tbuckley/cabot-search huggingface dataset:
Erratum. Use of Sodium–Glucose Cotransporter 2 Inhibitors in Patients With Type 1 Diabetes and Rates of Diabetic Ketoacidosis. Diabetes Care 2020;43:90–97
Authors: Christian Hampp, Richard S. Swain, Casie Horgan, Elizabeth Dee, Yandong Qiang, Sarah K. Dutcher, Andrew Petrone, Rong Chen Tilney, Judith C. Maro, Catherine A. Panozzo
Journal: Diabetes Care (2020)

To comply with a new (January 2020) legal interpretation of the Data Use Agreement between the U.S. Food and Drug Administration’s Sentinel Initiative and the Centers for Medicare & Medicaid Services, the authors have made changes to the presentation of data in this article and the online supplementary material …
Medical schools and other educational institutions need to tackle racism head on
Authors: Joanna Semlyen, Bhairavi Hariharan, Benz Josiah, Kaobi Okongwu, Louisa Sowah Quarshie, Veena Rodrigues
Journal: BMJ (2020)

We agree with Karan and Katz that “there is much work to be done” to stop racism.1 The #BlackLivesMatter movement shines a light on the fatal consequences of systemic racism suffered by black people in their ordinary lives, irrespective of the pandemic. To tackle racial prejudice in medicine, we need to speak directly to racial inequalities and create a workforce that is educated and reflective about …
P-288 Nerve fibers in the tumour microenvironment are co-localized with tertiary lymphoid structures and is associated with better survival in pancreatic cancer patients
Authors: L. Heij, X. Tan, J. Kather, J. Niehues, S. Sivakumar, N. Gaisa, G. Wiltberger, U. Neumann
Journal: Annals of Oncology (2020)
Meningococcal carriage 7 years after introduction of a serogroup A meningococcal conjugate vaccine in Burkina Faso: results from four cross-sectional carriage surveys
Authors: Sarah Mbaeyi, Emmanuel Sampo, Kambiré Dinanibè, Issaka Yaméogo, Malika Congo-Ouédraogo, Mamadou Tamboura, Guetawendé Sawadogo, Kalifa Ouattara, Mahamadou Sanou, Tanga Kiemtoré, Gerard Dioma, Barnabé Sanon, Hermann Somlaré, Augustin Kyetega, Absatou Ky Ba, Flavien Aké, Félix Tarbangdo, Frederic Acho Aboua, Yvette Donnou, Idrissa Kamaté, Jaymin C Patel, Susanna Schmink, Michael W Spiller, Nadav Topaz, Ryan Novak, Xin Wang, Brice Bicaba, Lassana Sangaré, Rasmata Ouédraogo-Traoré, Paul A Kristiansen
Journal: The Lancet Infectious Diseases (2020)

In the first 2 years after a nationwide mass vaccination campaign of 1-29-year-olds with a meningococcal serogroup A conjugate vaccine (MenAfriVac) in Burkina Faso, carriage and disease due to serogroup A Neisseria meningitidis were nearly eliminated. We aimed to assess the long-term effect of MenAfriVac vaccination on meningococcal carriage and herd immunity.We did four cross-sectional studies of meningococcal carriage in people aged 9 months to 36 years in two districts of Burkina Faso between May 2, 2016, and Nov 6, 2017. Demographic information and oropharyngeal swabs were collected. Meningococcal isolates were characterised using whole-genome sequencing.Of 14 295 eligible people, 13 758 consented and had specimens collected and laboratory results available, 1035 of whom were meningococcal carriers. Accounting for the complex survey design, prevalence of meningococcal carriage was 7·60% (95% CI 5·67-9·52), including 6·98% (4·86-9·11) non-groupable, 0·48% (0·01-0·95) serogroup W, 0·10% (0·01-0·18) serogroup C, 0·03% (0·00-0·80) serogroup E, and 0% serogroup A. Prevalence ranged from 5·44% (95% CI 4·18-6·69) to 9·14% (6·01-12·27) by district, from 4·67% (2·71-6·64) to 11·17% (6·75-15·59) by round, and from 3·39% (0·00-8·30) to 10·43% (8·08-12·79) by age group. By clonal complex, 822 (88%) of 934 non-groupable isolates were CC192, all 83 (100%) serogroup W isolates were CC11, and nine (69%) of 13 serogroup C isolates were CC10217.Our results show the continued effect of MenAfriVac on serogroup A meningococcal carriage, for at least 7 years, among vaccinated and unvaccinated cohorts. Carriage prevalence of epidemic-prone serogroup C CC10217 and serogroup W CC11 was low. Continued monitoring of N meningitidis carriage will be crucial to further assess the effect of MenAfriVac and inform the vaccination strategy for future multivalent meningococcal vaccines.Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance.
Coronavirus Disease 2019 (COVID-19) and Cardiac Injury—Reply
Authors: Shaobo Shi, Mu Qin, Bo Yang
Journal: JAMA Cardiology (2020)

To the Editor We read with great interest the important findings of Shi et al 1 exploring cardiac injury in patients with confirmed coronavirus disease 2019 (COVID-19).Approximately 20% of patients diagnosed with COVID-19 had signs of cardiac injury as measured by elevated high-sensitivity troponin I (hs-TNI) levels.Moreover, evidence of cardiac injury was associated with 4-fold increased mortality risk even after accounting for age and preexisting cardiovascular disease (CVD).Shi et al 1 acknowledged that with this severe acute respiratory infection may come cytokine storm syndrome leading to inflammation and cardiac myocyte apoptosis or necrosis.We wish to underscore a few key points.High-sensitivity troponin I is detectable in more than 80% of the general population and, as a reflection of subclinical myocardial damage, has been shown to predict all-cause mortality even in those without CVD. 2 High hs-TNI levels within the normal range may be a marker of patients with increased vulnerability to experiencing the more severe complications resulting from the systemic inflammatory effects of COVID-19.While elevated hs-TNI levels clearly portend poor prognosis, the question remains-why?Is hs-TNI a marker of underlying subclinical CVD that confers risk in the setting of hypoxia from profound respiratory disease or hypoperfusion from viral sepsis (ie, type 2 myocardial infarction reflecting supply/demand imbalance), both made worse in the presence of comorbidities?Is it a reflection of direct viral myocarditis or a marker of cardiac damage from the cytokine storm?Effective treatment will likely be guided by the underlying cause of the elevated hs-TNI levels (eg, interleukin 6 inhibitors for cytokine toxic effects).Ethnic and racial variation in the US will bring unique challenges for diagnosis, prognosis, and management of COVID-19.The Chinese experience has shown a high comorbidity of hypertension, diabetes, and CVD in patients with COVID-19. 3 Shi et al 1 also noted that prominent comorbidities in those with cardiac injury included hypertension, diabetes, coronary disease, heart failure, and cerebrovascular disease-all more prevalent in African American individuals.African American individuals have higher circulating biomarkers of systemic inflammation and myocyte injury, 4 and subclinical CVD occurs at a young age in African American individuals. 5Thus, African American individuals may be a particularly vulnerable group in the US to the untoward effects of COVID-19.Finally, whether cardiac injury as a consequence of COVID-19 infection results in permanent cardiac damage in survivors also remains to be determined.Long-term cardiovascular consequences of COVID-19 will need to be monitored to ensure that this cytokine storm does not bring with it a secondary tsunami wave of cardiovascular events in the future.
Single‐cell RNA sequencing in breast cancer: Understanding tumor heterogeneity and paving roads to individualized therapy
Authors: Shuning Ding, Xiaosong Chen, Kunwei Shen
Journal: Cancer Communications (2020)

Abstract Single‐cell RNA sequencing (scRNA‐seq) is a novel technology that allows transcriptomic analyses of individual cells. During the past decade, scRNA‐seq sensitivity, accuracy, and efficiency have improved due to innovations including more sensitive, automated, and cost‐effective single‐cell isolation methods with higher throughput as well as ongoing technological development of scRNA‐seq protocols. Among the variety of current approaches with distinct features, researchers can choose the most suitable method to carry out their research. By profiling single cells in a complex population mix, scRNA‐seq presents great advantages over traditional sequencing methods in dissecting heterogeneity in cell populations hidden in bulk analysis and exploring rare cell types associated with tumorigenesis and metastasis. scRNA‐seq studies in recent years in the field of breast cancer research have clustered breast cancer cell populations with different molecular subtypes to identify distinct populations that may correlate with poor prognosis and drug resistance. The technology has also been used to explain tumor microenvironment heterogeneity by identifying distinct immune cell subsets that may be associated with immunosurveillance and are potential immunotherapy targets. Moreover, scRNA‐seq has diverse applications in breast cancer research besides exploring heterogeneity, including the analysis of cell‐cell communications, regulatory single‐cell states, immune cell distributions, and more. scRNA‐seq is also a promising tool that can facilitate individualized therapy due to its ability to define cell subsets with potential treatment targets. Although scRNA‐seq studies of therapeutic selection in breast cancer are currently limited, the application of this technology in this field is prospective. Joint efforts and original ideas are needed to better implement scRNA‐seq technologies in breast cancer research to pave the way for individualized treatment management. This review provides a brief introduction on the currently available scRNA‐seq approaches along with their corresponding strengths and weaknesses and may act as a reference for the selection of suitable methods for research. We also discuss the current applications of scRNA‐seq in breast cancer research for tumor heterogeneity analysis, individualized therapy, and the other research directions mentioned above by reviewing corresponding published studies. Finally, we discuss the limitations of current scRNA‐seq technologies and technical problems that remain to be overcome.
Single-cell analysis of SARS-CoV-2 receptor ACE2 and spike protein priming expression of proteases in the human heart
Authors: Hanning Liu, Shujie Gai, Xiaoyi Wang, Juntong Zeng, Cheng Sun, Yan Zhao, Zhe Zheng
Journal: Cardiovascular Research (2020)

Abstract Aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly binds to ACE2 (angiotensin-converting enzyme 2) to facilitate cellular entry. Compared with the lung or respiratory tract, the human heart exhibits greater ACE2 expression. However, little substantial damage was found in the heart tissue, and no viral particles were observed in the cardiac myocytes. This study aims to analyse ACE2 and SARS-CoV-2 spike (S) protein proteases at the single-cell level, to explore the cardiac involvement in COVID-19 and improve our understanding of the potential cardiovascular implications of COVID-19. Methods and Results With meta-analysis, the prevalence of cardiac injury in COVID-19 patients varies from 2% [95% confidence interval (CI) 0–5%, I2 = 0%] in non-ICU patients to 59% (95% CI 48–71%, I2 = 85%) in non-survivors. With public single-cell sequence data analysis, ACE2 expression in the adult human heart is higher than that in the lung (adjusted P &amp;lt; 0.0001). Inversely, the most important S protein cleavage protease TMPRSS2 (transmembrane protease serine protease-2) in the heart exhibits an extremely lower expression than that in the lung (adjusted P &amp;lt; 0.0001), which may restrict entry of SARS-CoV-2 into cardiac cells. Furthermore, we discovered that other S protein proteases, CTSL (cathepsin L) and FURIN (furin, paired basic amino acid cleaving enzyme), were expressed in the adult heart at a similar level to that in the lung, which may compensate for TMPRSS2, mediating cardiac involvement in COVID-19. Conclusion Compared with the lung, ACE2 is relatively more highly expressed in the human heart, while the key S protein priming protease, TMPRSS2, is rarely expressed. The low percentage of ACE2+/TMPRSS2+ cells reduced heart vulnerability to SARS-CoV-2 to some degree. CTSL and FURIN may compensate for S protein priming to mediate SARS-CoV-2 infection of the heart.
Intravesical treatment of liposomal doxorubicin nanoparticles in mouse orthotopic bladder cancer model
Authors: Motoyoshi Tanaka, Satoshi Anai, Marco De Velasco, Atsushi Tomioka, Ikumi Sugiyama, Yasuyuki Sadzuka, Hirotsugu Uemura
Journal: Cancer Research (2007)

5589  Intravesicle instillation of doxorubicin (Dox) is one of the established modalities in the prophylaxis of superficial bladder cancer recurrence or progression. BCG instillation has been widely applied in high risk or recurrent superficial bladder cancer, however, BCG sometimes shows difficulty of completion of treatment due to its toxicity. In this study, we have investigated the efficacy of 3 types of liposomal Dox aiming high tumor concentrations by effective transportability and less toxicity in vivo. To examine the therapeutic effect of liposomal Dox nanoparticles, we used a human bladder cancer cell line KU-7/GFP, a stable transfectant with GFP, growing as superficial bladder tumors in nude mice. KU-7/GFP tumor cells were implanted transurethrally in female nude mice on day 0. Mice were then assigned into 6 groups and intravesically received a single instillation of liposome/Dox (Group 4), PEG-CHO liposome/Dox modified with polyethyleneglycol-cholesterol (Group 5), and mixed PEG liposome/Dox modified with polyethyleneglycol-distearoylglycerol and polyethyleneglycol -cholesterol (Group 6) at the Dox concentration of 100µg/100µl, which is clinically relevant concentration per body weight, compared to PBS (Group 1), empty liposome (Group 2), and Dox solution (Group 3) on day 10 after cell inoculation. Two weeks after treatment, the mice were then sacrificed and processed for histopathological examination. Tumor burden in the bladder was determined utilizing KU-7/GFP cancer cells containing GFP. Marked tumor regression was observed following liposomal Dox instillations in Group 4, 5, and 6 compared to the treatment with PBS or liposome, and no toxicity was observed. Tumor incidence (mean tumor area) by GFP observation is represented 6/6 (10.6mm2), 6/6 (11.7mm2), 5/6 (1.1mm2), 2/7 (0.58mm2), 5/6 (12.3mm2), and 4/7 (2.1mm2) in Groups 1, 2, 3, 4, 5, and 6, respectively. Treatments with liposomal Dox have a more significant therapeutic efficacy comparing to Dox itself, even in a single administration. These findings demonstrate that liposomal Dox nanoparticles can overcome a disadvantage of conventional Dox and can be a promising application for the treatment of superficial bladder cancer.
O-13 Efficacy and safety of ripretinib as ≥4th-line therapy for patients with gastrointestinal stromal tumor following crossover from placebo: Analyses from INVICTUS
Authors: C. Serrano, M. Heinrich, S. George, J. Zalcberg, S. Bauer, H. Gelderblom, P. Schöffski, R. Jones, S. Attia, G. D'Amato, P. Chi, P. Reichardt, J. Meade, V. Reichert, K. Shi, J. Blay, M. von Mehren
Journal: Annals of Oncology (2020)
Value of lipocalin 2 as a potential biomarker for bacterial meningitis
Authors: T.T. Thanh, C. Casals-Pascual, N.T.H. Ny, N.M. Ngoc, R. Geskus, L.N.T. Nhu, N.T.T. Hong, D.T. Duc, D.D.A. Thu, P.N. Uyen, V.B. Ngoc, L.T.M. Chau, V.X. Quynh, N.H.H. Hanh, N.T.T. Thuong, L.T. Diem, B.T.B. Hanh, V.T.T. Hang, P.K.N. Oanh, R. Fischer, N.H. Phu, H.D.T. Nghia, N.V.V. Chau, N.T. Hoa, B.M. Kessler, G. Thwaites, L.V. Tan
Journal: Clinical Microbiology and Infection (2020)

ObjectivesCentral nervous system (CNS) infections are common causes of morbidity and mortality worldwide. We aimed to discover protein biomarkers that could rapidly and accurately identify the likely cause of the infections, essential for clinical management and improving outcome.MethodsWe applied liquid chromatography tandem mass spectrometry on 45 cerebrospinal fluid (CSF) samples from a cohort of adults with and without CNS infections to discover potential diagnostic biomarkers. We then validated the diagnostic performance of a selected biomarker candidate in an independent cohort of 364 consecutively treated adults with CNS infections admitted to a referral hospital in Vietnam.ResultsIn the discovery cohort, we identified lipocalin 2 (LCN2) as a potential biomarker of bacterial meningitis (BM) other than tuberculous meningitis. The analysis of the validation cohort showed that LCN2 could discriminate BM from other CNS infections (including tuberculous meningitis, cryptococcal meningitis and virus/antibody-mediated encephalitis), with sensitivity of 0.88 (95% confident interval (CI), 0.77–0.94), specificity of 0.91 (95% CI, 0.88–0.94) and diagnostic odds ratio of 73.8 (95% CI, 31.8–171.4). LCN2 outperformed other CSF markers (leukocytes, glucose, protein and lactate) commonly used in routine care worldwide. The combination of LCN2, CSF leukocytes, glucose, protein and lactate resulted in the highest diagnostic performance for BM (area under the receiver operating characteristics curve, 0.96; 95% CI, 0.93–0.99). Data are available via ProteomeXchange with identifier PXD020510.ConclusionsLCN2 is a sensitive and specific biomarker for discriminating BM from a broad spectrum of other CNS infections. A prospective study is needed to assess the diagnostic utility of LCN2 in the diagnosis and management of CNS infections.
Differentiation of human embryonic stem cells into immunostimulatory dendritic cells under feeder-free culture conditions
Authors: Zhen Su, Fusheng Wei, Carole Frye, Kyun-mi Bae, Siqing Wang, Vicky Kelley, Johannes Vieweg
Journal: Cancer Research (2008)

4996  The objective of this study was to develop a scalable and broadly applicable active immunotherapy approach against cancer and infectious diseases, circumventing the limitations typically encountered with autologous vaccination strategies. We hypothesized that human embryonic stem cells (hESC) can serve as a virtually unlimited source for generating dendritic cells (DC) with potent antigen presenting function. Here, we investigated the developmental processes and requirements for generating large numbers of mature, antigen-presenting DC from pluripotent hESC. An animal product and feeder cell-free culture system was developed to differentiate hESC into mature DC sequentially through hematopoietic and myeloid precursor stages. Using this method, we were able to yield large numbers of mature immunostimulatory DC from hESC to enable clinical investigation. Upon activation with proinflammatory cytokines, the hESC-derived DC secreted IL-12p70, migrated in response to MIP-3beta and exhibited allo-stimulatory capacity. Most importantly, antigen loaded, hESC-derived DC were capable of stimulating potent antigen-specific CD8+ T-cell responses capable of recognizing and killing human target cells expressing tumor or viral antigens in a HLA class I-matched semi-allogeneic assay system. Moreover, HLA class II-mismatched hESC-derived DC induced a potent Th1-type cytokine response without expanding and activating FOXP3+ regulatory T cells in vitro. These data suggest the development of a novel active immunotherapy platform to stimulate potent T-cell immunity in patients with intractable diseases such as cancer or viral infection.
P-290 Neutrophil-to-lymphocyte ratio and platelet–lymphocyte ratio as predictive and prognostic markers in patients with pancreatic cancer in Tlemcenian patients
Authors: I. Boublenza, A. Saidi, S. Chaibdra Tani, H. Aliane, S. Djellouli, A. Hadjer, S. Ghomari-Bezzar
Journal: Annals of Oncology (2020)
Presymptomatic Awareness of Germline Pathogenic <i>BRCA</i> Variants and Associated Outcomes in Women With Breast Cancer
Authors: Tal Hadar, Pnina Mor, Gefen Amit, Sari Lieberman, David Gekhtman, Rachel Rabinovitch, Ephrat Levy-Lahad
Journal: JAMA Oncology (2020)

morbidity resulting from SARS-CoV-2.Although the asymptomatic SARS-CoV carrier rate in children in the general population is not known, our testing of 120 asymptomatic pediatric patients with cancer revealed only a 2.5% rate of SARS-CoV-2 positivity.By comparison, we observed a 14.7% rate of SARS-CoV-2 positivity in their asymptomatic caregivers (2.5%; 95% CI, 0.5%-7.1% vs 14.7%; 95% CI, 7.3%-25.4%;P = .002),which closely matches the asymptomatic carrier rate in pregnant women in New York (13.5%). 6Together, our results do not support the conjecture that children are a reservoir of unrecognized SARS-CoV-2 infection.
Palliative care for patients with severe covid-19
Authors: Ruth Ting, Polly Edmonds, Irene J Higginson, Katherine E Sleeman
Journal: BMJ (2020)

What you need to know• Many patients with severe covid-19 experience distressing symptoms, including breathlessness and agitation.Palliation of suffering is an important part of care irrespective of prognosis • Patients with severe covid-19 may deteriorate rapidly.It is therefore useful to have a strategy in place for managing deterioration and potential death (for those not suitable for escalation to intensive care), which runs alongside the acute medical management plan • Clear and timely communication with the patient (if they are able) and their carers is essential.Conveying hope that treatments will help needs to be sensitively balanced with explicit acknowledgement that patients are sick enough to die "To cure sometimes, to relieve often, and to comfort always.
Use of an inhibitor of differentiation-1 (Id1) expression (exp) to discriminate good prognosis (GP) from poor prognosis (PP) prostate cancer (PCa)
Authors: A. Calvo, M. Ponz-Sarvisé, D. Rosell, M. Redrado, P. A. Nguewa, J. García-Foncillas, L. Abella, A. Panizo, I. Gil- Bazo
Journal: Journal of Clinical Oncology (2009)

e16128 Background: In the PSA era a significant proportion of PCa patients (pts) at onset have potential indolent tumors that will not impact their life expectancy or quality of life. Most of them will be radically treated and suffer its consequences. Thus, PCa overtreatment is a great concern among clinicians. Pre-treatment molecular factors may help differentiate indolent from aggressive PCa. Id1, involved in cell differentiation and angiogenesis, has recently showed to mediate lung metastasis (mts) from breast cancer. Its role in PCa endothelial (end) cells is well established but its exp and role in PCa cells is controversial. Using a new monoclonal antibody (MoAb) (195–14) for immunohistochemistry (IHC), Id1 exp is limited to some PP breast and bladder tumors. Whether Id1 exp is relevant in PCa prognosis is unknown. We tested 195–14 in PP and GP PCa samples and matched mts where available. Methods: 52 PCa pts were studied, 20 GP + 32 PP. All formalin-fixed and paraffin-embedded primary biopsies and matched mts of 16 of them were stained for tumor and end cell Id1 exp. 195–14 (1:500), (Biocheck), was used for IHC. Results: GP group: median age 65, all pts T2N0M0, median Gleason score 6 (6–9), median PSA at onset 5,5 ng/ml. After a median follow-up of 38 months (ms) 1 pt showed radiological and PSA progression (P); other PSA P. All but one remain alive. PP group: median age was 70, T3-T4 (70%), Gleason 8–10 (61%), median PSA at onset 58 ng/ml, 2 or more mts locations (79%), 94% showed P to docetaxel, median time-to- progression and overall survival after chemotherapy were 18 weeks and 7 ms. Among PP, 39% of primary PCa and 38% of mts showed Id1 tumor cell exp and 79% of primary tumors and 81% of mts showed end Id1 exp. In the GP group 0% showed Id1 tumor cell exp, and 50% showed end Id1 exp. The unexpected Id1 exp difference in tumor cells in PP compared to GP pts predicted clinical outcome. Consistently with other reports end Id1 exp is high in both groups. PP showed higher levels. Conclusions: Id1 exp discriminated GP from PP in our PCa cohort. These novel results highlight Id1 as a prognostic marker in PCa. Whether Id1 exp in the diagnostic biopsy can impact PCa therapeutic decision-making needs further investigation. No significant financial relationships to disclose.