Miracle-dz/UniFAR-FTUs huggingface dataset:
MELK: a potential novel therapeutic target for TNBC and other aggressive malignancies

ABSTRACT Introduction: There is an unmet need in triple-negative breast cancer (TNBC) patients for targeted therapies. Maternal embryonic leucine zipper kinase (MELK) is a promising target for inhibition based on the abundance of correlative and functional data supporting its role in various cancer types. Areas covered: This review endeavors to outline the role of MELK in cancer. Studies covering a range of biological functions including proliferation, apoptosis, cancer stem cell phenotypes, epithelial-to-mesenchymal transition, metastasis, and therapy resistance are discussed here in order to understand the potential of MELK as a clinically significant target for TNBC patients. Expert opinion: Targeting MELK may offer a novel therapeutic opportunity in TNBC and other cancers. Despite the abundance of correlative data, there is still much we do not know. There are a lack of potent, specific inhibitors against MELK, as well as an insufficient understanding of MELK’s downstream substrates. Addressing these issues is the first step toward identifying a patient population that could benefit from MELK inhibition in combination with other therapies.
Evidence that cell surface localization of serine protease activity facilitates cleavage of the protease activated receptor CDCP1

Abstract The cellular receptor CUB domain containing protein 1 (CDCP1) is commonly elevated and functionally important in a range of cancers. CDCP1 is cleaved by serine proteases at adjacent sites, arginine 368 (R368) and lysine 369 (K369), which induces cell migration in vitro and metastasis in vivo. We demonstrate that membrane localization of serine protease activity increases efficacy of cleavage of CDCP1, and that both secreted and membrane anchored serine proteases can have distinct preferences for cleaving at CDCP1-R368 and CDCP1-K369. Approaches that disrupt membrane localization of CDCP1 cleaving serine proteases may interfere with the cancer promoting effects of CDCP1 proteolysis.
Transcriptional-Readthrough RNAs Reflect the Phenomenon of “A Gene Contains Gene(s)” or “Gene(s) within a Gene” in the Human Genome, and Thus Are Not Chimeric RNAs

Tens of thousands of chimeric RNAs, i.e., RNAs with sequences of two genes, have been identified in human cells. Most of them are formed by two neighboring genes on the same chromosome and are considered to be derived via transcriptional readthrough, but a true readthrough event still awaits more evidence and trans-splicing that joins two transcripts together remains as a possible mechanism. We regard those genomic loci that are transcriptionally read through as unannotated genes, because their transcriptional and posttranscriptional regulations are the same as those of already-annotated genes, including fusion genes formed due to genetic alterations. Therefore, readthrough RNAs and fusion-gene-derived RNAs are not chimeras. Only those two-gene RNAs formed at the RNA level, likely via trans-splicing, without corresponding genes as genomic parents, should be regarded as authentic chimeric RNAs. However, since in human cells, procedural and mechanistic details of trans-splicing have never been disclosed, we doubt the existence of trans-splicing. Therefore, there are probably no authentic chimeras in humans, after readthrough and fusion-gene derived RNAs are all put back into the group of ordinary RNAs. Therefore, it should be further determined whether in human cells all two-neighboring-gene RNAs are derived from transcriptional readthrough and whether trans-splicing truly exists.
Activating attachment representations impact how we retrieve autobiographical memories

ABSTRACT Although much research indicates that proximity to attachment figures confers many psychological benefits, there is little evidence pertaining to how attachment activation may impact autobiographical memory retrieval. Following a negative mood induction to elicit overgeneral autobiographical retrieval, participants (N = 70) were administered an induction in which they imagined a person who is a strong attachment figure or an acquaintance. Participants then completed an autobiographical memory task to retrieve memories in response to neutral and negative cue words. Attachment priming resulted in less distress, increased retrieval of specific memories, and reduced retrieval of categoric memories. These findings indicate that activation of mental representations of attachment figures can impact on the specificity of autobiographical memory retrieval, and extends prevailing models of autobiographical memory by integrating them with attachment theory.
Affective temperaments during pregnancy and postpartum period: a click to hyperthymic temperament

Abstract Background: Pregnancy and postpartum periods are the main reproductive periods during which women experience mood disorders. Affective temperaments are known antecedents of mood disorders and their importance is increasing in time for early diagnosis and determining risky groups. But data about affective temperaments during perinatal period is limited. Methods: Women during pregnancy and perinatal period and healthy controls who are not in perinatal period are included in the study. 83 pregnant women in 1st trimester, 94 pregnant women in 2nd trimester and 115 pregnant women in 3rd trimester; 32 women in 1st month postpartum and 89 women in 2nd month postpartum; and 88 healthy non-pregnant women with similar ages were evaluated regarding their temperament evaluation of Memphis, Pisa, Paris and San Diego auto-questionnaire (TEMPS-A) scores. Results: Women in perinatal period had higher scores of hyperthymic temperaments than the control group. Women in the 2nd month of postpartum period had also higher anxious temperament scores. And women in the second trimester had the highest hyperthymic temperament scores. Conclusion: Pregnancy and postpartum periods correlate with hyperthymic temperament characteristics in women without active psychiatric diagnosis. Future studies will help to understand if this is a mental quietness or increased risk for bipolarity.
The Impact of Laparoscopy with Carbon Dioxide versus Helium on Immunologic Function and Tumor Growth in a Rat Model

Background: The pathogenesis of port site recurrences after laparoscopic surgery for malignant disease is still unknown. Whether different gases used to establish pneumoperitoneum have an influence on immunologic function and therefore on promotion of tumor growth has not yet been investigated. Methods: Tumor growth of colon adenocarcinoma DHD/K12/TRb was evaluated in a rat model after insufflation either with CO2 (n = 25) or helium (n = 25) and in a control group (n = 25). Tumor growth was measured subcutaneously and intraperitoneally 5 weeks after insufflation. Beside tumor growth, immunologic changes (peripheral leukocyte subpopulations, plasma levels of TNFα and IL-10) were evaluated during the perioperative course in all animals. Results: Subcutaneous tumor growth was promoted by the CO2 (99 ± 55 mg; p < 0.01) compared to the helium (40 ± 41 mg) and control groups (36 ± 33 mg). Total intraperitoneal tumor weight was 718 ± 690 mg in the CO2 group compared to the helium (549 ± 233 mg) and control groups (521 ± 221 mg). While peripheral leukocyte subpopulations only differed between the laparoscopic groups and the control group during the perioperative course, TNFα plasma levels were significantly decreased and IL-10 plasma levels significantly increased in the CO2 group compared to the helium and control groups in the postoperative course. Conclusion: The insufflation of CO2 promotes tumor growth compared to the helium and control groups in a rat model. In addition, increased tumor growth was associated with a significant increase in IL-10 and a decrease in TNFα plasma levels.
Revocable ID-Based Signature with Short Size over Lattices

In the past, many ID-based signature (IBS) schemes based on the integer factorization or discrete logarithm problems were proposed. With the progress on the development of quantum technology, IBS schemes mentioned above would become vulnerable. Recently, several IBS schemes over lattices were proposed to be secure against attacks in the quantum era. As conventional public-key settings, ID-based public-key settings have to offer a revocation mechanism to revoke misbehaving or malicious users. However, in the past, little work focuses on the revocation problem in the IBS schemes over lattices. In this article, we propose a new revocable IBS (RIBS) scheme with short size over lattices. Based on the short integer solution (SIS) assumption, we prove that the proposed RIBS scheme provides existential unforgeability against adaptive chosen-message attacks. As compared to the existing IBS schemes over lattices, our RIBS scheme has better performance in terms of signature size, signing key size, and the revocation mechanism with public channels.
What can we learn from pulmonary function testing in heart failure?

Pulmonary diseases frequently coexist in heart failure (HF), thus posing diagnostic and therapeutic challenges to cardiologists evaluating patients with overlapping symptoms and implementing recommended HF treatments. There is a growing body of evidence suggesting that pulmonary function testing might provide useful information for the best management of these patients. The availability of portable devices, allowing the measurement of spirometry and lung diffusion capacity for carbon monoxide outside of hospital‐based pulmonary lung function laboratories, provides an opportunity for a more widespread use of these measures in the cardiology community, but their interpretation can be challenging. In this work, after a brief review of the methodologies, we discuss the interpretation of pulmonary function testing in patients with HF alone or associated with pulmonary diseases, and its contribution in differentiating cardiac and pulmonary symptoms and preventing acute cardiac decompensation. In addition, we examined recent evidence suggesting how the use of pulmonary function testing may provide independent prognostic information in HF patients with and without pulmonary disorders, and help therapeutic decisions to fill the treatment gap that still exists in HF patients with concomitant pulmonary diseases.
Serum fibroblast growth factor-23 and incident hypertension: the Atherosclerosis Risk in Communities (ARIC) Study

Objective: : Elevated serum fibroblast growth factor-23 (FGF23), an endogenous hormone, is associated with disturbed mineral homeostasis, cardiovascular disease, and chronic kidney disease. It is unclear whether FGF23 impacts the development of incident hypertension. We examined the association between elevated FGF23 and incident hypertension in a community-based cohort. Method: We investigated the association of serum FGF23, measured at baseline (1990–1992), with incident hypertension at two follow-up visits (1993–1995 and 1996–1998) in 7948 middle-aged men and women without hypertension at baseline participating in the Atherosclerosis Risk in Communities Study. Incident hypertension was determined by measured blood pressure (DBP ≥ 90 mmHg or SBP ≥ 140 mmHg) and/or self-reported hypertension medication use at follow-up exams. Complementary log–log models that accounted for interval censoring were used to model the association between FGF23 and incident hypertension. Results: During a median follow-up of 5.9 years, 27% (2152/7948) participants developed hypertension. A nonlinear association between serum FGF23 and incident hypertension was observed; only persons in the highest decile of serum FGF23 had an increased risk of incident hypertension. After adjustment for demographics, behaviors, and adiposity, the hazard ratio for incident hypertension was 1.24 (95% confidence interval: 1.11, 1.39) for the highest decile of FGF23 compared with the lowest quintile. The association was further attenuated in the final model after adjusting for renal function (hazard ratio: 1.21, 95% confidence interval: 1.08, 1.35). Conclusion: : High levels (≥60.6 pg/ml) of FGF23 are associated with a modestly increased risk of incident hypertension in the general population, independent of kidney function.
Longitudinal analysis of HIV risk behaviour patterns and their predictors among public primary care patients with tuberculosis in South Africa

Abstract The goal of this study was to identify various HIV risk behaviours among tuberculosis (TB) patients in a longitudinal study design in South Africa. In 42 public primary healthcare facilities in three districts in three provinces, adult new TB and TB retreatment patients with hazardous or harmful alcohol use were interviewed within 1 month of initiation of anti-TB treatment and were followed up at 6 months. The total sample with a complete 6-month follow-up assessment was 853. At the follow-up assessment, several HIV risk behaviours significantly reduced from baseline to follow-up. In multivariate Generalized Estimating Equations logistic regression analyses, high poverty (odds ratio (OR): 2.68, 95% confidence interval (CI): 1.56–4.62), Posttraumatic Stress Disorder (PTSD) symptoms (OR = 1.55, 95% CI = 1.03–2.36), and sexual partner on antiretroviral therapy (ART) (OR = 1.84, 95% CI = 1.09–3.10) were associated with a higher odds, and excellent/very good perceived health status (OR: 0.61, 95% CI: 0.37–0.98), severe psychological stress (OR = 0.51, 95% CI = 0.34–0.77), and HIV non-disclosure to most recent sexual partner (OR = 0.40, 95% CI = 0.25–0.65) were associated with a lower odds of inconsistent condom use. Being HIV positive (OR = 4.18, 95% CI = 2.68–6.53) and excellent/very subjective health status (OR = 2.98, 95% CI = 1.73–5.13) were associated with a higher odds, and having PTSD symptoms (OR = 0.60, 95% CI = 0.36–0.99), being on ART (OR = 0.48, 95% CI = 0.25–0.95), having a sexual partner on ART (OR = 0.41, 95% CI = 0.18–0.96), and HIV status non-disclosure (OR = 0.25, 95% CI = 0.15–0.41) were associated with a lower odds of having sex with an HIV-positive or HIV status unknown person. High poverty index (OR = 1.97, 95% CI = 1.19–3.25) and having a sexual partner on ART (OR = 4.37, 95% CI = 1.82–10.48) were associated with a higher odds, and having a partner with HIV-negative status (OR = 0.29, 95% CI = 0.16–0.51) and inconsistent condom use (OR = 0.39, 95% CI = 0.24–0.64) were associated with a lower odds of HIV status non-disclosure at last sex. The study found that among TB patients with problem drinking over a 6-month TB treatment period, the frequency of some HIV risk behaviours (inconsistent condom use) declined (OR = 0.64, 95% CI = 0.41–0.98), but also persisted at a high-level calling for a strengthening and integration of HIV prevention into TB management.
Pulmonary Function and Regional Distribution of Emphysema as Determined by High-Resolution Computed Tomography

In patients with pulmonary emphysema, emphysematous changes are not uniform and vary from minimum alveolar destruction to advanced bullous formation, depending on the lobe or site in the lungs. However, we have little knowledge on whether or how this nonuniformity or localization affects pulmonary function in PE patients. Therefore, we measured the computed tomography (CT) density of divided sites in lungs with high-resolution CT images from 25 PE patients (FEV1.0%, mean ± SD 36 ± 9%, %DLCO 48 ± 16%, all men, 68 ± 4 years) and compared them to various parameters of pulmonary function. The mean CT density of whole lungs correlated with 12 pulmonary function parameters including FEV1.0 and diffusion capacity. When both lung fields were divided into peripheral, intermediate and central portions, the CT density of the central portion correlated with all pulmonary function parameters with which CT density of whole lungs correlated. In contrast, the CT density of the peripheral portion significantly correlated with only 7 parameters with smaller correlation coefficient values than those of the central portion. When divided into upper, middle and lower portions, the CT densities of upper, middle and lower portions correlated with 6, 8 and 10 of the 12 pulmonary function parameters which correlated with the density of whole lungs, respectively. The delta value of CT densities between the upper and lower portions or between the lateral and medial portions correlated with obstructive impairment (FEV1.0 and FEV1.0%). These findings suggest that (1) central rather than peripheral emphysematous changes affect pulmonary function, and (2) uniformity of emphysematous change correlates with the severity of airway obstruction in PE patients.
Haplotype Association of the MAP2K5 Gene with Antipsychotics-Induced Symptoms of Restless Legs Syndrome among Patients with Schizophrenia

Objective Restless legs syndrome (RLS) is considered a genetic disease and, following a genome-wide association study conducted in 2007, the mitogen-activated protein kinase 5 (MAP2K5) gene has been regarded as the promising candidate gene for RLS. The present study investigated whether polymorphisms of MAP2K5 are associated with antipsychotics-induced RLS in schizophrenia. Methods We assessed antipsychotics-induced RLS symptoms in 190 Korean schizophrenic patients using the diagnostic criteria of the International Restless Legs Syndrome Study Group. Five single-nucleotide polymorphisms (SNPs) of MAP2K5 were genotyped. We investigated genetic and haplotypic associations of these five SNPs with the risk of antipsychotics-induced RLS symptoms. Results We divided the 190 subjects into 2 groups: 1) those with RLS symptoms (n=96) and 2) those without RLS symptoms (n=94). There were no significant intergroup differences in the distributions of the genotypes and alleles of the rs1026732, rs11635424, rs12593813, rs4489954, and rs3784709 SNPs. However, the haplotype analysis showed that the G-G-G-G-T (rs1026732-rs11635424-rs12593813-rs4489954-rs3784709) haplotype was associated with RLS symptoms (permutation p=0.033). Conclusion These data suggest that a haplotype of MAP2K5 polymorphisms confers increased susceptibility to antipsychotics-induced RLS symptoms in schizophrenic patients.
Motivation for Treatment in Substance-Dependent Patients

The objective of this paper is to analyze the psychometric properties of the TCU Motivation for Treatment (MfT) scale in alcohol- and drug-dependent patients in an inpatient treatment facility in the Netherlands, to see whether it is useful in European populations as well. In the study, 279 consecutive patients were enrolled: 132 drug and 147 alcohol dependents. Exploratory and confirmatory factor analysis revealed 4 subscales: recognition of general problems (4 items), recognition of specific problems (5), desire for help (5) and treatment readiness (8). The results of the analyses showed that the MfT scale is a valid instrument for measuring treatment motivation, both in drug- and in alcohol-dependent patients. We demonstrated evidence for consistency of the scale through cultural barriers, in different populations and in different treatment settings.
Xanthohumol prevents dextran sulfate sodium-induced colitis via inhibition of IKKβ/NF-κB signaling in mice

Xanthohumol (XN), a prenylated chalcone isolated from the hop plant, has been reported to exhibit multiple biological functions including anti-inflammation. However, the pharmacological function of XN on colitis remains unknown. In this study, we investigated the anti-inflammatory effect of synthesized XN and molecular mechanism on dextran sulfate sodium (DSS)-induced experimental colitis. XN attenuated the colitis symptoms along with the prevention of colonic lesions after DSS challenge. XN inhibited the production of pro-inflammatory cytokines, oxidative stress and cyclooxygenase-2 expression in DSS-treated mice. Moreover, XN inhibited the phosphorylation of IκBα, the nuclear translocation of NF-κB subunits and the transcriptional activity of NF-κB in vivo and in vitro. In contrast to XN, isoXN showed much less effects on the kinase activity of IKKβ and IκBα phosphorylation induced by XN in this study, suggesting that an electrophilic carbon center present in XN is critical for the anti-inflammation in colitis, especially inhibition of IKKβ/NF-κB signaling pathway. Consistently, our docking analysis revealed that XN could bind to the active site, presumably at the Cys99 of IKKβ. Taken together, these findings demonstrate a new function of XN to inhibit IKKβ/NF-κB signaling, suggesting XN could be the potential therapeutic agent for the prevention of colitis.
Yoga posture recognition by detecting human joint points in real time using microsoft kinect

Musculoskeletal disorder is increasing in humans due to accidents or aging which is a great concern for future world. Physical exercises can reduce this disorder. Yoga is a great medium of physical exercise. For doing yoga a trainer is important who can monitor the perfectness of different yoga poses. In this paper, we have proposed a system which can monitor human body parts movement and monitor the accuracy of different yoga poses which aids the user to practice yoga. We have used Microsoft Kinect to detect different joint points of human body in real time and from those joint points we calculate various angles to measure the accuracy of a certain yoga poses for a user. Our proposed system can successfully recognize different yoga poses in real time.
Selective Inhibition of Magnocellular Vasopressin Neurons by Hypoosmolality: Effect on Histamine- and Stress-Induced Secretion of Adrenocorticotropin and Prolactin

We investigated the effect of selective inhibition of magnocellular arginine vasopressin (AVP) and oxytocin neurons on histamine (HA)- and restraint-stress-induced adrenocorticotropin (ACTH) and prolactin (PRL) secretion in conscious male rats. The inhibition of magnocellular neurons was obtained by inducing chronic hypoosmolality via continuous exposure of the rats to the AVP V2 receptor agonist 1-deamino(8-D-arginine)vasopressin (DDAVP) which was released from osmotic pumps implanted subcutaneously. In DDAVP-treated rats, plasma osmolality and sodium concentration were 273 mosm/l and 130 mmol/l, respectively. In control rats, the corresponding values were 291 mosm/l and 139 mmol/l. HA (270 nmol) administered intracerebroventricularly or 5 min of restraint stress stimulated ACTH and PRL secretion 4- to 11-fold in normoosmolar rats. In hypoosmolar rats, the HA-induced ACTH response was inhibited more than 40% whereas the restraint-stress-induced ACTH response was unaffected. Conversely, the PRL response to HA in hypoosmolar rats was unaffected whereas the PRL response to restraint stress was inhibited by 40%. In summary, chronic hypoosmolality inhibits HA-induced ACTH and restraint-stress-induced PRL secretion indicating involvement of magnocellular AVP in these responses.