Miracle-dz/UniFAR-FTUs huggingface dataset:
Lymphoma Heterogeneity Unraveled by Single-Cell Transcriptomics

High-definition transcriptomic studies through single-cell RNA sequencing (scRNA-Seq) have revealed the heterogeneity and functionality of the various microenvironments across numerous solid tumors. Those pioneer studies have highlighted different cellular signatures correlated with clinical response to immune checkpoint inhibitors. scRNA-Seq offers also a unique opportunity to unravel the intimate heterogeneity of the ecosystems across different lymphoma entities. In this review, we will first cover the basics and future developments of the technology, and we will discuss its input in the field of translational lymphoma research, from determination of cell-of-origin and functional diversity, to monitoring of anti-cancer targeted drugs response and toxicities, and how new improvements in both data collection and interpretation will further foster precision medicine in the upcoming years.
Loss of Basal Forebrain Cholinergic Neurons Following Adolescent Binge Ethanol Exposure: Recovery With the Cholinesterase Inhibitor Galantamine

Binge drinking and alcohol abuse are common during adolescence and cause both cognitive deficits and lasting cholinergic pathology in the adult basal forebrain. Acetylcholine is anti-inflammatory and studies using the preclinical adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2 day on/2 day off from postnatal day [P]25 to P54) model of human adolescent binge drinking report decreased basal forebrain cholinergic neurons (BFCNs) and induction of proinflammatory genes that persist long into adulthood. Recent studies link AIE-induced neuroimmune activation to cholinergic pathology, but the underlying mechanisms contributing to the persistent loss of BFCNs are unknown. We report that treatment with the cholinesterase inhibitor galantamine (4.0 mg/kg, i.p.) administered during AIE (i.e., P25–P54) or following the conclusion of AIE (i.e., P57–P72) recovered the persistent loss of cholinergic neuron phenotype markers (i.e., ChAT, TrkA, and p75NTR) and somal shrinkage of residual ChAT + neurons known to persist in AIE-exposed adults. Galantamine treatment also recovered the AIE-increased expression of the proinflammatory receptors TLR4 and RAGE, the endogenous TLR4/RAGE agonist HMGB1, and the transcription activation marker pNF-κB p65. Interestingly, we find BFCNs express TLR4 and RAGE, and that AIE treatment increased pNF-κB p65 expression in adult ChAT + IR neurons, consistent with intracellular HMGB1-TLR4/RAGE signaling within BFCNs. AIE increased epigenetic transcription silencing markers (i.e., H3K9me2 and H3K9me3) in the adult basal forebrain and H3K9me2 occupancy at cholinergic phenotype gene promoters (i.e., ChAT and TrkA). The finding of no AIE-induced changes in total basal forebrain NeuN + neurons with galantamine reversal of AIE-induced ChAT + neuron loss, TLR4/RAGE-pNF-κB p65 signals, and epigenetic transcription silencing markers suggests that AIE does not cause cell death, but rather the loss of the cholinergic phenotype. Together, these data suggest that AIE induces HMGB1-TLR4/RAGE-pNF-κB p65 signals, causing the loss of cholinergic phenotype (i.e., ChAT, TrkA, and p75NTR) through epigenetic histone transcription silencing that result in the loss of the BFCN phenotype that can be prevented and restored by galantamine.
IFT20 Mediates the Transport of Cell Migration Regulators From the Trans-Golgi Network to the Plasma Membrane in Breast Cancer Cells

IFT20 is a subunit of the intraflagellar transport (IFT) system essential for the formation and function of cilia. Besides predominant research in the cilia field, some IFT subunits perform extraciliary roles in non-ciliated cancer cells. However, the specific roles of IFT subunits in tumorigenesis remain unknown. Here, we found that knockout of IFT20 in mouse breast cancer cells lacking primary cilia promoted epithelial mesenchymal transitions (EMTs), active lamellipodia formation, and cell migration. IFT20 localized at the trans-Golgi and trans-Golgi network (TGN), and displayed vesicular co-distributions with Rab8a, the marker of TGN-to-plasma membrane vesicular trafficking. Proximity-dependent biotin identification (BioID) and colocalization analyzes showed that Numb and Ctnnal1, whose depletion promoted cell migration, co-localized with IFT20 at the trans-Golgi/TGN or intracellular transport vesicles. Furthermore, Strep-Tactin pulldown assays revealed an interaction between IFT20 and Ctnnal1 or Numb. Loss of IFT20 lowered the expression of actin-associated Tagln2, whose knockdown promoted cell migration. Thus, the extraciliary function of ITF20 in breast cancer cell was associated with the negative regulation of migration.
Mindfulness Training Improves Quality of Life and Reduces Depression and Anxiety Symptoms Among Police Officers: Results From the POLICE Study—A Multicenter Randomized Controlled Trial

Background: Police officers' high-stress levels and its deleterious consequences are raising awareness to an epidemic of mental health problems and quality of life (QoL) impairment. There is a growing evidence that mindfulness-based interventions are efficacious to promote mental health and well-being among high-stress occupations. Methods: The POLICE study is a multicenter randomized controlled trial (RCT) with three assessment points (baseline, post-intervention, and 6-month follow-up) where police officers were randomized to mindfulness-based health promotion (MBHP) (n = 88) or a waiting list (n = 82). This article focuses on QoL, depression and anxiety symptoms, and religiosity outcomes. Mechanisms of change and MBHP feasibility were evaluated. Results: Significant group × time interaction was found for QoL, depression and anxiety symptoms, and non-organizational religiosity. Between-group analysis showed that MBHP group exhibited greater improvements in QoL, and depression and anxiety symptoms at both post-intervention (QoL d = 0.69 to 1.01; depression d = 0.97; anxiety d = 0.73) and 6-month follow-up (QoL d = 0.41 to 0.74; depression d = 0.60; anxiety d = 0.51), in addition to increasing non-organizational religiosity at post-intervention (d = 0.31). Changes on self-compassion mediated the relationship between group and pre-to-post changes for all QoL domains and facets. Group effect on QoL overall health facet at post-intervention was moderated by mindfulness trait and spirituality changes. Conclusion: MBHP is feasible and efficacious to improve QoL, and depression and anxiety symptoms among Brazilian officers. Results were maintained after 6 months. MBHP increased non-organizational religiosity, although the effect was not sustained 6 months later. To our knowledge, this is the first mindfulness-based intervention RCT to empirically demonstrate these effects among police officers. Self-compassion, mindfulness trait, and spirituality mechanisms of change are examined. Clinical Trial Registration: www.ClinicalTrials. gov. identifier: NCT03114605.
SHCBP1 Promotes Papillary Thyroid Carcinoma Carcinogenesis and Progression Through Promoting Formation of Integrin and Collagen and Maintaining Cell Stemness

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer with a rapidly increasing incidence globally. Bioinformatics analyses suggested that SHCBP1 (SHC SH2 Domain-Binding Protein 1) was significantly up-regulated in PTC tumor tissues, which was further confirmed by immunohistochemical staining and qPCR analyses in Xuzhou cohort. Moreover, the results indicated that the mRNA level of SHCBP1 was negatively associated with patients’ disease-free survival rate, and further analysis reveals that patients with high SHCBP1 expression tend to have more lymph node metastasis. Afterward, MTT, colony formation, cell-cycle assay, FACS apoptosis assay, invasion, migration, as well as scratch assay were performed to study the phenotypes change of PTC cells after knocking down SHCBP1. The in vivo subcutaneous tumor model was developed to study the proliferation ability of PTC cells after SHCBP1 knockdown. We show that knock down of SHCBP1 significantly inhibits PTC cell proliferation, cell cycle, invasion and migration in vivo and in vitro. Western blot and qRT-PCR showed that knockdown of SHCBP1 could significantly reduce MYC, KLF4, CD44, ITGA6, ITGB1, ITGB5, and COL4A2 expression at both RNA and protein levels, which indicated that SHCBP1 might be involved in PTC carcinogenesis and progression through targeting formation of integrin and collagen and cell stemness pathways, and can be a potential diagnosis biomarker and therapeutic target for PTC.
Genetic Code Expansion of Vibrio natriegens

Escherichia coli has been considered as the most used model bacteria in the majority of studies for several decades. However, a new, faster chassis for synthetic biology is emerging in the form of the fast-growing gram-negative bacterium Vibrio natriegens. Different methodologies, well established in E. coli, are currently being adapted for V. natriegens in the hope to enable a much faster platform for general molecular biology studies. Amongst the vast technologies available for E. coli, genetic code expansion, the incorporation of unnatural amino acids into proteins, serves as a robust tool for protein engineering and biorthogonal modifications. Here we designed and adapted the genetic code expansion methodology for V. natriegens and demonstrate an unnatural amino acid incorporation into a protein for the first time in this organism.
Hospital Resilience After the 2015 Earthquake in Nepal: Results From Semi-structured Interviews With Hospital Staff

Background: Resilient hospitals are increasingly recognized as a cornerstone of disaster reduction in global policies such as the Sendai Framework for Action. However, current hospital resilience frameworks emerged from pre-disaster conceptualizations, and have not been verified in real-life disaster contexts nor in the frontlines. Our aim was to study a tertiary hospital's resilience after the 2015 earthquake in Nepal, as experienced by its staff. Methods: We undertook a qualitative study in the Tribhuvan University Teaching Hospital (TUTH), where we conducted 18 semi-structured interviews with hospital staff. We inductively created themes to describe the earthquake burden to the hospital, and to analyze individual resilience of hospital staff. In addition, we deductively documented the resilience of the hospital as a system, according to the system resilience dimensions: means of resilience (redundancy and resourcefulness), and ends of resilience (robustness and rapidity). Results: In terms of robustness, TUTH increased its capacity for earthquake victims as elective activities were temporarily interrupted and quality of care was not a priority. Three stages of rapidity were identified: critical rapidity to address immediate needs, stabilizing rapidity until the hospital re-started routine activities, and recovery rapidity. In addition to the disaster plan, emerging adaptations played a major role in redundancy and resourcefulness. We found that individual resilience depended on three determinants: safety, meaningfulness, and sense of belonging. Conclusions: Hospital resilience results from a complexity of emerging and planned adaptations, as well as from interdependencies with individual resilience. Frameworks and plans to improve hospital resilience must reflect flexibility of response, and a concern for well-being of hospital staff is central for sustainable disaster response and improved resilience.
Dietary Fiber Is Essential to Maintain Intestinal Size, L-Cell Secretion, and Intestinal Integrity in Mice

Dietary fiber has been linked to improved gut health, yet the mechanisms behind this association remain poorly understood. One proposed mechanism is through its influence on the secretion of gut hormones, including glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2). We aimed to: 1) investigate the impact of a fiber deficient diet on the intestinal morphological homeostasis; 2) evaluate L-cell secretion; and 3) to ascertain the role of GLP-1, GLP-2 and Takeda G protein-receptor-5 (TGR5) signaling in the response using GLP-1 receptor, GLP-2 receptor and TGR5 knockout mice. Female C57BL/6JRj mice (n = 8) either received a standard chow diet or were switched to a crude fiber-deficient diet for a short (21 days) and long (112 days) study period. Subsequent identical experiments were performed in GLP-1 receptor, GLP-2 receptor and TGR5 knockout mice. The removal of fiber from the diet for 21 days resulted in a decrease in small intestinal weight (p < 0.01) and a corresponding decrease in intestinal crypt depth in the duodenum, jejunum and ileum (p < 0.001, p < 0.05, and p < 0.01, respectively). Additionally, colon weight was decreased (p < 0.01). These changes were associated with a decrease in extractable GLP-1, GLP-2 and PYY in the colon (p < 0.05, p < 0.01, and p < 0.01). However, we could not show that the fiber-dependent size decrease was dependent on GLP-1 receptor, GLP-2 receptor or TGR5 signaling. Intestinal permeability was increased following the removal of fiber for 112 days. In conclusion, our study highlights the importance of dietary fiber to maintain intestinal weight, colonic L-cell secretion and intestinal integrity.
Impact of COVID-19 on Educational Services in Canadian Children With Attention-Deficit/Hyperactivity Disorder

The COVID-19 pandemic led to school closures and a rapid transition to online classes. However, little is known about the impact of online learning in Canadian children with Attention-Deficit/Hyperactivity Disorder (ADHD). An online survey created on Qualtrics was distributed to families across Canada. Data collection was conducted over a total of five weeks in May and June 2020. We reviewed 587 surveys (4% margin of error using a 95% confidence interval) completed by caregivers/parents of children with ADHD (mean child age 10.14 years, SD = 3.06). Survey questions focused on hours of schoolwork completed and whether the learning needs of children with ADHD were met during school closures. Results indicated 90% of children with ADHD received web-based learning during the pandemic. Parents (41%) reported < 5 h of schoolwork per week, and 35% indicated between 5 to 10 h. Of the parents who said their child with ADHD had a modified curriculum (68%), 40% reported receiving educational materials that met their learning expectations during online classes. Parents (59%) reported that their child found it “very challenging” adjusting to online classes. The results indicated that children with ADHD faced significant challenges in adapting to online learning during the pandemic. Binary logistic regression indicated significant associations between depression severity, difficulties with starting and managing tasks and challenges adjusting to online learning. Long-term consequences of these challenges will need to be determined to ensure children with ADHD are able to meet their academic expectations.
How Australian Health Care Services Adapted to Telehealth During the COVID-19 Pandemic: A Survey of Telehealth Professionals

Background: In Australia, telehealth services were used as an alternative method of health care delivery during the COVID-19 pandemic. Through a realist analysis of a survey of health professionals, we have sought to identify the underlying mechanisms that have assisted Australian health services adapt to the physical separation between clinicians and patients. Methods: Using a critical realist ontology and epistemology, we undertook an online survey of health professionals subscribing to the Australian Telehealth Society newsletter. The survey had close- and open-ended questions, constructed to identify contextual changes in the operating environment for telehealth services, and assess the mechanisms which had contributed to these changes. We applied descriptive and McNemar's Chi-square analysis for the close-ended component of the survey, and a reflexive thematic analysis approach for the open-ended questions which were framed within the activity based funding system which had previously limited telehealth services to regional Australia. Results: Of the 91 respondents most (73%) reported a higher volume of telephone-based care since COVID and an increase in use of video consultations (60% of respondents). Respondents felt that the move to provide care using telehealth services had been a “forced adoption” where clinicians began to use telehealth services (often for the first time) to maintain health care. Respondents noted significant changes in managerial and medical culture which supported the legitimisation of telehealth services as a mode of access to care. The support of leaders and the use personal and organisational networks to facilitate the operation of telehealth service were felt to be particularly valuable. Access to, and reliability of, the technology were considered extremely important for services. Respondents also welcomed the increased availability of more human and financial resources. Conclusions: During the pandemic, mechanisms that legitimise practise, build confidence, support relationships and supply resources have fostered the use of telehealth. This ongoing interaction between telehealth services, contexts and mechanisms is complex. The adoption of telehealth access to enable physically separated care, may mark a “new context;” or it could be that once the pandemic passes, previous policies and practises will re-assert themselves and curb support for telehealth-enabled care.
Effects of Emotional Stimulations on the Online Operation of a P300-Based Brain–Computer Interface

Using P300-based brain–computer interfaces (BCIs) in daily life should take into account the user’s emotional state because various emotional conditions are likely to influence event-related potentials (ERPs) and consequently the performance of P300-based BCIs. This study aimed at investigating whether external emotional stimuli affect the performance of a P300-based BCI, particularly built for controlling home appliances. We presented a set of emotional auditory stimuli to subjects, which had been selected for each subject based on individual valence scores evaluated a priori, while they were controlling an electric light device using a P300-based BCI. There were four conditions regarding the auditory stimuli, including high valence, low valence, noise, and no sound. As a result, subjects controlled the electric light device using the BCI in real time with a mean accuracy of 88.14%. The overall accuracy and P300 features over most EEG channels did not show a significant difference between the four auditory conditions (p > 0.05). When we measured emotional states using frontal alpha asymmetry (FAA) and compared FAA across the auditory conditions, we also found no significant difference (p > 0.05). Our results suggest that there is no clear evidence to support a hypothesis that external emotional stimuli influence the P300-based BCI performance or the P300 features while people are controlling devices using the BCI in real time. This study may provide useful information for those who are concerned with the implementation of a P300-based BCI in practice.
Source Mechanism of Seismic Explosion Signals at Santiaguito Volcano, Guatemala: New Insights From Seismic Analysis and Numerical Modeling

Volcanic activity at the Santiaguito dome complex (Guatemala) is characterized by lava extrusion interspersed with small, regular, gas-and-ash explosions that are believed to result from shallow magma fragmentation; yet, their triggering mechanisms remain debated. Given that the understanding of source processes at volcanoes is essential to risk assessments of future eruptions, this study seeks to shed light on those processes. We use data from a permanent seismic and infrasound network at Santiaguito volcano, Guatemala, established in 2018 and additional temporary stations, including a seismic array deployed during a 13-day field investigation in January 2019 to analyze and resolve the source characteristics of fragmentation leading to gas-and-ash explosions. Seismic data gathered within a distance of 4.5 km from the vent show a weak seismic signal 2–6 s prior to the explosions and associated main seismic signal. To resolve the source location and origin of the seismic signals, we first used ambient noise analysis to assess seismic velocities in the subsurface and then used two-dimensional spectral element modeling (SPECFEM2D) to simulate seismic waveforms. The analyzed data revealed a two-layer structure beneath the array, with a shallow, low-velocity layer (vs = 650 m/s) above deeper, high-velocity rocks (vs = 2,650 m/s). Using this velocity structure, possible source mechanisms and depths were constrained using array and particle motion analyses. The comparison of simulated and observed seismic data indicated that the precursory signal is associated with particle motion in the RZ-plane, pointing toward the opening of tensile cracks at a depth of ∼600 m below the summit; in contrast, the main signal is accompanied by a vertical single force, originating at a shallow depth of about ∼200 m. This suggests that the volcanic explosions at Santiaguito are following a bottom-up process in which tensile fractures develop at depth and enable rapid gas rise which leads to the subsequent explosion. The result indicates that explosions at Santiaguito do not occur from a single source location, but from a series of processes possibly associated with magma rupture, gas channeling and accumulation, and fragmentation. Our study provides a good foundation for further investigations at Santiaguito and shows the value of comparing seismic observations with synthetic data calculated for complex media to investigate in detail the processes leading up to gas-ash-rich explosions found at various other volcanoes worldwide.
Responses of Maize Internode to Water Deficit Are Different at the Biochemical and Histological Levels

Maize feeding value is strongly linked to plant digestibility. Cell wall composition and structure can partly explain cell wall digestibility variations, and we recently showed that tissue lignification and lignin spatial distribution also contribute to cell wall digestibility variations. Although the genetic determinism of digestibility and cell wall composition has been studied for more than 20 years, little is available concerning that of tissue lignification. Moreover, maize yield is negatively impacted by water deficit, and we newly highlighted the impact of water deficit on cell wall digestibility and composition together with tissue lignification. Consequently, the aim of this study was to explore the genetic mechanisms of lignin distribution in link with cell wall composition and digestibility under contrasted water regimes. Maize internodes from a recombinant inbred line (RIL) population grown in field trials with contrasting irrigation scenarios were biochemically and histologically quantified. Results obtained showed that biochemical and histological traits have different response thresholds to water deficit. Histological profiles were therefore only modified under pronounced water deficit, while most of the biochemical traits responded whatever the strength of the water deficit. Three main clusters of quantitative trait locus (QTL) for histological traits were detected. Interestingly, overlap between the biochemical and histological clusters is rare, and one noted especially colocalizations between histological QTL/clusters and QTL for p-coumaric acid content. These findings reinforce the suspected role of tissue p-coumaroylation for both the agronomic properties of plants as well as their digestibility.