tbuckley/cabot-search huggingface dataset:
Anti-tumor activity of docetaxel is enhanced by dietary genistein in an experimental bone metastasis model of prostate cancer
Authors: Yiwei Li, Sunita Bhagat, Maha Hussain, Omer Kucuk, Judith Abrams, Michael Cher, Fazlul Sarkar
Journal: Cancer Research (2005)

5116  Bone metastasis is very common in advanced prostate cancer. For chemotherapy, docetaxel combined with other chemotherapeutic agents has shown improved clinical response in patients with metastatic prostate cancer. However, the combination treatment contributes to added toxicity. Therefore, it is necessary to develop an optimized and mechanism-based combination therapy for prostate cancer. Genistein, derived primarily from soy products, has been found to inhibit cancer cell growth in vitro and in vivo without toxicity. We have previously reported that dietary genistein inhibits prostate cancer bone metastasis in a SCID-hu (SCID-human) model. In this study, we investigated whether dietary genistein could potentiate the anti-tumor activity of docetaxel in a SCID-hu model. PC-3 prostate cancer cells were injected into human bone fragments previously implanted in SCID mice (SCID-hu model). The mice were divided into four groups: control, genistein, docetaxel, and genistein plus docetaxel treatment groups. In the genistein and genistein plus docetaxel groups, the mice were fed a genistein-containing diet (1 g/kg) beginning on the day of intraosseous tumor cell injection. The mice in docetaxel and genistein plus docetaxel groups received a total of 3 doses of docetaxel (5 mg/kg, iv) in 6 days as soon as the majority of the bone implants began to enlarge as determined by caliper measurements (24th day after cancer cell injection) showing tumor growth. The volume of the bone tumor in each group was determined by twice weekly caliper measurements. Microarray analysis was conducted to determine the gene expression profiles altered by genistein or docetaxel in genistein treated bone metastatic PC-3 cells and docetaxel treated PC-3 cells. Real-time RT-PCR, Western Blot analysis, cDNA transfection, and siRNA analysis were conducted to confirm microarray data. We found that genistein significantly inhibited PC-3 bone tumor growth (control group: 1930 mm3; genistein group: 1490 mm3; p
Role of colon capsule in colorectal cancer screening: lights and shadows
Authors: Enrique Quintero
Journal: Endoscopy (2021)

The implementation of screening has greatly contributed to the decrease in incidence and mortality of colorectal cancer (CRC) in many developed countries over the past two decades. Screening from the age of 50 years prevents CRC by enabling the detection and removal of precancerous lesions (advanced adenomatous or serrated polyps) and reduces mortality through early detection (stages I and II) of curable CRC [1].
Succinate Ubiquinone Reductase Activity Predicts Multiple Myeloma Sensitivity to Venetoclax
Authors: Richa Bajpai, Changyong Wei, Shannon Matulis, Ajay K. Nooka, Samuel McBrayer, Sagar Lonial, Vikas A. Gupta, Lawrence H. Boise, Mala Shanmugam
Journal: Blood (2017)
PTU-098 Tace for hcc: long term outcome in a regional centre
Authors: A Liaros, J Deosaran, A Ahmed, M Priest, S Barclay, E Forrest, R Gillespie, J Evans, J Graham, D Kay, R Kasthuri, A Stanley
Journal: Gut (2017)

Introduction  The incidence of hepatocellular carcinoma (HCC) is rising.1,2 Transarterial chemoembolisation (TACE) is frequently used as a palliative treatment or as a bridge to surgery. TACE can be offered alone, or together with radiofrequency ablation (RFA) or Sorafenib. Child-Pugh grade and Barcelona Clinic Liver Cancer Staging System (BCLC) are useful prognostic tools. Our aim was to assess outcome for patients receiving TACE over a 6 year period in our regional centre.  Method  Patients with HCC were prospectively entered onto a regional HCC database between 01.01.09–01.01.15. Patients who underwent TACE (in addition to other therapies) were identified and clinical data obtained from electronic records. Child-Pugh grade and BCLC were calculated at time of diagnosis, with survival our primary outcome.  Results  497 patients were diagnosed with HCC during this period. 121 (99 male, 22 females; mean age 68 years) underwent TACE. 20, 47 and 54 patients had TACE during the periods 2009–10, 2011–12 and 2013–14 respectively. 102 (84%) had TACE alone, 6 (5%) each had TACE with RFA and TACE with Sorafenib, 5 (4%) had TACE then transplant, and two TACE then resection. 87 (72%), 31 (26%) and 3 (2%) had Child-Pugh grade A, B and C disease respectively and 38 (31%), 61 (50%), 20 (17%) and 2 (2%) BCLC stage A, B, C and D.  Of the 102 patients having TACE alone, survival is shown in table:  Two year survival for patients having TACE and RFA was 80%; for TACE and Sorafenib 17% and for TACE then transplant/resection 100%.  Conclusion  There has been a steady rise in the number of patients with HCC undergoing TACE procedures in our unit. Survival following TACE compares favourably to other studies.3,4  References  . Cancer Mortality in Scotland (2015). Information Services Division publication report. https://isdscotland.scot.nhs.uk/Health-Topics/Cancer/Publications/2016-10-25/2016-10-25-Cancer-Mortality-Report.pdf [Accessed 26/10/16].  . Liver Cancer Incidence Trends Great Britain 1979-2013. Available from: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/liver-cancer/incidence#heading-Two [Accessed: 31/10/16].  . EASL–EORTC clinical practice guidelines: Management of hepatocellular carcinoma. Journal of Hepatology, 201256: 908–943.  . Greten T.F., Papendorf F., Bleck J.S., Kirschhoff T., Wohlberedt T., Kubicka S., Klempnauer J., Galanski M., Manns M.P. Survival rate in patients with hepatoceullar carcinoma: a retrospective analysis of 389 patients. British Journal of Cancer, 2005. 92: 1862–1868.  Disclosure of Interest  None Declared
Associations between Residential Proximity to Oil and Gas Drilling and Term Birth Weight and Small-for-Gestational-Age Infants in Texas: A Difference-in-Differences Analysis
Authors: Mary D. Willis, Elaine L. Hill, Andrew Boslett, Molly L. Kile, Susan E. Carozza, Perry Hystad
Journal: Environmental Health Perspectives (2021)

Background: Oil and natural gas extraction may produce environmental pollution at levels that affect reproductive health of nearby populations. Available studies have primarily focused on unconventional gas drilling and have not accounted for local population changes that can coincide with drilling activity. Objective: Our study sought to examine associations between residential proximity to oil and gas drilling and adverse term birth outcomes using a difference-in-differences study design. Methods: We created a retrospective population-based term birth cohort in Texas between 1996 and 2009 composed of mother–infant dyads (n=2,598,025) living <10km from an oil or gas site. We implemented a difference-in-differences approach to estimate associations between drilling activities and infant health: term birth weight and term small for gestational age (SGA). Using linear and logistic regression, we modeled interactions between births before (unexposed) or during (exposed) drilling activity and residential proximity near (0–1, 1–2, or 2–3km) or far (3–10km) from an active or future drilling site, adjusting for individual- and neighborhood-level characteristics. Results: The adjusted mean difference in term birth weight for mothers living 0–1 vs. 3–10km from a current or future drilling site was –7.3g [95% confidence interval (CI): –11.6, –3.0] for births during active vs. future drilling. The corresponding adjusted odds ratio for SGA was 1.02 (95% CI: 0.98, 1.06). Negative associations with term birth weight were observed for the 1–2 and 2–3km near groups, and no consistent differences were identified by type of drilling activity. Larger, though imprecise, adverse associations were found for infants born to Hispanic women, women with the lowest educational attainment, and women living in cities. Conclusions: Residing near oil and gas drilling sites during pregnancy was associated with a small reduction in term birth weight but not SGA, with some evidence of environmental injustices. Additional work is needed to investigate specific drilling-related exposures that might explain these associations. https://doi.org/10.1289/EHP7678
Psyllium reduces insulin-induced colonic gas production in irritable bowel syndrome: MRI and in vitro fermentation studies
Authors: David Gunn, Zainab Abbas, Hannah Harris, Giles Major, Caroline Hoad, Penny Gowland, Luca Marciani, Samantha Gill, Fred Warren, Megan Rossi, Jose Remes-Troche, Kevin Whelan, Robin Spiller
Journal: Gut (2021)

Objective: Health promoting dietary fibre including inulin often triggers gastrointestinal symptoms in patients with irritable bowel syndrome (IBS), limiting their intake. Our aim was to test if co-administering psyllium with inulin would reduce gas production. 

Design: A randomised, four-period, four-treatment, placebo-controlled, crossover trial in 19 patients with IBS. Subjects ingested a 500ml test drink containing either inulin 20g, psyllium 20g, inulin 20g + psyllium 20g, or dextrose 20g (placebo). Breath hydrogen was measured every 30 minutes with MRI scans hourly for 6 hours. Faecal samples from a subset of the IBS patients were tested using an in vitro fermentation model. Primary endpoint was colonic gas assessed by MRI. 

Results: Colonic gas rose steadily from 0-6 hours, with inulin causing the greatest rise, median (IQR) AUC(0-360 min) 3145 (848-6502) ml.min. This was significantly reduced with inulin and psyllium co-administration to 618 (62-2345) ml.min (p=0.02), not significantly different from placebo. Colonic volumes AUC(0-360 min) were significantly larger than placebo for both inulin (p=0.002) and inulin and psyllium co-administration (p=0.005). Breath hydrogen rose significantly from 120 minutes after inulin but not psyllium; co-administration of psyllium with inulin delayed and reduced the maximum increase, AUC(0-360 min) from 7230 (3255-17910) ppm.hr to 1035 (360-4320) ppm.hr, p=0.007. 

Fermentation in vitro produced more gas with inulin than psyllium. Combining psyllium with inulin did not reduce gas production. 
Conclusions: Psyllium reduced inulin-related gas production in IBS patients but does not directly inhibit fermentation. Whether co-administration with psyllium increases the tolerability of prebiotics in IBS warrants further study.
Hydroxychloroquine dose tapering or discontinuation in cutaneous lupus erythematosus after remission: A retrospective multicenter cohort study of 56 patients
Authors: Gabrielle Sonigo, Marie Jachiet, Didier Bessis, Nadège Cordel, Caroline Faucon, Antoine Petit, Florence Cordoliani, Martine Bagot, Patricia Senet, Annick Barbaud, Jean-David Bouaziz, Camille Francès, François Chasset
Journal: Journal of the American Academy of Dermatology (2021)
Contrasting Stage Dependent Requirements for the Histone Methyltransferase EZH2 during the Evolution of Acute Myeloid Leukemia
Authors: Faisal Basheer, George Giotopoulos, Eshwar Meduri, Haiyang Yun, Milena Mazan, Olivia Sheppard, Daniel Sasca, Malgorzata Gozdecka, George S. Vassiliou, Brian J.P Huntly
Journal: Blood (2017)
Adaptive Introgression Facilitates Adaptation to High Latitudes in European Aspen (<i>Populus tremula</i> L.)
Authors: Martha Rendón-Anaya, Jonathan Wilson, Sæmundur Sveinsson, Aleksey Fedorkov, Joan Cottrell, Mark E S Bailey, Dainis Ruņǵis, Christian Lexer, Stefan Jansson, Kathryn M Robinson, Nathaniel R Street, Pär K Ingvarsson
Journal: Molecular Biology and Evolution (2021)

Understanding local adaptation has become a key research area given the ongoing climate challenge and the concomitant requirement to conserve genetic resources. Perennial plants, such as forest trees, are good models to study local adaptation given their wide geographic distribution, largely outcrossing mating systems, and demographic histories. We evaluated signatures of local adaptation in European aspen (Populus tremula) across Europe by means of whole-genome resequencing of a collection of 411 individual trees. We dissected admixture patterns between aspen lineages and observed a strong genomic mosaicism in Scandinavian trees, evidencing different colonization trajectories into the peninsula from Russia, Central and Western Europe. As a consequence of the secondary contacts between populations after the last glacial maximum, we detected an adaptive introgression event in a genome region of ∼500 kb in chromosome 10, harboring a large-effect locus that has previously been shown to contribute to adaptation to the short growing seasons characteristic of Northern Scandinavia. Demographic simulations and ancestry inference suggest an Eastern origin-probably Russian-of the adaptive Nordic allele which nowadays is present in a homozygous state at the north of Scandinavia. The strength of introgression and positive selection signatures in this region is a unique feature in the genome. Furthermore, we detected signals of balancing selection, shared across regional populations, that highlight the importance of standing variation as a primary source of alleles that facilitate local adaptation. Our results, therefore, emphasize the importance of migration-selection balance underlying the genetic architecture of key adaptive quantitative traits.
The Potential Role of Clinical Metagenomics in Infectious Diseases: Therapeutic Perspectives
Authors: Camille d’Humières, Maud Salmona, Sarah Dellière, Stefano Leo, Christophe Rodriguez, Cécile Angebault, Alexandre Alanio, Slim Fourati, Vladimir Lazarevic, Paul-Louis Woerther, Jacques Schrenzel, Etienne Ruppé
Journal: Drugs (2021)
P5-5 Phase 2/3 study of bintrafusp alfa with gemcitabine plus cisplatin as first-line treatment of biliary tract cancer
Authors: Do-Youn Oh, Filippo de Braud, John Bridgewater, Junji Furuse, Chih-Hung Hsu, Masafumi Ikeda, Sunyoung Lee, Markus Moehler, Joon Oh Park, Lin Shen, Changhoon Yoo, Christoph Helwig, Motonobu Osada, Mitesh Borad
Journal: Annals of Oncology (2021)
Micronutrient powders and diarrhoea risk in infants and young children
Authors: Parminder S Suchdev, Maria Elena Jefferds, Kathryn G Dewey, Stanley Zlotkin, Victor M Aguayo, Saskia de Pee, Klaus Kraemer, Alison Greig, Mandana Arabi, Luz Maria De-Regil
Journal: The Lancet Child & Adolescent Health (2021)
Repopulation of decellularized retinas with hiPSC-derived retinal pigment epithelial and ocular progenitor cells shows cell engraftment, organization and differentiation
Authors: Maria Maqueda, Jose Luis Mosquera, José García-Arumí, Anna Veiga, Anna Duarri
Journal: Biomaterials (2021)

The retinal extracellular matrix (ECM) provides architectural support, adhesion and signal guidance that controls retinal development. Decellularization of the ECM affords great potential to tissue engineering; however, how structural retinal ECM affects in vitro development, differentiation and maturation of ocular cells remains to be elucidated. Here, mouse and porcine retinas were decellularized and the protein profile analyzed. Acellular retinal ECM (arECM) scaffolds were then repopulated with human iPSC-derived retinal pigment epithelial (RPE) cells or ocular progenitor cells (OPC) to assess their integration, proliferation and organization. 3837 and 2612 unique proteins were identified in mouse and porcine arECM, respectively, of which 93 and 116 proteins belong to the matrisome. GO analysis shows that matrisome-related proteins were associated with the extracellular region and cell junction and KEGG pathways related to signalling transduction, nervous and endocrine systems and cell junctions were enriched. Interestingly, mouse and porcine arECMs were successfully repopulated with both RPE and OPC, the latter exhibiting cell lineage-specific clusters. Retinal cells organized into different layers containing well-defined areas with pigmented cells, photoreceptors, Müller glia, astrocytes, and ganglion cells, whereas in other areas, conjunctival/limbal, corneal and lens cells re-arranged in cell-specific self-organized areas. In conclusion, our results demonstrated that decellularization of both mouse and porcine retinas retains common native ECM components that upon cell repopulation could guide similar ocular cell adhesion, migration and organization.
Dual-AAV delivering split prime editor system for in vivo genome editing
Authors: Shengyao Zhi, Yuxi Chen, Guanglan Wu, Jinkun Wen, Jinni Wu, Qianyi Liu, Yang Li, Rui Kang, Sihui Hu, Jiahui Wang, Puping Liang, Junjiu Huang
Journal: Molecular Therapy (2021)

Prime editor (PE), a new genome editing tool, can generate all 12 possible base-to-base conversions, insertion, and deletion of short fragment DNA. PE has the potential to correct the majority of known human genetic disease-related mutations. Adeno-associated viruses (AAVs), the safe vector widely used in clinics, are not capable of delivering PE (∼6.3 kb) in a single vector because of the limited loading capacity (∼4.8 kb). To accommodate the loading capacity of AAVs, we constructed four split-PE (split-PE994, split-PE1005, split-PE1024, and split-PE1032) using Rma intein (Rhodothermus marinus). With the use of a GFP-mutated reporter system, PE reconstituting activities were screened, and two efficient split-PEs (split-PE1005 and split-PE1024) were identified. We then demonstrated that split-PEs delivered by dual-AAV1, especially split-PE1024, could mediate base transversion and insertion at four endogenous sites in human cells. To test the performance of split-PE in vivo, split-PE1024 was then delivered into the adult mouse retina by dual-AAV8. We demonstrated successful editing of Dnmt1 in adult mouse retina. Our study provides a new method to deliver PE to adult tissue, paving the way for in vivo gene-editing therapy using PE.
Polymeric microneedle‐mediated sustained release systems: Design strategies and promising applications for drug delivery
Authors: Li Yang, Yao Yang, Hongzhong Chen, Lin Mei, Xiaowei Zeng
Journal: Asian Journal of Pharmaceutical Sciences (2021)

Parenteral sustained release drug formulations, acting as preferable platforms for long-term exposure therapy, have been wildly used in clinical practice. However, most of these delivery systems must be given by hypodermic injection. Therefore, issues including needle-phobic, needle-stick injuries and inappropriate reuse of needles would hamper the further applications of these delivery platforms. Microneedles (MNs) as a potential alternative system for hypodermic needles can benefit from minimally invasive and self-administration. Recently, polymeric microneedle-mediated sustained release systems (MN@SRS) have opened up a new way for treatment of many diseases. Here, we reviewed the recent researches in MN@SRS for transdermal delivery, and summed up its typical design strategies and applications in various diseases therapy, particularly focusing on the applications in contraception, infection, cancer, diabetes, and subcutaneous disease. An overview of the present clinical translation difficulties and future outlook of MN@SRS was also provided.
A woman with recurrent erythema and vesicles on her legs
Authors: Min Zhang, Mengli Zhang, Mei Ju, Haoxiang Xu
Journal: BMJ (2021)

A woman in her 20s presented with a two year history of recurrent (20 episodes) erythema and painful vesicles on her legs and recurrent (24 episodes) small clusters of pruritic blisters on her right lower buttock. The blisters coincided with fatigue and menstruation. On six occasions over the past year and a half she had experienced erosions on her tongue and buccal mucosa. Within the past month red papules, with unclear ring-shaped borders and mild scaling, had appeared on her left buttock. Occasionally, she had scattered erythema with blisters on her arms and trunk.

Oral steroids were initially tried for suspected Behcet’s disease and Sweet syndrome. The lesions on the limbs, trunk, tongue, and buccal mucosa improved but recurred when the patient stopped treatment. Thalidomide and tetracycline were also tried for Behcet’s disease and Sweet syndrome, but response was poor. The patient had used ibuprofen for pain relief when the leg vesicles ruptured and became erosions.

On examination, lesions were observed on the right lower buttock, and tender erythematous lesions had developed on the legs and thighs three days earlier. Grouped vesicles on an erythematous base …
Cervical Cancer Screening in Developing Countries—Reply
Authors: Sue J. Goldie
Journal: JAMA (2001)

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Dissecting indirect genetic effects from peers in laboratory mice
Authors: Amelie Baud, Francesco Paolo Casale, Amanda M. Barkley-Levenson, Nilgoun Farhadi, Charlotte Montillot, Binnaz Yalcin, Jerome Nicod, Abraham A. Palmer, Oliver Stegle
Journal: Genome biology (2021)

Abstract Background The phenotype of an individual can be affected not only by the individual’s own genotypes, known as direct genetic effects (DGE), but also by genotypes of interacting partners, indirect genetic effects (IGE). IGE have been detected using polygenic models in multiple species, including laboratory mice and humans. However, the underlying mechanisms remain largely unknown. Genome-wide association studies of IGE (igeGWAS) can point to IGE genes, but have not yet been applied to non-familial IGE arising from “peers” and affecting biomedical phenotypes. In addition, the extent to which igeGWAS will identify loci not identified by dgeGWAS remains an open question. Finally, findings from igeGWAS have not been confirmed by experimental manipulation. Results We leverage a dataset of 170 behavioral, physiological, and morphological phenotypes measured in 1812 genetically heterogeneous laboratory mice to study IGE arising between same-sex, adult, unrelated mice housed in the same cage. We develop and apply methods for igeGWAS in this context and identify 24 significant IGE loci for 17 phenotypes (FDR &lt; 10%). We observe no overlap between IGE loci and DGE loci for the same phenotype, which is consistent with the moderate genetic correlations between DGE and IGE for the same phenotype estimated using polygenic models. Finally, we fine-map seven significant IGE loci to individual genes and find supportive evidence in an experiment with a knockout model that Epha4 gives rise to IGE on stress-coping strategy and wound healing. Conclusions Our results demonstrate the potential for igeGWAS to identify IGE genes and shed light into the mechanisms of peer influence.
Reaction on the Interpretation of the Hippocampus Avoidance Prophylactic Cranial Irradiation Trial in SCLC (NCT01780675)
Authors: José S.A. Belderbos, Dirk K.M. De Ruysscher, Katrien De Jaeger, Friederike Koppe, Maarten L.F. Lambrecht, Yolande N. Lievens, Edith M.T. Dieleman, Jaap P.M. Jaspers, Jan P. Van Meerbeeck, Fred Ubbels, Margriet H. Kwint, Marianne A. Kuenen, Sabine Deprez, Michiel B. De Ruiter, Willem Boogerd, Karolina Sikorska, Harm Van Tinteren, Sanne B. Schagen
Journal: Journal of Thoracic Oncology (2021)