Miracle-dz/UniFAR-FTUs huggingface dataset:
The protective mechanism underlying total flavones of Dracocephalum (TFD) effects on rat cerebral ischemia reperfusion injury

ABSTRACT Previously, total flavones of Dracocephalum (TFD), derived from Dracocephalum, were found to exert protective effects in cerebral ischemia reperfusion injury (CIRI) in middle cerebral artery occlusion (MCAO) rat model. However, the mechanisms underlying these observed effects of TFD on MCAO-induced rats still remain to be determined. Therefore, the aim of this study was to examine whether TFD alleviated MCAO through mechanisms involving anti-inflammatory and anti-apoptotic using MCAO rats. The following parameters were measured: (1) percentage (%) area of brain infarction; (2) serum levels of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and (3) expression protein levels of caspase-3 and AMP-activated protein kinase (AMPK). Results showed that MCAO significantly increased the % area of brain infarction, while TFD administration in these animals markedly reduced % area of brain infarction. A significant elevation on serum levels of TNF-α and IL-6 was noted with MCAO which was markedly reduced by TFD. In addition, MCAO produced a significant rise in protein expression levels of caspase-3 and AMPK. In contrast, TFD markedly lowered protein expression levels of caspase-3 and AMPK. Data suggest that the protective effects of TFD in MCAO model animals may involve inhibition of inflammatory mediator release associated with apoptosis through down regulation of AMPK signaling pathway.
The Evolving Understanding of the Molecular and Therapeutic Landscape of Pancreatic Ductal Adenocarcinoma

Pancreatic cancer is the third leading cause of cancer-related deaths, characterised by poor survival, marked molecular heterogeneity and high intrinsic and acquired chemoresistance. Only 10–20% of pancreatic cancer patients present with surgically resectable disease and even then, 80% die within 5 years. Our increasing understanding of the genomic heterogeneity of cancer suggests that the failure of definitive clinical trials to demonstrate efficacy in the majority of cases is likely due to the low proportion of responsive molecular subtypes. As a consequence, novel treatment strategies to approach this disease are urgently needed. Significant developments in the field of precision oncology have led to increasing molecular stratification of cancers into subtypes, where individual cancers are selected for optimal therapy depending on their molecular or genomic fingerprint. This review provides an overview of the current status of clinically used and emerging treatment strategies, and discusses the advances in and the potential for the implementation of precision medicine in this highly lethal malignancy, for which there are currently no curative systemic therapies.
The association of multiple anti-hypertensive medication classes with Alzheimer’s disease incidence across sex, race, and ethnicity

Background Antihypertensive treatments have been shown to reduce the risk of Alzheimer’s disease (AD). The renin-angiotensin system (RAS) has been implicated in AD, and thus RAS-acting AHTs (angiotensin converting enzyme inhibitors (ACEIs), and angiotensin-II receptor blockers (ARBs)) may offer differential and additional protective benefits against AD compared with other AHTs, in addition to hypertension management. Methods In a retrospective cohort design, we examined the medical and pharmacy claims of a 20% sample of Medicare beneficiaries from 2007 to 2013, and compared rates of AD diagnosis for 1,343,334 users of six different AHT drug treatments, 65 years of age or older (4,215,338 person-years). We compared AD risk between RAS and non-RAS AHT drug users, and between ACEI users and ARB users, by sex and race/ethnicity. Models adjusted for age, socioeconomic status, underlying health, and comorbidities. Findings RAS-acting AHTs were slightly more protective against onset of AD than non-RAS-acting AHTs for males, (male OR = 0.931 (CI: 0.895–0.969)), but not so for females (female OR = 0.985 (CI: 0.963–1.007)). Relative to other AHTs, ARBs were superior to ACEIs for both men (male ARB OR = 0.834 (CI: 0.788–0.884); male ACEI OR = 0.978 (CI: 0.939–1.019)) and women (female ARB OR = 0.941 (CI: 0.913–0.969); female ACEI OR = 1.022 (CI: 0.997–1.048)), but only in white men and white and black women. No association was shown for Hispanic men and women. Conclusion Hypertension management treatments that include RAS-acting ARBs may, in addition to lowering blood pressure, reduce AD risk, particularly for white and black women and white men. Additional studies and clinical trials that include men and women from different racial and ethnic groups are needed to confirm these findings. Understanding the potentially beneficial effects of certain RAS-acting AHTs in high-risk populations is of great importance.
Sodium-glucose transporter 2 is a diagnostic and therapeutic target for early-stage lung adenocarcinoma

Lung premalignancy and early-stage adenocarcinoma use a mechanism of glucose transport that can be targeted for early diagnosis and treatment. Lung cancer search and destroy Like many cancer types, lung cancer is easier to treat when it is detected in its early stages, but this can be difficult to achieve. Scafoglio et al. discovered that a glucose transporter called sodium-glucose transporter 2 is not only expressed in lung cancer but also specifically found in early-stage tumors. Using a radiolabeled tracer specific for this receptor, the authors were able to perform positron emission tomography to identify early tumors that would otherwise remain undetectable. In addition, they found that a class of diabetes drugs called gliflozins, which target the same receptor, is effective at targeting these lung tumors in mouse models. The diagnostic definition of indeterminate lung nodules as malignant or benign poses a major challenge for clinicians. We discovered a potential marker, the sodium-dependent glucose transporter 2 (SGLT2), whose activity identified metabolically active lung premalignancy and early-stage lung adenocarcinoma (LADC). We found that SGLT2 is expressed early in lung tumorigenesis and is found specifically in premalignant lesions and well-differentiated adenocarcinomas. SGLT2 activity could be detected in vivo by positron emission tomography (PET) with the tracer methyl 4-deoxy-4-[18F] fluoro-alpha-d-glucopyranoside (Me4FDG), which specifically detects SGLT activity. Using a combination of immunohistochemistry and Me4FDG PET, we identified high expression and functional activity of SGLT2 in lung premalignancy and early-stage/low-grade LADC. Furthermore, selective targeting of SGLT2 with FDA-approved small-molecule inhibitors, the gliflozins, greatly reduced tumor growth and prolonged survival in autochthonous mouse models and patient-derived xenografts of LADC. Targeting SGLT2 in lung tumors may intercept lung cancer progression at early stages of development by pairing Me4FDG PET imaging with therapy using SGLT2 inhibitors.
MRI evaluation of vulvar squamous‐cell carcinoma in fresh radical local excision specimens for cancer localization and prediction of surgical tumor‐free margins

In the surgical treatment of vulvar squamous‐cell carcinoma (VSCC), tumor‐free margins of 8 mm or more are considered adequate. However, limited perioperative information on the tumor‐free margins other than the surgeon's own estimation is available. The purpose of this study was therefore to investigate the feasibility of ex vivo MRI in localizing VSCC and to assess the surgical tumor‐free margins in fresh radical local excision (RLE) specimens to guide the surgeon during resections. Nine patients with biopsy‐proven VSCC scheduled for RLE were prospectively included. Intact fresh specimens were scanned using a 7 T preclinical MR‐scanner. Whole mount H&E‐stained slides were obtained every 3 mm and correlated with ex vivo MRI. A pathologist annotated VSCC and minimal tumor‐free margins (3 o'clock, 9 o'clock, basal) on the digitalized histological slides. An observer with knowledge of histology (the non‐blinded annotation) and a radiologist blinded to histology (the blinded annotation) separately performed annotation of the same features on ex vivo MRI. Linear correlation and agreement of the ex vivo MRI measurements with histology were assessed. Diagnostic performance for VSCC localization and identification of margins less than 8 mm was expressed as positive and negative predictive values (PPV, NPV). In 153 matched ex vivo MRI slices, the observer correctly identified 79/91 margins as less than 8 mm (PPV 87%) and 110/124 margins as 8 mm or greater (NPV 89%). The radiologist correctly annotated absence of VSCC in 73/81 (NPV 90%) and presence in 65/72 (PPV 90%) slices. Sixty‐four of 90 margins were correctly identified as less than 8 mm (PPV 71%) and 83/102 margins as 8 mm or greater (NPV 81%). Both non‐blinded and blinded annotations were linearly correlated and demonstrated good agreement with histology. Accurate localization of VSCC and measurements of the surgical tumor‐free margins in fresh RLE specimens using ex vivo MRI seems feasible. High diagnostic performance in VSCC localization and identification of margins less than 8 mm suggest ex vivo MRI to be clinically applicable.
The Early Phases of Ankylosing Spondylitis: Emerging Insights From Clinical and Basic Science

In our paper, we discuss how the early phases of ankylosing spondylitis (AS) are linked to peri-firbocartilagenous osteitis in the sacroiliac joint and entheseal bone related anchoring sites. This skeletal proclivity is linked to an abnormal immunological response to skeletal biomechanical stress and associated microdamage. A key event in the early stages of AS appears to be the association with subclinical Crohn's-like colitis with this gut inflammation being pivotal to the osteitis reaction. Whether this osteitis is consequent to non-specific intestinal innate immune activation or adaptive immune responses against specific microbiotal or self-antigens is unknown. Recurrent iritis is an HLA-B27 associated feature that may predate AS and pursues a course independent of joint involvement, and points toward the pivotal role of organ specific immunology over generalized systemic immune responses in disease expression. Human genetics and animal model studies strongly incriminate the IL23/17 axis and TNF-α in disease pathogenesis. Preliminary work shows a strong convergence of innate immune cells including type 3 innate lymphoid-cells (ILC3) and γδ T-cells in skin, gut, entheseal, and eye inflammation. Despite the HLA-B27 association, the role of adaptive immunity, especially CD8+ T-cells mediated responses remains unproven and alternative theories have been proposed. The emerging non-dependence of axial inflammation on IL-23 but dependence on IL-17A is an unexpected new twist that awaits full explanation. In this mini-review, we discuss the key events in the early stages of human AS from clinical and basic science aspects, which could be crucial for attempted disease prevention studies in at risk subjects.
Metabolic Analyses Revealed Time-Dependent Synergistic Killing by Colistin and Aztreonam Combination Against Multidrug-Resistant Acinetobacter baumannii

Background: Polymyxins are a last-line class of antibiotics against multidrug-resistant Acinetobacter baumannii; however, polymyxin resistance can emerge with monotherapy. Therefore, synergistic combination therapy is a crucial strategy to reduce polymyxin resistance. Methods: This study conducted untargeted metabolomics to investigate metabolic responses of a multidrug-resistant (MDR) A. baumannii clinical isolate, AB090342, to colistin and aztreonam alone, and their combination at 1, 4, and 24 h. Metabolomics data were analyzed using univariate and multivariate statistics; metabolites showing ≥ 2-fold changes were subjected to bioinformatics analysis. Results: The synergistic action of colistin-aztreonam combination was initially driven by colistin via significant disruption of bacterial cell envelope, with decreased phospholipid and fatty acid levels at 1 h. Cell wall biosynthesis was inhibited at 4 and 24 h by aztreonam alone and the combination as shown by the decreased levels of two amino sugars, UDP-N-acetylglucosamine and UDP-N-acetylmuramate; these results suggested that aztreonam was primarily responsible for the synergistic killing at later time points. Moreover, aztreonam alone and the combination significantly depleted pentose phosphate pathway, amino acid, peptide and nucleotide metabolism, but elevated fatty acid and key phospholipid levels. Collectively, the combination synergy between colistin and aztreonam was mainly due to the inhibition of cell envelope biosynthesis via different metabolic perturbations. Conclusion: This metabolomics study is the first to elucidate multiple cellular pathways associated with the time-dependent synergistic action of colistin-aztreonam combination against MDR A. baumannii. Our results provide important mechanistic insights into optimizing synergistic colistin combinations in patients.
Comparison of palonosetron and dexamethasone with ondansetron and dexamethasone for postoperative nausea and vomiting in postchemotherapy ovarian cancer surgeries requiring opioid-based patient-controlled analgesia: A randomised, double-blind, active controlled study

Background and Aims: Patients undergoing ovarian cancer surgery after chemotherapy and requiring opioid-based patient-controlled analgesia (PCA) are at high-risk of postoperative nausea and vomiting (PONV). We aimed to assess the effect of palonosetron and dexamethasone combination for these patients for prevention of PONV. Methods: This study included 2 groups and 150 patients. At the time of wound closure, patients in group A received ondansetron 8 mg intravenous (IV) + dexamethasone 4 mg IV and group B received palonosetron 0.075 mg IV + dexamethasone 4 mg IV. Postoperatively for 48 hours, group A patients received ondansetron 4 mg 8 hourly IV, group B patients received normal saline 8 hourly IV in 2 cc syringe. The primary objective was the overall incidence of PONV. Independent t-test, Chi-square test, and Fisher's exact test were used and multivariate regression analysis was done. Results: Vomiting was significantly higher in group A (37.3%) as compared with group B (21.3%) at 0–48 hours (P = 0.031). Significantly more patients in Group A had nausea as compared with group B at 90–120 minutes (30.66% vs 18.66%, P = 0.043) and 6–24 hours (32.0% vs 22.66%, P = 0.029). PCA opioid usage in microgram was significantly higher in group A at 0–24 hours (690.53 ± 332.57 vs 576.85 ± 250.79, P = 0.024) and 0–48 hours (1126.10 ± 512.18 vs 952.13 ± 353.85, P = 0.030). Conclusion: Palonosetron with dexamethasone is more effective than ondasetron with dexamethasone for prevention of PONV in post-chemotherapy ovarian cancer surgeries receiving opioid-based patient controlled analgesia.
‘Governor vessel-unblocking and mind-regulating’ acupuncture therapy ameliorates cognitive dysfunction in a rat model of middle cerebral artery occlusion

Acupuncture is a traditional Chinese medicinal therapy, which is used for the amelioration of cognitive dysfunction. The aim of this study was to investigate the effectiveness and relevancy mechanisms of ‘governor vessel-unblocking and mind-regulating’ acupuncture therapy for cognitive dysfunction in rats with ischemia. For this purpose, we used the middle cerebral artery occlusion (MCAO) method to induce cognitive dysfunction in rats. The behavioral changes in the rats were examined using the Morris water maze (MWM) test. The effects of the treatment on oxidative stress response and the function of the mitochondria in brain tissues were also assessed. The results revealed that ‘governor vessel-unblocking and mind-regulating’ acupuncture therapy markedly improved the cognitive ability of the rats with cognitive dysfunction. The production of pro-oxidative stress factors, including nitric oxide (NO) and inducible nitric oxide synthase (iNOS), was also blocked along with the amelioration of cognitive function, while the production of adenosine triphosphate (ATP), superoxide dismutase (SOD) and cyclooxygenase (COX) was restored. At the molecular level, the accumulation of amyloid β (Aβ) in the mitochondria was suppressed by ‘governor vessel-unblocking and mind-regulating’ acupuncture therapy, which may be attributed to the inhibition of the function of translocase of outer mitochondrial membrane 40 (TOMM40) and translocase of inner mitochondrial membrane 17A (TIMM17A). On the whole, the findings of the present study confirm the effects of ‘governor vessel-unblocking and mind-regulating’ acupuncture therapy on cognitive dysfunction induced by brain ischemia in rats, and that the mechanisms underlying the effects of this treatment might be mediated through the inhibition of TOMM40 and TIMM17A synthesis, which can relieve mitochondrial dysfunction from the accumulation of Aβ.
Extending the NFComms framework for bulk data transfers

In this paper we present the design and implementation of an indirect messaging extension for the existing NFComms framework that provides communication between a network flow processor and host CPU. This extension addresses the bulk throughput limitations of the framework and is intended to work in conjunction with existing communication mediums. Testing of the framework extensions shows an increase in throughput performance of up to 300× that of the current direct message passing framework at the cost of increased single message latency of up to 2×. This trade-off is considered acceptable as the proposed extensions are intended for bulk data transfer only while the existing message passing functionality of the framework is preserved and can be used in situations where low latency is required for small messages.
Channel Selection of EEG-Based Cybersickness Recognition during Playing Video Game Using Correlation Feature Selection (CFS)

Recently, the rapid development of 3D movie or video games, causing the phenomenon of cybersickness. Cybersickness is an unpleasant symptom (dizziness, nausea, vomiting, and disorientation) that occur to humans when exposure in 3D movie or video games within a certain time. It can disrupt psychic and physical condition of the human if not handled appropriately. Many studies have been done to investigate cybersickness using physiological measurements, one of which is EEG. However, earlier studies have not discussed an optimal channel location for identifying cybersickness on EEG. In this paper, we proposed Correlation Feature Selection (CFS) method to select features in order to determine best channel selection. The power percentage (PP) features of alpha ($\alpha$), beta ($\beta$) and theta ($\theta$) bands were extracted on all channels. CFS method obtained 3 optimal channels location on F3, O1, and O2 from PP feature of beta ($\beta$) band. The investigating of cybersickness employs three compare classifiers i.e. SVM-RBF, k-NN, and LDA. According to our result, LDA is the best classifier for identifying cybersickness. By using CFS method, it can improve performance accuracy from 83% to 100%. Hence, we conclude that beta frequency band on frontal and occipital area is suitable to measure EEG-based cybersickness.
There is limited existing evidence to support the common assumption that strenuous endurance exercise bouts impair immune competency

Research from the 1980s and 1990s led to three principles of exercise immunology being formed which imply that an acute bout of moderate-to-vigorous intensity endurance exercise can induce a short-term period of immuno-suppression. This prevailing dogma has been challenged recently [1]. Following acute bouts of exercise, particularly endurance activities, such as running for several hours, it has generally been accepted that (i) infection risk is increased; (ii) salivary IgA temporarily declines; and (iii) transient decreases in the number and function of immune cells in blood represents immuno-suppression. These observations led to the ‘open-window hypothesis’ which purports that the immune system can be transiently compromised after some forms of acute exercise. In this editorial, we briefly summarize key messages from a recent narrative review that challenges these conclusions [1]. Our focus herein is on the immunological effects of moderate-tovigorous intensity endurance exercise bouts. Other forms of exercise, such as strengthening or resistance exercise, are beyond the scope of this editorial. Overall, we state that there is limited robust evidence to support an immunosuppressive effect of any exercise form. We highlight that further research is required to fully understand the immunological effects of endurance exercise training that is particularly prolonged (i.e. at least several hours) regular (i.e. once or twice a day) demanding (i.e. moderate-to-vigorous intensity) and chronic (i.e. performed over weeks or months). In summary, the belief that forms of exercise can be immunosuppressive is counterproductive for encouraging exercise as a preventative and therapeutic strategy for chronic disease. Indeed, we advocate research that examines the benefits of exercise for immune competency, and briefly highlight areas that could be prioritized.
A 25-year dynamic ecological analysis of psychiatric hospital admissions and prison committals: Penrose’s hypothesis updated

Aims There is renewed interest in the inverse association between psychiatric hospital and prison places, with reciprocal time trends shown in more than one country. We hypothesised that the numbers of admissions to psychiatric hospitals and committals to prisons in Ireland would also correlate inversely over time (i.e. dynamic measures of admission and committal rather than static, cross-sectional numbers of places). Method Publicly available activity statistics for psychiatric hospitals and prisons in Ireland were collated from 1986 to 2010. Results There was a reciprocal association between psychiatric admissions and prison committals (Pearson r=−0.788, p<0.001), an increase of 91 prison committals for every 100 psychiatric hospital admissions foregone. Conclusion Penrose’s hypothesis applies to admissions to psychiatric hospitals and prisons in Ireland over time (dynamic measures), just as it does to the numbers of places in psychiatric hospitals and prisons in Ireland and elsewhere (static, cross-sectional measures). Although no causal connection can be definitively established yet, mentally disordered prisoners are usually known to community mental health services. Psychiatric services for prisons and the community should be linked to ensure that the needs of those currently accessing care through prisons can also be met in the community.