tbuckley/cabot-search huggingface dataset:
Biomedical information, peer review, and conflict of interest as they influence public health
Authors: E. I. Cantekin
Journal: JAMA (1990)

The peer review process serves a vital role in the publication of biomedical information. When properly functioning, review should focus exclusively on questions of scientific validity and should avoid becoming enmeshed in questions such as authorization and  ownership. We present a case in which the dissenting views of a coinvestigator were suppressed because the principal investigator and grantee institution informed a medical journal that the coinvestigator was not authorized to use the data generated by a publicly funded grant and because the editor of a scholarly journal refused to review the dissenting manuscript and to submit that dissent to external reviewers for peer review. The current peer review system, as shown by this case, is unable to embrace dissent within the peer review process and to use dissent to serve scientific truth and the public interest.  ( JAMA . 1990;263:1427-1430)
The CD39+ HBV surface protein-targeted CAR-T and personalized tumor-reactive CD8+ T cells exhibit potent anti-HCC activity
Authors: Fan Zou, Jizhou Tan, Ting Liu, Bingfeng Liu, Yaping Tang, Hui Zhang, Jiaping Li
Journal: Molecular Therapy (2021)

CD39, expressed by tumor-infiltrating lymphocytes (TILs), is a marker to identify tumor-reactive T cells, which is frequently associated with stronger antitumor activity than bystander T cells in a variety of malignancies. Therefore, CD39 could be a promising marker for identifying the active antitumor immune cells used for cellular immunotherapy. To test this possibility, we constructed the hepatitis B virus (HBV) surface protein-specific chimeric antigen receptor T cells (HBVs-CAR-T cells) and generated the personalized tumor-reactive CD8+ T cells. We subsequently assessed their antitumor efficiency mainly with a co-culture system for autologous HBVs+ HCC organoid and T cells. We found that both CD39+ HBVs-CAR-T and CD39+ personalized tumor-reactive CD8+ T cells induced much more apoptosis in HCC organoids. Although the exhaustion status of CAR-T cells increased in CD39+ CAR-T cells, triple knockdown of PD-1, Tim-3, and Lag-3 with shRNAs further enhanced antitumor activity in CD39+ CAR-T cells. Furthermore, these CD39+ CAR-T cells exerted an increased secretion of interferon-γ and stronger antitumor effect in a patient-derived xenograft mouse model. Our findings demonstrated that CD39 could be a promising biomarker to enrich active immune cells and become an indicator marker for evaluating the prognosis of immunotherapy for HCC patients.
OP0050 Immunogenetic aspects of erosive osteoarthritis of the hand
Authors: R Ramonda, L Punzi, A Businaro, E Musacchio, F Schiavon, M Podswiadek, G Cardinale, S Todesco
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Erosive osteoarthritis of hand (EOA) is believed to be a subset of generalised OA characterised by frequent inflammatory episodes and an aggressive clinical course. <h3>Objectives</h3> Since rare studies are available on the risk factors of EOA, we investigated its immunogenetic predisposition. <h3>Methods</h3> In 47 patients with EOA (42 F, mean age 62.8 ± 8 years), HLA typing for A, B, C, DRB1 loci was performed. In the same patients we also evaluated the number of active joints (NAJ), the number of X-ray erosions (NEJ), the radiographic score (RS, Kallman), along with ESR and CRP. <h3>Results</h3> The HLA antigens most frequently found in the 47 patients with EOA were A2 (16 = 34%), B5 (13 = 27.7%), Cw4 (13 = 27.7%), and DRB1011 (11 = 23.4%) and DRB103 (8 = 17%). Interestingly, the frequency of these two latter antigens were higher in EOA than in non-EOA patients (DRB1011 = 10%; DRB103 no found). NAJ (p &lt; 0.01), RS (p &lt; 0.001) and ESR (p &lt; 0.01) were higher in EOA than in non-EOA. No differences were observed (ANOVA test) in NAJ, NEJ, RS, ESR and CRP, among the various HLA antigens found in EOA. <h3>Conclusion</h3> EOA seems characterised by a high frequency, higher than in non-EOA, of some HLA antigens, in particular DRB103 and DRB1011, thus suggesting an immunogenetic predisposition in these patients. HLA antigens do not seem to be associated with the disease severity of EOA. However, more information may derive from an adequately long follow-up of these patients.
Correspondence on ‘Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients’
Authors: Tanaz A Kermani
Journal: Annals of the Rheumatic Diseases (2021)

<h3>Abstract</h3> A SARS-CoV-2 DNA vaccine targeting the spike protein and delivered by jet injection, nCOV-S(JET), previously shown to protect wild-type and immunosuppressed Syrian hamsters (<i>Mesocricetus auratus</i>), was evaluated via two needle-free delivery methods in rhesus macaques (<i>Macaca mulatta</i>). The methods included intramuscular delivery of 2 mg per vaccination with the PharmaJet Stratis device and intradermal delivery of 0.4 mg per vaccination with the PharmaJet Tropis device. We hypothesized that the nCOV-S(JET) vaccine would mount detectable neutralizing antibody responses when delivered by needle-free jet injection by either the intradermal or intramuscular route. When delivered intramuscularly, the vaccines elicited neutralizing and variant (Beta, Gamma, and Delta) cross-neutralizing antibodies against SARS-CoV-2 in all six animals after three vaccinations. When delivered at a lower dose by the intradermal route, strong neutralizing antibody responses were only detected in two of six animals. This study confirms that a vaccine previously shown to protect in a hamster model can elicit neutralizing and cross-neutralizing antibodies against SARS-CoV-2 in nonhuman primates. We posit that nCOV-S(JET) has the potential for use as booster vaccine in heterologous vaccination strategies against COVID-19.
Real-world one-year overall survival among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with liposomal irinotecan in the NAPOLI-1 based regimen.
Authors: George P. Kim, Paul Cockrum, Andy Surinach, Laith I. Abushahin
Journal: Journal of Clinical Oncology (2021)

392 Background: Pancreatic cancer remains one of the most lethal cancers in the United States (US) with a 5-year relative survival of 9%. Among patients who received liposomal irinotecan + 5-fluorouracil (5-FU) and leucovorin in the NAPOLI-1 study, a randomized phase 3 study in patients with mPDAC previously treated with gemcitabine-based therapy, 25% (n = 29) were alive at ≥ 1 year. This study examines the real world one-year survival of patients with mPDAC treated with liposomal irinotecan as a doublet with 5-FU in the NAPOLI-1 based regimen. Methods: This retrospective observational study utilized the Flatiron Health EHR database from over 280 cancer clinics in the US. Data were analyzed for adult patients with mPDAC treated with liposomal irinotecan-based regimens between November 2015 and July 2020. Patient characteristics and one-year overall survival (OS) based on Kaplan-Meier estimates were assessed. Cycles were defined as unique days with an administration of liposomal irinotecan. Results: There were 669 patients (median age: 69y, IQR: 62-75) included in the study. ECOG performance status (PS) of 0-1 and 2+ were reported for 78.3% (n = 396) and 21.7% (n = 110) of patients, respectively. ECOG PS was not captured for 24.4% (n = 163) of patients. 16.3% (n = 109) of patients initiated liposomal irinotecan-based in the first line (1L) metastatic setting, 47.5% (n = 318) in second line (2L), and 36.2% (n = 242) in the third line or later (3L+). The median number of cycles received was 4 (IQR: 2 – 8). Among all patients, one-year OS was 17.2% (95% CI: 14.3% - 20.7%). One-year OS was 31.5% (22.1% – 41.3%) for patients treated in 1L, 16.4% (12.2% - 21.1%) for patients treated in 2L, and 12.2% (7.5% - 18.0%) for patients treated in 3L. The median number of cycles for 1L, 2L, and 3L were 5, 4, and 3, respectively. One-year OS increased as patients were able to receive more cycles of liposomal irinotecan. Patients who received at least 2 cycles of liposomal irinotecan (n = 551) had a one-year OS of 20.4% (16.8% - 24.2%). Among patients who received at least 4 cycles (n = 359) and at least 8 cycles (n = 170), the one-year OS estimates were 29.1% (24.0% - 34.3%) and 47.9% (39.7% - 55.7%), respectively. Conclusions: In this real-world cohort of patients with mPDAC treated with liposomal irinotecan, as expected, one-year OS increased as patients remained on therapy. Patients in this cohort were older, had more prior lines of therapy, worse ECOG PS, and similar exposure to treatment compared with patients in the registrational phase 3 NAPOLI-1 study. Among patients who received at least 4 cycles of liposomal irinotecan, one-year OS (29%) was similar to both the intent-to-treat (25%) and per protocol treated patient populations in the NAPOLI-1 trial (34%). Further studies are needed to understand the predictors of long-term survival among patients with mPDAC.
What coronavirus 3C‐like protease tells us: From structure, substrate selectivity, to inhibitor design
Authors: Muya Xiong, Haixia Su, Wenfeng Zhao, Hang Xie, Qiang Shao, Yechun Xu
Journal: Medicinal Research Reviews (2021)

Abstract The emergence of a variety of coronaviruses (CoVs) in the last decades has posed huge threats to human health. Especially, the ongoing pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has led to more than 70 million infections and over 1.6 million of deaths worldwide in the past few months. None of the efficacious antiviral agents against human CoVs have been approved yet. 3C‐like protease (3CL pro ) is an attractive target for antiviral intervention due to its essential role in processing polyproteins translated from viral RNA, and its conserved structural feature and substrate specificity among CoVs in spite of the sequence variation. This review focuses on all available crystal structures of 12 CoV 3CL pro s and their inhibitors, and intends to provide a comprehensive understanding of this protease from multiple aspects including its structural features, substrate specificity, inhibitor binding modes, and more importantly, to recapitulate the similarity and diversity among different CoV 3CL pro s and the structure–activity relationship of various types of inhibitors. Such an attempt could gain a deep insight into the inhibition mechanisms and drive future structure‐based drug discovery targeting 3CL pro s.
SAT0233 A randomised comparison of care provided by a clinical nurse specialist, inpatient team care and day patient team care in rheumatoid arthritis (ra)
Authors: GJ Tijhuis, AH Zwinderman, JM Hazes, WB Van den Hout, FC Breedveld, TP Vliet Vlieland
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The role of clinical nurse specialists in the management of patients with RA is evolving, and their effectiveness in comparison with care provided by a rheumatologist alone has been established. However, controlled studies showing how the effectiveness of clinical nurse specialists compares to that of multi-disciplinary team care, a treatment strategy that is considered to be optimal in chronic disease management, are lacking. <h3>Objectives</h3> The first aim of the study was to compare the clinical effectiveness of care delivered by a clinical nurse specialist with inpatient team care and day patient team care in patients with RA. The second aim was to determine factors predicting clinical response. <h3>Methods</h3> A multi-centre, randomised controlled clinical trial including consecutive outpatients with RA and progressive functional limitations over the past 6 weeks. Clinical assessments recorded on study entry, weeks 6, 12, 26 and 52 comprised the HAQ, MACTAR functional index, RAND-36 quality of life questionnaire, health utility rating scale (RS) and DAS. Patients? satisfaction with care was measured on a visual analogue scale. Within-group differences between baseline and follow-up scores were tested with the Wilcoxon signed rank matched-pairs test. Co-variance analysis was used to analyse between-group differences and to determine factors predicting clinical response. <h3>Results</h3> 210 patients (median age 58 years, median disease duration 1.8 years and median HAQ score 1.25) were included in the study. Within all 3 groups functional status, quality of life, health utility and disease activity improved significantly over time (all P-values &lt;0.05). A comparison of clinical outcome among the three groups and a comparison between the nurse specialist group and the inpatient and day patient care groups together did not show any sustained significant differences. Subgroup analysis showed that with increasing age, the most favourable outcome according to the HAQ shifted from care provided by a clinical nurse specialist and inpatient care to day patient care. Patients? satisfaction with care was significantly lower in the nurse specialist group than in the inpatient and day patient care groups (P &lt; 0.001). <h3>Conclusion</h3> Care provided by a clinical nurse specialist appears to have a similar clinical outcome in comparison with inpatient and day patient team care in patients with RA. Age was the only factor related to differences in functional outcome between the three treatment groups. The choice of management strategy may, apart from age, further be dependent on the availability of facilities, the preferences of patients and health care providers and on economic considerations.
Pneumococcal Colonization and Virulence Factors Identified Via Experimental Evolution in Infection Models
Authors: Angharad E Green, Deborah Howarth, Chrispin Chaguza, Haley Echlin, R Frèdi Langendonk, Connor Munro, Thomas E Barton, Jay C D Hinton, Stephen D Bentley, Jason W Rosch, Daniel R Neill
Journal: Molecular Biology and Evolution (2021)

Abstract Streptococcus pneumoniae is a commensal of the human nasopharynx and a major cause of respiratory and invasive disease. We examined adaptation and evolution of pneumococcus, within nasopharynx and lungs, in an experimental system where the selective pressures associated with transmission were removed. This was achieved by serial passage of pneumococci, separately, in mouse models of nasopharyngeal carriage or pneumonia. Passaged pneumococci became more effective colonizers of the respiratory tract and we observed several examples of potential parallel evolution. The cell wall-modifying glycosyltransferase LafA was under strong selection during lung passage, whereas the surface expressed pneumococcal vaccine antigen gene pvaA and the glycerol-3-phosphate dehydrogenase gene gpsA were frequent targets of mutation in nasopharynx-passaged pneumococci. These mutations were not identified in pneumococci that were separately evolved by serial passage on laboratory agar. We focused on gpsA, in which the same single nucleotide polymorphism arose in two independently evolved nasopharynx-passaged lineages. We describe a new role for this gene in nasopharyngeal carriage and show that the identified single nucleotide change confers resistance to oxidative stress and enhanced nasopharyngeal colonization potential. We demonstrate that polymorphisms in gpsA arise and are retained during human colonization. These findings highlight how within-host environmental conditions can determine trajectories of bacterial evolution. Relative invasiveness or attack rate of pneumococcal lineages may be defined by genes that make niche-specific contributions to bacterial fitness. Experimental evolution in animal infection models is a powerful tool to investigate the relative roles played by pathogen virulence and colonization factors within different host niches.
Sixty seconds on . . . TikTok doctors
Authors: Elisabeth Mahase
Journal: BMJ (2021)

No, we’re talking about the video sharing social media platform TikTok. The app has gained huge popularity during the pandemic, with more people at home and in search of distraction.

No, you’re safe for now. Some doctors are, however, using the platform to provide health related information to the public, on both covid-19 and non-covid-19 related matters. There are videos on everything from bed …
A practical approach to imaging characteristics and standardized reporting of COVID-19: a radiologic review
Authors: Deniz Esin Tekcan Sanli, Duzgun Yildirim, Ahmet Necati Sanli, Suha Turkmen, Neval Erozan, Guray Husmen, Aytug Altundag, Filiz Tuzuner
Journal: Military Medical Research (2021)

Abstract Novel coronavirus (2019-nCoV), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a pathogen that has caused a rapidly spreading pandemic all over the world. The primary mean of transmission is inhalation with a predilection for respiratory system involvement, especially in the distal airways. The disease that arises from this novel coronavirus is named coronavirus disease 2019 (COVID-19). COVID-19 may have a rapid and devastating course in some cases leading to severe complications and death. Radiological imaging methods have an invaluable role in diagnosis, follow-up, and treatment. In this review, radiological imaging findings of COVID-19 have been systematically reviewed based on the published literature so far. Radiologic reporting templates are also emphasized from a different point of view, considering specific distinctive patterns of involvement.
Chemotherapy use in early-stage anal canal squamous cell carcinoma and its impact on outcome.
Authors: Deanna Huffman, Thejus Thayyil Jayakrishnan, Rodney E. Wegner, Brittany Vannatter, Dulabh K. Monga, Gene Grant Finley, James McCormick, Alexander V. Kirichenko
Journal: Journal of Clinical Oncology (2021)

2 Background: The standard of care for non-metastatic squamous cell carcinoma of the anal canal (SCCA) is concurrent chemoradiotherapy with high rates of local control. There is some thought that perhaps chemotherapy can be omitted for the earliest stages without worse outcomes. We used the National Cancer Database (NCDB) to identify predictors of chemotherapy receipt or omission to assess the impact on outcomes. Methods: We queried the NCDB from 2004-2016 for patients with cT1N0M0 SCCA treated non-operatively with radiation with and without chemotherapy and at least 2 months of follow-up. Logistic regression was used to generate predictors of chemotherapy use. Cox regression identified predictors of survival. Propensity matching was done to help account for indication bias. Results: We identified 2,959 patients meeting eligibility, of which 8% (n = 237) were treated without chemotherapy. The vast majority (n = 2722, 92%) were recorded as having multi-agent chemotherapy. Median radiation dose was 50.4 Gy (IQR 45-54) in 28 fractions (IQR 49.4-59.4) with chemotherapy and 54.0 Gy (IQR 49.4-59.4) in 30 fractions (IQR 25-33) in those who had chemotherapy omitted. Predictors of omission of chemotherapy were older age (OR 0.66, 95% CI [0.49-0.90], P = 0.0087), higher comorbidity score (OR 0.62, 95% CI [0.38-0.99], P = 0.0442), African American race (OR 0.57, 95% CI [0.36-0.90], P = 0.0156) and more remote year of treatment (OR 1 1 for years 2004-2006). Predictors of survival were younger age (HR 1.73 for age &gt; 58 years, 95% CI [1.41-2.11], P &lt; 0.001), multi-agent chemotherapy use (HR 0.48, 95% CI [0.38-0.62], P &lt; 0.0001), higher income (HR 0.57, 95% CI [0.40-0.81], P = 0.0016), female gender (HR 0.68, 95% CI [0.57-0.82], P = 0.0016), and private insurance (HR 0.54, 95% CI [0.34-0.87], P = 0.0104). After propensity matching, overall survival at 120 months for patients treated with and without chemotherapy was 86% and 65%, respectively (p &lt; 0.0001). Conclusions: Chemotherapy is utilized the majority of the time in early stage SCCA. Being mindful of the limitations of a retrospective database analysis, our results suggest an association with worse survival outcomes when chemotherapy is omitted.
Community Outbreak Investigation of SARS-CoV-2 Transmission Among Bus Riders in Eastern China—More Detailed Studies Are Needed—Reply
Authors: Ye Shen, Changwei Li, Feng Ling
Journal: JAMA Internal Medicine (2021)

In Reply Tambyah et al raise several reasons why they do not believe that our case report of bus riders in eastern China1 supports an airborne transmission route of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Abstract 13: Adherence to Various Dietary Patterns and Risk of Recurrent Coronary Heart Disease and Mortality in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: James M Shikany, Monika M Safford, Joanna Bryan, PK Newby, Joshua S Richman, Raegan W Durant, Todd M Brown, Suzanne Judd
Journal: Circulation (2017)

Background: We have shown that the Southern dietary pattern, characterized by added fats, fried foods, organ and processed meats, and sugar-sweetened beverages, is associated with a greater risk of incident CHD in REGARDS, a national, population-based, longitudinal cohort. We sought to determine if the Southern pattern, other dietary patterns, and the Mediterranean diet score were associated with CHD events and mortality in REGARDS participants who previously reported CHD. Methods: REGARDS enrolled white and black adults aged ≥45 years between 2003-2007. Data were analyzed from 3,562 participants with CHD at baseline. Participants completed an FFQ at baseline, from which 5 dietary patterns were derived through factor analysis (Table). The Mediterranean diet score was calculated for each participant. Expert-adjudicated CHD events included myocardial infarction and CHD death. Cox proportional hazards regression was used to model the association of the dietary patterns and score with CHD events and death, adjusting for sociodemographics, lifestyle factors, energy intake, anthropometrics, and medical conditions. Results: Over 7 years of follow-up, there were 581 recurrent CHD events and 1,098 deaths. In fully-adjusted analyses, the highest quartile of adherence to the alcohol/salads pattern and highest group of the Mediterranean diet score were associated with lower risk of recurrent CHD compared to the lowest quartile/group (HR: 0.76; 95% CI: 0.59 – 0.98, HR: 0.78; 95% CI: 0.62 – 0.98, respectively). The highest quartile of adherence to the Southern pattern was associated with higher mortality (HR: 1.57; 95% CI: 1.28 – 1.91), while the highest group of the Mediterranean diet score was associated with lower mortality (HR: 0.80; 95% CI: 0.68 – 0.95). Conclusions: While the Southern dietary pattern was not related to risk of recurrent CHD, it was associated with higher mortality in REGARDS participants with existing CHD. Greater adherence to a Mediterranean diet was associated with lower risk of recurrent CHD and mortality.