Dysregulation of miRNA expression and excitation in MEF2C autism patient hiPSC-neurons and cerebral organoids.

MEF2C is a critical transcription factor in neurodevelopment, whose loss-of-function mutation in humans results in MEF2C haploinsufficiency syndrome (MHS), a severe form of autism spectrum disorder (ASD)/intellectual disability (ID). Despite prior animal studies of MEF2C heterozygosity to mimic MHS, MHS-specific mutations have not been investigated previously, particularly in a human context as hiPSCs afford. Here, for the first time, we use patient hiPSC-derived cerebrocortical neurons and cerebral organoids to characterize MHS deficits. Unexpectedly, we found that decreased neurogenesis was accompanied by activation of a micro-(mi)RNA-mediated gliogenesis pathway. We also demonstrate network-level hyperexcitability in MHS neurons, as evidenced by excessive synaptic and extrasynaptic activity contributing to excitatory/inhibitory (E/I) imbalance. Notably, the predominantly extrasynaptic (e)NMDA receptor antagonist, NitroSynapsin, corrects this aberrant electrical activity associated with abnormal phenotypes. During neurodevelopment, MEF2C regulates many ASD-associated gene networks, suggesting that treatment of MHS deficits may possibly help other forms of ASD as well.

The use of fractional radiofrequency in Asian patients to improve skin texture.

BACKGROUND AND OBJECTIVES: Fractional radiofrequency devices have been demonstrated to improve skin texture, such as smoothness, rhytides, brightness, and atrophic acne scars, by increasing dermal thickness, dermal collagen content, and dermal fibrillin content. The objective of the study is to assess the efficacy and adverse effects of this device on Asian patients of skin type III and IV with skin textural changes. MATERIALS AND METHODS: The study was designed as a prospective, open-labeled single-arm study, which was conducted with 20 Chinese patients aged 21-60 years and having irregularities in their skin texture, rhytides, and acne scars. The patients received six treatments at intervals of 4 weeks. Treatment was initiated with the maximum energy tolerated, which was then adjusted during the course of treatment if the patients felt excessive discomfort. A total of two passes were delivered in each session. Physician assessment results and standardized photographs were collected at the baseline, after all treatment visits, and at 1, 2, and 6 months after the final treatment visit. RESULTS: A total of 17 patients completed the study according to the established protocol. At the 6-month follow-up, 71% of patients were satisfied and 24% of patients were very satisfied with the received treatments, and the treatment physician reported varying degrees of improvement based on the global assessment scale in 60% of the subjects. While the anticipated side effects, such as erythema, edema, pinpoint bleeding, scab formation, and flare of acne, were noted in the patients, no serious adverse effects occurred. CONCLUSION: The use of fractional radiofrequency improves skin texture and is safe for use in Asian patients of skin type III and IV. No long-term serious adverse effects were noted.

fNIRS as a biomarker for individuals with subjective memory complaints and MCI.

INTRODUCTION: Identifying individuals at risk of developing dementia is crucial for early intervention. Mild cognitive impairment (MCI) and subjective memory complaints (SMCs) are considered its preceding stages. This study aimed to assess the utility of functional near-infrared spectroscopy (fNIRS) in identifying individuals with MCI and SMC. METHODS: One hundred fifty-one participants were categorized into normal cognition (NC); amnestic MCI (aMCI); non-amnestic MCI (naMCI); and mild, moderate, and severe SMC groups. Task-related prefrontal hemodynamics were measured using fNIRS during a visual memory span task. RESULTS: Results showed significantly lower oxyhemoglobin (HbO) levels in aMCI, but not in naMCI, compared to the NC. In addition, severe SMC had lower HbO levels than the NC, mild, and moderate SMC. Receiver operating characteristic analysis demonstrated 69.23% and 69.70% accuracy in differentiating aMCI and severe SMC from NC, respectively. DISCUSSION: FNIRS may serve as a potential non-invasive biomarker for early detection of dementia. HIGHLIGHTS: Only amnestic mild cognitive impairment (aMCI), but not non-amnestic MCI, showed lower oxyhemoglobin (HbO) than normal individuals. Reduced HbO was observed in those with severe subjective memory complaints (SMCs) compared to normal cognition (NC), mild, and moderate SMCs. Functional near-infrared spectroscopy measures were associated with performance in memory assessments. Prefrontal hemodynamics could distinguish aMCI and severe SMC from NC.

A rare presentation of pemphigus vegetans as an isolated vegetative lesion-Review of histopathological clues and treatment effects in multiple biopsy specimens.

BACKGROUND: Pemphigus is a group of immunobullous dermatoses characterized by the presence of autoantibodies directed against adhesion molecules of keratinocytes, with pemphigus vegetans being the rarest form, accounting for 1%-2% of all cases of pemphigus. Pemphigus vegetans is characterized by verrucous vegetative lesions in addition to vesiculobullous lesions. METHODS: We report a rare case of pemphigus vegetans presenting as an isolated vegetative lesion in the groin 3 months prior to the development of blisters. Owing to the atypical presentation, multiple biopsies were performed before and after corticosteroid treatment. RESULTS: Comparing the histopathology of pre-treatment and post-treatment biopsy specimens, the resolution of intraepidermal microabscesses, and reduction in intraepidermal and dermal inflammatory infiltrates, spongiosis and interface change, attributable to treatment, were noted. However, direct immunofluorescence showed persistent intracellular intraepidermal deposition of IgG and C3 2 weeks into treatment, despite near-complete resolution of blisters on clinical examination. Clinical regression of the vegetative lesion was noted only after 6 weeks into corticosteroid treatment, while histopathological evidence of treatment was apparent at the second week. CONCLUSION: The current case illustrates the importance of a liberal use of immunofluorescence studies in establishing the uncommon yet significant diagnosis of pemphigus vegetans, particularly for vegetative lesions that are persistent, in the intertriginous areas and/or in the setting of concurrent cutaneous or mucosal symptoms.

First uterine transplant case at the Royal Prince Alfred Hospital.

Uterine transplantation (UT) is an emerging medical treatment for women affected by absolute uterine factor infertility (AUFI). To date there have been over 90 documented cases of UT performed worldwide, with over 50 live births. UT allows women affected by AUFI the opportunity to carry and deliver a childd. The Royal Prince Alfred Hospital (RPAH) introduced a UT study in 2019; however, due to the impacts of the COVID pandemic the study was placed on hold for two years. In February 2023, RPAH performed the centre's first UT from a living unrelated donor to a 25-year-old woman with Mayer-Rokitansky-Küster-Hauser syndrome. The donor and recipient surgeries were uncomplicated and both are recovering well in the early post-operative period.

Predicting antimicrobial mechanism-of-action from transcriptomes: A generalizable explainable artificial intelligence approach.

To better combat the expansion of antibiotic resistance in pathogens, new compounds, particularly those with novel mechanisms-of-action [MOA], represent a major research priority in biomedical science. However, rediscovery of known antibiotics demonstrates a need for approaches that accurately identify potential novelty with higher throughput and reduced labor. Here we describe an explainable artificial intelligence classification methodology that emphasizes prediction performance and human interpretability by using a Hierarchical Ensemble of Classifiers model optimized with a novel feature selection algorithm called Clairvoyance; collectively referred to as a CoHEC model. We evaluated our methods using whole transcriptome responses from Escherichia coli challenged with 41 known antibiotics and 9 crude extracts while depositing 122 transcriptomes unique to this study. Our CoHEC model can properly predict the primary MOA of previously unobserved compounds in both purified forms and crude extracts at an accuracy above 99%, while also correctly identifying darobactin, a newly discovered antibiotic, as having a novel MOA. In addition, we deploy our methods on a recent E. coli transcriptomics dataset from a different strain and a Mycobacterium smegmatis metabolomics timeseries dataset showcasing exceptionally high performance; improving upon the performance metrics of the original publications. We not only provide insight into the biological interpretation of our model but also that the concept of MOA is a non-discrete heuristic with diverse effects for different compounds within the same MOA, suggesting substantial antibiotic diversity awaiting discovery within existing MOA.

Cost-effectiveness of immune checkpoint inhibitors in the treatment of non-small-cell lung cancer as a second line in Taiwan.

Objectives: To evaluate the cost-effectiveness of immune checkpoint inhibitors versus docetaxel in patients with advanced non-small-cell lung cancer. Methods: A Markov model was constructed to simulate the clinical outcomes and costs of advanced non-small-cell lung cancer. Clinical outcomes data were derived from randomized clinical trials. Drug acquisition cost and other health resource use were obtained from the claim data of a tertiary hospital and the National Health Insurance. The outcome was an incremental cost-effectiveness ratio expressed as cost per quality-adjusted life year gained. One-way and probabilistic sensitivity analyses were performed to evaluate the uncertainty of the model parameters. Results: In the base case, patients treated with immunotherapies in the second line were associated with higher costs and higher mean survival. The incremental costs per quality-adjusted life year gained for pembrolizumab, nivolumab, or atezolizumab compared to docetaxel were NT$416,102, NT$1,572,912 and NT$1,580,469, respectively. Conclusion: The results showed that pembrolizumab was more cost effective than nivolumab and atezolizumab compared with docetaxel as a second-line regimen for patients with previously treated advanced non-small-cell lung cancer at willingness to pay threshold in Taiwan.

Plain language summary Lung cancer is the first leading cause of cancer death in Taiwan. About 75% of patients have advanced disease at the time of diagnosis (stage III/IV) with a median survival of 13.2 months. Most non-small-cell lung cancer (NSCLC) patients are usually diagnosed at a late stage. The conventional chemotherapy, surgery or radiation regimens may not be of significant benefits. Fortunately, newer immunotherapies or targeted therapies have improved the 5-year survival rates of advanced NSCLC from 15 to 50% with high cost. This study aimed to assess if the newer targeted therapies are cost effective and provide 'value for money' compared with chemotherapy in NSCLC patients with advanced stage. A cost­effectiveness model was created based on the data from the real-world and published phase III randomized controlled trials. The results showed that pembrolizumab is more cost effective than nivolumab and atezolizumab compared with docetaxel as a second-line regimen for patients with previously treated advanced NSCLC at willingness to pay threshold in Taiwan.

A Systematic Review of the Application of Functional Near-Infrared Spectroscopy to the Study of Cerebral Hemodynamics in Healthy Aging.

Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies have shown that healthy aging is associated with functional brain deterioration that preferentially affects the prefrontal cortex. This article reviews the application of an alternative method, functional near-infrared spectroscopy (fNIRS), to the study of age-related changes in cerebral hemodynamics and factors that influence cerebral hemodynamics in the elderly population. We conducted literature searches in PudMed and PsycINFO, and selected only English original research articles that used fNIRS to study healthy individuals with a mean age of ≥ 55 years. All articles were published in peer-reviewed journals between 1977 and May 2019. We synthesized 114 fNIRS studies examining hemodynamic changes that occurred in the resting state and during the tasks of sensation and perception, motor control, semantic processing, word retrieval, attentional shifting, inhibitory control, memory, and emotion and motivation in healthy older adults. This review, which was not registered in a registry, reveals an age-related reduction in resting-state cerebral oxygenation and connectivity in the prefrontal cortex. It also shows that aging is associated with a reduction in functional hemispheric asymmetry and increased compensatory activity in the frontal lobe across multiple task domains. In addition, this article describes the beneficial effects of healthy lifestyles and the detrimental effects of cardiovascular disease risk factors on brain functioning among nondemented older adults. Limitations of this review include exclusion of gray and non-English literature and lack of meta-analysis. Altogether, the fNIRS literature provides some support for various neurocognitive aging theories derived from task-based PET and fMRI studies. Because fNIRS is relatively motion-tolerant and environmentally unconstrained, it is a promising tool for fostering the development of aging biomarkers and antiaging interventions.

Comparison of phasing strategies for whole human genomes.

Humans are a diploid species that inherit one set of chromosomes paternally and one homologous set of chromosomes maternally. Unfortunately, most human sequencing initiatives ignore this fact in that they do not directly delineate the nucleotide content of the maternal and paternal copies of the 23 chromosomes individuals possess (i.e., they do not 'phase' the genome) often because of the costs and complexities of doing so. We compared 11 different widely-used approaches to phasing human genomes using the publicly available 'Genome-In-A-Bottle' (GIAB) phased version of the NA12878 genome as a gold standard. The phasing strategies we compared included laboratory-based assays that prepare DNA in unique ways to facilitate phasing as well as purely computational approaches that seek to reconstruct phase information from general sequencing reads and constructs or population-level haplotype frequency information obtained through a reference panel of haplotypes. To assess the performance of the 11 approaches, we used metrics that included, among others, switch error rates, haplotype block lengths, the proportion of fully phase-resolved genes, phasing accuracy and yield between pairs of SNVs. Our comparisons suggest that a hybrid or combined approach that leverages: 1. population-based phasing using the SHAPEIT software suite, 2. either genome-wide sequencing read data or parental genotypes, and 3. a large reference panel of variant and haplotype frequencies, provides a fast and efficient way to produce highly accurate phase-resolved individual human genomes. We found that for population-based approaches, phasing performance is enhanced with the addition of genome-wide read data; e.g., whole genome shotgun and/or RNA sequencing reads. Further, we found that the inclusion of parental genotype data within a population-based phasing strategy can provide as much as a ten-fold reduction in phasing errors. We also considered a majority voting scheme for the construction of a consensus haplotype combining multiple predictions for enhanced performance and site coverage. Finally, we also identified DNA sequence signatures associated with the genomic regions harboring phasing switch errors, which included regions of low polymorphism or SNV density.

Uterus transplantation and pregnancy induction: Approved protocol at the Royal Prince Alfred Hospital.

Absolute uterine factor infertility (AUFI) is defined as the absence of a uterus or the presence of a non-functional uterus. Before the first live birth from a uterus transplant in 2014, the only fertility options for women with AUFI were surrogacy and adoption. In November 2019, our team was granted approval for the first uterus transplant trial in Australia using known living donors. Our program is based on that of our overseas collaborators in Dallas, Texas; this team will also be proctoring us for our first two cases.

Hepatic Arterial Infusion Chemotherapy Followed by Lipiodol Infusion for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Single-Center Experience.

Background and Objectives: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) followed by lipiodol infusion in advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Materials and Methods: Thirty-two patients with advanced HCC and PVTT who received HAIC with regimens of cisplatin, mitomycin-C, and 5-fluorouracil followed by lipiodol infusion were enrolled. The primary efficacy endpoint was tumor response rate. The modified Response Evaluation Criteria in Solid Tumors (mRECIST) was used for assessment of treatment response. The secondary endpoints were overall survival (OS) and progression free survival (PFS). Prognostic factors for survival also were evaluated. Results: The median OS and PFS were 11.9 and 9.5 months, respectively. Seventeen patients (53.1%) achieved objective response, and 23 patients (71.9%) achieved disease control. The length of survival in the responder and disease control groups was longer than in the non-responder and progressive disease groups after two cycles of HAIC (responder vs. non-responder: 16.5 vs. 7.9 months, p = 0.001; disease control vs. progressive disease: 12.3 vs. 5.6 months, p < 0.001) and after completing HAIC (responder vs. non-responder: 15.7 vs. 6.9 months, p = 0.001; disease control vs. progressive disease: 13.6 vs. 6.9 months, p < 0.001). Better survival was associated with Child-Pugh A liver function (p = 0.013), with early response to two HAIC cycles (p = 0.009), and with response (p = 0.02) and disease control (p = 0.001) after completing HAIC treatment. Conclusion: HAIC followed by lipiodol infusion is a safe and feasible treatment for advanced HCC with PVTT. Patients with early response could continue HAIC treatment with expected prolonged survival.

An 'eFP-Seq Browser' for visualizing and exploring RNA sequencing data.

Improvements in next-generation sequencing technologies have resulted in dramatically reduced sequencing costs. This has led to an explosion of '-seq'-based methods, of which RNA sequencing (RNA-seq) for generating transcriptomic data is the most popular. By analysing global patterns of gene expression in organs/tissues/cells of interest or in response to chemical or environmental perturbations, researchers can better understand an organism's biology. Tools designed to work with large RNA-seq data sets enable analyses and visualizations to help generate hypotheses about a gene's function. We present here a user-friendly RNA-seq data exploration tool, called the 'eFP-Seq Browser', that shows the read map coverage of a gene of interest in each of the samples along with 'electronic fluorescent pictographic' (eFP) images that serve as visual representations of expression levels. The tool also summarizes the details of each RNA-seq experiment, providing links to archival databases and publications. It automatically computes the reads per kilobase per million reads mapped expression-level summaries and point biserial correlation scores to sort the samples based on a gene's expression level or by how dissimilar the read map profile is from a gene splice variant, to quickly identify samples with the strongest expression level or where alternative splicing might be occurring. Links to the Integrated Genome Browser desktop visualization tool allow researchers to visualize and explore the details of RNA-seq alignments summarized in eFP-Seq Browser as coverage graphs. We present four cases of use of the eFP-Seq Browser for ABI3, SR34, SR45a and U2AF65B, where we examine expression levels and identify alternative splicing. The URL for the browser is https://bar.utoronto.ca/eFP-Seq_Browser/. OPEN RESEARCH BADGES: This article has earned an Open Data Badge for making publicly available the digitally-shareable data necessary to reproduce the reported results. Tool is at https://bar.utoronto.ca/eFP-Seq_Browser/; RNA-seq data at https://s3.amazonaws.com/iplant-cdn/iplant/home/araport/rnaseq_bam/ and https://s3.amazonaws.com/iplant-cdn/iplant/home/araport/rnaseq_bam/Klepikova/. Code is available at https://github.com/BioAnalyticResource/eFP-Seq-Browser.

Mechanism-of-Action Classification of Antibiotics by Global Transcriptome Profiling.

Antimicrobial resistance (AMR) is an ever-growing public health problem worldwide. The low rate of antibiotic discovery coupled with the rapid spread of drug-resistant bacterial pathogens is causing a global health crisis. To facilitate the drug discovery processes, we present a large-scale study of reference antibiotic challenge bacterial transcriptome profiles, which included 37 antibiotics across 6 mechanisms of actions (MOAs) and provide an economical approach to aid in antimicrobial dereplication in the discovery process. We demonstrate that classical MOAs can be sorted based upon the magnitude of gene expression profiles despite some overlap in the secondary effects of antibiotic exposures across MOAs. Additionally, using gene subsets, we were able to subdivide broad MOA classes into subMOAs. Furthermore, we provide a biomarker gene set that can be used to classify most antimicrobial challenges according to their canonical MOA. We also demonstrate the ability of this rapid MOA diagnostic tool to predict and classify the expression profiles of pure compounds and crude extracts to their expression profile-associated MOA class.

A mind-body lifestyle intervention enhances emotional control in patients with major depressive disorder: a randomized, controlled study.

To investigate the effects of the Dejian mind-body intervention (DMBI), on depressive symptoms and electroencephalography (EEG) changes in relation to emotional processing in patients with depression. Seventy-five age-, gender-, and education-matched participants with depression were randomly assigned to receive either Cognitive Behavior Therapy (CBT) or DMBI or were placed in a control group. Overall depressive syndrome, specific mood-related symptoms (Hamilton Psychiatric Rating Scale for Depression, Beck Depression Inventory), and EEG data were collected individually during a resting state and during affective image viewing before and after 10 weeks of intervention. After intervention, both the DMBI and CBT groups showed significantly reduced levels of overall depressive syndrome and mood-related symptoms (Ps ≤ 0.002) than the control group. In addition, the DMBI group demonstrated a significantly greater extent of elevation in fronto-posterior EEG theta coherence on the right hemisphere when viewing different mood-induction (neutral, positive, and negative) stimuli than the CBT and control groups (Ps < 0.03). The elevated intra-right fronto-posterior coherence when viewing mood-induction stimuli correlated with improved mood levels after the intervention (Ps < 0.05). Our findings also showed that, only in the DMBI group, there was a significant suppression of theta source activity at the posterior and subcortical brain regions that are known to mediate negative emotional responses and the self-absorbed mode of thinking. The findings of reduced depressive symptoms and elevated frontoposterior coherence suggest that the DMBI can enhance emotional control in depression.

AbGRI4, a novel antibiotic resistance island in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates.

OBJECTIVES: To investigate the genomic context of a novel resistance island (RI) in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates and global isolates. METHODS: Using a combination of long and short reads generated from the Oxford Nanopore and Illumina platforms, contiguous chromosomes and plasmid sequences were determined. BLAST-based analysis was used to identify the RI insertion target. RESULTS: Genomes of four multiply antibiotic-resistant A. baumannii clinical strains, from a US hospital system, belonging to prevalent MLST ST2 (Pasteur scheme) and ST281 (Oxford scheme) clade F isolates were sequenced to completion. A class 1 integron carrying aadB (tobramycin resistance) and aadA2 (streptomycin/spectinomycin resistance) was identified. The class 1 integron was 6.8 kb, bounded by IS26 at both ends, and embedded in a new target location between an α/ß-hydrolase and a reductase. Due to its novel insertion site and unique RI composition, we suggest naming this novel RI AbGRI4. Molecular analysis of global A. baumannii isolates identified multiple AbGRI4 RI variants in non-ST2 clonal lineages, including variations in the resistance gene cassettes, integron backbone and insertion breakpoints at the hydrolase gene. CONCLUSIONS: A novel RI insertion target harbouring a class 1 integron was identified in a subgroup of ST2/ST281 clinical isolates. Variants of the RI suggested evolution and horizontal transfer of the RI across clonal lineages. Long- and short-read hybrid assembly technology completely resolved the genomic context of IS-bounded RIs, which was not possible using short reads alone.

Neurocognitive development of flanker and Stroop interference control: A near-infrared spectroscopy study.

The abilities to resolve flanker and Stroop interference, which are primarily mediated by the prefrontal cortex (PFC), have been shown to be dissociable at the individual difference level. However, the relationship between the neurocognitive development of these two aspects of interference control remains unclear. This study examined developmental changes in inhibition performance and PFC activation during flanker and Stroop interference control using functional near-infrared spectroscopy (fNIRS). Twenty-eight healthy children and adolescents aged 7-16 years (16 males) underwent the arrow flanker and color-word matching Stroop paradigms while changes in oxyhemoglobin concentration in the PFC were monitored by fNIRS. We found developmental improvements in inhibition performance in terms of the interference scores on both the flanker and Stroop tasks. There were also developmental increases in PFC activation, particularly in the medial region, while resolving flanker and Stroop interference. Despite developmental changes in inhibition performance and medial PFC activation during both tasks, the developmental changes that we observed for these two aspects of interference control were found to be relatively independent of each other. Our findings support the heterogeneous view of interference control and suggest that the neurocognitive development of flanker and Stroop interference control is only weakly associated, if not dissociable.

Co-occurrence of Anaerobes in Human Chronic Wounds.

Chronic wounds are wounds that have failed to heal after 3 months of appropriate wound care. Previous reports have identified a diverse collection of bacteria in chronic wounds, and it has been postulated that bacterial profile may contribute to delayed healing. The purpose of this study was to perform a microbiome assessment of the Wound Healing and Etiology (WE-HEAL) Study cohort, including underlying comorbidities less commonly studied in the context of chronic wounds, such as autoimmune diseases, and investigate possible relationships of the wound microbiota with clinical healing trends. We examined chronic wound specimens from 60 patients collected through the WE-HEAL Study using 16S ribosomal RNA gene sequencing. A group of co-occurring obligate anaerobes was identified from taxonomic analysis guided by Dirichlet multinomial mixtures (DMM) modeling. The group includes members of the Gram-positive anaerobic cocci (GPAC) of the Clostridia class (i.e., Anaerococcus, Finegoldia, and Peptoniphilus) and additional strict anaerobes (i.e., Porphyromonas and Prevotella). We showed that the co-occurring group of obligate anaerobes not only co-exists with commonly identified wound species (such as Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas, Corynebacterium, and Streptococcus), but importantly, they could also predominate the wound microbiota. Furthermore, examination of clinical comorbidities of the WE-HEAL specimens showed that specific obligate and facultative anaerobes were significantly reduced in wounds presented with autoimmune disease. With respect to future healing trends, no association with the wound microbiome community or the abundance of individual wound species could be established. In conclusion, we identified a co-occurring obligate anaerobic community type that predominated some human chronic wounds and underrepresentation of anaerobes in wounds associated with autoimmune diseases. Possible elucidation of host environments or key factors that influence anaerobe colonization warrants further investigation in a larger cohort.

Photobiomodulation improves the frontal cognitive function of older adults.

OBJECTIVES: The frontal lobe hypothesis of age-related cognitive decline suggests that the deterioration of the prefrontal cortical regions that occurs with aging leads to executive function deficits. Photobiomodulation (PBM) is a newly developed, noninvasive technique for enhancing brain function, which has shown promising effects on cognitive function in both animals and humans. This randomized, sham-controlled study sought to examine the effects of PBM on the frontal brain function of older adults. METHODS/DESIGNS: Thirty older adults without a neuropsychiatric history performed cognitive tests of frontal function (ie, the Eriksen flanker and category fluency tests) before and after a single 7.5-minute session of real or sham PBM. The PBM device consisted of three separate light-emitting diode cluster heads (633 and 870 nm), which were applied to both sides of the forehead and posterior midline, and delivered a total energy of 1349 J. RESULTS: Significant group (experimental, control) × time (pre-PBM, post-PBM) interactions were found for the flanker and category fluency test scores. Specifically, only the older adults who received real PBM exhibited significant improvements in their action selection, inhibition ability, and mental flexibility after vs before PBM. CONCLUSIONS: Our findings support that PBM may enhance the frontal brain functions of older adults in a safe and cost-effective manner.

Araport11: a complete reannotation of the Arabidopsis thaliana reference genome.

The flowering plant Arabidopsis thaliana is a dicot model organism for research in many aspects of plant biology. A comprehensive annotation of its genome paves the way for understanding the functions and activities of all types of transcripts, including mRNA, the various classes of non-coding RNA, and small RNA. The TAIR10 annotation update had a profound impact on Arabidopsis research but was released more than 5 years ago. Maintaining the accuracy of the annotation continues to be a prerequisite for future progress. Using an integrative annotation pipeline, we assembled tissue-specific RNA-Seq libraries from 113 datasets and constructed 48 359 transcript models of protein-coding genes in eleven tissues. In addition, we annotated various classes of non-coding RNA including microRNA, long intergenic RNA, small nucleolar RNA, natural antisense transcript, small nuclear RNA, and small RNA using published datasets and in-house analytic results. Altogether, we identified 635 novel protein-coding genes, 508 novel transcribed regions, 5178 non-coding RNAs, and 35 846 small RNA loci that were formerly unannotated. Analysis of the splicing events and RNA-Seq based expression profiles revealed the landscapes of gene structures, untranslated regions, and splicing activities to be more intricate than previously appreciated. Furthermore, we present 692 uniformly expressed housekeeping genes, 43% of whose human orthologs are also housekeeping genes. This updated Arabidopsis genome annotation with a substantially increased resolution of gene models will not only further our understanding of the biological processes of this plant model but also of other species.