gebhart/patrepeval huggingface dataset:
Recent Advances in Antiretroviral Therapy and HIV Infection Monitoring (1997)

Potent new antiretroviral drugs combined with updated treatment strategies have now achieved efficient inhibition of HIV replication in most patients. The major targets for antiretroviral therapy are the reverse transcriptase and the protease of HIV. Up to date, 11 antiretroviral drugs have been licensed in the US. New nucleoside reverse transcriptase inhibitors (NRTI), i.e. abacavir, and adefovir dipivoxil proved to be effective in clinical trials. The antiretroviral activity and impact on clinical outcome of nonnucleoside reverse transcriptase inhibitors (NNRTI) are mostly short lived. Compared to NRTIs, protease inhibitors (PIs) have the highest antiretroviral activity. New PIs that conserve activity against mutant HIV strains or derivatives that have a simpler biosynthesis are being developed. A major drawback of highly active antiretroviral therapy is the selection of resistant mutants under suboptimal dosage, in advanced stages of disease or after pre-treatment with mono- or double-combination regimens. Monitoring of antiretroviral therapy is achieved by measurement of viral load using nucleic acid amplification techniques. The goal of antiretroviral therapy should be to reduce viral load below the detection limit of current assays in order to delay the emergence of resistant mutants and to maximally reduce disease progression. Recommendations for antiretroviral therapy and monitoring are evolving constantly due to the rapid progress in the development of active compounds and new insights into HIV pathogenesis. Resistance determination of HIV patient isolates seems to play a progressively increasing role in monitoring of antiretroviral treatment since treatment-naive patients may already harbour drug-resistant virus. Due to cross-resistance between different compounds, the choice of the treatment regimen should be guided by resistance patterns of HIV in order to warrant maximal and long-lasting efficiency.
Uterine and ovarian carcinosarcomas overexpressing Trop-2 are sensitive to hRS7, a humanized anti-Trop-2 antibody (2011)

Trop-2 is overexpressed in a proportion of UMMT and OMMT, and hRS7 may represent a novel, potentially highly effective treatment option for patients with treatment-refractory carcinosarcomas overexpressing Trop-2.
The neurobiology of neuropsychiatric syndromes in dementia (2006)

Neuropsychiatric disturbances are a core feature of dementia and worsen many clinical outcomes. Among the most validated syndromes are depression, psychosis, and sleep disturbance of Alzheimer's disease. Neuropathology, neuroimaging, and genetic studies increasingly provide insight into the origins of these psychiatric symptoms in dementia.
Development of Light‐Activated CRISPR Using Guide RNAs with Photocleavable Protectors (2016)

The ability to remotely trigger CRISPR/Cas9 activity would enable new strategies to study cellular events with greater precision and complexity. In this work, we have developed a method to photocage the activity of the guide RNA called "CRISPR-plus" (CRISPR-precise light-mediated unveiling of sgRNAs). The photoactivation capability of our CRISPR-plus method is compatible with the simultaneous targeting of multiple DNA sequences and supports numerous modifications that can enable guide RNA labeling for use in imaging and mechanistic investigations.
Architectural support for copy and tamper resistant software (2000)

Although there have been attempts to develop code transformations that yield tamper-resistant software, no reliable software-only methods are know. This paper studies the hardware implementation of a form of execute-only memory (XOM) that allows instructions stored in memory to be executed but not otherwise manipulated. To support XOM code we use a machine that supports internal compartments---a process in one compartment cannot read data from another compartment. All data that leaves the machine is encrypted, since we assume external memory is not secure. The design of this machine poses some interesting trade-offs between security, efficiency, and flexibility. We explore some of the potential security issues as one pushes the machine to become more efficient and flexible. Although security carries a performance penalty, our analysis indicates that it is possible to create a normal multi-tasking machine where nearly all applications can be run in XOM mode. While a virtual XOM machine is possible, the underlying hardware needs to support a unique private key, private memory, and traps on cache misses. For efficient operation, hardware assist to provide fast symmetric ciphers is also required.
Pulse-spray pharmacomechanical thrombolysis of thrombosed hemodialysis access grafts: long-term experience and comparison of original and current techniques. (1995)

Pulse-spray pharmacomechanical thrombolysis is a reliable, rapid, and safe method for recanalization of occluded dialysis grafts. The current technique has been proven as safe and effective as the original technique but offers the advantage of a significant reduction in the time required for the infusion of thrombolytic agent.
Investigating Mechanisms of Alkalinization for Reducing Primary Breast Tumor Invasion (2013)

The extracellular pH (pHe) of many solid tumors is acidic as a result of glycolytic metabolism and poor perfusion. Acidity promotes invasion and enhances metastatic potential. Tumor acidity can be buffered by systemic administration of an alkaline agent such as sodium bicarbonate. Tumor-bearing mice maintained on sodium bicarbonate drinking water exhibit fewer metastases and survive longer than untreated controls. We predict this effect is due to inhibition of tumor invasion. Reducing tumor invasion should result in fewer circulating tumor cells (CTCs). We report that bicarbonate-treated MDA-MB-231 tumor-bearing mice exhibited significantly lower numbers of CTCs than untreated mice (P < 0.01). Tumor pHe buffering may reduce optimal conditions for enzymes involved in tumor invasion such as cathepsins and matrix metalloproteases (MMPs). To address this, we tested the effect of transient alkalinization on cathepsin and MMP activity using enzyme activatable fluorescence agents in mice bearing MDA-MB-231 mammary xenografts. Transient alkalinization significantly reduced the fluorescent signal of protease-specific activatable agents in vivo (P ≤ 0.003). Alkalinization, however, did not affect expression of carbonic anhydrase IX (CAIX). The findings suggest a possible mechanism in a live model system for breast cancer where systemic alkalinization slows the rate of invasion.
TheRET/PTCOncogene Is Frequently Activated in Oncocytic Thyroid Tumors (Hurthle Cell Adenomas and Carcinomas), but Not in Oncocytic Hyperplastic Lesions (2002)

Hurthle cell adenomas and carcinomas, characterized by the presence of oncocytic cells, are unusual thyroid neoplasms, the treatment of which is still controversial. We analyzed specimens from 49 patients with oncocytic cell nodular lesions including 20 adenomas, 19 carcinomas, and 10 hyperplasias for RET/PTC (papillary thyroid carcinoma) activation, which is the most frequent genetic alteration in PTCs. RET/PTC activation was detected in a significant number of cases of Hurthle cell adenomas and carcinomas, but in 0 of 10 patients with hyperplastic nodules. In particular, the RET/PTC1 isoform was found in 7 of 12 adenomas and 4 of 7 carcinomas. These results would indicate that RET/PTC is a genetic event common to papillary carcinomas and to Hurthle cell neoplasias.
Thromboembolism after insertion of the Mobin-Uddin caval filter. (1980)

The occurrence, in one patient, of a life-threatening pulmonary embolus 3 days following insertion of a Mobin-Uddin umbrella filter promoted a review of our experience with this device. Over the past 5 years, 41 patients had umbrella filters inserted at the Beth Israel Hospital. Five patients (12%) had proven or probable pulmonary embolization following filer placement. In four of the seven autopsied patients, thrombus was found on the cardiac side of the umbrella, and in one of these patients a fresh embolus was also found in the pulmonary artery. We conclude that the standard (nonheparin-impregnated) Mobin-Uddin umbrella device offers incomplete protection against pumonary embolization in patients who cannot concurrently receive anticoagulant drugs.
Cell Membrane Proteomic Analysis Identifies Proteins Differentially Expressed in Osteotropic Human Breast Cancer Cells (2008)

Metastatic breast cancer cells are characterized by their high propensity to colonize the skeleton and form bone metastases, causing major morbidity and mortality. Identifying key proteins involved in the osteotropic phenotype would represent a major step toward the development of both new prognostic markers and new effective therapies. Cell surface proteins differentially expressed in cancer cells are preferred potential targets for antibody-based targeted therapies. In this study, using cell surface biotinylation and a mass spectrometric approach, we have compared the profile of accessible cell surface proteins between the human breast cancer cell line MDA-MB-231 and its highly osteotropic B02 subclone. This strategy allowed the identification of several proteins either up- or downregulated in the osteotropic cell line, and differential protein expressions were validated using antibody-based techniques. Class I HLAs were down-regulated in the bone metastatic variant, whereas alpha(v)beta(3) integrins, among others, were consistently up-regulated in this latter cell line. These results show that comprehensive profiling of the cell surface proteome of mother cancerous cell lines and derived organ-specific metastatic cell lines provides an effective approach for the identification of potential accessible marker proteins for both prognosis and antibody-based targeted therapies.
Detection of Mutations in EGFR in Circulating Lung-Cancer Cells (2008)

Molecular analysis of circulating tumor cells from the blood of patients with lung cancer offers the possibility of monitoring changes in epithelial tumor genotypes during the course of treatment.
The Clinical Course of Patients with Suspected Pulmonary Embolism and a Negative Pulmonary Arteriogram (1978)

Selective pulmonary arteriography, with superselective magnification views of the lung bases or other areas where abnormalities are shown on perfusion lung scans, performed within 24-48 hours after the onset of symptoms, can effectively rule out clinically significant pulmonary thromboembolism. One hundred and eighty consecutive patients (minimum follow up, six months) with suspected pulmonary embolism and negative pulmonary arteriograms were studied. Not one of the 167 untreated patients died as a result of thromboembolic disease during the acute illness (20 died from unrelated causes), and none of the 147 patients who survived suffered "recurrent embolism" during follow up.
Use of pulse transit time as a measure of inspiratory effort in patients with obstructive sleep apnoea (1995)

Pulse transit time (PTT) is the time taken for the arterial pulse pressure wave to travel from the aortic valve to a peripheral site. For convenience, it is usually measured from the R wave on the electrocardiogram to the pulse wave arrival at the finger. Pulse transit time is inversely proportional to blood pressure, and the falls in blood pressure which occur with inspiration (pulsus paradoxus) correspond to rises (lengthening) in pulse transit time. In awake normal subjects, the size of these inspiratory rises in pulse transit time correlate well with the degree of inspiratory effort. The aim of this study was to investigate whether inspiratory rises in pulse transit time could provide a quantitative measure of inspiratory effort in patients with obstructive sleep apnoea. Eight patients with obstructive sleep apnoea, attending the laboratory for institution of nasal continuous positive airway pressure, took part in the study. Once asleep, airway pressure was varied between optimal treatment level and minimum pressure, to produce a range of inspiratory efforts whilst continuous recordings of oesophageal pressure and pulse transit time were made. There was an excellent correlation between the size of the swings in oesophageal pressure and the size of the swings in pulse transit time (mean r = 0.94). Pulse transit time may, therefore, provide a clinically useful noninvasive and quantitative measure of inspiratory effort in patients with sleep-related breathing disorders.
Robotics for Surgery (1999)

Robotic technology is enhancing surgery through improved precision, stability, and dexterity. In image-guided procedures, robots use magnetic resonance and computed tomography image data to guide instruments to the treatment site. This requires new algorithms and user interfaces for planning procedures; it also requires sensors for registering the patient's anatomy with the preoperative image data. Minimally invasive procedures use remotely controlled robots that allow the surgeon to work inside the patient's body without making large incisions. Specialized mechanical designs and sensing technologies are needed to maximize dexterity under these access constraints. Robots have applications in many surgical specialties. In neurosurgery, image-guided robots can biopsy brain lesions with minimal damage to adjacent tissue. In orthopedic surgery, robots are routinely used to shape the femur to precisely fit prosthetic hip joint replacements. Robotic systems are also under development for closed-chest heart bypass, for microsurgical procedures in ophthalmology, and for surgical training and simulation. Although results from initial clinical experience is positive, issues of clinician acceptance, high capital costs, performance validation, and safety remain to be addressed.
Immune Checkpoints as Therapeutic Targets in Autoimmunity (2018)

Antibodies that block the immune checkpoint receptors PD1 and CTLA4 have revolutionized the treatment of melanoma and several other cancers, but in the process, a new class of drug side effect has emerged-immune related adverse events. The observation that therapeutic blockade of these inhibitory receptors is sufficient to break self-tolerance, highlights their crucial role in the physiological modulation of immune responses. Here, we discuss the rationale for targeting immune checkpoint receptors with agonistic agents in autoimmunity, to restore tolerance when it is lost. We review progress that has been made to date, using Fc-fusion proteins, monoclonal antibodies or other novel constructs to induce immunosuppressive signaling through these pathways. Finally, we explore potential mechanisms by which these receptors trigger and modulate immune cell function, and how understanding these processes might shape the design of more effective therapeutic agents in future.
Antirheumatic Agents:  Novel Methotrexate Derivatives Bearing a Benzoxazine or Benzothiazine Moiety (1997)

Novel methotrexate (MTX) derivatives bearing dihydro-2H-1,4-benzothiazine or dihydro-2H-1,4-benzoxazine were synthesized and tested for in vitro antiproliferative activities against human synovial cells (hSC) and human peripheral blood mononuclear cells (hPBMC) obtained from patients with rheumatoid arthritis and healthy volunteers, respectively. In vivo antiarthritic activities of these derivatives were also evaluated in a rat adjuvant arthritis model. N-[[4-[(2,4-Diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzothiazin-7-yl]carbonyl]-L-glutamic acid (3c) exhibited more potent antiproliferative activities in hSC and hPBMC than MTX in vitro. Antiproliferative activities of N-[[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzoxazin-7-yl]carbonyl]-L-homoglutamic acid (3b) and N-[[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzothiazin-7-yl]carbonyl]-L-homoglutamic acid (3d) (MX-68) were comparable to that of MTX in these in vitro assays. Compounds 3b,d (MX-68) significantly suppressed progression of the adjuvant arthritis in a dose-dependent manner ranging from 0.5 to 2.5 mg/kg (po). In addition, 3d (MX-68) completely suppressed this progression at the dose of 2.5 mg/kg (po). Importantly, 3d (MX-68) having benzothiazine and homoglutamate, as expected, did not undergo polyglutamation, a process which may be responsible for the associated side effects of MTX. These results suggest that 3d (MX-68) is a potent and safe candidate antirheumatic agent, absent of the side effects of MTX.
Interleukin-12 in infectious diseases. (1997)

Interleukin-12 (IL-12) is a potent immunoregulatory cytokine that is crucially involved in a wide range of infectious diseases. In several experimental models of bacterial, parasitic, viral, and fungal infection, endogenous IL-12 is required for early control of infection and for generation and perhaps maintenance of acquired protective immunity, directed by T helper type 1 (Th1) cells and mediated by phagocytes. Although the relative roles of IL-12 and gamma interferon in Th1-cell priming may be to a significant extent pathogen dependent, common to most infections is that IL-12 regulates the magnitude of the gamma interferon response at the initiation of infection, thus potentiating natural resistance, favoring Th1-cell development; and inhibiting Th2 responses. Treatment of animals with IL-12, either alone or as a vaccine adjuvant, has been shown to prevent disease by many of the same infectious agents, by stimulating innate resistance or promoting specific reactivity. Although IL-12 may enhance protective memory responses in vaccination or in combination with antimicrobial chemotherapy, it is yet unclear whether exogenous IL-12 can alter established responses in humans. Continued investigation into the possible application of IL-12 therapy to human infections is warranted by the role of the cytokine in inflammation, immunopathology, and autoimmunity.
The emerging role of apolipoprotein C-III: beyond effects on triglyceride metabolism (2016)

Apolipoprotein C-III has been referred to as an important participant in the metabolism of triglyceride-rich lipoproteins, leading to hypertriglyceridemia and thereafter cardiovascular disease. Accumulating evidence indicates that apolipoprotein C-III is a multifaceted protein which not only regulates triglyceride metabolism, but also participates in the atherosclerotic lesion formation and several other pathological processes involved in atherosclerosis. Based on data from experiments and clinical trials, some novel therapies such as antisense technology emerge.
How Scholarly Is Google Scholar? A Comparison to Library Databases (2009)

Google Scholar was released as a beta product in November of 2004. Since then, Google Scholar has been scrutinized and questioned by many in academia and the library field. Our objectives in undertaking this study were to determine how scholarly Google Scholar is in comparison with traditional library resources and to determine if the scholarliness of materials found in Google Scholar varies across disciplines. We found that Google Scholar is, on average, 17.6 percent more scholarly than materials found only in library databases and that there is no statistically significant difference between the scholarliness of materials found in Google Scholar across disciplines.
Enhanced Photoluminescence from Si Nano-organosols by Functionalization with Alkenes and Their Size Evolution (2006)

Silicon nanoparticles ranging from 2 to 16 nm were synthesized by a facile wet chemical route, in which SiO amorphous powder was annealed at 1000 °C, etched in hydrofluoric acid, and surface modified by alkene. After alkyl-termination of the particle surfaces, size selective precipitation technique was applied to separate the nanoparticles into uniform sized fractions. Transmission electron microscopy showed well-dispersed and highly crystalline silicon nanoparticles after the treatment by alkene. Visible room-temperature photoluminescence in the range 800−500 nm was observed from these nanoparticles. The photoluminescence intensity has significantly been enhanced by the surface functionalization. Moreover, the PL peak energy of the size-selected nanoparticles shifted to blue as the size decreased due to quantum confinement effect. The experimental result was also compared with the theoretical predictions and was found to follow the general trend of the model calculations.
Distribution and Function of Genes Concerned with Aromatic Biosynthesis in Escherichia coli (1966)

Pittard, James (School of Microbiology, University of Melbourne, Victoria, Australia), and B. J. Wallace. Distribution and function of genes concerned with aromatic biosynthesis in Escherichia coli. J. Bacteriol. 91:1494-1508. 1966.-A number of mutant strains of Escherichia coli K-12, which are blocked in the biosynthesis of the aromatic amino acids, were examined biochemically to determine their particular enzymatic deficiencies. The mutations carried by these strains were mapped by use of the methods of conjugation and transduction. Structural genes for five of the enzymes of the common pathway leading to chorismate and for the two enzymes converting chorismate to phenylpyruvate and p-hydroxyphenylpyruvate, respectively, were identified. Unlike the genes of the tryptophan operon most of these genes are distributed over widely separated regions of the chromosome.
Benzothiadiazole, a novel class of inducers of systemic acquired resistance, activates gene expression and disease resistance in wheat. (1996)

Systemic acquired resistance is an important component of the disease resistance repertoire of plants. In this study, a novel synthetic chemical, benzo(1,2,3)thiadiazole-7-carbothioic acid S-methyl ester (BTH), was shown to induce acquired resistance in wheat. BTH protected wheat systemically against powdery mildew infection by affecting multiple steps in the life cycle of the pathogen. The onset of resistance was accompanied by the induction of a number of newly described wheat chemically induced (WCI) genes, including genes encoding a lipoxygenase and a sulfur-rich protein. With respect to both timing and effectiveness, a tight correlation existed between the onset of resistance and the induction of the WCI genes. Compared with other plant activators, such as 2,6-dichloroisonicotinic acid and salicylic acid, BTH was the most potent inducer of both resistance and gene induction. BTH is being developed commercially as a novel type of plant protection compound that works by inducing the plant's inherent disease resistance mechanisms.
Current medical management of diabetic foot infections (2010)

Foot infections are a serious complication of diabetes associated with substantial morbidity and occasional mortality. Antibiotic therapy for mild infections in patients who have not recently received antibiotic therapy can often be directed at just staphylococci and streptococci. Empiric therapy for infections that are chronic, moderate or severe, or that occur in patients who have failed previous antibiotic treatment, should usually be more broad spectrum. Bone infection also complicates a substantial percentage of diabetic foot wounds and increases the likelihood of treatment failure, requiring lower extremity amputation. An increasing body of evidence supports the effectiveness of nonsurgical treatment of diabetic foot osteomyelitis in selected patients, although the optimal choice of agent, route of administration and duration of therapy have yet to be defined. This article examines the potential role of standard and newer antibiotics that may be appropriate for treating diabetic foot infections, including ertapenem, vancomycin, moxifloxacin, daptomycin, telavancin and tigecycline, as well as several investigational agents, such as dalbavancin, ceftobiprole and nemonoxacin.