tbuckley/cabot-search huggingface dataset:
Moving toward precision: Understanding the heterogeneity of obesity.
Authors: Kin Wai (Tony) Hung, Tien Dong, David Elashoff, Emeran Mayer, Jonathan Jacobs, Venu Lagishetty, Arpana (Annie) Gupta
Journal: Journal of Clinical Oncology (2020)

12054 Background: Obesity is a global health epidemic and has been linked to detrimental impact on cancer incidence, recurrence, and mortality. Growing evidence have recognized the complex biopsychosocial relationship including microbial phenotypes that undermines the carcinogenic potential and heterogeneity of obesity. A precision understanding on obesity while at its infancy is necessary to accelerate reduction of its impact on cancer outcomes. Methods: With our aim to better understand the biopsychosocial relationship on obesity, we conducted a cross sectional study in healthy and obese individuals. Univariate and multivariate logistic regression models were used to examine obesity and its association with sociodemographic (age, gender, ethnicity, education, income, and marital status), clinical (waist to hip ratio), dietary-behavioral (daily calorie, fat, carbohydrate, protein consumption, and preference on cultural diet), and biological factors (gut microbiome). Parameters were controlled and corrected for multiple hypothesis testing. Gut microbial data using 16S rRNA sequencing were analyzed for alpha diversity, beta diversity, and association of taxa abundance. Results: Among 171 participants between July 2013 and August 2018, individuals were found to have a higher BMI if they were Hispanic [Adjusted Odds Ratio (AOR) 3.36, 95% CI 1.27-8.90], had an obese waist to hip ratio (AOR 8.51, 95% CI 3.45-21.02), and consumed an American diet (AOR 4.82, 95% CI 1.74-13.34). Multivariate permutation analysis controlling for BMI, sociodemographic, clinical, and dietary parameters found that Hispanic have a significantly different microbiome profile than non-Hispanic (p = 0.042). While microbial species richness (Chao1) were similar (p = 0.22), Hispanic had a lower microbial species evenness (Shannon) compared to non-Hispanic (p = 0.029). Differential expression of microbial species revealed a positive correlation of Firmicutes:Bacteroidetes ratio in individuals with higher BMI and consumed an American diet whereas a negative correlation to Hispanic ethnicity. Conclusions: Obesity association to Hispanic ethnicity uniquely expressed through microbial signature despite sociodemographic, clinical, and dietary differences. Microbial characterization as an emerging predictive marker for oncology therapeutics may also serve as selection biomarker in onco-obesity practices and clinical trials. Addressing ethnic disparities guided by microbial phenotypes may unlock novel understanding of obesity heterogeneity and transform its impact on cancer care.
Risk for COVID-19 Resurgence Related to Duration and Effectiveness of Physical Distancing in Ontario, Canada
Authors: Ashleigh R. Tuite, Amy L. Greer, Steven De Keninck, David N. Fisman
Journal: Annals of Internal Medicine (2020)

Background: Insights from epidemiologic models have helped to guide and improve understanding of mitigation policies for coronavirus disease 2019 (COVID-19) across the globe.As the pandemic progresses, models can be used to quantify what may unfold when such measures are relaxed.Objective: To explore the effect of physical distancing measures on COVID-19 transmission in the population of Ontario, Canada.Methods and Findings: We previously described a transmission model of COVID-19, stratified by age and health status, in the Canadian province of Ontario (1).It evaluated nonpharmaceutical interventions to control the COVID-19
Non-surgical therapy for 412 patients with early lower extremity deep venous thrombosis
Authors: Kun-mei Gong, Le Xiao, Kun-hua Wang, Yong-xue Zhang, Yi-ming Ouyang, Jian Zhang, Ya-xin Long, Lin-hai Li
Journal: BMJ (2008)

Objective This report was to discuss the efficacy and complications of non-surgical therapy for patients with early lower extremity deep vein thrombosis.Methods A total of 412 patients were treated with thrombolysis or anticoagulation in our department during January 2000 and December 2006.Their clinical data were retrospectively analyzed.Results All patients were followed up for 12 to 83 months (mean,41 months).After treatment,42 patients(10.2%)were completely recovered,331 patients (80.3%)experienced large improvement,32 patients(7.8%)had mild improvement and 7 patients (1.7%)were failed,resulting in total effective rate of 98.3%.In comparison with long clinical course group(>7 days),the recovery rate and improvement rate of short clinical course group(≤7 days)was significantly increased(11.0% vs 5.4%,χ2=4.17,P<0.05;8.7%vs 1.8%,χ2=4.96,P<0.05).Complications included bleeding(2.2%),pulmonary embolism(1.9%),cerebral accident(0.7%),post-thrombotic syndrome(84.0%)and recurrence(6.1%).Bleeding rate in patients≥60 years was significantly higher(4.3%vs 0.8%,χ2=6.82,P<0.01).Incidence of post-thrombotic syndrome was significantly increased in long clinical course group(98.2% vs 81.7%,χ2=3.67,P<0.05).Condusions Non-surgical therapy,including thrombolysis and anticoagulation,might be safe and effective for patients with early lower extremity deep vein thrombosis.Early identification and management would be helpful to improve outcomes and reduce post-thrombotic syndrome.

Key words: 
Venom thrombosis; Thrombolytie therapy; Lower extremity
Glutathione system in the blood of gastric cancer patients with various tumor histotypes and prevalence of the disease.
Authors: Irina A. Goroshinskaya, Ekaterina I. Surikova, Elena M. Frantsiyants, Ludmila A. Nemashkalova, Polina S. Kachesova, Anastasiya V. Chudilova, Dar'ja E. Medvedeva, Andrey A. Maslov, Sergey A. Malinin, Oleg I. Kit, Yuriy A. Fomenko, Dmitry S. Petrov
Journal: Journal of Clinical Oncology (2020)

e16534 Background: The role of oxidative stress in tumor growth and the multifaceted functional significance of glutathione have led to an interest in studying the components of the glutathione-dependent system in gastric cancer (GC), which occupies a leading position in cancer incidence and mortality. The aim of this work was to study the functioning of the glutathione system in the red blood cells of patients with gastric cancer in a comparative aspect depending on the histotype of the tumor and the prevalence of the disease. Methods: The study included 89 patients with GC divided into 6 groups depending on the histotype of the tumor. Separately, the results of the study were analyzed in patients with T4 status according to TNM and in patients with stage IV cancer. The content of reduced glutathione and the activity of glutathione-dependent enzymes were studied by conventional spectrophotometric methods in the red blood cells of patients. Statistical processing of the results was performed using the Statistika 6.0 program with Student’s t-test for two independent groups. Results: An increase in the content of glutathione in patients with GC compared with the group without oncopathology was revealed. The maximum increase was observed in patients with low-grade adenocarcinoma - by 42.5%, while in signet ring cell cancer (SRCC) there was only a tendency to increase by 17.8%. Glutathione reductase activity was reduced in adenocarcinoma by 23.4-26.2% and did not change in SRCC. The activity of the antioxidant enzymes glutathione peroxidase and glutathione transferase was increased in all groups and especially in SRCC - by 76% and 23-29%, respectively. In patients with T4 status and at stage 4 of the process, lower activity of the studied glutathione-dependent enzymes was revealed compared with all other groups of patients. Conclusions: The data indicate a greater functional potential of the glutathione system in SRCC. A significant increase in the activity of glutathione transferase with a sufficiently high level of reduced glutathione contributes to the development of treatment resistance in patients with SRCC.
Intervention provided by family doctors improves loneliness status for people who lost their only child
Authors: Jun Zhao, Guangzheng Xu, Yuanyuan Song, Lei Peng, Li Liu, Xiaobing Ding
Journal: BMJ (2018)

Objective
To investigate the intervention of family doctor management system on the loneliness in people who lost their only child.


Methods
Sixty two residents who lost their only child in Shanghai Xujiahui district were enrolled in the study from December 2015 to June 2016. The participants were randomly divided into study group and control group with 31 cases in each group; the participants in study group were signed by family doctors and the psychological intervention was provided, those in control group had no intervention, the participants were followed up for 6 months, the psychological status was evaluated with UCLA loneliness scale in two groups.


Results
There were no significant differences in UCLA scores (63.26±7.17 vs. 60.03±7.59, t=1.709, P>0.05) and in the severity of loneliness (mild 0/30 vs. 1/31, moderate 9/30 vs. 11/31, severe 21/30 vs. 19/31, χ2=1.284, P>0.05) between study and control groups before the intervention. There were significant differences in UCLA scores (63.26±7.17 vs. 40.13±5.61, t=15.631, P 0.05) and in the severity of loneliness (mild 1/31 vs. 0/31, moderate 11/31 vs. 14/31, severe 19/31 vs. 17/30, χ2=1.471, P>0.05) in control group after 6-month follow-up. The UCLA scores (40.13±5.61 vs. 59.64±6.90, t=12.086, P<0.05) and the severity of loneliness (mild 17/30 vs. 0/31, moderate 13/30 vs. 14/31, severe 0/30 vs.17/31, χ2=34.030, P<0.05) in study group were significantly lower than those in control group after intervention.


Conclusion
The family doctor management system can improve the loneliness and mental health status of people who lost the only child, to reduce the risk of mental illness and the family and social burden.


Key words: 
Loneliness; Family doctor; Lost the only child
Impact of chronic constipation on quality of life and economic burden of patients
Authors: Ya Jiang
Journal: BMJ (2017)

Chronic constipation (CC) is one of the most common digestive diseases with high prevalence and long course. CC patients often suffer from sleep disorders and psychological problems such as anxiety and depression. Somatic and mental symptoms may affect with each other, so a vicious circle will develop to impair patients′ quality of life (QOL) and increase their economic burden. The article reviews the impact of chronic constipation on QOL and economic burden of patients, indicating that clinician should pay sufficient attentions on chronic constipation.


Key words: 
Constipation; Quality of life; Economic burden
FOENIX-CCA2: A phase II, open-label, multicenter study of futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring <i>FGFR2</i> gene fusions or other rearrangements.
Authors: Lipika Goyal, Funda Meric-Bernstam, Antoine Hollebecque, Juan W. Valle, Chigusa Morizane, Thomas Benjamin Karasic, Thomas Adam Abrams, Junji Furuse, Yaohua He, Nital Soni, Karim A. Benhadji, John A. Bridgewater
Journal: Journal of Clinical Oncology (2020)

108 Background: Patients (pts) with intrahepatic cholangiocarcinoma (iCCA) have a 5-year survival rate of 24%. There is no standard treatment for advanced disease after first-line chemotherapy. Fibroblast growth factor receptor-2 ( FGFR2) gene fusions occur in 10% to 20% of pts with iCCA, offering a promising therapeutic avenue for this disease. Futibatinib is a highly selective irreversible FGFR1-4 inhibitor given as a continuous once-daily (QD) oral regimen. This phase 2 registrational trial was initiated because of results from a phase 1 dose escalation/expansion study showing tolerability and preliminary efficacy of futibatinib in pts with iCCA with FGFR2 fusions. Methods: FOENIX-CCA2 (NCT02052778), a single-arm multicenter phase 2 study, enrolled pts with locally advanced/metastatic unresectable iCCA harboring FGFR2 gene fusions or other rearrangements, disease progression after ≥1 line of systemic therapy (including gemcitabine plus platinum-based chemotherapy), no prior FGFR inhibitor treatment, and an ECOG performance status of 0 or 1. Pts received futibatinib 20 mg QD until disease progression/unacceptable toxicity. The primary endpoint is objective response rate (ORR) based on independent central radiology review. Secondary endpoints include disease control rate (DCR), duration of response (DOR), and safety. Results: A total of 103 pts were enrolled. For this interim analysis, data are reported for the 67 pts (65%) with ≥6 months of follow-up. Of these, 82.1% of pts had tumors harboring an FGFR2 fusion. One, 2, or ≥3 prior therapies were received by 44.8%, 28.4%, and 26.9% of pts, respectively. ORR was 34.3% (all partial response, n = 23), and DCR was 76.1%; assessment was pending for 8 pts. Median time to response was 1.6 months (range, 1.0-4.9), and median DOR was 6.2 months (range, 2.1-14.2). The most common treatment-related adverse events (AEs; all grade, grade ≥3) were hyperphosphatemia (79.1%, 25.4%), diarrhea (37.3%, 0%), and dry mouth (32.8%, 0%). Any-cause grade ≥3 AEs were reported in 73.1% of pts. Dose delay or dose reduction was required in 65.7% and 53.7% of pts, respectively; 6.0% of pts discontinued treatment because of AEs. Conclusions: Preliminary assessment of these phase 2 data indicate efficacy and tolerability of futibatinib for treatment of pts with iCCA harboring FGFR2 fusions or other rearrangements who have progressed after chemotherapy. Continued analysis of the study population is underway. Clinical trial information: NCT02052778.
Patient-centered community management for a obese patient with type 2 diabetes mellitus
Authors: Huijun Lin, Yue Jiang, Yue Sha
Journal: BMJ (2018)

A 70-year female patient with a 14-year history of type 2 diabetes mellitus (T2DM) complains poor blood sugar control and body weight gain after insulin use for 3 years. A patient-centered community management was applied to this patient. The management scheme included defining the purpose of patient visit, completing the relevant medical history and examination, confirming the current major diagnosis, analyzing causes of insulin-induced weight gain, eliminating concerns about insulin use, choosing the type of insulin, determining the insulin treatment plan and the diet plan, as well as giving health education of hypoglycemia accordingly. The general practitioner and the patient worked together on the individualized management plan. After 3 months of treatment, the patient′s weight, fasting blood glucose, glycosylated hemoglobin, blood lipids and BMI levels were significantly decreased.


Key words: 
Diabetes; Patient-centered care; Community health services
Chronic neurogenic pain activates growth factors in the blood of patients with cutaneous melanoma.
Authors: Valeria A. Bandovkina, Elena M. Frantsiyants, Ludmila Ya. Rozenko, Viktoria V. Pozdnyakova, Natalia D. Cheryarina, Yuriy V. Przhedetskiy, Olga V. Khokhlova, Viktoria Yu. Przhedetskaya, Natalia A. Zakharova, Oleg I. Kit
Journal: Journal of Clinical Oncology (2020)

e22082 Background: Clusters of tumor cells in blood vessels secrete VEGF family factors necessary for the formation of premetastatic niches. TGF-β activates the epidermal-mesenchymal transition (EMT). The purpose of the study was to analyze levels of angiogenesis and EMT factors in the blood of patients with cutaneous melanoma (M) and chronic neurogenic pain (CNP). Methods: Blood levels of VEGF-A, VEGF-C, VEGFR-1, VEGFR-3, TGF-β1 and TGF-βR2 were measured by ELISA in patients with Т 3-4 N x M 0 melanoma: 21 women with CNP (pelvic pain - 7, osteochondrosis – 14), mean age 67.2±2.7 years; 17 men with CNP (osteochondrosis), mean age 65.6±3.1 years. The control group included patients with melanoma similar in age, gender and disease stages without CNP. Results: VEGF-A in women and men with M+CNP was higher than in controls by 2.7 and 24.9 times respectively; VEGFR-1 was decreased in women by 1.8 times and increased in men by 1.8 times. VEGF-С was unchanged in women and 1.5 times higher in men, and VEGFR-3 was increased by 2.2 times in women and unchanged in men. TGF-β1 was elevated in women and men with M+CNP by 1.4 and 1.8 times, compared to controls, TGF-βR2 – by 1.9 and 2 times respectively. Conclusions: In the blood of women with M+CNP, CNP activates the blood vascular endothelial growth factor VEGF-A and the factor of epidermal-mesenchymal transition TGF-β, while in the blood of men with M+CNP it activates the blood vascular endothelial growth factor VEGF-A, the lymphatic vascular endothelial growth factor VEGF-C and the factor of epidermal-mesenchymal transition TGF-β. VEGF mediates vascular permeability and is associated with the mobilization of endothelial progenitor cells from the bone marrow into premetastatic niches. Activation of TGF-β signaling promotes the induction of the epidermal-mesenchymal transition and supports the properties of cancer stem cells.
AVIDIO as a novel oncolytic immunotherapy platform for the treatment of colorectal cancer.
Authors: Bijan Almassian, Bhaskara R Madina, Ju Chen, Xiaoyang Ye, Marie M Krady, Xianyong Ma, Timur O Yarovinsky, Stephen W Mason, Valerian Nakaar, Kepeng Wang
Journal: Journal of Clinical Oncology (2020)

e15210 Background: Colorectal cancer is the third deadliest of all cancers causing more than 50,000 deaths per year in the U.S. Oncolytic viruses have seen limited use for the treatment of cancers, and further improvement of these methods with immune-modulating activities may prove crucial for the effectiveness of these agents in the treatment of human malignancies. To this end, we developed an artificial virus for infectious diseases and immuno-oncology (AVIDIO) platform that employs virus-like vesicles (VLV) for both the delivery of immunomodulatory agents to tumors and oncolytic activity. Methods: The AVIDIO platform is comprised of in vitro evolved RNA-dependent RNA polymerase from an alphavirus, Semliki forest virus, and envelope glycoproteins from vesicular stomatitis virus, which together form VLVs. Both unarmed VLVs and VLVs armed with the p35 subunit of IL-12 (VLV-IL12p35), an immunomodulatory cytokine that can induce Th1-mediated immunity, were tested for oncolytic activity against various cancer cell lines, including MC38 colorectal cancer cells, in vitro. Using the MC38 syngeneic murine tumor model, we evaluated the antitumor activity of VLV-IL-12p35 in vivo. We used tumor growth measurements and analyses of tumor-infiltrating cells after consecutive treatments with VLV-IL-12p35 to monitor its antitumor and immunomodulatory activities, respectively. Results: VLV-IL-12p35 showed robust oncolytic activity against MC38 cells in vitro, killing over 80% of cells within 24 h. Treatment of intradermal MC38 tumors by intra-tumoral delivery of VLV-IL-12p35 resulted in more than 65% suppression of tumor growth within 2 weeks ( p&lt; 0.05). VLV-IL-12p35-treated tumors also harbored significantly more CD8 + T cells, IFN-gamma-producing CD4 + T cells, and reduced numbers of Foxp3 + regulatory T cells. Conclusions: Our results show that VLV-IL-12p35 derived from the AVIDIO platform has oncolytic activity in vitro and antitumor and immunomodulatory activities in vivo. Therefore, AVIDIO is a promising platform for the delivery of immunomodulatory agents to tumors. Further optimization of the platform, including the addition of other immunomodulatory agents, is in progress to advance the AVIDIO platform to clinical applications for colorectal cancer.
Psychosocial Factors in Disease and Treatment—A Call for the Biopsychosocial Model
Authors: Veronika Engert, Joshua A. Grant, Bernhard Strauss
Journal: JAMA Psychiatry (2020)

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Association of pectoralis muscle area and survival outcomes after chemotherapy.
Authors: Christina Gu, Jason Wiederin, Patricia Jewett, Anne Hudson Blaes
Journal: Journal of Clinical Oncology (2020)

e24094 Background: Chemotherapy use may be associated with muscle wasting, a marker of frailty that can predispose individuals to poor outcomes. We assessed the association between pre-treatment pectoralis muscle area and overall mortality following chemotherapy. Methods: We identified individuals diagnosed with breast cancer (N=221), lymphoma (N=216), or sarcoma (N=115) who received chemotherapy at the University of Minnesota Masonic Cancer Clinic and had CT scans prior to chemotherapy 2009-2014. Using CoreSlicer, right pectoral muscle area was measured at baseline and indexed to body surface (right pectoralis muscle area [cm 2 ] / body surface [m 2 ]) and divided into quartiles. Restricting to individuals who started chemotherapy within 6 months after their CT, we used cox regression (adjusted for age, sex, cancer type, stage, ever-smoking, BMI, and chemotherapy type) to assess associations between baseline muscle area and overall survival, testing for nonlinear effects using cubic splines. Results: 536 individuals (66% female) were identified who were treated with anthracyclines based chemotherapy (N=408), Trastuzumab (N=64), or both (N=64). Mean baseline muscle area was 14.9 (4.6) cm 2 in females and 26.3 (9.3) cm 2 in males. Median follow-up was 4.6 years. Larger baseline pectoralis muscle area (per m 2 body surface) was associated with improved survival (adjusted model, overall effect, P=0.01), with some nonlinear effects (P=0.05). With muscle area (per m 2 body surface) categorized as quartiles, individuals in the 3 rd and 4 th quartiles were at lower risk of dying (compared with people in the 1 st quartile, hazard ratios 0.59 and 0.55 respectively, 95% CI range 0.35-0.90, P=0.01). There were no differences comparing the 4 th vs the 3 rd quartile (P=0.79), or the 2 nd vs the 1 st quartile (P=0.5). Conclusions: We found a protective association between larger right pectoral muscle size (relative to body surface) and overall survival after chemotherapy. There may be ceiling and threshold effects given evidence for nonlinear effects, since neither the 2 nd vs. 1 st quartile, nor the 4 th vs. 3 rd quartile comparisons in the categorical model were significant. Hazard ratios and confidence intervals of overall mortality by pectoral muscle area at baseline indexed to body surface, N=536, 2009-14. [Table: see text]