gebhart/patrepeval huggingface dataset:
Clinical Use of Hemoglobin A1c to Improve Diabetes Management (2006)

F or more than 25 years, the hemoglobin A1c (A1C) test has been the most widely accepted outcome measure for evaluating glycemic control in individuals with diabetes. The test provides an index of a patient's average blood glucose level during the past 2-3 months1 and is considered to be the most objective and reliable measure of long-term metabolic control.2,3 The Diabetes Control and Complications Trial established that maintaining A1C levels as close as possible to the normal range results in considerable reductions in long-term health complications.4 Thus, as the “gold standard” measure of diabetes control, this test provides important feedback to health care professionals and patients. It follows that patients' understanding of this test and its implications for long-term health risk is essential.

Research has shown that regular measurement of A1C over the long term can identify patients with poor glycemic control and facilitate their improvement.5 The established relationship between A1C measurements and long-term complications,4 as well as the association between regular A1C testing and improved metabolic control,5 underscore the importance of determining the extent of patients' understanding of this important test and how its results are used in the clinical setting.

### Patient Knowledge of A1C

Relatively few studies have examined diabetic patients' knowledge and understanding of A1C testing. Findings from one recent study conducted in Norway6 revealed that the majority (82.6%) of 201 adult patients with type 1 diabetes knew what their last A1C was, and most patients (90%) knew what a satisfactory A1C value would be. But a significant number of patients (42%) reported they had low knowledge of A1C testing in general. Furthermore, 25% of patients did not think that treatment intensification should occur at an A1C value of 10%.

A recent cross-sectional study …
Abasic DNA structure, reactivity, and recognition (1999)

Loss of a base in DNA, i.e., creation of an abasic site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously, or under the action of radiations and alkylating agents, or enzymatically as an intermediate in the repair of modified or abnormal bases. The abasic site lesion is mutagenic or lethal if not repaired. From a chemical point of view,the abasic site is an alkali-labile residue that leads to strand breakage through beta- and delta- elimination. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of synthetic abasic duplexes. Several efficient synthetic methods have thus been developed to introduce the lesion (or a stable analogue) at defined position in the sequence. Physicochemical and spectroscopic examination of such duplexes, including calorimetry, melting temperature, high-field nmr and molecular modeling indicate that the lesion strongly destabilizes the duplex, although remaining in the canonical B-form with structural modifications strictly located at the site of the lesion. Probes have been developed to titrate the damage in DNA in vitro. Series of molecules have been devised to recognize specifically the abasic site, exhibiting a cleavage activity and mimicking the AP nucleases. Others have been prepared that bind strongly to the abasic site and show promise in potentiating the cytotoxic and antitumor activity of the clinically used nitrosourea (bis-chloroethylnitrosurea).
The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation (2004)

The Ezh2 protein endows the Polycomb PRC2 and PRC3 complexes with histone lysine methyltransferase (HKMT) activity that is associated with transcriptional repression. We report that Ezh2 expression was developmentally regulated in the myotome compartment of mouse somites and that its down-regulation coincided with activation of muscle gene expression and differentiation of satellite-cell-derived myoblasts. Increased Ezh2 expression inhibited muscle differentiation, and this property was conferred by its SET domain, required for the HKMT activity. In undifferentiated myoblasts, endogenous Ezh2 was associated with the transcriptional regulator YY1. Both Ezh2 and YY1 were detected, with the deacetylase HDAC1, at genomic regions of silent muscle-specific genes. Their presence correlated with methylation of K27 of histone H3. YY1 was required for Ezh2 binding because RNA interference of YY1 abrogated chromatin recruitment of Ezh2 and prevented H3-K27 methylation. Upon gene activation, Ezh2, HDAC1, and YY1 dissociated from muscle loci, H3-K27 became hypomethylated and MyoD and SRF were recruited to the chromatin. These findings suggest the existence of a two-step activation mechanism whereby removal of H3-K27 methylation, conferred by an active Ezh2-containing protein complex, followed by recruitment of positive transcriptional regulators at discrete genomic loci are required to promote muscle gene expression and cell differentiation.
Single Step Extractions of Metals in Coal Fly Ash (2012)

There is an increasing use of coal and subsequently large amounts of fly ash is generated in the thermal power plants in India and elsewhere in the world. Hence it becomes increasingly important to be able to assess the environmental risks involved in the management and disposal of fly ash materials. The fly ashes contain toxic metals that can be released into the environment through the coal combustion processes and through the leaching during disposal/ wet storage/ reuse of fly ash. The evaluation of the optimum time for leaching of the toxic metals and metalloids present in the three fly ashes was determined using the single step extraction procedure. The optimum time of 4 hours agitation was determined for the water soluble step as well as that for ion exchangeable step while the optimum time was 24 hours agitation in the acid soluble and reducible steps.
Quantifying person-level brain network functioning to facilitate clinical translation (2017)

Although advances in neuroimaging have yielded insights into the intrinsic organization of human brain networks and their relevance to psychiatric and neurological disorders, there has been no translation of these insights into clinical practice. One necessary step toward clinical translation is identifying a summary metric of network function that is reproducible, reliable, and has known normative data, analogous to normed neuropsychological tests. Our aim was therefore to establish the proof of principle for such a metric, focusing on the default mode network (DMN). We compared three candidate summary metrics: global clustering coefficient, characteristic path length, and average connectivity. Across three samples totaling 322 healthy, mostly Caucasian adults, average connectivity performed best, with good internal consistency (Cronbach's α=0.69-0.70) and adequate eight-week test-retest reliability (intra-class coefficient=0.62 in a subsample N=65). We therefore present normative data for average connectivity of the DMN and its sub-networks. These proof of principle results are an important first step for the translation of neuroimaging to clinical practice. Ultimately, a normed summary metric will allow a single patient's DMN function to be quantified and interpreted relative to normative peers.
Brief Communication: Atrial–Esophageal Fistulas after Radiofrequency Ablation (2006)

Formation of atrial-esophageal fistulas is a rare but potentially devastating complication of atrial fibrillation ablation. This disorder may have an indolent presentation and may mimic other disease states, such as stroke or sepsis.
Microbiological and histopathological findings in acute pelvic inflammatory disease (1987)

Summary Upper genital tract infection was investigated in 45 women admitted to hospital for suspected acute pelvic inflammatory disease (PID). Salpingitis was diagnosed by laparoscopy in 30 (67%) women. Histopathological evidence of endometritis was found significantly more often in the 30 women with salpingitis (87%) than in the other 15 women without salpingitis (33%). C. trachomatis or N. gonorrhoeas , or both, were isolated from the upper genital tract in 14 of the 31 women who had both salpingitis and endometritis or endometritis only but in none of the four women who had salpingitis alone and in none of the 10 women who had no evidence of PID. Bacterial vaginosis was associated with histopathological evidence of upper tract infection. Non‐chlamydial nongonococcal organisms were frequently isolated from the upper genital tract. No organisms were isolated from the upper genital tract from 9 of 35 women with laparoscopic or histopathological evidence of PID compared with 7 of 10 women without evidence of PID. C, trachomatis or N. gonorrhoeae in the endometrium was associated with lymphoid follicles comprising transformed lymphocytes, and correlated with the density of plasma cells on biopsy. The microbiological results support the recommendations of broad spectrum antimicrobial therapy for PID.
Structure-based design of conformation- and sequence-specific antibodies against amyloid β (2011)

Conformation-specific antibodies that recognize aggregated proteins associated with several conformational disorders (e.g., Parkinson and prion diseases) are invaluable for diagnostic and therapeutic applications. However, no systematic strategy exists for generating conformation-specific antibodies that target linear sequence epitopes within misfolded proteins. Here we report a strategy for designing conformation- and sequence-specific antibodies against misfolded proteins that is inspired by the molecular interactions governing protein aggregation. We find that grafting small amyloidogenic peptides (6-10 residues) from the Aβ42 peptide associated with Alzheimer's disease into the complementarity determining regions of a domain (V(H)) antibody generates antibody variants that recognize Aβ soluble oligomers and amyloid fibrils with nanomolar affinity. We refer to these antibodies as gammabodies for grafted amyloid-motif antibodies. Gammabodies displaying the central amyloidogenic Aβ motif (18VFFA21) are reactive with Aβ fibrils, whereas those displaying the amyloidogenic C terminus (34LMVGGVVIA42) are reactive with Aβ fibrils and oligomers (and weakly reactive with Aβ monomers). Importantly, we find that the grafted motifs target the corresponding peptide segments within misfolded Aβ conformers. Aβ gammabodies fail to cross-react with other amyloidogenic proteins and scrambling their grafted sequences eliminates antibody reactivity. Finally, gammabodies that recognize Aβ soluble oligomers and fibrils also neutralize the toxicity of each Aβ conformer. We expect that our antibody design strategy is not limited to Aβ and can be used to readily generate gammabodies against other toxic misfolded proteins.
An Automated MALDI Mass Spectrometry Approach for Optimizing Cyclosporin Extraction and Quantitation (1997)

A combinatorial extraction method and an automated matrix-assisted laser desorption/ionization (MALDI) mass spectrometry procedure were used to improve the clinical analysis of the immunosuppressant drug cyclosporin A. Cyclosporin extracts from whole blood were analyzed by MALDI and electrospray ionization (ESI) mass spectrometry, allowing for their identification and quantification. Due to limitations associated with the current multistep cyclosporin extraction procedure from whole blood, a combinatorial approach was devised to optimize this extraction. Optimization was performed by generating an array of solvent systems to be used for extraction from blood, and an automated analysis was carried out on a MALDI mass spectrometer to identify successful extractions. The first generation of experiments revealed four binary solvent systems to be effective for cyclosporin extraction (hexane/EtOH, ACN/H2O, ACN/MeOH, and hexane/CHCl3). A new array based on these solvent systems was generated, and a second iteration of these experiments was then performed. In the second generation of experiments, hexane/CHCl3 (70:30) was found to provide the most effective single-step extraction of these solvent systems for cyclosporin and its metabolites. The limits of detection were determined to be 15 ng/mL in whole blood for ESI/MS and MALDI-MS and could also be used for identifying major drug metabolites. In addition to applying this combinatorial approach to extraction procedures, this experimental design could easily be extended to examine other approaches, such as optimizing chemical reactions and screening inhibitors in enzymatic reactions.
Determination of oxygen concentrations by luminescence quenching of a polymer-immobilized transition-metal complex (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetermination of oxygen concentrations by luminescence quenching of a polymer-immobilized transition-metal complexJ. R. Bacon and J. N. DemasCite this: Anal. Chem. 1987, 59, 23, 2780–2785Publication Date (Print):December 1, 1987Publication History Published online1 May 2002Published inissue 1 December 1987https://pubs.acs.org/doi/10.1021/ac00150a012https://doi.org/10.1021/ac00150a012research-articleACS PublicationsRequest reuse permissionsArticle Views2231Altmetric-Citations309LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Artificial liver support systems. (2004)

Though artificial support systems for kidney failure have been widely available for the past several decades, it is only recently that they have become a promising treatment modality for liver failure. The various liver support systems include conventional dialysis, charcoal hemoperfusion, high volume plasma exchange, liver dialysis using sorbent technology, molecular readsorption recirculating system using albumin as the dialysate, bioartificial livers, extracorporeal liver assist device and extracorporeal organ perfusion. They are mainly used as a bridge to liver transplantation and occasionally in acute liver failure till the liver regenerates. The various methods of extracorporeal liver support that are available at present are assessed and those that appear to be promising are described.
Substrate Reduction Augments the Efficacy of Enzyme Therapy in a Mouse Model of Fabry Disease (2010)

Fabry disease is an X-linked glycosphingolipid storage disorder caused by a deficiency in the activity of the lysosomal hydrolase α-galactosidase A (α-gal). This deficiency results in accumulation of the glycosphingolipid globotriaosylceramide (GL-3) in lysosomes. Endothelial cell storage of GL-3 frequently leads to kidney dysfunction, cardiac and cerebrovascular disease. The current treatment for Fabry disease is through infusions of recombinant α-gal (enzyme-replacement therapy; ERT). Although ERT can markedly reduce the lysosomal burden of GL-3 in endothelial cells, variability is seen in the clearance from several other cell types. This suggests that alternative and adjuvant therapies may be desirable. Use of glucosylceramide synthase inhibitors to abate the biosynthesis of glycosphingolipids (substrate reduction therapy, SRT) has been shown to be effective at reducing substrate levels in the related glycosphingolipidosis, Gaucher disease. Here, we show that such an inhibitor (eliglustat tartrate, Genz-112638) was effective at lowering GL-3 accumulation in a mouse model of Fabry disease. Relative efficacy of SRT and ERT at reducing GL-3 levels in Fabry mouse tissues differed with SRT being more effective in the kidney, and ERT more efficacious in the heart and liver. Combination therapy with ERT and SRT provided the most complete clearance of GL-3 from all the tissues. Furthermore, treatment normalized urine volume and uromodulin levels and significantly delayed the loss of a nociceptive response. The differential efficacies of SRT and ERT in the different tissues indicate that the combination approach is both additive and complementary suggesting the possibility of an improved therapeutic paradigm in the management of Fabry disease.
Patient positioning in the proton radiotherapy era (2010)

The main hindrance to the diffusion of proton therapy facilities is the high cost for gantry installations. An alternative technical option is provided by fixed-beam treatment rooms, where the patient is rotated and translated in space with a robotic arm solution to enable beam incidence from various angles. The technological efforts based on robotic applications made up to now for patient positioning in proton beam facilities are described here, highlighting their limitations and perspectives.
积极的心态能给人战胜一切的信心——约翰·D．洛克菲勒致儿子的一封信 (2015)

我亲爱的儿子查理：你好！我想在这封信里，接着和你谈谈心态方面的问题，你不会厌烦吧？心态是一把双刃剑，是人人都有的精神特性。心态这一看不见的法宝会产生两种惊人的力量：它既能让你获得财富、拥有幸福、健康长寿；也能让这些东西远离于你，剥夺一切使你的生活富有意义的东西。在这两种力量中，前者--积极心态--可以使你达到人生的顶峰，尽享成功的快乐与美好；后者--消极心态--则可使你在整个一生中都处于一种底层的地位，困苦与不幸一直缠身。还有一种情况，当某些人已经到达顶峰的时候，也许会让后者将他们从顶峰拖滑而下，跌入低谷。
Delineation of the dendritic cell lineage by generating large numbers of Birbeck granule-positive Langerhans cells from human peripheral blood progenitor cells in vitro (1995)

It is well established by in vivo and in vitro studies that dendritic cells (DCs) originate from hematopoietic progenitor cells. However, the presumed intermediate of Birbeck granule (BG)+ Langerhans cells (LCs) has not been detected in cultures derived from bone marrow or peripheral blood progenitor cells (PBPCs), thus contrasting with the data obtained with cord blood. We show here that large numbers of BG+ LCs can be generated from human CD34+ PBPCs in vitro, when granulocyte-macrophage colony-stimulating factor and interleukin-4, potent promotors of LC/DC differentiation, are combined with a cocktail of early acting hematopoietic growth factors. LCs were found to emerge from CD33+CD11b+CD14-progenitor cells that they share with the monocytic lineage. During culture, these cells exhibited a sequence of dramatic morphologic changes, starting with a major increase in granularity followed by an increase in size herein exceeding that of all peripheral blood cells. At the same time, CD1a and major histocompatibility complex class II expression were upregulated and virtually all CD1a++ cells were BG+ by electron microscopy. With prolonged culture, CD1a was downregulated on a major population of cells, paralleled by a loss of BG and an increase of CD4, CD25, and CD80 expression that may correspond to the maturation of epidermal LC in vitro. However, these cells were consistently CD5- and did not exhibit changes in the CD45-isoform expression during culture. The availability of large numbers of these highly purified BG+ LCs and mature DCs allows for specific analysis of these subpopulations and provides a source of potent antigen-presenting cells from individual patients for vaccination protocols against infectious or tumor-associated antigens.
Human cortical prostheses: lost in translation? (2009)

Direct brain control of a prosthetic system is the subject of much popular and scientific news. Neural technology and science have advanced to the point that proof-of-concept systems exist for cortically-controlled prostheses in rats, monkeys, and even humans. However, realizing the dream of making such technology available to everyone is still far off. Fortunately today there is great public and scientific interest in making this happen, but it will only occur when the functional benefits of such systems outweigh the risks. In this article, the authors briefly summarize the state of the art and then highlight many issues that will directly limit clinical translation, including system durability, system performance, and patient risk. Despite the challenges, scientists and clinicians are in the desirable position of having both public and fiscal support to begin addressing these issues directly. The ultimate challenge now is to determine definitively whether these prosthetic systems will become clinical reality or forever unrealized.
OX40 engagement depletes intratumoral Tregs via activating FcγRs, leading to antitumor efficacy (2014)

Antibodies targeting checkpoint inhibitors or co-stimulatory receptors on T cells have shown significant antitumor efficacy in preclinical and clinical studies. In mouse tumor models, engagement of activating Fcγ receptor (FcγR)-expressing immune cells was recently shown to be required for the tumoricidal activity of antibodies recognizing the tumor necrosis factor superfamily receptor (TNFR) GITR (CD357) and CTLA-4 (CD152). In particular, activating FcγRs facilitated the selective elimination of intratumoral T-cell populations. However, it remains unclear whether FcγRs contribute to the antitumor efficacy of other immunomodulatory antibodies. Here, we explored the mechanism of antitumor activity mediated by an agonistic antibody (clone OX86) to the co-stimulatory TNFR OX40 (CD134). OX40 was highly expressed by intratumoral T cells, particularly those of the FoxP3(+) regulatory T-cell (Treg) lineage. OX86 administration resulted in the depletion of intratumoral regulatory T cells in an activating FcγR-dependent manner, which correlated with tumor regression. Together with previous data from our group and others, these findings support a mechanism whereby antibodies targeting antigens highly expressed by intratumoral T cells can mediate their elimination by FcγR-expressing immune cells, and facilitate subsequent antitumor immunity.
Demonstration of specific high affinity binding sites in plasmid DNA by photoaffinity labeling with an ethidium analog. (1982)

We have used photoaffinity labeling of pBR322 DNA with 8-azido-3-amino-5-ethyl-6-phenylphenanthridinium chloride to demonstrate high affinity ethidiumbinding sites.Plasmid equilibrated with as little as 1 drug/DNA molecule was photoactivated, freed of uncomplexed drug by ethanol precipitation, and subjected to restriction analysis.There was highly specific, rather than random, blockage of HhuI sites (d(GCGC)) at low drug concentrations.Furthermore, the same 7 new digestion fragments were generated at drug to nucleotide ratios ranging from 1:lOO to 1:8000.All the new DNA fragments had chain lengths greater than the largest HhuI fragment (393 base pairs).At higher ligand concentrations closely approximating those needed for equilibrium binding studies, detection of the high affinity sites was greatly masked.Drug binding to HhuI restriction fragments which had been prepared prior to the action of drug did not induce new bands.Furthermore, the larger DNA fragments from drug-labeled plasmid were resistant to HhaI digestion over a wide range of enzyme concentrations.These findings suggest that ligand binding can be highly selective even between sites which have the same tetranucleotide sequence.Therefore, selective drug binding must be dictated not only by local base sequence preference, but also by other long range parameters.' G. V. Paddock, personal communication.