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We use self-assembly to fabricate and to connect precise graphene nanoribbons end to end. Combining scanning tunneling microscopy, Raman spectroscopy, and density functional theory, we characterize the chemical and electronic aspects of the interconnections between ribbons. We demonstrate how the substrate effects of our self-assembly can be exploited to fabricate graphene structures connected to desired electrodes.

Acorn worms, also known as enteropneust (literally, 'gut-breathing') hemichordates, are marine invertebrates that share features with echinoderms and chordates. Together, these three phyla comprise the deuterostomes. Here we report the draft genome sequences of two acorn worms, Saccoglossus kowalevskii and Ptychodera flava. By comparing them with diverse bilaterian genomes, we identify shared traits that were probably inherited from the last common deuterostome ancestor, and then explore evolutionary trajectories leading from this ancestor to hemichordates, echinoderms and chordates. The hemichordate genomes exhibit extensive conserved synteny with amphioxus and other bilaterians, and deeply conserved non-coding sequences that are candidates for conserved gene-regulatory elements. Notably, hemichordates possess a deuterostome-specific genomic cluster of four ordered transcription factor genes, the expression of which is associated with the development of pharyngeal 'gill' slits, the foremost morphological innovation of early deuterostomes, and is probably central to their filter-feeding lifestyle. Comparative analysis reveals numerous deuterostome-specific gene novelties, including genes found in deuterostomes and marine microbes, but not other animals. The putative functions of these genes can be linked to physiological, metabolic and developmental specializations of the filter-feeding ancestor.

Abstract Background The objective of this study was to explore the underlying etiologies associated with the resolution and improvement of delirium in ill‐hospitalized cancer patients. Methods We conducted a secondary analysis of a multicenter, prospective, observational study to estimate the effectiveness of pharmacotherapy for delirium. Participants were cancer patients with delirium. We assessed the Delirium Rating Scale, Revised‐98 (DRS‐R98) severity scale score at baseline and three days after pharmacotherapy initiation. Delirium resolution was defined as a DRS‐R98 severity scale score ≤9, and improvement was defined as ≥50% reduction at Day 3. Results We enrolled 566 patients (491 patients had performance status of 3 or 4). The resolution and improvement rates in all patients were 22.6% and 19.3%, respectively. Univariate analysis determined that nonrespiratory infection (OR 2.18, 95% CI 1.38‐3.45) was significantly associated with greater resolution, while dehydration (0.40, 0.19‐0.87), organic damage to the central nervous system (CNS) (0.32, 0.43‐0.72), hypoxia (0.25, 0.12‐0.52), and hyponatremia (0.34, 0.12‐0.97) were significantly associated with no resolution. Potential causes associated with delirium improvement were nonrespiratory infection (1.93, 1.19‐3.13), organic damage to the CNS (0.40, 0.18‐1.90), and hypoxia (0.32, 0.16‐0.65). After multivariate analysis, dehydration (0.34, 0.15‐0.76), organic damage to the CNS (0.25, 0.10‐0.60), and hypoxia (0.29, 0.14‐0.61) were significantly associated with no resolution. Conclusions Delirium caused by nonrespiratory infection may be reversible, while delirium associated with dehydration, organic damage to the CNS, hypoxia, or hyponatremia seems to be irreversible in ill‐hospitalized cancer patients.

We produce precise chiral-edge graphene nanoribbons on Cu{111} using self-assembly and surface-directed chemical reactions. We show that, using specific properties of the substrate, we can change the edge conformation of the nanoribbons, segregate their adsorption chiralities, and restrict their growth directions at low surface coverage. By elucidating the molecular-assembly mechanism, we demonstrate that our method constitutes an alternative bottom-up strategy toward synthesizing defect-free zigzag-edge graphene nanoribbons.

Clinical walk tests may not predict the development of frailty in healthy older adults. With advancements in wearable technology, it may be possible to predict the development of frailty using loading asymmetry parameters during clinical walk tests. This prospective cohort study aimed to test the hypothesis that increased limb loading asymmetry predicts frailty risk in community-living older adults. Sixty-three independently ambulant community-living adults aged ≥ 65 years were recruited, and forty-seven subjects completed the ten-month follow-up after baseline. Loading asymmetry index of net and regional (forefoot, midfoot, and rearfoot) plantar forces were collected using force sensing insoles during a 10 m walk test with their maximum speed. Development of frailty was defined if the participant progressed from baseline at least one grading group of frailty at the follow-up period using the Kihon Checklist. Fourteen subjects developed frailty during the follow-up period. Increased risk of frailty was associated with each 1% increase in loading asymmetry of net impulse (Odds ratio 1.153, 95%CI 1.001 to 1.329). Net impulse asymmetry significantly correlated with asymmetry of peak force in midfoot force. These results indicate the feasibility of measuring plantar forces of gait during clinical walking tests and underscore the potential of using load asymmetry as a tool to augment frailty risk assessment in community-dwelling older adults. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is an incurable B‐cell malignancy often accompanied by profound immunodeficiency. Lenalidomide (Len) is an immunomodulatory drug that exerts promising therapeutic effects on MM through the immune system. However, predictive markers related to the effects of Len treatment are not fully understood. This study aimed to identify candidate biomarkers for predicting the clinical efficacy of Len and dexamethasone (Ld) therapy through a comprehensive analysis of serum cytokines. The levels of 48 cytokines in the serum of patients with MM just before Ld therapy (n = 77), at the time of best response (n = 56), and at disease progression (n = 49) were measured and evaluated. Patients with high IL‐18 and M‐CSF levels showed significantly shorter progression‐free survival and overall survival (OS). In contrast, patients with high PDGF‐BB levels had longer survival. Moreover, low levels of G‐CSF, IL‐7, IL‐8, and SDF‐1α were associated with shorter OS after Ld therapy. During Ld therapy, pro‐inflammatory cytokines such as IL‐2Rα, IL‐18, and TNF‐α were decreased, while IFN‐γ was increased. IL‐4 and IL‐6 levels increased during disease progression. In conclusion, this study provides a better understanding of the association between cytokines and the efficacy of Ld therapy as well as the unique changes in cytokines related to inflammatory and immune responses during Ld therapy. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis is a common pathological feature of cardiovascular diseases that arises from the hyperactivation of fibroblasts and excessive extracellular matrix (ECM) deposition, leading to impaired cardiac function and potentially heart failure or arrhythmia. Extracellular vesicles (EVs) released by cardiomyocytes (CMs) regulate various physiological functions essential for myocardial homeostasis, which are disrupted in cardiac disease. Therefore, healthy CM‐derived EVs represent a promising cell‐free therapy for the treatment of cardiac fibrosis. To this end, we optimized the culture conditions of human adult CMs to obtain a large yield of EVs without compromising cellular integrity by using a defined combination of small molecules. EVs were isolated by ultracentrifugation, and their characteristics were analysed. Finally, their effect on fibrosis was tested. Treatment of TGFβ‐activated human cardiac fibroblasts with EVs derived from CMs using our culture system resulted in a decrease in fibroblast activation markers and ECM accumulation. The rescued phenotype was associated with specific EV cargo, including multiple myocyte‐specific and antifibrotic microRNAs, although their effect individually was not as effective as the EV treatment. Notably, pathway analysis showed that EV treatment reverted the transcription of activated fibroblasts and decreased several signalling pathways, including MAPK, mTOR, JAK/STAT, TGFβ, and PI3K/Akt, all of which are involved in fibrosis development. Intracardiac injection of CM‐derived EVs in an animal model of cardiac fibrosis reduced fibrotic area and increased angiogenesis, which correlated with improved cardiac function. These findings suggest that EVs derived from human adult CMs may offer a targeted and effective treatment for cardiac fibrosis, owing to their antifibrotic properties and the specificity of cargo. [ABSTRACT FROM AUTHOR]

Background and Aims: Mild cognitive impairment (MCI) is a widespread condition in older individuals, posing significant risk of dementia. However, limited research has been conducted to explore effective interventions and clarify their impact at the neural level. Therefore, this study aimed to investigate the effects of computerized cognitive training (CCT) and explore the associated neural mechanisms in preventing dementia in older individuals with MCI, with a view to inform future intervention efforts. Methods: We reviewed the effects of CCT on biomarker outcomes in older adults with MCI. The search was conducted for studies published between 2010 and May 10, 2023, using three search engines: PubMed, Scopus, and Cumulative Index to Nursing and Allied Health Literature. The inclusion criteria were as follows: studies that involved participants diagnosed with MCI, included CCT, included quantitative assessment of biomarker results, and conducted randomized controlled trials. Results: Sixteen studies that used biomarkers, including magnetic resonance imaging, electroencephalography (EEG), functional near‐infrared spectroscopy (fNIRS), and blood or salivary biomarkers, were extracted. The results showed that CCT caused changes in structure and function within the main brain network, including the default mode network, and decreased both theta rhythm activity on EEG and prefrontal activity on fNIRS, with improvement in cognitive function. Furthermore, CCT combined with physical exercise showed more significant structural and functional changes in extensive brain regions compared with CCT alone. Virtual reality‐based cognitive training improved not only executive function but also instrumental activities of daily living. Conclusion: CCT causes functional and structural changes in extensive brain regions and improves cognitive function in older adults with MCI. Our findings highlight the potential of individualized intervention methods and biomarker assessment according to the specific causes of MCI. Future research should aim to optimize these personalized therapeutic strategies to maximize the benefits of CCT in older adults with MCI. Key points: Computerized cognitive training (CCT) causes functional and structural changes in extensive brain regions in older adults with mild cognitive impairment (MCI), with improvement in cognitive function.The effect of CCT combined with physical exercise may be stronger and longer‐lasting than that of CCT alone.Virtual reality‐based cognitive training may improve not only executive function but also instrumental activities of daily living. [ABSTRACT FROM AUTHOR]