Miracle-dz/UniFAR-FTUs huggingface dataset:
Periprosthetic Fungal Infections in Severe Endoprosthetic Infections of the Hip and Knee Joint—A Retrospective Analysis of a Certified Arthroplasty Centre of Excellence

The treatment of periprosthetic joint infections (PJI), and especially of re-infections, poses a highly complex problem in orthopaedic surgery. While fungal infections are rare, they present a special challenge. The therapy is often protracted and based on limited evidence. A total of 510 hip and knee revision surgeries were analysed for the occurrence of bacterial and fungal PJI. In patients with PJI, the duration of the hospital stay and the incidence of disarticulation of the infected joint were recorded. Out of the analysed revision arthroplasties, 43.5% were due to PJI. Monomicrobial infection occurred in 55.2%, dual microbial infection in 21.4%, and polymicrobial (≥3 different bacterial or fungal species) infection in 17.2% of the cases. Overall, Candida species were detected in 12.4% cases. Candida albicans was the main fungal pathogen. In 6.9% of cases, disarticulation of the joint was the only option to control PJI. The detection of polymicrobial infection more than doubled in follow-up revisions and there was a strong association between detection of Candida infection and disarticulation (OR 9.39). The majority of fungal infections were mixed infections of bacteria and Candida albicans. The choice of a biofilm penetrating antimycotic, e.g., caspofungin, together with a sufficient standard procedure for detection and surgical treatment can help to control the infection situation. Fungal infection often proves to be more difficult to treat than anticipated and is more frequent than expected.
Physiologically Based Pharmacokinetic Modelling of Cabozantinib to Simulate Enterohepatic Recirculation, Drug–Drug Interaction with Rifampin and Liver Impairment

Cabozantinib (CAB) is a receptor tyrosine kinase inhibitor approved for the treatment of several cancer types. Enterohepatic recirculation (EHC) of the substance is assumed but has not been further investigated yet. CAB is mainly metabolized via CYP3A4 and is susceptible for drug–drug interactions (DDI). The goal of this work was to develop a physiologically based pharmacokinetic (PBPK) model to investigate EHC, to simulate DDI with Rifampin and to simulate subjects with hepatic impairment. The model was established using PK-Sim® and six human clinical studies. The inclusion of an EHC process into the model led to the most accurate description of the pharmacokinetic behavior of CAB. The model was able to predict plasma concentrations with low bias and good precision. Ninety-seven percent of all simulated plasma concentrations fell within 2-fold of the corresponding concentration observed. Maximum plasma concentration (Cmax) and area under the curve (AUC) were predicted correctly (predicted/observed ratio of 0.9–1.2 for AUC and 0.8–1.1 for Cmax). DDI with Rifampin led to a reduction in predicted AUC by 77%. Several physiological parameters were adapted to simulate hepatic impairment correctly. This is the first CAB model used to simulate DDI with Rifampin and hepatic impairment including EHC, which can serve as a starting point for further simulations with regard to special populations.
Pan-Genome Analysis Reveals Host-Specific Functional Divergences in Burkholderia gladioli

Burkholderia gladioli has high versatility and adaptability to various ecological niches. Here, we constructed a pan-genome using 14 genome sequences of B. gladioli, which originate from different niches, including gladiolus, rice, humans, and nature. Functional roles of core and niche-associated genomes were investigated by pathway enrichment analyses. Consequently, we inferred the uniquely important role of niche-associated genomes in (1) selenium availability during competition with gladiolus host; (2) aromatic compound degradation in seed-borne and crude oil-accumulated environments, and (3) stress-induced DNA repair system/recombination in the cystic fibrosis-niche. We also identified the conservation of the rhizomide biosynthetic gene cluster in all the B. gladioli strains and the concentrated distribution of this cluster in human isolates. It was confirmed the absence of complete CRISPR/Cas system in both plant and human pathogenic B. gladioli and the presence of the system in B. gladioli living in nature, possibly reflecting the inverse relationship between CRISPR/Cas system and virulence.
Radiotracers for Bone Marrow Infection Imaging

Introduction: Radiotracers are widely used in medical imaging, using techniques of gamma-camera imaging (scintigraphy and SPECT) or positron emission tomography (PET). In bone marrow infection, there is no single routine test available that can detect infection with sufficiently high diagnostic accuracy. Here, we review radiotracers used for imaging of bone marrow infection, also known as osteomyelitis, with a focus on why these molecules are relevant for the task, based on their physiological uptake mechanisms. The review comprises [67Ga]Ga-citrate, radiolabelled leukocytes, radiolabelled nanocolloids (bone marrow) and radiolabelled phosphonates (bone structure), and [18F]FDG as established radiotracers for bone marrow infection imaging. Tracers that are under development or testing for this purpose include [68Ga]Ga-citrate, [18F]FDG, [18F]FDS and other non-glucose sugar analogues, [15O]water, [11C]methionine, [11C]donepezil, [99mTc]Tc-IL-8, [68Ga]Ga-Siglec-9, phage-display selected peptides, and the antimicrobial peptide [99mTc]Tc-UBI29-41 or [68Ga]Ga-NOTA-UBI29-41. Conclusion: Molecular radiotracers allow studies of physiological processes such as infection. None of the reviewed molecules are ideal for the imaging of infections, whether bone marrow or otherwise, but each can give information about a separate aspect such as physiology or biochemistry. Knowledge of uptake mechanisms, pitfalls, and challenges is useful in both the use and development of medically relevant radioactive tracers.
Targeting Natural Killer T Cells in Solid Malignancies

Natural killer T (NKT) cells are a unique subset of lymphocytes that recognize lipid antigens in the context of the non-classical class I MHC molecule, CD1d, and serve as a link between the innate and adaptive immune system through their expeditious release of cytokines. Whereas NKT have well-established roles in mitigating a number of human diseases, herein, we focus on their role in cancer. NKT cells have been shown to directly and indirectly mediate anti-tumor immunity and manipulating their effector functions can have therapeutic significances in treatment of cancer. In this review, we highlight several therapeutic strategies that have been used to harness the effector functions of NKT cells to target different types of solid tumors. We also discuss several barriers to the successful utilization of NKT cells and summarize effective strategies being developed to harness the unique strengths of this potent population of T cells. Collectively, studies investigating the therapeutic potential of NKT cells serve not only to advance our understanding of this powerful immune cell subset, but also pave the way for future treatments focused on the modulation of NKT cell responses to enhance cancer immunotherapy.
Novel Biomarkers of Hepatitis B Virus and Their Use in Chronic Hepatitis B Patient Management

Even though an approved vaccine for hepatitis B virus (HBV) is available and widely used, over 257 million individuals worldwide are living with chronic hepatitis B (CHB) who require monitoring of treatment response, viral activity, and disease progression to reduce their risk of HBV-related liver disease. There is currently a lack of predictive markers to guide clinical management and to allow treatment cessation with reduced risk of viral reactivation. Novel HBV biomarkers are in development in an effort to improve the management of people living with CHB, to predict disease outcomes of CHB, and further understand the natural history of HBV. This review focuses on novel HBV biomarkers and their use in the clinical setting, including the description of and methodology for quantification of serum HBV RNA, hepatitis B core-related antigen (HBcrAg), quantitative hepatitis B surface antigen (qHBsAg), including ultrasensitive HBsAg detection, quantitative anti-hepatitis B core antigen (qAHBc), and detection of HBV nucleic acid-related antigen (HBV-NRAg). The utility of these biomarkers in treatment-naïve and treated CHB patients in several clinical situations is further discussed. Novel HBV biomarkers have been observed to provide critical clinical information and show promise for improving patient management and our understanding of the natural history of HBV.
The visual cortex produces gamma band echo in response to broadband visual flicker

The aim of this study is to uncover the network dynamics of the human visual cortex by driving it with a broadband random visual flicker. We here applied a broadband flicker (1–720 Hz) while measuring the MEG and then estimated the temporal response function (TRF) between the visual input and the MEG response. This TRF revealed an early response in the 40–60 Hz gamma range as well as in the 8–12 Hz alpha band. While the gamma band response is novel, the latter has been termed the alpha band perceptual echo. The gamma echo preceded the alpha perceptual echo. The dominant frequency of the gamma echo was subject-specific thereby reflecting the individual dynamical properties of the early visual cortex. To understand the neuronal mechanisms generating the gamma echo, we implemented a pyramidal-interneuron gamma (PING) model that produces gamma oscillations in the presence of constant input currents. Applying a broadband input current mimicking the visual stimulation allowed us to estimate TRF between the input current and the population response (akin to the local field potentials). The TRF revealed a gamma echo that was similar to the one we observed in the MEG data. Our results suggest that the visual gamma echo can be explained by the dynamics of the PING model even in the absence of sustained gamma oscillations.
Organizing Variables Affecting fMRI Estimates of Language Dominance in Patients with Brain Tumors

Numerous variables can affect the assessment of language dominance using presurgical functional magnetic resonance (fMRI) in patients with brain tumors. This work organizes the variables into confounding and modulating factors. Confounding factors give the appearance of changed language dominance. Most confounding factors are fMRI-specific and they can substantially disrupt the evaluation of language dominance. Confounding factors can be divided into two categories: tumor-related and fMRI analysis. The tumor-related confounds further subdivide into tumor characteristics (e.g., tumor grade) and tumor-induced conditions (aphasia). The fMRI analysis confounds represent technical aspects of fMRI methods (e.g., a fixed versus an individual threshold). Modulating factors can modify language dominance without confounding it. They are not fMRI-specific, and they can impact language dominance both in healthy individuals and neurosurgical patients. The effect of most modulating factors on fMRI language dominance is smaller than that of confounding factors. Modulating factors include demographics (e.g., age) and linguistic variables (e.g., early bilingualism). Three cases of brain tumors in the left hemisphere are presented to illustrate how modulating confounding and modulating factors can impact fMRI estimates of language dominance. Distinguishing between confounding and modulating factors can help interpret the results of presurgical language mapping with fMRI.
Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk

In the phase 3 BOSTON study, patients with multiple myeloma (MM) after 1–3 prior regimens were randomized to once‐weekly selinexor (an oral inhibitor of exportin 1 [XPO1]) plus bortezomib‐dexamethasone (XVd) or twice‐weekly bortezomib‐dexamethasone (Vd). Compared with Vd, XVd was associated with significant improvements in median progression‐free survival (PFS), overall response rate (ORR), and lower rates of peripheral neuropathy, with trends in overall survival (OS) favoring XVd. In BOSTON, 141 (35.1%) patients had MM with high‐risk (presence of del[17p], t[4;14], t[14;16], or ≥4 copies of amp1q21) cytogenetics (XVd, n = 70; Vd, n = 71), and 261 (64.9%) exhibited standard‐risk cytogenetics (XVd, n = 125; Vd, n = 136). Among patients with high‐risk MM, median PFS was 12.91 months for XVd and 8.61 months for Vd (HR, 0.73 [95% CI, (0.4673, 1.1406)], p = 0.082), and ORRs were 78.6% and 57.7%, respectively (OR 2.68; p = 0.004). In the standard‐risk subgroup, median PFS was 16.62 months for XVd and 9.46 months for Vd (HR 0.61; p = 0.004), and ORRs were 75.2% and 64.7%, respectively (OR 1.65; p = 0.033). The safety profiles of XVd and Vd in both subgroups were consistent with the overall population. These data suggest that selinexor can confer benefits to patients with MM regardless of cytogenetic risk. ClinicalTrials.gov identifier: NCT03110562.
Emerging Role of Fascin-1 in the Pathogenesis, Diagnosis, and Treatment of the Gastrointestinal Cancers

Simple Summary Gastrointestinal (GI) cancers, including esophageal, gastric, colorectal, liver, and pancreatic cancers, remain as one of the leading causes of death worldwide, with a large proportion accounting for fatalities related to metastatic disease. The active involvement of fascin-1 in forming membrane protrusions crucial for cellular movement has been identified as an important molecular mechanism behind the phenotypic switch from the localized to the metastatic tumor. Thus, fascin-1 expression status in the malignant tissue has been utilized as an important component in determining the patient’s clinicopathological outcomes. In this review, we provide an up-to-date literature review of the role of fascin-1 in the initiation and metastatic progression of GI tract cancers, its involvement in patients’ clinical outcomes, and its potential as a therapeutic target. Abstract Gastrointestinal (GI) cancers, including esophageal, gastric, colorectal, liver, and pancreatic cancers, remain as one of the leading causes of death worldwide, with a large proportion accounting for fatalities related to metastatic disease. Invasion of primary cancer occurs by the actin cytoskeleton remodeling, including the formation of the filopodia, stereocilia, and other finger-like membrane protrusions. The crucial step of actin remodeling in the malignant cells is mediated by the fascin protein family, with fascin-1 being the most active. Fascin-1 is an actin-binding protein that cross-links filamentous actin into tightly packed parallel bundles, giving rise to finger-like cell protrusions, thus equipping the cell with the machinery necessary for adhesion, motility, and invasion. Thus, fascin-1 has been noted to be a key component for determining patient diagnosis and treatment plan. Indeed, the overexpression of fascin-1 in GI tract cancers has been associated with a poor clinical prognosis and metastatic progression. Moreover, fascin-1 has received attention as a potential therapeutic target for metastatic GI tract cancers. In this review, we provide an up-to-date literature review of the role of fascin-1 in the initiation of GI tract cancers, metastatic progression, and patients’ clinical outcomes.
Perceived Stress in Dentists and Dental Students of Latin America and the Caribbean during the Mandatory Social Isolation Measures for the COVID-19 Pandemic: A Cross-Sectional Study

This study aims to determine the impact of the COVID-19 pandemic, specifically considering the mandatory social isolation measures implemented, on the perceived stress of a sample of dentists and dental students from Latin America and the Caribbean, as well as the associated sociodemographic and pandemic-related variables. A cross-sectional survey was conducted with a sample of 2036 dentists and dental students (1433 women). For the main outcome, the 14-item Perceived Stress Scale (PSS-14) was used. The survey also questioned sociodemographic aspects, questions on the COVID-19 pandemic, health variables, and habits. Descriptive, bivariate, and multivariate analyses (linear regression) were applied to observe the factors associated with perceived stress. The PSS-14 mean score was 24.76 (±11.76). Hierarchical regression models showed significant variables associated with the PSS-14 scores: income level during mandatory social isolation, having older adults under care during mandatory social isolation, self-perceived level of concern regarding COVID-19, self-perceived health, Coffee consumption during mandatory social isolation. In general terms, the pandemic has influenced the personal, social, labor, and everyday life of dental staff and affected the mental health of this population specifically when perceived stress is considered. Public policies, strategies, and mental health surveillance systems are required for this population.
Maximum Strength Benchmarks for Difficult Static Elements on Rings in Male Elite Gymnastics

On rings, in men’s artistic gymnastics, the general strength requirements for important static elements remain elusive. Therefore, the aim was to describe the relationship between a new conditioning strength test and a maximum strength test of static elements on rings in order to determine the minimal strength level (benchmarks) required to maintain these elements with one’s own body weight. Nineteen elite gymnasts performed a concentric (1RM isoinertial) and eccentric (isokinetic: 0.1 m/s) conditioning strength test for swallow/support scale (supine position) and inverted cross (seated position) on a computer-controlled device and a maximum strength test maintaining these elements for 5 s on rings with counterweight or additional weight. High correlation coefficients were found between the conditioning maximum strength for swallow/support scale (r: 0.65 to 0.92; p < 0.05) and inverted cross (r: 0.62 to 0.69; p > 0.05) and the maximum strength of the elements on rings. Strength benchmarks varied between 56.66% (inverted cross concentric) and 94.10% (swallow eccentric) of body weight. Differences in biomechanical characteristics and technical requirements of strength elements on rings may (inter alia) explain the differences between correlations. Benchmarks of conditioning strength may help coaches and athletes systematize the training of strength elements on rings.
Leukocyte cell population data from the blood cell analyzer as a predictive marker for severity of acute pancreatitis

The prediction for severe acute pancreatitis (SAP) is the key to give timely targeted treatment. Leukocyte cell population data (CPD) have been widely applied in early prediction and diagnosis of many diseases, but their predictive ability for SAP remains unexplored. We aim to testify whether CPD could be an indicator of AP severity in the early stage of the disease.
miR‐9 modulates and predicts the response to radiotherapy and EGFR inhibition in HNSCC

Radiotherapy (RT) plus the anti‐EGFR monoclonal antibody Cetuximab (CTX) is an effective combination therapy for a subset of head and neck squamous cell carcinoma (HNSCC) patients. However, predictive markers of efficacy are missing, resulting in many patients treated with disappointing results and unnecessary toxicities. Here, we report that activation of EGFR upregulates miR‐9 expression, which sustains the aggressiveness of HNSCC cells and protects from RT‐induced cell death. Mechanistically, by targeting KLF5, miR‐9 regulates the expression of the transcription factor Sp1 that, in turn, stimulates tumor growth and confers resistance to RT+CTX in vitro and in vivo. Intriguingly, high miR‐9 levels have no effect on the sensitivity of HNSCC cells to cisplatin. In primary HNSCC, miR‐9 expression correlated with Sp1 mRNA levels and high miR‐9 expression predicted poor prognosis in patients treated with RT+CTX. Overall, we have discovered a new signaling axis linking EGFR activation to Sp1 expression that dictates the response to combination treatments in HNSCC. We propose that miR‐9 may represent a valuable biomarker to select which HNSCC patients might benefit from RT+CTX therapy.
Urine and Plasma Metabolome of Healthy Adults Consuming the DASH (Dietary Approaches to Stop Hypertension) Diet: A Randomized Pilot Feeding Study

We aimed to identify plasma and urine metabolites altered by the Dietary Approaches to Stop Hypertension (DASH) diet in a post-hoc analysis of a pilot feeding trial. Twenty adult participants with un-medicated hypertension consumed a Control diet for one week followed by 2 weeks of random assignment to either Control or DASH diet. Non-missing fasting plasma (n = 56) and 24-h urine (n = 40) were used to profile metabolites using untargeted gas chromatography/mass spectrometry. Linear models were used to compare metabolite levels between the groups. In urine, 19 identifiable untargeted metabolites differed between groups at p < 0.05. These included a variety of phenolic acids and their microbial metabolites that were higher during the DASH diet, with many at false discovery rate (FDR) adjusted p < 0.2. In plasma, eight identifiable untargeted metabolites were different at p < 0.05, but only gamma-tocopherol was significantly lower on DASH at FDR adjusted p < 0.2. The results provide insights into the mechanisms of benefit of the DASH diet.
Glycosylation Biomarkers Associated with Age-Related Diseases and Current Methods for Glycan Analysis

Ageing is a complex process which implies the accumulation of molecular, cellular and organ damage, leading to an increased vulnerability to disease. In Western societies, the increase in the elderly population, which is accompanied by ageing-associated pathologies such as cardiovascular and mental diseases, is becoming an increasing economic and social burden for governments. In order to prevent, treat and determine which subjects are more likely to develop these age-related diseases, predictive biomarkers are required. In this sense, some studies suggest that glycans have a potential role as disease biomarkers, as they modify the functions of proteins and take part in intra- and intercellular biological processes. As the glycome reflects the real-time status of these interactions, its characterisation can provide potential diagnostic and prognostic biomarkers for multifactorial diseases. This review gathers the alterations in protein glycosylation profiles that are associated with ageing and age-related diseases, such as cancer, type 2 diabetes mellitus, metabolic syndrome and several chronic inflammatory diseases. Furthermore, the review includes the available techniques for the determination and characterisation of glycans, such as liquid chromatography, electrophoresis, nuclear magnetic resonance and mass spectrometry.