tbuckley/cabot-search huggingface dataset:
Development of prediction system of chemosensitivity to anti-cancer drugs towards personalized-medicine
Authors: Toyomasa Katagiri, Yoshitoyo Kagami, Ryuzo Ohno, Yusuke Nakamura
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4201 

One of the most critical issues to be solved in regard to cancer chemotherapy is establishment of ways to predict efficacy of anti-cancer drugs for individual patients. Development of the ABL-selective tyrosine kinase inhibitor imanitib mesylate (IM) (Glivec; Novartis Pharmaceuticals, Basel, Switzerland) was an important advance in the management of chronic myeloid leukemia (CML). IM is highly effective in the first line therapy of CML without severe adverse effects. However, it remains unknown whether IM cures CML or not, and other therapeutic modalities like stem cell transplantation sometimes become necessary. To develop a prediction system based on expression of specific genes, we initially analyzed expression profiles of mononuclear cells from 22 CML patients who had previously failed in interferon-alfa therapy. cDNA microarrays representing 23,040 genes identified 79 genes that were expressed differentially between the responders and the non-responders to IM using random permutation method. On the basis of expression patterns of 15 out of these genes, we developed a prediction system that could clearly separate the responders from the non-responders. We further verified this prediction system by a cDNA microarray using 42 additional CML patients who would receive IM as monotherapy. Of 40 patients who attained major cytogenetic response (MCR) by 6 months after treatment of IM, 38 (95%) had been predicted as the responder by the prediction system, whereas two patients whose effect was less than MCR had been predicted as the non-responder. Hence, selection of the CML patients prior to the treatment of IM by our prediction system could increase the efficiency of the protocol up to nearly 100%. These results suggest that the chemosensitivity to anti-cancer drugs can be predicted by gene expression levels of a set of genes, and may eventually, lead to the achievement of “personalized therapy” for this treatment.
A Martian view of the Hardinian taboo
Authors: G. Gardner, M. King
Journal: BMJ (1998)

In an article published in the British Medical Journal (BMJ) in 1997 M. King and C. Elliott praise the ideas of Garrett Hardin.  Hardin however is a eugenicist a former director of the American Eugenics Society who was an active member at the same time that the Nazi eugenicist Otmar Von Verschuer became a foreign member in 1956.  Verschuer was a teacher of Josef Mengele who helped to finance Mengeles experiments at Auschwitz.  Even though Verschuers activities were well known the eugenics establishment accorded him honors and academic favors.  It is no surprise that Hardin would associate with people who so blatantly ignored human rights.  The links between population control and eugenics are easy to uncover.  For example the International Planned Parenthood Federation was a member of the Eugenics Society in 1977 and still financially supports Chinas coercive and eugenics-based population policy.  Contrary to King and Elliotts claim that the genocide in Rwanda was due to population pressures it was actually the result of eugenic racism.  Rather than die out in 1945 eugenics continues to flourish among population control groups and intellectual elites and is now also upon the pages of the BMJ.
Congenital Lobar Emphysema
Authors: Aida Omerctahić-Dizdarević, Ediba Saracević, Fedzet Jonuzi, Verica Misanović, Dusko Anić, Ismeta Kalkan, Amra Cengić
Journal: JAMA (1963)

Congenital lobar emphysema is characterized by overinflation of pulmonary lobe and is caused by localised bronchial obstruction. The disease may result in severe respiratory distress in early infancy.Records of children, with congenital lobar emphysema, who were treated at our department between 1997-2003, were reviewed.Three males, aged 16 days till 1 year, were diagnosticed as congenital lobar emphysema. Presenting symptoms were dyspnea in 2 patients, cyanosis in 2 patients, wheesing in 2 patients, recurrent respiratory tract infection in 2 patients. Chest x rays and computerized tomography scans showed hyperinflation of the affected lobe in all patients. The affected sites were left upper lobe in 2 patients and right upper lobe in 1 patient. All patients underwent lobectomy.It is necessary to suspect on this uncommon anomaly in early infancy. The diagnosis was established by chest x rays and CT scans. Intensive therapy and urgent lobectomy, in severe respiratory distress, are condition for successfully treatment.
Abstract 4434: 12 Months and Beyond: Long-Term Results of the Direct Flow Medical Repositionable and Retrievable Pericardial Valve for Percutaneous Aortic Valve Replacement
Authors: Joachim Schofer, Thilo Tubler, Andrea Pascotto, Ralf Muller, Reginald Low, Steven Bolling, Eberhard Grube
Journal: Circulation (2009)

Background Percutaneous aortic valve replacement is considered an alternative for patients at high risk for open surgical repair. The Direct Flow Medical (Santa Rosa, CA) Percutaneous Aortic Valve ...
The syndrome of identity diffusion
Authors: Salman Akhtar
Journal: American Journal of Psychiatry (1984)

The author delineates the syndrome of identity diffusion as consisting of six clinical features: 1) contradictory character traits, 2) temporal discontinuity in the self, 3) lack of authenticity, 4) feelings of emptiness, 5) gender dysphoria, and 6) inordinate ethnic and moral relativism. This syndrome implies severe character pathology and is distinct from adolescent identity crisis. The conceptualization has a significant bearing on the differential diagnosis and psychotherapy of personality disorders.
Abstract 16060: Electrocardiographic Analysis of Arrhythmogenic Right Ventricular Cardiomyopathy: Cardiovascular Events and the Epsilon Wave
Authors: Yosuke Otsuka, Kazuhiro Satomi, Ikutarou Nakajima, Kohei Ishibashi, Kouji Miyamoto, Yuko Yamada, Hideo Okamura, Takashi Noda, Takeshi Aiba, Toshihisa Anzai, Masaharu Ishihara, Satoshi Yasuda, Hisao Ogawa, Shiro Kamakura, Kengo Kusano
Journal: Circulation (2013)

Background:  The abnormal ECG parameters, such as epsilon wave are specific observations in diagnostic criteria of arrhythmogenic right ventricular cardiomyopathy (ARVC). However, little is known in the relationship between cardiovascular events and ECG observation during follow-up in ARVC.   Methods:  91 patients with ARVC (mean age of 47 ± 14 and 73 males) were enrolled in this study. We examined ECG characteristics recorded at the beginning of follow-up. The epsilon wave distribution (e wave distribution) was defined as the number of leads showing the epsilon wave among 12 lead ECG. Right ventricular ejection fraction (RVEF) was analyzed by the contrast-enhanced CT, MRI, or myocardial scintigraphy. The primary endpoint was cardiovascular mortality and secondary endpoint was hospitalization due to heart failure (HF).   Results:  During the 8.6±6.7 yrs follow-up, cardiac death was observed in 11 patients (fatal group; 12%). The e wave in any of 12 leads was observed significantly higher in the fatal group than the survival group (64% vs 24%, p=0.01). Furthermore, the fatal group had significantly wider e wave distribution compared with the survival group (3.8 of 12 leads vs. 1.6 of 12 leads, p=0.045) and also the wider e wave distribution correlated to a lower RVEF (p=0.04). Especially patients with the e wave in the aVR lead had significantly higher cardiac mortality (33% vs. 15%, p=0.03), hospitalization due to HF (47% vs 15%, p=0.006) and lower RVEF (21% vs. 30%, p=0.01) compared with those without the e wave in the aVR lead. There was no significant difference in the events of ventricular tachyarrhythmias in patients with or without e wave in aVR.   Conclusion:  In ARVC, the wide distribution of e wave and the e wave in the aVR lead correlated to severe right ventricle impairment and cardiovascular mortality.
乳腺疾病基础知识（三）早期乳腺癌的内科治疗（III）：化疗
Authors: Ian, Smith, Susan, Chua, 王佳玉（译）, 徐兵河（校）
Journal: BMJ (2006)

对于年龄小于70岁的具有中、高度危险因素的乳腺癌患者来说，辅助化疗具有显著的生存益处，并且患者越年轻受益越大。这是因为年轻患者往往具有一些特殊的生物学表现，如：雌激素受体（ER）阴性，组织学分级Ⅲ级等，这些因素提示高危。另外，化疗诱导的卵巢功能减退，对于那些ER阳性的患者来说似乎是一种有益因素。50岁以上高危患者也可从化疗中受益，但是除了肿瘤分化差、人表皮生长因子受体2（HER-2）过表达或腋淋巴结转移数目多的患者以外，其中许多患者单用内分泌治疗即可有效。由于化疗的毒性较大，考虑风险及受益始终是重要的，目前的治疗共识标准有助于选择患者进行治疗。
Junior doctors' hours
Authors: V V. Kumar
Journal: BMJ (1996)

Junior doctors' hoursShift work is poisoning juniors EDrrOR,-Christopher Wong is right when he says that the current trend towards a reduction in junior doctors' working hours has gone too far.'Doctors have always worked long hours and were paid nothing for being on call until the 1970s, when they began to be paid some 30% of their standard pay for night duty, weekends, etc.All that was needed to improve the system was to pay more than 100% for on call duties and perhaps double on bank holidays and for uncivilised hours.I can guarantee that no doctor would complain of overwork under this system.After all, what happens now is that they do locums and so earn a similar amount in a roundabout way.Keith Reid's reply to Wong's letter is woolly.2Absence of evidence is not evidence of absence, and therefore I cannot accept his point that British specialists may be no better than European specialists.If training has indeed been so bad in Britain should we let doctors who were ill trained decide what is good for junior doctors' training?To quote accident and emergency departments as
Abstract 13510: Management of Pulmonary Hypertension in Association with Bronchopulmonary Dysplasia: Medium Term Follow-up.
Authors: Usha Krishnan, Sankaran Krishnan, Boriana Parvez, Michael Gewitz
Journal: Circulation (2010)

Background: Pulmonary Hypertension (PH) significantly worsens outcome in infants with bronchopulmonary dysplasia (BPD). Current treatment strategies include early use of pulmonary vasodilators, gen...
Abstract 4359: Adjusting for Major Clinical Covariates Improves the Diagnostic Performance of Brain Natriuretic Peptide for Distinguishing Cardiac from Non-cardiac Dyspnea
Authors: R. Kevin Rogers, Genaro Fernandez, Andrew Freeman, John Nord, Greg Stoddard, Josef Stehlik
Journal: Circulation (2008)

AHA 2008 Abstract #1   Introduction:  Dyspneic patients with a BNP    Methods:  Patients presenting to the Salt Lake City VA Medical Center with dyspnea in 2007 were eligible. Data were collected by retrospective chart review. Physicians blinded to BNP values adjudicated outcomes. Dyspnea was attributed to HF if Framingham criteria for HF were met. The diagnostic characteristics of a BNP of 100 pg/mL were determined for the entire cohort and for the following subgroups: age > 75 years, history of AF, creatinine > 2 mg/dL, and BMI °¥ 30 kg/m 2 . Adjusted BNP cutoff values for each subgroup were determined that retained the sensitivity of the BNP cutoff value of 100 pg/mL in the entire cohort.   Results:  349 patients met inclusion criteria. The adjusted BNP cutoff values that correspond to 91% sensitivity (the sensitivity of the BNP cutoff value of 100 pg/mL in the entire cohort) in the different subgroups were higher in those > 75 years of age, those with AF, and those with creatinine > 2 mg/dL but lower for the subgroup with BMI °¥ 30 kg/m 2  (Table). Due to improved specificity of these subgroup-specific BNP cutoff values, 22 (14%) patients > 75 years old, 5 (4%) patients with AF, and 12 (23%) patients with a creatinine > 2 mg/dL could be correctly reclassified as having non-cardiac dyspnea. The cutoff adjusted for BMI identified an additional 7 (4%) of obese patients as having HF but lacked sufficient specificity to increase overall diagnostic accuracy in this subgroup.   Conclusions:  Adjusting for the presence of clinical covariates may improve the accuracy of BNP in distinguishing cardiac from non-cardiac dyspnea. This approach is undergoing validation.
Commentary: A conservative management plan from a place where barracuda are rare
Authors: J. Rees
Journal: BMJ (1996)

The general availability of chest x ray examinations has prompted some clinicians to diminish the importance of physical examination of the chest. Faced with a barracuda wound to the chest in a remote part of the Solomon Islands there is nothing else to fall back on, and percussion, tactile vocal fremitus, and breath sounds resume their true importance. Dr Berger had to advise at the end of a telephone line before managing to reach the patient. It was then that the main dilemma arose: was it to be …
肥胖基础知识（四） 治疗：第二部分——药物疗法
Authors: Mike, Nick, Finer, 谢超（译）
Journal: BMJ (2007)

尽管目前已经可以获得经过评估和认可的减肥药物，但医生仍然一直不愿意使用减肥药——即使一些患者在非药物治疗后体重不能减轻。导致这一现象的原因是，人们对苯丙胺和苯丙胺类药物引起的不良事件，以及芬特明和芬氟拉明联用时发生的严重并发症还记忆犹新。目前推荐用于治疗肥胖症的药物都已得到规范标准的评估和认可，这些标准适用于所有药物治疗。应用减肥药物应该遵循与其他治疗领域相同的原则——即在评估可能的获益和风险（包括临床和经济学方面）后方可应用，同时正确告知患者并对疗效进行医学监测。
Role of the DNA repair and redox enzyme Ape1/Ref-1 in neurotoxicity of cisplatin on dorsal root ganglion neurons: Implications for peripheral neuropathy
Authors: Yanlin Jiang, Chunlu Guo, Michael Vasko, Mark Kelley
Journal: Cancer Research (2007)

1973   Cisplatin or platin analogues are some of the most commonly used cytotoxic agents in the treatment of a variety of solid malignant tumors. Although treatment with this drug can be effective, about 20% of patients are unable to complete a full course of cisplatin therapy due to sensory neuropathy. Current understanding of cisplatin toxicity demonstrates the formation of intrastrand and interstrand cross-links in DNA. However, there is growing evidence suggesting that cisplatin cytotoxicity is also closely associated with the increased generation of reactive oxygen species (ROS). Thus, it is possible that cisplatin causes damage to sensory neurons through oxidative DNA damage such that this toxicity contributes to peripheral neuropathy.  Apurinic/apyrimidinic endonuclease/redox factor (Ape1) is a ubiquitous multifunctional portion involved in the DNA base excision repair (BER) pathway of oxidative DNA damage. In addition, Ape1 is a major redox factor which augments the binding activity of a number of transcription factors to DNA, such as NF-kB, p53, HIF-1a, AP-1 and others. In neurons these transcription factors play important roles in neuronal survival and function. Therefore, the question we chose to address concerns whether altering Ape1 functions would influence cisplatin induced neurotoxicity. When sensory neuronal cultures were exposed to increasing concentrations of cisplatin there was a concentration dependent increase in cell death and in ROS production measured using carboxy-H2DCFDA and FACS analysis. Reducing Ape1 content in the cells using Ape1siRNA increased cell loss at all concentrations of cisplatin tested, whereas treament with scrambled Ape1siRNA (SCsiRNA) did not augment cell death. Overexpressing wild-type Ape1 (wtApe1) led to protection against cisplatin-induced cell death in cultures with either normal levels of Ape1 (SCsiRNA treated) or in those with decreased Ape1 levels (Ape1siRNA treated). A redox-deficient/repair-competent Ape1 only partially corrected against the cisplatin killing of the neuronal cells.  We also examined the effects of cisplatin in the absence or presence of Ape1 manipulations on the release of CGRP from DRG cells as a major integrated output of neurons. Cisplatin treatment of the cells caused a significant decrease in capsaicin-evoked release of iCGRP which was greater in cells with a reduction in Ape1 expression. When the wtApe1 was added back to the cells using viral vectors, the effect of cisplatin on release was completely blocked, whereas, adding back the redox mutant Ape1 only partially protected the cells. These results strongly support the notion that manipulations of Ape1 function in neurons influences toxicity by cisplatin. We conclude that Ape1 is a potential translational target such that protecting Ape1 levels could reduce peripheral neuropathy in patients undergoing treatments.
IDH1 Mutant Inhibitor Induces Cellular Differentiation and Offers a Combination Benefit With Ara-C In a Primary Human Idh1 Mutant AML Xenograft Model
Authors: Katharine Yen, Rene Lemieux, Janeta Popovici-Muller, Yue Chen, Hua Yang, Kim Straley, Sung Choe, Marion Dorsch, Samuel Agresta, David P. Schenkein, Scott Biller, Michael Su, Fang Wang
Journal: Blood (2013)
Cancer stem cell phenotype may have malignant potential in breast cancer.
Authors: Daisuke Shimizu, Takashi Ishikawa, Takeshi Sasaki, Kae Kawachi, Akinori Nozawa, Takashi Chishima, Yasushi Ichikawa, Shinji Togo, Hiroshi Shimada
Journal: Cancer Research (2008)

5494   Background:  The theory that cancer may be originated and sustained by a small proportion of stem-like, self-renewing cells has gained support in recent years. Breast cancer stem cells have been identified as CD44 + /CD24 -/low  cells and have recently been isolated and propagated in vitro. Another study group demonstrated that breast cancer with gene expression specific for cancer stem cell phenotype (CSCP) showed worse clinical outcome.  Aim:  This study was done to clarify the association of CSCP with other pathological features of breast cancer.  Materials and Methods:  We constructed tissue microarray with clinical samples from 117 patients with breast cancer. CSCP was identified with CD44 + /CD24 -/low  by immunohistochemistry. Routine histopathological features were also examined including ER, PgR, HER2, p53, ki67, and histological grade, etc. These cases were subdivided into “intrinsic subtypes”. The correlation of CSCP and other clinicopathological features was investigated.  Results:  Of 117 samples, 20(17%) demonstrated CSCP of CD44 + /CD24 -/low . In terms of “intrinsic subtypes”, Luminal A, Luminal B, Basal and HER2 were 74(63%), 10(9%), 22(18%), and 11(10%), respectively. CSCP was correlated with higher nuclear grade (histological grade 3: CSCP 35% vs non-CSCP 22%) and higher Ki67 index (index>10 CSCP 50% vs non- CSCP 35%). There was no correlation between CSCP and other clinicopathological features like age, “intrinsic subtypes”, p53 mutation, and lymph node involvement, etc.  Conclusion:  CSCP may be a specific subgroup of cancer cells with higher malignant potential independent with other pathological features. Recent studies with sentinel lymph node biopsy demonstrated that occult metastatic foci in the axillary lymph nodes may not become clinically overt. It is plausible that only cancer stem cells in a metastatic focus might important for the development of metastases. We will present our preliminary data of CSCP in metastatic axillary lymph nodes from corresponding tumors of this study.
Quantification of gene expression of pro and anti-inflammatory cytokines in relation to apoptotic genes in hepatocarcinogenesis
Authors: Abdel-Rahman Zekri, Abeer Bahnassy, Sabrin Abdel-Wahab, Sabry Sharrawy, Medhat Khafagy, Hussein Khalied
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2771 

Molecular markers are considered an important tool for assessment of both CAH and HCC prognosis. Thus, quantification of gene expression of pro and anti-inflammatory cytokines (TNFα, TNFRI, TNFRII, IL-6, IL-6R and IL-10), genes related to apoptosis (GSK3-β, AKT-1, and Bcl-2), CRP and αFP could help to understand the disease progression from HCV infection to HCC development, recurrence and metastasis. Our study aim to identify the interplay between this group of genes and the potential use of any of them as markers of hepatocarcinogenesis Which may be helpful for prediction of disease progression in patients with HCV-associated liver disease (LD) and HCC.: Our study showed down regulation of TNF-α, TNFRI and IL-10 in about 95% of the studied groups. Statistical significant difference between HCC and Liver disease (LD) in the expression of GSK3- β, TNFRII, AKT-1, Bcl-2, and AFP (P= 0.00194, 0.0001, 0.0001 , 0.0001, 0.0001) respectively, also significant relation between HCC (on top of cirrhosis) and over expression of AKT-1, IL-6 , AFP, CRP ( P= 0.018, 0.0001 , 0.0001, 0.0001), down expression of GSK3- β, TNFRII (P= 0.0018, 0.0001) respectively. As well as between LD associated with cirrhosis and over expression of AKT-1, IL-6 (P= 0.0001, 0.0001), down expression of GSK3- β (P= 0.02) respectively. Conclusions: TNF-a, TNFRI and IL-10 are the most commonly genes affected in HCC and LD. Aberrant expression of (GSK3-â, TNFRII, AKT-1, Bcl-2, and AFP) and (AKT-1, IL-6, GSK3-â) is a frequent event in HCC and LD associated with cirrhosis respectively. Over expression of Bcl-2 has a role in tumor invasion and meatstatic. GSK3-β mRNA is one of the main priorities targets of HCV by both direct and indirect effect. Down expression of GSK3-β, TNFRII and over expression of Bcl-2, AKT-1 Could be used as good prognostic markers for disease progression as well as prognostic markers to predict clinical out come Our data proposed that AKT-1 and GSK3-β are candid genes for molecular target therapy of HCC.
THE THEORY OF DIABETES
Authors: R T Woodyatt
Journal: JAMA (1930)

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