Miracle-dz/UniFAR-FTUs huggingface dataset:
CSF sphingolipids, β -amyloid, and tau in adults at risk for Alzheimer's disease

Cellular studies suggest sphingolipids may cause or accelerate amyloid-beta (A β ) and tau pathology but in vivo human studies are lacking. We determined cerebrospinal fluid (CSF) levels of sphingolipids (ceramides, sphingomyelins), amyloid-beta (A β 1–42, A β X-38, A β X-40, A β X-42) and tau (T-tau, p-tau181) in 91 cognitively normal individuals, aged 36–69 years, with a parental history of Alzheimer's disease (AD). The 18-carbon acyl chain length ceramide species was associated with A β X-38 ( r = 0.312, p = 0.003), genotype. These results suggest in vivo relationships between CSF ceramides and sphingomyelins and A β and tau levels in cognitively normal individuals at increased risk for AD, indicating these sphingolipids may be associated with early pathogenesis.
Protein Kinase C ε inhibits ultraviolet radiation-induced expression of FADD, an adaptor protein, linked to both Fas and TNFR1-mediated apoptosis 1

PKC ε overexpression in FVB/N transgenic mice sensitized skin to ultraviolet radiation (UVR)-induced development of squamous cell carcinomas (SCC) (Wheeler et al. , 2004; Wheeler et al. , 2005) and suppressed formation of sunburn cells, which are DNA-damaged keratinocytes undergoing apoptosis (Wheeler et al. , 2004). Here, we elucidated the mechanisms associated with inhibition of UVR-induced appearance of sunburn cells in PKC ε transgenic mice. We found that the inhibition of UVR-induced sunburn cell formation in PKC ε transgenic mice may be the result of the inhibition of the expression of Fas, Fas ligand (Fas-L) and the mammalian death adaptor protein termed Fas-associated with death domain (FADD). The adaptor protein FADD is the key component of the death inducing signaling complex of both Fas and tumor necrosis factor receptor 1 (TNF-R1). A decreased expression of epidermal FADD was observed after a single UVR exposure. However, a complete loss of FADD expression was found after four (Monday, Wednesday, Friday and Monday) repeated UVR exposures. FADD transmits apoptotic signals from death receptors to the downstream initiator caspase-8 and connects to the mitochondrial intrinsic apoptotic signal transduction pathway by the cleavage of Bid, a Bcl-2 family member. PKC ε -mediated loss of FADD expression inhibited UVR signals to the activation of both extrinsic and intrinsic apoptotic pathways. results led us to hypothesize that UVR-induced activated PKC ε mediates two potential signals including one that facilitates accumulation of UVR-induced DNA-damaged keratinocytes and the other to promote the proliferation of these DNA-damaged keratinocytes (preneoplastic cells) to form SCC. PKC ε exerts these effects through Stat3 activation (Aziz), TNF α expression (Wheeler et al. , 2004) and the inhibition of FADD, component of the death inducing signaling complex.
Short Communication miR-125b Regulates Calcification of Vascular Smooth Muscle Cells

Vascular calcification is a prominent feature of atherosclerosis and is closely linked to osteoporosis. Cellular differentiation is regulated by various microRNAs (miRs), including miR-125b, which is known to be involved in osteoblast differentiation. However, no specific miR has been defined that modulates vascular calcification. Herein, we assessed the impact of miR-125b in osteogenic transformation of vascular smooth muscle cells. Osteogenic transdifferentiation of human coronary artery smooth muscle cells was induced by osteogenic medium and enhanced the formation of mineralized matrix, resulting in a significantly higher mineral deposition after 21 days. Increased expression of miR-125b was time-dependent in human coronary artery smooth muscle cells and diminished during osteogenic transdifferentiation. At day 21, miR-125b was significantly reduced ( (cid:1) 42%) compared with that in the untreated control. The expression of miR-process-ing enzymes, RNase III endonucleases DICER1 and DROSHA, was also decreased. Furthermore, inhibition of endogenous miR-125b promoted osteogenic transdifferentiation, as measured by increased alkaline phosphatase activity and matrix mineralization. Expression analysis revealed the osteoblast transcription factor SP7 (osterix) as a target of miR-125b. In vivo , miR-125b was decreased in calcified aortas of apolipoprotein E knockout mice. In conclusion, our results suggest that miR-125b is involved in vascular calcification ; SP7, forward-5 = -AG-GCACAAAGAAGCCATACG-3 = and reverse-5 = -GCCC-AGGAAATGAGTGAGG-3 and mouse RUNX2, forward-5 = -CCCAGCCACCTTTACCTACA-3 and reverse-5 = -TATG-GAGTGCTGCTGGTCTG-3 = . was normalized to (cid:2) -actin (human, forward-5 = -CCAACCGCGAGAAGATGA-3 = and reverse-5 = -CCAGAGGCGTACAGGGATAG-3 = ; mouse, forward-5 = -GATCTGGCACCACACCTTCT-3 and reverse-5 -GGGGTGTTGAAGGTCTCAAA-3 relative expression was calculated using the (cid:2)(cid:2) C T method gene expression (cid:3) 2 (cid:2) C T sample (cid:4) (cid:2) C T control)] and is presented in fold increase relative to
R eview Mitonuclear Ecology

Eukaryotes were born of a chimeric union between two prokaryotes—the progenitors of the mitochondrial and nuclear genomes. Early in eukaryote evolution, most mitochondrial genes were lost or transferred to the nucleus, but a core set of genes that code exclusively for products associated with the electron transport system remained in the mitochondrion. The products of these mitochondrial genes work in intimate association with the products of nuclear genes to enable oxidative phosphorylation and core energy production. The need for coadaptation, the challenge of cotransmission, and the possibility of genomic conﬂict between mitochondrial and nuclear genes have profound consequences for the ecology and evolution of eukaryotic life. An emerging interdisciplinary ﬁeld that I call “mitonuclear ecology” is reassessing core concepts in evolutionary ecology including sexual reproduction, two sexes, sexual selection, adaptation, and speciation in light of the interactions of mitochondrial and nuclear genomes.
ANGINA PECTORIS: A CASE STUDY.

IT is evident from a survey of the medical literature of the last five decades that the attempt to secure an adequate clinical content for the term "angina pectoris" has met with three outstanding difficulties, confused definition, failure to agree upon the pathogenesis, and the difficulty of an intelligent prognosis in the individual case. Recent years have seen notable progress in the clarification of these matters. This has been due in large part to the increasing knowledge of coronary artery problems. There is a better general understanding of what is meant by the term. Angina pectoris can no longer be viewed as a loose expression to denote the symptom of pain in the chest. The greater knowledge of the etiology of such pain has served to differentiate such conditions as coronary thrombosis, syphilis of the aorta, and rheumatic heart disease, thus permitting a more accurate definition of the term. In regard to the pathogenesis of the syndrome, although the last word has not been said, the coronary origin of the disorder is now generally accepted. And although the prognosis in the individual case must always be relatively uneertain, a broader viewpoint in this particular has been achieved. In short, the term "angina pectoris" is less a symptom than it was ten years ago. It may now be regarded as a syndrome capable of definition clinically, with a pathological basis generally agreed upon. This has served in large measure to free physician and layman alike from the tyranny of a term which in the past was inadequately understood. What do we mean by "angina pectoris"? In a summary way it may be defined as follows: (1) Angina pectoris is a disease of the heart manifested by pain on exertion, such pain being experienced across the chest, usually in the region of the sternum, sometimes radiating, and, if so, most commonly to the arms. (2) It is a symptom-complex or syndrome of coronary artery disease, and is due to deficient coronary blood supply, the pain arising from
Critical Care Perspective Gene Silencing in Severe Systemic Inflammation

This critical care perspective appraises reprogramming of gene expression in inflammatory diseases as an emerging concept of clinical importance. We emphasize gene reprogramming that “si- lences” acute proinflammatory genes during severe systemic inflammation, wherein in the systemic inflammatory response syn- drome (SIRS) exists as a continuum during severe sepsis, septic shock,andthemultiorgan dysfunctionandfailurephenotypes with- out infection. In contrast, silencing of acute proinflammatory genes is not apparent in sites of localized inflammatory processes like rheumatoid arthritis. We discuss in three parts the clinical context and the translational basic science associated with gene silencing during the SIRS continuum of severe systemic inflammation: ( 1 ) reprogramming of acute proinflammatory genes; ( 2 ) a “nuclear factor- (cid:2) B paradox,” coupled with RelB expression, that combine to silence genes using an epigenetic (inherited and reversible) signa- ture on the nucleosome; and ( 3 ) the potential clinical importance of compartmentalization in gene silencing. Our emergent under- standing of these physiologic processes may provide a novel framework for developing treatments. We turn every defense at our disposal; we defoliate, blockade, seal off, destroy all the tissues of the area.
Cell Cycle Expression of Two Replicative DNA Polymerases a and a from Schizosaccharomyces pombe

We have investigated the expression of two Schizosaccharomyces pombe replicative DNA polymerases a and 6 during the cell cycle. The pola' and pol6+ genes encoding DNA polymerases a and 6 were isolated from S. pombe. Both pola' and pol6+ genes are single copy genes in haploid cells and are essential for cell viability. In contrast to Saccharomyces cerevisiae homologs, the steady-state transcripts of both S. pombe pola' and pol6+ genes were present throughout the cell cycle. Sequence analysis of the pola' and pol6+ genes did not reveal the Mlu I motifs in their upstream sequences that are involved in cell cycle-dependent transcription of S. cerevisiae DNA synthesis genes as well as the S. pombe cdc22+ gene at the G1/S boundary. However, five near-match Mlu I motifs were found in the upstream region of the pola' gene. S. pombe DNA polymerases a and 6 proteins were also expressed constantly throughout the cell cycle. In addition, the enzymatic activity of the S. pombe DNA polymerase a measured by in vitro assay was detected at all stages of the cell cycle. Thus, these S. pombe replicative DNA polymerases, like that of S. pombe cdc17+ gene, are expressed throughout the cell cycle at the transcriptional and protein level. These results indicate that S. pombe has at least two regulatory modes for the expression of genes involved in DNA replication and DNA precursor synthesis. was amplified by PCR using 5'-TATGGATCCCAGCAAATCGATAGT- GAGGAG-3' as upstream primer and 5'-AATGGATCCTACTT-GTGTTCCACCGATTTG-3' as downstream primer. The PCR was performed under the same conditions used for generating the probe to isolate S. pombe DNA polymerase 6 genomic clones. This PCR frag- ment was digested with BamHI and cloned into the BamHI site of pGEX-2T to generate pGT-polS. Both constructs were checked for correct reading frame with GST protein by DNA sequencing.
Financial Current Realities and Challenges for Physicians

Of managed care’s many features, financial incentives to physicians have received the most attention. 3 Particular attention has been focused on HMOs that use risk-based capitation financing. Such financing arrangements encourage prevention and cost-effective practice, but also have the potential to discourage care that may be medically appropriate, especially if the omission of such care is unlikely to lead to other negative consequences (e.g., enrollment turnover because of dissatisfaction, revenue losses associated with malpractice cases). Policy makers are concerned that payment incentives confronting individual physicians under some managed care arrangements may distort physicians’ clinical judgment. 4
Reply on CC3

"Since small ice fragments have lower terminal fall velocity, their residence time in the undersaturated environment may be long enough to result in their complete evaporation before they can re-enter a supersaturated environment. This appears to be a significant limitation of the SIP mechanism due to sublimation breakup. This mechanism is also unlikely to explain explosive concentrations of small ice crystals frequently observed in convective and stratiform frontal clouds (e.g., Lawson et al., 2017; Korolev et al., 2020) . Activation of SIP due to the fragmentation of sublimating ice requires spatial proximity of undersaturated and supersaturated cloud regions. In this case, secondary ice particles formed in the undersaturated cloud regions can be rapidly transported into the supersaturated regions prior their sublimation. Such conditions may occur in cloud regions affected by entrainment and mixing with out-of-cloud dry air. "
Adolescents demonstrate improvement in obesity risk behaviors following completion of Choice, Control, and Change, a curriculum addressing personal agency and autonomous motivation

Background— The rapid increase of obesity and diabetes risk beginning in youth, particularly those from disadvantaged communities, calls for prevention efforts. Objective— To examine the impact of a curriculum intervention, Choice, Control, and Change (C3), on the adoption of the energy balance related behaviors of decreasing sweetened drinks, packaged snacks, fast food, and leisure screen time, and increasing water, fruits and vegetables, and physical activity, and on potential psychosocial mediators of the behaviors. Design— Ten middle schools in low-income New York City neighborhoods were randomly assigned within matched pairs to either intervention Intervention— Students received the 24 C3 lessons that used science inquiry-based investigations to enhance motivation for action, and social cognitive and self-determination theories to increase personal agency and autonomous motivation to take action. Main outcome measures— Self-report instruments to measure energy balance related behaviors targeted by the curriculum, and potential psychosocial mediators of the behaviors. Analyses— ANCOVA with group (intervention/control) as a fixed factor and pre-test as covariate. Results— Students in intervention schools compared to the delayed intervention controls reported consumption of significantly fewer sweetened drinks and packaged snacks, smaller sizes of fast food, increased intentional walking for exercise, and decreased leisure screen-time, but showed no increases in their intakes of water, fruits, and vegetables. They showed significant increases in positive outcome expectations about the behaviors, self-efficacy, goal intentions, competence, and autonomy. Conclusions— The C3 curriculum was effective in improving many of the specifically targeted behaviors related to reducing obesity risk, indicating that combining inquiry-based science education and behavioral theory is a promising approach.
A randomized controlled trial of a phone-based cognitive-behavioral intervention to improve PTSD treatment utilization among returning service members

Objectives— Many service members do not seek care for mental health and addiction problems, often with serious consequences for them, their families, and their communities. This study tested the effectiveness of a brief, telephone-based, cognitive-behavioral intervention designed to improve treatment engagement among returning service members who screened positive for PTSD. Method— OEF/OIF service members who screened positive for PTSD but had not engaged in PTSD treatment were recruited (N=300), randomly assigned to either control or intervention conditions, and administered the baseline interview. Intervention participants received the brief CBT intervention; control condition participants had access to usual services. All participants received follow-up phones calls at months 1, 3 and 6 to assess symptoms and service utilization. Results— Participants in both conditions had comparable rates of treatment engagement and PTSD symptom reduction over the course of the six-month trial, but receiving the telephone-based intervention accelerated service utilization (treatment engagement and number of sessions) and PTSD symptom reduction. Conclusions— A one-time brief telephone intervention can engage service members in PTSD treatment earlier than conventional methods and can lead to immediate symptom reduction. There were no differences at longer-term follow-up, suggesting the need for additional intervention to build upon initial gains.
The Reaction of Oxidizing Agents with Wool

It has long been recognized that the reaction between wool keratin and oxidizing agents is extremely complex (see Stoves, 1946). Although most oxidizing agents act on the disulphide bond, other groups are also oxidized and considerable general degradation is found. As the disruption of the disulphide bond alone causes a great reduction in the strength of the, fibres, it is difficult to detect limited main chain breakdown. In the work described below, one of the reagents used was peracetic acid which acts specifically on the disulphide bonds and tryptophan side groups and undesirable reactions are eliminated (Alexander, Hudson & Fox, 1950). It has hitherto been customary to interpret the reaction of the combined cystine in keratin in the same way as the reactions of cystine or similar disulphides. Cystine is oxidized by perbenzoic acid in chloroform to a disulphoxide which is readily converted to the corresponding sulphonic and sulphinic acids by 95% methanol and hydrochloric acid (Lavine, Toennis & Wagner, 1934).
Current and Future Approaches to the Treatment of IgG4-Related Disease

IgG4-related disease (IgG-RD) is capable of causing great morbidity and even mortality if the condition remains undiagnosed or poorly treated, yet is typically a treatment-responsive disorder. Glucocorticoids have not been studied rigorously and practices with regard to dosing and duration of treatment remain largely empiric. In addition, IgG4-RD patients are often particularly susceptible to and intolerant of the deleterious effects of glucocorticoid therapy. B cell depletion with anti-CD20 monoclonal antibodies appears to be a rapid, effective means of obtaining disease control and limiting patients’ glucocorticoid exposure, but this option is frequently available. Other therapies targeting the B cell lineage may also be efficacious, and one is under study. The means by which depletion or inhibition of B cells and their progeny ameliorate IgG4-RD is coming into focus now through careful mechanistic studies of samples from treated patients. The mechanistic understanding of IgG4-RD will bring an array of specific targets for therapeutic intervention. Plasmablast-directed therapy with a CD19 monoclonal antibody is currently in clinical trials. CD4+ cytotoxic T lymphocytes and fibrosis, both observed nearly universally in the tissue of IgG4-RD patients, present two unexploited vulnerabilities in controlling and even reversing the effects of the disease. Further development of such therapies is a major goal of the next few years.
Developing Useful HAART Adherence Measures for India: The Prerana Study

Excellent adherence to antiretroviral regimens is closely associated with achieving HIV viral suppression and preventing the development of drug resistant virus. Missed doses, interruptions in therapy, and improper dosing can all lead to HIV drug resistance [e.g. 1–3]. Like many other areas of behavior change, long term maintenance of consistent adherence has been a challenge for behavior change in the U.S., and data from Africa [4] indicate that adherence levels may decline over time in developing country settings as well. Reliable and valid adherence measures are essential to the study of HAART adherence and to evaluate the impact of adherence interventions, [e.g. 5–9]. To be useful in clinical settings, they also need to be brief and relatively simple to administer [10]. Although multiple adherence measures have been found to predict viral load, there is no single gold standard for the assessment of adherence [8] and most measures have been developed in the US [e.g. 11,12]. In India, Shah et al. [13] found a cross-sectional association between past 4 day adherence and viral load in a subsample of their study in Pune and Delhi. However, no Indian studies to date have examined, in a prospective fashion, the impact of adherence on viral load, the predictive validity of combined measures, or the relationship between multiple adherence measures. This study was designed to address this gap by assessing the relationship between multiple self-reported adherence measures and HIV viral suppression in a longitudinal cohort of HIV infected patients in Bangalore, India.
IMPROVING SOCIAL SKILLS AND DISRUPTIVE BEHAVIOR IN CHILDREN WITH AUTISM THROUGH SELF-MANAGEMENT

The literature suggests that children with autism typically are unresponsive to verbal initiations from others in community settings, and that such unresponsiveness can lead to problematic social interactions and severely disruptive behavior. The present study assessed whether self-management could be used as a technique to produce extended improvements in responsiveness to verbal initiations from others in community, home, and school settings without the presence of a treatment provider. The results showed that children with autism who displayed severe deficits in social skills could learn to self-manage responsivity to others in multiple community settings, and that such improvements were associated with concomitant reductions in disruptive behavior without the need for special intervention. The results are discussed in terms of their significance for improved development of social skills in children with autism.
Designing Cash Transfer Programs for an Older Population: The Mexican Case

Aging populations and the prevalence of poverty in old age have led to the introduction of noncontributory pensions in many countries. We consider a number of alternative targeting approaches and simulate their effects in an empirical application in the State of Yucatan, Mexico. We compare the approaches with respect to leakage, under-coverage, and their effects on government budgets. We are also able to compare the simulated effects of one alternative with the observed effect of a recently introduced demogrant and find that the simulation is a close approximation of the empirical outcomes. We discuss issues of implementation and political feasibility.
Evaluating the Performance of GFR Estimating Equations

GFR is an important indicator of kidney function, critical for detection, evaluation, and management of CKD. GFR cannot be practically measured in most clinical or research settings, and therefore estimating equations are used as a primary measure of kidney function. A considerable body of literature now evaluates the performance of the GFR estimating equations. The results of these studies are often not comparable due to variation in GFR measurement methods, endogenous filtration marker assays and tools by which the equations were evaluated. In this article, methods for evaluation of GFR estimating equations is discussed. Topics addressed include: statistical methods used in development and validation of equations; explanation of measures of performance used for evaluation with focus on distinction between bias, precision and accuracy, and with reference to examples of published evaluations of creatinine and cystatin C based equations; explanation for errors in GFR estimates; and challenges and questions in reporting performance of GFR estimating equations.