tbuckley/cabot-search huggingface dataset:
Taxonomy of the Oaks
Authors: Matthew Joel Goodman
Journal: JAMA (2021)

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TIMP1 expression underlies sex disparity in liver metastasis and survival in pancreatic cancer
Authors: Chris D. Hermann, Benjamin Schoeps, Celina Eckfeld, Enkhtsetseg Munkhbaatar, Lukas Kniep, Olga Prokopchuk, Nils Wirges, Katja Steiger, Daniel Häußler, Percy Knolle, Emily Poulton, Rama Khokha, Barbara T. Grünwald, Ihsan Ekin Demir, Achim Krüger
Journal: The Journal of Experimental Medicine (2021)

Sex disparity in cancer is so far inadequately considered, and components of its basis are rather unknown. We reveal that male versus female pancreatic cancer (PC) patients and mice show shortened survival, more frequent liver metastasis, and elevated hepatic metastasis-promoting gene expression. Tissue inhibitor of metalloproteinases 1 (TIMP1) was the secreted factor with the strongest male-biased expression in patient-derived pancreatic tumors. Male-specific up-regulation of systemic TIMP1 was demonstrated in PC mouse models and patients. Using TIMP1-competent and TIMP1-deficient PC mouse models, we established a causal role of TIMP1 in determining shortened survival and increased liver metastasis in males. Observing TIMP1 expression as a risk parameter in males led to identification of a subpopulation exhibiting increased TIMP1 levels (T1HI males) in both primary tumors and blood. T1HI males showed increased risk for liver metastasis development not only in PC but also in colorectal cancer and melanoma. This study reveals a lifestyle-independent sex disparity in liver metastasis and may open new avenues toward precision medicine.
Letter by Nguyen et al Regarding Article, “Coronary Optical Coherence Tomography and Cardiac Magnetic Resonance Imaging to Determine Underlying Causes of Myocardial Infarction With Nonobstructive Coronary Arteries in Women”
Authors: Thanh Ha Nguyen, Gao-Jing Ong, John D. Horowitz
Journal: Circulation (2021)
Особливості хронічних панкреатитів на Закарпатті
Authors: V.Yu. Koval, E.Y. Arkhiy, O.O. Boldіzhar
Journal: GASTROENTEROLOGY (2013)

У статті наведено аналіз показників поширеності хвороб підшлункової залози, хвороб органів травлення та захворюваності на них серед усього населення на Закарпатті. Вивчено особливості хронічних захворювань підшлункової залози залежно від статі, віку пацієнтів, тривалості, анамнезу захворювання та клінічної форми. Незважаючи на зменшення показників поширеності хронічних хвороб органів травлення та захворюваності на них серед усього населення в період із 2009 по 2011 рік, відмічається збільшення показників поширеності хвороб підшлункової залози та захворюваності на них серед усього населення в структурі хвороб органів травлення.
Development and outcomes of a virtual triage pathway for cancer diagnosis in vague symptom patients.
Authors: Kathryn Tremble, Maria J. Monroy-Iglesias, Sabine Martin, Geraint Jones, Charlotte Moss, Beth Russell, Lindsay Steward, Colette Murtagh, Carlos Cargaleiro, Graham Roberts, Mieke Van Hemelrijck, Luigi De Michele, Saoirse Dolly
Journal: Journal of Clinical Oncology (2021)

326 Background: At the Rapid Access Diagnostic Unit at Guy’s Hospital London, we review patients with vague symptoms that are concerning for malignancy. As part of our response to the COVID-19 pandemic, we developed a virtual triage pathway with the aim to reduce face-to-face appointments and prioritise resources towards patients with an underlying cancer diagnosis. Methods: Patients were triaged by clinicians based on a telephone consultation with the patient and history and blood tests provided in the referral. Those triaged as high risk were either directly booked for investigation (“straight-to-test”) or booked for a face-to-face consultation for further history and examination. Low risk patients were either put on a watch-and-wait pathway with a telephone follow-up in 3-4 weeks or discharged back to the GP with a robust plan on symptom management. The patient outcomes were tracked and compared to the outcomes from the face-to-face assessment service used prior to the COVID-19 pandemic (Dec 2016-Feb 2020). Patients triaged as low risk and discharged were tracked to monitor for any subsequent cancer diagnoses. Results: There were 804 referrals triaged between March 2020-January 2021. 75% were triaged to a face-to-face assessment and 18% triaged straight-to-test. 4% were placed on the watch-and-wait pathway and 3% were returned to the GP with advice. In those triaged as high risk, 8.2% were diagnosed with cancer, 54% were diagnosed with a serious-benign condition and 38% with a non-serious or no condition. In the patients triaged as low risk and placed on the watch-and-wait pathway, 14% were brought in for a face-to-face assessment based on their follow-up telephone assessment. None of the patients on the watch-and-wait pathway were found to have a cancer diagnosis, 11% were diagnosed with a serious-benign condition, and 89% were diagnosed with a non-serious or no condition. There was an overall cancer diagnosis rate of 7.6% compared with a pre-COVID-19 diagnosis rate of 6.6%. Conclusions: The virtual triage pathway effectively risk-assessed patients, with those triaged as high risk having an 8.2% cancer diagnosis rate compared to a 0% cancer diagnosis rate in those triaged as low risk. Furthermore, the virtual triage service had a higher cancer diagnosis rate compared to the pre-COVID-19 face-to-face assessment service. Therefore the virtual triage service provides an efficient pathway for cancer diagnosis in patients presenting with vague symptoms, reducing the number of face-to-face appointments and supporting management of low risk patients in the community.
Monitoring the SARS-CoV-2 pandemic: screening algorithm with single nucleotide polymorphism detection for the rapid identification of established and emerging variants
Authors: Joachim Mertens, Jasmine Coppens, Katherine Loens, Marie Le Mercier, Basil Britto Xavier, Christine Lammens, Sarah Vandamme, Hilde Jansens, Herman Goossens, Veerle Matheeussen
Journal: Clinical Microbiology and Infection (2021)
Discerning the Role of Autoimmunity and Autoantibodies in Epilepsy
Authors: Claude Steriade, Lisa Gillinder, Kirsty Rickett, Gunter Hartel, Lindsay Higdon, Jeffrey Britton, Jacqueline French
Journal: JAMA Neurology (2021)

<h3>Importance</h3> The literature on neural autoantibody positivity in epilepsy has expanded over the last decade, with an increased interest among clinicians in identifying potentially treatable causes of otherwise refractory seizures. <h3>Observations</h3> Prior studies have reported a wide range of neural autoantibody positivity rates among various epilepsy populations, with the highest frequency reported in individuals with focal epilepsy of unknown cause and new-onset seizures. The antibodies in some cases are of uncertain significance, and their presence can cause conundrums regarding therapy. <h3>Conclusions and Relevance</h3> There is likely some role for neural autoantibody assessment in patients with unexplained epilepsy who lack clear evidence of autoimmune encephalitis, but the clinical implications of such testing remain unclear owing to limitations in previous published studies. A framework for study design to bridge the current gaps in knowledge on autoimmune-associated epilepsy is proposed.
Engineered gold/black phosphorus nanoplatforms with remodeling tumor microenvironment for sonoactivated catalytic tumor theranostics
Authors: Ting Chen, Weiwei Zeng, Changjun Tie, Mian Yu, Huisong Hao, Yang Deng, Qianqian Li, Hairong Zheng, Meiying Wu, Lin Mei
Journal: Bioactive Materials (2021)

The imbalance between oxidants and antioxidants in cancer cells would evoke oxidative stress-induced cell death, which has been demonstrated to be highly effective in treating malignant tumors. Sonodynamic therapy (SDT) adopts ultrasound (US) as the excitation source to induce the production of reactive oxygen species (ROS), which emerges as a noninvasive therapeutic strategy with deep tissue penetration depth and high clinical safety. Herein, we construct novel sonoactivated oxidative stress amplification nanoplatforms by coating MnO2 on Au nanoparticle-anchored black phosphorus nanosheets and decorating soybean phospholipid subsequently (Au/BP@MS). The Au/BP@MS exhibit increased ROS generation efficiency under US irradiation in tumor tissues due to Au/BP nanosensitizer-induced improvement of electron-hole separation as well as MnO2-mediated O2 generation and GSH depletion, thus leading to notable inhibition effect on tumor growth. Moreover, tumor microenvironment-responsive biodegradability of Au/BP@MS endows them with enhanced magnetic resonance imaging guidance and clinical potential for cancer theranostics.
Association of Public Reporting of Medicare Dialysis Facility Quality Ratings With Access to Kidney Transplantation
Authors: Joel T. Adler, Lingwei Xiang, Joel S. Weissman, James R. Rodrigue, Rachel E. Patzer, Sushrut S. Waikar, Thomas C. Tsai
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Improving the quality of dialysis care and access to kidney transplantation for patients with end-stage kidney disease is a national clinical and policy priority. The role of dialysis facility quality in increasing access to kidney transplantation is not known. <h3>Objective</h3> To determine whether patient, facility, and kidney transplant waitlisting characteristics are associated with variations in dialysis center quality. <h3>Design, Setting, and Participants</h3> This population-based cohort study is an analysis of US Renal Data System data and Medicare Dialysis Facility Compare (DFC) data from 2013 to 2018. Participants included all adult (aged ≥18 years) patients in the US Renal Data System beginning long-term dialysis in the US from 2013 to 2017 with follow-up through the end of 2018. Patients with a prior kidney transplant and matched Medicare DFC star ratings to each annual cohort of recipients were excluded. Patients at facilities without a star rating in that year were also excluded. Data analysis was performed from January to April 2021. <h3>Exposures</h3> Dialysis center quality, as defined by Medicare DFC star ratings. <h3>Main Outcomes and Measures</h3> The primary outcome was the proportion of patients undergoing incident dialysis who were waitlisted within 1 year of dialysis initiation. Secondary outcomes were patient and facility characteristics. <h3>Results</h3> Of 507 581 patients beginning long-term dialysis in the US from 2013 to 2017, 291 802 (57.4%) were male, 266 517 (52.5%) were White, and the median (interquartile range) age was 65 (55-75) years. Of 5869 dialysis facilities in 2017, 132 (2.2%) were 1-star, 436 (7.4%) were 2-star, 2047 (34.9%) were 3-star, 1660 (28.3%) were 4-star, and 1594 (27.2%) were 5-star. Higher-quality dialysis facilities were associated with 47% higher odds of transplant waitlisting (odds ratio [OR], 1.47; 95% CI, 1.39-1.57 for 5-star facilities vs 1-star facilities;<i>P</i> &lt; .001). Black patients were less likely than White patients to be waitlisted for transplantation (OR, 0.74; 95% CI, 0.72-0.76). In addition, patients at for-profit (OR, 0.78; 95% CI, 0.74-0.81) and rural (OR, 0.63; 95%, CI 0.58-0.68) facilities were less likely to be waitlisted for transplantation compared with those at nonprofit and urban facilities, respectively. <h3>Conclusions and Relevance</h3> In this cohort study, patients at higher-quality dialysis facilities had higher odds than patients at lower-quality facilities of being waitlisted for kidney transplantation within 1 year. Waitlisting rates for kidney transplantation should be considered for integration into the current Centers for Medicare &amp; Medicaid Services DFC star ratings to incentivize dialysis facility referral to transplant centers, inform patient choice, and drive quality improvement by increasing transplant waitlisting rates.
Results of a multistate, multi-institution implementation of a multidisciplinary cancer conference quality measurement tool.
Authors: Lijo Simpson, Anju Mathew, Robert Wojciechowski, Irina Hill
Journal: Journal of Clinical Oncology (2021)

212 Background: The 2006 ASCO and the ESMO consensus statement on quality cancer care defined the delivery of multimodality treatment by a multidisciplinary team of appropriately skilled health professionals as an essential component of quality cancer care. Furthermore, MDCs have demonstrated improved survival in breast, head and neck, ovarian and colorectal cancers. Despite these advantages, health care systems struggle to implement and sustain MDCs due to the heavy burden imposed by the required work processes. We report on the large-scale utilization of a propriety quality measurement platform OncoLens to run MDCs across the country. Methods: Technology quality metrics were collected from the ongoing daily usage of the platform including cancer characteristics, care team utilization metrics, average attendance, quality metrics collected for accreditation and clinical trials matching on the OncoLens platform. Results: The virtual platform was accessible to around 8000 providers across the United States. In 2020, 13771 cases were discussed. Attendance of the required specialties for high quality care of Medical Oncology, Radiation Oncology, Surgery, Pathology and Radiology was attained, with the average conference attendance being 14. Race/ethnicity data on the cases revealed White (9197, 67%), Black (1817,13%), Hispanic (363,3%) and Other (2356,17%). Optional quality metrics were collected during discussions for CoC, NAPBC and NAPRC accreditation. These included NCCN guidelines discussed, Staging discussed, clinical trials discussed, Genetics discussion, palliative care discussion, rehabilitation services, reproductive counselling discussed, psychosocial counselling discussed, nutritional counselling discussed, reconstructive surgery discussion, tobacco cessation discussion across General and Site-specific conferences. Most of the case presentations were prospective. This format does enable cancer programs to collect quality metrics around Cancer program accreditation by the American College of Surgeons. 66% of patients discussed potentially matched to clinical trials during the discussion. Conclusions: A technology platform can assist cancer programs to collect quality metrics around cancer care. This gives them the ability to run data driven quality programs targeting specific quality metrics. Hispanics have a lower percentage of cases presented at MDC compared to other race/ethnicities. It is possible to have high quality discussions and attain metrics for Commission on Cancer accreditation utilizing a virtual platform.
Perioperative sleep disturbance following mastectomy: A longitudinal investigation of the relationship to pain, opioid use, treatment, and psychosocial symptoms.
Authors: Desiree Rachel Azizoddin, Mieke A. Soens, Meghan Beck, Kelsey Mikayla Flowers, Robert R. Edwards, Kristin L. Schreiber
Journal: Journal of Clinical Oncology (2021)

192 Background: Sleep disturbance negatively impacts quality of life and recovery. Our objective was to evaluate the relationship between individual patient factors (demographic, surgical, pain, opioid use, and psychosocial factors) and greater sleep disturbance. Methods: In this prospective longitudinal study, patients completed validated measures regarding their sleep disturbance, pain, opioid use, and psychological symptoms preoperatively and then 2 weeks, 6 and 12 months postoperatively. Objective pain sensitivity measures were evaluated at baseline using quantitative sensory testing. Univariable and multivariable generalized estimating equations (GEE) evaluated demographic, surgical, pain, and psychological predictors of sleep disturbance during the first year after surgery for breast cancer. Results: Female patients (n = 259) reported varying degrees of sleep disturbance, which were longitudinally associated with pain, psychosocial factors such as anxiety, depression, and affect. While the mean degree of sleep disturbance did not change substantially over time, the link to pain severity appeared to strengthen over the first postoperative year. Independent preoperative predictors of worse sleep disturbance on multivariable longitudinal GEE included younger age (B = -.09, p =.006), opioid use (B = 3.09, p =.02), higher pain (B =.19, p = &lt;.001) and anxiety (B =.45, p = &lt;.001) at baseline. On the other hand, higher basline positive affect (B = -.14, p = &lt;.012) and the surgical category total mastectomy without reconstruction (B = -2.81, p = &lt;.006) were indepently associated with lower sleep disturbance. Those with worse baseline sleep required more opioid analgesics during surgical recovery, and continued use of opioids at 2 weeks post-surgery was associated with disturbed sleep. Conclusions: Sleep disturbance in the first year following surgery for breast cancer varied substantially between individuals. Certain demographic, psychosocial, and pain factors explained more of this variance than surgical procedure, with the exception of total mastectomy without reconstruction that was associated with lower sleep disturbance. Sleep disturbance was associated with increased need for opioids in the perioperative period, and a propensity for more prolonged postoperative opioid use. Pre-surgical interventions in high risk individuals such as anxiety management, boosting positive affect, and controlling pain that have been shown to improve sleep quality could enhance postoperative recovery and decrease opioid use following breast surgery.
Letter to the Editor: On the mechanisms of biliary flux
Authors: Norman B. Javitt, James L. Boyer
Journal: Hepatology (2021)

To the editor, Vartak et al.’s recent publication[1] reviews their previous provocative data[2] that water flow into the bile canaliculus is not in response to an osmotic gradient, as initially proposed by Sperber. However, their technique (photoactivation of a nonfluorescent precursor of fluorescein) has not been validated. In contrast, a similar technique, enzymatic activation of a nonfluorescent precursor of fluorescein,[3] supported the concept of osmotically generated canalicular water flow and confirmed that peristalsis also participates in the flow of fluid from the canaliculi into the duct system, as originally described by Philips. The photoactivation technique used by Vartak et al. has been critiqued in considerable detail by others questioning that photoactivation delineates only the canalicular and ductular network.[4] In this review they discuss the role of aquaporins and claudin‐2, a water channel, which suggests that they may be changing their initial interpretation that there is no osmotically determined canalicular water flow. However they discount their role without strong evidence. Moreover, they question the initial proposal that mannitol is a specific biomarker for canalicular water flow, as not supported by subsequent studies. However, they do not mention the quantitative studies indicating that much less mannitol enters bile when secretin choleresis is induced, compared with intravenous injection of sodium dehydrocholate, which produces a marked choleresis (Figure 1), again indicating two sources for the entry of water into bile.FIGURE 1: Biliary clearance of 14C‐Mannnitol in man following stimulation of bile flow with sodium dehydrocholate versus secretin.[ 5 ]Finally, we also draw attention to observations in the isolated hepatocyte couplet, where bile acids stimulate the expansion and collapse of the canalicular space more rapidly when the initial bile lumen is larger than when it is smaller, a finding that supports canalicular osmotic flow.[6] CONFLICT OF INTEREST Nothing to report.
Targeting the DNA damage response enhances CD70 CAR-T cell therapy for renal carcinoma by activating the cGAS-STING pathway
Authors: Feng Ji, Fan Zhang, Miaomiao Zhang, Kaili Long, Mingyue Xia, Fei Lu, Enjie Li, Jiannan Chen, Jun Li, Zhengliang Chen, Li Jing, Shaochang Jia, Rong Yang, Zhigang Hu, Zhigang Guo
Journal: Journal of Hematology & Oncology (2021)

Abstract Chimeric antigen receptor T-cell (CAR-T) therapy has shown tremendous success in eradicating hematologic malignancies. However, this success has not yet been extrapolated to solid tumors due to the limited infiltration and persistence of CAR-T cells in the tumor microenvironment (TME). In this study, we screened a novel anti-CD70 scFv and generated CD70 CAR-T cells that showed effective antitumor functions against CD70 + renal carcinoma cells (RCCs) both in vitro and in vivo. We further evaluated the effect and explored the molecular mechanism of a PARP inhibitor (PARPi) in CAR-T cell immunotherapy by administering the PARPi to mouse xenografts model derived from human RCC cells. Treatment with the PARPi promoted CAR-T cell infiltration by stimulating a chemokine milieu that promoted CAR-T cell recruitment and the modulation of immunosuppression in the TME. Moreover, our data demonstrate that PARPi modulates the TME by activating the cGAS-STING pathway, thereby altering the balance of immunostimulatory signaling and enabling low-dose CAR-T cell treatment to induce effective tumor regression. These data demonstrate the application of CD70 CAR-T cell therapeutic strategies for RCC and the cross-talk between targeting DNA damage responses and antitumor CAR-T cell therapy. These findings provide insight into the mechanisms of PARPis in CAR-T cell therapy for RCC and suggest a promising adjuvant therapeutic strategy for CAR-T cell therapy in solid tumors.