Miracle-dz/UniFAR-FTUs huggingface dataset:
Avoiding insufficient therapies and overdosing with co-reporting eGFRs (estimated glomerular filtration rate) for personalized drug therapy and improved outcomes – a simulation of the financial benefits

Patients with impaired renal function are at high risk for morbidity and mortality. Chronic kidney disease (CKD) even in the early stages can be associated with significant side effects of drug therapy, longer length of stay, and high costs. Correct assessment of renal function in the hospital is important to detect CKD, to avoid further damage to the kidneys, and to optimize pharmacological therapy. Current protocols for renal function testing in drug dosing are only creatinine based, are not robust enough, and can wrongly classify certain patients. Goal of our simulation study is to optimize noninvasive renal function estimates and to allow for optimal dosing of pharmacological treatment without further renal damage. Co-reporting of creatinine- and of cystatin C-derived estimated glomerular filtration rates (eGFR) allows a personalized approach for patients with large discrepancies in eGFR and it enabled us in detecting patients at high risk for side effects due to incorrect drug dosing. This approach might be highly effective for patients as well as for clinicians. In addition, we simulated the efficiency by estimating savings for the hospital administration and the payor with a benefit cost ratio of 58 to 1.
Anti-Apoptotic Effect of Apelin in Human Placenta: Studies on BeWo Cells and Villous Explants from Third-Trimester Human Pregnancy

Previously, we demonstrated the expression of apelin and G-protein-coupled receptor APJ in human placenta cell lines as well as its direct action on placenta cell proliferation and endocrinology. The objective of this study was to examine the effect of apelin on placenta apoptosis in BeWo cells and villous explants from the human third trimester of pregnancy. The BeWo cells and villous explants were incubated with apelin (2 and 20 ng/mL) alone or with staurosporine for 24 to 72 h. First, we analysed the dose- and time-dependent effect of apelin on the expression of apoptotic factors on the mRNA level by real-time PCR and on the protein level using Western blot. Next, we checked caspase 3 and 7 activity by Caspase-Glo 3/7, DNA fragmentation by the Cell Death Detection ELISA kit and oxygen consumption by the MitoXpress-Xtra Oxygen Consumption assay. We found that apelin increased the expression of pro-survival and decreased proapoptotic factors on mRNA and protein levels in both BeWo cells and villous explants. Additionally, apelin inhibited caspase 3 and 7 activity and DNA fragmentation in staurosporine-induced apoptosis as also attenuated oxidative stress by increasing extracellular oxygen consumption. The antiapoptotic effect of apelin in BeWo cells was mediated by the APJ receptor and mitogen-activated protein kinase (ERK1/2/MAP3/1) and protein kinase B (AKT). The obtained results showed the antiapoptotic effect of apelin on trophoblast cells, suggesting its participation in the development of the placenta.
The Impact of Depression Symptoms in Patients with Parkinson’s Disease: A Novel Case-Control Investigation

Parkinson’s disease is a common neurodegenerative disease and it is known to cause motor disturbances associated with musculoskeletal problems of the locomotor apparatus, and non-motor symptoms, that are believed to have a harmful effect on health, social functioning and mobility. The aim of this study was to evaluate depression in patients with Parkinson’s Disease (PD) compared to subjects who do not have it. The sample consisted of 124 participants (mean age 69.18 ± 9.12). Patients with PD were recruited from a center of excellence for Parkinson’s disease (cases n = 62) and healthy subjects without PD from their relatives and caregivers (control n = 62). The Spanish version of Beck’s Depression Inventory (BDI) scores and categories were collected. A clear statistically significant difference (p < 0.05) was evident in the BDI scores between both groups. Parkinson’s patients presented worse results on the BDI = 15.48 ± 7.24 points compared to healthy subjects with BDI = 7.03 ± 6.99 points. Regarding BDI categories, there were statistically significant differences (p < 0.001) for the greater BDI categories in the Parkinson’s group compared with healthy subjects. The depression represents an important potential risk for increased symptoms and negative impact among patients with PD compared with healthy subjects.
Exploiting albumin as a mucosal vaccine chaperone for robust generation of lung-resident memory T cells

Pulmonary immunization with albumin-binding peptide vaccines promotes resident memory CD8+ T cell generation in the lung. Chaperoned vaccine primes pulmonary TRMs Lung-dwelling tissue-resident memory T cells (TRMs) protect the lower respiratory system after exposure to previously encountered viral pathogens. Using a previously established amphiphilic vaccine formulation that binds avidly to albumin, Rakhra et al. investigated whether coordinated delivery to the lung mucosa of peptide antigen adjuvanted with a CpG oligonucleotide improved the generation of vaccine antigen-specific CD8+ pulmonary TRMs in mice compared with subcutaneous delivery. Intratracheal vaccine administration of the amphiphilic vaccine resulted in a substantial increase in cytokine-producing CD8+ TRMs in the lung and enhanced T cell–mediated protection against both virus and tumor cell challenges. These findings lay the groundwork for further development of amphiphilic mucosal vaccines delivered via an aerosol for induction of robust TRM-based immunity to viruses that threaten the human respiratory health. Tissue-resident memory T cells (TRMs) can profoundly enhance mucosal immunity, but parameters governing TRM induction by vaccination remain poorly understood. Here, we describe an approach exploiting natural albumin transport across the airway epithelium to enhance mucosal TRM generation by vaccination. Pulmonary immunization with albumin-binding amphiphile conjugates of peptide antigens and CpG adjuvant (amph-vaccines) increased vaccine accumulation in the lung and mediastinal lymph nodes (MLNs). Amph-vaccines prolonged antigen presentation in MLNs over 2 weeks, leading to 25-fold increased lung-resident T cell responses over traditional immunization and enhanced protection from viral or tumor challenge. Mimicking such prolonged exposure through repeated administration of soluble vaccine revealed that persistence of both antigen and adjuvant was critical for optimal TRM induction, mediated through T cell priming in MLNs after prime, and directly in the lung tissue after boost. Thus, vaccine persistence strongly promotes TRM induction, and amph-conjugates may provide a practical approach to achieve such kinetics in mucosal vaccines.
Androgen Receptor Signaling and the Emergence of Lethal Neuroendocrine Prostate Cancer With the Treatment-Induced Suppression of the Androgen Receptor: A Literature Review

Androgen receptor signaling primarily influences both the normal growth and proliferation of the prostate gland and the development of prostatic carcinoma. While localized prostate cancers are typically managed with definitive therapies like surgery and radiotherapy, many patients have recurrences in the form of metastatic disease. Androgen deprivation therapy, by way of castration via orchiectomy or with drugs like luteinizing hormone-releasing hormone (commonly called gonadotropin-releasing hormone) agonists and luteinizing hormone-releasing hormone antagonists, is the primary mode of therapy for advanced castration-sensitive prostate cancer. Castration resistance invariably develops in these patients. Further treatment has shifted to newer anti-androgen drugs like enzalutamide or abiraterone and taxane-based chemotherapy. Prolonged inhibition of the androgen receptor signaling pathway causes androgen receptor-independent clonal evolution which leads to the development of treatment-emergent neuroendocrine prostate cancer. All prostate cancers at the initial presentation should undergo evaluation for the markers of neuroendocrine differentiation. Detection of serum biomarkers of neuroendocrine differentiation and circulating tumor cells is a prospective non-invasive method of detecting neuroendocrine transdifferentiation in patients undergoing treatment with androgen receptor pathway inhibitors. It is essential to perform a biopsy in the presence of red flags of neuroendocrine differentiation. Alisertib, an Aurora kinase inhibitor, showed promising clinical benefit in a subgroup of patients with certain molecular alterations. A thorough understanding of the molecular and clinical programming of treatment-emergent neuroendocrine prostate cancer can potentially lead to the development of drugs to prevent the development of this lethal variant of prostate cancer.
Novel drug discovery platform for spinocerebellar ataxia, using fluorescence technology targeting β-III-spectrin

Numerous diseases are linked to mutations in the actin-binding domains (ABDs) of conserved cytoskeletal proteins, including β-III-spectrin, α-actinin, filamin, and dystrophin. A β-III-spectrin ABD mutation (L253P) linked to spinocerebellar ataxia type 5 (SCA5) causes a dramatic increase in actin binding. Reducing actin binding of L253P is thus a potential therapeutic approach for SCA5 pathogenesis. Here, we validate a high-throughput screening (HTS) assay to discover potential disrupters of the interaction between the mutant β-III-spectrin ABD and actin in live cells. This assay monitors FRET between fluorescent proteins fused to the mutant ABD and the actin-binding peptide Lifeact, in HEK293-6E cells. Using a specific and high-affinity actin-binding tool compound, swinholide A, we demonstrate HTS compatibility with an excellent Z’-factor of 0.67 ± 0.03. Screening a library of 1280 pharmacologically active compounds in 1536-well plates to determine assay robustness, we demonstrate high reproducibility across plates and across days. We identified nine Hits that reduced FRET between Lifeact and ABD. Four of those Hits were found to reduce Lifeact cosedimentation with actin, thus establishing the potential of our assay for detection of actin-binding modulators. Concurrent to our primary FRET assay, we also developed a high-throughput compatible counter screen to remove undesirable FRET Hits. Using the FRET Hits, we show that our counter screen is sensitive to undesirable compounds that cause cell toxicity or ABD aggregation. Overall, our FRET-based HTS platform sets the stage to screen large compound libraries for modulators of β-III-spectrin, or disease-linked spectrin-related proteins, for therapeutic development.
Supernovae Detection with Fully Convolutional One-Stage Framework

A series of sky surveys were launched in search of supernovae and generated a tremendous amount of data, which pushed astronomy into a new era of big data. However, it can be a disastrous burden to manually identify and report supernovae, because such data have huge quantity and sparse positives. While the traditional machine learning methods can be used to deal with such data, deep learning methods such as Convolutional Neural Networks demonstrate more powerful adaptability in this area. However, most data in the existing works are either simulated or without generality. How do the state-of-the-art object detection algorithms work on real supernova data is largely unknown, which greatly hinders the development of this field. Furthermore, the existing works of supernovae classification usually assume the input images are properly cropped with a single candidate located in the center, which is not true for our dataset. Besides, the performance of existing detection algorithms can still be improved for the supernovae detection task. To address these problems, we collected and organized all the known objectives of the Panoramic Survey Telescope and Rapid Response System (Pan-STARRS) and the Popular Supernova Project (PSP), resulting in two datasets, and then compared several detection algorithms on them. After that, the selected Fully Convolutional One-Stage (FCOS) method is used as the baseline and further improved with data augmentation, attention mechanism, and small object detection technique. Extensive experiments demonstrate the great performance enhancement of our detection algorithm with the new datasets.
Optimal Application of Forced Air Warming to Prevent Peri-Operative Hypothermia during Abdominal Surgery: A Systematic Review and Meta-Analysis

Patients who undergo abdominal surgery under general anesthesia develop hypothermia in 80–90% of the cases within an hour after induction of anesthesia. Side effects include shivering, bleeding, and infection at the surgical site. However, the surgical team applies forced air warming to prevent peri-operative hypothermia, but these methods are insufficient. This study aimed to confirm the optimal application method of forced air warming (FAW) intervention for the prevention of peri-operative hypothermia during abdominal surgery. A systematic review and meta-analysis were conducted to provide a synthesized and critical appraisal of the studies included. We used PubMed, EMBASE, CINAHL, and Cochrane Library CENTRAL to systematically search for randomized controlled trials published through March 2020. Twelve studies were systematically reviewed for FAW intervention. FAW intervention effectively prevented peri-operative hypothermia among patients undergoing both open abdominal and laparoscopic surgery. Statistically significant effect size could not be confirmed in cases of only pre- or peri-operative application. The upper body was the primary application area, rather than the lower or full body. These findings could contribute detailed standards and criteria that can be effectively applied in the clinical field performing abdominal surgery.
Automatic Ankle Angle Detection by Integrated RGB and Depth Camera System

Depth cameras are developing widely. One of their main virtues is that, based on their data and by applying machine learning algorithms and techniques, it is possible to perform body tracking and make an accurate three-dimensional representation of body movement. Specifically, this paper will use the Kinect v2 device, which incorporates a random forest algorithm for 25 joints detection in the human body. However, although Kinect v2 is a powerful tool, there are circumstances in which the device’s design does not allow the extraction of such data or the accuracy of the data is low, as is usually the case with foot position. We propose a method of acquiring this data in circumstances where the Kinect v2 device does not recognize the body when only the lower limbs are visible, improving the ankle angle’s precision employing projection lines. Using a region-based convolutional neural network (Mask RCNN) for body recognition, raw data extraction for automatic ankle angle measurement has been achieved. All angles have been evaluated by inertial measurement units (IMUs) as gold standard. For the six tests carried out at different fixed distances between 0.5 and 4 m to the Kinect, we have obtained (mean ± SD) a Pearson’s coefficient, r = 0.89 ± 0.04, a Spearman’s coefficient, ρ = 0.83 ± 0.09, a root mean square error, RMSE = 10.7 ± 2.6 deg and a mean absolute error, MAE = 7.5 ± 1.8 deg. For the walking test, or variable distance test, we have obtained a Pearson’s coefficient, r = 0.74, a Spearman’s coefficient, ρ = 0.72, an RMSE = 6.4 deg and an MAE = 4.7 deg.
Why Are Workplace Social Support Programs Not Improving the Mental Health of Canadian Correctional Officers? An Examination of the Theoretical Concepts Underpinning Support

In Canada, public safety personnel, including correctional officers, experience high rates of mental health problems. Correctional officers’ occupational stress has been characterized as insidious and chronic due to multiple and unpredictable occupational risk factors such as violence, unsupportive colleagues and management, poor prison conditions, and shift work. Given the increased risk of adverse mental health outcomes associated with operational stressors, organizational programs have been developed to provide correctional officers with support to promote mental well-being and to provide mental health interventions that incorporate recovery and reduction in relapse risk. This paper uses two theories, the Job Demand Control Support (JDCS) Model and Social Ecological Model (SEM), to explore why workplace social support programs may not been successful in terms of uptake or effectiveness among correctional officers in Canada. We suggest that structural policy changes implemented in the past 15 years have had unintentional impacts on working conditions that increase correctional officer workload and decrease tangible resources to deal with an increasingly complex prison population. Notably, we believe interpersonal support programs may only have limited success if implemented without addressing the multilevel factors creating conditions of job strain.
Transcriptome analysis of sinensetin-treated liver cancer cells guided by biological network analysis

Hepatocellular carcinoma is recognized as one of the most frequently occurring malignant types of liver cancer globally, making the identification of biomarkers critically important. The aim of the present study was to identify the genes involved in the anticancer effects of flavonoid compounds so that they may be used as targets for cancer treatment. Sinensetin (SIN), an isolated polymethoxyflavone monomer compound, possesses broad antitumor activities in vitro. Therefore, the identification of a transcriptome profile on the condition of cells treated with SIN may aid to better understand the genes involved and its mechanism of action. Genomic profiling studies of cancer are increasing rapidly in order to provide gene expression data that can reveal prognostic biomarkers to combat liver cancer. In the present study, high-throughput RNA sequencing (RNA-seq) was performed to reveal differential gene expression patterns between SIN-treated and SIN-untreated human liver cancer HepG2 cells. A total of 43 genes were identified to be differentially expressed (39 downregulated and 4 upregulated in the SIN-treated group compared with the SIN-untreated group). An extensive network analysis for these 43 genes resulted in the identification of 10 upregulated highly interconnected hub genes that contributed to the progression of cancer. Functional enrichment analysis of these 10 hub genes revealed their involvement in the regulation of apoptotic processes, immune response and tumor necrosis factor production. Additionally, the mRNA expression levels of these 10 genes were evaluated using reverse transcription-quantitative PCR, and the results were consistent with the RNA-seq data. Overall, the results of the present study revealed differentially expressed genes involved in cancer after SIN treatment in HepG2 cells and may help to develop strategies targeting these genes for treating liver cancer.
Impact of World Trade Center-Related Health Research: An Application of the NIEHS Translational Framework

The World Trade Center Health Program (WTCHP) has a research mission to identify physical and mental health conditions that may be related to the 9/11 terrorist attacks as well as effective diagnostic procedures and treatments for WTC-related health conditions. The ability of the WTCHP to serve its members and realize positive impacts on all of its stakeholders depends on effective translation of research findings. As part of an ongoing assessment of the translational impact of World Trade Center (WTC)-related research, we applied the National Institute of Environmental Health Sciences (NIEHS) translational framework to two case studies: WTC-related research on post-traumatic stress disorder (PTSD) and cancer. We conducted a review of 9/11 health-related research in the peer-reviewed literature through October 2017, grey literature, and WTCHP program documentation. We mapped peer-reviewed studies in the literature to the NIEHS framework and used WTCHP program documentation and grey literature to find evidence of translation of research into clinical practice and policy. Using the NIEHS framework, we identified numerous translational milestones and bridges, as well as areas of opportunity, within each case study. This application demonstrates the utility of the NIEHS framework for documenting progress toward public health impact and for setting future research goals.
‘Should I Stay, or Should I Go?’ Psychological Distress Predicts Career Change Ideation among Intensive Care Staff in Lithuania and the UK Amid COVID-19 Pandemic

The COVID-19 pandemic had a significant effect on healthcare globally. Additional pressure created by coronavirus adversely affected the mental health and psychological well-being of healthcare workers, leading many to question their desire and willingness to continue working in healthcare. This study aimed to identify predictors for career change ideation among healthcare professionals in two countries; Lithuania and the United Kingdom amid the coronavirus pandemic. In total, 610 healthcare professionals from Lithuania and the UK (285 and 325, respectively) participated in a survey from May to August 2020. Psychological distress and psychological well-being were measured using the self-report scales “DASS-21” and “WHO-5”. Almost half of the sample (49.2%), 59.6% and 40.0% in Lithuanian and the UK, respectively, exhibited career change ideation, the country effect was significant (AOR = 2.21, p < 0.001). Stronger ideation to leave healthcare was predicted by higher levels of depression (AOR = 1.10, p = 0.005), stress (AOR = 1.10, p = 0.007), anxiety surrounding inadequate personal protective equipment (AOR = 2.27, p = 0.009), and lower psychological well-being scores (AOR = 1.10, p = 0.007). We conclude that psychosocial support must be provided for healthcare professionals to prevent burnout and loss of staff amid the pandemic.
Evaluation of Antibiotic Resistance Pattern, Alginate and Biofilm Production in Clinical Isolates of Pseudomonas aeruginosa

Background: Pseudomonas aeruginosa is one of the most common opportunistic bacteria causing nosocomial infections, which has significant resistance to antimicrobial agents. This bacterium is a biofilm and alginate producer. Biofilm increases the bacterial resistance to antibiotics and the immune system. Therefore, the present study was conducted to investigate the biofilm formation, alginate production and antimicrobial resistance patterns in the clinical isolates of P. aeruginosa. Methods: One hundred isolates of P. aeruginosa were collected during the study period (from Dec 2017 to Jul 2018) from different clinical samples of the patients admitted to Milad and Pars Hospitals at Tehran, Iran. Isolates were identified and confirmed by phenotypic and genotypic methods. Antimicrobial susceptibility was specified by the disk diffusion method. Biofilm formation and alginate production were measured by microtiter plate and carbazole assay, respectively. Results: Sixteen isolates were resistant to all the 12 studied antibiotics. Moreover, 31 isolates were Multidrug-Resistant (MDR). The highest resistance rate was related to ofloxacin (36 isolates) and the least resistance was related to piperacillin-tazobactam (21 isolates). All the isolates could produce the biofilm and alginate. The number of isolates producing strong, medium and weak biofilms was equal to 34, 52, and 14, respectively. Alginate production was more than 400 μg/ml in 39 isolates, 250–400 μg/ml in 51 isolates and less than 250 μg/ml in 10 isolates. Conclusion: High prevalence of MDR, biofilm formation, and alginate production were observed among the clinical isolates of P. aeruginosa. The results also showed a significant relationship between the amount of alginate production and the level of biofilm formation.