tbuckley/cabot-search huggingface dataset:
Ancient DNA Suggests Single Colonization and Within-Archipelago Diversification of Caribbean Caviomorph Rodents
Authors: Roseina Woods, Ian Barnes, Selina Brace, Samuel T Turvey
Journal: Molecular Biology and Evolution (2020)

Reconstructing the evolutionary history of island biotas is complicated by unusual morphological evolution in insular environments. However, past human-caused extinctions limit the use of molecular analyses to determine origins and affinities of enigmatic island taxa. The Caribbean formerly contained a morphologically diverse assemblage of caviomorph rodents (33 species in 19 genera), ranging from ∼0.1 to 200 kg and traditionally classified into three higher-order taxa (Capromyidae/Capromyinae, Heteropsomyinae, and Heptaxodontidae). Few species survive today, and the evolutionary affinities of living and extinct Caribbean caviomorphs to each other and to mainland taxa are unclear: Are they monophyletic, polyphyletic, or paraphyletic? We use ancient DNA techniques to present the first genetic data for extinct heteropsomyines and heptaxodontids, as well as for several extinct capromyids, and demonstrate through analysis of mitogenomic and nuclear data sets that all sampled Caribbean caviomorphs represent a well-supported monophyletic group. The remarkable morphological and ecological variation observed across living and extinct caviomorphs from Cuba, Hispaniola, Jamaica, Puerto Rico, and other islands was generated through within-archipelago evolutionary radiation following a single Early Miocene overwater colonization. This evolutionary pattern contrasts with the origination of diversity in many other Caribbean groups. All living and extinct Caribbean caviomorphs comprise a single biologically remarkable subfamily (Capromyinae) within the morphologically conservative living Neotropical family Echimyidae. Caribbean caviomorphs represent an important new example of insular mammalian adaptive radiation, where taxa retaining "ancestral-type" characteristics coexisted alongside taxa occupying novel island niches. Diversification was associated with the greatest insular body mass increase recorded in rodents and possibly the greatest for any mammal lineage.
Trends in germline genetic testing and results into survivorship for women diagnosed with breast cancer or ovarian cancer, 2013 to 2017.
Authors: Steven J. Katz, Monica Morrow, Allison W. Kurian
Journal: Journal of Clinical Oncology (2020)

273 Background: Genetic testing is increasingly central to breast and ovarian cancer prevention and treatment. Yet, little is known about trends and disparities in receipt of testing and test results after diagnosis. Methods: We linked all female patients with breast or ovarian cancer diagnosed from 2013-2017 in Georgia and California and reported to SEER registries to genetic testing results from four laboratories (Ambry Genetics, GeneDx, Invitae, Myriad Genetics). We combined test results from all labs with SEER data. We classified a test as a multigene panel (MGP) if it included other genes in addition to BRCA1/2. We grouped pathogenic variants (PVs) by level of evidence that supported clinical testing: BRCA1/2; other genes associated with well-established syndromes (syndromic genes); genes whose cancer association is less certain (emerging genes); and any other tested genes (other genes). We categorized patients with a variant of unknown significance (VUS) in any gene but no PVs as VUS-only. We examined trends in receipt of testing and test results overall and by race/ethnic groups. Results: One quarter (25.5%) of 198,001 breast cancer patients, and 34.5% of 15,461 ovarian cancer patients had genetic tests. Test rates increased by only 2% annually; while the number of genes tested per patient increased by 28%. The mean number of genes tested rose from 10 to 35 during the study period. In early 2013, 18.3% of testers had a PV or VUS result, which increased to 37.2% in late 2017. The upward trend was largely due to increase in VUS-only findings. The proportion of tested breast cancer patients with any PV increased from 9.1% to 9.9%: PVs in BRCA1/2 decreased from 7.5% to 5.0% (p&lt;.001), while PV yield for the two other clinical categories (syndromic and emerging genes) increased from 1.6% to 4.9% (p&lt;.001). PVs in any of the other 61 genes were very rare (&lt;1%). By contrast, the VUS rate in breast cancer patients increased markedly from 9.6% in 2013 to 26.2% in 2017. The VUS rate was higher in racial/ethnic minorities (41.0% Asian, 36.5%% Black, 28.0% Latinas versus 25.6% non-Hispanic Whites diagnosed in 2017; p&lt;.001). We observed similar findings for patients with ovarian cancer. Conclusions: A large gap persists in testing ovarian cancer patients (35% versus 100% recommended). Testing more genes per patient was associated with a substantial racial/ethnic gap in VUS with little difference in yield on clinically relevant PVs. Testing a limited subset of genes may optimize yield-to-noise of genetic testing, particularly for racial/ethnic minorities.
The Doctor Is Out—Reflections on Being a Black, Queer Physician
Authors: Jasmyne Jackson
Journal: JAMA Pediatrics (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Use of a rapid access multidisciplinary bone metastases clinic to decrease financial toxicity for patients undergoing single-fraction palliative radiation.
Authors: Jose Alberto Maldonado, Minsoo Kim, Prasamsa Pandey, Sarah Todd, Kaitlin Marie Christopherson, Matthew S. Ning, David R Grosshans, Lilie L. Lin, Jay Reddy, Justin E. Bird, Robert L. Satcher, Valerae O. Lewis, Chad Tang, Albert C. Koong, Lauren Elizabeth Colbert
Journal: Journal of Clinical Oncology (2020)

24 Background: A rapid access bone metastases clinic (RABC) was instituted at MD Anderson Cancer Center (MDACC) to allow outpatient consult, simulation and radiation treatment (RT) initiation in &lt; 6 hours for patients with painful bone metastases. Patients underwent multidisciplinary evaluation with orthopedics and radiation oncology. One aspect of financial toxicity is distress due to out-of-pocket (OOP) cost associated with a treatment. We hypothesized the RABC would decrease financial toxicity for MDACC patients over traditional RT. Methods: RABC patients surveyed between April 2018 and January 2020 were included. Patients were asked to estimate OOP cost for RT (including travel and treatment cost) and perceived cost burden of treatment. Travel distance was hometown distance to MDACC. Subset analyses were performed for patients receiving single fraction (1fx) and 2-5 fractions (2-5fx). Estimated OOP cost (1fx: RABC N = 34, nonRABC N = 20; 2-5fx: RABC N = 4, nonRABC N = 22), perceived cost burden (1fx: RABC N = 32, nonRABC N = 27; 2-5fx: RABC N = 7, nonRABC N = 38) and travel distance (1fx: RABC N = 34, nonRABC N = 28; 2-5fx: RABC N = 7, nonRABC N = 38) were compared using a Mann-Whitney U Test. Travel distance was also compared to OOP cost. Patients treated with 6+ fractions were excluded. Results: Median estimated OOP cost was significantly lower for 1fx RABC patients vs. 1fx non-RABC patients ($450 [IQR $187.5-$1,050] vs. $2,000 [$625-$4,000]; p = 0.008), but there was no significant difference for 2-5fx ($1,900 vs. $1,375; p = 0.593). Overall patient satisfaction with cost burden was high regardless of treatment setting (1fx: 10 [8-10]; 2-5fx: 10 [8-10]). Median travel distance was not significantly different between clinics (1fx: 245 [39.8-351.5] vs. 262.5 [83-879.3], p = 0.3651; 2-5fx: 274 [36-1293] vs. 176 [25-626], p = 0.2721). Travel distance was directly correlated with out of pocket cost for single fraction (1fx: R 2 = 0.125, p = 0.0109; 2-5fx: R 2 = 0.037, p = 0.3433). Conclusions: The establishment of a RABC at MDACC significantly decreased financial toxicity for 1fx patients receiving palliative RT, but not in the 2-5fx cohort. Increased financial toxicity was associated with longer travel distance for 1fx palliative radiation. Implementation of a similar model in local community centers may decrease financial toxicity for patients receiving palliative radiation.
Improving the referral rate of universal genetic counseling for pancreatic ductal adenocarcinoma (PDAC) at the Cleveland Clinic Taussig Cancer Center: A quality improvement project.
Authors: Kanika G. Nair, Brandie Leach, Selina Sledge, Megan Kilbane, Jennifer Bates, Meghan O'Brien, Bassam N. Estfan, Alok A. Khorana, Pauline Funchain
Journal: Journal of Clinical Oncology (2020)

196 Background: While most PDAC are sporadic, up to 10% are inherited. In 2018, ASCO and NCCN guidelines were updated to recommend that all patients with PDAC be considered for genetic counseling (GC) and germline testing. Furthermore, interest in treating patients with targeted therapy, such as olaparib, for germline mutations is increasing. We implemented a quality improvement project to identify the referral rate to GC for patients with PDAC, with the goal of improving the referral rate to 60%. Methods: Barriers to GC referral were identified using quality improvement tools developed at the ASCO Quality Training Program. Three “plan, do, study, act” (PDSA) cycles were implemented: 1) updating the electronic order and tumor board template to include GC recommendation (Aug–Oct 2019), 2) physician education (Nov–Dec 2019) and 3) patient education and physician reinforcement (Jan–Feb 2020). Baseline data to evaluate impact of PDSA intervention (from April to June 2019) on documented discussions about GC and placement of the referral order was completed via chart review. Results: Between April 2019 to January 2020, 199 patients with PDAC were seen in medical oncology clinic as new patient visits. Thirteen patients had previously completed GC. For the remainder, baseline discussion and referral rates were 25% and 9%, respectively. Discussion and referral rates improved to 55% and 30% after PDSA 1, to 73% and 33% after PDSA 2, and to 95% and 58% after PDSA 3, respectively. Forty-nine patients were referred at the first visit and 23 were referred at a subsequent visit. Forty-six patients underwent GC. In patients who completed germline testing 8.9% (4/45) were found to have a pathogenic variant in BRCA2, TP53, ATM, and MUTYH. Conclusions: With increased physician and patient education, we were able to improve the GC discussion rate from 25% to 95% and referral rate from 9% to 58%. While we did not meet our aim of 60% GC referral rate, we identified obstacles and outlined an improved process for early GC referrals. Enacting processes to reinforce GC referrals for patients with PDAC is likely to increase detection of germline mutations in this population.
Pre-treatment with high molecular weight free PEG effectively suppresses anti-PEG antibody induction by PEG-liposomes in mice
Authors: Morgan D. McSweeney, Limei Shen, Alexander C. DeWalle, Jordan B. Joiner, Elizabeth C. Ciociola, Dharmendra Raghuwanshi, Matthew S. Macauley, Samuel K. Lai
Journal: Journal of Controlled Release (2020)
Rescuing Over-activated Microglia Restores Cognitive Performance in Juvenile Animals of the Dp(16) Mouse Model of Down Syndrome
Authors: Bruno Pinto, Giovanni Morelli, Mohit Rastogi, Annalisa Savardi, Amos Fumagalli, Andrea Petretto, Martina Bartolucci, Emilio Varea, Tiziano Catelani, Andrea Contestabile, Laura E. Perlini, Laura Cancedda
Journal: Neuron (2020)

Microglia are brain-resident immune cells and regulate mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by a supernumerary chromosome 21, containing also genes related to the immune system. In the hippocampus of the Dp(16) mouse model of DS and DS individuals, we found activated microglia, as assessed by their morphology; activation markers; and, for DS mice, electrophysiological profile. Accordingly, we found increased pro-inflammatory cytokine levels and altered interferon signaling in Dp(16) hippocampi. DS mice also showed decreased spine density and activity of hippocampal neurons and hippocampus-dependent cognitive behavioral deficits. Depletion of defective microglia or treatment with a commonly used anti-inflammatory drug rescued the neuronal spine and activity impairments and cognitive deficits in juvenile Dp(16) mice. Our results suggest an involvement of microglia in Dp(16)-mouse cognitive deficits and identify a new potential therapeutic approach for cognitive disabilities in DS individuals.
Abstract 16612: Absence of BKCa Channels Causes Cardiac Hypertrophy and Dysfuntion
Authors: Swaiman Singh, Aaron J Wengrofsky, Kajol shah, Shubha G Rao, Devasena Ponnalagu, Ahmed T Hussain, Andrew R Kohut, Harpreet Singh
Journal: Circulation (2017)

Background: The large conductance Ca2+ and voltage-activated K+ channel (BKCa), encoded by the Kcnma1 gene have been known to localize to the plasma membrane of all cell types except for the adult ...
PD-1 restraint of regulatory T cell suppressive activity is critical for immune tolerance
Authors: Catherine L. Tan, Juhi R. Kuchroo, Peter T. Sage, Dan Liang, Loise M. Francisco, Jessica Buck, Youg Raj Thaker, Qianxia Zhang, Shannon L. McArdel, Vikram R. Juneja, Sun Jung Lee, Scott B. Lovitch, Christine Lian, George F. Murphy, Bruce R. Blazar, Dario A.A. Vignali, Gordon J. Freeman, Arlene H. Sharpe
Journal: The Journal of Experimental Medicine (2020)

Inhibitory signals through the PD-1 pathway regulate T cell activation, T cell tolerance, and T cell exhaustion. Studies of PD-1 function have focused primarily on effector T cells. Far less is known about PD-1 function in regulatory T (T reg) cells. To study the role of PD-1 in T reg cells, we generated mice that selectively lack PD-1 in T reg cells. PD-1–deficient T reg cells exhibit an activated phenotype and enhanced immunosuppressive function. The in vivo significance of the potent suppressive capacity of PD-1–deficient T reg cells is illustrated by ameliorated experimental autoimmune encephalomyelitis (EAE) and protection from diabetes in nonobese diabetic (NOD) mice lacking PD-1 selectively in T reg cells. We identified reduced signaling through the PI3K–AKT pathway as a mechanism underlying the enhanced suppressive capacity of PD-1–deficient T reg cells. Our findings demonstrate that cell-intrinsic PD-1 restraint of T reg cells is a significant mechanism by which PD-1 inhibitory signals regulate T cell tolerance and autoimmunity.
Assessing burnout among oncologists in Ontario, Canada.
Authors: Simron Singh, Ashley C Farrelly, Catherine Chan, Narges Nazeri-Rad, Brett Nicholls, Glenn Bauman, Daniela Bellicoso, Andrea Eisen, Conrad B Falkson, Colleen Fox, Claire MB Holloway, Erin Kennedy, Robin McLeod, David A. Rothenberger, Maureen E. Trudeau, Tait D. Shanafelt
Journal: Journal of Clinical Oncology (2020)

41 Background: Provider experience and physician burnout has been recognized as a critical issue in medicine. Ontario, Canada has a single payer cancer system run by Ontario Health (Cancer Care Ontario) with a mandate covering system level planning and delivery of cancer services, funding, and quality improvement. As part of a larger provincial initiative to address clinician burnout, we examined the prevalence and drivers of burnout in practicing physician oncologists in Ontario. Methods: In November-December 2019, surgical, medical, hematological, and radiation oncologists in Ontario were invited to complete an anonymous online survey to assess burnout and its drivers. Burnout prevalence was assessed through the Maslach Burnout Inventory – Human Services Survey for Medical Personnel (MBI-HSS MP). Data on demographic, workplace, engagement, and practice profiles were collected. Logistic regression modeling was conducted to assess key variables associated with “high” burnout using a common definition of high scores on the MBI subscales of emotional exhaustion (EE) (&gt; 27) and/or depersonalization (DP) (&gt;10). Results: Response rate to the survey was 44% (n=418) with 72% reporting high levels of burnout. Mean scores for EE (30.7, SD 12.1) and DP (9.9, SD 6.7) were consistent with high burnout. Participants endorsed known drivers of burnout including: 1) a poor culture of wellness at work (e.g., not comfortable talking to leadership (72%), 2) inefficiencies of practice (e.g. feeling insufficient documentation time (67%)) and 3) personal resilience (e.g. not feeling they are contributing professionally in ways they value (21%)). Age (&lt;45yrs) (OR: 2.15), poor/marginal control over workload (OR: 4.42), feeling used/unappreciated (OR: 2.63), working atmosphere that feels hectic/chaotic (OR: 2.68), and insufficient time for documentation requirements (OR: 2.52) significantly impacted the odds of high burnout in the regression model (p&lt;0.05). Conclusions: The high rate of burnout among oncology physicians in a single payer public cancer system in Ontario is concerning for the wellbeing of providers, patients and system sustainability. Drivers important for maintaining a culture of wellness and efficiency of practice will require local, regional and provincial health policy to improve. Next steps will include raising awareness with provincial initiatives/policy to address key burnout drivers, and examining the impact of working under pandemic conditions (Covid-19) on oncologist burnout.
Prevalence of Mental Illness and Mental Health Care Use Among Police Officers
Authors: Katelyn K. Jetelina, Rebecca J. Molsberry, Jennifer Reingle Gonzalez, Alaina M. Beauchamp, Trina Hall
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Limited literature has characterized patterns of mental illnesses and barriers in seeking mental health care among police officers. <h3>Objectives</h3> To assess the prevalence of mental illness (diagnosis) and symptoms of mental illness, evaluate the characteristics of officers interested in seeking mental health care, and characterize perceptions of mental health care use. <h3>Design, Setting, and Participants</h3> This survey study was conducted among officers at a large police department in Dallas–Fort Worth, Texas. Focus group sessions were conducted from April 1, 2019, to November 30, 2019, and the survey was conducted from January 1 to February 27, 2020. A total of 446 sworn, employed patrol officers who were present during the recruitment briefing were eligible to participate in surveys and focus groups. <h3>Main Outcomes and Measures</h3> Officers reported lifetime or current diagnosis of depression, anxiety, and posttraumatic stress disorder, as well as current mental health symptoms (using validated screeners of depression, anxiety, posttraumatic stress disorder, and suicidal ideation or self-harm) and mental health care use in the past 12 months. Focus group data were collected to contextualize mental health care use. Logistic regression analyses were used for quantitative data, and focus groups were iteratively coded by 4 coders using inductive and deductive thematic identification. <h3>Results</h3> Of the 446 officers invited to participate, 434 (97%) completed the survey (mean [SD] age, 37 [10] years; 354 [82%] male; 217 White [50%]). A total of 54 officers (12%) reported a lifetime mental health diagnosis, and 114 (26%) had positive screening results for current mental illness symptoms. Of these 114 officers, 19 (17%) had sought mental health care services in the past 12 months. Among officers with positive screening results, the odds of interest in using mental health services was significantly higher for officers with suicidal ideation or self-harm than for those who did not (adjusted odds ratio, 7.66; 95% CI, 1.70-34.48). Five focus groups were conducted with 18 officers and found 4 primary barriers in accessing mental health services: (1) inability to identify when they are experiencing a mental illness, (2) concerns about confidentiality, (3) belief that psychologists cannot relate to their occupation, and (4) stigma that officers who seek mental health services are not fit for duty. <h3>Conclusions and Relevance</h3> The study found that although few officers were seeking treatment, they were interested in seeking help, particularly those with suicidal ideation or self-harm. Additional interventions appear to be needed to systematically identify and refer officers to health care services while mitigating their concerns, such as fear of confidentiality breach.
Redefining fatty liver disease: an international patient perspective
Authors: Gamal Shiha, Marko Korenjak, Wayne Eskridge, Teresa Casanovas, Patricia Velez-Moller, Sari Högström, Ben Richardson, Christopher Munoz, Sólveig Sigurðardóttir, Alioune Coulibaly, Miskovikj Milan, Fabiana Bautista, Nancy Wai Yee Leung, Vicki Mooney, Solomon Obekpa, Eva Bech, Naveen Polavarapu, Abd Elkhalek Hamed, Temur Radiani, Edhie Purwanto, Bisi Bright, Mohammad Ali, Cecil Kwaku Dovia, Lone McColaugh, Yiannoula Koulla, Jean-François Dufour, Reham Soliman, Mohammed Eslam
Journal: The Lancet. Gastroenterology & hepatology (2020)