High expression of EBP is an adverse prognostic factor for de novo acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease, for which identifying reliable prognostic markers is critical for accurate clinical prognosis and treatment optimization. The inhibition of emopamil-binding protein gene (EBP) expression has been demonstrated to induce cancer cell death via depleting downstream sterols. Nevertheless, no comprehensive studies have been conducted specifically in tumors, including AML. METHOD: Herein, survival analyses were performed on the dataset obtained from The Cancer Genome Atlas (TCGA). Besides, the EBP levels were quantified using real-time qPCR in a cohort of 120 AML patients, and the value of EBP was further assessed using our clinical data. RESULTS: Patients with high EBP expression had worse overall survival (OS) and event-free survival (EFS) than patients with low EBP expression, both in the TCGA dataset and our clinical data. Additionally, white blood cell (WBC) counts were higher in patients with high EBP expression (P = 0.032). Moreover, in patients with intermediate-risk AML, it was discovered that elevated EBP expression was linked to a worse EFS (P = 0.038). Multivariate analysis demonstrated that high EBP expression was an independent prognostic factor in AML patients and was associated with a shorter OS and EFS (OS: P = 0.041; EFS: P = 0.017). Furthermore, the data revealed that transplantation in the high-EBP group led to an improvement in survival (OS: P = 0.001; EFS: P = 0.001). The same benefit was also observed in intermediate-risk AML patients (OS: P = 0.026; EFS: P = 0.026). CONCLUSION: Collectively, our findings indicated that high expression of EBP in AML patients was an adverse prognostic factor, but transplantation had the otential to alleviate its negative effects.

Cavitary Consolidation in Pulmonary Infarct Secondary to Embolism: A Rare Presentation.

Obstruction of the pulmonary artery or one of its branches, often due to thrombi from the deep veins of the lower extremities can result in a life-threatening condition known as pulmonary embolism. Pulmonary infarction, an unusual complication of pulmonary embolism occurs when the blood supply to lung tissue is obstructed, leading to tissue necrosis. An 80-year-old man presented with a cough, breathlessness, and generalized weakness. He was vitally stable with no oxygen requirement, which could have suggested an infective etiology like pneumonia or tuberculosis. However, the presence of calf tenderness prompted us to perform a venous Doppler ultrasonography, which revealed deep venous thrombosis. This, combined with right atrial and ventricular dilation and moderate pulmonary artery hypertension observed on transthoracic echocardiography (2D ECHO), led us to recommend a CT pulmonary angiography. The angiography revealed an uncommon presentation of pulmonary embolism with multiple pulmonary infarcts. Here, we chronicle an unusual case of pulmonary infarction secondary to pulmonary embolism, which presented radiologically as consolidation with an aseptic cavity, a rare and atypical triple occurrence.

Lateralization of acquisition and consolidation in direction but not amplitude of a motor skill task.

Previous research suggests that the neural processes underlying specification of movement direction and amplitude are independently represented in the nervous system. However, our understanding of acquisition and consolidation processes in the direction and distance learning remains limited. We designed a virtual air hockey task, in which the puck direction is determined by the hand direction at impact, while the puck distance is determined by the amplitude of the velocity. In two versions of this task, participants were required to either specify the direction or the distance of the puck, while the alternate variable did not contribute to task success. Separate groups of right-handed participants were recruited for each task. Each participant was randomly assigned to one of two groups with a counter-balanced arm practice sequence (right to left, or left to right). We examined acquisition and, after 24 h, we examined two aspects of consolidation: 1) same hand performance to test the durability and 2) the opposite hand to test the effector-independent consolidation (interlimb transfer) of learning. The distance task showed symmetry between hands in the extent of acquisition as well as in both aspects of consolidation. In contrast, the direction task showed asymmetry in both acquisition and consolidation: the dominant right arm showed faster and greater acquisition and greater transfer from the opposite arm training. The asymmetric acquisition and consolidation processes shown in the direction task might be explained by lateralized control and mapping of direction, an interpretation consistent with previous findings on motor adaptation paradigms.

A Rare Case of Bare Lymphocyte Syndrome Presenting As Chronic Type 2 Respiratory Failure.

Type 2 respiratory failure, or hypercapnic respiratory failure, is brought on by low oxygenation (hypoxemia) and inadequate breathing (hypercapnia). It is produced by factors that can create an imbalance between the requirement and capacity of the respiratory system. The factors can include an increased requirement for muscles of respiration, reduction in their strength or effectiveness, or impediment of the ventilatory drive. Rarely, it can be caused by the bare lymphocyte syndrome (BLS), which usually affects young children and has a poor prognosis with accompanying debilitating disabilities. This is a case report that shares the unique findings of a 13-year-old patient with type 1 BLS and atopy, who is suffering from type 2 respiratory failure. She is susceptible to respiratory tract infections and has been treated for bronchopneumonia and tuberculosis in the past. She has been on assisted ventilation for the past 3.5 months, along with supplementary nutrition. She has been evaluated meticulously and methodically, ruling out other causes of her respiratory failure. Recognizing the root cause aided in her therapy and preventing mortality. This has been determined using clinical findings, lab results, and radiological reports. The diagnosis of hypercapnic respiratory failure was confirmed via an arterial blood gas analysis, whereas that of BLS was confirmed through a whole genome sequence test. Management entailed addressing the underlying cause, optimizing ventilation, and using mechanical ventilation to maintain respiratory function. Early detection and timely intervention were critical in enhancing the outcome for the patient.

Accurate Selection of Sublobar Resection for Small Non-small Cell Lung Cancer.

BACKGROUND: Although sublobar resection (wedge resection [Wed] or segmentectomy [Seg]) has become a standard operative procedure for clinical stages IA1 and IA2 non-small cell lung cancer (NSCLC) in Japan, the impact of this procedure on the prognosis and postoperative complications in real-world clinical practice is unknown. METHODS: This study retrospectively analyzed risk factors for a poor prognosis and postoperative complications of 470 patients with clinical stage ≤ IA2 NSCLC who underwent surgery from 2012 to 2021. RESULTS: Among the patients with a consolidation-to-tumor ratio (CTR) higher than 0.5, the 5-year relapse-free survival (RFS) rate was significantly lower in the Wed group (72.1%) than in the Seg (85.8%) and Lob (86.8%) groups (p < 0.01), but the difference between the Seg and Lob groups was not significant. Among patients with a CTR of 0.5 or lower, the 5-year RFS rate did not differ significantly among the three groups. Multivariable analysis of RFS showed that the prognosis was significantly worse in the Wed group than in the Lob group (hazard ratio, 2.83; p < 0.01), but the difference between the Wed and Seg groups or the between Seg and Lob groups was not significant. Multivariable analysis of postoperative complications showed a significantly lower risk in the Wed group than in the Seg group (odds ratio, 0.31; p < 0.01). CONCLUSIONS: Seg could become the standard operative procedure for clinical stages IA1 and IA2 NSCLC patients. Wed is suggested to be an option for patients with a CTR of 0.5 or lower and has the advantage of avoiding postoperative complications.

The effects of shared, depression-specific, and anxiety-specific internalizing symptoms on negative and neutral episodic memories following post-learning sleep.

Emotional memory bias is a common characteristic of internalizing symptomatology and is enhanced during sleep. The current study employs bifactor S-1 modeling to disentangle depression-specific anhedonia, anxiety-specific anxious arousal, and the common internalizing factor, general distress, and test whether these internalizing symptoms interact with sleep to influence memory for emotional and neutral information. Healthy adults (N = 281) encoded scenes featuring either negative objects (e.g., a vicious looking snake) or neutral objects (e.g., a chipmunk) placed on neutral backgrounds (e.g., an outdoor scene). After a 12-hour period of daytime wakefulness (n = 140) or nocturnal sleep (n = 141), participants judged whether objects and backgrounds were the same, similar, or new compared with what they viewed during encoding. Participants also completed the mini version of the Mood and Anxiety Symptom Questionnaire. Higher anxious arousal predicted worse memory across all stimuli features, but only after a day spent being awake-not following a night of sleep. No significant effects were found for general distress and anhedonia in either the sleep or wake condition. In this study, internalizing symptoms were not associated with enhanced emotional memory. Instead, memory performance specifically in individuals with higher anxious arousal was impaired overall, regardless of emotional valence, but this was only the case when the retention interval spanned wakefulness (i.e., not when it spanned sleep). This suggests that sleep may confer a protective effect on general memory impairments associated with anxiety.

Targeted memory reactivation to augment treatment in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder with traumatic memories at its core. Post-treatment sleep may offer a unique time window to increase therapeutic efficacy through consolidation of therapeutically modified traumatic memories. Targeted memory reactivation (TMR) enhances memory consolidation by presenting reminder cues (e.g., sounds associated with a memory) during sleep. Here, we applied TMR in PTSD patients to strengthen therapeutic memories during sleep after one treatment session with eye movement desensitization and reprocessing (EMDR). PTSD patients received either slow oscillation (SO) phase-targeted TMR, using modeling-based closed-loop neurostimulation (M-CLNS) with EMDR clicks as a reactivation cue (n = 17), or sham stimulation (n = 16). Effects of TMR on sleep were assessed through high-density polysomnography. Effects on treatment outcome were assessed through subjective, autonomic, and fMRI responses to script-driven imagery (SDI) of the targeted traumatic memory and overall PTSD symptom level. Compared to sham stimulation, TMR led to stimulus-locked increases in SO and spindle dynamics, which correlated positively with PTSD symptom reduction in the TMR group. Given the role of SOs and spindles in memory consolidation, these findings suggest that TMR may have strengthened the consolidation of the EMDR-treatment memory. Clinically, TMR vs. sham stimulation resulted in a larger reduction of avoidance level during SDI. TMR did not disturb sleep or trigger nightmares. Together, these data provide first proof of principle that TMR may be a safe and viable future treatment augmentation strategy for PTSD. The required follow-up studies may implement multi-night TMR or TMR during REM sleep to further establish the clinical effect of TMR for traumatic memories.

Regulation of long-term memory by a few clock neurons in Drosophila.

Identification of the neural circuits in the brain regulating animal behavior and physiology is critical for understanding brain functions and is one of the most challenging goals in neuroscience research. The fruitfly Drosophila melanogaster has often been used to identify the neural circuits involved in the regulation of specific behaviors because of the many neurogenetic tools available to express target genes in particular neurons. Neurons controlling sexual behavior, feeding behavior, and circadian rhythms have been identified, and the number of neurons responsible for controlling these phenomena is small. The search for a few neurons controlling a specific behavior is an important first step to clarify the overall picture of the neural circuits regulating that behavior. We previously found that the clock gene period (per), which is essential for circadian rhythms in Drosophila, is also essential for long-term memory (LTM). We have also found that a very limited number of per-expressing clock neurons in the adult brain are required for the consolidation and maintenance of LTM. In this review, we focus on LTM in Drosophila, introduce the concept of LTM regulation by a few clock neurons that we have recently discovered, and discuss how a few clock neurons regulate Drosophila LTM.

The Consolidation of Risk Pools in the National Health Insurance Program of the Republic of Korea: Analysis of the Political Processes.

South Korea is one of the few countries that has successfully consolidated its national risk pools into a single-payer health insurance system. This study analyzes national health insurance (NHI) consolidation in South Korea between 1980 and 2003, drawing lessons for countries seeking to consolidate their risk pools. The paper contextualizes the development of the South Korean national health insurance system and the consolidation of its risk pools in the changes in the political environment, particularly the processes of political democratization. It examines how these processes have affected the societal meanings and roles of the health insurance system. The paper focuses on two policy stages. During the agenda-setting stage, the government and employers emphasized the efficiency of the health insurance system. This emphasis contributed to the failure of a consolidation plan that emphasized equity over efficiency. However, as democratization expanded, the power of civil society movements and the popular demand for equity grew stronger. During the policy adoption phase, consolidation of health insurance trusts in South Korea was achieved through social and political processes that influenced public opinion, expanded civil society participation in decision-making, and worked with the government to integrate health insurance organizations and funds.

Acoustically evoked K-complexes together with sleep spindles boost verbal declarative memory consolidation in healthy adults.

Over the past decade, phase-targeted auditory stimulation (PTAS), a neuromodulation approach which presents auditory stimuli locked to the ongoing phase of slow waves during sleep, has shown potential to enhance specific aspects of sleep functions. However, the complexity of PTAS responses complicates the establishment of causality between specific electroencephalographic events and observed benefits. Here, we used down-PTAS during sleep to specifically evoke the early, K-complex (KC)-like response following PTAS without leading to a sustained increase in slow-wave activity throughout the stimulation window. Over the course of two nights, one with down-PTAS, the other without, high-density electroencephalography (hd-EEG) was recorded from 14 young healthy adults. The early response exhibited striking similarities to evoked KCs and was associated with improved verbal memory consolidation via stimulus-evoked spindle events nested into the up-phase of ongoing 1 Hz waves in a central region. These findings suggest that the early, KC-like response is sufficient to boost memory, potentially by orchestrating aspects of the hippocampal-neocortical dialogue.

Consolidation Enhances Sequential Multistep Anticipation but Diminishes Access to Perceptual Features.

Many experiences unfold predictably over time. Memory for these temporal regularities enables anticipation of events multiple steps into the future. Because temporally predictable events repeat over days, weeks, and years, we must maintain-and potentially transform-memories of temporal structure to support adaptive behavior. We explored how individuals build durable models of temporal regularities to guide multistep anticipation. Healthy young adults (Experiment 1: N = 99, age range = 18-40 years; Experiment 2: N = 204, age range = 19-40 years) learned sequences of scene images that were predictable at the category level and contained incidental perceptual details. Individuals then anticipated upcoming scene categories multiple steps into the future, immediately and at a delay. Consolidation increased the efficiency of anticipation, particularly for events further in the future, but diminished access to perceptual features. Further, maintaining a link-based model of the sequence after consolidation improved anticipation accuracy. Consolidation may therefore promote efficient and durable models of temporal structure, thus facilitating anticipation of future events.

FLUEnT: Transformer for detecting lung consolidations in videos using fused lung ultrasound encodings.

Pneumonia is the leading cause of death among children around the world. According to WHO, a total of 740,180 lives under the age of five were lost due to pneumonia in 2019. Lung ultrasound (LUS) has been shown to be particularly useful for supporting the diagnosis of pneumonia in children and reducing mortality in resource-limited settings. The wide application of point-of-care ultrasound at the bedside is limited mainly due to a lack of training for data acquisition and interpretation. Artificial Intelligence can serve as a potential tool to automate and improve the LUS data interpretation process, which mainly involves analysis of hyper-echoic horizontal and vertical artifacts, and hypo-echoic small to large consolidations. This paper presents, Fused Lung Ultrasound Encoding-based Transformer (FLUEnT), a novel pediatric LUS video scoring framework for detecting lung consolidations using fused LUS encodings. Frame-level embeddings from a variational autoencoder, features from a spatially attentive ResNet-18, and encoded patient information as metadata combiningly form the fused encodings. These encodings are then passed on to the transformer for binary classification of the presence or absence of consolidations in the video. The video-level analysis using fused encodings resulted in a mean balanced accuracy of 89.3 %, giving an average improvement of 4.7 % points in comparison to when using these encodings individually. In conclusion, outperforming the state-of-the-art models by an average margin of 8 % points, our proposed FLUEnT framework serves as a benchmark for detecting lung consolidations in LUS videos from pediatric pneumonia patients.

Protocol for a single-arm, multicenter, prospective, confirmatory phase III trial of wedge resection for invasive ground glass opacity-featured lung cancer with a size ≤2 cm and a consolidation tumor ratio between 0.25 and 0.5 (ECTOP-1020 study).

Background: Segmentectomy is the current standard treatment for ground glass opacity (GGO)-featured lung cancer patients with a tumor size ≤2 cm and a consolidation tumor ratio (CTR) between 0.25 and 0.5. However, compared with wedge resection, segmentectomy destroys the patient's hilar structure and consumes more lung parenchyma. A recent study demonstrated that wedge resection could yield comparable results for this group of patients. Methods: This study aimed to confirm the noninferiority of wedge resection over standard surgery in invasive GGO-featured lung cancer patients with a size ≤2 cm and a CTR between 0.25 and 0.5, as measured by 5-year overall survival (OS). The primary endpoint is 5-year OS. The secondary endpoints are 5-year recurrence-free survival (RFS), the R0 resection rate, pulmonary function, recurrence and metastasis sites, and adverse events after surgery. During the trial period, 286 patients are enrolled from six Chinese institutions. Discussion: The primary results of this study will be actively disseminated through manuscript publications and conference presentations. This prospective study will evaluate the surgical efficacy and safety of wedge resection for small (tumor size ≤2 cm with a CTR between 0.25 and 0.5) invasive GGO-featured lung cancer and will support the standardization of this surgical strategy. Trial Registration: This trial has been registered on ClinicalTrial.gov (No. NCT06102161).

Identification of a Hippocampus-to-Zona Incerta Projection involved in Motor Learning.

Motor learning (ML), which plays a fundamental role in growth and physical rehabilitation, involves different stages of learning and memory processes through different brain regions. However, the neural mechanisms that underlie ML are not sufficiently understood. Here, a previously unreported neuronal projection from the dorsal hippocampus (dHPC) to the zona incerta (ZI) involved in the regulation of ML behaviors is identified. Using recombinant adeno-associated virus, the projections to the ZI are surprisingly identified as originating from the dorsal dentate gyrus (DG) and CA1 subregions of the dHPC. Furthermore, projection-specific chemogenetic and optogenetic manipulation reveals that the projections from the dorsal CA1 to the ZI play key roles in the acquisition and consolidation of ML behaviors, whereas the projections from the dorsal DG to the ZI mediate the retrieval/retention of ML behaviors. The results reveal new projections from the dorsal DG and dorsal CA1 to the ZI involved in the regulation of ML and provide insight into the stages over which this regulation occurs.

High-dose cytarabine plus gemtuzumab ozogamicin as consolidation therapy in patients with favorable- or intermediate-risk acute myeloid leukemia.

Previous prospective randomized trials have investigated the efficacy of gemtuzumab ozogamicin in the frontline treatment of acute myeloid leukemia (AML). We evaluated the efficacy of high-dose cytarabine with GO as consolidation therapy in 20 patients with favorable- or intermediate-risk AML in first complete remission. They included six patients with wild-type nucleophosmin (NPM1) core binding factor (CBF), ten with NPM1-mutated non-CBF, and four with wild-type NPM1 non-CBF. The median follow-up for the entire cohort was 62.0 months. The three-year overall survival (OS) and relapse-free survival (RFS) rates were 72.2% and 77.8%, respectively. OS and RFS were significantly higher for NPM1-mutated non-CBF AML than for wild-type NPM1 non-CBF AML (p = 0.001). We also examined the CD33 single-nucleotide polymorphism (SNP) rs12459419, which has been reported to influence the therapeutic efficacy of GO and CD33 expression. The CD33 expression ratio was higher in CD33 SNP C/C than in C/T (83.1% vs. 49.8%, p = 0.035), but 3-year OS and RFS did not differ significantly. These results suggest that consolidation therapy with high-dose cytarabine plus GO is highly effective in transplant-ineligible elderly patients and may be a reasonable treatment, especially for NPM1-mutated AML.

Acquisitions of behavioral health treatment facilities from 2010 to 2021.

Private equity (PE) and other for-profit ownership of behavioral health (mental health and substance use) treatment facilities have become increasingly prevalent, but data on these acquisitions are not readily available. In this study, we describe a novel database that contains information on the universe of behavioral health acquisitions that occurred between 2010 and 2021. We found that the frequency of behavioral health facilities involved in acquisitions increased substantially, from 32 facilities in 2010 to 1330 in 2021. The total number of facilities involved in acquisitions was 2806. Most of these facilities provided outpatient services only (N = 2073) and offered only mental health services (N = 1428). Private equity-backed acquisitions accounted for around 60% of all acquisition activity (N = 1678 facilities PE, N = 1128 facilities other for-profit). 25% of acquired facilities were located within 20 miles of one another (N = 561), 50% occurred within 80 miles (N = 1403), and 75% occurred within 319 miles (N = 2104). Future research should evaluate the effects of this consolidation on behavioral healthcare access, quality, spending, and patient outcomes.

How does land consolidation affect nongrain production? Evidence from county-level data in Jiangsu Province, China.

Using county-level panel data for Jiangsu Province from 2008 to 2018, this study adopted a fixed effect model to analyze the impact of land consolidation on crop planting structure, also considering the moderating effect of distance from the city center and the heterogeneous effect of various types of land consolidation. The results revealed that farmland consolidation and land reclamation had a negative impact on the proportion of grain crops (rice, wheat, and corn) cultivated, which declined by 0.0051 % (0.0069 %), 0.0055 % (0.0124 %), and 0.0101 % (0.0123 %) for every 1 % increase in investment, construction area, and newly added arable land from farmland consolidation (land reclamation), respectively, demonstrating that land consolidation has not prevented, or even encouraged nongrain production expansion. The production conditions of reclaimed arable land and land transfer practices following consolidation may be factors affecting these declines. Notably, the negative effect of land consolidation on crop planting structure weakens when the land is further away from the city center. To ensure food security, priority should be given to follow-up management after land consolidation and rational oversight and guidance following land transfer.

[On the issue of logistic support of export of medicinal preparations of national production].

The current geopolitical situation raised pointed question of developing new supply chains and looking for rolling stock to develop newly formed cargo flows, including medicinal preparations transportation. Considering necessity in timely and safe supply of medicines, it is necessary to develop set of measures permitting to implement export of this production of national industry to ensure ultimate independence from unfriendly states. The article considers main indicators of import and export operations of medicinal preparations and measures taken by the state to support industry in current conditions, requirements for international transportation of this category of goods. The measures increasing exports within the framework of the Pharmaceutical Industry Development Strategy until 2030, such as expansion of fleet of autonomous refrigerated containers, use of consolidation warehouses in Turkey and Kazakhstan to ensure decreasing of cost of multi-modal transportation of medicinal preparations, as well as validation of rolling stock in accordance with GDP requirements.

Selective consolidation of learning and memory via recall-gated plasticity.

In a variety of species and behavioral contexts, learning and memory formation recruits two neural systems, with initial plasticity in one system being consolidated into the other over time. Moreover, consolidation is known to be selective; that is, some experiences are more likely to be consolidated into long-term memory than others. Here, we propose and analyze a model that captures common computational principles underlying such phenomena. The key component of this model is a mechanism by which a long-term learning and memory system prioritizes the storage of synaptic changes that are consistent with prior updates to the short-term system. This mechanism, which we refer to as recall-gated consolidation, has the effect of shielding long-term memory from spurious synaptic changes, enabling it to focus on reliable signals in the environment. We describe neural circuit implementations of this model for different types of learning problems, including supervised learning, reinforcement learning, and autoassociative memory storage. These implementations involve synaptic plasticity rules modulated by factors such as prediction accuracy, decision confidence, or familiarity. We then develop an analytical theory of the learning and memory performance of the model, in comparison to alternatives relying only on synapse-local consolidation mechanisms. We find that recall-gated consolidation provides significant advantages, substantially amplifying the signal-to-noise ratio with which memories can be stored in noisy environments. We show that recall-gated consolidation gives rise to a number of phenomena that are present in behavioral learning paradigms, including spaced learning effects, task-dependent rates of consolidation, and differing neural representations in short- and long-term pathways.

Get out of my head: social evaluative brain states carry over into post-feedback rest and influence remembering how others view us.

Learning how others perceive us helps us tune our behavior to form adaptive relationships. But which perceptions stick with us? And when in the learning process are they codified in memory? We leveraged a popular television series-The Office-to answer these questions. Prior to their functional magnetic resonance imaging (fMRI) session, viewers of The Office reported which characters they identified with, as well as which characters they perceived another person (i.e. counterpart) was similar to. During their fMRI scan, participants found out which characters other people thought they and the counterpart were like, and also completed rest scans. Participants remembered more feedback inconsistent with their self-views (vs. views of the counterpart). Although neural activity while encoding self-inconsistent feedback did not meaningfully predict memory, returning to the inconsistent self feedback during subsequent rest did. During rest, participants reinstated neural patterns engaged while receiving self-inconsistent feedback in the dorsomedial prefrontal cortex (DMPFC). DMPFC reinstatement also quadratically predicted self-inconsistent memory, with too few or too many reinstatements compromising memory performance. Processing social feedback during rest may impact how we remember and integrate the feedback, especially when it contradicts our self-views.