tbuckley/cabot-search huggingface dataset:
A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer
Authors: Joan M. Romero, Barbara Grünwald, Gun-Ho Jang, Prashant P. Bavi, Aaditeya Jhaveri, Mehdi Masoomian, Sandra E. Fischer, Amy Zhang, Robert E. Denroche, Ilinca M. Lungu, Angela De Luca, John M.S. Bartlett, Jing Xu, Niandong Li, Sharon Dhaliwal, Sheng-Ben Liang, Dianne Chadwick, Foram Vyas, Peter Bronsert, Rama Khokha, Tracy L. McGaha, Faiyaz Notta, Pamela S. Ohashi, Susan J. Done, Grainne M. O'Kane, Julie M. Wilson, Jennifer J. Knox, Ashton Connor, Yifan Wang, George Zogopoulos, Steven Gallinger
Journal: Clinical Cancer Research (2020)

The molecular drivers of antitumor immunity in pancreatic ductal adenocarcinoma (PDAC) are poorly understood, posing a major obstacle for the identification of patients potentially amenable for immune-checkpoint blockade or other novel strategies. Here, we explore the association of chemokine expression with effector T-cell infiltration in PDAC.Discovery cohorts comprised 113 primary resected PDAC and 107 PDAC liver metastases. Validation cohorts comprised 182 PDAC from The Cancer Genome Atlas and 92 PDACs from the Australian International Cancer Genome Consortium. We explored associations between immune cell counts by immunohistochemistry, chemokine expression, and transcriptional hallmarks of antitumor immunity by RNA sequencing (RNA-seq), and mutational burden by whole-genome sequencing.Among all known human chemokines, a coregulated set of four (CCL4, CCL5, CXCL9, and CXCL10) was strongly associated with CD8+ T-cell infiltration (P < 0.001). Expression of this "4-chemokine signature" positively correlated with transcriptional metrics of T-cell activation (ZAP70, ITK, and IL2RB), cytolytic activity (GZMA and PRF1), and immunosuppression (PDL1, PD1, CTLA4, TIM3, TIGIT, LAG3, FASLG, and IDO1). Furthermore, the 4-chemokine signature marked tumors with increased T-cell activation scores (MHC I presentation, T-cell/APC costimulation) and elevated expression of innate immune sensing pathways involved in T-cell priming (STING and NLRP3 inflammasome pathways, BATF3-driven dendritic cells). Importantly, expression of this 4-chemokine signature was consistently indicative of a T-cell-inflamed phenotype across primary PDAC and PDAC liver metastases.A conserved 4-chemokine signature marks resectable and metastatic PDAC tumors with an active antitumor phenotype. This could have implications for the appropriate selection of PDAC patients in immunotherapy trials.
Recurrence at the Nipple-Areola Complex and Safety of Nipple-Sparing Mastectomy
Authors: Wonshik Han, Han-Byoel Lee
Journal: JAMA Surgery (2020)

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Broadly Neutralizing Antibodies for HIV Prevention
Authors: Shelly T. Karuna, Lawrence Corey
Journal: Annual Review of Medicine (2020)

In the last decade, over a dozen potent broadly neutralizing antibodies (bnAbs) to several HIV envelope protein epitopes have been identified, and their in vitro neutralization profiles have been defined. Many have demonstrated prevention efficacy in preclinical trials and favorable safety and pharmacokinetic profiles in early human clinical trials. The first human prevention efficacy trials using 10 sequential, every-two-month administrations of a single anti-HIV bnAb are anticipated to conclude in 2020. Combinations of complementary bnAbs and multi-specific bnAbs exhibit improved breadth and potency over most individual antibodies and are entering advanced clinical development. Genetic engineering of the Fc regions has markedly improved bnAb half-life, increased mucosal tissue concentrations of antibodies (especially in the genital tract), and enhanced immunomodulatory and Fc effector functionality, all of which improve antibodies' preventative and therapeutic potential. Human-derived monoclonal antibodies are likely to enter the realm of primary care prevention and therapy for viral infections in the near future.
B27 IHH Acts as a Tumor Suppressor of Lung Adenocarcinoma by Repressing Reactive Oxygen Species
Authors: S. Kasiri, B. Chen, A. Wilson, A. Reczek, S. Mazambani, J. Gadhvi, E. Noel, U. Marriam, B. Mino, W. Lu, L. Girard, L. Solis, K. Luby-Phelps, J. Bishop, J. Kim, J. Kim
Journal: Journal of Thoracic Oncology (2020)
Bridget Concepta “Connie” Fahey
Authors: Tom Fahey
Journal: BMJ (2020)

Bridget Concepta “Connie” Fahey (nee MacDonagh) was part of the Irish medical generation who migrated to the UK in the 1950s. She initially trained in anaesthesia in the north of England but after meeting and marrying her husband, Sean, she joined him in general practice in 1960, initially in Wolverhampton and then in Oldbury. Together they ran a busy general practice in a deprived area of Birmingham, during a period with significant …
The Lung Cancer Symptom Scale (LCSS) as a prognostic indicator of overall survival in malignant pleural mesothelioma (MPM) patients: Post hoc analysis of a phase III study.
Authors: Ping Wang, Lee Bowman, Wei Shen, Katherine B. Winfree, Patrick Peterson, William J. John
Journal: Journal of Clinical Oncology (2012)

7075 Background: To determine the patients likely to benefit from therapy, clinicians seek factors associated with outcomes. This analysis investigates prognostic effect of baseline patient-reported symptoms on overall survival (OS) in the presence of demographic/clinical factors among MPM patients. Methods: Intent-to-treat patients (N=448) were included in the analysis. LCSS consists of 6 symptom items and 3 general items, each ranging from 0 (no symptoms) to 100 (worst). Average symptom burden index (ASBI) was the mean of 6 symptom items. Patients were classified into subgroups based on ASBI: low symptom burden (LSB; ASBI&lt;25) and high symptom burden (HSB; ASBI ≥25). Univariate Cox models were used to determine the prognostic effect of 7 demographic/clinical factors, 9 LCSS items, and ASBI on OS. Multivariate Cox model was used to determine the prognostic effect of ASBI in the presence of 7 demographic/clinical factors. Kaplan-Meier curves of OS were generated for patients with LSB and HSB and compared using both univariate and multivariate Cox models. Results: In the univariate analysis, significant prognostic effects on OS were observed for baseline Karnofsky performance status (KPS; 90-100 vs. 70-80, hazard ratio [HR]=0.45, p&lt;0.0001) and baseline stage (I/II/III vs. IV, HR=0.63, p&lt;0.0001). In addition, significant prognostic effects were observed for 5 LCSS symptom items (anorexia, cough, dyspnea, fatigue, and pain), 3 LCSS general items (interference with activity level, symptom distress, and quality of life; HRs=1.08-1.20 for every 10 points worsening, all p&lt;0.02), as well as ASBI (HR=1.32, p&lt;0.0001). In the multivariate Cox model, ASBI remained a significant prognostic factor of OS (HR=1.22, p&lt;0.0001), along with baseline KPS and stage. Patients with LSB (N=265) had significantly better OS than those with HSB (N=181) (12.9 vs. 6.9 months, HR=0.46, unadjusted p&lt;0.0001; HR=0.59, p&lt;0.0001 adjusted for the 7 demographic/clinical variables). Conclusions: The results suggest that baseline patient-reported symptoms as measured by LCSS provide distinct prognostic information in the presence of demographic and clinical measures in MPM.
Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression
Authors: Anouschka S Ramsteijn, Eldin Jašarević, Danielle J Houwing, Tracy L Bale, Jocelien DA Olivier
Journal: Gut Microbes (2020)

Up to 10% of women use selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy and postpartum. Recent evidence suggests that SSRIs are capable of altering the gut microbiota. However, the interaction between maternal depression and SSRI use on bacterial community composition and the availability of microbiota-derived metabolites during pregnancy and lactation is not clear. We studied this using a rat model relevant to depression, where adult females with a genetic vulnerability and stressed as pups show depressive-like behaviors. Throughout pregnancy and lactation, females received the SSRI fluoxetine or vehicle. High-resolution 16S ribosomal RNA marker gene sequencing and targeted metabolomic analysis were used to assess the fecal microbiome and metabolite availability, respectively. Not surprisingly, we found that pregnancy and lactation segregate in terms of fecal microbiome diversity and composition, accompanied by changes in metabolite availability. However, we also showed that fluoxetine treatment altered important features of this transition from pregnancy to lactation most clearly in previously stressed dams, with lower fecal amino acid concentrations. Amino acid concentrations, in turn, correlated negatively with the relative abundance of bacterial taxa such as Prevotella and Bacteroides. Our study demonstrates an important relationship between antidepressant use during the perinatal period and maternal fecal metabolite availability in a rat model relevant to depression, possibly through parallel changes in the gut microbiome. Since microbial metabolites contribute to homeostasis and development, insults to the maternal microbiome by SSRIs might have health consequences for mother and offspring.
Dietary restriction increases protective gut bacteria to rescue lethal methotrexate-induced intestinal toxicity
Authors: Duozhuang Tang, Ting Zeng, Yiting Wang, Hui Cui, Jianying Wu, Bing Zou, Zhendong Tao, Liu Zhang, George B. Garside, Si Tao
Journal: Gut Microbes (2020)

Methotrexate (MTX) is a typical chemotherapeutic drug that is widely used in the treatment of various malignant diseases as well as autoimmune diseases, with gastrointestinal toxicity being its most prominent complication which could have a significant effect on the prognosis of patients. Yet effective ways to alleviate such complications remains to be explored. Here we show that 30% dietary restriction (DR) for 2 weeks dramatically increased the survival rate of 2-month-old female mice after lethal-dose MTX exposure. DR significantly reduced intestinal inflammation, preserved the number of basal crypt PCNA-positive cells, and protected the function of intestinal stem cells (ISCs) after MTX treatment. Furthermore, ablating intestinal microbiota by broad-spectrum antibiotics completely eliminated the protective effect achieved by DR. 16S rRNA gene deep-sequencing analysis revealed that short-term DR significantly increased the Lactobacillus genus, with Lactobacillus rhamnosus GG gavage partially mimicking the rescue effect of DR on the intestines of ad libitum fed mice exposed to lethal-dose MTX. Together, the current study reveals that DR could be a highly effective way to alleviate the lethal injury in the intestine after high-dose MTX treatment, which is functionally mediated by increasing the protective intestinal microbiota taxa in mice. Keywords: Dietary restriction, Methotrexate, Gut microbiota, Intestinal stem cells, intestinal toxicity
Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion
Authors: Xiuqing Han, Steffen H. Raun, Michala Carlsson, Kim A. Sjøberg, Carlos Henriquez-Olguín, Mona Ali, Anne-marie Lundsgaard, Andreas M. Fritzen, Lisbeth L.V. Møller, Zhen Li, Jinwen Li, Thomas E. Jensen, Bente Kiens, Lykke Sylow
Journal: Metabolism (2020)
Caspase-8 Induces Lysosome-Associated Cell Death in Cancer Cells
Authors: Benfu Zhong, Miao Liu, Changsen Bai, Yuxia Ruan, Yuanyuan Wang, Li Qiu, Yang Hong, Xin Wang, Lifang Li, Binghui Li
Journal: Molecular Therapy (2020)

Caspase-8, a well-characterized initiator of apoptosis, has also been found to play non-apoptotic roles in cells. In this study, we reveal that caspase-8 can induce cell death in a special way, which does not depend on activation of caspases and mitochondrial initiation. Instead, we prove that caspase-8 can cause lysosomal deacidification and thus lysosomal membrane permeabilization. V-ATPase is a multi-subunit proton pump that acidifies the lumen of lysosome. Our results demonstrate that caspase-8 can bind to the V0 domain of lysosomal Vacuolar H+-ATPase (V-ATPase), but not the V1 domain, to block the assembly of functional V-ATPase and alkalinize lysosomes. We further demonstrate that the C-terminal of caspase-8 is mainly responsible for the interaction with V-ATPase and can suffice to inhibit survival of cancer cells. Interestingly, regardless of the protein level, it is the expression rate of caspase-8 that is the major cause of cell death. Taken together, we identify a previously unrevealed caspase-8-mediated cell death pathway different form typical apoptosis, which could render caspase-8 a particular physiological function and may be potentially applied in treatments for apoptosis-resistant cancers.
Donor glucose-6-phosphate dehydrogenase deficiency decreases blood quality for transfusion
Authors: Richard O. Francis, Angelo D’Alessandro, Andrew Eisenberger, Mark Soffing, Randy Yeh, Esther Coronel, Arif Sheikh, Francesca Rapido, Francesca La Carpia, Julie A. Reisz, Sarah Gehrke, Travis Nemkov, Tiffany Thomas, Joseph Schwartz, Chaitanya Divgi, Debra Kessler, Beth H. Shaz, Yelena Ginzburg, James C. Zimring, Steven L. Spitalnik, Eldad A. Hod
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. Glucose-6-phosphate dehydrogenase (G6PD) deficiency decreases the ability of red blood cells (RBCs) to withstand oxidative stress. Refrigerated storage of RBCs induces oxidative stress. We hypothesized that G6PD-deficient donor RBCs would have inferior storage quality for transfusion as compared with G6PD-normal RBCs.
Abstract 10546: Cardiorespiratory Fitness, Obesity, and Incidence of Atrial Fibrillation
Authors: Shirit Kamil-Rosenberg, Peter Kokkinos, Christina Grüne de Souza e Silva, Win Leth Shwe Yee, Joshua Abella, Khin Chan, Jonathan Myers
Journal: Circulation (2019)

Objective: The interaction between obesity, CRF and incidence of AF has been debated. Therefore, we evaluated the association between CRF, body mass index (BMI), and risk of developing AF in a coho...
BNP2000以上を認めた重症心不全の臨床的検討 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: 清水明徳, 河合勇介, 難波経立, 田原達哉, 川村比呂志, 廣畑敦, 雪入一志, 山地博介, 村上正明, 村上充, 難波宏文, 山本桂三, 日名一誠, 喜多利正
Journal: Circulation (2006)
How can we realise the full potential of health systems for nutrition?
Authors: Rebecca A Heidkamp, Emily Wilson, Purnima Menon, Helen Kuo, Shelley Walton, Giovanna Gatica-Domínguez, Inacio Crochemore da Silva, Tricia Aung, Nemat Hajeebhoy, Ellen Piwoz
Journal: BMJ (2020)

Poor nutrition contributes substantially to global disease, diminishing the wellbeing of women and children in low and middle income countries, and better nutrition must be part of the universal health coverage agenda, say <b>Rebecca Heidkamp and colleagues</b>
Functions of human liver CD69+CD103-CD8+ T cells depend on HIF-2α activity in healthy and pathologic livers
Authors: Jong Hoon Kim, Ji Won Han, Young Joon Choi, Min-Seok Rha, June Young Koh, Kyung Hwan Kim, Chang Gon Kim, Yong Joon Lee, A Reum Kim, Junsik Park, Hong Kwan Kim, Byung Soh Min, Seong Il Seo, Minyong Kang, Hye Jung Park, Dai Hoon Han, Soon Il Kim, Myoung Soo Kim, Jae Geun Lee, Dong Hyeon Lee, Won Kim, Jun Yong Park, Su-Hyung Park, Dong Jin Joo, Eui-Cheol Shin
Journal: Journal of Hepatology (2020)
Posttreated POEMS Syndrome With Concurrent Follicular Lymphoma Revealed by 18F-FDG and 68Ga-Pentixafor PET/CT
Authors: Qingqing Pan, Yaping Luo, Xinxin Cao, Jian Li, Fang Li
Journal: Clinical Nuclear Medicine (2019)

Abstract A 59-year-old man with history of POEMS syndrome was found with a painless mass in the right neck for 9 months. In 18 F-FDG and 68 Ga-pentixafor PET/CT, there were multiple neck nodes and left inguinal nodes that showed intense 18 F-FDG and 68 Ga-pentixafor uptake. In addition, osteoblastic bone lesions with mild 18 F-FDG and 68 Ga-pentixafor uptake were noted in the pelvis, which was consistent with posttreated osseous involvement of POEMS syndrome. However, considering lymphoadenopathy with such intense 18 F-FDG uptake is not usually seen in POEMS syndrome, the patient underwent biopsy of the right cervical nodes. The histopathology with immunohistochemistry confirmed follicular lymphoma.
Abstract 358: Three-Sided Chest Compression is Beneficial to Rats Suffering From Cardiac Arrest
Authors: Yu Okuma, Koichiro Shinozaki, Tsukasa Yagi, Kota Saeki, Tai Yin, Junhwan Kim, Lance B Becker
Journal: Circulation (2019)

Objective: Rat models are necessary to study targeted interventions to improve survivability in patients suffered from a cardiac arrest (CA). For translational researchers, increasing the rate of return of spontaneous circulation (ROSC) is important to reduce the number of rats being used to obtain sufficient data. Yet, few studies have demonstrated how to perform better chest compression on rats. Methods: Rats underwent 10 min of asphyxia to induce CA. All rats were placed in a supine position. Three types of chest compression were examined: 1-sided method (classic) with 2 fingers on the sternum; 2-sided method with 2 fingers on the chest from both sides; and the 3-sided method with 2 hands (2 fingers on the sternum and with 2 fingers on the chest). ROSC rates, cardiac function, arterial pressure(s), intrathoracic pressure, cerebral oxygenation, and end-tidal CO 2 (EtCO 2 ) were measured. In addition, survival after 14-min asphyxia was assessed. Results: Male Sprague-Dawley rats were used and there were no differences in chest compression rates among the three groups. The ROSC rate was 100% (8/8) with the 3-sided method, 80% (4/5) with the 1-sided method, and 60% (3/5) with the 2-sided method. The 3-sided group showed significantly shorter time to ROSC (105.0±36.0 sec for the 1-sided method vs.141.0±21.7 sec for the 2-sided method vs. 57.8±12.3 sec for the 3-sided method, p&lt;.05). The 3-sided method significantly increased the left ventricular stroke volume (the ratio of baseline: 1.2±0.6, 1.3±0.1, vs. 2.1±0.6, p&lt;.05) and pressure (24.0±5.5, 19.8±3.4, vs. 29.4±1.8 mmHg, p&lt;.05), the difference of common carotid arterial pressure to femoral artery pressure (4.0±2.5, 0.3±1.6, vs. 8.4±2.6 mmHg, p&lt;.01), intrathoracic pressure (esophagus: 7.6±1.9, 7.3±2.8, vs. 12.7±2.2 mmHg, p&lt;.01), cerebral oxygenation (the ratio of baseline: 1.4±0.1, 1.3±0.2, vs. 1.6±0.04, p&lt;.05) and EtCO 2 (the ratio of baseline: 12.4±2.0, 14.2±1.9, vs. 17.5±1.7 mmHg, p&lt;.05). The 3-sided chest compression achieved 75% (3/4) ROSC from 14-min asphyxia CA. Conclusions: The 3-sided chest compression was associated with the most successful ROSC. It is likely that the 3-sided method increased intrathoracic pressure and stabilized cardiac function, which might be beneficial to the brain.
‘Efficacy and safety of imiquimod 5% cream for basal cell carcinoma: a meta‐analysis of randomized controlled trial’: a critical appraisal
Authors: B. Olabi, F. Tasker, H.C. Williams
Journal: British Journal of Dermatology (2020)

Jia and He aimed 'to compare the efficacy and safety of imiquimod with other treatments in patients with basal cell carcinoma' (BCC).Meta-analysis of studies that included patients with histologically confirmed BCC treated with imiquimod 5% cream compared with all other treatments, including vehicle, excisional surgery, cryosurgery, fluorouracil and methyl aminolaevulinate photodynamic therapy.The main outcome measures included histological and composite clearance rates, success rates, complete response rates, tumour-free survival and adverse events.Thirteen studies with a total of 4265 patients were included in the review. Pooled analyses comparing imiquimod with all or any of the listed comparators, including vehicle, demonstrated higher histological clearance rates [risk ratio (RR) 9·28, 95% confidence interval (CI) 5·56-15·5; P < 0·001], higher composite clearance rates (RR 34·2, 95% CI 21·3, 55·1; P = 0·001), no significant difference in success rates (RR 0·98, 95% CI 0·89-1·08; P = 0·73), higher complete response rates (RR 3·15, 95% CI 1·55-6·38; P = 0·001), no significant difference in tumour-free survival (RR 1·15, 95% CI 0·98-1·35; P = 0·088) and increased incidence of adverse events (RR 2·00, 95% CI 1·39-2·88; P < 0·001).The authors state that 'imiquimod significantly exhibited benefit effect in improving the histological/composite clearance rates' compared with other treatments, and they suggest it could be used as the first-choice treatment for patients with BCC.The main concerns related to the article by Jia and He are that the research question is replicative, it makes little sense to combine all BCC types in a meta-analysis, and it also makes no sense to combine an active treatment against a combination of vehicle and other active treatments. There are also concerns about bias related to the use of the same study data more than once in a meta-analysis. Furthermore, we have identified an example of covert duplicate publication, which further compounds the profusion of misleading systematic reviews.
Assessment of ST2 for risk of death following graft-versus-host disease in pediatric and adult age groups
Authors: Courtney M. Rowan, Francis Pike, Kenneth R. Cooke, Robert Krance, Paul A. Carpenter, Christine Duncan, David A. Jacobsohn, Catherine M. Bollard, Conrad Russell Y. Cruz, Abhijeet Malatpure, Sherif S. Farag, Jamie Renbarger, Hao Liu, Giorgos Bakoyannis, Samir Hanash, Sophie Paczesny
Journal: Blood (2020)
B09 The CANOPY Program: Three Phase 3 Studies Evaluating Canakinumab in Patients with Non-Small Cell Lung Cancer (NSCLC)
Authors: E.B. Garon, A. Ardizzoni, F. Barlesi, B.C. Cho, G. de Castro, E. Felip, Y. Goto, A. Greystoke, S. Lu, D.W.-T. Lim, M. Reck, B.J. Solomon, D.R. Spigel, D.S.W. Tan, M. Thomas, J.C.-H. Yang, B.E. Johnson
Journal: Journal of Thoracic Oncology (2020)
Activated pyrin domain containing 3 (NLRP3) inflammasome in neutrophilic chronic rhinosinusitis with nasal polyps (CRSwNP)
Authors: Yi Wei, Jia Zhang, Xingmei Wu, Wei Sun, Fanqin Wei, Wendong Liu, Tong Lu, Weidong Ji, Huabin Li, Weiping Wen
Journal: Journal of Allergy and Clinical Immunology (2020)
Phylogenomic analysis of Neisseria gonorrhoeae transmission to assess sexual mixing and HIV transmission risk in England: a cross-sectional, observational, whole-genome sequencing study
Authors: Katy Town, Nigel Field, Simon R Harris, Leonor Sánchez-Busó, Michelle J Cole, Rachel Pitt, Helen Fifer, Hamish Mohammed, Gwenda Hughes
Journal: The Lancet Infectious Diseases (2020)

Characterising sexual networks with transmission of sexually transmitted infections might allow identification of individuals at increased risk of infection. We aimed to investigate sexual mixing in Neisseria gonorrhoeae transmission networks between women, heterosexual men, and men who report sex with men (MSM), and between people with and without HIV.