tbuckley/cabot-search huggingface dataset:
DEVELOPMENTAL ROOTS OF SCHIZOPHRENIA
Authors: J. S. KASANIN
Journal: American Journal of Psychiatry (1945)

1. A diagnosis of schizophrenia rests partly on the data obtained from the mental status and observation of the patient; and to a greater degree on a history disclosing a faulty development of a special personality developing this particular disease entity. 2. It occurred to the author that a more intensive study of the genetic factors may help not only in aiding the diagnosis of schizophrenia but also to explain the content of schizophrenic thought. 3. A study of certain regressive phenomena in schizophrenia recalls a close analogy with certain dominant ideas in early child development. 4. A young child in his development goes through stages when he feels omnipotent, when he is not sure as to what will be his ultimate sex, and he has a feeling that adults know his thoughts. 5. The very same ideas appear in greater elaboration in schizophrenia, thus schizophrenics frequently express ideas of omnipotence, being endowed with great power, and somehow being mixed up with great cosmic events; they are very often confused as to whether they are men or women, and frequently express the idea that other people read their thoughts. 5. A greater knowledge of thinking of children may give us further clues in the understanding of schizophrenia as a disorder in which an individual regresses to earlier phases in his development.
Does the severity of primary sclerosing cholangitis influence the clinical course of associated ulcerative colitis?
Authors: L. Marelli, E. Xirouchakis, G. Kalambokis, E. Cholongitas, M. I. Hamilton, A. K. Burroughs
Journal: Gut (2011)

Ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC) is usually clinically mild. The aim of the study was to assess whether there is an association between severity of PSC and activity of UC, comparing the course of UC in patients with PSC not needing liver transplantation (LT) and those eventually transplanted.Between 1990 and 2009, 96 consecutive patients with PSC/UC were seen in the authors' institution. Data were evaluated from a database regarding UC activity (median follow-up 144 months). Follow-up was censored at time of LT or last clinical review.Patients with PSC/UC were divided into two groups: 46 did not need LT (no-LT) and 50 were transplanted (LT). There were no significant differences concerning duration of UC or PSC and extent of UC. The LT group had significantly (p=0.002) more clinically quiescent UC compared with the no-LT group. The LT group had fewer UC flare-ups (p=0.04) and required fewer steroid courses (p=0.025) with shorter duration (p=0.022) and less use of azathioprine (p=0.003). There was an increased need for surgery in the no-LT group (p=0.006). Colon carcinoma and high grade dysplasia were more frequent in the no-LT group (p=0.004). The no-LT group had increased inflammation in the colonic mucosa at histology (p=0.011), but without visual difference at colonoscopy.Clinically progressive PSC requiring LT is associated with a milder course of UC (reduced disease activity and less use of steroids, azathioprine and surgery). This is paralleled by less histological activity and reduced incidence of dysplasia and colon carcinoma.
Hormone Therapy Can Wait in PSA-Only Relapse
Authors: C. Schmidt
Journal: JNCI Journal of the National Cancer Institute (2014)

Men who had prostate cancer can be in for a shock if their prostate-specific antigen (PSA) levels start rising. Only prostate cells release PSA—and in large amounts by those that are cancerous. When PSA levels rise sharply without other evidence of cancer, it suggests hidden metastatic cells somewhere in the body, beyond sight of modern technologies. Up to 60,000 men face this biochemical relapse every year in the United States—most within 10 years of primary treatment— yet no clinical guidelines exist for how to handle it. One standard approach is to give androgen-deprivation therapy (ADT), which denies prostate cancer cells the testosterone they need to grow. However, ADT has challenging sexual and metabolic side effects. So depending on a patient’s age, anxiety, or other health problems, a doctor might also delay ADT until cancer becomes more evident. When to start ADT after biochemical recurrence is controversial, and many experts view the decision as a therapeutic dilemma. But mounting evidence suggests that waiting causes no harm. A study presented at the June 2014 annual meeting of the American Society of Clinical Oncology reveals no difference in overall survival between men who waited on ADT after biochemical relapse and those who started ADT immediately. According to Xabier Garcia-Albeniz, Ph.D., a research associate at the Harvard School of Public Health in Boston and the study’s lead author, many doctors feel comfortable deferring ADT on the basis of their own clinical experience. “They see patients doing well without therapy,” he said. “Now these data support their observations.” “The results show that the timing of ADT doesn’t matter,” added Joel Nelson, M.D., chair of the department of urology at the University of Pittsburgh School of Medicine, who wasn’t involved in the study. “As long as patients aren’t symptomatic, it’s reasonable to hold off on ADT for as long as possible and spare patients the effects of treatment.”
B cell activation. I. Anti-immunoglobulin-induced receptor cross-linking results in a decrease in the plasma membrane potential of murine B lymphocytes.
Authors: J G Monroe, J C Cambier
Journal: The Journal of Experimental Medicine (1983)

We report analyses of the effect of anti-Fab antibodies on plasma membrane potential of mouse B lymphocytes. Results indicate that divalent fragments of anti-Fab antibodies mitogenic for B cells stimulate membrane depolarization detectable by cytofluorometric analysis of 3,3'-dipentyloxacarbocyanine iodide-stained cells. Depolarization is detectable within 5 min of exposure to ligand and maximal within 1 h of exposure when greater than or equal to 80% of splenic B cells exhibit decreased membrane potential. The ineffectiveness of monovalent Fab antibody fragments in inducing this event suggests that receptor immunoglobulin cross-linking is essential. Frequencies of cells induced to enter cell cycle, as assessed by acridine orange cell cycle analysis, are equal to those induced to depolarize by lipopolysaccharide plus dextran sulfate or anti-Fab, which suggests a relationship between these events. However, membrane depolarization is itself an insufficient signal to promote subsequent thymidine uptake, as evidenced by the fact that doses of anti-Fab that are suboptimal for thymidine uptake induce maximal depolarization. These results suggest that cross-linking of surface immunoglobulin on B cells may provide an initial signal for activation but is itself insufficient to drive B cell proliferation.
αβ T cell antigen receptor recognition of CD1a presenting self lipid ligands
Authors: Richard W Birkinshaw, Daniel G Pellicci, Tan-Yun Cheng, Andrew N Keller, Maria Sandoval-Romero, Stephanie Gras, Annemieke de Jong, Adam P Uldrich, D Branch Moody, Dale I Godfrey, Jamie Rossjohn
Journal: Nature Immunology (2015)
Nature of T lymphocyte recognition of macrophage-associated antigens. V. Contribution of individual peptide residues of human fibrinopeptide B to T lymphocyte responses.
Authors: D W Thomas, K H Hsieh, J L Schauster, M S Mudd, G D Wilner
Journal: The Journal of Experimental Medicine (1980)

Guinea pig T lymphocyte responses to a decapeptide antigen (NH1-Asp5-Ans6-Glu7-Glu8-Gly9-Phe10-Phe11-Ser12-Ala13-Arg14-OH) of human fibrinopeptide B (hFPB) were examined using various synthetic peptide analogues containing single residue substitutions. Each analogue was examined for antigenicity as determined by an in vitro proliferative responses of hFPN-immune strain 2 guinae pig T cells. In addition, both strain 2 and strain 13 animals were immunized with each analogue and immunogenicity assessed by in vitro T cell-proliferative responses with the homologous immunizing analogue and the parent peptide. Replacement of arginine14 with lysine formed an immunogenic analogue which showed no antigenic cross-reactivity with the native peptide in strain 2 T cell responses. In addition, substitution of arginine14 with blocked lysine again produced a unique immunogenic analogue that showed little or no antigenic identity with the intact lysine analogue or the native peptide. In similar fashion, substitution of resideu phenylalanie10 with tyrosine or Phe(4-NO2) created unique immunogenic analogues with little or no antigenic identity to the native peptide with strain 2 T cells. By contrast, replacement of phenylalanine11 with either tyrosine or Phe(4-NO2) resulted in analogues with a total loss of immunogenicity and antigenicity in strain 2 T cell responses. An analogue in which glutamic acid7,8 were replaced with glutamine retained a small degree of antigenicity with hFPB-immune T cells, but T cells from strain 2 animals immunized with the Gln analogue responded only marginally to the Gln analogue while producing good proliferative responses with the native peptide. On the other hand, an analogue in which asparatic acid5 was replaced with asparagine retained most of the antigenic identity with hFPB for strain 2 T cell responses. None of thee analogues were immunogenic for strain 13 guinea pigs. These observations are discussed with respect to the contribution of each substituted residue to T cell respones, mechanism of Ir gene function, and a model for T cell recognition of small peptide antigens.
At Loose Ends: Telomere Theories of Aging and Cancer Begin To Converge
Authors: K. Garber
Journal: JNCI Journal of the National Cancer Institute (2012)

“One person’s funny story may be another person’s pain. It’s tricky to use humor if you’re not sure how it’s going to be interpreted by someone else. You have to know your patients, who they are, where they come from, and what their context is.” “The more you know a person, the better your intuition will be,” added Goodman. “Look for nonverbal cues, for what makes them laugh or brings a smile to their face.” He suggested that clinicians interested in lightening their visits assemble a collection of amusing but inoffensive sayings and quotes. He offered one of his favorites, from Robert Frost: “The brain is a wonderful organ. It starts when you wake up in the morning and does not stop until you get to work.” When all else fails, Goodman uses the AT&T test: “Is it
A/T mutagenesis in hypermutated immunoglobulin genes strongly depends on PCNAK164 modification
Authors: Petra Langerak, Anders O.H. Nygren, Peter H.L. Krijger, Paul C.M. van den Berk, Heinz Jacobs
Journal: The Journal of Experimental Medicine (2007)

B cells use translesion DNA synthesis (TLS) to introduce somatic mutations around genetic lesions caused by activation-induced cytidine deaminase. Monoubiquitination at lysine(164) of proliferating cell nuclear antigen (PCNA(K164)) stimulates TLS. To determine the role of PCNA(K164) modifications in somatic hypermutation, PCNA(K164R) knock-in mice were generated. PCNA(K164R/K164R) mutants are born at a sub-Mendelian frequency. Although PCNA(K164R/K164R) B cells proliferate and class switch normally, the mutation spectrum of hypermutated immunoglobulin (Ig) genes alters dramatically. A strong reduction of mutations at template A/T is associated with a compensatory increase at G/C, which is a phenotype similar to polymerase eta (Poleta) and mismatch repair-deficient B cells. Mismatch recognition, monoubiquitinated PCNA, and Poleta likely cooperate in establishing mutations at template A/T during replication of Ig genes.
Quantification of the physiological and performance characteristics of on-court tennis drills
Authors: M Reid, R Duffield, B Dawson, J Baker, M Crespo
Journal: British Journal of Sports Medicine (2007)

Objective: To determine the physiological responses and stroke characteristics of common on-court tennis training drills. Methods: Six high-performance players performed 1×6 repetitions of four common on-court training drills on two separate occasions; once with 30:30 seconds work:rest, and once with 60:30 seconds work:rest. Heart rate (HR), blood lactate [La − ], distance covered by the player (GPS) and rate of perceived exertion (RPE) were measured before the start of each drill and after the first and last repetition. Measures of shot count and accuracy and post-impact ball velocity per drill were also recorded. Results: Significant differences were observed between drills in measures of [La − ] and RPE both during ([La − ] 2.1–4.4 mmol/l; RPE 2.6–5.1) and after ([La − ] 4.4–10.6 mmol/l; RPE 4.3–7.6) drills, yet individual HR responses (160–182 beats/minute) were similar. Increased work times (60 v 30 seconds) also produced consistently raised [La − ] and RPE responses, yet players’ average movement velocities and forehand ball speed and accuracy remained consistent. Significant decreases in forehand ball speed and accuracy were observed during higher-intensity training drills, whereas significantly lower mean movement velocities underpinned performance of less intensive drills. Conclusions: The four drills produced physiological responses that reflect previously reported normal or maximal matchplay demands. These results point to the adaptations possible with adjustment of training drill type and load specific to matchplay demands or training phase.
Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial
Authors: Calvin J Cohen, Jaime Andrade-Villanueva, Bonaventura Clotet, Jan Fourie, Margaret A Johnson, Kiat Ruxrungtham, Hao Wu, Carmen Zorrilla, Herta Crauwels, Laurence T Rimsky, Simon Vanveggel, Katia Boven
Journal: The Lancet (2011)
Acetyl-Keto-β-Boswellic Acid Induces Apoptosis through a Death Receptor 5–Mediated Pathway in Prostate Cancer Cells
Authors: Min Lu, Lijuan Xia, Huiming Hua, Yongkui Jing
Journal: Cancer Research (2008)

Acetyl-keto-beta-boswellic acid (AKBA), a triterpenoid isolated from Boswellia carterri Birdw and Boswellia serrata, has been found to inhibit tumor cell growth and to induce apoptosis. The apoptotic effects and the mechanisms of action of AKBA were studied in LNCaP and PC-3 human prostate cancer cells. AKBA induced apoptosis in both cell lines at concentrations above 10 microg/mL. AKBA-induced apoptosis was correlated with the activation of caspase-3 and caspase-8 as well as with poly(ADP)ribose polymerase (PARP) cleavage. The activation of caspase-8 was correlated with increased levels of death receptor (DR) 5 but not of Fas or DR4. AKBA-induced apoptosis, caspase-8 activation, and PARP cleavage were inhibited by knocking down DR5 using a small hairpin RNA. AKBA treatment increased the levels of CAAT/enhancer binding protein homologous protein (CHOP) and activated a DR5 promoter reporter but did not activate a DR5 promoter reporter with the mutant CHOP binding site. These results suggest that AKBA induces apoptosis in prostate cancer cells through a DR5-mediated pathway, which probably involves the induced expression of CHOP.
Extensively drug-resistant tuberculosis: early access to bedaquiline for a UK patient
Authors: Clare van Halsema, Susan Humphreys, Alec Bonington
Journal: European Respiratory Journal (2013)

To the Editor: 

The prevalence of drug resistance among tuberculosis (TB) cases is increasing in the UK [1] and worldwide [2], with increasing proportions of cases with multidrug- and extensively drug-resistant TB (MDR-/XDR-TB) being reported [1, 2]. Toxicity and poor efficacy of treatment are major problems and long durations with culture-positive disease increase the risk of transmission. This report describes difficulties in managing XDR-TB and the pre-license use of bedaquiline outside of clinical trials.

Bedaquiline is an anti-tuberculous drug of the diarylquinoline class, which inhibits bacterial adenosine triphosphate synthase, and represents the first new class of anti-tuberculous agents for at least four decades. Its unique mechanism means that there is no cross-resistance with other drugs in current use. In phase II clinical trials, in combination with background MDR-TB regimens, bedaquiline resulted in reduced time to sputum culture conversion, reduced emergence of resistance to companion drugs and little additional toxicity compared with background regimens alone [3]. At present it is not yet licensed in Europe and the World Health Organization (WHO) has recently issued interim policy guidance for its use as part of combination therapy for adults with MDR-TB under specific conditions, based on currently available evidence [3].

A 28-year-old, HIV-negative Indian female with no prior history of TB treatment or contact was diagnosed with TB through screening on arrival in the UK. A pre-departure chest radiograph 3 months before assessment in the UK was reported to be normal. A bacille Calmette–Guerin scar was seen on examination. A tuberculin skin …
A combination of interferon-gamma and interleukin-2 production by Coxiella burnetii-stimulated circulating cells discriminates between chronic Q fever and past Q fever
Authors: T. Schoffelen, T. Sprong, C.P. Bleeker-Rovers, M.C.A. Wegdam-Blans, A. Ammerdorffer, M.J.H. Pronk, Y.E.P. Soethoudt, M.E.E. van Kasteren, T. Herremans, H.A. Bijlmer, M.G. Netea, J. W. M. van der Meer, L.A.B. Joosten, M. van Deuren
Journal: Clinical Microbiology and Infection (2013)
Toward a Philosophical Structure for Psychiatry
Authors: Kenneth S. Kendler
Journal: American Journal of Psychiatry (2005)

This article, which seeks to sketch a coherent conceptual and philosophical framework for psychiatry, confronts two major questions: how do mind and brain interrelate, and how can we integrate the multiple explanatory perspectives of psychiatric illness? Eight propositions are proposed and defended: 1) psychiatry is irrevocably grounded in mental, first-person experiences; 2) Cartesian substance dualism is false; 3) epiphenomenalism is false; 4) both brain-->mind and mind-->brain causality are real; 5) psychiatric disorders are etiologically complex, and no more "spirochete-like" discoveries will be made that explain their origins in simple terms; 6) explanatory pluralism is preferable to monistic explanatory approaches, especially biological reductionism; 7) psychiatry must move beyond a prescientific "battle of paradigms" to embrace complexity and support empirically rigorous and pluralistic explanatory models; 8) psychiatry should strive for "patchy reductionism" with the goal of "piecemeal integration" in trying to explain complex etiological pathways to illness bit by bit.
Calreticulin Is the Dominant Pro-Phagocytic Signal on Multiple Human Cancers and Is Counterbalanced by CD47
Authors: Mark P. Chao, Siddhartha Jaiswal, Rachel Weissman-Tsukamoto, Ash A. Alizadeh, Andrew J. Gentles, Jens Volkmer, Kipp Weiskopf, Stephen B. Willingham, Tal Raveh, Christopher Y. Park, Ravindra Majeti, Irving L. Weissman
Journal: Science Translational Medicine (2010)

Calreticulin-induced phagocytosis of cancer cells can be counterbalanced by CD47 expression.
The Cullin 4B–Based UV-Damaged DNA-Binding Protein Ligase Binds to UV-Damaged Chromatin and Ubiquitinates Histone H2A
Authors: Jennifer Guerrero-Santoro, Maria G. Kapetanaki, Ching L. Hsieh, Ilya Gorbachinsky, Arthur S. Levine, Vesna Rapić-Otrin
Journal: Cancer Research (2008)

Abstract By removing UV-induced lesions from DNA, the nucleotide excision repair (NER) pathway preserves the integrity of the genome. The UV-damaged DNA-binding (UV-DDB) protein complex is involved in the recognition of chromatin-embedded UV-damaged DNA, which is the least understood step of NER. UV-DDB consists of DDB1 and DDB2, and it is a component of the cullin 4A (CUL4A)–based ubiquitin ligase, DDB1-CUL4ADDB2. We previously showed that DDB1-CUL4ADDB2 ubiquitinates histone H2A at the sites of UV lesions in a DDB2-dependent manner. Mutations in DDB2 cause a cancer prone syndrome, xeroderma pigmentosum group E (XP-E). CUL4A and its paralog, cullin 4B (CUL4B), copurify with the UV-DDB complex, but it is unclear whether CUL4B has a role in NER as a separate E3 ubiquitin ligase. Here, we present evidence that CUL4A and CUL4B form two individual E3 ligases, DDB1-CUL4ADDB2 and DDB1-CUL4BDDB2. To investigate CUL4B's possible role in NER, we examined its subcellular localization in unirradiated and irradiated cells. CUL4B colocalizes with DDB2 at UV-damaged DNA sites. Furthermore, CUL4B binds to UV-damaged chromatin as a part of the DDB1-CUL4BDDB2 E3 ligase in the presence of functional DDB2. In contrast to CUL4A, CUL4B is localized in the nucleus and facilitates the transfer of DDB1 into the nucleus independently of DDB2. Importantly, DDB1-CUL4BDDB2 is more efficient than DDB1-CUL4ADDB2 in monoubiquitinating histone H2A in vitro. Overall, this study suggests that DDB1-CUL4BDDB2 E3 ligase may have a distinctive function in modifying the chromatin structure at the site of UV lesions to promote efficient NER. [Cancer Res 2008;68(13):5014–22]
Self reported stress and risk of breast cancer: prospective cohort study
Authors: Naja Rod Nielsen, Zuo-Feng Zhang, Tage S Kristensen, Bo Netterstr⊘m, Peter Schnohr, Morten Gr⊘nbæk
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To assess the relation between self reported intensity and frequency of stress and first time incidence of primary breast cancer. <b>Design</b> Prospective cohort study with 18 years of follow-up. <b>Setting</b> Copenhagen City heart study, Denmark. <b>Participants</b> The 6689 women participating in the Copenhagen City heart study were asked about their perceived level of stress at baseline in 1981-3. These women were followed until 1999 in the Danish nationwide cancer registry, with &lt; 0.1% loss to follow-up. <b>Main outcome measure</b> First time incidence of primary breast cancer. <b>Results</b> During follow-up 251 women were diagnosed with breast cancer. After adjustment for confounders, women with high levels of stress had a hazard ratio of 0.60 (95% confidence interval 0.37 to 0.97) for breast cancer compared with women with low levels of stress. Furthermore, for each increase in stress level on a six point stress scale an 8% lower risk of primary breast cancer was found (hazard ratio 0.92, 0.85 to 0.99). This association seemed to be stable over time and was particularly pronounced in women receiving hormone therapy. <b>Conclusion</b> High endogenous concentrations of oestrogen are a known risk factor for breast cancer, and impairment of oestrogen synthesis induced by chronic stress may explain a lower incidence of breast cancer in women with high stress. Impairment of normal body function should not, however, be considered a healthy response, and the cumulative health consequences of stress may be disadvantageous.