gebhart/patrepeval huggingface dataset:
Obstructive sleep apnea screening by integrating snore feature classes (2013)

Obstructive sleep apnea (OSA) is a serious sleep disorder with high community prevalence. More than 80% of OSA suffers remain undiagnosed. Polysomnography (PSG) is the current reference standard used for OSA diagnosis. It is expensive, inconvenient and demands the extensive involvement of a sleep technologist. At present, a low cost, unattended, convenient OSA screening technique is an urgent requirement. Snoring is always almost associated with OSA and is one of the earliest nocturnal symptoms. With the onset of sleep, the upper airway undergoes both functional and structural changes, leading to spatially and temporally distributed sites conducive to snore sound (SS) generation. The goal of this paper is to investigate the possibility of developing a snore based multi-feature class OSA screening tool by integrating snore features that capture functional, structural, and spatio-temporal dependences of SS. In this paper, we focused our attention to the features in voiced parts of a snore, where quasi-repetitive packets of energy are visible. Individual snore feature classes were then optimized using logistic regression for optimum OSA diagnostic performance. Consequently, all feature classes were integrated and optimized to obtain optimum OSA classification sensitivity and specificity. We also augmented snore features with neck circumference, which is a one-time measurement readily available at no extra cost. The performance of the proposed method was evaluated using snore recordings from 86 subjects (51 males and 35 females). Data from each subject consisted of 6-8 h long sound recordings, made concurrently with routine PSG in a clinical sleep laboratory. Clinical diagnosis supported by standard PSG was used as the reference diagnosis to compare our results against. Our proposed techniques resulted in a sensitivity of 93±9% with specificity 93±9% for females and sensitivity of 92±6% with specificity 93±7% for males at an AHI decision threshold of 15 events/h. These results indicate that our method holds the potential as a tool for population screening of OSA in an unattended environment.
The SERCA pump as a therapeutic target: Making a “smart bomb” for prostate cancer (2005)

Prostate cancer is uniformly fatal once it has spread outside of the prostate gland. Prostate cancers have a remarkably low proliferative rate, which may in part explain their relative unresponsiveness to conventional antiproliferative chemotherapy. New therapies for prostate cancer that activate proliferation independent cell death are therefore needed. The endoplasmic reticulum (ER) has emerged as an organelle that plays a major role in cell signaling pathways, cellular response to stress and cellular activation of apoptosis. In this review, the SERCA pump is identified as an ER protein whose normal function is required by all cells and represents a potential therapeutic target for cancer therapy. Sustained SERCA inhibition by agents such as thapsigargin results in activation of ER-stress response and simultaneous activation of apoptotic pathways within the ER and the mitochondria. Due to the SERCA pump's critical role in normal cellular metabolism, agents like thapsigargin directed toward inhibiting SERCA function would likely produce significant toxicity to normal cells and, therefore, must be selectively targeted to cancer sites. The cytotoxicity of thapsigargin can be attenuated, however by coupling to a targeting peptide to produce an inactive prodrug that is only activated by prostate cancer specific proteases such as the serine protease prostate-specific antigen (PSA). PSA-activated thapsigargin prodrugs have been characterized that are selectively toxic to PSA-producing prostate cancer cells in vitro and in vivo. These prodrugs are currently undergoing preclinical evaluation as potential targeted therapy for prostate cancer.
Early Increases in Breast Tumor Xenograft Water Mobility in Response to Paclitaxel Therapy Detected by Non-Invasive Diffusion Magnetic Resonance Imaging (1999)

An important goal in cancer chemotherapy is to sensitively and quantitatively monitor the response of individual patients' tumors to successful, or unsuccessful, therapy so that regimens can be altered iteratively. Currently, tumor response is monitored by frank changes in tumor morphology, yet these markers take long to manifest and are not quantitative. Recent studies suggest that the apparent diffusion coefficient of water (ADCw), measured noninvasively with magnetic resonance imaging, is sensitively and reliably increased in response to successful CTx. In the present study, we investigate the combination chemotherapy response of human breast cancer tumor xenografts sensitive or resistant to Paclitaxel by monitoring changes in the ADCw. Our results indicate that there is a clear, substantial, and early increase in the ADCw after successful therapy in drug sensitive tumors and that there is no change in the ADCw in p-glycoprotein-positive tumors, which are resistant to Paclitaxel. The mechanism underlying these changes is unknown yet is consistent with apoptotic cell shrinkage and a concomitant increase in the extracellular water fraction.
Expert opinion on available options treating pulmonary arterial hypertension (2007)

Until in the early nineties, pulmonary arterial hypertension (PAH) was a uniformly fatal disease, with a median life expectancy of approximately 2.5 years. Uncontrolled studies showed that a small proportion of patients responded to high-dose calcium channel blockers, retrospective studies supported the use of anticoagulant therapy and heart-lung or lung transplantation remained the only option. In 1996, a 3-month randomised, placebo-controlled trial showed that chronic intravenous epoprostenol (synthetic prostacyclin) improved functional state, exercise capacity, haemodynamics, and even survival in patients with idiopathic PAH. Similar benefits were subsequently reported and extended to all PAH categories, and confirmed with more stable prostacyclin analogues administered subcutaneously (treprostinil), by inhalation (iloprost), or even orally (beraprost). In the early 2000s, two randomised controlled trials showed efficacy of the oral intake of the dual endothelin A/B receptor antagonist bosentan. Two selective endothelin-A receptor antagonists, sitaxsentan and ambrisentan, are being developed. Finally, a randomised controlled trial has established the therapeutic efficacy of phosphodiesterase-5 inhibition with sildenafil, introducing a third signalling pathway to be targeted by the pharmacological treatment of PAH. Another phosphodiesterase-5 inhibitor, tadalafil, is already being evaluated. While all these treatments have markedly improved the lives of PAH patients, they have not offered yet a cure of the disease. Multi-drug approaches are now under evaluation, with more ambitious therapeutic goals. Alternative approaches with stem cells, RhoA-Rho-kinase inhibitors, platelet derived growth factor inhibitors and vasoactive intestinal peptides are being considered.
Programmed Cell Death in Plants. (1997)

Programmed cell death (PCD) is a physiological cell death process involved in the selective elimination of unwanted cells (Ellis et al., 1991). In animals, these unwanted cells include those that have served temporary functions, such as tadpole tail cells at metamorphosis; cells that are overproduced, such as vertebrate neurons; cells that are unwanted or present in inappropriate positions, such as cells between the developing digits and Mullerian duct cells required in females but not males; and cells that die during the process of cell specialization, such as keratinocytes at the surface of the skin (Jacobsen et al., 1997). PCD in specific cell types can also give rise to disease. These cell types include helper T cells, which undergo PCD in AIDS, and selected brain neurons, which die during Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and Lou Gehrig’s disease (Duke et al., 1996). Thus, PCD plays an important role in cell and tissue homeostasis and specialization, tissue sculpting, and disease. PCD in Caenorhabditis elegans and other animals depends on the induction and action of specific genes that bring about the controlled disassembly of a cell (Wadewitz and Lockshin, 1988; Ellis et al., 1991). This disassembly involves the condensation, shrinkage, and fragmentation of the cytoplasm and nucleus and the fragmentation of the nuclear DNA into -50-kb and, in some cases, -0.14-kb pieces that represent oligonucleosomes (Cohen, 1993; Eastman et al., 1994). These DNA fragments can be detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) of DNA 3’-OH groups in sections of cells (Gavrieli et al., 1992). When PCD features marginalization of the chromatin in the nucleus, breakage of the cytoplasm and nucleus into small, sealed packets, and processing and fragmentation of the DNA at nucleosome linker sites, the process is termed apoptosis (Cohen, 1993). However, not all PCD involves all of these changes (Schwartz et al., 1993). Many of the proteins responsible for PCD in animal cells have now been identified. Proteases of the interleukin-1 pconverting enzyme (ICE) family bring about cell condensation and shrinkage (Martin and Green, 1995), and endonucleases cause the fragmentation of nuclear DNA (Eastman et al., 1994). The basic leucine zipper transcription factor ces-2 (for
Radiation Dosimetry of 89Zr-Labeled Chimeric Monoclonal Antibody U36 as Used for Immuno-PET in Head and Neck Cancer Patients (2009)

(89)Zr immuno-PET can be safely used to quantitatively assess biodistribution, uptake, organ residence times, and radiation dose, justifying its further clinical exploitation in the detection of tumors and planning of mAb-based therapy.
Multi-PDZ Domain Protein MUPP1 Is a Cellular Target for both Adenovirus E4-ORF1 and High-Risk Papillomavirus Type 18 E6 Oncoproteins (2000)

A general theme that has emerged from studies of DNA tumor viruses is that otherwise unrelated oncoproteins encoded by these viruses often target the same important cellular factors. Major oncogenic determinants for human adenovirus type 9 (Ad9) and high-risk human papillomaviruses (HPV) are the E4-ORF1 and E6 oncoproteins, respectively, and although otherwise unrelated, both of these viral proteins possess a functional PDZ domain-binding motif that is essential for their transforming activity and for binding to the PDZ domain-containing and putative tumor suppressor protein DLG. We report here that the PDZ domain-binding motifs of Ad9 E4-ORF1 and high-risk HPV-18 E6 also mediate binding to the widely expressed cellular factor MUPP1, a large multi-PDZ domain protein predicted to function as an adapter in signal transduction. With regard to the consequences of these interactions in cells, we showed that Ad9 E4-ORF1 aberrantly sequesters MUPP1 within the cytoplasm of cells whereas HPV-18 E6 targets this cellular protein for degradation. These effects were specific because mutant viral proteins unable to bind MUPP1 lack these activities. From these results, we propose that the multi-PDZ domain protein MUPP1 is involved in negatively regulating cellular proliferation and that the transforming activities of two different viral oncoproteins depend, in part, on their ability to inactivate this cellular factor.
Recombinant Semliki Forest virus particles encoding the prME or NS1 proteins of louping ill virus protect mice from lethal challenge. (1999)

Recombinant Semliki Forest virus (rSFV) vaccines encoding louping ill virus (LIV) genes prME and NS1 were examined. Cells transfected with rSFV-prME RNA showed correct processing of the precursor prME and the release into the medium of M and E proteins in particulate form, whilst rSFV-NS1-transfected cells secreted glycosylated, heat-labile NS1 dimers. Mice immunized with rSFV particles produced antibodies against prME and NS1 that were mainly of the IgG2a subtype, indicating that a T-helper 1 immune response was induced. Immunization with prME- or NS1-encoding particles induced T-cell proliferation. Mice vaccinated intraperitoneally (i.p.) with rSFV-prME and/or rSFV-NS1 were significantly protected from lethal i.p. challenge by two strains of LIV, the virulent LI/31 strain, from which the commercial LIV vaccine is derived, and the less-virulent LI/I antibody-escape variant. Intranasal (i.n.) vaccination was protective for rSFV-prME only against LI/31 challenge and not against challenge with LI/I. Immunization with rSFV-NS1 was protective against i.p. and i.n. challenge with both virus strains when given i.p., but was not protective when given i.n. For unvaccinated mice infected with LIV, all animals showing clinical signs had severe degenerative and inflammatory lesions in the central nervous system. None of the rSFV-vaccinated mice that survived challenge showed central nervous system pathology, with the exception of mild leptomeningitis in a minority of LI/31-infected mice. This suggests that protection following immunization with rSFV must occur at early stages of LIV infection.
CURRICULUM OF CONNECTIVITY: A GROWTH ENVIRONMENT FOR SPECIAL LEARNERS (1988)

Connectivity refers to the web of social links between people and the experiences that arise from those links. Language activities take basic acts of connectivity and create a sense of history and belonging in a classroom community as well as serving as the foundation for educational curriculum. Four levels of connectivity and their impact on educational curriculum are discussed and an effective example of connectivity from a classroom is given to illustrate the critical role of language activities. The difference between connectivity and functional or survival activities is considered. The use of individualized educational program objectives in an environment of connectivity is also discussed. It is concluded that connectivity is an essential part of a child's education and the result of a teacher's assumptions as to how children's life experiences are to be implemented in the classroom.
The effectiveness of subcutaneously implanted epidural ports for relief of severe pain in patients with advanced-stage gynecological cancer: a prospective study (2014)

Morphine administration via SIEP provided excellent pain relief without creating side effects, increased patient quality of life, and contributed to the patient's ability to enjoy life.
Conformation‐activity relationships of cyclo‐constrained µ/δ opioid agonists derived from the N‐terminal tetrapeptide segment of dermorphin/deltorphin (2008)

The N-terminal tetrapeptide segments of dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH(2)) and deltorphin (Tyr-D-Ala-Phe-Asp/Glu-Val-Val-Gly-NH(2)) are agonists at the opioid receptors micro and delta, respectively. [D-Arg(2), Lys(4)]-dermorphin-(1-4) amide (Tyr-D-Arg-Phe-Lys-NH(2), DALDA) and [Dmt(1)]DALDA (where Dmt is 2',6'-dimethyltyrosine) are among the most potent and selective micro-agonists reported to date, both in vitro (having picomolar micro receptor affinity) and in vivo. In this communication, conformation-activity studies of the following four cyclic analogs of DALDA are presented and discussed: the lead peptide S(2),S(4)-cyclo (Tyr-D-Cys-Phe-Cys-NH(2)), constrained by means of an S(4.2)--S(4.4) disulfide between Cys(2) and Cys(4); its two cis and trans C(4.2)--C(4.4)-olefinic dicarba analogs, and the product of saturation of them both. They are potent nonselective or moderately micro-selective opioid agonists in vitro.They have been synthesized and tested earlier [Berezowska I, Chung NN, Lemieux C, Wilkes BC, and Schiller PW, Acta Biochim Polon 53, 2006, 73-76]. We have studied their conformations using NMR and molecular dynamics. With major conformational constraints imposed by the 11-membered ring spanning residues 2-4, they show well defined conformations of this ring, while the exocylic Tyr(1) and Phe(3) side chains still have significant conformational freedom. The more active and selective micro versus delta disulfide and saturated dicarba agonists seem to have in common: (i) their ring structures more flexible than those of the other two and (ii) their ring structures similar to each other and more diverse than those in the other two. Given this and the small size of the peptides having confirmed bioactivity profiles, there is a chance that their conformations determined in solution approach receptor-bound conformations.
Biosynthesis and Function of Modified Bases in Bacteria and Their Viruses (2016)

Naturally occurring modification of the canonical A, G, C, and T bases can be found in the DNA of cellular organisms and viruses from all domains of life. Bacterial viruses (bacteriophages) are a particularly rich but still underexploited source of such modified variant nucleotides. The modifications conserve the coding and base-pairing functions of DNA, but add regulatory and protective functions. In prokaryotes, modified bases appear primarily to be part of an arms race between bacteriophages (and other genomic parasites) and their hosts, although, as in eukaryotes, some modifications have been adapted to convey epigenetic information. The first half of this review catalogs the identification and diversity of DNA modifications found in bacteria and bacteriophages. What is known about the biogenesis, context, and function of these modifications are also described. The second part of the review places these DNA modifications in the context of the arms race between bacteria and bacteriophages. It focuses particularly on the defense and counter-defense strategies that turn on direct recognition of the presence of a modified base. Where modification has been shown to affect other DNA transactions, such as expression and chromosome segregation, that is summarized, with reference to recent reviews.
Molecular and Pathologic Aspects of Endometrial Carcinogenesis (2006)

Endometrial cancer is the most common gynecological malignancy, with 41,000 new cases projected in the United States for 2006. Two different clinicopathologic subtypes are recognized: the estrogen-related (type I, endometrioid) and the non-estrogen-related types (type II, nonendometrioid such as papillary serous and clear cell). The morphologic differences in these cancers are mirrored in their molecular genetic profile with type I showing defects in DNA-mismatch repair and mutations in PTEN, K-ras, and beta-catenin, and type II showing aneuploidy and p53 mutations. This article reviews the genetic aspects of endometrial carcinogenesis and progression. We will define the precursor lesion of type I endometrioid cancer and the role of genetics and estrogen in its progression.
Comprehensive Study of Lateral Grain Growth in Poly-Si Films by Excimer Laser Annealing and Its Application to Thin Film Transistors (1994)

Lateral grain growth in nondoped poly-Si films was studied by using Si thin films (500 Å) with different structures as a starting material for excimer laser crystallization. It was clarified that the lateral grain growth phenomenon (micron-size grains with strong (111) orientation) upon excimer laser annealing was strongly affected by both the microstructure and the orientation of the initial Si thin films. This result supports our previous speculation that the principal driving force of the lateral grain growth phenomenon is surface energy anisotropy. Poly-Si thin-film transistors using these films show a high field effect mobility of 440 cm 2 /V·s, achieved through a low-temperature process below 600° C. This excellent electrical characteristic is thought to be due to the large grain size of poly-Si thin film with controlled orientation, good crystallinity, and a smooth surface.
Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation (2003)

Protein acetylation, especially histone acetylation, is the subject of both research and clinical investigation. At least four small-molecule histone deacetylase inhibitors are currently in clinical trials for the treatment of cancer. These and other inhibitors also affect microtubule acetylation. A multidimensional, chemical genetic screen of 7,392 small molecules was used to discover "tubacin," which inhibits alpha-tubulin deacetylation in mammalian cells. Tubacin does not affect the level of histone acetylation, gene-expression patterns, or cell-cycle progression. We provide evidence that class II histone deacetylase 6 (HDAC6) is the intracellular target of tubacin. Only one of the two catalytic domains of HDAC6 possesses tubulin deacetylase activity, and only this domain is bound by tubacin. Tubacin treatment did not affect the stability of microtubules but did decrease cell motility. HDAC6 overexpression disrupted the localization of p58, a protein that mediates binding of Golgi elements to microtubules. Our results highlight the role of alpha-tubulin acetylation in mediating the localization of microtubule-associated proteins. They also suggest that small molecules that selectively inhibit HDAC6-mediated alpha-tubulin deacetylation, a first example of which is tubacin, might have therapeutic applications as antimetastatic and antiangiogenic agents.
Respiratory Syncytial Virus Infection in Elderly and High-Risk Adults (2005)

RSV infection is an important illness in elderly and high-risk adults, with a disease burden similar to that of nonpandemic influenza A in a population in which the prevalence of vaccination for influenza is high. An effective RSV vaccine may offer benefits for these adults.
Laparoscopic diagnosis of adnexal cystic masses: A 12-year experience with long-term follow-up (1995)

Using cautious management and strict guidelines, laparoscopic diagnosis of adnexal masses appears reliable and safe, allowing immediate and adequate surgical treatment.
Moyamoya Disease in Asia (2012)

Moyamoya disease is a rare cerebrovascular disorder, characterised by progressive stenosis and/or occlusion of the intracranial internal carotid artery and its proximal branches with the development of a basal collateral network. Moyamoya disease has a high prevalence in Asia, particularly in Japan, Korea and China. Ischemic events and intracranial bleeding are the most common clinical manifestation of moyamoya disease. Although the benefi cial effect on hemorrhage is still not clear, revascularisation surgery remains the most effective way to prevent the progression of ischemic symptoms. Moyamoya disease has been investigated by numerous studies since it was fi rst described 50 years ago, many conundrums remain to be solved. In this article, we review the history, epidemiology, aetiology, clinical manifestation, diagnosis and treatment of moyamoya disease. Recent advances and future challenges of moyamoya disease are also discussed.