Miracle-dz/UniFAR-FTUs huggingface dataset:
Urinary 3-Methoxytyramine Is a Biomarker for MYC Activity in Patients With Neuroblastoma

PURPOSE Elevated urinary 3-methoxytyramine (3MT) level at diagnosis was recently put forward as independent risk factor for poor prognosis in neuroblastoma. Here, we investigated the biologic basis underlying the putative association between elevated 3MT levels and poor prognosis. METHODS Urinary 3MT levels and prognosis were investigated in both retrospective Italian (N = 90) and prospective Dutch (N = 95) cohorts. From the Dutch Cancer Oncology Group cohort (N = 122), patients with available urinary 3MT and gene expression data (n = 90) were used to generate a 3MT gene signature. The 3MT gene signature score was then used to predict survival outcome in the Children's Oncology Group (N = 247) and German Pediatric Oncology Group (N = 498) cohorts and compared with other known gene signatures. Immunohistochemistry of MYCN and dopamine β-hydroxylase proteins was performed on primary tumors. RESULTS Elevated urinary 3MT levels were associated with poor prognosis in a retrospective cohort and a prospective cohort. Moreover, elevated urinary 3MT levels were associated with eight differentially expressed genes, providing a 3MT gene signature that successfully predicted poor clinical outcome. Even among low-risk patients, high 3MT signature score was associated with poor 5-year overall survival (72% v 99% among low-risk patients with a low 3MT signature score), and the 3MT signature score was correlated with MYC activity in the tumor (R = 82%, P < .0001). Finally, a strong MYCN and weak dopamine β-hydroxylase staining of tumors derived from patients with elevated urinary 3MT levels was observed, linking MYC activity in the tumor to both catecholamine biosynthesis and elevated urinary 3MT levels. CONCLUSION Elevated urinary 3MT is a promising biomarker for poor prognosis and reflects increased MYC activity in the tumor. Therefore, urinary 3MT levels should be measured at diagnosis and may assist in assessing risk. Elevated urinary 3-methoxytyramine (3MT) at diagnosis is an independent risk factor for poor event-free survival and poor overall survival in neuroblastoma. Our analysis including gene-expression data and urinary 3MT showed that increased urinary 3MT corresponds with tumor MYC activity.
Novel antibodies which have an impact on immune status after allogeneic hematopoietic cell transplantation

ABSTRACT Introduction In the field of hematological malignancy, we often have the opportunity to use antibodies such as immune checkpoint inhibitors that can alter a patient’s immune status before or after allo-HCT. The appropriate use of these novel agents is highly necessary to optimize disease control and reduce the risk of complications associated with adverse allo-immune reactions. Areas covered Clinical data on several monoclonal antibodies targeting programmed cell death 1 (PD-1) (nivolumab or pembrolizumab), C-C chemokine receptor 4 (CCR4) (mogamulizumab), CD30 (brentuximab vedotin), or cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) (ipilimumab) are reviewed, with a focus on the incidence and severity of graft-versus-host disease (GVHD). Expert opinion While previous studies demonstrated a favorable prognosis in patients who received nivolumab prior to transplantation, the pretransplant use of nivolumab increases the incidence of GVHD, partly due to the expansion and activation of preexisting T cells. Mogamulizumab also has a significant impact on GVHD, caused by persistent depletion of regulatory T cells with CCR4 positivity. Regarding brentuximab vedotin, phase 1 trials have demonstrated considerable efficacy for steroid-refractory acute or chronic GVHD. In the future, sophisticated methods will be needed to determine the impact of each agent on immune status after allo-HCT.
A Genuine Interindividual Variability in Number and Anatomical Localization of Face-Selective Regions in the Human Brain.

Neuroimaging studies have reported regions with more neural activation to face than nonface stimuli in the human occipitotemporal cortex for three decades. Here we used a highly sensitive and reliable frequency-tagging functional magnetic resonance imaging paradigm measuring high-level face-selective neural activity to assess interindividual variability in the localization and number of face-selective clusters. Although the majority of these clusters are located in the same cortical gyri and sulci across 25 adult brains, a volume-based analysis of unsmoothed data reveals a large amount of interindividual variability in their spatial distribution and number, particularly in the ventral occipitotemporal cortex. In contrast to the widely held assumption, these face-selective clusters cannot be objectively related on a one-to-one basis across individual brains, do not correspond to a single cytoarchitectonic region, and are not clearly demarcated by estimated posteroanterior cytoarchitectonic borders. Interindividual variability in localization and number of cortical face-selective clusters does not appear to be due to the measurement noise but seems to be genuine, casting doubt on definite labeling and interindividual correspondence of face-selective "areas" and questioning their a priori definition based on cytoarchitectony or probabilistic atlases of independent datasets. These observations challenge conventional models of human face recognition based on a fixed number of discrete neurofunctional information processing stages.
Fusion Siamese network with drift correction for target tracking in ultrasound sequences

Motion tracking techniques can revise the bias arising from respiration-caused motion in radiation therapy. Tracking key structures accurately and at a real-time speed is necessary for effective motion tracking. In this work, we propose a fusion Siamese network with drift correction for target tracking in ultrasound sequences. Specifically, the network fuses four response maps generated by the cross-correlation between convolution layers at different resolutions to reduce up-sampling error. A correction strategy combining local structural similarity and target trajectory is proposed to revise the target drift predicted by the network. Moreover, a coarse-to-fine strategy is proposed to train the network with a limited number of annotated images, in which an augmented dataset is generated by corner points to learn network features with high generalizability. The proposed method is evaluated on the basis of the public dataset of the MICCAI 2015 Challenge on Liver UltraSound Tracking (CLUST) and our ultrasound image dataset, which is provided by the Chinese People’s Liberation Army General Hospital (CPLAGH). A tracking error of 0.80 ± 1.16 mm is observed for 85 targets across 39 ultrasound sequences in the CLUST dataset. A tracking error of 0.61 ± 0.36 mm is observed for 20 targets across 10 ultrasound sequences in the CPLAGH dataset. The effectiveness of the proposed fusion and correction strategies is verified via two ablation experiments. Overall, the experimental results demonstrate the effectiveness of the proposed fusion Siamese network with drift correction and reveal its potential in clinical practice.
A Novel Rat Model of Dry Eye Induced by Aerosol Exposure of Particulate Matter

Purpose The purpose of this study was to introduce a novel dry eye rat model induced by aerosol exposure of particulate matter (PM). Methods A total of 30 female Sprague Dawley (SD) rats divided into 3 groups: the control group, the low-level exposed group, and the high-level exposed group. The rats in the experience groups were directly exposed to PM samples in the exposure chamber over 14 days. The clinical observation, including tear volume, corneal fluorescein staining, breakup time (BUT), inflammation index, corneal irregularity score, and corneal confocal microscopy. Eyeballs were collected on day 14 for hematoxylin and eosin (H&E) staining and PAS staining. TUNEL assay, CD45, and Ki67 immunostaining was performed and corneal ultrastructural changes were detected by electron microscopy. IL-1β, TNF-α, IFN-γ, and NF-κB Western blot analysis were used to observe the possible pathogenesis. Results In the PM-treated groups, the number of layers in the corneal epithelium and corneal nerve fiber length were significantly decreased compared with that of the control group. The number of corneal epithelial microvilli and chondriosome/desmosomes were drastically reduced in PM-treated groups. Confocal microscopy and CD45 immunohistochemistry showed inflammatory cell infiltration in the PM-treated groups. PM caused apoptosis of corneal and conjunctival epithelial cells while leading to abnormal epithelial cell proliferation, meanwhile, conjunctival goblet cells in the PM-treated group were also significantly reduced. PM significantly increased the levels of IL-1β, TNF-α, IFN-γ, and p-NF-κB-p65 in the cornea. Conclusions Aerosol exposure of PM can reduce the stability of tear film and cause the change of ocular surface, which is similar to the performance of human dry eye, suggesting a novel animal model of dry eye.
Association of thyroid function with insulin resistance: data from two population-based studies

Objective Thyroid dysfunction is associated with relevant disturbances in glucose metabolism. Moreover, thyroid function undergoes important changes with ageing. The objective of this study was to investigate the association of thyroid function with insulin resistance with particular consideration of possible age-related effect modifications. Design A sample of 4193 participants from two independent epidemiological studies, the Study of Health in Pomerania-TREND-0 and the Berlin Aging Study II, was included in this cross-sectional analysis. Methods Insulin resistance was estimated by homeostasis model of insulin resistance (HOMA-IR) and the insulin sensitivity index (ISI). Associations of thyroid biomarkers (thyroid-stimulating hormone, free thyroxine, and free triiodothyronine (fT3)) with parameters of glucose metabolism were analysed by regression models adjusted for age, sex, smoking status, and study site. Results A higher fT3 was significantly associated with higher fasting glucose and higher fasting and 2-h postload insulin levels, a higher HOMA-IR, and lower ISI. A higher fT3 was also associated with a higher risk for impaired fasting glucose (RR 1.09, 95 CI 1.02; 1.18; P = 0.017). Many of these associations between thyroid markers and parameters of glucose metabolism were significant in young and middle-aged participants but not in older individuals. Conclusions The main finding of this study was a consistent association of fT3 with almost all markers of insulin resistance. However, this effect seems to be wearing off in higher age highlighting a potential age-related modification of the interaction between thyroid function and glucose metabolism. Further studies are needed to clarify causal relationships.
Auditory Nerve Fiber Discrimination and Representation of Naturally-Spoken Vowels in Noise

Abstract To understand how vowels are encoded by auditory nerve (AN) fibers, a number of representation schemes have been suggested that extract the vowel’s formant frequencies from AN-fiber spiking patterns. The current study aims to apply and compare these schemes for AN-fiber responses to naturally-spoken vowels in a speech-shaped background noise. Responses to three vowels were evaluated; based on behavioral experiments in the same species, two of these were perceptually difficult to discriminate from each other (/e/ vs /i/), and one was perceptually easy to discriminate from the other two (/a:/). Single-unit AN fibers were recorded from ketamine/xylazine-anesthetized Mongolian gerbils of either sex (n = 8). First, single-unit discrimination between the three vowels was studied. Compared with the perceptually easy discriminations, the average spike timing-based discrimination values were significantly lower for the perceptually difficult vowel discrimination. This was not true for an average rate-based discrimination metric, the rate d-prime (d’). Consistently, spike timing-based representation schemes, plotting the temporal responses of all recorded units as a function of their best frequency (BF), i.e., dominant component schemes, average localized interval rate, and fluctuation profiles, revealed representation of the vowel’s formant frequencies, whereas no such representation was apparent in the rate-based excitation pattern. Making use of perceptual discrimination data, this study reveals that discrimination difficulties of naturally-spoken vowels in speech-shaped noise originate peripherally and can be studied in the spike timing patterns of single AN fibers.
Transtemporal Sigmoid Sinus Decompression: A Novel Surgical Procedure for the Treatment of Idiopathic Pulsatile Tinnitus

Objective: Idiopathic pulsatile tinnitus (IPT) is associated with high patient morbidity although treatment methods remain unsatisfactory. In the present study, the transtemporal sigmoid sinus decompression is used in the treatment of idiopathic pulsatile tinnitus. Study Design: Retrospective case study. Setting: Tertiary referral center. Patients: From 2005 to 2020, 287 patients presented with a complaint of pulsatile tinnitus. After exclusion criteria, 25 patients were diagnosed with IPT. Those patients underwent treatment and were included in a retrospective study. Interventions: Following failed conservative therapies, the primary author performed a transtemporal sigmoid sinus decompression surgery on the patients under general anesthesia. Main Outcome Measures: Long-term resolution of IPT was measured using the Tinnitus Handicap Inventory (THI). Outcome measurements were taken preoperatively, immediately postoperatively, three months postoperatively, and the status of all 25 patients is known at the time of this study. Results: Transtemporal sigmoid sinus decompression was performed on 25 patients (mean age: 51.7 years, 80.0% female). Out of the 25 patients, 23 (92.0%) patients experienced complete resolution of their IPT. Statistically significant differences based on preoperative THI (mean THI: 4.19) were evident immediately after surgery (mean THI: 1.31; p < 0.001), at 3 months postoperatively (mean THI: 1.19; p < 0.001), and over a mean follow-up time of 68.7 months (range, 3–168 months) (mean THI: 1.38; p < 0.001). Out of the two patients considered unsuccessful, Case 21 experienced a partial resolution. No major postoperative complications occurred. Conclusions: Transtemporal sigmoid sinus decompression is a safe and effective surgical procedure demonstrated to give near total resolution in properly selected patients and provides long-term relief for patients with IPT.
Taste and Smell Disorders in COVID-19 Patients at a Local Healthcare Trust in Northern Italy: a Cross-Sectional Study.

Background In Italy, since the beginning of the COVID-19 pandemic, patients testing positive for SARS-CoV-2 through nasopharyngeal swab have reported taste and smell alterations. As these symptoms are quite uncommon in other respiratory infections, their specificity and prevalence are useful features for the differential diagnosis of COVID-19. The objective was to describe taste and smell alterations in patients diagnosed with SARS-CoV-2 infection and to define the onset of those disorders during the clinical course of the disease. Study design Cross-sectional study. Methods This study was conducted on adult patients testing positive for SARS-CoV-2 infection through nasopharyngeal swab at a Local Healthcare Trust in Northern Italy between April 27th and May 27th, 2020. In order to investigate the clinical course, the onset of the first symptoms, smell and/or taste alterations, a phone-based questionnaire was administered during the programming of the second nasopharyngeal swab. Results We recruited 168 patients; the mean age was 52 years old, and 94 (56.0%) were female. Among the 135 symptomatic patients, 87 (64.4%) reported taste and smell alterations. Patients with a mild clinical course showed the highest prevalence for taste and smell disorders (76.6%), which were also associated with a more benign clinical course of the disease (P = 0.0166). Furthermore, in 33 (37.9%) of these patients, changes in smell and taste perception appeared before the acute phase of the disease. Among the 14 patients with a severe clinical course of SARS-CoV-2 infection, 8 reported a variation of taste and smell perception before the hospitalization, with a median of 4 days (IQR 2-7). Conclusions Smell and taste disorders can be listed among the first symptoms of SARS-CoV-2 infection and may anticipate the acute phase of the disease. Noteworthy, they seem to be associated with a more benign clinical course.
Trunk Muscle Activation during Bridge Exercise with Various Shoulder Supporting Surfaces

【PURPOSE: Bridge exercises are broadly used to develop trunk co-activation patterns that promote spine stability. This study was to analyze the trunk muscle activity during bridge exercise with various shoulder support surface(stable, sling, Swiss ball). METHODS: The subjects were 20 healthy subjects in their twenties. Subjects were performed bridge exercise on 4 different shoulder support surfaces using stable and labile instruments. 1) Bridge exercise on a stable surface. 2) Bridge exercise with their shoulder on a stable bench. 3) Bridge exercise with their shoulder on a sling. 4) Bridge exercise with their shoulder on a Swiss ball. Rectus abdominis, erector spinae, internal oblique, external oblique muscle activities were measured using electromyography. RESULTS: There were significant differences in RA, EO muscles between performing each of the 4 exercises(p】
Drug resistance characteristics of Mycobacterium tuberculosis isolates obtained between 2018 and 2020 in Sichuan, China

Abstract We investigated the drug resistance of Mycobacterium tuberculosis isolates from patients with tuberculosis (TB) and HIV, and those diagnosed with only TB in Sichuan, China. TB isolates were obtained from January 2018 to December 2020 and subjected to drug susceptibility testing (DST) to 11 anti-TB drugs and to GeneXpert MTB/RIF testing. The overall proportion of drug-resistant TB (DR-TB) isolates was 32.1% (n = 10 946). HIV testing was not universally available for outpatient TB cases, only 29.5% (3227/10 946) cases had HIV testing results. The observed proportion of multidrug-resistant TB (MDR-TB) isolates was almost double than that of the national level, with approximately 1.5% and 0.1% of the isolates being extensively drug resistant and universally drug resistant, respectively. The proportions of resistant isolates were generally higher in 2018 and 2019 than in 2020. Furthermore, the sensitivities of GeneXpert during 2018–2020 demonstrated a downward trend (80.9, 95% confidence intervals (CI) 76.8–85.0; 80.2, 95% CI 76.4–84.1 and 75.4, 95% CI 70.7–80.2, respectively). Approximately 69.0% (7557/10 946) of the TB cases with DST results were subjected to GeneXpert detection. Overall, the DR-TB status and the use of GeneXpert in Sichuan have improved, but DR-TB challenges remain. HIV testing for all TB cases is recommended.
The Top 100 Most-Cited Papers in Erosive Tooth Wear: A Bibliometric Analysis

Citation rates can be used as an indicator of the influence and relevance of scientific papers. The present study analyzed the 100 most-cited articles related to erosive tooth wear (ETW). The top 100 most-cited papers focusing on ETW topics were collected from the Web of Science database on November 11, 2020. The following bibliometric data were extracted from papers: title, authorship, institutions, countries, number of citations, year of publication, journal title, study design, topic, and keywords. Scopus and Google Scholar were searched to compare the number of citations. The VOSviewer software was used to generate collaborative network maps for the authors and keywords. The number of citations of the 100 most-cited papers ranged from 71 to 330 (average: 97.44). The papers were published between 1949 and 2015. Caries Research (28%) and The Journal of Dentistry (16%) presented the majority of papers. Laboratorial (44%) and observational studies (33%) were the most common study designs. The most studied topics were epidemiology (31%) and the erosive potential of substances (drinks, foods, or medicines) (22%). The countries with the highest number of most-cited papers were England (32%), Germany (18%), and Switzerland (10%). The University of Bern was the institution with the most papers (10%). Lussi A was the author with the highest number of papers in the top 100 (14%). The most common keyword was “dental erosion” with 64 occurrences. The top 100 most-cited papers related to ETW were composed mainly of laboratorial and observational studies focusing on epidemiology and the erosive potential of substances.
Combined serum free light chain predicts prognosis in acute kidney injury following cardiovascular surgery

Abstract Objectives Increased polyclonal free light chains (FLCs) are found in inflammatory conditions. Inflammation is recognized in the progression of acute kidney injury (AKI). This study was aimed to determine whether polyclonal combined FLC (cFLC) was associated with prognosis of AKI patients. Methods This prospective cohort included 145 adults with hospital-acquired AKI following cardiovascular surgery between 2014 and 2016, according to the KDIGO creatinine criteria. The primary end point of the study was all-cause death during follow-up. Results The median of serum cFLC concentration in the cohort was 42.0 (31.9–60.3 mg/L) and levels of cFLC in patients with AKI stage 3 were higher than those in AKI stage 1 and stage 2. cFLC levels correlated significantly with renal function biomarkers, high sensitivity C-reactive protein (hsCRP), and sequential organ failure assessment (SOFA) score. Patients were organized into the following two groups: the low-cFLC group (cFLC <43.3 mg/L) and the high-cFLC group (cFLC ≥ 43.3 mg/L). A total of 17 (11.0%) patient deaths occurred within 90 d, 13 (18.8%) in the high-cFLC group. Kaplan–Meier analysis revealed that the two groups differed significantly with respect to 90-d survival (log-rank p = .012), and Cox regression analysis showed that an cFLC level ≥43.3 mg/L was significantly associated with a 5.0-fold increased risk of death (adjusted hazard ratio [HR], 5.95; 95% confidence interval [CI], 1.04– 33.91; p = .045) compared with an cFLC level <43.3 mg/L. Conclusions Serum cFLC levels were significantly elevated and might be an independent predictor of mortality in patients with AKI following cardiovascular surgery.