bluuebunny/crossref_metadata_2025_split huggingface dataset:
One session of fMRI-Neurofeedback training on motor imagery modulates whole-brain effective connectivity and dynamical complexity
Authors: De Filippi Eleonora , Marins Theo , Escrichs Anira , Gilson Matthieu , Moll Jorge , Tovar-Moll Fernanda , Deco Gustavo 
Published: July 2022

Abstract
In the past decade, several studies have shown that Neurofeedback (NFB) by functional magnetic resonance imaging can alter the functional coupling of targeted and non-targeted areas. However, the causal mechanisms underlying these changes remain uncertain. Here, we applied a whole-brain dynamical model to estimate Effective Connectivity (EC) profiles of resting-state data acquired before and immediately after a single-session NFB training for 17 participants who underwent motor imagery NFB training and 16 healthy controls who received sham feedback. Within-group and between-group classification analyses revealed that only for the NFB group it was possible to accurately discriminate between the 2 resting-state sessions. NFB training-related signatures were reflected in a support network of direct connections between areas involved in reward processing and implicit learning, together with regions belonging to the somatomotor, control, attention, and default mode networks, identified through a recursive-feature elimination procedure. By applying a data-driven approach to explore NFB-induced changes in spatiotemporal dynamics, we demonstrated that these regions also showed decreased switching between different brain states (i.e. metastability) only following real NFB training. Overall, our findings contribute to the understanding of NFB impact on the whole brain’s structure and function by shedding light on the direct connections between brain areas affected by NFB training.
Age‐Related Perturbations in the Sarcolemmal Environment are Attenuated by Lifelong Caloric Restriction and Voluntary Wheel Running
Authors: Hord Jeffrey M , Garcia Marcela , Lawler John M 
Published: July 2022

Sarcopenia is the age‐related reduction in skeletal muscle mass and strength. Previously we observed that lifelong mild caloric restriction (CR) and wheel running (WR) attenuated sarcopenia, in part by reducing the age‐induced disruptions of the sarcolemmal dystrophin‐glycoprotein complex (DGC) proteins. The purpose of this study was to determine if mild (8%) CR and lifelong CR + voluntary WR could maintain a phenotypically young sarcolemmal environment in plantaris muscle fibers. Fischer 344 rats were assigned into four groups: 6‐month‐old sedentary ad libitum (YAL), 24‐month‐old sedentary ad libitum group (OAL), 8% caloric restriction from 11 months – 24 months (OCR), and 8% CR plus voluntary wheel running from 11 months – 24 months (OCRWR). We observed significant age‐related increases in key membrane repair proteins (MG53, p < 0.0001; dysferlin, p < 0.0001; annexin A6, p < 0.0001; and annexin A2, p = 0.004) in the OAL plantaris. Lifelong mild CR and CRWR interventions were effective at maintaining membrane repair proteins near YAL levels. Consistent with a perturbed sarcolemmal environment, we also found reduced protein content of NADPH oxidase isoform 2 (Nox2) subunits (p67phox, p = 0.03; p47phox, p = 0.01; and gp91phox, p = 0.096). Lifelong CR and CRWR protected against the age‐related reduction in gp91phox, p47phox, and p67phox proteins. Nox2 subunit abundance in OCR and OCRWR were not significantly different than YAL, while p67phox was significantly higher in OCR than YAL (p = 0.03). Novel data presented here are consistent with the hypothesis that lifelong CR and WR mitigate sarcopenia, in part, by ameliorating age‐induced alterations in the myofiber membrane environment.Support or Funding InformationNIH (AR054084), NASA (NNX12AR62G), the Sydney and J.L. Huffines Institute, and the College of Health and Education at Texas A&M University
Anthocyanin‐rich blueberry diets enhance protection of critical brain regions exposed to acute levels of 56Fe cosmic radiation
Authors: Poulose Shibu M , Kelly Megan E , Bielinski Donna F , Miller Marshall G , Rabin Bernard , Shukitt‐Hale Barbara 
Published: July 2022

The protective effects of anthocyanin‐rich blueberries on brain health are well documented and are particularly important under conditions of high oxidative stress which can lead to “accelerated aging”. One such scenario is exposure to space radiation, which consists of high‐energy and ‐charge particles (HZE), which are known to cause cognitive dysfunction, carcinogenic effects, and deleterious neurochemical alterations. In the current study we assessed the effects of 8 weeks of blueberry supplementation in young animals exposed to 56Fe‐HZE particles, particularly those effects related to behavior and neurochemical alteration. Acute effects were measured within 4 to 48 h after radiation exposure. Animals were randomized into a “learning” group, which were irradiated prior to conditioning and a “memory” group, which were irradiated between conditioning and testing. Results indicated that the radiation primarily affected the memory group but not the learning group. These effects were dependent on the resilience of the brain to readjust its endogenous anti‐oxidant and anti‐inflammatory systems within specific brain regions, particularly the hippocampus and frontal cortex. Dietary blueberry significantly attenuated hippocampal and fronto‐cortical 56Fe irradiation‐induced declines in protein carbonyl content, a marker for oxidative protein degradation, relative to controls. Furthermore, dietary blueberry significantly attenuated 56Fe irradiation‐induced increases in pro‐oxidant NOX2 and pro‐inflammatory COX2 and up‐regulated Nrf2, a key regulatory protein which is critical for antioxidant response elements (AREs), in both hippocampus and frontal cortex. These findings support the role of diet in combatting the negative effects of exposure to space radiation through the consumption of anthocyanin‐rich foods such as blueberry.Support or Funding InformationSupported by NASA Grant No. NNX13AB73G.
Comparative Analysis of Gastrointestinal and Bone Inflammation in Hindlimb Unloading
Authors: Narayanan Anand , Metzger Corinne , Brezicha Jessica , Lenfest Scott , Bloomfield Susan , Hogan Harry , Zawieja David 
Published: July 2022

The hindlimb unloading (HU) rodent model is used to mimic changes incurred in spaceflight due to microgravity. Previously in 2‐weeks of rat HU, we found systemically impaired lymphatic transport. Recently we reported gastrointestinal (GI) inflammation and lymphatic immune cell alterations after 4‐weeks of HU in rats paralleling the GI pathology observed in inflammatory bowel disease (IBD) animal models. A known comorbidity of IBD is inflammation‐induced bone loss; prior work in our lab with a 4‐week IBD rodent model documented bone loss as well as an increased prevalence of cancellous osteocytes positive for tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and insulin‐like growth factor‐I (IGF‐I) concurrent with GI inflammation. The implications of a potential inflammatory link between gut and bone in HU and spaceflight have not been reported. In this study we quantified TNF‐α, IL‐6, and IGF‐I (via immunohistochemistry) in both bone and colon samples after 4‐weeks of HU in male Sprague Dawley rats (comparing HU and age‐matched controls). Proximal tibia cancellous bone volume, osteoid surface area, bone formation rate, and trabecular number were lower in HU versus controls, while osteoclast surface area and trabecular separation were higher. Measures of osteocytes in cancellous bone positive for IL‐6 and IGF‐I levels were lowered, but there was no change in TNF‐α. Colon histopathology showed elevated structural damage in the mucosa region with a corresponding cellularity elevation in HU compared to controls. HU colons also had elevated TNF‐α and IL‐6 expression across the mucosal and submucosal regions with IGF‐I a trending increase. Furthermore cytokine changes were dependent on the colon compartment. Fecal calprotectin (a clinical IBD marker of GI inflammation) was collected throughout the 4‐week time course; calprotectin was significantly increased at 2‐weeks of HU and trended towards elevation at 4‐weeks. After HU we did not find the same cytokine pattern in bone compared to what we have seen in an IBD model induced by the haptenizing agent TNBS, suggesting different inflammatory mechanisms. However there may be a time course impact of IBD development in the models.Support or Funding InformationStudy support received from NASA Grants: NNX15AG54G, NNX13AN33G, NNX13AQ87G. AN, JB, and SL were supported by the NASA‐NSBRI Predoctoral Fellowship.
Intracranial Pressure Increases During Hindlimb Suspension
Authors: Gompf Heinrich S , Robinson Edward L , Hoban‐Higgins Tana M , Fuller Charles A 
Published: July 2022

IntroductionOne of the responses following exposure to the microgravity spaceflight environment is a pronounced cephalic fluid shift. Recent evidence documents ocular changes in astronauts following long‐duration missions including optic disc edema, globe flattening, choroidal folds and hyperopic shifts. These changes are hypothesized to result from this cephalic fluid shift, as these ocular effects are similar to those seen in terrestrial Idiopathic Intracranial Hypertension (IIH) and are associated with increased intraocular pressure (IOP). Long duration missions are currently being undertaken on the International Space Station (ISS) and planning for manned missions to Mars has begun. This project aims to simulate long‐term microgravity cephalic fluid shift using a well‐established terrestrial rat model to provide a means for study of the mechanisms underlying ocular changes seen in spaceflight.MethodsWe are using the rat hindlimb suspension (HLS) model, functionally equivalent to human head‐down bedrest (a human terrestrial model of cephalic fluid shift), to examine the relationship between cephalic fluid shifts and the regulation of intracranial pressure (ICP) as well as visual system structure and function. As we are investigating the role of sex and age in these responses, the study includes three cohorts: young adult male, young adult female, and older middle‐age adult males, roughly equivalent to the ages of most mission‐ready astronauts. Rats are placed in HLS for up to 90 days, a time frame roughly equivalent to the proportion of an astronaut's lifespan that would be dedicated to an exploration class mission. This is followed by up to 90 days of post‐suspension recovery in a vivarium cage. All HLS subjects have age‐matched vivarium cage controls. All subjects have ad lib access to food and water. A 12:12 LD cycle is present. An implanted telemetry unit is used to measure body temperature, EEG and ICP. The pressure probe catheter is implanted in the lateral ventricle and continuous recordings are performed for one week prior to and after the start of HLS, after 30, 60 and 90 days of suspension and after 0, 30, 60 and 90 days of post‐suspension recovery. MRI images of the eyes and brain, and IOP measurements were also performed in additional animals exposed to HLS.Results and ConclusionsOur hypothesis is that HLS leads to 1.) increased ICP; which, when sustained over long time periods, results in 2.) increased IOP and can lead to 3.) morphological changes such as globe flattening of the eye as well as distension of the optic nerve complex. Results to date indicate a pronounced and sustained increase in ICP during the entire HLS period. Analysis of MRI images and IOPs suggest a pattern similar to that seen in astronauts on longer‐term missions as a subset of rats exhibit globe flattening, distension of the optic nerve complex, and increased IOP.Support or Funding InformationSupported by NASA Grant NNX13AD94G
Erythropoietin Provides Neuroprotective Benefits Against Low‐Dose Proton Exposure
Authors: King Scott E. , DeWesse Theodore L , Roma Peter G , Hienz Robert D , Davis Catherine M 
Published: July 2022

As NASA quickly approaches the ability to embark on long‐term space travel, it becomes increasingly important to discover effective methods to shield astronauts from the damaging effects from exposure to space radiation. To investigate possible neuroprotective strategies for ameliorating radiation‐induced cognitive deficits, the present study describes the effects of erythropoietin (EPO) for attenuating proton‐induced deficits in sustained attention, obtained by measuring performance of rats on the rodent Psychomotor Vigilance Test (rPVT). The rPVT is a rodent version of the human PVT that is routinely used as a “fitness‐for‐duty” test across a wide range of professions. Performance on the human PVT requires responding to a visual stimulus as soon as it appears; a response terminates the stimulus presentation and the subject's reaction time is recorded and displayed. In the present study, male Long‐Evans rats were trained to perform the rPVT to baseline performance levels, defined as ≥75% correct and ≤ 25% premature responses. For 7 days before irradiation, rats received daily injections of human EPO (Epoetin alfa, human recombinant erythropoietin) at either of 1,000, 3,000, or 5,000 U/kg/day (7 total injections). Two control groups were also utilized: a sham‐irradiated group administered the EPO vehicle, and a sham‐irradiated group receiving 5,000 U/kg/day EPO. Rats were then irradiated with head‐only protons (150 MeV/n) at 100 cGy or sham‐irradiation. Similar to previous results, 100 cGy exposures induced deficits in accuracy and increased lapses in attention in a subgroup of rats on the rPVT; these rats were characterized as “radiation‐sensitive”. EPO dose‐dependently improved performance in “radiation‐sensitive” rats, producing higher performance accuracy and lower lapses in attention. EPO showed no effects on rPVT performance in radiation insensitive rats or in the sham‐irradiated rats. The data presented in the current study supports the role of vascular growth factors in ameliorating radiation‐induced cognitive deficits and the use of EPO as a treatment for ameliorating the CNS effects of radiation exposure for astronauts embarking on long‐term space travel.Support or Funding InformationThis work supported by NSBRI through NASA NCC 9‐58‐NBPF04201, NASA NNX15AC71G and an ASPET Summer Undergraduate Research Fellowship.
Treatment of juvenile localized scleroderma: current recommendations, response factors, and potential alternative treatments
Authors: Li Suzanne C. 
Published: July 2022

Purpose of review
Juvenile localized scleroderma (jLS) is a chronic autoimmune and fibrosing disease associated with a high risk for functional impairment. Antifibrotic options are limited, so current treatment strategies are focused on disease activity control. Pediatric rheumatologists are in consensus on the need to treat with systemic immunosuppressants, in particular, methotrexate. However, more than 30% of patients fail initial methotrexate treatment. This review provides an update on current management and reviews reports on potential alternative treatments.

Recent findings
An overview of current treatment recommendations and its efficacy are discussed. Recent studies have identified several factors associated with likelihood of treatment response. These include time to initiation of treatment, certain subtypes, and extracutaneous involvement. Findings from recent reports of alternative systemic immunomodulators, including biologic medications, will be summarized.

Summary
Methotrexate treatment has greatly improved outcome for most jLS patients but a substantial portion have refractory cutaneous and/or extracutaneous disease. Treatment response factors are being identified, which could lead to improved management strategies. Recent studies provide further support on mycophenolate mofetil as an alternative treatment. Data on biologic therapies is encouraging, with data suggesting efficacy for many extracutaneous manifestations but more studies are needed to evaluate these and other options for jLS.
Correlation between plasma sphingosine-1-phosphate and the occurrence and severity of coronary heart disease in postmenopausal women
Authors: Deng Songbai , Ao Zehui , Liu Bin , She Qiang , Du Jianlin , Liu Yajie , Jing Xiaodong 
Published: July 2022

Abstract

Objective
Sphingosine-1-phosphate (S1P) is a bioactive sphingosine with antiatherosclerotic effects. The incidence of coronary heart disease (CHD) increases significantly among women after menopause. We explored the relationship between plasma S1P levels and the occurrence and severity of CHD in postmenopausal women.

Methods
Postmenopausal women admitted to our hospital for coronary angiography because of chest pain–like symptoms were included in our study. By 1:1 age matching (age difference ≤5 y), 166 women in the CHD group and control group were enrolled. The plasma S1P concentration was determined, and the Gensini score was calculated to decide the severity of CHD.

Results
Plasma S1P levels were significantly lower in the CHD group of postmenopausal women (P < 0.001). S1P (odds ratio, 0.952; 95% CI, 0.934-0.970) was an independent predictor of the occurrence of CHD in postmenopausal women. The area under the curve for S1P to predict the occurrence of CHD was 0.653 (95% CI, 0.595-0.712), and the cutoff value was 96.89 ng/mL. The plasma S1P level was the lowest in the high-tertile group of the Gensini score (P < 0.001), and the plasma S1P (odds ratio, 0.948; 95% CI, 0.926-0.970) was an independent predictor of a high Gensini score in postmenopausal women with CHD.

Conclusions
Plasma S1P is an independent risk factor of the occurrence and severity of CHD in postmenopausal women. The occurrence and aggravation of CHD in postmenopausal women may be related to levels of S1P.
Prasterone in the treatment of mild to moderate urge incontinence: an observational study
Authors: Collà Ruvolo Claudia , Gabrielli Olimpia , Formisano Carmen , Califano Gianluigi , Manna Paolo , Venturella Roberta , Di Carlo Costantino 
Published: July 2022

Abstract

Objective
To assess the effects of prasterone compared with hyaluronic acid on symptoms of mild to moderate urinary urgency in women with genitourinary syndrome of menopause.

Methods
This is an observational prospective cohort study. A total of 58 postmenopausal women were enrolled (from December 2019 to May 2021). Overactive Bladder Screener questionnaire, Patient Global Impression of Improvement questionnaire, International Consultation on Incontinence Questionnaire–Short Form, and International Quality of Life questionnaire were used.

Results
Fifty-eight women, 29 (50%) and 29 (50%), were treated with prasterone and hyaluronic acid for 12 weeks, respectively. At the end of the study, 26 (89.7%) versus 3 (10.3%) women reported an improvement (Patient Global Impression of Improvement score ≤3) of the symptoms in the prasterone versus hyaluronic acid group. According to the International Consultation on Incontinence Questionnaire–Short Form, no statistically significant difference was recorded before treatment between the prasterone and hyaluronic acid groups (median, 12 [6-12] vs 11 [8-12]; P = 0.8). Conversely, a statistically significant difference was recorded after treatment between the two groups (median, 8 [5-11] vs 10 [8-11]; P = 0.03). According to the International Quality of Life, a statistically significantly lower median score was recorded in the prasterone compared with the hyaluronic acid group, before (73 [interquartile range {IQR}, 55-81] vs 89 [IQR, 67-94]; P < 0.01) and after (78 [IQR, 65-86] vs 87 [IQR, 72-99]; P = 0.04) treatment.

Conclusions
The current observational study supports the hypothesis that prasterone might improve the severity of urinary urge incontinence in this set of women. However, these results need to be confirmed in further studies with a controlled design and a larger population.
A Community-Informed Virtual World-Based Cardiac Rehabilitation Program as an Extension of Center-Based Cardiac Rehabilitation
Authors: Brewer LaPrincess C. , Abraham Helayna , Kaihoi Brian , Leth Shawn , Egginton Jason , Slusser Joshua , Scott Christopher , Penheiter Sumedha , Albertie Monica , Squires Ray , Thomas Randal , Scales Robert , Trejo-Gutierrez Jorge , Kopecky Stephen 
Published: July 2022

Purpose:
Innovative methods for delivering cardiac rehabilitation (CR) that provide strategies to circumvent the mounting barriers to traditional CR have the potential to widen access to a well-established secondary prevention strategy. Our study assesses the feasibility and acceptability of a novel virtual world-based CR (VWCR) program, Destination Rehab, as an extension of a conventional center-based CR program.

Methods:
Adult cardiac patients hospitalized at Mayo Clinic hospitals with a diagnosis for CR and ≥1 modifiable, lifestyle risk factor target—sedentary lifestyle (<3 hr physical activity/wk), unhealthy diet (<5 servings fruits and vegetables/d), or current smoking (>1 yr)—were recruited. Patients participated in an 8-wk health education program using a virtual world (VW) platform from a prior proof-of-concept study and a post-intervention focus group. Primary outcome measures included feasibility and acceptability. Secondary outcome measures included changes from baseline to post-intervention in cardiovascular (CV) health behaviors and biometrics, CV health knowledge, and psychosocial factors.

Results:
Of the 30 enrolled patients (age 59.1 ± 9.7 yr; 50% women), 93% attended ≥1 session and 71% attended ≥75% of sessions. The overall VWCR experience received an 8 rating (scale 0-10) and had high acceptability. Clinically relevant trends were noted in CV health behaviors and biometrics, although not statistically significant.

Conclusions:
The VWCR program is a feasible, highly acceptable, and innovative platform to potentially influence health behaviors and CV risk and may increase accessibility to disadvantaged populations with higher CV disease burdens.
Inverse salt sensitivity: an independent risk factor for cardiovascular damage in essential hypertension
Authors: Cuka Ermira , Simonini Marco , Lanzani Chiara , Zagato Laura , Citterio Lorena , Messaggio Elisabetta , Faienza Sipontina , Brioni Elena , Hamlyn John M. , Manunta Paolo 
Published: July 2022

Objective:
Salt sensitivity is a powerful risk factor for cardiovascular (CV) disease and mortality in both normotensive and hypertensive patients. We investigated the predictive value of the salt sensitivity phenotype in the development of CV events and hypertensive target organ damage (TOD) among essential hypertensive patients.

Methods:
Eight hundred forty-four naive hypertensive patients were recruited and underwent an acute saline test during which blood pressure (BP) displayed either no substantial variation (salt-resistant, SR individuals), an increase (salt-sensitive, SS), or a paradoxical decrease (inverse salt-sensitive, ISS). Sixty-one patients with the longest monitored follow-up (median 16 years) for blood pressure and organ damage were selected for the present study. A clinical score for TOD development based on the severity and the age of onset was set up by considering hypertensive heart disease, cerebrovascular damage, microalbuminuria, and vascular events.

Results:
CV events were significantly higher among SS and ISS than in SR patients. The relative risk of developing CV events was 12.67 times higher in SS than SR and 5.94 times higher in ISS than SR patients. The development of moderate to severe TOD was 10-fold higher in SS and over 15-fold higher in ISS than in SR patients. Among the three phenotypes, changes in plasma endogenous ouabain were linked with the blood pressure effects of saline.

Conclusions:
Salt sensitivity and inverse salt sensitivity appear to be equivalent risk factors for CV events. The response to an acute saline test is predictive of CV damage for newly identified ISS individuals.