Miracle-dz/UniFAR-FTUs huggingface dataset:
Patient specific parameter thresholding to support domiciliary monitoring in COPD

Introduction: Domiciliary monitoring is increasingly used in COPD. There is a trade off between the number of false-alarms raised by such systems and the sensitivity of the system to detect exacerbations. Arbitrary limits are often set, but we hypothesised that limits set for an individual patient based on an assessment of their own data would increase the sensitivity and specificity of monitoring. Here we report the effect on false-alarm calls. Based on the American guidelines, normal heart rate is 60 – 100 bpm and standard SpO2 is ≥ 95%. Aim: Set the appropriate alarm limits to an individual patient to reduce the number of false alarms. Method: In this pilot study, we recorded five weeks of HR and SpO2 %, data were collected once each day prospectively from 8 COPD patients from the domiciliary telehealth project following pulmonary rehabilitation. Data collected in the first two weeks were used to set the appropriate limits for each patient by calculating the mean and SD over that period, and setting the alarm at +/- 1.5 and 1.96 SD. Result: The mean age of 8 Patients was 69.6 years (10.47 SD), 75% males, and FEV1% mean 42% (19.7 SD). The table shows the alarm frequency for each algorithm. Results are expressed as alarms/day. Setting alarms by individual parameters versus did not alter the frequency of HR alarms but reduced the frequency of SpO2 alarms. Conclusion: In this study we show that alarm rates vary by arbitrary versus patient specific thresholding. We were able to decrease the false alarms and reduce the volume of calls on the team.
Food Science of Animal Resources

In this study, ovalbumin (OVA) hydrolysates were prepared using various proteolytic enzymes and the anti-inflammatory activities of the hydrolysates were determined. Also, the potential application of OVA as a functional food material was discussed. The effect of OVA hydrolysates on the inhibition of nitric oxide (NO) production was evaluated via the Griess reaction, and their effects on the expression of inducible NO synthase (inducible nitric oxide synthase, iNOS) were assessed using the quantitative real-time PCR and Western blotting. To determine the mechanism by which OVA hydrolysates activate macrophages, pathways associated with the mitogen-activated protein kinase (MAPK) signaling were evaluated. When the OVA hydrolysates were added to RAW 264.7 cells without lipopolysaccharide (LPS) stimulation, they did not affect the production of NO. However, both the OVA-Protex 6L hydrolysate (OHPT) and OVA-trypsin hydrolysate (OHT) inhibited NO production dose-dependently in LPSstimulated RAW 264.7 cells. Especially, OHT showed a strong NO-inhibitory activity (62.35% at 2 mg/mL) and suppressed iNOS production and the mRNA expression for iNOS (p<0.05). Also, OHT treatment decreased the phosphorylation levels of Jun aminoterminal kinases (JNK) and extracellular signal-regulated kinases (ERK) in the MAPK signaling pathway. These findings suggested that OVA hydrolysates could be used as an anti-inflammatory agent that prevent the overproduction of NO.
Mesoporous silica particles as potential carriers for protein drug delivery: protein immobilization and the effect of displacer on γ-globulin release

Abstract The adsorption of γ-globulin was evaluated with experiments with silica particles marketed as Syloid AL1-FP (SAL), XDP-3150 (SXDP), and 244FP (SFP). The influence of pH, pore sizes, and degree of surface porosity on the extent of γ-globulin immobilization was examined. Protein adsorption on these particles was largely related to their surface porosity and pore sizes. The adsorption capacity was established to be greater with mesoporous SFP and SXDP particles at 474 and 377 mg/g, respectively, when compared to significantly low-porosity SAL (16 mg/g). Additionally, γ-globulin immobilization was favored at pH closer to iso-electric point. A key aim of this work was to better understand and improve the limited reversibility of protein adsorption. Protein desorption was found to be lower in simulated intestinal fluid (SIF) in comparison to pH 7.4 phosphate buffer (PB). The use of displacer molecules (sodium dodecyl sulfate [SDS]/Tween 80/Pluronic F127 [PF127]) promoted protein desorption from the adsorbent surface by the exchange mechanism. The PF127 provided substantial release in both studied condition but the highest release of 83% of γ-globulin from SXDP was obtained with tween 80 in PB. The released protein was analyzed with circular dichroism (CD) spectroscopy which indicated that the secondary structure of desorbed γ-globulin was dependent on the pH and displacer molecule. The conformation largely remained unchanged when desorption was carried out in SIF but changed markedly in PB specially in the presence of SDS.
Changes in cell membrane fatty acid composition of Streptococcus thermophilus in response to gradually increasing heat temperature.

In this study, a method of heat adaptation was implemented in an attempt to increase the upper thermal threshold of two Streptococcus thermophilus found in South Korea and identified the alterations in membrane fatty acid composition to adaptive response to heat. In order to develop heat tolerant lactic acid bacteria, heat treatment was continuously applied to bacteria by increasing temperature from 60°;C until the point that no surviving cell was detected. Our results indicated significant increase in heat tolerance of heat-adapted strains compared to the wild type (WT) strains. In particular, the survival ratio of basically low heat-tolerant strain increased even more. In addition, the strains with improved heat tolerance acquired cross protection, which improved their survival ratio in acid, bile salts and osmotic conditions. A relation between heat tolerance and membrane fatty acid composition was identified. As a result of heat adaptation, the ratio of unsaturated to saturated fatty acids (UFA/SFA) and C18:1 relative concentration were decreased. C6:0 in only heat-adapted strains and C22:0 in only the naturally high heat tolerant strain were detected. These results support the hypothesis, that the consequent increase of SFA ratio is a cellular response to environmental stresses such as high temperatures, and it is able to protect the cells from acid, bile salts and osmotic conditions via cross protection. This study demonstrated that the increase in heat tolerance can be utilized as a mean to improve bacterial tolerance against various environmental stresses.
Workplace Stress in the University Clinical Settings: Comparison between the Cardiac Unit snd Emergency Center Medical Staff.

BACKGROUND Stress at work is a specific type of stress arising from the work environment. Stress of the medical staff has been investigated in recent years by the medical institutions of different countries. The aim of this study was to examine the stress levels in medical staff of Department of Cardiac Surgery and Center of emergency medicine (CEM) in the Clinical settings, and to compare them. SUBJECTS AND METHODS We conducted a cross-sectional study which included 55 patients between 21 and 50 years of age. The study group consisted of 30 employees from the Department of Cardiac Surgery of Mostar University Clinical Hospital, while the control group comprised 25 employees from the CEM. Research instruments were the Occupational Stress Questionnaire for Hospital Health Care Workers (OSQ-HHCW), General Health Questionnaire (GHQ 28) and a Stress MGMT-TEST A. RESULTS The subjects from the control group had significantly higher stress experience in "bombing" with new information (p=0.028), unavailability of literature (p=0.039), poor communication with superiors (p<0.001), conflicts with patients (p=0.042) and inappropriate public criticism (p=0.007). The highest stress level showed F1 group of stressors, concerning the organization of work and funding. CEM employees had statistically significantly higher level of stress on public criticism and lawsuits compared to the study group (p=0.013), as well as higher score on the anxiety/insomnia subscale (p<0.001), social dysfunction scale (p=0.002) and on the depression subscale (p<0.001). CONCLUSIONS Stressors from the group of organizational factors have proven to be the most common stressors in both groups. However, in some areas within the impact of workplace stress, CEM employees had significantly greater vulnerability compared to employees of the Department of cardiac surgery. Further studies are needed to establish the frequency and intensity of stress among health professionals, and to clearly determine the risk factors for its development.
Destruction of a Microtubule-Bound MYC Reservoir during Mitosis Contributes to Vincristine's Anticancer Activity

Tightly regulated activity of the transcription factor MYC is essential for orderly cell proliferation. Upon deregulation, MYC elicits and promotes cancer progression. Proteasomal degradation is an essential element of MYC regulation, initiated by phosphorylation at Serine62 (Ser62) of the MB1 region. Here, we found that Ser62 phosphorylation peaks in mitosis, but that a fraction of nonphosphorylated MYC binds to the microtubules of the mitotic spindle. Consequently, the microtubule-destabilizing drug vincristine decreases wild-type MYC stability, whereas phosphorylation-deficient MYC is more stable, contributing to vincristine resistance and induction of polyploidy. PI3K inhibition attenuates postmitotic MYC formation and augments the cytotoxic effect of vincristine. Implications: The spindle's function as a docking site for MYC during mitosis may constitute a window of specific vulnerability to be exploited for cancer treatment.
Experience of Job Stress among Nurses Working in Long-term Care Hospital: A Phenomenological Approach

Purpose: The purpose of this study was to explore the subjective experience of job stress among nurses working in long-term care hospitals. Methods: A phenomenological approach was used for the study. Data were collected from May to June, 2016 using open-ended questions during in-depth interviews. Participants were nurses working in long-term care hospitals and had reported experiences of stress. Six nurses participated in this study. Results: Six themes emerged from the analysis using Colaizzi ’ s method: (a) Heavy workload and responsibility due to nurse shortage, (b) Getting exhausted by caring for cognitively impaired patients, (c) Feeling pressure due to conflict with patients ’ family, (d) compassion for patients who are getting worse, (e) Low value in being a long-term hospital nurse, and (f) Efforts to overcome stress. Conclusion: Sufficient labor supply, environmental improvements, pro-gram for improving interpersonal skills, education and counseling on end-of-life care, and recognition improve-ment about long term hospital are suggested to reduce the job stress of long-term hospital nurses.
Optimization of Nebulized Budesonide in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Background Clinical studies have suggested nebulized budesonide (NB) as an alternative to systemic corticosteroids for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, the optimal budesonide dose for AECOPD remains unclear. Objectives To compare the efficacy and safety of different doses of NB in the management of AECOPD. Patients and Methods A total of 321 AECOPD patients with moderate-to-severe exacerbation were randomly divided into three groups and treated with NB. The low dose group (L) was given 4 mg/day (n=95, 1 mg Q6h), while high-dose group 1 (H1, n=111, 2 mg Q6h) and high-dose group 2 (H2, n=115, 4 mg Q12h) were given 8 mg/day. Patients also received routine treatment including oxygen therapy, expectorant, nebulization bronchodilators, antibiotics, and fluid rehydration. The COPD assessment test (CAT), lung function, and artery blood gas were evaluated before and after 3 hrs and 5 days of treatment. In addition, hospital stay, frequency of acute exacerbations within 3 months of discharge, and adverse events during treatment were compared. Results H1 and H2 showed improved spirograms and CAT score faster than L. In H2, forced expiratory volume in 1 s (FEV1%) at 3 hrs and FEV1%, forced expiratory flow after 50% of the forced vital capacity has been exhaled (FEF50%), mean forced expiratory flow between 25% and 75% of forced vital capacity (FEF25–75%) and CAT score at 5 days were significantly improved compared to L. FEV1% improved most in H2, moderately in H1, and least in L, with significant differences between groups at 5 days. No differences between groups were observed in adverse effects, hospital stay, and frequency of exacerbations within 3 months of discharge. Conclusion Compared to the conventional dose (4 mg/day), a high dose (8 mg/day) of NB improved pulmonary function and symptoms more effectively in the early treatment of AECOPD, especially when given as 4 mg twice daily.
The First Known Case of Liver Abscess Caused by Aggregatibacter aphrophilus in Japan

A 48-year-old man presented with a sustained fever. Abdominal computed tomography revealed multilocular liver abscesses. He underwent percutaneous needle aspiration, yielding straw-colored pus. Gram staining revealed Gram-negative coccobacilli. The organism grew only on chocolate II agar in a 7% carbon dioxide atmosphere. Identification of Aggregatibacter aphrophilus was confirmed using mass spectrometry and 16S rRNA gene sequencing. He was successfully treated with antibiotics. Liver abscess caused by A. aphrophilus is extremely rare. We herein report the first such case in Japan. Even fastidious organisms, such as A. aphrophilus, should be correctly identified using mass spectrometry or 16S rRNA gene sequencing for adequate treatment.
Temporal specificity and heterogeneity of Drosophila immune cells

Immune cells provide defense against non‐self and have recently been shown to also play key roles in diverse processes such as development, metabolism, and tumor progression. The heterogeneity of Drosophila immune cells (hemocytes) remains an open question. Using bulk RNA sequencing, we find that the hemocytes display distinct features in the embryo, a closed and rapidly developing system, compared to the larva, which is exposed to environmental and metabolic challenges. Through single‐cell RNA sequencing, we identify fourteen hemocyte clusters present in unchallenged larvae and associated with distinct processes, e.g., proliferation, phagocytosis, metabolic homeostasis, and humoral response. Finally, we characterize the changes occurring in the hemocyte clusters upon wasp infestation, which triggers the differentiation of a novel hemocyte type, the lamellocyte. This first molecular atlas of hemocytes provides insights and paves the way to study the biology of the Drosophila immune cells in physiological and pathological conditions.
Detecting Lung Cancer Trends by Leveraging Real-World and Internet-Based Data: Infodemiology Study

Background Internet search data on health-related terms can reflect people’s concerns about their health status in near real time, and hence serve as a supplementary metric of disease characteristics. However, studies using internet search data to monitor and predict chronic diseases at a geographically finer state-level scale are sparse. Objective The aim of this study was to explore the associations of internet search volumes for lung cancer with published cancer incidence and mortality data in the United States. Methods We used Google relative search volumes, which represent the search frequency of specific search terms in Google. We performed cross-sectional analyses of the original and disease metrics at both national and state levels. A smoothed time series of relative search volumes was created to eliminate the effects of irregular changes on the search frequencies and obtain the long-term trends of search volumes for lung cancer at both the national and state levels. We also performed analyses of decomposed Google relative search volume data and disease metrics at the national and state levels. Results The monthly trends of lung cancer-related internet hits were consistent with the trends of reported lung cancer rates at the national level. Ohio had the highest frequency for lung cancer-related search terms. At the state level, the relative search volume was significantly correlated with lung cancer incidence rates in 42 states, with correlation coefficients ranging from 0.58 in Virginia to 0.94 in Oregon. Relative search volume was also significantly correlated with mortality in 47 states, with correlation coefficients ranging from 0.58 in Oklahoma to 0.94 in North Carolina. Both the incidence and mortality rates of lung cancer were correlated with decomposed relative search volumes in all states excluding Vermont. Conclusions Internet search behaviors could reflect public awareness of lung cancer. Research on internet search behaviors could be a novel and timely approach to monitor and estimate the prevalence, incidence, and mortality rates of a broader range of cancers and even more health issues.
TBK1 regulates YAP/TAZ and fibrogenic fibroblast activation.

Idiopathic pulmonary fibrosis (IPF) results in scarring of the lungs by excessive extracellular matrix (ECM) production. Resident fibroblasts are the major cell type involved in ECM deposition. The biochemical pathways that facilitate pathological fibroblast activation leading to aberrant ECM deposition are not fully understood. Tank Binding Protein Kinase-1 (TBK1), is a kinase that regulates multiple signaling pathways, and was recently identified as a candidate regulator of fibroblast activation in a large-scale siRNA screen. In order to determine the effect of TBK1 on fibroblast activation, TBK1 was inhibited pharmacologically (MRT68601) and genetically (siRNA) in normal and IPF human lung fibroblasts. Reducing the activity or expression of TBK1 led to reduction in α-SMA stress fiber levels by 40-60% and deposition of ECM components collagen I and fibronectin by 50% in TGF-β stimulated normal and IPF fibroblasts. YAP and TAZ are homologous mechanoregulatory, profibrotic transcription co-factors known to regulate fibroblast activation. TBK1 knockdown or inhibition decreased the total and nuclear protein levels of YAP/TAZ. Additionally, low cell-cell contact and increased ECM substrate stiffness augmented the phosphorylation and activation of TBK1, consistent with cues that regulate YAP/TAZ. The action of TBK1 towards YAP/TAZ activation was independent of LATS1/2 and canonical downstream TBK1 signaling mediator IRF3, but dependent on proteasomal machinery of the cell. This study identifies TBK1 as a fibrogenic activator of human pulmonary fibroblasts, suggesting TBK1 may be a novel therapeutic target in pulmonary fibrosis.
Psychophysiological anxiety response of a rescue helicopter crew in a crane rescue manoeuvre

Background This research aimed to analyse the psychophysiological modifications of a rescuer helicopter crew in a crane rescue manoeuvre. Methods We analysed in eight participants (32.5±6.6 years) divided in four categories (pilot, mechanic, rescuer and control) with variables of anxiety, rating of perceived exertion (RPE), stress subjective perception (SSP), heart rate, blood oxygen saturation (BOS), skin temperature, blood lactate, cortical arousal, autonomic modulation, legs and hands strength, legs flexibility, spirometry, urine, and short-term memory before and after a helicopter crane rescue manoeuvre. Results The manoeuvre produced a significant (p≤0.05) increment in the RPE, SSP, anxiety, blood lactate and sympathetic modulation, and a decrease in BOS and pulmonary capacity. Conclusion A helicopter rescue crane manoeuvre produced an increase in the sympathetic nervous system modulation, increasing the psychophysiological response of the crew independently of their experience or role. This information allowed us to improve actual specific operative training in this population.
Postbiotics: A novel strategy in food allergy treatment

Abstract During the last two decades, the prevalence and severity of clinical appearances of food allergy (FA) have a significant rise. FA derives from a breakdown of immune tolerance. In recent year’s clinical evidence have shown that the probiotics have significant influences on FA by improving the immune tolerance. Besides, postbiotics due to their unique characteristics (safe profile, more shelf life, resistance to mammalian enzymes and stable to digestive system conditions), may have safety superiority against their parent live cells and as a novel strategy can be applied for improvement immune tolerance and treatment of FA without any undesirable side-effects or human opportunistic infections, particularly in infants and pediatrics.
Are primary/elementary school‐based interventions effective in preventing/ameliorating excess weight gain? A systematic review of systematic reviews

This systematic review of systematic reviews addresses a current gap in evidence by synthesizing findings relating to weight management interventions set entirely in primary/elementary schools targeting, diet, and/or physical activity as key strategies. Eight databases were searched for systematic reviews of trials of school‐based interventions targeting children aged 4 to 12 years that looked at biometric and behavioral outcomes. From the 10 selected systematic reviews, we found that interventions designed to promote physical activity or reduce sedentary behavior were most effective for weight loss. Interventions designed to improve diet and nutrition had a small effect on behavioral and cognitive outcomes, and these outcomes could be enhanced through the use of experiential learning. The most effective interventions involved a range of stakeholders in the development process and included parents and families in implementation. This systematic review of systematic reviews offers evidence‐based guidance for the development and implementation of multistrategy weight‐management interventions in primary/elementary schools.
Improved Myeloma Targeting by Combination of the Human Anti-CD38 Antibody Daratumumab with Lenalidomide and Bortezomib

Abstract 3030 Although multiple myeloma (MM) is considered an incurable malignancy of antibody-producing clonal plasma cells, over the past decade significant progress has been made in MM treatment by the availability of novel immunomodulating agents such as lenalidomide (LEN) and bortezomib (BORT). We are currently exploring the possibility to further improve MM therapy by combining LEN and BORT with novel agents, such as daratumumab (DARA), a human antibody directed against CD38 which mediates MM cell lysis via ADCC (antibody dependent cellular cytotoxicity), CDC (complement dependent cytotoxicity) and apoptosis. Our initial in vitro work show significantly improved MM cell killing by combined DARA with LEN treatment. We now investigated whether further improvement of this combination therapy is possible by addition of BORT. In ex vivo assays, which allow us to address killing directly in BM-MNC isolated from MM patients, we demonstrate that the DARA+LEN+BORT combination significantly exceeds the effectiveness of LEN+BORT treatment (P<0.001). Remarkably, triple therapy was also very effective, even when there was little or no response against LEN+BORT (P=0.0001). In other assays we further mimicked the in vivo conditions by incubating BM-MNC not only with LEN, BORT and DARA for 48 hours but also by adding complement. Addition of complement resulted in substantial enhancement of DARA-mediated MM tumor cell killing. This killing could not be further improved by addition of LEN and BORT. In conclusion, we demonstrate that addition of DARA to a LEN+BORT treatment regime increases overall clearance of MM cells ex vivo , suggesting that patients, even when not responding to LEN+BORT treatment, might benefit from a DARA+LEN+BORT combination therapy. Disclosures: Veer: GenMab, Utrecht, NL: Research Funding. Weers: Genmab: Employment. Bakker: GenMab, Utrecht, Netherlands: Employment. Parren: Genmab: Employment. Lokhorst: GenMab, Utrecht,NL: Research Funding. Mutis: GenMab, Utrecht, NL: Research Funding.