Miracle-dz/UniFAR-FTUs huggingface dataset:
Timely N-Acetyl-Cysteine and Environmental Enrichment Rescue Oxidative Stress-Induced Parvalbumin Interneuron Impairments via MMP9/RAGE Pathway: A Translational Approach for Early Intervention in Psychosis

Abstract Research in schizophrenia (SZ) emphasizes the need for new therapeutic approaches based on antioxidant/anti-inflammatory compounds and psycho-social therapy. A hallmark of SZ is a dysfunction of parvalbumin-expressing fast-spiking interneurons (PVI), which are essential for neuronal synchrony during sensory/cognitive processing. Oxidative stress and inflammation during early brain development, as observed in SZ, affect PVI maturation. We compared the efficacy of N-acetyl-cysteine (NAC) and/or environmental enrichment (EE) provided during juvenile and/or adolescent periods in rescuing PVI impairments induced by an additional oxidative insult during childhood in a transgenic mouse model with gluthation deficit (Gclm KO), relevant for SZ. We tested whether this rescue was promoted by the inhibition of MMP9/RAGE mechanism, both in the mouse model and in early psychosis (EP) patients, enrolled in a double-blind, randomized, placebo-controlled clinical trial of NAC supplementation for 6 months. We show that a sequential combination of NAC+EE applied after an early-life oxidative insult recovers integrity and function of PVI network in adult Gclm KO, via the inhibition of MMP9/RAGE. Six-month NAC treatment in EP patients reduces plasma sRAGE in association with increased prefrontal GABA, improvement of cognition and clinical symptoms, suggesting similar neuroprotective mechanisms. The sequential combination of NAC+EE reverses long-lasting effects of an early oxidative insult on PVI/perineuronal net (PNN) through the inhibition of MMP9/RAGE mechanism. In analogy, patients vulnerable to early-life insults could benefit from a combined pharmacological and psycho-social therapy.
Covid‐19 Infection and Parkinsonism: Is There a Link?

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an opportunistic pathogen that infects the upper respiratory tract in humans and causes serious illness, including fatal pneumonia and neurological disorders. Several studies have reported that SARS‐CoV‐2 may worsen the symptoms of Parkinson's disease (PD), with the potential to increase mortality rates in patients with advanced disease. The potential risk of SARS‐CoV‐2 to induce PD has also been suggested because the virus can enter the brain, where it can trigger cellular processes involved in neurodegeneration. In this review, we will discuss the potential of SARS‐CoV‐2 to exacerbate and cause certain neurological disorders, including PD. We will then elucidate its impact on the brain while examining its pathways and mechanisms of action. © 2021 International Parkinson and Movement Disorder Society
An overview of the first decade of Polly NET : an emerging network of automated Raman-polarization lidars for continuous aerosol profiling

Abstract. A global vertically resolved aerosol data set covering more than 10 years of observations at more than 20 measurement sites distributed from 63° N to 52° S and 72° W to 124° E has been achieved within the Raman and polarization lidar network PollyNET. This network consists of portable, remote-controlled multiwavelength-polarization-Raman lidars (Polly) for automated and continuous 24/7 observations of clouds and aerosols. PollyNET is an independent, voluntary, and scientific network. All Polly lidars feature a standardized instrument design with different capabilities ranging from single wavelength to multiwavelength systems, and now apply unified calibration, quality control, and data analysis. The observations are processed in near-real time without manual intervention, and are presented online at http://polly.tropos. de/ . The paper gives an overview of the observations on four continents and two research vessels obtained with eight Polly systems. The specific aerosol types at these locations (mineral dust, smoke, dust-smoke and other dusty mixtures, urban haze, and volcanic ash) are identified by their Angstrom exponent, lidar ratio, and depolarization ratio. The vertical aerosol distribution at the PollyNET locations is discussed on the basis of more than 55 000 automatically retrieved 30 min particle backscatter coefficient profiles at 532 nm as this operating wavelength is available for all Polly lidar systems. A seasonal analysis of measurements at selected sites revealed typical and extraordinary aerosol conditions as well as seasonal differences. These studies show the potential of PollyNET to support the establishment of a global aerosol climatology that covers the entire troposphere.
Suicidality risk among adults with binge‐eating disorder

Abstract Objective To estimate relative suicidality risk associated with binge‐eating disorder (BED). Methods Retrospective study of patients identified as having BED (N = 1042) and a matched general population cohort (N = 10,420) from the Optum electronic health record database between January 2009 and September 2015. Patients had ≥1 outpatient encounter with a provider who recognized BED during the 12‐month baseline preceding entry date. Incidence and relative risk of suicidality were assessed. Results Incidence per 1000 person‐years (95% CI) of suicidal ideation and suicide attempts, respectively, was 31.1 (23.1, 41.0) and 12.7 (7.9, 19.4) in the BED cohort and 5.8 (4.7, 7.1) and 1.4 (0.9, 2.2) in the comparator cohort. Risk of suicidal ideation and suicide attempts was greater in the BED cohort (HR [95% CIs], 6.43 [4.42, 9.37]) than in the comparator cohort (HR [95% CI], 9.47 [4.99, 17.98]) during follow‐up. After adjusting for psychiatric comorbidities, associations of suicidal ideation and suicide attempts with BED remained elevated in patients with BED having histories of suicidality. Conclusions Findings suggest that history of suicidality may result in an increased risk of suicidal ideation and suicide attempts in patients with BED relative to the general population. Psychiatric comorbidity burden may explain the elevated risk of these conditions in BED.
Type 2 diabetes mellitus duration and obesity alter the efficacy of autologously transplanted bone marrow‐derived mesenchymal stem/stromal cells

Human bone marrow‐derived mesenchymal stem/stromal cells (BM‐MSCs) represent promising stem cell therapy for the treatment of type 2 diabetes mellitus (T2DM), but the results of autologous BM‐MSC administration in T2DM patients are contradictory. The purpose of this study was to test the hypothesis that autologous BM‐MSC administration in T2DM patient is safe and that the efficacy of the treatment is dependant on the quality of the autologous BM‐MSC population and administration routes. T2DM patients were enrolled, randomly assigned (1:1) by a computer‐based system into the intravenous and dorsal pancreatic arterial groups. The safety was assessed in all the treated patients, and the efficacy was evaluated based on the absolute changes in the hemoglobin A1c, fasting blood glucose, and C‐peptide levels throughout the 12‐month follow‐up. Our data indicated that autologous BM‐MSC administration was well tolerated in 30 T2DM patients. Short‐term therapeutic effects were observed in patients with T2DM duration of <10 years and a body mass index <23, which is in line with the phenotypic analysis of the autologous BM‐MSC population. T2DM duration directly altered the proliferation rate of BM‐MSCs, abrogated the glycolysis and mitochondria respiration of BM‐MSCs, and induced the accumulation of mitochondria DNA mutation. Our data suggest that autologous administration of BM‐MSCs in the treatment of T2DM should be performed in patients with T2DM duration <10 years and no obesity. Prior to further confirming the effects of T2DM on BM‐MSC biology, future work with a larger cohort focusing on patients with different T2DM history is needed to understand the mechanism underlying our observation.
Effects of Including Sprints in LIT Sessions during a 14-d Camp on Muscle Biology and Performance Measures in Elite Cyclists

ABSTRACT Purpose This study investigated the effects of including sprints within low-intensity training (LIT) sessions during a 14-d training camp focusing on LIT, followed by 10-d recovery (Rec), on performance and performance-related measures in elite cyclists. Methods During the camp, a sprint training group (SPR; n = 9) included 12 × 30-s maximal sprints during five LIT sessions, whereas a control group (CON; n = 9) performed distance-matched LIT only. Training load was equally increased in both groups by 48% ± 27% during the training camp and subsequently decreased by −56% ± 23% during the recovery period compared with habitual training. Performance tests were conducted before the training camp (Pre) and after Rec. Muscle biopsies, hematological measures, and stress/recovery questionnaires were collected Pre and after the camp (Post). Results Thirty-second sprint (SPR vs CON: 4% ± 4%, P < 0.01) and 5-min mean power (SPR vs CON: 4% ± 8%, P = 0.04) changed differently between groups. In muscle, Na+-K+ β1 protein content changed differently between groups, decreasing in CON compared with SPR (−8% ± 14%, P = 0.04), whereas other proteins showed similar changes. SPR and CON displayed similar increases in red blood cell volume (SPR: 2.6% ± 4.7%, P = 0.07; CON: 3.9% ± 4.5%, P = 0.02) and V˙O2 at 4 mmol·L−1 [BLa−] (SPR: 2.5% ± 3.3%, P = 0.03; CON: 2.2% ± 3.0%, P = 0.04). No changes were seen for V˙O2max, Wmax, hematological measures, muscle enzyme activity, and stress/recovery measures. Conclusions Inclusion of 30-s sprints within LIT sessions during a high-volume training camp affected competition-relevant performance measures and Na+-K+ β1 protein content differently from LIT only, without affecting sport-specific stress/recovery or any other physiological measure in elite cyclists.
Patients and Professionals as Partners in Hypertension Care: Qualitative Substudy of a Randomized Controlled Trial Using an Interactive Web-Based System Via Mobile Phone

Background The use of technology has the potential to support the patient´s active participation regarding treatment of hypertension. This might lead to changes in the roles of the patient and health care professional and affect the partnership between them. Objective The aim of this qualitative study was to explore the partnership between patients and health care professionals and the roles of patients and professionals in hypertension management when using an interactive web-based system for self-management of hypertension via the patient’s own mobile phone. Methods Focus group interviews were conducted with 22 patients and 15 professionals participating in a randomized controlled trial in Sweden aimed at lowering blood pressure (BP) using an interactive web-based system via mobile phones. The interviews were audiorecorded and transcribed and analyzed using thematic analysis. Results Three themes were identified: the technology, the patient, and the professional. The technology enabled documentation of BP treatment, mainly for sharing knowledge between the patient and the professional. The patients gained increased knowledge of BP values and their relation to daily activities and treatment. They were able to narrate about their BP treatment and take a greater responsibility, inspired by new insights and motivation for lifestyle changes. Based on the patient’s understanding of hypertension, professionals could use the system as an educational tool and some found new ways of communicating BP treatment with patients. Some reservations were raised about using the system, that it might be too time-consuming to function in clinical practice and that too much measuring could result in stress for the patient and an increased workload for the professionals. In addition, not all professionals and patients had adopted the instructions regarding the use of the system, resulting in less realization of its potential. Conclusions The use of the system led to the patients taking on a more active role in their BP treatment, becoming more of an expert of their BP. When using the system as intended, the professionals experienced it as a useful resource for communication regarding BP and lifestyle. Patients and professionals described a consultation on more equal grounds. The use of technology in hypertension management can promote a constructive and person-centered partnership between patient and professional. However, implementation of a new way of working should bring benefits and not be considered a burden for the professionals. To establish a successful partnership, both the patient and the professional need to be motivated toward a new way of working. Trial Registration ClinicalTrials.gov NCT03554382; https://clinicaltrials.gov/ct2/show/NCT03554382
Epidemiology, prognosis and management of potassium disorders in Covid‐19

Coronavirus disease (Covid‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is currently the largest health crisis facing most countries. Several factors have been linked with a poor prognosis for this disease, including demographic factors, pre‐existing comorbidities and laboratory parameters such as white blood cell count, D‐dimer, C‐reactive protein, albumin, lactate dehydrogenase, creatinine and electrolytes. Electrolyte abnormalities particularly potassium disorders are common among Covid‐19 patients. Based on our pooled analysis, hypokalemia and hyperkalemia occur in 24.3% and 4.15% of Covid‐19 patients, respectively. Potassium level deviation from the normal range may increase the chances of unfavorable outcomes and even death. Therefore, this article reviewed the epidemiology of potassium disorders and explained how hypokalemia and hyperkalemia are capable of deteriorating cardiac outcomes and the prognosis of Covid‐19 for infected patients. The article finishes by highlighting some important considerations in the management of hypokalemia and hyperkalemia in these patients.
Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis

Macrophages destroy pathogens and diseased cells through Fcγ receptor (FcγR)-driven phagocytosis of antibody-opsonized targets. Phagocytosis requires activation of multiple FcγRs, but the mechanism controlling the threshold for response is unclear. We developed a DNA origami-based engulfment system that allows precise nanoscale control of the number and spacing of ligands. When the number of ligands remains constant, reducing ligand spacing from 17.5 nm to 7 nm potently enhances engulfment, primarily by increasing efficiency of the engulfment-initiation process. Tighter ligand clustering increases receptor phosphorylation, as well as proximal downstream signals. Increasing the number of signaling domains recruited to a single ligand-receptor complex was not sufficient to recapitulate this effect, indicating that clustering of multiple receptors is required. Our results suggest that macrophages use information about local ligand densities to make critical engulfment decisions, which has implications for the mechanism of antibody-mediated phagocytosis and the design of immunotherapies.
Genome-Inferred Correspondence between Phylogeny and Metabolic Traits in the Wild Drosophila Gut Microbiome

Abstract Annotated genome sequences provide valuable insight into the functional capabilities of members of microbial communities. Nevertheless, most studies on the microbiome in animal guts use metagenomic data, hampering the assignment of genes to specific microbial taxa. Here, we make use of the readily culturable bacterial communities in the gut of the fruit fly Drosophila melanogaster to obtain draft genome sequences for 96 isolates from wild flies. These include 81 new de novo assembled genomes, assigned to three orders (Enterobacterales, Lactobacillales, and Rhodospirillales) with 80% of strains identified to species level using average nucleotide identity and phylogenomic reconstruction. Based on annotations by the RAST pipeline, among-isolate variation in metabolic function partitioned strongly by bacterial order, particularly by amino acid metabolism (Rhodospirillales), fermentation, and nucleotide metabolism (Lactobacillales) and arginine, urea, and polyamine metabolism (Enterobacterales). Seven bacterial species, comprising 2–3 species in each order, were well-represented among the isolates and included ≥5 strains, permitting analysis of metabolic functions in the accessory genome (i.e., genes not present in every strain). Overall, the metabolic function in the accessory genome partitioned by bacterial order. Two species, Gluconobacter cerinus (Rhodospirillales) and Lactiplantibacillus plantarum (Lactobacillales) had large accessory genomes, and metabolic functions were dominated by amino acid metabolism (G. cerinus) and carbohydrate metabolism (La. plantarum). The patterns of variation in metabolic capabilities at multiple phylogenetic scales provide the basis for future studies of the ecological and evolutionary processes shaping the diversity of microorganisms associated with natural populations of Drosophila.
COVID‐19 school closures and educational achievement gaps in Canada: Lessons from Ontario summer learning research

Abstract The 2020 COVID‐19 pandemic closed most Canadian public schools for six consecutive months between March and September. This paper explores possible impacts of that closure on student achievement. Longstanding research suggests that lengthy periods of time out of school generally create losses of literacy and numeracy skills and widen student achievement gaps. New American studies have attributed sizeable learning losses to the COVID‐19 closures. In lieu of comparable Canadian data, this paper extrapolates from summer learning research to estimate likely shortfalls in literacy and numeracy skills. We draw on data from 14 cohorts of Ontario primary‐grade students collected between 2010 and 2015 in which 3,723 attended summer programs and 12,290 served as controls. Across three plausible scenarios, we use meta analyses and OLS and quintile regression models to predict learning losses of 3.5 and 6.5 months among typically‐performing and lower‐performing students respectively, and achievement gaps that grow up to 1.5 years among same grade peers. After qualifying these predictions, we recommend that provincial ministries offer targeted supplementary programs during the summer and synchronous instruction in the event of future school closures.
A fast and sensitive nucleic acid extraction method for the detection of Cryptosporidium by PCR in environmental water samples

A new protocol based on a combination of an excystation process followed by a nucleic acid extraction that combines the lysing and nuclease-inactivating properties of the chaotropic agent guanidinium thiocyanate and the nucleic acid-binding properties of silica particles is described for the extraction and purification of nucleic acids from Cryptosporidium. The application of nested and/or semi-nested PCR using different external and internal primers to DNA extracted by this method from seeded and naturally occurring Cryptosporidium oocysts concentrated and purified from environmental samples detects numbers of oocysts ranging from 20 to 50. The method is feasible, detects mostly excystable oocysts and no problems of inhibition of PCR were observed when applied to environmental samples.
Quality and Safety of Nurse Practitioner Care: The Case for Full Practice Authority in Pennsylvania.

Pennsylvania is one of the most restrictive states in the nation for nurse practitioners (NP) despite having a shortage of primary care throughout the state, especially in rural areas and low-income urban neighborhoods (Association of American Medical College, 2012; Brown, Polsky, Barbu, Seymour, & Grande, 2016). Pennsylvania requires nationally-certified and fully-licensed NPs to maintain formal, written collaborative agreements with at least two physicians. Independent research estimates that removing NP practice restrictions could save the Commonwealth $6.4 billion and improve access to care over the next 10 years without any harm to patients (Jeap & Bailey, 2015). Improving access to primary care in Pennsylvania now depends upon the Pennsylvania House of Representatives adopting SB 717, companion legislation to HB 765, that removes the outdated and unnecessary requirement that each NP has written collaborative agreements with at least two physicians.In July 2016, the Pennsylvania State Senate voted 41 to 9 in support of SB 717 to eliminate these required collaborative agreements. Major stakeholders in Pennsylvania favor the adoption of SB 717 and granting NPs full practice authority, including: consumers; the Hospital and Healthsystems Association of Pennsylvania (HAP); AARP; the Pennsylvania Higher Education Nursing Schools Association (PHENSA) and its 43 nursing school members whose NP graduates leave Pennsylvania because of practice restrictions; the Pennsylvania State Nurses Association (PSNA); and the Pennsylvania Coalition of Nurse Practitioners (PCNP) representing more than 172,000 nurses in Pennsylvania. Additionally, full practice authority for NPs to practice to the full extent of their education and training is supported by the National Academy of Medicine (Institute of Medicine, 2010), the Federal Trade Commission (Gilman & Koslov, 2014) and the National Governors’ Association (National Governors Association, 2012).
Lumbar muscle atrophy and increased relative intramuscular lipid concentration are not mitigated by daily artificial gravity after 60-day head-down tilt bedrest.

Exposure to axial unloading induces adaptations in paraspinal muscles, as shown after spaceflights. This study investigated whether daily exposure to artificial gravity (AG) mitigated lumbar spine flattening and muscle atrophy associated with 60-day head-down tilt (HDT) bed rest (Earth-based space analogue). Twenty-four healthy individuals participated in the study: Eight received 30 minutes continuous AG; eight received 6x5 minutes AG, interspersed with rest periods; eight received no AG exposure (control group). Magnetic Resonance Imaging (MRI) of the lumbopelvic region was conducted at baseline (BDC) and at day 59 of HDT (HDT59). T1-weighted images were used to assess morphology of the lumbar spine (spinal length, intervertebral disc angles, disc area) and volumes of the lumbar multifidus (LM), lumbar erector spinae (LES), quadratus lumborum (QL), and psoas major (PM) muscles from L1/L2 to L5/S1 vertebral levels. A chemical shift-based 2-point lipid/water Dixon sequence was used to evaluate muscle composition. Results showed that: spinal length and disc area increased (P<0.05); intervertebral disc angles (P<0.05) and muscle volumes of LM, LES, and QL reduced (P<0.01); and fat/water ratio for the LM and LES muscles increased (P<0.01) after HDT59 in all groups. Neither of the AG protocols mitigated the lumbar spinal deconditioning induced by HDT bed rest. The increase in lipid/water ratio in LM and LES muscles indicates an increased relative intramuscular lipid concentration. Altered muscle composition in atrophied muscles may impair lumbar spine function after body unloading, which could increase injury risk to vulnerable soft tissues. This relationship needs further investigation.