Tau-PET imaging in Parkinson's disease: a systematic review and meta-analysis

BackgroundPathological tau accumulates in the cerebral cortex of Parkinson's disease (PD), resulting in cognitive deterioration. Positron emission tomography (PET) can be used for in vivo imaging of tau protein. Therefore, we conducted a systematic review and meta-analysis of tau protein burden in PD cognitive impairment (PDCI), PD dementia (PDD), and other neurodegenerative diseases and explored the potential of the tau PET tracer as a biomarker for the diagnosis of PDCI.MethodsPubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched for studies published till 1 June 2022 that used PET imaging to detect tau burden in the brains of PD patients. Standardized mean differences (SMDs) of tau tracer uptake were calculated using random effects models. Subgroup analysis based on the type of tau tracers, meta-regression, and sensitivity analysis was conducted.ResultsA total of 15 eligible studies were included in the meta-analysis. PDCI patients (n = 109) had a significantly higher tau tracer uptake in the inferior temporal lobe than healthy controls (HCs) (n = 237) and had a higher tau tracer uptake in the entorhinal region than PD with normal cognition (PDNC) patients (n = 61). Compared with progressive supranuclear palsy (PSP) patients (n = 215), PD patients (n = 178) had decreased tau tracer uptake in the midbrain, subthalamic nucleus, globus pallidus, cerebellar deep white matter, thalamus, striatum, substantia nigra, dentate nucleus, red nucleus, putamen, and frontal lobe. Tau tracer uptake values of PD patients (n = 178) were lower than those of patients with Alzheimer's disease (AD) (n = 122) in the frontal lobe and occipital lobe and lower than those in patients with dementia with Lewy bodies (DLB) (n = 55) in the occipital lobe and infratemporal lobe.ConclusionIn vivo imaging studies with PET could reveal region-specific binding patterns of the tau tracer in PD patients and help in the differential diagnosis of PD from other neurodegenerative diseases.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/

The Mechanical Properties of Epoxy Composites Filled with Rubbery Copolymer Grafted SiO\u3csub\u3e2\u3c/sub\u3e

This study demonstrated a method for toughening a highly crosslinked anhydride cured DGEBA epoxy using rubbery block copolymer grafted SiO2 nanoparticles. The particles were synthesized by a sequential reversible addition-fragmentation chain transfer (RAFT) polymerization. The inner rubbery block poly(n-hexyl methacrylate) (PHMA) had a glass transition temperature below room temperature. The outer block poly(glycidyl methacrylate) (PGMA) was matrix compatible. A rubbery interlayer thickness of 100% and 200% of the particle core radius was achieved by grafting a 20 kg/mol and a 40 kg/mol PHMA at a graft density of 0.7 chains/nm2 from the SiO2 surface. The 20 kg/mol rubbery interlayer transferred load more efficiently to the SiO2 cores than the 40 kg/mol rubbery interlayer and maintained the epoxy modulus up to a loading of 10 vol% of the rubbery interlayer. Both systems enabled cavitation or plastic dilatation. Improvement of the strain-to-break and the tensile toughness was found in both systems. We hypothesize that plastic void growth in the matrix is the primary mechanism causing the improvement of the ductility

CHIME/FRB Discovery of 25 Repeating Fast Radio Burst Sources

We present the discovery of 25 new repeating fast radio burst (FRB) sources found among CHIME/FRB events detected between 2019 September 30 and 2021 May 1. The sources were found using a new clustering algorithm that looks for multiple events co-located on the sky having similar dispersion measures (DMs). The new repeaters have DMs ranging from $\sim$220 pc cm$^{-3}$ to $\sim$1700 pc cm$^{-3}$, and include sources having exhibited as few as two bursts to as many as twelve. We report a statistically significant difference in both the DM and extragalactic DM (eDM) distributions between repeating and apparently nonrepeating sources, with repeaters having lower mean DM and eDM, and we discuss the implications. We find no clear bimodality between the repetition rates of repeaters and upper limits on repetition from apparently nonrepeating sources after correcting for sensitivity and exposure effects, although some active repeating sources stand out as anomalous. We measure the repeater fraction and find that it tends to an equilibrium of $2.6_{-2.6}^{+2.9}$% over our exposure thus far. We also report on 14 more sources which are promising repeating FRB candidates and which merit follow-up observations for confirmation.Comment: Submitted to ApJ. Comments are welcome and follow-up observations are encouraged

The Genomes of Oryza sativa: A History of Duplications

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000–40,000. Only 2%–3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The airway neuro-immune axis as a therapeutic target in allergic airway diseases

Abstract Recent evidence has increasingly underscored the importance of the neuro-immune axis in mediating allergic airway diseases, such as allergic asthma and allergic rhinitis. The intimate spatial relationship between neurons and immune cells suggests that their interactions play a pivotal role in regulating allergic airway inflammation. Upon direct activation by allergens, neurons and immune cells engage in interactions, during which neurotransmitters and neuropeptides released by neurons modulate immune cell activity. Meanwhile, immune cells release inflammatory mediators such as histamine and cytokines, stimulating neurons and amplifying neuropeptide production, thereby exacerbating allergic inflammation. The dynamic interplay between the nervous and immune systems suggests that targeting the neuro-immune axis in the airway could represent a novel approach to treating allergic airway diseases. This review summarized recent evidence on the nervous system’s regulatory mechanisms in immune responses and identified potential therapeutic targets along the peripheral nerve-immune axis for allergic asthma and allergic rhinitis. The findings will provide novel perspectives on the management of allergic airway diseases in the future

An Effective Negotiating Agent Framework based on Deep Offline Reinforcement Learning

Learning is crucial for automated negotiation, and recent years have witnessed a remarkable achievement in application of reinforcement learning (RL) for various negotiation tasks. Conventional RL methods focus generally on learning from active interactions with opposing negotiators. However, collecting online data is expensive in many realistic negotiation scenarios. While previous studies partially mitigate this problem through the use of opponent simulators (i.e., agents following known strategies), in reality it is usually hard to fully capture an opponent's negotiation strategy. Moreover, a further challenge lies in an agent's capability of adapting to dynamic variations of an opponent's preferences or strategies, which may happen from time to time for different reasons in subsequent negotiations. In response to these challenges, this article proposes a novel Deep Offline Reinforcement learning Negotiating Agent framework that allows to learn an effective strategy using previously collected negotiation datasets without requiring interaction with an opponent. This is in contrast to existing RL-based negotiation approaches that all rely on active interaction with opponents. Furthermore, the strategy fine-tuning mechanism is included to adjust the learned strategy in response to the preferences or strategy changes of the opponent. The performance of the proposed framework is evaluated based on a diverse set of state-of-the-art baselines under different settings. Experimental results show that the framework allows to learn effective strategies exclusively with offline datasets, and is also capable of effectively adapting to changes of an opponent's preferences or strategy