Miracle-dz/UniFAR-FTUs huggingface dataset:
RPS23RG1 is Required for Synaptic Integrity and Rescues Alzheimer’s Associated Cognitive Deficits

BACKGROUND: Although synaptic impairment is prerequisite to cognitive deficiencies in Alzheimer’s disease (AD), mechanisms underlying the dysregulation of essential synaptic scaffolding components and their integrity remain elusive. RPS23RG1 is a newly identified protein implicated in AD. However, the physiological function of RPS23RG1 has yet to be determined. METHODS: We investigated the role of RPS23RG1 in maintaining synaptic structure and function in cell cultures and in Rps23rg1 knockout mice, and determined whether targeting RPS23RG1-mediated pathway has therapeutic potential in APP/PS1 AD model mice. RESULTS: Deletion of the Rps23rg1 gene resulted in severe memory deficits and impairment of post-synaptic structure and function, with marked reductions in PSD-93 and PSD-95 levels. RPS23RG1 interacted with PSD-93/PSD-95 through its intracellular domain, consequently sequestering PSD-93/PSD-95 from MDM2-mediated ubiquitination and degradation, thereby maintaining synaptic function. Restoration of PSD-93/PSD95 levels reversed synaptic and memory deficits in Rps23rg1 KO mice. We further observed attenuated RPS23RG1 expression in human AD, which positively correlated with PSD-93/PSD-95 levels. Importantly, an RPS23RG1-derived peptide comprising a unique PSD-93/PSD-95 interaction motif rescued synaptic and cognitive defects in Rps23rg1 KO and AD mouse models. CONCLUSIONS: Our results reveal a role for RPS23RG1 in maintaining synaptic integrity and function and provide a new mechanism for synaptic dysfunction in AD pathogenesis. This demonstrates that RPS23RG1-mediated pathways show good therapeutic potential in AD intervention.
Galanin: A Role in Mesolimbic Dopamine-Mediated Instrumental Behavior?

ROBINSON, J.K. and Brewer, A. Galanin: A Role in Mesolimbic-Dopamine Mediated Instrumental Behavior? NEUROSCI BIOBEHAV REV XX(X) XXX-XXX, 2008. The involvement of the neuropeptide galanin in the consumption of the primary “commodities” of food and water is well established. However, the present review describes anatomical and behavioral evidence that suggests that galanin may also modulate ascending mesolimbic dopamine function and thereby play an inhibitory role in the systems by which instrumental behavior is energized toward acquiring primary commodities. General anatomical frameworks for this interaction are presented and future studies that could evaluate it are discussed.
Widowhood and Mortality: Gender, Race/Ethnicity, and the Role of Economic Resources

Purpose: We examine widowhood effects on mortality across gender and race-ethnicity, with attention to variation in the mediating role of economic resources. Methods: Data were drawn from the Health and Retirement Study (1992-2016). The analytic sample included 34,777 respondents aged 51 and older who contributed 208,470 person-period records. Discrete-time hazard models were estimated to predict the odds of death among white men, black men, Hispanic men, white women, black women, and Hispanic women separately. Karlson–Holm–Breen analysis was conducted to examine the mediating role of economic resources across groups. Results: Across all gender and racial-ethnic subgroups, widowhood effects on mortality were largest for Hispanic men. Black women and Hispanic women also suffered stronger effects of widowhood on mortality than white women. For both men and women, economic resources were an important pathway through which widowhood increased mortality risk for whites and blacks but not for Hispanics. Conclusions: Findings highlight that gender and race-ethnicity intersect with widowhood status to disadvantage some groups more than others. It is important to explore the complex pathways that contribute to the higher mortality risk of racial-ethnic minorities, especially Hispanic men, following widowhood so that effective interventions can be implemented to reduce those risks
Sensitivity of frequency-domain optical measurements to brain hemodynamics: simulations and human study of cerebral blood flow during hypercapnia

: This study characterizes the sensitivity of noninvasive measurements of cerebral blood flow (CBF) by using frequency-domain near-infrared spectroscopy (FD-NIRS) and coherent hemodynamics spectroscopy (CHS). We considered six FD-NIRS methods: single-distance intensity and phase (SDI and SD ϕ ), single-slope intensity and phase (SSI and SS ϕ ), and dual-slope intensity and phase (DSI and DS ϕ ). Cerebrovascular reactivity (CVR) was obtained from the relative change in measured CBF during a step hypercapnic challenge. Greater measured values of CVR are assigned to a greater sensitivity to cerebral hemodynamics. In a first experiment with eight subjects, CVR SD φ was greater than CVR SDI ( p < 0.01), whereas CVR DSI and CVR DS ϕ showed no significant difference ( p > 0.5). In a second experiment with four subjects, a 5 mm scattering layer was added between the optical probe and the scalp tissue to increase the extracerebral layer thickness ( L ec ), which caused CVR DS ϕ to become significantly greater than CVR DSI ( p < 0.05). CVR SS measurements yielded similar results as CVR DS measurements but with a greater variability, possibly resulting from instrumental artifacts in SS measurements. Theoretical simulations with two-layered media confirmed that, if the top (extracerebral) layer is more scattering than the bottom (brain) layer, the relative values of CVR DSI and CVR DS ϕ depend on L ec . Specifically, the sensitivity to the brain is greater for DSI than DS ϕ for a thin extracerebral layer ( L ec < 13 mm), whereas it is greater for DS ϕ than DSI for a thicker extracerebral layer.
Physical Activity is Associated with MR-based Knee Cartilage T2 Measurements in Asymptomatic Subjects With and Without Osteoarthritis Risk Factors

Objective— To evaluate the association of exercise and knee-bending activities with magnetic resonance (MR)-based knee cartilage T2 relaxation times and morphologic abnormalities in asymptomatic subjects with and without osteoarthritis (OA) risk factors from the Osteoarthritis Initiative. Methods— We studied 128 subjects with knee OA risk factors and 33 normal controls aged 45– 55 years, with a body mass index of 18–27 kg/m 2 , and no knee pain. Subjects were categorized by exercise level, using the leisure activity component of the Physical Activity Scale for the Elderly, and by self-reported frequent knee-bending activities. Two radiologists graded the cartilage using the Whole Organ MR Imaging Score (WORMS) of right knee MR images. Cartilage was segmented and compartment specific T2 values were calculated. Statistical significance between the exercise groups and knee-bending groups was determined using multiple linear and logistic regression models. Results— Among subjects with risk factors, light exercisers had lower T2 measurements than sedentary and moderate-strenuous exercisers (p=0.001); in women, moderate-strenuous exercise was associated with higher T2 values (p=0.001). Subjects without risk factors displayed no NIH-funded multicenter longitudinal cohort study of risk factors and biomarkers for the onset and progression of knee OA, the goal of our study was to assess the cross-sectional association of (i) exercise and (ii) knee-bending activities with knee cartilage T2 relaxation times and morphologic abnormalities determined from knee MRIs of middle-aged, asymptomatic subjects with and without risk factors for knee OA.
Intensity dependent effects of tDCS on corticospinal excitability in chronic Spinal Cord Injury

Objective— To investigate the effects of anodal transcranial direct current stimulation (a-tDCS) intensity on corticospinal excitability and affected muscle activation in individuals with chronic spinal cord injury (SCI). Design— Single blind, randomized, sham-controlled, crossover study. Setting— Medical Research Institute and Rehabilitation Hospital. Participants— Nine volunteers with chronic SCI and motor dysfunction in wrist extensor muscles. Intervention— Three single session exposures to 20 minutes of a-tDCS (anode over the extensor carpi radialis (ECR) muscle representation on the left primary motor cortex, cathode over the right supraorbital area), using 1 mA, 2 mA or sham stimulation, delivered at rest, with at least one week between sessions. Outcome Measures— Corticospinal excitability was assessed with motor evoked potentials (MEPs) from the ECR muscle using surface electromyography (EMG) following transcranial magnetic stimulation. Changes in spinal excitability, sensory threshold and muscle strength were also investigated. Results— Mean MEP amplitude significantly increased by ~40% immediately following 2 mA a-tDCS (Pre 0.36±0.1 mV; Post 0.47±0.11 mV; p=0.001), but not with 1 mA or sham. Maximal voluntary EMG measures remained unaltered across all conditions. Sensory threshold significantly decreased over time following 1 mA (p=0.002) and 2 mA (p=0.039) a-tDCS, and did not change with sham. F-wave persistence showed a non-significant trend for increase (Pre: 32±12%; Post: 41±10%; Follow-up: 46±12%) following 2 mA stimulation. No adverse effects were reported with any of the experimental conditions. Conclusion— Anodal-tDCS can transiently raise corticospinal excitability to affected muscles in chronic SCI patients following 2 mA stimulation. Sensory perception can improve with both 1 and 2 mA stimulation. This study gives support to the safe and effective use of a-tDCS using small electrodes in SCI patients, and highlights the importance of stimulation intensity. interventions at different intensities (1 mA, 2 mA, sham) when targeting upper-limb muscles, caudal to the spinal lesion, with diminished motor output in individuals with chronic SCI. Smaller electrodes have been shown to increase focality and local intensity in the produced electric fields, compared to standard larger electrodes (35 cm 2 ), 21,22 therefore smaller Pi electrodes (3.14 cm 2 ) have been used to deliver the direct current stimulation in the present study. A secondary aim was to test the safety of 1 and 2 mA a-tDCS using 3.14 cm 2 (Pi) electrodes on individuals with chronic SCI. We hypothesized that a-tDCS would be a safe and effective method for enhancing corticospinal excitability and the magnitude of change would be dependent upon stimulation strength.
Murine V (cid:108) x and V (cid:108) x-containing Antibodies Bind Human Myelin Basic Protein

Myelin basic protein (MBP) is highly immunogenic and a known autoantigen capable of inducing experimental allergic encephalomyelitis (EAE), the animal model of multiple sclerosis. We have previously described a murine monoclonal antibody (mAb), F28C4, directed against the encephalitogenic MBP peptide acetyl (Ac) 1-9, which contains a V (cid:108) x light chain. Considering the rarity of V (cid:108) x usage, we determined whether other Abs having V (cid:108) x light chains shared similar antigen (Ag) specificity. We screened a panel of V (cid:108) x-containing monoclonal and polyclonal Abs, of unknown specificity for reactivity with MBP. All such Ab, but not heavy chain isotype matched controls, bound MBP but were not polyreactive with other potential self Ags. The binding of a recombinant form of V (cid:108) x alone to MBP dem-onstrated the important contribution of the V (cid:108) x light chain to the reaction. With the exception of mAb F28C4 which recognizes MBP Ac1-9, the epitope specificity of all other V (cid:108) x-bearing Abs was localized to MBP residues 25–34. These results demonstrate a unique association between V (cid:108) x expression and MBP reactivity. Given that V (cid:108) x shares sequence homology with T cell receptors (TCR) from encephalitogenic T lymphocytes, these results imply a potential role for V (cid:108) x in the pathogenesis of EAE. ( J. Clin. Invest. 1996. 97:486–492.)
Short time scale variability at gamma rays in FSRQs and implications on the current models

We studied the rapid variability at GeV gamma rays of the flat-spectrum radio quasar PKS 1222+216, which was recently found by the MAGIC Cerenkov telescope to display very short variability (minutes time scale) at hundreds of GeV. We analyzed the time period between 2010 April 29 and June 20, when the source generated a few gamma-ray flares with flux in the MeV-GeV band in excess of 10^-5 ph cm^-2 s^-1 on daily basis. We set tight upper limits on the observed doubling time scale (about 1 hour on 2010 April 30), the smallest measured to date at MeV-GeV energies, which can constrain the size of the gamma-ray emitting region. We also studied the spectra measured during two flares (2010 April 30 and June 17-18). The combination of spectral and variability studies obtained in the present work favors the hypothesis that gamma rays are generally produced inside the broad-line region (BLR), but sometimes the dissipation can occur at larger distances, nearby the infrared torus.
Tau expression varies in different brain regions and disease state

Progressive supranuclear palsy (PSP) is the most common atypical parkinsonian disorder. Abnormal tau inclusions, in selected regions of the brain, are a hallmark of the disease and the H1 haplotype of MAPT, the gene encoding tau, is the major risk factor in PSP. A 3-repeat and 4-repeat tau isoform ratio imbalance has been strongly implicated as a cause of disease. Thus, understanding tau isoform regional expression in disease and pathology-free states is crucial to elucidating mechanisms involved in PSP and other tauopathies. We used a tau-isoform specific fluorescent assay to investigate relative 4R-tau expression in 6 different brain regions in PSP cases and healthy controls. We identified marked difference in 4R-tau relative expression, both across brain regions and between MAPT haplotypes. Highest 4R-tau expression levels were identified in the globus pallidus as compared to pons, cerebellum and frontal cortex. 4R-tau expression levels were related to both the MAPT H1 and H1c haplotypes. Similar regional variation was seen in both PSP cases and controls.
Advanced Circularly Polarised Microstrip Patch Antennas

The thesis describes outcomes of research on advanced circularly polarised antennas. The proposed designs are intended for integration into small mobile devices, therefore low profile and easy manufacturability are key parameters, along with good CP radiation properties. The designs were validated by simulation and measurement, and are also backed by theory and design guidelines. The primary focus is on the development of planar omnidirectional circularly polarised antennas, which are fabricated using multilayer PCB techniques and thus are lightweight and cost-efficient. Unlike in classical microstrip patch antenna designs, the groundplane of the proposed antenna was substantially reduced. This helps to achieve an omnidirectional circular polarisation pattern and miniaturize the antenna, however at the cost of increased feed circuit complexity. The basic design, its advantages and disadvantages are discussed in Section 3. In the next step, the omnidirectional circularly polarised antenna was extended with additional, advanced features. A miniaturized version is investigated, which offers a 20% footprint reduction by folding parts of the patch underneath itself. Further miniaturization is possible by increasing the dielectric constant of the substrate. A method to adjust the omnidirectional circularly polarised antenna performance by trimming four lumped capacitors is also investigated. Manufacturing inaccuracy in large scale production may cause some of the units to radiate outside of the desired frequencies. By integrating four trimmed capacitors into the antenna it can be precisely tuned to the desired band.
Airway Clearance Devices for Cystic Fibrosis An Evidence-Based Analysis

s were reviewed and studies meeting the inclusion criteria outlined above were obtained. Reference lists were also hand-checked for relevant studies. HbA1c outcomes from individual studies were meta-analyzed using RevMan 5.0 by the Cochrane Collaboration using a random-effects model to account for between-study differences. Methods for calculating standard deviations for intra-group changes from baseline to final in HbA1c levels are described below (see Statistical Challenges – Meta-analysis below). Assessment of Quality of Evidence The quality assigned to individual studies was determined using the MAS’ adaptation of the levels-ofevidence hierarchy proposed by Goodman. (11) The overall quality of the evidence was examined according to the GRADE Working Group criteria (see Appendix 2). (12)  Quality refers to criteria such as the adequacy of allocation concealment, blinding, and follow-up.  Consistency refers to the similarity of estimates of effect across studies. If there is important unexplained inconsistency in the results, our confidence in the estimate of effect for that outcome decreases. Differences in the direction of effect, the size of the differences in effect, and the significance of the differences guide the decision about whether an important inconsistency exists.  Directness refers to the extent to which the interventions and outcome measures are similar to those of interest, i.e., the generalizability of the interventions and outcomes. Table 1 outlines the definitions used in grading the quality of the evidence, as stated by the GRADE Working Group.
E ﬀ ectiveness of using teachers to screen eyes of school-going children in Satna district of Madhya Pradesh, India visual

Aim: To assess the e ﬀ ectiveness of teachers in a vision screening program for children in classes 5th to 12th a tt ending school in two blocks of a district of north central India. Materials and Methods: Ophthalmic assistants trained school teachers to measure visual acuity and to identify obvious ocular abnormalities in children. Children with visual acuity worse than 20/30 in any eye and/or any obvious ocular abnormality were referred to an ophthalmic assistant. Ophthalmic assistants also repeated eye examinations on a random sample of children identi ﬁ ed as normal (approximately 1%, n=543) by the teachers. Ophthalmic assistants prescribed spectacles to children needing refractive correction and referred children needing further examination to a pediatric ophthalmologist at the base hospital. Results: Five hundred and thirty teachers from 530 schools enrolled 77,778 children in the project and screened 68,833 (88.50%) of enrolled children. Teachers referred 3,822 children (4.91%) with eye defects for further examination by the ophthalmic assistant who con ﬁ rmed eye defects in 1242 children (1.80% of all screened children). Myopia (n=410, 33.01%), Vitamin A de ﬁ ciency (n=143, 11.51%) and strabismus (n=134, 10.79%) were the most common eye problems identi ﬁ ed by the ophthalmic assistant. Ophthalmic assistants identi ﬁ ed 57.97% referrals as false positives and 6.08% children as false negatives from the random sample of normal children. Spectacles were prescribed to 39.47% of children con ﬁ rmed with eye defects. Conclusions: Primary vision screening by teachers has e ﬀ ectively reduced the workload of ophthalmic assistants. High false positive and false negative rates need to be studied further.
tomography/computed tomography staging of mucinous tubular and spindle cell carcinoma of the kidney

Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC-K) is an extremely rare carcinoma of the kidney, which develops by malignant differentiation of the collecting ducts or the loop of Henle. The tumor can occur at all ages, with 4 times higher prevalence in females than in males. A 62-year-old female patient presented with an asymptomatic mass lesion in the left kidney. The ultrasound revealed a hyperechogenic mass lesion measuring 4 cm in diameter and centrally located in the left kidney. Computed tomography (CT) revealed an isodense mass lesion measuring 4 cm in diameter and posterolaterally located in the left kidney. Magnetic resonance imaging revealed a renal mass of 4 cm in diameter with hypervascular contrast uptake. For primary staging, 18 F‑fluorodeoxyglucose‑positron‑emission tomography ( 18 FDG‑PET)/CT revealed left renal cell carcinoma (RCC) with a maximum standard uptake value of 6.7. The patient underwent transperitoneal radical nephrectomy. The immunohistochemical examination revealed MTSCC-K. 18 FDG‑PET/CT provides 81 - 89% sensitivity and 83 - 100% specificity in primary staging of the renal cancers, in diagnosing metastatic RCC, and monitoring the response to therapy. Its use in the staging of MTSCC of the kidney has not been previously described in the literature. This case highlights the usefulness of 18 FDG‑PET/CT in the staging of this rare tumor. ABSTRACT
APOC3 Gene Polymorphism and Antiretroviral Therapy-Induced Dyslipidemia in HIV-Infected Children

Children exposed to antiretroviral therapy (ART) are at risk of developing metabolic complications. The association between gene polymorphisms and the development of dyslipidemia in children post ART initiation was studied. Children initiating ﬁrst-line ART were followed for 2 years at the National Institute for Research in Tuberculosis (Chennai, India), and St. John’s Medical College Hospital (Bangalore, India). Clinical examination and fasting serum lipid proﬁles were measured every 6 months. Participants were genotyped for the polymorphisms in the APOC3 gene (rs2854116; rs2854117, and rs5128). Changes in lipid levels from baseline to months 6, 12, and 24, and the difference between the various genotype variants were analyzed using a modiﬁed analysis of variance test. Study enrolled 393 ART-naive HIV-infected children (mean age: 7.6 – 3 years, mean weight: 18 – 6) of whom 289 (75%) were started on nevirapine (NVP)-based ART and the remaining 96 (25%) were started on efavirenz-based ART. Only children carrying the GG allele of rs5128 genotype showed a decrease in CD4% and serum triglycerides pre-ART. An increasing trend of total cholesterol, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol were seen at 6 months in both EFZ and NVP groups, which subsequently stabilized by 12 months irrespective of genotype variants. Genotype variants of APOC3 (rs2854116 and rs2854117 polymorphism) did not show signiﬁcant changes in serum lipid levels after 24 months of ART, whereas rs5128 polymorphism with ‘‘G’’ allele showed an association with HDL-c levels when on NVP-based ART. Our results suggest that ART plays a major role in normalizing lipid levels in HIV-infected children and APOC3 polymorphisms may not play a signiﬁcant role in ART-induced dyslipidemia.
Antiretroviral treatment of acute HIV infection normalizes CSF markers of CNS inflammation. A consequence of reduced CNS reservoir?

EDITORIAL COMMENTARY • jid 2019:220 (15 december) • 1867 Received 11 January 2019; editorial decision 11 January 2019; accepted 14 January 2019; published online January 21, 2019. Correspondence: M. Gisslén, MD, PhD, Dpt of Infectious Diseases, Sahlgrenska Academy at University of Gothenburg, SE-41685 Gothenburg, Sweden (magnus.gisslen@infect. gu.se). The Journal of Infectious Diseases 2019;220:1867–9 © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. DOI: 10.1093/infdis/jiz031 Antiretroviral Treatment of Acute HIV Infection Normalizes Levels of Cerebrospinal Fluid Markers of Central Nervous System (CNS) Inflammation: A Consequence of a Reduced CNS Reservoir?