Miracle-dz/UniFAR-FTUs huggingface dataset:
Cognitive, Genetic, Brain Volume, and Diffusion Tensor Imaging Markers as Early Indicators of Dementia

Background: Although associated with dementia and cognitive impairment, microstructural white matter integrity is a rarely used marker of preclinical dementia. Objective: We aimed to evaluate the individual and combined effects of multiple markers, with special focus on microstructural white matter integrity, in detecting individuals with increased dementia risk. Methods: A dementia-free subsample (n = 212, mean age = 71.33 years) included in the population-based Swedish National Study on Aging and Care (SNAC-K) underwent magnetic resonance imaging (T1-weighted, fluid-attenuated inversion recovery, diffusion tensor imaging), neuropsychological testing (perceptual speed, episodic memory, semantic memory, letter and category fluency), and genotyping (APOE). Incident dementia was assessed during six years of follow-up. Results: A global model (global cognition, APOE, total brain tissue volume: AUC = 0.920) rendered the highest predictive value for future dementia. Of the models based on specific markers, white matter integrity of the forceps major tract was included in the most predictive model, in combination with perceptual speed and hippocampal volume (AUC = 0.911). Conclusion: Assessment of microstructural white matter integrity may improve the early detection of dementia, although the added benefit in this study was relatively small.
Management of Graves Thyroidal and Extrathyroidal Disease: An Update

Abstract Context Invited update on the management of systemic autoimmune Graves disease (GD) and associated Graves orbitopathy (GO). Evidence acquisition Guidelines, pertinent original articles, systemic reviews, and meta-analyses. Evidence synthesis Thyrotropin receptor antibodies (TSH-R-Abs), foremost the stimulatory TSH-R-Abs, are a specific biomarker for GD. Their measurement assists in the differential diagnosis of hyperthyroidism and offers accurate and rapid diagnosis of GD. Thyroid ultrasound is a sensitive imaging tool for GD. Worldwide, thionamides are the favored treatment (12-18 months) of newly diagnosed GD, with methimazole (MMI) as the preferred drug. Patients with persistently high TSH-R-Abs and/or persistent hyperthyroidism at 18 months, or with a relapse after completing a course of MMI, can opt for a definitive therapy with radioactive iodine (RAI) or total thyroidectomy (TX). Continued long-term, low-dose MMI administration is a valuable and safe alternative. Patient choice, both at initial presentation of GD and at recurrence, should be emphasized. Propylthiouracil is preferred to MMI during the first trimester of pregnancy. TX is best performed by a high-volume thyroid surgeon. RAI should be avoided in GD patients with active GO, especially in smokers. Recently, a promising therapy with an anti-insulin-like growth factor-1 monoclonal antibody for patients with active/severe GO was approved by the Food and Drug Administration. COVID-19 infection is a risk factor for poorly controlled hyperthyroidism, which contributes to the infection–related mortality risk. If GO is not severe, systemic steroid treatment should be postponed during COVID-19 while local treatment and preventive measures are offered. Conclusions A clear trend towards serological diagnosis and medical treatment of GD has emerged.
Distal Convoluted Tubule Sexual Dimorphism Revealed by Advanced 3D-Imaging.

The thiazide-sensitive sodium chloride cotransporter (NCC) is more abundant in kidneys of females than of males. Because morphological remodeling of the distal convoluted tubule (DCT) is dependent on NCC activity, it has been generally assumed that there is a corresponding sexual dimorphism in the structure of the DCT, leading to a larger female DCT. Until now, this has never been directly examined. Here, optical clearing techniques were combined with antibody labeling of DCT segment markers, state-of-the-art high-speed volumetric imaging and analysis tools to visualize and quantify DCT morphology in male and female mice and study the DCT remodeling response to furosemide. We found an unexpected sex difference in the structure of the DCT. Compared to the males, females have a shorter DCT, a higher cellular density of NCC, and a greater capacity to elongate in response to loop-diuretics. Our study reveals a sexual dimorphism of the DCT. Females express a greater density of NCC transporters in a shorter structure to protect sodium balance in the face of greater basal distal sodium delivery yet have a larger reserve and structural remodeling capacity to adapt to unique physiological stresses. These observations provide insight into mechanisms that may drive sex differences in the therapeutic responses to diuretics.
Vibrational Spectroscopy Saliva Profiling as Biometric Tool for Disease Diagnostics: A Systematic Literature Review

Saliva is a biofluid that can be considered as a “mirror” reflecting our body’s health status. Vibrational spectroscopy, Raman and infrared, can provide a detailed salivary fingerprint that can be used for disease biomarker discovery. We propose a systematic literature review based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to evaluate the potential of vibrational spectroscopy to diagnose oral and general diseases using saliva as a biological specimen. Literature searches were recently conducted in May 2020 through MEDLINE-PubMed and Scopus databases, without date limitation. Finally, over a period of 10 years, 18 publications were included reporting on 10 diseases (three oral and seven general diseases), with very high diagnostic performance rates in terms of sensitivity, specificity, and accuracy. Thirteen articles were related to six different cancers of the following anatomical sites: mouth, nasopharynx, lung, esophagus, stomach, and breast. The other diseases investigated and included in this review were periodontitis, Sjögren’s syndrome, diabetes, and myocardial infarction. Moreover, most articles focused on Raman spectroscopy (n = 16/18) and more specifically surface-enhanced Raman spectroscopy (n = 12/18). Interestingly, vibrational spectroscopy appears promising as a rapid, label-free, and non-invasive diagnostic salivary biometric tool. Furthermore, it could be adapted to investigate subclinical diseases—even if developmental studies are required.
Prospective observational study of respiratory Aspergillus colonization or disease in patients with various stages of chronic obstructive pulmonary disease utilizing culture versus nonculture techniques.

Chronic obstructive pulmonary disease (COPD) patients have been recognized to be at increased risk of Aspergillus spp. colonization, which may progress to invasive pulmonary aspergillosis (IPA). The objective of this study was to determine the frequency of Aspergillus colonization, or disease, in a cohort of COPD patients. A prospective observational study was undertaken to determine Aspergillus colonization, or disease, in consecutive COPD patients undergoing bronchoscopy. Fungal culture as well as galactomannan antigen (GM) and Aspergillus nucleic acid detection (PCR) were performed on bronchoalveolar lavage fluid (BAL) samples. One hundred and fifty patients were recruited. One hundred and twelve (74.7%) were outpatients, 38 (25.33%) were inpatients, of whom 6 (4%) were in the intensive care unit. Most patients (N = 122, 81.3%) were either COPD GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages 1 or 2. Nine (6%) patients were on systemic steroids, 64 (42.7%) on inhaled steroids, and 9 (6%) on both. Seventeen patients (11.3%) had at least one positive test for Aspergillus detection (culture ± galactomannan ± polymerase chain reaction [PCR]), 13 (76.4%) of whom were COPD GOLD stages 1 or 2. Five patients had probable or putative IPA. Aspergillus sp. was detected in five patients (3.3%) by culture, but detection increased to 17 (11.3%) by the additional testing for GM or Aspergillus DNA. The frequency of Aspergillus detection in this cohort of COPD patients may reflect the predominance of early GOLD stages among the study population but deserves further investigation to determine its relevance as a predictive risk factor for IPA. LAY SUMMARY COPD is a risk factor for Aspergillus spp. colonization. Bronchoalveolar lavage samples of 150 COPD patients were tested for presence of Aspergillus fumigatus, which was detected in five patients (3.3%) by culture, but detection of Aspergillus increased to 17 (11.3%) by additional GM and PCR testing.
Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle

Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the medial forebrain bundle in treatment‐resistant depressed patients—one of several targets under investigation—has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself. In the context of precision and customized medicine, the current paper focuses on clinical and experimental research of medial forebrain bundle DBS in depression or in animal models of depression, demonstrating how clinical and scientific progress can work in tandem to test the therapeutic value and investigate the mechanisms of this experimental treatment. As one of the hypotheses is that depression engenders changes in the reward and motivational networks, the review looks at how stimulation of the medial forebrain bundle impacts the dopaminergic system.
Intracranial EEG Validation of Single-Channel Subgaleal EEG for Seizure Identification

Purpose: A device that provides continuous, long-term, accurate seizure detection information to providers and patients could fundamentally alter epilepsy care. Subgaleal (SG) EEG is a promising modality that offers a minimally invasive, safe, and accurate means of long-term seizure monitoring. Methods: Subgaleal EEG electrodes were placed, at or near the cranial vertex, simultaneously with intracranial EEG electrodes in 21 epilepsy patients undergoing intracranial EEG studies for up to 13 days. A total of 219, 10-minute single-channel SGEEG samples, including 138 interictal awake or sleep segments and 81 seizures (36 temporal lobe, 32 extra-temporal, and 13 simultaneous temporal/extra-emporal onsets) were reviewed by 3 expert readers blinded to the intracranial EEG results, then analyzed for accuracy and interrater reliability. Results: Using a single-channel of SGEEG, reviewers accurately identified 98% of temporal and extratemporal onset, intracranial, EEG-verified seizures with a sensitivity of 98% and specificity of 99%. All focal to bilateral tonic-–clonic seizures were correctly identified. Conclusions: Single-channel SGEEG, placed at or near the vertex, reliably identifies focal and secondarily generalized seizures. These findings demonstrate that the SG space at the cranial vertex may be an appropriate site for long-term ambulatory seizure monitoring.
Astragaloside IV ameliorates preeclampsia-induced oxidative stress through Nrf2/HO-1 pathway in a rat model.

Preeclampsia (PE) can cause serious health problems for pregnant women and their infants. Astragaloside IV has been shown to exert cardioprotective, anti-inflammatory, and anti-oxidative effects on various disorders. We aimed to study the effects of Astragaloside IV on PE symptoms using an NG-Nitro-L-arginine-methyl ester (L-NAME)-induced rat model of PE. The pregnant rats' physiological features, including blood pressure, urine protein, serum sFlt-1/PIGF ratio, and weight of placenta, as well as the weight, length, and survival of pups, were documented. The expression levels of target genes were analyzed by western blot assay and qRT-PCR assay. The levels of target secreted proteins were determined by ELISA assay. We demonstrated that the administration of Astragaloside IV might exert a multitude of beneficial effects on attenuated PE symptoms in a rat model of PE. We further revealed that the effects of Astragaloside IV on PE rats were achieved at least partially through elimination of oxidative stress and stimulation of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) signaling pathway. Our study indicated that Astragaloside IV may serve as a promising candidate for the development of new therapeutically methods for patients with PE.
Co-Occurring Psychopathology Moderates Social Skills Improvement in a Randomized Controlled Trial of a Collaborative School-Home Intervention for Children with ADHD

ABSTRACT Objective Children with ADHD often exhibit marked impairment in their social skills, but evidence-based psychosocial interventions for ADHD have shown limited efficacy in remediating these deficits. Co-occurring psychopathology exacerbates social deficits in children with ADHD and is a plausible moderator of treatment response. To identify factors contributing to variable social skills treatment response, we examined co-occurring externalizing, depression, and anxiety symptoms as moderators of social skills outcomes in a randomized controlled trial of the Collaborative Life Skills (CLS) program, an evidence-based collaborative school-home ADHD intervention. Method Participants were 159 children with ADHD (M age = 8.35 years, 28.3% female) at 27 schools in an urban public school district. Twenty-three schools were randomly assigned to CLS or usual services, with an additional four schools assigned to Spanish-adapted CLS or usual services. Multi-informant measures of co-occurring psychopathology and social skills were collected at baseline and post-treatment. Results Parent-rated externalizing and depression symptoms moderated treatment effects on social skills, whereby higher symptomatology in each domain was unrelated to social skills improvement in the CLS group but predicted worsening social skills in response to usual services. In contrast, teacher-rated anxiety moderated treatment effects on social skills, whereby higher anxiety predicted greater social skills improvement in response to CLS but was unrelated to social skills outcomes following usual services. Conclusions Findings reflect novel evidence that child psychopathology domains exhibit unique moderating effects on social skills treatment response in children with ADHD. We discuss implications for optimizing evidence-based interventions to target social impairment in this population.
Regenerative strategies of three species of Ligularia (Asteraceae)in eastern of Qinghai-Xizang plateau of China I From flowering to germination

The three species, L. virgaurea (Lv) and L. sagitta (Ls) and L. przewalskii (Lp) , of Ligularia are poisonous weeds in eastern of Qing Zang plateau of China and Lv and Ls are encroaching upon the pasture seriously. This study focused on the regenerative strategies of these plants species from flower production to seed germination to identify possible weak points that might contribute to their control. Flowering rate was low in the three species and contacted with interspecies competition. In intense competition, flowering rate was lower and in low competition, it was relatively high. Light could promote germination. Lv had a wide range of germination temperatures (5~27 ℃). The optimum germination temperatures of Ls and Lp were 18/27 ℃ and 25/32 ℃ respectively, but Ls was slight light dependent. Lv and Ls produced a large mean number of flowers ( 1 065 and 1 491 per individual, respectively),but relatively few of these formed fruits and seeds( 13.2 and 12.4% , respectively). In decreasing importance, flowers were lost to predation( macroparasite, 6%~55%) and might lack of pollinator. In the subalpine grassland, these species adopted the strategy producing a large number of flowers to compensate for the loss. Lv and Ls reproduced asexually by underground rhizomes to recruit new individual into populations. In future, the poisonous weeds could be controlled by natural enemy (insect) and more reasonable grassland utilization prevent it from degeneration continuously.
Carbon Nanodots in Photodynamic Antimicrobial Therapy: A Review

Antibiotic resistance development in bacteria is an ever-increasing global health concern as new resistant strains and/or resistance mechanisms emerge each day, out-pacing the discovery of novel antibiotics. Increasingly, research focuses on alternate techniques, such as antimicrobial photodynamic therapy (APDT) or photocatalytic disinfection, to combat pathogens even before infection occurs. Small molecule “photosensitizers” have been developed to date for this application, using light energy to inflict damage and death on nearby pathogens via the generation of reactive oxygen species (ROS). These molecular agents are frequently limited in widespread application by synthetic expense and complexity. Carbon dots, or fluorescent, quasi-spherical nanoparticle structures, provide an inexpensive and “green” solution for a new class of APDT photosensitizers. To date, reviews have examined the overall antimicrobial properties of carbon dot structures. Herein we provide a focused review on the recent progress for carbon nanodots in photodynamic disinfection, highlighting select studies of carbon dots as intrinsic photosensitizers, structural tuning strategies for optimization, and their use in hybrid disinfection systems and materials. Limitations and challenges are also discussed, and contemporary experimental strategies presented. This review provides a focused foundation for which APDT using carbon dots may be expanded in future research, ultimately on a global scale.
Recent Advances in the Development of In Situ Gelling Drug Delivery Systems for Non-Parenteral Administration Routes

In situ gelling drug delivery systems have gained enormous attention over the last decade. They are in a sol-state before administration, and they are capable of forming gels in response to different endogenous stimuli, such as temperature increase, pH change and the presence of ions. Such systems can be administered through different routes, to achieve local or systemic drug delivery and can also be successfully used as vehicles for drug-loaded nano- and microparticles. Natural, synthetic and/or semi-synthetic polymers with in situ gelling behavior can be used alone, or in combination, for the preparation of such systems; the association with mucoadhesive polymers is highly desirable in order to further prolong the residence time at the site of action/absorption. In situ gelling systems include also solid polymeric formulations, generally obtained by freeze-drying, which, after contact with biological fluids, undergo a fast hydration with the formation of a gel able to release the drug loaded in a controlled manner. This review provides an overview of the in situ gelling drug delivery systems developed in the last 10 years for non-parenteral administration routes, such as ocular, nasal, buccal, gastrointestinal, vaginal and intravesical ones, with a special focus on formulation composition, polymer gelation mechanism and in vitro release studies.
Functional and Structural Neuroimaging Correlates of Repetitive Low-Level Blast Exposure in Career Breachers

Combat military and civilian law enforcement personnel may be exposed to repetitive low-intensity blast events during training and operations. Persons who use explosives to gain entry (i.e., breach) into buildings are known as “breachers” or dynamic entry personnel. Breachers operate under the guidance of established safety protocols, but despite these precautions, breachers who are exposed to low-level blast throughout their careers frequently report performance deficits and symptoms to healthcare providers. Although little is known about the etiology linking blast exposure to clinical symptoms in humans, animal studies demonstrate network-level changes in brain function, alterations in brain morphology, vascular and inflammatory changes, hearing loss, and even alterations in gene expression after repeated blast exposure. To explore whether similar effects occur in humans, we collected a comprehensive data battery from 20 experienced breachers exposed to blast throughout their careers and 14 military and law enforcement controls. This battery included neuropsychological assessments, blood biomarkers, and magnetic resonance imaging measures, including cortical thickness, diffusion tensor imaging of white matter, functional connectivity, and perfusion. To better understand the relationship between repetitive low-level blast exposure and behavioral and imaging differences in humans, we analyzed the data using similarity-driven multi-view linear reconstruction (SiMLR). SiMLR is specifically designed for multiple modality statistical integration using dimensionality-reduction techniques for studies with high-dimensional, yet sparse, data (i.e., low number of subjects and many data per subject). We identify significant group effects in these data spanning brain structure, function, and blood biomarkers.
Mass Spectrometry and Structural Biology Techniques in the Studies on the Coronavirus-Receptor Interaction

Mass spectrometry and some other biophysical methods, have made substantial contributions to the studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human proteins interactions. The most interesting feature of SARS-CoV-2 seems to be the structure of its spike (S) protein and its interaction with the human cell receptor. Mass spectrometry of spike S protein revealed how the glycoforms are distributed across the S protein surface. X-ray crystallography and cryo-electron microscopy made huge impact on the studies on the S protein and ACE2 receptor protein interaction, by elucidating the three-dimensional structures of these proteins and their conformational changes. The findings of the most recent studies in the scope of SARS-CoV-2-Human protein-protein interactions are described here.