Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxygen-Carrying Polymer Nanoconstructs for Radiodynamic Therapy of Deep Hypoxic Malignant Tumors

Radiodynamic therapy (RDT) is an emerging non-invasive anti-cancer treatment based on the generation of the reactive oxygen species (ROS) at the lesion site following the interaction between X-rays and a photosensitizer drug (PS). The broader application of RDT is impeded by the tumor-associated hypoxia that results in low availability of oxygen for the generation of sufficient amounts of ROS. Herein, a novel nanoparticle drug formulation for RDT, which addresses the problem of low oxygen availability, is reported. It consists of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with a PS drug verteporfin (VP), and the clinically approved oxygen-carrying molecule, perfluorooctylbromide (PFOB). When triggered by X-rays (4 Gy), under both normoxic and hypoxic conditions, PLGA–VP–PFOB nanoconstructs (NCs) induced a significant increase of the ROS production compared with matching PLGA–VP nanoparticles. The RDT with NCs effectively killed ~60% of human pancreatic cancer cells in monolayer cultures, and almost completely suppressed the outgrowth of tumor cells in 2-weeks clonogenic assay. In a 3D engineered model of pancreatic cancer metastasis to the liver, RDT with NCs destroyed ~35% of tumor cells, demonstrating an exceptional efficiency at a tissue level. These results show that PLGA–VP–PFOB is a promising agent for RDT of deep-seated hypoxic tumors.
Can Big Data and Machine Learning Improve Our Understanding of Acute Respiratory Distress Syndrome?

Acute respiratory distress syndrome (ARDS) accounts for 10% of all diagnoses in the Intensive Care Unit, and about 40% of the patients succumb to the disease. Clinical methods alone can result in the under-recognition of this heterogeneous syndrome. The purpose of this study is to evaluate the role that big data and machine learning (ML) have played in understanding the heterogeneity of the disease and the development of various prediction algorithms. Most of the work in the field of ML in ARDS has been in the development of prediction models that have comparable efficacies to that of traditional models. Prediction algorithms have been useful in identifying new variables that may be important to consider in the future, supplementing the unknown information with the help of available noninvasive parameters, as well as predicting mortality. Phenotype identification using an unsupervised ML algorithm has been pivotal in classifying the heterogeneous population into more homogenous classes. Big data generated from ventilators in the form of ventilator waveform analysis and images in the form of radiomics have also been leveraged for the identification of the syndrome and can be incorporated into a clinical decision support system. Although the results are promising, lack of generalizability, “black box” nature of algorithms and concerns about “alarm fatigue” should be addressed for more mainstream adoption of these models.
A New Classification System to Predict Functional Outcome after Laryngectomy and Laryngopharyngectomy

Simple Summary Evaluation of the long-term functional outcome after primary or salvage laryngopharyngectomy. Long term functional outcome mainly depends on extent of pharyngectomy and salvage situation, which is reflected by our new classification system. Abstract (1) Objective: To evaluate long-term functional outcome in patients who underwent primary or salvage total laryngectomy (TL), TL with partial (TLPP), or total pharyngectomy (TLTP), and to establish a new scoring system to predict complication rate and long-term functional outcome; (2) Material and Methods: Between 1993 and 2019, 258 patients underwent TL (n = 85), TLPP (n = 101), or TLTP (n = 72). Based on the extent of tumor resection, all patients were stratified to (i) localization I: TL; II: TLPP; III: TLTP and (ii) surgical treatment (A: primary resection; B: salvage surgery). Type and rate of complication and functional outcome, including oral nutrition, G-tube dependence, pharyngeal stenosis, and voice rehabilitation were evaluated in 163 patients with a follow-up ≥ 12 months and absence of recurrent disease; (3) Results: We found 61 IA, 24 IB, 63 IIA, 38 IIB, 37 IIIA, and 35 IIIA patients. Complications and subsequently revision surgeries occurred most frequently in IIIB cases but rarely in IA patients (57.1% vs. 18%; p = 0.001 and 51.4% vs. 14.8%; p = 0.002), respectively. Pharyngocutaneous fistula (PCF) was the most common complication (33%), although it did not significantly differ among cohorts (p = 0.345). Pharyngeal stenosis was found in 27% of cases, with the highest incidence in IIIA (45.5%) and IIIB (72.7%) patients (p < 0.001). Most (91.1%) IA patients achieved complete oral nutrition compared to only 41.7% in class IIIB patients (p < 0.001). Absence of PCF (odds ratio (OR) 3.29; p = 0.003), presence of complications (OR 3.47; p = 0.004), and no need for pharyngeal reconstruction (OR 4.44; p = 0.042) represented independent favorable factors for oral nutrition. Verbal communication was achieved in 69.3% of patients and was accomplished by the insertion of voice prosthesis in 37.4%. Acquisition of esophageal speech was reached in 31.9% of cases. Based on these data, we stratified patients regarding the extent of surgery and previous treatment into subgroups reflecting risk profiles and expectable functional outcome; (4) Conclusions: The extent of resection accompanied by the need for reconstruction and salvage surgery both carry a higher risk of complications and subsequently worse functional outcome. Both factors are reflected in our classification system that can be helpful to better predict patients’ functional outcome.
Daily Life Changes and Life Satisfaction among Korean School-Aged Children in the COVID-19 Pandemic

The recent COVID-19 pandemic has been disrupting the daily lives of people across the world, causing a major concern for psychological well-being in children. This study aimed to examine (1) how life satisfaction and its potential predictors have been affected by the pandemic among school-aged children in Korea, and (2) which factors would predict their life satisfaction during the pandemic. We surveyed 166 fourth-graders in the Seoul metropolitan area to assess their psychological well-being and potentially related variables during the pandemic. The data were compared with those available from two pre-COVID-19 surveys, the 2018 Korean Children and Youth Panel Survey (n = 1236) and the 2019 Korean Children and Youth Well-being Index Survey (n = 334). Higher levels of stress were observed in children during the COVID-19 pandemic; however, the level of their life satisfaction remained unchanged when compared with data from the pre-COVID-19 surveys. The pandemic also affected peer relationship quality and susceptibility to smartphone addiction, but not perceived parenting style nor academic engagement. Interestingly, peer relationship quality no longer predicted life satisfaction during the pandemic; perceived parenting styles and parent-child conversation time predicted life satisfaction. The results suggest a central role of parent-child relationship in supporting the psychological well-being of school-aged children during the pandemic.
Ability of a Risk Prediction Tool to Stratify Quality and Cost for Older Patients With Operative Distal Radius Fractures

Introduction: Distal radius fractures are the second most common fracture in the elderly population. The incidence of these fractures has increased over time, and is projected to continue to do so. The aim of this study is to utilize a validated trauma risk prediction tool to stratify middle-aged and geriatric patients with operative distal radius fractures as well as compare hospital quality metrics and inpatient hospitalization costs among the risk groups. Materials and Methods: Patients were prospectively enrolled in an orthopedic trauma registry. The Score for Trauma Triage in Geriatric and Middle Aged (STTGMA) was calculated using patient demographics, injury severity, and functional status. Patients were then stratified into minimal-risk, moderate-risk, and high-risk cohorts based on their scores. Length of stay, need for escalation of care, complications, mortality, discharge location, 1-year patient reported outcomes, and index admission costs were evaluated. Results: Ninety-two patients met inclusion criteria. Sixty-three (68.5%) patients were managed with outpatient surgery. The mean inpatient length of stay for the high-risk cohort was 2.9x and 2.2x higher than the minimal and moderate-risk cohorts, respectively (2.0 + 2.9 days vs. 0.7 + 0.9 and 0.9 + 1.1 days, P = .019). There were no complications or mortality in any of the risk groups. No patients required intensive care and all patients were discharged home. There was no difference in readmission rates, inpatient cost, or 1-year patient reported outcomes among the risk cohorts. Discussion/Conclusions: The Score for Trauma Triage in Geriatric and Middle-Aged is able to risk-stratify patients that undergo operative intervention of distal radius fractures. Middle aged and elderly patients with isolated closed distal radius fractures can be safely managed on an outpatient basis regardless of risk. Standardized pathways can be created in the management of these injuries, thereby optimizing value-based care. Level of evidence: Prognostic Level III
Outcomes and Risk Factors in Prosthetic Joint Infections by multidrug-resistant Gram-negative Bacteria: A Retrospective Cohort Study

Gram-negative bacteria (GNB), including multidrug-resistant (MDR) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). This retrospective observational study identified independent risk factors (RFs) associated with MDR-GNB PJI and their influence on treatment outcomes. We assessed MDR bacteria causing hip and knee PJIs diagnosed at a Brazilian tertiary hospital from January 2014 to July 2018. RFs associated with MDR-GNB PJI were estimated by bivariate and multivariate analyses using prevalence ratios (PRs) with significance at p < 0.05. Kaplan–Meier analysis was performed to evaluate treatment outcomes. Overall, 98 PJI patients were analysed, including 56 with MDR-GNB and 42 with other bacteria. Independent RFs associated with MDR-GNB PJI were revision arthroplasty (p = 0.002), postoperative hematoma (p < 0.001), previous orthopaedic infection (p = 0.002) and early infection (p = 0.001). Extensively drug-resistant GNB (p = 0.044) and comorbidities (p = 0.044) were independently associated with MDR-GNB PJI treatment failure. In sum, MDR-GNB PJI was independently associated with previous orthopaedic surgery, postoperative local complications and pre-existing infections and was possibly related to selective pressure on bacterial skin colonisation by antibiotics prescribed for early PJI. Infections due to MDR-GNB and comorbidities were associated with higher treatment failure rates.
Molecular dynamic simulation study on structure of water in crosslinked poly(N-isopropylacrylamide) hydrogels

The arrangement of water molecules within poly(N-isopropylacrylamide) (P-NIPAM) gels was analysed using molecular dynamic (MD) simulations of P-NIPAM polymer chains crosslinked by N,N′-methylenebisacrylamide (BIS) molecules in an aqueous solution. The generation of the polymer was performed in three steps, first the crosslinker molecules were placed randomly, then the crosslinkers were connected by NIPAM monomer chains, and finally the water molecules were inserted. We extracted simulation trajectories from simulations, with N, V and T fixed, for different polymer concentrations at 285, 300 and 325 K. The trajectory data were used for analysis of the polymer–water structure and for determination of the diffusion coefficients, which were compared with experimental data.
Stoichiometric Thiol Redox Proteomics for Quantifying Cellular Responses to Perturbations

Post-translational modifications regulate the structure and function of proteins that can result in changes to the activity of different pathways. These include modifications altering the redox state of thiol groups on protein cysteine residues, which are sensitive to oxidative environments. While mass spectrometry has advanced the identification of protein thiol modifications and expanded our knowledge of redox-sensitive pathways, the quantitative aspect of this technique is critical for the field of redox proteomics. In this review, we describe how mass spectrometry-based redox proteomics has enabled researchers to accurately quantify the stoichiometry of reversible oxidative modifications on specific cysteine residues of proteins. We will describe advancements in the methodology that allow for the absolute quantitation of thiol modifications, as well as recent reports that have implemented this approach. We will also highlight the significance and application of such measurements and why they are informative for the field of redox biology.
The TDDFT Excitation Energies of the BODIPYs; The DFT and TDDFT Challenge Continues

The derivatives of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) are pivotal ingredients for a large number of functional, stimuli-responsive materials and therapeutic molecules based on their photophysical properties, and there is a urgent need to understand and predict their optical traits prior to investing a large amount of resources in preparing them. Density functional theory (DFT) and time-dependent DFT (TDDFT) computations were performed to calculate the excitation energies of the lowest-energy singlet excited state of a large series of common BODIPY derivatives employing various functional aiming at the best possible combination providing the least deviations from the experimental values. Using the common “fudge” correction, a series of combinations was investigated, and a methodology is proposed offering equal or better performances than what is reported in the literature.
Antiviral Cyanometabolites—A Review

Global processes, such as climate change, frequent and distant travelling and population growth, increase the risk of viral infection spread. Unfortunately, the number of effective and accessible medicines for the prevention and treatment of these infections is limited. Therefore, in recent years, efforts have been intensified to develop new antiviral medicines or vaccines. In this review article, the structure and activity of the most promising antiviral cyanobacterial products are presented. The antiviral cyanometabolites are mainly active against the human immunodeficiency virus (HIV) and other enveloped viruses such as herpes simplex virus (HSV), Ebola or the influenza viruses. The majority of the metabolites are classified as lectins, monomeric or dimeric proteins with unique amino acid sequences. They all show activity at the nanomolar range but differ in carbohydrate specificity and recognize a different epitope on high mannose oligosaccharides. The cyanobacterial lectins include cyanovirin-N (CV-N), scytovirin (SVN), microvirin (MVN), Microcystis viridis lectin (MVL), and Oscillatoria agardhii agglutinin (OAA). Cyanobacterial polysaccharides, peptides, and other metabolites also have potential to be used as antiviral drugs. The sulfated polysaccharide, calcium spirulan (CA-SP), inhibited infection by enveloped viruses, stimulated the immune system’s response, and showed antitumor activity. Microginins, the linear peptides, inhibit angiotensin-converting enzyme (ACE), therefore, their use in the treatment of COVID-19 patients with injury of the ACE2 expressing organs is considered. In addition, many cyanobacterial extracts were revealed to have antiviral activities, but the active agents have not been identified. This fact provides a good basis for further studies on the therapeutic potential of these microorganisms.
Co-Occurrence of Regulated and Emerging Mycotoxins in Corn Silage: Relationships with Fermentation Quality and Bacterial Communities

Sixty-four corn silages were characterized for chemicals, bacterial community, and concentrations of several fungal metabolites. Silages were grouped in five clusters, based on detected mycotoxins, and they were characterized for being contaminated by (1) low levels of Aspergillus- and Penicillium-mycotoxins; (2) low levels of fumonisins and other Fusarium-mycotoxins; (3) high levels of Aspergillus-mycotoxins; (4) high levels of non-regulated Fusarium-mycotoxins; (5) high levels of fumonisins and their metabolites. Altersetin was detected in clusters 1, 3, and 5. Rugulusovin or brevianamide F were detected in several samples, with the highest concentration in cluster 3. Emodin was detected in more than 50.0% of samples of clusters 1, 3 and 5, respectively. Kojic acid occurred mainly in clusters 1 and 2 at very low concentrations. Regarding Fusarium mycotoxins, high occurrences were observed for FB3, FB4, FA1, whereas the average concentrations of FB6 and FA2 were lower than 12.4 µg/kg dry matter. Emerging Fusarium-produced mycotoxins, such as siccanol, moniliformin, equisetin, epiequisetin and bikaverin were detected in the majority of analyzed corn silages. Pestalotin, oxaline, phenopirrozin and questiomycin A were detected at high incidences. Concluding, this work highlighted that corn silages could be contaminated by a high number of regulated and emerging mycotoxins.
Disagreement between Cardiac Troponin Tests Yielding a Higher Incidence of Myocardial Injury in the Emergency Setting

Differences in patient classification of myocardial injury between high-sensitivity cardiac troponin (hs-cTn) assays have largely been attributed to assay design and analytical sensitivity aspects. Our objective was to compare Ortho Clinical Diagnostics’ (OCD) hs-cTnI assay to OCD’s contemporary/conventional assay (cTnI ES) and another hs-cTnI assay (Abbott hs-cTnI) in samples obtained from different emergency departments (EDs). Two different sample types were evaluated (lithium heparin and ethylenediaminetetraacetic acid (EDTA) plasma) in a non-selected ED population (study 1, n = 469 samples) and in patients for which ED physicians ordered cardiac troponin testing (study 2, n = 1147 samples), from five different EDs. The incidence of injury in study 1 was higher with the OCD hs-cTnI assay (30.9%; 95% CI: 26.9 to 35.2) compared to that of the Abbott hs-cTnI (17.3%; 95% CI: 14.1 to 21.0) and the OCD cTnI ES (15.4%; 95% CI: 12.4 to 18.9) assays, with repeat testing identifying 4.8% (95% CI: 3.0 to 7.5) of the OCD hs-cTnI results with poor reproducibility. In study 2, 4.6% (95% CI: 3.5 to 6.0) of the results were not reported for the OCD hs-cTnI assay (i.e., poor reproducibility) with 12.7% (95%CI: 8.7 to 17.8) of the OCD hs-cTnI results positive for injury being negative for injury with the Abbott hs-cTnI assay. In summary, the OCD hs-cTnI assay yields higher rates of biochemical injury with a higher rate of poor reproducible results in different ED populations.
Associations between Well-Being State and Match External and Internal Load in Amateur Referees

The main aim of this paper was to examine the association between prematch well-being status with match internal and external load in field (FR) and assistant (AR) soccer referees. Twenty-three FR and 46 AR participated in this study. The well-being state was assessed using the Hooper Scale and the match external and internal loads were monitored with Stryd Power Meter and heart monitors. While no significant differences were found in Hooper indices between match officials, FR registered higher external loads (p < 0.01; ES: 0.75 to 5.78), spent more time in zone 4 and zone 5, and recorded a greater training impulse (TRIMP) value (p < 0.01; ES: 1.35 to 1.62) than AR. Generally, no associations were found between the well-being variables and external loads for FR and AR. Additionally, no associations were found between the Hooper indices and internal loads for FR and AR. However, several relationships with different magnitudes were found between internal and external match loads, for FR, between power and speed with time spent in zone 2 (p < 0.05; r = −0.43), ground contact time with zone 2 and zone 3 (p < 0.05; r = 0.50 to 0.60) and power, speed, cadence and ground contact time correlated with time spent in zone 5 and TRIMP (p < 0.05 to 0.01; r = 0.42 to 0.64). Additionally, for AR, a relationship between speed and time in zone 1 was found (p < 0.05; r = −0.30; CL = 0.22). These results suggest that initial well-being state is not related to match officials’ performances during match play. In addition, the Stryd Power Meter can be a useful device to calculate the external load on soccer match officials.
Incidence, Risk-Factors and Associated Mortality of Complications in Orthogeriatric Co-Managed Inpatients

Introduction: Pneumonia, thromboembolic and ischemic events, urinary tract infections (UTI), delirium and acute kidney injury (AKI) are common complications during the treatment of fragility fractures. In a 2 years-follow-up we determined the according incidence and risk factors of these and other complications in orthogeriatric inward patients, as well as the respective associated mortality. Methods: All patients treated on an orthogeriatric co-managed ward over the course of a year were included. Besides injury, therapy and geriatric assessment parameters, we evaluated the inward incidence of common complications. In a 2 years-follow-up the associated death rates were aquired. SPSS (IBM) was used to determine the importance of risk factors predisposing to the respective occurrence of a complication and accordingly determine it’s impact on the patients’ 1- and 2-years-mortality. Results: 830 orthogeriatric patients were initially assessed with a remaining follow-up cohort of 661 (79.6%). We observed very few cases of thrombosis (0.6%), pulmonary embolism (0.5%), apoplex (0.5%) and myocardial infarction (0.8%). Pneumonia was seen in 42 (5.1%), UTI in 85 (10.2%), delirium in 186 (22.4%) and AKI in 91 (11.0%) patients. Consistently ADL on admission was found to be a relevant risk factor in the development of each complication. After adjustment only AKI showed a significant increased mortality risk of 1.60 (95%CI:1.086-2.350). Discussion: In our fracture-independent assessment of complications in the orthogeriatric treatment of inward patients we’ve seen very rare cases of cardiac and thrombotic complications. Typical fragility-fracture associated common events like pneumonia, UTI, delirium and AKI were still more incidental. No complication except AKI was associated to significant increased mortality risk. Conclusions: The relevance of orthogeriatric care in prevention and outcome of inward complications seems promising, needing still more controlled studies, evaluating not just hip fracture patients but more diverse groups. Consensus is needed in the scholar evaluation of orthogeriatric complications.