tbuckley/cabot-search huggingface dataset:
Is There an Association Between Social Media Use and Mental Health? The Timing of Confounding Measurement Matters
Authors: Katherine M. Keyes, Noah Kreski
Journal: JAMA Psychiatry (2020)

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Doctors slam “unacceptable” move after hospital asks clinicians to discharge patients early
Authors: Gareth Iacobucci
Journal: BMJ (2020)

Medical leaders have warned that doctors and patients are being placed at risk after it emerged that an NHS hospital had encouraged doctors to discharge patients early because of a lack of beds.

The internal email to senior clinicians, seen by the BBC,1 was sent by the Royal Cornwall Hospitals Trust in response to “significant pressure” on services.

To free up capacity the trust said that it was having to consider discharging patients “earlier than some clinicians would like.” It admitted that these patients could come to harm, describing the move as a “proportionate risk.”

Chaand Nagpaul, BMA council chair, …
Impact of the prior chemotherapy with two different fluoropyrimidines on the efficacy of CapeIRI or FOLFIRI in metastatic colorectal cancer: An exploratory analysis of the phase III AXEPT trial.
Authors: Tae Won Kim, Kei Muro, Rui-hua Xu, Young Suk Park, Wei Wang, Sae-Won Han, Mitsuyoshi Ota, Joong Bae Ahn, Yanhong Deng, Kohei Akiyoshi, Sang Hee Cho, Yi Ba, Tadamichi Denda, Keun-Wook Lee, Tao Zhang, Chu Matsuda, Yasuhide Yamada, Satoshi Morita, Satoru Iwasa, Junichi Sakamoto
Journal: Journal of Clinical Oncology (2019)

711 Background: Modified CapeIRI (irinotecan 200 mg/m 2 on day 1, capecitabine 1600 mg/m 2 on days 1–14 every 3 weeks) with or without bevacizumab (± BV) has shown non-inferiority of overall survival compared with FOLFIRI ± BV based on the phase III study, AXEPT, as second-line chemotherapy for patients with mCRC. In this exploratory analysis of the AXEPT trial, we evaluated the impact of the prior chemotherapy with two different fluoropyrimidine backbones (fluorouracil and leucovorin vs oral fluoropyrimidine) on the efficacy of CapeIRI and FOLFIRI. Methods: Patients were randomized to receive standard FOLFIRI ± bevacizumab or modified CapeIRI ± bevacizumab after failure to fluoropyrimidine-based chemotherapy in the AXEPT study. Prior fluoropyrimidine backbones were categorized into oral fluoropyrimidine-based (eg, capecitabine or S-1) regimen (oral 5-FU group) and fluorouracil and leucovorin-based regimen (infusional 5-FU group). Assessed endpoints included overall survival, progression-free survival, response rate, and safety. Results: Prior fluoropyrimidine backbone was available for 642 patients among all 650 randomized patients (oral 5-FU group in 291, and infusional 5-FU group in 351). Median overall survival was 17.0 and 16.7 months for FOLFIRI ± BV and CapeIRI ± BV in the prior oral 5-FU group, and 14.9 and 16.7 months for FOLFIRI ± BV and CapeIRI ± BV in the prior infusional 5-FU group. Median progression-free survival was 7.9 and 8.6 months for FOLFIRI ± BV and CapeIRI ± BV in the prior oral 5-FU group, and 6.8 and 8.3 months for FOLFIRI ± BV and CapeIRI ± BV in the prior infusional 5-FU group. Conclusions: There was no significant difference in the efficacy of CapeIRI or FOLFIRI regardless of prior fluoropyrimidine backbones. Therefore, CapeIRI ± BV could also be effective for patients after failure of oral fluoropyrimidine-based chemotherapy (eg, CapeOX ± BV). Clinical trial information: NCT01996306. [Table: see text]
Testing for Afirma in Thyroid Nodules with High-Risk Indeterminate Cytology (TIR3B): First Italian Experience
Authors: Massimiliano Andrioli, Silvia Carocci, Stefania Alessandrini, Mostafa Amini, Dominique Van Doorne, Daniela Pace, Angelo Lauria, Marco Raffaelli, Pierpaolo Trimboli
Journal: Endocrine Pathology (2020)
Subcutaneous Injection of Trastuzumab – Analysis of Administration Time and Injection Site Reactions
Authors: X. Pivot, V. Semiglazov, S. Chen, S.D. Moodley, A. Manihkas, M.A. Coccia-Portugal, M. Johnston, T. van der Horst, A. Bouhlel, C. Jackisch
Journal: Annals of Oncology (2012)
Phase II Trial of Single-Agent Pemetrexed in Chemonaive Elderly Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC) and its Accrual Rate in a Community-Based Clinical Trial Group: LCEN1001
Authors: N. Seki, T. Yokoyama, K. Kishi, T. Takao, I. Tsujino, N. Takahashi, H. Yoshifumi, S. Maho, S. Morita, K. Eguchi
Journal: Annals of Oncology (2012)
P-0177 Effect of Bevacizumab on P-Glycoprotein Activity and on the Pharmacokinetics of Irinotecan and its Main Active Metabolite (SN-38) in Vivo
Authors: Jean-Meidi Alili, Marie-Sophie Noel-Hudson, Celine Chu, Chadi Abbara, Robert Farinotti, Laurence Bonhomme-Faivre
Journal: Annals of Oncology (2012)
Histiocytic/Dendritic Neoplasm with Marked Blood Coagulation Disorder
Authors: R. Sakai, H. Tsuchihashi, Y. Ishii, W. Yamamoto, H. Takasaki, H. Takahashi, R. Watanabe, Y. Ishigatsubo, S. Motomura
Journal: Annals of Oncology (2012)
Worm expulsion is independent of alterations in composition of the colonic bacteria that occur during experimental <i>Hymenolepis diminuta</i>-infection in mice
Authors: Adam Shute, Arthur Wang, Timothy S. Jayme, Marc Strous, Kathy D. McCoy, Andre G. Buret, Derek M. McKay
Journal: Gut Microbes (2020)

The tapeworm Hymenolepis diminuta fails to establish in mice. Given the potential for helminth-bacteria interaction in the gut and the influence that commensal bacteria exert on host immunity, we tested if worm expulsion was related to alterations in the gut microbiota. Specific pathogen-free (SPF) mice, treated with broad-spectrum antibiotics, or germ-free wild-type mice were infected with H. diminuta, gut bacterial composition assessed by 16S rRNA gene sequencing, and worm counts, blood eosinophilia, goblet cells, splenic IL-4, -5 and -10, and colonic cytokines/chemokines mRNA were assessed. Effects of a PBS-soluble extract of adult H. diminuta on bacterial growth in vitro was tested. H. diminuta-infected mice displayed increased α and β diversity in colonic mucosa-associated and fecal bacterial communities, characterized by increased Lachnospiraceae and clostridium cluster XIVa. In vitro analysis revealed that the worm extract promoted the growth of anaerobic bacteria on M2GSC agar. H. diminuta-infection was accompanied by increased Th2 immune responses, and colon from infected mice had increased levels of IL-10, IL-25, Muc2, trefoil factor 3, and β2-defensin mRNA. SPF-mice treated with antibiotics, or germ-free mice, expelled H. diminuta with kinetics similar to control SPF mice. In both settings, measurements of Th2-immune responses were not significantly different across the groups. Thus, while infection with H. diminuta results in subtle but distinct changes to the colonic microbiota, we have no evidence to support an essential role for gut bacteria in the expulsion of the worm from the mouse host.
冠動脈CTで器質的狭窄が疑われた冠動脈squeezingの1例 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: 阪口和滋, 後藤亮, 土山高明, 萩元宣彦, 安達進, 磯部光章
Journal: Circulation (2009)
Seven-day vonoprazan and low-dose amoxicillin dual therapy as first-line <i>Helicobacter pylori</i> treatment: a multicentre randomised trial in Japan
Authors: Sho Suzuki, Takuji Gotoda, Chika Kusano, Hisatomo Ikehara, Ryoji Ichijima, Motoki Ohyauchi, Hirotaka Ito, Masashi Kawamura, Yohei Ogata, Masahiko Ohtaka, Moriyasu Nakahara, Koichi Kawabe
Journal: Gut (2020)

To date, no randomised trials have compared the efficacy of vonoprazan and amoxicillin dual therapy with other standard regimens for Helicobacter pylori treatment. This study aimed to investigate the efficacy of the 7-day vonoprazan and low-dose amoxicillin dual therapy as a first-line H. pylori treatment, and compared this with vonoprazan-based triple therapy.This prospective, randomised clinical trial was performed at seven Japanese institutions. Patients with H. pylori-positive culture test and naive to treatment were randomly assigned in a 1:1 ratio to either VA-dual therapy (vonoprazan 20 mg+amoxicillin 750 mg twice/day) or VAC-triple therapy (vonoprazan 20 mg+amoxicillin 750 mg+clarithromycin 200 mg twice/day) for 7 days, with stratification by age, sex, H. pylori antimicrobial resistance and institution. Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment.Between October 2018 and June 2019, 629 subjects were screened and 335 were randomised. The eradication rates of VA-dual and VAC-triple therapies were 84.5% and 89.2% (p=0.203) by intention-to-treat analysis, respectively, and 87.1% and 90.2% (p=0.372) by per-protocol analysis, respectively. VA-dual was non-inferior to VAC-triple in the per-protocol analysis. The eradication rates in strains resistant to clarithromycin for VA-dual were significantly higher than those for VAC-triple (92.3% vs 76.2%; p=0.048). The incidence of adverse events was equal between groups.The 7-day vonoprazan and low-dose amoxicillin dual therapy provided acceptable H. pylori eradication rates and a similar effect to vonoprazan-based triple therapy in regions with high clarithromycin resistance.UMIN000034140.
The Immunosuppressive Microenvironment in BRCA1-IRIS–Overexpressing TNBC Tumors Is Induced by Bidirectional Interaction with Tumor-Associated Macrophages
Authors: Eman Sami, Bibbin T. Paul, James A. Koziol, Wael M. ElShamy
Journal: Cancer Research (2020)

Tumor-associated macrophages (TAM) promote triple-negative breast cancer (TNBC) progression. Here, we report BRCA1-IRIS-overexpressing (IRISOE) TNBC cells secrete high levels of GM-CSF in a hypoxia-inducible factor-1α (HIF1α)- and a NF-κB-dependent manner to recruit macrophages to IRISOE cells and polarize them to protumor M2 TAMs. GM-CSF triggered TGFβ1 expression by M2 TAMs by activating STAT5, NF-κB, and/or ERK signaling. Despite expressing high levels of TGFβ1 receptors on their surface, IRISOE TNBC cells channeled TGFβ1/TβRI/II signaling toward AKT, not SMAD, which activated stemness/EMT phenotypes. In orthotopic and syngeneic mouse models, silencing or inactivating IRIS in TNBC cells lowered the levels of circulating GM-CSF, suppressed TAM recruitment, and decreased the levels of circulating TGFβ1. Coinjecting macrophages with IRISOE TNBC cells induced earlier metastasis in athymic mice accompanied by high levels of circulating GM-CSF and TGFβ1. IRISOE TNBC cells expressed low levels of calreticulin (the "eat me" signal for macrophages) and high levels of CD47 (the "do not eat me" signal for macrophages) and PD-L1 (a T-cell inactivator) on their surface. Accordingly, IRISOE TNBC tumors had significantly few CD8+/PD-1+ cytotoxic T cells and more CD25+/FOXP3+ regulatory T cells. These data show that the bidirectional interaction between IRISOE cells and macrophages triggers an immunosuppressive microenvironment within TNBC tumors that is favorable for the generation of immune-evading/stem-like/IRISOE TNBC metastatic precursors. Inhibiting this interaction may inhibit disease progression and enhance patients' overall survival. SIGNIFICANCE: The BRCA1-IRIS oncogene promotes breast cancer aggressiveness by recruiting macrophages and promoting their M2 polarization.
The earlier, the better or the worse? Towards accurate management of patients with arthralgia at risk for RA
Authors: Annette van der Helm-van Mil, Robert B M Landewé
Journal: Annals of the Rheumatic Diseases (2020)

The favourable long-term results of early treatment in patients with classified rheumatoid arthritis have resulted in an increasing interest in the diseases phases preceding clinical arthritis. The hypothesis to test is that an intervention in these early phases may better prevent or reduce disease persistence than an intervention when arthritis has become clinically manifest. While several placebo-controlled trials are still ongoing, to date there is no firm evidence that this hypothesis truly holds. Therefore, it is important to reflect on the current status of arthralgia preceding clinical arthritis. Inherent to every new field of research, attitudes are conflicting, with opinions propagating innovation (based on the fear of undertreatment) on the one hand, and critical sounds pleading for more restraint (fear of overtreatment) on the other hand. In this Viewpoint, we will examine these divergent opinions, relate them to a preferred ultimate scenario and provide considerations for future studies and daily practice.
Small Cell Lung Cancer (SCLC) Treated in First Line with Hybrid Scheme with Carboplatin and Etoposide intravenous (IV) and Oral. Comparison Between Patients Until 65 Years Old and Older
Authors: A. Ruiz-Valdepeñas, M. Palka, E. Almagro Casado, D. Pérez Callejo, P. Ibeas, B.G. Doger de Speville, C. Maximiano, B. Cantos, G. Diaz, M. Provencio Pulla
Journal: Annals of Oncology (2012)
Phase II Study of Biweekly Dose-Intense Paclitaxel Plus Gemcitabine (GEM/TAX) in Patients with Recurrent Locoregional or Metastatic Head and Neck Squamous Cell Carcinoma
Authors: A. Sukari, M. Salem, M. Al-Hajeili, J. Jacobs, S. Taylo, G. Yoo, H. Lin, L. Heilbrun, A. Alousi, O. Kucuk
Journal: Annals of Oncology (2012)
Microencapsulation of luteinizing hormone-releasing hormone agonist in poly (lactic-co-glycolic acid) microspheres by spray-drying
Authors: Nian-Qiu Shi, Jia Zhou, Jennifer Walker, Li Li, Justin K.Y. Hong, Karl F. Olsen, Jie Tang, Rose Ackermann, Yan Wang, Bin Qin, Anna Schwendeman, Steven P. Schwendeman
Journal: Journal of Controlled Release (2020)
Tumor Response and Survival in Patients with Advanced Non-Small-Cell Lung Cancer: The Predictive Value of Chemotherapy-Induced Changes in Fibrinogen
Authors: X. Qu, J. Zhao, M. Zhao, B. Jin, P. Yu, X. Hu, Y. Teng, J. Zhang, Y. Luo, S. Zheng, Q. Zhou, Y. Liu
Journal: Annals of Oncology (2012)
Patient-Reported Outcomes (PROS) From EMILIA, a Phase 3 Study of Trastuzumab Emtansine (T-DM1) vs Capecitabine and Lapatinib (XL) In HER2-Positive Locally Advanced or MBC
Authors: M. Welslau, V. Diéras, J. Sohn, S. Hurvitz, D. Lalla, L. Fang, E. Guardino, D. Miles
Journal: Annals of Oncology (2012)
Control of human hemoglobin switching by LIN28B-mediated regulation of BCL11A translation
Authors: Anindita Basak, Mathias Munschauer, Caleb A. Lareau, Kara E. Montbleau, Jacob C. Ulirsch, Christina R. Hartigan, Monica Schenone, John Lian, Yaomei Wang, Yumin Huang, Xianfang Wu, Lee Gehrke, Charles M. Rice, Xiuli An, Helen A. Christou, Narla Mohandas, Steven A. Carr, Jane-Jane Chen, Stuart H. Orkin, Eric S. Lander, Vijay G. Sankaran
Journal: Nature Genetics (2020)
Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study
Authors: Kristina E Rudd, Sarah Charlotte Johnson, Kareha M Agesa, Katya Anne Shackelford, Derrick Tsoi, Daniel Rhodes Kievlan, Danny V Colombara, Kevin S Ikuta, Niranjan Kissoon, Simon Finfer, Carolin Fleischmann-Struzek, Flavia R Machado, Konrad K Reinhart, Kathryn Rowan, Christopher W Seymour, R Scott Watson, T Eoin West, Fatima Marinho, Simon I Hay, Rafael Lozano, Alan D Lopez, Derek C Angus, Christopher J L Murray, Mohsen Naghavi
Journal: The Lancet (2020)

BackgroundSepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017.MethodsWe used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990–2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates.FindingsIn 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9–62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1–12·0) sepsis-related deaths were reported, representing 19·7% (18·2–21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8–54·5) and mortality decreased by 52·8% (47·7–57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia.InterpretationDespite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa.FundingThe Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.
Safety of Everolimus For Women Over 65 Years of Age With Advanced Breast Cancer: 18-Mo Follow-Up of BOLERO-2
Authors: M. Gnant, S. Noguchi, Y. Ito, M. Piccart, J. Baselga, A. Panneerselvam, T. Taran, T. Sahmoud, G.N. Hortobagyi, K. Pritchard
Journal: Annals of Oncology (2012)
Pilot Study of Tigatuzumab (CS-1008) in Combination with Folfiri in Patients with Metastatic Colorectal Cancer (CRC)
Authors: G. Kim, M. Borad, H. Pitot, J. Rubin, J. Greenberg, P. McCroskery, R. Beckman, A. Grothey
Journal: Annals of Oncology (2012)
Undermining Glutaminolysis Bolsters Chemotherapy While NRF2 Promotes Chemoresistance in KRAS-Driven Pancreatic Cancers
Authors: Suman Mukhopadhyay, Debanjan Goswami, Pavan P. Adiseshaiah, William Burgan, Ming Yi, Theresa M. Guerin, Serguei V. Kozlov, Dwight V. Nissley, Frank McCormick
Journal: Cancer Research (2020)

Abstract Pancreatic cancer is a disease with limited therapeutic options. Resistance to chemotherapies poses a significant clinical challenge for patients with pancreatic cancer and contributes to a high rate of recurrence. Oncogenic KRAS, a critical driver of pancreatic cancer, promotes metabolic reprogramming and upregulates NRF2, a master regulator of the antioxidant network. Here, we show that NRF2 contributed to chemoresistance and was associated with a poor prognosis in patients with pancreatic cancer. NRF2 activation metabolically rewired and elevated pathways involved in glutamine metabolism. This curbed chemoresistance in KRAS-mutant pancreatic cancers. In addition, manipulating glutamine metabolism restrained the assembly of stress granules, an indicator of chemoresistance. Glutaminase inhibitors sensitized chemoresistant pancreatic cancer cells to gemcitabine, thereby improving the effectiveness of chemotherapy. This therapeutic approach holds promise as a novel therapy for patients with pancreatic cancer harboring KRAS mutation. Significance: These findings illuminate the mechanistic features of KRAS-mediated chemoresistance and provide a rationale for exploiting metabolic reprogramming in pancreatic cancer cells to confer therapeutic opportunities that could be translated into clinical trials.
Phase 1 and 2 Trials of Combination Therapy with Gemcitabine and Candesartan in Advanced Pancreatic Cancer
Authors: Y. Nakai, H. Isayama, H. Ijichi, T. Sasaki, Y. Ito, S. Matsubara, H. Yagioka, R. Nagano, K. Kawakubo, H. Kogure, N. Yamamoto, N. Sasahira, K. Hirano, M. Tada, K. Koike
Journal: Annals of Oncology (2012)
Prognostic Relevance of Fibroblast Growth Factor Receptor 1 (FGFR1) Gene Copy Number in Pure Lung Squamous-Cell Carcinoma
Authors: L. Terracciano, E. Rossi, L. Landi, M. Roncalli, A. D'Incecco, M. D'Arcangelo, A. Destro, M. Incarbone, M. Andreozzi, F. Cappuzzo
Journal: Annals of Oncology (2012)
P-0059 is Radiofrequency Ablation is Effective for Metachronous Liver Metastasis from Gastric Cancer?
Authors: Jun-Eul Hwang, Dae-Eun Kim, Shim Hyun-Jeong, Woo-Kyun Bae, Sang-Hee Cho, Ik-Joo Chung
Journal: Annals of Oncology (2012)
Phenome-based approach identifies RIC1-linked Mendelian syndrome through zebrafish models, biobank associations and clinical studies
Authors: Gokhan Unlu, Xinzi Qi, Eric R. Gamazon, David B. Melville, Nisha Patel, Amy R. Rushing, Mais Hashem, Abdullah Al-Faifi, Rui Chen, Bingshan Li, Nancy J. Cox, Fowzan S. Alkuraya, Ela W. Knapik
Journal: Nature Medicine (2020)
P-0231 Occurrence of 2152 C&gt;T –MHS2 Mutation in Brazilian Lynch Syndrome Families
Authors: Ingrid Ewald, Silvia Cossio, Patrícia Koehler-Santos, Patricia da Silva, Cristina Netto, Carla Pinto, Manuel Teixeira, Patricia Ashton-Prolla
Journal: Annals of Oncology (2012)
Preclinical and Clinical Evaluation of the Combination of Sorafenib and Everolimus in Patients with Advanced Solid Tumors
Authors: W.W. Ma, C. Weekes, D.K. Pawaskar, G. Fetterly, W.A. Messersmith, G.K. Dy, R.M. Straubinger, W.J. Jusko, S.G. Eckhardt, A.A. Adjei
Journal: Annals of Oncology (2012)
What is the best method for managing early miscarriage?
Authors: Justin Chu, Pollyanna Hardy, Leanne Beeson, Arri Coomarasamy
Journal: BMJ (2020)

### What you need to know

An early miscarriage is the loss of pregnancy at ≤13 weeks’ gestation.1 It is a major life event and can have a potentially devastating psychological impact on the woman in addition to the physical effects such as bleeding and pain.2 About one in four pregnancies, where a woman has missed a menstrual period and has a positive pregnancy test, ends in early miscarriage.3 Nearly 125 000 early miscarriages occur annually in the UK, accounting for 50 000 hospital admissions.4

Early miscarriage is usually diagnosed by pelvic ultrasound after a woman has experienced vaginal bleeding or abdominal pain. Women with a complete miscarriage, where expulsion of pregnancy tissue is complete, are managed conservatively without further intervention. Women with a missed or incomplete miscarriage (box 1) may require further intervention.

Box 1 
### Categories of early miscarriageRETURN TO TEXT

Surgery under general anaesthesia used to be the standard treatment for miscarriage,6 but a wider choice of management options is now available (fig 1).3 Over the past two decades there has been a shift towards individualised care and shared decision making between clinician and patient. Up to 70% of women with miscarriage opted for …