Miracle-dz/UniFAR-FTUs huggingface dataset:
Bioactive Lipids as Chronic Myeloid Leukemia’s Potential Biomarkers for Disease Progression and Response to Tyrosine Kinase Inhibitors

Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm that expresses the Philadelphia chromosome and constitutively activated Bcr-Abl tyrosine kinase in hematopoietic progenitor cells. Bcr-Abl tyrosine-kinase inhibitors (TKI) do not definitively cure all CML patients. The efficacy of TKI is reduced in CML patients in the blastic phase—the most severe phase of the disease—and resistance to this drug has emerged. There is limited knowledge on the underlying mechanisms of disease progression and resistance to TKI beyond BCR-ABL1, as well as on the impact of TKI treatment and disease progression on the metabolome of CML patients. The present study reports the metabolomic profiles of CML patients at different phases of the disease treated with TKI. The plasma metabolites from CML patients were analyzed using liquid chromatography, mass spectrometry, and bioinformatics. Distinct metabolic patterns were identified for CML patients at different phases of the disease and for those who were resistant to TKI. The lipid metabolism in CML patients at advanced phases and TKI-resistant patients is reprogrammed, as detected by analysis of metabolomic data. CML patients who were responsive and resistant to TKI therapy exhibited distinct enriched pathways. In addition, ceramide levels were higher and sphingomyelin levels were lower in resistant patients compared with control and CML groups. Taken together, the results here reported established metabolic profiles of CML patients who progressed to advanced phases of the disease and failed to respond to TKI therapy as well as patients in remission. In the future, an expanded study on CML metabolomics may provide new potential prognostic markers for disease progression and response to therapy.
Estimating the Neutralizing Effect and Titer Correlation of Semi-Quantitative Anti-SARS-CoV-2 Antibody Immunoassays

For the clinical application of semi-quantitative anti-SARS-CoV-2 antibody tests, the analytical performance and titer correlation of the plaque reduction neutralization test (PRNT) need to be investigated. We evaluated the analytical performance and PRNT titer-correlation of one surrogate virus neutralization test (sVNT) kit and three chemiluminescent assays. We measured the total antibodies for the receptor-binding domain (RBD) of the spike protein, total antibodies for the nucleocapsid protein (NP), and IgG antibodies for the RBD. All three chemiluminescent assays showed high analytical performance for the detection of SARS-CoV-2 infection, with a sensitivity ≥ 98% and specificity ≥ 99%; those of the sVNT were slightly lower. The representativeness of the neutralizing activity of PRNT ND50 ≥ 20 was comparable among the four immunoassays (Cohen’s kappa ≈ 0.80). Quantitative titer correlation for high PRNT titers of ND50 ≥ 50, 200, and 1,000 was investigated with new cut-off values; the anti-RBD IgG antibody kit showed the best performance. It also showed the best linear correlation with PRNT titer in both the acute and convalescent phases (Pearson’s R 0.81 and 0.72, respectively). Due to the slowly waning titer of anti-NP antibodies, the correlation with PRNT titer at the convalescent phase was poor. In conclusion, semi-quantitative immunoassay kits targeting the RBD showed neutralizing activity that was correlated by titer; measurement of anti-NP antibodies would be useful for determining past infections.
Advanced Neuroimaging Role in Traumatic Brain Injury: A Narrative Review

Traumatic brain injury (TBI) is a common source of morbidity and mortality among civilians and military personnel. Initial routine neuroimaging plays an essential role in rapidly assessing intracranial injury that may require intervention. However, in the context of TBI, limitations of routine neuroimaging include poor visualization of more subtle changes of brain parenchymal after injury, poor prognostic ability and inability to analyze cerebral perfusion, metabolite and mechanical properties. With the development of modern neuroimaging techniques, advanced neuroimaging techniques have greatly boosted the studies in the diagnosis, prognostication, and eventually impacting treatment of TBI. Advances in neuroimaging techniques have shown potential, including (1) Ultrasound (US) based techniques (contrast-enhanced US, intravascular US, and US elastography), (2) Magnetic resonance imaging (MRI) based techniques (diffusion tensor imaging, magnetic resonance spectroscopy, perfusion weighted imaging, magnetic resonance elastography and functional MRI), and (3) molecular imaging based techniques (positron emission tomography and single photon emission computed tomography). Therefore, in this review, we aim to summarize the role of these advanced neuroimaging techniques in the evaluation and management of TBI. This review is the first to combine the role of the US, MRI and molecular imaging based techniques in TBI. Advanced neuroimaging techniques have great potential; still, there is much to improve. With more clinical validation and larger studies, these techniques will be likely applied for routine clinical use from the initial research.
Preliminary Results of the First 50 Patients Undergoing Sclerotherapy for II-Degree Hemorrhoidal Disease Using an Automated Device

Background Sclerotherapy is defined as the injection of sclerosant agents causing fibrosis and scarring of the surrounding tissue. It is currently employed for the treatment of I-III degree hemorrhoidal disease (HD). The aim of this study is to investigate the use of a new automated device for the injection of 3% polidocanol foam. Methods This is an observational study including 50 patients who underwent a sclerotherapy procedure with 3% polidocanol foam for II-degree HD according to Goligher classification. Patients were evaluated through validated scores [Giamundo score, Hemorrhoidal Disease Symptom Score (HDSS), Short Health Scale (SHS-HD) and Vaizey score]. Follow-up was conducted until 3 months from the procedure. Results Complete resolution of bleeding was achieved in 72% and 78% of patients, respectively, at 1 week and after 3 months from the procedure. Forty eight percent of patients were symptom free after the last follow-up visit (HDSS = 0). No major surgical complications were reported. Three patients out of 36 successfully treated, recurred, and needed a second sclerotherapy injection, which was successful in 2 of them. Conclusion These preliminary results of 3% polidocanol foam injection on 50 patients suggest the efficacy and reproducibility of the technique with this new device in the short-term follow-up.
Management of Postoperative Myocardial Injury After Non-cardiac Surgery in Patients Aged ≥ 80 Years: Our 10 Years' Experience

Background Postoperative myocardial injury (PMI) is associated with short- and long-term mortality. The incidence of PMI in very old patients is currently unknown. There is currently neither known effective prophylaxis nor a uniform strategy for the elderly with PMI. Objective To share our 10 years of experience in the comprehensive management of PMI after non-cardiac surgery in patients aged ≥ 80 years. Methods In this case series, we retrospectively collected and assessed the 2,984 cases aged ≥ 80 years who accepted non-cardiac surgery from 2011 to 2021 at the second Medical Center, Chinese PLA General Hospital. The incidence, risk factors, management strategy, and prognosis of surgical patients with PMI were analyzed. Results A total of 2,984 patients met our inclusion criteria. The overall incidence of PMI was 14%. In multivariable analysis, coronary artery disease, chronic heart failure, and hypotension were independently associated with the development of PMI. The patients with PMI were at a higher risk of death (OR, 2.69; 95% CI, 1.78–3.65). They were more likely to have received low molecular heparin, anti-plantlet therapy, beta-blocker, early coronary angiography, and statin than patients without PMI. The 30-day (0.96% vs. 0.35%; OR 3.46; 95% CI, 1.49–7.98; P < 0.001) and 1-year mortality (5.37% vs. 2.60%; OR 2.35; 95% CI, 1.12–6.53; P < 0.001) was significantly higher in patients with PMI compared with those without PMI. Conclusions The incidence of PMI in very old patients was high. The PMI is associated with an increased risk of 30 days and 1-year mortality. These patients can benefit from intensification of assessment and individualized care of multi-morbidities during the perioperative period. Especially cardiovascular medical treatments, such as antiplatelet, anticoagulation, β-blockers, and statins are very important for patients with PMI.
A Comparison of Sprint Mechanical Parameters Measured With Timing Gates and a Laser Gun

The aim of the study was to compare sprint mechanical parameters measured with timing gates and a laser gun. Thirty-four female team handball players (age: 17.0 ± 2.3 years, height: 1.70 ± 0.07 m, body mass: 66.7 ± 9.7 kg) performed three 30 m sprints in which the times were measured at 5, 10, 20 and 30 m with timing gates (accuracy 0.01 s) together with the distance over time by a laser gun. The main findings were that with a correction of +0.21 s (timing gates) the times and sprint mechanical properties calculated with the spreadsheet of Morin between timing gates and laser gun were not different. But when peak velocity was derived directly from the laser gun (MusclelabTM system) this was significantly higher than maximal velocity (vmax), and lower than the theoretical maximal velocity (v0) calculated with the spreadsheet. It was concluded that a correction of +0.21 s should be used to get correct mechanical properties when measuring with timing gates compared with laser gun measurements on an indoor court.
Understanding the Genetic Diversity of Mycobacterium africanum Using Phylogenetics and Population Genomics Approaches

A total of two lineages of Mycobacterium tuberculosis var. africanum (Maf), L5 and L6, which are members of the Mycobacterium tuberculosis complex (MTBC), are responsible for causing tuberculosis in West Africa. Regions of difference (RDs) are usually used for delineation of MTBC. With increased data availability, single nucleotide polymorphisms (SNPs) promise to provide better resolution. Publicly available 380 Maf samples were analyzed for identification of “core-cluster-specific-SNPs,” while additional 270 samples were used for validation. RD-based methods were used for lineage-assignment, wherein 31 samples remained unidentified. The genetic diversity of Maf was estimated based on genome-wide SNPs using phylogeny and population genomics approaches. Lineage-based clustering (L5 and L6) was observed in the whole genome phylogeny with distinct sub-clusters. Population stratification using both model-based and de novo approaches supported the same observations. L6 was further delineated into three sub-lineages (L6.1–L6.3), whereas L5 was grouped as L5.1 and L5.2 based on the occurrence of RD711. L5.1 and L5.2 were further divided into two (L5.1.1 and L5.1.2) and four (L5.2.1–L5.2.4) sub-clusters, respectively. Unassigned samples could be assigned to definite lineages/sub-lineages based on clustering observed in phylogeny along with high-confidence posterior membership scores obtained during population stratification. Based on the (sub)-clusters delineated, “core-cluster-specific-SNPs” were derived. Synonymous SNPs (137 in L5 and 128 in L6) were identified as biomarkers and used for validation. Few of the cluster-specific missense variants in L5 and L6 belong to the central carbohydrate metabolism pathway which include His6Tyr (Rv0946c), Glu255Ala (Rv1131), Ala309Gly (Rv2454c), Val425Ala and Ser112Ala (Rv1127c), Gly198Ala (Rv3293) and Ile137Val (Rv0363c), Thr421Ala (Rv0896), Arg442His (Rv1248c), Thr218Ile (Rv1122), and Ser381Leu (Rv1449c), hinting at the differential growth attenuation. Genes harboring multiple (sub)-lineage-specific “core-cluster” SNPs such as Lys117Asn, Val447Met, and Ala455Val (Rv0066c; icd2) present across L6, L6.1, and L5, respectively, hinting at the association of these SNPs with selective advantage or host-adaptation. Cluster-specific SNPs serve as additional markers along with RD-regions for Maf delineation. The identified SNPs have the potential to provide insights into the genotype–phenotype correlation and clues for endemicity of Maf in the African population.
Detection of Phenuiviridae, Chuviridae Members, and a Novel Quaranjavirus in Hard Ticks From Danube Delta

Ticks are involved in the transmission of various pathogens and several tick-borne diseases cause significant problems for the health of humans and livestock. The members of the Quaranjavirus genus are mainly associated with argas ticks but recent studies demonstrated the presence of novel quaranjaviruses-like in ixodid ticks. In 2020, 169 Rhipicephalus sanguineus ticks were collected in Southern Romania from small ruminants and analyzed by high-throughput transcriptome sequencing. Among the viral families that infect Romanian ticks, we have identified sequences from Phenuiviridae (Brown dog tick phlebovirus 1 [BDTPV1] and Brown dog tick phlebovirus 2 [BDTPV2]) and Chuviridae families (Cataloi mivirus [CTMV]), and numerous sequences from a new quaranjavirus-like, tentatively named Cataloi tick quaranjavirus (CTQV). Phylogenetic analyses performed on the five segments show that CTQV is phylogenetically positioned within a clade that encompasses Ixodidae-borne viruses associated with iguanas, small ruminants, seabirds, and penguins distributed across different geographical areas. Furthermore, CTQV is positioned differently depending on the segment considered. This is the first report on the detection of a quaranjavirus-like in Eastern Europe. Further investigations are needed to discern its infectivity and pathogenicity against vertebrates.
Effects of Sub-threshold Transcutaneous Auricular Vagus Nerve Stimulation on Cingulate Cortex and Insula Resting-state Functional Connectivity

Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive alternative to vagus nerve stimulation (VNS) with implantable devices, has shown promise in treating disorders such as depression, migraine, and insomnia. Studies of these disorders with resting-state functional magnetic resonance imaging (MRI) (rsfMRI) have found sustained changes in resting-state functional connectivity (rsFC) in patients treated with low frequency (1–20 Hz) taVNS. A recent study has reported reductions in pain scores in patients with rheumatoid arthritis after a 12-week treatment of high-frequency (20 kHz) sub-threshold taVNS. However, no studies to date have examined the effects of high-frequency sub-threshold taVNS on rsFC. The objective of this study was to determine whether high-frequency sub-threshold taVNS induces changes in rsFC using seed regions from the cingulate cortex and insula, brain regions that play a key role in interoception and processing of pain. With a single-blind placebo-controlled repeated measures experimental design, rsfMRI scans were acquired before and after 15 min of either sub-threshold taVNS treatment or a sham control. Significant taVNS-related changes in functional connections to the cingulate cortex were detected between the anterior cingulate cortex and right superior temporal gyrus and between the midcingulate cortex and right inferior parietal lobule. In addition, significant changes in functional connections to the insula were detected between the posterior insula and right precuneus and between the anterior insula and right cuneus gyrus. These results suggest that high-frequency sub-threshold taVNS can lead to sustained effects on the rsFC of brain regions involved in interoception and processing of pain in a cohort of healthy subjects. This study lays the foundation for future rsfMRI studies of high-frequency sub-threshold taVNS in clinical populations.
Embodied Object Representation Learning and Recognition

Scene understanding and decomposition is a crucial challenge for intelligent systems, whether it is for object manipulation, navigation, or any other task. Although current machine and deep learning approaches for object detection and classification obtain high accuracy, they typically do not leverage interaction with the world and are limited to a set of objects seen during training. Humans on the other hand learn to recognize and classify different objects by actively engaging with them on first encounter. Moreover, recent theories in neuroscience suggest that cortical columns in the neocortex play an important role in this process, by building predictive models about objects in their reference frame. In this article, we present an enactive embodied agent that implements such a generative model for object interaction. For each object category, our system instantiates a deep neural network, called Cortical Column Network (CCN), that represents the object in its own reference frame by learning a generative model that predicts the expected transform in pixel space, given an action. The model parameters are optimized through the active inference paradigm, i.e., the minimization of variational free energy. When provided with a visual observation, an ensemble of CCNs each vote on their belief of observing that specific object category, yielding a potential object classification. In case the likelihood on the selected category is too low, the object is detected as an unknown category, and the agent has the ability to instantiate a novel CCN for this category. We validate our system in an simulated environment, where it needs to learn to discern multiple objects from the YCB dataset. We show that classification accuracy improves as an embodied agent can gather more evidence, and that it is able to learn about novel, previously unseen objects. Finally, we show that an agent driven through active inference can choose their actions to reach a preferred observation.
A New Flow Cytometry-Based Single Platform for Universal and Differential Serodiagnosis of HTLV-1/2 Infection

In the present work, we developed and evaluated the performance of a new flow cytometry-based single platform, referred to as “FC-Duplex IgG1 (HTLV-1/2)”, for universal and differential serodiagnosis of HTLV-1/2 infection. The proposed technology employs a system for detection of IgG1 antibodies in a single competitive immunofluorescence platform by flow cytometry using fluorescently labeled MT-2/MoT cell line mix coupled to a highly sensitive development system (Biotin/Streptavidin/Phycoerythrin). The stability of fluorescent labeling and the antigenicity of MT-2 and MoT cell lines were confirmed upon storage at −20°C for 2, 6, and 12 months. The anti-HTLV-1/2 IgG1 reactivity, expressed as percentage of positive fluorescent cells (PPFC), was evaluated for each target antigen along the titration curve of test serum samples (1:32 to 1:4,096). Upon selection of target cell line and serum dilutions with higher segregation score between groups, the performance of “FIX” and “FIX & PERM” protocols was evaluated. The “FIX” protocol presented excellent performance indices (Se = 92%/Sp = 94%/AUC = 0.96; Se = 96%/Sp = 100%/AUC = 0.99) for the universal (HTLV-1/2 vs. NI) and differential (HTLV-1 vs. HTLV-2) diagnosis of HTLV-1 infection, respectively. Optimization of the “FIX” protocol using the principle of synchronous and asynchronous pairwise analysis further improved the performance of “FC-Duplex IgG1 (HTLV-1/2)”, using the “FIX” protocol for differential diagnosis of HTLV-1 and HTLV-2 infections (Se = 100%/Sp = 100%/AUC = 1.00). In conclusion, the “FC-Duplex IgG1 (HTLV-1/2)” method represents an innovation in the biotechnology segment with the potential to compose a serological kit for differential diagnosis of HTLV-1/2 infection for reference laboratories and blood centers.
Comparison of Mortality Outcomes in Acute Myocardial Infarction Patients With or Without Standard Modifiable Cardiovascular Risk Factors

Background Acute myocardial infarction (AMI) cases have decreased in part due to the advent of targeted therapies for standard modifiable cardiovascular disease risk factors (SMuRF). Recent studies have reported that ST-elevation myocardial infarction (STEMI) patients without SMuRF (termed “SMuRF-less”) may be increasing in prevalence and have worse outcomes than “SMuRF-positive” patients. As these studies have been limited to STEMI and comprised mainly Caucasian cohorts, we investigated the changes in the prevalence and mortality of both SMuRF-less STEMI and non-STEMI (NSTEMI) patients in a multiethnic Asian population. Methods We evaluated 23,922 STEMI and 62,631 NSTEMI patients from a national multiethnic registry. Short-term cardiovascular and all-cause mortalities in SMuRF-less patients were compared to SMuRF-positive patients. Results The proportions of SMuRF-less STEMI but not of NSTEMI have increased over the years. In hospitals, all-cause and cardiovascular mortality and 1-year cardiovascular mortality were significantly higher in SMuRF-less STEMI after adjustment for age, creatinine, and hemoglobin. However, this difference did not remain after adjusting for anterior infarction, cardiopulmonary resuscitation (CPR), and Killip class. There were no differences in mortality in SMuRF-less NSTEMI. In contrast to Chinese and Malay patients, SMuRF-less patients of South Asian descent had a two-fold higher risk of in-hospital all-cause mortality even after adjusting for features of increased disease severity. Conclusion SMuRF-less patients had an increased risk of mortality with STEMI, suggesting that there may be unidentified nonstandard risk factors predisposing SMuRF-less patients to a worse prognosis. This group of patients may benefit from more intensive secondary prevention strategies to improve clinical outcomes.
Impact of IDO1 and IDO2 on the B Cell Immune Response

Indoleamine-2,3-dioxygenase (IDO)1 and IDO2 are closely related tryptophan catabolizing enzymes that have immunomodulatory properties. Although initially studied as modifiers of T cell activity, emerging evidence suggests IDO1 and IDO2 also have important roles as modulators of B cell function. In this context, IDO1 and IDO2 appear to play opposite roles, with IDO1 inhibiting and IDO2 driving inflammatory B cell responses. In this mini review, we discuss the evidence for IDO1 and IDO2 modulation of B cell function, focusing on the effect of these enzymes on autoimmunity, allergic responses, protective immunity, and response to pathogens. We summarize strategies to target IDO1 and/or IDO2 as potential therapeutics for inflammatory autoimmune disease and highlight outstanding questions and areas that require future study.
Case Report: A Case With MOGAD and Anti-NMDAR Encephalitis Overlapping Syndrome Mimicing Radiological Characteristics of CLIPPERS

Herein, we reported a case of a young man diagnosed with MNOS (anti-myelin oligodendrocyte glycoprotein associated disease (MOGAD) and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis overlapping syndrome, i.e., MNOS), whose imaging findings in magnetic resonance imaging (MRI) mimicked chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). We reported a case of refractory anti-NMDAR encephalitis that recurred after standard first-line and second-line treatment. The patient presented with CLIPPERS on imaging at recent hospital admission, and his MOG antibodies were seropositive. After intravenous methylprednisolone (IVMP) treatment, the patient’s symptoms were significantly alleviated. In this case, we demonstrated that MNOS could mimic the radiological characteristics of CLIPPERS. Future studies should focus on the diagnosis and treatment of antibody overlap syndrome.