. In vitro analysis revealed the ability of the extracts to scavenge 1,1-diphenyl-2-picryl-hydrazyl (DPPH), nitric oxide (NO) and hydroxyl radical. They also inhibited the activities of α-glucosidase, α-amylase and lipase enzymes. Gas chromatography-mass spectroscopic (GC-MS) analysis of the extracts revealed the presence of sterols, aromatics, aliphatic acids and esters. The identified compounds were molecularly docked with α-glucosidase, α-amylase and lipase enzymes. All compounds showed good binding affinities with the enzymes studied. The strongest binding affinities were observed for β-amyrin, 4-phenylbenzophenone and lupenone for α-glucosidase, α-amylase and lipase enzymes, respectively. The data suggest antioxidant and antidiabetic potential of the different parts of B. ferruginea, with the leaves having the highest potential. These properties can be explored for development of novel anti-diabetic drugs. Communicated by Ramaswamy H. Sarma
The Role of Mitochondrial Calcium Homeostasis in Alzheimer’s and Related Diseases

Calcium signaling is essential for neuronal function, and its dysregulation has been implicated across neurodegenerative diseases, including Alzheimer’s disease (AD). A close reciprocal relationship exists between calcium signaling and mitochondrial function. Growing evidence in a variety of AD models indicates that calcium dyshomeostasis drastically alters mitochondrial activity which, in turn, drives neurodegeneration. This review discusses the potential pathogenic mechanisms by which calcium impairs mitochondrial function in AD, focusing on the impact of calcium in endoplasmic reticulum (ER)–mitochondrial communication, mitochondrial transport, oxidative stress, and protein homeostasis. This review also summarizes recent data that highlight the need for exploring the mechanisms underlying calcium-mediated mitochondrial dysfunction while suggesting potential targets for modulating mitochondrial calcium levels to treat neurodegenerative diseases such as AD.
Weekly iron–folic acid supplements containing 2.8 mg folic acid are associated with a lower risk of neural tube defects than the current practice of 0.4 mg: a randomised controlled trial in Malaysia

Introduction Weekly iron–folic acid (IFA) supplements are recommended for all menstruating women in countries where anaemia prevalence is >20%. Anaemia caused by folate deficiency is low worldwide, and the need to include folic acid is in question. Including folic acid might reduce the risk of a neural tube defect (NTD) should a woman become pregnant. Most weekly supplements contain 0.4 mg folic acid; however, WHO recommends 2.8 mg because it is seven times the daily dose effective in reducing NTDs. There is a reluctance to switch to supplements containing 2.8 mg of folic acid because of a lack of evidence that this dose would prevent NTDs. Our aim was to investigate the effect of two doses of folic acid, compared with placebo, on red blood cell (RBC) folate, a biomarker of NTD risk. Methods We conducted a three-arm double-blind efficacy trial in Malaysia. Non-pregnant women (n=331) were randomised to receive 60 mg iron and either 0, 0.4, or 2.8 mg folic acid once weekly for 16 weeks. Results At 16 weeks, women receiving 0.4 mg and 2.8 mg folic acid per week had a higher mean RBC folate than those receiving 0 mg (mean difference (95% CI) 84 (54 to 113) and 355 (316 to 394) nmol/L, respectively). Women receiving 2.8 mg folic acid had a 271 (234 to 309) nmol/L greater mean RBC folate than those receiving 0.4 mg. Moreover, women in the 2.8 mg group were seven times (RR 7.3, 95% CI 3.9 to 13.7; p<0.0001) more likely to achieve an RBC folate >748 nmol/L, a concentration associated with a low risk of NTD, compared with the 0.4 mg group. Conclusion Weekly IFA supplements containing 2.8 mg folic acid increases RBC folate more than those containing 0.4 mg. Increased availability and access to the 2.8 mg formulation is needed. Trail registration number This trial is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12619000818134).
Anthocyanins attenuate endothelial dysfunction through regulation of uncoupling of nitric oxide synthase in aged rats

Endothelial dysfunction is one of the main age‐related arterial phenotypes responsible for cardiovascular disease (CVD) in older adults. This endothelial dysfunction results from decreased bioavailability of nitric oxide (NO) arising downstream of endothelial oxidative stress. In this study, we investigated the protective effect of anthocyanins and the underlying mechanism in rat thoracic aorta and human vascular endothelial cells in aging models. In vitro, cyanidin‐3‐rutinoside (C‐3‐R) and cyanidin‐3‐glucoside (C‐3‐G) inhibited the d‐galactose (d‐gal)‐induced senescence in human endothelial cells, as indicated by reduced senescence‐associated‐β‐galactosidase activity, p21, and p16INK4a. Anthocyanins blocked d‐gal‐induced reactive oxygen species (ROS) formation and NADPH oxidase activity. Anthocyanins reversed d‐gal‐mediated inhibition of endothelial nitric oxide synthase (eNOS) serine phosphorylation and SIRT1 expression, recovering NO level in endothelial cells. Also, SIRT1‐mediated eNOS deacetylation was shown to be involved in anthocyanin‐enhanced eNOS activity. In vivo, anthocyanin‐rich mulberry extract was administered to aging rats for 8 weeks. In vivo, mulberry extract alleviated endothelial senescence and oxidative stress in the aorta of aging rats. Consistently, mulberry extract also raised serum NO levels, increased phosphorylation of eNOS, increased SIRT1 expression, and reduced nitrotyrosine in aortas. The eNOS acetylation was higher in the aging group and was restored by mulberry extract treatment. Similarly, SIRT1 level associated with eNOS decreased in the aging group and was restored in aging plus mulberry group. These findings indicate that anthocyanins protect against endothelial senescence through enhanced NO bioavailability by regulating ROS formation and reducing eNOS uncoupling.
Barriers and facilitators to the HPV vaccine among mothers of adolescent girls: a qualitative study conducted in Trinidad and Tobago

ABSTRACT Cervical cancer is a major public health problem in Latin America and the Caribbean and the human papillomavirus (HPV) vaccine may prevent thousands of cases of cervical cancer. The current study explored barriers and facilitators that affected the acceptance of the HPV vaccine by mothers of adolescents. This paper explores the qualitative findings from a larger mixed-methods study. Six focus groups were conducted (N = 33) throughout Trinidad and Tobago with mothers of adolescent girls. Three major themes emerged: a) cervical cancer and vaccine knowledge, b) barriers to uptake, and c) rephrasing the vaccine strategy. Data indicated that no widespread strategies to educate the population about the vaccine had occurred. Barriers to uptake of the vaccine were related to a lack of information on the efficacy and safety of HPV vaccines. Parents were unaware that the HPV caused cervical cancer. It is recommended that physicians and other health professionals be used to deliver targeted messages to parents and adolescents to improve uptake of the vaccine.
SS-Detect: Development and Validation of a New Strategy for Source-Based Morphometry in Multi-Scanner Studies

Background and Purpose Source-based morphometry (SBM) is a data-driven multivariate approach for interrogating covariation in structural brain patterns (SBPs) across subjects and quantifying the subject-specific loading parameters of these patterns. This approach has been used in multi-centre studies pooling magnetic resonance imaging (MRI) data across different scanners to advance the reproducibility of neuroscience research. In the present study, we developed an analysis strategy for Scanner-Specific Detection (SS-Detect) of SBPs in multiscanner studies, and evaluated its performance relative to a conventional strategy. Methods We conducted two simulation experiments. In the first experiment, the SimTB toolbox was used to generate simulation datasets mimicking twenty different scanners with common and scanner-specific SBPs. In the second experiment, we generated one simulated SBP from empirical datasets from two different scanners. Results The outputs of the conventional strategy were limited to whole-sample-level results across all scanners; the outputs of SS-Detect included whole-sample-level and scanner-specific results. In the first simulation experiment, SS-Detect successfully estimated all simulated SBPs, including the common and scanner-specific SBPs whereas the conventional strategy detected only some of the whole-sample SBPs. The second simulation experiment showed that both strategies could detect the simulated SBP. Quantitative evaluations of both experiments demonstrated greater accuracy of the SS-Detect in estimating spatial SBPs and subject-specific loading parameters. Conclusions SS-Detect outperformed the conventional strategy in terms of accurately estimating spatial SBPs and loading parameters both at whole-sample and scanner-specific levels and can be considered advantageous when SBM is applied to a multi-scanner study.
The Change in Core Temperature and Sweating Response during Exercise Are Unaffected by Time of Day within the Wake Period

ABSTRACT Introduction Exercise thermoregulation studies typically control for time of day. The present study assessed whether circadian rhythm independently alters time-dependent changes in core temperature and sweating during exercise at a fixed rate of metabolic heat production (Hprod) during the wake period. Methods Ten men (26 ± 2 yr, 76.6 ± 6.3 kg, 1.95 ± 0.10 m2) cycled for 60 min in three combinations of ambient temperature and Hprod (23°C–7.5 W·kg−1, 33°C–5.5 W·kg−1, and 33°C–7.5 W·kg−1) at two times of day (a.m.: 0800 h, p.m.: 1600 h). Rectal temperature (Tre), local sweat rate, and whole-body sweat losses were measured. Results Absolute Tre was lower at baseline in a.m. versus p.m. for all three conditions (a.m.: 36.8°C ± 0.2°C, p.m.: 37.0°C ± 0.2°C, P < 0.01). The ΔTre was not altered by time of day (P > 0.22) and not different at 60 min between a.m. and p.m. for 23°C–7.5 W·kg−1 (a.m.: 0.83°C ± 0.14°C, p.m.: 0.75°C ± 0.20°C; P = 0.20), 33°C–5.5 W·kg−1 (a.m.: 0.51°C ± 0.14°C, p.m.: 0.47°C ± 0.14°C; P = 0.22), and 33°C–7.5 W·kg−1 (a.m.: 0.77°C ± 0.20°C, p.m.: 0.73°C ± 0.21°C; P = 0.80). The change in local sweat rate was unaffected by time of day (P > 0.16) and not different at 60 min in 23°C–7.5 W·kg−1 (a.m.: 0.67 ± 0.20 mg·cm−2·min−1, p.m.: 0.62 ± 0.21 mg·cm−2·min−1; P = 0.55), 33°C–5.5 W·kg−1 (a.m.: 0.59 ± 0.13 mg·cm−2·min−1, p.m.: 0.57 ± 0.12 mg·cm−2·min−1; P = 0.65), and 33°C–7.5 W·kg−1 (a.m.: 0.91 ± 0.19 mg·cm−2·min−1, p.m.: 0.84 ± 0.15 mg·cm−2·min−1; P = 0.33). Whole-body sweat loss was not different between a.m. and p.m. for 23°C–7.5 W·kg−1 (a.m.: 579 ± 72 g, p.m.: 579 ± 96 g; P = 0.99), 33°C–5.5 W·kg−1 (a.m.: 558 ± 48 g, p.m.: 555 ± 83 g; P = 0.89), and 33°C–7.5 W·kg−1 (a.m.: 796 ± 72 g, p.m.: 783 ± 75 g; P = 0.31). Conclusions The change in core temperature and sweating throughout a 60-min exercise bout in 23°C and 33°C were unaffected by circadian rhythm during the wake period when exercise intensity was prescribed to elicit comparable rates of Hprod, suggesting that scheduling thermoregulatory exercise trials for the same time of day is unnecessary.
High-throughput glycomic analyses reveal unique oligosaccharide profiles of canine and feline milk samples

Oligosaccharides are important components of milk, serving as substrates for the intestinal microbiota, acting as antimicrobials that prevent pathogen colonization, and supporting the developing gastrointestinal immune system of neonates. Nutrient composition of canine and feline milk samples has been described previously, but little is known about the oligosaccharide content. Therefore, the objective of this study was to characterize canine and feline milk samples using a high-throughput glycomics approach. 23 dogs (9 Labrador retriever and 14 Labrador retriever x golden retriever crossbreed) and 6 domestic shorthair cats were recruited to the study. Milk samples were collected by manual expression at time points after parturition. Samples were collected across 2 phases per species, differentiated by maternal diet. Following extraction, oligosaccharide content was determined by liquid chromatography-mass spectrometry (LC-MS). In canine milk samples, 3 structures accounted for over 90% of all oligosaccharides detected across two diet groups. These were 3’-sialyllactose, 6’-sialyllactose, and 2’-fucosyllactose. In feline samples, a more diverse range of oligosaccharides was detected, with up to 16 structures present at relative abundance >1% of the total. Difucosyllactose-N-hexaose b, 3’-sialyllactose and lacto-N-neohexaose were all detected at abundances >10% in feline milk samples. Statistically significant differences (p<0.05) in oligosaccharide abundances were observed between collection time points and between diet groups within species. These data explore the oligosaccharide content of canine and feline maternal milk, representing an opportunity to generate a fundamental understanding of the nutritional needs of new-born puppies and kittens.
Graph theory analysis of the dopamine D2 receptor network in Parkinson’s disease patients with cognitive decline

Cognitive decline in Parkinson's disease (PD) is a common sequela of the disorder that has a large impact on patient well‐being. Its physiological etiology, however, remains elusive. Our study used graph theory analysis to investigate the large‐scale topological patterns of the extrastriatal dopamine D2 receptor network. We used positron emission tomography with [11C]FLB‐457 to measure the binding potential of cortical dopamine D2 receptors in two networks: the meso‐cortical dopamine network and the meso‐limbic dopamine network. We also investigated the application of partial volume effect correction (PVEC) in conjunction with graph theory analysis. Three groups were investigated in this study divided according to their cognitive status as measured by the Montreal Cognitive Assessment score, with a score ≤25 considered cognitively impaired: (a) healthy controls (n = 13, 11 female), (b) cognitively unimpaired PD patients (PD‐CU, n = 13, 5 female), and (c) PD patients with mild cognitive impairment (PD‐MCI, n = 17, 4 female). In the meso‐cortical network, we observed increased small‐worldness, normalized clustering, and local efficiency in the PD‐CU group compared to the PD‐MCI group, as well as a hub shift in the PD‐MCI group. Compensatory reorganization of the meso‐cortical dopamine D2 receptor network may be responsible for some of the cognitive preservation observed in PD‐CU. These results were found without PVEC applied and PVEC proved detrimental to the graph theory analysis. Overall, our findings demonstrate how graph theory analysis can be used to detect subtle changes in the brain that would otherwise be missed by regional comparisons of receptor density.
Die Lebenszeitprävalenz von Schuldgefühlen in der deutschen Erwachsenenbevölkerung – Ergebnisse einer bundesweiten telefonischen Bevölkerungsbefragung

Zusammenfassung Ziel Bestimmung der Lebenszeitprävalenz von Schuldgefühlen in der deutschen Erwachsenenbevölkerung basierend auf den Daten einer bundesweiten telefonischen Bevölkerungsbefragung (n = 1003; 18+ Jahre; Mai–Juni 2019). Methodik Berechnung gewichteter Prävalenzraten mit Konfidenzintervallen (95 %-KI) und Untersuchung des Zusammenhangs mit Kofaktoren anhand multivariabler logistischer Regressionsanalysen. Ergebnisse Die ermittelte Lebenszeitprävalenz empfundener Schuldgefühle beträgt 68,5 % (95 %-KI = 65,6–71,3). Jüngeres Alter, höhere Bildung und aktuelle depressive Symptomatik waren mit höheren Prävalenzraten assoziiert. Kein Zusammenhang zeigte sich für Geschlecht und majore Depression. Schlussfolgerung Ein substanzieller Anteil der deutschen Erwachsenenbevölkerung hat schon einmal Schuldgefühle empfunden. Weiterer Forschungsbedarf besteht v. a. zu der Frage, inwieweit Schuldgefühle zu einem erhöhten Depressionsrisiko beitragen und nicht nur als Kriterium für die Störung anzusehen sind.
Stabilization of n‐type semiconductors to photoanodic dissolution: II–VI and III–V compound semiconductors and recent results for n‐type silicon

Semiconductor‐based photoelectrochemical cells for the conversion of light to electricity are described. Such cells consist of a semiconductor photoelectrode, a counterelectrode, and an electrolyte solution containing electroactive species. Results for cells employing certain n‐type II–VI (CdS, CdSe, CdTe) and III–V (GaP, GaAs, InP) photoelectrodes in solutions of electroactive X2−/Xn2−(X=S, Se, Te) species are reviewed. The key fact is that for a number of photoelectrode /X2−/Xn2− combinations we find that photoanodic decomposition of the semiconductor is virtually totally suppressed, allowing the sustained conversion of light to electricity. Preliminary results for n‐type Si photoelectrodes derivatized with electroactive ferrocene reagents are also outlined, and the associated photoelectrochemical activity of the surface species is compared to results for naked Si exposed to solutions of ferrocene.
CORR Insights®: Do Cohabitants Reliably Complete Questionnaires for Patients in a Terminal Cancer Stage When Assessing Quality of Life, Pain, Depression, and Anxiety?

Patients with terminal stage cancer often are debilitated, and their functional and emotional challenges can increase rapidly. Our healthcare system often struggles with measuring this patient population’s capacity for adapting to their declining quality of life (QoL). Patient-reported outcomes (PROs) for patients with terminal illnesses can help physicians determine clinically relevant treatment options. In this patient cohort, both caregivers and physicians need to support patients’ needs and desires in order to provide proper care under difficult circumstances. Late-stage cancer affects all aspects of a patient’s life as well as the life of the patient’s caregiver. For example, the cost of end-of-life care is extremely expensive, and treatment modalities such as chemotherapy and surgery top the list of costs. Based on a study by Mariotto et al. [3], the 2015 national cost for medical services for cancer survivors of all ages was estimated to be USD 183 billion. These costs were highest in the continuing phase (USD 68 billion), followed by the initial (USD 48 billion), and end-of-life cancer death (USD 40 billion) phases [3]. As we gain a better understanding of how to measure QoL issues, we need to incorporate the information gained into more personalized care plans for each patient. In the current study, Groot and colleagues [1] provide the first report I know of that demonstrates that we can accurately assess patients with bone metastases using only information from cohabitants rather than other surrogates. Cohabitants likely know
Is There an Association Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Streptococcus pneumoniae?

e76 • cid 2021:72 (1 March) • EDITORIAL COMMENTARY Received 27 November 2020; editorial decision 30 November 2020; published online 3 December 2020. Correspondence: Leigh Meredith Howard, Vanderbilt University Medical Center, CCC-5317 MCN, 1161 21st Ave South Nashville, TN (leigh.howard@vumc.org). Clinical Infectious Diseases 2021;72(5):e76–8 © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. DOI: 10.1093/cid/ciaa1812 Is There an Association Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Streptococcus pneumoniae?
Double Constructions of Frobenius Hom-Algebras and Connes Cocycles

In this paper, we give an explicit and systematic study on the double constructions of Frobenius Hom-algebras and introduce the close relations between O-operators and Homdendriform algebras. Furthermore, we study the double constructions of Connes cocycles in terms of Hom-dendriform algebras. Finally, we give a clear analogy between antisymmetric infinitesimal Hom-bialgebras and Hom-dendriform D-bialgebras.
Recent Advancements of Macrolide Hybrids Against Staphylococcus Aureus.

Staphylococcus aureus (S. aureus), recognized as one of the deadliest pathogens responsible for nosocomial and community acquired infections, is highly contagious and associated with significant morbidity and mortality. The increasing emergency and rapid spread of various forms of drug-resistant S. aureus have already posed heavy burden on world health system, but new-fangled antibiotics are right now being created at a much slower pace than our developing requirement. Macrolides could inhibit protein synthesis by targeting the bacterial ribosome and are a class of basic and widely used antibacterial agents in clinical practice to control infections caused by various bacteria including S. aureus. However, emer-gence of bacterial resistance to macrolide antibiotics, particularly in Gram-positive bacteria such as macrolide-resistant S. aureus, has already become one of the significant obstacles for effective chemotherapy. Therefore, there is a critical need for the development of novel macrolide candidates. This review provides an overview of macrolide hybrids with potential activity against S. aureus including drug-resistant forms developed in recent decade, with special emphasis on the structure-activity relationships and mechanism of actions.