tbuckley/cabot-search huggingface dataset:
<i>Notes from the Field:</i> Multistate Outbreak of <i>Salmonella</i> Agbeni Associated with Consumption of Raw Cake Mix — Five States, 2018
Authors: Stephen G. Ladd-Wilson, Karim Morey, Sarah E. Koske, Bailey Burkhalter, Lyndsay Bottichio, Joshua Brandenburg, John Fontana, Kristina Tenney, Kirthi K. Kutumbaka, Mansour Samadpour, Katherine Kreil, Paul R. Cieslak
Journal: MMWR Morbidity and Mortality Weekly Report (2019)
A Critical Review of Microelectrode Arrays and Strategies for Improving Neural Interfaces
Authors: Morgan Ferguson, Dhavan Sharma, David Ross, Feng Zhao
Journal: Advanced Healthcare Materials (2019)

Though neural interface systems (NISs) can provide a potential solution for mitigating the effects of limb loss and central nervous system damage, the microelectrode array (MEA) component of NISs remains a significant limiting factor to their widespread clinical applications. Several strategies can be applied to MEA designs to increase their biocompatibility. Herein, an overview of NISs and their applications is provided, along with a detailed discussion of strategies for alleviating the foreign body response (FBR) and abnormalities seen at the interface of MEAs and the brain tissue following MEA implantation. Various surface modifications, including natural/synthetic surface coatings, hydrogels, and topography alterations, have shown to be highly successful in improving neural cell adhesion, reducing gliosis, and increasing MEA longevity. Different MEA surface geometries, such as those seen in the Utah and Michigan arrays, can help alleviate the resultant FBR by reducing insertion damage, while providing new avenues for improving MEA recording performance and resolution. Increasing overall flexibility of MEAs as well as reducing their stiffness is also shown to reduce MEA induced micromotion along with FBR severity. By combining multiple different properties into a single MEA, the severity and duration of an FBR postimplantation can be reduced substantially.
Functional implications of novel <i>ADAM10</i> mutations in reticulate acropigmentation of Kitamura
Authors: D.J. Ralser, G.G. Lestringant, A. Du-Thanh, P. Kokordelis, J. Fischer, F.B.Ünalan Basmanav, S. Wolf, H. Thiele, J. Altmüller, P. Nürnberg, V. Oji, G. Fritz, J. Frank, R.C. Betz
Journal: British Journal of Dermatology (2017)
A unified encyclopedia of human functional DNA elements through fully automated annotation of 164 human cell types
Authors: Maxwell W. Libbrecht, Oscar L. Rodriguez, Zhiping Weng, Jeffrey A. Bilmes, Michael M. Hoffman, William Stafford Noble
Journal: Genome biology (2019)

Semi-automated genome annotation methods such as Segway take as input a set of genome-wide measurements such as of histone modification or DNA accessibility and output an annotation of genomic activity in the target cell type. Here we present annotations of 164 human cell types using 1615 data sets. To produce these annotations, we automated the label interpretation step to produce a fully automated annotation strategy. Using these annotations, we developed a measure of the importance of each genomic position called the "conservation-associated activity score." We further combined all annotations into a single, cell type-agnostic encyclopedia that catalogs all human regulatory elements.
Of funding and finches
Authors: Verena Jantsch, Michael Jantsch
Journal: Genome biology (2019)

Funding research is a challenge faced by most scientists around the world. Genome Biology has invited four scientists based in three different countries to share their own experience and opinions regarding funding, the difficulties young scientists must overcome, and how the process of securing funding can be improved. In this part, Verena and Michael Jantsch describe their thoughts on funding research from a European perspective.
P120 IL-23 receptor signaling is important during physiological bone remodeling and radial bone growth through regulation of osteoblast differentiation
Authors: W Razawy, M Schreuders-koedam, P Asmawidjaja, A Mus, H Den Braanker, M Oukka, V Kuchroo, B Van der Eerden, E Lubberts
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> In mice, systemic exposure of IL-23 induces chronic arthritis, increased osteoclast differentiation and systemic bone loss. However, the role of IL-23R signaling during physiological bone remodeling is not fully elucidated. <h3>Objectives</h3> To examine the role of IL-23R signaling during physiological bone remodeling. <h3>Methods</h3> Femurs of naïve 7-, 12- and 26-week-old IL-23R<sup>GFP/GFP</sup> (IL-23R<sup>-/-</sup>) and IL-23R<sup>+/+</sup> (WT) littermate mice were used for micro-CT analysis of the bone and a three-point bending test for bone strength. Bone marrow (BM) cells were either cultured towards osteoclasts with M-CSF and RANKL or were cultured towards osteoblasts with β-glycerophosphate and vitamin C. Osteoclast differentiation and activity were assessed using tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assay, respectively. Osteoblast differentiation was assessed by alkaline phosphatase staining and activity was determined by calcium measurement in the supernatant. <h3>Results</h3> Trabecular bone volume, thickness and number as well as cortical volume and thickness, and femur length were significantly lower in 12-week-old IL-23R<sup>-/-</sup> mice compared to WT. In addition, three-point bending data revealed reduced maximum force in IL-23R<sup>-/-</sup> femurs. Surprisingly, bone volume was similar between both groups at the age of 26 weeks. However, similar to 12-week-old mice, endocortical volume and femur perimeter were significantly lower in IL-23R<sup>-/-</sup> mice compared to WT. To further study the temporal differences in bone phenotype, we studied osteoclasts and osteoblasts from 7- and 12-week-old mice<i> in vitro</i>. Osteoclast differentiation and function were similar at both ages between WT and IL-23R<sup>-/-</sup> mice. Interestingly, BM cells of 7-week-old IL-23R<sup>-/-</sup> mice had reduced capacity to differentiate towards osteoblasts, compared to WT. In contrast, these cells showed higher differentiation and significantly higher calcium uptake than WT mice at 12 weeks. <h3>Conclusions</h3> IL-23R<sup>-/-</sup> mice have temporally dynamic changes in bone metabolism, which is possibly related to alterations in osteoblasts, however, the exact mechanism still needs to be elucidated. <h3>Disclosure of Interest</h3> None declared.
Prognostic significance of circulating tumor cell (CTC) levels at various times during first- and second-line chemotherapy for metastatic breast cancer (MBC).
Authors: Rafael Arteta-Bulos, Paul J. E. Miller, Rebecca S. Overbury, Alison Schwartzberg, Mark S. Walker, Lee Steven Schwartzberg
Journal: Journal of Clinical Oncology (2012)

e21077 Background: CTCs have prognostic capability in the treatment of MBC based on a dichotomous level of ≥5/7.5 ml blood (Hi) vs. &lt;5/7.5 ml blood (Lo) at baseline and first follow-up. The value of CTCs beyond baseline is not well established, and the implication of values that are reduced but remain high has not been explored. Methods: Chart review of patients (pts) on 1 st or 2 nd line treatment of MBC, with CTC determinations between 2/2008 and 9/2011, were retrospectively identified at a large community oncology practice. Pts with ≥2 CTCs or 1 CTC ≥5 were eligible. Demographics, treatment regimens and progression-free survival (PFS) were assessed. The Veridex Cell Search system was utilized for all CTC determinations. Qualifying baseline CTCs were those drawn -14 days to +30 days from start of treatment. Results: 221 eligible pts were identified, 71 with baseline CTCs in 1 st line, and 84 in 2 nd line. Median age was 59.5 (range 26-90), 40.7% were African-American, 17.6% HER2+, and 63%/49% ER/PR+. The median time to baseline CTC was 5 days in the 1 st line and 1 day in the 2 nd line. 1 st line PFS was 8.0 vs. 5.8 mo among baseline Hi vs. Lo groups (p = 0.085). 2 nd line PFS was 3.7 vs. 4.0 mo for Hi and Lo groups, respectively, (ns). Follow-up CTCs were obtained at clinical convenience. A 90 day landmark was used for analysis of PFS by four baseline/follow-up CTC pattern groups. 1 st line PFS showed medians ranging from 6.0 mo (Hi/Hi) to 10.2 mo (Lo/Lo). In 1 st line pts with Hi baseline CTCs (n=24), median PFS was 6.0 vs. 7.0 mo for Hi vs. Lo at follow-up (p = .64). Grouping pts with Hi baseline CTCs by reductions in absolute CTC count at follow-up (&lt;33% vs. ≥33%) showed median PFS 3.5 mo for &lt;33% reduction, 8.8 mo for ≥33% reduction (p = .0179). Sensitivity analyses with other cutoffs in reduction from 20-80% showed similar results. Conclusions: In the community setting, baseline and subsequent CTCs obtained at various times after baseline yield clinically useful prognostic information. Pts with positive baseline CTC levels experiencing a reduction of ≥33% exhibit significantly longer PFS, indicating that a simple high/low approach to the test can be modified to yield more prognostic value.
Human papillomavirus pevalence and persistence after chemoradiotherapy for carcinoma of the uterine cervix.
Authors: Maria Fernanda Noriega-Iriondo, Laura Elia Martinez Garza, Juan Francisco Gonzalez Guerrero, Oralia Barboza Quintana, Daneli Ruiz Sanchez, Michelle Zamudio Osuna, Jorge Luis Martinez Rodriguez, Jose Luis Gonzalez Vela
Journal: Journal of Clinical Oncology (2012)

e15525 Background: Human papillomavirus (HPV) is associated with carcinoma of the cervix (CC). There is evidence that clearance of the virus occurs after chemoradiotherapy which is the standard treatment for this disease. Methods: Eligible patients with bulky IB to IVA CC were treated with once weekly cisplatin (40 mg/m2) chemotherapy and standard pelvic teletherapy and brachyterapy. HPV detection and typing was performed with DNA microarrays from liquid based cytologies before and 4 to 6 weeks after treatment completion. Clinical response was assesed by physical exam and liquid based cytology. Results: 23 patients (pt) with CC , were tested for HPV. Their age ranged from 33 to 80 years (mean 65), clinical stage I 8.6%, StageII 39%, stageIII 25.9% and stageIV 26.5%.VPH was found in 20 patients (87%). 34% of the patients had more than one type of HPV. 13 types of VPH were found,the most prevalent type was 16 in 47.8%, followed by type 72 in 13%.7 patients were lost to follow up during therapy. 16 patients were tested after completion of therapy ,there was HPV persistence in 5 patients (38.5%),whereas 61.5% cleared the virus. Of the persisting HPV the most prevalent type was 16 in two pt. and 61 in two pt. three pt had more than one HPV type after completion of therapy (types 11,81,35,39,56,84,66were found in different combinations in the pts). Response rate was as follows, 84.6% complete response,and two pt. had partial response. Viral clearance did not correlate with complete response in this study. Conclusions: HPV types 16 and 72 were the most prevalent in this population from northern Mexico. Infection with multiple viral types was common. Viral clearance occured in 61.5% and this did not correlate with complete clinical response. Persistence of multiple HPV types after completion of therapy may have unknown clinical and prognostic implications.
William “Ed” Kois: whistleblower who exposed substandard care at a US veterans hospital
Authors: Ned Stafford
Journal: BMJ (2019)

Peter Biello/New Hampshire Public Radio

A specialist in rehabilitation and pain management, William “Ed” Kois was not your typical doctor. He swore a lot,1 he wore a goatee and muttonchop whiskers that would have made him feel at home in the 19th century, and although bald on the top of his head, he wore the rest of his hair in a long ponytail.

Kois also had an uncompromising attitude and fighting spirit, which he had inherited from his father who had worked in coal mines and was an amateur boxer. Unlike many American doctors, Kois did not play golf nor did he belong to a country club. He had worked in a car factory and a steel mill.

His patients loved him, and he loved his patients.

“I think I’m a blue collar doctor,” Kois once said in a newspaper interview.2 “My roots are blue collar, and I’m proud of that. I think I relate to my patients because of that.”

During the final years of his life, Kois fought a prolonged battle—at great cost to his own personal health—to improve medical care for patients at the US Veterans Administration (VA) Medical Center in Manchester, New Hampshire. The hospital is part of the massive VA medical system in the US that provides healthcare for men and women who have served in the military.

Kois, with a reputation as one of the best diagnosticians in New Hampshire, quit his private practice in Nashua in 2012 to join the Manchester VA hospital as head of the spinal cord clinic. A few years later he led a mutiny of 10 other doctors and medical staff, who risked their careers to fight poor hospital management that resulted in substandard care.

After nearly two years of internal attempts to convince management to take action to improve care proved …
OC-074 A 5- year tertiary centre experience of endoscopic ultrasound guided fine needle aspiration for diagnosis of solid pancreatic mass lesions
Authors: T Skouras, L Bonnet, M Swaminathan, R Mcgalliard, A Metussin, J Evans, S Sarkar, T Giles, J Sheard, A Cullen, K Brougham, J Ramesh
Journal: Gut (2017)

Introduction  EUS FNA is accepted as the primary modality for tissue diagnosis of solid pancreatic lesions. The presence of on-site cytopathology for immediate evaluation during endoscopic ultrasound-guided fine needle aspiration (EUS FNA) has previously been shown to improve performance characteristics. Due to service pressures EUS FNA is also undertaken in the absence of in-room cytopathology assistance. This is a review of current practice.  Method  We retrospectively assessed 700 consecutive EUS-FNA procedures from January 2011 to January 2016. 459 (65.5%) solid pancreatic lesions were included in the final analysis after excluding 230 for biliary strictures, hepatic lesions, lymph nodes, gastric, oesophageal lesions, pancreatic cysts and 11 for insufficient information.  Results  In 399 (86.9%) cases on-site cytopathology support was available, while the remaining was unsupported. There were 228 males (57.1%) in the supported and 29 (48.3%) in the unsupported group. Mean age was 64.6(SD: 11.4) and 67.4(SD: 11.9) respectively. The mean number of passes in the two groups were 2.8 (SD: 1.12) and 1.9 (SD: 1.0) (p  Conclusion  This review confirms high performance characteristics of EUS FNA. The presence of on-site cytopathologist significantly increases the diagnostic yield.  Disclosure of Interest  None Declared
An assessment of clinical and economic outcomes of U.S. veteran lung cancer patients.
Authors: Elyse Fritschel, Li Wang, Lu Li, J Zhang, Onur Baser
Journal: Journal of Clinical Oncology (2013)

e19122 Background: More people die from lung cancer in the United States than any other cancer type, and despite improvements in survival for other cancer types, 5-year lung cancer survival has remained low (Centers for Disease Control and Prevention. Lung Cancer. Available at www.cdc.gov/cancer/lung. Accessed February 04 , 2013; Youlden DR, Cramb SM, Baade PD. The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol. 2008; 8(3): 819-31.). This study aimed to describe the outcomes of lung cancer patients in the U.S. Department of Veterans Affairs (VA) population. Methods: A retrospective study of patients diagnosed with lung cancer during the study period of October 1, 2005 to September 30, 2010 was conducted using the Veterans Health Administration datasets. Lung cancer patients were identified using International Classification of Disease 9 th Revision Clinical Modification (ICD-9-CM) diagnosis code 162.xx. Descriptive statistics were calculated as means ± standard deviation (SD) and percentages. Comorbidities were measured for the 1-year baseline period before the disease identification date. Health care costs and utilization were measured for the 1-year follow-up period after the identification date. Results: In patients identified with lung cancer (n=73,150), common comorbidities included hypertension (n=21,377, 29.22%), chronic airway obstruction (n=14,305, 19.56%), abnormal findings on radiological and other lung field examination (n=12,437, 17.00%), and diabetes (n=11,569, 15.82%). Nearly half of all lung cancer patients had follow-up inpatient visits (46.47%), which translated to an average inpatient cost of $21,420 annually per patient. Nearly every patient studied had at least one follow-up outpatient visit (99.11%), and the average cost per patient totaled $12,986 annually ($12,110 for outpatient office and $411 for outpatient ER service costs). Conclusions: Inpatient and outpatient visits result in considerable health care costs for veteran lung cancer patients. Comorbid conditions are also relatively frequent in this population. Further research could elucidate economic outcomes for lung cancer patients by comorbidity severity.
Retrospective mathematical analysis of serial prostate specific antigen (PSA) measurements for patients with M0 prostate cancer treated with intermittent androgen suppression (IAS).
Authors: Celestia S. Higano, Yoshito Hirata, Koichiro Akakura, Nicholas Bruchovsky, Kazuyuki Aihara
Journal: Journal of Clinical Oncology (2012)

e15201 Background: Recently a phase III trial demonstrated that IAS was non-inferior to continuous AS in men with M0 disease after primary or salvage radiation and quality of life was better in the intermittent arm (Crook ASCO 2011). In that trial, men were treated with 8 months of AS followed by a variable time off AS driven by the absolute PSA value. The Hirata mathematical model describes the dynamics of prostate cancer treated with IAS (Hirata et al, J of Theoretical Biol 2010). In the model, there are three classes of cancer cells: a class of androgen dependent (AD) cells and two classes of androgen independent (AI:X1 and AI:X2) cells. During AS, AD cells will change to the two AI classes, and during the off treatment period, AI:X1 cells will revert to AD cells whereas AI:X2 cells cannot revert to either AD or AI:X1 cells. Methods: After IRB approval, we applied the Hirata model using serial monthly PSAs from men with M0 disease treated with IAS from Japan, Canada, and the United States. The proportions of men from each country who fell into the 3 categories of patients previously defined by the Hirata model were compared. Results: Serial PSAs from 26 men from Japan, 72 from Canada, and 79 from US were put into the model. The 3 categories of patients from the model include: (i) those with disease that will remain androgen sensitive and will respond to IAS without development of castration resistance (CRPC) (ii) those who will benefit from IAS but will develop CRPC sooner than those in group (i), (iii) those for whom continuous AS is superior to IAS. The datasets from each country show a similar distribution among the categories, and overall there were 42%, 51%, and 7% falling into groups i, ii, and iii respectively. Conclusions: This retrospective analysis shows that men with M0 disease treated with IAS fall into the 3 categories predicted by the Hirata model in similar proportions, regardless of country of origin. The ability to apply this model to the individual patient in the clinic is currently under development. The model may ultimately be able to optimize both the on and off treatment durations of IAS and to predict those patients who will most benefit from this approach.
Stop funding expensive pneumonia vaccine, MSF urges vaccine alliance
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Gavi, the Vaccine Alliance, which is part funded by the UK, should stop giving Pfizer and GlaxoSmithKline special funding for the pneumonia vaccine and instead focus on finding a cheaper version, Medecins Sans Frontieres (MSF) has urged.1

MSF said that the two drug companies had “already earned more than their fair share” of subsidies, as well as “billions made from global sales,” and called for Gavi to use its remaining funds on a new manufacturer offering a more affordable version of the pneumonia vaccine.

Pfizer and GSK are currently …
Prospective assessment of circulating endothelial cells (CECs) as pharmacodynamic marker in first line clear cell renal cell carcinoma (CCRCC): The CIRCLES study (SOGUG 2011-01).
Authors: Daniel E. Castellano, Emilio Esteban, Luis Leon Mateos, Aranzazu Gonzalez del Alba, Maria Jose Mendez Vidal, Jose Angel Arranz Arija, Xavier Garcia del Muro, Laura Basterretxea, Miguel Angel Climent Duran, Juan Antonio Virizuela, Francisco Javier Perez, Susana Hernando Polo, Jesús García-Donas
Journal: Journal of Clinical Oncology (2013)

e15586 Background: Angiogenesis inhibitors have become a cornerstone in the management of CCRCC. Since CECs counts have been proposed as a surrogate biomarker of antiangiogenic activity they could potentially be used to assess the efficacy of such drugs. Methods: An observational prospective multicenter study was designed. Patients with confirmed CCRCC on first line treatment (any drug) who have not progressed after 3 months on therapy were considered eligible. CECs (CD146+, CD 105+,CD 45- DAPI + cells assessed by the Cell Search system), were determined every 6 weeks for 15 months or radiological tumor progression. External monitoring of clinical data was performed. Results: 75 patients (29% female, 71% male) were included between June 2011 and January 2013 from 11 Spanish institutions. Median age was 62 years (range 37-81). Distribution of patients according to MSKCC risk cathegories was: good 32%, intermediate 66% and poor 1.5%. 90% of patients have received sunitinib, 6% pazopanib, 1% temsirolimus, and was not available in 3%. With a median follow-up of 7 months (range 0-11.8) 13 patients have progressed and median progression free survival (PFS) has not been reached. At baseline median CECs count was 47 cells/4 ml (range 4-485). A trend towards worse PFS has been identified in patients with basal CEC levels below the median (p= 0.063 Breslow test). When baseline CEC counts were compared to counts at tumor progression no significant difference was found. Patient and/or tumor characteristics (sex, MSKCC prognostic cathegory, number of metastatic sites, and prior response to therapy) did not seem to influence CECs levels at baseline. Conclusions: CEC counts remain estable in CCRCC patients treated with antiangiogenic inhibitors whohad not progressed to first line therapy. Low CEC counts seem to identify a population with shorter response to therapy. Thus, CEC could be a reliable pharmacodynamic marker able to assess the antiangiogenic activity of a drug. Long-term follow-up results will be presented.
A Difficult Conversation
Authors: Martin B. Wice
Journal: JAMA (2019)

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