Miracle-dz/UniFAR-FTUs huggingface dataset:
Persistent IDH1/2 mutations in remission can predict relapse in patients with acute myeloid leukemia

Persistence of IDH1 or IDH2 mutations in remission bone marrow specimens of patients with acute myeloid leukemia has been observed, but the clinical impact of these mutations is not well known. In this study, we evaluated 80 acute myeloid leukemia patients with known IDH1 R132 or IDH2 R140/R172 mutations and assessed their bone marrow at the time of remission to determine the potential impact of persistent IDH1/2 mutations. Approximately 40% of acute myeloid leukemia patients given standard treatment in this cohort had persistent mutations in IDH1/2. Patients with an IDH1/2 mutation had an increased risk of relapse after 1 year of follow-up compared to patients without a detectable IDH1/2 mutation (59% versus 24%; P<0.01). However, a persistent mutation was not associated with a shorter time to relapse. High IDH1/2 mutation burden (mutant allelic frequency ≥10%) did not correlate with relapse rate (77% versus 86% for patients with a low burden, i.e., mutant allelic frequency <10%; P=0.66). Persistent mutations were also observed in NPM1, DNMT3A and FLT3 during remission, but IDH1/2 mutations remained significant in predicting relapse by multivariate analysis. Flow cytometry was comparable and complementary to next-generation sequencing-based assay for predicting relapse. Monitoring for persistent IDH1/2 mutations in patients with acute myeloid leukemia in remission can provide information that could be used to justify early interventions, with the hope of facilitating longer remissions and better outcomes in these patients.
European Myeloma Network recommendations on tools for the diagnosis and monitoring of multiple myeloma: what to use and when

The diagnosis of multiple myeloma can be challenging, even for experienced physicians, and requires close collaboration between numerous disciplines (orthopedics, radiology, nuclear medicine, radiation therapy, hematology and oncology) before the final diagnosis of myeloma is made. The definition of multiple myeloma is based on the presence of clinical, biochemical, histopathological, and radiological markers of disease. Specific tests are needed both at presentation and during follow-up in order to reach the correct diagnosis and characterize the disease precisely. These tests can also serve prognostic purposes and are useful for follow-up of myeloma patients. Molecular analyses remain pivotal for defining high-risk myeloma and are used in updated patient stratifications, while minimal residual disease assessment via flow cytometry, molecular techniques and radiological approaches provides additional prognostic information on patients’ long-term outcome. This pivotal information will guide our future treatment decisions in forthcoming clinical trials. The European Myeloma Network group updated their guidelines on different diagnostic recommendations, which should be of value to enable appropriate use of the recommendations both at diagnosis and during follow-up.
Acoustic communication in marine shallow waters: testing the acoustic adaptive hypothesis in sand gobies

ABSTRACT Acoustic communication is an important part of social behaviour of fish species that live or breed in shallow noisy waters. Previous studies have shown that some fish species exploit a quiet window in the background noise for communication. However, it remains to be examined whether hearing abilities and sound production of fish are adapted to marine habitats presenting high hydrodynamism. Here, we investigated whether the communication system of the painted (Pomatoschistus pictus) and the marbled (Pomatoschistus marmoratus) gobies is adapted to enhance sound transmission and reception in Atlantic shallow water environments. We recorded and measured the sound pressure levels of social vocalisations of both species, as well as snapshots of ambient noise of habitats characterised by different hydrodynamics. Hearing thresholds (in terms of both sound pressure and particle acceleration) and responses to conspecific signals were determined using the auditory evoked potential recording technique. We found that the peak frequency range (100–300 Hz) of acoustic signals matched the best hearing sensitivity in both species and appeared well adapted for short-range communication in Atlantic habitats. Sandy/rocky exposed beaches presented a quiet window, observable even during the breaking of moderate waves, coincident with the main sound frequencies and best hearing sensitivities of both species. Our data demonstrate that the hearing abilities of these gobies are well suited to detect conspecific sounds within typical interacting distances (a few body lengths) in Atlantic shallow waters. These findings lend support to the acoustic adaptive hypothesis, under the sensory drive framework, proposing that signals and perception systems coevolve to be effective within local environment constraints. Summary: The communication system of sand gobies is adapted to enhance sound transmission and reception in Atlantic shallow-water environments, supporting the acoustic adaptive hypothesis.
Reduced Time to Surgery Improves Patient-Reported Outcome After Achilles Tendon Rupture

Background: Patient outcome after an acute Achilles tendon rupture (ATR) continues to be suboptimal and heterogeneous. Thus, prognostic factors are called for to optimize evidence-based ATR treatment protocols; however, the influence of delayed time from injury to surgery (TTS) on patient outcome after ATR remains largely unknown. Purpose: To determine whether patient outcomes and adverse events after surgical repair of acute ATR are related to delayed TTS. Study Design: Cohort study; Level of evidence, 3. Methods: Two hundred twenty-eight patients with ATR who were treated with uniform anesthetic and surgical techniques, within 10 days after injury, were retrospectively assessed. TTS depended on availability of the operating theater, and neither surgeon nor patient could influence the TTS. Patients were assigned to 1 of 3 groups: short TTS (<48 hours), intermediate TTS (48-72 hours), and long TTS (>72 hours). Patient-reported outcome at 1 year was assessed with the validated Achilles tendon Total Rupture Score, with scores higher than 80 on a 0- to 100-point scale indicating an overall good outcome. The incidences of adverse events (perioperative and postoperative) and deep venous thrombosis were assessed. Results: Short TTS was significantly associated with increased rate of good outcome and reduced risk of adverse events. Seventy-one percent (95% CI, 60%-83%) of the patients with short TTS attained a good outcome compared with 44% (95% CI, 33%-56%) of the patients with long TTS (P = .002), with the intermediate TTS group in between, 63% (95% CI, 47%-78%). The incidence of adverse events was significantly reduced among patients with short TTS, 1.4% (95% CI, 1%-4%) compared with those with intermediate TTS, 11% (95% CI, 2%-21%) (P = .035) and those with long TTS, 14.8% (95% CI, 7%-23%) (P = .003). The risk of sustaining a deep venous thrombosis was not statistically significantly different among the 3 groups (P = .15). Conclusion: Patients with acute ATR undergoing operation within 48 hours after injury had better outcomes and a lower number of adverse events compared with patients undergoing operation after 72 hours. These results align with evidence-based recommendations from other surgical disciplines and should be used as guidelines for optimizing ATR treatment protocols. Registration: NTC01317160 (ClinicalTrials.gov identifier).
Paracrine potential of adipose stromal vascular fraction cells to recover hypoxia‐induced loss of cardiomyocyte function

Cell‐based therapies show promising results in cardiac function recovery mostly through paracrine‐mediated processes (as angiogenesis) in chronic ischemia. In this study, we aim to develop a 2D (two‐dimensional) in vitro cardiac hypoxia model mimicking severe cardiac ischemia to specifically investigate the prosurvival paracrine effects of adipose tissue‐derived stromal vascular fraction (SVF) cell secretome released upon three‐dimensional (3D) culture. For the 2D‐cardiac hypoxia model, neonatal rat cardiomyocytes (CM) were cultured for 5 days at < 1% (approaching anoxia) oxygen (O2) tension. Typical cardiac differentiation hallmarks and contractile ability were used to assess both the cardiomyocyte loss of functionality upon anoxia exposure and its possible recovery following the 5‐day‐treatment with SVF‐conditioned media (collected following 6‐day‐perfusion‐based culture on collagen scaffolds in either normoxia or approaching anoxia). The culture at < 1% O 2 for 5 days mimicked the reversible condition of hibernating myocardium with still living and poorly contractile CM (reversible state). Only SVF‐medium conditioned in normoxia expressing a high level of the prosurvival hepatocyte‐growth factor (HGF) and insulin‐like growth factor (IGF) allowed the partial recovery of the functionality of damaged CM. The secretome generated by SVF‐engineered tissues showed a high paracrine potential to rescue the nonfunctional CM, therefore resulting in a promising patch‐based treatment of specific low‐perfused areas after myocardial infarction.
The Role of Cholinergic Midbrain Neurons in Startle and Prepulse Inhibition

One of the two major cholinergic centers of the mammalian brain is located in the midbrain, i.e., the pedunculopontine tegmentum (PPTg) and the adjacent laterodorsal tegmentum. These cholinergic neurons have been shown to be important for e.g., arousal, reward associations, and sleep. They also have been suggested to mediate sensorimotor gating, measured as prepulse inhibition of startle (PPI). PPI disruptions are a hallmark of schizophrenia and are observed in various other psychiatric disorders, where they are associated with, and often predictive of, other cognitive symptoms. PPI has been proposed to be mediated by a short midbrain circuitry including inhibitory cholinergic projections from PPTg to the startle pathway. Although the data indicating the involvement of the PPTg is very robust, some more recent evidence challenges that there is a cholinergic contribution to PPI. We here use transient optogenetic activation of specifically the cholinergic PPTg neurons in male and female rats to address their role in startle modulation in general, and in PPI specifically. Although we could confirm the crucial role of PPTg cholinergic neurons in associative reward learning, validating our experimental approach, we found that activation of cholinergic PPTg neurons did not inhibit startle responses. In contrast, activation of cholinergic PPTg neurons enhanced startle, which is in accordance with their general role in arousal and indicate a potential involvement in sensitization of startle. We conclude that noncholinergic PPTg neurons mediate PPI in contrast to the longstanding hypothetical view that PPI is mediated by cholinergic PPTg neurons. SIGNIFICANCE STATEMENT Activation of cholinergic neurons in the midbrain has been assumed to mediate prepulse inhibition of startle (PPI), a common measure of sensorimotor gating that is disrupted in schizophrenia and other psychiatric disorders. We here revisit this long-standing hypothesis using optogenetic activation of these specific neurons combined with startle testing in rats. In contrast to the hypothetical role of these neurons in startle modulation, we show that their activation leads to an increase of baseline startle and to prepulse facilitation. This supports recent data by others that have started to cast some doubt on the cholinergic hypothesis of PPI, and calls for a revision of the theoretical construct of PPI mechanisms.
Efficacy of Add-on Pregabalin in the Treatment of Patients with Generalized Anxiety Disorder and Unipolar Major Depression With an Early Nonresponse to Escitalopram: A Double-Blind Placebo-Controlled Study

Abstract Introduction This study tests the efficacy of pregabalin versus placebo as adjunctive treatment in patients with generalized anxiety disorder (GAD) comorbid with unipolar major depression (UMD) and with an early nonresponse to escitalopram. Methods This is a double-blind, placebo-controlled 8-week add-on study of pregabalin, 75–600 mg/day (n=31) versus placebo (n=29) on open-label escitalopram in outpatients meeting the DSM-IV-TR criteria for GAD and UMD. The main outcome measures were change from baseline to endpoint in total STAI-S, Trail-Making Test B (TMT-B) and the Center of Epidemiological Studies Depression Scale (CES-D). Also changes in the parameters of the pupil’s reaction to light stimuli. Results There was no significant difference in any of the primary or secondary outcomes or response and remission rates concerning any analysis (last observation carried-forward of at least visit 2 or completers) between the 2 treatment arms. One additional finding of the current study is that adding pregabalin does not have a significant effect on autonomic function. Discussion This study does not support the usefulness of adding pregabalin in patients with GAD and UMD and with an early nonresponse to escitalopram (EudraCT Number: 2012-004062-17, Sponsor’s Protocol Code Number: WS1702721).
Assessment of quantitative magnetic resonance imaging metrics in the brain through the use of a novel phantom

ABSTRACT Objective: Multisite and longitudinal neuroimaging studies are important in uncovering trajectories of recovery and neurodegeneration following traumatic brain injury (TBI) and concussion through the use of diffusion tensor imaging (DTI) and other imaging modalities. This study assessed differences in anisotropic diffusion measurement across four scanners using a human and a novel phantom developed in conjunction with the Chronic Effects of Neurotrauma Consortium. Method: Human scans provided measurement within biological tissue, and the novel physical phantom provided measures of anisotropic intra-tubular diffusion to serve as a model for intra-axonal water diffusion. Intra- and inter-scanner measurement variances were compared, and the impact on effect size was calculated. Results: Intra-scanner test–retest reliability estimates for fractional anisotropy (FA) demonstrated relative stability over testing intervals. The human tissue and phantom showed similar FA ranges, high linearity and large within-device effect sizes. However, inter-scanner measures of FA indicated substantial differences, some of which exceeded typical DTI effect sizes in mild TBI. Conclusion: The diffusion phantom may be used to better elucidate inter-scanner variability in DTI-based measurement and provides an opportunity to better calibrate results obtained from scanners used in multisite and longitudinal studies. Novel solutions are being evaluated to understand and potentially overcome these differences.
Tree-in-Bud Pattern of Pulmonary Tuberculosis on Thin-Section CT: Pathological Implications

The “tree-in-bud-pattern” of images on thin-section lung CT is defined by centrilobular branching structures that resemble a budding tree. We investigated the pathological basis of the tree-in-bud lesion by reviewing the pathological specimens of bronchograms of normal lungs and contract radiographs of the post-mortem lungs manifesting active pulmonary tuberculosis. The tree portion corresponds to the intralobular inflammatory bronchiole, while the bud portion represents filling of inflammatory substances within alveolar ducts, which are larger than the corresponding bronchioles. Inflammatory bronchiole per se represents the “tree” (stem) and inflammatory alveolar ducts constitute the “buds” or clubbing. “Clusters of micronodules”, seen on 7-mm thick post-mortem radiographs with tuberculosis proved to be clusters of tree-in-bud lesions within the three-dimensional space of secondary pulmonary lobule based on radiological/pathological correlation. None of the post-mortem lung specimens showed findings of lung parenchymal lymphatics involvement.
COach2Quit: a pilot randomized controlled trial of a personal carbon monoxide monitor for smoking cessation.

Introduction Mobile phone messaging support and biomarker feedback independently show evidence of increasing an individual's likelihood of quitting smoking. However, the combination of these two strategies to facilitate smoking cessation has not been adequately explored. Methods We conducted a randomized controlled trial in Baltimore, Maryland to assess the efficacy of COach2Quit, a smartphone application that provides exhaled carbon monoxide readings with message support. The primary outcome was self-reported and biochemically verified smoking cessation at 30-day follow-up. Secondary outcomes were smoking reduction, motivation to quit, use of, and satisfaction with COach2Quit. An intent to treat analysis was conducted. Results Adult smokers were randomized 1:1 to receive brief advice and COach2Quit (intervention, n=50) or brief advice only (control, n=52). Thirteen participants were lost to follow-up. At 30-day follow-up, one participant in each arm quit smoking. Median change in CO levels (parts per million, ppm) (intervention: -3.0 IQR -12.0, 2.0) (control: -2.5 IQR -9.0, 2.0) and median change in number of cigarettes smoked/day (intervention: -5.5 IQR -14.0, -1.0) (control: -6.0 IQR -10.0, -2.0) was similar between study arms. There was no significant difference in mean percent change in the reasons for quitting (RFQ) scale score (intervention: 6.3 95% CI -2.2, 14.8) (control: -3.6 95% CI -9.2, 2.1). A majority (n=32, 91%) of participants liked having COach2Quit to help them quit smoking. Conclusions There were no significant differences in smoking cessation, smoking reduction and motivation to quit between study arms. However, high satisfaction with the COach2Quit application indicates its feasibility and acceptability as a smoking cessation tool. Implications Smoking is the leading preventable cause of morbidity and mortality in the United States. Although counseling and pharmacotherapy are efficacious for smoking cessation, they are not easily accessible or desirable to all smokers, highlighting the need for identifying other interventions. There is evidence for the efficacy of mobile phone based messaging support for smoking cessation. However, there is limited research on the efficacy of biomarker feedback, much less interventions that combine these two approaches. This research contributes to filling this gap and identifying novel interventions to facilitate smoking cessation.
The Effect of Methylphenidate on Cervical Vertebral Maturation and Dental Age in Patients with Attention Deficit Hyperactivity Disorder

Statement of the Problem: It is postulated that attention deficit/hyperactivity disorder (ADHD) with or without medication has an inhibitory effect on the children’s growth and development. Purpose: This study aimed to assess the dental age and cervical vertebral maturation (CVM) stage in ADHD patients with or without medication. Materials and Method: This cross-sectional study evaluated the pretreatment panoramic and lateral cephalograms of 129 patients (70 males, 59 females aged 8-14 years). Demirjian index and Baccetti’s CVM index were used to determine the dental age and CVM stage, respectively. The subjects were evaluated in two groups of ADHD (case, n=59) and healthy individuals (control, n=70). The ADHD patients were divided into two groups of AWT (ADHD with Treatment, n=43) and AW (ADHD without treatment, n=16) based on the use of methylphenidate. Paired t-test was used to compare the mean dental age between the groups. Linear and ordered logistic regression models were used to detect differences between the groups. The association between dental and chronological age was assessed by using Pearson correlation coefficient (p< 0.05). Results: After age and sex adjustment, the skeletal maturity stage was found to be similar to the control group based on the presence of the disorder or use of medication (p= 0.711 and p= 0.436, respectively). Similarly, the patients’ dental age was similar to the controls in AW and AWT groups (p= 0.180 and p= 0.421, respectively). The correlation between dental age and chronological age was 0.79 in AWT, 0.88 in AW, and 0.88 in control group (p< 0.001 for all the three). Conclusion: After age and sex adjustment, the dental and skeletal age of ADHD patients with or without Methylphenidate treatment do no manifest a significant delay compared with the controls.
Hippocampal Engagement During Recall Depends on Memory Content.

The hippocampus is considered pivotal to recall, allowing retrieval of information not available in the immediate environment. In contrast, neocortex is thought to signal familiarity, contributing to recall only when called upon by the hippocampus. However, this view is not compatible with representational accounts of memory, which reject the mapping of cognitive processes onto brain regions. According to representational accounts, the hippocampus is not engaged by recall per se, rather it is engaged whenever hippocampal representations are required. To test whether hippocampus is engaged by recall when hippocampal representations are not required, we used functional imaging and a non-associative recall task, with images (objects, scenes) studied in isolation, and image patches as cues. As predicted by a representational account, hippocampal activation was modulated by the content of the recalled memory, increasing during recall of scenes—which are known to be processed by hippocampus—but not during recall of objects. Object recall instead engaged neocortical regions known to be involved in object-processing. Further supporting the representational account, effective connectivity analyses revealed that changes in functional activation during recall were driven by increased information flow from neocortical sites, rather than by the spreading of recall-related activation from hippocampus back to neocortex.
Ratio of Blood Glucose Level Change Measurement for Flap Monitoring

Background: In a setting of flap congestion, early detection and rapid reexploration are important. Some studies described the efficacy of blood glucose measurement for flap monitoring.1 However, the sensitivity and specificity of this method were not high enough to determine whether reexploration should be done or not. The purpose of this study was to evaluate and establish a method using the ratio of blood glucose level change (RBGC) measurement for detecting venous thrombosis and to propose an algorithm for flap salvage after congestion. Methods: Blood glucose level was measured in 36 free tissue transfers over time postoperatively and RBGC was calculated. When flap congestion was suspected, frequent blood glucose measurement and some countermeasures were performed complying with an algorithm. If the venous thrombus was suspected, the reexploration was performed. The RBGCs at the points in time when the venous thrombosis was detected were compared with those at the points in time when the flap demonstrated no venous thrombosis. Results: Of the 36 flaps, 30 flaps demonstrated no venous thrombosis and 6 flaps demonstrated venous thrombosis. Four flaps demonstrated signs of congestion but improved after the reexploration. The mean RBGCs at the points in time when the venous thrombosis was detected was −7.61 mg/dl h and those at times when the flap demonstrated no venous thrombosis was 0.10 mg/dl h, the former being significantly lower than the latter. Conclusion: Using the flap monitoring method using RBGC measurement, we could salvage some flaps from the congestion due to the venous thrombosis without unnecessary reexploration.