Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection and Characterization of Carbapenemases in Enterobacterales With a New Rapid and Simplified Carbapenemase Detection Method Called rsCDM

Objective This study aimed to develop a new rapid and simplified carbapenemase detection method (rsCDM) for detection and characterization of carbapenemase with 3-aminophenylboronic acid (APBA), ethylenediaminetetraacetic acid (EDTA), and cloxacillin (CLO) β-lactamase inhibitors. Methods A panel of 182 carbapenem-resistant Enterobacterales (CRE) strains with blaKPC (88), blaNDM (60), blaIMP (10), blaVIM (3), blaOXA-181 (5), blaKPC, and blaNDM (7), porin changes in combination with an extended-spectrum β-lactamase (ESBL) (3) or AmpC hyper-production (6) and 43 carbapenem-susceptible Enterobacterales isolates were used to evaluate the performance of rsCDM and EDTA-carbapenem inactivation method (eCIM). Carbapenemase class was determined with specific inhibitors at 4, 6, and 18 h by rsCDM, and the difference between imipenem (IMI) and meropenem (MEM) disks was simultaneously compared. Results The sensitivity of rsCDM using IMI was 97.1% at the three time points, with a specificity of 100%, independent of the culture duration. Similar to IPM, MEM disk also showed high sensitivity (97.1%) and specificity (100%) at 6 h. And the sensitivity of eCIM was 95.4% and the specificity was 100%. Based on a decision algorithm, the characterization number of IMI and MEM in KPC-producing isolates was 88 vs. 87, metallo-β-lactamases (MBLs) was 73 vs. 72, KPC and NDM carbapenemase was 7 vs. 7 at 4 h, respectively. After 6 h, the category number changed insignificantly except for isolates with combined AmpC overproduction and porin changes, showing an increase in IMI (6) and MEM (2), and there was no difference in the results between 6 and 18 h for the two tablets. OXA-181-producing strains can’t be distinguished by rsCDM. For eCIM, the characterization number in KPC-, OXA- 181-, and MBLs-producing strains was 88, 5, and 72, but it failed to detect multi-enzyme-producing isolates (KPC and NDM). Conclusion rsCDM accurately discriminated carbapenemase within 4 h and could differentiate multi-enzyme (KPC and NDM) and AmpC in conjunction with porin changes strains. Hence, rsCDM represents a rapid, simple, easy readout, and accurate tool that can be used without any specialized equipment.
Using Non-linear Dynamics of EEG Signals to Classify Primary Hand Movement Intent Under Opposite Hand Movement

Decoding human hand movement from electroencephalograms (EEG) signals is essential for developing an active human augmentation system. Although existing studies have contributed much to decoding single-hand movement direction from EEG signals, decoding primary hand movement direction under the opposite hand movement condition remains open. In this paper, we investigated the neural signatures of the primary hand movement direction from EEG signals under the opposite hand movement and developed a novel decoding method based on non-linear dynamics parameters of movement-related cortical potentials (MRCPs). Experimental results showed significant differences in MRCPs between hand movement directions under an opposite hand movement. Furthermore, the proposed method performed well with an average binary decoding accuracy of 89.48 ± 5.92% under the condition of the opposite hand movement. This study may lay a foundation for the future development of EEG-based human augmentation systems for upper limbs impaired patients and healthy people and open a new avenue to decode other hand movement parameters (e.g., velocity and position) from EEG signals.
Safety and Efficacy of Tirofiban During Intravenous Thrombolysis Bridging to Mechanical Thrombectomy for Acute Ischemic Stroke Patients: A Meta-Analysis

Introduction The safety and efficacy of tirofiban in intravenous thrombolysis (IVT) bridging to mechanical thrombectomy in patients with acute ischemic stroke (AIS) is unknown. The purpose of this meta-analysis was to evaluate the safety and efficacy of tirofiban in IVT bridging to mechanical thrombectomy in acute ischemic stroke. Methods We systematically searched PubMed, EMBASE, Web of Science, and The Cochrane Library, CNKI, and Wan Fang databases for randomized controlled trials and observational studies (case-control studies and cohort studies) comparing the tirofiban and non-tirofiban groups in AIS intravenous thrombolysis bridging to mechanical thrombectomy (Published by November 20, 2021). Our primary safety endpoints were symptomatic cerebral hemorrhage (sICH), intracranial hemorrhage (ICH), postoperative re-occlusion, and 3-month mortality; the efficacy endpoints were 3-month favorable functional outcome (MRS ≤ 2) and successful recanalization rate (modified thrombolytic therapy in cerebral infarction (mTICI) 2b or 3). Results A total of 7 studies with 1,176 patients were included in this meta-analysis. A comprehensive analysis of the included literature showed that the difference between the tirofiban and non-tirofiban groups in terms of successful recanalization (OR = 1.19, 95% Cl [0.69, 2.03], p = 0.53, I2 = 22%) and favorable functional outcome at 3 months (OR = 1.13, 95% Cl [0.81, 1.60], p = 0.47, I2 = 17%) in patients with IVT bridging mechanical thrombectomy of AIS was not statistically significant. Also, the differences in the incidence of sICH (OR = 0.97, 95% Cl [0.58, 1.62], p = 0.89) and ICH (OR = 0.83, 95% Cl [0.55, 1.24], p = 0.36) between the two groups were not statistically significant. However, the use of tirofiban during IVT bridging mechanical thrombectomy reduced the rate of postoperative re-occlusion (OR = 0.36, 95% Cl [0.14, 0.91], p = 0.03) and mortality within 3 months (OR = 0.54, 95% Cl [0.33, 0.87], p = 0.01) in patients. Conclusion The use of tirofiban during IVT bridging mechanical thrombectomy for AIS does not increase the risk of sICH and ICH in patients and reduces the risk of postoperative re-occlusion and mortality in patients within 3 months. However, this result needs to be further confirmed by additional large-sample, multicenter, prospective randomized controlled trials. Systematic Review Registration http://www.crd. york.ac. uk/PROSPERO/, identifier: CRD42022297441.
Elevated Axonal Protein Markers Following Repetitive Blast Exposure in Military Personnel

Blast exposures that occur during training are common in military personnel; however, the biomarkers that relate to these subtle injuries is not well understood. Therefore, the purpose of this study is to identify the acute biomarkers related to blast injury in a cohort of military personnel exposure to blast-related training. Thirty-four military personnel who participated in the training program were included in this study. Blood samples were collected before and after repetitive blast-related training on days 2 (n = 19) and days 7 (n = 15). Serum concentration (pg/mL) of tau, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau181 (p-tau181) were measured using an ultrasensitive immunoassay platform. We observed that serum p-tau181 concentrations were elevated after exposed to repetitive blast on days 2 (z = −2.983, p = 0.003) and days 7 (z = −2.158, p = 0.031). Serum tau (z = −2.272, p = 0.023) and NfL (z = −2.158, p = 0.031) levels were significantly elevated after exposure to repetitive blasts on days 7. Our findings indicate that blast exposure affects serum biomarkers indicating axonal injury.
A Combined Effect of G-Quadruplex and Neuro-Inducers as an Alternative Approach to Human Glioblastoma Therapy

Cancer cell reprogramming based on treatment with G-quadruplex, having antiproliferative power, along with small molecules able to develop iPSCs into neurons, could create a novel approach to diminish the chance of glioblastoma recurrence and circumvent tumor resistance to conventional therapy. In this research, we have tested several combinations of factors to affect both total cell cultures, derived from tumor tissue of patients after surgical resection and two subfractions of this cell culture after dividing them into CD133-enriched and CD133-depleted populations (assuming CD133 to be a marker of glioblastoma stem-like cells). CD133+ and CD133− cells exhibit different responses to the same combinations of factors; CD133+ cells have stem-like properties and are more resistant. Therefore, the ability to affect CD133+ cells provides a possibility to circumvent resistance to conventional therapy and to build a promising strategy for translation to improve the treatment of patients with glioblastoma.
Clinical Features and Genetic Spectrum of Patients With Clinically Suspected Hereditary Progressive Spastic Paraplegia

Background and Purpose A variety of hereditary diseases overlap with neurological phenotypes or even share genes with hereditary spastic paraplegia (HSP). The aim of this study was to determine the clinical features and genetic spectrum of patients with clinically suspected HSPs. Methods A total of 52 patients with clinically suspected HSPs were enrolled in this study. All the patients underwent next-generation sequencing (NGS) and triplet repeat primed PCR to screen for the dynamic mutations typical of spinocerebellar ataxia (SCA). Multiplex ligation-dependent probe amplification (MLPA) was further conducted in patients with no causative genetic mutations detected to examine for large deletions and duplications in genes of SPAST, ATL1, REEP1, PGN, and SPG11. Clinical characteristics and findings of brain MRI were analyzed in patients with definite diagnoses. Results The mean age of the patients studied was 36.90 ± 14.57 years. 75% (39/52) of patients manifested a phenotype of complex form of HSPs. A genetic diagnosis was made in 51.9% (27/52) of patients, of whom 40.3% (21/52) of patients had mutations in HSPs genes (SPG4/SPG6/SPG8/SPG11/SPG15/SPG78/SPG5A) and 11.5% (6/52) of patients had mutations in SCAs genes (SCA3/SCA17/SCA28). SPG4 and SPG11 were the most common cause of pure form of HSPs (5/6, 83.3%) and complex form of HSPs (5/15, 33.3%), respectively. Gait disturbance was the most common initial symptom in both the patients with HSPs (15/21) and in patients with SCAs (5/6). Dysarthria and cerebellar ataxia were detected in 28.5% (6/21) and 23.8% (5/21) of patients with HSPs, respectively, and were the most common symptoms in addition to progressive weakness and spasticity of the lower limbs. Cerebellar atrophy was seen on the brain MRI of patients with SPG5A, SCA3, and SCA28. Conclusion Causative genetic mutations were identified in 51.9% of patients with clinically suspected HSPs by NGS and triplet repeat primed PCR. A final diagnosis of HSPs or SCAs was made in 40.3% and 11.5% of patients, respectively. The clinical manifestations and neuroimaging findings overlapped between patients with HSPs and patients with SCAs. Dynamic mutations should be screened in patients with clinically suspected HSPs, especially in those with phenotypes of complex form of HSPs.
Response: Commentary: Deformation Pattern of the Northern Sector of the Malta Escarpment (Offshore SE Sicily, Italy): Fault Dimension, Slip Prediction, and Seismotectonic Implications

Department of Biological, Geological and Environment Sciences, University of Catania, Catania, Italy, CRUST—Interuniversity Center for 3D Seismotectonics with Territorial Applications, Chieti, Italy, Institute of Geosciences, Kiel University, Kiel, Germany, Center for Ocean and Society, Kiel University, Kiel, Germany, Istituto Nazionale di Geofisica e Vulcanologia, Osservatorio Etneo, Catania, Italy, Laboratoire Géosciences Ocean, CNRS/University of Brest, Catania, France
Association of Mild Thyroid Dysfunction and Adverse Prognosis Among Chinese Patients With Acute ST Segment Elevation Myocardial Infarction

Aims Thyroid hormones widely affect the cardiovascular system, but the effects of mild thyroid dysfunction on the clinical prognosis of patients with acute ST segment elevation myocardial infarction (STEMI) remains unclear. Our aims were to analyze the relations between mild thyroid dysfunction at admission and clinical outcomes in Chinese patients with STEMI. Methods A total of 1,176 STEMI patients with the available data of thyroid function and follow-up were analyzed, including 348 patients with mild thyroid dysfunction [subclinical hypothyroidism (n=81), hyperthyroidism (SHyper) (n=51), and low triiodothyronine syndrome (LT3S) (n=216)] and 828 patients with euthyroid function. During a median 4.4-year follow-up, in-hospital mortality, cardiac and all-cause mortalities were subsequently compared among the four groups. Results Compared with the euthyroid group, STEMI patients in the SHyper and LT3S groups faced obviously increased risks of in-hospital death [odds ratio (OR): 5.007, 95% confidence interval (CI): 1.246–20.124, p = 0.023 and OR: 2.491, 95% CI: 1.054–5.887, p = 0.037, respectively) even after adjustment for various confounding factors. During a median 4.4-year follow-up, STEMI patients with LT3S at baseline had higher cardiovascular mortality [hazard ratio (HR): 1.880, 95% CI: 1.178–2.998, p = 0.008] and all-cause mortality HR: 1.647, 95% CI: 1.072–2.531, p = 0.023] than those with euthyroid at baseline, whereas no significantly increased mortality was found for STEMI patients with SCH and SHyper at baseline. Conclusions STEMI patients with SHyper at admission had increased risk of in-hospital mortality, and STEMI patients with LT3S at baseline had worse prognosis and higher incidences of in-hospital mortality and cardiovascular and all-cause deaths compared with euthyroid patients.
Contralaterally Controlled Functional Electrical Stimulation Combined With Brain Stimulation for Severe Upper Limb Hemiplegia—Study Protocol for a Randomized Controlled Trial

Background Approximately two-thirds of stroke survivors experience chronic upper limb paresis, and of them, 50% experience severe paresis. Treatment options for severely impaired survivors are often limited. Rehabilitation involves intensively engaging the paretic upper limb, and disincentivizing use of the non-paretic upper limb, with the goal to increase excitability of the ipsilesional primary motor cortex (iM1) and suppress excitability of the undamaged (contralesional) motor cortices, presumed to have an inhibitory effect on iM1. Accordingly, brain stimulation approaches, such as repetitive transcranial magnetic stimulation (rTMS), are also given to excite iM1 and/or suppress contralesional motor cortices. But such approaches aimed at ultimately increasing iM1 excitability yield limited functional benefit in severely impaired survivors who lack sufficient ipsilesional substrate. Aim Here, we test the premise that combining Contralaterally Controlled Functional Electrical Stimulation (CCFES), a rehabilitation technique that engages the non-paretic upper limb in delivery of neuromuscular electrical stimulation to the paretic upper limb, and a new rTMS approach that excites intact, contralesional higher motor cortices (cHMC), may have more favorable effect on paretic upper limb function in severely impaired survivors based on recruitment of spared, transcallosal and (alternate) ipsilateral substrate. Methods In a prospective, double-blind, placebo-controlled RCT, 72 chronic stroke survivors with severe distal hand impairment receive CCFES plus cHMC rTMS, iM1 rTMS, or sham rTMS, 2X/wk for 12wks. Measures of upper limb motor impairment (Upper Extremity Fugl Meyer, UEFM), functional ability (Wolf Motor-Function Test, WMFT) and perceived disability are collected at 0, 6, 12 (end-of-treatment), 24, and 36 wks (follow-up). TMS is performed at 0, 12 (end-of-treatment), and 36 wks (follow-up) to evaluate inter-hemispheric and ipsilateral mechanisms. Influence of baseline severity is also characterized with imaging. Conclusions Targeting of spared neural substrates and rehabilitation which engages the unimpaired limb in movement of the impaired limb may serve as a suitable combinatorial treatment option for severely impaired stroke survivors. ClinicalTrials No NCT03870672.
Video Head Impulse Test Changes Related to Obstructive Sleep Apnea: In Reply to the Work of Xin-Da Xu et al.

We read with interest the last issue of your Journal in which the following article has been published by Xin-Da Xu et al.: “Uneven Effects of Sleep Apnea on Semicircular Canals andOtolithic Organs” (1). In their valuable work, the authors discussed different works depicting changes in vestibular evoked myogenic potentials and caloric testing in patients with obstructive sleep apnea (OSA). However, they highlighted that only a few works focused on semicircular canal weakness in patients affected by OSA when studied by means of video head impulse test (vHIT) and pointed attention to the lack of control groups in previous works [see for example Birk et al. (2)]. Although we agree that few published works exist in this field, we believe that the researchers interested in the topic may appreciate that one previous study not only found a vestibulo-ocular reflex (VOR) gain deficit in patients with OSA, when studied by means of vHIT and compared with a group of healthy subjects, but this finding was significantly related to changes in oxygen saturation (3). To corroborate such relationships, a further study by Alessandrini et al. demonstrated a significant improvement in VOR gain after 1 year of continuous positive airway pressure treatment in the same sample of participants with OSA (4). Furthermore, an interesting debate arose in 2018 in an issue of SleepMedicine Reviews between the research groups of Besnard S and Alessandrini M. They finally assessed that beyond the impaired higher-level vestibular neural inflow related to sleep deprivation, the functional alterations of the vestibular nuclei may be an indirect indicator of abnormal activity of the respiratory nuclei during OSA, considering their anatomical contiguity and the susceptibility of the posterior labyrinth to a hypoxic state (5–7). In this scenario, we believe that although more studies are needed to better understand vHIT changes in the course of the natural history of OSA, a certain degree of evidence has been already obtained and we believe that it could be helpful to integrate the work of Xin-Da Xu et al. with these notions.
Practical Protocols for Efficient Sampling of Kinase-Inhibitor Binding Pathways Using Two-Dimensional Replica-Exchange Molecular Dynamics

Molecular dynamics (MD) simulations are increasingly used to study various biological processes such as protein folding, conformational changes, and ligand binding. These processes generally involve slow dynamics that occur on the millisecond or longer timescale, which are difficult to simulate by conventional atomistic MD. Recently, we applied a two-dimensional (2D) replica-exchange MD (REMD) method, which combines the generalized replica exchange with solute tempering (gREST) with the replica-exchange umbrella sampling (REUS) in kinase-inhibitor binding simulations, and successfully observed multiple ligand binding/unbinding events. To efficiently apply the gREST/REUS method to other kinase-inhibitor systems, we establish modified, practical protocols with non-trivial simulation parameter tuning. The current gREST/REUS simulation protocols are tested for three kinase-inhibitor systems: c-Src kinase with PP1, c-Src kinase with Dasatinib, and c-Abl kinase with Imatinib. We optimized the definition of kinase-ligand distance as a collective variable (CV), the solute temperatures in gREST, and replica distributions and umbrella forces in the REUS simulations. Also, the initial structures of each replica in the 2D replica space were prepared carefully by pulling each ligand from and toward the protein binding sites for keeping stable kinase conformations. These optimizations were carried out individually in multiple short MD simulations. The current gREST/REUS simulation protocol ensures good random walks in 2D replica spaces, which are required for enhanced sampling of inhibitor dynamics around a target kinase.
Fat-Free Mass Index, Visceral Fat Level, and Muscle Mass Percentage Better Explain Deviations From the Expected Value of Aortic Pressure and Structural and Functional Arterial Properties Than Body Fat Indexes

Bioelectrical impedance analysis (BIA)-derived indexes [e.g., fat (FMI) and fat-free mass indexes (FFMI), visceral fat level (VFL)] are used to characterize obesity as a cardiovascular risk factor (CRF). The BIA-derived index that better predicts arterial variability is still discussed. Aims To determine: (1) the association of classical [weight, height, body mass index (BMI), basal metabolic rate (BMR)] and BIA-derived indexes, with arterial properties deviations from expected values (arterial z-scores); (2) maximum arterial variations attributable to BIA-derived indexes; (3) whether the composition of total body, trunk and/or limbs is most closely associated with arterial variations. Methods Hemodynamic, structural, and functional parameters of different histological types of arteries were assessed (n = 538, 7–85 years). Classical and BIA-derived indexes [fat mass and percentage, FMI, VFL, muscle mass percentage (PMM), FFMI, and percentage] were measured (mono- and multi-segmental devices). Arterial z-scores were obtained using age-related equations derived from individuals not-exposed to CRFs (n = 1,688). Results First, regardless of the classical index considered, the associations with the arterial properties showed a specific hierarchy order: diameters and local stiffness > aortic and brachial blood pressure (BP) > regional stiffness. Second, all the associations of FMI and FFMI with z-scores were positive. Third, FFMI exceeded the association obtained with BMI and BMR, considering structural z-scores. In contrast, FMI did not exceed the association with z-scores achieved by BMI and BMR. Fourth, regardless of CRFs and classical indexes, arterial z-scores would be mainly explained by FFMI, VFL, and PMM. Fifth, regardless of the body-segment considered, the levels of association between FMI and z-scores did not exceed those found for classic and FFMI. Total fat mass and trunk indexes showed a greater strength of association with z-scores than the FMI of limbs. Sixth, compared to lower limb FFMI indexes, total and upper limbs FFMI showed higher levels of association with z-scores. Conclusions FFMI (but not FMI) exceeded the strength of association seen between BMI or BMR and structural z-scores. Regardless of the body segment analyzed, the associations between FMI and z-scores did not exceed those found with classic and FFMI. Arterial z-scores could be independently explained by FFMI, VFL, and PMM.
D2 Marrow via Proresolving Mediators Resolvin Facilitates Macrophage Efferocytosis in Bone Cutting Edge: Parathyroid Hormone

Bone marrow macrophages stimulate skeletal wound repair and osteoblastic bone formation by poorly de-ﬁned mechanisms. Specialized proresolving mediators of inﬂammation drive macrophage efferocytosis (phago-cytosis of apoptotic cells) and resolution, but little is known regarding this process in the bone marrow. In this study, metabololipidomic proﬁling via liquid chromatography mass spectrometry revealed higher levels of specialized proresolving mediators in the bone marrow relative to the spleen. The endocrine and bone anabolic agent parathyroid hormone increased specialized proresolving mediator levels, including resolvins (Rvs), in bone marrow. Human and murine primary macrophages efferocytosed apoptotic osteoblasts in vitro, and RvD1 and RvD2 (10 pM–10 nM) enhanced this process. These ﬁndings support a unique proﬁle of specialized lipid mediators in bone marrow that contribute to a feedback system for resolution of inﬂammation and maintenance of skeletal homeostasis. The Journal of Immunology , 2014, 193: 000–000.