tbuckley/cabot-search huggingface dataset:
The physical examination in office practice
Authors: W H Anderson
Journal: American Journal of Psychiatry (1980)

Physical illness may first declare itself as a disturbance in thinking, mood, or behavior. Recognition of physical disorders is enhanced by informed use of the relevant procedures of physical examination. Objections to physical examination are based on the assumptions that it is overly timeconsuming, is psychotherapeutically contraindicated, or requires unusual skill, but observation and minimally intrusive procedures can provide much information that may exclude emergent organic conditions. Different patients, illnesses, and settings require different levels of examination; the author describes the appropriate procedure for psychotic patients, substance abusers, patients taking psychotropic medications, and other patients.
Targeting protein homeostasis in sporadic inclusion body myositis
Authors: Mhoriam Ahmed, Pedro M. Machado, Adrian Miller, Charlotte Spicer, Laura Herbelin, Jianghua He, Janelle Noel, Yunxia Wang, April L. McVey, Mamatha Pasnoor, Philip Gallagher, Jeffrey Statland, Ching-Hua Lu, Bernadett Kalmar, Stefen Brady, Huma Sethi, George Samandouras, Matt Parton, Janice L. Holton, Anne Weston, Lucy Collinson, J. Paul Taylor, Giampietro Schiavo, Michael G. Hanna, Richard J. Barohn, Mazen M. Dimachkie, Linda Greensmith
Journal: Science Translational Medicine (2016)

Augmenting the heat shock response with arimoclomol ameliorates pathology in cellular and animal models of inclusion body myositis.
PTH-235 Small bowel obstruction in pregnancy is a complex surgical problem with a high risk of foetal loss
Authors: P Webster, M Bailey, J Wilson, D Burke
Journal: Gut (2015)

<h3>Introduction</h3> Small bowel obstruction (SBO) in pregnancy is rare and is most commonly caused by adhesions from previous abdominal surgery. Previous literature reviews have emphasised the need for prompt laparotomy in all cases of SBO because of the significant risks of foetal loss and maternal mortality. Since the last review, magnetic resonance imaging (MRI) and computed tomography (CT) scans have become more widely available and can determine the exact aetiology of SBO in pregnancy. We undertook a systematic review of the contemporary literature to determine if immediate laparotomy is still always necessary with the advent of these improved imaging modalities. <h3>Method</h3> The Medline and PubMed databases were searched for cases of SBO in pregnancy between 1992 and 2014. Two cases from our own institution were also reviewed. <h3>Results</h3> Forty-six cases of SBO in pregnancy were identified, with adhesions being the most common aetiology (50%), followed by small bowel volvulus (15%) and internal hernia (13%). The overall risk of foetal loss was 17% and maternal mortality was 2%. In cases of adhesional SBO, 91% of cases were managed surgically, with 14% foetal loss. Two cases (9%) were managed conservatively with no complications. MRI scan was used to diagnose SBO in 11% of cases and CT scan in 13% of cases. <h3>Conclusion</h3> Based on our experience, and the contemporary literature, we recommend that if available, an urgent MRI of the abdomen should be undertaken to diagnose the aetiology of SBO in pregnancy. In cases of adhesional SBO, conservative treatment may be safely commenced, with a low threshold for laparotomy. In other causes, such as volvulus or internal hernia, prompt laparotomy remains the treatment of choice. <h3>Disclosure of interest</h3> None Declared.
Syncope Induced by Tobacco Smoking in the Head-up Position.
Authors: Noriko Inoue, Tomoko Ohkusa, Tomoko Nitta, Masahiko Harada, Kazuya Murata, Masunori Matsuzaki
Journal: Circulation (2001)

A 26-year-old man had a loss consciousness for a few minutes while smoking in the standing position, and was referred to hospital. No abnormalities were found in a computed tomography examination of his head, in a 24-h electrocardiogram or in an exercise tolerance test. The head-up tilt test (HUT) while tobacco smoking elicited a positive response in the tilted position, but the HUT without tobacco smoking was negative. The most noteworthy effect of tobacco smoking during the HUT was the high level of plasma epinephrine compared to the levels seen during supine smoking or the HUT alone. Syncope induced by tobacco smoking in the standing position is rare and the mechanism may be the same as that underlying neurally mediated syncope.
Abstract 736: Combining PD1- and CTLA4-inhibiting antibodies with cisplatin or PARP inhibition in an attempt to eradicate BRCA1-deficient mouse mammary tumors
Authors: Sohvi Blatter, Charlotte Guyader, Aslı Küçükosmanoğlu, Stephan Freriks, Karin de Visser, Piet Borst, Sven Rottenberg
Journal: Cancer Research (2015)

Abstract Solid tumors are usually not eradicated by conventional chemotherapy resulting in disease relapse and mortality. An intriguing example is BRCA-associated breast cancer. A genetically engineered mouse model for BRCA1-associated breast cancer (K14Cre;Brca1F/F;p53F/F), which highly resembles disease in human patients, can be used to study therapy escape and residual disease in BRCA-deficient tumors. Due to the BRCA inactivation, the tumors that arise in this model lack homologous recombination-directed DNA repair, an Achilles heel that has provided a therapeutic opportunity to eradicate tumors with DNA damage-inducing agents. Despite repeated sensitivity some residual cancer cells escape the deadly effect of anticancer therapy and lead to disease relapse. A special histopathological feature of BRCA1-mutated tumors in both humans and mice is the presence of infiltrating lymphocytes. This may be explained by the high frequency of genomic alterations of BRCA1-mutated tumors resulting in the generation of many neo-antigens. Our hypothesis is that blocking inhibitory T-cell signaling, using antibodies directed against CTLA4 and PD1, may increase the activity of the T-cell compartment towards a diverse pool of antigens, and successfully eliminate residual tumor cells in combination with DNA damage-inducing drugs. In particular, we will present data of combining CTLA4- and PD1- targeting antibodies with PARP inhibition or cisplatin to eliminate residual tumor cells in this mouse model for BRCA1-mutated breast cancer. Citation Format: Sohvi Blatter, Charlotte Guyader, Aslı Küçükosmanoğlu, Stephan Freriks, Karin de Visser, Piet Borst, Sven Rottenberg. Combining PD1- and CTLA4-inhibiting antibodies with cisplatin or PARP inhibition in an attempt to eradicate BRCA1-deficient mouse mammary tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 736. doi:10.1158/1538-7445.AM2015-736
miR-146b-5p within BCR-ABL1–Positive Microvesicles Promotes Leukemic Transformation of Hematopoietic Cells
Authors: Hong-Mei Zhang, Qing Li, Xiaojian Zhu, Wei Liu, Hui Hu, Teng Liu, Fanjun Cheng, Yong You, Zhaodong Zhong, Ping Zou, Qiubai Li, Zhichao Chen, An-Yuan Guo
Journal: Cancer Research (2016)

Abstract Evidence is accumulating that extracellular microvesicles (MV) facilitate progression and relapse in cancer. Using a model in which MVs derived from K562 chronic myelogenous leukemia (CML) cells transform normal hematopoietic transplants into leukemia-like cells, we defined the underlying mechanisms of this process through gene-expression studies and network analyses of transcription factors (TF) and miRNAs. We found that antitumor miRNAs were increased and several defense pathways were initiated during the early phases of oncogenic transformation. Later, oncomiRs and genes involved in cell cycle, DNA repair, and energy metabolism pathways were upregulated. Regulatory network analyses revealed that a number of TFs and miRNAs were responsible for the pathway dysregulation and the oncogenic transformation. In particular, we found that miR-146b-5p, which was highly expressed in MVs, coordinated the regulation of cancer-related genes to promote cell-transforming processes. Notably, treatment of recipient cells with MV derived from K562 cells expressing mimics of miR-146b-5p revealed that it accelerated the transformation process in large part by silencing the tumor-suppressor NUMB. High levels of miR-146b-5p also enhanced reactive oxygen species levels and genome instability of recipient cells. Taken together, our finding showed how upregulation of oncogenic miRNAs in MVs promote hematopoetic cells to a leukemic state, as well as a demonstration for TF and miRNA coregulatory analysis in exploring the dysregulation of cancers and discovering key factors. Cancer Res; 76(10); 2901–11. ©2016 AACR.
Comparative analysis of the zeta-crystallin/quinone reductase gene in guinea pig and mouse.
Authors: P Gonzalez, C Hernández-Calzadilla, P V Rao, I R Rodriguez, J S Zigler, T Borrás
Journal: Molecular Biology and Evolution (1994)

zeta-Crystallin is a novel nicotinamide adenine dinucleotide phosphate:quinone reductase, present at enzymatic levels in various tissues of different species, which is highly expressed in the lens of some hystricomorph rodents and camelids. We report here the complementary DNA (cDNA) cloning of zeta-crystallin from liver libraries in guinea pig (Cavia porcellus), where zeta-crystallin is highly expressed in the lens, and in the laboratory mouse (Mus musculus), where expression in the lens occurs only at enzymatic levels. A 5' untranslated sequence different from the one previously reported for the guinea pig lens cDNA was found in these clones. We also report the isolation of genomic clones including the complete guinea pig zeta-crystallin gene and the 5' region of this gene in mouse. These results show the presence of two promoters in the guinea pig zeta-crystallin gene, one responsible for expression at enzymatic levels and the other responsible for the high expression in the lens. The guinea pig lens promoter is not present in the mouse gene. This is the first example in which the recruitment of an enzyme as a lens crystallin can be explained by the acquisition of an alternative lens-specific promoter.
Effect of Covered Metallic Stents Compared With Plastic Stents on Benign Biliary Stricture Resolution
Authors: Gregory A. Coté, Adam Slivka, Paul Tarnasky, Daniel K. Mullady, B. Joseph Elmunzer, Grace Elta, Evan Fogel, Glen Lehman, Lee McHenry, Joseph Romagnuolo, Shyam Menon, Uzma D. Siddiqui, James Watkins, Sheryl Lynch, Cheryl Denski, Huiping Xu, Stuart Sherman
Journal: JAMA (2016)

<h3>Importance</h3> Endoscopic placement of multiple plastic stents in parallel is the first-line treatment for most benign biliary strictures; it is possible that fully covered, self-expandable metallic stents (cSEMS) may require fewer endoscopic retrograde cholangiopancreatography procedures (ERCPs) to achieve resolution. <h3>Objective</h3> To assess whether use of cSEMS is noninferior to plastic stents with respect to stricture resolution. <h3>Design, Setting, and Participants</h3> Multicenter (8 endoscopic referral centers), open-label, parallel, randomized clinical trial involving patients with treatment-naive, benign biliary strictures (N = 112) due to orthotopic liver transplant (n = 73), chronic pancreatitis (n = 35), or postoperative injury (n = 4), who were enrolled between April 2011 and September 2014 (with follow-up ending October 2015). Patients with a bile duct diameter less than 6 mm and those with an intact gallbladder in whom the cystic duct would be overlapped by a cSEMS were excluded. <h3>Interventions</h3> Patients (N = 112) were randomized to receive multiple plastic stents or a single cSEMS, stratified by stricture etiology and with endoscopic reassessment for resolution every 3 months (plastic stents) or every 6 months (cSEMS). Patients were followed up for 12 months after stricture resolution to assess for recurrence. <h3>Main Outcomes and Measures</h3> Primary outcome was stricture resolution after no more than 12 months of endoscopic therapy. The sample size was estimated based on the noninferiority of cSEMS to plastic stents, with a noninferiority margin of −15%. <h3>Results</h3> There were 55 patients in the plastic stent group (mean [SD] age, 57 [11] years; 17 women [31%]) and 57 patients in the cSEMS group (mean [SD] age, 55 [10] years; 19 women [33%]). Compared with plastic stents (41/48, 85.4%), the cSEMS resolution rate was 50 of 54 patients (92.6%), with a rate difference of 7.2% (1-sided 95% CI, −3.0% to ∞;<i>P</i> &lt; .001). Given the prespecified noninferiority margin of −15%, the null hypothesis that cSEMS is less effective than plastic stents was rejected. The mean number of ERCPs to achieve resolution was lower for cSEMS (2.14) vs plastic (3.24; mean difference, 1.10; 95% CI, 0.74 to 1.46;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> Among patients with benign biliary strictures and a bile duct diameter 6 mm or more in whom the covered metallic stent would not overlap the cystic duct, cSEMS were not inferior to multiple plastic stents after 12 months in achieving stricture resolution. Metallic stents should be considered an appropriate option in patients such as these. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01221311
Assessing the therapeutic potential of lab‐made hepatocytes
Authors: Milad Rezvani, Andrew A. Grimm, Holger Willenbring
Journal: Hepatology (2016)

Hepatocyte transplantation has potential as a bridge or even alternative to whole‐organ liver transplantation. Because donor livers are scarce, realizing this potential requires the development of alternative cell sources. To be therapeutically effective, surrogate hepatocytes must replicate the complex function and ability to proliferate of primary human hepatocytes. Ideally, they are also autologous to eliminate the need for immune suppression, which can have severe side effects and may not be sufficient to prevent rejection long term. In the past decade, several methods have been developed to generate hepatocytes from other readily and safely accessible somatic cells. These lab‐made hepatocytes show promise in animal models of liver diseases, supporting the feasibility of autologous liver cell therapies. Here, we review recent preclinical studies exemplifying different types of lab‐made hepatocytes that can potentially be used in autologous liver cell therapies. To define the therapeutic efficacy of current lab‐made hepatocytes, we compare them to primary human hepatocytes, focusing on engraftment efficiency and posttransplant proliferation and function. In addition to summarizing published results, we discuss animal models and assays effective in assessing therapeutic efficacy. This analysis underscores the therapeutic potential of current lab‐made hepatocytes, but also highlights deficiencies and uncertainties that need to be addressed in future studies aimed at developing liver cell therapies with lab‐made hepatocytes. (H epatology 2016;64:287–294)
Thoughts on the “Cancer Industry”
Authors: Joan S. McClure
Journal: Journal of the National Comprehensive Cancer Network (2007)

Thoughts on the "Cancer Industry"Recently, someone I met-an educated, reasonably intelligent, otherwise very personable man-told me he truly believes that the "cancer industry" is a big con.He said that cancer will never be cured because it is too profitable to all involved.Further, he thinks that, although I "apparently believe in" what I do, my job-supervising the development of NCCN's clinical information-is loathsome.My first reaction was shock that someone I actually knew thought like this, but the conversation forced me to think about and evaluate what I think about cancer and its treatment.This list is what I have come to believe in the past 20 years of working in and around oncology:
Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families
Authors: K S Kendler, C J MacLean, F A O'Neill, J Burke, B Murphy, F Duke, R Shinkwin, S M Easter, B T Webb, J Zhang, D Walsh, R E Straub
Journal: American Journal of Psychiatry (1996)

This study was an attempt to replicate evidence for a vulnerability locus for schizophrenia and associated disorders in the 8p22-21 region reported by Pulver and colleagues.The linkage sample of the Irish Study of High-Density Schizophrenia Families consists of 265 multiplex families containing 1,408 individuals. Fifteen markers covering 30 centimorgans on chromosome 8p were tested. Three statistical methods were used: two-point and multipoint heterogeneity lod scores and a multipoint nonparametric test.According to two-point heterogeneity lod scores, the strongest evidence for linkage was found for markers D8S1731 (maximum lod score = 2.00), D8S1715 (maximum lod score = 2.52), and D8S133 (maximum lod score = 2.08) by assuming a phenotypic definition of all psychiatric illness and a range of genetic models. According to multipoint heterogeneity lod scores, the strongest evidence for linkage (maximum lod score = 2.34), found by using a dominant genetic model and a broad definition of the schizophrenia spectrum, extended over a 10-cM region between markers D8S1715 and D8S1739. Multipoint nonparametric linkage found the strongest evidence (maximum z = 2.51) over a broader region when either a diagnosis of core schizophrenia or a narrow definition of the schizophrenia spectrum was used. This putative vulnerability locus was segregating in 10%-25% of the families studied.This study supports the existence of a vulnerability locus for schizophrenia on chromosome 8p. In this sample, this locus appears to influence the risk of illness in only a modest proportion of families and predisposes to a range of schizophrenia spectrum and possibly nonspectrum disorders.
APC alternative splicing as responsible for phenotypic variability in familial adenomatous polyposis
Authors: S. Gonzalez, I. Blanco, A. Obrador-Hevia, M. Pineda, M. Peris, J. R. Germà Lluch, C. Lázaro, G. Capellá
Journal: Journal of Clinical Oncology (2008)

11091 Background: Familial adenomatous polyposis (FAP) is a dominantly inherited colorectal tumor predisposition that results from germ-line mutations in the Adenomatous Polyposis Coli (APC) gene. FAP shows substantial phenotypic variability: classical polyposis patients develop more than 100 colorectal adenomas, whereas those with attenuated polyposis (AAPC) have fewer than 100 adenomas usually associated with late onset. Abnormalities of pre-mRNA splicing are increasingly recognized as an important mechanism through which gene mutations cause disease and may affect disease expression, leading to phenotypic variability. Methods: Six members of family A characterized by the presence thyroid cancer in most cases, desmoids tumors and more than a classical FAP phenotype, were studied. Eight members of family B, characterized by three generations of affected members displaying AFAP were also analyzed as well as 5 healthy controls. The complete coding sequence and intron-exon boundaries of APC were studied. To assess the impact on splicing RNA-based analyses of exons 5–9 was done. Results: Affected relatives of family A harbor a heterozygous c.834+1G>A (IVS7+1 G>A) mutation in the APC gene predicted to abolish the splicing donor site of exon 7. RNA-based analyses of exons 5–9 showed the appearance of two APC isoforms (wt - 426 bp - and a 11 bp frameshift deletion (r.825_835del) that will generate a truncated protein (p.Gly275GlyfsX9). The 11bp deletion was absent from healthy controls. Affected relatives of family B harbor a heterozygous c.834+1G>A (IVS7+1 G>A) mutation in the APC gene as well as an intronic change c.730–29A>T (IVS6A>T) not predicted to change the splicing (Splice Site Prediction by Neural Network and Rescue ESE). Family B members displayed a third transcript with an in-frame exon 7 skipping [r.730_834del (p.Arg244_Gln278del)]. Conclusions: These findings suggest that aberrations in the post-transcriptional mechanisms which regulate APC gene expression may modify the pathogenicity of APC gene mutations. No significant financial relationships to disclose.
Comparing clinic and private practice of psychiatry
Authors: D G Langsley
Journal: American Journal of Psychiatry (1978)

The author compared data on 2,020 cases treated by private psychiatrists with those on 2,052 cases treated by clinic psychiatrists in California. He also compared data on private treatment in California with those from a national survey of private psychiatrists. Private psychiatrists in California treated as many psychotic patients and used relatively brief psychotherapy about as often as clinic psychiatrists and were more likely to use hospitalization and to see patients individually. In comparison with the national sample, private psychiatrists in California treated more children and patients with situational disturbances and were more likely to receive payment from government sources.
Reliability of the quantitative assessment of peripheral blood perfusion by laser speckle contrast analysis in a systemic sclerosis cohort
Authors: Valérie Lambrecht, Maurizio Cutolo, Filip De Keyser, Saskia Decuman, Barbara Ruaro, Alberto Sulli, Ellen Deschepper, Vanessa Smith
Journal: Annals of the Rheumatic Diseases (2016)

In systemic sclerosis (SSc), microvasculopathy is an important feature, resulting in digital ulcers in 30% of patients with SSc each year.1 ,2 Assessment of microvasculopathy in SSc is of clinical interest mostly for diagnostic and therapeutic purposes.

Nailfold videocapillaroscopy has in recent years earned its place in SSc as it makes early diagnosis of SSc possible in a Raynaud's population by evaluating morphological capillary abnormalities.3–5 Within an SSc population however, there is need for a technique that can evaluate blood perfusion in a dynamic way, to evaluate evolution of disease and more importantly response to therapy. For the latter, there is no validated technique available so far. Laser speckle contrast analysis (LASCA) is a relatively new technique that measures peripheral blood perfusion (PBP) in real time over a large area, in a non-contact manner, and is less time-consuming; it is thus convenient to implement in daily practice. …