Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular Vesicles in Smoking-Mediated HIV Pathogenesis and their Potential Role in Biomarker Discovery and Therapeutic Interventions

In the last two decades, the mortality rate in people living with HIV/AIDS (PLWHA) has decreased significantly, resulting in an almost normal longevity in this population. However, a large portion of this population still endures a poor quality of life, mostly due to an increased inclination for substance abuse, including tobacco smoking. The prevalence of smoking in PLWHA is consistently higher than in HIV negative persons. A predisposition to cigarette smoking in the setting of HIV potentially leads to exacerbated HIV replication and a higher risk for developing neurocognitive and other CNS disorders. Oxidative stress and inflammation have been identified as mechanistic pathways in smoking-mediated HIV pathogenesis and HIV-associated neuropathogenesis. Extracellular vesicles (EVs), packaged with oxidative stress and inflammatory agents, show promise in understanding the underlying mechanisms of smoking-induced HIV pathogenesis via cell-cell interactions. This review focuses on recent advances in the field of EVs with an emphasis on smoking-mediated HIV pathogenesis and HIV-associated neuropathogenesis. This review also provides an overview of the potential applications of EVs in developing novel therapeutic carriers for the treatment of HIV-infected individuals who smoke, and in the discovery of novel biomarkers that are associated with HIV-smoking interactions in the CNS.
Impact of interruptions on the duration of nursing interventions: A study in a chemotherapy unit.

OBJECTIVE To investigate interruptions during nursing interventions in a chemotherapy unit (sources and causes); measure their frequency, duration and the total elapsed time to complete the interventions. METHOD This is an observational analytical study performed using a digital stopwatch. It was conducted in a teaching hospital between 2015/2016. The interventions performed and their interruptions were mapped and classified according to the Nursing Interventions Classifications (NIC) taxonomy. RESULTS There were 492 interruptions recorded in the 107 hours observed, especially in indirect care interventions. They were mainly caused by nursing professionals (n = 289; 57.3%) to supply materials (n = 65; 12.8%) and exchange care information (n = 65; 12.8%). The duration of interruptions ranged from 0:08 to 9:09 (average 1:15; SD 1:03) minutes. On average, interventions took 2:16 (SD 0:27) minutes to complete without interruption; however, the average was 5:59 (SD 3:01) minutes when interrupted. CONCLUSION The interruptions were constant during the nursing work in the chemotherapy unit, including during the preparation and administration of medications, and increased the time to complete the interventions by an average of 163.9%.
Micro-stepping extended focus reduces photobleaching and preserves structured illumination super-resolution features

ABSTRACT Despite progress made in confocal microscopy, even fast systems still have insufficient temporal resolution for detailed live-cell volume imaging, such as tracking rapid movement of membrane vesicles in three-dimensional space. Depending on the shortfall, this may result in undersampling and/or motion artifacts that ultimately limit the quality of the imaging data. By sacrificing detailed information in the Z-direction, we propose a new imaging modality that involves capturing fast ‘projections’ from the field of depth and shortens imaging time by approximately an order of magnitude as compared to standard volumetric confocal imaging. With faster imaging, radiation exposure to the sample is reduced, resulting in less fluorophore photobleaching and potential photodamage. The implementation minimally requires two synchronized control signals that drive a piezo stage and trigger the camera exposure. The device generating the signals has been tested on spinning disk confocal and instant structured-illumination-microscopy (iSIM) microscopes. Our calibration images show that the approach provides highly repeatable and stable imaging conditions that enable photometric measurements of the acquired data, in both standard live imaging and super-resolution modes. This article has an associated First Person interview with the first author of the paper. Summary: We present an upgrade to spinning disk confocal microscopes that dramatically improves photon balance and imaging speed for various imaging applications in projections, while simultaneously preserving super-resolution features.
Detection of Hepatocellular Carcinoma in CT Images Using Deep Learning

– The purpose of this paper is to develop a method to detect hepatocellular carcinoma, namely liver cancer in CT (Computerized Tomography) images using the deep learning that is a kind of AI (Artificial Intelligence). Firstly, the learning and recognition programs were developed using Python as a programming language and TensorFlow provided by Google that is a machine learning library. The CT images of 30 clinical subjects were selected from the DICOM format data provided by Graduate School of Medicine of Ehime University. Then 150 sets of CT images were selected where one set consists of two CT images for early and late phases in the cases with hepatocellular carcinoma. In addition, 150 sets of CT images were also selected in the cases without hepatocellular carcinoma. The 450 sets of CT images to each the 150 sets, namely 900 sets in total were created by rotating each original CT image. Consequently, 1,200 sets of CT images (2,400 CT images) in total were used for the learning. Then validity and usefulness of the learning and recognition programs were proved by examining the calculated results. This time, the hepatocellular carcinoma could be detected with relatively high sensitivity of 92.2% even with a relatively small number of learning data, namely 1,200 sets of CT images.
Exploring the Synergy between PARP and CHK1 Inhibition in Matched BRCA2 Mutant and Corrected Cells

PARP inhibition results in the accumulation of DNA SSBs, causing replication stress (RS) and lesions that can only be resolved by homologous recombination repair (HRR). Defects in HRR, e.g., due to BRCA2 mutation, confer profound sensitivity to PARP inhibitor (PARPi) cytotoxicity. In response to RS, CHK1 is activated to signal to S and G2/M cell cycle checkpoints and also to HRR. To determine the relative contribution of these two functions of CHK1 to survival following PARPi exposure, we investigated the effects of rucaparib (a PARPi) and PF-477736 (a CHK1 inhibitor) alone and in combination in cells with mutated and corrected BRCA2. The BRCA2 mutated V-C8 cells were 1000× more sensitive to rucaparib cytotoxicity than their matched BRCA2 corrected V-C8.B2 cells, but no more sensitive to PF-477736 despite having seven-fold higher levels of RS. PF-477736 caused a five-fold enhancement of rucaparib cytotoxicity in the V-C8.B2 cells, but no enhancement in the V-C8 cells. This differential sensitivity was not due to a difference in PARP1 or CHK1 expression or activity. PF-477736 increased rucaparib-induced RS (γH2AX foci) and completely inhibited RAD51 focus formation, indicating a profound suppression of HRR. Our data suggested that inhibition of HRR was the main mechanism of sensitisation to rucaparib, compounded with an inhibition of cell cycle checkpoints by PF-477736.
Lehrbuch Assessments in der Rehabilitation

Assessments (Testund Messverfahren) gewinnen immer mehr Bedeutung zur Beurteilung von Gesundheitszustand und Funktionsfähigkeit von Patienten und zur Kontrolle des Therapieverlaufs. Assessments sind eine systematische Form der Patientenuntersuchung. Sie dienen einerseits zur Identifikation von Schwächen, Funktionsdefiziten und Risikofaktoren, können aber auch im Sinne der ICF Fähigkeiten und Fertigkeiten als Ressourcen erfassen. Praktikable, standardisierte, klinisch relevante, zuverlässige, valide und verlaufsempfindliche Assessments machen die Individualität des Patienten, im Gegensatz zu beschreibenden Berichten, messbar.
RF Channel-Selectivity Sensing by a Small Antenna of Metamaterial Channel Filters for 5G Sub-6-GHz Bands

In this paper, a new small antenna is suggested for 5G Sub-6-GHz band mobile communication. It can change the channel among the three given bands (called the 3.5-GHz area), as a wide-band antenna is connected to a small multiplexer comprising three metamaterial channel filters. The function of channel selection of this antenna system is experimentally demonstrated to prove the validity of the presented scheme. The channel selection for 5G mobile communication is conducted from f1 (channel 1) through f2 (channel 2) to f3 (channel 3), when TX and RX antennas with gains over 0 dBi and S11 less than −10 dB are located far-field apart (RFar ≫ 2.1 cm), and result in the transmission coefficient (S21) being the greatest at the selected channel, which is detected by a vector network analyzer.
The prevalence of germline mutations in Chinese colorectal cancer patients with mismatch repair deficiency.

e13518Background: Mismatch repair deficiency (dMMR) assessed by microsatellite instability (MSI) or immunohistochemistry (IHC) is a feature of Lynch syndrome, a major hereditary colorectal cancer (CRC). Chinese Lynch syndrome criteria was proposed based on the decreasing family numbers: In a pedigree, it should have at least 2 CRCs, and at least 2 of them are first-degree relatives of each other. Besides, any one of following criteria should be met: 1) at least 1 CRC should have multiple primary synchronous/metachronous colorectal carcinoma/adenoma; 2) at least 1 CRC should be diagnosed before 50 years old; 3) in the pedigree, at least 1 should be diagnosed with other Lynch syndrome-related cancer (i.e. gastric, endometrial, small bowel, ureter, or renal-pelvic, ovarian and hepatobiliary cancers). The purpose of this multi-center study is to derive prevalence of germline mutations in Chinese dMMR CRC, especially taking different screen criteria for Lynch syndrome into consideration. Methods: ColonCore pan.
Food-Grade PE Recycling: Effect of Nanoclays on the Decontamination Efficacy

Although PE-based nanocomposites are gaining interest within the food packaging industry for their outstanding functional properties, their end-of-life has been poorly studied. The lack of identification of such materials suggests that they could end-up in the recycling pathway optimized for the decontamination of un-filled PE. The objective of the present work is to understand and quantify the mechanisms involved in the high temperature desorption of surrogates for PE nanocomposites filled with organo-modified montmorillonite (PNC), compared to conventional PE. An original experimental setup was coupled with a modelling approach to identify the two phenomena involved in the decontamination process: diffusion of the surrogate into the bulk and its evaporation at the surface. A sweep of experimental temperatures enabled the determination of diffusion and evaporation parameters for PE and PNC and the activation energies related to the diffusivity among those two materials. The effects of the introduction of clay nanofillers onto the decontamination process have been explained and recommendations for the recycling pathway have been put forward.
Border closure for island nations? Analysis of pandemic and bioweapon‐related threats suggests some scenarios warrant drastic action

The risk to human populations from new and pandemic infectious agents has probably never been higher.1,2 Synthetic bioweapons are an additional threat. Two recent publications have speculated on the possibility of island nation refuges closing their borders to protect a human population against a catastrophic pandemic that poses an existential risk to humanity.3,4 The most recent paper described an index based on characteristics of an island nation’s population, location, resources and society. The authors used this index to conclude that Australia and New Zealand are the island nations most likely to be able to be both isolated from the rest of humanity in a pandemic and to also have the resources to reboot a thriving technological society following a pandemic that devastated the rest of global society as we know it, thereby acting as ‘island refuges’. 4 Previous analysis in this journal has argued the economic case for border closure by island nations in the face of extreme pandemics.5 This work reported that 100 per cent border closure for six months by New Zealand, that results in the country avoiding any pandemic cases, could have a net present value of NZ$7.86 (US$5.29) billion for its “Scenario A” (involving half the mortality rate of the 1918 influenza pandemic) and NZ$144 (US$96.9) billion for preventing a pandemic with 10 times this mortality. There is evidence for travel restrictions being successful in controlling the spread of influenza between countries, and small islands successfully used protective sequestration and maritime quarantine to avoid the 1918–1919 influenza pandemic ). However, the 1918- 19 pandemic still appeared to reach most of the world’s islands. Drastic measures such as border closure have potentially large benefits (if successful) but also potentially major harmful consequences including economic harm. Some of these potential trade-offs are illustrated by the 2014 Ebola outbreak where the GDP of countries affected fell by 12% during the emergency even without successful complete border closures. The question remains, which pandemics, if any, might ever plausibly justify partitioning a segment of the human population through border closure by island nations to reduce major burdens of morbidity and mortality? It is this question we address in the present commentary.
Bariatric Surgery Improves HDL Function Examined by ApoA1 Exchange Rate and Cholesterol Efflux Capacity in Patients with Obesity and Type 2 Diabetes

Bariatric surgery improves glycemic control better than medical therapy; however, the effect of bariatric surgery on HDL function is not well characterized. Serum samples were available at baseline, 1-, and 5-years post procedures, for 90 patients with obesity and type 2 diabetes who were randomized to intensive medical therapy (n = 20), Roux-en-Y gastric bypass (RYGB, n = 37), or sleeve gastrectomy (SG, n = 33) as part of the STAMPEDE clinical trial. We examined serum HDL function by two independent assays, apolipoprotein A-1 exchange rate (AER) and cholesterol efflux capacity (CEC). Compared with baseline, AER was significantly higher at 5 years for participants in all treatment groups, but only increased significantly at 1 year in the RYGB and SG groups. CEC was divided into ABCA1-dependent and independent fractions, and the later was correlated with AER. ABCA1-independent CEC increased significantly only at 5 years in both surgical groups, but did not significantly change in the medical therapy group. There was no significant change in ABCA1-dependent CEC in any group. The increase in AER, but not ABCA1-independent CEC, was correlated with the reduction in body mass index and glycated hemoglobin levels among all subjects at 5 years, indicating that AER as a measure of HDL function would be a better reflection of therapy versus CEC.
Chemokines and chemokine receptors: A new strategy for breast cancer therapy

Chemokines and chemokine receptors not only participate in the development of tissue differentiation, hematopoiesis, inflammation, and immune regulation but also play an important role in the process of tumor development. The role of chemokines and chemokine receptors in tumors has been emphasized in recent years. More and more studies have shown that chemokines and chemokine receptors are closely related to the occurrence, angiogenesis, metastasis, drug resistance, and immunity of breast cancer. Here, we review recent progression on the roles of chemokines and chemokine receptors in breast cancer, and discuss the possible mechanism in breast cancer that might facilitate the development of new therapies by targeting chemokines as well as chemokine receptors. Chemokines and chemokine receptors play an important role in the occurrence and development of breast cancer. In‐depth study of chemokines and chemokine receptors can provide intervention targets for breast cancer biotherapy. The regulation of chemokines and chemokine receptors may become a new strategy for breast cancer therapy.
Patterns of Late Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with T-Cell Prolymphocytic Leukemia

Initial treatment with the monoclonal anti-CD52 antibody alemtuzumab induces responses in the majority of patients with T-cell prolymphocytic leukemia (T-PLL). In eligible patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an option to consolidate hematological remissions. Here, we report our experience with 10 patients who received allo-HSCT against T-PLL. Notably, 3 patients with complete remission at transplantation and durable full-donor chimerism relapsed at months 12, 59, and 84 after transplantation, respectively. This relapse was associated with rapid progressive leukemia in 1 patient and extralymphatic lymphoma growth in the other 2. Despite CD52 positivity at relapse, alemtuzumab retreatment, donor lymphocyte infusions, and/or chemotherapy including salvage therapy, allo-HSCT yielded a transient partial response, only. Alemtuzumab induction and consolidative allo-HSCT enabled prolonged disease-free survival in these patients but failed to procure cure.
Shenmai injection suppresses multidrug resistance in MCF-7/ADR cells through the MAPK/NF-κB signalling pathway

Abstract Context Shenmai Injection (SMI) is usually used to treat atherosclerotic coronary heart disease and viral myocarditis in China. However, the effect of SMI on multidrug resistance has not been reported. Objective To investigate the reversal effect of SMI in adriamycin (ADR) resistant breast cancer cell line (MCF-7/ADR) and explore the related molecular mechanisms. Materials and methods The effect of SMI (0.25, 0.5, 1 mg/mL) to reverse chemoresistance in MCF-7/ADR cells was elucidated by MTT, HPLC-FLD, DAPI staining, flow cytometric analysis, western blotting. At the same time, in vivo test was conducted to probe into the effect of SMI on reversing ADR resistance, and verapamil (10 μM) was used as a positive control. Results The results showed that the toxicity of ADR to MCF-7/ADR cells was strengthened significantly after treated with SMI (0.25, 0.5, 1 mg/mL), the IC50 of ADR was decreased 54.4-fold. The intracellular concentrations of ADR were increased 2.2-fold (p < 0.05) and ADR accumulation was enhanced in the nuclei (p < 0.05). SMI could strongly enhance the ADR-induced apoptosis and increase intracellular rhodamine 123 accumulation in MCF-7/ADR cells. Additionally, a combination of ADR and SMI (5 mg/kg) could dramatically reduce the weight and volume of tumour (p < 0.05). Furthermore, the results revealed that SMI might reverse MDR via inhibiting ADR-induced activation of the mitogen-activated protein kinase/nuclear factor (NF)-κB pathway to down-regulated the expression of P-glycoprotein (P-gp). Discussion and conclusions SMI could potentially be used to treat ADR-resistance. This suggests possibilities for future clinical research.
The window of opportunity for treatment of progressive multiple sclerosis.

PURPOSE OF REVIEW Based on the knowledge of disease mechanisms in the progressive course of multiple sclerosis and the experience from randomized clinical trials, we assessed the timing of disease-modifying therapy in patients with progressive multiple sclerosis to define the optimal window of opportunity for treatment of progressive multiple sclerosis. RECENT FINDINGS In progressive multiple sclerosis both small molecules that cross the blood--brain barrier (siponimod) and monoclonal antibodies (ocrelizumab) have shown therapeutic efficacy and have been approved for treatment of progressive multiple sclerosis. However, the majority of phase II and phase III trials in progressive forms of multiple sclerosis have been negative, probably owing to either late start of treatment or use of drugs that are ineffective for treatment of progressive multiple sclerosis. SUMMARY Results from phase II and III trials suggest that the window of opportunity for treatment of progressive multiple sclerosis with anti-inflammatory drugs is predominantly in the early phase of the progressive disease course when patients have lower age, shorter duration of progressive multiple sclerosis, and more pronounced clinical and MRI inflammatory activity. Ongoing trials of neuroprotective drugs may widen the window of opportunity by expanding targeted pathophysiologies.
A comparative study on accuracy and fatigue in hands-only CPR and traditional CPR by voice instruction

Purpose : The purpose of the present study is to analyze the accuracy and fatigue felt by lay persons receiving CPR training when they perform hands only CPR (HOCPR) and traditional CPR (TCPR). The performance of CPR data will provide the criteria of dispatcher guidelines for the general public. Methods : For 2 minutes duration, HOCPR was conducted by 51 subjects and TCPR was conducted by 48 subjects. The accuracy measurement of chest compressions was based on the 2010 AHA guideline; the subjective fatigue level in before and after experiment was measured by a self-administered questionnaire. Results : There were no significant differences between the average depth, chest compression depth and chest compression location in terms of chest compression accuracy. However, there were significant differences between the two experimental groups in the accuracies for average speed and chest compression speed. The subjective fatigue level showed no significant difference. Conclusion : The experimental group performing HOCPR showed more accurate compression speed and lower fatigue level. These results suggested that HOCPR would be more effective in training the lay persons in accordance with the voice-instructed CPR.
Management of Traumatic Brain Injury: From Present to Future

TBI (traumatic brain injury) is a major cause of death among youth in industrialized societies. Brain damage following traumatic injury is a result of direct and indirect mechanisms; indirect or secondary injury involves the initiation of an acute inflammatory response, including the breakdown of the blood–brain barrier (BBB), brain edema, infiltration of peripheral blood cells, and activation of resident immunocompetent cells, as well as the release of numerous immune mediators such as interleukins and chemotactic factors. TBI can cause changes in molecular signaling and cellular functions and structures, in addition to tissue damage, such as hemorrhage, diffuse axonal damages, and contusions. TBI typically disturbs brain functions such as executive actions, cognitive grade, attention, memory data processing, and language abilities. Animal models have been developed to reproduce the different features of human TBI, better understand its pathophysiology, and discover potential new treatments. For many years, the first approach to manage TBI has been treatment of the injured tissue with interventions designed to reduce the complex secondary-injury cascade. Several studies in the literature have stressed the importance of more closely examining injuries, including endothelial, microglia, astroglia, oligodendroglia, and precursor cells. Significant effort has been invested in developing neuroprotective agents. The aim of this work is to review TBI pathophysiology and existing and potential new therapeutic strategies in the management of inflammatory events and behavioral deficits associated with TBI.