Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of self-reported middle ear disease, hearing loss and vertigo in two adult population-based cohorts over a 20-year period in Greenland

ABSTRACT To estimate the frequencies of self-reported middle ear and hearing complaints and vertigo/dizziness in adult Greenlanders. Furthermore, to examine if there has been a development in the frequency of these complaints within a 20-year period. A structured questionnaire concerning middle ear disease and related neuro-otological symptoms was mailed to 400 randomly selected adult Greenlanders between 18 and 60 years of age in 1995. In 2014, the questions were included for the same age group in the general Greenlandic Health Survey. The questionnaires contained a total of six identical questions. In 1995, 281 participants (70%) replied to the questionnaire. In 2014, 1,639 participants (78%) replied. We found that in 1995 the two youngest age groups (18–29- and 30–39-year-olds) had the highest relative number of ear discharge. Approximately one-third of the participants in these two age groups reported to have had ear discharge, while this was only reported by 17% of the 18–29-year-olds and 16% of the 30–39-year-olds in 2014 (95% CI [0.03, 0.3] and [0.1, 0.3], respectively). The oldest age group indicated the lowest relative number of experiences of ear discharge in both 1995 and 2014 (18% and 17%, respectively). In 1995, 30% in the age group 30–39-year-olds reported hearing loss, whereas only 18% reported hearing loss in 2014 (p < 0.05, 95% CI [-0.003,0.2]). There was no significant difference in reported ear discharge since childhood and otitis media in childhood among the age groups between 1995 and 2014. However, in 1995 significantly more females had experienced ear discharge in the age groups 18–29 and 30–39 year-olds compared to 2014. Females in the age group 18–29 year-olds also showed a significant difference in having experienced otitis media in childhood, where 32% answered “yes” in 1995, and 18% answered “yes” in 2014 (p < 0.05). In 2014, females reported more frequent complaints of vertigo compared to males, 16% and 9%, respectively (p < 0.05). In 1995, there was no significant difference in experienced vertigo between males and females. Ear and hearing health problems and vertigo are reported frequently in the Greenlandic population. Overall, a tendency of less complaints in 2014 compared to 1995 except for vertigo. It is important to follow this trend and increase the prophylactic efforts to reduce common health disabilities like early otitis media in childhood and noise created symptoms even more.
Sea urchin mass mortalities 40 y apart further threaten Caribbean coral reefs

Significance A historically abundant sea urchin has been struck by two mass mortalities separated by 40 y. The 1983 event was across the Western Atlantic and populations never fully recovered. The 2022 event has thus far has reduced population densities in many regions of the Caribbean. On St. John, US Virgin Islands, the geographical epicenter of the 2022 event, these sequential mortality events transitioned the distribution of D. antillarum from highly abundant prior to 1984, to a locally patchy species associated with small areas of high coral recruitment, to a rare species in 2022, eliminating their characteristic grazing that once promoted coral recruitment and survival.
Comparison of GATA-3, Mammaglobin and GCDFP-15 Expression in Primary, Metastatic and Triple Negative Breast Carcinomas: An Indian Scenario

Background and objective: Mammaglobin and GCDFP-15 are traditional immunohistochemistry (IHC) markers utilized to recognize metastasis of breast carcinoma in an unknown primary. GATA-3 is increasingly being used as a marker of primary breast origin. This study was done to evaluate and compare GATA-3 with GCDFP-15 and Mammaglobin in invasive primary including metastatic and triple negative breast carcinomas. Methods: Immunohistochemistry for GATA-3, GCDFP-15 and Mammaglobin was applied on 100 cases of primary breast carcinomas, including 20 triple negative cases and 30 cases of metastatic breast carcinomas. Staining scores were given for each marker by multiplying the percentage of positive tumor cells by the intensity of staining (1+, 2+ or 3+), with scores ranging from 0 to 300. Staining score of 1 or more was considered positive. Results: GATA-3 was expressed in 92% of primary, 80% of metastatic and 60% of triple negative breast carcinomas, with an average staining score of 270. Mammaglobin was expressed in 68% of primary, 56.6% of metastatic and 25% of triple negative breast carcinomas, with an average staining score of 180. GCDFP-15 was expressed in 48% of primary, 26.6% of metastatic and 05% of breast carcinomas, with an average staining score of 60. GATA-3 demonstrated to have higher staining score (average of 270) than other two markers in maximum number of cases. Conclusion: GATA-3 has a higher sensitivity and increased staining scores in primary breast carcinomas, metastatic breast carcinomas as well as in triple negative breast carcinomas.
Nonmetastatic Rhabdomyosarcoma in Children and Adolescents: Overall Results of the European Pediatric Soft Tissue Sarcoma Study Group RMS2005 Study

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The RMS2005 study included two phase III randomized trials for high-risk (HR) and observational trials for low (LR), standard (SR), and very high-risk (VHR) patients who have been partially reported. Herein, we present a comprehensive report of results achieved for the complete unselected nonmetastatic cohort and analyze the evolution of treatment in comparison with previous European protocols. After a median follow-up of 73.1 months, the 5-year event-free survival (EFS) and overall survival (OS) of the 1,733 patients enrolled were 70.7% (95% CI, 68.5 to 72.8) and 80.4% (95% CI, 78.4 to 82.3), respectively. The results by subgroup: LR (80 patients) EFS 93.7% (95% CI, 85.5 to 97.3), OS 96.7% (95% CI, 87.2 to 99.2); SR (652 patients) EFS 77.4% (95% CI, 73.9 to 80.5), OS 90.6% (95% CI, 87.9 to 92.7); HR (851 patients) EFS 67.3% (95% CI, 64.0 to 70.4), OS 76.7% (95% CI, 73.6 to 79.4); and VHR (150 patients) EFS 48.8% (95% CI, 40.4 to 56.7), OS 49.7% (95% CI, 40.8 to 57.9). The RMS2005 study demonstrated that 80% of children with localized rhabdomyosarcoma could be long-term survivors. The study has established the standard of care across the European pediatric Soft tissue sarcoma Study Group countries with the confirmation of a 22-week vincristine/actinomycin D regimen for LR patients, the reduction of the cumulative ifosfamide dose in the SR group, and for HR disease, the omission of doxorubicin and the addition of maintenance chemotherapy.
Sensory input-dependent gain modulation of the optokinetic nystagmus by mid-infrared stimulation in pigeons

Neuromodulation serves as a cornerstone for brain sciences and clinical applications. Recent reports suggest that mid-infrared stimulation (MIRS) causes non-thermal modulation of brain functions. Current understanding of its mechanism hampers the routine application of MIRS. Here, we examine how MIRS influences the sensorimotor transformation in awaking-behaving pigeons, from neuronal signals to behavior. We applied MIRS and electrical stimulation (ES) to the pretectal nucleus lentiformis mesencephali (nLM), an essential retinorecipient structure in the pretectum, and examined their influences on the optokinetic nystagmus, a visually guided eye movement. We found MIRS altered eye movements by modulating a specific gain depending on the strength of visual inputs, in a manner different than the effect of ES. Simultaneous extracellular recordings and stimulation showed that MIRS could either excite and inhibit the neuronal activity in the same pretectal neuron depending on its ongoing sensory responsiveness levels in awake-behaving animals. Computational simulations suggest that MIRS modulates the resonance of a carbonyl group of the potassium channel, critical to the action potential generation, altering neuronal responses to sensory inputs and as a consequence, guiding behavior. Our findings suggest that MIRS could be a promising approach toward modulating neuronal functions for brain research and treating neurological diseases.
Long-term persistence and functionality of adoptively transferred antigen-specific T cells with genetically ablated PD-1 expression

Significance Adoptive transfer of antigen-specific T cells has shown impressive clinical success in cancer and infectious diseases. However, due to constant stimulation, the transferred cells can switch into dysfunctional states marked by the expression of programmed cell death protein 1 (PD-1). Recent breakthroughs in cell engineering enabled the precise genetic ablation of this inhibitory receptor via CRISPR/Cas9 technology. First studies have shown benefits of PD-1 knockout for T cell functionality in short-term experiments but potential loss of fitness at later stages. Here, we could show that PD-1 ablation is not necessarily detrimental for long-term functionality and persistence of engineered T cells. These findings are of particular importance since the first PD-1 KO T cell products have recently entered into the clinics.
Increased clonal hematopoiesis involving DNA damage response genes in patients undergoing lung transplantation

BACKGROUND Cellular stressors influence the development of clonal hematopoiesis (CH). We hypothesized that environmental, inflammatory, and genotoxic stresses drive the emergence of CH in lung transplant recipients. METHODS We performed a cross-sectional cohort study of 85 lung transplant recipients to characterize CH prevalence. We evaluated somatic variants using duplex error-corrected sequencing and germline variants using whole exome sequencing. We evaluated CH frequency and burden using χ2 and Poisson regression, and we evaluated associations with clinical and demographic variables and clinical outcomes using χ2, logistic regression, and Cox regression. RESULTS CH in DNA damage response (DDR) genes TP53, PPM1D, and ATM was increased in transplant recipients compared with a control group of older adults (28% versus 0%, adjusted OR [aOR], 12.9 [1.7–100.3], P = 0.0002). Age (OR, 1.13 [1.03–1.25], P = 0.014) and smoking history (OR 4.25 [1.02–17.82], P = 0.048) were associated with DDR CH. Germline variants predisposing to idiopathic pulmonary fibrosis were identified but not associated with CH. DDR CH was associated with increased cytomegalovirus viremia versus patients with no (OR, 7.23 [1.95–26.8], P = 0.018) or non-DDR CH (OR, 7.64 [1.77–32.89], P = 0.024) and mycophenolate discontinuation (aOR, 3.8 [1.3–12.9], P = 0.031). CONCLUSION CH in DDR genes is prevalent in lung transplant recipients and is associated with posttransplant outcomes including cytomegalovirus activation and mycophenolate intolerance. FUNDING NIH/NHLBI K01HL155231 (LKT), R25HL105400 (LKT), Foundation for Barnes-Jewish Hospital (LKT), Evans MDS Center at Washington University (KAO, MJW), ASH Scholar Award (KAO), NIH K12CA167540 (KAO), NIH P01AI116501 (AEG, DK), NIH R01HL094601 (AEG), and NIH P01CA101937 (DCL).
Nasal residence time and rheological properties of a new bentonite-based thixotropic gel emulsion nasal spray – AM-301

Abstract Objective The present work provides characterization of rheological properties of a new bentonite-based thixotropic gel emulsion nasal spray (AM-301), its nasal residence time, distribution, safety and tolerability. Significance The nasal epithelium is a portal of entry for allergens and primary infection by airborne pathogens. Non-pharmacological interventions, which enhance physical and biological barriers, protect against allergens and pathogens without drug-related side effects. AM-301 has shown promising efficacy and safety in the nasal epithelium against viruses (in vitro) and pollen (clinical). Methods Technical part (i) spray characterization was performed with a validated droplet size distribution method; evaluation of the rheological properties of the formulation was performed by a validated amplitude sweep method and a validated oscillation, rotation, oscillation; Clinical part (ii) nasal and oropharyngeal endoscopy were used to provide a semi-quantitative evaluation of distribution and residence time of fluorescein-labelled AM-301 in the nose and oropharynx of healthy volunteers; (iii) tolerability and safety. Results (i) The non-Newtonian rheological properties of the formulation allow AM-301 to be sprayed and then to revert to a gel to prevent run-off from the nasal cavity; (ii) the formulation remains on the inferior turbinate, septum and oropharynx of volunteers for up to 210 min and on the middle turbinate for up to 60 min; two nasal sprays provide no substantial benefit over a single application with regards to coverage or retention; (iii) the spray is well tolerated Conclusions Single dose spray delivery of AM-301 provides extended coverage of the nasal mucosa up to the inferior turbinates.
Neural substrates of verbal memory impairment in schizophrenia: A multimodal connectomics study

While verbal memory is among the most compromised cognitive domains in schizophrenia (SZ), its neural substrates remain elusive. Here, we explored the structural and functional brain network correlates of verbal memory impairment in SZ. We acquired diffusion and resting‐state functional MRI data of 49 SZ patients, classified as having preserved (VMP, n = 22) or impaired (VMI, n = 26) verbal memory based on the List Learning task, and 55 healthy controls (HC). Structural and functional connectivity matrices were obtained and analyzed to assess associations with disease status (SZ vs. HC) and verbal memory impairment (VMI vs. VMP) using two complementary data‐driven approaches: threshold‐free network‐based statistics (TFNBS) and hybrid connectivity independent component analysis (connICA). TFNBS showed altered connectivity in SZ patients compared with HC (p < .05, FWER‐corrected), with distributed structural changes and functional reorganization centered around sensorimotor areas. Specifically, functional connectivity was reduced within the visual and somatomotor networks and increased between visual areas and associative and subcortical regions. Only a tiny cluster of increased functional connectivity between visual and bilateral parietal attention‐related areas correlated with verbal memory dysfunction. Hybrid connICA identified four robust traits, representing fundamental patterns of joint structural‐functional connectivity. One of these, mainly capturing the functional connectivity profile of the visual network, was significantly associated with SZ (HC vs. SZ: Cohen's d = .828, p < .0001) and verbal memory impairment (VMP vs. VMI: Cohen's d = −.805, p = .01). We suggest that aberrant connectivity of sensorimotor networks may be a key connectomic signature of SZ and a putative biomarker of SZ‐related verbal memory impairment, in consistency with bottom‐up models of cognitive disruption.
King-Devick Test in Wheelchair Sports: Identifying Normative Values and Effects of Exertion on Outcomes

Objective: To establish normative baseline values on the King-Devick (KD) Test for contact wheelchair sport participants. The secondary purpose was to examine the effect of physical exertion on test score. Design: Quasiexperimental. Setting: Competitive disability sport venues before practices or games. Participants: One-hundred 43 wheelchair rugby or wheelchair basketball (WBB) players completed the study. Participants were predominantly men (87.5%) and played WBB (84%). Intervention: 30-m wheelchair sprint test to fatigue. Main Outcome Measure: King-Devick Baseline Score. Results: Mean KD baseline score was 59.16 ± 15.56 seconds with significant differences (P < 0.05) identified by sport and impairment type, but not sex. Athletes with spina bifida and cerebral palsy had significantly higher mean baseline KD times than athletes with spinal cord injury. KD scores improved by 3.5% in athletes who reported “light” to “somewhat hard” exertion (RPE = 13). In a subset of athletes who performed sprints until an RPE of 18 was reached, 8 of 12 players (66.7%) demonstrated an improvement in KD score; however, large increases by a few participants caused the noticeable change. Conclusions: Normative values for wheelchair contact sport athletes are meaningfully slower than able-bodied sports participants. KD score improved with exertion with the greater improvement after moderate-intensity compared with vigorous-intensity exercise. These findings can be applied clinically to monitor athlete safety.
A Retrospective Analysis of Risk Factors and Impact of Acute Kidney Injury in Critically Ill Children

Abstract Background Acute kidney injury (AKI) is a serious clinical condition in critically ill children and is associated with worse outcomes. A few pediatric studies focused on the risk factors of AKI. We aimed to identify the incidence, risk factors, and outcomes of AKI in the pediatric intensive care unit (PICU). Patients and methods All the patients admitted to PICU over a period of 20 months were included. We compared both groups the risk factors between AKI and non-AKI. Results A total of 63 patients (17.5%) of the 360 patients developed AKI during PICU stay. The presence of comorbidity, diagnosis of sepsis, increased PRISM III score, and positive renal angina index were found to be risk factors for AKI on admission. Thrombocytopenia, multiple organ failure syndrome, the requirement of mechanical ventilation, use of inotropic drugs, intravenous iodinated contrast media, and exposure to an increased number of nephrotoxic drugs were independent risk factors during the hospital stay. The patients with AKI had a lower renal function on discharge and had worse overall survival. Conclusions AKI is prevalent and multifactorial in critically sick children. The risk factors of AKI may be present on admission and during the hospital stay. AKI is related to prolonged mechanical ventilation days, longer PICU stays, and a higher mortality rate. Based on the presented results early prediction of AKI and consequent modification of nephrotoxic medication may generate positive effects on the outcome of critically ill children.
Sample Sizes for Confidence Intervals on the Increase in the Squared Multiple Correlation Coefficient

The increase in the squared multiple correlation coefficient (δR 2) associated with a variable in a regression equation is a commonly used measure of importance in regression analysis. The probability that an asymptotic confidence interval will include δρ2 was investigated. With sample sizes typically used in regression analyses, when δρ2 = 0.00 and the confidence level is . 95 or greater, the probability will be at least . 999. For δρ2≥ . 01 and a confidence level of . 95 or greater, the probability will be smaller than the nominal confidence level. For δρ2≥ . 05 and a confidence level of . 95, tables are provided for the sample size necessary for the probability to be at least . 925 and to be at least . 94.
Nonlinear deep-water waves: theory and experiment. Part 2. Evolution of a continuous wave train

Results of an experimental investigation of the evolution of a nonlinear wave train on deep water are reported. The initial stage of evolution is found to be characterized by exponential growth of a modulational instability, as was first discovered by Benjamin ' Feir. At later stages of evolution it is found that the instability does not lead to wave-train disintegration or loss of coherence. Instead, the modulation periodically increases and decreases, and the wave train exhibits the Fermi–Pasta–Ulam recurrence phenomenon. Results of an earlier study of nonlinear wave packets by Yuen ' Lake, in which solutions of the nonlinear Schrödinger equation were shown to provide quantitatively correct descriptions of the properties of nonlinear wave packets, are applied to describe the experimentally observed wave-train phenomena. A comparison between the laboratory data and numerical solutions of the nonlinear Schrödinger equation for the long-time evolution of nonlinear wave trains is given.
Robust quantum-based interatomic potentials for multiscale modeling in transition metals

First-principles generalized pseudopotential theory (GPT) provides a fundamental basis for transferable multi-ion interatomic potentials in transition metals and alloys within density-functional quantum mechanics. In the central body-centered cubic (bcc) metals, where multi-ion angular forces are important to materials properties, simplified model GPT (MGPT) potentials have been developed based on canonical d bands to allow analytic forms and large-scale atomistic simulations. Robust, advanced-generation MGPT potentials have now been obtained for Ta and Mo and successfully applied to a wide range of structural, thermodynamic, defect, and mechanical properties at both ambient and extreme conditions. Selected applications to multiscale modeling discussed here include dislocation core structure and mobility, atomistically informed dislocation dynamics simulations of plasticity, and thermoelasticity and high-pressure strength modeling. Recent algorithm improvements have provided a more general matrix representation of MGPT beyond canonical bands, allowing improved accuracy and extension to f -electron actinide metals, an order of magnitude increase in computational speed for dynamic simulations, and the development of temperature-dependent potentials.
Can local vibration alter the contribution of persistent inward currents to human motoneuron firing?

The response of spinal motoneurons to synaptic input greatly depends on the activation of persistent inward currents (PICs), which in turn are enhanced by the neuromodulators serotonin and noradrenaline. Local vibration (LV) induces excitatory Ia input onto motoneurons and may alter neuromodulatory inputs. Therefore, we investigated whether LV influences the contribution of PICs to motoneuron firing. This was assessed in voluntary contractions with concurrent, ongoing LV, as well as after a bout of prolonged LV. High‐density surface electromyograms (HD‐EMG) of the tibialis anterior were recorded with a 64‐electrode matrix. Twenty males performed isometric, triangular, dorsiflexion contractions to 20% and 50% of maximal torque at baseline, during LV of the tibialis anterior muscle, and after 30‐min of LV. HD‐EMG signals were decomposed, and motor units tracked across time points to estimate PICs through a paired motor unit analysis, which quantifies motor unit recruitment–derecruitment hysteresis (ΔF). During ongoing LV, ΔF was lower for both 20% and 50% ramps. Although significant changes in ΔF were not observed after prolonged LV, a differential effect across the motoneuron pool was observed. This study demonstrates that PICs can be non‐pharmacologically modulated by LV. Given that LV leads to reflexive motor unit activation, it is postulated that lower PIC contribution to motoneuron firing during ongoing LV results from decreased neuromodulatory inputs associated with lower descending corticospinal drive. A differential effect in motoneurons of different recruitment thresholds after prolonged LV is provocative, challenging the interpretation of previous observations and motivating future investigations.