gebhart/patrepeval huggingface dataset:
Actual causes of death in the United States (1993)

<h3>Objective.</h3> —To identify and quantify the major external (nongenetic) factors that contribute to death in the United States. <h3>Data Sources.</h3> —Articles published between 1977 and 1993 were identified through MEDLINE searches, reference citations, and expert consultation. Government reports and compilations of vital statistics and surveillance data were also obtained. <h3>Study Selection.</h3> —Sources selected were those that were often cited and those that indicated a quantitative assessment of the relative contributions of various factors to mortality and morbidity. <h3>Data Extraction.</h3> —Data used were those for which specific methodological assumptions were stated. A table quantifying the contributions of leading factors was constructed using actual counts, generally accepted estimates, and calculated estimates that were developed by summing various individual estimates and correcting to avoid double counting. For the factors of greatest complexity and uncertainty (diet and activity patterns and toxic agents), a conservative approach was taken by choosing the lower boundaries of the various estimates. <h3>Data Synthesis.</h3> —The most prominent contributors to mortality in the United States in 1990 were tobacco (an estimated 400000 deaths), diet and activity patterns (300 000), alcohol (100 000), microbial agents (90 000), toxic agents (60 000), firearms (35 000), sexual behavior (30 000), motor vehicles (25 000), and illicit use of drugs (20 000). Socioeconomic status and access to medical care are also important contributors, but difficult to quantify independent of the other factors cited. Because the studies reviewed used different approaches to derive estimates, the stated numbers should be viewed as first approximations. <h3>Conclusions.</h3> —Approximately half of all deaths that occurred in 1990 could be attributed to the factors identified. Although no attempt was made to further quantify the impact of these factors on morbidity and quality of life, the public health burden they impose is considerable and offers guidance for shaping health policy priorities. (<i>JAMA</i>. 1993;270:2207-2212)
Insertional inactivation of streptolysin S expression in Streptococcus pyogenes (1983)

The inactivation of a genetic determinant critical for streptolysin S production was accomplished by transfer and insertion of the transposon Tn916 into the DNA of a group A streptococcal strain. The group D strain CG110 was able to efficiently transfer Tn916 into the group A strain CS91 when donor and recipient cells were concentrated and incubated together on membrane filters. Among tetracycline-resistant transconjugants, nonhemolytic mutants that no longer produced streptolysin S and retained the capacity to produce streptolysin O were discovered. Hemolytic revertants from these mutants regained tetracycline sensitivity; other revertants still retained a tetracycline resistance phenotype. Hybridization studies employing Tn916 DNA located Tn916 sequences in EcoRI and HindIII fragments of DNA from mutants devoid of streptolysin S; one carried a single copy of Tn916, and the other two carried multiple copies of the transposon.
Detection of vertical root fractures in intact and endodontically treated premolar teeth by designing a probabilistic neural network: an ex vivo study (2016)

The designed neural network can be used as a proper model for the diagnosis of VRFs on CBCT images of endodontically treated and intact teeth; in this context, CBCT images are more effective than similar periapical radiographs. Limitations of this study are the use of sound one-rooted premolar teeth without carious lesions and dental fillings and not simulating the adjacent anatomic structures. Further in vitro work using a full-skull simulation for CBCT and skin/bone simulation is needed.
The neurotrophic factor concept: a reexamination (1993)

The neurotrophic factor concept in its basic form envisages that innervated tissues produce a signal for the innervating neurons for the selective limitation of neuronal death occurring during development (Purves, 1986; Oppenheim, 1991). This concept arose several decades ago on the basis of the observation that experimental manipulation of the amount of target tissue could modulate the size of neuronal populations. By making the survival of neurons dependent on their target, nature would provide a means to match neuron and target cell populations. NGF, discovered in the 1950s, represents the first known molecular realization of the neurotrophic factor concept. NGF was found to regulate survival, neurite growth, and neurotransmitter production of a particular neuronal type, the sympathetic neurons of the PNS. NGF produced by target cells is specifically bound and internalized by sympathetic neurons, followed by retrograde axonal transport of NGF to the cell soma, where NGF exerts its effects via the cotransported receptor molecule (Levi-Montalcini, 1987; Thoenen et al., 1987). Strictly speaking, increased neurite growth and neurotransmitter production are not trophic effects; however, I will use the term "neurotrophic" in the extended meaning of enhancing neuronal differentiation as well as neuronal survival. It was expected that these results could be generalized to a model of multiple, mutually independent, retrograde trophic messengers, which are synthesized in distinct target areas and act on restricted neuronal types (Fig. 1). This assumption leads to a conceptually simple way to arrange and maintain a variety of neuronal subsystems. One might call this a modular approach to the construction of the nervous system. The hypothesis of multiple retrograde signals has gained widespread experimental support in recent years. Originally proposed for the PNS, the model could be extended to the CNS, in which target neurons synthesize trophic factors for their afferent neurons (Ernfors et al., 1990b). In addition to NGF, a family of NGF-related molecules (now commonly called neurotrophins), which are thought to exert retrograde trophic influences (DiStefano et al., 1992), has been identified.
Photoconductivity of Ultrathin Zinc Oxide Films (1994)

Electrical and photoelectrical properties of nondoped and doped zinc oxide films coated on glass plates by the dip-coating method are investigated at room temperature in various ambient atmospheres. The dark conductivity of the nondoped films exponentially decreased with decreasing film thickness while the conductivity under illumination of 350 nm light was almost constant at 10 0 S·cm -1 irrespective of the film thickness. Consequently thinner films showed larger photoresponse than thicker films. This thickness dependence is explained by the variation of ZnO particle size with the film thickness (fine particle model) and the additional effect of the Schottky barrier generated between the film and gold electrodes.
Anterior Compartment Pressures in Patients with Tibial Fractures (1980)

Twenty patients with tibial fractures had measurements of tissue pressure in the anterior compartment acutely and for the first 72 hours following injury. Measurements were made using a mercury monometric indicator similar to that described by Whitesides. Patients with fractures of the proximal third of the tibia, those with displacement of the fracture fragments greater than 50%, and those whose injury was the result of high-energy trauma developed higher compartment pressures and we conclude that such patients should be observed closely for the development of a compartment syndrome. In normotensive patients in this series fasciotomy was not necessary for tissue pressures less than 50 mm Hg in the absence of any sensory or motor compromise.
In the absence of endogenous IFN-gamma, mice develop unimpaired IL-12 responses to Toxoplasma gondii while failing to control acute infection (1996)

The relationship between IFN-gamma and IL-12 in generating innate immune responses and resistance to acute Toxoplasma gondii infection was assessed in T. gondii-exposed IFN-gamma knockout (gko) mice. Gko mice, in contrast to wild-type (wt) animals, rapidly succumbed to infection with either the avirulent ME49 strain or, surprisingly, an attenuated temperature-sensitive mutant strain, ts4. Microscopic examination of peritoneal exudates from infected gko mice demonstrated that mortality is associated with unchecked tachyzoite replication. Nevertheless, both wt and gko animals developed a peritoneal inflammatory response that in gko animals was greater due to a 5- to 10-fold increase in the number of granulocytes recruited to the site of infection. In addition, IL-12 production in gko mice was both unimpaired and functional since a significant, albeit lower than wt, IL-12-dependent NK cell response developed in these animals. Regardless, no evidence for an IFN-gamma-independent protective function for IL-12 or NK cells was apparent since in vivo treatment of gko mice with an IL-12-neutralizing mAb ablated the NK cell response, but did not decrease survival. Together, these data identify distinct functions for IL-12 and IFN-gamma in host resistance to T. gondii: IL-12 precedes and initiates synthesis of IFN-gamma, while the latter lymphokine directly controls parasite growth and diminishes the contribution of IL-4- and IL-5-producing T cell subsets.
강원, 충남지역의 농한기 농촌 노인의 급식식단 개발과 적용 (2009)

Meal menus were developed and applied for rural elderly of Gangwon and Chungnam areas at agricultural off-season. Amounts of the major nutrients of carbohydrate, protein, lipid, and calorie considered in the menu based on the dietary reference intakes(DRI) of the elderly aged over 65 years were 97.5g, 22.5g, 13.3g, and 600㎉, respectively. In Chungnam, softness and overall acceptance of rice in menu 4, consisted of cereals and rice, kimchi stew with tuna, pan-fried bulgogi mushroom, seasoned dropwort carrot, kimchi, and banana, scored the highest values of 8.5 out of 9.0point hedonic scale (p＜0.05). In Gangwon, soup and side dish of menu 3 (rice, frozen pollack pot stew, meatball fried in egg, seasoned sea lettuce, and banana) scored significantly the highest of all (p＜0.05). Overall acceptance of all the menus were high over 7.8 without significance in Chungnam. Overall acceptance of the menu 3 scored significantly the highest with value of 8.5 and menu 4 (rice, spicy chicken soup, seasoned bean sprouts, broiled brown seaweed trunk, kimchi, tomato) had significantly the lowest value with value of 7.8 in Gangwon(p＜0.05). The total leftover volume of menu 4 was significantly the highest with score of 56g and the menu 4 showed the highest unit cost of 2,900won in Chungnam. However, the total leftover volume of all menus did not show significance ranging from 9g to 19g in Gangwon.
Making CAPTCHAs clickable (2008)

We show how to convert regular keyboard-entry CAPTCHAs into clickable CAPTCHAs. The goal of this conversion is to simplify and speed-up the entry of the CAPTCHA solution, to minimize user frustration and permit the use of CAPTCHAs on devices where they would otherwise be unsuitable. We propose a technique for producing secure clickable CAPTCHAs that are well suited for use on cell phones and other mobile devices. We support the practical viability of our approach by results from a user study, and an analysis of its security guarantees.
Roles of Chemokine CXCL12 and its Receptors in Ischemic Stroke (2012)

Chemokine CXC ligand 12 (CXCL12), originally named stromal cell-derived factor-1 (SDF-1), is a member of the CXC chemokine subfamily. CXCL12 is found to be expressed by all cell types that are presented in the central nervous system (CNS). It works in conjunction with the G-protein coupled receptor CXCR4, which is found at the surface of a variety of cells including neurons, astrocytes, microglia, bone marrow-derived cells, as well as other progenitor cells. Recent studies revealed that CXCL12 could also bind and signal through receptor CXCR7. CXCL12 and CXCR4 are constitutively expressed in the brain but are up-regulated in the ischemic penumbra regions following ischemic stroke. CXCL12/CXCR4 play important roles in multiple processes after ischemic stroke, which include inflammatory response, focal angiogenesis, and the recruitment of bone marrow-derived cells (BMCs) and neural progenitor cell (NPC) to injury. In addition to its roles in stroke pathology, CXCL12 is also thought to be a key regulator in stroke repairing. This review will focus on the function of CXCL12/CXCR4 in post-stroke inflammation and neurovascular repairing. The potential application of CXCL12 modulation in clinical stroke treatment is also discussed.
Use of Endotoxin in Cancer Immunotherapy and Characterization of Its Nontoxic but Active Lipid A Components (1983)

When crude endotoxin from the heptose-less mutant of Salmonella typhimurium is combined with trehalose dimycolate from mycobacteria in oil droplets and injected directly into established tumors (line 10 hepatocellular carcinoma) in syngeneic guinea pigs, rapid regression of the tumors occurs and over 90% of the animals are cured. The three required components for activity in this tumor model are: (a) the endotoxin; (b) the mycobacterial adjuvant, trehalose dimycolate; and (c) a compound satisfying the minimal structural requirement (muramyl dipeptide) for adjuvant activity by bacterial cell wall materials. The mycobacterial cell wall skeleton is able to replace the latter two components. Since endotoxin is very toxic to humans, a method was sought to render it nontoxic and yet retain its tumor regression activity. We detoxified endotoxic extracts and diphosphoryl lipid A obtained from S. typhimurium G30/C21 by controlled acid hydrolysis to yield a product that retained the ability to synergistically enhance
Second-generation antipsychotics in major depressive disorder: update and clinical perspective (2010)

Both SGA monotherapy and adjunctive therapy showed greater efficacy in the treatment of MDD than placebo, but augmentation is more widely utilized in treatment-resistant depression. Clinicians should routinely monitor for cardiometabolic side-effects and extrapyramidal symptoms during SGA therapy.
The SmgGDS Splice Variant SmgGDS-558 Is a Key Promoter of Tumor Growth and RhoA Signaling in Breast Cancer (2013)

This study defines a new mechanism to regulate the activities of RhoA and NF-κB in breast cancer cells, and identifies SmgGDS-558 as a novel promoter of breast cancer malignancy.
Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival (2005)

Based on the hypothesis that features of the molecular program of normal wound healing might play an important role in cancer metastasis, we previously identified consistent features in the transcriptional response of normal fibroblasts to serum, and used this “wound-response signature” to reveal links between wound healing and cancer progression in a variety of common epithelial tumors. Here, in a consecutive series of 295 early breast cancer patients, we show that both overall survival and distant metastasis-free survival are markedly diminished in patients whose tumors expressed this wound-response signature compared to tumors that did not express this signature. A gene expression centroid of the wound-response signature provides a basis for prospectively assigning a prognostic score that can be scaled to suit different clinical purposes. The wound-response signature improves risk stratification independently of known clinico-pathologic risk factors and previously established prognostic signatures based on unsupervised hierarchical clustering (“molecular subtypes”) or supervised predictors of metastasis (“70-gene prognosis signature”).
Animal and human antibodies to distinct Staphylococcus aureus antigens mutually neutralize opsonic killing and protection in mice (2010)

New prophylactic approaches are needed to control infection with the Gram-positive bacterium Staphylococcus aureus, which is a major cause of nosocomial and community-acquired infections. To develop these, greater understanding of protective immunity against S. aureus infection is needed. Human immunity to extracellular Gram-positive bacterial pathogens is primarily mediated by opsonic killing (OPK) via antibodies specific for surface polysaccharides. S. aureus expresses two such antigens, capsular polysaccharide (CP) and poly-N-acetyl glucosamine (PNAG). Here, we have shown that immunization-induced polyclonal animal antisera and monoclonal antibodies specific for either CP or PNAG antigens have excellent in vitro OPK activity in human blood but that when mixed together they show potent interference in OPK activity. In addition, reductions in antibody binding to the bacterial surface, complement deposition, and passive protection were seen in two mouse models of S. aureus infection. Electron microscopy, isothermal calorimetry, and surface plasmon resonance indicated that antibodies to CP and PNAG bound together via an apparent idiotype-anti-idiotype interaction. This interaction was also found in sera from humans with S. aureus bacteremia. These findings suggest that the lack of effective immunity to S. aureus infections in humans could be due, in part, to interference in OPK when antibodies to CP and PNAG antigens are both present. This information could be used to better design S. aureus vaccine components.
Direct tissue analysis using matrix‐assisted laser desorption/ionization mass spectrometry: practical aspects of sample preparation (2003)

Practical guidelines for the preparation of tissue sections for direct analysis by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry are presented. Techniques for proper sample handling including tissue storage, sectioning and mounting are described. Emphasis is placed on optimizing matrix parameters such as the type of matrix molecule used, matrix concentration, and solvent composition. Several different techniques for matrix application are illustrated. Optimal instrument parameters and the necessity for advanced data analysis approaches with regards to direct tissue analysis are also discussed.
Myelodysplastic/Myeloproliferative Neoplasms (2009)

Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are rare de novo myeloid neoplasms that exhibit hybrid dysplastic and proliferative features at presentation. This SHP/EAHP Workshop session was uniquely problematic owing to the overlap between MDS/MPNs and both chronic myeloproliferative neoplasms and myelodysplasia. The borderline between MDS/MPNs and overt acute myeloid leukemias was also an issue, mainly related to the accurate and consistent delineation of blast equivalents such as promonocytes. Aside from juvenile myelomonocytic leukemia, genetic features defining specific MDS/MPN subtypes have not been identified. Consequently, there is little change in the 2008 World Health Organization classification of MDS/MPNs compared with the 2001 version.
Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel (2008)

Influenza A and B viruses contain proton-selective ion channels, A/M2 and BM2, respectively, and the A/M2 channel activity is inhibited by the drugs amantadine and its methyl derivative rimantadine. The structure of the pore-transmembrane domain has been determined by both x-ray crystallography [Stouffer et al. (2008) Nature 451:596-599] and by NMR methods [Schnell and Chou (2008) Nature 451:591-595]. Whereas the crystal structure indicates a single amantadine molecule in the pore of the channel, the NMR data show four rimantadine molecules bound on the outside of the helices toward the cytoplasmic side of the membrane. Drug binding includes interactions with residues 40-45 with a polar hydrogen bond between rimantadine and aspartic acid residue 44 (D44) that appears to be important. These two distinct drug-binding sites led to two incompatible drug inhibition mechanisms. We mutagenized D44 and R45 to alanine as these mutations are likely to interfere with rimantadine binding and lead to a drug insensitive channel. However, the D44A channel was found to be sensitive to amantadine when measured by electrophysiological recordings in oocytes of Xenopus laevis and in mammalian cells, and when the D44 and R45 mutations were introduced into the influenza virus genome. Furthermore, transplanting A/M2 pore residues 24-36 into BM2, yielded a pH-activated chimeric ion channel that was partially inhibited by amantadine. Thus, taken together our functional data suggest that amantadine/rimantadine binding outside of the channel pore is not the primary site associated with the pharmacological inhibition of the A/M2 ion channel.
Structures, Reactivities, and Antibiotic Properties of the Marinopyrroles A−F (2010)

Cultivation of actinomycete strain CNQ-418, retrieved from a deep ocean sediment sample off the coast of La Jolla, CA, has provided marinopyrroles A-F. Sharing just 98% 16S rRNA gene sequence identity with S. sannurensis, the strain likely represents a new Streptomyces species. The metabolites contain an unusual 1,3'-bipyrrole core decorated with several chlorine and bromine substituents and possess marked antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The congested N,C-biaryl bond establishes an axis of chirality that, for marinopyrroles A-E, is configurationally stable at room temperature. Moreover, the natural products are fashioned strictly in the M-configuration. The Paal-Knorr condensation was adapted for the synthesis of the 1,3'-bipyrrole core. Halogenation of this material with N-bromosuccinimide cleanly furnished the 4,4',5,5'-tetrahalogenated core that characterizes this class of marine-derived metabolites.
Gene Transfer In Vivo with DNA–Liposome Complexes: Lack of Autoimmunity and Gonadal Localization (1992)

Direct gene transfer into localized arterial segments can be performed in vivo by transfection with DNA-liposome complexes. This technique holds promise for the treatment of human diseases, including malignancy and cardiovascular disorders. We have previously characterized the potential toxicity of this form of treatment in mice in vivo (Stewart et al., 1992). In this report, we examined two issues relevant to long-term expression of foreign recombinant genes: (i) the potential for autoimmune damage to major organs and (ii) DNA localization in gonadal tissue. Autoimmunity and toxicity of allogeneic major histocompatibility (MHC) gene transfer was assessed in mice after induction of an immune response to a recombinant murine class I MHC gene by direct gene transfer in vivo. Histological examination of brain, heart, lung, liver, kidney, spleen, and skeletal muscle revealed no clinically significant immunopathology or organ damage. The toxicity of gene delivery by DNA liposomes was also analyzed in pigs and rabbits in vivo. No histopathology was observed following the introduction of plasmids encoding several different gene products, and analysis of serum following DNA liposome delivery revealed no abnormalities of serum biochemical parameters. The potential for transfer of recombinant DNA into testes and ovary in animals was evaluated by the polymerase chain reaction. Although evidence of recombinant plasmid was consistently observed in transfected, but not untransfected, arterial sites and occasionally in lung, kidney, spleen, and liver, no plasmid DNA was detected in testes or ovary. These studies suggest that uptake of recombinant DNA following direct gene transfer by liposomal transfection in major organs is not associated with autoimmunity, toxicity, or gonadal localization.(ABSTRACT TRUNCATED AT 250 WORDS)