Miracle-dz/UniFAR-FTUs huggingface dataset:
Heat-Shock Protein 27 (HSPB1) Is Upregulated and Phosphorylated in Human Platelets during ST-Elevation Myocardial Infarction

Heat-shock proteins are a family of proteins which are upregulated in response to stress stimuli including inflammation, oxidative stress, or ischemia. Protective functions of heat-shock proteins have been studied in vascular disease models, and malfunction of heat-shock proteins is associated with vascular disease development. Heat-shock proteins however have not been investigated in human platelets during acute myocardial infarction ex vivo. Using two-dimensional electrophoresis and immunoblotting, we observed that heat-shock protein 27 (HSPB1) levels and phosphorylation are significantly increased in platelets of twelve patients with myocardial infarction compared to patients with nonischemic chest pain (6.4 ± 1.0-fold versus 1.0 ± 0.9-fold and 5.9 ± 1.8-fold versus 1.0 ± 0.8-fold; p < 0.05). HSP27 (HSPB1) showed a distinct and characteristic intracellular translocation from the cytoskeletal fraction into the membrane fraction of platelets during acute myocardial infarction that did not occur in the control group. In this study, we could demonstrate for the first time that HSP27 (HSPB1) is upregulated and phosphorylated in human platelets during myocardial infarction on a cellular level ex vivo with a characteristic intracellular translocation pattern. This HSP27 (HSPB1) phenotype in platelets could thus represent a measurable stress response in myocardial infarction and potentially other acute ischemic events.
Plasma Levels of snoRNAs are Associated with Platelet Activation in Patients with Peripheral Artery Disease

In addition to supervised walking therapy, antithrombotic therapy and the management of risk factors, the treatment of peripheral artery disease (PAD) is limited to endovascular and surgical interventions, i.e., angioplasty with stent implantation and bypass surgery, respectively. Both are associated with a high restenosis rate. Furthermore, patients with PAD often suffer atherothrombotic events like myocardial infarction, transient ischemic attacks or stroke. Small ribonucleic acids (RNAs) have proven reliable biomarkers because of their remarkable stability. Small nucleolar RNAs (snoRNAs) guide modifications to small nuclear RNAs and ribosomal RNAs, enabling protein synthesis. In the current study, we measured four snoRNAs in 104 consecutive PAD patients who underwent elective infrainguinal angioplasty with stent implantation. We selected snoRNAs that showed significant overexpression in the plasma of end-stage PAD patients in a previous study. All four snoRNAs are transcribed from the 14q32 locus, which is strongly linked to human cardiovascular disease, including PAD and restenosis. We showed that the four selected 14q32 snoRNAs were abundantly expressed in the plasma of PAD patients. The plasma levels of these snoRNAs were not directly associated with target vessel restenosis, however, levels of SNORD113.2 and SNORD114.1 were strongly linked to platelet activation, which is an important determinant of long-term outcome, in PAD, and in cardiovascular disease in general.
New Insights on Lilium Phylogeny Based on a Comparative Phylogenomic Study Using Complete Plastome Sequences

The genus Lilium L. is widely distributed in the cold and temperate regions of the Northern Hemisphere and is one of the most valuable plant groups in the world. Regarding the classification of the genus Lilium, Comber’s sectional classification, based on the natural characteristics, has been primarily used to recognize species and circumscribe the sections within the genus. Although molecular phylogenetic approaches have been attempted using different markers to elucidate their phylogenetic relationships, there still are unresolved clades within the genus. In this study, we constructed the species tree for the genus using 28 Lilium species plastomes, including three currently determined species (L. candidum, L. formosanum, and L. leichtlinii var. maximowiczii). We also sought to verify Comber’s classification and to evaluate all loci for phylogenetic molecular markers. Based on the results, the genus was divided into two major lineages, group A and B, consisting of eastern Asia + Europe species and Hengduan Mountains + North America species, respectively. Sectional relationships revealed that the ancestor Martagon diverged from Sinomartagon species and that Pseudolirium and Leucolirion are polyphyletic. Out of all loci in that Lilium plastome, ycf1, trnF-ndhJ, and trnT-psbD regions are suggested as evaluated markers with high coincidence with the species tree. We also discussed the biogeographical diversification and long-distance dispersal event of the genus.
Sex differences within sleep in gonadally-intact rats.

Sleep impacts diverse physiological and neural processes and is itself affected by the menstrual cycle; however, few studies have examined the effects of the estrous cycle on sleep in rodents. Studies of disease mechanisms in females therefore lack critical information regarding estrous cycle influences on relevant sleep characteristics. We recorded electroencephalographic (EEG) activity from multiple brain regions to assess sleep states as well as sleep traits such as spectral power and interregional spectral coherence in freely cycling females across the estrous cycle and compared with males. Our findings show that the high hormone phase of proestrus decreases the amount of non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep and increases the amount of time spent awake compared with other estrous phases and to males. This spontaneous sleep deprivation of proestrus was followed by a sleep rebound in estrus which increased NREM and REM sleep. In proestrus, spectral power increased in the delta (0.5-4 Hz) and the gamma (30-60 Hz) ranges during NREM sleep, and increased in the theta range (5-9 Hz) during REM sleep during both proestrus and estrus. Slow wave activity and cortical sleep spindle density also increased in NREM sleep during proestrus. Finally, interregional NREM and REM spectral coherence increased during proestrus. This work demonstrates that the estrous cycle affects more facets of sleep than previously thought and reveals both sex differences in features of the sleep-wake cycle related to estrous phase that likely impact the myriad physiological processes influenced by sleep.
GATA2 mutations in myeloid malignancies: Two zinc fingers in many pies

The GATA family of transcription factors are zinc finger (ZF) DNA‐binding proteins that regulate transcription during development and cell differentiation. GATA2 plays an essential role in the regulation of hematopoiesis. As a result, mutations in this gene or alterations in its expression level or function have been linked to a variety of human hematologic disorders. In this review, we summarize the findings and developments over the recent years regarding the clinical correlations and functional properties of distinct GATA2 mutations in hematopoietic malignancies, with particular focus on the mutational hotspots in the ZF domains.
Electrophysiological evidence of the differential modulation of approach‐related processes toward attractive foods by immersive or mindful viewing conditions

Awareness of mental events as mere representations rather than as accurate depictions of reality, also known as dereification, is one of the key features of mindfulness meditation. Dereification is juxtaposed to subjective realism, the process of being lost or totally immersed in the contents of one's mind. Excessive subjective realism is a hallmark of several psychiatric disorders. Here, we investigated whether a “mindful” (dereified) compared with an “immersed” (highly subjectively real) attitude, induced by instructions, differentially modulates approach‐avoidance tendencies when processing visual stimuli. We presented novices and experienced meditators with neutral and attractive food images under both mindful and immersed states. Then, participants performed an approach–avoidance Task (AAT) during which we obtained behavioral data, salivary volume, EEG recordings, and self‐report measures. The approach bias toward attractive food was correlated with N2 amplitude, a marker of response inhibition, and the regulation of this bias by the mindful instruction compared to the immersed instruction was associated with a modulation of the visual N1 amplitude, a marker of early selective attention. Individuals with more expertise in mindfulness meditation engaged in less late affective reappraisal during mindfulness than during immersion, as measured by lower amplitude in the late positive potential (LPP). Additionally, the ERPs sensitive to the AAT manipulation was also associated to self‐report measures of subjective realism, food bias, and mindfulness meditation expertise but not to salivation measures. These findings provide novel insights into the mechanisms by which mindfulness‐based interventions could be effective in a range of psychiatric conditions.
Intratumoral Immunotherapy—Update 2019

Abstract Intratumoral immunotherapies aim to trigger local and systemic immunologic responses via direct injection of immunostimulatory agents with the goal of tumor cell lysis, followed by release of tumor‐derived antigens and subsequent activation of tumor‐specific effector T cells. In 2019, a multitude of intratumoral immunotherapies with varied mechanisms of action, including nononcolytic viral therapies such as PV‐10 and toll‐like receptor 9 agonists and oncolytic viral therapies such as CAVATAK, Pexa‐Vec, and HF10, have been extensively evaluated in clinical trials and demonstrated promising antitumor activity with tolerable toxicities in melanoma and other solid tumor types. Talimogene laherparepvec (T‐VEC), a genetically modified herpes simplex virus type 1–based oncolytic immunotherapy, is the first oncolytic virus approved by the U.S. Food and Drug Administration for the treatment of unresectable melanoma recurrent after initial surgery. In patients with unresectable metastatic melanoma, T‐VEC demonstrated a superior durable response rate (continuous complete response or partial response lasting ≥6 months) over subcutaneous GM‐CSF (16.3% vs. 2.1%; p < .001). Responses were seen in both injected and uninjected lesions including visceral lesions, suggesting a systemic antitumor response. When combined with immune checkpoint inhibitors, T‐VEC significantly improved response rates compared with single agent; similar results were seen with combinations of checkpoint inhibitors and other intratumoral therapies such as CAVATAK, HF10, and TLR9 agonists. In this review, we highlight recent results from clinical trials of key intratumoral immunotherapies that are being evaluated in the clinic, with a focus on T‐VEC in the treatment of advanced melanoma as a model for future solid tumor indications. Implications for Practice This review provides oncologists with the latest information on the development of key intratumoral immunotherapies, particularly oncolytic viruses. Currently, T‐VEC is the only U.S. Food and Drug Administration (FDA)‐approved oncolytic immunotherapy. This article highlights the efficacy and safety data from clinical trials of T‐VEC both as monotherapy and in combination with immune checkpoint inhibitors. This review summarizes current knowledge on intratumoral therapies, a novel modality with increased utility in cancer treatment, and T‐VEC, the only U.S. FDA‐approved oncolytic viral therapy, for medical oncologists. This review evaluates approaches to incorporate T‐VEC into daily practice to offer the possibility of response in selected melanoma patients with manageable adverse events as compared with other available immunotherapies.
Validation of revised patient measures of safety: PMOS-30 and PMOS-10

Objectives There is growing evidence that patients can provide feedback on the safety of their care. The 44-item Patient Measure of Safety (PMOS) was developed for this purpose. While valid and reliable, the length of this questionnaire makes it potentially challenging for routine use. Our study aimed to produce revised, shortened versions of PMOS (PMOS-30 and PMOS-10), which retained the psychometric properties of the longer version. Participants To produce a shortened diagnostic measure, we analysed data from 2002 patients who completed PMOS-44, and examined the reliability of the revised measure (PMOS-30) in a sample of 751 patients. To produce a brief standalone measure, we again analysed data from 2002 patients who completed PMOS-44, and tested the reliability and validity of the brief standalone measure (PMOS-10) in a sample of 165 patients. Methods The process of shortening the questionnaire involved a combination of secondary data analysis (eg, Standard Deviation and inter-item correlations) and a consensus group exercise to produce PMOS-30 and examine face validity. Analysis of PMOS-30 data examined reliability (eg, Cronbach’s alpha). Further secondary data analysis (ie, corrected item-total correlations) produced PMOS-10, and primary data collection assessed its reliability and validity (eg, Cronbach’s alpha, analysis of variance). Results Fourteen items were removed to produce PMOS-30 and the percentage of negatively worded items was reduced from 57% to 33%. PMOS-30 demonstrated good internal reliability (α=0.89). The 10 items with the highest corrected item-total correlations across both PMOS-44 and PMOS-30 composed PMOS-10. PMOS-10 had good internal reliability (α=0.79), demonstrated convergent validity; however, discriminant validity was not established. Conclusions Two revised, shortened versions of the original PMOS-44 (PMOS-30 and PMOS-10) were produced to capture patient feedback about safety in hospital. The measures demonstrated good reliability and validity, and preserved the psychometric properties of the original measure.
Observation of Single Nanoparticle Collisions with Green Synthesized Pt, Au, and Ag Nanoparticles Using Electrocatalytic Signal Amplification Method

This work describes the tailored design, green synthesis and characterization of noble metal (Pt, Ag and Au) nanoparticles (NPs) using Sapinduss Mukkorossi fruit extract (SMFE) and its signal NP collision signal response, based on the principle of the electrocatatlytic amplication (EA) method. Here, the SMFE can act as both the reducing and the capping agent for the fabrication of noble nanometals. The SMFE-capped NPs was available for the observation of a single NP collision signal. Two general types of current response were observed: a staircase current response for the Pt or Au NPs, and a blip/spike current response for Ag NPs. These results demonstrated that the eco-friendly synthesized SMFE-capped NPs maintained their electrocatalytic activity, therefore they can be used for the single NP experiments and place an arena for future biosensing applications.
Cardiorespiratory fitness and muscular endurance responses immediately and two-months after a whole-body Tabata or vigorous-intensity continuous training intervention.

Young adults (n=68 [52 F]; age=21±3 y; VO2peak: 41±6 mL/kg/min) were randomized into a no-exercise control (CTL: n=15), Tabata (n=26), or vigorous-intensity continuous training (VICT; n=27) group for a four-week supervised training period (4 sessions/wk). VO2peak, time-to-fatigue (TTF), 5 km time-trial performance (TT), and muscular endurance were assessed at baseline, post-training (POST) and two-month follow-up (FU). Response confidence intervals (CI) were used to classify individuals as likely responders (R; CI>0). Both exercise interventions increased TTF and TT at POST (both p<0.01), but these benefits were maintained at FU after VICT only (p<0.01). Push-up performance was increased at POST and FU (both p<0.01) after Tabata. VICT resulted in a greater proportion of TTF R versus both groups at POST (CTL: 1/15; VICT: 19/26; Tabata: 9/27) and versus Tabata at FU (3/15; 13/26; 4/27). VICT also had a greater proportion of TT R versus CTL at POST (2/15; 17/26; 10/27). Tabata had a greater proportion of R for max push-up repetitions versus both groups at POST (3/15; 6/26; 18/27) and versus CTL at FU (2/15; 10/26; 18/27). Collectively, VICT appears to be more effective for improving cardiorespiratory fitness, whereas whole-body Tabata confers larger improvements in push-up performance following short-term training. Novelty bullets: o Vigorous-intensity continuous training elicits larger improvements in cardiorespiratory fitness versus whole-body Tabata. o Individual response profiles parallel group-level changes in cardiorespiratory fitness and muscular endurance.
Continuing Education in the Health Professions

Bargaining with reading habit is no need. Reading is not kind of something sold that you can take or not. It is a thing that will change your life to life better. It is the thing that will give you many things around the world and this universe, in the real world and here after. As what will be given by this continuing education in the health professions, how can you bargain with the thing that has many benefits for you?
Photoimmunotherapy of Ovarian Cancer: A Unique Niche in the Management of Advanced Disease

Ovarian cancer (OvCa) is the leading cause of gynecological cancer-related deaths in the United States, with five-year survival rates of 15–20% for stage III cancers and 5% for stage IV cancers. The standard of care for advanced OvCa involves surgical debulking of disseminated disease in the peritoneum followed by chemotherapy. Despite advances in treatment efficacy, the prognosis for advanced stage OvCa patients remains poor and the emergence of chemoresistant disease localized to the peritoneum is the primary cause of death. Therefore, a complementary modality that is agnostic to typical chemo- and radio-resistance mechanisms is urgently needed. Photodynamic therapy (PDT), a photochemistry-based process, is an ideal complement to standard treatments for residual disease. The confinement of the disease in the peritoneal cavity makes it amenable for regionally localized treatment with PDT. PDT involves photochemical generation of cytotoxic reactive molecular species (RMS) by non-toxic photosensitizers (PSs) following exposure to non-harmful visible light, leading to localized cell death. However, due to the complex topology of sensitive organs in the peritoneum, diffuse intra-abdominal PDT induces dose-limiting toxicities due to non-selective accumulation of PSs in both healthy and diseased tissue. In an effort to achieve selective damage to tumorous nodules, targeted PS formulations have shown promise to make PDT a feasible treatment modality in this setting. This targeted strategy involves chemical conjugation of PSs to antibodies, referred to as photoimmunoconjugates (PICs), to target OvCa specific molecular markers leading to enhanced therapeutic outcomes while reducing off-target toxicity. In light of promising results of pilot clinical studies and recent preclinical advances, this review provides the rationale and methodologies for PIC-based PDT, or photo-immunotherapy (PIT), in the context of OvCa management.
Lanatoside C Induces G2/M Cell Cycle Arrest and Suppresses Cancer Cell Growth by Attenuating MAPK, Wnt, JAK-STAT, and PI3K/AKT/mTOR Signaling Pathways

Cardiac glycosides (CGs) are a diverse family of naturally derived compounds having a steroid and glycone moiety in their structures. CG molecules inhibit the α-subunit of ubiquitous transmembrane protein Na+/K+-ATPase and are clinically approved for the treatment of cardiovascular diseases. Recently, the CGs were found to exhibit selective cytotoxic effects against cancer cells, raising interest in their use as anti-cancer molecules. In this current study, we explored the underlying mechanism responsible for the anti-cancer activity of Lanatoside C against breast (MCF-7), lung (A549), and liver (HepG2) cancer cell lines. Using Real-time PCR, western blot, and immunofluorescence studies, we observed that (i) Lanatoside C inhibited cell proliferation and induced apoptosis in cell-specific and dose-dependent manner only in cancer cell lines; (ii) Lanatoside C exerts its anti-cancer activity by arresting the G2/M phase of cell cycle by blocking MAPK/Wnt/PAM signaling pathways; (iii) it induces apoptosis by inducing DNA damage and inhibiting PI3K/AKT/mTOR signaling pathways; and finally, (iv) molecular docking analysis shows significant evidence on the binding sites of Lanatoside C with various key signaling proteins ranging from cell survival to cell death. Our studies provide a novel molecular insight of anti-cancer activities of Lanatoside C in human cancer cells.
Urinary leukotriene E4 in children with wheezing associated respiratory illness from influenza infection

Abstract Background: Influenza virus can cause bronchiolitis and recurrent wheezing in young children. Although the pathophysiology is unclear, leukotriene is thought to play an important role. Objectives: We conducted a prospective case-control study to measure urinary leukotriene E4 (uLTE4) levels in children with wheezing associated respiratory illness (WARI) from influenza infection, compared to children without respiratory tract infection and to identify the association between clinical features and uLTE4 levels in influenza-infected children. Methods: Nasopharygeal secretions from patients less than 6-years-old hospitalized due to WARI were tested for influenza virus by RT-PCR. The uLTE4 levels were measured in the patients with influenza infection and compared with normal controls. The correlation between clinical features and uLTE4 levels was also studied. Results: The study included 10 patients with influenza infection (median age 23.5 months) and 10 children as control group (median age 23 months). The uLTE4 levels were not significantly different between influenza and control group; 191.63 ng/mM creatinine (IQR 162.57-244.25) vs. 132.32 ng/mM creatinine (IQR 93.79-215.65), respectively (p = 0.096). There was no significant correlation between uLTE4 levels and clinical features including pulmonary index, eosinophil count, and length of hospital stay. Conclusion: The uLTE4 level does not increase in pediatric patients with wheezing associated influenza infection and does not correlate with clinical features during infection. Although there is a trend towards increased uLTE4 in influenza patients and a correlation to the pulmonary index, the small sample size may have altered the significance of these results.
Human Papillomavirus Vaccine Effectiveness Against HPV Infection: Evaluation of One, Two, and Three Doses.

BACKGROUND Highly effective human papillomavirus (HPV) vaccines are used in many national programs in 3- or 2-dose schedules. We examined HPV vaccine effectiveness against HPV prevalence by number of doses. METHODS We collected residual liquid-based cytology samples from US women aged 20-29 years who were screened for cervical cancer. Women continuously enrolled from 2006 through the specimen collection date were analyzed. Specimens were tested using the Linear Array assay. We analyzed prevalence of quadrivalent HPV vaccine (4vHPV) types (HPV 6,11,16,18) and other HPV-type categories and determined prevalence ratios (PRs) and 95% confidence intervals (CIs) for 1, 2, and 3 compared with no vaccine doses. RESULTS Among 4269 women, 1052 (24.6%) were unvaccinated, 2610 (61.1%) received 3 doses, 304 (7.1%) received 2 doses, and 303 (7.1%) received 1 dose. The 4vHPV-type prevalence was 7.4% among unvaccinated women compared with 1.7%, 1.0%, and 1.0% among 1-, 2-, and 3-dose recipients. Among women vaccinated at ≤18 years, adjusted PRs for 1, 2, and 3 doses were 0.06 (95% CI, 0.01-0.42), 0.05 (95% CI, 0.01-0.39), and 0.06 (95% CI, 0.04-0.12). CONCLUSIONS Among women who received their first dose at age ≤18, estimated HPV vaccine effectiveness was high regardless of number of doses.