tbuckley/cabot-search huggingface dataset:
Profiteering from vaccine inequity: nudge pharma towards “doing well by doing good”
Authors: Helena Earl
Journal: BMJ (2021)

I read with interest your editorial about profiteering from vaccine inequity.1 Fortunately the UK government seems to have listened to views about prioritising vaccination of the world ahead of routine booster vaccinations this year. The benefits of booster vaccination to the “normal” population are marginal at best when compared with the benefits for all of us if we can …
P11.04 Autonomy duration as analyzed by KPS≥70 cumulative time in patients with biopsy-only glioblastoma (BO-GBM). A sub-analysis of the Timone cohort
Authors: V Harlay, A Loundou, C Boucard, G Petrirena, M Barrie, C Campello, D Autran, L Padovani, D Figarella, S Boissonneau, H Dufour, K Baumstarck, E Tabouret, O Chinot
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Improvement or maintenance of autonomy is a crucial and understudied issue for glioblastoma (GBM) patients whose outcome is poor. Biopsy-only GBM (BO-GBM) is a situation where survival is short and independence is of particular importance. Our objective was to explore functional outcome in biopsy-only patients. MATERIAL AND METHODS A regional glioma SIRIC cohort was conducted at CHU Timone in 2014–2017 and we retrospectively reviewed the BO-GBM subgroup. We prospectively collected age, corticosteroid dose, tumoral surface, treatment allocated and completed, and survival outcome. Functional independence was analyzed as a cumulative time of Karnofsky performance status (KPS) ≥70 from the date of diagnosis until death. We analyzed potential factors associated to time with KPS ≥70. RESULTS Among 535 patients enrolled in the cohort, surgery was restricted to biopsy in 139 patients (BO-GBM). Mean tumoral surface measured on gadolinium-enhanced T1-weighted MRI was 1198mm2 (min: 65; max: 4515mm2). Mean steroid dose at diagnosis was 50mg prednisolone per day. Corticosteroid dose was ≥50mg prednisolone per day for 77 patients and &amp;lt;50mg per day for 56 patients. Fifty-four patients (39%) were referred to radiotherapy-temozolomide (RT-TMZ), 68 (49%) considered unfitted for RT received chemotherapy upfront only (CT-UF), and 17 patients (12%) were referred to palliative care only. Median overall survival (OS) was 7.5 months (95%CI: 6.0–9.2), 14.0 months (95%CI: 9.7–18.7) and 6.0 months (95%CI: 4.6–7.7) for BO-GBM, RT-TMZ and CT-UF respectively. At diagnosis, 81 (58.3%) patients presented with self-care capacity (KPS ≥ 70%). For these patients, median time of autonomy preservation was 7.6 months (95%CI: 6.1–9.0). Median time of autonomy preservation differed according to treatment modalities: it was 8.6 months (95%CI: 5.9–11.3) versus 6.3 months (95%CI: 2.9–9.7) for RT-TMZ versus CT-UF group respectively (p&amp;lt;0.001). In univariate analysis, time with KPS ≥ 70% was correlated with age (p=0.001), initial KPS (p&amp;lt;0.001), tumoral surface measured on gadolinium-enhanced T1-weighted MRI (p=0.03) and corticosteroid dose (p=0.001). In multivariate analysis, time with KPS≥70 was correlated with age (p=0.001) and KPS at diagnosis (p&amp;lt;0.001). CONCLUSION Patients with inoperable GBM referred to radiotherapy-temozolomide present a valuable duration of functional independence, although shorter in patients not referred to RT. Duration of functional independence could be considered in addition to PFS and OS for treatment evaluation in patients with GBM.
Safety and efficacy of COVID-19 vaccination in patients receiving systemic anticancer therapy.
Authors: Mahir Khan, Ryan Huu-Tuan Nguyen, James Love, Alexander Krule, Michael Weinfeld, Kristy Abraham, Amy Eisenberg, Joseph Horowitz, Prianka Raju, Amina Ramadan, Jack VanOverloop, Shikha Jain
Journal: Journal of Clinical Oncology (2021)

245 Background: Patients with cancer who have been treated with systemic anticancer therapy are at increased risk of morbidity and mortality from COVID-19 and have been considered a high-priority group for COVID-19 vaccination in the United States. There is limited guidance and data on the appropriate timing of COVID-19 vaccination relative to receipt of systemic anticancer therapy. Methods: We queried the electronic medical record at the University of Illinois Hospital for patients with gastrointestinal, breast, lung, genitourinary, and head and neck tumors who had received intravenous systemic anticancer therapy between January 1, 2021 and May 25, 2021. Baseline variables were obtained as well as details of cancer treatment, vaccination timing relative to cancer treatment, and clinical outcomes. Results: A total of 274 patients received intravenous systemic anticancer therapy during the study period, of which 161 (58.8%) received at least one vaccine dose, and 138 (42.7%) were fully vaccinated. Of the 122 patients who received cancer treatment within 30 days of any vaccine dose, the median age was 64, and 72 (59%) were female gender. Race distribution was 50% Black, 15.6% White, 3.3% Asian; ethnicity was 24.6% Hispanic and 73% not-Hispanic. Treatment regimens consisted of 37.7% chemotherapy, 25.4% immunotherapy, 27.9% combination therapy, and 9.0% targeted therapy. For those who received anticancer therapy within 30 days of a vaccine, median time between any vaccination and treatment was 10 days (range 0-29 days). For those who had at least 60 days of follow-up after first vaccination, all-cause hospitalization rate was 22.4% (23/106). There was no statistical difference in all-cause 60-day hospitalization rate between those who received vaccination within 5 days of anticancer therapy versus those who received it between 6 and 30 days from anticancer therapy (14.3% vs 28.1%, p = 0.1). One patient (0.8%) developed a COVID-19 illness after any vaccine and did not require hospitalization. Conclusions: We observed safe and efficacious COVID-19 vaccination of patients with cancer receiving systemic IV anticancer therapy. COVID-19 infection after vaccination was rare, with no cases requiring hospitalization for COVID-19 illness post-vaccination in this cohort. All-cause hospitalization rates were similar among patients who received a vaccine within or after 5 days of receiving systemic anticancer therapy, suggesting vaccination side effect tolerability. Further quality improvement studies are needed on interventions to increase vaccination rates in this vulnerable population.
Biodiversity in European agricultural landscapes: transformative societal changes needed
Authors: Anne-Christine Mupepele, Helge Bruelheide, Carsten Brühl, Jens Dauber, Michaela Fenske, Annette Freibauer, Bärbel Gerowitt, Andreas Krüß, Sebastian Lakner, Tobias Plieninger, Thomas Potthast, Sabine Schlacke, Ralf Seppelt, Hartmut Stützel, Wolfgang Weisser, Wolfgang Wägele, Katrin Böhning-Gaese, Alexandra-Maria Klein
Journal: Trends in Ecology & Evolution (2021)
Using synthetic data generation to train a cardiac motion tag tracking neural network
Authors: Michael Loecher, Luigi E. Perotti, Daniel B. Ennis
Journal: Medical Image Analysis (2021)

A CNN based method for cardiac MRI tag tracking was developed and validated. A synthetic data simulator was created to generate large amounts of training data using natural images, a Bloch equation simulation, a broad range of tissue properties, and programmed ground-truth motion. The method was validated using both an analytical deforming cardiac phantom and in vivo data with manually tracked reference motion paths. In the analytical phantom, error was investigated relative to SNR, and accurate results were seen for SNR>10 (displacement error <0.3 mm). Excellent agreement was seen in vivo for tag locations (mean displacement difference = −0.02 pixels, 95% CI [−0.73, 0.69]) and calculated cardiac circumferential strain (mean difference = 0.006, 95% CI [−0.012, 0.024]). Automated tag tracking with a CNN trained on synthetic data is both accurate and precise.
Non-invasive tests and advanced chronic liver disease in NAFLD: two steps forward and one step back?
Authors: Avik Majumdar, Emmanuel A Tsochatzis
Journal: Gut (2021)

We read with great interest the study by Mozes et al on non-invasive tests (NITs) in non-alcoholic fatty liver disease (NAFLD)1 and commend the authors on their comprehensive individual patient data meta-analysis. The authors have confirmed that a two-step algorithm of fibrosis-4 index (FIB-4) and liver stiffness measurement with vibration controlled transient elastography (LSM-VCTE) has superior diagnostic performance for ruling in and ruling out advanced fibrosis and/or cirrhosis. Indeed, this concept has been demonstrated previously, including in our own work.2–4 However, we would like to highlight a few points for clarification.

First, the authors suggest a reduction in liver biopsies from 33% to as low as 19% when using the proposed rule-in cut-offs for cirrhosis, as summarised in Sankey diagrams. In our opinion, this comparative reduction in biopsies is not justified as the first diagnostic algorithm …
P-147 Epigenetic gene somatic mutations in gastric cancer
Authors: A. Kalinkin, E. Kuznetsova, I. Bykov, E. Alekseeva, T. Deryagina, I. Bure, D. Mikhaylenko, A. Tanas, V. Strelnikov, M. Nemtsova
Journal: Annals of Oncology (2021)
Gut check: can other microbes or communities phenocopy H. pylori’s early gastric pathology?
Authors: Jeffrey W Brown
Journal: Gut (2021)

The gastric mucosa is exposed to billions of diverse microorganisms every day. To stymie gastric colonisation as well as to limit passage of potential pathogens to more distal segments of the GI tract, the stomach has several broadly active defence mechanisms: acidity, mucus and proteolytic enzymes. Other extragastric mechanisms may contribute: for example, glycosylation epitopes like 3′-Sulfo-Lewis A on salivary mucins cotransit with swallowed bacteria and associate with them when the pH drops in the stomach,1 presumably preventing the bacteria from binding the mucosa.

Despite these defenses, at least one bacterial species, Helicobacter pylori is able to colonise the human stomach. This pathogen initially invades the gastric antrum, but it can also spread to the gastric body by inducing a metaplastic glandular response,2 characterised by loss of acid-secreting parietal cells (oxyntic atrophy) and metaplastic glandular changes (ie, Spasmolytic Expressing Polypeptide Metaplasia or SPEM). In a small proportion of individuals, metaplasia can progress to dysplasia and gastric adenocarcinoma. Thus, identifying the early histological changes associated with H. pylori infection becomes clinically important.3

The decrease in or absence of acidity associated with oxyntic atrophy creates an environment permissive for colonisation by opportunistic microbes. Although the presence of these ectopic microbial communities correlates with oxyntic atrophy,4 previously there has been no clear demonstration that …
Drug development of lyso-thermosensitive liposomal doxorubicin: Combining hyperthermia and thermosensitive drug delivery
Authors: Nicholas Borys, Mark W. Dewhirst
Journal: Advanced Drug Delivery Reviews (2021)

We review the drug development of lyso-thermosensitive liposomal doxorubicin (LTLD) which is the first heat-activated formulation of a liposomal drug carrier to be utilized in human clinical trials. This class of compounds is designed to carry a payload of a cytotoxic agent and adequately circulate in order to accumulate at a tumor that is being heated. At the target the carrier is activated by heat and releases its contents at high concentrations. We summarize the preclinical and clinical experience of LTLD including its successes and challenges in the development process.
Incidence and disease burden of coal workers’ pneumoconiosis worldwide, 1990–2019: evidence from the Global Burden of Disease Study 2019
Authors: Dongming Wang, Ruyi Liang, Meng Yang, Jixuan Ma, Wenzhen Li, Min Mu, Yang Xiao, Xiaobing Feng, Chaoqian Dong, Linling Yu, Wei Liu, Qiyou Tan, Min Zhou, Bin Wang, Tingming Shi, Liang Yuan, Weihong Chen
Journal: European Respiratory Journal (2021)

<b>Coal workers' pneumoconiosis (CWP) remains a public health issue worldwide, especially in developing countries. More efforts are needed to control or reduce exposure to coal dust in the workplace and protect workers from CWP.</b>https://bit.ly/3zwbWz4
Accurate detection of MET exon 14 skipping using a liquid biopsy assay in NSCLC patients in the GEOMETRY mono-1 study.
Authors: Rebecca S. Heist, Edward B. Garon, Daniel S. Tan, Harry J. Groen, Takashi Seto, Egbert F. Smit, Mike Zou, Yiqun Yang, Ying Li, Andrea Chassot Agostinho, Juergen Wolf
Journal: Cancer Research (2021)
Diagnostic Performance of Proton Magnetic Resonance Spectroscopy and 18F-Fluorocholine PET to Differentiate Benign From Malignant Breast Lesions
Authors: Li-An Wu, Ruoh-Fang Yen, Tiffany Ting-Fang Shih, Kuan-Lin Chen, Jane Wang
Journal: Clinical Nuclear Medicine (2021)

The aim of this study was to evaluate the diagnostic performance of the proton magnetic resonance spectroscopy (MRS) and 18F-fluorocholine (FCH) PET for suspicious breast findings on conventional imaging (mammography and breast ultrasound).From September 2012 to December 2015, 37 women with 39 breast lesions on conventional imaging were enrolled and underwent proton MRS and FCH PET. The MRS parameters of choline signal-to-noise ratio (SNR), choline integral (I(cho)), and the PET parameters including SUVmax in the prone (SUV1) and supine (SUV2) positions were analyzed. Receiver operating characteristic curves with the area under the curve, sensitivity, and specificity under the optimal cutoff points for the different parameters were determined.Twenty-three lesions (59%) were malignant, and 16 (41.0%) were benign. The malignant lesions tended to show significantly higher MRS and PET parameters than benign lesions (choline SNR, P = 0.007; I(cho), P = 0.003; SUV1 and SUV2, P < 0.0001). Fair to moderate correlations were noted between the choline SNR and PET parameters (SUV1, Spearman rank correlation coefficient, ρ = 0.477; SUV2, ρ = 0.483), as well as I(cho) and PET parameters (SUV1, ρ = 0.493; SUV2, ρ = 0.549). The SUV2 showed the highest diagnostic performance (area under the curve, 0.918). Using 2.5 as the optimal cutoff point, the SUV2 yields 89.5% sensitivity and 87.5% specificity for differentiating malignant from benign lesions.The MRS parameters were fairly to moderately correlated with FCH PET parameters, and both could differentiate malignant from benign breast lesions with SUV2 showing best diagnostic performance.
Blood culture diagnostics: a Nordic multicenter survey comparison of practices in clinical microbiology laboratories
Authors: Anna Åkerlund, Alexandros Petropoulos, Karin Malmros, Thomas Tängdén, Christian G. Giske
Journal: Clinical Microbiology and Infection (2021)

Accurate and rapid microbiological diagnostics are crucial to tailor treatment and improve outcomes in patients with severe infections. This study aimed to assess blood culture diagnostics in the Nordic countries and to compare them with those of a previous survey conducted in Sweden in 2013.An online questionnaire was designed and distributed to the Nordic clinical microbiology laboratories (CMLs) (n = 76) in January 2018.The response rate was 64% (49/76). Around-the-clock incubation of blood cultures (BCs) was supported in 82% of the CMLs (40/49), although in six of these access to the incubators around the clock was not given to all of the cabinets in the catchment area, and 41% of the sites (20/49) did not assist with satellite incubators. Almost half (49%, 24/49) of the CMLs offered opening hours for ≥10 h during weekdays, more commonly in CMLs with an annual output ≥30 000 BCs. Still, positive BCs were left unprocessed for 60-70% of the day due to restrictive opening hours. Treatment advice was given by 23% of CMLs (11/48) in ≥75% of the phone contacts. Rapid analyses (species identification and susceptibility testing with short incubation), performed on aliquots from positive cultures, were implemented in 18% of CMLs (9/49). Compared to 2013, species identification from subcultured colonies (<6 h) had become more common.CMLs have taken action to improve aspects of BC diagnostics, implementing satellite incubators, rapid species identification and susceptibility testing. However, the limited opening hours and availability of clinical microbiologists are confining the advantages of these changes.
The viral hepatitis B care cascade: A population‐based comparison of immigrant groups
Authors: Abdool S. Yasseen, Jeffrey C. Kwong, Jordan J. Feld, Rafal Kustra, Liane MacDonald, Christina C. Greenaway, Naveed Z. Janjua, Tony Mazzulli, Morris Sherman, Lauren Lapointe‐Shaw, Beate Sander, Natasha S. Crowcroft
Journal: Hepatology (2021)

Background and Aims The global burden of viral hepatitis B is substantial, and monitoring infections across the care cascade is important for elimination efforts. There is little information on care disparities by immigration status, and we aimed to quantify disease burden among immigrant subgroups. Approach and Results In this population‐based, retrospective cohort study, we used linked laboratory and health administrative records to describe the HBV care cascade in five distinct stages: (1) lifetime prevalence; (2) diagnosis; (3) engagement with care; (4) treatment initiation; and (5) treatment continuation. Infections were identified based on at least one reactive antigen or nucleic acid test, and lifetime prevalence was estimated as the sum of diagnosed and estimated undiagnosed cases. Care cascades were compared between long‐term residents and immigrant groups, including subgroups born in hepatitis B endemic countries. Stratified analyses and multivariable Poisson regression were used to identify drivers for cascade progression. Between January 1997 and December 2014, 2,014,470 persons were included, 50,475 with infections, of whom 30,118 were engaged with care, 11,450 initiated treatment, and 6554 continued treatment &gt;1 year. Lifetime prevalence was estimated as 163,309 (1.34%) overall, 115,722 (3.42%) among all immigrants, and 50,876 (9.37%) among those from highly endemic countries. Compared to long‐term residents, immigrants were more likely to be diagnosed (adjusted rate ratio [aRR], 4.55; 95% CI, 4.46, 4.63), engaged with care (aRR, 1.07; 95% CI, 1.04, 1.09), and initiate treatment (aRR, 1.09; 95% CI, 1.03, 1.16). Conclusions In conclusion, immigrants fared well compared to long‐term residents along the care cascade, having higher rates of diagnosis and slightly better measures in subsequent cascade stages, although intensified screening efforts and better strategies to facilitate linkage to care are still needed.
Ministers should have to seek advice from local doctors before closing services, say leaders
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Plans to give ministers extensive new powers over local service changes, such as hospital closures, should be amended to require them to take advice from senior local doctors and justify why the decisions are being made, service leaders have urged.

The NHS Confederation, the Local Government Association, and the Centre for Governance and Scrutiny have issued the joint call for an amendment to the government’s Health and Social Care Bill amid concerns that the plans risk undermining public confidence if they result in “political meddling” in the daily running of the health service.

A failure to insert …
A Meta-Analysis on the Global Prevalence, Risk factors and Screening of Coronary Heart Disease in Nonalcoholic Fatty Liver Disease
Authors: Jonathan Zhi Kai Toh, Xin-Hui Pan, Phoebe Wen Lin Tay, Cheng Han Ng, Jie Ning Yong, Jieling Xiao, Jin Hean Koh, En Ying Tan, Eunice Xiang Xuan Tan, Yock Young Dan, Poay Huan Loh, Roger Foo, Nicholas W S Chew, Arun J Sanyal, Mark D Muthiah, Mohammad Shadab Siddiqui
Journal: Clinical Gastroenterology and Hepatology (2021)
P07.04 Rapid-CNS2: Rapid comprehensive adaptive nanopore-sequencing of CNS tumors, a proof of concept study
Authors: H Dogan, A Patel, C Herold-Mende, S Pfister, W Wick, M Loose, A von Deimling, M Sill, D Jones, F Sahm
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The WHO classification 2021 includes multiple molecular markers for routine diagnostics in addition to histology. Sequencing setup for complete molecular profiling requires considerable investment, while batching samples for sequencing and methylation profiling can delay turnaround time. We introduce RAPID-CNS2, a nanopore adaptive sequencing pipeline that enables comprehensive mutational, methylation and copy number profiling of CNS tumours with a single third generation sequencing assay. It can be run for single samples and offers highly flexible target selection requiring no additional library preparation. MATERIAL AND METHODS Utilising ReadFish, a toolkit enabling targeted nanopore sequencing, we sequenced DNA from 22 diffuse glioma patient samples on a MinION device. Target regions comprised our Heidelberg brain tumour NGS panel and pre-selected CpG sites for methylation classification by an adapted random forest classifier. Pathognomonic alterations, copy number profiles, and methylation classes were called using a custom bioinformatics pipeline. Results were compared to their corresponding NGS panel-seq and EPIC array outputs. RESULTS Complete concordance with the EPIC array was found for copy number profiles from RAPID-CNS2. 94% pathognomonic mutations were congruent with NGS panel-seq. MGMT promoter status was correctly identified in all samples. Methylation families were detected with 96% congruence. Among the alterations decisive for rendering a classification-compatible integrated diagnosis, 97% of the alterations were consistent over the entire cohort (completely congruent in 19/22 cases and sufficient for unequivocal diagnosis in all). CONCLUSION RAPID-CNS2 provides a swift and highly flexible alternative to conventional NGS and array-based methods for SNV/Indel analysis, detection of copy number alterations and methylation classification. The turnaround time of ~4 days can be further shortened to &amp;lt;12h by altering target sizes. It offers a low-capital approach that would be cost-efficient for low throughput settings and invaluable in cases requiring immediate diagnoses.