gebhart/patrepeval huggingface dataset:
Immune Checkpoint Blockade: A New Paradigm in Treating Advanced Cancer (2014)

The approval of the immune checkpoint inhibitor ipilimumab for the treatment of advanced melanoma in 2011 spearheaded the development of other anticancer therapies with immune mechanisms of action, including other immune checkpoint inhibitors. Instead of acting directly on the tumor, these therapies work to "remove the brakes" on the immune system to restore antitumor immune responses. In addition to ipilimumab, which targets the cytotoxic T lymphocyte-associated antigen 4 pathway, several new drugs that target the programmed death-1 pathway are in phase III trials across tumor types, including melanoma, lung cancer, and renal cell carcinoma. In keeping with their unique mechanism of action, these immune checkpoint inhibitors have shown both conventional and unconventional response patterns, including initial apparent tumor progression followed by regression, and adverse events (AEs) that are likely immune-related. Advanced practitioners (APs) treating patients receiving immuno-oncology agents are in a key position to educate patients about expectations with these therapies and to screen patients for AEs and initiate appropriate and timely interventions. This review summarizes current immune checkpoint inhibitor data and provides patient management strategies for APs to optimize patient outcomes with these novel therapies.
Calcium phosphate deposition on titanium surfaces in the presence of fibronectin (2000)

Titanium implants are known to nucleate spontaneously a calcium phosphate (apatite-like) layer when in contact with biological model fluids. The presence of proteins either in solution or pre-adsorbed on the titanium surface may influence the process of calcium phosphate deposition. The role of fibronectin, a protein known to promote cell adhesion in spite of its low concentration in biological fluids, was dissolved in Hanks' balanced salt solution (HBSS) and investigated. Several techniques of surface analysis, namely wettability, XPS, and SEM studies, were applied. The concentration of fibronectin in the HBSS solution was an important parameter in the process of calcium phosphate deposition. Concentrations as low as 0.01 mg/mL did not significantly affect the ionic precipitation; however, if the protein concentration was increased to 0.05 mg/mL, a value still far below the concentration in blood (0.2 mg/mL), the formation of a calcium phosphate layer was strongly inhibited. The influence of fibronectin pre-adsorbed on titanium surface also was investigated. It was found, as in the first case, that the extent of ionic precipitation that occurred during the immersion in HBSS depended on the protein concentration in the NaCl solution used to pre-immerse the titanium sample.
New Molecular Targeted Therapeutic Drugs Clinical Results of Bevacizumab in Non-Small Cell Lung Cancer (NSCLC) (2006)

肺癌による死亡は全癌死の約3分の1を占め，乳癌，前立腺癌及び結腸癌による死亡を総合した数よりも多い．肺癌を発症した患者の約85％はその疾患により死亡する．ヒト化抗VEGF MAb（モノクローナル抗体）であるベバシズマブ（bevacizumab; AvastinTM）のこの肺癌における臨床成績を紹介する． 肺癌における化学療法と組合せたベバシズマブの安全性ならびに有効性の最初の検討は，無作為化第II相試験にて検討された．NSCLCを有する99例の患者が，カルボプラチン/パクリタキセル（CP）を3週間毎に6サイクルを投与する群，これに7.5 mg/kgのベバシズマブを3週間毎に併用投与する群，及び15 mg/kgのベバシズマブを3週間毎に併用投与する群，の3治療群に無作為に割付けられた．致死性の出血がベバシズマブの併用群で9％（6/66）の発現頻度で観察され，これらの発現には，ベースラインにおける喀血及び組織学所見，という2つの危険因子が認められた．扁平上皮の組織学所見を有する患者を除いてサブグループ解析を行ったところ，CPとベバシズマブの併用の有効性はより明確になることが示された． ここで注目すべきことは，この無作為化第II相試験では，治療群と対照群では予後に影響を与える主要な背景因子が均衡しておらず，ベバシズマブの至適用量について決定的な結論は得られない点であった． その後米国の共同グループであるECOGは，上述の治験の所見に基づいて，第III相試験，E4599を計画し，カルボプラチン/パクリタキセル（CP）3週間毎の投与×6回と比較して，CP＋ベバシズマブ15 mg/kg 3週間毎の投与×6回に次いで疾患進行までベバシズマブを単剤投与する治療の効果を検討した．この試験には878例の患者が登録された（対照群：444例，ベバシズマブ治療群：434例）．2回目の中間解析が484番目の死亡例が出た時点で行われた（2005年のASCOで結果公表）．ベースラインにおける諸因子は，2治療群間で良く均衡がとれていた．有効性に関しては，ベバシズマブによる治療は奏効率を10.0％から27.2％（p＜0.0001）に，無増悪生存期間を4.5から6.4ヶ月（HR 0.62;p＜0.0001）に，全生存期間を10.2ヶ月から12.5ヶ月（HR＝0.77；p＝0.007）に増加した．安全性に関しては，好中球減少症はベバシズマブ併用群においてより高頻度（16.4対24％）に発現したが，血小板減少症，貧血及び発熱性好中球減少症においては有意な差は認められなかった．ベバシズマブの使用に伴って生じると考えられている出血及び高血圧等の典型的な有害事象は，ベバシズマブ併用群においてより一般的にみられた．静脈性及び動脈性血栓症の発現に関しては，2治療群間で差はみられなかった． E4599はNSCLCに関して標準的なプラチナ含有2剤併用に対し生物学的製剤を加えた3剤併用において，「生存期間の延長」を明確に示した最初の第III相比較試験である．ベバシズマブは非扁平上皮NSCLCを有する患者においてカルボプラチン/パクリタキセル化学療法と併用された場合，全生存期間を有意に改善することが確認された．又，ベバシズマブの併用により奏効率及び無増悪生存率が有意に改善された．一方，ベバシズマブは喀血を含む重篤な出血の僅かな増加を伴うことが示された．ベバシズマブ＋カルボプラチン/パクリタキセルは今やECOGの進行非扁平上皮NSCLCに対するファーストラインの治療の基準となっている．
Treatment options for hormone-refractory prostate cancer. (2007)

Hormone-refractory prostate cancer is a disease that includes a variety of patients and represents a treatment dilemma for the practicing physician. Because of the diversity of this group, management strategies must be targeted to the clinical situations of the individual patients and their wishes. This article outlines a logical progression of treatment choices that currently exist in this rapidly evolving field, and the landmark chemotherapy trials involving docetaxel (SWOG 9916 and TAX 327) are reviewed. Although significant progress has been made in understanding and treating hormone-refractory prostate cancer, current treatments do not yet provide a cure, and important clinical trials continue to recruit patients.
Multiple sclerosis : clinical and pathogenetic basis (1997)

Part 1 Clinical aspects: Clinical features and diagnosis. Optic neuritis and MS. Ocular motility disorders. Pathophysiology and evoked potentials. Magnetic resonance and X-ray imaging. Risk factors. Part 2 Pathology: Pathology of MS. Immunology of MS. Immunocytochemistry in MS. Ultrastructural pathology of MS and EAE. Cerebrospinal fluid in MS. Myelin basic protein and its antibody in CSF. Virology of human and animal demyelinating diseases. Studies of the molecular biology of MS. Part 3 Investigative aspects: Epidemiology of MS. Family and twin studies. HLA system and other genetic markers. Part 4 Management: Assessment of MS disease progression in clinical trials. The bladder in MS. Treating impotence. Immunosuppressant and immunomodulatory therapy. Comprehensive management. Rehabilitation.
Percutaneous Electro Stimulation of the Trigeminal Nerve in Patients with Atypical Trigeminal Neuralgia (1978)

In eleven patients with atypical trigeminal neuralgia, following herpes infections or radiation therapy of cancer of the epipharynx, percutaneous electrical stimulation of the trigeminal tract or in the vicinity of the nucleus area was performed. Relief of pain lasting from fourteen days up to six weeks could be obtained.
The effect of Fc glycan forms on human IgG2 antibody clearance in humans (2008)

Several studies using a variety of approaches have investigated the impact of the Fc glycan structure on IgG clearance rates. Most, but not all, of these studies have concluded that glycan structural differences do not affect clearance. Here we investigated the impact of glycan on the clearance of a human antibody in humans. To monitor glycan-dependent changes, a human IgG2 was affinity purified in a single step from serum samples from a human pharmacokinetic study. The glycan profile from the purified antibody samples was determined by RP-HPLC/MS analysis of the 2-aminobenzamide-labeled glycans. Relative levels of high-mannose species (M6-M9) decreased over circulation time. Differences in the individual high-mannose structural isoform clearance rates were measured from extracted ion current profiles. Similar changes to the glycan profile could be achieved through incubation of the antibody in serum in vitro, suggesting that the changes observed in vivo were the result of glycan cleavage, not differential antibody clearance. These results confirm that antibody clearance is not significantly affected by the Fc glycan structure and provide evidence for the presence of circulating mannosidase activity in humans.
Disorders of Orgasm in Women (2004)

More research is needed in understanding management of women with orgasmic dysfunction.
Sex-Related Differences in Patients Treated Surgically for Aneurysmal Subarachnoid Hemorrhage (2006)

Sex-related differences were examined in the clinical course of patients treated surgically for aneurysmal subarachnoid hemorrhage. Retrospective analyses were carried out to evaluate sex-related differences in aneurysm location, aneurysm size, preoperative neurological condition, preoperative computed tomography findings, and outcome among 2577 patients who underwent surgical repair of ruptured aneurysms. The internal carotid artery was most frequently affected in women and the anterior cerebral artery in men. Intracerebral or intraventricular hematoma was more common in men than in women. Some differences may be related to the location of the aneurysm. Sex-related differences were prominent in the 5th decade of life. These findings might be related to the menopause. Sex hormones may be involved in aneurysm formation.
PD-1/PD-L1 Blockade Therapy for Tumors with Downregulated MHC Class I Expression (2017)

The therapy of different advanced-stage malignancies with monoclonal antibodies blocking programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling has had an impressive long-lasting effect in a portion of patients, but in most cases, this therapy was not successful, or a secondary resistance developed. To enhance its efficacy in treated patients, predictive biomarkers are searched for and various combination treatments are intensively investigated. As the downregulation of major histocompatibility complex (MHC) class I molecules is one of the most frequent mechanisms of tumor escape from the host's immunity, it should be considered in PD-1/PD-L1 checkpoint inhibition. The potential for the use of a PD-1/PD-L1 blockade in the treatment of tumors with aberrant MHC class I expression is discussed, and some strategies of combination therapy are suggested.
Synthesis, Photophysical Properties, in Vivo Photosensitizing Efficacy, and Human Serum Albumin Binding Properties of Some Novel Bacteriochlorins (1997)

The synthesis, photophysical characteristics, in vivo photosensitizing efficacy, human serum albumin (HSA) binding properties, and skin phototoxicity of some stable bacteriochlorins were investigated. The novel bacteriochlorins, obtained from chlorophyll-a, have long-wavelength absorptions in the range lambda max = 734-758 nm. Preferential migration of ethyl over methyl substituents among ketobacteriochlorins obtained in the pinacol-pinacolone rearrangements of vic-dihydroxybacteriochlorins was confirmed by NOE studies. The bacteriochlorins show relatively low fluorescence quantum yields. Among all the bacteriochlorins the triplet states were quenched by ground state molecular oxygen in a relatively similar manner, yielding comparable singlet oxygen quantum yields. In preliminary in vivo studies (DBA/2 mice, transplanted with SMT/F tumors), ketobacteriochlorins were found to be more photodynamically active than the related vic-dihydroxy analogues. Replacement of the methyl ester functionalities with di-tert-butylaspartic acids enhanced the in vivo efficacy. Site specific human serum albumin (HSA) binding studies indicated a direct correlation between the ability of the compound to bind to the diazepam binding site (albumin site II) and the in vivo photosensitizing efficacy.
Pyruvate Dehydrogenase Complex from Higher Plant Mitochondria and Proplastids (1977)

The pyruvate dehydrogenase complex from pea (Pisum sativum L.) mitochondria was purified 23-fold by high speed centrifugation and glycerol gradient fractionation. The complex had a s(20,w) of 47.5S but this is a minimal value since the complex is unstable. The complex is specific for NAD(+) and pyruvate; NADP(+) and other keto acids give no reaction. Mg(2+), thiamine pyrophosphate, and cysteine are also required for maximal activity. The pH optimum for the complex was between 6.5 and 7.5.Continuous sucrose density gradients were used to separate castor bean (Ricinus communis L.) endosperm proplastids from mitochondria. Pyruvate dehydrogenase complex activity was found to be coincident with the proplastid peak on all of the gradients. Some separation of proplastids and mitochondria could be achieved by differential centrifugation and the ratios of the activities of the pyruvate dehydrogenase complex to succinic dehydrogenase and acetyl-CoA carboxylase to succinic dehydrogenase were consistent with both the pyruvate dehydrogenase complex and acetyl-CoA carboxylase being present in the proplastid. The proplastid fraction has to be treated with a detergent, Triton X-100, before maximal activity of the pyruvate dehydrogenase complex activity is expressed, indicating that it is bound in the organelle. The complex had a sharp pH optimum of 7.5. The complex required added Mg(2+), cysteine, and thiamine pyrophosphate for maximal activity but thiamine pyrophosphate was inhibitory at higher concentrations.
Feature selection and classifiers for the computerized detection of mass lesions in digital mammography (2002)

We have investigated various methods of feature selection for two different data classifiers used in the computerized detection of mass lesions in digital mammograms. Numerous features were extracted from abnormal and normal breast regions from a database consisting of 210 individual mammograms. A step-wise method, a genetic algorithm and individual feature analysis were employed to select a subset of features to be used with linear discriminants. Similar techniques were also employed for an artificial neural network classifier. In both tests the genetic algorithm was able to either outperform or equal the performance of other methods.
Apical Transport and Folding of Prostate-specific Membrane Antigen Occurs Independent of Glycan Processing (2005)

Prostate-specific membrane antigen (PSMA) is an integral cell-surface membrane glycoprotein that is overexpressed in prostate carcinomas rendering it an appropriate target for antibody-based therapeutic strategies. The biosynthesis of PSMA in transfected COS-1 cells reveals a slow conversion of mannose-rich to complex glycosylated PSMA compatible with slow transport kinetics from the endoplasmic reticulum to the Golgi. Importantly, mannose-rich PSMA persists as a trypsin-sensitive protein throughout its entire life cycle, and only Golgi-located PSMA glycoforms acquire trypsin resistance. This resistance, used here as a tool to examine correct folding, does not depend on the type of glycosylation, because different PSMA glycoforms generated in the presence of inhibitors of carbohydrate processing in the Golgi are also trypsin resistant. The conformational transition of PSMA to a correctly folded molecule is likely to occur in the Golgi and does not implicate ER molecular chaperones, such as BiP. We show here that PSMA is not only heavily N-but also O-glycosylated. The question arising is whether glycans, which do not play a role in folding of PSMA, are implicated in its transport to the cell surface. Neither the cell-surface expression of PSMA nor its efficient apical sorting in polarized Madin-Darby canine kidney cells are influenced by modulators of N- and O-glycosylation. The acquisition of folding determinants in the Golgi, therefore, is an essential prerequisite for protein trafficking and sorting of PSMA and suggests that altered or aberrant glycosylation often occurring during tumorigenesis has no regulatory effect on the cell-surface expression of PSMA.
Relationship between Prostate‐Specific Antigen, Clinical Stage, and Degree of Bone Metastasis in Patients with Prostate Cancer: Comparison with Prostatic Acid Phosphatase and Alkaline Phosphatase (1997)

PSA was the best marker for differentiating clinical stages, but showed limited reliability for stratifying the extent of bone metastasis.
Cortical Language Activation in Stroke Patients Recovering From Aphasia With Functional MRI (1999)

The results indicate that the restoration of left-hemisphere language networks is associated with better recovery and inversely related to activity in the compensated or recruited areas of the right hemisphere.
Clinical efficacy and tolerability of 2.5 mg zolmitriptan for the acute treatment of migraine (1997)

Previous studies demonstrated that zolmitriptan at doses of 1 to 25 mg was highly effective in treating acute migraine attacks. The 2.5-mg dose had a favorable therapeutic effect with high efficacy and good tolerability. The objective of this study was to further evaluate the efficacy of a single 2.5-mg dose of zolmitriptan (Zomig, formerly known as 311C90) for acute treatment of a single moderate or severe migraine attack. The study was a randomized, double-blind, placebo-controlled clinical trial. Female and male patients, 12 to 65 years old, with migraine (with or without aura) for > or = 1 year, one to six migraines per month, and age at onset < 50 years were included; 327 patients were screened and randomized to receive either zolmitriptan (n = 219) or placebo (n = 108). Patients treated a single moderate or severe migraine headache with 2.5 mg zolmitriptan or placebo and recorded clinical efficacy and adverse events on a diary form. Headache response at 2 hours was 62% for zolmitriptan compared with 36% for placebo (p < 0.001); at 4 hours, headache response was 70% with zolmitriptan and 37% with placebo (p < 0.001). Headache recurrence in patients treated with 2.5 mg zolmitriptan was 22% (versus placebo 30%). The headache response at 4 hours, pain-free rate, and response rate of nonheadache symptoms favored zolmitriptan over placebo. No serious adverse events were associated with zolmitriptan treatment. A 2.5-mg dose of zolmitriptan is clinically effective and well tolerated for the acute treatment of migraine.
Interbody Device Shape and Size Are Important to Strengthen the Vertebra–Implant Interface (2005)

The cloverleaf-shaped indentor displayed an improved strength and stiffness profile when compared to oval or kidney-shaped indentors of similar surface areas.
I-CeuI reveals conservation of the genome of independent strains of Salmonella typhimurium (1995)

The enzyme I-CeuI, encoded by a class I mobile intron inserted in the gene for 23S rRNA in Chlamydomonas eugamatos, cleaves a specific 19-bp sequence in this gene. This sequence is present only in the seven genes for rRNA in Salmonella typhimurium and Escherichia coli. Partial digestion with I-CeuI of DNA from 17 wild-type strains of S. typhimurium indicates that the chromosome of these strains is strongly conserved, for the digestion products closely resemble those of strain LT2. The lengths and order of chromosomal segments are conserved in 15 of the strains; 2 show some rearrangements. XbaI digestion indicated heterogeneity without revealing the genomic structure. Because of conservation of I-CeuI sites in genes for rRNA and conservation of the number and locations of these genes, I-CeuI provides an excellent tool for the rapid examination of the chromosomes of related species of bacteria; differences in the fingerprints indicate the occurrence of chromosomal rearrangements such as insertions or inversions.
Herpes zoster and postherpetic neuralgia (1986)

Department of Neurological Surgery, and Multidisciplinary Pain Center, University of Washington, RI-20, Seattle, WA98195 U.S.A. *Correspondence and reprint requests to: John D. Loeser, M.D., Department of Neurological Surgery, RI-20, University of Washington, Seattle, WA 98195, U.S.A. Submitted August 20, 1985; accepted November 1, 1985.
Repression of autocrine transforming growth factor beta 1 and beta 2 in quiescent CBS colon carcinoma cells leads to progression of tumorigenic properties. (1993)

Previous work has shown that repression of negative autocrine transforming growth factor (TGF) beta 1 did not alter the growth rate of a human colon carcinoma cell line, but the time required for the cells to enter exponential growth from lag phase was reduced (S. P. Wu, D. Theodorescu, R. Kerbel, J. K. V. Willson, K. M. Mulder, L. E. Humphrey, and M. G. Brattain, J. Cell Biol., 116: 187-196, 1992). These results have led to the hypothesis that the tumor suppressive activity of autocrine TGF-beta 1 was directed at quiescent nondividing cells rather than actively dividing cells. In order to test this hypothesis, a weakly tumorigenic, well-differentiated human colon carcinoma cell line designated CBS, which expressed autocrine TGF-beta 1 and -beta 2 activity in quiescent cells, but not in exponential growth phase cells, was identified. This cell line was stably transfected with a full-length TGF-beta 1 antisense complementary DNA. Constitutive expression of TGF-beta 1 antisense mRNA in CBS cells resulted in repression of autocrine TGF-beta 1 and -beta 2 protein activity in quiescent cells of approximately 10-fold. TGF-beta 2 repression could have been due to interaction with TGF-beta 1 antisense mRNA, since these two isoforms have a high degree of homology, or it could have been indirectly due to TGF-beta 1 repression, since this isoform has been shown to affect transcriptional and posttranscriptional control of TGF-beta 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification and Quantification of Apneas by Computer-based Analysis of Oxygen Saturation (1988)

Manual detection and quantitation of apneas from an all-night polysomnogram is very time-consuming. Because SaO2 changes with virtually every apnea event, we reasoned that by identifying cyclical SaO2 changes, we could calculate (1) an apnea-hypopnea index that would correlate very well with the manually derived apnea-hypopnea index, and (2) the duration of apnea-hypopnea events. We developed a computer algorithm to scan and detect dips in SaO2 data digitally stored as a time series by computer throughout overnight studies. Desaturations detected by computer were compared with the events detected manually in 9 all-night polysomnograms from 6 patients with typical obstructive sleep apnea. Events detected by one method but not the other were subsequently verified to determine the overall number of apnea-hypopnea events present and to determine false positive and false negative rates for the 2 methods of detection. The total number of apneas was 4,008. Both methods agreed on 3,639 of them. Of 77 manually recorded apneas not detected by computer, 24 were subsequently discounted (manual false positives, 24 of 4,007 = 0.6%) and 53 confirmed (computer false negatives, 1.32%). Of 358 events not detected manually, 316 were confirmed (manual false negatives, 7.9%) and 42 discounted (computer false positives, 1.1%). Using the final manual scoring as the reference, the computer program detected apneas with a sensitivity of 97.9%, and the predictive value of a computer-detected event was 90.8%. for event duration, a regression was performed on 3,623 matched apneas-hypopnea events, giving a coefficient of r = 0.9431, p < 10−6. We conclude that computer-based analysis of continuous SaO2 will detect apneas and hypopneas with a very high sensitivity and a very low false positive and false negative rate, and thus can be used to calculate event number and duration.
Potentially Pathogenic Airway Bacteria and Neutrophilic Inflammation in Treatment Resistant Severe Asthma (2014)

Airway colonisation with potentially pathogenic micro-organisms in asthma is associated with more severe airways obstruction and neutrophilic airway inflammation. This altered colonisation may have a role in the development of an asthma phenotype that responds less well to current asthma therapies.