tbuckley/cabot-search huggingface dataset:
Therapeutic targeting of TMPRSS2 andACE2 as a potential strategy to combat COVID-19
Authors: Qu Deng, Reyaz Ur Rasool, Ramakrishnan Natesan, Irfan A. Asangani
Journal: Clinical Cancer Research (2020)

The novel SARS-CoV-2 infection responsible for the COVID-19 pandemic is expected to have an adverse effect onthe progression of multiple cancers, including prostate cancer, due to the ensuing cytokine storm associatedoncogenic signaling  A better understanding of the host cell factors and their regulators will help identify potentialtherapies to block SARS-CoV-2 infection at an early stage and thereby prevent cancer progression  Host cellinfection by SARS-CoV-2 requires the binding of the viral spike S protein to ACE2 receptor and priming by theserine protease TMPRSS2-encoded by a well-known androgen response gene and highly expressed in patientsdiagnosed with prostate cancer  Epidemiologic data showing increased severity and mortality of SARS-CoV-2disease in men suggest a possible role for androgen in the transcriptional activation of ACE2 and TMPRSS2 in thelungs and other primary infection sites  Here, by performing in vivo castration in mice, RT-PCR, immunoblotting, Co-IP, and pseudovirus infection assays in multiple cell lines, we present evidence for the transcriptional regulation ofTMPRSS2 and ACE2 by androgen, their endogenous interaction, as well as a novel combination of drugs inblocking viral infection  In adult male mice, castration led to a significant loss in the expression of ACE2 andTMPRSS2 at the transcript and protein levels in the lung, heart, and small intestine  Intriguingly, castrated micedisplayed a substantial increase in ACE2 in the kidney, which could potentially be due to the low blood pressureresulting from androgen deprivation  Endogenous TMPRSS2 and ACE2 were found to be physically interacting, asobserved by reciprocal immunoprecipitation followed by immunoblotting  Importantly, along with full-length zymogenform, a prominent novel small isoform of TMPRSS2 was found to be associated with ACE2 in lung and prostatecells  In an overexpression system, camostat-a serine protease inhibitor specific to TMPRSS2-inhibited thecleavage of spike S, suggesting a direct role of this serine protease in priming the viral spike S protein, aprerequisite for an active infection  Furthermore, a combination of camostat, antiandrogen, and epigenetic drugs atsublethal concentrations blocked SARS-CoV-2 pseudovirus infection in multiple cell types  Together, our preclinicaldata provide a strong rationale for clinical evaluation of TMRPSS2 inhibitors, antiandrogens, and epigenetic drugcombinations along with antiviral drug remdesivir as early as clinically possible to prevent progression to pneumoniaand multiorgan failure as a result of hyperinflammatory responses in COVID-19 patients
Closing the gap in health care disparities by improving the rate of lung cancer screening in an intercity hospital.
Authors: Anika Bhargava, Akshay Kohli, Irina Veytsman
Journal: Journal of Clinical Oncology (2020)

195 Background: The National Lung Cancer Screening Trial showed reduced lung cancer mortality with low-dose computed tomography (LDCT) screening. Although LDCT is generally covered by private and government insurance, the rate of LDCT screening has been reported to be very low (2-3%) in previous studies. One of the main barriers in adequate screening was assessment of smoking history to identify eligible populations. Purpose: To increase the rate of lung cancer screening in Medstar Washington Hospital Center Internal Medicine (WHCIM) clinics from a baseline rate of 2.88% by 50% over a 3-month period. Methods: Retrospective baseline data was collected over a 2-week period 01/06/2020–01/17/2020 from patients visits at WHCIM to assess the rate of lung cancer screening. A session was held with physicians and nursing staff to find the barriers in identifying eligible patients for lung cancer screening and to create a fishbone diagram. The first plan-do-study act cycle (PDSA) was initiated from 02/24/2020–03/13/2020 where we piloted a clinical reminder in the form of a print-out filled out by the medical assistants at check in and then given to physicians. The form included the patient's age and simple smoking questionnaire according to the lung cancer screening guidelines. Data was collected during this time period which included documentation of patient’s smoking history, lung cancer screening eligibility and referral to LDCT. Results: By retrospective analysis from the time period of 01/06/2020-01/17/2020 providers documented a smoking history in only 16% of patients seen and only 2.88% of all patients seen over the age of 55 were referred for lung cancer screening. Post intervention for the time period of 02/24/2020-03/13/2020 increased the amount of documented smoking history by providers to 26% and number of patients sent for lung cancer screening to 6.0%. Of patients who met the criteria for lung cancer screening, prior to the intervention only 42% of patients were referred. However, after the clinical reminder has been initiated, 86% of patients who did meet the criteria were sent for screening. Conclusions: The clinical reminder has increased documentation of smoking history by 62% and lung cancer screening for those who meet the criteria according to the guidelines by a relative increase of 105%. We are currently working on PDSA cycle 2 to incorporate education materials in the encounter room and PDSA cycle 3 to incorporate this clinical reminder into the electronic medical record and to implement hospital wide.
Potential Benefits and Harms of Gastric Bypass Surgery in Obese Individuals With Type 1 Diabetes: A Nationwide, Matched, Observational Cohort Study
Authors: Gudrun Höskuldsdóttir, Jan Ekelund, Mervete Miftaraj, Ville Wallenius, Johan Ottosson, Ingmar Näslund, Soffia Gudbjörnsdottir, Naveed Sattar, Ann-Marie Svensson, Björn Eliasson
Journal: Diabetes Care (2020)

OBJECTIVE To study the potential long-term benefits and possible complications of bariatric surgery in patients with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS In this register-based nationwide cohort study, we compared individuals with T1D and obesity who underwent Roux-en-Y gastric bypass (RYGB) surgery with patients with T1D and obesity matched for age, sex, BMI, and calendar time that did not undergo surgery. By linking the Swedish National Diabetes Register and Scandinavian Obesity Surgery Registry study individuals were included between 2007 and 2013. Outcomes examined included all-cause mortality, cardiovascular disease, stroke, heart failure, and hospitalization for serious hypo- or hyperglycemic events, amputation, psychiatric disorders, changes in kidney function, and substance abuse. RESULTS We identified 387 individuals who had undergone RYGB and 387 control patients. Follow-up for hospitalization was up to 9 years. Analysis showed lower risk for cardiovascular disease (hazard ratio [HR] 0.43; 95% CI 0.20–0.9), cardiovascular death (HR 0.15; 95% CI 0.03–0.68), hospitalization for heart failure (HR 0.32; 95% CI 0.15–0.67), and stroke (HR 0.18; 95% CI 0.04–0.82) for the RYGB group. There was a higher risk for serious hyperglycemic events (HR 1.99; 95% CI 1.07–3.72) and substance abuse (HR 3.71; 95% CI 1.03–3.29) after surgery. CONCLUSIONS This observational study suggests bariatric surgery may yield similar benefits on risk for cardiovascular outcomes and mortality in patients with T1D and obesity as for patients with type 2 diabetes. However, some potential serious adverse effects suggest need for careful monitoring of such patients after surgery.
Employment concerns experienced by ovarian cancer patients and caregivers.
Authors: Margaret Irene Liang, Janice Leahgrace Simons, Ivan I. Herbey, Jaclyn Wall, Lindsay Rucker, Warner King Huh, Nataliya V. Ivankova, Maria Pisu
Journal: Journal of Clinical Oncology (2020)

69 Background: Our aim was to obtain patient input on the impact of cancer treatment on employment. Methods: We recruited patients with ovarian cancer receiving systemic therapy who screened positive for financial distress using Comprehensive Score for Financial Toxicity &lt;26. Participants completed a 45-minute interview with 2 interviewers on their costs of care, including employment concerns. Interviews were recorded, transcribed, and coded by 3 analysts using inductive thematic analysis. Results: Of 22 participants, 86% were &lt;65 years old and 28% were on curative intent treatment. There were 18 with currently evaluable interviews. Themes are shown in the table. Conclusions: Cancer care has a negative impact on patient and caregiver work productivity, income, and employer benefits. Incorporating resources to navigate workplace factors, such as Family Medical Leave Act benefits and negotiating accommodations with an employer, could improve care delivery. [Table: see text]
Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology
Authors: Michael W. Deininger, Neil P. Shah, Jessica K. Altman, Ellin Berman, Ravi Bhatia, Bhavana Bhatnagar, Daniel J. DeAngelo, Jason Gotlib, Gabriela Hobbs, Lori Maness, Monica Mead, Leland Metheny, Sanjay Mohan, Joseph O. Moore, Kiran Naqvi, Vivian Oehler, Arnel M. Pallera, Mrinal Patnaik, Keith Pratz, Iskra Pusic, Michal G. Rose, B. Douglas Smith, David S. Snyder, Kendra L. Sweet, Moshe Talpaz, James Thompson, David T. Yang, Kristina M. Gregory, Hema Sundar
Journal: Journal of the National Comprehensive Cancer Network (2020)

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.
Ribonuclease 7-driven activation of ROS1 is a potential therapeutic target in hepatocellular carcinoma
Authors: Chunxiao Liu, Zhengyu Zha, Chenhao Zhou, Yeh Chen, Weiya Xia, Ying-Nai Wang, Heng-Huan Lee, Yirui Yin, Meisi Yan, Chiung-Wen Chang, Li-Chuan Chan, Yufan Qiu, Hui Li, Chia-Wei Li, Jung-Mao Hsu, Jennifer L. Hsu, Shao-Chun Wang, Ning Ren, Mien-Chie Hung
Journal: Journal of Hepatology (2020)
Healthy lifestyle challenges among older female cancer survivors.
Authors: Jessica L. Krok-Schoen, Janell Pisegna, Elizabeth Arthur, Emily Ridgway, Christian Stephens, Ashley Elizabeth Rosko
Journal: Journal of Clinical Oncology (2020)

156 Background: Healthy lifestyles including consuming a healthy diet, being physically active, and maintaining a normal weight can improve prognosis and health-related quality of life (HRQoL) among cancer survivors. The largest proportion of cancer survivors are older adults (≥65 years), yet their lifestyle behaviors are understudied. This study examined the lifestyle behaviors (diet quality, physical activity, maintaining healthy weight) of older female cancer survivors and associations with HRQoL. Methods: Women aged 65 years or older, with all cancer subtypes and stages, who had completed primary cancer treatment (i.e., chemotherapy, surgery, radiation) within the past five years, were eligible to participate. Older female cancer survivors (n = 171) completed one-time surveys to assess HRQoL (RAND-36), unintentional weight loss, body mass index (BMI), diet quality (Diet History Questionnaire II), and physical activity. Demographic information and medical record data were also collected. Diet History Questionnaire II results were converted to Healthy Eating Index (HEI)-2015 scores. Descriptive analyses, correlations, and stepwise linear regressions were utilized. Results: The majority of the sample (median age = 74.50±8.43 years) were white (90%), married (54.7%), breast cancer survivors (67.7%), and completed at least a bachelor’s degree (54.7%). Physical and mental HRQoL of the sample were low; 41.94±10.50 and 48.47±7.18, respectively, out of 100. Physical activity was low; 75.3%, 54.2%, and 68.1% reported no strenuous, moderate, and mild physical activity, respectively. Mean BMI was 27.71±6.24 (overweight), with 64% of the participants being overweight or obese. Mean HEI-2015 scores were 66.54+10.0 out of 100 and below the cutoff score of 80, which represents a “good diet”. Participating in moderate physical activity was associated with higher physical HRQoL (β = 0.42, p = 0.004). Being older (β = 0.27, p = 0.025), white (β = 0.53, p &lt; 0.001), and having higher HEI scores (β = 0.30, p = 0.011) was associated with higher mental HRQoL. Conclusions: Older female cancer survivors reported lifestyle challenges including poor diet quality, low levels of physical activity, and high rates of being overweight or obese, which were associated with HRQoL. Results indicate the need for tailored health interventions for older female cancer survivors regarding their lifestyle behaviors to improve prognosis and HRQoL.
The prevention of anticancer therapy extravasation events in the oncology clinic infusion patient: A quality improvement study.
Authors: Lisa Ciafre, Matthew Bigbee, Holley Stallings, Chelsea Strom, Patricia Reiser, Emily Graham, Raven Lowery, Courtney Scheerer, Dana Haines
Journal: Journal of Clinical Oncology (2020)

192 Background: The Allegheny Health Network Cancer Institute (AHNCI) Medical Oncology is comprised of 19 infusion clinics located in the western Pennsylvania region. Safety quality assurance data revealed an extravasation rate of 0.12% for vesicant anticancer therapies. A literature review identified a benchmark for these extravasations to be 0.09% confirming that the AHNCI had an opportunity to improve patient safety. Methods: A multidisciplinary quality team with support from ASCO’s Quality Training Program was developed to decrease extravasation occurrences utilizing problem solving tools and PDSA methodology. A process flow map and cause and effect diagram revealed opportunities in the following categories: People–Lack of formal IV training resulting in care dependent on experiential knowledge only; Process–There is not a standardized process for IV starts; Plant–Supply standardization was non-existent. Offices and staff utilized the catheter of their choice with varying levels of technology for early detection of vein cannulation. The use of catheter stabilizing dressings or devices did not exist. Diagnostic data analysis revealed that a majority of extravasation events occurred peripherally in the forearm with a 24g, 0.75” catheter. Therefore, this quality team’s focus was on the prevention of peripheral extravasations. Gemba walk utilizing an observation tool identified that nurses often made decisions based on personal comfort rather than best practice. Process measures: Process Change #1: Standardize IV Catheters across the network to reduce variation and ensure that the chosen catheter’s manufacture technology includes early vein cannulation technology and to implement IV start kits with a securement dressing. Process Change#2: Educate nurses in vein assessment technique, catheter selection and insertion skill. Results: Allegheny Health Network Cancer Institute was able to decrease extravasation events from 0.12% to 0.02% due to the innovation of this quality improvement team by standardizing supplies and ensuring staff competency with peripheral IV insertion knowledge and skills. Conclusions: Validating a problem through data is essential–we can’t manage what we can’t measure.Validating a problem’s value through evidence is necessary (patient harm). Benchmarking must be supported with a high level of evidence. Eliminating variation improves investigative outcomes. Implementing process measures through best practice evidence and not hypothesis is essential.
Prevalence of Dermatitis Herpetiformis Within the iCureCeliac Patient-Powered Research Network—Patient Characteristics and Dietary Counseling
Authors: Bridget E. Shields, Joel M. Gelfand, Lynne Allen-Taylor, Misha Rosenbach
Journal: JAMA Dermatology (2020)

This survey study describes the frequency of dermatitis herpetiformis among patients included in the iCureCeliac network as well as the demographics of patients with dermatitis herpetiformis and underlying celiac disease.
AB0059 Combination of plasmapheresis and intravenous bolus administration of methotrexate and methylprednisolone in refractory rheumatoid arthritis
Authors: HA Asseeva, SK Soloviev, AS Chiklikchy
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate the effect of synchronic program of intensive therapy (SPIT) on patients with refractory RA. <h3>Methods</h3> 20 RA patients with systemic manifestations: rheumatoid nodules (65%), lymphadenopathia (45%), fever (35%), livedo vasculitis (10%). 19 patients (95%) demonstrated intorelability of inefficacy of previous basic therapy, 6 (30%) had a corticosteroid dependency. Before the treatment Wilke?s Index activity was 7,06, Index severity was 11,38.6 courses of plasmapheresis synchronised with pulse-therapy of Methylprednisolone (1500 mg) and Methotrexat (240 mg) during 1 month, after that all patients were prescribed Methotrexat in dosage of 20 mg i.m. for 11 months. <h3>Results</h3> 4 patients (20%) had a clinico-laboratory remission in a year after beginning of treatment (Wilke,1993). In all group clinico-laboratory improvement was observed in a month and prolonged during the year. In all causes were no systemic manifestations in a month of the treatment. All 20 patients demonstrated the significant decrease of arthralgies, morning stiffness, number of inflamed joints, growth of indices of functional activity. Prednisolone was abolished in 2 patients and daily dosage was decreased in 4 patients/In a 6 months 16 patients (80%) had a low clinico- laboratory activity. Side effects were minimal and were arrested without additional treatment. <h3>Conclusion</h3> Synchronic program of intensive therapy can be considered the effective method of RA therapy enabling to achieve speedy clinical improvement, espessially during severe variants of the disease progressing with systemic manifestations, resistance to basic medication, corticosteroid dependency.
Review of time to treatment for head and neck cancer patients at a rural Maine cancer center.
Authors: Antoine Joseph Harb, Adam Curtis
Journal: Journal of Clinical Oncology (2020)

292 Background: Time to Treatment (TTT) for head and neck (H&amp;N) malignancies were reviewed for all patients treated at Northern Light Cancer Institute, from 2013 to 2017. A total of 297 cases were identified. Methods: TTT was defined as time of tissue diagnosis by biopsy to the first treatment day. Data was compared to a comprehensive study of 51,655 cases conducted by Murphy et al (JCO, 34; 2, Jan 10, 2016). Median days to treatment were compared by tumor site and treatment modality. Comparison of the distribution of cases where TTT exceeded the critical time point of 67 days (determined by Murphy) was also made. The primary mode of treatment was a combination of chemotherapy and radiation (concomitant) in 39.5% of patients. Other treatment modalities included radiation only (17.2%), and surgery, either as stand-alone treatment, or followed by subsequent additional treatment (32.4%). These treatment modalities comprise 89.1% of all cases. Results: We identified 82 (27.7%) patients with oral cancer, 99 (33.5%) with oropharyngeal malignancy and 92 (31.1%) with laryngeal cancer. Median TTT was 40 days (compared to 34 days found by Murphy) for chemo-radiation patients, 42 (versus 31) for radiation only, and 34 (versus 17) for surgery. TTT for surgery patients was significantly shorter than the other two treatment modalities (p &lt; 0.05). There were no significant differences in TTT based on primary site. All comparisons to Murphy (treatment and primary site) were significantly lower than our median values (p &lt; 0.05). Median TTT over 5 years maintained the same relationship between the treatment modalities. 29.2% of our patients were treated within 30 days, 50% from 31-52 days, 10.6% from 53-67 days, and 10.2% beyond 67 days, compared with 59.5, 23.3, 8.3, and 9% respectively found by Murphy. Conclusions: TTT for H&amp;N cancers has been relatively stable over the 5-year time course examined. The majority of our patients (50%) are treated in the 31-52 day timeframe compared with the first 30 days (59.5%) with Murphy. Our data suggest similar percentages (10.2 versus 9%) after which patients had poorer outcome. Further efforts should be entertained to make sure patients are seen sooner in the oncology clinic.
Sub-second Dopamine and Serotonin Signaling in Human Striatum during Perceptual Decision-Making
Authors: Dan Bang, Kenneth T. Kishida, Terry Lohrenz, Jason P. White, Adrian W. Laxton, Stephen B. Tatter, Stephen M. Fleming, P. Read Montague
Journal: Neuron (2020)

Recent animal research indicates that dopamine and serotonin, neuromodulators traditionally linked to appetitive and aversive processes, are also involved in sensory inference and decisions based on such inference. We tested this hypothesis in humans by monitoring sub-second striatal dopamine and serotonin signaling during a visual motion discrimination task that separates sensory uncertainty from decision difficulty in a factorial design. Caudate nucleus recordings (n = 4) revealed multi-scale encoding: in three participants, serotonin tracked sensory uncertainty, and, in one participant, both dopamine and serotonin tracked deviations from expected trial transitions within our factorial design. Putamen recordings (n = 1) supported a cognition-action separation between caudate nucleus and putamen—a striatal sub-division unique to primates—with both dopamine and serotonin tracking decision times. These first-of-their-kind observations in the human brain reveal a role for sub-second dopamine and serotonin signaling in non-reward-based aspects of cognition and action.