tbuckley/cabot-search huggingface dataset:
Codon use and the rate of divergence of land plant chloroplast genes.
Authors: B R Morton
Journal: Molecular Biology and Evolution (1994)

Codon fitnesses for chloroplast genes were estimated using the relative synonymous codon use of psbA, which has a different pattern of codon use than other chloroplast genes and is the major translation product of the chloroplast. These estimates were used to calculate the codon adaptation index (CAI) of chloroplast genes from Marchantia polymorpha, Nicotiana tabacum, and Chlamydomonas reinhardtii. The genes with the highest CAI values in M. polymorpha correspond to those that are expressed at the highest levels. The rate of divergence between M. polymorpha and both C. reinhardtii and N. tabacum is inversely related to the CAI value of the M. polymorpha gene. The data suggest that selection is acting on the synonymous codon use of the highly expressed genes of the M. polymorpha chloroplast genome. The data set is inconclusive about N. tabacum genes, but, as there is a weaker correspondence between CAI value and expression level, it suggests that selection is not operating in this lineage.
Incident Hepatitis B Virus Infection in HIV-Infected and HIV-Uninfected Men Who Have Sex With Men From Pre-HAART to HAART Periods
Authors: Oluwaseun Falade-Nwulia, Eric C. Seaberg, Anna E. Snider, Charles R. Rinaldo, John Phair, Mallory D. Witt, Chloe L. Thio
Journal: Annals of Internal Medicine (2015)

Men who have sex with men (MSM) are at high risk for hepatitis B virus (HBV) infection. Data on the effect of highly active antiretroviral therapy (HAART) on incident HBV infection in HIV-infected and HIV-uninfected MSM are limited.To determine predictors of incident HBV infection in MSM during pre-HAART and HAART periods.Observational cohort study.Cohort of MSM who have, or are at risk for, HIV infection.2375 HBV-uninfected MSM in the Multicenter AIDS Cohort Study.Poisson regression was used to compare incidence rates of HBV infection in the pre-HAART and HAART eras and to identify factors associated with incidence of HBV infection.In 25,322 person-years of follow-up, 244 incident HBV infections occurred. The unadjusted incidence rate was higher in HIV-infected MSM than in HIV-uninfected MSM (incidence rate ratio [IRR], 1.9 [95% CI, 1.5 to 2.4]) and was significantly lower in the HAART era than in the pre-HAART era among HIV-infected (IRR, 0.2 [CI, 0.1 to 0.4]) and HIV-uninfected (IRR, 0.3 [CI, 0.2 to 0.4]) MSM. Age younger than 40 years (IRR, 2.3 [CI, 1.7 to 3.0]), more than 1 recent sexual partner (IRR, 3.1 [CI, 2.3 to 4.2]), and HIV infection (IRR, 2.4 [CI, 1.8 to 3.1]) were independently associated with higher incidence of HBV infection, whereas HBV vaccination was protective (IRR, 0.3 [CI, 0.2 to 0.4]). Highly active antiretroviral therapy with HIV RNA levels less than 400 copies/mL was associated with protection (IRR, 0.2 [CI, 0.1 to 0.5]), but HAART in those with HIV RNA levels of 400 copies/mL or greater was not.The observational nature limits inferences about causality.Effective HAART is associated with lower incidence of HBV infection; however, even in the HAART era, incidence of HBV infection remains high among MSM.National Institute of Allergy and Infectious Diseases.
An Analysis of SV40-Induced Transformation of Hamster Kidney Tissue &lt;italic&gt;In Vitro&lt;/italic&gt;. IV. Studies of the Pathology of Hamster Tumors Induced With SV40-Transformed Hamster Cell Clones
Authors: Paul H. Black, Leonard D. Berman, Richard Maloof
Journal: JNCI Journal of the National Cancer Institute (1966)

Clones were established from continuous lines of SV40-transformed weanling hamster kidney cells by isolation of single cells in microdrop cultures. Mixed tumors (sarcomas with areas of tubule formation) resulted from subcutaneous inoculation of hamsters with 5 of the 16 clones tested, but areas of epithelial cells in various stages of differentiation were observed in the predominantly sarcomatous tumors resulting from transplantation of 15 of the 16 clones. These findings prove that tumors containing both sarcomatous and carcinomatous elements may arise from the progeny of a single cell. Such tumors were classified as nephroblastomas, and it was postulated that the target cell for SV40 transformation in weanling hamster kidney cultures was a primitive metanephric blastema cell which may undergo differentiation to either epithelial or fibroblastic cells during in vivo growth. The extent of epithelialization in the tumors varied. Cell lines established from the first clonal isolations gave rise to tumors that had more epithelialization and were more malignant than the tumors induced with cell lines originating from the third clonal isolations; infectious SV40 virus could be recovered from the former but not from the latter cell lines. It is suggested that the presence of the viral genome in the transformed cells might alter or influence the state of differentiation of the cell.
Re: Alessandro Volpe, Kamran Ahmed, Prokar Dasgupta, et al. Pilot Validation Study of the European Association of Urology Robotic Training Curriculum. Eur Urol 2015;68:292–9
Authors: Marco Oderda, Francois Audenet, Alberto Briganti, Matthew Brown, Vincenzo De Marco, Melanie Gan, Martin Janssen, Remi Navarro, Rodolfo Sanchez-Salas, Esther Wit
Journal: European Urology (2014)
Cystinosin is a Component of the Vacuolar H+-ATPase-Ragulator-Rag Complex Controlling Mammalian Target of Rapamycin Complex 1 Signaling
Authors: Zuzanna Andrzejewska, Nathalie Nevo, Lucie Thomas, Cerina Chhuon, Anne Bailleux, Véronique Chauvet, Pierre J. Courtoy, Marie Chol, Ida Chiara Guerrera, Corinne Antignac
Journal: Journal of the American Society of Nephrology (2015)

Cystinosis is a rare autosomal recessive storage disorder characterized by defective lysosomal efflux of cystine due to mutations in the CTNS gene encoding the lysosomal cystine transporter, cystinosin. Lysosomal cystine accumulation leads to crystal formation and functional impairment of multiple organs. Moreover, cystinosis is the most common inherited cause of renal Fanconi syndrome in children. Oral cysteamine therapy delays disease progression by reducing intracellular cystine levels. However, because cysteamine does not correct all complications of cystinosis, including Fanconi syndrome, we hypothesized that cystinosin could have novel roles in addition to transporting cystine out of the lysosome. By coimmunoprecipitation experiments and mass spectrometry, we found cystinosin interacts with almost all components of vacuolar H(+)-ATPase and the Ragulator complex and with the small GTPases Ras-related GTP-binding protein A (RagA) and RagC. Furthermore, the mammalian target of rapamycin complex 1 (mTORC1) pathway was downregulated in proximal tubular cell lines derived from Ctns(-/-) mice. Decrease of lysosomal cystine levels by cysteamine did not rescue mTORC1 activation in these cells, suggesting that the downregulation of mTORC1 is due to the absence of cystinosin rather than to the accumulation of cystine. Our results show a dual role for cystinosin as a cystine transporter and as a component of the mTORC1 pathway, and provide an explanation for the appearance of Fanconi syndrome in cystinosis. Furthermore, this study highlights the need to develop new treatments not dependent on lysosomal cystine depletion alone for this devastating disease.
Halting progressive neurodegeneration in advanced retinitis pigmentosa
Authors: Susanne F. Koch, Yi-Ting Tsai, Jimmy K. Duong, Wen-Hsuan Wu, Chun-Wei Hsu, Wei-Pu Wu, Luis Bonet-Ponce, Chyuan-Sheng Lin, Stephen H. Tsang
Journal: Journal of Clinical Investigation (2015)

Hereditary retinal degenerative diseases, such as retinitis pigmentosa (RP), are characterized by the progressive loss of rod photoreceptors followed by loss of cones. While retinal gene therapy clinical trials demonstrated temporary improvement in visual function, this approach has yet to achieve sustained functional and anatomical rescue after disease onset in patients. The lack of sustained benefit could be due to insufficient transduction efficiency of viral vectors ("too little") and/or because the disease is too advanced ("too late") at the time therapy is initiated. Here, we tested the latter hypothesis and developed a mouse RP model that permits restoration of the mutant gene in all diseased photoreceptor cells, thereby ensuring sufficient transduction efficiency. We then treated mice at early, mid, or late disease stages. At all 3 time points, degeneration was halted and function was rescued for at least 1 year. Not only do our results demonstrate that gene therapy effectively preserves function after the onset of degeneration, our study also demonstrates that there is a broad therapeutic time window. Moreover, these results suggest that RP patients are treatable, despite most being diagnosed after substantial photoreceptor loss, and that gene therapy research must focus on improving transduction efficiency to maximize clinical impact.
A randomized, multicentre study of directed daylight exposure times of 1½ vs. 2½ h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp
Authors: S.R. Wiegell, S. Fabricius, I.M. Stender, B. Berne, S. Kroon, B.L. Andersen, C. Mørk, C. Sandberg, G.B.E. Jemec, M. Mogensen, K.M. Brocks, P.A. Philipsen, J. Heydenreich, M. Haedersdal, H.C. Wulf
Journal: British Journal of Dermatology (2011)

Actinic keratoses (AKs) are common dysplastic skin lesions that may differentiate into invasive squamous cell carcinomas. Although a superior cosmetic outcome of photodynamic therapy (PDT) is advantageous compared with equally effective treatments such as cryotherapy and curettage, the inconvenience of clinic attendance and discomfort during therapy are significant drawbacks. Daylight-mediated PDT could potentially reduce these and may serve as an alternative to conventional PDT.To compare the efficacy of methyl aminolaevulinate (MAL)-PDT with 1½ vs. 2½ h of daylight exposure in a randomized multicentre study.One hundred and twenty patients with a total of 1572 thin AKs of the face and scalp were randomized to either 1½- or 2½-h exposure groups. After gentle lesion preparation and application of a sunscreen of sun protection factor 20, MAL was applied to the entire treatment area. Immediately after, patients left the clinic and exposed themselves to daylight according to the randomization. Daylight exposure was monitored with a wristwatch dosimeter and patients scored their pain sensation during treatment.The mean lesion response rate at 3 months was 77% in the 1½-h group and 75% in the 2½-h group (P = 0·57). The mean duration of daylight exposure was 131 and 187 min in the two groups. The mean overall effective light dose was 9·4 J cm(-2) (range 0·2-28·3). Response rate was not associated with effective daylight dose, exposure duration, treatment centre, time of day or time of year during which the treatment was performed. Treatment was well tolerated, with a mean ± SD maximal pain score of 1·3 ± 1·5.Daylight-mediated MAL-PDT is an effective, convenient and nearly pain-free treatment for patients with multiple thin AKs. Daylight-mediated PDT procedures were easily performed and 2 h of daylight exposure resulted in uniformly high response rates when conducted in the period from June to October in Nordic countries.
Mycobiota of the pharynx in patients with persistent bronchial asthma who constantly applying the inhaled corticosteroids
Authors: Irina Reshetnikova, Rustem Fassakhov, Nadegda Glushco, Elena Khaldeeva, Svetlava Lisovskaya
Journal: European Respiratory Journal (2012)

The aim: to investigate fungal colonization the pharyngeal mucosa in patients with persistent asthma, who constantly applying the inhaled corticosteroids (iGCS).  Methods: There were examined 30 patients with bronchial asthma (13 men and 17 women, mean age 51.8 years) using iGCS at high and moderate doses of at least year. Mycological study of mucous pharynx (posterior wall of the pharynx, tongue root) for finding of Candida was performed on the Sabourau agar medium. Fungi growing was carried out at 28-30C for 48 hours. To study the adhesive there was used the model of a nitrocellulose film with immobilized hemoglobin.  Results: Fungi of the Candida genus were isolated from the mucosa in 23 patients (76,6%): C.albicans - 22 cases (of which in one case, there was marked the combination of C.albicans and Geotrihum candidum), C.tropicalis – 1case. In 73.9% of the cases intensity of the pharynx colonization by yeastlike fungi was high and was10  3 , 10  5  CFU / ml.  It has been stated that 16 out of 22 isolated Candida albicans cultures (72,7%) have less vivid ability to form tube germination and psevdomitsely in comparison with clinical cultures, isolated from the pharynx of patient with the diagnose pharyngomikoze, the adhesive activity of these cultures shoved at the middle level and made 15-32%. 8 out of 22 patients (27.3%) have cultures with a high ability for germination tubes formation and adhesive activity at the level of 35-45%, which corresponded to the level of clinical cultures with high virulence.The causes of differences in the activity of the fungus Candida in asthmatic patients receiving iGCS, require further study.
A randomized clinical trial of chemotherapy compared to chemotherapy in combination with cetuximab in k-RAS wild-type patients with operable metastases from colorectal cancer: The new EPOC study.
Authors: John Neil Primrose, Stephen Falk, Meg Finch-Jones, Juan W. Valle, David Sherlock, Joanne Hornbuckle, James Gardner-Thorpe, David Smith, Charles Imber, Tamas Hickish, Brian Davidson, David Cunningham, Graeme John Poston, Tim Maughan, Myrrdyn Rees, Louise Stanton, Louisa Little, Megan Bowers, Wendy Wood, John A. Bridgewater
Journal: Journal of Clinical Oncology (2013)

3504 Background: Resection of liver metastases from colorectal cancer with or without neoadjuvant chemotherapy is the standard of care. The EPOC study (Nordlinger et al, Lancet 2008) randomised patients between surgery and surgery with chemotherapy and demonstrated an improvement in 3 year progression free survival (PFS) of 7·3% (from 28·1% to 35·4%). As a rational extension to the EPOC study data, the New EPOC study evaluates the benefit of cetuximab, an EGF receptor antibody, in addition to standard chemotherapy in patients with operable liver metastases. Methods: 272 patients were randomised between February 2007 and November 2012 into the New EPOC study. Eligible patients were required to be k-RAS wild type, have operable liver metastases and to be sufficiently fit for chemotherapy and surgery. Patients with the primary tumour in situ, and those who required short course rectal radiation were eligible. Patients were randomised to receive a fluoropyrimidine and oxaliplatin plus or minus cetuximab for 12 weeks before, then 12 weeks following surgery. Patients who had been treated with adjuvant oxaliplatin could receive irinotecan and 5 – fluorouracil. Results: Following a recommendation from the Independent Data Monitoring Committee on 19/11/2012, the New EPOC study was stopped when the study met a protocol pre-defined futility analysis. With 45.3% (96/212) of the expected events observed, progression free survival was significantly worse in the cetuximab arm (14.8 vs 24.2 months, HR (95%CI) 1.50037 (1.000707 to 2.249517) p&lt; 0.048). The result of a pre-planned analysis excluding the 23 patients treated with irinotecan based chemotherapy was similar (15.2 vs 24.2 months, HR 1.565546 (1.014967-2.414793) P&lt;0.043). Conclusions: Although the data are immature, the accumulation of more events is unlikely to change this result. In patients with resectable liver metastases and K-RAS wt tumours the addition of cetuximab to chemotherapy is not beneficial. Clinical trial information: ISRCTN22944367.
Preliminary Data Suggest a Role for Bacterial Superinfection of a Viral Keratitis after Zosteriform Spread of Herpes Simplex virus to the Eye of the Mouse
Authors: C Claoué
Journal: Journal of the Royal Society of Medicine (1988)

After inoculation of herpes simplex virus (HSV) on the snout of the mouse, spread to the eye occurs via neural pathways. The keratitis which ensued was clinically atypical for a pure herpetic keratitis, leading to a search for other causative agents. Preliminary data suggests that bacteriological super-infection of the viral keratitis occurs frequently, producing a unique experimental model.
TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors
Authors: Linda J Valentijn, Jan Koster, Danny A Zwijnenburg, Nancy E Hasselt, Peter van Sluis, Richard Volckmann, Max M van Noesel, Rani E George, Godelieve A M Tytgat, Jan J Molenaar, Rogier Versteeg
Journal: Nature Genetics (2015)
Neuropsychiatric side effects of tuberculosis
Authors: L. Fekih, W. Ben hamad, D. Greb, H. Abdeghaffar, H. Hassene, Mahamed Lamine Megdiche
Journal: European Respiratory Journal (2012)

Accurency of neurological or psychiatric complications secondary to the administration of antituberculosis may be at the origin of diagnosis and therapeutic problems. This work aims at studying the frequency of these manifestations, their clinical presentations and their therapeutic approach.  Patients and methods: this retrospective study was carried on from January 1990 to June 2008 at Ibn Nafis Pulmonary Department of Abderrahmen Mami Hospital in Ariana. It dealt with 18 in-patients with a neurologic or psychiatric complication due to antituberculosis drugs. Peripheral neuropathy was noted in 6 patients (33%). One of them had a history of chronic alcoolism, another one had a history of diabetes mellitus and 2 other patients were more than 72 years old. We had definitively stopped isoniazide in 2 cases and decreased the dosage in 4 other patients. However, all patients received B6 vitamin. Convulsions occured in 2 women without any history of epileptic status. Anticonvulsivant treatment was prescribeb and isoniazid definitively stopped. Hallucinosis was noted in 4 patients, with one having a history of chronic alcoolism. Isoniazid was stopped in all cases. Aggressivety,insomia and memory problems were noted in 6 patients. Isoniazid was interrupted in only one women who had history of depression. In 5 other patients, anxiolytics were prescribed. Isoniazid was incrimined in all cases and evolution was favorable for the 18 patients. A close monitoring of patients on antituberculosis treatment is required to detect the onset of any neuropsychiatric complications incriminating usually isoniazid. Definitive interruption or decrease of the dose of isoniazid depending of the acetylation test were necessary.
Culture conversion rates of multi-drug resistant (MDR-TB) patients treated in the community versus an inpatient setting in a rural area of the Western Cape (WC) of South Africa
Authors: Martha Van der Walt, Karen Shean, Devesh Upadhya, Sweetnes Siwendu
Journal: European Respiratory Journal (2012)

Introduction: The MDR programme to theWest Coast Winelands area consists of inpatient treatment centres and an outreach programme, for treatment of patients in the community.  Objective: To compare baseline demographic and culture conversion rates among patients initiating MDR-TB treatment in the community versus those initiated as inpatients.  Methods: We retrospectively reviewed clinical records at the inpatient Centre of patients diagnosed between 2000 – 2006 with a first episode of MDR-TB. Patients were included if started on a regimen with 3 or more second-line anti-TB drugs (SLD), came from this area and had a bacteriological confirmed diagnosis. Time from diagnosis to treatment initiation and from initiation to culture conversion were determined, and demographic and clinical indicators at baseline.  Results: 502 patients were diagnosed with new MDR-TB, among which 324 (64.5%) started on SLD. Median age was 34, with 105 females (32%). 145/324 (45%) started in the community vs. 179 (55%) as inpatients. Inpatients and community-based were similar in baseline age and AFB result; but inpatients were more likely to be female (40% v. 23%; p  Conclusion: Algorithms are needed for identifying patients suitable for treatment in the community.
RIG-I receptors induced by dsRNA challenges in an HDM-mouse model of asthma exacerbation
Authors: Irma Mahmutovic Persson, Mandy Menzel, Hamid Akbarshahi, Lena Uller
Journal: European Respiratory Journal (2014)

Exacerbations of asthma caused by viral infections are serious conditions in need of novel treatment. We previously showed similarities between exacerbation produced by dsRNA challenges and viral infection in OVA-induced allergic inflammation. We hypothesized that dsRNA challenges in mice with house dust mice (HDM)-induced ″asthma″ would produce further translational features of exacerbations.

Method: Mice were challenged with HDM (or saline) 3 times/week for 3 weeks established experimental asthma. Exacerbation was induced by superimposed dsRNA challenges (50or100μg) for 3 days. BALF was analysed for total- and differential cell counts, total protein, and necrosis markers LDH and ATP. Lung histology was examined and lung homogenates analysed for mRNA expression of TSLP, IFNβ, IFNλ, CCL2, TNFα and RIG-I (RT-qPCR), cytokine release of CXCL1 and CCL2 (ELISA) and protein expression of RIG-I (Western Blot).

Results: HDM challenge alone increased total protein in BALF, white blood cellcount and lung tissue expression of TSLP, IL-33, TNFα and IFNβ compared to saline. dsRNA-induced exacerbations involved these effects compared to HDM alone: BALF eosinophilia persisted and neutrophilia increased (p‹0.01); BALF protein, LDH, and ATP were increased (p‹0.05); lung protein levels of IL-33, CXCL1 and CCL2 were increased (p‹0.05); lung expression of TSLP, IL-33, TNFα, CCL2, and IFNλ was increased (p‹0.01). Most dsRNA-induced responses, including LDH, were dose-dependent and associated with RIG-I expression.

Conclusion: Similar to viral induced human asthma, LDH biomarkers were present in dsRNA-induced exacerbation. Our findings suggest a role for RIG-I in exacerbation-induced hub cytokines including IL-33.
Exploitation or a woman's right?
Authors: M. V Sauer
Journal: BMJ (1997)

Paying women to donate oocytes has sparked much controversy. Interestingly, a duality of practice has evolved. In many parts of the world compensation is prohibited, while in some countries, particularly the United States, donating gametes is handsomely rewarded. It seems naive to presume a consensus will be reached regarding the correct approach. Furthermore, the United States is highly unlikely to curtail or regulate payments by law. Thus, supply and demand will inevitably continue to dictate policy, and the price of oocyte donation will escalate along with donor fees.

There exists an inherent moral ambiguity in a practice of medicine that simultaneously places young women at risk of infertility while treating the childlessness of other women. Which need is paramount? Do benefits to one group far outweigh the risks posed to the other? These …